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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) 2022. Retrieved 12/3/2021. Available on the World Wide Web at https://goldcopd.org/wp-content/uploads/2021/11/GOLD-REPORT-2022-v1.1-22Nov2021_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) 2022. Retrieved 12/3/2021. Available on the World Wide Web at https://goldcopd.org/wp-content/uploads/2021/11/GOLD-REPORT-2022-v1.1-22Nov2021_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
    • supraventricular tachycardia (SVT)
    • wheezing

    Severe

    • anaphylactoid reactions
    • angioedema
    • asthma-related death
    • atrial fibrillation
    • bronchospasm
    • increased intracranial pressure
    • ocular hypertension

    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]

    Formoterol, like other beta2-agonists and sympathomimetic amines, can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate (sinus tachycardia), systolic or diastolic blood pressure (hypertension), and/or symptoms or cardiac arrhythmias, such as supraventricular tachycardia (SVT) and extrasystoles (palpitations). Although such effects are uncommon after administration of formoterol at recommended doses, if such effects occur then budesonide; formoterol may need to be discontinued. Beta-agonists have been reported to produce ECG changes, such as flattening of the T wave, QT prolongation, and ST segment depression; the clinical significance of these findings is unknown. Beta2-agonist medications may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects. The decrease in serum potassium is usually transient, not requiring supplementation. During long-term safety studies in adolescent and adult patients 12 years of age and older, treated for up to 1 year, no significant or unexpected chemistry, ECG, or Holter monitor assessments occurred. During postmarketing experience, angina pectoris, cardiac arrhythmias (e.g., atrial fibrillation, ventricular extrasystoles, and tachyarrhythmias), palpitations, QT interval prolonged on ECG, increased blood pressure, including hypertension, hypotension, and hypokalemia have been reported with formoterol; budesonide or other products containing formoterol.[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]

    Clinically significant changes in blood glucose were seen infrequently during clinical studies with budesonide; formoterol at recommended doses. Hyperglycemia has been reported postmarketing.[32950] [65232]

    Revision Date: 11/03/2022, 11:44:44 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=Eloqua65232 - 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/

    Contraindications/Precautions

    Absolute contraindications are italicized.

    • status asthmaticus
    • acute bronchospasm
    • asthma-related death
    • breast-feeding
    • cardiac arrhythmias
    • cataracts
    • children
    • coronary artery disease
    • corticosteroid hypersensitivity
    • corticosteroid therapy
    • diabetes mellitus
    • fungal infection
    • glaucoma
    • growth inhibition
    • hepatic disease
    • herpes infection
    • hyperglycemia
    • hypertension
    • hyperthyroidism
    • hypokalemia
    • hypothalamic-pituitary-adrenal (HPA) suppression
    • increased intracranial pressure
    • increased intraocular pressure
    • infants
    • infection
    • labor
    • MAOI therapy
    • measles
    • neonates
    • osteopenia
    • osteoporosis
    • paradoxical bronchospasm
    • pheochromocytoma
    • pregnancy
    • QT prolongation
    • seizure disorder
    • 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.

    Formoterol, like other beta2-agonists and sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency (coronary artery disease), cardiac arrhythmias, and hypertension. Formoterol can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, and cardiac arrhythmias, such as supraventricular tachycardia and extrasystoles. If such effects occur, budesonide; formoterol inhalation may need to be discontinued. In addition, beta-agonists have been reported to produce electrocardiographic changes, such as flattening of the T wave, QT prolongation, and ST segment depression, although the clinical significance of these findings is unknown. Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Beta-adrenergic agonist therapies like formoterol may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects. The decrease in serum potassium is usually transient, not requiring supplementation.[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 (thyrotoxicosis), seizure disorder, pheochromocytoma, or other unusual responsiveness to sympathomimetic amines.[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: 11/01/2022, 03:42:53 PM

    References

    27616 - Butani L. Corticosteroid-induced hypersensitivity reactions. Ann Allergy Asthma Immunol 2002;89(5):439-445.32950 - 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;185:279-28062717 - 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.

    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
    • Metyrapone

    Level 2 (Major)

    • Abarelix
    • Arformoterol
    • Aspirin, ASA; Citric Acid; Sodium Bicarbonate
    • Ceritinib
    • Dabrafenib
    • Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
    • Desmopressin
    • Dofetilide
    • Duvelisib
    • Fluticasone; Salmeterol
    • Fluticasone; Umeclidinium; Vilanterol
    • Fluticasone; Vilanterol
    • Fosamprenavir
    • grapefruit juice
    • Idelalisib
    • Indacaterol
    • Indacaterol; Glycopyrrolate
    • Lopinavir; Ritonavir
    • Macimorelin
    • Methacholine
    • Mifepristone
    • Natalizumab
    • Nirmatrelvir; Ritonavir
    • Olodaterol
    • Ombitasvir; Paritaprevir; Ritonavir
    • Omeprazole; Sodium Bicarbonate
    • Penicillamine
    • Procarbazine
    • Racepinephrine
    • Ritonavir
    • Salmeterol
    • Saquinavir
    • Sargramostim, GM-CSF
    • Sodium Bicarbonate
    • Tiotropium; Olodaterol
    • Umeclidinium; Vilanterol
    • Vigabatrin

    Level 3 (Moderate)

    • Abatacept
    • Acebutolol
    • Acetaminophen; Aspirin
    • Acetaminophen; Aspirin, ASA; Caffeine
    • Acetaminophen; Aspirin; Diphenhydramine
    • Acetaminophen; Caffeine
    • Acetaminophen; Caffeine; Dihydrocodeine
    • Acetaminophen; Caffeine; Pyrilamine
    • Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine
    • Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine
    • Acetaminophen; Chlorpheniramine; Phenylephrine
    • 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
    • Albiglutide
    • Alemtuzumab
    • 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
    • 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)
    • Antacids
    • Antithymocyte Globulin
    • Arsenic Trioxide
    • Articaine; Epinephrine
    • Asparaginase Erwinia chrysanthemi
    • Aspirin, ASA
    • Aspirin, ASA; Butalbital; Caffeine
    • Aspirin, ASA; Butalbital; Caffeine; Codeine
    • Aspirin, ASA; Caffeine
    • 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
    • Atracurium
    • Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
    • Azilsartan; Chlorthalidone
    • Benazepril; Hydrochlorothiazide, HCTZ
    • Bendroflumethiazide; Nadolol
    • Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
    • Benzphetamine
    • Berotralstat
    • Beta-adrenergic blockers
    • Betaxolol
    • Bismuth Subsalicylate
    • Bismuth Subsalicylate; Metronidazole; Tetracycline
    • Bisoprolol
    • Bisoprolol; Hydrochlorothiazide, HCTZ
    • Brimonidine; Timolol
    • Brompheniramine; Carbetapentane; Phenylephrine
    • Brompheniramine; Dextromethorphan; Phenylephrine
    • Brompheniramine; Phenylephrine
    • Brompheniramine; Pseudoephedrine
    • Brompheniramine; Pseudoephedrine; Dextromethorphan
    • Bumetanide
    • Bupivacaine; Epinephrine
    • Bupropion
    • Bupropion; Naltrexone
    • Butabarbital
    • Butalbital; Acetaminophen
    • Butalbital; Acetaminophen; Caffeine
    • Butalbital; Acetaminophen; Caffeine; Codeine
    • Caffeine
    • Caffeine; Sodium Benzoate
    • Calcium Carbonate
    • Calcium Carbonate; Famotidine; Magnesium Hydroxide
    • Calcium Carbonate; Magnesium Hydroxide
    • Calcium Carbonate; Magnesium Hydroxide; Simethicone
    • Calcium Carbonate; Risedronate
    • Calcium Carbonate; Simethicone
    • Calcium; Vitamin D
    • Canagliflozin
    • Canagliflozin; Metformin
    • Candesartan; Hydrochlorothiazide, HCTZ
    • Captopril; Hydrochlorothiazide, HCTZ
    • Carbetapentane; Chlorpheniramine; Phenylephrine
    • Carbetapentane; Diphenhydramine; Phenylephrine
    • Carbetapentane; Guaifenesin; Phenylephrine
    • Carbetapentane; Phenylephrine
    • Carbetapentane; Phenylephrine; Pyrilamine
    • Carbetapentane; Pseudoephedrine
    • Carbinoxamine; Dextromethorphan; Pseudoephedrine
    • Carbinoxamine; Phenylephrine
    • Carbinoxamine; Pseudoephedrine
    • Carteolol
    • Carvedilol
    • Cetirizine; Pseudoephedrine
    • Chlophedianol; Dexchlorpheniramine; Pseudoephedrine
    • Chlophedianol; Guaifenesin; Phenylephrine
    • Chlorothiazide
    • Chlorpheniramine; Dextromethorphan; Phenylephrine
    • Chlorpheniramine; Dextromethorphan; Pseudoephedrine
    • Chlorpheniramine; Dihydrocodeine; Phenylephrine
    • Chlorpheniramine; Ibuprofen; Pseudoephedrine
    • Chlorpheniramine; Phenylephrine
    • Chlorpheniramine; Pseudoephedrine
    • Chlorpropamide
    • Chlorthalidone
    • Chlorthalidone; Clonidine
    • Choline Salicylate; Magnesium Salicylate
    • Cimetidine
    • Ciprofloxacin
    • Cisatracurium
    • Clarithromycin
    • Cobicistat
    • Cocaine
    • Codeine; Guaifenesin; Pseudoephedrine
    • Codeine; Phenylephrine; Promethazine
    • Conivaptan
    • Crizotinib
    • Cyclosporine
    • Daclatasvir
    • Danazol
    • Dapagliflozin
    • Dapagliflozin; Metformin
    • Dapagliflozin; Saxagliptin
    • Darunavir
    • Darunavir; Cobicistat
    • Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
    • Deferasirox
    • Delafloxacin
    • Delavirdine
    • Denosumab
    • Desloratadine; Pseudoephedrine
    • Dexamethasone
    • Dexbrompheniramine; Pseudoephedrine
    • Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine
    • Dextroamphetamine
    • Dextromethorphan; Bupropion
    • Dextromethorphan; Diphenhydramine; Phenylephrine
    • Dextromethorphan; Guaifenesin; Phenylephrine
    • Dextromethorphan; Guaifenesin; Pseudoephedrine
    • Dichlorphenamide
    • Diethylpropion
    • Dipeptidyl Peptidase-4 Inhibitors
    • Diphenhydramine; Phenylephrine
    • Dobutamine
    • Dopamine
    • Dorzolamide; Timolol
    • Doxacurium
    • Dronedarone
    • Droperidol
    • Dulaglutide
    • Dyphylline
    • Dyphylline; Guaifenesin
    • Echinacea
    • Elexacaftor; tezacaftor; ivacaftor
    • Eliglustat
    • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
    • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
    • Empagliflozin
    • Empagliflozin; Linagliptin
    • Empagliflozin; Linagliptin; Metformin
    • Empagliflozin; Metformin
    • Enalapril; Hydrochlorothiazide, HCTZ
    • Encorafenib
    • Ephedrine
    • Ephedrine; Guaifenesin
    • Epinephrine
    • Eprosartan; Hydrochlorothiazide, HCTZ
    • Ergotamine; Caffeine
    • Erlotinib
    • Ertugliflozin
    • Ertugliflozin; Metformin
    • Ertugliflozin; Sitagliptin
    • Erythromycin
    • Esmolol
    • Estrogens
    • Ethacrynic Acid
    • Etravirine
    • Exenatide
    • Famotidine
    • Fedratinib
    • Fexofenadine; Pseudoephedrine
    • Fluconazole
    • Fluoxymesterone
    • Fluvoxamine
    • Fosinopril; Hydrochlorothiazide, HCTZ
    • Furosemide
    • Gallium Ga 68 Dotatate
    • Gemifloxacin
    • Glecaprevir; Pibrentasvir
    • Glimepiride
    • Glimepiride; Rosiglitazone
    • Glipizide
    • Glipizide; Metformin
    • Glyburide
    • Glyburide; Metformin
    • Glycerol Phenylbutyrate
    • Griseofulvin
    • Guaifenesin; Hydrocodone; Pseudoephedrine
    • Guaifenesin; Phenylephrine
    • Guaifenesin; Pseudoephedrine
    • Haloperidol
    • Hemin
    • Hydralazine; Hydrochlorothiazide, HCTZ
    • Hydrochlorothiazide, HCTZ
    • Hydrochlorothiazide, HCTZ; Methyldopa
    • Hydrochlorothiazide, HCTZ; Moexipril
    • Hydrocodone; Pseudoephedrine
    • Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate
    • Ibritumomab Tiuxetan
    • Ibuprofen; Famotidine
    • Ibuprofen; Pseudoephedrine
    • Incretin Mimetics
    • Indapamide
    • Inebilizumab
    • Insulin Degludec; Liraglutide
    • Insulin Glargine; Lixisenatide
    • Insulins
    • Irbesartan; Hydrochlorothiazide, HCTZ
    • Isavuconazonium
    • Isocarboxazid
    • Isoproterenol
    • Itraconazole
    • Ivacaftor
    • Ivosidenib
    • Ketoconazole
    • L-Asparaginase Escherichia coli
    • Labetalol
    • Lansoprazole; Amoxicillin; Clarithromycin
    • Lefamulin
    • Letermovir
    • Levobetaxolol
    • Levobunolol
    • Levofloxacin
    • Levoketoconazole
    • Levothyroxine
    • Levothyroxine; Liothyronine (Porcine)
    • Levothyroxine; Liothyronine (Synthetic)
    • Lidocaine; Epinephrine
    • Linagliptin; Metformin
    • Linezolid
    • Liothyronine
    • Liraglutide
    • Lisinopril; Hydrochlorothiazide, HCTZ
    • Lixisenatide
    • Lonafarnib
    • Lonapegsomatropin
    • Loop diuretics
    • Loratadine; Pseudoephedrine
    • Losartan; Hydrochlorothiazide, HCTZ
    • Lumacaftor; Ivacaftor
    • Lumacaftor; Ivacaftor
    • Magnesium Hydroxide
    • Magnesium Salicylate
    • Mannitol
    • Mecasermin rinfabate
    • Mecasermin, Recombinant, rh-IGF-1
    • Meglitinides
    • Metformin
    • Metformin; Repaglinide
    • Metformin; Rosiglitazone
    • Metformin; Saxagliptin
    • Metformin; Sitagliptin
    • Methamphetamine
    • Methazolamide
    • Methenamine; Sodium Acid Phosphate
    • Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine
    • Methenamine; Sodium Salicylate
    • Methyclothiazide
    • Metolazone
    • Metoprolol
    • Metoprolol; Hydrochlorothiazide, HCTZ
    • Micafungin
    • Midodrine
    • Mitotane
    • Mivacurium
    • Modafinil
    • Monoamine oxidase inhibitors
    • Moxifloxacin
    • Nadolol
    • Nafcillin
    • Naproxen; Pseudoephedrine
    • Nateglinide
    • Nebivolol
    • Nebivolol; Valsartan
    • Nefazodone
    • Nelfinavir
    • Neostigmine
    • Neuromuscular blockers
    • Nizatidine
    • Nonsteroidal antiinflammatory drugs
    • Norepinephrine
    • Ofatumumab
    • Ofloxacin
    • Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ
    • Olmesartan; Hydrochlorothiazide, HCTZ
    • Oxymetholone
    • Palbociclib
    • Pancuronium
    • Pazopanib
    • Pegaspargase
    • Penbutolol
    • Phendimetrazine
    • Phenelzine
    • Phenobarbital
    • Phenobarbital; Hyoscyamine; Atropine; Scopolamine
    • Phentermine
    • Phentermine; Topiramate
    • Phenylephrine
    • Physostigmine
    • Pimozide
    • Pindolol
    • Pioglitazone; Glimepiride
    • Pioglitazone; Metformin
    • Ponesimod
    • Posaconazole
    • Potassium Phosphate; Sodium Phosphate
    • Pramlintide
    • Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements)
    • Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved)
    • Prilocaine; Epinephrine
    • Primidone
    • Promethazine; Phenylephrine
    • Propranolol
    • Propranolol; Hydrochlorothiazide, HCTZ
    • Pseudoephedrine
    • Pseudoephedrine; Triprolidine
    • Pyridostigmine
    • Quinapril; Hydrochlorothiazide, HCTZ
    • Rapacuronium
    • Rasagiline
    • Repaglinide
    • Ribociclib
    • Ribociclib; Letrozole
    • Rituximab
    • Rituximab; Hyaluronidase
    • Rocuronium
    • Salicylates
    • Salsalate
    • SARS-CoV-2 (COVID-19) vaccines
    • Semaglutide
    • SGLT2 Inhibitors
    • Sodium Benzoate; Sodium Phenylacetate
    • Sodium Phenylbutyrate
    • Sodium Phenylbutyrate; Taurursodiol
    • Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous
    • Sofosbuvir; Velpatasvir; Voxilaprevir
    • Somatropin, rh-GH
    • Spironolactone; Hydrochlorothiazide, HCTZ
    • Succinylcholine
    • Sulfonylureas
    • Telbivudine
    • Telmisartan; Hydrochlorothiazide, HCTZ
    • Temsirolimus
    • Testosterone
    • Tezacaftor; Ivacaftor
    • Theophylline, Aminophylline
    • Thiazide diuretics
    • Thiazolidinediones
    • Thyroid hormones
    • Timolol
    • Tirzepatide
    • Tolazamide
    • Tolbutamide
    • Torsemide
    • Trandolapril; Verapamil
    • Tranylcypromine
    • Triamterene; Hydrochlorothiazide, HCTZ
    • Tuberculin Purified Protein Derivative, PPD
    • Tucatinib
    • Valsartan; Hydrochlorothiazide, HCTZ
    • Vecuronium
    • Vemurafenib
    • Verapamil
    • Vincristine Liposomal
    • Vonoprazan; Amoxicillin
    • Vonoprazan; Amoxicillin; Clarithromycin
    • Voriconazole
    • Vorinostat
    • Voxelotor
    • Warfarin

    Level 4 (Minor)

    • Aldesleukin, IL-2
    • Altretamine
    • Aminolevulinic Acid
    • Aprepitant, Fosaprepitant
    • Azathioprine
    • Basiliximab
    • Bexarotene
    • Bortezomib
    • Cabozantinib
    • Carmustine, BCNU
    • Chlorambucil
    • Clofarabine
    • Denileukin Diftitox
    • Dexlansoprazole
    • Diltiazem
    • Econazole
    • Elbasvir; Grazoprevir
    • Esomeprazole
    • Estramustine
    • Hydroxyurea
    • Indinavir
    • Interferon Alfa-2a
    • Interferon Alfa-2b
    • Interferon Alfa-2b; Ribavirin
    • Isotretinoin
    • Lansoprazole
    • Lansoprazole; Naproxen
    • Ledipasvir; Sofosbuvir
    • Lomustine, CCNU
    • Methoxsalen
    • Mitoxantrone
    • Naproxen; Esomeprazole
    • Nelarabine
    • Nicardipine
    • Omeprazole
    • Omeprazole; Amoxicillin; Rifabutin
    • Oritavancin
    • Pantoprazole
    • Photosensitizing agents (topical)
    • Potassium-sparing diuretics
    • Proton pump inhibitors
    • Purine analogs
    • Rabeprazole
    • Simeprevir
    • Telithromycin
    • Tositumomab
    • Tretinoin, ATRA
    • 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) 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. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's 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. [28618] [43675] [44979] [51834] [58220] Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists. [66338] (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. [24574] [28502] Acetaminophen; Aspirin: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. [24574] [28502] Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. [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; Pyrilamine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists. [66338] 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) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] 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; 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) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] 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) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] 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) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] 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 blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Acrivastine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] Albiglutide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [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] Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] Alogliptin; Metformin: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [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 more than 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 more than 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 more than 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 more than 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 more than 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) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] 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) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. [24574] [28502] Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] 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] (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) Monitor blood pressure and heart rate during concomitant amphetamine; dextroamphetamine and formoterol use. Concomitant use may potentiate sympathetic effects. [31563] [33259] Amphetamine; Dextroamphetamine Salts: (Moderate) Monitor blood pressure and heart rate during concomitant amphetamine; dextroamphetamine and formoterol use. Concomitant use may potentiate sympathetic effects. [31563] [33259] Amphetamine; Dextroamphetamine: (Moderate) Monitor blood pressure and heart rate during concomitant amphetamine; dextroamphetamine and formoterol use. Concomitant use may potentiate sympathetic effects. [31563] [33259] 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] Antacids: (Moderate) Enteric-coated budesonide granules dissolve at a pH more than 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] 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] Arsenic Trioxide: (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] Articaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] [56575] (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine. [26417] [56575] 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) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. [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) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. [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) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. [24574] [28502] Aspirin, ASA; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists. [66338] (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. [24574] [28502] Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists. [66338] (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. [24574] [28502] Aspirin, ASA; Carisoprodol: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. [24574] [28502] Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. [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) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. [24574] [28502] Aspirin, ASA; Dipyridamole: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. [24574] [28502] Aspirin, ASA; Omeprazole: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. [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) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. [24574] [28502] Aspirin, ASA; Pravastatin: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. [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) 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. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's 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. [28618] [43675] [44979] [51834] [58220] Atenolol; Chlorthalidone: (Moderate) 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. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's 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. [28618] [43675] [44979] [51834] [58220] (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] 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) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. [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) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] 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] Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] Bendroflumethiazide; Nadolol: (Moderate) 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. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's 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. [28618] [43675] [44979] [51834] [58220] (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. [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] 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) 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. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's 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. [28618] [43675] [44979] [51834] [58220] Betaxolol: (Moderate) 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. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's 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. [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 Subsalicylate: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. [24574] [28502] Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. [24574] [28502] Bisoprolol: (Moderate) 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. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's 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. [28618] [43675] [44979] [51834] [58220] Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) 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. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's 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. [28618] [43675] [44979] [51834] [58220] (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] 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] Brimonidine; Timolol: (Moderate) 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. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's 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. [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; 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) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] Bumetanide: (Moderate) Use beta-agonists and loop diuretics with caution due to risk for ECG changes and/or hypokalemia. The ECG changes and/or hypokalemia that may result from administration of loop diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. [43675] [44979] [49951] Bupivacaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] [56575] (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine. [26417] [56575] Bupropion: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk. [44094] Bupropion; Naltrexone: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk. [44094] 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] 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: (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. 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: (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. 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 loss of oral, enteric-coated budesonide efficacy during concomitant famotidine use. Since the dissolution of oral, enteric-coated budesonide is pH dependent, the release properties and uptake of the drug may be altered when used after H2-blockers. [34979] [52910] Calcium Carbonate; 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. 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; 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. 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: (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. 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: (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. 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; Vitamin D: (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. 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 blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Canagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] 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) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] 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) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] 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) 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. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's 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. [28618] [43675] [44979] [51834] [58220] Carvedilol: (Moderate) 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. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's 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. [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] Cetirizine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] 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] Chlorothiazide: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] 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) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] 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; Ibuprofen; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] 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) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] Chlorpropamide: (Moderate) Monitor blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Chlorthalidone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] Chlorthalidone; Clonidine: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] Choline Salicylate; Magnesium Salicylate: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. [24574] [28502] Cimetidine: (Moderate) Monitor for loss of oral, enteric-coated budesonide efficacy and budesonide-related adverse events during concomitant cimetidine use. Since the dissolution of oral, enteric-coated budesonide is pH dependent, the release properties and uptake of the drug may be altered when used after H2-blockers. In an open, non-randomized, cross-over study, coadministration of cimetidine resulted in a 52% and 31% increase in the budesonide peak plasma concentration and AUC, respectively, after administration of cimetidine 1 g/day (200 mg with meals and 400 mg at night) for 2 separate 3-day periods where oral, delayed-release budesonide 4 mg was administered either alone or on the last day of a cimetidine treatment period. [34979] [52910] Ciprofloxacin: (Moderate) Avoid coadministration of oral budesonide with ciprofloxacin due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and ciprofloxacin is a moderate CYP3A inhibitor. Also, 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. [28764] [34979] [56579] 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] 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] 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] 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) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] Codeine; Phenylephrine; Promethazine: (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] 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] Cyclosporine: (Moderate) Avoid coadministration of oral budesonide and cyclosporine if possible due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure of budesonide may also increase. Budesonide is a CYP3A4 substrate; cyclosporine is a CYP3A4 inhibitor. In the presence of another CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [67192] 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 blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Dapagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Dapagliflozin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [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] 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] Delafloxacin: (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. [62028] 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] Desloratadine; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] Desmopressin: (Major) Desmopressin is contraindicated with concomitant inhaled or systemic corticosteroid use due to an increased risk of hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer. [42295] [61806] 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) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] 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] Dextroamphetamine: (Moderate) Monitor blood pressure and heart rate during concomitant amphetamine; dextroamphetamine and formoterol use. Concomitant use may potentiate sympathetic effects. [31563] [33259] Dextromethorphan; Bupropion: (Moderate) Monitor for seizure activity during concomitant bupropion and corticosteroid use. Bupropion is associated with a dose-related seizure risk; concomitant use of other medications that lower the seizure threshold, such as systemic corticosteroids, increases the seizure risk. [44094] 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) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] 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] 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 blood glucose during concomitant corticosteroid and dipeptidyl peptidase-4 (DPP-4) inhibitor use; a DPP-4 dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] 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] 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] 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) 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. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's 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. [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] Dronedarone: (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] Dulaglutide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [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] 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] 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 blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Empagliflozin; Linagliptin: (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Empagliflozin; Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Empagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] 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] 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) Monitor blood pressure and heart rate during concomitant epinephrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] [56575] (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine. [26417] [56575] Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] Ergotamine; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists. [66338] 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 blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Ertugliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Ertugliflozin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Erythromycin: (Moderate) Avoid coadministration of oral budesonide with erythromycin due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. [28251] [34979] Esmolol: (Moderate) 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. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's 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. [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) Monitor for corticosteroid-related adverse events if corticosteroids are used with estrogens. Concurrent use may increase the exposure of corticosteroids. Estrogens may decrease the hepatic clearance of corticosteroids thereby increasing their effect. [29779] [54049] Ethacrynic Acid: (Moderate) Use beta-agonists and loop diuretics with caution due to risk for ECG changes and/or hypokalemia. The ECG changes and/or hypokalemia that may result from administration of loop diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. [43675] [44979] [49951] 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 blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Famotidine: (Moderate) Monitor for loss of oral, enteric-coated budesonide efficacy during concomitant famotidine use. Since the dissolution of oral, enteric-coated budesonide is pH dependent, the release properties and uptake of the drug may be altered when used after H2-blockers. [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) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] Fluconazole: (Moderate) Avoid coadministration of oral budesonide with fluconazole due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor. [28674] [34979] 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] 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] Fosamprenavir: (Major) Avoid coadministration of oral budesonide with fosamprenavir due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. [29012] [34979] Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] Furosemide: (Moderate) Use beta-agonists and loop diuretics with caution due to risk for ECG changes and/or hypokalemia. The ECG changes and/or hypokalemia that may result from administration of loop diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. [43675] [44979] [49951] Gallium Ga 68 Dotatate: (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] Gemifloxacin: (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. [28424] 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 blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Glimepiride; Rosiglitazone: (Moderate) Monitor blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Glipizide: (Moderate) Monitor blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Glipizide; Metformin: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] (Moderate) Monitor blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Glyburide: (Moderate) Monitor blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Glyburide; Metformin: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] (Moderate) Monitor blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [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] 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) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] 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) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] 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] Hemin: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Corticosteroids increase the activity of this enzyme should not be used with hemin. [6702] Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] Hydrocodone; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] 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] Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. [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) 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; Famotidine: (Moderate) Monitor for loss of oral, enteric-coated budesonide efficacy during concomitant famotidine use. Since the dissolution of oral, enteric-coated budesonide is pH dependent, the release properties and uptake of the drug may be altered when used after H2-blockers. [34979] [52910] Ibuprofen; Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] 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] Incretin Mimetics: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [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] Insulin Degludec; Liraglutide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Insulin Glargine; Lixisenatide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Insulins: (Moderate) Monitor blood glucose during concomitant corticosteroid and insulin use; an insulin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [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) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] 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: (Moderate) Use beta-agonists with caution in patients receiving concomitant monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping treatment with MAOIs because the action of beta-agonists on the cardiovascular system may be potentiated. [27957] [28309] [28467] [29656] [30438] [32901] [44979] [49951] [51793] [54633] [57710] 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) 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] Ketoconazole: (Moderate) Formoterol, as with other long-acting beta-agonists, should be administered with extreme caution to patients being treated with drugs known to prolong the QTc interval like ketoconazole because the effect of adrenergic agonists on the cardiovascular system may be potentiated. Drugs that are known to prolong the QTc interval have an increased risk of ventricular arrhythmias. Ketoconazole has been associated with prolongation of the QT interval and torsade de pointes (TdP). [27982] [62731] (Moderate) Monitor for corticosteroid-related adverse effects during chronic concomitant use of inhaled or nasal budesonide and ketoconazole. Avoid concomitant use of oral budesonide and ketoconazole. Budesonide is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. Ketoconazole has been observed to increase the overall exposure of oral budesonide by 8-fold. The total absolute bioavailability of inhaled and nasal budesonide products ranges from 6% to 39% of the labeled dose. [31824] [33486] [34376] [34979] [52910] [67192] Labetalol: (Moderate) 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. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's 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. [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] (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] 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] 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] Levobetaxolol: (Moderate) 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. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's 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. [28618] [43675] [44979] [51834] [58220] Levobunolol: (Moderate) 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. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's 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. [28618] [43675] [44979] [51834] [58220] Levofloxacin: (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. [65562] Levoketoconazole: (Moderate) Formoterol, as with other long-acting beta-agonists, should be administered with extreme caution to patients being treated with drugs known to prolong the QTc interval like ketoconazole because the effect of adrenergic agonists on the cardiovascular system may be potentiated. Drugs that are known to prolong the QTc interval have an increased risk of ventricular arrhythmias. Ketoconazole has been associated with prolongation of the QT interval and torsade de pointes (TdP). [27982] [62731] (Moderate) Monitor for corticosteroid-related adverse effects during chronic concomitant use of inhaled or nasal budesonide and ketoconazole. Avoid concomitant use of oral budesonide and ketoconazole. Budesonide is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. Ketoconazole has been observed to increase the overall exposure of oral budesonide by 8-fold. The total absolute bioavailability of inhaled and nasal budesonide products ranges from 6% to 39% of the labeled dose. [31824] [33486] [34376] [34979] [52910] [67192] Levothyroxine: (Moderate) Monitor blood pressure and heart rate during concomitant beta-agonist and thyroid hormone use. 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) Monitor blood pressure and heart rate during concomitant beta-agonist and thyroid hormone use. 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) Monitor blood pressure and heart rate during concomitant beta-agonist and thyroid hormone use. 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] Lidocaine; Epinephrine: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] [56575] (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine. [26417] [56575] Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [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) Monitor blood pressure and heart rate during concomitant beta-agonist and thyroid hormone use. 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 blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] Lixisenatide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] 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) Monitor potassium concentrations during concomitant corticosteroid and loop diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and loop diuretics cause increased renal potassium loss. [26417] [28429] [29779] (Moderate) Use beta-agonists and loop diuretics with caution due to risk for ECG changes and/or hypokalemia. The ECG changes and/or hypokalemia that may result from administration of loop diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. [43675] [44979] [49951] Lopinavir; 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] (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) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] 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] Magnesium Hydroxide: (Moderate) Enteric-coated budesonide granules dissolve at a pH more than 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) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. [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] 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] 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] Metformin: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Metformin; Repaglinide: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [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 blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Metformin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Metformin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Methacholine: (Major) Discontinue use of formoterol 36 hours before a methacholine challenge test. Beta-agonists inhibit the airway response to methacholine. [43792] [65783] 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] Methenamine; Sodium Salicylate: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. [24574] [28502] 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) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] Metolazone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] Metoprolol: (Moderate) 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. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's 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. [28618] [43675] [44979] [51834] [58220] Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) 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. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's 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. [28618] [43675] [44979] [51834] [58220] (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] 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] 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] 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] 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] 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: (Moderate) Use beta-agonists with caution in patients receiving concomitant monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping treatment with MAOIs because the action of beta-agonists on the cardiovascular system may be potentiated. [27957] [28309] [28467] [29656] [30438] [32901] [44979] [49951] [51793] [54633] [57710] Moxifloxacin: (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] Nadolol: (Moderate) 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. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's 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. [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) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] 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) 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. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's 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. [28618] [43675] [44979] [51834] [58220] Nebivolol; Valsartan: (Moderate) 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. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's 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. [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] Nicardipine: (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] Nirmatrelvir; 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] Nizatidine: (Moderate) Monitor for loss of oral, enteric-coated budesonide efficacy during concomitant nizatidine use. Since the dissolution of oral, enteric-coated budesonide is pH dependent, the release properties and uptake of the drug may be altered when used after H2-blockers. [34979] [52910] Nonsteroidal antiinflammatory drugs: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and nonsteroidal antiinflammatory drug (NSAID) use. Concomitant use increases the risk of GI bleeding. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection. [24574] [29611] [35893] [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] 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) 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. [30738] Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] 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] 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] Oxymetholone: (Moderate) Concomitant use of oxymetholone with corticosteroids or corticotropin, ACTH may cause increased edema. Manage edema with diuretic and/or digitalis therapy. [48342] 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] 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] 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] Pazopanib: (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) Monitor for an increase in glucocorticoid-related adverse reactions such as hyperglycemia and osteonecrosis during concomitant use of pegaspargase and glucocorticoids. [61310] Penbutolol: (Moderate) 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. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's 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. [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] 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: (Moderate) Use beta-agonists with caution in patients receiving concomitant monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping treatment with MAOIs because the action of beta-agonists on the cardiovascular system may be potentiated. [27957] [28309] [28467] [29656] [30438] [32901] [44979] [49951] [51793] [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) Monitor blood pressure and heart rate during concomitant phentermine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] Phentermine; Topiramate: (Moderate) Monitor blood pressure and heart rate during concomitant phentermine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] 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] 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] Pimozide: (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) 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. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's 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. [28618] [43675] [44979] [51834] [58220] Pioglitazone; Glimepiride: (Moderate) Monitor blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Pioglitazone; Metformin: (Moderate) Monitor blood glucose during concomitant corticosteroid and metformin use; a metformin dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Ponesimod: (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] 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-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) Monitor blood pressure and heart rate during concomitant epinephrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] [56575] (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine. [26417] [56575] 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] 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] Promethazine; 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] Propranolol: (Moderate) 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. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's 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. [28618] [43675] [44979] [51834] [58220] (Moderate) Monitor blood sugar during concomitant corticosteroid and propranolol use due to risk for hypoglycemia. Concurrent use may increase risk of hypoglycemia because of loss of the counter-regulatory cortisol response. [56853] Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) 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. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's 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. [28618] [43675] [44979] [51834] [58220] (Moderate) Monitor blood sugar during concomitant corticosteroid and propranolol use due to risk for hypoglycemia. Concurrent use may increase risk of hypoglycemia because of loss of the counter-regulatory cortisol response. [56853] (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] 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] Pseudoephedrine: (Moderate) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] Pseudoephedrine; Triprolidine: (Moderate) Monitor blood pressure and heart rate during concomitant pseudoephedrine and formoterol use. Concomitant use may potentiate sympathetic effects. [33259] 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] Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] 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] 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] 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] 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] Salicylates: (Moderate) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. [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) Monitor for gastrointestinal toxicity during concurrent corticosteroid and salicylate use. Concomitant use increases the risk of GI bleeding. In patients receiving concomitant corticosteroids and chronic use of salicylates, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance. [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] 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] Semaglutide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] SGLT2 Inhibitors: (Moderate) Monitor blood glucose during concomitant corticosteroid and SGLT2 inhibitor use; a SGLT2 inhibitor dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [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] 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 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 Phenylbutyrate; Taurursodiol: (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] 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] Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] 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 blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] 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: (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) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] 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) Monitor for fluid retention during concurrent corticosteroid and testosterone use. Concurrent use may result in increased fluid retention. [33698] 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) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] (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 blood glucose during concomitant corticosteroid and thiazolidinedione use; a thiazolidinedione dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Thyroid hormones: (Moderate) Monitor blood pressure and heart rate during concomitant beta-agonist and thyroid hormone use. 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] Timolol: (Moderate) 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. Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patient's 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. [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] Tirzepatide: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Tolazamide: (Moderate) Monitor blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Tolbutamide: (Moderate) Monitor blood glucose during concomitant corticosteroid and sulfonylurea use; a sulfonylurea dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose 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] [51324] [62853] Torsemide: (Moderate) Use beta-agonists and loop diuretics with caution due to risk for ECG changes and/or hypokalemia. The ECG changes and/or hypokalemia that may result from administration of loop diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. [43675] [44979] [49951] 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 systemic budesonide with verapamil due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and verapamil is a moderate CYP3A inhibitor. [29702] [31824] [34695] [34979] [40025] Tranylcypromine: (Moderate) Use beta-agonists with caution in patients receiving concomitant monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping treatment with MAOIs because the action of beta-agonists on the cardiovascular system may be potentiated. [27957] [28309] [28467] [29656] [30438] [32901] [44979] [49951] [51793] [54633] [57710] 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) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] 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] 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) Monitor potassium concentrations during concomitant corticosteroid and thiazide diuretic use due to risk for additive hypokalemia; potassium supplementation may be necessary. Both corticosteroids and thiazide diuretics cause increased renal potassium loss. [26417] [29779] 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] Verapamil: (Moderate) Avoid coadministration of systemic budesonide with verapamil due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and verapamil is a moderate CYP3A inhibitor. [29702] [31824] [34695] [34979] [40025] 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] Vonoprazan; Amoxicillin: (Moderate) Monitor for altered response to budesonide in patients receiving vonoprazan with enteric-coated or extended-release formulations of oral budesonide. Enteric-coated budesonide granules (Entocort EC) dissolve at a pH greater than 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and drugs that increase gastric pH levels, such as vonoprazan, can cause these products to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. [34979] [52910] [67585] Vonoprazan; 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) Monitor for altered response to budesonide in patients receiving vonoprazan with enteric-coated or extended-release formulations of oral budesonide. Enteric-coated budesonide granules (Entocort EC) dissolve at a pH greater than 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and drugs that increase gastric pH levels, such as vonoprazan, can cause these products to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. [34979] [52910] [67585] 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] Vorinostat: (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] Voxelotor: (Moderate) Avoid coadministration of systemic budesonide with voxelotor due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor. [34979] [64778] 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] 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: 11/22/2022, 02:26:00 AM

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    Monitoring Parameters

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

    US Drug Names

    • Symbicort
    ;