Elsevier Logo

English

ThisiscontentfromElsevier'sDrugInformation

TRANSFORM HOW YOU USE DRUG INFORMATION

Learn more about Elsevier's Drug Information today! Get the drug data and decision support you need, including TRUE Daily Updates™ including every day including weekends and holidays.

May.26.2021

Budesonide; Formoterol

Indications/Dosage

Labeled

  • asthma maintenance
  • chronic bronchitis
  • chronic obstructive pulmonary disease (COPD)
  • emphysema

Off-Label

  • bronchospasm
  • exercise-induced bronchospasm prophylaxis
† Off-label indication

For asthma maintenance treatment

Oral Inhalation dosage (inhalation aerosol; e.g., Symbicort)

Adults

2 oral inhalations of either 80/4.5 (80 mcg budesonide with 4.5 mcg formoterol per actuation) or 160/4.5 (160 mcg budesonide with 4.5 mcg formoterol per actuation) twice daily, morning and evening, at the same times each day. Choose dose based on asthma severity and previous therapy. Max: 2 oral inhalations of 160/4.5 twice daily (640 mcg budesonide with 18 mcg formoterol per day).[32950]

Children and Adolescents 12 to 17 years

2 oral inhalations of either 80/4.5 (80 mcg budesonide with 4.5 mcg formoterol per actuation) or 160/4.5 (160 mcg budesonide with 4.5 mcg formoterol per actuation) twice daily, morning and evening, at the same times each day. Choose dose based on asthma severity and previous therapy. Max: 2 oral inhalations of 160/4.5 twice daily (640 mcg budesonide with 18 mcg formoterol per day).[32950]

Children 6 to 11 years

2 oral inhalations of 80/4.5 (80 mcg budesonide with 4.5 mcg formoterol per actuation) twice daily is the recommended and max dosage (Max: 320 mcg budesonide with 18 mcg formoterol per day).[32950]

Oral Inhalation dosage [NAEPP Recommendations; inhaler product not specified]

Adults†

1 or 2 oral inhalations (for a total per dose of 160 to 320 mcg budesonide with 9 mcg formoterol) given once or twice daily (depending on asthma severity and ICS dose in the ICS-formoterol preparation). When this combination is used as both a controller and a reliever therapy, the maximum total dosage for formoterol per NAEPP is 54 mcg/day or 12 oral inhalations of a product containing 4.5 mcg/actuation of formoterol.[66299]

Children† and Adolescents† 12 to 17 years

1 or 2 oral inhalations (for a total per dose of 160 to 320 mcg budesonide with 9 mcg formoterol) given once or twice daily (depending on asthma severity and ICS dose in the ICS-formoterol preparation). When this combination is used as both a controller and a reliever therapy, the maximum total dosage for formoterol per NAEPP is 54 mcg/day or 12 oral inhalations of a product containing 4.5 mcg/actuation of formoterol.[66299]

Oral Inhalation dosage [GINA Recommendations] (Symbicort Turbohaler inhalation powder†)

Adults†

100 mcg budesonide/6 mcg formoterol (1 oral inhalation) or 200 mcg budesonide/6 mcg formoterol (1 oral inhalation) twice daily. Some patients may require increased controller dosage, up to 800 mcg budesonide/24 mcg formoterol via oral inhalation twice daily. When this combination is used as both a controller and a reliever therapy, the maximum total dosage for formoterol per GINA is 72 mcg/day (12 oral inhalations of a formoterol 6 mcg/actuation product per day). The Symbicort Turbohaler is an approved drug in the UK for maintenance and reliever therapy, and thus maximum dosages and product strengths vary from U.S. available products.[64807] [65232]

Children† and Adolescents† 12 to 17 years

100 mcg budesonide/6 mcg formoterol (1 oral inhalation) or 200 mcg budesonide/6 mcg formoterol (1 oral inhalation) twice daily. Some patients may require increased controller dosage, up to 400 mcg budesonide/12 mcg formoterol twice daily. When this combination is used as both a controller and a reliever therapy, the maximum total dosage per GINA for formoterol is 72 mcg/day (12 oral inhalations of a formoterol 6 mcg/actuation product per day). The Symbicort Turbohaler is an approved drug in the UK for maintenance and reliever therapy, and thus maximum dosages and product strengths vary from U.S. available products.[64807] [65232]

Oral Inhalation dosage [SMART pediatric data]

Children† 4 to 11 years

80 mcg budesonide/4.5 mcg formoterol (1 oral inhalation) once daily as a controller dose, with additional inhalations allowed "as needed", has been used per the SMART dosing strategy. Max: 8 oral inhalations/day (Max formoterol: 36 mcg/day).[66020] Data are limited for "as needed" use in this age group.[64807] [66299] Symbicort Turbohaler is approved in the UK for maintenance therapy for children 6 to 11 years of age; the recommended dose for that product is 2 oral inhalations of 100/6 (100 mcg budesonide/6 mcg formoterol per actuation) twice daily; however, the product is not labeled for reliever therapy for this age group.[65232]

For transient increase in bronchospasm† (e.g., episodic wheezing) as asthma reliever therapy

Oral Inhalation dosage (NAEPP recommendation; inhaler product not specified)

Adults†

1 or 2 oral inhalations (for a total per dose of 160 to 320 mcg budesonide with 9 mcg formoterol) as needed in addition to daily maintenance dosing; may repeat dose after 5 minutes if needed. The maximum total dosage for formoterol per NAEPP is 54 mcg/day or 12 oral inhalations of a product containing 4.5 mcg/actuation of formoterol.[66299]

Children† and Adolescents† 12 to 17 years

1 or 2 oral inhalations (for a total per dose of 160 to 320 mcg budesonide with 9 mcg formoterol) as needed in addition to daily maintenance dosing; may repeat dose after 5 minutes if needed. The maximum total dosage for formoterol per NAEPP is 54 mcg/day or 12 oral inhalations of a product containing 4.5 mcg/actuation of formoterol.[66299]

Oral Inhalation dosage (GINA recommendation)

Adults†

100 mcg budesonide/6 mcg formoterol (1 oral inhalation) or 200 mcg budesonide/6 mcg formoterol (1 oral inhalation) as needed in addition to a daily maintenance dose; may repeat after 5 minutes. GINA Max: 12 oral inhalations/day (do not exceed formoterol 72 mcg/day).[64807] Dosing for reliever therapy is based on a product not available in U.S.[65232]

Children† and Adolescents† 12 to 17 years

100 mcg budesonide/6 mcg formoterol (1 oral inhalation) or 200 mcg budesonide/6 mcg formoterol (1 oral inhalation) as needed in addition to a daily maintenance dose; may repeat after 5 minutes. GINA Max: 12 oral inhalations/day (do not exceed formoterol 72 mcg/day).[64807] Dosing for reliever therapy is based on a product not available in U.S.[65232]

Oral Inhalation dosage [SMART pediatric data]

Children† 4 to 11 years

80 mcg budesonide/4.5 mcg formoterol (1 oral inhalation) has been used "as needed" in addition to a daily maintenance dose per the SMART dosing strategy. Max: 8 oral inhalations total/day (Max formoterol: 36 mcg/day).[66020] Per guidelines, data are limited for "as needed" use in this age group due to varying doses and protocols in studies.[64807] [66299] Symbicort Turbohaler is approved in the UK for asthma controller therapy for children 6 to 11 years of age; however, the product is not labeled for reliever therapy for this age group.[65232]

For exercise-induced bronchospasm prophylaxis†

Oral Inhalation dosage (oral inhalation powder; e.g., Symbicort)

Adults

1 oral inhalation of 160/4.5 (160 mcg budesonide with 4.5 mcg formoterol per actuation) 5 to 20 minutes prior to exercise has been used in a clinical trial and was efficacious. FDA-approved Max: 2 oral inhalations of 160/4.5 twice daily (640 mcg budesonide with 18 mcg formoterol per day). Regular ICS controller therapy is also known to reduce the incidence of EIB.[32950] [56291] [64814] [64807]

For the maintenance treatment of chronic obstructive pulmonary disease (COPD) (e.g., chronic bronchitis or emphysema), and to reduce COPD exacerbations

Oral Inhalation dosage (inhalation aerosol; e.g., Symbicort)

Adults

2 oral inhalations of 160/4.5 (160 mcg of budesonide with 4.5 mcg of formoterol per actuation) twice daily, approximately 12 hours apart, is the recommended and max dosage (max: 640 mcg budesonide with 18 mcg formoterol per day).[32950] Not indicated for the relief of acute bronchospasm. Use an inhaled short-acting beta-2 agonist (SABA) for immediate relief of acute symptoms. Do not use other long-acting beta-agonists (LABAs) concurrently. If on oral corticosteroids, wean the OCS slowly after transferring to budesonide; formoterol by reducing the daily dose by 2.5 mg prednisone or equivalent on a weekly basis.[32950] According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, budesonide; formoterol may be used as initial therapy in group D (those with a high risk of exacerbation). At follow-up, if the patient is still experiencing dyspnea, consider switching inhaler device and investigate for other causes of dyspnea. If the patient has exacerbations, consider triple therapy with a long-acting muscarinic antagonist (LAMA), a long-acting beta-2 agonist (LABA), and an inhaled corticosteroid (ICS).[63765]

Therapeutic Drug Monitoring

Maximum Dosage Limits

  • Adults

    640 mcg of budesonide and 18 mcg of formoterol via oral inhalation/day. The maximum number of inhalations to be administered/day regardless of strength of Symbicort is 4.

  • Geriatric

    640 mcg of budesonide and 18 mcg of formoterol via oral inhalation/day. The maximum number of inhalations to be administered/day regardless of strength of Symbicort is 4.

  • Adolescents

    640 mcg of budesonide and 18 mcg of formoterol via oral inhalation/day. The maximum number of inhalations to be administered/day regardless of strength of Symbicort is 4.

  • Children

    12 years: 640 mcg of budesonide and 18 mcg of formoterol via oral inhalation/day. The maximum number of inhalations to be administered/day regardless of strength of Symbicort is 4.

    6 to 11 years: 320 mcg of budesonide and 18 mcg of formoterol via oral inhalation/day. The maximum number of inhalations to be administered/day of Symbicort is 4.

    1 to 5 years: Safety and efficacy have not been established.

Patients with Hepatic Impairment Dosing

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Patients with Renal Impairment Dosing

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

† Off-label indication
Revision Date: 05/26/2021, 11:21:31 AM

References

32950 - Symbicort (budesonide; formoterol fumarate dihydrate) inhalation aerosol package insert. Wilmington, DE: AstraZeneca LP; 2017 Dec.56291 - Parsons JP, Hallstrand TS, Mastronarde JG, et al. An official American Thoracic Society clinical practice guideline exercise induced bronchoconstriction. Am J Respir Crit Care Med 2013;187:1016-1027.63765 - Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2021. Retrieved 3/8/2021. Available on the World Wide Web at https://goldcopd.org/wp-content/uploads/2020/11/GOLD-REPORT-2021-v1.1-25Nov20_WMV.pdf64807 - Global Strategy for Asthma Management and Prevention. Global Initiative for Asthma (GINA) 2020. Available from: http://www.ginasthma.org. Accessed May 20th, 2020.64814 - Lazarinis N, Jorgensen L, Ekstrom T, et al. Combination of budesonide/formoterol on demand improves asthma control by reducing exercise-induced bronchoconstriction. Thorax 2014;2:130-6.65232 - Symbicort Turbohaler 100/6, 200/6, and 400/12 Inhalation Powder (budesonide; formoterol) European Medicines Agency official product labels. Bedfordshire, UK; AstraZeneca UK Limited: 2019 Aug. Available at: www.medicines.org.uk/emc/66020 - Bisgaard H, Le Roux P, Bjamer D, et al. Budesonide/formoterol maintenance plus reliever therapy: a new strategy in pediatric asthma. Chest. 2006;130:1733-1743.66299 - Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC), et al. 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020;146:1217-1270.

How Supplied

Budesonide, Formoterol Fumarate Pressurized inhalation, suspension

Budesonide/Formoterol Fumarate Dihydrate 80mcg-4.5mcg/actuation Inhalation Aerosol (00310-7372) (Prasco Laboratories) null

Budesonide, Formoterol Fumarate Pressurized inhalation, suspension

Symbicort 80mcg-4.5mcg/actuation Inhalation Aerosol (00186-0372) (AstraZeneca LP) nullSymbicort 80mcg-4.5mcg/actuation Inhalation Aerosol package photo

Budesonide, Formoterol Fumarate Pressurized inhalation, suspension

Symbicort 80mcg-4.5mcg/actuation Inhalation Aerosol (00186-0372) (AstraZeneca LP) null

Budesonide, Formoterol Fumarate Pressurized inhalation, suspension

Budesonide/Formoterol Fumarate Dihydrate 160mcg-4.5mcg/actuation Inhalation Aerosol (00310-7370) (Prasco Laboratories) nullBudesonide/Formoterol Fumarate Dihydrate 160mcg-4.5mcg/actuation Inhalation Aerosol package photo

Budesonide, Formoterol Fumarate Pressurized inhalation, suspension

Symbicort 160mcg-4.5mcg/actuation Inhalation Aerosol (00186-0370) (AstraZeneca LP) null

Budesonide, Formoterol Fumarate Pressurized inhalation, suspension

Symbicort 160mcg-4.5mcg/actuation Inhalation Aerosol (00186-0370) (AstraZeneca LP) nullSymbicort 160mcg-4.5mcg/actuation Inhalation Aerosol package photo

Description/Classification

Description

Budesonide; formoterol is a combination of an inhaled corticosteroid (ICS), budesonide, and a long-acting beta-2 agonist (LABA), formoterol. It is administered by oral inhalation twice daily. The combination is indicated for the maintenance treatment of asthma in adult and pediatric patients 6 years and older. Budesonide; formoterol is also indicated for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adults and to reduce the risk of exacerbations of COPD.[32950] According to the FDA-approved label, budesonide; formoterol is not recommended for acute bronchospasm or acute asthmatic attacks [32950]; however, guidelines promote the use of "SMART" (single maintenance and reliever therapy) inhaler dosing strategies for daily and "as-needed" formoterol-ICS as the preferred combined controller and reliever regimen in adults and adolescents 12 years and older with mild to moderate asthma.[64807][66299] For children 4 to 11 years of age, NAEPP additionally recommends maintenance and "as-needed" ICS-formoterol "SMART" regimens as an option for those needing step 3 (moderate) and step 4 (moderate to severe) level persistent asthma treatment.[66299] GINA recommends that in children 6 to 11 years with moderate to severe asthma, an ICS in combination with LABA is the preferred controller regimen and is used with an as-needed short-acting beta-agonist (SABA) as the preferred reliever.[64807] Budesonide; formoterol is approved as both a reliever and controller asthma therapy in other countries.[65232] Clinical trials have demonstrated the beneficial effects of the concurrent use of budesonide; formoterol on lung function and the subsequent reduction of asthma symptoms.[32953] Budesonide; formoterol may be used as initial therapy in patients with a high risk of COPD exacerbation. An ICS combined with a LABA is more effective than the individual components in improving lung function and health status and reducing exacerbations in patients with exacerbations and moderate to very severe COPD; however clinical trials failed to demonstrate a statistically significant effect on survival.[63765]

Classifications

  • Respiratory System
    • Agents for Reactive and Obstructive Airway Diseases
      • Reactive and Obstructive Airway Disease Combinations
        • Respiratory Corticosteroids in Combination with Respiratory Long-Acting Beta-2 Agonists
Revision Date: 01/25/2021, 12:43:16 PM

References

32950 - Symbicort (budesonide; formoterol fumarate dihydrate) inhalation aerosol package insert. Wilmington, DE: AstraZeneca LP; 2017 Dec.32953 - Noonan M, Rosenwasser LJ, et al. Efficacy and safety of budesonide and formoterol in one pressurized metered-dose inhaler in adults and adolescents with moderate to severe asthma: a randomized clinical trial. Drugs 2006;66:2235-54. Abstract63765 - Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2021. Retrieved 3/8/2021. Available on the World Wide Web at https://goldcopd.org/wp-content/uploads/2020/11/GOLD-REPORT-2021-v1.1-25Nov20_WMV.pdf64807 - Global Strategy for Asthma Management and Prevention. Global Initiative for Asthma (GINA) 2020. Available from: http://www.ginasthma.org. Accessed May 20th, 2020.65232 - Symbicort Turbohaler 100/6, 200/6, and 400/12 Inhalation Powder (budesonide; formoterol) European Medicines Agency official product labels. Bedfordshire, UK; AstraZeneca UK Limited: 2019 Aug. Available at: www.medicines.org.uk/emc/66299 - Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC), et al. 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020;146:1217-1270.

Administration Information

General Administration Information

For storage information, see the specific product information within the How Supplied section.

NOTE: Patients should be instructed to never use budesonide; formoterol to treat acute bronchospasm. If any patient who uses budesonide; formoterol experiences wheezing that worsens and cannot be relieved during an acute asthma attack, they should be instructed to seek immediate medical attention.

Route-Specific Administration

Inhalation Administration

Oral Inhalation Administration

  • Instruct patient on proper inhalation technique. Make sure the canister is firmly seated in the plastic mouthpiece adapter before each use. The inhaler should be primed before the first use, when more than 7 days have elapsed since the last use, or if it has been dropped. To prime the inhaler, shake the canister for 5 seconds and release a test spray away from the face; repeat steps for a second test spray.
  • For patients of any age unable to coordinate inhalation and actuation, a spacer or valved holding chamber (VHC) should be used.
  • The choice of using a mouthpiece versus a face mask with a spacer/VHC device must be made based on the skills and understanding of each individual patient. However, in general, children < 4 years require administration with a tight fitting face mask and spacer/VHC device to achieve optimal delivery. If a face mask is used, allow 3—5 inhalations per actuation.
  • Following administration, instruct patient to rinse mouth with water to minimize dry mouth and local infection.
  • To avoid the spread of infection, do not use the inhaler for more than one person.
  • Encourage patient to keep track of the number of inhalations taken from the Symbicort inhaler; the inhaler should be discarded after the number of inhalations on the product label and box have been used or within 3 months of removing from foil pouch, whichever comes first.

Clinical Pharmaceutics Information

From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database
    Revision Date: 07/01/2015, 10:40:00 AM

    References

    Adverse Reactions

    Mild

    • agitation
    • back pain
    • cough
    • dizziness
    • ecchymosis
    • headache
    • infection
    • influenza
    • muscle cramps
    • nasal congestion
    • nausea
    • pharyngitis
    • restlessness
    • rhinitis
    • sinusitis
    • tremor
    • urticaria
    • vomiting

    Moderate

    • adrenocortical insufficiency
    • angina
    • candidiasis
    • cataracts
    • depression
    • growth inhibition
    • hyperglycemia
    • hypertension
    • hypokalemia
    • hypotension
    • hypothalamic-pituitary-adrenal (HPA) suppression
    • osteopenia
    • osteoporosis
    • palpitations
    • QT prolongation
    • sinus tachycardia
    • wheezing

    Severe

    • anaphylactoid reactions
    • angioedema
    • arrhythmia exacerbation
    • asthma-related death
    • atrial tachycardia
    • bronchospasm
    • increased intracranial pressure
    • ocular hypertension
    • ventricular tachycardia

    The safety of orally inhaled budesonide; formoterol for asthma was studied in patients 12 years or older in three 12-week controlled clinical trials. Studies included 277 and 124 patients receiving the two available strengths of budesonide; formoterol 80/4.5 mcg and 160/4.5 mcg, respectively. The most commonly reported adverse reactions (occurring at an incidence of 3% or more) in the two dosing groups are listed regardless of causality and at increased incidence vs. placebo: back pain (3.2%, 1.6%), headache (6.5%, 11.3%), influenza (3.2%, 2.4%), nasal congestion (2.5%, 3.2%), naso-pharyngitis (10.5%, 9.7%), vomiting (1.4%, 3.2%), pharyngo-laryngeal pain (6.1%, 8.9%), sinusitis (5.8%, 4.8%), stomach discomfort (1.1%, 6.5%), and upper respiratory tract infection (7.6%, 10.5%). The safety profile in pediatric patients 6 to 11 years old with asthma was similar to that of older patients. Reactions occurring in 3% or more included upper respiratory tract infection, pharyngitis, headache, and rhinitis. In clinical trials for COPD, 771 patients received budesonide; formoterol 160/4.5 mcg for an average duration of 255.2 days. The most commonly reported adverse reactions (occurring at an incidence of 3% or more) relative to placebo included naso-pharyngitis (7.3%), bronchitis (5.4%), sinusitis (3.5%), and viral respiratory tract infection (3.5%). Lung infections other than pneumonia (mostly bronchitis) occurred in 7.9% of patients receiving active drug. Other adverse reactions reported with budesonide; formoterol use include nausea, muscle cramps, tremor, dizziness, dysphonia, cough, and throat irritation.[32950]

    Budesonide; formoterol, like other products containing inhaled beta-2 agonists, can produce life-threatening paradoxical bronchospasm. In the event of a paradoxical bronchospasm, discontinue budesonide; formoterol immediately and initiate an alternative therapy.[32950]

    An increase in the need for rescue inhaler use and/or worsening wheezing may occur during therapy with budesonide; formoterol and are symptoms of a deterioration of the underlying respiratory condition, a potentially life-threatening condition. Advise patients not to exceed recommended doses of this medicine, but instead, seek immediate medical attention if such symptoms occur.[32950] When long-acting beta agonists (LABAs) such as formoterol are used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone.[62717] The use of a LABA as monotherapy to treat asthma, without inhaled corticosteroids [ICS], is associated with an increased risk of asthma-related death. Available data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patients.[37481] [41282] These findings are considered a class effect of LABA monotherapy. In most cases, serious acute respiratory events have occurred in patients with severe asthma and/or in patients in whom asthma has been acutely deteriorating, but such events have also occurred in patients with less severe asthma. These findings pertain only to patients who have asthma.[32950]

    Immediate and delayed hypersensitivity reactions, including anaphylactoid reactions, angioedema, bronchospasm, urticaria, exanthema, dermatitis, and pruritus have been reported with budesonide; formoterol use.[32950]

    As with other beta-2 agonists, a number of metabolic disturbances can develop including hyperglycemia and hypokalemia; these events were seen infrequently during clinical studies in patients receiving inhaled budesonide; formoterol at recommended dosages but have been reported with postmarketing use. Beta-agonist-induced hypokalemia may increase the risk of cardiac arrhythmia exacerbation in predisposed patients. Angina pectoris, sinus tachycardia, atrial tachycardia, ventricular tachycardia, atrial fibrillation, extrasystoles, palpitations, hypotension, and hypertension have been reported with postmarketing use of budesonide; formoterol. Treatment with long-acting beta-agonists, like formoterol, has been reported to produce clinically significant QT prolongation, which can lead to ventricular arrhythmias. Excessive beta-adrenergic stimulation has been associated with angina, hypertension or hypotension, tachycardia, arrhythmias, and palpitations.[32950]

    Orally inhaled budesonide; formoterol has a relatively low risk of hypothalamic-pituitary-adrenal (HPA) suppression when used at recommended doses. Pharmacologic doses of budesonide administered for prolonged periods may, however, result in adrenocortical insufficiency.[32950] Adrenal suppression and increased intracranial pressure have been reported with the use and/or withdrawal of orally inhaled steroids in pediatric patients.[51792] Local immunosuppression associated with inhaled budesonide use may be manifested as an overgrowth of fungus in the nose, mouth, and throat. Oral candidiasis (thrush) is a well-known adverse reaction of oral inhalation steroid therapy and occurred in 1.4% to 6% of adult patients receiving inhaled budesonide; formoterol during clinical trials.[32950]

    Growth inhibition has been observed in some children following therapy with orally inhaled corticosteroids including budesonide. Growth inhibition has been observed in the absence of laboratory evidence of hypothalamic-pituitary-adrenal (HPA) suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients. With orally inhaled corticosteroids, the mean reduction in growth velocity is approximately one centimeter per year (range 0.3 to 1.8 cm per year) and appears to be related to the dose and duration of exposure. In general, the benefits of regular inhaled corticosteroid (ICS) use outweigh the potential risk of relatively small and non-cumulative growth suppression in children with asthma; however, growth should be monitored.[57670] Further study is needed to determine the long-term effects of growth velocity reduction in children, including the impact on final adult height. To minimize the effects of inhaled corticosteroids, each patient should be titrated to the lowest effective dose.[32950]

    Corticosteroids, even orally inhaled doses like budesonide, can induce cataracts and have the potential to induce or worsen ocular hypertension (glaucoma). Although rarely reported during treatment with budesonide; formoterol, patients are encouraged to keep up with routine ophthalmological exams.[32950]

    Behavior disturbances, sleep disturbances, agitation, depression, nervousness, restlessness, and skin bruising (ecchymosis) have been reported with postmarketing use of budesonide; formoterol.[32950]

    Prolonged use (e.g., more than 1 year) of high doses of inhaled corticosteroids, like budesonide, especially when used in combination with frequent courses of systemic corticosteroids, may be associated with reduced bone mineral density (BMD), which may increase the risk of osteopenia or osteoporosis. The clinical significance of small changes in BMD with regard to long-term outcomes, such as fracture, is unknown.[32950]

    Revision Date: 05/26/2021, 11:42:16 AM

    References

    32950 - Symbicort (budesonide; formoterol fumarate dihydrate) inhalation aerosol package insert. Wilmington, DE: AstraZeneca LP; 2017 Dec.37481 - Nelson H, Weiss S, Bleecker E, Yancey S, Dorinsky P, SMART Study Group. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest 2006;129(1):15-26.41282 - Castle W, Fuller R, Hall J, Palmer J. Serevent nationwide surveillance study: comparison of salmeterol with salbutamol in asthmatic patients who require regular bronchodilator treatment. BMJ 1993;306(6884):1034-3107.51792 - Patradoon-Ho P, Gunasekera H, Ryan MM. Inhaled corticosteroids, adrenal suppression and benign intracranial hypertension. Med J Aust 2006;185:279-28057670 - Zhang L, Prietsch SO, Ducharme FM. Inhaled corticosteroids in children with persistent asthma: effects on growth. Cochrane Database Syst Rev 2014;7:CD009471. doi: 10.1002/14651858.CD009471.pub262717 - FDA Medwatch -Long-Acting Beta Agonists (LABAs) and Inhaled Corticosteroids (ICS): Boxed Warning About Asthma-Related Death Removed. Retrieved December 21, 2017. Available on the World Wide Web https://www.fda.gov/Drugs/DrugSafety/ucm589587.htm?utm_campaign=New%20FDA%20Drug%20Safety%20Communication%20update%20on%20long-acting%20beta%20agonists%20%28LABAs%29&utm_medium=email&utm_source=Eloqua

    Contraindications/Precautions

    Absolute contraindications are italicized.

    • status asthmaticus
    • acute bronchospasm
    • apheresis
    • asthma-related death
    • AV block
    • bradycardia
    • breast-feeding
    • cardiac arrhythmias
    • cardiac disease
    • cardiomyopathy
    • cataracts
    • celiac disease
    • children
    • coronary artery disease
    • corticosteroid hypersensitivity
    • corticosteroid therapy
    • diabetes mellitus
    • females
    • fever
    • fungal infection
    • glaucoma
    • growth inhibition
    • heart failure
    • hepatic disease
    • herpes infection
    • human immunodeficiency virus (HIV) infection
    • hyperglycemia
    • hyperparathyroidism
    • hypertension
    • hyperthyroidism
    • hypocalcemia
    • hypokalemia
    • hypomagnesemia
    • hypothalamic-pituitary-adrenal (HPA) suppression
    • hypothermia
    • hypothyroidism
    • increased intracranial pressure
    • increased intraocular pressure
    • infants
    • infection
    • labor
    • long QT syndrome
    • MAOI therapy
    • measles
    • myocardial infarction
    • neonates
    • osteopenia
    • osteoporosis
    • paradoxical bronchospasm
    • pheochromocytoma
    • pregnancy
    • QT prolongation
    • rheumatoid arthritis
    • seizure disorder
    • sickle cell disease
    • systemic lupus erythematosus (SLE)
    • tachycardia
    • thyrotoxicosis
    • tuberculosis
    • varicella
    • viral infection

    NOTE: This monograph discusses the use of budesonide; formoterol combination product for treating asthma. Clinicians may wish to consult the individual monographs for more information about the specific contraindications and precautions for each agent.

     

    Do not exceed recommended dosages of beta-agonists; fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs in patients with asthma. The exact cause of death is unknown, but cardiac arrest after an unexpected development of a severe acute asthmatic crisis and subsequent hypoxia is suspected.[32950][49951]

    Hypersensitivity to any of the ingredients in budesonide; formoterol contraindicates its use. Although true corticosteroid hypersensitivity is rare, patients who have demonstrated a prior hypersensitivity reaction to budesonide should not receive any form of budesonide. It is possible, though also rare, that such patients will display cross-hypersensitivity to other corticosteroids. It is advisable that patients who have a hypersensitivity reaction to any corticosteroid undergo skin testing, which, although not a conclusive predictor, may help to determine if hypersensitivity to another corticosteroid exists. Such patients should be carefully monitored during and following the administration of any corticosteroid.[27616] Immediate hypersensitivity reactions may also occur after the administration of budesonide; formoterol, as demonstrated by rare cases of urticaria, angioedema, rash, and bronchospasm.

    Budesonide; formoterol use is contraindicated as a primary treatment of status asthmaticus or other acute episodes of asthma or COPD where intensive measures are required. Do not initiate during rapidly deteriorating or potentially life-threatening episodes of asthma or COPD. Long-acting beta-2 agonists (LABAs), when used alone, have been associated with increased risk of severe asthma exacerbation and asthma-related death; this is considered a class effect. When a LABA is used in fixed-dose combination with an inhaled corticosteroid (ICS), data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone. Available data do not suggest an increased risk of death with the use of LABAs in patients with COPD.[32950] [41230] [62717] Budesonide; formoterol should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of asthma or COPD; this product has not been studied in patients with these acutely deteriorating conditions. Do not use budesonide; formoterol for the relief of acute symptoms (i.e., as rescue therapy for the treatment of acute bronchospasm). Acute symptoms should be treated with an inhaled, short-acting beta-agonist (SABA).[32950] When initiating treatment with budesonide; formoterol, patients who have been taking oral or inhaled SABAs on a regular basis should be instructed to discontinue the regular use of these drugs and to use them only for symptomatic relief of acute respiratory symptoms. Prescribe an inhaled SABA, such as albuterol, for rescue treatment of an acute asthma or COPD attack and inform patients that increased use of an inhaled SABA is a signal of deteriorating disease. Loss of symptom control with budesonide; formoterol is also a marker of deterioration of disease; in this setting, a re-evaluation of the patient and the asthma or COPD treatment regimen should be undertaken at once, giving special consideration to the possible need for replacing the current strength of budesonide; formoterol with a higher strength, adding additional inhaled corticosteroid, or initiating systemic corticosteroids. Patients should not use budesonide; formoterol more often than recommended, at higher doses than recommended, or in conjunction with other LABAs as this would be considered duplicative therapy and may lead to additive untoward effects. Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs in patients with asthma.[32950]

    Discontinue the regular use of short acting beta-2 agonists (i.e., four times daily) upon budesonide; formoterol initiation; however, short acting beta-2 agonists can be continued for symptomatic relief of acute asthma symptoms, often referred to as rescue inhalers. Furthermore, patients should not use budesonide; formoterol in conjunction with other long acting beta-2 agonists or other inhaled corticosteroid therapy as this would be considered duplicative therapy and may lead to additive untoward effects.

    Budesonide; formoterol should be used with caution in patients with cardiovascular disorders, particularly coronary insufficiency, cardiac arrhythmias (including tachycardia), and hypertension. Formoterol, like other beta-2 agonists, can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, blood pressure, and/or cardiac symptoms. If such effects occur, the inhaler may need to be discontinued.[32950] In addition, beta-agonists have been reported to produce electrocardiographic changes, such as flattening of the T wave, prolongation of the QTc interval, and ST-segment depression, although the clinical significance of these findings is unknown. Use budesonide; formoterol with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, cardiac disease, cardiac arrhythmias, coronary artery disease, hypertension, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, people 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.[28432] [28457] [56592] [65180] [32950] Correct pre-existing hypokalemia and use with caution in patients at risk for developing hypokalemia. Formoterol, like all beta-agonists, may produce significant hypokalemia and related CV adverse effects in some patients, possibly through intracellular shunting (the decrease is usually transient, not requiring supplementation). In patients with severe COPD, hypokalemia may be potentiated by hypoxia and concomitant treatment, which may increase the susceptibility for cardiac arrhythmias.[32950]

    Budesonide; formoterol should be used with caution in patients with diabetes mellitus. Inhalation of high doses of beta-2 agonists may cause transient, but clinically relevant, hyperglycemia in some patients. Corticosteroids are also associated with increases in blood glucose in some patients. Such increases in blood glucose are most relevant for patients with diabetes mellitus.[32950]

    Budesonide; formoterol should be used cautiously in patients with hyperthyroidism or thyrotoxicosis, unusual responsiveness to sympathomimetic amines, pheochromocytoma, or a seizure disorder.[32950]

    Budesonide; formoterol should be administered with extreme caution to patients being treated with MAOI therapy (see Drug Interactions).

    Budesonide; formoterol should be used cautiously in patients with glaucoma or other visual disturbance or with a family history of glaucoma. Rare instances of glaucoma, increased intraocular pressure, and cataracts have been reported following the inhaled administration of corticosteroids, including budesonide. Patients receiving corticosteroids chronically should be periodically assessed for cataract formation.

    Although the risk of developing hypothalamic-pituitary-adrenal (HPA) suppression is very low with inhaled budesonide; formoterol, patients should, nevertheless, be monitored for this possibility. Particular care is needed for patients who are transferred from systemic to inhaled corticosteroids because deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic to less systemically absorbed inhaled corticosteroids. Patients previously maintained on doses equivalent to 20 mg/day or more of prednisone may be at increased risk. After withdrawal from systemic corticosteroids, a number of months are required for recovery of HPA-axis function.[32950]

    Although inhaled budesonide; formoterol is absorbed systemically to a lesser extent than other corticosteroids, significant amounts can be absorbed when large doses are administered. This can increase the risk for infection. In general, inhaled corticosteroid therapy used with caution, if at all, in patients with active or quiescent tuberculosis infections of the respiratory tract; untreated systemic fungal infection, bacterial infection, viral infection, or a parasitic infection, especially those not adequately controlled by anti-infective agents. Inhaled corticosteroids should be used cautiously, if at all, in patients with an active herpes infection (including ocular herpes simplex). If a patient on immunosuppressant doses of corticosteroids is exposed to chickenpox, therapy with varicella-zoster immune globulin or pooled intramuscular immunoglobulin may be indicated. If a patient is exposed to measles, prophylaxis with pooled intramuscular immunoglobulin may be indicated. Budesonide oral inhalation has been associated with the development of localized infection with Candida albicans in the nose, mouth, and pharynx. If this develops, discontinuation of inhaled budesonide is warranted, and appropriate local therapy should be instituted. Patients who are on long-term budesonide inhalation therapy should receive a periodic evaluation for Candida infection or other adverse effects.[32950]

    Long-term use of orally inhaled corticosteroids, such as budesonide, may affect normal bone metabolism resulting in a loss of bone mineral density or osteopenia. Use budesonide; formoterol with caution in patients with risk factors for decreased bone mineral content, including tobacco use, advanced age, sedentary lifestyle, poor nutrition, family history of osteoporosis, or chronic use of drugs that decrease bone mass.[32950]

    Formal pharmacokinetic studies using budesonide; formoterol inhalation have not been conducted in patients with hepatic impairment. However, since budesonide and formoterol are predominantly cleared by hepatic metabolism, impairment of liver function may lead to increased exposure of budesonide and formoterol. Therefore, patients with severe hepatic disease should be closely monitored.[32950]

    The safety and efficacy of budesonide; formoterol have not been established in neonates, infants, or children younger than 6 years. For pediatric patients with persistent asthma, limit use to those who have asthma that is not adequately controlled with a long-term asthma control medication, such as an inhaled corticosteroid. When long-acting beta-agonists (LABAs) are used in fixed-dose combination with inhaled corticosteroids (ICS), data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone.[32950] Available data from clinical trials suggest that asthma treatment with LABA monotherapy, without an inhaled corticosteroid, increases the risk of asthma-related hospitalization and death in children and adolescents.[37481] [41230] Pediatric patients may be more susceptible to developing systemic toxicity from corticosteroids. Growth inhibition has been observed in some children following therapy with corticosteroids, including inhaled budesonide therapy.[32950] Adrenal suppression and increased intracranial pressure have been reported with the use and/or withdrawal of orally inhaled corticosteroid formulations in young patients.[51792] To minimize the effects of orally inhaled corticosteroids, each patient should be titrated to the lowest effective dose. The growth of pediatric patients should be monitored regularly.[32950]

    There are no adequate and well-controlled studies of budesonide; formoterol during human pregnancy; however, studies of pregnant women taking inhaled budesonide alone have not shown increases in the risk of abnormalities when given during pregnancy. In animal studies, formoterol fumarate has only shown adverse effects when administered systemically at high systemic exposures greatly exceeding the maximum recommended human daily inhalational dose (MRHDID). No teratogenic, embryocidal, or developmental effects were seen in rats that received formoterol inhalation doses up to 375 times the MRHDID. Women with asthma who become pregnant while stabilized on budesonide; formoterol therapy should discuss their asthma management with a qualified health care professional.[32950] A review of Swedish registries indicated that in over 2,000 births there was no increased risk for congenital malformations during early pregnancy with budesonide inhalation powder or solution.[32950] It is known that improved maternal and perinatal outcomes are achieved with optimal control of asthma during pregnancy.[45934] Large studies of women with asthma have confirmed the lack of relationship between the use of inhaled beta-2 agonists and adverse maternal or fetal outcomes; however, less data are available for long-acting beta agonists (LABAs) such as formoterol vs. short-acting beta agonists (SABAs).[45934] However, most inhaled beta-2 agonists, as well as inhaled budesonide, are considered acceptable for use during pregnancy because of the low bioavailability and maternal serum levels after use.[45934] [49764] [63021] According to the 2004 guidelines of the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group, long-acting beta-2 agonists (LABAs), in combination with inhaled corticosteroids (ICS), are one of the preferred treatment options for the long-term control of moderate asthma during pregnancy and lactation; use of medium dose ICS is also a preferred option. Although a preferred LABA is not recommended, the guideline states that more experience is available with salmeterol. Due to the availability of safety information during pregnancy, budesonide is preferred over other ICS.[45934] Infants born to mothers taking substantial corticosteroid doses during pregnancy should be monitored for signs of hypoadrenalism.[32950] There are no well-controlled human studies that have investigated the effects of budesonide; formoterol on preterm labor or labor at term. Because of the potential for beta-2 agonist interference with uterine contractility, use of budesonide; formoterol should be restricted to those patients in whom the benefits clearly outweigh the risks.[32950]

    There are no well-controlled human studies that have investigated the effects of budesonide; formoterol during breast-feeding. Formoterol was excreted in milk in reproductive studies in rats; however, it is unknown whether formoterol is excreted in human milk. Glucocorticoids, such as budesonide, are excreted into human breast milk. Data from a small number (n = 8) of lactating women showed an estimated oral daily dose of budesonide available to the nursing infants which was approximately 0.3% to 1% of the dose inhaled by the mothers. Budesonide plasma concentrations obtained in five of the infants at about 140 minutes after drug administration to the mother and 90 minutes after breast-feeding were below quantifiable levels.[32950] The amount of inhaled budesonide excreted in breast-milk is minute, and infant exposure is negligible. While not measured, the amount of formoterol absorbed into the maternal bloodstream and excreted into breast-milk after inhalation is expected to be very low; therefore, it is unlikely that nursing infants would be exposed to clinically significant amounts of formoterol via breast milk. Most inhaled bronchodilators are considered acceptable for use during the postpartum period and breast-feeding because of the low bioavailability and maternal serum levels after use.[45934] [63021] The 2004 guidelines of the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group consider a combination of inhaled corticosteroids with long-acting inhaled beta-2 agonists (LABAs) a preferred treatment option for moderate asthma in pregnancy and lactation.[45934] Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Similar to other inhaled beta-agonists, budesonide; formoterol can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs, it should be treated immediately with a short-acting, inhaled bronchodilator, and budesonide; formoterol should be discontinued immediately and alternative therapy instituted.[32950]

    Revision Date: 08/04/2020, 05:16:38 PM

    References

    27616 - Butani L. Corticosteroid-induced hypersensitivity reactions. Ann Allergy Asthma Immunol 2002;89(5):439-445.28432 - Roden, DM. Drug-induced prolongation of the QT interval. New Engl J Med 2004;350:1013-22.28457 - Crouch MA, Limon L, Cassano AT. Clinical relevance and management of drug-related QT interval prolongation. Pharmacotherapy 2003;23:881-908.32950 - Symbicort (budesonide; formoterol fumarate dihydrate) inhalation aerosol package insert. Wilmington, DE: AstraZeneca LP; 2017 Dec.37481 - Nelson H, Weiss S, Bleecker E, Yancey S, Dorinsky P, SMART Study Group. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest 2006;129(1):15-26.41230 - Food and Drug Administration Drug Safety and Availability. Post marketing Drug Safety Information for Patients and Providers: New safety requirements for long-acting inhaled asthma medications called Long-Acting Beta-Agonists (LABAs). Accessed: January 27, 2011. Available on the World Wide Web at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm200776.htm45934 - National Heart , Lung, and Blood Institute, National Asthma Education and Prevention Program Asthma and Pregnancy Working Group. NAEPP expert panel report. Managing asthma during pregnancy: recommendations for pharmacologic treatment-2004 update. 2004;1-57. http://www.nhlbi.nih.gov/health/prof/lung/asthma/astpreg.htm49764 - Hardy-Fairbanks AJ, Baker ER. Asthma in pregnancy: pathophysiology, diagnosis and management. Obstet Gynecol Clin North Am. 2010;37:159-172.49951 - Ventolin HFA (albuterol sulfate) Inhalation Aerosol package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Aug.51792 - Patradoon-Ho P, Gunasekera H, Ryan MM. Inhaled corticosteroids, adrenal suppression and benign intracranial hypertension. Med J Aust 2006;185:279-28056592 - van Noord C, Eijgelsheim M, Stricker BH. Drug- and non-drug-associated QT interval prolongation. Br J Clin Pharmacol 2010;70(1):16-23.62717 - FDA Medwatch -Long-Acting Beta Agonists (LABAs) and Inhaled Corticosteroids (ICS): Boxed Warning About Asthma-Related Death Removed. Retrieved December 21, 2017. Available on the World Wide Web https://www.fda.gov/Drugs/DrugSafety/ucm589587.htm?utm_campaign=New%20FDA%20Drug%20Safety%20Communication%20update%20on%20long-acting%20beta%20agonists%20%28LABAs%29&utm_medium=email&utm_source=Eloqua63021 - Giles W, Murphy V. Asthma in pregnancy: a review. Obstet Med. 2013;6:58-63. Epub 2013 May 3. Review.65180 - Woosley RL, Heise CW, Gallo T, et al. QTFactors List. Oro Valley, AZ: AZCERT, Inc.; Accessed March 31, 2020. Available on the World Wide Web at: https://crediblemeds.org/ndfa-list/

    Mechanism of Action

    Budesonide is an antiinflammatory corticosteroid; formoterol is a long-acting, selective beta-agonist; when used together, the combination is more effective than either drug alone.

    •Budesonide: In the treatment of asthma, orally inhaled corticosteroids are believed to reduce the immediate and late-phase allergic responses associated with allergies and chronic bronchial asthma. Mediators involved in the pathogenesis of asthma include histamine, leukotrienes (slow releasing substance of anaphylaxis, SRS-A), eosinophil chemotactic factor of anaphylaxis (ECF-A), neutrophil chemotactic factor (NCF), cytokines, hydroxyeicosatetraenoic acids, prostaglandin-generating factor of anaphylaxis (PGF-A), prostaglandins, major basic protein, bradykinin, adenosine, peroxides, and superoxide anions. Different cell types are responsible for release of these mediators including airway epithelium, eosinophils, basophils, lung parenchyma, lymphocytes, macrophages, mast cells, neutrophils, and platelets. Corticosteroids inhibit the release of these mediators as well as inhibit IgE synthesis, attenuate mucous secretion and eicosanoid generation, up-regulate beta-receptors, promote vasoconstriction, and suppress inflammatory cell influx and inflammatory processes. Clinical effects in asthma include a reduction in bronchial hyperresponsiveness to allergens, a decreased number of asthma exacerbations, and an improvement in FEV1, peak-flow rate, and respiratory symptoms.

    •Formoterol: Similar to other beta-2 agonists, formoterols mechanism of action involves stimulation of adenyl cyclase leading to the production of cyclic adenosine monophosphate (cAMP) via adenosine triphosphate (ATP). Increased levels of cAMP result in relaxation of the bronchial smooth muscle.Formoterol, like salmeterol, is highly lipophilic. It enters the plasma cell membrane in the form of a depot and is gradually released into the aqueous phase to react with the beta-2 receptor, resulting in a long duration of action. The aqueous phase activity, not demonstrated by salmeterol, is responsible for the rapid onset of action of formoterol. Formoterol has more than a 200-fold greater agonist activity at beta-2 receptors (primarily in the lung) than at beta-1 receptors (primarily in the heart). However, 10% to 50% of the beta receptors in the heart are beta-2 receptors and raise the possibility that even highly selective beta-2 receptor agonists may have adverse cardiovascular effects, such as tachycardia, palpitations, and ischemia (see Adverse Reactions). As with other beta-2 agonists, formoterol may possess antiinflammatory activity, but the clinical significance of this effect is unknown.[26424]In vitro studies have demonstrated inhibition of mast cell mediators such as histamine and leukotrienes. Monotherapy with formoterol is inappropriate due to lack of proven antiinflammatory and disease-modifying properties.

    Revision Date: 07/08/2015, 06:08:13 PM

    References

    26424 - Tattersfield AE. Long-acting beta-2 agonists. Clin Exp Allergy 1992;22:600-605.

    Pharmacokinetics

    Budesonide; formoterol is administered via oral inhalation.

    Route-Specific Pharmacokinetics

    Inhalation Route

    The median time to onset of clinically significant bronchodilation (>15% improvement in FEV1), following administration from metered-dose inhaler (MDI) of formoterol, is seen within 15 minutes. Maximum improvement in FEV1 occurs within 3 hours, and clinically significant improvement is maintained over 12 hours.

    • Budesonide: After administration from MDI, budesonide is rapidly absorbed in the lungs and peak plasma concentrations occur at approximately 20 minutes. Most of the dose delivered to the lungs via oral inhalation is systemically absorbed; however, the absolute systemic availability from an MDI is roughly 30% lower than that from a dry powder inhaler (DPI). In asthmatic patients, budesonide shows a linear increase in AUC and Cmax with increasing dose after both single dose and repeated dose inhaled administration; there is some accumulation with repeated dosing. Budesonide is 85—90% bound to plasma proteins. In vitro studies with human liver homogenates have shown that it is rapidly and extensively metabolized. Two major metabolites, 16 alpha-hydroxyprednisolone and 6 beta-hydroxybudesonide, form via CYP3A4 catalyzed biotransformation. The activity of each of these metabolites is less than 1% of that of the parent compound. The mean terminal half life of budesonide is 4.7 hours; it is excreted in urine (about 60%) and feces in the form of metabolites. After dosing, no unchanged budesonide is detected in the urine.
    • Formoterol: Following oral inhalation, formoterol is rapidly absorbed in the lungs and peak plasma concentrations are typically reached within 5—10 minutes. Most formoterol seen in the bloodstream following oral inhalation is due to the drug being swallowed and absorbed from the GI tract. Some accumulation in plasma occurs with multiple doses. Plasma protein binding for the RR and SS enantiomers of formoterol is 46 and 58%, respectively. Formoterol is extensively metabolized in the liver by direct glucuronidation and O-demethylation followed by glucuronide conjugation. Four cytochrome P450 isoenzymes (CYP2D6, CYP2C19, CYP2C9, and CYP2A6) are involved in the O-demethylation of formoterol. Formoterol has not been shown to inhibit CYP450 isoenzymes. About 62% of a dose is eliminated in the urine and 24% in the feces over a period of 104 hours. In the urine, roughly 10% of a dose is excreted unchanged and roughly 15% is eliminated as the direct glucuronide conjugate. The mean terminal elimination half-life of formoterol is roughly 8 hours.

    Special Populations

    Hepatic Impairment

    No data is available regarding use of budesonide; formoterol in patients with hepatic impairment. Because formoterol is primarily eliminated via hepatic metabolism, an increased exposure can be expected in patients with severe hepatic impairment.

    Renal Impairment

     No data are available regarding use of budesonide; formoterol in patients with renal impairment. Although budesonide metabolites are renally excreted, their activity is negligible.

    Pediatrics

    No differences in the pharmacokinetics of pediatric patients between the age of 6 and 12 years have been identified. Limited data are available in patients less than 12 years; in a single dose study in patients ages 6—11 years, peak plasma concentrations of budesonide were similar to adult patients and approximately 3.5% of the delivered formoterol dose was recovered in the urine as unchanged formoterol.

    Elderly

     Pharmacokinetic parameters in geriatric patients have not been assessed.

    Gender Differences

     No gender differences have been noted.

    Ethnic Differences

     No race differences have been noted.

    Revision Date: 12/20/2009, 01:17:43 PM

    Pregnancy/Breast-feeding

    labor, pregnancy

    There are no adequate and well-controlled studies of budesonide; formoterol during human pregnancy; however, studies of pregnant women taking inhaled budesonide alone have not shown increases in the risk of abnormalities when given during pregnancy. In animal studies, formoterol fumarate has only shown adverse effects when administered systemically at high systemic exposures greatly exceeding the maximum recommended human daily inhalational dose (MRHDID). No teratogenic, embryocidal, or developmental effects were seen in rats that received formoterol inhalation doses up to 375 times the MRHDID. Women with asthma who become pregnant while stabilized on budesonide; formoterol therapy should discuss their asthma management with a qualified health care professional.[32950] A review of Swedish registries indicated that in over 2,000 births there was no increased risk for congenital malformations during early pregnancy with budesonide inhalation powder or solution.[32950] It is known that improved maternal and perinatal outcomes are achieved with optimal control of asthma during pregnancy.[45934] Large studies of women with asthma have confirmed the lack of relationship between the use of inhaled beta-2 agonists and adverse maternal or fetal outcomes; however, less data are available for long-acting beta agonists (LABAs) such as formoterol vs. short-acting beta agonists (SABAs).[45934] However, most inhaled beta-2 agonists, as well as inhaled budesonide, are considered acceptable for use during pregnancy because of the low bioavailability and maternal serum levels after use.[45934] [49764] [63021] According to the 2004 guidelines of the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group, long-acting beta-2 agonists (LABAs), in combination with inhaled corticosteroids (ICS), are one of the preferred treatment options for the long-term control of moderate asthma during pregnancy and lactation; use of medium dose ICS is also a preferred option. Although a preferred LABA is not recommended, the guideline states that more experience is available with salmeterol. Due to the availability of safety information during pregnancy, budesonide is preferred over other ICS.[45934] Infants born to mothers taking substantial corticosteroid doses during pregnancy should be monitored for signs of hypoadrenalism.[32950] There are no well-controlled human studies that have investigated the effects of budesonide; formoterol on preterm labor or labor at term. Because of the potential for beta-2 agonist interference with uterine contractility, use of budesonide; formoterol should be restricted to those patients in whom the benefits clearly outweigh the risks.[32950]

    breast-feeding

    There are no well-controlled human studies that have investigated the effects of budesonide; formoterol during breast-feeding. Formoterol was excreted in milk in reproductive studies in rats; however, it is unknown whether formoterol is excreted in human milk. Glucocorticoids, such as budesonide, are excreted into human breast milk. Data from a small number (n = 8) of lactating women showed an estimated oral daily dose of budesonide available to the nursing infants which was approximately 0.3% to 1% of the dose inhaled by the mothers. Budesonide plasma concentrations obtained in five of the infants at about 140 minutes after drug administration to the mother and 90 minutes after breast-feeding were below quantifiable levels.[32950] The amount of inhaled budesonide excreted in breast-milk is minute, and infant exposure is negligible. While not measured, the amount of formoterol absorbed into the maternal bloodstream and excreted into breast-milk after inhalation is expected to be very low; therefore, it is unlikely that nursing infants would be exposed to clinically significant amounts of formoterol via breast milk. Most inhaled bronchodilators are considered acceptable for use during the postpartum period and breast-feeding because of the low bioavailability and maternal serum levels after use.[45934] [63021] The 2004 guidelines of the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group consider a combination of inhaled corticosteroids with long-acting inhaled beta-2 agonists (LABAs) a preferred treatment option for moderate asthma in pregnancy and lactation.[45934] Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Revision Date: 04/05/2018, 02:27:23 PM

    References

    32950 - Symbicort (budesonide; formoterol fumarate dihydrate) inhalation aerosol package insert. Wilmington, DE: AstraZeneca LP; 2017 Dec.45934 - National Heart , Lung, and Blood Institute, National Asthma Education and Prevention Program Asthma and Pregnancy Working Group. NAEPP expert panel report. Managing asthma during pregnancy: recommendations for pharmacologic treatment-2004 update. 2004;1-57. http://www.nhlbi.nih.gov/health/prof/lung/asthma/astpreg.htm49764 - Hardy-Fairbanks AJ, Baker ER. Asthma in pregnancy: pathophysiology, diagnosis and management. Obstet Gynecol Clin North Am. 2010;37:159-172.49951 - Ventolin HFA (albuterol sulfate) Inhalation Aerosol package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Aug.63021 - Giles W, Murphy V. Asthma in pregnancy: a review. Obstet Med. 2013;6:58-63. Epub 2013 May 3. Review.

    Interactions

    Level 1 (Severe)

    • Cisapride
    • Dronedarone
    • Halofantrine
    • Levomethadyl
    • Mesoridazine
    • Metyrapone
    • Pimozide
    • Thioridazine

    Level 2 (Major)

    • Abarelix
    • Amiodarone
    • Amisulpride
    • Arformoterol
    • Aspirin, ASA; Citric Acid; Sodium Bicarbonate
    • Azithromycin
    • Boceprevir
    • Calcium Carbonate
    • Calcium Carbonate; Famotidine; Magnesium Hydroxide
    • Calcium Carbonate; Magnesium Hydroxide
    • Calcium Carbonate; Risedronate
    • Calcium Carbonate; Simethicone
    • Ceritinib
    • Chloroquine
    • Dabrafenib
    • Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
    • Desmopressin
    • Dofetilide
    • Duvelisib
    • Fluticasone; Salmeterol
    • Fluticasone; Umeclidinium; Vilanterol
    • Fluticasone; Vilanterol
    • Foscarnet
    • grapefruit juice
    • Hydroxychloroquine
    • Idelalisib
    • Indacaterol
    • Indacaterol; Glycopyrrolate
    • Isocarboxazid
    • Ketoconazole
    • Lopinavir; Ritonavir
    • Macimorelin
    • Methacholine
    • Mifepristone
    • Monoamine oxidase inhibitors
    • Natalizumab
    • Olodaterol
    • Ombitasvir; Paritaprevir; Ritonavir
    • Omeprazole; Sodium Bicarbonate
    • Penicillamine
    • Phenelzine
    • Procarbazine
    • Racepinephrine
    • Ritodrine
    • Ritonavir
    • Salmeterol
    • Saquinavir
    • Sargramostim, GM-CSF
    • Sodium Bicarbonate
    • Telaprevir
    • Tiotropium; Olodaterol
    • Tranylcypromine
    • Umeclidinium; Vilanterol
    • Vigabatrin

    Level 3 (Moderate)

    • Abatacept
    • Acebutolol
    • Acetaminophen; Aspirin, ASA; Caffeine
    • Acetaminophen; Caffeine
    • Acetaminophen; Caffeine; Dihydrocodeine
    • Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine
    • Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide
    • Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine
    • Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine
    • Acetaminophen; Chlorpheniramine; Phenylephrine
    • Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine
    • Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine
    • Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine
    • Acetaminophen; Dextromethorphan; Phenylephrine
    • Acetaminophen; Dextromethorphan; Pseudoephedrine
    • Acetaminophen; Dichloralphenazone; Isometheptene
    • Acetaminophen; Guaifenesin; Phenylephrine
    • Acetaminophen; Pseudoephedrine
    • Acetazolamide
    • Acetohexamide
    • Acrivastine; Pseudoephedrine
    • Adalimumab
    • Albiglutide
    • Alemtuzumab
    • Alfuzosin
    • Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ
    • Aliskiren; Hydrochlorothiazide, HCTZ
    • Alogliptin; Metformin
    • Alpha-glucosidase Inhibitors
    • Aluminum Hydroxide
    • Aluminum Hydroxide; Magnesium Carbonate
    • Aluminum Hydroxide; Magnesium Hydroxide
    • Aluminum Hydroxide; Magnesium Hydroxide; Simethicone
    • Aluminum Hydroxide; Magnesium Trisilicate
    • Ambenonium Chloride
    • Amifampridine
    • Amiloride; Hydrochlorothiazide, HCTZ
    • Aminosalicylate sodium, Aminosalicylic acid
    • Amitriptyline
    • Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ
    • Amoxicillin; Clarithromycin; Omeprazole
    • Amphetamine
    • Amphetamine; Dextroamphetamine
    • Amphetamine; Dextroamphetamine Salts
    • Amphotericin B
    • Amphotericin B cholesteryl sulfate complex (ABCD)
    • Amphotericin B lipid complex (ABLC)
    • Amphotericin B liposomal (LAmB)
    • Anagrelide
    • Antacids
    • Antithymocyte Globulin
    • Apomorphine
    • Argatroban
    • Aripiprazole
    • Arsenic Trioxide
    • Artemether; Lumefantrine
    • Articaine; Epinephrine
    • Asenapine
    • Asparaginase Erwinia chrysanthemi
    • Aspirin, ASA
    • Aspirin, ASA; Butalbital; Caffeine
    • Aspirin, ASA; Butalbital; Caffeine; Codeine
    • Aspirin, ASA; Caffeine
    • Aspirin, ASA; Caffeine; Dihydrocodeine
    • Aspirin, ASA; Caffeine; Orphenadrine
    • Aspirin, ASA; Carisoprodol
    • Aspirin, ASA; Carisoprodol; Codeine
    • Aspirin, ASA; Dipyridamole
    • Aspirin, ASA; Omeprazole
    • Aspirin, ASA; Oxycodone
    • Aspirin, ASA; Pravastatin
    • Atazanavir
    • Atazanavir; Cobicistat
    • Atenolol
    • Atenolol; Chlorthalidone
    • Atomoxetine
    • Atracurium
    • Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
    • Azilsartan; Chlorthalidone
    • Bedaquiline
    • Belladonna Alkaloids; Ergotamine; Phenobarbital
    • Benazepril; Hydrochlorothiazide, HCTZ
    • Bendroflumethiazide; Nadolol
    • Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
    • Benzphetamine
    • Bepridil
    • Berotralstat
    • Beta-adrenergic blockers
    • Betaxolol
    • Bismuth Subcitrate Potassium; Metronidazole; Tetracycline
    • Bismuth Subsalicylate
    • Bismuth Subsalicylate; Metronidazole; Tetracycline
    • Bisoprolol
    • Bisoprolol; Hydrochlorothiazide, HCTZ
    • Bivalirudin
    • Brigatinib
    • Brimonidine; Timolol
    • Brompheniramine; Carbetapentane; Phenylephrine
    • Brompheniramine; Dextromethorphan; Phenylephrine
    • Brompheniramine; Hydrocodone; Pseudoephedrine
    • Brompheniramine; Phenylephrine
    • Brompheniramine; Pseudoephedrine
    • Brompheniramine; Pseudoephedrine; Dextromethorphan
    • Bumetanide
    • Buprenorphine
    • Buprenorphine; Naloxone
    • Bupropion
    • Bupropion; Naltrexone
    • Butabarbital
    • Butalbital; Acetaminophen
    • Butalbital; Acetaminophen; Caffeine
    • Butalbital; Acetaminophen; Caffeine; Codeine
    • Cabotegravir; Rilpivirine
    • Caffeine
    • Caffeine; Sodium Benzoate
    • Canagliflozin
    • Canagliflozin; Metformin
    • Candesartan; Hydrochlorothiazide, HCTZ
    • Captopril; Hydrochlorothiazide, HCTZ
    • Carbamazepine
    • Carbetapentane; Chlorpheniramine; Phenylephrine
    • Carbetapentane; Diphenhydramine; Phenylephrine
    • Carbetapentane; Guaifenesin; Phenylephrine
    • Carbetapentane; Phenylephrine
    • Carbetapentane; Phenylephrine; Pyrilamine
    • Carbetapentane; Pseudoephedrine
    • Carbinoxamine; Dextromethorphan; Pseudoephedrine
    • Carbinoxamine; Hydrocodone; Phenylephrine
    • Carbinoxamine; Hydrocodone; Pseudoephedrine
    • Carbinoxamine; Phenylephrine
    • Carbinoxamine; Pseudoephedrine
    • Carteolol
    • Carvedilol
    • Cetirizine; Pseudoephedrine
    • Chlophedianol; Dexchlorpheniramine; Pseudoephedrine
    • Chlophedianol; Guaifenesin; Phenylephrine
    • Chlordiazepoxide; Amitriptyline
    • Chlorothiazide
    • Chlorpheniramine; Dextromethorphan; Phenylephrine
    • Chlorpheniramine; Dextromethorphan; Pseudoephedrine
    • Chlorpheniramine; Dihydrocodeine; Phenylephrine
    • Chlorpheniramine; Dihydrocodeine; Pseudoephedrine
    • Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine
    • Chlorpheniramine; Hydrocodone; Phenylephrine
    • Chlorpheniramine; Hydrocodone; Pseudoephedrine
    • Chlorpheniramine; Ibuprofen; Pseudoephedrine
    • Chlorpheniramine; Phenylephrine
    • Chlorpheniramine; Pseudoephedrine
    • Chlorpromazine
    • Chlorpropamide
    • Chlorthalidone
    • Chlorthalidone; Clonidine
    • Choline Salicylate; Magnesium Salicylate
    • Cimetidine
    • Ciprofloxacin
    • Cisatracurium
    • Citalopram
    • Clarithromycin
    • Clindamycin
    • Clofazimine
    • Clomipramine
    • Clozapine
    • Cobicistat
    • Cocaine
    • Codeine; Guaifenesin; Pseudoephedrine
    • Codeine; Phenylephrine; Promethazine
    • Codeine; Promethazine
    • Conivaptan
    • Crizotinib
    • Daclatasvir
    • Danazol
    • Dapagliflozin
    • Dapagliflozin; Metformin
    • Dapagliflozin; Saxagliptin
    • Darunavir
    • Darunavir; Cobicistat
    • Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
    • Dasatinib
    • Deferasirox
    • Degarelix
    • Delavirdine
    • Denosumab
    • Desipramine
    • Desloratadine; Pseudoephedrine
    • Deutetrabenazine
    • Dexamethasone
    • Dexbrompheniramine; Pseudoephedrine
    • Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine
    • Dextran
    • Dextroamphetamine
    • Dextromethorphan; Diphenhydramine; Phenylephrine
    • Dextromethorphan; Guaifenesin; Phenylephrine
    • Dextromethorphan; Guaifenesin; Pseudoephedrine
    • Dextromethorphan; Quinidine
    • Dichlorphenamide
    • Diethylpropion
    • Digoxin
    • Dihydrocodeine; Guaifenesin; Pseudoephedrine
    • Dipeptidyl Peptidase-4 Inhibitors
    • Diphenhydramine; Hydrocodone; Phenylephrine
    • Diphenhydramine; Phenylephrine
    • Disopyramide
    • Dobutamine
    • Dolasetron
    • Dolutegravir; Rilpivirine
    • Donepezil
    • Donepezil; Memantine
    • Dopamine
    • Dorzolamide; Timolol
    • Doxacurium
    • Doxepin
    • Droperidol
    • Dulaglutide
    • Dyphylline
    • Dyphylline; Guaifenesin
    • Echinacea
    • Efavirenz
    • Efavirenz; Emtricitabine; Tenofovir
    • Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate
    • Elexacaftor; tezacaftor; ivacaftor
    • Eliglustat
    • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
    • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
    • Empagliflozin
    • Empagliflozin; Linagliptin
    • Empagliflozin; Linagliptin; Metformin
    • Empagliflozin; Metformin
    • Emtricitabine; Rilpivirine; Tenofovir alafenamide
    • Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate
    • Enalapril; Hydrochlorothiazide, HCTZ
    • Encorafenib
    • Enflurane
    • Entrectinib
    • Ephedrine
    • Ephedrine; Guaifenesin
    • Epinephrine
    • Eprosartan; Hydrochlorothiazide, HCTZ
    • Ergotamine; Caffeine
    • Eribulin
    • Erlotinib
    • Ertugliflozin
    • Ertugliflozin; Metformin
    • Ertugliflozin; Sitagliptin
    • Erythromycin
    • Erythromycin; Sulfisoxazole
    • Escitalopram
    • Esmolol
    • Estrogens
    • Ethacrynic Acid
    • Ethotoin
    • Etravirine
    • Exenatide
    • Ezogabine
    • Famotidine
    • Famotidine; Ibuprofen
    • Fedratinib
    • Fexofenadine; Pseudoephedrine
    • Fingolimod
    • Flecainide
    • Fluconazole
    • Fluoxetine
    • Fluoxymesterone
    • Fluvoxamine
    • Fosamprenavir
    • Fosinopril; Hydrochlorothiazide, HCTZ
    • Fosphenytoin
    • Fostemsavir
    • Furosemide
    • Gallium Ga 68 Dotatate
    • Gemcitabine
    • Gemifloxacin
    • Gemtuzumab Ozogamicin
    • Gentamicin
    • Gilteritinib
    • Glasdegib
    • Glecaprevir; Pibrentasvir
    • Glimepiride
    • Glimepiride; Rosiglitazone
    • Glipizide
    • Glipizide; Metformin
    • Glyburide
    • Glyburide; Metformin
    • Glycerol Phenylbutyrate
    • Goserelin
    • Granisetron
    • Griseofulvin
    • Guaifenesin; Hydrocodone; Pseudoephedrine
    • Guaifenesin; Phenylephrine
    • Guaifenesin; Pseudoephedrine
    • H2-blockers
    • Haloperidol
    • Halothane
    • Hemin
    • Heparin
    • Hetastarch
    • Histrelin
    • Hydantoins
    • Hydralazine; Hydrochlorothiazide, HCTZ
    • Hydrochlorothiazide, HCTZ
    • Hydrochlorothiazide, HCTZ; Methyldopa
    • Hydrochlorothiazide, HCTZ; Moexipril
    • Hydrocodone; Phenylephrine
    • Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine
    • Hydrocodone; Pseudoephedrine
    • Hydroxyzine
    • Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate
    • Ibritumomab Tiuxetan
    • Ibuprofen; Pseudoephedrine
    • Ibutilide
    • Iloperidone
    • Imipramine
    • Incretin Mimetics
    • Indapamide
    • Inebilizumab
    • Inotuzumab Ozogamicin
    • Insulin Degludec; Liraglutide
    • Insulin Glargine; Lixisenatide
    • Insulins
    • Irbesartan; Hydrochlorothiazide, HCTZ
    • Isavuconazonium
    • Isoflurane
    • Isoproterenol
    • Itraconazole
    • Ivacaftor
    • Ivosidenib
    • L-Asparaginase Escherichia coli
    • Labetalol
    • Lansoprazole; Amoxicillin; Clarithromycin
    • Lapatinib
    • Lefamulin
    • Lenvatinib
    • Letermovir
    • Leuprolide
    • Leuprolide; Norethindrone
    • Levetiracetam
    • Levobetaxolol
    • Levobunolol
    • Levofloxacin
    • Levothyroxine
    • Levothyroxine; Liothyronine (Porcine)
    • Levothyroxine; Liothyronine (Synthetic)
    • Linagliptin; Metformin
    • Linezolid
    • Liothyronine
    • Liraglutide
    • Lisinopril; Hydrochlorothiazide, HCTZ
    • Lithium
    • Lixisenatide
    • Lofexidine
    • Lonafarnib
    • Lonapegsomatropin
    • Loop diuretics
    • Loperamide
    • Loperamide; Simethicone
    • Loratadine; Pseudoephedrine
    • Losartan; Hydrochlorothiazide, HCTZ
    • Lumacaftor; Ivacaftor
    • Lumacaftor; Ivacaftor
    • Magnesium Hydroxide
    • Magnesium Salicylate
    • Mannitol
    • Maprotiline
    • Mecasermin rinfabate
    • Mecasermin, Recombinant, rh-IGF-1
    • Mefloquine
    • Meglitinides
    • Meperidine; Promethazine
    • Mephobarbital
    • Metformin
    • Metformin; Repaglinide
    • Metformin; Rosiglitazone
    • Metformin; Saxagliptin
    • Metformin; Sitagliptin
    • Methadone
    • Methamphetamine
    • Methazolamide
    • Methenamine; Sodium Acid Phosphate
    • Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine
    • Methyclothiazide
    • Metolazone
    • Metoprolol
    • Metoprolol; Hydrochlorothiazide, HCTZ
    • Metronidazole
    • Micafungin
    • Midazolam
    • Midodrine
    • Midostaurin
    • Mirtazapine
    • Mitotane
    • Mivacurium
    • Mobocertinib
    • Modafinil
    • Moxifloxacin
    • Nadolol
    • Nafcillin
    • Naproxen; Pseudoephedrine
    • Nateglinide
    • Nebivolol
    • Nebivolol; Valsartan
    • Nefazodone
    • Nelfinavir
    • Neostigmine
    • Neuromuscular blockers
    • Nevirapine
    • Nicardipine
    • Nilotinib
    • Nizatidine
    • Nonsteroidal antiinflammatory drugs
    • Norepinephrine
    • Norfloxacin
    • Nortriptyline
    • Octreotide
    • Ofatumumab
    • Ofloxacin
    • Olanzapine
    • Olanzapine; Fluoxetine
    • Olanzapine; Samidorphan
    • Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ
    • Olmesartan; Hydrochlorothiazide, HCTZ
    • Ondansetron
    • Osilodrostat
    • Osimertinib
    • Oxaliplatin
    • Oxymetholone
    • Ozanimod
    • Palbociclib
    • Paliperidone
    • Pancuronium
    • Panobinostat
    • Pasireotide
    • Pazopanib
    • Pegaspargase
    • Penbutolol
    • Pentamidine
    • Perphenazine; Amitriptyline
    • Phendimetrazine
    • Phenobarbital
    • Phenobarbital; Hyoscyamine; Atropine; Scopolamine
    • Phentermine
    • Phentermine; Topiramate
    • Phenylephrine
    • Phenytoin
    • Physostigmine
    • Pimavanserin
    • Pindolol
    • Pioglitazone; Glimepiride
    • Pioglitazone; Metformin
    • Pitolisant
    • Ponesimod
    • Posaconazole
    • Potassium
    • Potassium Chloride
    • Potassium Phosphate; Sodium Phosphate
    • Pramlintide
    • Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements)
    • Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved)
    • Prilocaine; Epinephrine
    • Primaquine
    • Primidone
    • Procainamide
    • Promethazine
    • Promethazine; Dextromethorphan
    • Promethazine; Phenylephrine
    • Propafenone
    • Propranolol
    • Propranolol; Hydrochlorothiazide, HCTZ
    • Protriptyline
    • Pseudoephedrine
    • Pseudoephedrine; Triprolidine
    • Pyridostigmine
    • Quetiapine
    • Quinapril; Hydrochlorothiazide, HCTZ
    • Quinidine
    • Quinine
    • Quinolones
    • Ranitidine
    • Ranolazine
    • Rapacuronium
    • Rasagiline
    • Regular Insulin
    • Relugolix
    • Relugolix; Estradiol; Norethindrone acetate
    • Repaglinide
    • Ribociclib
    • Ribociclib; Letrozole
    • Rilpivirine
    • Risperidone
    • Rituximab
    • Rituximab; Hyaluronidase
    • Rocuronium
    • Romidepsin
    • Salicylates
    • Salsalate
    • SARS-CoV-2 (COVID-19) vaccines
    • Selpercatinib
    • Semaglutide
    • Sertraline
    • Sevoflurane
    • SGLT2 Inhibitors
    • Siponimod
    • Sodium Benzoate; Sodium Phenylacetate
    • Sodium Chloride
    • Sodium Phenylbutyrate
    • Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous
    • Sofosbuvir; Velpatasvir; Voxilaprevir
    • Solifenacin
    • Somatropin, rh-GH
    • Sorafenib
    • Sotalol
    • Spironolactone; Hydrochlorothiazide, HCTZ
    • St. John's Wort, Hypericum perforatum
    • Succinylcholine
    • Sulfonylureas
    • Sunitinib
    • Tacrolimus
    • Tamoxifen
    • Telavancin
    • Telbivudine
    • Telithromycin
    • Telmisartan; Hydrochlorothiazide, HCTZ
    • Temsirolimus
    • Testosterone
    • Tetrabenazine
    • Tezacaftor; Ivacaftor
    • Theophylline, Aminophylline
    • Thiazide diuretics
    • Thiazolidinediones
    • Thyroid hormones
    • Timolol
    • Tobramycin
    • Tolazamide
    • Tolbutamide
    • Tolterodine
    • Toremifene
    • Torsemide
    • Trandolapril; Verapamil
    • Tranexamic Acid
    • Trazodone
    • Triamterene; Hydrochlorothiazide, HCTZ
    • Triclabendazole
    • Tricyclic antidepressants
    • Trimipramine
    • Triptorelin
    • Tuberculin Purified Protein Derivative, PPD
    • Tubocurarine
    • Tucatinib
    • Valsartan; Hydrochlorothiazide, HCTZ
    • Vancomycin
    • Vandetanib
    • Vardenafil
    • Vecuronium
    • Vemurafenib
    • Venlafaxine
    • Verapamil
    • Vincristine Liposomal
    • Voclosporin
    • Voriconazole
    • Vorinostat
    • Warfarin
    • Ziprasidone

    Level 4 (Minor)

    • Aldesleukin, IL-2
    • Altretamine
    • Aminolevulinic Acid
    • Aprepitant, Fosaprepitant
    • Azathioprine
    • Basiliximab
    • Bexarotene
    • Bortezomib
    • Bosentan
    • Cabozantinib
    • Carmustine, BCNU
    • Chlorambucil
    • Clofarabine
    • Denileukin Diftitox
    • Dexlansoprazole
    • Diltiazem
    • Econazole
    • Elbasvir; Grazoprevir
    • Esomeprazole
    • Estramustine
    • Fluphenazine
    • Hydroxyurea
    • Indinavir
    • Interferon Alfa-2a
    • Interferon Alfa-2b
    • Interferon Alfa-2b; Ribavirin
    • Isotretinoin
    • Ixabepilone
    • Lansoprazole
    • Lansoprazole; Naproxen
    • Ledipasvir; Sofosbuvir
    • Lomustine, CCNU
    • Mepenzolate
    • Methoxsalen
    • Mitoxantrone
    • Naproxen; Esomeprazole
    • Nelarabine
    • Omeprazole
    • Omeprazole; Amoxicillin; Rifabutin
    • Oritavancin
    • Pantoprazole
    • Perphenazine
    • Photosensitizing agents (topical)
    • Potassium-sparing diuretics
    • Prochlorperazine
    • Proton pump inhibitors
    • Purine analogs
    • Rabeprazole
    • Simeprevir
    • Tositumomab
    • Tretinoin, ATRA
    • Trifluoperazine
    • Zafirlukast
    • Zonisamide
    Abarelix: (Major) Since abarelix can cause QT prolongation, abarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of abarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval. Agents associated with a lower, but possible risk for QT prolongation and torsade de pointes (TdP) based on varying levels of documentation include the beta-agonists. Beta-agonists may cause cardiovascular effects, particularly when used in high doses and/or when associated with hypokalemia. [28318] [28406] [32901] [33925] [41231] [46800] Abatacept: (Moderate) Concomitant use of immunosuppressives, as well as long-term corticosteroids, may potentially increase the risk of serious infection in abatacept treated patients. Advise patients taking abatacept to seek immediate medical advice if they develop signs and symptoms suggestive of infection. [8565] Acebutolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. [28618] [43675] [44979] [51834] [58220] Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists. [66338] (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Acetaminophen; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists. [66338] Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists. [66338] Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists. [66338] (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists. [66338] (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Acetaminophen; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Acetazolamide: (Moderate) Corticosteroids may increase the risk of hypokalemia if used concurrently with acetazolamide. Hypokalemia may be especially severe with prolonged use of corticotropin, ACTH. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy. [26417] [28267] Acetohexamide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Acrivastine; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Adalimumab: (Moderate) Closely monitor for the development of signs and symptoms of infection if coadministration of a corticosteroid with adalimumab is necessary. Adalimumab treatment increases the risk for serious infections that may lead to hospitalization or death. Patients taking concomitant immunosuppressants including corticosteroids may be at greater risk of infection. [27939] Albiglutide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Aldesleukin, IL-2: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [41853] [7592] [7714] Alemtuzumab: (Moderate) Concomitant use of alemtuzumab with immunosuppressant doses of corticosteroids may increase the risk of immunosuppression. Monitor patients carefully for signs and symptoms of infection. [58461] Alfuzosin: (Moderate) Use caution when administering alfuzosin with long-acting beta-agonists due to the potential for QT prolongation. Alfuzosin may prolong the QT interval in a dose-dependent manner. Long-acting beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28261] [32901] [41231] [44979] [57710] [59321] Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Alogliptin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] Alpha-glucosidase Inhibitors: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Altretamine: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects. [4661] [7714] Aluminum Hydroxide: (Moderate) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. [34979] [52910] Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. [34979] [52910] Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. [34979] [52910] Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. [34979] [52910] Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. [34979] [52910] Ambenonium Chloride: (Moderate) Concomitant use of anticholinesterase agents, such as ambenonium chloride, and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents used to treat myasthenia should be withdrawn at least 24 hours before initiating corticosteroid therapy. [29779] [30015] [30028] [42863] [56146] [64165] Amifampridine: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients. [45339] [63790] Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Aminolevulinic Acid: (Minor) Corticosteroids administered prior to or concomitantly with photosensitizing agents used in photodynamic therapy may decrease the efficacy of the treatment. [6625] Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Amiodarone: (Major) Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia, including corticosteroids. Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. [26417] [28224] [29377] (Moderate) Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation. The use of amiodarone with other drugs known to prolong the QT interval, such as the long-acting beta-agonists, should only be done after careful assessment of risks versus benefits. Long-acting beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28224] [28432] [32901] [41231] [44979] [57710] [59321] Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with long-acting beta-agonists. Amisulpride causes dose- and concentration- dependent QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [32901] [41231] [44979] [54633] [57710] [65068] Amitriptyline: (Moderate) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with TCAs include the beta-agonists. Beta agonists infrequently produce cardiovascular adverse effects, mostly with high doses or in the setting of beta-agonist-induced hypokalemia. [28225] [28318] [28416] [33925] [41231] Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Avoid coadministration of oral budesonide and clarithromycin due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [28238] [28278] [34376] [34979] (Moderate) The coadministration of beta-agonists with clarithromycin may increase the risk for adverse effects, including prolongation of the QT interval. Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Long-acting beta-agonists (LABAs) may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Pharmacokinetic interactions may occur between clarithromycin and some LABAs. Clarithromycin is a strong CYP3A4 inhibitor and the co-administration of salmeterol with strong CYP3A4 inhibitors can result in elevated concentrations that may increase the risk for cardiovascular events. [28238] [28467] [32901] [33156] [41231] [44979] [54633] [56564] [57710] (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. [34979] Amphetamine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Amphetamine; Dextroamphetamine Salts: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Amphetamine; Dextroamphetamine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Amphotericin B cholesteryl sulfate complex (ABCD): (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly. [30011] [40134] Amphotericin B lipid complex (ABLC): (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly. [30011] [40134] Amphotericin B liposomal (LAmB): (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly. [30011] [40134] Amphotericin B: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly. [30011] [40134] Anagrelide: (Moderate) Beta-agonists should be used cautiously and with close monitoring with anagrelide. Torsades de pointes (TdP) and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, vilanterol) than with shorter-acting beta-agonists. [30163] [32901] [41231] [44979] [57710] [59321] Antacids: (Moderate) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. [34979] [52910] Antithymocyte Globulin: (Moderate) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [6303] [7714] Apomorphine: (Moderate) Exercise caution when administering apomorphine concomitantly with long-acting beta-agonists since there may be an increased risk of QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting or systemic beta-agonists. [28467] [28661] [32901] [33156] [41231] [44979] [57710] [59321] Aprepitant, Fosaprepitant: (Minor) Use caution if budesonide and aprepitant are used concurrently and monitor for an increase in budesonide-related adverse effects for several days after administration of a multi-day aprepitant regimen; however, due to low systemic exposure, clinically significant drug interactions are unlikely with budesonide for oral or intranasal inhalation. After administration, fosaprepitant is rapidly converted to aprepitant and shares the same drug interactions. Budesonide is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer; substitution of fosaprepitant 115 mg IV on day 1 of the 3-day regimen may lessen the inhibitory effects of CYP3A4. The AUC of a single dose of another CYP3A4 substrate, midazolam, increased by 2.3-fold and 3.3-fold on days 1 and 5, respectively, when coadministered with a 5-day oral aprepitant regimen. After a 3-day oral aprepitant regimen, the AUC of midazolam increased by 25% on day 4, and decreased by 19% and 4% on days 8 and 15, respectively, when given on days 1, 4, 8, and 15. As a single 40-mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.2-fold; the midazolam AUC increased by 1.5-fold after a single 125-mg dose of oral aprepitant. After single doses of IV fosaprepitant, the midazolam AUC increased by 1.8-fold (150 mg) and 1.6-fold (100 mg); less than a 2-fold increase in the midazolam AUC is not considered clinically important. Due to low systemic exposure, clinically significant drug interactions are unlikely with budesonide for oral or intranasal inhalation. [30676] [34354] [40027] Arformoterol: (Major) Formoterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist for any reason, as overdose may result. Coadministration can result in overdosage. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with inhaled short-acting beta-2 agonists (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking formoterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if formoterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual. Use formoterol and drugs known to prolong the QTc interval together with extreme caution; this combination may increase the risk of cardiovascular effects and ventricular arrhythmias; this includes combination with other beta-agonists. [28318] [33925] [41231] [60746] Argatroban: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Aripiprazole: (Moderate) Use caution when using aripiprazole with long-acting beta-agonists (LABAs) due to the potential for QT prolongation. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. LABAs may be associated with cardiovascular effects including QT interval prolongation, usually at higher doses or if hypokalemia occurs. [32901] [41231] [42845] [44979] [57710] [59321] Arsenic Trioxide: (Moderate) Beta-agonists should be used cautiously and with close monitoring with arsenic trioxide. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Avoid concomitant use of arsenic trioxide with other drugs that may cause QT interval prolongation; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated. [28226] [28318] [28432] [28457] [33925] [41231] (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide. [26417] [59438] Artemether; Lumefantrine: (Moderate) The administration of artemether; lumefantrine is associated with prolongation of the QT interval. Although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation and should be avoided. Consider ECG monitoring if other QT prolonging drugs must be used with or after artemether; lumefantrine treatment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated. [28318] [32901] [33925] [35401] [41231] Articaine; Epinephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Asenapine: (Moderate) Asenapine has been associated with QT prolongation. According to the manufacturer of asenapine, the drug should be avoided in combination with other agents also known to have this effect. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated. [28318] [32901] [33925] [36343] [41231] Asparaginase Erwinia chrysanthemi: (Moderate) Concomitant use of L-asparaginase with corticosteroids can result in additive hyperglycemia. L-Asparaginase transiently inhibits insulin production contributing to hyperglycemia seen during concurrent corticosteroid therapy. Insulin therapy may be required in some cases. Administration of L-asparaginase after rather than before corticosteroids reportedly has produced fewer hypersensitivity reactions. [55362] Aspirin, ASA: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Butalbital; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists. [66338] (Moderate) Coadministration may result in decreased exposure to budesonide. Butalbital is a CYP3A4 inducer; budesonide is a CYP3A4 substrate. Monitor for decreased response to budesonide during concurrent use. [28001] (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists. [66338] (Moderate) Coadministration may result in decreased exposure to budesonide. Butalbital is a CYP3A4 inducer; budesonide is a CYP3A4 substrate. Monitor for decreased response to budesonide during concurrent use. [28001] (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists. [66338] (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists. [66338] (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists. [66338] (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Carisoprodol: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. [52910] [6865] (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Dipyridamole: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Omeprazole: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. [34979] Aspirin, ASA; Oxycodone: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Pravastatin: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Atazanavir: (Moderate) Coadministration of budesonide with atazanavir may cause elevated budesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 substrate; atazanavir is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. [28001] [58000] Atazanavir; Cobicistat: (Moderate) Avoid coadministration of oral budesonide and cobistat due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Elevated budesonide serum concentrations may result in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 and P-glycoprotein (P-gp) substrate; cobicistat is a strong inhibitor of CYP3A4 and P-gp. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. [31824] [34354] [34979] [51664] [58000] (Moderate) Coadministration of budesonide with atazanavir may cause elevated budesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 substrate; atazanavir is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. [28001] [58000] Atenolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. [28618] [43675] [44979] [51834] [58220] Atenolol; Chlorthalidone: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. [28618] [43675] [44979] [51834] [58220] Atomoxetine: (Moderate) Use caution if atomoxetine is administered with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonistsas compared to short-acting beta-agonists. [28318] [28405] [33925] [41231] [59321] Atracurium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Azathioprine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [4710] [7714] Azilsartan; Chlorthalidone: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Azithromycin: (Major) Avoid coadministration of azithromycin with long-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [28855] [32901] [41231] [43974] [44979] [54633] [57710] [65157] [65170] Basiliximab: (Minor) Because systemically administered corticosteroids have immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives. [4746] Bedaquiline: (Moderate) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with beta-agonists. Bedaquiline has been reported to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy. [28318] [33925] [41231] [52746] Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Coadministration may result in decreased exposure to budesonide. Phenobarbital is a CYP3A4 inducer; budesonide is a CYP3A4 substrate. Monitor for decreased response to budesonide during concurrent use. Dose adjustments may be necessary. [28001] Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Bendroflumethiazide; Nadolol: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. [28618] [43675] [44979] [51834] [58220] Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Benzphetamine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Bepridil: (Moderate) Hypokalemia-producing agents, including corticosteroids, may increase the risk of bepridil-induced arrhythmias and should therefore be administered cautiously in patients receiving bepridil therapy. [3085] [4953] Berotralstat: (Moderate) Avoid coadministration of systemic budesonide with berotralstat due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A4 substrate and berotralstat is a moderate CYP3A4 inhibitor. [34979] [66159] Beta-adrenergic blockers: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. [28618] [43675] [44979] [51834] [58220] Betaxolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. [28618] [43675] [44979] [51834] [58220] Bexarotene: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents, such as bexarotene. [30943] Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and long-acting beta-agonists may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The risk for QT/QTc prolongation may be greater with long-acting beta-agonists than short-acting beta-agonists. [28467] [32901] [36894] [41231] [44979] [54633] [57710] Bismuth Subsalicylate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and long-acting beta-agonists may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The risk for QT/QTc prolongation may be greater with long-acting beta-agonists than short-acting beta-agonists. [28467] [32901] [36894] [41231] [44979] [54633] [57710] (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Bisoprolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. [28618] [43675] [44979] [51834] [58220] Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. [28618] [43675] [44979] [51834] [58220] Bivalirudin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Boceprevir: (Major) Concurrent administration of budesonide and boceprevir is not recommended unless the benefits outweigh the risks. If they are coadministered, close monitoring for corticosteroid-related adverse events is advised. If budesonide dose adjustments are made, readjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of budesonide. Budesonide is metabolized by the hepatic isoenzyme CYP3A4 and the drug efflux transporter P-glycoprotein (P-gp); boceprevir inhibits both the isoenzyme and the drug efflux pump. Coadministration may result in elevated budesonide plasma concentrations. [34979] [44314] Bortezomib: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Bosentan: (Minor) A dose adjustment of budesonide may be necessary if bosentan is initiated or withdrawn during therapy. Bosentan may increase the metabolism of budesonide resulting in decreased exposure. Bosentan is an inducer of CYP3A4; budesonide is a CYP3A4 substrate. [28496] Brigatinib: (Moderate) Monitor for a decrease in the efficacy of budesonide if coadministration with brigatinib is necessary. Budesonide is a sensitive CYP3A4 substrate. At clinically relevant concentrations, brigatinib induced CYP3A via activation of the pregnane X receptor (PXR); this may decrease concentrations of sensitive CYP3A substrates. [34979] [61909] Brimonidine; Timolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. [28618] [43675] [44979] [51834] [58220] Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Brompheniramine; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Brompheniramine; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Bumetanide: (Moderate) Loop diuretics may potentiate hypokalemia and ECG changes seen with beta agonists. Hypokalemia due to beta agonists appears to be dose related and is more likely with high dose therapy. Caution is advised when loop diuretics are coadministered with high doses of beta agonists; potassium levels may need to be monitored. [33925] [43675] [44979] Buprenorphine: (Moderate) Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated. [41231] [59321] [60270] Buprenorphine; Naloxone: (Moderate) Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated. [41231] [59321] [60270] Bupropion: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Bupropion; Naltrexone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Butabarbital: (Moderate) Coadministration may result in decreased exposure to budesonide. Butabarbital is a CYP3A4 inducer; budesonide is a CYP3A4 substrate. Monitor for decreased response to budesonide during concurrent use. [28001] Butalbital; Acetaminophen: (Moderate) Coadministration may result in decreased exposure to budesonide. Butalbital is a CYP3A4 inducer; budesonide is a CYP3A4 substrate. Monitor for decreased response to budesonide during concurrent use. [28001] Butalbital; Acetaminophen; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists. [66338] (Moderate) Coadministration may result in decreased exposure to budesonide. Butalbital is a CYP3A4 inducer; budesonide is a CYP3A4 substrate. Monitor for decreased response to budesonide during concurrent use. [28001] Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists. [66338] (Moderate) Coadministration may result in decreased exposure to budesonide. Butalbital is a CYP3A4 inducer; budesonide is a CYP3A4 substrate. Monitor for decreased response to budesonide during concurrent use. [28001] Cabotegravir; Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists, such as arformoterol, as compared to short-acting beta-agonists. [28318] [32901] [33925] [41231] [44376] Cabozantinib: (Minor) Monitor for an increase in budesonide-related adverse reactions if coadministration with cabozantinib is necessary. Budesonide is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown. [34354] [52506] [60738] Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists. [66338] Caffeine; Sodium Benzoate: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists. [66338] (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia. [8083] Calcium Carbonate: (Major) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. In addition, calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function. [31468] [31469] Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Major) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. In addition, calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function. [31468] [31469] (Moderate) Monitor for altered response to budesonide in patients receiving H2-blockers with enteric-coated or extended-release formulations of oral budesonide. Enteric-coated budesonide granules (Entocort EC) dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause these products to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. When cimetidine (1 gram/day PO) is administered with an uncoated formulation of oral budesonide, a slight increase in absorption and peak plasma concentrations occur, resulting in significant cortisol suppression. [34979] [52910] Calcium Carbonate; Magnesium Hydroxide: (Major) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. In addition, calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function. [31468] [31469] Calcium Carbonate; Risedronate: (Major) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. In addition, calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function. [31468] [31469] Calcium Carbonate; Simethicone: (Major) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. In addition, calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function. [31468] [31469] Canagliflozin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Canagliflozin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Carbamazepine: (Moderate) Hepatic microsomal enzyme inducers, including carbamazepine, can increase the metabolism of budesonide. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with budesonide. [41237] Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Carbetapentane; Guaifenesin; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Carbetapentane; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Carbetapentane; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Carbinoxamine; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Carbinoxamine; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Carmustine, BCNU: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [5946] [7714] [7944] Carteolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. [28618] [43675] [44979] [51834] [58220] Carvedilol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. [28618] [43675] [44979] [51834] [58220] (Minor) Increased concentrations of budesonide may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and budesonide is a P-gp substrate. [34354] [51834] [58220] Ceritinib: (Major) Avoid coadministration of oral budesonide and ceritinib due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [34979] [57094] (Moderate) Periodically monitor electrolytes and ECGs in patients receiving concomitant treatment with ceritinib and long-acting beta-agonists; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28318] [33925] [41231] [44979] [57094] Cetirizine; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Chlophedianol; Guaifenesin; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Chlorambucil: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [4757] [7714] Chlordiazepoxide; Amitriptyline: (Moderate) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with TCAs include the beta-agonists. Beta agonists infrequently produce cardiovascular adverse effects, mostly with high doses or in the setting of beta-agonist-induced hypokalemia. [28225] [28318] [28416] [33925] [41231] Chloroquine: (Major) Avoid coadministration of chloroquine with long-acting beta-agonists due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists (LABAs) as compared to short-acting beta-agonists.. [28229] [29758] [41231] [44026] [44063] [44979] [59321] [65157] [65170] Chlorothiazide: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Chlorpheniramine; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Chlorpheniramine; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Chlorpromazine: (Moderate) Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with chlorpromazine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28318] [28415] [28416] [28417] [32901] [33925] [41231] [43065] Chlorpropamide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Chlorthalidone: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Chlorthalidone; Clonidine: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Choline Salicylate; Magnesium Salicylate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Cimetidine: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] (Moderate) Monitor for altered response to budesonide in patients receiving H2-blockers with enteric-coated or extended-release formulations of oral budesonide. Enteric-coated budesonide granules (Entocort EC) dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause these products to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. When cimetidine (1 gram/day PO) is administered with an uncoated formulation of oral budesonide, a slight increase in absorption and peak plasma concentrations occur, resulting in significant cortisol suppression. [34979] [52910] Ciprofloxacin: (Moderate) Rare cases of QT prolongation and torsade de pointe (TdP) have been reported with ciprofloxacin during post-marketing surveillance. Ciprofloxacin should be used with caution in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with ciprofloxacin include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28225] [28318] [28419] [28775] [29833] [32901] [33925] [41231] [43411] Cisapride: (Contraindicated) QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, have been reported with cisapride. Because of the potential for TdP, use of other drugs that might increase the QT interval is contraindicated with cisapride. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28318] [28978] [32901] [33925] [41231] [47221] Cisatracurium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] Citalopram: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram. [26417] [28269] (Moderate) Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with citalopram include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28269] [28318] [32901] [33925] [41231] Clarithromycin: (Moderate) Avoid coadministration of oral budesonide and clarithromycin due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [28238] [28278] [34376] [34979] (Moderate) The coadministration of beta-agonists with clarithromycin may increase the risk for adverse effects, including prolongation of the QT interval. Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Long-acting beta-agonists (LABAs) may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Pharmacokinetic interactions may occur between clarithromycin and some LABAs. Clarithromycin is a strong CYP3A4 inhibitor and the co-administration of salmeterol with strong CYP3A4 inhibitors can result in elevated concentrations that may increase the risk for cardiovascular events. [28238] [28467] [32901] [33156] [41231] [44979] [54633] [56564] [57710] Clindamycin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Clofarabine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7557] [7714] Clofazimine: (Moderate) Monitor ECGs for QT prolongation when clofazimine is administered with long-acting beta-agonists. QT prolongation and torsade de pointes have been reported in patients receiving clofazimine in combination with QT prolonging medications. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [32901] [41231] [44979] [54633] [57710] [63936] Clomipramine: (Moderate) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with TCAs include the beta-agonists. Beta agonists infrequently produce cardiovascular adverse effects, mostly with high doses or in the setting of beta-agonist-induced hypokalemia. [28225] [28318] [28416] [33925] [41231] Clozapine: (Moderate) Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. The manufacturer of clozapine recommends caution during concurrent use with medications known to cause QT prolongation. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with clozapine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28262] [28318] [32901] [33925] [41231] Cobicistat: (Moderate) Avoid coadministration of oral budesonide and cobistat due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Elevated budesonide serum concentrations may result in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 and P-glycoprotein (P-gp) substrate; cobicistat is a strong inhibitor of CYP3A4 and P-gp. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. [31824] [34354] [34979] [51664] [58000] Cocaine: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects. [28318] [32901] [33925] [41231] [5275] Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Codeine; Phenylephrine; Promethazine: (Moderate) Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Use cautiously with promethazine, which has been reported to cause QT prolongation. [28225] [29318] [32901] [33925] [41231] [55578] (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Codeine; Promethazine: (Moderate) Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Use cautiously with promethazine, which has been reported to cause QT prolongation. [28225] [29318] [32901] [33925] [41231] [55578] Conivaptan: (Moderate) Avoid coadministration of systemic budesonide with conivaptan due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor. [31764] [34979] Crizotinib: (Moderate) Avoid coadministration of systemic budesonide with crizotinib due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A4 substrate and crizotinib is a moderate CYP3A inhibitor. [34979] [45458] (Moderate) Monitor ECGs for QT prolongation and monitor electrolytes in patients receiving crizotinib concomitantly with long-acting beta-agonists. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib patients if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and when associated with hypokalemia or used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [32901] [41231] [44979] [45458] Dabrafenib: (Major) The concomitant use of dabrafenib and budesonide may lead to decreased budesonide concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of budesonide efficacy. Dabrafenib is a moderate CYP3A4 inducer and budesonide is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%. [34979] [54802] Daclatasvir: (Moderate) Systemic exposure of budesonide, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of budesonide; monitor patients for potential adverse effects. [34354] [60001] Danazol: (Moderate) Avoid coadministration of oral budesonide and danazol due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; danazol is a moderate CYP3A4 inhibitor. In the presence of a strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [28278] [34376] [34979] Dapagliflozin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Dapagliflozin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Dapagliflozin; Saxagliptin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Darunavir: (Moderate) Coadministration of budesonide with darunavir may cause elevated budesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 substrate; darunavir is an inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. [32432] [34979] [58000] Darunavir; Cobicistat: (Moderate) Avoid coadministration of oral budesonide and cobistat due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Elevated budesonide serum concentrations may result in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 and P-glycoprotein (P-gp) substrate; cobicistat is a strong inhibitor of CYP3A4 and P-gp. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. [31824] [34354] [34979] [51664] [58000] (Moderate) Coadministration of budesonide with darunavir may cause elevated budesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 substrate; darunavir is an inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. [32432] [34979] [58000] Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Avoid coadministration of oral budesonide and cobistat due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Elevated budesonide serum concentrations may result in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 and P-glycoprotein (P-gp) substrate; cobicistat is a strong inhibitor of CYP3A4 and P-gp. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. [31824] [34354] [34979] [51664] [58000] (Moderate) Coadministration of budesonide with darunavir may cause elevated budesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 substrate; darunavir is an inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. [32432] [34979] [58000] Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Avoid coadministration of oral budesonide and ritonavir due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [28315] [31824] [34979] [47165] Dasatinib: (Moderate) Use dasatinib with caution in combination with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [32901] [41231] [44979] [54633] [57710] [60087] Deferasirox: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including corticosteroids. [31807] Degarelix: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving long-acting beta-agonists. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval, such as degarelix. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists [28467] [32901] [41231] [44979] [46869] [54633] [57710] Delavirdine: (Moderate) Avoid coadministration of oral budesonide and delavirdine due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; delavirdine is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [28279] [34979] Denileukin Diftitox: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Denosumab: (Moderate) The safety and efficacy of denosumab use in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with denosumab may be at a greater risk of developing an infection. [40862] Desipramine: (Moderate) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with TCAs include the beta-agonists. Beta agonists infrequently produce cardiovascular adverse effects, mostly with high doses or in the setting of beta-agonist-induced hypokalemia. [28225] [28318] [28416] [33925] [41231] Desloratadine; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Desmopressin: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer. [61806] Deutetrabenazine: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and long-acting beta-agonists. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [32901] [41231] [44979] [54633] [57710] [61845] Dexamethasone: (Moderate) Theoretically, induction of the cytochrome P450 (CYP) 3A4 isoenzyme may result in a lowering of budesonide plasma concentrations, reducing the clinical effect. Drugs known to induce the 3A4 isoenzyme include dexamethasone. [28001] Dexbrompheniramine; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Dexlansoprazole: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. [34979] Dextran: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Dextroamphetamine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Dextromethorphan; Quinidine: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated. [28318] [32901] [33925] [41231] [47357] Dichlorphenamide: (Moderate) Use dichlorphenamide and arformoterol or formoterol together with caution. Metabolic acidosis is listed by the manufacturers of arformoterol and formoterol as an adverse reaction seen with beta-2 agonists but would be rare with normal doses of arformoterol or formoterol. Metabolic acidosis has been reported with dichlorphenamide. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy. [32901] [33259] [41231] Diethylpropion: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Digoxin: (Moderate) Hypokalemia, hypomagnesemia, or hypercalcemia increase digoxin's effect. Corticosteroids can precipitate digoxin toxicity via their effect on electrolyte balance. It is recommended that serum potassium, magnesium, and calcium be monitored regularly in patients receiving digoxin. [28272] [29377] Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Diltiazem: (Minor) Diltiazem may increase plasma concentrations of oral budesonide due to inhibition of the CYP3A4 isoenzymet, and can enhance the cortisol suppression associated with budesonide administered via inhalation. [6192] Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Diphenhydramine; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Disopyramide: (Moderate) Beta-agonists should be used cautiously and with close monitoring with disopyramide. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated. [28228] [28318] [32901] [33925] [41231] Dobutamine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Dofetilide: (Major) Corticosteroids can cause increases in blood pressure, sodium and water retention, and hypokalemia, predisposing patients to interactions with certain other medications. Corticosteroid-induced hypokalemia could also enhance the proarrhythmic effects of dofetilide. [49489] (Moderate) Coadministration of dofetilide and long-acting beta-agonists may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28221] [28432] [28457] [32901] [41231] [44979] Dolasetron: (Moderate) Administer dolasetron with caution in combination with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. [28318] [28467] [32901] [33925] [41231] [42844] [44979] [54633] [57710] Dolutegravir; Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists, such as arformoterol, as compared to short-acting beta-agonists. [28318] [32901] [33925] [41231] [44376] Donepezil: (Moderate) Use donepezil with caution in combination with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28318] [33925] [41231] [59321] [59322] Donepezil; Memantine: (Moderate) Use donepezil with caution in combination with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28318] [33925] [41231] [59321] [59322] Dopamine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Dorzolamide; Timolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. [28618] [43675] [44979] [51834] [58220] Doxacurium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] Doxepin: (Moderate) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with TCAs include the beta-agonists. Beta agonists infrequently produce cardiovascular adverse effects, mostly with high doses or in the setting of beta-agonist-induced hypokalemia. [28225] [28318] [28416] [33925] [41231] Dronedarone: (Contraindicated) Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. The concomitant use of dronedarone with other drugs that prolong the QTc may induce Torsade de Pointes (TdP) and is contraindicated. Contraindicated drugs include the beta-agonists. [28318] [32901] [33925] [36101] [41231] (Moderate) Dronedarone is metabolized by and is an inhibitor of CYP3A; drondarone also inhibits P-gp. Budesonide is a substrate for CYP3A4 and P-gp. The concomitant administration of dronedarone with CYP3A4 and P-gp substrates may result in increased exposure of the substrate and should, therefore, be undertaken with caution. [36101] Droperidol: (Moderate) Caution is advised when using droperidol in combination with corticosteroids which may lead to electrolyte abnormalities, especially hypokalemia or hypomagnesemia, as such abnormalities may increase the risk for QT prolongation or cardiac arrhythmias. [5468] (Moderate) Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsade de pointes (TdP). Any drug known to have potential to prolong the QT interval should not be coadministered with droperidol. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with droperidol include beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28235] [28236] [28467] [28737] [32901] [33156] [41231] [44979] [54633] [56564] [57710] [59724] Dulaglutide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Duvelisib: (Major) Avoid coadministration of systemic budesonide with duvelisib due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. [34979] [63571] Dyphylline: (Moderate) Concomitant use of formoterol and dyphylline may potentiate the hypokalemic effect of formoterol. Tremors, insomnia, seizures, or cardiac arrhythmias are also possible. Monitor the patient appropriately and consider checking serum potassium concentrations if clinically indicated. [60746] Dyphylline; Guaifenesin: (Moderate) Concomitant use of formoterol and dyphylline may potentiate the hypokalemic effect of formoterol. Tremors, insomnia, seizures, or cardiac arrhythmias are also possible. Monitor the patient appropriately and consider checking serum potassium concentrations if clinically indicated. [60746] Echinacea: (Moderate) Echinacea possesses immunostimulatory activity and may theoretically reduce the response to immunosuppressant drugs like corticosteroids. For some patients who are using corticosteroids for serious illness, such as cancer or organ transplant, this potential interaction may result in the preferable avoidance of Echinacea. Although documentation is lacking, coadministration of echinacea with immunosuppressants is not recommended by some resources. [25398] [32073] [61902] [61905] Econazole: (Minor) In vitro studies indicate that corticosteroids inhibit the antifungal activity of econazole against C. albicans in a concentration-dependent manner. When the concentration of the corticosteroid was equal to or greater than that of econazole on a weight basis, the antifungal activity of econazole was substantially inhibited. When the corticosteroid concentration was one-tenth that of econazole, no inhibition of antifungal activity was observed. [6968] Efavirenz: (Moderate) Consider alternatives to efavirenz when coadministering with long-acting beta-agonists. QTc prolongation has been observed with the use of efavirenz. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with efavirenz. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28442] [28467] [32901] [41231] [44979] [54633] [57710] Efavirenz; Emtricitabine; Tenofovir: (Moderate) Consider alternatives to efavirenz when coadministering with long-acting beta-agonists. QTc prolongation has been observed with the use of efavirenz. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with efavirenz. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28442] [28467] [32901] [41231] [44979] [54633] [57710] Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with long-acting beta-agonists. QTc prolongation has been observed with the use of efavirenz. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with efavirenz. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28442] [28467] [32901] [41231] [44979] [54633] [57710] Elbasvir; Grazoprevir: (Minor) Administering budesonide with grazoprevir may result in elevated budesonide plasma concentrations. Budesonide is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events. [60523] Elexacaftor; tezacaftor; ivacaftor: (Moderate) Use caution when administering ivacaftor and budesonide concurrently. Ivacaftor is an inhibitor of CYP3A and P-glycoprotein (Pgp). Co-administration of ivacaftor with CYP3A and Pgp substrates, such as budesonide, can increase budesonide exposure leading to increased or prolonged therapeutic effects and adverse events. [34354] [34979] [48524] Eliglustat: (Moderate) Coadministration of oral budesonide and eliglustat may result in increased plasma concentrations of budesonide. Monitor patients closely for corticosteroid-related adverse effects; if appropriate, consider reducing the budesonide dosage and titrating to clinical effect. Budesonide is a substrate of the intestinal drug efflux pump, P-glycoprotein (P-gp); eliglustat is a P-gp inhibitor. [34354] [57803] (Moderate) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with eliglustat include beta-agonists. [57803] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Avoid coadministration of oral budesonide and cobistat due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Elevated budesonide serum concentrations may result in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 and P-glycoprotein (P-gp) substrate; cobicistat is a strong inhibitor of CYP3A4 and P-gp. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. [31824] [34354] [34979] [51664] [58000] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Avoid coadministration of oral budesonide and cobistat due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Elevated budesonide serum concentrations may result in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 and P-glycoprotein (P-gp) substrate; cobicistat is a strong inhibitor of CYP3A4 and P-gp. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. [31824] [34354] [34979] [51664] [58000] Empagliflozin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Empagliflozin; Linagliptin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Empagliflozin; Linagliptin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Empagliflozin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Caution is advised when administering rilpivirine with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists, such as arformoterol, as compared to short-acting beta-agonists. [28318] [32901] [33925] [41231] [44376] Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Moderate) Caution is advised when administering rilpivirine with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists, such as arformoterol, as compared to short-acting beta-agonists. [28318] [32901] [33925] [41231] [44376] Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Encorafenib: (Moderate) Coadministration of encorafenib with budesonide may result in increased toxicity or decreased efficacy of budesonide. Budesonide is a sensitive CYP3A4 substrate. In vitro studies with encorafenib showed time-dependent inhibition of CYP3A4 and induction of CYP3A4. The clinical relevance of the in vivo effect of encorafenib on CYP3A4 is not established. [56579] [63317] (Moderate) If encorafenib is coadministered with a long-acting beta-agonist, consider monitoring ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib has been associated with dose-dependent QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [32901] [41231] [44979] [54633] [57710] [63317] Enflurane: (Moderate) Enflurane, like other halogenated anesthetics, can prolong the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously with halogenated anesthetics include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. The action of beta-agonists on the cardiovascular system may be potentiated by a halogenated anesthetic. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28318] [28457] [28458] [32901] [33925] [41231] Entrectinib: (Moderate) Coadministration of entrectinib and long-acting beta-agonists may increase the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [32901] [41231] [44979] [54633] [57710] Ephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) Ephedrine may enhance the metabolic clearance of corticosteroids. Decreased blood concentrations and lessened physiologic activity may necessitate an increase in corticosteroid dosage. [8844] Ephedrine; Guaifenesin: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) Ephedrine may enhance the metabolic clearance of corticosteroids. Decreased blood concentrations and lessened physiologic activity may necessitate an increase in corticosteroid dosage. [8844] Epinephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Ergotamine; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists. [66338] Eribulin: (Moderate) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28318] [32901] [33925] [41231] [42449] Erlotinib: (Moderate) Monitor for symptoms of gastrointestinal (GI) perforation (e.g., severe abdominal pain, fever, nausea, and vomiting) if coadministration of erlotinib with budesonide is necessary. Permanently discontinue erlotinib in patients who develop GI perforation. The pooled incidence of GI perforation clinical trials of erlotinib ranged from 0.1% to 0.4%, including fatal cases; patients receiving concomitant budesonide may be at increased risk. [30555] Ertugliflozin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Ertugliflozin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Ertugliflozin; Sitagliptin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Erythromycin: (Moderate) Avoid coadministration of oral budesonide and erythromycin due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; erythromycin is a moderate CYP3A4 inhibitor. In the presence of a strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [28251] [34979] (Moderate) Erythromycin administration is associated with QT prolongation and torsade de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with erythromycin include the long-acting beta-agonists (LABAs). The effects of these beta-agonists on the cardiovascular system may be potentiated. Beta agonists infrequently produce cardiovascular adverse effects, mostly with high doses or in the setting of beta-agonist-induced hypokalemia. [28309] [32950] [41138] [41231] [48676] Erythromycin; Sulfisoxazole: (Moderate) Avoid coadministration of oral budesonide and erythromycin due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; erythromycin is a moderate CYP3A4 inhibitor. In the presence of a strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [28251] [34979] (Moderate) Erythromycin administration is associated with QT prolongation and torsade de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with erythromycin include the long-acting beta-agonists (LABAs). The effects of these beta-agonists on the cardiovascular system may be potentiated. Beta agonists infrequently produce cardiovascular adverse effects, mostly with high doses or in the setting of beta-agonist-induced hypokalemia. [28309] [32950] [41138] [41231] [48676] Escitalopram: (Moderate) Use escitalopram with caution in combination with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. Escitalopram has been associated with a risk of QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28270] [28467] [32901] [41231] [44979] [54633] [57710] Esmolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. [28618] [43675] [44979] [51834] [58220] Esomeprazole: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. [34979] Estramustine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [4744] [7714] Estrogens: (Moderate) Estrogens have been associated with elevated serum concentrations of corticosteroid binding globulin (CBG), leading to increased total circulating corticosteroids, although the free concentrations of these hormones may be lower; the clinical significance is not known. Estrogens are CYP3A4 substrates and dexamethasone is a CYP3A4 inducer; concomitant use may decrease the clinical efficacy of estrogens. Patients should be monitored for signs of decreased clinical effects of estrogens (e.g., breakthrough bleeding), oral contraceptives, or non-oral combination contraceptives if these drugs are used together. [4718] [4744] [6395] Ethacrynic Acid: (Moderate) Loop diuretics may potentiate hypokalemia and ECG changes seen with beta agonists. Hypokalemia due to beta agonists appears to be dose related and is more likely with high dose therapy. Caution is advised when loop diuretics are coadministered with high doses of beta agonists; potassium levels may need to be monitored. [33925] [43675] [44979] Ethotoin: (Moderate) Hydantoin anticonvulsants induce hepatic microsomal enzymes and may increase the metabolism of budesonide, leading to reduced efficacy. Depending on the individual clinical situation and the indication for the interacting medication, enzyme-induction interactions may not always produce reductions in treatment efficacy. [28001] [28771] Etravirine: (Moderate) Etravirine is a CYP3A4 inducer and a P-glycoprotein (PGP) inhibitor and budesonide is a CYP3A4 substrate and a substrate/inhibitor of PGP. Caution is warranted if these drugs are coadministered. [11210] [33718] [6865] Exenatide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Ezogabine: (Moderate) Use ezogabine and long-acting beta-agonists together with caution as concurrent use may increase the risk of QT prolongation. Ezogabine has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28318] [32901] [33925] [41231] [44800] [44979] Famotidine: (Moderate) Monitor for altered response to budesonide in patients receiving H2-blockers with enteric-coated or extended-release formulations of oral budesonide. Enteric-coated budesonide granules (Entocort EC) dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause these products to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. When cimetidine (1 gram/day PO) is administered with an uncoated formulation of oral budesonide, a slight increase in absorption and peak plasma concentrations occur, resulting in significant cortisol suppression. [34979] [52910] Famotidine; Ibuprofen: (Moderate) Monitor for altered response to budesonide in patients receiving H2-blockers with enteric-coated or extended-release formulations of oral budesonide. Enteric-coated budesonide granules (Entocort EC) dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause these products to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. When cimetidine (1 gram/day PO) is administered with an uncoated formulation of oral budesonide, a slight increase in absorption and peak plasma concentrations occur, resulting in significant cortisol suppression. [34979] [52910] Fedratinib: (Moderate) Avoid coadministration of systemic budesonide with fedratinib due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A4 substrate and fedratinib is a moderate CYP3A4 inhibitor. [34979] [64568] Fexofenadine; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Fingolimod: (Moderate) Exercise caution when administering fingolimod concomitantly with a long-acting beta-agonist as concurrent use may increase the risk of QT prolongation. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with fingolimod. This risk may be more clinically significant with long-acting beta-agonistst as compared to short-acting beta-agonists. [28318] [33925] [41231] [41823] [44979] Flecainide: (Moderate) Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsade de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with flecainide include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [23774] [28318] [32901] [33925] [41231] [44979] Fluconazole: (Moderate) Avoid coadministration of oral budesonide and fluconazole due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; fluconazole is a moderate CYP3A4 inhibitor. In the presence of a strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [28674] [34979] (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] (Moderate) Use fluconazole with caution in combination with beta-agonists as concurrent use may increase the risk of QT prolongation. Fluconazole has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [28674] [32901] [33156] [41231] [44979] [53057] [54633] [56564] [57710] [59321] Fluoxetine: (Moderate) Avoid coadministration of oral budesonide and fluoxetine due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; fluoxetine a weak CYP3A4 inhibitor and the active metabolite norfluoxetine is a moderate CYP3A4 inhibitor. In the presence of a strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [29003] [29190] [34979] (Moderate) Coadministration of fluoxetine and long-acting beta-agonists may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation and TdP have been reported in patients treated with fluoxetine. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [32127] [41231] Fluoxymesterone: (Moderate) Coadministration of corticosteroids and fluoxymesterone may increase the risk of edema, especially in patients with underlying cardiac or hepatic disease. Corticosteroids with greater mineralocorticoid activity, such as fludrocortisone, may be more likely to cause edema. Administer these drugs in combination with caution. [11342] Fluphenazine: (Minor) Fluphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. This risk is generally higher at elevated drugs concentrations of phenothiazines. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with fluphenazine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28318] [28415] [32901] [33925] [41231] Fluticasone; Salmeterol: (Major) Formoterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist for any reason, as overdose may result. Coadministration can result in overdosage. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with inhaled short-acting beta-2 agonists (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking formoterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if formoterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual. Use formoterol and drugs known to prolong the QTc interval together with extreme caution; this combination may increase the risk of cardiovascular effects and ventricular arrhythmias; this includes combination with other beta-agonists. [28318] [33925] [41231] [60746] Fluticasone; Umeclidinium; Vilanterol: (Major) Formoterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist for any reason, as overdose may result. Coadministration can result in overdosage. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with inhaled short-acting beta-2 agonists (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking formoterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if formoterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual. Use formoterol and drugs known to prolong the QTc interval together with extreme caution; this combination may increase the risk of cardiovascular effects and ventricular arrhythmias; this includes combination with other beta-agonists. [28318] [33925] [41231] [60746] Fluticasone; Vilanterol: (Major) Formoterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist for any reason, as overdose may result. Coadministration can result in overdosage. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with inhaled short-acting beta-2 agonists (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking formoterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if formoterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual. Use formoterol and drugs known to prolong the QTc interval together with extreme caution; this combination may increase the risk of cardiovascular effects and ventricular arrhythmias; this includes combination with other beta-agonists. [28318] [33925] [41231] [60746] Fluvoxamine: (Moderate) Avoid coadministration of oral budesonide and fluvoxamine if possible due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; fluvoxamine is a moderate CYP3A4 inhibitor. In the presence of a strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [28902] [34979] (Moderate) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of fluvoxamine and long-acting beta-agonists. Coadminister with caution. QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists than short-acting beta-agonists. [28467] [32901] [41231] [44979] [50507] [54633] [57710] Fosamprenavir: (Moderate) Caution is advised when administering budesonide with fosamprenavir, as concurrent use may alter the plasma concentrations of budesonide. Budesonide is a substrate for the hepatic isoenzyme CYP3A4 and the drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is an inducer of P-gp and a potent inhibitor and moderate inducer of CYP3A4. [29012] [34354] Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as long-acting beta-agonists. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment. [28377] [28467] [32901] [41231] [44979] [54633] [57710] Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Fosphenytoin: (Moderate) Hydantoin anticonvulsants induce hepatic microsomal enzymes and may increase the metabolism of budesonide, leading to reduced efficacy. Depending on the individual clinical situation and the indication for the interacting medication, enzyme-induction interactions may not always produce reductions in treatment efficacy. [28001] [28771] Fostemsavir: (Moderate) Use beta-agonists and fostemsavir together with caution due to the potential for QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation. [28467] [32901] [41231] [44979] [54633] [57710] [65666] Furosemide: (Moderate) Loop diuretics may potentiate hypokalemia and ECG changes seen with beta agonists. Hypokalemia due to beta agonists appears to be dose related and is more likely with high dose therapy. Caution is advised when loop diuretics are coadministered with high doses of beta agonists; potassium levels may need to be monitored. [33925] [43675] [44979] Gallium Ga 68 Dotatate: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia. Also, corticotropin may cause calcium loss and sodium and fluid retention. Mannitol itself can cause hypernatremia. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly. [6524] (Moderate) Repeated administration of high corticosteroid doses prior to gallium Ga 68 dotatate may result in false negative imaging. High-dose corticosteroid therapy is generally defined as at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. Corticosteroids can down-regulate somatostatin subtype 2 receptors: thereby, interfering with binding of gallium Ga 68 dotatate to malignant cells that overexpress these receptors. [60852] Gemcitabine: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Gemifloxacin: (Moderate) Gemifloxacin should be used cautiously with beta-agonists as concurrent use may increase the risk of QT prolongation. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28318] [28419] [28420] [28424] [33925] [41231] Gemtuzumab Ozogamicin: (Moderate) Use gemtuzumab ozogamicin and long-acting beta-agonists together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [32901] [41231] [44979] [54633] [57710] [62292] Gentamicin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Gilteritinib: (Moderate) Use caution and monitor for additive QT prolongation if concurrent use of gilteritinib and a long-acting beta agonist is necessary. Gilteritinib has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [32901] [41231] [44979] [54633] [57710] [63787] Glasdegib: (Moderate) Consider increased frequency of ECG monitoring if coadministration of glasdegib and long-acting beta-agonists is necessary. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [32901] [41231] [44979] [54633] [57710] [63777] Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and budesonide as coadministration may increase serum concentrations of budesonide and increase the risk of adverse effects. Glecaprevir is a P-glycoprotein (P-gp) inhibitor; budesonide is a P-gp substrate. [34354] [62201] (Moderate) Caution is advised with the coadministration of pibrentasvir and budesonide as coadministration may increase serum concentrations of budesonide and increase the risk of adverse effects. Pibrentasvir is a P-glycoprotein (P-gp) inhibitor; budesonide is a P-gp substrate. [34354] [62201] Glimepiride: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Glimepiride; Rosiglitazone: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Glipizide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Glipizide; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Glyburide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Glyburide; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Glycerol Phenylbutyrate: (Moderate) Corticosteroids may induce elevated blood ammonia concentrations. Corticosteroids should be used with caution in patients receiving glycerol phenylbutyrate. Monitor ammonia concentrations closely. [53022] Goserelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., goserelin) outweigh the potential risks of QT prolongation in patients receiving long-acting beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28318] [28592] [33925] [41231] Granisetron: (Moderate) Use granisetron with caution in combination with long-acting beta-agonists due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28318] [31723] [32901] [33925] [41231] Grapefruit juice: (Major) Grapefruit juice, an inhibitor of gut mucosal CYP3A4, roughly doubles the bioavailability of oral budesonide. Patients should not eat grapefruit or drink grapefruit juice during the entire treatment period with oral budesonide. [34979] Griseofulvin: (Moderate) Theoretically, induction of the cytochrome P450 3A4 isoenzyme by griseofulvin may result in a lowering of budesonide plasma concentrations, reducing the clinical effect. [28001] Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Guaifenesin; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Guaifenesin; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] H2-blockers: (Moderate) Monitor for altered response to budesonide in patients receiving H2-blockers with enteric-coated or extended-release formulations of oral budesonide. Enteric-coated budesonide granules (Entocort EC) dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause these products to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. When cimetidine (1 gram/day PO) is administered with an uncoated formulation of oral budesonide, a slight increase in absorption and peak plasma concentrations occur, resulting in significant cortisol suppression. [34979] [52910] Halofantrine: (Contraindicated) Halofantrine is considered to have a well-established risk for QT prolongation and torsade de pointes (TdP). Halofantrine should be avoided in patients receiving drugs which may induce QT prolongation. These drugs include the beta-agonists. Beta-agonists may be associated with cardiovascular effects, usually at higher doses and/or when associated with hypokalemia. [28318] [32901] [33925] [41231] [4951] [4968] [5618] (Major) Due to the risks of cardiac toxicity of halofantrine in patients with hypokalemia and/or hypomagnesemia, the use of halofantrine should be avoided in combination with agents that may lead to electrolyte losses, such as corticosteroids. [4968] Haloperidol: (Moderate) Caution is advisable during concurrent use of haloperidol and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with haloperidol. [28307] (Moderate) QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated. [23500] [23779] [28225] [28307] [28318] [28415] [28416] [32901] [33925] [41231] Halothane: (Moderate) Halothane, like other halogenated anesthetics, can prolong the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously with halogenated anesthetics include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. The action of beta-agonists on the cardiovascular system may be potentiated by a halogenated anesthetic. [28318] [28457] [28458] [32901] [33925] [41231] Hemin: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Corticosteroids increase the activity of this enzyme should not be used with hemin. [6702] Heparin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Hetastarch: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Histrelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving long-acting beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [30369] [32901] [41231] [44979] [54633] [57710] Hydantoins: (Moderate) Hydantoin anticonvulsants induce hepatic microsomal enzymes and may increase the metabolism of budesonide, leading to reduced efficacy. Depending on the individual clinical situation and the indication for the interacting medication, enzyme-induction interactions may not always produce reductions in treatment efficacy. [28001] [28771] Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Hydrocodone; Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Hydrocodone; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Hydroxychloroquine: (Major) Avoid coadministration of long-acting beta-agonists and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28229] [32901] [41231] [41806] [44026] [44063] [44979] [59321] [65157] [65170] Hydroxyurea: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Hydroxyzine: (Moderate) Caution is recommended if hydroxyzine is administered with long-acting beta-agonists due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28318] [32901] [33925] [41231] [47129] Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia. [57713] [57714] [57715] Ibritumomab Tiuxetan: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia. [57713] [57714] [57715] (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Ibuprofen; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Ibutilide: (Moderate) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated. [28318] [32901] [33925] [41231] [41830] Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with budesonide, a CYP3A substrate, as budesonide toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. [57675] [6865] Iloperidone: (Moderate) Iloperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported. According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect. Drugs with a possible risk for QT prolongation that should be avoided with iloperidone include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28318] [32901] [33925] [36146] [41231] Imipramine: (Moderate) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with TCAs include the beta-agonists. Beta agonists infrequently produce cardiovascular adverse effects, mostly with high doses or in the setting of beta-agonist-induced hypokalemia. [28225] [28318] [28416] [33925] [41231] Incretin Mimetics: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Indacaterol: (Major) Formoterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist for any reason, as overdose may result. Coadministration can result in overdosage. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with inhaled short-acting beta-2 agonists (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking formoterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if formoterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual. Use formoterol and drugs known to prolong the QTc interval together with extreme caution; this combination may increase the risk of cardiovascular effects and ventricular arrhythmias; this includes combination with other beta-agonists. [28318] [33925] [41231] [60746] Indacaterol; Glycopyrrolate: (Major) Formoterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist for any reason, as overdose may result. Coadministration can result in overdosage. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with inhaled short-acting beta-2 agonists (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking formoterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if formoterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual. Use formoterol and drugs known to prolong the QTc interval together with extreme caution; this combination may increase the risk of cardiovascular effects and ventricular arrhythmias; this includes combination with other beta-agonists. [28318] [33925] [41231] [60746] Indapamide: (Moderate) Additive hypokalemia may occur when indapamide is coadministered with other drugs with a significant risk of hypokalemia such as systemic corticosteroids. Coadminister with caution and careful monitoring. [26417] Indinavir: (Minor) Use caution when budesonide is coadministered with drugs that inhibit CYP3A enzymes, such as indinavir, and consider dose reduction. Toxicity may occur, particularly excessive HPA-axis suppression. [5462] Inebilizumab: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab. [65576] Inotuzumab Ozogamicin: (Moderate) Coadministration of inotuzumab ozogamicin with long-acting beta-agonists may increase the potential for additive QT prolongation and risk of torsade de pointes (TdP). Inotuzumab has been associated with QT interval prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [32901] [41231] [44979] [54633] [57710] [62245] Insulin Degludec; Liraglutide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Insulin Glargine; Lixisenatide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Insulins: (Moderate) Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Interferon Alfa-2a: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Interferon Alfa-2b: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Interferon Alfa-2b; Ribavirin: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with budesonide may result in increased serum concentrations of budesonide. Budesonide is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together. [34354] [59042] Isocarboxazid: (Major) Beta-agonists should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors (MAOIs) due to their sympathomimetic effects. Weigh the risks of coadministration, and where possible, allow a washout period after discontinuation of the MAOI before instituring beta-agonist treatment or vice-versa. The cardiovascular effects of beta-agonists may be potentiated by concomitant use of MAOIs. Close observation for such effects is prudent, particularly if beta-agonists are administered within 2 weeks of stopping the MAOI. Monitor blood pressure and heart rate. [27957] [28309] [28467] [29656] [30438] [32901] [44979] [49951] [51022] [54633] [57710] Isoflurane: (Moderate) Isoflurane, like other halogenated anesthetics, can prolong the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously with halogenated anesthetics include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. The action of beta-agonists on the cardiovascular system may be potentiated by a halogenated anesthetic. [28318] [28457] [28458] [32901] [33925] [41231] Isoproterenol: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The risk of cardiac toxicity with isoproterenol in asthma patients appears to be increased with the coadministration of corticosteroids. Intravenous infusions of isoproterenol in refractory asthmatic children at rates of 0.05 to 2.7 mcg/kg/min have caused clinical deterioration, myocardial infarction (necrosis), congestive heart failure and death. [28004] Isotretinoin: (Minor) Both isotretinoin and corticosteroids can cause osteoporosis during chronic use. Patients receiving systemic corticosteroids should receive isotretinoin therapy with caution. [5283] Itraconazole: (Moderate) Avoid coadministration of oral budesonide and itraconazole due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; itraconazole is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [28278] [34376] [34979] (Moderate) Use itraconazole with caution in combination with beta-agonists as concurrent use may increase the risk of QT prolongation. Itraconazole has been associated with prolongation of the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28318] [33925] [40233] [41231] [57441] Ivacaftor: (Moderate) Use caution when administering ivacaftor and budesonide concurrently. Ivacaftor is an inhibitor of CYP3A and P-glycoprotein (Pgp). Co-administration of ivacaftor with CYP3A and Pgp substrates, such as budesonide, can increase budesonide exposure leading to increased or prolonged therapeutic effects and adverse events. [34354] [34979] [48524] Ivosidenib: (Moderate) Coadministration of ivosidenib with long-acting beta-agonists may increase the risk of QT prolongation. If concomitant use is necessary, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [32901] [41231] [44979] [57710] [63368] (Moderate) Monitor for loss of efficacy of budesonide during coadministration of ivosidenib; a budesonide dose adjustment may be necessary. Budesonide is a sensitive substrate of CYP3A4; ivosidenib induces CYP3A4 and may lead to decreased budesonide concentrations. [34979] [63368] Ixabepilone: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp).[10415] Budesonide is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in budesonide concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate. [10415] Ketoconazole: (Major) Ketoconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ketoconazole include the beta-agonists. In addition, the long-acting beta agonists (LABAs) indacaterol, vilanterol, salmeterol are CYP3A4 substrates. The coadministration of these LABAs with strong CYP3A4 inhibitors such as ketoconazole may result in elevated LABA plasma concentrations and increased risk for adverse reactions, particularly systemic side effects such as nervousness, tremor, or cardiovascular effects. In a placebo-controlled, drug interaction study of 20 healthy subjects, coadministration of salmeterol (50 mcg twice daily), and ketoconazole (400 mg PO once daily) for 7 days resulted in a 16-fold increase in salmeterol AUC. Three of the 20 subjects were withdrawn from the study due to cardiovascular adverse effects (2 with QTc prolongation and 1 with palpitations and sinus tachycardia). An increase in AUC also occurred when ketoconazole was coadministered with indacaterol. Similar interactions may occur when ketoconazole is added to vilanterol, such as umeclidinium; vilanterol. [27982] [28318] [33925] [41231] [50004] [5197] (Moderate) Ketoconazole may increase plasma concentrations of oral budesonide more than 7-fold due to inhibition of the CYP3A4 isoenzyme in the liver, as well as in the gut, and can enhance the cortisol suppression associated with budesonide administered via inhalation. Inhibition of CYP3A4 may be clinically significant for inhaled forms of budesonide, including budesonide nasal spray. [27982] [28001] [28279] [28761] [31824] [34535] Labetalol: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. [28618] [43675] [44979] [51834] [58220] Lansoprazole: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. [34979] Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Avoid coadministration of oral budesonide and clarithromycin due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [28238] [28278] [34376] [34979] (Moderate) The coadministration of beta-agonists with clarithromycin may increase the risk for adverse effects, including prolongation of the QT interval. Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Long-acting beta-agonists (LABAs) may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Pharmacokinetic interactions may occur between clarithromycin and some LABAs. Clarithromycin is a strong CYP3A4 inhibitor and the co-administration of salmeterol with strong CYP3A4 inhibitors can result in elevated concentrations that may increase the risk for cardiovascular events. [28238] [28467] [32901] [33156] [41231] [44979] [54633] [56564] [57710] (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. [34979] Lansoprazole; Naproxen: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. [34979] Lapatinib: (Moderate) Monitor for evidence of QT prolongation if lapatinib is administered with long-acting beta-agonists. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists, such as formoterol, as compared to short-acting beta-agonists. [28467] [32901] [33156] [33192] [41231] [44979] [54633] [56564] [57710] L-Asparaginase Escherichia coli: (Moderate) Concomitant use of L-asparaginase with corticosteroids can result in additive hyperglycemia. L-Asparaginase transiently inhibits insulin production contributing to hyperglycemia seen during concurrent corticosteroid therapy. Insulin therapy may be required in some cases. Administration of L-asparaginase after rather than before corticosteroids reportedly has produced fewer hypersensitivity reactions. [55362] Ledipasvir; Sofosbuvir: (Minor) Caution and close monitoring of budesonide-associated adverse reactions is advised with concomitant administration of ledipasvir. Budesonide is a substrate of the drug transporter P-glycoprotein (P-gp); ledipasvir is a P-gp inhibitor. Taking these drugs together may increase budesonide plasma concentrations. [34354] [58167] Lefamulin: (Moderate) Avoid coadministration of systemic budesonide with oral lefamulin due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A4 substrate and oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin. [34979] [64576] (Moderate) Coadministration of lefamulin and long-acting beta-agonists may increase the risk of QT prolongation. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [32901] [41231] [44979] [54633] [57710] [64576] Lenvatinib: (Moderate) Beta-agonists should be used cautiously and with close monitoring with lenvatinib. Prolongation of the QT interval has been reported with lenvatinib therapy. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia; the risk may be more clinically significant with long-acting beta-agonists. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated. [28467] [32901] [33156] [41231] [44979] [54633] [56564] [57710] [58782] Letermovir: (Moderate) A clinically relevant increase in the plasma concentration of budesonide may occur when given concurrently with letermovir; monitor for adverse events. Avoid coadministration of oral budesonide and letermovir in patients who are also receiving treatment with cyclosporine, because the magnitude of this interaction may be amplified. Budesonide is a sensitive CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. Concurrent use of a strong inhibitor increased the AUC of oral budesonide by 8-fold. [34979] [62611] Leuprolide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving long-acting beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28318] [33925] [41231] [43800] Leuprolide; Norethindrone: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving long-acting beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28318] [33925] [41231] [43800] Levetiracetam: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Levobetaxolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. [28618] [43675] [44979] [51834] [58220] Levobunolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. [28618] [43675] [44979] [51834] [58220] Levofloxacin: (Moderate) Levofloxacin should be used cautiously with long-acting beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. Levofloxacin has also been associated with a risk of QT prolongation and TdP. Although extremely rare, TdP has been reported during postmarketing surveillance of levofloxacin. [28318] [28421] [28467] [32901] [33925] [41231] [44979] [54633] [57710] Levomethadyl: (Contraindicated) Levomethadyl is associated with an established risk of QT prolongation and/or torsade de pointes, particularly at high drug concentrations. Levomethadyl is contraindicated in combination with other agents that may prolong the QT interval. Agents with potential to prolong the QT interval include the beta agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28318] [32901] [33925] [41231] [4951] [5079] [5081] [5146] (Major) Caution is advised when using levomethadyl in combination with other agents, such as corticosteroids, that may lead to electrolyte abnormalities, especially hypokalemia or hypomagnesemia. [3085] Levothyroxine: (Moderate) Based on the cardiovascular stimulatory effects of beta-agonists and other sympathomimetics, concomitant use with thyroid hormones might enhance the effects on the cardiovascular system. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease. [43942] [43952] Levothyroxine; Liothyronine (Porcine): (Moderate) Based on the cardiovascular stimulatory effects of beta-agonists and other sympathomimetics, concomitant use with thyroid hormones might enhance the effects on the cardiovascular system. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease. [43942] [43952] Levothyroxine; Liothyronine (Synthetic): (Moderate) Based on the cardiovascular stimulatory effects of beta-agonists and other sympathomimetics, concomitant use with thyroid hormones might enhance the effects on the cardiovascular system. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease. [43942] [43952] Linagliptin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] Linezolid: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists. [28599] [32308] Liothyronine: (Moderate) Based on the cardiovascular stimulatory effects of beta-agonists and other sympathomimetics, concomitant use with thyroid hormones might enhance the effects on the cardiovascular system. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease. [43942] [43952] Liraglutide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Lithium: (Moderate) Lithium should be used cautiously and with close monitoring with beta-agonists. Lithium has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated. [28318] [32901] [33925] [41231] [59809] [59810] [59811] Lixisenatide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Lofexidine: (Moderate) Monitor ECG if lofexidine is coadministered with long-acting beta-agonists due to the potential for additive QT prolongation. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of torsade de pointes. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [32901] [41231] [44979] [63161] Lomustine, CCNU: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [5946] [7714] [7944] Lonafarnib: (Moderate) Avoid coadministration of oral budesonide and lonafarnib due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; lonafarnib is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [34979] [66129] Lonapegsomatropin: (Moderate) Corticosteroids can retard bone growth and therefore, can inhibit the growth-promoting effects of somatropin. If corticosteroid therapy is required, the corticosteroid dose should be carefully adjusted. [6807] Loop diuretics: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly. [26417] [28429] [29779] (Moderate) Loop diuretics may potentiate hypokalemia and ECG changes seen with beta agonists. Hypokalemia due to beta agonists appears to be dose related and is more likely with high dose therapy. Caution is advised when loop diuretics are coadministered with high doses of beta agonists; potassium levels may need to be monitored. [33925] [43675] [44979] Loperamide: (Moderate) Coadministration of loperamide with beta-agonist may increase the risk for QT prolongation and torsade de pointes (TdP). At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, TdP and cardiac arrest. Beta-agonists have also been associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated. [28318] [32901] [33925] [41231] [60864] Loperamide; Simethicone: (Moderate) Coadministration of loperamide with beta-agonist may increase the risk for QT prolongation and torsade de pointes (TdP). At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, TdP and cardiac arrest. Beta-agonists have also been associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated. [28318] [32901] [33925] [41231] [60864] Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with long-acting beta-agonists due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28318] [28341] [32901] [33925] [41231] [65157] [65170] (Major) Avoid coadministration of oral budesonide and ritonavir due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [28315] [31824] [34979] [47165] (Moderate) Decreased lopinavir plasma concentrations have been observed when systemic budesonide and lopinavir are coadministered, increasing the risk for HIV treatment failure. Consider use of an alternative corticosteroid. If concurrent use is required, caution and careful monitoring of HIV treatment status is recommended. [28341] [31824] [34979] [51080] Loratadine; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Lumacaftor; Ivacaftor: (Moderate) Concomitant use of budesonide and lumacaftor; ivacaftor may alter the therapeutic effects of budesonide; caution and close monitoring are advised if these drugs are used together. Budesonide is a primary substrate of CYP3A4 and a substrate of the P-glycoprotein (P-gp) efflux transporter. Lumacaftor is a strong CYP3A inducer; in vitro data also suggest lumacaftor; ivacaftor may induce and/or inhibit P-gp. Although induction of budesonide through the CYP3A pathway may lead to decreased drug efficacy, the net effect of lumacaftor; ivacaftor on P-gp transport is not clear. Monitor the patient for decreased corticosteroid efficacy or increased or prolonged therapeutic effects and adverse events. [34354] [34979] [59891] Lumacaftor; Ivacaftor: (Moderate) Use caution when administering ivacaftor and budesonide concurrently. Ivacaftor is an inhibitor of CYP3A and P-glycoprotein (Pgp). Co-administration of ivacaftor with CYP3A and Pgp substrates, such as budesonide, can increase budesonide exposure leading to increased or prolonged therapeutic effects and adverse events. [34354] [34979] [48524] Macimorelin: (Major) Avoid use of macimorelin with drugs that directly affect pituitary growth hormone secretion, such as corticosteroids. Healthcare providers are advised to discontinue corticosteroid therapy and observe a sufficient washout period before administering macimorelin. Use of these medications together may impact the accuracy of the macimorelin growth hormone test. [62723] (Moderate) Concurrent use of macimorelin with long-acting beta-agonists may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [32901] [41231] [44979] [54633] [57710] [62723] Magnesium Hydroxide: (Moderate) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. [34979] [52910] Magnesium Salicylate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Mannitol: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia. Also, corticotropin may cause calcium loss and sodium and fluid retention. Mannitol itself can cause hypernatremia. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly. [6524] Maprotiline: (Moderate) Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Drugs with a possible risk for QT prolongation that should be used cautiously with maprotiline include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT prolongation, usually at higher doses and/or when associated with hypokalemia. [28318] [28759] [32901] [33925] [41231] [44979] Mecasermin rinfabate: (Moderate) Additional monitoring may be required when coadministering systemic or inhaled corticosteroids and mecasermin, recombinant, rh-IGF-1. In animal studies, corticosteroids impair the growth-stimulating effects of growth hormone (GH) through interference with the physiological stimulation of epiphyseal chondrocyte proliferation exerted by GH and IGF-1. Dexamethasone administration on long bone tissue in vitro resulted in a decrease of local synthesis of IGF-1. Similar counteractive effects are expected in humans. If systemic or inhaled glucocorticoid therapy is required, the steroid dose should be carefully adjusted and growth rate monitored. [8314] [8315] Mecasermin, Recombinant, rh-IGF-1: (Moderate) Additional monitoring may be required when coadministering systemic or inhaled corticosteroids and mecasermin, recombinant, rh-IGF-1. In animal studies, corticosteroids impair the growth-stimulating effects of growth hormone (GH) through interference with the physiological stimulation of epiphyseal chondrocyte proliferation exerted by GH and IGF-1. Dexamethasone administration on long bone tissue in vitro resulted in a decrease of local synthesis of IGF-1. Similar counteractive effects are expected in humans. If systemic or inhaled glucocorticoid therapy is required, the steroid dose should be carefully adjusted and growth rate monitored. [8314] [8315] Mefloquine: (Moderate) While there is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QT interval, mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously with mefloquine include the beta-agonists. Beta agonists may cause adverse cardiovascular effects, usually with higher doses or when associated with hypokalemia. [28301] [28318] [32901] [33925] [41231] Meglitinides: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Mepenzolate: (Minor) Anticholinergics, such as mepenzolate, antagonize the effects of antiglaucoma agents. Mepenzolate is contraindicated in patients with glaucoma and therefore should not be coadministered with medications being prescribed for the treatment of glaucoma. In addition, anticholinergic drugs taken concurrently with corticosteroids in the presence of increased intraocular pressure may be hazardous. [42281] Meperidine; Promethazine: (Moderate) Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Use cautiously with promethazine, which has been reported to cause QT prolongation. [28225] [29318] [32901] [33925] [41231] [55578] Mephobarbital: (Moderate) Coadministration may result in decreased exposure to budesonide. Mephobarbital is a CYP3A4 inducer; budesonide is a CYP3A4 substrate. Monitor for decreased response to budesonide during concurrent use. [28001] Mesoridazine: (Contraindicated) Mesoridazine is associated with an established risk of QT prolongation and/or torsade de pointes (TdP). Agents that prolong the QT interval could lead to torsade de pointes are contraindicated with mesoridazine and include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28225] [28318] [29096] [32901] [33925] [41231] Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] Metformin; Repaglinide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Metformin; Rosiglitazone: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] Metformin; Saxagliptin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] Metformin; Sitagliptin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] Methacholine: (Major) Discontinue use of formoterol 36 hours before a methacholine challenge test. Beta-agonists inhibit the airway response to methacholine. [43792] [65783] Methadone: (Moderate) The need to coadminister methadone with drugs known to prolong the QT interval should be done with extreme caution and a careful assessment of treatment risks versus benefits. Methadone is considered to be associated with an increased risk for QT prolongation and torsade de pointes (TdP), especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day in adult patients). Methadone inhibits cardiac potassium channels and prolongs the QT interval. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with methadone include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28318] [28319] [28320] [28321] [28322] [32901] [33136] [33925] [41231] [44979] Methamphetamine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Methazolamide: (Moderate) Corticosteroids may increase the risk of hypokalemia if used concurrently with methazolamide. Hypokalemia may be especially severe with prolonged use of corticotropin, ACTH. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy. The chronic use of corticosteroids may augment calcium excretion with methazolamide leading to increased risk for hypocalcemia and/or osteoporosis. [5023] Methenamine; Sodium Acid Phosphate: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia. [57713] [57714] [57715] Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia. [57713] [57714] [57715] Methoxsalen: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Methyclothiazide: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Metolazone: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Metoprolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. [28618] [43675] [44979] [51834] [58220] Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. [28618] [43675] [44979] [51834] [58220] Metronidazole: (Moderate) Concomitant use of metronidazole and long-acting beta-agonists may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The risk for QT/QTc prolongation may be greater with long-acting beta-agonists than short-acting beta-agonists. [28467] [32901] [36894] [41231] [44979] [54633] [57710] Metyrapone: (Contraindicated) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of nasal corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results. [33528] Micafungin: (Moderate) Leukopenia, neutropenia, anemia, and thrombocytopenia have been associated with micafungin. Patients who are taking immunosuppressives such as the corticosteroids with micafungin concomitantly may have additive risks for infection or other side effects. In a pharmacokinetic trial, micafungin had no effect on the pharmacokinetics of prednisolone. Acute intravascular hemolysis and hemoglobinuria was seen in a healthy volunteer during infusion of micafungin (200 mg) and oral prednisolone (20 mg). This reaction was transient, and the subject did not develop significant anemia. [44913] Midazolam: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Midodrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Midostaurin: (Moderate) Concomitant use may result in additive effects on the QT interval. In clinical trials, QT prolongation was reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [32901] [41231] [44979] [54633] [57710] [61906] Mifepristone: (Major) Mifepristone for termination of pregnancy is contraindicated in patients on long-term corticosteroid therapy and mifepristone for Cushing's disease or other chronic conditions is contraindicated in patients who require concomitant treatment with systemic corticosteroids for life-saving purposes, such as serious medical conditions or illnesses (e.g., immunosuppression after organ transplantation). For other situations where corticosteroids are used for treating non-life threatening conditions, mifepristone may lead to reduced corticosteroid efficacy and exacerbation or deterioration of such conditions. This is because mifepristone exhibits antiglucocorticoid activity that may antagonize corticosteroid therapy and the stabilization of the underlying corticosteroid-treated illness. Mifepristone may also cause adrenal insufficiency, so patients receiving corticosteroids for non life-threatening illness require close monitoring. Because serum cortisol levels remain elevated and may even increase during treatment with mifepristone, serum cortisol levels do not provide an accurate assessment of hypoadrenalism. Patients should be closely monitored for signs and symptoms of adrenal insufficiency, If adrenal insufficiency occurs, stop mifepristone treatment and administer systemic glucocorticoids without delay; high doses may be needed to treat these events. Factors considered in deciding on the duration of glucocorticoid treatment should include the long half-life of mifepristone (85 hours). [28003] [48697] (Moderate) Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Drugs with a possible risk for QT prolongation that should be used cautiously with mifepristone include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28318] [32901] [33925] [41231] [48697] Mirtazapine: (Moderate) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of mirtazapine and long-acting beta-agonists. Coadminister with caution. Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during postmarketing use of mirtazapine, primarily following overdose or in patients with other risk factors for QT prolongation, including concomitant use of other medications associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [32901] [40942] [41231] [44979] [54633] [57710] Mitotane: (Moderate) Use caution if mitotane and budesonide are used concomitantly, and monitor for decreased efficacy of budesonide and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and budesonide is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of budesonide. Theoretically, inhibition of CYP3A may also be clinically significant for inhaled forms of budesonide, including budesonide nasal spray. [34354] [41934] Mitoxantrone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Mivacurium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] Mobocertinib: (Moderate) Concomitant use of mobocertinib and long-acting beta-agonists may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The risk for QT/QTc prolongation may be greater with long-acting beta-agonists than short-acting beta-agonists. [28467] [32901] [41231] [44979] [54633] [57710] [66990] Modafinil: (Moderate) Theoretically, induction of the cytochrome P450 3A4 isoenzyme by modafinil may result in a lowering of budesonide plasma concentrations, reducing the clinical effect. [28001] [28529] Monoamine oxidase inhibitors: (Major) Beta-agonists should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors (MAOIs) due to their sympathomimetic effects. Weigh the risks of coadministration, and where possible, allow a washout period after discontinuation of the MAOI before instituring beta-agonist treatment or vice-versa. The cardiovascular effects of beta-agonists may be potentiated by concomitant use of MAOIs. Close observation for such effects is prudent, particularly if beta-agonists are administered within 2 weeks of stopping the MAOI. Monitor blood pressure and heart rate. [27957] [28309] [28467] [29656] [30438] [32901] [44979] [49951] [51022] [54633] [57710] Moxifloxacin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] (Moderate) Prolongation of the QT interval has been reported with administration of moxifloxacin. Post-marketing surveillance has identified very rare cases of ventricular arrhythmias including torsade de pointes (TdP), usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded. According to the manufacturer, moxifloxacin should be avoided in patients taking drugs that can result in prolongation of the QT interval. Drugs with a possible risk for QT prolongation include beta-agonists. Beta-agonists may cause adverse cardiovascular effects, usually at higher doses and/or when associated with hypokalemia. [28318] [28423] [32901] [33925] [41231] Nadolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. [28618] [43675] [44979] [51834] [58220] Nafcillin: (Moderate) Theoretically, induction of the cytochrome P450 3A4 isoenzyme, such as nafcillin, may result in a lowering of budesonide plasma concentrations, reducing the clinical effect. [28001] Naproxen; Esomeprazole: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. [34979] Naproxen; Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Natalizumab: (Major) Ordinarily, patients receiving chronic immunosuppressant therapy should not be treated with natalizumab. Treatment recommendations for combined corticosteroid therapy are dependent on the underlying indication for natalizumab therapy. Corticosteroids should be tapered in those patients with Crohn's disease who are on chronic corticosteroids when they start natalizumab therapy, as soon as a therapeutic benefit has occurred. If the patient cannot discontinue systemic corticosteroids within 6 months, discontinue natalizumab. The concomitant use of natalizumab and corticosteroids may further increase the risk of serious infections, including progressive multifocal leukoencephalopathy, over the risk observed with use of natalizumab alone. In multiple sclerosis (MS) clinical trials, an increase in infections was seen in patients concurrently receiving short courses of corticosteroids. However, the increase in infections in natalizumab-treated patients who received steroids was similar to the increase in placebo-treated patients who received steroids. Short courses of steroid use during natalizumab, such as when they are needed for MS relapse treatment, appear to be acceptable for use concurrently. [30470] [62264] Nateglinide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Nebivolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. [28618] [43675] [44979] [51834] [58220] Nebivolol; Valsartan: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. [28618] [43675] [44979] [51834] [58220] Nefazodone: (Moderate) Avoid coadministration of oral budesonide and nefazodone due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; nefazodone is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [28683] [34979] Nelarabine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Nelfinavir: (Moderate) Avoid coadministration of oral budesonide and nelfinavir due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; nelfinavir is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [28839] [34979] Neostigmine: (Moderate) Concomitant use of anticholinesterase agents, such as neostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating systemic corticosteroid therapy. [29779] [30015] [30028] [31123] [54891] [56146] [64165] Neuromuscular blockers: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] Nevirapine: (Moderate) Theoretically, induction of the cytochrome P450 3A4 isoenzyme by nevirapine may result in a lowering of budesonide plasma concentrations, reducing the clinical effect. [28492] Nicardipine: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] (Minor) Nicardipine may increase plasma concentrations of budesonide due to inhibition of the CYP3A4 isoenzyme. Use caution when budesonide is coadministered with drugs that inhibit CYP3A enzymes and consider dose reduction. [4718] Nilotinib: (Moderate) Coadministration of nilotinib with long-acting beta-agonists may increase the potential for additive QT prolongation. Sudden death and QT interval prolongation have occurred in patients who received nilotinib therapy. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [32901] [33156] [41231] [44979] [54633] [56564] [57710] [58766] Nizatidine: (Moderate) Monitor for altered response to budesonide in patients receiving H2-blockers with enteric-coated or extended-release formulations of oral budesonide. Enteric-coated budesonide granules (Entocort EC) dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause these products to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. When cimetidine (1 gram/day PO) is administered with an uncoated formulation of oral budesonide, a slight increase in absorption and peak plasma concentrations occur, resulting in significant cortisol suppression. [34979] [52910] Nonsteroidal antiinflammatory drugs: (Moderate) Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged concomitant administration should be avoided. Concomitant use of corticosteroids appears to increase the risk of adverse GI events due to NSAIDs. Corticosteroids can have profound effects on sodium-potassium balance; NSAIDs also can affect sodium and fluid balance. Monitor serum potassium concentrations; potassium supplementation may be necessary. In addition, NSAIDs may mask fever, pain, swelling and other signs and symptoms of an infection; use NSAIDs with caution in patients receiving immunosuppressant dosages of corticosteroids. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection. [24574] [29890] [63923] Norepinephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Norfloxacin: (Moderate) Quinolones have been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, TdP has been reported during post-marketing surveillance of norfloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory. Norfloxacin should be used cautiously with other agents that may prolong the QT interval such as the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28225] [28432] [28457] [29818] Nortriptyline: (Moderate) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with TCAs include the beta-agonists. Beta agonists infrequently produce cardiovascular adverse effects, mostly with high doses or in the setting of beta-agonist-induced hypokalemia. [28225] [28318] [28416] [33925] [41231] Octreotide: (Moderate) Use octreotide with caution in combination with long-acting beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of torsade de pointes (TdP), the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. [28318] [28432] [29113] [30624] [32901] [33925] [41231] Ofatumumab: (Moderate) Concomitant use of ofatumumab with corticosteroids may increase the risk of immunosuppression. Monitor patients carefully for signs and symptoms of infection. Ofatumumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis, including immunosuppressant doses of corticosteroids. [65850] Ofloxacin: (Moderate) Ofloxacin should be used cautiously with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. Quinolones have been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, torsade de pointes has been reported during postmarketing surveillance of ofloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory. [28225] [28318] [28432] [28457] [29818] [30738] [32901] [33925] [41231] Olanzapine: (Moderate) Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Therefore, caution is advised when administering olanzapine with drugs having an established causal association with QT prolongation. Drugs with a possible risk for QT prolongation include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28318] [28785] [32732] [32734] [32745] [32746] [32901] [33925] [41231] Olanzapine; Fluoxetine: (Moderate) Avoid coadministration of oral budesonide and fluoxetine due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; fluoxetine a weak CYP3A4 inhibitor and the active metabolite norfluoxetine is a moderate CYP3A4 inhibitor. In the presence of a strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [29003] [29190] [34979] (Moderate) Coadministration of fluoxetine and long-acting beta-agonists may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation and TdP have been reported in patients treated with fluoxetine. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [32127] [41231] (Moderate) Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Therefore, caution is advised when administering olanzapine with drugs having an established causal association with QT prolongation. Drugs with a possible risk for QT prolongation include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28318] [28785] [32732] [32734] [32745] [32746] [32901] [33925] [41231] Olanzapine; Samidorphan: (Moderate) Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Therefore, caution is advised when administering olanzapine with drugs having an established causal association with QT prolongation. Drugs with a possible risk for QT prolongation include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28318] [28785] [32732] [32734] [32745] [32746] [32901] [33925] [41231] Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Olodaterol: (Major) Formoterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist for any reason, as overdose may result. Coadministration can result in overdosage. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with inhaled short-acting beta-2 agonists (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking formoterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if formoterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual. Use formoterol and drugs known to prolong the QTc interval together with extreme caution; this combination may increase the risk of cardiovascular effects and ventricular arrhythmias; this includes combination with other beta-agonists. [28318] [33925] [41231] [60746] Ombitasvir; Paritaprevir; Ritonavir: (Major) Avoid coadministration of oral budesonide and ritonavir due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [28315] [31824] [34979] [47165] Omeprazole: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. [34979] Omeprazole; Amoxicillin; Rifabutin: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. [34979] Omeprazole; Sodium Bicarbonate: (Major) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. [52910] [6865] (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. [34979] Ondansetron: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] (Moderate) Ondansetron has been associated with QT prolongation and post-marketing reports of torsade de pointes (TdP). Among 42 patients receiving a 4 mg IV bolus dose of ondansetron for postoperative nausea and vomiting, the mean maximal QTc interval prolongation was 20 +/- 13 msec at the third minute after administration (p < 0.0001). Risk for QT prolongation increases with increased dosage, and a 32 mg IV dose must no longer be used for prevention of chemotherapy induced emesis. If ondansetron and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with ondansetron include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28318] [31266] [32901] [33925] [41231] [44979] Oritavancin: (Minor) Budesonide is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of oral budesonide may be reduced if these drugs are administered concurrently. [56076] [57741] Osilodrostat: (Moderate) Monitor ECGs in patients receiving osilodrostat with long-acting beta-agonists. Osilodrostat is associated with dose-dependent QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [32901] [41231] [44979] [54633] [57710] [59321] [65098] Osimertinib: (Moderate) Use osimertinib and formoterol together with caution due to the risk of QT prolongation. The manufacturer of osimertinib recommends avoiding coadministration with other drugs that prolong the QT, if possible; if unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes. An interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists such as formoterol as compared to short-acting beta-agonists. [41231] [60297] Oxaliplatin: (Moderate) Monitor ECGs and electrolytes in patients receiving oxaliplatin concomitantly with long-acting beta-agonists; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Beta-agonists may also be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists (i.e., formoterol, arformoterol, indacaterol, olodaterol, salmeterol, fluticasone; vilanterol, umeclidinium; vilanterol) than with short-acting beta-agonists. [28467] [32901] [41231] [41958] [44979] [54633] [57710] Oxymetholone: (Moderate) Concomitant use of oxymetholone with corticosteroids or corticotropin, ACTH may cause increased edema. Manage edema with diuretic and/or digitalis therapy. [48342] Ozanimod: (Moderate) Coadministration of ozanimod with long-acting beta-agonists may increase the potential for additive QT prolongation. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with torsade de pointes in patients with bradycardia. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [32901] [41231] [44979] [54633] [57710] [65169] Palbociclib: (Moderate) Monitor for an increase in budesonide-related adverse reactions if coadministration with palbociclib is necessary, including excessive HPA-axis suppression; this may also be clinically significant for inhaled forms of budesonide. Palbociclib is a weak time-dependent inhibitor of CYP3A while budesonide is a CYP3A4 substrate. [56579] [58768] [64721] Paliperidone: (Moderate) Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturer, paliperidone should be avoided in combination with other drugs that may cause QT prolongation. Long-acting beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists compared to short-acting beta-agonists. If coadministration is necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential. [32901] [40936] [41231] [44979] Pancuronium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] Panobinostat: (Moderate) QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended. Obtain an electrocardiogram at baseline and periodically during treatment. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve. Drugs with a possible risk for QT prolongation and torsade de pointes that should be used cautiously and with close monitoring with panobinostat include beta-agonists. [28318] [33925] [41231] [58821] Pantoprazole: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. [34979] Pasireotide: (Moderate) Use caution when using pasireotide in combination with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28318] [32901] [33925] [41231] [52611] Pazopanib: (Moderate) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation that should be used cautiously with pazopanib include the long-acting beta-agonists (LABAs). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28467] [32901] [33156] [37098] [41231] [44979] [54633] [56564] [57710] (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and budesonide, a CYP3A4 substrate, may cause an increase in systemic concentrations of budesonide. Use caution when administering these drugs concomitantly. [37098] Pegaspargase: (Moderate) Concomitant use of pegaspargase with corticosteroids can result in additive hyperglycemia. Insulin therapy may be required in some cases. [55362] Penbutolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. [28618] [43675] [44979] [51834] [58220] Penicillamine: (Major) Agents such as immunosuppressives have adverse reactions similar to those of penicillamine. Concomitant use of penicillamine with these agents is contraindicated because of the increased risk of developing severe hematologic and renal toxicity. [5567] Pentamidine: (Moderate) Pentamidine has been associated with QT prolongation. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) should be used cautiously with pentamidine. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QTprolongation, usually at higher doses and/or when associated with hypokalemia. [23620] [23778] [28318] [28419] [28879] [32901] [33925] [41231] Perphenazine: (Minor) Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with perphenazine include the beta-agonists. Beta-agonists may cause adverse cardiovascular effects such as QT prolongation, usually at higher doses and/or when associated with hypokalemia. [28318] [28415] [32901] [33925] [41231] Perphenazine; Amitriptyline: (Moderate) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with TCAs include the beta-agonists. Beta agonists infrequently produce cardiovascular adverse effects, mostly with high doses or in the setting of beta-agonist-induced hypokalemia. [28225] [28318] [28416] [33925] [41231] (Minor) Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with perphenazine include the beta-agonists. Beta-agonists may cause adverse cardiovascular effects such as QT prolongation, usually at higher doses and/or when associated with hypokalemia. [28318] [28415] [32901] [33925] [41231] Phendimetrazine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Phenelzine: (Major) Beta-agonists should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors (MAOIs) due to their sympathomimetic effects. Weigh the risks of coadministration, and where possible, allow a washout period after discontinuation of the MAOI before instituring beta-agonist treatment or vice-versa. The cardiovascular effects of beta-agonists may be potentiated by concomitant use of MAOIs. Close observation for such effects is prudent, particularly if beta-agonists are administered within 2 weeks of stopping the MAOI. Monitor blood pressure and heart rate. [27957] [28309] [28467] [29656] [30438] [32901] [44979] [49951] [51022] [54633] [57710] Phenobarbital: (Moderate) Coadministration may result in decreased exposure to budesonide. Phenobarbital is a CYP3A4 inducer; budesonide is a CYP3A4 substrate. Monitor for decreased response to budesonide during concurrent use. Dose adjustments may be necessary. [28001] Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Coadministration may result in decreased exposure to budesonide. Phenobarbital is a CYP3A4 inducer; budesonide is a CYP3A4 substrate. Monitor for decreased response to budesonide during concurrent use. Dose adjustments may be necessary. [28001] Phentermine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [28309] Phentermine; Topiramate: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [28309] Phenylephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Phenytoin: (Moderate) Hydantoin anticonvulsants induce hepatic microsomal enzymes and may increase the metabolism of budesonide, leading to reduced efficacy. Depending on the individual clinical situation and the indication for the interacting medication, enzyme-induction interactions may not always produce reductions in treatment efficacy. [28001] [28771] Photosensitizing agents (topical): (Minor) Corticosteroids administered prior to or concomitantly with photosensitizing agents used in photodynamic therapy may decrease the efficacy of the treatment. [6625] Physostigmine: (Moderate) Concomitant use of anticholinesterase agents. such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy. [29779] [30015] [30028] [31123] [56146] [64165] Pimavanserin: (Moderate) Pimavanserin may cause QT prolongation and should be used with caution with beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. This risk may be more clinically significant with long-acting beta-agonists than with short-acting beta-agonists. Beta-agonists should be administered with caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated. [28318] [32901] [33925] [41231] [60748] Pimozide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP) and should not be used with other drugs that might prolong the QT interval. Because of the potential for TdP, use of beta-agonists with pimozide is contraindicated. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28318] [32901] [33925] [41231] [43463] (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact. [28225] [43463] Pindolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. [28618] [43675] [44979] [51834] [58220] Pioglitazone; Glimepiride: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Pioglitazone; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] Pitolisant: (Moderate) Coadministration of pitolisant and long-acting beta-agonists may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [32901] [41231] [44979] [64562] Ponesimod: (Moderate) In general, do not initiate ponesimod in patients taking lon-acting beta-agonists due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [32901] [41231] [44979] [54633] [57710] [66527] (Moderate) Monitor for signs and symptoms of infection. Additive immune suppression may result from concomitant use of ponesimod and high-dose corticosteroid therapy which may extend the duration or severity of immune suppression. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. [66527] Posaconazole: (Moderate) Avoid coadministration of oral budesonide and posaconazole due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of budesonide. Further, both budesonide and posaconazole are substrates of the drug efflux protein, P-glycoprotein (P-gp), which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and budesonide, ultimately resulting in an increased risk of adverse events. [32723] [34354] [34979] (Moderate) Posaconazole has been associated with QT prolongation and in rare cases, torsade de pointes. When possible, avoid concurrent administration of posaconazole with other drugs that may also prolong the QT interval, such as the long-acting beta-agonists (LABAs). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28467] [32723] [32901] [33156] [41231] [44979] [54633] [56564] [57710] [59321] Potassium Chloride: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Potassium Phosphate; Sodium Phosphate: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia. [57713] [57714] [57715] Potassium: (Moderate) Corticotropin can cause alterations in serum potassium levels. The use of potassium salts or supplements would be expected to alter the effects of corticotropin on serum potassium levels. Also, there have been reports of generalized tonic-clonic seizures and/or loss of consciousness associated with use of bowel preparation products in patients with no prior history of seizure disorder. Therefore, magnesium sulfate; potassium sulfate; sodium sulfate should be administered with caution during concurrent use of medications that lower the seizure threshold such as systemic corticosteroids. [30015] [41573] Potassium-sparing diuretics: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics. [26417] [29016] [30011] Pramlintide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Moderate) Corticosteroids blunt the adrenal secretion of endogenous DHEA and DHEAS, resulting in reduced DHEA and DHEAS serum concentrations. [2460] Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Moderate) Corticosteroids blunt the adrenal secretion of endogenous DHEA and DHEAS, resulting in reduced DHEA and DHEAS serum concentrations. [2460] Prilocaine; Epinephrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Primaquine: (Moderate) Exercise caution when administering primaquine in combination with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. Primaquine is associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28318] [33925] [41231] [41984] Primidone: (Moderate) Coadministration may result in decreased exposure to budesonide. Primidone is a CYP3A4 inducer; budesonide is a CYP3A4 substrate. Monitor for decreased response to budesonide during concurrent use. [28001] Procainamide: (Moderate) Beta-agonists should be used cautiously with procainamide. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated. [28250] [28318] [32901] [33925] [41231] Procarbazine: (Major) Procarbazine has MAOI activity and the cardiovascular effects of beta-2 agonists may be potentiated by concomitant use of MAOIs. Although no data are available, procarbazine may interact similarly. Close observation for such effects is prudent, particularly if beta-agonists are administered within two weeks of stopping the MAOI. [28318] [28625] [32901] [33925] [41231] [44979] Prochlorperazine: (Minor) Phenothiazines like prochlorperazine have been associated with a risk of QT prolongation. This risk is generally higher at elevated drugs concentrations. Agents that prolong the QT interval and that should be used cautiously with prochlorperazine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28225] [28318] [28415] [32901] [33925] [41231] Promethazine: (Moderate) Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Use cautiously with promethazine, which has been reported to cause QT prolongation. [28225] [29318] [32901] [33925] [41231] [55578] Promethazine; Dextromethorphan: (Moderate) Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Use cautiously with promethazine, which has been reported to cause QT prolongation. [28225] [29318] [32901] [33925] [41231] [55578] Promethazine; Phenylephrine: (Moderate) Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Use cautiously with promethazine, which has been reported to cause QT prolongation. [28225] [29318] [32901] [33925] [41231] [55578] (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Propafenone: (Moderate) Propafenone is a Class IC antiarrhythmic which increases the QT interval, but largely due to prolongation of the QRS interval.. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with propafenone include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28287] [28318] [32901] [33925] [41231] [44979] Propranolol: (Moderate) Patients receiving corticosteroids during propranolol therapy may be at increased risk of hypoglycemia due to the loss of counter-regulatory cortisol response. This effect may be more pronounced in infants and young children. If concurrent use is necessary, carefully monitor vital signs and blood glucose concentrations as clinically indicated. [56853] (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. [28618] [43675] [44979] [51834] [58220] Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] (Moderate) Patients receiving corticosteroids during propranolol therapy may be at increased risk of hypoglycemia due to the loss of counter-regulatory cortisol response. This effect may be more pronounced in infants and young children. If concurrent use is necessary, carefully monitor vital signs and blood glucose concentrations as clinically indicated. [56853] (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. [28618] [43675] [44979] [51834] [58220] Proton pump inhibitors: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. [34979] Protriptyline: (Moderate) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with TCAs include the beta-agonists. Beta agonists infrequently produce cardiovascular adverse effects, mostly with high doses or in the setting of beta-agonist-induced hypokalemia. [28225] [28318] [28416] [33925] [41231] Pseudoephedrine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Pseudoephedrine; Triprolidine: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Purine analogs: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects. [5504] Pyridostigmine: (Moderate) Concomitant use of anticholinesterase agents. such as pyridostigmine, and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating corticosteroid therapy. [29779] [30015] [30028] [31123] [34253] [56146] [64002] [64165] Quetiapine: (Moderate) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with quetiapine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28318] [29118] [32901] [33068] [33072] [33074] [33925] [41231] (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids). [26417] [29118] Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Quinidine: (Moderate) Beta-agonists should be used cautiously with quinidine. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated. [28318] [32901] [33925] [41231] [47357] Quinine: (Moderate) Quinine has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Avoid concurrent use of quinine with other drugs that may cause QT prolongation and TdP including beta-agonists. [28318] [31403] [33925] [41231] Quinolones: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon. [28423] [28424] [28764] [29818] [30738] [62028] [65562] Rabeprazole: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. [34979] Racepinephrine: (Major) Racepinephrine is a sympathomimetic drug with agonist actions at both the alpha and beta receptors. Patients using prescription beta-agonists for the treatment of asthma should generally avoid the concurrent use of racepinephrine inhalation since additive cardiovascular and nervous system adverse effects are possible, some which may be undesirable. [54280] [54298] Ranitidine: (Moderate) Monitor for altered response to budesonide in patients receiving H2-blockers with enteric-coated or extended-release formulations of oral budesonide. Enteric-coated budesonide granules (Entocort EC) dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause these products to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. When cimetidine (1 gram/day PO) is administered with an uncoated formulation of oral budesonide, a slight increase in absorption and peak plasma concentrations occur, resulting in significant cortisol suppression. [34979] [52910] Ranolazine: (Moderate) Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. The mean increase in QTc is about 6 milliseconds, measured at the Tmax of the maximum dosage (1000 mg PO twice daily). However, in 5% of the population studied, increases in the QTc of at least 15 milliseconds have been reported. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with ranolazine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28318] [31938] [32901] [33925] [41231] [44979] Rapacuronium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] Rasagiline: (Moderate) The concomitant use of rasagiline and sympathomimetic agents was not allowed in clinical studies; therefore, caution is advised during concurrent use of rasagiline and respiratory adrenergic agents (e.g., the beta-agonists). Although sympathomimetic agents are contraindicated for use with traditional non-selective monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with rasagiline because of the selective monoamine oxidase-B (MAO-B) inhibition of rasagiline at manufacturer recommended doses. However, the cardiovascular effects of beta-2 agonists may be potentiated by concomitant use of MAOIs. At least one case of hypertension occurred in a patient with previous episodes of high blood pressure who was receiving albuterol and selegiline, a selective MAOI related to rasagiline, concurrently. Close observation for such effects is prudent, particularly if beta-2 agonists are administered during or within 2 weeks of use of an MAOI. [28309] [28467] [28532] [32223] [32901] [33631] Regular Insulin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Relugolix: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [32901] [41231] [44979] [54633] [57710] [66183] Relugolix; Estradiol; Norethindrone acetate: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [32901] [41231] [44979] [54633] [57710] [66183] Repaglinide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Ribociclib: (Moderate) Avoid coadministration of oral budesonide and ribociclib due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; ribociclib is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [34979] [61816] (Moderate) Due to a possible risk for QT prolongation, ribociclib and long-acting beta-agonists should be used together cautiously. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval like ribociclib. This risk may be more clinically significant with long-acting beta-agonists such as formoterol as compared to short-acting beta-agonists. [28467] [32901] [41231] [44979] [54633] [57710] [61816] Ribociclib; Letrozole: (Moderate) Avoid coadministration of oral budesonide and ribociclib due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; ribociclib is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [34979] [61816] (Moderate) Due to a possible risk for QT prolongation, ribociclib and long-acting beta-agonists should be used together cautiously. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval like ribociclib. This risk may be more clinically significant with long-acting beta-agonists such as formoterol as compared to short-acting beta-agonists. [28467] [32901] [41231] [44979] [54633] [57710] [61816] Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with long-acting beta-agonists as concurrent use may increase the risk of QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists, such as arformoterol, as compared to short-acting beta-agonists. [28318] [32901] [33925] [41231] [44376] Risperidone: (Moderate) Use risperidone and long-acting beta-agonists together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28225] [28318] [28414] [28416] [32901] [33925] [41231] [44979] Ritodrine: (Major) Ritodrine has caused maternal pulmonary edema, which appears more often in patients treated concomitantly with corticosteroids. Patients so treated should be closely monitored in the hospital. [7110] [7111] [7572] Ritonavir: (Major) Avoid coadministration of oral budesonide and ritonavir due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [28315] [31824] [34979] [47165] Rituximab: (Moderate) Rituximab and corticosteroids are commonly used together; however, monitor the patient for immunosuppression and signs and symptoms of infection during combined chronic therapy. [30943] [49773] [56233] Rituximab; Hyaluronidase: (Moderate) Rituximab and corticosteroids are commonly used together; however, monitor the patient for immunosuppression and signs and symptoms of infection during combined chronic therapy. [30943] [49773] [56233] Rocuronium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] Romidepsin: (Moderate) Romidepsin has been reported to prolong the QT interval. If romidepsin must be coadministered with another drug that prolongs the QT interval, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of serum electrolytes and the ECG at baseline and periodically during treatment. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with romidepsin include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28318] [32901] [33925] [37292] [41231] Salicylates: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Salmeterol: (Major) Formoterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist for any reason, as overdose may result. Coadministration can result in overdosage. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with inhaled short-acting beta-2 agonists (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking formoterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if formoterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual. Use formoterol and drugs known to prolong the QTc interval together with extreme caution; this combination may increase the risk of cardiovascular effects and ventricular arrhythmias; this includes combination with other beta-agonists. [28318] [33925] [41231] [60746] Salsalate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Saquinavir: (Major) Avoid coadministration of saquinavir and orally administered budesonide and use inhaled formulations with caution. Saquinavir may inhibit CYP3A4 metabolism of budesonide, resulting in increased plasma budesonide concentrations and reduced serum cortisol concentrations. Theoretically, inhibition of CYP3A4 may be clinically significant for inhaled forms of budesonide, including budesonide nasal spray. There have been reports of clinically significant drug interactions in patients receiving ritonavir with other corticosteroids, resulting in systemic corticosteroid effects including Cushing syndrome and adrenal suppression. Similar results are expected with saquinavir. Consider using an alternative treatment to budesonide, such as a corticosteroid not metabolized by CYP3A4 (i.e., beclomethasone or prednisolone). If corticosteroid therapy is to be discontinued, consider tapering the dose over a period of time to decrease the potential for withdrawal. [28995] [34979] [46711] (Moderate) Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as torsades de pointes (TdP). Avoid administering saquinavir boosted with ritonavir with other drugs that may prolong the QT interval, such as beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. If no acceptable alternative therapy is available, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations. The coadministration of salmeterol with CYP3A4 inhibitors, such as the anti-retroviral protease inhibitors, can result in elevated salmeterol plasma concentrations. Avoid coadministration of salmeterol with the anti-retroviral protease inhibitors. [28318] [28995] [32901] [33156] [33925] [41231] Sargramostim, GM-CSF: (Major) Avoid the concomitant use of sargramostim and systemic corticosteroid agents due to the risk of additive myeloproliferative effects. If coadministration of these drugs is required, frequently monitor patients for clinical and laboratory signs of excess myeloproliferative effects (e.g., leukocytosis). Sargramostim is a recombinant human granulocyte-macrophage colony-stimulating factor that works by promoting proliferation and differentiation of hematopoietic progenitor cells. [61087] SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving corticosteroids in greater than physiologic doses may have a diminished response to the SARS-CoV-2 virus vaccine. Counsel patients receiving corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine. [65107] [66080] Selpercatinib: (Moderate) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with long-acting beta-agonists is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [32901] [41231] [44979] [57710] [65387] Semaglutide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Sertraline: (Moderate) Use caution and monitor patients for QT prolongation when administering long-acting beta-agonists with sertraline. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. Sertraline's FDA-approved labeling recommends avoiding concomitant use with drugs known to prolong the QTc interval; however, the risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. Its effect on QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease (e.g., recent myocardial infarction, unstable angina, chronic heart failure). [28343] [32901] [41231] [64391] [64392] [64394] [64395] [64396] Sevoflurane: (Moderate) Sevoflurane, like other halogenated anesthetics, can prolong the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously with halogenated anesthetics include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. The action of beta-agonists on the cardiovascular system may be potentiated by a halogenated anesthetic. [28318] [28457] [28458] [32901] [33925] [41231] SGLT2 Inhibitors: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Simeprevir: (Minor) Simeprevir, a P-glycoprotein (P-gp) inhibitor and a mild intestinal CYP3A4 inhibitor, may increase the side effects of budesonide, which is a CYP3A4 and P-gp substrate. Monitor patients for adverse effects of budesonide, such as excessive HPA-axis suppresion. [34354] [56076] [56471] Siponimod: (Moderate) In general, do not initiate treatment with siponimod in patients receiving long-acting beta-agonists due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists compared to short-acting beta-agonists. [32901] [41231] [44979] [64031] Sodium Benzoate; Sodium Phenylacetate: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia. [8083] Sodium Bicarbonate: (Major) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. [52910] [6865] Sodium Chloride: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Sodium Phenylbutyrate: (Moderate) The concurrent use of corticosteroids with sodium phenylbutyrate may increase plasma ammonia levels (hyperammonemia) by causing the breakdown of body protein. Patients with urea cycle disorders being treated with sodium phenylbutyrate usually should not receive regular treatment with corticosteroids. [57685] Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia. [57713] [57714] [57715] Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Plasma concentrations of budesonide, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with voxilaprevir, a P-gp inhibitor. Monitor patients for increased side effects if these drugs are administered concurrently. [34354] [62131] Solifenacin: (Moderate) Solifenacin has been associated dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with post-marketing use, although causality was not determined. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. The action of beta-agonists on the cardiovascular system may be potentiated. [28318] [30515] [32901] [33925] [41231] Somatropin, rh-GH: (Moderate) Corticosteroids can retard bone growth and therefore, can inhibit the growth-promoting effects of somatropin. If corticosteroid therapy is required, the corticosteroid dose should be carefully adjusted. [6807] Sorafenib: (Moderate) Use caution if coadministration of sorafenib with long-acting beta-agonists is necessary due to the risk of additive QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. Sorafenib is also associated with QTc prolongation. [28318] [31832] [32901] [33156] [33925] [41231] Sotalol: (Moderate) Use caution when administering sotalol together with beta-agonists. The effects of beta-agonists can be reduced with concurrent use of sotalol, which is a non-selective beta-blocker. Monitor for altered therapeutic response to the beta-agonist. In addition, sotalol is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28234] [28318] [33925] [41231] Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] St. John's Wort, Hypericum perforatum: (Moderate) Theoretically, induction of the cytochrome P450 3A4 isoenzyme by St. John's Wort may result in a lowering of budesonide plasma concentrations, reducing the clinical effect. [28211] Succinylcholine: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] Sulfonylureas: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Sunitinib: (Moderate) Monitor patients for QT prolongation if coadministration of long-acting beta-agonists with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [31970] [32901] [41231] Tacrolimus: (Moderate) Consider ECG and electrolyte monitoring periodically during treatment if tacrolimus is administered with a long-acting beta-agonist. Tacrolimus may prolong the QT interval and cause torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [27353] [27354] [28225] [28318] [32901] [33925] [41231] Tamoxifen: (Moderate) Caution is advised with the concomitant use of tamoxifen and long-acting beta-agonists due to an increased risk of QT prolongation. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists compared to short-acting beta-agonists. [28467] [32901] [41231] [44979] [54633] [57710] [61870] [61871] [61872] Telaprevir: (Major) Concurrent administration of budesonide and telaprevir is not recommended unless the benefits outweigh the risks. If they are coadministered, close monitoring for corticosteroid-related adverse events is advised. If budesonide dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of budesonide. Budesonide is metabolized by the hepatic isoenzyme CYP3A4 and the drug efflux transporter P-glycoprotein (P-gp); telaprevir inhibits both the isoenzyme and the drug efflux pump. Coadministration may result in elevated budesonide plasma concentrations. [44393] [6865] Telavancin: (Moderate) Due to increased risk of QT interval prolongation and torsade de pointes (TdP), use caution if telavancin is administered with a beta-agonist. Telavancin has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28318] [32901] [33925] [36615] [41231] Telbivudine: (Moderate) The risk of myopathy may be increased if corticosteroids are coadministered with telbivudine. Monitor patients for any signs or symptoms of unexplained muscle pain, tenderness, or weakness, particularly during periods of upward dosage titration. [9671] Telithromycin: (Moderate) Use caution if telithromycin is administered with a long-acting beta-agonist as concurrent use may increase the risk of QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28156] [28318] [32901] [33156] [33925] [41231] (Minor) Concentrations of budesonide may be increased with concomitant use of telithromycin. Budesonide is a CYP3A4 and P-glycoprotein (PGP) substrate and telithromycin is a strong CYP3A4 inhibitor and potential PGP inhibitor. Patients should be monitored for increased side effects. [11210] [28156] [34329] [6856] Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Temsirolimus: (Moderate) Monitor for an increase in budesonide-related adverse reactions if coadministration with temsirolimus is necessary. Budesonide is a P-glycoprotein (P-gp) substrate and temsirolimus is a P-gp inhibitor. Concomitant use is likely to lead to increased concentrations of budesonide. [34354] [50586] Testosterone: (Moderate) Coadministration of corticosteroids and testosterone may increase the risk of edema, especially in patients with underlying cardiac or hepatic disease. Corticosteroids with greater mineralocorticoid activity, such as fludrocortisone, may be more likely to cause edema. Administer these drugs in combination with caution. [33698] Tetrabenazine: (Moderate) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval because the action of beta-agonists on the cardiovascular system may be potentiated. [28318] [32901] [33925] [34389] [41231] Tezacaftor; Ivacaftor: (Moderate) Use caution when administering ivacaftor and budesonide concurrently. Ivacaftor is an inhibitor of CYP3A and P-glycoprotein (Pgp). Co-administration of ivacaftor with CYP3A and Pgp substrates, such as budesonide, can increase budesonide exposure leading to increased or prolonged therapeutic effects and adverse events. [34354] [34979] [48524] Theophylline, Aminophylline: (Moderate) Beta-agonists are commonly used in conjunction with aminophylline or theophylline therapy. Concomitant use can cause additive CNS stimulation; some patients may experience tremor or nervousness with combined use. More serious effects are rare, but may result in additive cardiovascular effects such as increased blood pressure and heart rate. Methylxanthine derivatives, ((e.g., theophylline and aminophylline) may rarely aggravate the hypokalemic effect seen with beta-agonists. Consider checking potassium levels if clinically indicated. [28318] [32901] [44026] [44979] [50760] (Moderate) Beta-agonists are commonly used in conjunction with aminophylline or theophylline therapy. Concomitant use can cause additive CNS stimulation; some patients may experience tremor or nervousness with combined use. More serious effects are rare, but may result in additive cardiovascular effects such as increased blood pressure and heart rate. Methylxanthine derivatives, (e.g., theophylline, aminophylline) may rarely aggravate the hypokalemic effect seen with beta-agonists. Consider checking potassium levels if clinically indicated. [28318] [32901] [44026] [44979] [50760] Thiazide diuretics: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated. [28532] [33925] [43675] [44979] Thiazolidinediones: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Thioridazine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Because of the potential for QR prolongation, use of beta-agonists with thioridazine is contraindicated. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28225] [28293] [28318] [28415] [28416] [28417] [32901] [33925] [41231] [43069] Thyroid hormones: (Moderate) Based on the cardiovascular stimulatory effects of beta-agonists and other sympathomimetics, concomitant use with thyroid hormones might enhance the effects on the cardiovascular system. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease. [43942] [43952] (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents. [29779] [30015] [43942] Timolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. [28618] [43675] [44979] [51834] [58220] Tiotropium; Olodaterol: (Major) Formoterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist for any reason, as overdose may result. Coadministration can result in overdosage. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with inhaled short-acting beta-2 agonists (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking formoterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if formoterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual. Use formoterol and drugs known to prolong the QTc interval together with extreme caution; this combination may increase the risk of cardiovascular effects and ventricular arrhythmias; this includes combination with other beta-agonists. [28318] [33925] [41231] [60746] Tobramycin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Tolazamide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Tolbutamide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Tolterodine: (Moderate) Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. This should be taken into consideration when prescribing tolterodine to patients taking other drugs that are associated with QT prolongation. Drugs with a possible risk for QT prolongation that should be used cautiously with tolterodine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28318] [31112] [32901] [33925] [41231] Toremifene: (Moderate) Use toremifene and long-acting beta agonists together with caution due to the risk of QT prolongation. The manufacturer of toremifene recommends avoiding toremifene with other drugs that prolong the QT, if possible. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28318] [28822] [32901] [33925] [41231] Torsemide: (Moderate) Loop diuretics may potentiate hypokalemia and ECG changes seen with beta agonists. Hypokalemia due to beta agonists appears to be dose related and is more likely with high dose therapy. Caution is advised when loop diuretics are coadministered with high doses of beta agonists; potassium levels may need to be monitored. [33925] [43675] [44979] Tositumomab: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Trandolapril; Verapamil: (Moderate) Avoid coadministration of oral budesonide and verapamil due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; verapamil a weak CYP3A4 inhibitor and the active metabolite norverapamil is a moderate CYP3A4 inhibitor. In the presence of a strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [31824] [34979] Tranexamic Acid: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Tranylcypromine: (Major) Beta-agonists should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors (MAOIs) due to their sympathomimetic effects. Weigh the risks of coadministration, and where possible, allow a washout period after discontinuation of the MAOI before instituring beta-agonist treatment or vice-versa. The cardiovascular effects of beta-agonists may be potentiated by concomitant use of MAOIs. Close observation for such effects is prudent, particularly if beta-agonists are administered within 2 weeks of stopping the MAOI. Monitor blood pressure and heart rate. [27957] [28309] [28467] [29656] [30438] [32901] [44979] [49951] [51022] [54633] [57710] Trazodone: (Moderate) Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are post-marketing reports of torsade de pointes (TdP). Therefore, the manufacturer recommends avoiding trazodone in patients receiving other drugs that increase the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Coadministration with other drugs known to prolong the QT interval may potentiate the action of beta-agonists on the cardiovascular system. [28318] [32901] [33925] [38831] [41231] Tretinoin, ATRA: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Triclabendazole: (Moderate) Monitor ECGs in patients receiving triclabendazole with long-acting beta-agonists. Transient prolongation of the mean QTc interval was noted on the ECG recordings in dogs administered triclabendazole. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [32901] [41231] [44979] [54633] [57710] [63962] Tricyclic antidepressants: (Moderate) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with TCAs include the beta-agonists. Beta agonists infrequently produce cardiovascular adverse effects, mostly with high doses or in the setting of beta-agonist-induced hypokalemia. [28225] [28318] [28416] [33925] [41231] Trifluoperazine: (Minor) Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. Drugs with a possible risk for QT prolongation that should be used cautiously with trifluoperazine include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28225] [28318] [28415] [32901] [33925] [41231] Trimipramine: (Moderate) Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with TCAs include the beta-agonists. Beta agonists infrequently produce cardiovascular adverse effects, mostly with high doses or in the setting of beta-agonist-induced hypokalemia. [28225] [28318] [28416] [33925] [41231] Triptorelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving long-acting beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [32901] [41231] [44979] [45411] [54633] [57710] Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy. [43298] [43299] Tubocurarine: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] Tucatinib: (Moderate) Avoid coadministration of oral budesonide and tucatinib due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; tucatinib is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [34979] [65295] Umeclidinium; Vilanterol: (Major) Formoterol should not be used in conjunction with other medications containing a long-acting beta-2 agonist for any reason, as overdose may result. Coadministration can result in overdosage. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Acute symptoms should be treated with inhaled short-acting beta-2 agonists (SABA) such as albuterol. SABAs should not be used on a regular basis (e.g., 4 times a day) while taking formoterol. Increasing SABA use is a sign of deteriorating disease for which prompt medical attention is required. Prompt re-evaluation of the patient and their COPD treatment regimen should occur if formoterol no longer controls symptoms of bronchoconstriction, the patient's SABA rescue becomes less effective, or the patient requires more SABA rescue doses than usual. Use formoterol and drugs known to prolong the QTc interval together with extreme caution; this combination may increase the risk of cardiovascular effects and ventricular arrhythmias; this includes combination with other beta-agonists. [28318] [33925] [41231] [60746] Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Vancomycin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Vandetanib: (Moderate) If concomitant use of vandetanib with long-acting beta-agonists is necessary, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. [32901] [41231] [43901] Vardenafil: (Moderate) Coadministration of vardenafil and long-acting beta-agonists may increase the risk of QT prolongation. Vardenafil has been associated with QT prolongation. Therapeutic and supratherapeutic doses of vardenafil can produce an increase in QTc interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28216] [59321] Vecuronium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] Vemurafenib: (Moderate) Concomitant use of vemurafenib and budesonide may result in altered concentrations of budesonide and increased concentrations vemurafenib. Vemurafenib is a substrate/inducer of CYP3A4 and a substrate/inhibitor of P-glycoprotein (PGP). Budesonide is a substrate of CYP3A4 and a substrate/inhibitor of PGP. Use caution and monitor patients for toxicity and efficacy. [11210] [45335] [6865] (Moderate) Vemurafenib has been associated with QT prolongation. If vemurafenib and another drug that is associated with a possible risk for QT prolongation and torsade de pointes (TdP) must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation that should be used cautiously with vemurafenib include the long-acting beta-agonists (LABAs). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28467] [32901] [33156] [41231] [44979] [45335] [54633] [56564] [57710] Venlafaxine: (Moderate) Venlafaxine administration is associated with a possible risk of QT prolongation; torsade de pointes (TdP) has been reported with post-marketing use. Drugs with a possible risk for QT prolongation that should be used cautiously with venlafaxine include the beat-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28318] [32901] [33715] [33925] [41231] Verapamil: (Moderate) Avoid coadministration of oral budesonide and verapamil due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; verapamil a weak CYP3A4 inhibitor and the active metabolite norverapamil is a moderate CYP3A4 inhibitor. In the presence of a strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [31824] [34979] Vigabatrin: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks. [36250] Vincristine Liposomal: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia. [57713] [57714] [57715] Voclosporin: (Moderate) Concomitant use of voclosporin and long-acting beta-agonists may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists. [28467] [32901] [41231] [44979] [66336] Voriconazole: (Moderate) Monitor for potential adrenal dysfunction with concomitant use of voriconazole and budesonide. In patients taking corticosteroids, voriconazole-associated CYP3A4 inhibition of their metabolism may lead to corticosteroid excess and adrenal suppression. Corticosteroid exposure is likely to be increased. Concomitant oral administration of another strong CYP3A4 inhibitor increased oral budesonide systemic exposure by 8-fold. Voriconazole is a strong CYP3A4 inhibitor, and budesonide is a CYP3A4 substrate. [28158] [34447] [34979] (Moderate) Voriconazole has been associated with QT prolongation and rare cases of torsade de pointes. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with voriconazole include the long-acting beta-agonists (LABAs). Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Pharmacokinetic interactions may occur with some LABAs. Voriconazole and its major metabolite, voriconazole N-oxide, inhibit CYP3A4. Salmeterol, a CYP3A4 substrate, may have its concentrations increased by voriconazole, which may increase the risk for side effects like tremor, nervousness, headache and increased risk for fast, irregular heart rate. [28158] [28467] [32901] [33156] [41231] [44979] [54633] [56564] [57710] [59321] Vorinostat: (Moderate) Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. Beta-agonists should be administered with extreme caution to patients being treated with drugs known to prolong the QT interval, such as vorinostat, because the action of beta-agonists on the cardiovascular system may be potentiated. [28318] [32789] [32901] [33925] [41231] [44979] (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary. [26417] [32789] Warfarin: (Moderate) Monitor the INR if warfarin is administered with corticosteroids. The effect of corticosteroids on warfarin is variable. There are reports of enhanced as well as diminished effects of anticoagulants when given concurrently with corticosteroids; however, limited published data exist, and the mechanism of the interaction is not well described. High-dose corticosteroids appear to pose a greater risk for increased anticoagulant effect. In addition, corticosteroids have been associated with a risk of peptic ulcer and gastrointestinal bleeding. [28549] [29779] Zafirlukast: (Minor) Zafirlukast inhibits the CYP3A4 isoenzymes and should be used cautiously in patients stabilized on drugs metabolized by CYP3A4, such as corticosteroids. [4718] [4948] Ziprasidone: (Moderate) Ziprasidone should be administered with caution to patients receiving other agents that may prolong the QT interval; ziprasidone has been associated with a risk for QT prolongation. The long-acting beta-agonists may be associated with adverse cardiovascular effects including tachycardia and QT interval prolongation, usually at higher doses and/or when associated with hypokalemia. [28233] [32901] [41231] [44979] [57710] [59321] Zonisamide: (Minor) Zonisamide is a weak inhibitor of P-glycoprotein (P-gp), and budesonide is a substrate of P-gp. There is theoretical potential for zonisamide to affect the pharmacokinetics of drugs that are P-gp substrates. Use caution when starting or stopping zonisamide or changing the zonisamide dosage in patients also receiving drugs which are P-gp substrates. [28843] [34354]
    Revision Date: 10/14/2021, 02:26:00 AM

    References

    2460 - Robinson B, Cutolo M. Should dehydroepiandrosterone replacement therapy be provided with chronic glucocorticoids? Rheumatology (Oxford) 1999;38:488-495.3085 - Cohn JN, Kowey PR, Whelton PK, Prisant LM. New guidelines for potassium replacement in clinical practice: a contemporary review by the National Council on Potassium in Clinical Practice. Arch Intern Med 2000;160:2429-2436.4661 - Hexalen® (alretamine) package insert. Bloomington, MN: MGI Pharma, Inc.; 2001 Jan.4710 - Imuran (azathioprine) package insert. East Brunswisk, NJ: Casper Pharma, LLC; 2018 Dec.4718 - Hansten PD, Horn JR. Cytochrome P450 Enzymes and Drug Interactions, Table of Cytochrome P450 Substrates, Inhibitors, Inducers and P-glycoprotein, with Footnotes. In: The Top 100 Drug Interactions - A guide to Patient Management. 2008 Edition. Freeland, WA: H&H Publications; 2008:142-157.4744 - Premarin (conjugated estrogens, equine) package insert. Philadelphia, PA: Wyeth Pharmaceuticals Inc.; 2003 Jul.4746 - Celestone (betamethasone) package insert. Kenilworth, NJ: Schering Corporation; 1999 Oct.4757 - Leukeran (chlorambucil) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2011 Oct.4948 - Accolate (zafirlukast) package insert. Wilmington, DE: AstraZeneca; 2015 Dec.4951 - CredibleMeds. Drugs to avoid in congenital long QT. Available on the World Wide Web at http://www.crediblemeds.org.4953 - Vascor (bepridil) package insert. Raritan, NJ: Ortho-McNeil Pharmaceutical, Inc.; 2000 Mar.4968 - Halfan (halofantrine) package insert. Philadelphia, PA: Smith Kline Beecham Pharmaceuticals; 2001 Oct.5023 - Methazolamide tablet package insert. Basking Ridge, NJ: Micro Labs USA, Inc.; 2019 Nov.5038 - Foradil Aerolizer (formoterol fumarate inhalation powder capsules) package insert. Novartis Pharma AG: 2012 Nov.5079 - Orlaam® (levomethadyl) package insert. Columbus, OH: Roxane Laboratories,Inc.; 2000 Jan. NOTE: In August 2003, levomethadyl was voluntarily removed from the US market due to cited reasons such as decreasing sales, safety concerns and the availability of other options for the management of opiate dependance.5081 - Deamer RL, Wilson DR, Clark DS, et al. Torsades de pointes associated with high dose levomethadyl acetate (ORLAAM). J Addict Dis 2001;20:7-14.5146 - Hansten PD, Horn JR. Drug Interactions with Drugs that Increase QTc Intervals. In: The Top 100 Drug Interactions - A Guide to Patient Management. 2007 Edition. Freeland, WA: H&H Publications; 2007:144-8.5197 - Serevent Diskus (salmeterol xinafoate inhalation powder) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2019 July.5275 - Yagiela JA. Adverse drug interactions in dental practice: interactions associated with vasoconstrictors. Part V of a series. J Am Dent Assoc 1999;130:701-9. Review.5283 - Accutane (isotretinoin) package insert. Nutley, NJ: Roche Laboratories Inc.; 2008 Nov.5462 - Crixivan (indinavir) package insert. Whitehouse Station, NJ: Merck & Co., Inc.; 2016 Sept.5468 - Inapsine (Droperidol) Injection package insert. Lake Forest, IL: Akorn, Inc.; 2011 Oct.5504 - Purinethol® (Mercaptopurine) package insert. Sellersville, PA: Gate Pharmaceuticals, div of Teva Pharmaceuticals USA; 2003 Aug.5567 - Cuprimine (penicillamine) package insert. Lawrenceville, NJ: Atom Pharma; 2010 Mar.5618 - Touze JE, Heno P, Fourcade L, et al. Effect of antimalarial drugs on ventricular repolarization. Am J Trop Med Hyg 2000;67:54-60.5946 - BiCNU (carmustine) injection package insert. Edison, NJ: Heritage Pharmaceuticals Inc.; 2013 Apr.6192 - Cardizem LA (diltiazem) package insert. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC; 2016 Nov.6303 - Thymoglobulin (anti-thymocyte [antithymocyte] globulin-rabbit) package insert. Fremont, CA: SangStat Medical Corporation; 2002 Apr.6395 - US Food and Drug Administration (FDA). Guidance for Industry. Noncontraceptive Estrogen Drug Products for the Treatment of Vasomotor Symptoms and Vulvar and Vaginal Atrophy Symptoms - Recommended Prescribing Information for Health Care Providers and Patient Labeling. Document No. 6932. Division of Dockets Management (HFA-305), Food and Drug Administration, Rockville, MD; Issued November 2005. Retrieved Sept 2016. Available at: http://www.fda.gov/cder/guidance/guidance.htm.6524 - Deltasone (prednisone) tablet package insert. Petaluma, CA: Oculus Innovative Sciences, Inc.; 2017 Nov.6625 - Photofrin (porfimer) package insert. Birmingham, AL: Axcan Scandipharm Inc.; 2003 Aug.6702 - Panhematin® (hemin for injection) package insert. Deerfield, IL: Ovation Pharmaceuticals, Inc.; 2006 Aug.6807 - Humatrope (somatropin) package insert. Indianapolis, IN: Eli Lilly and Company; 2019 Oct.6856 - Sato J, Nakata H, Owada E, et al. Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects. Eur J Clin Pharmacol 1993;44:295-8.6865 - Entocort EC (budesonide) capsules package insert. Sodertalje, Sweden: AstraZeneca Pharmaceuticals; 2005 Apr.6968 - Raab W, Gmeiner B. Interactions between econazole, a broad-spectrum antimicrobic substance, and topically active glucocorticoids. Dermatologica 1976;153(1):14-22.7110 - Philipsen T, Eriksen PS, Lynggard F. Pulmonary edema following ritodrine-saline infusion in premature labor. Obstet Gynecol 1981;58(3):304-8.7111 - Semchyshyn S, Zuspan FP, O'Shaughnessy R. Pulmonary edema associated with the use of hydrocortisone and a tocolytic agent for the management of premature labor. J Reprod Med 1983;28(1):47-52.7557 - Clolar (clofarabine) package insert. Cambridge, MA: Genzyme Corporation; 2010 Dec.7572 - Yutopar® (ritodrine) package insert. Westborough, MA; Astra USA Inc.: 1998.7592 - Mier JW, Vachino G, Klempner MS, et al. Inhibition of interleukin-2-induced tumor necrosis factor release by dexamethasone: Prevention of an acquired neutrophil chemotaxis defect and differential suppression of interleukin-2 associated side effects. Blood 1990;76:1933-40.7714 - Schimmer B, Parker K. Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Hardman JG, Limbird LE, Molinoff PB, et al., eds. Goodman and Gilman's the Pharmacological Basis of Therapeutics, 10th edition. New York: McGraw Hill, 2001;1649-1674.7944 - Alkeran® injection (melphalan) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2007 Jun.8083 - Ammonul® (sodium phenylacetate and sodium benzoate) package insert. Baltimore, MD: Chesapeake Biological Laboratories, Inc.; 2005 Feb.8314 - Jux C, Leiber K, Hugel U, et al. Dexamethasone impairs growth hormone (GH)-stimulated growth by suppression of local insulin-like growth factor (IGF)-1 production and expression of GH- and IGF-1 receptor in cultured rat chondrocytes. Endocrinology 1998;139:3296-305.8315 - Allen DB. Inhaled corticosteroid therapy for asthma in preschool children: growth issues. Pediatrics 2002;109:373-80.8565 - Orencia (abatacept) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2020 Jun.8844 - Dexamethasone tablets, USP, dexamethasone oral solution, and dexamethasone Intensol oral solution (concentrate) package insert. Columbus, OH: Roxane Laboratories; 2005 Oct.9671 - Tyzeka (telbivudine) package insert. East Hanover, NJ: Novartis Pharmaceuticals, Corp.; 2018 Dec.10415 - Ixempra (ixabepilone) for injection package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2011 Oct.11210 - Dilger K, Schwab M, Fromm MF. Identification of budesonide and prednisone as substrates of the intestinal drug efflux pump P-glycoprotein. Inflamm Bowel Dis 2004; 10: 578-83.11342 - Halotestin® (fluoxymesterone) package insert. New York, NY: Pharmacia and Upjohn Company a Division of Pfizer, Inc; 2002 May.23500 - Wilt JL, Minnema AM, Johnson RF, et al. Torsade de pointes associated with the use of intravenous haloperidol. Ann Intern Med 1993;119:391-4.23620 - Green PT, Reents S, Harman E, et al. Pentamidine-induced torsades de pointes in a renal tranplant recipient with Pneumocystis carinii pneumonia. S Med J 1990;83:481-4.23774 - Lui HK, Lee G, Dietrich P, et al. Flecainide-induced QT prolongation and ventricular tachycardia. Am Heart J 1982;103:567-9.23778 - Wharton JM, Demopulos PA, Goldschlager N. Torsade de pointes during administration of pentamidine isethionate. Am J Med 1987;83:571-6.23779 - Kriwisky M, Perry GY, Tarchitsky D, et al. Haloperidol-induced torsades de pointes. Chest 1990;98:482-3.24574 - Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. Ann Intern Med 1991;115:787-96.25398 - Melchart D, Linde K, Worku F, et al. Results of five randomized studies on the immunomodulatory activity of preparations of Echinacea. J Altern Complement Med 1995;1:145-60.26417 - Cohn JN, Kowey PR, Whelton PK, Prisant LM. New guidelines for potassium replacement in clinical practice: a contemporary review by the National Council on Potassium in Clinical Practice. Arch Intern Med 2000;160:2429-2436.27353 - Hodak SP, Moubarak JB, Rodriguez I, et al. QT Prolongation and near fatal cardiac arrhythmia after intravenous tacrolimus administration: a case report. Transplantation 1998;66:535-7.27354 - Johnson MC, So S, Marsh JW, et al. QT prolongation and Torsades de Pointes after administration of FK506. Transplantation 1992;53:929-30.27939 - Humira (adalimumab) package insert. North Chicago, IL: AbbVie Inc; 2021 Feb.27957 - Nardil (phenelzine) tablet package insert. New York, NY: Pfizer; 2009 Feb.27982 - Ketoconazole tablets package insert. Morgantown, WV: Mylan Pharmaceuticals, Inc.; 2017 Sept.28001 - Hansten PD, Horn JR. Cytochrome P450 Enzymes and Drug Interactions, Table of Cytochrome P450 Substrates, Inhibitors, Inducers and P-glycoprotein, with Footnotes. In: The Top 100 Drug Interactions - A guide to Patient Management. 2008 Edition. Freeland, WA: H&H Publications; 2008:142-157.28003 - Mifepristone, RU-486 package insert. New York, NY: GenBioPro, Inc.; 2019 Feb.28004 - Isuprel (isoproterenol) package insert. Lake Forest, IL: Hospira, Inc.; 2013 Mar.28032 - McMahon M, Gerich J, Rizza R. Effects of glucocorticoids on carbohydrate metabolism. Diabetes Metab Rev 1988;4:17-30.28156 - Ketek (telithromycin) package insert. Bridgewater, NJ: Sanofi-Aventis Pharmaceuticals; 2015 Oct.28158 - VFEND (voriconazole) tablets, suspension, and injection package insert. New York, NY: Pfizer Inc; 2021 Oct.28211 - Henderson L, Yue QY, Bergquist C, et al. St John's wort (Hypericum perforatum): drug interactions and clinical outcomes. Br J Clin Pharmacol 2002;54:349-56.28216 - Levitra (vardenafil) package insert. Kenilworth, NJ: Schering-Plough; 2017 Aug.28221 - Tikosyn (dofetilide) package insert. New York, NY: Pfizer Labs; 2019 Aug.28224 - Pacerone (amiodarone) tablets package insert. Maple Grove, MN: Upsher-Smith Laboratories, LLC.; 2018 Nov.28225 - CredibleMeds. Drugs to avoid in congenital long QT. Available on the World Wide Web at http://www.crediblemeds.org.28226 - Trisenox (arsenic trioxide) package insert. Frazer, PA: Cephalon, Inc; 2010 Jun.28228 - Norpace and Norpace CR (disopyramide) package insert. Chicago, IL: G.D. Searle LLC division of Pfizer Inc; 2016 Aug.28229 - Demaziere J, Fourcade JM, Busseuil CT, et al. The hazards of chloroquine self prescription in west Africa. J Toxicol Clin Toxicol 1995;33:369-70.28233 - Geodon (ziprasidone) package insert. New York, NY: Pfizer: 2021 May.28234 - Betapace (sotalol) package insert. Wayne, NJ: Berlex Laboratories; 2011 Aug.28235 - Richards JR, Schneir AB. Droperidol in the emergency department: is it safe? J Emerg Med 2003;24:441-7.28236 - Kao LW, Kirk MA, Evers SJ, et al. Droperidol, QT prolongation, and sudden death: what is the evidence? Ann Emerg Med 2003;41:546-58.28238 - Biaxin (clarithromycin) package insert. North Chicago, IL: AbbVie, Inc.; 2019 Sep.28250 - Procanbid (procainamide) package insert. Bristol, TN: Monarch Pharmaceuticals; 2002 Jan.28251 - Ery-tab (erythromycin delayed-release tablets) package insert. Atlanta, GA: Arbor Pharmaceuticals, Inc.; 2018 Oct.28261 - Uroxatral (alfuzosin) package insert. Cary, NC: Covis Pharmaceuticals, Inc.; 2013 Sep.28262 - Clozaril (clozapine) tablets package insert. Rosemont, PA: HLS Therapeutics (USA), Inc.; 2021 Feb.28267 - Acetazolamide package insert. Mahwah, NJ: Lifestar Pharma LLC; 2020 Mar.28269 - Celexa (citalopram) package insert. Madison, NJ: Allergan USA, Inc.; 2021 Sept.28270 - Lexapro (escitalopram) package insert. Madison, NJ: Allergan USA, Inc.; 2021 Sept.28272 - Lanoxin (digoxin) tablets package insert. St. Michael, Barbados: Concordia Pharmaceuticals Inc.; 2020 Apr..28278 - Raaska K, Niemi M, Neuvonen M, et al. Plasma concentrations of inhaled budesonide and its effects on plasma cortisol are increased by the cytochrome P4503A4 inhibitor itraconazole. Clin Pharmacol Ther 2002 Oct;72:362-9.28279 - Falcoz C, et al. Effects of CYP4503A inhibition by ketoconazole on systemic activity of inhaled fluticasone propionate and budesonide. Eur Respir J 1997;10(suppl 25):175-6.28287 - Rythmol SR (propafenone hydrochloride) capsule extended release package insert. Research Triangle Park, NC: GlaxoSmithKline; 2018 Nov.28293 - Thioridazine package insert. Morgantown, WV: Mylan Pharmaceuticals Inc.; 2016 Nov.28301 - Mefloquine package insert. Princeton, NJ: Sandoz Inc.; 2013 Jul.28307 - Haldol (haloperidol) injection for immediate release package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2020 Feb.28309 - Foradil Aerolizer (formoterol fumarate inhalation powder capsules) package insert. Novartis Pharma AG: 2012 Nov.28315 - Norvir (ritonavir capsules) package insert. North Chicago, IL: AbbVie Inc; 2020 Oct.28318 - Xopenex (levalbuterol) package insert. Marlborough, MA: Sepracor Inc.; 2009 Feb.28319 - Krantz MJ, Kutinsky IB, Robertson AD, et al. Dose-related effects of methadone on QT prolongation in a series of patients with torsade de pointes. Pharmacotherapy 2003;23:802-5.28320 - Walker PW, Klein D, Kasza L. High dose methadone and ventricular arrhythmias: a report of three cases. Pain 2003;103:321-4.28321 - Kornick CA, Kilborn MJ, Santiago-Palma J, et al. QTc interval prolongation associated with intravenous methadone. Pain 2003;105:499-506.28322 - Gil M, Sala M, Anguera I, et al. QT prolongation and Torsades de Pointes in patients infected with human immunodeficiency virus and treated with methadone. Am J Cardiol 2003;92:995-7.28341 - Kaletra (lopinavir; ritonavir) tablet and solution package insert. North Chicago, IL: AbbVie Inc; 2020 Oct.28343 - Zoloft (sertraline) package insert. New York, NY: Pfizer; 2021 Sept.28377 - Foscavir (foscarnet) package insert. Lake Forest, IL: Clinigen Healthcare, Ltd.; 2017 Feb.28405 - Strattera (atomoxetine) package insert. Indianapolis, IN: Eli Lilly and Company; 2020 Feb.28406 - Plenaxis (abarelix) package insert. Waltham, MA: Praecis Pharmaceuticals Inc.; 2003 Nov.28414 - Risperdal (risperidone tablets, oral solution, and orally disintegrating tablets) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2021 Feb.28415 - Nora Goldschlager, Andrew E Epstein, Blair P Grubb, et al. Etiologic considerations in the patient with syncope and an apparently normal heart. Arch Intern Med 2003;163:151-62.28416 - Hansten PD, Horn JR. Drug Interactions with Drugs that Increase QTc Intervals. In: The Top 100 Drug Interactions - A Guide to Patient Management. 2007 Edition. Freeland, WA: H&H Publications; 2007:144-8.28417 - Hoehns JD, Stanford RH, Geraets DR, et al. Torsades de pointes associated with chlorpromazine: case report and review of associated ventricular arrhythmias. Pharmacotherapy 2001;21:871-83.28419 - Owens RC Jr. Risk assessment for antimicrobial agent-induced QTc interval prolongation and torsades de pointes. Pharmacotherapy 2001;21:301-19.28420 - Iannini PB. Cardiotoxicity of macrolides, ketolides and fluoroquinolones that prolong the QTc interval. Expert Opin Drug Saf 2002;1:121-8.28421 - Levaquin (levofloxacin) tablet package insert. Titusville, NJ: Janssen Pharmaceutical, Inc.; 2020 Jun.28423 - Avelox (moxifloxacin) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2020 May.28424 - Factive (gemifloxacin mesylate) package insert. Toronto, ON: Merus Labs International, Inc.; 2019 May.28429 - Lasix (furosemide) package insert. Bridgewater, NJ: Aventis Pharmaceuticals; 2018 Aug.28432 - Roden, DM. Drug-induced prolongation of the QT interval. New Engl J Med 2004;350:1013-22.28442 - Sustiva (efavirenz) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2019 Oct.28457 - Crouch MA, Limon L, Cassano AT. Clinical relevance and management of drug-related QT interval prolongation. Pharmacotherapy 2003;23:881-908.28458 - Schmeling WT, Warltier DC, McDonald DJ, et al. Prolongation of the QT interval by enflurane, isoflurane, and halothane in humans. Anesth Analg 1991;72:137-44.28467 - Serevent Diskus (salmeterol xinafoate inhalation powder) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2019 July.28492 - Viramune (nevirapine) package insert. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2011 Mar.28496 - Tracleer (bosentan) package insert. South San Francisco, CA: Actelion Pharmaceuticals US, Inc.; 2019 May.28502 - Fiorinal (butalbital; aspirin; caffeine) capsules package insert. Madison, NJ: Allergan USA, Inc.; 2021 Apr.28529 - Provigil® (modafinil) package insert. West Chester, PA: Cephalon, Inc; 2004 Feb.28532 - Proventil HFA (albuterol sulfate) Inhalational Aerosol package insert. Whitehouse Station, NJ: Merck Sharp & Dohme Corp., a subsidiary of MERCK & CO., INC.; 2017 Sept.28549 - Coumadin (warfarin tablets) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2017 Aug.28550 - Glucophage and Glucophage XR (metformin HCl tablets and extended-release tablets) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2018 May.28592 - Zoladex (goserelin acetate 3.6 mg implant) package insert. Lake Forest, IL: TerSera Therapeutics LLC; 2019 Feb.28599 - Zyvox (linezolid) package insert. New York, NY: Pharmacia and Upjohn Company; 2021 Sep.28618 - Tenormin (atenolol) package insert. Morristown, NJ: Almatica Pharma, Inc.; 2019 Apr28625 - Matulane (procarbazine) package insert. Gaithersburg, MD: sigma-tau Pharmaceuticals, Inc.; 2002 July.28661 - Apokyn and Apokyn Pen (apomorphine) injection package insert. Louisville, KY: US WorldMeds LLC; 2020 Apr.28674 - Diflucan oral tablet and suspension (fluconazole) package insert. New York, NY: Pfizer; 2020 Sept.28683 - Nefazodone tablet package insert. North Wales, PA: Teva Pharmaceuticals USA, Inc.; 2015 Sept.28737 - Inapsine (Droperidol) Injection package insert. Lake Forest, IL: Akorn, Inc.; 2011 Oct.28759 - Maprotiline HCl tablet package insert. Morgantown WV: Mylan Pharmaceuticals Inc; 2014 Dec.28761 - Albengres E, Le Louet H, Tillement JP. Systemic antifungal agents. Drug interactions of clinical significance. Drug Saf. 1998;18:83-97.28764 - Cipro (ciprofloxacin intravenous solution) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2020 May.28771 - Dilantin Kapseals (extended phenyotin sodium capsules, USP) package insert. Morris Plains, NJ: Parke Davis; 1999 Aug.28775 - Owens RC. QT Prolongation with antimicrobial agents: Understanding the significance. Drugs 2004;64:1091-1124.28785 - Zyprexa (olanzapine, all formulations) package insert. Indianapolis, IN: Eli Lilly and Company; 2020 Apr.28822 - Fareston (toremifene citrate) tablets package insert. Bedminster, NJ: Kyowa Kirin Inc.; 2017 May.28839 - Viracept (nelfinavir mesylate) package insert. Research Triangle Park, NC: ViiV Healthcare Company; 2021 Mar.28843 - Zonegran (zonisamide) package insert. Dublin, Ireland: Concordia Pharmaceuticals, Inc.; 2020 Apr.28855 - Zithromax (azithromycin 250 mg and 500 mg tablets and azithromycin oral suspension) package insert. New York, NY: Pfizer Inc.; 2019 Apr.28879 - Pentamidine isethionate injection package insert. East Brunswick, NJ: Avet Pharmaceuticals Inc.; 2021 Jan.28902 - Fluvoxamine maleate package insert. Laurelton, NY: Eon Labs, Inc.; March 2005.28978 - Michalets EL, Williams CR. Drug interactions with cisapride: clinical implications. Clin Pharmacokinet 2000;39:49-75.28995 - Invirase (saquinavir) package insert. South San Francisco, CA: Genentech Inc.; 2020 Sept.29003 - OPEN REFERENCE29012 - Lexiva (fosamprenavir calcium) package insert. Research Triangle Park, NC: ViiV Healthcare; 2019 Mar29016 - Aldactone (spironolactone) package insert. New York, NY: G.D. Searle LLC; 2008 Jan.29096 - Serentil (mesoridazine) package insert. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2001 March.29113 - Sandostatin (octreotide) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2021 May.29118 - Seroquel (quetiapine fumarate) package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020 Sept.29190 - DeVane CL, Donovan JL, Liston HL, et al. Comparative CYP3A4 inhibitory effects of venlafaxine, fluoxetine, sertraline, and nefazodone in healthy volunteers. J Clin Psychopharmacol. 2004;24:4-10.29318 - Pelgrims J, DeVos F, Van den Brande J, et al. Methylene blue in the treatment and prevention of ifosfamide-induced encephalopathy: Report of 12 cases and a review of the literature. Br J Cancer 2000;82:291-4.29377 - Nanji AA. Drug-induced electrolyte disorders. Drug Intell Clin Pharm 1983;17:175-85.29656 - Parnate (tranylcypromine) package insert. St. Michael, Barbados: Concordia Pharmaceuticals; 2018 Jan.29758 - Aralen (chloroquine) package insert. Bridgewater, NJ: Sanofi-aventis U.S. LLC.; 2018 Oct.29779 - Deltasone (prednisone) tablet package insert. Petaluma, CA: Oculus Innovative Sciences, Inc.; 2017 Nov.29818 - Noroxin (norfloxacin) tablets package insert. Whitehouse Station, NJ: Merck and C., Inc.; 2016 Jul.29833 - Frothingham R. Rates of torsades de pointes associated with ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin. Pharmacotherapy 2001;21:1468-72.29890 - Florinef Acetate (fludrocortisone acetate) package insert. Bristol, TN: Monarch Pharmaceuticals; 2003 Jul.30011 - Dexamethasone tablets USP, Dexamethasone oral solution, and Dexamethasone Intensol (oral solution concentrate) package insert. Eatontown, NJ: West-Ward Pharmaceuticals Corp; 2016 March.30015 - Medrol (methylprednisolone) tablet package insert. New York, NY: Pfizer; Pharmacia and Upjohn Company LLC; 2019 Jan.30028 - Pediapred (prednisolone sodium phosphate) oral solution package insert. Manasquan, NJ: Royal Pharmaceuticals; 2018 Feb.30163 - Agrylin (anagrelide) capsules package insert. Lexington, MA: Takeda Pharmaceuticals USA, Inc.; 2021 Oct.30369 - Vantas (histrelin implant) package insert. Chadds Ford, PA: Endo Pharmaceuticals Solutions Inc.; 2020 Dec.30438 - Marplan (isocarboxazid) package insert. Parsippany, NJ: Validus Pharmaceuticals; 2018 Nov.30470 - Tysabri (natalizumab) package insert. Cambridge, MA: Biogen Idec Inc.; 2020 Jun.30515 - Vesicare (solifenacin) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2012 Jul.30555 - Tarceva (erlotinib) package insert. Northbrook, IL: OSI Pharmaceuticals, LLC; 2016 Sept.30585 - Pandit MK, Burke J, Gustafson AB, et al. Drug-induced disorders of glucose tolerance. Ann Intern Med 1993;118:529-39.30624 - Herrington AM, George KW, Moulds CC. Octreotide-induced bradycardia. Pharmacotherapy 1998;18:413-6.30676 - Emend (aprepitant oral products) package insert. Whitehouse Station, NJ: Merck & Co.,Inc.; 2019 Nov.30738 - Ofloxacin tablets package insert. Sacramento, CA: Nivagen Pharmaceuticals, Inc.; 2019 Feb.30943 - Schimmer B, Parker K. Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Hardman JG, Limbird LE, Molinoff PB, et al., eds. Goodman and Gilman's the Pharmacological Basis of Therapeutics, 10th edition. New York: McGraw Hill, 2001;1649-1674.31112 - Detrol (tolterodine tartrate) package insert. New York, NY: Pharmacia and Upjohn Co., division of Pfizer; 2016 Nov.31123 - Patten BM, Oliver KL, Engel WK. Adverse interaction between steroid hormones and anticholinesterase drugs. Neurology 1974;24:442-9.31266 - Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 May.31403 - Qualaquin (quinine sulfate) capsules package insert. Cranbury, NJ: Sun Pharmaceutical Industries, Inc.; 2019 Jun.31468 - Actonel with Calcium (risedronate sodium with calcium carbonate) package insert. Rockaway, NJ: Warner Chilcott, LLC; 2015 Mar.31469 - Kumar R. Glucocorticoid-induced osteoporosis. Curr Opin Nephrol Hypertens 2001;10:585-9.31723 - Kytril injection (granisetron) package insert. Nutley, NJ: Roche Pharmaceuticals; 2011 Nov.31764 - Vaprisol (conivaptan hydrochloride injection) package insert. Deerfield, IL: Baxter Healthcare Corporation; 2016 Oct.31807 - Exjade (deferasirox) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2020 Jul.31824 - Rhinocort Aqua (budesonide) nasal spray package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2012 Feb.31832 - Nexavar (sorafenib) package insert. Wayne, NJ; Bayer HealthCare Pharmaceuticals Inc.; 2020 July.31938 - Ranexa (ranolazine extended-release tablets) package insert. Foster City, CA: Gilead Sciences, Inc. 2019 Oct.31970 - Sunitinib (Sutent) package insert. New York, NY: Pfizer Labs; 2020 Aug.32073 - Lee AN, Werth VP. Activation of autoimmunity following use of immunostimulatory herbal supplements. Arch Dermatol 2004;140:723-7.32127 - Prozac (fluoxetine) capsules package insert. Indianapolis, IN: Eli Lilly and Company; 2021 Oct.32223 - Azilect (rasagiline mesylate) tablets. Kansas City, MO: Teva Neurosciences, Inc.; 2020 Jun.32308 - Lawrence KR, Adra M, Gillman PK. Serotonin toxicity associated with the use of linezolid: A review of postmarketing data. Clin Infect Dis 2006;42:1578-83.32432 - Prezista (darunavir) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2021 Jul.32723 - Noxafil (posaconazole) package insert. Whitehouse Station, NJ: Merck & Co. Inc.: 2021 Jun.32732 - Stollberger C, Huber JO, Finsterer J. Antipsychotic drugs and QT prolongation. Int Clin Psychopharmacol 2005;20:243-51.32734 - Su KP, Lane HY, Chuang CL, et al. Olanzapine-induced QTc prolongation in a patient with wolff-parkinson-white syndrome. Schizophrenia Research 2004;66:191-2.32745 - Dineen S, Withrow K, Voronovitch L, et al. QTc prolongation and high-dose olanzapine. Psychosomatics 2003;44:174-5.32746 - Gurovich, I. QTc prolongation: chlorpromazine and high-dosage olanzapine. Can J Psychiatry 2003;48:348.32789 - Zolinza (vorinostat) capsules package insert. Whitehouse Station, NJ: Merck & Co., Inc.; 2018 Dec.32901 - Brovana (arformoterol tartrate) inhalation solution package insert. Marlborough, MA: Sunovion Pharmaceuticals, Inc..; 2019 May.32950 - Symbicort (budesonide; formoterol fumarate dihydrate) inhalation aerosol package insert. Wilmington, DE: AstraZeneca LP; 2017 Dec.33068 - Gajwani P, Pozuelo L, Tesar G, et al. QT interval prolongation associated with quetiapine (seroquel) overdose. Psychosomatics 2000;41:63-5.33072 - Beelen AP, Yeo KTJ, Lewis LD. Asymptomatic QTc prolongation associated with quetiapine fumarate overdose in a patient being treated with risperidone. Hum Exp Toxicol 2001;20:215-9.33074 - Furst BA, Champion KM, Pierre JM, et al. Possible association of QTc interval prolongation with co-administration of quetiapine and lovastatin. Biol Psychiatry 2002;51:264-5.33136 - Dolophine (methadone) tablets package insert. Eatontown, NJ: West-Ward Pharmaceuticals Corp.; 2021 Jun.33156 - Advair Diskus (fluticasone propionate; salmeterol inhalation powder) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2017 Dec.33192 - Tykerb (lapatinib) tablet package insert. Research Triangle Park, NC: GlaxoSmithKline; 2018 Dec.33259 - Perforomist inhalation solution (formoterol) package insert. Napa, CA: Dey; 2019 May.33528 - Metopirone (metyrapone) capsule package insert. Farmingdale, NJ: Direct Success, Inc; 2020 Feb.33631 - Food and Drug Administration (FDA). Background document. Psychopharmacologic Drugs Advisory Committee. NDA 21,336-708 Emsam (selegiline transdermal system) Somerset, October 26, 2005. Retrieved December 10, 2007. Available on the World Wide Web at: http://www.fda.gov/ohrms/dockets/AC/05/briefing/2005-4186B2_01_01_Somerset-EMSAM.pdf.33698 - Androgel 1% (testosterone gel) package insert. North Chicago, IL: Abbott Laboratories; 2019 May.33715 - Effexor XR (venlafaxine extended-release capsules) package insert. Philadelphia, PA: Wyeth Pharmaceuticals, Inc; 2021 Sept.33718 - Intelence (etravirine) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2019 July.33925 - Ventolin HFA (albuterol sulfate) Inhalation Aerosol package insert. Research Triangle Park, NC: GlaxoSmithKline; 2008 Mar.34253 - Regonol (pyridostigmine bromide injection, USP) package insert. Princeton, NJ: Sandoz, Inc.; 2019 Jan.34329 - Eberl S, Renner B, Neubert A, et al. Role of p-glycoprotein inhibition for drug interactions: evidence from in vitro and pharmacoepidemiological studies. Clin Pharmacokinet 2007;46:1039-49.34354 - Dilger K, Schwab M, Fromm MF. Identification of budesonide and prednisone as substrates of the intestinal drug efflux pump P-glycoprotein. Inflamm Bowel Dis 2004; 10: 578-83.34376 - Pulmicort Flexhaler (budesonide inhalation powder) package insert. Wilmington, DE: AstraZeneca LP; 2018 Dec.34389 - Xenazine (tetrabenazine) package insert. Deerfield, IL: Lundbeck, Inc.; 2017 Sep.34447 - Niwa T, Shiraga T, Takagi A. Effect of antifungal drugs on cytochrome P450 (CYP) 2C9, CYP2C19, and CYP3A4 activities in human liver microsomes. Biol Pharm Bull. 2005;28:1805-1808.34535 - Zurcher RM, Frey BM, Frey FJ, et al. Impact of ketoconazole on the metabolism of prednisolone. Clin Pharmacol Ther 1989;45:366-72.34979 - Entocort EC (budesonide) capsules package insert. Wilmington, DE: AstraZeneca LP; 2020 July35401 - Coartem (artemether; lumefantrine) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2019 Aug.36101 - Multaq (dronedarone) package insert. Bridgewater, NJ: Sanofi-aventis U.S. LLC; 2020 Nov.36146 - Fanapt (iloperidone) package insert. Rockville, MD: Vanda Pharmaceuticals, Inc.; 2017 Mar.36250 - Sabril (vigabatrin) tablet/powder for oral solution package insert. Deerfield, IL: Lundbeck Inc.; 2020 Jan.36343 - Saphris (asenapine) sublingual tablet package insert. St. Louis, MO: Forest Pharmaceuticals, Inc.; 2017 Mar.36615 - Vibativ (telavancin) package insert. Nashville, TN: Cumberland Pharmaceuticals Inc.; 2020 July.36894 - Metronidazole injection package insert. Deerfield, IL: Baxter Healthcare Corporation; 2021 Mar.37098 - Votrient (pazopanib) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2011 Oct.37292 - Istodax (romidepsin) injection package insert. Summit, NJ: Celgene Corporation; 2021 July.38831 - Oleptro (trazodone hydrochloride) extended-release tablets package insert. Dublin, Ireland: Labopharm Europe Limited; 2014 Jul.40027 - Emend (fosaprepitant dimeglumine injection) package insert. Whitehouse Station, NJ: Merck & Co.,Inc.; 2019 Nov.40134 - Amphotericin B injection package insert. Big Flats, NY: X-Gen Pharmaceuticals, Inc.; 2009 Dec.40233 - Sporanox (itraconazole) oral solution package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2019 Mar.40862 - Prolia (denosumab) solution for injection package insert. Thousand Oaks, CA: Amgen, Inc.; 2021 May.40936 - Invega Sustenna (paliperidone palmitate injectable suspension) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2021 Feb.40942 - Remeron and RemeronSolTabs (mirtazapine tablets and ODT tablets) package insert. Roseland, NJ: Organon USA, Inc.; 2020 Apr.41057 - Wellbutrin XL (bupropion) package insert. Bridgewater, NJ: Bausch Health US, LLC; 2021 July.41086 - Wellbutrin (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2020 Oct.41138 - Dulera (mometasone furate; formoterol fumarate inhalation aerosol) package insert. Whitehouse Station, NJ: Schering Corporation; 2019 Aug.41231 - Foradil inhalation powder (formoterol fumarate) package insert. Kenilworth, NJ: Schering Corporation; 2012 Nov.41237 - Tegretol (carbamazepine) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2018 Mar.41361 - Solu-Medrol (methylprednisolone sodium succinate for injection) package insert. New York, NY: Pharmacia and Upjohn Co; 2021 May.41573 - Suprep (sodium sulfate, potassium sulfate, and magnesium sulfate) oral solution concentrate package insert. Braintree, MA: Braintree Laboratories, Inc.; 2020 July.41806 - Plaquenil (hydroxychloroquine) package insert. St. Michael, Barbados: Concordia Pharmaceuticals, Inc.; 2021 May.41823 - Gilenya (fingolimod) package insert. East Hanover, New Jersey: Novartis Pharmaceuticals Corporation; 2019 Dec.41830 - Corvert (ibutilide) package insert. New York, NY: Pharmacia and Upjohn Company; 2016 Aug.41853 - Proleukin (aldesleukin) package insert. San Diego, CA: Prometheus Laboratories Inc.; 2012 Jul.41934 - Lysodren (mitotane) package insert. Princeton, NJ: Bristol-Myers Squibb Oncology; 2021 June.41958 - Eloxatin (oxaliplatin) package insert. Bridgewater, NJ: Sanofi-aventis U.S. LLC; 2020 April.41961 - Pancuronium injection package insert. Lake Forest, IL: Hospira, Inc; 2019 Jan.41984 - Primaquine phosphate package insert. Bridgewater, NJ: Sanofi-aventis; 2017 Jun.42031 - Rocuronium bromide package insert. Lake Zurich, IL: Fresenius Kabi; 2020 Apr.42281 - Cantil (mepenzolate bromide USP) package insert. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; 2006 Feb.42449 - Halaven (eribulin mesylate) injection package insert. Woodcliffe Lake, NJ: Eisai Inc.; 2016 Oct.42844 - FDA Drug Safety Communication: Abnormal heart rhythms associated with use of Anzemet (dolasetron mesylate). Retrieved December 17, 2010. Available on the World Wide Web at: http://www.fda.gov/Drugs/DrugSafety/ucm237081.htm.42845 - Abilify (aripiprazole) tablets, discmelt orally-disintegrating tablets, oral solution, and intramuscular injection package insert. Tokyo, Japan: Otsuka America Pharmaceutical, Inc.; 2020 Mar.42863 - Mytelase (ambenonium chloride) package insert. Bridgewater, NJ:Sanofi-Aventis U.S. LLC; 2011 Aug.43065 - Chlorpromazine package insert. Princeton, NJ: Sandoz Inc; 2019 Dec.43069 - Thioridazine package insert. Philadelphia, PA:Mutual Pharmaceutical Company, Inc;2010 Sept.43298 - Aplisol (tuberculin purified protein derivative, diluted) package insert. Chestnut Ridge, NY: Par Pharmaceuticals; 2016 Mar.43299 - Tubersol (tuberculin purified protein derivative, mantoux) package insert. Swiftwater, PA: Sanofi Pasteur, Inc.; 2020 Nov.43319 - Prednisone tablet package insert. Salisbury, MD: Cadista Pharmaceuticals Inc.; 2016 Mar.43411 - Cipro (ciprofloxacin tablet; suspension) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2021 Mar.43463 - Orap (pimozide) package insert. Sellersville, PA: Teva Pharmaceuticals USA; 2014 Mar.43675 - DuoNeb (ipratropium bromide / albuterol sulfate) Inhalation Solution for Nebulizer package insert. Napa, CA: Dey; 2011 Mar.43792 - Provocholine (methacholine chloride) powder for inhalation package insert. Brantford, Ontario, Canada: Methapharm Inc.; 2020 Nov.43800 - Lupron Depot (leuprolide acetate for depot suspension) package insert. North Chicago, IL: AbbVie Inc; 2019 March.43901 - Caprelsa (vandetanib) package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020 June.43942 - Levothroid (levothyroxine sodium tablet) package insert. Shenandoah, IA: Lloyd Pharmaceutical; 2011 June.43952 - Levothyroxine injection package insert. Chestnut Ridge, NY: PAR Pharmaceutical; 2019 April.43974 - Zithromax (azithromycin injection) package insert. New York, NY: Pfizer Inc.; 2019 Apr.44026 - Advair HFA (fluticasone propionate; salmeterol inhalation aerosol) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Aug.44063 - Advair Diskus (fluticasone propionate; salmeterol inhalation powder) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2019 Jan.44314 - Victrelis (boceprevir) capsule package insert. Whitehouse Station, NJ: Merck and Co, Inc; 2017 Jan.44376 - Edurant (rilpivirine) package insert. Titusville, NJ: Janssen Therapeutics; 2021 Jan.44393 - Incivek (telaprevir) tablet package insert. Cambridge, MA: Vertex Pharmaceuticals, Inc; 2013 Oct.44800 - Potiga (ezogabine) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2016 May.44913 - Mycamine (micafungin) for Injection package insert. Northbrook, IL: Astellas Pharma US, Inc; 2019 Dec.44979 - Arcapta Neohaler (indacaterol inhalation powder) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2021 July.45335 - Zelboraf (vemurafenib) tablet package insert. South San Francisco, CA: Genentech USA, Inc.; 2020 May.45339 - Flo-Pred (prendisolone acetate) package insert. Hawthorne, NY: TaroPharma; 2021 July.45411 - Trelstar (triptorelin pamoate for injectable suspension) package insert. Parsipanny, NJ: Watson Pharma, Inc; 2018 Dec.45458 - Xalkori (crizotinib) package insert. New York, NY: Pfizer Labs; 2021 Sept.46711 - Pulmicort Turbuhaler (budesonide) package insert. Wilmington, DE: AstraZeneca, LP; 2006 Oct.46800 - Terbutaline sulfate injection package insert. Eatontown, NJ: West-ward Pharmaceutical Corp.; 2011 Apr.46869 - Firmagon (degarelix) package insert. Parsippany, NJ: Ferring Pharmaceuticals Inc.; 2020 Dec.47129 - Hydroxyzine hydrochloride injection package insert. Shirley, NY: American Regent, Inc.; 2016 Oct.47165 - Norvir (ritonavir tablets, solution, and powder) package insert. North Chicago, IL: AbbVie Inc; 2020 Oct.47221 - Propulsid (cisapride) package insert. Titusville, NJ; Janssen Pharmaceutica; 2006 Oct. NOTE: As of May 2000; Propulsid has only been available in the United States via an investigational limited access program to ensure proper patient screening and prescribing.47357 - Quinidine gluconate extended-release tablet package insert. Richmond, VA: Richmond Pharmaceuticals, Inc.; 2017 Feb.48342 - ANADROL-50 (oxymetholone) package insert. Marietta, GA: Alaven Pharmaceutical; 2006 Nov.48524 - Kalydeco (ivacaftor) package insert. Boston, MA: Vertex Pharmaceuticals Incorporated; 2020 Dec.48676 - Erythrocin (erythromycin lactobionate injection) package insert. Lake Forest, IL: Hospira Inc.; 2019 Nov48697 - Korlym (mifepristone) tablet package insert. Menlo Park, CA: Corcept Therapeutics; 2019 Nov.49489 - Cortisone acetate tablet package insert. Eatontown, N.J.: Hikma Pharmaceuticals USA Inc.; 2016 July49773 - Rituxan (rituximab) injection package insert. South San Francisco, CA: Genentech, Inc.; 2018 Apr.49951 - Ventolin HFA (albuterol sulfate) Inhalation Aerosol package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Aug.50004 - Wright RS, Anderson JL, Adams CD, et al. 2011 ACCF/AHA Focused Update Incorporated Into the ACC/AHA 2007 Guidelines for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction. Circulation 2011;123:e426-e579.50507 - Luvox CR (fluvoxamine maleate extended-release capsules) package insert. Palo Alto, CA: Jazz Pharmaceuticals, Inc.; 2017 Jan.50586 - Torisel (temsirolimus) injection package insert. Philadelphia, PA: Wyeth Pharmaceuticals Inc; 2018 March.50760 - Uniphyl (theophylline, anhydrous) tablets package insert. Stamford, CT: Purdue Pharmaceutical Products LP; 2004 Mar.51002 - Chan JC, Cockram CS, Critchley JA. Drug-induced disorders of glucose metabolism. Mechanisms and management. Drug Saf 1996;15:135—57.51022 - Xopenex HFA (levalbuterol) metered aerosol package insert. Marlborough, MA: Sunovion Pharmaceuticals Inc.; 2017 Mar.51080 - Kaletra (lopinavir; ritonavir) capsule package insert. North Chicago, IL: AbbVie Inc; 2020 Oct.51664 - Stribild (elvitegravir; cobicistat; emtricitabine; tenofovir disoproxil fumarate) package insert. Foster City, CA: Gilead Sciences, Inc; 2021 Sept.51834 - Food and Drug Administration (FDA): Drug development and drug interactions. Retrieved Sep 19, 2012. Available on the World Wide Web http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm#transporter.52506 - Cometriq (Cabozantinib) capsules package insert. South San Francisco, CA:Exelixis, Inc.; 2020 Jan52611 - Signifor (pasireotide diaspartate) package insert. Stein, Switzerland: Novartis Pharma Stein AG; 2020 Jan.52746 - Sirturo (bedaquiline) tablet package insert. Titusville, NJ: Janssen Therapeutics; 2021 Sept.52910 - Uceris (budesonide) tablets package insert. San Diego, CA: Santarus Inc.; 2020 April.53022 - Ravicti (Glycerol phenylbutyrate) package insert. Lake Forest, IL: Horizon Pharma USA, Inc.; 2021 Sept.53057 - Diflucan (fluconazole) European package insert. United Kingdom: Pfizer Limited. Available on the world wide web at: https://www.medicines.org.uk/emc/product/5144/smpc#gref; Accessed Aug 2, 2021.54246 - Hydrocortone (hydrocortisone sodium phosphate) injection package insert. Whitehouse Station, NJ: Merck & Co., Inc.; 2001 Nov.54278 - Solu-Cortef (hydrocortisone sodium succinate) injection package insert. New York, NY: Pharmacia and Upjohn Co.; 2021 May.54280 - S2 (racepinephrine) inhalation solution 2.25% package insert. Orlando, FL: Nephron Pharmaceuticals Corporation: 2015 Feb.54298 - Asthmanefrin (racepinephrine) inhalation solution 2.25% product label. Orlando, FL: Nephron Pharmaceuticals Corporation; 2014 Dec.54374 - Phenylephrine hydrochloride injection. Eatontown, NJ: West-Ward Pharmaceuticals; 12 Dec.54506 - Sodium chloride 0.45% and 0.9% injection package insert. Deerfield, IL: Baxter Healthcare Corporation. 2019 May.54633 - Breo Ellipta (fluticasone; vilanterol) package insert. Research Triangle Park, NC: GlaxoSmithkline; 2019 Jan.54802 - Tafinlar (dabrafenib) capsules package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2021 May.54891 - Bloxiverz (neostigmine methylsulfate injection) package insert. Lenoir, NC: Exela Pharma Sciences, LLC; 2020 Nov.55362 - Elspar (asparaginase) injection package insert. Deerfield, IL: Lundbeck; 2013 July.55578 - Owczuk R, Twardowski P, Dylczyk-Sommer A, et al. Influence of promethazine on cardiac repolarization: a double-blind, midazolam-controlled study. Anaesthesia 2009;64:609-614.56076 - Edsbacker S, Andersson T. Pharmacokinetics of budesonide (Entocort EC) capsules for Crohn's disease. Clin Pharmacokinet 2004;43:803-821.56146 - Kenalog-40 (triamcinolone acetonide) injection package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2019 April.56233 - Singh JA, Furst DE, Bharat A, et al. 2012 Update of the 2008 American College of Rheumatology Recommendations for the Use of Disease-Modifying Antirheumatic Drugs and Biologic Agents in the Treatment of Rheumatoid Arthritis. Arthritis Care & Research 2012;64(5):625-639.56471 - Olysio (simeprevir) capsule package insert. Titusville, NJ: Janssen Therapeutics; 2017 Nov.56564 - Anoro Ellipta (umeclidinium; vilanterol) package insert. Research Triangle Park, NC: GlaxoSmithkline; 2019 Jun.56575 - Adrenalin (epinephrine) 1 mg/mL injection package insert. Chestnut Ridge, NJ: Par Pharmaceutical Companies, Inc.; 2019 Jan.56579 - Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. Updated Mar 10, 2020. Retrieved from the World Wide Web at www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm56853 - Hemangeol (propranolol hydrochloride) oral solution package insert. Parsippany, NJ: Pierre Fabre Pharmaceuticals, Inc.; 2021 Jun.57094 - Zykadia (ceritinib) package insert. Indianapolis, IN: Novartis; 2021 Oct.57441 - Iribarren C, Round AD, Peng JA, et al. Validation of a population-based method to assess drug-induced alterations in QT interval: a self-controlled crossover study. Pharmacoepidemiol Drug Saf 2013;22;1222-32.57578 - Vazculep (phenylephrine) injection package insert. Chesterfield, Mo: Avadel Legacy Pharmaceuticals, LLC; 2019 Oct.57675 - Zydelig (idelalisib) tablet package insert. Foster City, CA:Gilead Sciences, Inc.; 2018 Oct.57685 - Buphenyl (sodium phenylbutyrate) oral tablet and powder package insert. South San Francisco, CA: Hyperion Therapeutics, Inc.; 2013 Jun.57710 - Striverdi Respimat (olodaterol) package insert. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2019 May.57713 - K Phos Neutral (potassium phosphate; sodium phosphate) tablets package insert. Tampa, FL: Beach Pharmaceuticals; 2005 Jun.57714 - Virt Phos 250 Neutral (potassium phosphate; sodium phosphate) tablets package insert. Tampa, FL: Virtus Pharmaceuticals; 2014 Mar.57715 - Phospha 250 Neutral (potassium phosphate; sodium phosphate) tablets package insert. Columbus, OH: Rising Pharmaceuticals, Inc.; 2011 Feb.57741 - Orbactiv (oritavancin) package insert. Lincolnshire, IL: Melinta Therapeutics, LLC; 2021 July.57803 - Cerdelga (eliglustat) capsules. Waterford, Ireland: Genzyme Ireland, Ltd.;2018 Sept.58000 - Tybost (cobicistat) package insert. Foster City, CA: Gilead Sciences, Inc; 2021 Sept.58167 - Harvoni (ledipasvir; sofosbuvir) tablet and oral pellets package insert. Foster City, CA: Gilead Sciences, Inc; 2020 Mar.58220 - Bachmakov I, Werner U, Endress B, et al. Characterization of beta-adrenoceptor antagonists as substrates and inhibitors of the drug transporter P-glycoprotein. Fundam Clin Pharmacol 2006;20:273-82.58461 - Lemtrada (alemtuzumab) injection package insert. Cambridge, MA: Genzyme Corporation; 2021 Aug.58766 - Tasigna (nilotinib) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2021 Oct.58768 - Ibrance (palbociclib) capsules package insert. New York, NY: Pfizer Inc; 2019 Sept.58782 - Lenvima (lenvatinib) package insert. Woodcliff Lake, NJ:Eisai Inc; 2021 Aug.58821 - Farydak (panobinostat) capsules package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2016 June.59042 - Cresemba (isavuconazonium) package insert. Northbrook, IL: Astellas Pharma US, Inc; 2021 May.59321 - CredibleMeds. QT drug lists. Available on the World Wide Web at http://www.crediblemeds.org.59322 - Howes LG. Cardiovascular effects of drugs used to treat alzheimer's disease. Drug Saf. 2014;37:391–395.59438 - Trisenox (arsenic trioxide) injection package insert. Parsippany, NJ: Teva Pharmaceuticals USA, Inc.; 2020 Oct.59724 - Stiolto Respimat (tiotropium; olodaterol) package insert. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2020 Aug.59809 - Mamiya K, Sadanaga T, Sekita A, et al. Lithium concentration correlates with QTc in patients with psychosis. J Electrocardiol 2005;38:148-51.59810 - van Noord C, Straus SM, Sturkenboom MC, et al. Psychotropic drugs associated with corrected QT interval prolongation. J Clin Psychopharmacol 2009;29:9-15.59811 - Altinbas K, Guloksuz S, Caglar IM, et al. Electrocardiography changes in bipolar patients during long-term lithium monotherapy. Gen Hosp Psychiatry 2014;36:694-7.59891 - Orkambi (lumacaftor; ivacaftor) tablet package insert. Boston, MA: Vertex Pharmaceuticals, Inc. 2018 August60001 - Daklinza (daclatasvir) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2019 Oct.60087 - Sprycel (dasatinib) tablet package insert. Princeton, NJ Bristol-Myers Squibb Company; 2021 June.60270 - Belbuca (buprenorphine) buccal film package insert. BioDeliviery Sciences International, Inc.: Raleigh, NC; 2021 Mar.60297 - Tagrisso (osimertinib) tablet package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2021 July.60523 - Zepatier (elbasvir; grazoprevir) tablet package insert. Whitehouse Station, NJ: Merck, Inc; 2019 Dec.60738 - Cabometyx (Cabozantinib) tablets package insert. Alameda, CA: Exelixis, Inc.; 2021 Sept.60746 - Bevespi Aerosphere (glycopyrolate; formoterol fumarate) inhalation aerosol package insert. Wilmington, DE: AstaZeneca Pharmaceuticals LP; 2020 Nov.60748 - Nuplazid (pimavanserin) package insert. San Diego, CA: Acadia; 2020 Nov.60760 - Dexamethasone sodium phosphate injection package insert. Eatontown, NJ:West-Ward Pharmaceuticals;2014 Sept.60852 - Netspot (gallium Ga 68 dotatate) injection package insert. Millburn, NJ: Advanced Accelerator Applications USA, Inc. 2021 Jun.60864 - US Food and Drug Administration (FDA). FDA Drug Safety Communication: FDA warns about serious heart problems with high doses of the antidiarrheal medicine loperamide (Imodium), including from abuse and misuse. Retrieved June 7, 2016. Available on the World Wide Web at: http://www.fda.gov/Drugs/DrugSafety/ucm504617.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery61087 - Leukine (sargramostim) injection package insert. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; 2018 Mar.61750 - Emflaza (deflazacort) tablets and oral suspension. South Plainfield, NJ: PTC Therapeutics; 2021 Jul.61806 - Noctiva nasal spray (desmopressin acetate) package insert. Milford, PA: Serenity Pharmaceuticals LLC; 2017 Mar.61816 - Kisqali (ribociclib) tablets package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2021 Sept.61845 - Austedo (deutetrabenazine) tablets package insert. Parsippany, NJ: Teva Pharmaceuticals USA, Inc.; 2021 Jun.61870 - Chiu MH, Al-Majed NS, Stubbins R, et al. A case report of QT prolongation with glycopyrronium bromide in a patient with chronic tamoxifen use. BMC Res Notes. 2016;9:310.61871 - Slovacek L, Priester P, Petera J, et al. Tamoxifen/norfloxacin interaction leading to QT interval prolongation in a female patient with extracranial meningioma. Bratisl Lek Listy. 2011;112(6):353-4.61872 - Slovacek L, Ansorgova V, Macingova Z, et al. Tamoxifen-induced QT interval prolongation. J Clin Pharm Ther. 2008;33(4):453-5.61902 - Stimpel M, Proksch A, Wagner H, et al. Macrophage activation and induction of macrophage cytotoxicity by purified polysaccharide fractions from the plant Echinacea purpurea. Infect Immun 1984;46:845-961905 - Chavez ML, Jordan MA, Chavez PI. Evidence-based drug-herbal interactions. Life Sci 2006;78:2146-57.61906 - Rydapt (midostaurin) capsule package insert. East Hanover,NJ: Novartis Pharmaceuticals Corporation; 2021 Apr.61909 - Alunbrig (brigatinib) tablet package insert. Cambridge, MA: Ariad Pharmaceuticals Inc.; 2021 Sept.61937 - Millipred (prednisolone) oral tablet package insert. Research Triangle Park, NC: Zylera Pharmaceuticals, LLC; 2015 Nov.62028 - Baxdela (delafloxacin) package insert. Lincolnshire, IL: Melinta Therapeutics, Inc.; 2019 Oct.62131 - Vosevi (sofosbuvir; velpatasvir; voxilaprevir) tablet package insert. Foster City, CA: Gilead Sciences, Inc; 2019 Nov.62201 - Mavyret (glecaprevir; pibrentasvir) tablets package insert. North Chicago, IL: AbbVie Inc.; 2021 Sept.62245 - Besponsa (inotuzumab ozogamicin) injection package insert. Philadelphia, PA: Wyeth Pharmaceuticals Inc; 2017 Aug.62264 - National Clinical Guideline Centre (UK). Multiple Sclerosis: Management of Multiple Sclerosis in Primary and Secondary Care. London: National Institute for Health and Care Excellence (UK); (NICE Clinical Guideline No 186). 2014 Oct. Accessed: August 25 2017. Available at: www.ncbi.nlm.nih.gov/pubmedhealth/PMH0068954/pdf/PubMedHealth_PMH0068954.pdf62292 - Mylotarg (gemtuzumab ozogamicin) injection package insert. Philadelphia, PA: Pfizer Inc.; 2020 Feb.62611 - Prevymis (letermovir) package insert. Whitehouse Station, NJ: Merck and Co, Inc.; 2020 Mar.62723 - Macrilen (macimorelin) package insert. Frankfurt am Main, Germany: Aeterna Zentaris GmbH; 2018 Jan.62853 - Amin M, Suksomboon N. Pharmacotherapy of type 2 diabetes mellitus: an update on drug-drug interactions. Drug Saf. 2014;37:903-919.63161 - Lucemyra (lofexidine) tablets package insert. Louisville, KY: US WorldMeds, LLC; 2018 May.63317 - Braftovi (encorafenib) capsules package insert. Boulder, CO: Array BioPharma Inc.; 2020 April.63368 - Tibsovo (ivosidenib) tablet package insert. Cambridge, MA: Agios Pharmaceuticals; 2021 Aug.63571 - Copiktra (duvelisib) capsules package insert. Las Vegas, NV: Secura Bio, Inc.; 2021 Sept.63777 - Daurismo (glasdegib) tablets package insert. New York, NY: Pfizer Labs; 2020 Mar.63787 - Xospata (gilteritinib) tablets package insert. Northbrook, IL: Astellas Pharma US, Inc.; 2019 May.63790 - Firdapse (amifampridine) tablets package insert. Coral Gables, FL: Catalyst Pharmaceuticals, Inc.; 2021 Feb.63923 - The American Geriatrics Society 2019 Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2019;00:1-21.63936 - Lamprene (clofazimine) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2019 Jan.63962 - Egaten (triclabendazole) package insert. East Hanover, NJ: Novartis Pharmaceuticals; 2019 Feb.64002 - Pyridostigmine Bromide oral solution package insert. East Windsor, NJ: Novitium Pharma LLC; 2019 Mar.64031 - Mayzent (siponimod) tablets package insert. East Hanover, NJ: Novartis Pharmaceutical Corporation; 2021 Aug.64165 - Dexamethasone (Decadron) tablets package insert. Whitehouse Station, NJ: Merck & Co., Inc.; 2019 May.64391 - Beach SR, Kostis WJ, Celano CM, et al. Meta-analysis of selective serotonin reuptake inhibitor-associated QTc prolongation. J Clin Psychiatry 2014;75:e441-e449.64392 - Glassman AH, O'Connor CM, Califf RM, et al. Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA 2002;288:701-709.64394 - O'Connor CM, Jiang W, Kuchibhatla M, et al. Safety and efficacy of sertraline for depression in patients with heart failure: results of the SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial. J Am Coll Cardiol 2010;56:692-699.64395 - Brouillette J, Nattel S. A practical approach to avoiding cardiovascular adverse effects of psychoactive medications. Can J Cardiol 2017;33:1577-1586.64396 - Beach SR, Celano CM, Sugrue AM, et al. QT prolongation, torsades de pointes, and psychotropic medications: a 5-year update. Psychosomatics 2018;59:105-122.64562 - Wakix (pitolisant) tablets package insert. Plymouth Meeting, PA: Harmony Biosciences, LLC; 2020 Oct.64568 - Inrebic (fedratinib) capsules package insert. Summit, NJ: Celgene Corporation; 2019 Aug.64576 - Xenleta (lefamulin) package insert. Dublin, Ireland: Nabriva Therapeutics US, Inc.; 2021 Mar.64721 - Ibrance (palbociclib) tablets package insert. New York, NY: Pfizer Inc; 2019 Nov.65068 - Barhemsys (amisulpride) package insert. Indianapolis, IN: Acacia Pharma Inc; 2021 May.65098 - Isturisa (osilodrostat) tablet package insert. Lebanon, NJ: Recordati Rare Disease, Inc.; 2020 Mar.65107 - Kroger A, Bahta L, Hunter P. General Best Practice Guidelines for Immunization. Best Practices Guidance of the Advisory Committee on Immunization Practices (ACIP). Available on the world wide web at https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/downloads/general-recs.pdf. Accessed on July 26, 202165157 - CredibleMeds. COVID-19 experimental therapies and TdP risk. Available on the World Wide Web at http://https://crediblemeds.org/blog/covid-19-experimental-therapies-and-tdp-risk. Accessed March 23, 2020.65169 - Ozanimod (Zeposia) capsules package insert. Summit, NJ: Celgene Corporation; 2021 May.65170 - Giudicessi JR, Noseworthy PA, Friedman PA, Ackerman MJ. Urgent guidance for navigating and circumventing the QTc prolonging and torsadogenic potential of possible pharmacotherapies for COVID-19 [published online ahead of print, March 25, 2020]. Mayo Clin Proc 2020;95.65295 - Tukysa (tucatinib) tablets package insert. Bothell, WA: Seattle Genetics, Inc.; 2020 April.65387 - Retevmo (selpercatinib) capsules package insert. Indianapolis, IN: Eli Lilly and Company; 2020 May.65562 - Levofloxacin tablets package insert. Livonia, MI; Major Pharmaceuticals: 2019 Nov.65576 - Uplizna (inebilizumab-edon) injection package insert. Gaithersburg, MD: Viela Bio, Inc.; 2020 Jun.65666 - Rukobia (fostemsavir) package insert. Research Triangle Park, NC: ViiV Healthcare; 2020 Jul.65783 - Coats AL, Wanger J, Cockcroft DW, et al. ERS technical standard on bronchial challenge testing: general considerations and performance of methacholine challenge tests. Eur Respir J 2017;49(5):1601526.65850 - Kesimpta (ofatumumab) injection package insert. East Hanover, NJ: Novartis Pharmaceutical Corporation; 2020 Aug.66080 - Food and Drug Administration (FDA). Fact Sheet for Healthcare Providers Administering Vaccine: Emergency Use Authorization (EUA) of Pfizer-BioNTech COVID-19 Vaccine to Prevent Coronavirus Disease 2019 (COVID-19). Retrieved Sept 22, 2021.66129 - Zokinvy (lonafarnib) capsules package insert. Palo Alto, CA: Eiger BioPharmaceuticals, Inc.; 2020 Nov.66159 - Orladeyo (berotralstat) package insert. Durham, NC;BioCryst Pharmaceuticals, Inc.: 2020 Dec.66183 - Orgovyx (relugolix) tablets package insert. Brisbane, CA: Myovant Sciences, Inc.; 2020 Dec.66336 - Lupkynis (voclosporin) capsules package insert. Rockville, MD: Aurinia Pharma U.S., Inc.; 2021 Jan.66338 - Caffeine, sodium benzoate injection package insert. Shirley, NY: American Regent, Inc; 2005 Nov.66527 - Ponvory (ponesimod) tablet package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2021 Mar.66990 - Exkivity (mobocertinib) capsules package insert. Lexington, MA: Takeda Pharmaceuticals America, Inc.; 2021 Sept.

    Monitoring Parameters

    • blood glucose
    • pulmonary function tests (PFTs)
    • serum potassium

    US Drug Names

    • Symbicort
    ;