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Jun.14.2021

Budesonide

Indications/Dosage

Labeled

  • allergic rhinitis
  • asthma maintenance
  • Crohn's disease
  • perennial allergies
  • seasonal allergies
  • ulcerative colitis

INHALED DOSAGE RANGES BY PRODUCT

The ranges presented help define low, medium, and high ICS daily dosing according to asthma treatment recommendations.[64807][33558] The NAEPP 2020 focused updates state that ICS ranges from the NAEPP 2007 guidelines need to be updated in future NAEPP guidance.[66299]

 

Budesonide dry powder inhaler

Children 4 years and younger: Not available

 

Children 5 years:

  • GINA: Not available
  • NAEPP
    • Low Dose: 180 mcg to 400 mcg
    • Medium Dose: more than 400 mcg and up to 800 mcg
    • High Dose: more than 800 mcg

 

Children 6 to 11 years:

  • GINA
    • Low Dose: 100 mcg to 200 mcg
    • Medium Dose: more than 200 mcg and up to 400 mcg
    • High Dose: more than 400 mcg
  • NAEPP
    • Low Dose: 180 mcg to 400 mcg
    • Medium Dose: more than 400 mcg and up to 800 mcg
    • High Dose: more than 800 mcg

 

Adults, Adolescents, and Children 12 years and older:

  • GINA
    • Low Dose: 200 mcg to 400 mcg
    • Medium Dose: more than 400 mcg and up to 800 mcg
    • High Dose: more than 800 mcg
  • NAEPP
    • Low Dose: 180 mcg to 600 mcg
    • Medium Dose: more than than 600 mcg and up to 1,200 mcg
    • High Dose: more than 1,200 mcg

 

Budesonide nebulizer suspension

Infants:

  • GINA: Not available
  • NAEPP:
    • Low Dose: 0.25 mg to 0.5 mg
    • Medium Dose: more than 0.5 mg and up to 1 mg
    • High Dose: more than 1 mg

 

Children 1 to 4 years:

  • GINA
    • Low Dose: 0.5 mg (for ages 1 year and older)
    • Medium Dose: NA
    • High Dose: NA
  • NAEPP
    • Low Dose: 0.25 mg to 0.5 mg
    • Medium Dose: more than 0.5 mg and up to 1 mg
    • High Dose: more than 1 mg

 

Children 5 years:

  • GINA
    • Low Dose: 0.5 mg
    • Medium Dose: NA
    • High Dose: NA
  • NAEPP
    • Low Dose: 0.5 mg
    • Medium Dose: 1 mg
    • High Dose: 2 mg

 

Children 6 to 11 years:

  • GINA
    • Low Dose: 0.25 mg to 0.5 mg
    • Medium Dose: more than 0.5 mg and up to 1 mg
    • High Dose: more than 1 mg
  • NAEPP
    • Low Dose: 0.5 mg
    • Medium Dose: 1 mg
    • High Dose: 2 mg

 

Adults, Adolescents, and Children 12 years and older: Not available

Off-Label

  • bronchospasm
  • chronic bronchitis
  • chronic obstructive pulmonary disease (COPD)
  • colitis
  • emphysema
  • exercise-induced bronchospasm prophylaxis
  • laryngotracheobronchitis (croup)
† Off-label indication

For asthma maintenance treatment

Oral Inhalation dosage (inhalation powder; e.g., Pulmicort Flexhaler)

Adults

360 mcg (2 oral inhalations of 180 mcg/actuation) twice daily is the recommended starting dosage; 180 mcg (1 actuation) twice daily may be appropriate for some patients. Max: 4 oral inhalations of 180 mcg/actuation twice daily (720 mcg twice daily). Titrate to the lowest effective dose once asthma stability is achieved.[34376]

Children and Adolescents 6 years and older

180 mcg (1 oral inhalation of 180 mcg/actuation or 2 oral inhalations of 90 mcg/actuation) twice daily is the recommended starting dosage; a higher dose of 360 mcg (2 oral inhalations of 180 mcg/actuation) twice daily may be appropriate for some patients. Max: 2 oral inhalations of 180 mcg/actuation twice daily (360 mcg twice daily). Titrate to the lowest effective dose once asthma stability is achieved.[34376]

for asthma maintenance treatment using nebulized dosage form

Nebulized Inhalation dosage (suspension for nebulization; e.g., Pulmicort Respules)

Adults†

Not FDA-approved in U.S. for adults. European usual dose for severe asthma is 1 to 2 mg via nebulizer twice daily. Usual maintenance dose is 0.5 to 1 mg via nebulizer twice daily; may increase during exacerbations or severe asthma. Max: 4 mg/day. Titrate to lowest effective dose once stable.[65955]

Children and Adolescents 12 years and older†

Not FDA-approved in U.S. in this age group. European usual dose for severe asthma is 1 to 2 mg via nebulizer twice daily. Usual maintenance dose is 0.5 to 1 mg via nebulizer twice daily; may increase during exacerbations or severe asthma. Max: 4 mg/day. Titrate to lowest effective dose once stable.[65955]

Children 9 to 11 years†

Not FDA-approved in U.S. for this age group. European usual dose for severe asthma is 0.5 to 1 mg via nebulizer twice daily. Usual maintenance dose is 0.25 to 0.5 mg via nebulizer twice daily; may increase during exacerbations or severe asthma. Max: 1 mg/day. Titrate to lowest effective dose once stable.[65955]

Children 1 to 8 years

Dosing is based on previous therapies: PREVIOUSLY ON BRONCHODILATORS ALONE: Give 0.5 mg once daily or 0.25 mg twice daily via nebulizer. A dose of 0.25 mg via nebulizer once daily may be considered for some patients. Max: 0.5 mg/day. PREVIOUSLY ON INHALED CORTICOSTEROIDS (CS): Give 0.5 mg once daily or 0.25 mg twice daily via nebulizer; may give 0.5 mg via nebulizer twice daily. Max: 1 mg/day. PREVIOUSLY TAKING ORAL CS: Give 0.5 mg twice daily or 1 mg once daily via nebulizer. Max: 1 mg/day. ADJUSTMENTS: If once-daily treatment does not provide adequate control, increase the daily dose and/or administer in divided doses twice daily. Titrate to the lowest effective dose once asthma stability is achieved.[33486] Short-term, high-dose nebulized budesonide can have an early clinical effect by day 2 of treatment.[26690]

Infants 3 months and older†

Safety and efficacy have not been established; not FDA-approved. In Europe, the usual maintenance dose is 0.25 to 0.5 mg via nebulizer twice daily.[65955] Limited data from small safety studies used 0.25 to 1 mg/day via nebulizer either once daily or divided into 2 doses. Infants who received budesonide for mild to moderate persistent/recurrent asthma experienced reduced growth velocity vs. the placebo group. These studies were not desgined to determine efficacy.[33594] [33595] 

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

Oral Inhalation dosage; (inhalation powder; e.g., Pulmicort Flexhaler)

Adults

GINA recommends 180 to 360 mcg (1 to 2 oral inhalations of 180 mcg/actuation) as needed whenever short-acting beta-2 agonist (SABA) is given.[64807] NAEPP only recommends as-needed ICS/SABA as an option for patients with mild persistent asthma.[66299] FDA-approved Max: 1,440 mcg/day.

Children and Adolescents 12 years and older

GINA recommends 180 to 360 mcg (1 to 2 oral inhalations of 180 mcg/actuation) as needed whenever short-acting beta-2 agonist (SABA) is given.[64807] NAEPP only recommends as-needed ICS/SABA as an option for patients with mild persistent asthma.[66299] FDA-approved Max: 720 mcg/day.

Children 6 to 11 years

GINA recommends 180 mcg (1 oral inhalation of 180 mcg/actuation or 2 oral inhalations of 90 mcg/actuation) as needed whenever short-acting beta-2 agonist (SABA) is given.[64807] FDA-approved Max: 720 mcg/day. NAEPP does not recommend intermittent as-needed ICS/SABA therapy in this age group because therapy has not been adequately studied.[66299]

for treating episodic wheezing† using nebulized dosage form

Nebulized Inhalation dosage (suspension for nebulization; e.g., Pulmicort Respules)

Children 1 to 8 years

GINA recommends 0.25 mg to 0.5 mg as needed whenever short-acting beta-2 agonist (SABA) is given.[64807] FDA-approved Max: 1 mg/day. NAEPP does not recommend intermittent as-needed ICS/SABA therapy in this age group because therapy has not been adequately studied.[66299]

for the treatment of episodic wheezing† at the start of a respiratory tract infection

Nebulized Inhalation dosage (suspension for nebulization; e.g., Pulmicort Respules)

Infants and Children 0 to 4 years

NAEPP recommends 1 mg via nebulizer twice daily for 7 days in combination with as-needed short-acting beta-2 agonist (SABA).[66299]

For exercise-induced bronchospasm prophylaxis†

Oral Inhalation dosage (inhalation powder; e.g., Pulmicort Flexhaler)

Adults

180 to 360 mcg (1 to 2 oral inhalations of 180 mcg/actuation) twice daily is usual dose range. FDA-approved Max: 4 oral inhalations of 180 mcg/actuation twice daily (720 mcg twice daily).[34376] The efficacy of budesonide in the treatment of EIB has been studied in adults.[56336] Titrate to the lowest effective dose. Regular ICS (controller) use reduces the incidence of EIB.[56291] [64807]

Children and Adolescents 6 years and older

180 to 360 mcg (1 to 2 oral inhalations of 180 mcg/actuation) twice daily is the usual dose range. Max: 2 oral inhalations of 180 mcg/actuation twice daily (360 mcg twice daily).[34376] The efficacy of budesonide for EIB has been studied in pediatric patients.[56422] [56423] [56424] Titrate to the lowest effective dose. Regular ICS (controller) use reduces the incidence of EIB.[56291] [64807]

For the treatment of chronic obstructive pulmonary disease (COPD)† (e.g., chronic bronchitis† or emphysema†)

Oral Inhalation dosage (inhalation powder; e.g., Pulmicort Flexhaler)

Adults

The optimal dose for the maintenance treatment of COPD is not established; typical doses of 180 to 360 mcg (1 to 2 actuations of 180 mcg/actuation strength) twice daily may be considered.[63765] [50611] Not for the relief of acute bronchospasm; use a short-acting beta-2 agonist (SABA). According to the Global Initiative for Chronic Lung Disease (GOLD) guidelines, ICS may be used in combination with an inhaled long-acting beta-2 agonist (LABA) as initial therapy in group D (those with a high risk of exacerbation), particularly in patients with blood eosinophil counts of 200 cells/microL or more. 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. 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 LABA, and an inhaled corticosteroid (ICS).[63765]

Nebulized Inhalation dosage (suspension for nebulization; e.g., Pulmicort Respules)

Adults

The optimal dose is not established; used for COPD exacerbations. 1 to 2 mg every 6 hours via nebulizer is a common dosage; some studies have used 2 mg twice daily. Reported total daily dose range for acute exacerbations of COPD: 4 to 8 mg/day. Usual Max: 2 mg/dose.[63369] [63370] [63371] Nebulized budesonide for the treatment of exacerbations may be an alternative to oral corticosteroids in some patients.[63765]

For the treatment of laryngotracheobronchitis (croup)†

Nebulized Inhalation dosage (suspension for nebulization; e.g., Pulmicort Respules)

Infants 3 months and older, Children, and Adolescents

2 mg via nebulizer as a single dose or alternatively, two 1 mg doses via nebulizer given 30 minutes apart.[24066] [25097] [56026] [56027] [56028] [56077] Budesonide is considered an alternative to a single dose of oral dexamethasone, particularly in those unable to take oral medication.[56026] [56027] [59632] [59639] Efficacy has been demonstrated in several studies.[44927] [56029] Most studies have shown comparable efficacy outcomes with dexamethasone for the treatment of croup [56030] [56032]; however, some studies have shown dexamethasone to be superior to budesonide.[25096] The addition of budesonide to dexamethasone therapy has not resulted in an additive benefit.[25097] [56028]

For the management of symptoms of seasonal allergies and perennial allergies, including allergic rhinitis

Nasal dosage (non-prescription OTC use, e.g., Rhinocort Allergy 32 mcg/spray or generic equivalent)

Adults

2 sprays (32 mcg/spray) in each nostril once daily. After clinical response has been obtained, decrease to 1 spray in each nostril once daily. If no response after 2 weeks, consult a health care provider.[59312]

Children and Adolescents 12 years and older

2 sprays (32 mcg/spray) in each nostril once daily. After clinical response has been obtained, decrease to 1 spray in each nostril once daily. If no response after 2 weeks, consult a health care provider.[59312]

Children 6 to 11 years

Initially, 1 spray (32 mcg/spray) in each nostril once daily. If symptoms do not improve, may increase to 2 sprays in each nostril once daily. After clinical response has been obtained, decrease to 1 spray in each nostril once daily. Non-prescription use in younger children is intended to be assisted by an adult. If the child uses this product for longer than 2 months per year, or, if there is no response to treatment after 2 weeks, consult a pediatrician.[59312]

For mild to moderate Crohn's disease involving the ileum and/or ascending colon

for treatment of active disease

Oral dosage (delayed-release capsules; e.g., Entocort EC)

Adults

9 mg PO once daily in the morning for up to 8 weeks. May taper to 6 mg PO once daily for 2 weeks prior to treatment cessation to minimize the risk of adrenal insufficiency. A repeat 8-week course may be given for recurring episodes of active Crohn's disease. If the patient was previously taking prednisolone, do not abruptly discontinue it; taper it downward with the initiation of budesonide.[24064] [34979]

Children and Adolescents 8 years and older and weight more than 25 kg

9 mg PO once daily in the morning for up to 8 weeks, followed by 6 mg PO once daily for 2 weeks prior to treatment cessation. If the patient was previously taking prednisolone, do not abruptly discontinue it; taper it downward with the initiation of budesonide.[34979] Repeat courses may be needed if active disease recurs.[56014]

Oral dosage (extended-release capsules; e.g., Ortikos)

Adults

9 mg PO once daily in the morning for up to 8 weeks. May taper to 6 mg PO once daily for 2 weeks prior to treatment cessation to minimize the risk of adrenal insufficiency. A repeat 8-week course of oral budesonide may be given for recurring episodes of active Crohn's disease. If the patient was previously taking prednisolone, do not abruptly discontinue it; taper it downward with the initiation of budesonide.[64318]

Children and Adolescents 8 years and older and weight more than 25 kg

9 mg PO once daily in the morning for up to 8 weeks, followed by 6 mg PO once daily for 2 weeks prior to treatment cessation. If the patient was previously taking prednisolone, do not abruptly discontinue it; taper it downward with the initiation of budesonide.[64318] Repeat courses may be needed if active disease recurs.[56014]

for maintenance of clinical remission for up to 3 months

Oral dosage (delayed-release capsules; e.g., Entocort EC)

Adults

6 mg PO once daily in the morning for up to 3 months. Consider dosage taper to complete drug cessation if symptom control is maintained at month 3. Treatment beyond 3 months has not been shown to provide substantial clinical benefit. A Crohn's Disease Activity Index (CDAI) less than 150 after 8 weeks of treatment for active disease is recommended before maintenance treatment is initiated.[34979] The American College of Gastroenterology strongly recommends that budesonide not be used to maintain remission of Crohn's disease beyond 4 months.[64397]

Oral dosage (extended-release capsules; e.g., Ortikos)

Adults

6 mg PO once daily in the morning for up to 3 months. Consider dosage taper to complete drug cessation if symptom control is maintained at month 3. Treatment beyond 3 months has not been shown to provide substantial clinical benefit. A Crohn's Disease Activity Index (CDAI) less than 150 after 8 weeks of treatment for active disease is recommended before maintenance treatment is initiated.[64318] The American College of Gastroenterology strongly recommends that budesonide not be used to maintain remission of Crohn's disease beyond 4 months.[64397]

For the induction of remission in patients with active, mild to moderate ulcerative colitis

Oral dosage (extended-release tablets, e.g., Uceris)

Adults

9 mg PO once daily in the morning for up to 8 weeks.[52910] The AGA and ACG both support the use of oral budesonide to induce remission in patients with UC; however, they recommend against systemic corticosteroids for the maintenance of remission.[64377] [64393]

Rectal dosage (rectal foam; Uceris)

Adults

2 mg (1 metered dose) rectally twice daily (in the morning and evening) for 2 weeks, then 2 mg (1 metered dose) rectally once daily (in the evening) for 4 weeks. Evening doses are applied immediately prior to bedtime. Rectal foam is indicated for active mild to moderate distal ulcerative colitis extending up to 40 cm from the anal verge.[58166]

For the treatment of collagenous colitis† (a form of microscopic colitis)

Oral dosage (extended-release capsules; e.g., Entocort EC)

Adults

9 mg PO once daily or on a tapering schedule for 8 weeks has been used in clinical trials. A Cochrane review of IBD and functional bowel disorder trials concluded that budesonide is effective and well-tolerated for inducing and maintaining clinical and histological response in patients with collagenous colitis.[64534] In a placebo-controlled, randomized trial (n = 28), 8 of 14 patients receiving 9 mg/daily were considered responders (p = 0.05), with patients reporting improved stool consistency. Histological findings included a significant decrease in the lamina propria infiltrates in the budesonide group (p is less than 0.001).[33153] Another controlled trial (n = 20) studied a tapering regimen of 9 mg PO for 4 weeks, 6 mg for 2 weeks, and 3 mg for 2 weeks. All 10 patients in the budesonide group experienced a clinical response, and treated patients reported reduced stool weight and frequency; histological inflammation was also significantly improved.[33154]

Therapeutic Drug Monitoring

Maximum Dosage Limits

  • Adults

    Maximum dose dependent on indication and specific drug formulation administered. Doses up to 8 mg/day of the nebulizer suspension have been used off-label.

  • Geriatric

    Maximum dose dependent on indication and specific drug formulation administered. Doses up to 8 mg/day of the nebulizer suspension have been used off-label.

  • Adolescents

    256 mcg/day intranasally; 720 mcg/day via dry powder inhaler (DPI) is the FDA-approved maximum dosage; doses of the nebulizer suspension as high as 4 mg/day have been used off-label. Safety and efficacy of oral formulations have not been established; however, doses up to 12 mg/day (oral capsules) have been used off-label.

  • Children

    12 years: 256 mcg/day intranasally; 720 mcg/day via dry powder inhaler (DPI) is the FDA-approved maximum dosage; nebulizer suspension doses as high as 4 mg/day have been used off-label. Safety and efficacy of oral formulations have not been established; however, doses up to 12 mg/day of the oral capsules have been used off-label.

    6 to 11 years: 128 mcg/day intranasally; 720 mcg/day via dry powder inhaler (DPI) is the FDA-approved maximum dosage; 1 mg/day of the nebulizer suspension is the FDA-approved maximum dosage (6 to 8 years); however, doses as high as 4 mg/day have been used off-label. Safety and efficacy of oral formulations have not been established; however, doses up to 12 mg/day of the oral capsules have been used off-label.

    1 to 5 years: 1 mg/day of the nebulizer suspension is the FDA-approved maximum dosage; however, doses as high as 4 mg/day have been used off-label. Safety and efficacy of other formulations have not been established.

  • Infants

    Safety and efficacy have not been established; however, doses up to 1 mg/day of the nebulizer suspension have been used off-label.

Patients with Hepatic Impairment Dosing

Nasal or Inhaled products: No dosage adjustment suggested.[59312][33486][34376]

 

Oral delayed-release capsules (e.g., Entocort EC)

Mild hepatic impairment (Child-Pugh Class A): No dosage adjustment is needed.

Moderate hepatic impairment (Child-Pugh Class B): Consider a reduced dose of 3 mg once daily. Monitor the patient for signs/symptoms of hypercorticism. Consider drug discontinuation in cases of hypercorticism.

Severe hepatic impairment (Child-Pugh Class C): Avoid use.[34979]

Oral extended-release capsules (i.e., Ortikos)

Mild hepatic impairment (Child-Pugh Class A): No dosage adjustment is needed.

Moderate or severe hepatic impairment (Child-Pugh Class B or C): Avoid use.[64318]

 

Oral delayed-release tablet (i.e., Uceris)

Mild hepatic impairment (Child-Pugh Class A): No dosage adjustment is needed.

Moderate or severe hepatic impairment (Child-Pugh Class B or C): Monitor the patient for signs/symptoms of hypercorticism. Consider drug discontinuation in cases of hypercorticism.[52910]

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: 06/14/2021, 12:04:18 PM

References

24064 - Greenberg GR, Feagan BG, Martin F, et al. Oral budesonide for active Crohn's disease. N Engl J Med 1994;331:836-41.24066 - Klassen TP, Feldman Me, Watters LK, et al. Nebulized budesonide for children with mild-to-moderate croup. N Engl J Med 1994;331:285-9.25096 - Johnson DW, Jacobson S, Edney PC, et al. A comparison of nebulized budesonide, intramuscular dexamethasone, and placebo for moderately severe croup. N Engl J Med 1998;339:498-503.25097 - Klassen TP, Craig WR, Moher D, et al. Nebulized budesonide and oral dexamethasone for treatment of croup. JAMA 1998;279:1629-32.26690 - Volovitz B, Soferman R, Blau H, et al. Rapid induction of clinical response with a short-term high-dose starting schedule of budesonide nebulizing suspension in young children with recurrent wheezing episodes. J Allergy Clin Immunol 1998;101(4 Pt 1):464-469.33153 - Baert F, Schmit A, D'Haens G, et al. Budesonide in collagenous colitis: a double-blind placebo-controlled trial with histologic follow-up. Gastroenterology 2002;122:20-5.33154 - Bonderup OK, Hansen JB, Birket-Smith L, et al. Budesonide treatment of collagenous colitis: a randomized, double blind, placebo controlled trial with morphometric analysis. Gut 2003;52:248-51.33486 - Pulmicort Respules (budesonide) inhalation suspension package insert. Wilmington, DE: AstraZeneca LP; 2018 Dec.33558 - National Asthma Education and Prevention Program Expert Panel 3. Expert panel report 3: guidelines for the diagnosis and management of asthma. Bethesda (MD): National Institutes of Health. National Heart, Lung, and Blood Institute; 2007 Aug. NIH Publication No. 07-4051.33594 - Baker JW, Mellon M, Wald J, et al. A multiple-dosing, placebo-controlled study of budesonide inhalation suspension given once or twice daily for treatment of persistent asthma in young children and infants. Pediatrics 1999;103:414-21.33595 - Berger WE, Qaqundah PY, Blake K, et al. Safety of budesonide inhalation suspension in infants aged six to twelve months with mild to moderate persistent asthma or recurrent wheeze. J Pediatr 2005;146:91-5.34376 - Pulmicort Flexhaler (budesonide inhalation powder) package insert. Wilmington, DE: AstraZeneca LP; 2018 Dec.34979 - Entocort EC (budesonide) capsules package insert. Wilmington, DE: AstraZeneca LP; 2020 July44927 - Russell KF, Liang Y, O'Gorman K, Johnson DW, Klassen TP. Glucocorticoids for croup. Cochrane Database Syst Rev. 2011:CD00195550611 - Pauwels RA, Lofdahl CG, Laitinen LA, et al. Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. European Respiratory Society Study on Chronic Obstructive Pulmonary Disease. N Engl J Med. 1999;340(25):1948-1953.52910 - Uceris (budesonide) tablets package insert. San Diego, CA: Santarus Inc.; 2020 April.56014 - Otley A, LeLeiko N, Langton C, et al. Budesonide use in pediatric Crohn disease. J Pediatr Gastroenterol Nutr 2012;55:200-204.56026 - Syed I. Acute management of croup in children. Br J Hosp Med (Lond) 2009;70:M4-6.56027 - Borland ML, Babl FE, Sheriff N, et al. Croup management in Australia and New Zealand. Pediatr Emerg Care 2008;24:452-456.56028 - Geelhoed GC. Budesonide offers no advantage when added to oral dexamethasone in the treatment of croup. Pediatr Emerg Care 2005;21:359-362.56029 - Griffin S, Ellis S, Fitzgerald-Barron A, et al. Nebulised steroid in the treatment of croup: a systematic review of randomised controlled trials. Br J Gen Pract 2000;50:135-141.56030 - Cetinkaya F, Tufekci BS, Kutluk G. A comparison of nebulized budesonide, and intramuscular, and oral dexamethasone for treatment of croup. Int J Pediatr Otorhinolaryngol 2004;68:453-456.56032 - Geelhoed GC, MacDonald WB. Oral and inhaled steroids in croup: a randomized, placebo-controlled trial. Pediatr Pulmonol 1995;20:355-361.56077 - Hvizdos KM, Jarvis B. Budesonide inhalation suspension: A review of its use in infants, children and adults with inflammatory disorders. Drugs 2000;60:1141-1178.56291 - 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;187:1016-1027.56336 - Vathenen AS, Know AJ, Wisniewski A. Effect of inhaled budesonide on bronchial reactivity to histamine, exercise, and eucapnic dry air hyperventilation in patients with asthma. Thorax 1991;46:811-816.56422 - Jonasson G, Carlsen KH, Hultquist C. Low-dose budesonide improves exercise-induced bronchospasm in schoolchildren. Pediatr Allergy Immunol 2000;11:120-125.56423 - Stelmach W, Grzelewski T, Majak P. Effect of different antiasthmatic treatments on exercise-induced bronchoconstriction in children with asthma. J Allergy Clin Immunol 2008;121:383-389.56424 - Vidal C, Fernandez-Ovide E, Pineiro J. Comparison of montelukast versus budesonide in the treatment of exercise-induced bronchoconstriction. Ann Allergy Asthma Immunol 2001;85:655-658.58166 - Uceris (budesonide) rectal foam package insert. Bridgewater, NJ: Salix Pharmaceuticals; 2020 April.59312 - Rhinocort Allergy Spray (budesonide) nasal spray package insert. Fort Washington, PA: McNeil Consumer Healthcare Division; 2017 May59632 - Toward Optimized Practice (TOP) Working Group for Croup. Guideline for the diagnosis and management of croup. Edmonton (AB): Toward Optimized Practice;2003 (revised 2014). Accessed on the World Wide Web: www.topalbertadoctors.org/download/252/croup_guideline.pdf May 15, 2015.59639 - Bjornson CL, Johnson DW. Croup in children. CMAJ 2013;185:1317-1323.63369 - Maltais F, Ostinelli J, Bourbeau J, et al. Comparison of nebulized budesonide and oral prednisolone with placebo in the treatment of acute exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial. Am J Respir Crit Care Med 2002;165: 698-703.63370 - Gunen H, Hacievliyagil SS, Yetkin O, et al. The role of nebulised budesonide in the treatment of exacerbations of COPD. Eur Respir J 2007;29:660-7.63371 - Gaude GS, Nadagouda S. Nebulized corticosteroids in the management of acute exacerbation of COPD. Lung India 2010;27:230-5.63765 - Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2021. Retrieved 3/8/2021. Available on the World Wide Web at https://goldcopd.org/wp-content/uploads/2020/11/GOLD-REPORT-2021-v1.1-25Nov20_WMV.pdf64318 - Ortikos (budesonide) capsules package insert. Cranbury, NJ: Sun Pharmaceutical Industries, Inc; 2019 June.64377 - Ko CW, Singh S, Feuerstein JD, et al; American Gastroenterological Association Institute Clinical Guidelines Committee. AGA Clinical Practice Guidelines on the Management of Mild-to-Moderate Ulcerative Colitis. Gastroenterology. 2019;156:748-764.64393 - Rubin DT, Ananthakrishnan AN, Siegel CA, et al.; American College of Gastroenterology Clinical Guideline: Ulcerative Colitis in Adults. Am J Gastroenterol. 2019;114:384–413.64397 - Lichtenstein GR, Loftus EV, Isaacs KL, et al. American College of Gastroenterology Clinical Guideline: Management of Crohn's Disease in Adults. Am J Gastroenterol. 2018;113:481–517.64534 - Chande N, MacDonald JK, McDonald JW. Interventions for treating microscopic colitis: a Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Review Group systematic review of randomized trials. Am J Gastroenterol 2009;104:235-41.64807 - Global Strategy for Asthma Management and Prevention. Global Initiative for Asthma (GINA) 2020. Available from: http://www.ginasthma.org. Accessed May 20th, 2020.65955 - Pulmicort Respules 1 mg (budesonide nebuliser suspension). Summary of product characteristics. European package labeling. Luton, LU1 3LU, UK; AstraZeneca UK Ltd.: 2017 Jun. Available at: www.medicines.org.uk/emc/product/881#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 Inhalation powder

Pulmicort Flexhaler 90mcg/actuation Powder for Inhalation (00186-0917) (AstraZeneca LP) nullPulmicort Flexhaler 90mcg/actuation Powder for Inhalation package photo

Budesonide Inhalation powder

Pulmicort Flexhaler 180mcg/actuation Powder for Inhalation (00186-0916) (AstraZeneca LP) nullPulmicort Flexhaler 180mcg/actuation Powder for Inhalation package photo

Budesonide Inhalation powder

Pulmicort Turbuhaler 200mcg/actuation Powder for Inhalation (00186-0915) (AstraZeneca LP) (off market)Pulmicort Turbuhaler 200mcg/actuation Powder for Inhalation package photo

Budesonide Nasal spray, solution

Rhinocort 32mcg/actuation Nasal Spray (00186-1075) (AstraZeneca LP) (off market)Rhinocort 32mcg/actuation Nasal Spray package photo

Budesonide Nasal spray, suspension

Budesonide 32mcg/actuation Nasal Spray (60505-0839) (Apotex Corp) (off market)Budesonide 32mcg/actuation Nasal Spray package photo

Budesonide Nasal spray, suspension

Budesonide 32mcg/actuation Nasal Spray (60505-6129) (Apotex Corp) nullBudesonide 32mcg/actuation Nasal Spray package photo

Budesonide Nasal spray, suspension

Budesonide 32mcg/actuation Nasal Spray (00186-1073) (Par Pharmaceuticals, an Endo Company) (off market)Budesonide 32mcg/actuation Nasal Spray package photo

Budesonide Nasal spray, suspension

Budesonide 32mcg/actuation Nasal Spray (49884-0157) (Par Pharmaceuticals, an Endo Company) (off market)Budesonide 32mcg/actuation Nasal Spray package photo

Budesonide Nasal spray, suspension

Budesonide 32mcg/actuation Nasal Spray (00536-1112) (Rugby Laboratories a Division of The Harvard Drug Group, LLC) null

Budesonide Nasal spray, suspension

CVS Budesonide 32mcg/actuation Nasal Spray (69842-0001) (CVS Health) nullCVS Budesonide 32mcg/actuation Nasal Spray package photo

Budesonide Nasal spray, suspension

GNP Budesonide Nasal Allergy 32mcg/actuation Nasal Spray (46122-0389) (AmerisourceBergen Corporation) null

Budesonide Nasal spray, suspension

Rhinocort Allergy 32mcg/actuation Nasal Spray (00045-0646) (McNeil Consumer Healthcare Division of McNEIL-PPC, Inc.) null

Budesonide Nasal spray, suspension

Rhinocort Aqua 32mcg/actuation Nasal Spray (00186-1070) (AstraZeneca LP) nullRhinocort Aqua 32mcg/actuation Nasal Spray package photo

Budesonide Nasal spray, suspension

Rhinocort Children's Allergy 32mcg/actuation Nasal Spray (00045-0646) (McNeil Consumer Healthcare Division of McNEIL-PPC, Inc.) (off market)

Budesonide Nasal spray, suspension

Walgreens 24-Hour Budesonide 32mcg/actuation Nasal Spray (00363-0048) (Walgreens Co) null

Budesonide Nebulizer suspension

Budesonide 0.25mg/2ml Suspension for Inhalation (00186-0425) (Par Pharmaceuticals, an Endo Company) (off market)

Budesonide Nebulizer suspension

Budesonide 0.25mg/2ml Suspension for Inhalation (00093-6815) (Teva Pharmaceuticals USA) (off market)Budesonide 0.25mg/2ml Suspension for Inhalation package photo

Budesonide Nebulizer suspension

Budesonide 0.25mg/2ml Suspension for Inhalation (00591-3767) (Teva/Actavis US) (off market)

Budesonide Nebulizer suspension

Budesonide 0.25mg/2mL Suspension for Inhalation (69097-0318) (Cipla USA, Inc) nullBudesonide 0.25mg/2mL Suspension for Inhalation package photo

Budesonide Nebulizer suspension

Budesonide 0.25mg/2mL Suspension for Inhalation (69097-0318) (Cipla USA, Inc) null

Budesonide Nebulizer suspension

Budesonide 0.25mg/2mL Suspension for Inhalation (76282-0640) (Exelan Pharmaceuticals, Inc.) null

Budesonide Nebulizer suspension

Budesonide 0.25mg/2mL Suspension for Inhalation (00591-3767) (Impax Generics, a division of Impax Laboratories, Inc.) (off market)

Budesonide Nebulizer suspension

Budesonide 0.25mg/2mL Suspension for Inhalation (00115-1687) (Impax Generics, a division of Impax Laboratories, Inc.) nullBudesonide 0.25mg/2mL Suspension for Inhalation package photo

Budesonide Nebulizer suspension

Budesonide 0.25mg/2mL Suspension for Inhalation (00487-9601) (Nephron Pharmaceuticals Corp) null

Budesonide Nebulizer suspension

Budesonide 0.25mg/2mL Suspension for Inhalation (16714-0018) (NorthStar Rx LLC) null

Budesonide Nebulizer suspension

Budesonide 0.25mg/2mL Suspension for Inhalation (00781-7515) (Sandoz Inc. a Novartis Company) nullBudesonide 0.25mg/2mL Suspension for Inhalation package photo

Budesonide Nebulizer suspension

Budesonide 0.25mg/2mL Suspension for Inhalation (47335-0631) (Sun Pharmaceutical Industries, Inc.) null

Budesonide Nebulizer suspension

Budesonide 0.25mg/2mL Suspension for Inhalation (00093-6815) (Teva Pharmaceuticals USA) nullBudesonide 0.25mg/2mL Suspension for Inhalation package photo

Budesonide Nebulizer suspension

Pulmicort 0.25mg/2ml Respules Suspension for Inhalation (00186-1988) (AstraZeneca LP) nullPulmicort 0.25mg/2ml Respules Suspension for Inhalation package photo

Budesonide Nebulizer suspension

Budesonide 0.5mg/2ml Suspension for Inhalation (00186-0426) (Par Pharmaceuticals, an Endo Company) (off market)

Budesonide Nebulizer suspension

Budesonide 0.5mg/2ml Suspension for Inhalation (00093-6816) (Teva Pharmaceuticals USA) (off market)Budesonide 0.5mg/2ml Suspension for Inhalation package photo

Budesonide Nebulizer suspension

Budesonide 0.5mg/2ml Suspension for Inhalation (00591-3768) (Teva/Actavis US) (off market)Budesonide 0.5mg/2ml Suspension for Inhalation package photo

Budesonide Nebulizer suspension

Budesonide 0.5mg/2mL Suspension for Inhalation (60687-0524) (American Health Packaging) null

Budesonide Nebulizer suspension

Budesonide 0.5mg/2mL Suspension for Inhalation (69097-0319) (Cipla USA, Inc) null

Budesonide Nebulizer suspension

Budesonide 0.5mg/2mL Suspension for Inhalation (69097-0319) (Cipla USA, Inc) nullBudesonide 0.5mg/2mL Suspension for Inhalation package photo

Budesonide Nebulizer suspension

Budesonide 0.5mg/2mL Suspension for Inhalation (76282-0641) (Exelan Pharmaceuticals, Inc.) null

Budesonide Nebulizer suspension

Budesonide 0.5mg/2mL Suspension for Inhalation (00115-1689) (Impax Generics, a division of Impax Laboratories, Inc.) nullBudesonide 0.5mg/2mL Suspension for Inhalation package photo

Budesonide Nebulizer suspension

Budesonide 0.5mg/2mL Suspension for Inhalation (00591-3768) (Impax Generics, a division of Impax Laboratories, Inc.) (off market)

Budesonide Nebulizer suspension

Budesonide 0.5mg/2mL Suspension for Inhalation (68180-0984) (Lupin Pharmaceuticals, Inc.) null

Budesonide Nebulizer suspension

Budesonide 0.5mg/2mL Suspension for Inhalation (00487-9701) (Nephron Pharmaceuticals Corp) nullBudesonide 0.5mg/2mL Suspension for Inhalation package photo

Budesonide Nebulizer suspension

Budesonide 0.5mg/2mL Suspension for Inhalation (16714-0019) (NorthStar Rx LLC) null

Budesonide Nebulizer suspension

Budesonide 0.5mg/2mL Suspension for Inhalation (00781-7516) (Sandoz Inc. a Novartis Company) nullBudesonide 0.5mg/2mL Suspension for Inhalation package photo

Budesonide Nebulizer suspension

Budesonide 0.5mg/2mL Suspension for Inhalation (47335-0632) (Sun Pharmaceutical Industries, Inc.) null

Budesonide Nebulizer suspension

Budesonide 0.5mg/2mL Suspension for Inhalation (00093-6816) (Teva Pharmaceuticals USA) nullBudesonide 0.5mg/2mL Suspension for Inhalation package photo

Budesonide Nebulizer suspension

Pulmicort 0.5mg/2ml Respules Suspension for Inhalation (00186-1989) (AstraZeneca LP) nullPulmicort 0.5mg/2ml Respules Suspension for Inhalation package photo

Budesonide Nebulizer suspension

Budesonide 1mg/2mL Suspension for Inhalation (69097-0321) (Cipla USA, Inc) nullBudesonide 1mg/2mL Suspension for Inhalation package photo

Budesonide Nebulizer suspension

Budesonide 1mg/2mL Suspension for Inhalation (69097-0321) (Cipla USA, Inc) null

Budesonide Nebulizer suspension

Budesonide 1mg/2mL Suspension for Inhalation (76282-0642) (Exelan Pharmaceuticals, Inc.) null

Budesonide Nebulizer suspension

Budesonide 1mg/2mL Suspension for Inhalation (16714-0020) (NorthStar Rx LLC) null

Budesonide Nebulizer suspension

Budesonide 1mg/2mL Suspension for Inhalation (00781-7517) (Sandoz Inc. a Novartis Company) nullBudesonide 1mg/2mL Suspension for Inhalation package photo

Budesonide Nebulizer suspension

Budesonide 1mg/2mL Suspension for Inhalation (47335-0633) (Sun Pharmaceutical Industries, Inc.) null

Budesonide Nebulizer suspension

Budesonide 1mg/2mL Suspension for Inhalation (00093-6817) (Teva Pharmaceuticals USA) nullBudesonide 1mg/2mL Suspension for Inhalation package photo

Budesonide Nebulizer suspension

Pulmicort 1mg/2ml Respules Suspension for Inhalation (00186-1990) (AstraZeneca LP) nullPulmicort 1mg/2ml Respules Suspension for Inhalation package photo

Budesonide Oral capsule, extended release

Ortikos 6mg Extended-Release Capsule (55566-1002) (Ferring Pharmaceuticals Inc) null

Budesonide Oral capsule, extended release

Ortikos 9mg Extended-Release Capsule (55566-1020) (Ferring Pharmaceuticals Inc) null

Budesonide Oral capsule, gastro-resistant pellets

Budesonide 3mg Capsule (47781-0146) (Alvogen, Inc.) (off market)

Budesonide Oral capsule, gastro-resistant pellets

Budesonide 3mg Capsule (60687-0596) (American Health Packaging) null

Budesonide Oral capsule, gastro-resistant pellets

Budesonide 3mg Capsule (60687-0421) (American Health Packaging) (off market)

Budesonide Oral capsule, gastro-resistant pellets

Budesonide 3mg Capsule (65162-0778) (Amneal Pharmaceuticals LLC) null

Budesonide Oral capsule, gastro-resistant pellets

Budesonide 3mg Capsule (60429-0264) (Golden State Medical Supply, Inc.) null

Budesonide Oral capsule, gastro-resistant pellets

Budesonide 3mg Capsule (51407-0128) (Golden State Medical Supply, Inc.) null

Budesonide Oral capsule, gastro-resistant pellets

Budesonide 3mg Capsule (51862-0582) (Mayne Pharma) (off market)

Budesonide Oral capsule, gastro-resistant pellets

Budesonide 3mg Capsule (51862-0580) (Mayne Pharma) null

Budesonide Oral capsule, gastro-resistant pellets

Budesonide 3mg Capsule (51079-0020) (Mylan Institutional LLC ) null

Budesonide Oral capsule, gastro-resistant pellets

Budesonide 3mg Capsule (00378-7155) (Mylan Pharmaceuticals Inc.) null

Budesonide Oral capsule, gastro-resistant pellets

Budesonide 3mg Capsule (16714-0829) (Northstar Rx LLC) null

Budesonide Oral capsule, gastro-resistant pellets

Budesonide 3mg Capsule (00574-9855) (Paddock Laboratories Inc, a Perrigo Family) null

Budesonide Oral capsule, gastro-resistant pellets

Budesonide 3mg Capsule (49884-0501) (Par Pharmaceuticals, an Endo Company) (off market)

Budesonide Oral capsule, gastro-resistant pellets

Budesonide 3mg Capsule (64980-0255) (Rising Pharmaceuticals Inc) null

Budesonide Oral capsule, gastro-resistant pellets

Budesonide 3mg Capsule (00093-7445) (Teva Pharmaceuticals USA) (off market)

Budesonide Oral capsule, gastro-resistant pellets

Budesonide 3mg Capsule (68382-0720) (Zydus Pharmaceuticals (USA) Inc.) null

Budesonide Oral capsule, gastro-resistant pellets

Entocort EC 3mg Capsule (65483-0702) (AstraZeneca LP) (off market)

Budesonide Oral capsule, gastro-resistant pellets

Entocort EC 3mg Capsule (00186-0702) (AstraZeneca LP) (off market)

Budesonide Oral capsule, gastro-resistant pellets

Entocort EC 3mg Capsule (00186-0702) (AstraZeneca LP) (off market)

Budesonide Oral capsule, gastro-resistant pellets

Entocort EC 3mg Capsule (00574-9850) (Paddock Laboratories Inc, a Perrigo Family) null

Budesonide Oral capsule, gastro-resistant pellets

Entocort EC 3mg Capsule (00186-0702) (Perrigo Pharmaceuticals) (off market)

Budesonide Oral capsule, gastro-resistant pellets

Entocort EC 3mg Capsule (00186-0702) (Prometheus Laboratories, Inc) (off market)

Budesonide Oral capsule, gastro-resistant pellets

Entocort EC 3mg Capsule (65483-0702) (Prometheus Laboratories, Inc) (off market)

Budesonide Oral tablet, extended release

Budesonide 9mg Extended-Release Tablet (51407-0224) (Golden State Medical Supply, Inc.) null

Budesonide Oral tablet, extended release

Budesonide 9mg Extended-Release Tablet (51407-0366) (Golden State Medical Supply, Inc.) null

Budesonide Oral tablet, extended release

Budesonide 9mg Extended-Release Tablet (00378-4500) (Mylan Pharmaceuticals Inc.) null

Budesonide Oral tablet, extended release

Budesonide 9mg Extended-Release Tablet (00591-2510) (Teva/Actavis US) null

Budesonide Oral tablet, extended release

BUDESONIDE 9mg Extended-Release Tablet (68682-0309) (Bausch Health US, LLC) null

Budesonide Oral tablet, extended release

UCERIS 9mg Extended-Release Tablet (68012-0309) (Bausch Health US, LCC) null

Budesonide Rectal foam

UCERIS 2mg/actuation Rectal Foam (65649-0651) (Bausch Health US, LLC) nullUCERIS 2mg/actuation Rectal Foam package photo

Budesonide Rectal foam

UCERIS 2mg/actuation Rectal Foam (65649-0651) (Bausch Health US, LLC) (off market)

Description/Classification

Description

Budesonide is a corticosteroid that is administered via intranasal inhalation, oral inhalation, rectally, or orally. Budesonide has potent glucocorticoid and weak mineralocorticoid activity. Budesonide formulations are used to manage symptoms associated with allergic rhinitis, selected lung diseases, or inflammatory bowel disease (Crohn's disease and ulcerative colitis), depending on the formulation chosen. Inhaled budesonide possesses high topical anti-inflammatory activity but low systemic activity. Inhaled corticosteroids (ICSs) are the preferred pharmacologic treatment in the long-term management of persistent asthma for most patients.[64807][66299] Maintenance ICS therapy may also decrease the frequency and severity of exercise-induced bronchoconstriction (EIB); short-acting beta-2 agonists (SABAs) also help prevent EIB but tolerance can develop with regular SABA use.[56291][64807] Budesonide may be used in combination with an inhaled long-acting beta-2 agonist (LABA) 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] Budesonide nasal spray allows for once-daily dosing for allergic rhinitis. Rhinitis guidelines strongly recommend intranasal corticosteroids as the preferred medication when choosing monotherapy for persistent allergic rhinitis; they may also be offered as first-line therapy for nonallergic rhinitis (NAR) although intranasal antihistamines are strongly recommended as a first-line monotherapy option for NAR.[66102] Oral budesonide has been shown to be superior to placebo and equivalent to prednisolone, but with fewer adverse reactions, in treating active Crohn's disease.[24064][24065] A budesonide oral tablet with a proprietary delivery system (MMX, a multi-matrix system) that delivers medicine to the colon, has been shown to be effective at inducing remission in patients with active, mild to moderate ulcerative colitis.[52909][52910] Several studies also indicate the benefit of oral budesonide in treating microscopic colitis and, specifically, collagenous colitis.[33152]

Classifications

  • Alimentary Tract and Metabolism
    • Antidiarrheals, Intestinal Antiinflammatories/Antiinfective Agents
      • Intestinal Antiinflammatory Agents
        • Corticosteroids, Locally Acting Intestinal Antiinflammatory Agents
  • Respiratory System
    • Agents for Reactive and Obstructive Airway Diseases
      • Corticosteroids
        • Respiratory Corticosteroids
    • Nasal Agents
      • Topical Nasal Corticosteroids
  • Systemic Hormonal Agents (excluding Sex Hormones)
    • Systemic Corticosteroids
      • Systemic Corticosteroids, Plain
Revision Date: 01/20/2021, 11:52:28 AM

References

24064 - Greenberg GR, Feagan BG, Martin F, et al. Oral budesonide for active Crohn's disease. N Engl J Med 1994;331:836-41.24065 - Rutgeerts P, Lofberg R, Malchow H, et al. A comparison of budesonide with prednisolone for active Crohn's disease. N Engl J Med 1994;331:842-5.33152 - Wall GC, Schirmer LL, Page MJ. Pharmacotherapy for microscopic colitis. Pharmacotherapy 2007;27:425-33.52909 - Sandborn WJ, Travis S, Moro L, et al. Once-daily budesonide MMX extended-release tablets induce remission in patients with mild to moderate ulcerative colitis: results from the CORE I study. Gastroenterology 2012;143:1218-26.52910 - Uceris (budesonide) tablets package insert. San Diego, CA: Santarus Inc.; 2020 April.56291 - Parsons JP, Hallstrand TS, Mastronarde JG, et al. An official American Thoracic Society clinical practice guideline exercise induced bronchoconstriction. Am J Respir Crit Care Med 2013;187:1016-1027.63765 - Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2021. Retrieved 3/8/2021. Available on the World Wide Web at https://goldcopd.org/wp-content/uploads/2020/11/GOLD-REPORT-2021-v1.1-25Nov20_WMV.pdf64807 - Global Strategy for Asthma Management and Prevention. Global Initiative for Asthma (GINA) 2020. Available from: http://www.ginasthma.org. Accessed May 20th, 2020.66102 - Dykewicz MS, Wallace DV, Amrol DJ, et al. Rhinitis 2020: a practice parameter update. J Allergy Clin Immunol. 2020;146:721-767.66299 - 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 specific product information within the How Supplied section.

Route-Specific Administration

Oral Administration

Oral Solid Formulations

Delayed-release capsules (e.g., Entocort EC and equivalent generics):

  • Administer the total daily dose in the morning, with or without food.
  • Administer whole; do not chew or crush.
  • For patients unable to swallow an intact capsule, open the capsules and empty the granules onto one tablespoonful (15 mL) of applesauce. Ensure the applesauce is not hot and that it is soft enough to be swallowed without chewing. Mix and consume the entire contents within 30 minutes. Do not chew or crush. Follow with 240 mL (8 ounces) of water.
  • Do not administer with grapefruit juice; patient should avoid consumption of grapefruit juice for the duration of therapy.[34979]

 

Extended-release tablets (e.g., Uceris):

  • Administer the total daily dose in the morning, with or without food.
  • Administer whole; do not chew, break, or crush.
  • Do not administer with grapefruit juice; patient should avoid consumption of grapefruit juice for the duration of therapy. [52910]

 

Extended-release capsules (e.g., Ortikos):

  • Administer the total daily dose in the morning, with or without food.
  • Administer whole; do not chew or crush.
  • Do not administer with grapefruit juice; patient should avoid consumption of grapefruit juice for the duration of therapy.[64318]

Extemporaneous Compounding-Oral

NOTE: Budesonide extemporaneous oral suspension is not approved by the FDA for oral administration.
  • For the treatment of eosinophilic esophagitis, an oral viscous suspension of budesonide should be used.
  • The patient should not consume food or drink for 30 minutes after the viscous suspension administration.[56034] [56035] [57689]

 

Extemporaneous compounding instructions for budesonide oral suspension:

  • Oral viscous suspension prepared with Splenda:
    • To compound, mix each 0.5 mg/2 mL ampule of the liquid inhalation suspension with 5 packets of sucralose (Splenda) to make a final volume of 8 to 12 mL.
    • The suspension should be administered immediately after compounding as no data are available regarding stability.[56034] [56035] [57689]
  • Oral viscous suspension prepared with Neocate Nutra:
    • For a 1-mg dose, add two 0.5 mg/2 mL ampules of the liquid inhalation suspension to 2.5 mL of Neocate Nutra and mix into a slurry.
    • For a 2-mg dose, add four 0.5 mg/2 mL ampules of the liquid inhalation suspension to 5 mL of Neocate Nutra and mix into a slurry.
    • The suspension should be administered immediately after compounding as no data are available regarding stability.[57689]

Inhalation Administration

Oral Inhalation Administration

Dry powder for inhalation (Pulmicort Flexhaler):

  • Instruct patient on proper administration technique. Most children younger than 4 years of age may not generate sufficient inspiratory flow to activate dry powder inhalers.
  • A new inhaler should be primed before use, per the priming instructions that come with the device. While priming the inhaler, the inhaler should always be held in an upright position.
  • To load the dose on a primed inhaler, keep the inhaler in an upright position and twist the brown grip fully to the right as far as it will go, then twist it back fully to the left; there will be the sound of a "click".
  • When inhaling, the inhaler may be held in an upright or horizontal position. Turn head away from the inhaler and breathe out. Place the mouthpiece between the lips and inhale deeply and forcefully. Remove the inhaler from the mouth and exhale normally. Do not blow or exhale into the mouthpiece. Do not chew or bite on the mouthpiece.
  • If more than 1 dose is required, repeat the steps described above.
  • After the last dose, rinse the mouth with water; do not swallow the water.
  • The inhaler should be kept clean and dry at all times. Do not immerse it in water. Wipe the outside of the mouthpiece 1 time each week with a dry tissue. The inhaler should not be used if it has been damaged or if the mouthpiece has become detached.
  • The inhaler contains either 60 puffs or 120 puffs after prepared for the first use. The dose indicator window shows approximately how much medicine is left. The indicator is marked in intervals of 10 doses. Markings are either with numbers or dashes (alternating), counting down to "0". Your inhaler is empty when the number "0" on the red background reaches the middle of the dose indicator window; when this occurs, throw away the inhaler.[34376]

 

Inhalation suspension for nebulization (Pulmicort Respules):

  • Administer via jet nebulizer connected to an air compressor with adequate airflow, and equipped with a mouthpiece or suitable face mask. Ultrasonic nebulizers are not suitable for administration and are not recommended.
  • See manufacturer's direction on the use of nebulizer and preparation of the solution.
  • Gently shake the ampule in a circular motion before opening it and placing the suspension in the nebulizer reservoir.
  • A Pari-LC-Jet Plus Nebulizer (with face mask or mouthpiece) connected to a Pari Master compressor was used to deliver budesonide inhalation suspension during the clinical trials. The safety and efficacy of budesonide inhalation suspension delivered by other nebulizers and compressors have not been studied.
  • The choice of using a mouthpiece versus a face mask must be made based on the skills and understanding of each patient.
  • Use of the 'blow by' technique (i.e., holding the face mask or open tube near the patient's nose and mouth) is not recommended.
  • The effects of mixing budesonide with other nebulizable medications have not been adequately assessed; administer budesonide inhalation suspension separately in the nebulizer.
  • Storage: Store inhalation suspension upright at controlled room temperature and protect from light. When the envelope has been opened, the shelf life of the unused ampules is 2 weeks; return unused ampules to the aluminum foil envelope to protect from light. Any opened ampule should be used promptly. Do not refrigerate or freeze.[33486]

Intranasal Inhalation Administration

  • Instruct patient on proper nasal inhalation priming and administration technique.
  • Shake the nasal spray well before administering.
  • Prior to initial use, the container must be shaken gently and the pump must be primed by actuating 8 times. If used daily, the pump does not need to be reprimed. If the spray is not used for 2 consecutive days, reprime with 1 spray or until a fine spray appears. If not used for more than 14 days, rinse the applicator and reprime with 2 sprays or until a fine spray appears.
  • The patient should blow nose gently prior to use. With head upright, spray the medicine into each nostril. The patient should sniff briskly while squeezing the bottle quickly and firmly.
  • After administration, wipe spray tip dry with a clean tissue and replace outer cap.
  • The cap and spray tip should be cleaned regularly. Remove the cap and gently pull the spray tip away from the bottle. Wash in warm water and rinse in cold tap water; shake to remove excess water. Allow cap and spray tip to air dry completely before reassembling.
  • To avoid the spread of infection, do not use the nasal spray container for more than 1 person.[31824][59312]

Rectal Administration

Rectal Foam

  • For rectal use only.
  • The product is flammable. Avoid fire, flames, and smoking during and immediately following administration.
  • Budesonide rectal foam should be temporarily discontinued prior to initiation of bowel preparation for colonoscopy and should not be resumed until a health care provider is consulted.
  • Prior to rectal foam use, the patient should use the bathroom to empty bowels.
  • The foam can be used in a standing, lying or sitting position (e.g., while using the toilet).
  • When budesonide rectal foam is applied in the evening, use immediately prior to bedtime. The patient should not try not to have a bowel movement again until the next morning.
  • Before the first use, remove the safety tab from under the pump dome. The canister cannot be used if safety tab is not removed.
  • The applicators are in a special tray. Applicators are for single use. Use a new applicator for each dose. Each applicator is coated with a lubricant; petrolatum or petroleum jelly can also be used if additional lubrication is needed. To remove an applicator from the tray, hold the tray firmly and pull.
  • Push the applicator firmly onto the nozzle of the canister.
  • To unlock the canister, twist the dome on the top of the canister until the semi-circular notch underneath the dome is in line with the nozzle.
  • Warm the canister by holding it in the hands while shaking it vigorously for 10 to 15 seconds. Place the forefinger on the top of pump dome and then turn the canister upside down. The canister will only work properly when held with the pump dome pointing down.
  • Insert the applicator into the rectum as far as it is comfortable. The easiest way for the patient to use budesonide rectal foam is to keep one foot on the floor and raise the other foot onto a firm surface such as a chair or stool.
  • To administer a dose of budesonide rectal foam- use the forefinger to fully push down the pump dome one time and hold it for about 2 seconds in that position. Release finger pressure on the pump dome and hold the applicator in place for 10 to 15 seconds. Remove the applicator. The foam will still expand a little and may drop out of the applicator or anus.
  • Remove the applicator from the canister and place the used applicator in the plastic bag provided. Throw the plastic bag away in household trash.
  • To prevent loss of budesonide rectal foam from the canister between uses, turn the pump dome around so that the semi-circular notch faces the opposite direction to the nozzle.
  • Wash hands with soap and water following administration.[58166]

Clinical Pharmaceutics Information

From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database
Revision Date: 07/17/2020, 10:49:49 AMCopyright 2004-2021 by Lawrence A. Trissel. All Rights Reserved.

References

31824 - Rhinocort Aqua (budesonide) nasal spray package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2012 Feb.33486 - Pulmicort Respules (budesonide) inhalation suspension package insert. Wilmington, DE: AstraZeneca LP; 2018 Dec.34376 - Pulmicort Flexhaler (budesonide inhalation powder) package insert. Wilmington, DE: AstraZeneca LP; 2018 Dec.34979 - Entocort EC (budesonide) capsules package insert. Wilmington, DE: AstraZeneca LP; 2020 July52910 - Uceris (budesonide) tablets package insert. San Diego, CA: Santarus Inc.; 2020 April.56034 - Aceves SS, Bastian JF, Newbury RO, et al. Oral viscous budesonide: A potential new therapy for eosinophilic esophagitis in children. Am J Gastroenterol 2007;102:2271-2279.56035 - Dohil R, Newbury R, Fox L, et al. Oral viscous budesonide is effective in children with eosinophilic esophagitis in a randomized, placebo-controlled trial. Gastroenterology 2010;139:418-429.57689 - Rubinstein E, Lee JJ, Fried A, et al. Comparison of two delivery vehicles for viscous budesonide to treat eosinophilic esophagitis in children. J Pediatr Gastroenterol Nutr 2014 May 11. [Epub ahead of print]58166 - Uceris (budesonide) rectal foam package insert. Bridgewater, NJ: Salix Pharmaceuticals; 2020 April.59312 - Rhinocort Allergy Spray (budesonide) nasal spray package insert. Fort Washington, PA: McNeil Consumer Healthcare Division; 2017 May64318 - Ortikos (budesonide) capsules package insert. Cranbury, NJ: Sun Pharmaceutical Industries, Inc; 2019 June.

Adverse Reactions

Mild

  • abdominal pain
  • acne vulgaris
  • agitation
  • alopecia
  • anorexia
  • anxiety
  • appetite stimulation
  • arthralgia
  • asthenia
  • back pain
  • cough
  • diarrhea
  • dizziness
  • drowsiness
  • dysgeusia
  • dysosmia
  • dyspepsia
  • ecchymosis
  • emotional lability
  • epistaxis
  • fatigue
  • fever
  • flatulence
  • flushing
  • headache
  • hirsutism
  • hoarseness
  • hyperhidrosis
  • hyperkinesis
  • infection
  • insomnia
  • irritability
  • leukocytosis
  • maculopapular rash
  • malaise
  • myalgia
  • nasal congestion
  • nasal irritation
  • nausea
  • otalgia
  • paresthesias
  • pharyngitis
  • pruritus
  • purpura
  • rash
  • rhinitis
  • sinusitis
  • syncope
  • throat irritation
  • tremor
  • urticaria
  • vertigo
  • vomiting
  • weight gain
  • xerostomia

Moderate

  • adrenocortical insufficiency
  • anemia
  • atopic dermatitis
  • candidiasis
  • cataracts
  • chest pain (unspecified)
  • confusion
  • constipation
  • contact dermatitis
  • Cushing's syndrome
  • depression
  • dysphonia
  • edema
  • eosinophilia
  • fluid retention
  • glossitis
  • growth inhibition
  • hematuria
  • hemorrhoids
  • hyperglycemia
  • hypertension
  • hypertonia
  • hypokalemia
  • hypothalamic-pituitary-adrenal (HPA) suppression
  • migraine
  • ocular infection
  • osteopenia
  • osteoporosis
  • palpitations
  • peripheral edema
  • psychosis
  • pyuria
  • sinus tachycardia
  • withdrawal

Severe

  • anaphylactoid reactions
  • angioedema
  • avascular necrosis
  • bronchospasm
  • Churg-Strauss syndrome
  • gastrointestinal fistula
  • GI bleeding
  • GI obstruction
  • increased intracranial pressure
  • nasal septum perforation
  • ocular hypertension
  • pancreatitis
  • skeletal changes
  • vasculitis
  • visual impairment

The most common adverse events during treatment with nasal budesonide are epistaxis (8%), pharyngitis (4%), cough (2%), and nasal irritation (2%). Dysosmia (reduced sense of smell) and nasal septum perforation have been reported with postmarketing use of nasal budesonide. During budesonide nebulization, the most common adverse reactions include respiratory infection (2.2% to 38% depending on the clinical trial), cough (5% to 9%), rhinitis (7% to 12%), and otitis media (9% to 12%). Otitis media occurred in 1.3% of patients who received budesonide inhalation powder in clinical trials. Other adverse events to oral or inhaled budesonide therapy include epistaxis (2% to 4% inhaled), pharyngitis (3% or more inhaled), rhinitis (greater than 2% to less than 5% oral, 2.2% to 12% inhaled), sinusitis (8% oral, 3% or more inhaled), nasal congestion (2.7 % inhaled), viral infection (6% oral, 2.2% to 5% inhaled), ear infection (less than 5% oral, 2% to 5% inhaled), otalgia (1 to less than 3% inhaled), urinary tract infection (greater than 2% to 5% oral), dysphonia (hoarseness) (1% to 3% inhaled), fever (more than 2% to less than 5% oral, greater than 3% inhaled, reported during postmarketing experience with rectal foam), and herpes simplex activation. Throat irritation has also been reported during postmarketing use of inhaled budesonide. Oral candidiasis is a well known adverse effect of inhaled corticosteroids; 3% to 4% of patients who received inhaled budesonide experienced oral candidiasis in clinical trials. Using an add-on spacer device, reducing the frequency of use, and rinsing the mouth after use may minimize the incidence of oropharyngeal thrush. In clinical trials of oral budesonide capsules, less than 5% of patients developed oral candidiasis. Monitor patients on long-term budesonide therapy for signs of infection. Discontinuation of budesonide may be required.[31824] [33486] [34376] [34979] [52910] [58166] [64318]

In general, oral budesonide is well tolerated. Delayed duodenal absorption and extensive first-pass metabolism reduces the amount of drug available for systemic absorption. The most common central nervous system reactions occurring with oral budesonide, independent of formulation (5% or more of patients, more than placebo) include headache (21% to 37%), dizziness (7%), and fatigue (5% to 8%). Many adverse events were reported with oral budesonide capsules in less than 5% of patients (but greater than placebo) including agitation, confusion, hyperkinesis, insomnia, nervousness, paresthesias, somnolence or drowsiness, tremor, and vertigo. Insomnia (4% to 6%), sleep changes (3% to 10%), and emotional lability (4% to 10%) have been reported with oral budesonide tablets. However, reports have noted the advantage of oral budesonide in lowering CNS toxicity that may occur with other oral steroids.[26692] [64318] Headache (3%), migraine (1% to 3%), insomnia (1% to 3%), and fatigue (1% to 3%) have also been reported with inhaled budesonide. Psychiatric adverse reactions reported in less than 1% of patients receiving inhaled budesonide include depression, aggressive reactions, irritability, anxiety, and psychosis.[33486] [34376] [34979] [52910] In patients using budesonide rectal foam, insomnia, sleep disorder, and depression were reported in less than 1% of patients. Mood swings and dizziness were also reported during postmarketing experience with budesonide rectal foam and oral capsules.[52910] [58166]

Immediate or delayed hypersensitivity reactions, including anaphylactoid reactions, urticaria, angioedema, rash (unspecified), and bronchospasm have been rarely reported with budesonide therapy. Bronchospasm has also been reported in 2% of patients receiving nasal budesonide in clinical trials. Rash (unspecified) has been reported in 4% or less of patients and pruritus and ecchymosis in 1% to 3% of patients receiving inhaled budesonide. Ecchymosis has been reported in 10% of patients receiving oral budesonide. Contact dermatitis was reported in less than 5% of patients receiving oral budesonide capsules and in 1% to 3% of patients receiving inhaled budesonide. Additional dermatologic adverse reactions occurring in less than 5% of patients receiving oral budesonide but occurring at a rate greater than those receiving placebo in clinical trials included alopecia, hyperhidrosis (increased sweating), purpura, and eczema (atopic dermatitis).[31824] [33486] [34376] [34979] [52910] [64318] In patients using budesonide rectal foam, anaphylactoid reactions, pruritis, maculopapular rash, and allergic dermatitis were reported during postmarketing experience.[58166]

Budesonide therapy, just like any corticosteroid, has been rarely associated with the development of cataracts, increased ocular pressure or ocular hypertension, and glaucoma in adults. The risk of cataracts increases with long-term and high-dose inhaled corticosteroid use. The mechanism of corticosteroid-induced cataract formation is uncertain but may involve disruption of sodium-potassium pumps in the lens epithelium leading to accumulation of water in lens fibers and agglutination of lens proteins.[24813] Visual impairment has been reported in less than 5% of patients receiving oral budesonide, but cataract development has not been noted. Prolonged use of glucocorticoids could result in glaucoma or ocular nerve damage including optic neuritis. Temporary or permanent visual impairment, including blindness, has been reported with glucocorticoid administration by several routes of administration including intranasal administration. Secondary fungal and viral infections of the eye can be exacerbated by corticosteroid therapy. Ocular infection was reported in 1 to less than 3% of patients receiving inhaled budesonide therapy.[31824] [33486] [34376] [34979] [52910] [64318]

Pharmacologic doses of corticosteroids administered for prolonged periods can result in hypothalamic-pituitary-adrenal (HPA) suppression; symptoms of hypocorticism have been reported rarely with inhaled budesonide use. Adrenal insufficiency and withdrawal symptoms may occur after treatment discontinuation or when transitioning from systemic corticosteroids to inhaled corticosteroids in some patients. Exogenously administered corticosteroids exert negative feedback on the pituitary, which inhibits the secretion of adrenocorticotropin (ACTH). This results in a decrease in ACTH-mediated synthesis of endogenous corticosteroids and androgens by the adrenal cortex. The mean decrease in the integrated 0 to 24 hour plasma cortisol concentration as determined by data from subjects in a crossover study was 45% after 5 days of budesonide capsules (9 mg/day) and 78% after 5 days of prednisolone 20 mg/day. In 17% of 268 patients using budesonide rectal foam 2 mg/25 mL, decreases in serum cortisol levels associated with budesonide were seen at weeks 1 and 2 (twice-daily treatment), but gradually returned to baseline levels during the 4 weeks of once-daily treatment. Adrenocortical insufficiency was reported in 4% of 268 patients using budesonide rectal foam 2 mg/25 mL. The severity of glucocorticoid-induced secondary adrenocortical insufficiency varies among individuals and is dependent on the dose, frequency, time of administration, and duration of therapy. Use of inhaled corticosteroids with systemic corticosteroids could increase the likelihood of HPA suppression as compared with a therapeutic dose of either one alone.[31824] [33486] [34376] [34979] [52910] [58166] [64318]

Controlled clinical trials have shown that intranasal or orally inhaled corticosteroids may cause growth inhibition in pediatric patients. 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 one study, children 5 to 12 years of age with asthma receiving inhaled budesonide experienced a 1.1 cm reduction in growth compared to the placebo group by the end of 1 year. By the end of 4 years, the growth velocities of both groups were similar.[33486] 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.[34376] [33486] [34979] [52910] [58166] [64318]

Oral and inhaled corticosteroids may impact bone and joint health. In two 8-week placebo-controlled trials of oral budesonide tablets, arthralgia (5%) was listed among the most common adverse events reported. Prolonged use (e.g., more than 1 year) of high doses of inhaled corticosteroids, such as budesonide, especially when used in combination with frequent courses of systemic corticosteroids, may be associated with skeletal changes and reduced bone mineral density (BMD), which may increase the risk of osteopenia and osteoporosis. The clinical significance of small changes in BMD with regard to long-term outcomes, such as fracture, is unknown. Bone disorders including avascular necrosis of the femoral head and osteoporosis have been reported in less than 1% of patients receiving inhaled budesonide. In long-term (12 months) open-label studies for oral budesonide tablets, 77% of patients had normal bone density scans compared to 74% with placebo.[33486] [34376] [34979] [52910] [58166] [64318]

In clinical evaluation of oral budesonide, decreased blood cortisol (6% to 11%) and acne (2% to 6%) were listed among the most common adverse events reported. Other glucocorticoid related effects reported with either short term induction therapy (8 to 16 weeks) or long-term treatment (12 months) included, moon face (3%), fluid retention (1% to 3%), hirsutism (1% to 3%), and flushing (1% tablets, less than 5% capsules).[52910] [64318] In clinical trials evaluating the incidence of symptoms of hypercorticism (Cushing's syndrome) with oral budesonide versus prednisolone, only acne vulgaris (15% vs. 23%, respectively) and moon face (11% vs. 37%, respectively) were statistically less than prednisolone. Easy bruising (15%) and hirsutism (5%) occurred at a rate slightly higher than with prednisolone. Buffalo hump, swollen ankles and skin striae occurred at incidences similar to prednisolone. From postmarketing surveillance with oral budesonide, increased intracranial pressure (benign) has been reported rarely, but a causal relationship has not been established.[34979] Acne and hyperglycemia have been reported in less than 1% of patients using budesonide rectal foam. In patients using budesonide rectal foam, benign increased intracranial pressure was reported during postmarketing experience.[58166]

Gastrointestinal (GI) adverse reactions reported in patients receiving budesonide include nausea (11% to 13% oral, 1.8% inhaled, 2% rectal foam), constipation (1% to 5% oral), dyspepsia (6% oral), abdominal distention (4% to 6% oral), abdominal pain (6% to 10% oral, 1% to 3% inhaled), flatulence (6% to 8% oral), vomiting (6% oral, 1% to 4% inhaled), diarrhea (10% oral, 2% to 4% inhaled), gastroenteritis (1.8% to 5% inhaled), weight gain (less than 5% oral, 1% to 3% inhaled), xerostomia (1% to 3% inhaled), dysgeusia (1% to 3% inhaled), and anorexia (1 to less than 3% inhaled). Additional GI adverse reactions occurring in less than 5% of patients receiving oral budesonide, but at an incidence higher than with placebo in clinical trials, included anus disorder, appetite stimulation, Crohn's disease aggravated, enteritis, epigastric pain, gastrointestinal fistula, glossitis, hemorrhoids, GI obstruction, tongue edema, and tooth disorder.[33486] [34376] [34979] [52910] [64318] Pancreatitis has been reported during postmarketing experience with budesonide rectal foam.[58166] Rectal GI bleeding has been reported during postmarketing experience with oral budesonide tablets.[52910]

Cardiovascular adverse reactions reported in patients receiving budesonide include chest pain (unspecified) (less than 5% oral, 1% to 3% inhaled) and syncope (1% to 3% inhaled). Additional cardiovascular adverse reactions occurring in less than 5% of patients receiving oral budesonide but greater than patients receiving placebo in clinical trials include edema, flushing, hypertension, palpitations, and sinus tachycardia.[33486] [34376] [34979] [64318] In patients using budesonide rectal foam, hypertension and peripheral edema were reported during postmarketing experience.[58166]

In rare cases, patients on inhaled budesonide may present with eosinophilia and clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition often treated with systemic corticosteroids. These events have happened most commonly in association with systemic corticosteroid withdrawal in conjunction with the introduction of inhaled corticosteroid therapy. Patients presenting with eosinophilia, vasculitis with granulomas, worsening pulmonary symptoms, and/or neuropathy may have this condition, which may be severe. Similar cases have been reported with the use of other inhaled corticosteroids. A causal relationship to budesonide has not yet been established.[34376]

Musculoskeletal adverse reactions reported with budesonide therapy include pain (5% oral; 3% or more inhaled), back pain (3% or more inhaled), neck pain (1% to 3% inhaled), hypertonia (1% to 3% inhaled), myalgia (less than 5% oral; 1% to 3% inhaled), muscle cramps (less than 5% oral), and arthritis (less than 5% oral).[33486] [34376] [34979] [64318]

Generalized adverse reactions reported with budesonide therapy include asthenia (less than 5% oral), flu-like disorder (1 to less than 3% inhaled, less than 5% oral), and malaise (less than 5% oral).[33486] [34979] [64318]

Laboratory abnormalities reported in 1% or more of patients receiving oral budesonide in clinical trials, regardless of relationship to budesonide, include hypokalemia (1% to less than 5%), leukocytosis (1% to less than 5%), elevated C-reactive protein (1% to less than 5%), anemia, hematuria, pyuria, elevated erythrocyte sedimentation rate, elevated alkaline phosphatase, and atypical neutrophils. Leukocytosis is a common physiologic effect of systemic corticosteroid therapy and may need to be differentiated from the leukocytosis that occurs with inflammatory or infectious processes.[30943] [34979] [52910] [65096] [65097] [64318]

Revision Date: 06/14/2021, 11:39:41 AM

References

24813 - Cumming RG, Mitchell P, Leeder SR, et al. Use of inhaled corticosteroids and the risk of cataracts. N Engl J Med 1997;337:8-14.26692 - Thomas MC, Schlup MM. Budesonide substitution in Crohn's disease relieves CNS toxicity of systemic steroids. Med J Aust 1998;169:560.30943 - Schimmer B, Parker K. Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Hardman JG, Limbird LE, Molinoff PB, et al., eds. Goodman and Gilman's the Pharmacological Basis of Therapeutics, 10th edition. New York: McGraw Hill, 2001;1649-1674.31824 - Rhinocort Aqua (budesonide) nasal spray package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2012 Feb.33486 - Pulmicort Respules (budesonide) inhalation suspension package insert. Wilmington, DE: AstraZeneca LP; 2018 Dec.34376 - Pulmicort Flexhaler (budesonide inhalation powder) package insert. Wilmington, DE: AstraZeneca LP; 2018 Dec.34979 - Entocort EC (budesonide) capsules package insert. Wilmington, DE: AstraZeneca LP; 2020 July52910 - Uceris (budesonide) tablets package insert. San Diego, CA: Santarus Inc.; 2020 April.57670 - 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.pub258166 - Uceris (budesonide) rectal foam package insert. Bridgewater, NJ: Salix Pharmaceuticals; 2020 April.64318 - Ortikos (budesonide) capsules package insert. Cranbury, NJ: Sun Pharmaceutical Industries, Inc; 2019 June.65096 - Abramson N, Melton B. Leukocytosis: basic of clinical assessment. Am Fam Physician 2000;62:2053-60.65097 - Shoenfeld Y, Gurewich Y, Gallant LA, et al. Prednisone-induced leukocytosis. Influenced of dosage, method and duration of administration on the degree of leukocytosis. Am J Med 1981;71:773-8.

Contraindications/Precautions

Absolute contraindications are italicized.

  • abrupt discontinuation
  • acute bronchospasm
  • adrenal insufficiency
  • breast-feeding
  • cataracts
  • children
  • corticosteroid hypersensitivity
  • corticosteroid withdrawal
  • Cushing's syndrome
  • diabetes mellitus
  • edema
  • fungal infection
  • gastroenteritis
  • geriatric
  • GI perforation
  • glaucoma
  • growth inhibition
  • heart failure
  • hepatic disease
  • herpes infection
  • hypercortisolism
  • hyperglycemia
  • hypertension
  • hyperthyroidism
  • hypothalamic-pituitary-adrenal (HPA) suppression
  • hypothyroidism
  • immunosuppression
  • increased intracranial pressure
  • increased intraocular pressure
  • infants
  • infection
  • malnutrition
  • measles
  • milk protein hypersensitivity
  • myasthenia gravis
  • nasal septal perforation
  • nasal surgery
  • nasal trauma
  • neonates
  • ocular infection
  • osteoporosis
  • peptic ulcer disease
  • pregnancy
  • psychosis
  • renal disease
  • seizure disorder
  • status asthmaticus
  • surgery
  • thyroid disease
  • tobacco smoking
  • trauma
  • tuberculosis
  • varicella
  • viral infection
  • visual disturbance

Use of budesonide should not contraindicate administration of live-virus vaccines. According to the Advisory Committee on Immunization Practices (ACIP), administration of live-virus vaccines is safe and effective when steroid therapy is administered topically or by inhalation.[43236]

Inhaled budesonide is contraindicated as primary therapy for patients with status asthmaticus or other types of acute bronchospasm for which intensive therapy is warranted. Patients should be advised that budesonide is not to be used as a bronchodilator and is not indicated for relief of acute bronchospasm.[33486] [34376] Although inhaled corticosteroids (ICSs) are not indicated for primary treatment of an acute exacerbation, they may be initiated at any time during an exacerbation for patients not using long-term control therapy. An ICS may also be continued during an exacerbation for patients previously using the drug for chronic control.[37445] Additionally, budesonide is contraindicated for use in any patient with a known hypersensitivity to budesonide or any ingredient in the formulation.[33486] [34376] Pulmicort Flexhaler contains micronized lactose, which may contain trace or residual levels of milk protein. Patients with a severe milk protein hypersensitivity may experience an allergic reaction to this product.[34376]

Although inhaled budesonide is absorbed systemically to a lesser extent than other corticosteroids, significant amounts can be absorbed when large doses are administered and immunosuppression may occur. In general, corticosteroid therapy can mask the symptoms of infection and should not be used in cases of bacterial or viral infection that are not adequately controlled by anti-infective agents, except in life-threatening circumstances. Secondary infections are common during corticosteroid therapy. Corticosteroids can reactivate tuberculosis and should not be used in patients with a history of active tuberculosis except when chemoprophylaxis is instituted concomitantly. Corticosteroids should be avoided in patients with active herpes infection, including herpes simplex ocular infection. Extended use of budesonide nasal spray or inhalations has been rarely associated with the development of localized fungal 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 periodic evaluation for nasal Candida infections or other adverse effects on the nasal mucosa.

Administration of corticosteroids may result in more serious or even fatal varicella (chickenpox) or measles infection in susceptible pediatric patients or adults. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is unknown. The clinical course of varicella infection or measles in patients treated with inhaled corticosteroids has not been studied; however, the immune-response to varicella vaccination in pediatric patients receiving budesonide therapy has. An open-label, non-randomized, clinical study examined the immune responsiveness of varicella vaccine in 243 asthma patients aged 12 months to 8 years who were treated with either budesonide inhalation suspension 0.25 to 1 mg daily (n=151) or non-corticosteroid asthma therapy (n=92) including beta-2-agonists and leukotriene receptor antagonists. The percentage of patients developing a seroprotective antibody titer of >= 5 (gpELISA value) in response to the vaccination was similar between the 2 groups (85% of patients treated with budesonide versus 90% of patients not receiving budesonide). None of the patients treated with budesonide developed chicken pox as a result of vaccination. Appropriate prophylactic medications should be considered in patients receiving budesonide who are exposed to varicella (VZIG or IVIG) or measles (IG). If varicella develops, treatment with antiviral agents may be needed.

The lowest dose of budesonide associated with appropriate therapeutic effect should be used in children, adolescents, and infants. Of particular concern in pediatric patients, budesonide, like other corticosteroids, may interfere with growth patterns, regardless of route of administration. Pediatric patients receiving any formulation of budesonide should be monitored closely for growth inhibition. Controlled clinical studies have shown that inhaled corticosteroids may cause a reduction in growth velocity in pediatric patients; therefore, growth should be routinely monitored during use.[33486] [34376] [31824] [34979] [52910] [57670] Other precautions in pediatric patients are related to hypothalamic-pituitary-adrenal (HPA) function and risk for HPA-axis suppression, which is generally low with inhaled budesonide, but must be monitored for carefully in pediatric patients on corticosteroids. Adrenal suppression and increased intracranial pressure have been reported with the use and/or withdrawal of systemic, intranasal, orally inhaled, and topical corticosteroids in pediatric patients.[44131] [51792] [58998] Budesonide respiratory inhalations have been evaluated for safety and efficacy in children and infants of varying ages, but the recommended ages for use vary by product. For nebulizer inhalation (Pulmicort Respules), the product is not approved in infants, but has been used off-label in infants as young as 3 months of age; efficacy in neonates has not been determined as limited trials have not shown benefit over systemic corticosteroids for indications such as prevention of bronchopulmonary dysplasia.[33486] [33594] [44927] [56029] The safety and efficacy of budesonide aerosol powder for inhalation (Pulmicort Flexhaler) has not been determined for pediatric patients less than 6 years of age.[34376] The safety and efficacy of rectal budesonide (e.g., Uceris) in pediatric patients has not been determined.[52910] Oral budesonide (e.g., Uceris, Ortikos) is safe and effective in pediatric patients 8 years and older with Crohn's disease.[34979] [64318] Nasal inhalations of budesonide (e.g., Rhinocort Aqua, Rhinocort Allergy) are safe and effective in children 6 years and older; however, prolonged administration requires careful monitoring by a health care provider.[31824] [59312]

Studies of pregnant women have not shown that inhaled budesonide increases the risk of abnormalities when administered during pregnancy.[31824] [33486] [34376] [46711] A review of Swedish registries of more than 2,000 births indicated that no increased risk for congenital malformations during early pregnancy with budesonide inhalation powder or solution.[46713] Despite adverse effects in animal studies, fetal harm appears remote. Corticosteroid treatment may not be necessary during pregnancy due to a natural increase in corticosteroid production; however, poorly controlled maternal asthma also poses risk to the mother and the fetus. Low-dose inhaled corticosteroids are considered first-line therapy for control of mild persistent asthma during pregnancy according to the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group; of the inhaled corticosteroids, more data are available for budesonide use in pregnancy. Data on the use of medium- to high-dose inhaled corticosteroid use during pregnancy are limited. However, dose titration may be considered for those with moderate to severe persistent asthma, preferably using budesonide. However, there are no data to indicate safety concerns with other inhaled corticosteroids, and maintaining a previously established treatment regimen may be more beneficial to the patient.[31822] Selection of any pharmacologic treatment for asthma control during pregnancy should include the specific needs of the patient, based on an individual evaluation, and consideration of the potential benefits or risks to the fetus. A position statement by the American College of Allergy, Asthma and Immunology also considers budesonide a good choice for pregnant women requiring high doses of inhaled steroids for effective asthma management.[46717] Oral budesonide products (e.g., Entocort EC, Ortikos, Uceris) have been teratogenic and embryocidal in animal studies. At doses smaller than the recommended human maximum dose, fetal loss, decreased pup weights, and skeletal anomalies occurred. There is a natural increase in endogenous corticosteroid production during pregnancy, and many women will require a lower exogenous dose or no corticosteroid treatment at all during pregnancy. Oral budesonide (e.g., Entocort EC, Ortikos, Uceris) products should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. Hypoadrenalism may occur in an infant born to a mother receiving corticosteroids during pregnancy, and the infant should be carefully observed.[34979] [52910] [64318]

Like other corticosteroids, budesonide is excreted into breast milk. Based on data from a small number (n = 8) of breast-feeding women taking inhaled dry powder budesonide 200 to 400 mcg twice daily, approximately 0.3 to 1% of the dose inhaled by the mother is available via breast milk to an exclusively breast-fed infant. Budesonide plasma concentrations obtained in five of the infants in this study about 140 minutes after maternal drug administration and 90 minutes after breast-feeding were below quantifiable levels.[33725] Low-dose inhaled corticosteroids are considered first line therapy for control of mild persistent asthma during pregnancy and lactation according to the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group. Due to greater availability of data, budesonide is considered the preferred agent in this population.[31822] The amount of inhaled budesonide excreted in breast-milk is minute, and infant exposure is negligible. Reviewers and an expert panel consider all inhaled corticosteroids acceptable to use during breast-feeding.[33723] [33724] [31822]. According to the manufacturer of oral budesonide (e.g., Entocort EC, Ortikos, Uceris), a decision should be made whether to discontinue nursing or to discontinue oral budesonide, taking into account the clinical importance of medication to the mother.[34979] [52910] [64318] Single- and repeated-dose pharmacokinetic studies have shown that maximum plasma budesonide concentrations after a 9 mg oral daily dose are up to 10-times greater than the concentrations measured after inhaled doses of 400 to 800 mcg/day. Assuming that the coefficient of extrapolation between inhaled and oral doses is constant across all doses, it is possible that budesonide exposure to breast-feeding infants after maternal oral ingestion may be up to 10-times higher than exposure to infants after maternally inhaled budesonide. However, the oral bioavailability of budesonide is low (approximately 9%) and would be also be expected to be minimal in infants who ingest budesonide through breast milk.[34979] [52910] Budesonide rectal foam (e.g., Uceris Rectal) is likely to result in budesonide in human milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.[58166]

Although the risk of developing hypothalamic-pituitary-adrenal (HPA) suppression is very low with inhaled budesonide, 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; abrupt discontinuation should be avoided. Patients previously maintained on doses equivalent to 20 mg/day or more of prednisone may be at increased risk. The transfer from systemic corticosteroid therapy to orally inhaled budesonide may also result in unmasking of allergies or other immunologic conditions, such as rhinitis, eczema, eosinophilia, conjunctivitis, or arthritis, that were previously controlled by treatment with systemic corticosteroids. After withdrawal from systemic therapy, a number of months are required for recovery of HPA-axis function. Symptoms attributable to acute corticosteroid withdrawal, such as adrenal suppression and increased intracranial pressure may occur. Adrenocortical function monitoring (plasma and urine cortisol levels and response to ACTH stimulation) may be required. In a 5 day study, 0 to 24 hour cortisol concentration suppression was 45% and 78% for oral budesonide 9 mg/day and prednisolone 20 mg/day, respectively. Switching from oral corticosteroids with higher bioavailability to oral budesonide should be undertaken with caution. Systemic oral steroid therapy, such as prednisolone, should be tapered when initiating oral budesonide.

If hypothalamic-pituitary-adrenal suppression occurs, patients will require systemic corticosteroids during periods of physiologic stress (e.g., trauma, surgery, infection especially gastroenteritis, or other conditions associated with electrolyte loss). Although inhaled or nebulized budesonide may provide control of asthma symptoms during these episodes, in recommended doses it supplies less than normal physiological amounts of corticosteroid systemically and does not provide mineralocorticoid activity. With the use of oral budesonide, supplementation with a systemic corticosteroid is recommended during physiologic stress. If surgery is required, patients should notify all health care providers that they have received corticosteroids within the last 12 months.

Glucocorticoids, such as budesonide, should be avoided in patients with Cushing's disease since they can produce or aggravate Cushing's syndrome. It is possible that systemic corticosteroid effects such as hypercortisolism may appear in a small number of patients receiving inhaled budesonide, particularly at higher doses. If features consistent with hypercorticism or Cushing's disease occur, the steroid should be reduced slowly, consistent with accepted procedures for management of symptoms and for tapering of systemic steroids.

Due to the inhibitory effects of glucocorticoids on wound healing, intranasal budesonide should be avoided in patients with a recent history of oral surgery or nasal surgery, nasal trauma, or nasal septal ulcers until their condition has healed. Intranasal budesonide overuse, improper use, or chronic use might lead to nasal septal perforation; patients who experience recurrent episodes of epistaxis (nosebleeds) or nasal septum discomfort while taking this medication should contact their prescriber for evaluation. If perforation occurs, the drug should be discontinued until healing is complete.

Detrimental effects on bone metabolism, such as osteoporosis are expected to be much lower with inhaled rather than systemically administered corticosteroids. Some patients receiving high-dose inhaled budesonide or oral budesonide may experience reduced bone mineral density and chronic use should be approached cautiously in patients with osteoporosis or risks for osteoporosis. Compounding risk factors include preexisting osteopenia, prolonged immobilization, family history of osteoporosis, tobacco smoking, malnutrition, and use of other medications that may reduce bone mass.[34376] [52910] [64318]

Although oral budesonide has weak mineralocorticoid properties, hypertension due to edema and electrolyte imbalance may occur. Prolonged administration of systemic glucocorticoids also can result in edema and hypertension. In a review of 93 studies of corticosteroid use, hypertension was found to develop 4 times as often in steroid recipients compared to control groups.[24362] Congestive heart failure can occur in susceptible patients.[34979] [52910] [64318]

Systemic corticosteroids, such as budesonide, should be used with caution in patients with psychosis, emotional instability, renal disease, diabetes mellitus or a family history of diabetes (due to risk of hyperglycemia), or a seizure disorder because the drug's pharmacologic actions can exacerbate these conditions. Monitor carefully those patients with peptic ulcer disease since oral corticosteroids in these patients can have untoward effects (exacerbate ulceration and GI perforation risks).[34979] [52910] [64318] Use caution in patients with thyroid disease. Patients with hyperthyroidism have an increased rate of corticosteroid elimination and may have a less than expected drug-effect, while those with hypothyroidism have decreased corticosteroid clearance and can have an exaggerated drug response.

Monitor for increased signs and/or symptoms of hypercorticism in all patients with mild to moderate hepatic disease receiving systemic corticosteroids. Patients who have moderate to severe hepatic impairment may be at an increased risk of hypercorticism and adrenal axis suppression due to an increased budesonide systemic exposure. For the oral delayed-release capsules (i.e, Entocort EC), it is recommended to consider reducing the oral dosage in patients with moderate hepatic impairment (Child-Pugh Class B) and avoiding use in severe hepatic impairment (Child-Pugh Class C); for the oral extended-release capsules (i.e, Ortikos), use should be avoided in patients with moderate to severe hepatic impairment (Child-Pugh Classes B and C); specific dosage adjustments are not available for the extended-release tablets (i.e., Uceris).[34979] [52910] [64318]

Corticosteroids, like budesonide, should be used cautiously in patients with glaucoma or other visual disturbance or with a family history of glaucoma. Corticosteroids are well known to cause cataracts and can exacerbate glaucoma during long-term administration. Rare instances of glaucoma, increased intraocular pressure, and cataracts have been reported following the inhaled administration of corticosteroids. Patients receiving topical or systemic corticosteroids chronically should be periodically assessed for ocular effects.

Systemic glucocorticoids, like budesonide, should be used with caution in patients with myasthenia gravis who are being treated with anticholinesterase agents. Muscle weakness may be transiently increased during the initiation of systemic glucocorticoid therapy in patients with myasthenia gravis, necessitating respiratory support.[34979] [52910] [64318]

True corticosteroid hypersensitivity is rare, nevertheless 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]

There is no special precaution needed for the dosage of inhaled, rectal, or nasal budesonide in older adults.[34376] [59312] [58166] In general, oral budesonide dose selection for a geriatric patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.[34979] [52910] [64318] According to the Beers Criteria, systemic corticosteroids are considered potentially inappropriate medications (PIMs) for use in geriatric patients with delirium or at high risk for delirium and should be avoided in these patient populations due to the possibility of new-onset delirium or exacerbation of the current condition. The Beers expert panel notes that oral corticosteroids may be required for chronic conditions but should be prescribed in the lowest effective dose and for the shortest possible duration.[63923] The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to the OBRA guidelines, the need for continued use of a glucocorticoid, with the exception of topical or inhaled formulations, should be documented, along with monitoring for and management of adverse consequences. Intermediate or longer-term use may cause hyperglycemia, psychosis, edema, insomnia, hypertension, osteoporosis, mood lability, or depression. Use caution with orally inhaled corticosteroids, such as budesonide, as these can cause throat irritation and oral candidiasis, particularly if the mouth is not rinsed after administration.[60742]

Revision Date: 01/15/2021, 12:41:43 PM

References

24362 - Conn HO, Poynard T. Corticosteroids and peptic ulcer: meta-analysis of adverse events during steroid therapy. J Intern Med 1994;236:619-32.27616 - Butani L. Corticosteroid-induced hypersensitivity reactions. Ann Allergy Asthma Immunol 2002;89(5):439-445.31822 - NAEPP Working Group Report on Managing Asthma During Pregnancy. Recommendations for Pharmacologic Treatment-Update 2004. NIH Publication No. 05-3279. Bethesda, MD: U.S. Department of Health and Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute, 200431824 - Rhinocort Aqua (budesonide) nasal spray package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2012 Feb.33486 - Pulmicort Respules (budesonide) inhalation suspension package insert. Wilmington, DE: AstraZeneca LP; 2018 Dec.33594 - Baker JW, Mellon M, Wald J, et al. A multiple-dosing, placebo-controlled study of budesonide inhalation suspension given once or twice daily for treatment of persistent asthma in young children and infants. Pediatrics 1999;103:414-21.33723 - Greenberger PA, Patterson R. The management of asthma during pregnancy and lactation. Clin Rev Allergy 1987;5:317-24.33724 - Ellsworth A. Pharmacotherapy of asthma while breastfeeding. J Hum Lact 1994;10:39-41.33725 - Falt A, Bengtsson T, Kennedy BM, et al. Exposure of infants to budesonide through breast milk of asthmatic mothers. J Allergy Clin Immunol 2007;120:798-802.34376 - Pulmicort Flexhaler (budesonide inhalation powder) package insert. Wilmington, DE: AstraZeneca LP; 2018 Dec.34979 - Entocort EC (budesonide) capsules package insert. Wilmington, DE: AstraZeneca LP; 2020 July37445 - National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program Expert Panel Report 3: guidelines for the diagnosis and management of asthma. Bethesda, MD: NIH; 2007.43236 - National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC). General recommendations on immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2011;60(2):1-64.44131 - Bond DW, Charlton CPJ. Benign intracranial hypertension secondary to nasal fluticasone propionate. BMJ 2001;322 (7291):987.44927 - Russell KF, Liang Y, O'Gorman K, Johnson DW, Klassen TP. Glucocorticoids for croup. Cochrane Database Syst Rev. 2011:CD00195546711 - Pulmicort Turbuhaler (budesonide) package insert. Wilmington, DE: AstraZeneca, LP; 2006 Oct.46713 - Kallen B, Rydhstroem H, Aberg A. Congenital malformations after the use of inhaled budesonide in early pregnancy. Obstet Gynecol 1999;93:392-5.46717 - Joint Committee of the American College of Obstetricians and Gynecologists (ACOG) and the American College of Allergy, Asthma, and Immunology (ACAAI). Position statement: The use of newer asthma and allergy medications during pregnancy. Ann Allergy Asthma Immunol 2000;84:475-80.51792 - Patradoon-Ho P, Gunasekera H, Ryan MM. Inhaled corticosteroids, adrenal suppression and benign intracranial hypertension. Med J Aust 2006;185:279-28052910 - Uceris (budesonide) tablets package insert. San Diego, CA: Santarus Inc.; 2020 April.56029 - Griffin S, Ellis S, Fitzgerald-Barron A, et al. Nebulised steroid in the treatment of croup: a systematic review of randomised controlled trials. Br J Gen Pract 2000;50:135-141.57670 - 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.pub258166 - Uceris (budesonide) rectal foam package insert. Bridgewater, NJ: Salix Pharmaceuticals; 2020 April.58998 - Neville BG, Wilson J. Benign intracranial hypertension following corticosteroid withdrawal in childhood. Br Med J 1970;3:554-556.59312 - Rhinocort Allergy Spray (budesonide) nasal spray package insert. Fort Washington, PA: McNeil Consumer Healthcare Division; 2017 May60742 - Health Care Financing Administration. Interpretive Guidelines for Long-term Care Facilities. Title 42 CFR 483.25(l) F329: Unnecessary Drugs. Revised 2015.63923 - The American Geriatrics Society 2019 Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2019;00:1-21.64318 - Ortikos (budesonide) capsules package insert. Cranbury, NJ: Sun Pharmaceutical Industries, Inc; 2019 June.

Mechanism of Action

Glucocorticoids are naturally occurring hormones that prevent or suppress inflammation and immune responses when administered at pharmacological doses. In general, glucocorticoids inhibit the activity of a variety of cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators involved in allergic and nonallergic/irritant-mediated inflammation (e.g., histamine, eicosanoids, leukotrienes, and cytokines). At the molecular level, unbound glucocorticoids readily cross cell membranes and bind with high affinity to specific cytoplasmic receptors. Subsequent to binding, transcription and, ultimately, protein synthesis are affected. The result can include inhibition of leukocyte infiltration at the site of inflammation, interference in the function of mediators of inflammatory response, and suppression of humoral immune responses. The anti-inflammatory actions of corticosteroids are thought to involve phospholipase A2 inhibitory proteins, collectively called lipocortins. Lipocortins, in turn, control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of the precursor molecule arachidonic acid. Some of the net effects include reduction in edema or scar tissue as well as a general suppression in immune response. The numerous adverse effects related to corticosteroid use usually depend on the dose administered and the duration of therapy.[30943][50600]

 

Oral inhaled corticosteroids are believed to reduce the immediate and late-phase allergic responses associated with allergies and chronic bronchial asthma. Proposed mechanisms of action include decreased IgE synthesis, increased number of beta-adrenergic receptors on leukocytes, and decreased arachidonic acid metabolism (which decreases the amount of prostaglandins and leukotrienes released). During an immediate allergic reaction, allergens bridge the IgE antibodies on the surface of mast cells, triggering these cells to release chemotactic substances. Mast cell influx and activation, therefore, is partially responsible for the inflammation and hyperirritability of the oral mucosa. This inflammation can be retarded by administration of adrenocorticoids. Intranasal budesonide provides relief of such symptoms as watery rhinorrhea, nasal congestion, postnasal drip, sneezing, and pharyngeal itching.[30943]

 

Oral budesonide is a controlled-release formulation that delivers drug locally to disease sites in the terminal ileum and ascending colon. The potential for reduced toxicity results from extensive first pass metabolism of budesonide that lowers systemic bioavailability and subsequently, the frequency of corticosteroid adverse reactions.[34979]

Revision Date: 08/07/2019, 06:08:40 PM

References

30943 - Schimmer B, Parker K. Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Hardman JG, Limbird LE, Molinoff PB, et al., eds. Goodman and Gilman's the Pharmacological Basis of Therapeutics, 10th edition. New York: McGraw Hill, 2001;1649-1674.34979 - Entocort EC (budesonide) capsules package insert. Wilmington, DE: AstraZeneca LP; 2020 July50600 - Barnes PJ. Anti-inflammatory actions of glucocorticoids: molecular mechanisms. Clin Sci (Lond). 1998;94(6):557-572.

Pharmacokinetics

Budesonide is administered orally, by nasal inhalation, by oral inhalation, and by nebulization. The volume of distribution is approximately 3 L/kg. The drug is roughly 90% bound to plasma proteins. Protein binding is constant over the concentration range (1 to 100 nmol/L). Budesonide shows little or no binding to corticosteroid binding globulin and the drug rapidly equilibrates with red blood cells in a concentration independent manner with a blood/plasma ratio of about 0.8. Limited data show distribution into breast milk of 0.39 and 0.78 nmol/L after dry powder oral inhalational administration of 400 mcg/day or 800 mcg/day, respectively. In vitro data show that metabolism occurs rapidly and primarily via CYP3A4. Budesonide undergoes approximately 85% first-pass metabolism to two inactive metabolites: 16-alpha-hydroxyprednisolone (24%) and 6-beta-hydroxybudesonide (5%). Budesonide is excreted in urine and feces in the form of metabolites. Following a single dose, complete elimination occurs in approximately 96 hours. The plasma elimination half-life, after administration of intravenous doses ranges between 2 and 3.6 hours.[31824][34979][34376][33486][52910]

 

Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, P-glycoprotein (P-gp)

In vitro data show that metabolism of budesonide occurs primarily by CYP3A4. Inhibitors of CYP3A4 may increase budesonide exposure. Budesonide is also a substrate and inhibitor of P-glycoprotein transport.[34354][31824][34979][34376][33486][52910]

Route-Specific Pharmacokinetics

Oral Route

  • Delayed-release capsules (Entocort EC): Oral budesonide capsules are an enteric-coated formulation that resists dissolution in acidic gastric contents but dissolves in the duodenum at a pH greater than 5.5. Budesonide is then released from a matrix into the GI lumen in a time-dependent fashion. Tmax varies in individual patients between 30 and 600 minutes, oral absorption averages 65%, and oral administration results in a bioavailability ranging from 9% to 21% both in diseased patients and in healthy subjects, demonstrating a high first-pass elimination of the drug.[24065] [34979] A high-fat meal has been shown to delay peak concentrations by 2.3 hours with no changes in AUC. The Cmax and AUC were similar when administration (in the fasted state) of a 9 mg intact capsule was compared to opening the capsule and sprinkling the granules on applesauce. Following oral administration of 9 mg PO once daily in patients with active Crohn's disease, the Cmax and AUC were 1.72 +/- 0.90 ng/L and 15.07 +/- 8.52 ng x hour/mL, respectively. Following repeated administration of 3 to 15 mg, budesonide pharmacokinetics were dose-proportional, and no accumulation was observed.[34979] In Crohn's disease, the onset of therapeutic effect with oral budesonide typically occurs by week 2 of treatment with peak remission rates at 8 weeks.[24064]
  • Extended-release tablets (Uceris): Pharmacokinetic parameters vary per individual with an average Cmax, Tmax, and AUC of roughly 1.35 ng/mL, 13.3 hours, and 16.43 ng x hour/mL, respectively after oral administration. No accumulation was observed following seven days of 9 mg PO once daily dosing. A high-fat meal decreases budesonide Cmax, but does not effect AUC; an absorption lag time of 2.4 hours is observed under fed conditions. Once absorbed, distribution of budesonide is extensive, and protein binding is roughly 90%.[52910]

Inhalation Route

  • Powder for Oral Inhalation Administration (Pulmicort Flexhaler): The absolute bioavailability of orally inhaled budesonide powder is 39%. Peak steady state plasma concentrations are achieved at approximately 10 minutes post-dose and averaged 0.6 and 1.6 nmol/L at doses of 180 mcg once daily and 360 mcg twice daily, respectively.[34376]
  • Nebulized Administration (Pulmicort Respules): In asthmatic children 4 to 6 years of age, the total absolute bioavailability of budesonide suspension via jet nebulizer was approximately 6% of the labeled dose. Peak steady state plasma concentrations occur at approximately 20 minutes post-dose in children.[33486]

Other Route(s)

Intranasal Route

Intranasal Administration (Rhinocort Aqua): Compared to budesonide administered intravenously, approximately 34% of an intranasal dose reaches the systemic circulation. Absorption occurs primarily through the nasal tissues. Tmax occurs approximately 0.5 hours after administration.[31824]

 

Rectal Route

In a population pharmacokinetic analysis in patients with distal ulcerative colitis, the estimated exposure (AUC) following administration of budesonide rectal foam (Uceris) 2 mg rectally twice daily was 4.31 ng x hour/mL with a CV of 64% in the target patient population.[58166]

Special Populations

Hepatic Impairment

Reduced liver function may affect the elimination of corticosteroids.[31824][33486] Systemic exposure of orally administered budesonide increases up to 3.5-fold in patients with moderate liver impairment or with hepatic cirrhosis compared to healthy controls while patients with mild hepatic impairment had an approximately 1.4 fold-higher AUC. The Cmax values demonstrated similar increases. Patients with mild liver disease appear to be minimally affected.[34979][52910]

Renal Impairment

Patients with severe renal disease have not been evaluated. Intact budesonide is not excreted renally. Although budesonide metabolites are renally excreted, their activity is negligible. An enhanced risk of adverse effects in renally compromised patients is not expected.[34979][52910][58166]

Pediatrics

Some differences have been noted between budesonide pharmacokinetics in pediatric and adult patients; these differences vary by dosage formulation. The plasma half-life may be slightly shorter in pediatric patients aged 10 to 14 years (1.5 hours) versus adult patients (2 hours) after receiving intravenous budesonide.

  • Nasal Administration: After nasal administration, plasma concentrations of budesonide in children are approximately twice those in adults; however, time to Cmax and plasma half-life are similar between the populations.[31824]
  • Nebulizer Administration: Systemic exposure, as measured by AUC and Cmax, is similar for young children and adults after inhalation of the same dose of budesonide suspension via nebulizer.[33486]
  • Oral Inhalation Administration: Absolute bioavailability of oral inhaled budesonide appears to be similar in children as compared to adults.[34376]
  • Oral Administration: In patients aged 9 to 14 years (n = 8) receiving oral budesonide 9 mg once daily for 7 days, the Tmax and Cmax were 5 hours and 2.58 +/- 1.51 ng/mL, respectively. The mean AUC was 17.78 +/- 5.25 ng x hour/mL which was 17% higher than in adult patients with Crohn's disease in the same study. The mean absolute oral availability was 9.2% (3% to 17%; n = 4).[34979]

Geriatric

The pharmacokinetic parameters of budesonide in geriatric patients have not been assessed. No differences in safety or efficacy due to age have been identified.[31824][34979][34376]

Gender Differences

No differences in pharmacokinetics of budesonide due to gender have been identified.[31824][34979][34376]

Ethnic Differences

No differences in pharmacokinetics of budesonide due to race have been identified.[33486]

Revision Date: 07/16/2020, 02:36:34 PM

References

24064 - Greenberg GR, Feagan BG, Martin F, et al. Oral budesonide for active Crohn's disease. N Engl J Med 1994;331:836-41.24065 - Rutgeerts P, Lofberg R, Malchow H, et al. A comparison of budesonide with prednisolone for active Crohn's disease. N Engl J Med 1994;331:842-5.31824 - Rhinocort Aqua (budesonide) nasal spray package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2012 Feb.33486 - Pulmicort Respules (budesonide) inhalation suspension package insert. Wilmington, DE: AstraZeneca LP; 2018 Dec.34354 - Dilger K, Schwab M, Fromm MF. Identification of budesonide and prednisone as substrates of the intestinal drug efflux pump P-glycoprotein. Inflamm Bowel Dis 2004; 10: 578-83.34376 - Pulmicort Flexhaler (budesonide inhalation powder) package insert. Wilmington, DE: AstraZeneca LP; 2018 Dec.34979 - Entocort EC (budesonide) capsules package insert. Wilmington, DE: AstraZeneca LP; 2020 July52910 - Uceris (budesonide) tablets package insert. San Diego, CA: Santarus Inc.; 2020 April.58166 - Uceris (budesonide) rectal foam package insert. Bridgewater, NJ: Salix Pharmaceuticals; 2020 April.

Pregnancy/Breast-feeding

pregnancy

Studies of pregnant women have not shown that inhaled budesonide increases the risk of abnormalities when administered during pregnancy.[31824] [33486] [34376] [46711] A review of Swedish registries of more than 2,000 births indicated that no increased risk for congenital malformations during early pregnancy with budesonide inhalation powder or solution.[46713] Despite adverse effects in animal studies, fetal harm appears remote. Corticosteroid treatment may not be necessary during pregnancy due to a natural increase in corticosteroid production; however, poorly controlled maternal asthma also poses risk to the mother and the fetus. Low-dose inhaled corticosteroids are considered first-line therapy for control of mild persistent asthma during pregnancy according to the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group; of the inhaled corticosteroids, more data are available for budesonide use in pregnancy. Data on the use of medium- to high-dose inhaled corticosteroid use during pregnancy are limited. However, dose titration may be considered for those with moderate to severe persistent asthma, preferably using budesonide. However, there are no data to indicate safety concerns with other inhaled corticosteroids, and maintaining a previously established treatment regimen may be more beneficial to the patient.[31822] Selection of any pharmacologic treatment for asthma control during pregnancy should include the specific needs of the patient, based on an individual evaluation, and consideration of the potential benefits or risks to the fetus. A position statement by the American College of Allergy, Asthma and Immunology also considers budesonide a good choice for pregnant women requiring high doses of inhaled steroids for effective asthma management.[46717] Oral budesonide products (e.g., Entocort EC, Ortikos, Uceris) have been teratogenic and embryocidal in animal studies. At doses smaller than the recommended human maximum dose, fetal loss, decreased pup weights, and skeletal anomalies occurred. There is a natural increase in endogenous corticosteroid production during pregnancy, and many women will require a lower exogenous dose or no corticosteroid treatment at all during pregnancy. Oral budesonide (e.g., Entocort EC, Ortikos, Uceris) products should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. Hypoadrenalism may occur in an infant born to a mother receiving corticosteroids during pregnancy, and the infant should be carefully observed.[34979] [52910] [64318]

breast-feeding

Like other corticosteroids, budesonide is excreted into breast milk. Based on data from a small number (n = 8) of breast-feeding women taking inhaled dry powder budesonide 200 to 400 mcg twice daily, approximately 0.3 to 1% of the dose inhaled by the mother is available via breast milk to an exclusively breast-fed infant. Budesonide plasma concentrations obtained in five of the infants in this study about 140 minutes after maternal drug administration and 90 minutes after breast-feeding were below quantifiable levels.[33725] Low-dose inhaled corticosteroids are considered first line therapy for control of mild persistent asthma during pregnancy and lactation according to the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group. Due to greater availability of data, budesonide is considered the preferred agent in this population.[31822] The amount of inhaled budesonide excreted in breast-milk is minute, and infant exposure is negligible. Reviewers and an expert panel consider all inhaled corticosteroids acceptable to use during breast-feeding.[33723] [33724] [31822]. According to the manufacturer of oral budesonide (e.g., Entocort EC, Ortikos, Uceris), a decision should be made whether to discontinue nursing or to discontinue oral budesonide, taking into account the clinical importance of medication to the mother.[34979] [52910] [64318] Single- and repeated-dose pharmacokinetic studies have shown that maximum plasma budesonide concentrations after a 9 mg oral daily dose are up to 10-times greater than the concentrations measured after inhaled doses of 400 to 800 mcg/day. Assuming that the coefficient of extrapolation between inhaled and oral doses is constant across all doses, it is possible that budesonide exposure to breast-feeding infants after maternal oral ingestion may be up to 10-times higher than exposure to infants after maternally inhaled budesonide. However, the oral bioavailability of budesonide is low (approximately 9%) and would be also be expected to be minimal in infants who ingest budesonide through breast milk.[34979] [52910] Budesonide rectal foam (e.g., Uceris Rectal) is likely to result in budesonide in human milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.[58166]

Revision Date: 01/15/2021, 12:41:43 PM

References

31822 - NAEPP Working Group Report on Managing Asthma During Pregnancy. Recommendations for Pharmacologic Treatment-Update 2004. NIH Publication No. 05-3279. Bethesda, MD: U.S. Department of Health and Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute, 200431824 - Rhinocort Aqua (budesonide) nasal spray package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2012 Feb.33486 - Pulmicort Respules (budesonide) inhalation suspension package insert. Wilmington, DE: AstraZeneca LP; 2018 Dec.33723 - Greenberger PA, Patterson R. The management of asthma during pregnancy and lactation. Clin Rev Allergy 1987;5:317-24.33724 - Ellsworth A. Pharmacotherapy of asthma while breastfeeding. J Hum Lact 1994;10:39-41.33725 - Falt A, Bengtsson T, Kennedy BM, et al. Exposure of infants to budesonide through breast milk of asthmatic mothers. J Allergy Clin Immunol 2007;120:798-802.34376 - Pulmicort Flexhaler (budesonide inhalation powder) package insert. Wilmington, DE: AstraZeneca LP; 2018 Dec.34979 - Entocort EC (budesonide) capsules package insert. Wilmington, DE: AstraZeneca LP; 2020 July43236 - National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC). General recommendations on immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2011;60(2):1-64.46711 - Pulmicort Turbuhaler (budesonide) package insert. Wilmington, DE: AstraZeneca, LP; 2006 Oct.46713 - Kallen B, Rydhstroem H, Aberg A. Congenital malformations after the use of inhaled budesonide in early pregnancy. Obstet Gynecol 1999;93:392-5.46717 - Joint Committee of the American College of Obstetricians and Gynecologists (ACOG) and the American College of Allergy, Asthma, and Immunology (ACAAI). Position statement: The use of newer asthma and allergy medications during pregnancy. Ann Allergy Asthma Immunol 2000;84:475-80.52910 - Uceris (budesonide) tablets package insert. San Diego, CA: Santarus Inc.; 2020 April.58166 - Uceris (budesonide) rectal foam package insert. Bridgewater, NJ: Salix Pharmaceuticals; 2020 April.64318 - Ortikos (budesonide) capsules package insert. Cranbury, NJ: Sun Pharmaceutical Industries, Inc; 2019 June.

Interactions

Level 1 (Severe)

  • Metyrapone

Level 2 (Major)

  • Amiodarone
  • Aspirin, ASA; Citric Acid; Sodium Bicarbonate
  • Boceprevir
  • Calcium Carbonate
  • Calcium Carbonate; Famotidine; Magnesium Hydroxide
  • Calcium Carbonate; Magnesium Hydroxide
  • Calcium Carbonate; Risedronate
  • Calcium Carbonate; Simethicone
  • Ceritinib
  • Dabrafenib
  • Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
  • Desmopressin
  • Dofetilide
  • Duvelisib
  • grapefruit juice
  • Halofantrine
  • Idelalisib
  • Levomethadyl
  • Lopinavir; Ritonavir
  • Macimorelin
  • Mifepristone
  • Natalizumab
  • Ombitasvir; Paritaprevir; Ritonavir
  • Omeprazole; Sodium Bicarbonate
  • Penicillamine
  • Ritodrine
  • Ritonavir
  • Saquinavir
  • Sargramostim, GM-CSF
  • Sodium Bicarbonate
  • Telaprevir
  • Vigabatrin

Level 3 (Moderate)

  • Abatacept
  • Acetaminophen; Aspirin, ASA; Caffeine
  • Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine
  • Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide
  • Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine
  • Acetaminophen; Chlorpheniramine; Phenylephrine
  • Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine
  • Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine
  • Acetaminophen; Dextromethorphan; Phenylephrine
  • Acetaminophen; Guaifenesin; Phenylephrine
  • Acetazolamide
  • Acetohexamide
  • Adalimumab
  • 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
  • Amphotericin B
  • Amphotericin B cholesteryl sulfate complex (ABCD)
  • Amphotericin B lipid complex (ABLC)
  • Amphotericin B liposomal (LAmB)
  • Antacids
  • Antithymocyte Globulin
  • Argatroban
  • Arsenic Trioxide
  • Articaine; Epinephrine
  • Asparaginase Erwinia chrysanthemi
  • Aspirin, ASA
  • Aspirin, ASA; Butalbital; Caffeine
  • Aspirin, ASA; Butalbital; Caffeine; Codeine
  • Aspirin, ASA; Caffeine
  • Aspirin, ASA; Caffeine; Dihydrocodeine
  • Aspirin, ASA; Caffeine; Orphenadrine
  • Aspirin, ASA; Carisoprodol
  • Aspirin, ASA; Carisoprodol; Codeine
  • Aspirin, ASA; Dipyridamole
  • Aspirin, ASA; Omeprazole
  • Aspirin, ASA; Oxycodone
  • Aspirin, ASA; Pravastatin
  • Atazanavir
  • Atazanavir; Cobicistat
  • Atenolol; Chlorthalidone
  • Atracurium
  • Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
  • Azilsartan; Chlorthalidone
  • Belladonna Alkaloids; Ergotamine; Phenobarbital
  • Benazepril; Hydrochlorothiazide, HCTZ
  • Bendroflumethiazide; Nadolol
  • Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
  • Bepridil
  • Berotralstat
  • Bismuth Subsalicylate
  • Bismuth Subsalicylate; Metronidazole; Tetracycline
  • Bisoprolol; Hydrochlorothiazide, HCTZ
  • Bivalirudin
  • Brigatinib
  • Brompheniramine; Carbetapentane; Phenylephrine
  • Brompheniramine; Dextromethorphan; Phenylephrine
  • Brompheniramine; Phenylephrine
  • Bupropion
  • Bupropion; Naltrexone
  • Butabarbital
  • Butalbital; Acetaminophen
  • Butalbital; Acetaminophen; Caffeine
  • Butalbital; Acetaminophen; Caffeine; Codeine
  • Caffeine; Sodium Benzoate
  • Canagliflozin
  • Canagliflozin; Metformin
  • Candesartan; Hydrochlorothiazide, HCTZ
  • Captopril; Hydrochlorothiazide, HCTZ
  • Carbamazepine
  • Carbetapentane; Chlorpheniramine; Phenylephrine
  • Carbetapentane; Diphenhydramine; Phenylephrine
  • Carbetapentane; Guaifenesin; Phenylephrine
  • Carbetapentane; Phenylephrine
  • Carbetapentane; Phenylephrine; Pyrilamine
  • Carbinoxamine; Hydrocodone; Phenylephrine
  • Carbinoxamine; Phenylephrine
  • Chlophedianol; Guaifenesin; Phenylephrine
  • Chlorothiazide
  • Chlorpheniramine; Dextromethorphan; Phenylephrine
  • Chlorpheniramine; Dihydrocodeine; Phenylephrine
  • Chlorpheniramine; Hydrocodone; Phenylephrine
  • Chlorpheniramine; Phenylephrine
  • Chlorpropamide
  • Chlorthalidone
  • Chlorthalidone; Clonidine
  • Choline Salicylate; Magnesium Salicylate
  • Cimetidine
  • Cisatracurium
  • Citalopram
  • Clarithromycin
  • Clindamycin
  • Cobicistat
  • Codeine; Phenylephrine; Promethazine
  • Conivaptan
  • Crizotinib
  • Daclatasvir
  • Danazol
  • Dapagliflozin
  • Dapagliflozin; Metformin
  • Dapagliflozin; Saxagliptin
  • Darunavir
  • Darunavir; Cobicistat
  • Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
  • Deferasirox
  • Delavirdine
  • Denosumab
  • Dexamethasone
  • Dextran
  • Dextromethorphan; Diphenhydramine; Phenylephrine
  • Dextromethorphan; Guaifenesin; Phenylephrine
  • Digoxin
  • Dipeptidyl Peptidase-4 Inhibitors
  • Diphenhydramine; Hydrocodone; Phenylephrine
  • Diphenhydramine; Phenylephrine
  • Doxacurium
  • Dronedarone
  • Droperidol
  • Dulaglutide
  • 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
  • Erlotinib
  • Ertugliflozin
  • Ertugliflozin; Metformin
  • Ertugliflozin; Sitagliptin
  • Erythromycin
  • Erythromycin; Sulfisoxazole
  • Estrogens
  • Ethotoin
  • Etravirine
  • Exenatide
  • Famotidine
  • Famotidine; Ibuprofen
  • Fedratinib
  • Fluconazole
  • Fluoxetine
  • Fluoxymesterone
  • Fluvoxamine
  • Fosamprenavir
  • Fosinopril; Hydrochlorothiazide, HCTZ
  • Fosphenytoin
  • Gallium Ga 68 Dotatate
  • Gemcitabine
  • Gentamicin
  • Glecaprevir; Pibrentasvir
  • Glimepiride
  • Glimepiride; Rosiglitazone
  • Glipizide
  • Glipizide; Metformin
  • Glyburide
  • Glyburide; Metformin
  • Glycerol Phenylbutyrate
  • Griseofulvin
  • Guaifenesin; Phenylephrine
  • H2-blockers
  • Haloperidol
  • Hemin
  • Heparin
  • Hetastarch
  • Hydantoins
  • Hydralazine; Hydrochlorothiazide, HCTZ
  • Hydrochlorothiazide, HCTZ
  • Hydrochlorothiazide, HCTZ; Methyldopa
  • Hydrochlorothiazide, HCTZ; Moexipril
  • Hydrocodone; Phenylephrine
  • Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate
  • Ibritumomab Tiuxetan
  • Incretin Mimetics
  • Indapamide
  • Inebilizumab
  • Insulin Degludec; Liraglutide
  • Insulin Glargine; Lixisenatide
  • Insulins
  • Irbesartan; Hydrochlorothiazide, HCTZ
  • Isavuconazonium
  • Isoproterenol
  • Itraconazole
  • Ivacaftor
  • Ivosidenib
  • Ketoconazole
  • L-Asparaginase Escherichia coli
  • Labetalol
  • Lansoprazole; Amoxicillin; Clarithromycin
  • Lefamulin
  • Letermovir
  • Levetiracetam
  • Linagliptin; Metformin
  • Liraglutide
  • Lisinopril; Hydrochlorothiazide, HCTZ
  • Lixisenatide
  • Lonafarnib
  • Lonapegsomatropin
  • Loop diuretics
  • Losartan; Hydrochlorothiazide, HCTZ
  • Lumacaftor; Ivacaftor
  • Lumacaftor; Ivacaftor
  • Magnesium Hydroxide
  • Magnesium Salicylate
  • Mannitol
  • Mecasermin rinfabate
  • Mecasermin, Recombinant, rh-IGF-1
  • Meglitinides
  • Mephobarbital
  • Metformin
  • Metformin; Repaglinide
  • Metformin; Rosiglitazone
  • Metformin; Saxagliptin
  • Metformin; Sitagliptin
  • Methazolamide
  • Methenamine; Sodium Acid Phosphate
  • Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine
  • Methyclothiazide
  • Metolazone
  • Metoprolol; Hydrochlorothiazide, HCTZ
  • Micafungin
  • Midazolam
  • Mitotane
  • Mivacurium
  • Modafinil
  • Moxifloxacin
  • Nafcillin
  • Nateglinide
  • Nefazodone
  • Nelfinavir
  • Neostigmine
  • Neuromuscular blockers
  • Nevirapine
  • Nicardipine
  • Nizatidine
  • Nonsteroidal antiinflammatory drugs
  • Ofatumumab
  • Olanzapine; Fluoxetine
  • Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ
  • Olmesartan; Hydrochlorothiazide, HCTZ
  • Ondansetron
  • Oxymetholone
  • Palbociclib
  • Pancuronium
  • Pazopanib
  • Pegaspargase
  • Phenobarbital
  • Phenobarbital; Hyoscyamine; Atropine; Scopolamine
  • Phenylephrine
  • Phenytoin
  • Physostigmine
  • Pimozide
  • Pioglitazone; Glimepiride
  • Pioglitazone; Metformin
  • Ponesimod
  • Posaconazole
  • Potassium
  • Potassium Chloride
  • Potassium Phosphate; Sodium Phosphate
  • Pramlintide
  • Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements)
  • Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved)
  • Prilocaine; Epinephrine
  • Primidone
  • Promethazine; Phenylephrine
  • Propranolol
  • Propranolol; Hydrochlorothiazide, HCTZ
  • Pyridostigmine
  • Quetiapine
  • Quinapril; Hydrochlorothiazide, HCTZ
  • Quinolones
  • Ranitidine
  • Rapacuronium
  • Regular Insulin
  • Repaglinide
  • Ribociclib
  • Ribociclib; Letrozole
  • Rituximab
  • Rituximab; Hyaluronidase
  • Rocuronium
  • Salicylates
  • Salsalate
  • SARS-CoV-2 (COVID-19) vaccines
  • Semaglutide
  • SGLT2 Inhibitors
  • Sodium Benzoate; Sodium Phenylacetate
  • Sodium Chloride
  • Sodium Phenylbutyrate
  • Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous
  • Sofosbuvir; Velpatasvir; Voxilaprevir
  • Somatropin, rh-GH
  • Spironolactone; Hydrochlorothiazide, HCTZ
  • St. John's Wort, Hypericum perforatum
  • Succinylcholine
  • Sulfonylureas
  • Telbivudine
  • Telmisartan; Hydrochlorothiazide, HCTZ
  • Temsirolimus
  • Testosterone
  • Tezacaftor; Ivacaftor
  • Thiazide diuretics
  • Thiazolidinediones
  • Thyroid hormones
  • Tobramycin
  • Tolazamide
  • Tolbutamide
  • Trandolapril; Verapamil
  • Tranexamic Acid
  • Triamterene; Hydrochlorothiazide, HCTZ
  • Tuberculin Purified Protein Derivative, PPD
  • Tubocurarine
  • Tucatinib
  • Valsartan; Hydrochlorothiazide, HCTZ
  • Vancomycin
  • Vecuronium
  • Vemurafenib
  • Verapamil
  • Vincristine Liposomal
  • Voriconazole
  • Vorinostat
  • Warfarin

Level 4 (Minor)

  • Aldesleukin, IL-2
  • Altretamine
  • Aminolevulinic Acid
  • Aprepitant, Fosaprepitant
  • Azathioprine
  • Basiliximab
  • Bexarotene
  • Bortezomib
  • Bosentan
  • Cabozantinib
  • Carmustine, BCNU
  • Carvedilol
  • Chlorambucil
  • Clofarabine
  • Denileukin Diftitox
  • Dexlansoprazole
  • Diltiazem
  • Econazole
  • Elbasvir; Grazoprevir
  • Esomeprazole
  • Estramustine
  • Hydroxyurea
  • Indinavir
  • Interferon Alfa-2a
  • Interferon Alfa-2b
  • Interferon Alfa-2b; Ribavirin
  • Isotretinoin
  • Ixabepilone
  • Lansoprazole
  • Lansoprazole; Naproxen
  • Ledipasvir; Sofosbuvir
  • Lomustine, CCNU
  • Mepenzolate
  • Methoxsalen
  • Mitoxantrone
  • Naproxen; Esomeprazole
  • Nelarabine
  • Omeprazole
  • Omeprazole; Amoxicillin; Rifabutin
  • Oritavancin
  • Pantoprazole
  • Photosensitizing agents (topical)
  • Potassium-sparing diuretics
  • Proton pump inhibitors
  • Purine analogs
  • Rabeprazole
  • Simeprevir
  • Telithromycin
  • Tositumomab
  • Tretinoin, ATRA
  • Zafirlukast
  • Zonisamide
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] Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) 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) 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; Phenylephrine: (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; Guaifenesin; Phenylephrine: (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] Acetazolamide: (Moderate) Corticosteroids may increase the risk of hypokalemia if used concurrently with acetazolamide. Hypokalemia may be especially severe with prolonged use of corticotropin, ACTH. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy. [26417] [28267] Acetohexamide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Adalimumab: (Moderate) Closely monitor for the development of signs and symptoms of infection if coadministration of a corticosteroid with adalimumab is necessary. Adalimumab treatment increases the risk for serious infections that may lead to hospitalization or death. Patients taking concomitant immunosuppressants including corticosteroids may be at greater risk of infection. [27939] Albiglutide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Aldesleukin, IL-2: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [41853] [7592] [7714] Alemtuzumab: (Moderate) Concomitant use of alemtuzumab with immunosuppressant doses of corticosteroids may increase the risk of immunosuppression. Monitor patients carefully for signs and symptoms of infection. [58461] Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Alogliptin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] Alpha-glucosidase Inhibitors: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Altretamine: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects. [4661] [7714] Aluminum Hydroxide: (Moderate) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. [34979] [52910] Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. [34979] [52910] Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. [34979] [52910] Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. [34979] [52910] Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. [34979] [52910] Ambenonium Chloride: (Moderate) Concomitant use of anticholinesterase agents, such as ambenonium chloride, and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents used to treat myasthenia should be withdrawn at least 24 hours before initiating corticosteroid therapy. [29779] [30015] [30028] [42863] [56146] [64165] Amifampridine: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients. [45339] [63790] Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Aminolevulinic Acid: (Minor) Corticosteroids administered prior to or concomitantly with photosensitizing agents used in photodynamic therapy may decrease the efficacy of the treatment. [6625] Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Amiodarone: (Major) Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia, including corticosteroids. Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. [26417] [28224] [29377] Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Avoid coadministration of oral budesonide and clarithromycin due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [28238] [28278] [34376] [34979] (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] 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 > 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] Argatroban: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] 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) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [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) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Butalbital; Caffeine: (Moderate) Coadministration may result in decreased exposure to budesonide. Butalbital is a CYP3A4 inducer; budesonide is a CYP3A4 substrate. Monitor for decreased response to budesonide during concurrent use. [28001] (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Coadministration may result in decreased exposure to budesonide. Butalbital is a CYP3A4 inducer; budesonide is a CYP3A4 substrate. Monitor for decreased response to budesonide during concurrent use. [28001] (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Caffeine: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Carisoprodol: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. [52910] [6865] (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Dipyridamole: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Omeprazole: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. [34979] Aspirin, ASA; Oxycodone: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Pravastatin: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Atazanavir: (Moderate) Coadministration of budesonide with atazanavir may cause elevated budesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 substrate; atazanavir is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. [28001] [58000] Atazanavir; Cobicistat: (Moderate) Avoid coadministration of oral budesonide and cobistat due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Elevated budesonide serum concentrations may result in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 and P-glycoprotein (P-gp) substrate; cobicistat is a strong inhibitor of CYP3A4 and P-gp. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. [31824] [34354] [34979] [51664] [58000] (Moderate) Coadministration of budesonide with atazanavir may cause elevated budesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 substrate; atazanavir is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. [28001] [58000] Atenolol; Chlorthalidone: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Atracurium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Azathioprine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [4710] [7714] Azilsartan; Chlorthalidone: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] 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] Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Coadministration may result in decreased exposure to budesonide. Phenobarbital is a CYP3A4 inducer; budesonide is a CYP3A4 substrate. Monitor for decreased response to budesonide during concurrent use. Dose adjustments may be necessary. [28001] Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Bendroflumethiazide; Nadolol: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Bepridil: (Moderate) Hypokalemia-producing agents, including corticosteroids, may increase the risk of bepridil-induced arrhythmias and should therefore be administered cautiously in patients receiving bepridil therapy. [3085] [4953] Berotralstat: (Moderate) Avoid coadministration of systemic budesonide with berotralstat due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A4 substrate and berotralstat is a moderate CYP3A4 inhibitor. [34979] [66159] 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) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Bivalirudin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Boceprevir: (Major) Concurrent administration of budesonide and boceprevir is not recommended unless the benefits outweigh the risks. If they are coadministered, close monitoring for corticosteroid-related adverse events is advised. If budesonide dose adjustments are made, readjust the dose upon completion of boceprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of budesonide. Budesonide is metabolized by the hepatic isoenzyme CYP3A4 and the drug efflux transporter P-glycoprotein (P-gp); boceprevir inhibits both the isoenzyme and the drug efflux pump. Coadministration may result in elevated budesonide plasma concentrations. [34979] [44314] Bortezomib: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Bosentan: (Minor) A dose adjustment of budesonide may be necessary if bosentan is initiated or withdrawn during therapy. Bosentan may increase the metabolism of budesonide resulting in decreased exposure. Bosentan is an inducer of CYP3A4; budesonide is a CYP3A4 substrate. [28496] Brigatinib: (Moderate) Monitor for a decrease in the efficacy of budesonide if coadministration with brigatinib is necessary. Budesonide is a sensitive CYP3A4 substrate. At clinically relevant concentrations, brigatinib induced CYP3A via activation of the pregnane X receptor (PXR); this may decrease concentrations of sensitive CYP3A substrates. [34979] [61909] Brompheniramine; Carbetapentane; Phenylephrine: (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) 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) 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] Bupropion: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Bupropion; Naltrexone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Butabarbital: (Moderate) Coadministration may result in decreased exposure to budesonide. Butabarbital is a CYP3A4 inducer; budesonide is a CYP3A4 substrate. Monitor for decreased response to budesonide during concurrent use. [28001] Butalbital; Acetaminophen: (Moderate) Coadministration may result in decreased exposure to budesonide. Butalbital is a CYP3A4 inducer; budesonide is a CYP3A4 substrate. Monitor for decreased response to budesonide during concurrent use. [28001] Butalbital; Acetaminophen; Caffeine: (Moderate) 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) 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; Sodium Benzoate: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia. [8083] Calcium Carbonate: (Major) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. In addition, calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function. [31468] [31469] Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Major) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. In addition, calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function. [31468] [31469] (Moderate) Monitor for altered response to budesonide in patients receiving H2-blockers with enteric-coated or extended-release formulations of oral budesonide. Enteric-coated budesonide granules (Entocort EC) dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause these products to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. When cimetidine (1 gram/day PO) is administered with an uncoated formulation of oral budesonide, a slight increase in absorption and peak plasma concentrations occur, resulting in significant cortisol suppression. [34979] [52910] Calcium Carbonate; Magnesium Hydroxide: (Major) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. In addition, calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function. [31468] [31469] Calcium Carbonate; Risedronate: (Major) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. In addition, calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function. [31468] [31469] Calcium Carbonate; Simethicone: (Major) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. In addition, calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function. [31468] [31469] Canagliflozin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Canagliflozin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Carbamazepine: (Moderate) Hepatic microsomal enzyme inducers, including carbamazepine, can increase the metabolism of budesonide. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with budesonide. [41237] Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) 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) 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) 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) 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) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Carbinoxamine; Hydrocodone; Phenylephrine: (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; Phenylephrine: (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] 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] Carvedilol: (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] Chlophedianol; Guaifenesin; Phenylephrine: (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) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Chlorpheniramine; Hydrocodone; Phenylephrine: (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; Phenylephrine: (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] Chlorpropamide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Chlorthalidone: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Chlorthalidone; Clonidine: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Choline Salicylate; Magnesium Salicylate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Cimetidine: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] (Moderate) Monitor for altered response to budesonide in patients receiving H2-blockers with enteric-coated or extended-release formulations of oral budesonide. Enteric-coated budesonide granules (Entocort EC) dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause these products to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. When cimetidine (1 gram/day PO) is administered with an uncoated formulation of oral budesonide, a slight increase in absorption and peak plasma concentrations occur, resulting in significant cortisol suppression. [34979] [52910] Cisatracurium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] Citalopram: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram. [26417] [28269] 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] Clindamycin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Clofarabine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7557] [7714] 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] Codeine; Phenylephrine; Promethazine: (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] Dabrafenib: (Major) The concomitant use of dabrafenib and budesonide may lead to decreased budesonide concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of budesonide efficacy. Dabrafenib is a moderate CYP3A4 inducer and budesonide is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%. [34979] [54802] Daclatasvir: (Moderate) Systemic exposure of budesonide, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of budesonide; monitor patients for potential adverse effects. [34354] [60001] Danazol: (Moderate) Avoid coadministration of oral budesonide and danazol due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; danazol is a moderate CYP3A4 inhibitor. In the presence of a strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [28278] [34376] [34979] Dapagliflozin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Dapagliflozin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Dapagliflozin; Saxagliptin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Darunavir: (Moderate) Coadministration of budesonide with darunavir may cause elevated budesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 substrate; darunavir is an inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. [32432] [34979] [58000] Darunavir; Cobicistat: (Moderate) Avoid coadministration of oral budesonide and cobistat due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Elevated budesonide serum concentrations may result in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 and P-glycoprotein (P-gp) substrate; cobicistat is a strong inhibitor of CYP3A4 and P-gp. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. [31824] [34354] [34979] [51664] [58000] (Moderate) Coadministration of budesonide with darunavir may cause elevated budesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 substrate; darunavir is an inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. [32432] [34979] [58000] Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Avoid coadministration of oral budesonide and cobistat due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Elevated budesonide serum concentrations may result in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 and P-glycoprotein (P-gp) substrate; cobicistat is a strong inhibitor of CYP3A4 and P-gp. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. [31824] [34354] [34979] [51664] [58000] (Moderate) Coadministration of budesonide with darunavir may cause elevated budesonide serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Budesonide is a CYP3A4 substrate; darunavir is an inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. [32432] [34979] [58000] Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Avoid coadministration of oral budesonide and ritonavir due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [28315] [31824] [34979] [47165] 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] 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] Desmopressin: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer. [61806] 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] Dexlansoprazole: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. [34979] Dextran: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Dextromethorphan; Diphenhydramine; Phenylephrine: (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) 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] Digoxin: (Moderate) Hypokalemia, hypomagnesemia, or hypercalcemia increase digoxin's effect. Corticosteroids can precipitate digoxin toxicity via their effect on electrolyte balance. It is recommended that serum potassium, magnesium, and calcium be monitored regularly in patients receiving digoxin. [28272] [29377] Diltiazem: (Minor) Diltiazem may increase plasma concentrations of oral budesonide due to inhibition of the CYP3A4 isoenzymet, and can enhance the cortisol suppression associated with budesonide administered via inhalation. [6192] Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Diphenhydramine; Phenylephrine: (Moderate) 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] 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] 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 patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Duvelisib: (Major) Avoid coadministration of systemic budesonide with duvelisib due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. [34979] [63571] 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 patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Empagliflozin; Linagliptin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Empagliflozin; Linagliptin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Empagliflozin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Encorafenib: (Moderate) Coadministration of encorafenib with budesonide may result in increased toxicity or decreased efficacy of budesonide. Budesonide is a sensitive CYP3A4 substrate. In vitro studies with encorafenib showed time-dependent inhibition of CYP3A4 and induction of CYP3A4. The clinical relevance of the in vivo effect of encorafenib on CYP3A4 is not established. [56579] [63317] Ephedrine: (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) 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) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Erlotinib: (Moderate) Monitor for symptoms of gastrointestinal (GI) perforation (e.g., severe abdominal pain, fever, nausea, and vomiting) if coadministration of erlotinib with budesonide is necessary. Permanently discontinue erlotinib in patients who develop GI perforation. The pooled incidence of GI perforation clinical trials of erlotinib ranged from 0.1% to 0.4%, including fatal cases; patients receiving concomitant budesonide may be at increased risk. [30555] Ertugliflozin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Ertugliflozin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Ertugliflozin; Sitagliptin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Erythromycin: (Moderate) Avoid coadministration of oral budesonide and erythromycin due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; erythromycin is a moderate CYP3A4 inhibitor. In the presence of a strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [28251] [34979] Erythromycin; Sulfisoxazole: (Moderate) Avoid coadministration of oral budesonide and erythromycin due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; erythromycin is a moderate CYP3A4 inhibitor. In the presence of a strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [28251] [34979] Esomeprazole: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. [34979] Estramustine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [4744] [7714] Estrogens: (Moderate) Estrogens have been associated with elevated serum concentrations of corticosteroid binding globulin (CBG), leading to increased total circulating corticosteroids, although the free concentrations of these hormones may be lower; the clinical significance is not known. Estrogens are CYP3A4 substrates and dexamethasone is a CYP3A4 inducer; concomitant use may decrease the clinical efficacy of estrogens. Patients should be monitored for signs of decreased clinical effects of estrogens (e.g., breakthrough bleeding), oral contraceptives, or non-oral combination contraceptives if these drugs are used together. [4718] [4744] [6395] Ethotoin: (Moderate) Hydantoin anticonvulsants induce hepatic microsomal enzymes and may increase the metabolism of budesonide, leading to reduced efficacy. Depending on the individual clinical situation and the indication for the interacting medication, enzyme-induction interactions may not always produce reductions in treatment efficacy. [28001] [28771] Etravirine: (Moderate) Etravirine is a CYP3A4 inducer and a P-glycoprotein (PGP) inhibitor and budesonide is a CYP3A4 substrate and a substrate/inhibitor of PGP. Caution is warranted if these drugs are coadministered. [11210] [33718] [6865] Exenatide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Famotidine: (Moderate) Monitor for altered response to budesonide in patients receiving H2-blockers with enteric-coated or extended-release formulations of oral budesonide. Enteric-coated budesonide granules (Entocort EC) dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause these products to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. When cimetidine (1 gram/day PO) is administered with an uncoated formulation of oral budesonide, a slight increase in absorption and peak plasma concentrations occur, resulting in significant cortisol suppression. [34979] [52910] Famotidine; Ibuprofen: (Moderate) Monitor for altered response to budesonide in patients receiving H2-blockers with enteric-coated or extended-release formulations of oral budesonide. Enteric-coated budesonide granules (Entocort EC) dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause these products to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. When cimetidine (1 gram/day PO) is administered with an uncoated formulation of oral budesonide, a slight increase in absorption and peak plasma concentrations occur, resulting in significant cortisol suppression. [34979] [52910] Fedratinib: (Moderate) Avoid coadministration of systemic budesonide with fedratinib due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A4 substrate and fedratinib is a moderate CYP3A4 inhibitor. [34979] [64568] Fluconazole: (Moderate) Avoid coadministration of oral budesonide and fluconazole due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; fluconazole is a moderate CYP3A4 inhibitor. In the presence of a strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [28674] [34979] (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Fluoxetine: (Moderate) Avoid coadministration of oral budesonide and fluoxetine due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; fluoxetine a weak CYP3A4 inhibitor and the active metabolite norfluoxetine is a moderate CYP3A4 inhibitor. In the presence of a strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [29003] [29190] [34979] 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] 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: (Moderate) Caution is advised when administering budesonide with fosamprenavir, as concurrent use may alter the plasma concentrations of budesonide. Budesonide is a substrate for the hepatic isoenzyme CYP3A4 and the drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is an inducer of P-gp and a potent inhibitor and moderate inducer of CYP3A4. [29012] [34354] Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Fosphenytoin: (Moderate) Hydantoin anticonvulsants induce hepatic microsomal enzymes and may increase the metabolism of budesonide, leading to reduced efficacy. Depending on the individual clinical situation and the indication for the interacting medication, enzyme-induction interactions may not always produce reductions in treatment efficacy. [28001] [28771] Gallium Ga 68 Dotatate: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia. Also, corticotropin may cause calcium loss and sodium and fluid retention. Mannitol itself can cause hypernatremia. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly. [6524] (Moderate) Repeated administration of high corticosteroid doses prior to gallium Ga 68 dotatate may result in false negative imaging. High-dose corticosteroid therapy is generally defined as at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. Corticosteroids can down-regulate somatostatin subtype 2 receptors: thereby, interfering with binding of gallium Ga 68 dotatate to malignant cells that overexpress these receptors. [60852] Gemcitabine: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Gentamicin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and budesonide as coadministration may increase serum concentrations of budesonide and increase the risk of adverse effects. Glecaprevir is a P-glycoprotein (P-gp) inhibitor; budesonide is a P-gp substrate. [34354] [62201] (Moderate) Caution is advised with the coadministration of pibrentasvir and budesonide as coadministration may increase serum concentrations of budesonide and increase the risk of adverse effects. Pibrentasvir is a P-glycoprotein (P-gp) inhibitor; budesonide is a P-gp substrate. [34354] [62201] Glimepiride: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Glimepiride; Rosiglitazone: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Glipizide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Glipizide; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Glyburide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Glyburide; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Glycerol Phenylbutyrate: (Moderate) Corticosteroids may induce elevated blood ammonia concentrations. Corticosteroids should be used with caution in patients receiving glycerol phenylbutyrate. Monitor ammonia concentrations closely. [53022] 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; Phenylephrine: (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] H2-blockers: (Moderate) Monitor for altered response to budesonide in patients receiving H2-blockers with enteric-coated or extended-release formulations of oral budesonide. Enteric-coated budesonide granules (Entocort EC) dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause these products to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. When cimetidine (1 gram/day PO) is administered with an uncoated formulation of oral budesonide, a slight increase in absorption and peak plasma concentrations occur, resulting in significant cortisol suppression. [34979] [52910] Halofantrine: (Major) Due to the risks of cardiac toxicity of halofantrine in patients with hypokalemia and/or hypomagnesemia, the use of halofantrine should be avoided in combination with agents that may lead to electrolyte losses, such as corticosteroids. [4968] Haloperidol: (Moderate) Caution is advisable during concurrent use of haloperidol and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with haloperidol. [28307] Hemin: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Corticosteroids increase the activity of this enzyme should not be used with hemin. [6702] Heparin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Hetastarch: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Hydantoins: (Moderate) Hydantoin anticonvulsants induce hepatic microsomal enzymes and may increase the metabolism of budesonide, leading to reduced efficacy. Depending on the individual clinical situation and the indication for the interacting medication, enzyme-induction interactions may not always produce reductions in treatment efficacy. [28001] [28771] Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Hydrocodone; Phenylephrine: (Moderate) 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] 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) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia. [57713] [57714] [57715] Ibritumomab Tiuxetan: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia. [57713] [57714] [57715] (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] 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 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] 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 patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Insulin Glargine; Lixisenatide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Insulins: (Moderate) Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Interferon Alfa-2a: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Interferon Alfa-2b: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Interferon Alfa-2b; Ribavirin: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with budesonide may result in increased serum concentrations of budesonide. Budesonide is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together. [34354] [59042] Isoproterenol: (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] 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] Ixabepilone: (Minor) Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp).[10415] Budesonide is a Pgp substrate, and concomitant use of ixabepilone with a Pgp substrate may cause an increase in budesonide concentrations. Use caution if ixabepilone is coadministered with a Pgp substrate. [10415] Ketoconazole: (Moderate) Ketoconazole may increase plasma concentrations of oral budesonide more than 7-fold due to inhibition of the CYP3A4 isoenzyme in the liver, as well as in the gut, and can enhance the cortisol suppression associated with budesonide administered via inhalation. Inhibition of CYP3A4 may be clinically significant for inhaled forms of budesonide, including budesonide nasal spray. [27982] [28001] [28279] [28761] [31824] [34535] Labetalol: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] 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] Levetiracetam: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Levomethadyl: (Major) Caution is advised when using levomethadyl in combination with other agents, such as corticosteroids, that may lead to electrolyte abnormalities, especially hypokalemia or hypomagnesemia. [3085] Linagliptin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] Liraglutide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Lixisenatide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Lomustine, CCNU: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [5946] [7714] [7944] Lonafarnib: (Moderate) Avoid coadministration of oral budesonide and lonafarnib due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; lonafarnib is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [34979] [66129] Lonapegsomatropin: (Moderate) Corticosteroids can retard bone growth and therefore, can inhibit the growth-promoting effects of somatropin. If corticosteroid therapy is required, the corticosteroid dose should be carefully adjusted. [6807] Loop diuretics: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly. [26417] [28429] [29779] 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] Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Lumacaftor; Ivacaftor: (Moderate) Concomitant use of budesonide and lumacaftor; ivacaftor may alter the therapeutic effects of budesonide; caution and close monitoring are advised if these drugs are used together. Budesonide is a primary substrate of CYP3A4 and a substrate of the P-glycoprotein (P-gp) efflux transporter. Lumacaftor is a strong CYP3A inducer; in vitro data also suggest lumacaftor; ivacaftor may induce and/or inhibit P-gp. Although induction of budesonide through the CYP3A pathway may lead to decreased drug efficacy, the net effect of lumacaftor; ivacaftor on P-gp transport is not clear. Monitor the patient for decreased corticosteroid efficacy or increased or prolonged therapeutic effects and adverse events. [34354] [34979] [59891] Lumacaftor; Ivacaftor: (Moderate) Use caution when administering ivacaftor and budesonide concurrently. Ivacaftor is an inhibitor of CYP3A and P-glycoprotein (Pgp). Co-administration of ivacaftor with CYP3A and Pgp substrates, such as budesonide, can increase budesonide exposure leading to increased or prolonged therapeutic effects and adverse events. [34354] [34979] [48524] Macimorelin: (Major) Avoid use of macimorelin with drugs that directly affect pituitary growth hormone secretion, such as corticosteroids. Healthcare providers are advised to discontinue corticosteroid therapy and observe a sufficient washout period before administering macimorelin. Use of these medications together may impact the accuracy of the macimorelin growth hormone test. [62723] Magnesium Hydroxide: (Moderate) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. [34979] [52910] Magnesium Salicylate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Mannitol: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia. Also, corticotropin may cause calcium loss and sodium and fluid retention. Mannitol itself can cause hypernatremia. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly. [6524] 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] Mepenzolate: (Minor) Anticholinergics, such as mepenzolate, antagonize the effects of antiglaucoma agents. Mepenzolate is contraindicated in patients with glaucoma and therefore should not be coadministered with medications being prescribed for the treatment of glaucoma. In addition, anticholinergic drugs taken concurrently with corticosteroids in the presence of increased intraocular pressure may be hazardous. [42281] Mephobarbital: (Moderate) Coadministration may result in decreased exposure to budesonide. Mephobarbital is a CYP3A4 inducer; budesonide is a CYP3A4 substrate. Monitor for decreased response to budesonide during concurrent use. [28001] Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] Metformin; Repaglinide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Metformin; Rosiglitazone: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] Metformin; Saxagliptin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] Metformin; Sitagliptin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] Methazolamide: (Moderate) Corticosteroids may increase the risk of hypokalemia if used concurrently with methazolamide. Hypokalemia may be especially severe with prolonged use of corticotropin, ACTH. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy. The chronic use of corticosteroids may augment calcium excretion with methazolamide leading to increased risk for hypocalcemia and/or osteoporosis. [5023] Methenamine; Sodium Acid Phosphate: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia. [57713] [57714] [57715] Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia. [57713] [57714] [57715] Methoxsalen: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Methyclothiazide: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Metolazone: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Metyrapone: (Contraindicated) Medications which affect pituitary or adrenocortical function, including all corticosteroid therapy, should be discontinued prior to and during testing with metyrapone. Patients taking inadvertent doses of corticosteroids on the test day may exhibit abnormally high basal plasma cortisol levels and a decreased response to the test. Although systemic absorption of nasal corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results. [33528] Micafungin: (Moderate) Leukopenia, neutropenia, anemia, and thrombocytopenia have been associated with micafungin. Patients who are taking immunosuppressives such as the corticosteroids with micafungin concomitantly may have additive risks for infection or other side effects. In a pharmacokinetic trial, micafungin had no effect on the pharmacokinetics of prednisolone. Acute intravascular hemolysis and hemoglobinuria was seen in a healthy volunteer during infusion of micafungin (200 mg) and oral prednisolone (20 mg). This reaction was transient, and the subject did not develop significant anemia. [44913] Midazolam: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] 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] Moxifloxacin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] 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] 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] Nefazodone: (Moderate) Avoid coadministration of oral budesonide and nefazodone due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; nefazodone is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [28683] [34979] Nelarabine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Nelfinavir: (Moderate) Avoid coadministration of oral budesonide and nelfinavir due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; nelfinavir is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [28839] [34979] Neostigmine: (Moderate) Concomitant use of anticholinesterase agents, such as neostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating systemic corticosteroid therapy. [29779] [30015] [30028] [31123] [54891] [56146] [64165] Neuromuscular blockers: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] Nevirapine: (Moderate) Theoretically, induction of the cytochrome P450 3A4 isoenzyme by nevirapine may result in a lowering of budesonide plasma concentrations, reducing the clinical effect. [28492] Nicardipine: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] (Minor) Nicardipine may increase plasma concentrations of budesonide due to inhibition of the CYP3A4 isoenzyme. Use caution when budesonide is coadministered with drugs that inhibit CYP3A enzymes and consider dose reduction. [4718] Nizatidine: (Moderate) Monitor for altered response to budesonide in patients receiving H2-blockers with enteric-coated or extended-release formulations of oral budesonide. Enteric-coated budesonide granules (Entocort EC) dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause these products to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. When cimetidine (1 gram/day PO) is administered with an uncoated formulation of oral budesonide, a slight increase in absorption and peak plasma concentrations occur, resulting in significant cortisol suppression. [34979] [52910] Nonsteroidal antiinflammatory drugs: (Moderate) Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged concomitant administration should be avoided. Concomitant use of corticosteroids appears to increase the risk of adverse GI events due to NSAIDs. Corticosteroids can have profound effects on sodium-potassium balance; NSAIDs also can affect sodium and fluid balance. Monitor serum potassium concentrations; potassium supplementation may be necessary. In addition, NSAIDs may mask fever, pain, swelling and other signs and symptoms of an infection; use NSAIDs with caution in patients receiving immunosuppressant dosages of corticosteroids. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection. [24574] [29890] [63923] 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] Olanzapine; Fluoxetine: (Moderate) Avoid coadministration of oral budesonide and fluoxetine due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; fluoxetine a weak CYP3A4 inhibitor and the active metabolite norfluoxetine is a moderate CYP3A4 inhibitor. In the presence of a strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [29003] [29190] [34979] Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Ombitasvir; Paritaprevir; Ritonavir: (Major) Avoid coadministration of oral budesonide and ritonavir due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [28315] [31824] [34979] [47165] Omeprazole: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. [34979] Omeprazole; Amoxicillin; Rifabutin: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. [34979] Omeprazole; Sodium Bicarbonate: (Major) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. [52910] [6865] (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. [34979] Ondansetron: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] 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) Concomitant use of pegaspargase with corticosteroids can result in additive hyperglycemia. Insulin therapy may be required in some cases. [55362] 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] 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] Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Phenytoin: (Moderate) Hydantoin anticonvulsants induce hepatic microsomal enzymes and may increase the metabolism of budesonide, leading to reduced efficacy. Depending on the individual clinical situation and the indication for the interacting medication, enzyme-induction interactions may not always produce reductions in treatment efficacy. [28001] [28771] Photosensitizing agents (topical): (Minor) Corticosteroids administered prior to or concomitantly with photosensitizing agents used in photodynamic therapy may decrease the efficacy of the treatment. [6625] Physostigmine: (Moderate) Concomitant use of anticholinesterase agents. such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy. [29779] [30015] [30028] [31123] [56146] [64165] 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] Pioglitazone; Glimepiride: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Pioglitazone; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] 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 Chloride: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Potassium Phosphate; Sodium Phosphate: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia. [57713] [57714] [57715] Potassium: (Moderate) Corticotropin can cause alterations in serum potassium levels. The use of potassium salts or supplements would be expected to alter the effects of corticotropin on serum potassium levels. Also, there have been reports of generalized tonic-clonic seizures and/or loss of consciousness associated with use of bowel preparation products in patients with no prior history of seizure disorder. Therefore, magnesium sulfate; potassium sulfate; sodium sulfate should be administered with caution during concurrent use of medications that lower the seizure threshold such as systemic corticosteroids. [30015] [41573] Potassium-sparing diuretics: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics. [26417] [29016] [30011] Pramlintide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Moderate) Corticosteroids blunt the adrenal secretion of endogenous DHEA and DHEAS, resulting in reduced DHEA and DHEAS serum concentrations. [2460] Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Moderate) Corticosteroids blunt the adrenal secretion of endogenous DHEA and DHEAS, resulting in reduced DHEA and DHEAS serum concentrations. [2460] Prilocaine; Epinephrine: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [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] Promethazine; Phenylephrine: (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) Patients receiving corticosteroids during propranolol therapy may be at increased risk of hypoglycemia due to the loss of counter-regulatory cortisol response. This effect may be more pronounced in infants and young children. If concurrent use is necessary, carefully monitor vital signs and blood glucose concentrations as clinically indicated. [56853] Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] (Moderate) Patients receiving corticosteroids during propranolol therapy may be at increased risk of hypoglycemia due to the loss of counter-regulatory cortisol response. This effect may be more pronounced in infants and young children. If concurrent use is necessary, carefully monitor vital signs and blood glucose concentrations as clinically indicated. [56853] 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] Purine analogs: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects. [5504] Pyridostigmine: (Moderate) Concomitant use of anticholinesterase agents. such as pyridostigmine, and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating corticosteroid therapy. [29779] [30015] [30028] [31123] [34253] [56146] [64002] [64165] Quetiapine: (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids). [26417] [29118] Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Quinolones: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon. [28423] [28424] [28764] [29818] [30738] [62028] [65562] Rabeprazole: (Minor) Enteric-coated budesonide granules dissolve at a pH greater than 5.5. Concomitant use of budesonide oral capsules and drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. [34979] Ranitidine: (Moderate) Monitor for altered response to budesonide in patients receiving H2-blockers with enteric-coated or extended-release formulations of oral budesonide. Enteric-coated budesonide granules (Entocort EC) dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause these products to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. When cimetidine (1 gram/day PO) is administered with an uncoated formulation of oral budesonide, a slight increase in absorption and peak plasma concentrations occur, resulting in significant cortisol suppression. [34979] [52910] 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] Regular Insulin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] 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] 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] Ritodrine: (Major) Ritodrine has caused maternal pulmonary edema, which appears more often in patients treated concomitantly with corticosteroids. Patients so treated should be closely monitored in the hospital. [7110] [7111] [7572] Ritonavir: (Major) Avoid coadministration of oral budesonide and ritonavir due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [28315] [31824] [34979] [47165] Rituximab: (Moderate) Rituximab and corticosteroids are commonly used together; however, monitor the patient for immunosuppression and signs and symptoms of infection during combined chronic therapy. [30943] [49773] [56233] Rituximab; Hyaluronidase: (Moderate) Rituximab and corticosteroids are commonly used together; however, monitor the patient for immunosuppression and signs and symptoms of infection during combined chronic therapy. [30943] [49773] [56233] Rocuronium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] Salicylates: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Salsalate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Saquinavir: (Major) Avoid coadministration of saquinavir and orally administered budesonide and use inhaled formulations with caution. Saquinavir may inhibit CYP3A4 metabolism of budesonide, resulting in increased plasma budesonide concentrations and reduced serum cortisol concentrations. Theoretically, inhibition of CYP3A4 may be clinically significant for inhaled forms of budesonide, including budesonide nasal spray. There have been reports of clinically significant drug interactions in patients receiving ritonavir with other corticosteroids, resulting in systemic corticosteroid effects including Cushing syndrome and adrenal suppression. Similar results are expected with saquinavir. Consider using an alternative treatment to budesonide, such as a corticosteroid not metabolized by CYP3A4 (i.e., beclomethasone or prednisolone). If corticosteroid therapy is to be discontinued, consider tapering the dose over a period of time to decrease the potential for withdrawal. [28995] [34979] [46711] 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 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] SGLT2 Inhibitors: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Simeprevir: (Minor) Simeprevir, a P-glycoprotein (P-gp) inhibitor and a mild intestinal CYP3A4 inhibitor, may increase the side effects of budesonide, which is a CYP3A4 and P-gp substrate. Monitor patients for adverse effects of budesonide, such as excessive HPA-axis suppresion. [34354] [56076] [56471] Sodium Benzoate; Sodium Phenylacetate: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia. [8083] Sodium Bicarbonate: (Major) Enteric-coated budesonide granules dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. In general, it may be prudent to avoid drugs such as antacids in combination with enteric-coated budesonide. [52910] [6865] Sodium Chloride: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Sodium Phenylbutyrate: (Moderate) The concurrent use of corticosteroids with sodium phenylbutyrate may increase plasma ammonia levels (hyperammonemia) by causing the breakdown of body protein. Patients with urea cycle disorders being treated with sodium phenylbutyrate usually should not receive regular treatment with corticosteroids. [57685] Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia. [57713] [57714] [57715] Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Plasma concentrations of budesonide, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with voxilaprevir, a P-gp inhibitor. Monitor patients for increased side effects if these drugs are administered concurrently. [34354] [62131] 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) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] St. John's Wort, Hypericum perforatum: (Moderate) Theoretically, induction of the cytochrome P450 3A4 isoenzyme by St. John's Wort may result in a lowering of budesonide plasma concentrations, reducing the clinical effect. [28211] Succinylcholine: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] Sulfonylureas: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Telaprevir: (Major) Concurrent administration of budesonide and telaprevir is not recommended unless the benefits outweigh the risks. If they are coadministered, close monitoring for corticosteroid-related adverse events is advised. If budesonide dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Predictions about the interaction can be made based on the metabolic pathway of budesonide. Budesonide is metabolized by the hepatic isoenzyme CYP3A4 and the drug efflux transporter P-glycoprotein (P-gp); telaprevir inhibits both the isoenzyme and the drug efflux pump. Coadministration may result in elevated budesonide plasma concentrations. [44393] [6865] 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) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Temsirolimus: (Moderate) Monitor for an increase in budesonide-related adverse reactions if coadministration with temsirolimus is necessary. Budesonide is a P-glycoprotein (P-gp) substrate and temsirolimus is a P-gp inhibitor. Concomitant use is likely to lead to increased concentrations of budesonide. [34354] [50586] Testosterone: (Moderate) Coadministration of corticosteroids and testosterone may increase the risk of edema, especially in patients with underlying cardiac or hepatic disease. Corticosteroids with greater mineralocorticoid activity, such as fludrocortisone, may be more likely to cause edema. Administer these drugs in combination with caution. [33698] 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] Thiazide diuretics: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Thiazolidinediones: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Thyroid hormones: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents. [29779] [30015] [43942] Tobramycin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Tolazamide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Tolbutamide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Tositumomab: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Trandolapril; Verapamil: (Moderate) Avoid coadministration of oral budesonide and verapamil due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; verapamil a weak CYP3A4 inhibitor and the active metabolite norverapamil is a moderate CYP3A4 inhibitor. In the presence of a strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [31824] [34979] Tranexamic Acid: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Tretinoin, ATRA: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy. [43298] [43299] Tubocurarine: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] Tucatinib: (Moderate) Avoid coadministration of oral budesonide and tucatinib due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; tucatinib is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [34979] [65295] Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Vancomycin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] 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 oral budesonide and verapamil due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; verapamil a weak CYP3A4 inhibitor and the active metabolite norverapamil is a moderate CYP3A4 inhibitor. In the presence of a strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold. [31824] [34979] Vigabatrin: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks. [36250] Vincristine Liposomal: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia. [57713] [57714] [57715] 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] 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: 10/14/2021, 02:26:00 AM

References

2460 - Robinson B, Cutolo M. Should dehydroepiandrosterone replacement therapy be provided with chronic glucocorticoids? Rheumatology (Oxford) 1999;38:488-495.3085 - Cohn JN, Kowey PR, Whelton PK, Prisant LM. New guidelines for potassium replacement in clinical practice: a contemporary review by the National Council on Potassium in Clinical Practice. Arch Intern Med 2000;160:2429-2436.4661 - Hexalen® (alretamine) package insert. Bloomington, MN: MGI Pharma, Inc.; 2001 Jan.4710 - Imuran (azathioprine) package insert. East Brunswisk, NJ: Casper Pharma, LLC; 2018 Dec.4718 - Hansten PD, Horn JR. Cytochrome P450 Enzymes and Drug Interactions, Table of Cytochrome P450 Substrates, Inhibitors, Inducers and P-glycoprotein, with Footnotes. In: The Top 100 Drug Interactions - A guide to Patient Management. 2008 Edition. Freeland, WA: H&H Publications; 2008:142-157.4744 - Premarin (conjugated estrogens, equine) package insert. Philadelphia, PA: Wyeth Pharmaceuticals Inc.; 2003 Jul.4746 - Celestone (betamethasone) package insert. Kenilworth, NJ: Schering Corporation; 1999 Oct.4757 - Leukeran (chlorambucil) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2011 Oct.4948 - Accolate (zafirlukast) package insert. Wilmington, DE: AstraZeneca; 2015 Dec.4953 - Vascor (bepridil) package insert. Raritan, NJ: Ortho-McNeil Pharmaceutical, Inc.; 2000 Mar.4968 - Halfan (halofantrine) package insert. Philadelphia, PA: Smith Kline Beecham Pharmaceuticals; 2001 Oct.5023 - Methazolamide tablet package insert. Basking Ridge, NJ: Micro Labs USA, Inc.; 2019 Nov.5283 - Accutane (isotretinoin) package insert. Nutley, NJ: Roche Laboratories Inc.; 2008 Nov.5462 - Crixivan (indinavir) package insert. Whitehouse Station, NJ: Merck & Co., Inc.; 2016 Sept.5468 - Inapsine (Droperidol) Injection package insert. Lake Forest, IL: Akorn, Inc.; 2011 Oct.5504 - Purinethol® (Mercaptopurine) package insert. Sellersville, PA: Gate Pharmaceuticals, div of Teva Pharmaceuticals USA; 2003 Aug.5567 - Cuprimine (penicillamine) package insert. Lawrenceville, NJ: Atom Pharma; 2010 Mar.5946 - BiCNU (carmustine) injection package insert. Edison, NJ: Heritage Pharmaceuticals Inc.; 2013 Apr.6192 - Cardizem LA (diltiazem) package insert. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC; 2016 Nov.6303 - Thymoglobulin (anti-thymocyte [antithymocyte] globulin-rabbit) package insert. Fremont, CA: SangStat Medical Corporation; 2002 Apr.6395 - US Food and Drug Administration (FDA). Guidance for Industry. Noncontraceptive Estrogen Drug Products for the Treatment of Vasomotor Symptoms and Vulvar and Vaginal Atrophy Symptoms - Recommended Prescribing Information for Health Care Providers and Patient Labeling. Document No. 6932. Division of Dockets Management (HFA-305), Food and Drug Administration, Rockville, MD; Issued November 2005. Retrieved Sept 2016. Available at: http://www.fda.gov/cder/guidance/guidance.htm.6524 - Deltasone (prednisone) tablet package insert. Petaluma, CA: Oculus Innovative Sciences, Inc.; 2017 Nov.6625 - Photofrin (porfimer) package insert. Birmingham, AL: Axcan Scandipharm Inc.; 2003 Aug.6702 - Panhematin® (hemin for injection) package insert. Deerfield, IL: Ovation Pharmaceuticals, Inc.; 2006 Aug.6807 - Humatrope (somatropin) package insert. Indianapolis, IN: Eli Lilly and Company; 2019 Oct.6856 - Sato J, Nakata H, Owada E, et al. Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects. Eur J Clin Pharmacol 1993;44:295-8.6865 - Entocort EC (budesonide) capsules package insert. Sodertalje, Sweden: AstraZeneca Pharmaceuticals; 2005 Apr.6968 - Raab W, Gmeiner B. Interactions between econazole, a broad-spectrum antimicrobic substance, and topically active glucocorticoids. Dermatologica 1976;153(1):14-22.7110 - Philipsen T, Eriksen PS, Lynggard F. Pulmonary edema following ritodrine-saline infusion in premature labor. Obstet Gynecol 1981;58(3):304-8.7111 - Semchyshyn S, Zuspan FP, O'Shaughnessy R. Pulmonary edema associated with the use of hydrocortisone and a tocolytic agent for the management of premature labor. J Reprod Med 1983;28(1):47-52.7557 - Clolar (clofarabine) package insert. Cambridge, MA: Genzyme Corporation; 2010 Dec.7572 - Yutopar® (ritodrine) package insert. Westborough, MA; Astra USA Inc.: 1998.7592 - Mier JW, Vachino G, Klempner MS, et al. Inhibition of interleukin-2-induced tumor necrosis factor release by dexamethasone: Prevention of an acquired neutrophil chemotaxis defect and differential suppression of interleukin-2 associated side effects. Blood 1990;76:1933-40.7714 - Schimmer B, Parker K. Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Hardman JG, Limbird LE, Molinoff PB, et al., eds. Goodman and Gilman's the Pharmacological Basis of Therapeutics, 10th edition. New York: McGraw Hill, 2001;1649-1674.7944 - Alkeran® injection (melphalan) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2007 Jun.8083 - Ammonul® (sodium phenylacetate and sodium benzoate) package insert. Baltimore, MD: Chesapeake Biological Laboratories, Inc.; 2005 Feb.8314 - Jux C, Leiber K, Hugel U, et al. Dexamethasone impairs growth hormone (GH)-stimulated growth by suppression of local insulin-like growth factor (IGF)-1 production and expression of GH- and IGF-1 receptor in cultured rat chondrocytes. Endocrinology 1998;139:3296-305.8315 - Allen DB. Inhaled corticosteroid therapy for asthma in preschool children: growth issues. Pediatrics 2002;109:373-80.8565 - Orencia (abatacept) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2020 Jun.8844 - Dexamethasone tablets, USP, dexamethasone oral solution, and dexamethasone Intensol oral solution (concentrate) package insert. Columbus, OH: Roxane Laboratories; 2005 Oct.9671 - Tyzeka (telbivudine) package insert. East Hanover, NJ: Novartis Pharmaceuticals, Corp.; 2018 Dec.10415 - Ixempra (ixabepilone) for injection package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2011 Oct.11210 - Dilger K, Schwab M, Fromm MF. Identification of budesonide and prednisone as substrates of the intestinal drug efflux pump P-glycoprotein. Inflamm Bowel Dis 2004; 10: 578-83.11342 - Halotestin® (fluoxymesterone) package insert. New York, NY: Pharmacia and Upjohn Company a Division of Pfizer, Inc; 2002 May.24574 - Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. Ann Intern Med 1991;115:787-96.25398 - Melchart D, Linde K, Worku F, et al. Results of five randomized studies on the immunomodulatory activity of preparations of Echinacea. J Altern Complement Med 1995;1:145-60.26417 - Cohn JN, Kowey PR, Whelton PK, Prisant LM. New guidelines for potassium replacement in clinical practice: a contemporary review by the National Council on Potassium in Clinical Practice. Arch Intern Med 2000;160:2429-2436.27939 - Humira (adalimumab) package insert. North Chicago, IL: AbbVie Inc; 2021 Feb.27982 - Ketoconazole tablets package insert. Morgantown, WV: Mylan Pharmaceuticals, Inc.; 2017 Sept.28001 - Hansten PD, Horn JR. Cytochrome P450 Enzymes and Drug Interactions, Table of Cytochrome P450 Substrates, Inhibitors, Inducers and P-glycoprotein, with Footnotes. In: The Top 100 Drug Interactions - A guide to Patient Management. 2008 Edition. Freeland, WA: H&H Publications; 2008:142-157.28003 - Mifepristone, RU-486 package insert. New York, NY: GenBioPro, Inc.; 2019 Feb.28004 - Isuprel (isoproterenol) package insert. Lake Forest, IL: Hospira, Inc.; 2013 Mar.28032 - McMahon M, Gerich J, Rizza R. Effects of glucocorticoids on carbohydrate metabolism. Diabetes Metab Rev 1988;4:17-30.28156 - Ketek (telithromycin) package insert. Bridgewater, NJ: Sanofi-Aventis Pharmaceuticals; 2015 Oct.28158 - VFEND (voriconazole) tablets, suspension, and injection package insert. New York, NY: Pfizer Inc; 2021 Oct.28211 - Henderson L, Yue QY, Bergquist C, et al. St John's wort (Hypericum perforatum): drug interactions and clinical outcomes. Br J Clin Pharmacol 2002;54:349-56.28224 - Pacerone (amiodarone) tablets package insert. Maple Grove, MN: Upsher-Smith Laboratories, LLC.; 2018 Nov.28225 - CredibleMeds. Drugs to avoid in congenital long QT. Available on the World Wide Web at http://www.crediblemeds.org.28238 - Biaxin (clarithromycin) package insert. North Chicago, IL: AbbVie, Inc.; 2019 Sep.28251 - Ery-tab (erythromycin delayed-release tablets) package insert. Atlanta, GA: Arbor Pharmaceuticals, Inc.; 2018 Oct.28267 - Acetazolamide package insert. Mahwah, NJ: Lifestar Pharma LLC; 2020 Mar.28269 - Celexa (citalopram) package insert. Madison, NJ: Allergan USA, Inc.; 2021 Sept.28272 - Lanoxin (digoxin) tablets package insert. St. Michael, Barbados: Concordia Pharmaceuticals Inc.; 2020 Apr..28278 - Raaska K, Niemi M, Neuvonen M, et al. Plasma concentrations of inhaled budesonide and its effects on plasma cortisol are increased by the cytochrome P4503A4 inhibitor itraconazole. Clin Pharmacol Ther 2002 Oct;72:362-9.28279 - Falcoz C, et al. Effects of CYP4503A inhibition by ketoconazole on systemic activity of inhaled fluticasone propionate and budesonide. Eur Respir J 1997;10(suppl 25):175-6.28307 - Haldol (haloperidol) injection for immediate release package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2020 Feb.28315 - Norvir (ritonavir capsules) package insert. North Chicago, IL: AbbVie Inc; 2020 Oct.28341 - Kaletra (lopinavir; ritonavir) tablet and solution package insert. North Chicago, IL: AbbVie Inc; 2020 Oct.28423 - Avelox (moxifloxacin) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2020 May.28424 - Factive (gemifloxacin mesylate) package insert. Toronto, ON: Merus Labs International, Inc.; 2019 May.28429 - Lasix (furosemide) package insert. Bridgewater, NJ: Aventis Pharmaceuticals; 2018 Aug.28492 - Viramune (nevirapine) package insert. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2011 Mar.28496 - Tracleer (bosentan) package insert. South San Francisco, CA: Actelion Pharmaceuticals US, Inc.; 2019 May.28502 - Fiorinal (butalbital; aspirin; caffeine) capsules package insert. Madison, NJ: Allergan USA, Inc.; 2021 Apr.28529 - Provigil® (modafinil) package insert. West Chester, PA: Cephalon, Inc; 2004 Feb.28549 - Coumadin (warfarin tablets) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2017 Aug.28550 - Glucophage and Glucophage XR (metformin HCl tablets and extended-release tablets) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2018 May.28674 - Diflucan oral tablet and suspension (fluconazole) package insert. New York, NY: Pfizer; 2020 Sept.28683 - Nefazodone tablet package insert. North Wales, PA: Teva Pharmaceuticals USA, Inc.; 2015 Sept.28761 - Albengres E, Le Louet H, Tillement JP. Systemic antifungal agents. Drug interactions of clinical significance. Drug Saf. 1998;18:83-97.28764 - Cipro (ciprofloxacin intravenous solution) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2020 May.28771 - Dilantin Kapseals (extended phenyotin sodium capsules, USP) package insert. Morris Plains, NJ: Parke Davis; 1999 Aug.28839 - Viracept (nelfinavir mesylate) package insert. Research Triangle Park, NC: ViiV Healthcare Company; 2021 Mar.28843 - Zonegran (zonisamide) package insert. Dublin, Ireland: Concordia Pharmaceuticals, Inc.; 2020 Apr.28902 - Fluvoxamine maleate package insert. Laurelton, NY: Eon Labs, Inc.; March 2005.28995 - Invirase (saquinavir) package insert. South San Francisco, CA: Genentech Inc.; 2020 Sept.29003 - OPEN REFERENCE29012 - Lexiva (fosamprenavir calcium) package insert. Research Triangle Park, NC: ViiV Healthcare; 2019 Mar29016 - Aldactone (spironolactone) package insert. New York, NY: G.D. Searle LLC; 2008 Jan.29118 - Seroquel (quetiapine fumarate) package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020 Sept.29190 - DeVane CL, Donovan JL, Liston HL, et al. Comparative CYP3A4 inhibitory effects of venlafaxine, fluoxetine, sertraline, and nefazodone in healthy volunteers. J Clin Psychopharmacol. 2004;24:4-10.29377 - Nanji AA. Drug-induced electrolyte disorders. Drug Intell Clin Pharm 1983;17:175-85.29779 - Deltasone (prednisone) tablet package insert. Petaluma, CA: Oculus Innovative Sciences, Inc.; 2017 Nov.29818 - Noroxin (norfloxacin) tablets package insert. Whitehouse Station, NJ: Merck and C., Inc.; 2016 Jul.29890 - Florinef Acetate (fludrocortisone acetate) package insert. Bristol, TN: Monarch Pharmaceuticals; 2003 Jul.30011 - Dexamethasone tablets USP, Dexamethasone oral solution, and Dexamethasone Intensol (oral solution concentrate) package insert. Eatontown, NJ: West-Ward Pharmaceuticals Corp; 2016 March.30015 - Medrol (methylprednisolone) tablet package insert. New York, NY: Pfizer; Pharmacia and Upjohn Company LLC; 2019 Jan.30028 - Pediapred (prednisolone sodium phosphate) oral solution package insert. Manasquan, NJ: Royal Pharmaceuticals; 2018 Feb.30470 - Tysabri (natalizumab) package insert. Cambridge, MA: Biogen Idec Inc.; 2020 Jun.30555 - Tarceva (erlotinib) package insert. Northbrook, IL: OSI Pharmaceuticals, LLC; 2016 Sept.30585 - Pandit MK, Burke J, Gustafson AB, et al. Drug-induced disorders of glucose tolerance. Ann Intern Med 1993;118:529-39.30676 - Emend (aprepitant oral products) package insert. Whitehouse Station, NJ: Merck & Co.,Inc.; 2019 Nov.30738 - Ofloxacin tablets package insert. Sacramento, CA: Nivagen Pharmaceuticals, Inc.; 2019 Feb.30943 - Schimmer B, Parker K. Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Hardman JG, Limbird LE, Molinoff PB, et al., eds. Goodman and Gilman's the Pharmacological Basis of Therapeutics, 10th edition. New York: McGraw Hill, 2001;1649-1674.31123 - Patten BM, Oliver KL, Engel WK. Adverse interaction between steroid hormones and anticholinesterase drugs. Neurology 1974;24:442-9.31468 - Actonel with Calcium (risedronate sodium with calcium carbonate) package insert. Rockaway, NJ: Warner Chilcott, LLC; 2015 Mar.31469 - Kumar R. Glucocorticoid-induced osteoporosis. Curr Opin Nephrol Hypertens 2001;10:585-9.31764 - Vaprisol (conivaptan hydrochloride injection) package insert. Deerfield, IL: Baxter Healthcare Corporation; 2016 Oct.31807 - Exjade (deferasirox) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2020 Jul.31824 - Rhinocort Aqua (budesonide) nasal spray package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2012 Feb.32073 - Lee AN, Werth VP. Activation of autoimmunity following use of immunostimulatory herbal supplements. Arch Dermatol 2004;140:723-7.32432 - Prezista (darunavir) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2021 Jul.32723 - Noxafil (posaconazole) package insert. Whitehouse Station, NJ: Merck & Co. Inc.: 2021 Jun.32789 - Zolinza (vorinostat) capsules package insert. Whitehouse Station, NJ: Merck & Co., Inc.; 2018 Dec.33528 - Metopirone (metyrapone) capsule package insert. Farmingdale, NJ: Direct Success, Inc; 2020 Feb.33698 - Androgel 1% (testosterone gel) package insert. North Chicago, IL: Abbott Laboratories; 2019 May.33718 - Intelence (etravirine) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2019 July.34253 - Regonol (pyridostigmine bromide injection, USP) package insert. Princeton, NJ: Sandoz, Inc.; 2019 Jan.34329 - Eberl S, Renner B, Neubert A, et al. Role of p-glycoprotein inhibition for drug interactions: evidence from in vitro and pharmacoepidemiological studies. Clin Pharmacokinet 2007;46:1039-49.34354 - Dilger K, Schwab M, Fromm MF. Identification of budesonide and prednisone as substrates of the intestinal drug efflux pump P-glycoprotein. Inflamm Bowel Dis 2004; 10: 578-83.34376 - Pulmicort Flexhaler (budesonide inhalation powder) package insert. Wilmington, DE: AstraZeneca LP; 2018 Dec.34447 - Niwa T, Shiraga T, Takagi A. Effect of antifungal drugs on cytochrome P450 (CYP) 2C9, CYP2C19, and CYP3A4 activities in human liver microsomes. Biol Pharm Bull. 2005;28:1805-1808.34535 - Zurcher RM, Frey BM, Frey FJ, et al. Impact of ketoconazole on the metabolism of prednisolone. Clin Pharmacol Ther 1989;45:366-72.34979 - Entocort EC (budesonide) capsules package insert. Wilmington, DE: AstraZeneca LP; 2020 July36101 - Multaq (dronedarone) package insert. Bridgewater, NJ: Sanofi-aventis U.S. LLC; 2020 Nov.36250 - Sabril (vigabatrin) tablet/powder for oral solution package insert. Deerfield, IL: Lundbeck Inc.; 2020 Jan.37098 - Votrient (pazopanib) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2011 Oct.40027 - Emend (fosaprepitant dimeglumine injection) package insert. Whitehouse Station, NJ: Merck & Co.,Inc.; 2019 Nov.40134 - Amphotericin B injection package insert. Big Flats, NY: X-Gen Pharmaceuticals, Inc.; 2009 Dec.40862 - Prolia (denosumab) solution for injection package insert. Thousand Oaks, CA: Amgen, Inc.; 2021 May.41057 - Wellbutrin XL (bupropion) package insert. Bridgewater, NJ: Bausch Health US, LLC; 2021 July.41086 - Wellbutrin (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2020 Oct.41237 - Tegretol (carbamazepine) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2018 Mar.41361 - Solu-Medrol (methylprednisolone sodium succinate for injection) package insert. New York, NY: Pharmacia and Upjohn Co; 2021 May.41573 - Suprep (sodium sulfate, potassium sulfate, and magnesium sulfate) oral solution concentrate package insert. Braintree, MA: Braintree Laboratories, Inc.; 2020 July.41853 - Proleukin (aldesleukin) package insert. San Diego, CA: Prometheus Laboratories Inc.; 2012 Jul.41934 - Lysodren (mitotane) package insert. Princeton, NJ: Bristol-Myers Squibb Oncology; 2021 June.41961 - Pancuronium injection package insert. Lake Forest, IL: Hospira, Inc; 2019 Jan.42031 - Rocuronium bromide package insert. Lake Zurich, IL: Fresenius Kabi; 2020 Apr.42281 - Cantil (mepenzolate bromide USP) package insert. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; 2006 Feb.42863 - Mytelase (ambenonium chloride) package insert. Bridgewater, NJ:Sanofi-Aventis U.S. LLC; 2011 Aug.43298 - Aplisol (tuberculin purified protein derivative, diluted) package insert. Chestnut Ridge, NY: Par Pharmaceuticals; 2016 Mar.43299 - Tubersol (tuberculin purified protein derivative, mantoux) package insert. Swiftwater, PA: Sanofi Pasteur, Inc.; 2020 Nov.43319 - Prednisone tablet package insert. Salisbury, MD: Cadista Pharmaceuticals Inc.; 2016 Mar.43463 - Orap (pimozide) package insert. Sellersville, PA: Teva Pharmaceuticals USA; 2014 Mar.43942 - Levothroid (levothyroxine sodium tablet) package insert. Shenandoah, IA: Lloyd Pharmaceutical; 2011 June.44314 - Victrelis (boceprevir) capsule package insert. Whitehouse Station, NJ: Merck and Co, Inc; 2017 Jan.44393 - Incivek (telaprevir) tablet package insert. Cambridge, MA: Vertex Pharmaceuticals, Inc; 2013 Oct.44913 - Mycamine (micafungin) for Injection package insert. Northbrook, IL: Astellas Pharma US, Inc; 2019 Dec.45335 - Zelboraf (vemurafenib) tablet package insert. South San Francisco, CA: Genentech USA, Inc.; 2020 May.45339 - Flo-Pred (prendisolone acetate) package insert. Hawthorne, NY: TaroPharma; 2021 July.45458 - Xalkori (crizotinib) package insert. New York, NY: Pfizer Labs; 2021 Sept.46711 - Pulmicort Turbuhaler (budesonide) package insert. Wilmington, DE: AstraZeneca, LP; 2006 Oct.47165 - Norvir (ritonavir tablets, solution, and powder) package insert. North Chicago, IL: AbbVie Inc; 2020 Oct.48342 - ANADROL-50 (oxymetholone) package insert. Marietta, GA: Alaven Pharmaceutical; 2006 Nov.48524 - Kalydeco (ivacaftor) package insert. Boston, MA: Vertex Pharmaceuticals Incorporated; 2020 Dec.48697 - Korlym (mifepristone) tablet package insert. Menlo Park, CA: Corcept Therapeutics; 2019 Nov.49489 - Cortisone acetate tablet package insert. Eatontown, N.J.: Hikma Pharmaceuticals USA Inc.; 2016 July49773 - Rituxan (rituximab) injection package insert. South San Francisco, CA: Genentech, Inc.; 2018 Apr.50586 - Torisel (temsirolimus) injection package insert. Philadelphia, PA: Wyeth Pharmaceuticals Inc; 2018 March.51002 - Chan JC, Cockram CS, Critchley JA. Drug-induced disorders of glucose metabolism. Mechanisms and management. Drug Saf 1996;15:135—57.51080 - Kaletra (lopinavir; ritonavir) capsule package insert. North Chicago, IL: AbbVie Inc; 2020 Oct.51664 - Stribild (elvitegravir; cobicistat; emtricitabine; tenofovir disoproxil fumarate) package insert. Foster City, CA: Gilead Sciences, Inc; 2021 Sept.51834 - Food and Drug Administration (FDA): Drug development and drug interactions. Retrieved Sep 19, 2012. Available on the World Wide Web http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm#transporter.52506 - Cometriq (Cabozantinib) capsules package insert. South San Francisco, CA:Exelixis, Inc.; 2020 Jan52910 - Uceris (budesonide) tablets package insert. San Diego, CA: Santarus Inc.; 2020 April.53022 - Ravicti (Glycerol phenylbutyrate) package insert. Lake Forest, IL: Horizon Pharma USA, Inc.; 2021 Sept.54246 - Hydrocortone (hydrocortisone sodium phosphate) injection package insert. Whitehouse Station, NJ: Merck & Co., Inc.; 2001 Nov.54278 - Solu-Cortef (hydrocortisone sodium succinate) injection package insert. New York, NY: Pharmacia and Upjohn Co.; 2021 May.54374 - Phenylephrine hydrochloride injection. Eatontown, NJ: West-Ward Pharmaceuticals; 12 Dec.54506 - Sodium chloride 0.45% and 0.9% injection package insert. Deerfield, IL: Baxter Healthcare Corporation. 2019 May.54802 - Tafinlar (dabrafenib) capsules package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2021 May.54891 - Bloxiverz (neostigmine methylsulfate injection) package insert. Lenoir, NC: Exela Pharma Sciences, LLC; 2020 Nov.55362 - Elspar (asparaginase) injection package insert. Deerfield, IL: Lundbeck; 2013 July.56076 - Edsbacker S, Andersson T. Pharmacokinetics of budesonide (Entocort EC) capsules for Crohn's disease. Clin Pharmacokinet 2004;43:803-821.56146 - Kenalog-40 (triamcinolone acetonide) injection package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2019 April.56233 - Singh JA, Furst DE, Bharat A, et al. 2012 Update of the 2008 American College of Rheumatology Recommendations for the Use of Disease-Modifying Antirheumatic Drugs and Biologic Agents in the Treatment of Rheumatoid Arthritis. Arthritis Care & Research 2012;64(5):625-639.56471 - Olysio (simeprevir) capsule package insert. Titusville, NJ: Janssen Therapeutics; 2017 Nov.56575 - Adrenalin (epinephrine) 1 mg/mL injection package insert. Chestnut Ridge, NJ: Par Pharmaceutical Companies, Inc.; 2019 Jan.56579 - Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. Updated Mar 10, 2020. Retrieved from the World Wide Web at www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm56853 - Hemangeol (propranolol hydrochloride) oral solution package insert. Parsippany, NJ: Pierre Fabre Pharmaceuticals, Inc.; 2021 Jun.57094 - Zykadia (ceritinib) package insert. Indianapolis, IN: Novartis; 2021 Oct.57578 - Vazculep (phenylephrine) injection package insert. Chesterfield, Mo: Avadel Legacy Pharmaceuticals, LLC; 2019 Oct.57675 - Zydelig (idelalisib) tablet package insert. Foster City, CA:Gilead Sciences, Inc.; 2018 Oct.57685 - Buphenyl (sodium phenylbutyrate) oral tablet and powder package insert. South San Francisco, CA: Hyperion Therapeutics, Inc.; 2013 Jun.57713 - K Phos Neutral (potassium phosphate; sodium phosphate) tablets package insert. Tampa, FL: Beach Pharmaceuticals; 2005 Jun.57714 - Virt Phos 250 Neutral (potassium phosphate; sodium phosphate) tablets package insert. Tampa, FL: Virtus Pharmaceuticals; 2014 Mar.57715 - Phospha 250 Neutral (potassium phosphate; sodium phosphate) tablets package insert. Columbus, OH: Rising Pharmaceuticals, Inc.; 2011 Feb.57741 - Orbactiv (oritavancin) package insert. Lincolnshire, IL: Melinta Therapeutics, LLC; 2021 July.57803 - Cerdelga (eliglustat) capsules. Waterford, Ireland: Genzyme Ireland, Ltd.;2018 Sept.58000 - Tybost (cobicistat) package insert. Foster City, CA: Gilead Sciences, Inc; 2021 Sept.58167 - Harvoni (ledipasvir; sofosbuvir) tablet and oral pellets package insert. Foster City, CA: Gilead Sciences, Inc; 2020 Mar.58220 - Bachmakov I, Werner U, Endress B, et al. Characterization of beta-adrenoceptor antagonists as substrates and inhibitors of the drug transporter P-glycoprotein. Fundam Clin Pharmacol 2006;20:273-82.58461 - Lemtrada (alemtuzumab) injection package insert. Cambridge, MA: Genzyme Corporation; 2021 Aug.58768 - Ibrance (palbociclib) capsules package insert. New York, NY: Pfizer Inc; 2019 Sept.59042 - Cresemba (isavuconazonium) package insert. Northbrook, IL: Astellas Pharma US, Inc; 2021 May.59438 - Trisenox (arsenic trioxide) injection package insert. Parsippany, NJ: Teva Pharmaceuticals USA, Inc.; 2020 Oct.59891 - Orkambi (lumacaftor; ivacaftor) tablet package insert. Boston, MA: Vertex Pharmaceuticals, Inc. 2018 August60001 - Daklinza (daclatasvir) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2019 Oct.60523 - Zepatier (elbasvir; grazoprevir) tablet package insert. Whitehouse Station, NJ: Merck, Inc; 2019 Dec.60738 - Cabometyx (Cabozantinib) tablets package insert. Alameda, CA: Exelixis, Inc.; 2021 Sept.60760 - Dexamethasone sodium phosphate injection package insert. Eatontown, NJ:West-Ward Pharmaceuticals;2014 Sept.60852 - Netspot (gallium Ga 68 dotatate) injection package insert. Millburn, NJ: Advanced Accelerator Applications USA, Inc. 2021 Jun.61087 - Leukine (sargramostim) injection package insert. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; 2018 Mar.61750 - Emflaza (deflazacort) tablets and oral suspension. South Plainfield, NJ: PTC Therapeutics; 2021 Jul.61806 - Noctiva nasal spray (desmopressin acetate) package insert. Milford, PA: Serenity Pharmaceuticals LLC; 2017 Mar.61816 - Kisqali (ribociclib) tablets package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2021 Sept.61902 - Stimpel M, Proksch A, Wagner H, et al. Macrophage activation and induction of macrophage cytotoxicity by purified polysaccharide fractions from the plant Echinacea purpurea. Infect Immun 1984;46:845-961905 - Chavez ML, Jordan MA, Chavez PI. Evidence-based drug-herbal interactions. Life Sci 2006;78:2146-57.61909 - Alunbrig (brigatinib) tablet package insert. Cambridge, MA: Ariad Pharmaceuticals Inc.; 2021 Sept.61937 - Millipred (prednisolone) oral tablet package insert. Research Triangle Park, NC: Zylera Pharmaceuticals, LLC; 2015 Nov.62028 - Baxdela (delafloxacin) package insert. Lincolnshire, IL: Melinta Therapeutics, Inc.; 2019 Oct.62131 - Vosevi (sofosbuvir; velpatasvir; voxilaprevir) tablet package insert. Foster City, CA: Gilead Sciences, Inc; 2019 Nov.62201 - Mavyret (glecaprevir; pibrentasvir) tablets package insert. North Chicago, IL: AbbVie Inc.; 2021 Sept.62264 - National Clinical Guideline Centre (UK). Multiple Sclerosis: Management of Multiple Sclerosis in Primary and Secondary Care. London: National Institute for Health and Care Excellence (UK); (NICE Clinical Guideline No 186). 2014 Oct. Accessed: August 25 2017. Available at: www.ncbi.nlm.nih.gov/pubmedhealth/PMH0068954/pdf/PubMedHealth_PMH0068954.pdf62611 - Prevymis (letermovir) package insert. Whitehouse Station, NJ: Merck and Co, Inc.; 2020 Mar.62723 - Macrilen (macimorelin) package insert. Frankfurt am Main, Germany: Aeterna Zentaris GmbH; 2018 Jan.62853 - Amin M, Suksomboon N. Pharmacotherapy of type 2 diabetes mellitus: an update on drug-drug interactions. Drug Saf. 2014;37:903-919.63317 - Braftovi (encorafenib) capsules package insert. Boulder, CO: Array BioPharma Inc.; 2020 April.63368 - Tibsovo (ivosidenib) tablet package insert. Cambridge, MA: Agios Pharmaceuticals; 2021 Aug.63571 - Copiktra (duvelisib) capsules package insert. Las Vegas, NV: Secura Bio, Inc.; 2021 Sept.63790 - Firdapse (amifampridine) tablets package insert. Coral Gables, FL: Catalyst Pharmaceuticals, Inc.; 2021 Feb.63923 - The American Geriatrics Society 2019 Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2019;00:1-21.64002 - Pyridostigmine Bromide oral solution package insert. East Windsor, NJ: Novitium Pharma LLC; 2019 Mar.64165 - Dexamethasone (Decadron) tablets package insert. Whitehouse Station, NJ: Merck & Co., Inc.; 2019 May.64568 - Inrebic (fedratinib) capsules package insert. Summit, NJ: Celgene Corporation; 2019 Aug.64576 - Xenleta (lefamulin) package insert. Dublin, Ireland: Nabriva Therapeutics US, Inc.; 2021 Mar.64721 - Ibrance (palbociclib) tablets package insert. New York, NY: Pfizer Inc; 2019 Nov.65107 - Kroger A, Bahta L, Hunter P. General Best Practice Guidelines for Immunization. Best Practices Guidance of the Advisory Committee on Immunization Practices (ACIP). Available on the world wide web at https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/downloads/general-recs.pdf. Accessed on July 26, 202165295 - Tukysa (tucatinib) tablets package insert. Bothell, WA: Seattle Genetics, Inc.; 2020 April.65562 - Levofloxacin tablets package insert. Livonia, MI; Major Pharmaceuticals: 2019 Nov.65576 - Uplizna (inebilizumab-edon) injection package insert. Gaithersburg, MD: Viela Bio, Inc.; 2020 Jun.65850 - Kesimpta (ofatumumab) injection package insert. East Hanover, NJ: Novartis Pharmaceutical Corporation; 2020 Aug.66080 - Food and Drug Administration (FDA). Fact Sheet for Healthcare Providers Administering Vaccine: Emergency Use Authorization (EUA) of Pfizer-BioNTech COVID-19 Vaccine to Prevent Coronavirus Disease 2019 (COVID-19). Retrieved Sept 22, 2021.66129 - Zokinvy (lonafarnib) capsules package insert. Palo Alto, CA: Eiger BioPharmaceuticals, Inc.; 2020 Nov.66159 - Orladeyo (berotralstat) package insert. Durham, NC;BioCryst Pharmaceuticals, Inc.: 2020 Dec.66527 - Ponvory (ponesimod) tablet package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2021 Mar.

Monitoring Parameters

  • growth rate
  • pulmonary function tests (PFTs)
  • weight

US Drug Names

  • Entocort EC
  • Ortikos
  • Pulmicort
  • Rhinocort
  • Rhinocort Aqua
  • UCERIS
;