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  • CLASSES

    Corticosteroids, Inhalant
    Corticosteroids, Locally Acting Intestinal Antiinflammatory Agents
    Systemic Corticosteroids, Plain
    Topical Nasal Corticosteroids

    DEA CLASS

    Rx, OTC

    DESCRIPTION

    Potent corticosteroid available for intranasal, inhaled, rectal, and oral administration
    Nasal form used for allergic rhinitis; available for prescription or non-prescription (OTC) use
    Respiratory inhalation used for asthma or COPD
    Used rectally to treat ulcerative colitis; used orally to treat Crohn's disease and ulcerative colitis

    COMMON BRAND NAMES

    Entocort EC, Pulmicort, Rhinocort, Rhinocort Aqua, UCERIS

    HOW SUPPLIED

    Budesonide/Entocort EC Oral Cap DR Pellets: 3mg
    Budesonide/Pulmicort Respiratory (Inhalation) Susp: 0.25mg, 0.5mg, 1mg, 2mL
    Budesonide/Rhinocort/Rhinocort Aqua Nasal Spray Met: 1actuation, 32mcg
    Pulmicort Respiratory (Inhalation) Inhalant: 1actuation, 90mcg, 180mcg
    UCERIS Oral Tab ER: 9mg
    UCERIS Rectal Aer Foam: 1actuation, 2mg

    DOSAGE & INDICATIONS

    For the management of nasal symptoms associated with perennial vasomotor rhinitis.
    Intranasal dosage (Rhinocort Aqua 32 mcg/spray)

    An improvement in nasal symptoms may occur within 10 hours of initial dose; however, clinical improvement usually takes 1 to 2 days with maximum benefit achieved in approximately 2 weeks.

    Adults, Adolescents, and Children >= 12 years

    Initially, 1 spray (32 mcg/spray) per nostril once daily in the morning. If satisfactory clinical improvement is not achieved, the dosage may be increased. The maximum dosage is 256 mcg/day delivered as 4 sprays (32 mcg/spray) per nostril once daily. After clinical response, decrease to lowest effective dose.

    Children 6 to < 12 years

    Initially, 1 spray (32 mcg/spray) per nostril once daily in the morning. Maximum dosage is 128 mcg/day delivered as 2 sprays (32 mcg/spray) per nostril once daily. After clinical response, decrease to lowest effective dose.

    Intranasal dosage (Rhinocort Nasal Spray)
    Adults

    NOTE: Rhinocort Nasal Inhaler has been discontinued in the US as of September 2004. Initially, 2 sprays (32 mcg/spray) per nostril in the morning and in the evening, or 4 sprays (32 mcg/spray) in each nostril in the morning. After clinical response has been obtained, decrease to lowest effective dose.

    For the management of nasal symptoms associated with allergic rhinitis.
    Intranasal dosage (non-prescription OTC use, e.g., Rhinocort Allergy 32 mcg/spray or generic equivalent)
    Adults, Adolescents, and Children >= 12 years

    2 sprays (32 mcg per 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.

    Children 6—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.

    Intranasal dosage (prescription-only intranasal suspension, e.g., Rhinocort Aqua 32 mcg/spray or generic equivalents)
    Adults, Adolescents, and Children >= 12 years

    Initially, 1 spray (containing 32 mcg per spray) per nostril once daily in the morning. If satisfactory clinical improvement is not achieved, the dosage may be increased. Maximum total daily dosage: 256 mcg/day (i.e., 4 sprays per nostril once daily). Once symptoms are under control, decrease to lowest effective dose that continues to control symptoms. Initial reduction in symptoms may be seen within 10 hours of starting treatment; however, maximal benefit may not be evident until after 2 weeks of initiation of treatment.

    Children 6—11 years

    Initially, 1 spray (containing 32 mcg per spray) in each nostril once daily in the morning. If clinical response is not sufficient, dose may be increased. Maximum total daily dosage: 128 mcg/day (i.e., 2 sprays per nostril once daily). After clinical symptoms are under control, decrease to the lowest dose that maintains symptom control. Initial reduction in symptoms may be seen within 10 hours of starting treatment; however, maximal benefit may not be evident until after 2 weeks of initiation of treatment.

    For maintenance treatment of asthma as prophylactic therapy (bronchospasm prophylaxis).
    NOTE: Budesonide is not indicated for the treatment of acute bronchospasm.
    In patients previously receiving bronchodilators alone.
    Oral inhalation dosage (Pulmicort Flexhaler inhalation powder; 180 mcg/dose or 90 mcg/dose)

    NOTE: One actuation of the 180 mcg strength delivers 160 mcg of budesonide from the mouthpiece. One actuation of the 90 mcg strength delivers 80 mcg of budesonide from the mouthpiece.
    NOTE: Clinical response to Pulmicort Flexhaler may be lower compared to Pulmicort Turbuhaler. Conversion dosages between products are not available. Individualize regimen based on response and tolerability, and in accordance with product labeling.

    Adults

    360 mcg twice daily by oral inhalation. The maximum recommended dose is 720 mcg twice daily. A maintenance or starting dose of 180 mcg twice daily may be appropriate in some patients. Titrate to the lowest effective dose once asthma stability is achieved.

    Children > = 6 years and Adolescents

    The recommended starting dosage is 180 mcg twice daily. In some patients a starting dosage of 360 mcg twice daily may be appropriate. Per manufacturer, maximum dosage should not exceed 360 mcg twice daily. The National Asthma Education and Prevention Program Expert Panel defines low dose therapy for budesonide dry powder inhalers as 180—400 mcg/day, medium dose therapy as > 400—800 mcg/day, and high dose therapy as > 800 mcg/day for children ages 5—11 years. Titrate to the lowest effective dose once asthma stability is achieved. Prolonged use of high doses, i.e. > 800 mcg/day, may be associated with additional adverse effects.

    Children 5 years†

    The National Asthma Education and Prevention Program Expert Panel defines low dose therapy for budesonide dry powder inhalers as 180—400 mcg/day, medium dose therapy as > 400—800 mcg/day, and high dose therapy as > 800 mcg/day for children ages 5—11 years. Total daily doses should be divided and administered twice daily. Titrate to the lowest effective dose once asthma stability is achieved. Prolonged use of high doses, i.e. > 800 mcg/day, may be associated with additional adverse effects.

    Nebulized dosage (Pulmicort Respules inhalation suspension for nebulization)
    Children 5—8 years

    0.5 mg/day inhaled via jet nebulizer either once daily or divided into 2 doses. The maximum manufacturer recommended total daily dose is 0.5 mg/day. The National Asthma Education and Prevention Program Expert Panel defines low dose therapy for budesonide inhalation suspension as 0.5 mg/day, medium dose therapy as 1 mg/day, and high dose therapy as 2 mg/day for children ages 5—11 years. Titrate to the lowest effective dose once asthma stability is achieved. Prolonged use of high doses, i.e., 2 mg/day, may be associated with additional adverse effects. In one clinical study, 42 children between the ages of 6 months and 3 years received either budesonide 0.25 mg twice daily or 1 mg twice daily, with a 25% decrease in dosage every 2 days for 6 days. On day 7, both treatment groups received 0.25 mg twice daily for the remainder of the 9 weeks. Only children in the high initial dose group had significant improvements in asthma symptoms during the first week. Short-term, high-dose nebulized budesonide can have an early clinical effect by day 2 of treatment that is maintained throughout 10 weeks.

    Children 1—4 years

    The manufacturer recommends 0.25—0.5 mg/day inhaled via jet nebulizer either once daily or divided into 2 doses,with a maximum daily dose of 0.5 mg/day. The National Asthma Education and Prevention Program Expert Panel defines low dose therapy for budesonide inhalation suspension as 0.25—0.5 mg/day, medium dose therapy as > 0.5—1 mg/day, and high dose therapy as > 1 mg/day for children ages 1—4 years. Titrate to the lowest effective dose once asthma stability is achieved. Prolonged use of high doses, i.e., > 1 mg/day, may be associated with additional adverse effects. In one clinical study, 42 children between the ages of 6 months and 3 years received either budesonide 0.25 mg twice daily or 1 mg twice daily, with a 25% decrease in dosage every 2 days for 6 days. On day 7, both treatment groups received 0.25 mg twice daily for the remainder of the 9 weeks. Only children in the high initial dose group had significant improvements in asthma symptoms during the first week. Short-term, high-dose nebulized budesonide can have an early clinical effect by day 2 of treatment that is maintained throughout 10 weeks.

    Infants >=6 months† and Children 12 months†

    Limited data suggest the use of 0.25—1 mg per day given by oral inhalation once daily or in 2 divided doses. One randomized, double-blind, placebo-controlled trial of 141 infants ages 6—12 months with mild to moderate persistent asthma or recurrent wheeze examined the safety of inhaled budesonide 0.5 mg and 1 mg per day. The primary outcome variable was the effect on adrenal function as assessed by 0.125 mg cosyntropin stimulation tests performed prior to and 12 weeks after therapy initiation. Adrenal function was assessed in 76 patients, and mean post-stimulation cortisol concentrations at 12 weeks were 674, 661, and 650 nmol/L for the budesonide 0.5 mg, budesonide 1 mg, and placebo groups respectively. Post-stimulation concentrations of < 500 nmol/L were considered abnormal. Shifts from normal baseline to subnormal post-treatment cortisol concentrations were observed in 4, 2, and 1 of the infants in the budesonide 0.5 mg, budesonide 1 mg, and placebo groups respectively. Infants who received budesonide experienced reduced growth velocity compared to the placebo group; however, the study was too short to assess long term effects on growth. The study was not powered to address efficacy.

    Oral inhalation dosage (Pulmicort Turbuhaler inhalation powder 200 mcg/dose)
    Adults

    NOTE: Pulmocort Turbuhaler is discontinued in the US. 200—400 mcg (1—2 puffs) twice daily by oral inhalation. The maximum recommended dose is 400 mcg twice daily. Titrate to the lowest effective dose once asthma stability is achieved.

    Children > = 6 years

    NOTE: Pulmocort Turbuhaler is discontinued in the US. 200 mcg (1 puff) twice daily by oral inhalation. The maximum manufacturer recommended dose is 400 mcg twice daily. The National Asthma Education and Prevention Program Expert Panel defines low dose therapy for budesonide dry powder inhalers as 180—400 mcg/day, medium dose as > 400—800 mcg/day, and high dose therapy as > 800 mcg/day for children ages 5—11 years. Titrate to the lowest effective dose once asthma stability is achieved. Prolonged use of high doses, i.e. > 800 mcg/day, may be associated with additional adverse effects.

    Children 5 years†

    NOTE: Pulmocort Turbuhaler is discontinued in the US. The National Asthma Education and Prevention Program Expert Panel defines low dose therapy for budesonide dry powder inhalers as 180—400 mcg/day, medium dose as > 400—800 mcg/day, and high dose therapy as > 800 mcg/day for children ages 5—11 years. Total daily doses should be divided and administered twice daily. Titrate to the lowest effective dose once asthma stability is achieved. Prolonged use of high doses, i.e. > 800 mcg/day, may be associated with additional adverse effects.

    In patients previously receiving inhaled corticosteroids.
    Oral inhalation dosage (Pulmicort Flexhaler inhalation powder; 180 mcg/dose or 90 mcg/dose)

    NOTE: One actuation of the 180 mcg strength delivers 160 mcg of budesonide from the mouthpiece. One actuation of the 90 mcg strength delivers 80 mcg of budesonide from the mouthpiece.
    NOTE: Clinical response to Pulmicort Flexhaler may be lower compared to Pulmicort Turbuhaler. Conversion dosages between products are not available. Individualize regimen based on response and tolerability, and in accordance with product labeling.

    Adults

    Clinical studies were not conducted; however, 360 mcg twice daily by oral inhalation may be used as a general guideline. The maximum recommended dose is 720 mcg twice daily. A maintenance or starting dose of 180 mcg twice daily may be appropriate in some patients. Reduce to the lowest effective dose once asthma stability is achieved.

    Children > = 6 years and Adolescents

    Clinical studies were not conducted; however 180—360 mcg twice daily by oral inhalation may be used as a general guideline. The maximum manufacturer recommended dose is 360 mcg twice daily. The National Asthma Education and Prevention Program Expert Panel defines low dose therapy for budesonide dry powder inhalers as 180—400 mcg/day, medium dose as > 400—800 mcg/day, and high dose therapy as > 800 mcg/day for children ages 5—11 years. Titrate to the lowest effective dose once asthma stability is achieved. Prolonged use of high doses, i.e. > 800 mcg/day, may be associated with additional adverse effects.

    Children 5 years†

    Clinical studies were not conducted; however 180 mcg twice daily by oral inhalation may be used as a general guideline. The National Asthma Education and Prevention Program Expert Panel defines low dose therapy for budesonide dry powder inhalers as 180—400 mcg/day, medium dose as > 400—800 mcg/day, and high dose therapy as > 800 mcg/day for children ages 5—11 years. Titrate to the lowest effective dose once asthma stability is achieved. Prolonged use of high doses, i.e. > 800 mcg/day, may be associated with additional adverse effects.

    Nebulized dosage (Pulmicort Respules inhalation suspension for nebulization)
    Children 5—8 years

    0.5 mg/day inhaled via jet nebulizer either once daily or divided into 2 doses. The maximum manufacturer recommended total dose is 1 mg/day. The National Asthma Education and Prevention Program Expert Panel defines low dose therapy for budesonide inhalation suspension as 0.5 mg/day, medium dose therapy as 1 mg/day, and high dose therapy as 2 mg/day for children ages 5—11 years. Titrate to the lowest effective dose once asthma stability is achieved. Prolonged use of high doses, i.e., 2 mg/day, may be associated with additional adverse effects.

    Children 1—4 years

    0.5 mg/day inhaled via jet nebulizer either once daily or divided into 2 doses. The maximum manufacturer recommended total dose is 1 mg/day. The National Asthma Education and Prevention Program Expert Panel defines low dose therapy for budesonide inhalation suspension as 0.25—0.5 mg/day, medium dose therapy as > 0.5—1 mg/day, and high dose therapy as > 1 mg/day for children ages 1—4 years. Titrate to the lowest effective dose once asthma stability is achieved. Prolonged use of high doses, i.e., > 1 mg/day, may be associated with additional adverse effects.

    Infants >=6 months† and Children 12 months†

    Clinical studies have not been published; however, limited data suggest 0.25—1 mg per day given by oral inhalation once daily or in 2 divided doses may be used as general guidance. Titrate to the lowest effective dose once asthma stability is achieved.

    Oral inhalation dosage (Pulmicort Turbuhaler inhalation powder 200 mcg/dose)
    Adults

    NOTE: This product is discontinued in the US. 200—400 mcg (1—2 puffs) twice daily by oral inhalation. The maximum recommended dose is 800 mcg twice daily. Titrate to the lowest effective dose once asthma stability is achieved.

    Children > = 6 years

    NOTE: This product is discontinued in the US. 200 mcg (1 puff) twice daily by oral inhalation. The maximum manufacturer recommended dose is 400 mcg twice daily. The National Asthma Education and Prevention Program Expert Panel defines low dose therapy for budesonide dry powder inhalers as 180—400 mcg/day, medium dose therapy as > 400—800 mcg/day, and high dose therapy as > 800 mcg/day for children ages 5—11 years. Titrate to the lowest effective dose once asthma stability is achieved. Prolonged use of high doses, i.e. > 800 mcg/day, may be associated with additional adverse effects.

    Children 5 years†

    NOTE: This product is discontinued in the US. The National Asthma Education and Prevention Program Expert Panel defines low dose therapy for budesonide dry powder inhalers as 180—400 mcg/day, medium dose therapy as > 400—800 mcg/day, and high dose therapy as > 800 mcg/day for children ages 5—11 years. Titrate to the lowest effective dose once asthma stability is achieved. Prolonged use of high doses, i.e., > 800 mcg/day, may be associated with additional adverse effects.

    In patients previously receiving oral corticosteroids.
    Oral inhalation dosage (Pulmicort Flexhaler inhalation powder; 180 mcg/dose or 90 mcg/dose)

    NOTE: One actuation of the 180 mcg strength delivers 160 mcg of budesonide from the mouthpiece. One actuation of the 90 mcg strength delivers 80 mcg of budesonide from the mouthpiece.
    NOTE: Clinical response to Pulmicort Flexhaler may be lower compared to Pulmicort Turbuhaler. Conversion dosages between products are not available. Individualize regimen based on response and tolerability, and in accordance with product labeling.

    Adults

    Clinical studies were not conducted; however, 360 mcg twice daily by oral inhalation may be used as a general guideline. The maximum recommended dose is 720 mcg twice daily. A maintenance or starting dose of 180 mcg twice daily may be appropriate in some patients. Reduce to the lowest effective dose once asthma stability is achieved.

    Children > = 6 years and Adolescents

    Clinical studies were not conducted; however 180—360 mcg twice daily by oral inhalation may be used as a general guideline. The maximum manufacturer recommended dose is 360 mcg twice daily. The National Asthma Education and Prevention Program Expert Panel defines low dose therapy for budesonide dry powder inhalers as 180—400 mcg/day, medium dose therapy as > 400—800 mcg/day, and high dose therapy as > 800 mcg/day for children ages 5—11 years. Titrate to the lowest effective dose once asthma stability is achieved. Prolonged use of high doses, i.e., > 800 mcg/day, may be associated with additional adverse effects.

    Children 5 years†

    Clinical studies were not conducted; however 180 mcg twice daily by oral inhalation may be used as a general guideline. The National Asthma Education and Prevention Program Expert Panel defines low dose therapy for budesonide dry powder inhalers as 180—400 mcg/day, medium dose therapy as > 400—800 mcg/day, and high dose therapy as > 800 mcg/day for children ages 5—11 years. Titrate to the lowest effective dose once asthma stability is achieved. Prolonged use of high doses, i.e., > 800 mcg/day, may be associated with additional adverse effects.

    Nebulized dosage (Pulmicort Respules inhalation suspension for nebulization)
    Children 5—8 years

    1 mg/day inhaled via jet nebulizer either once daily or divided into 2 doses. The maximum manufacturer recommended total dose is 1 mg/day. The National Asthma Education and Prevention Program Expert Panel defines low dose therapy for budesonide inhalation suspension as 0.5 mg/day, medium dose therapy as 1 mg/day, and high dose therapy as 2 mg/day for children ages 5—11 years. Titrate to the lowest effective dose once asthma stability is achieved. Prolonged use of high doses, i.e., 2 mg/day, may be associated with additional adverse effects.

    Children 1—4 years

    1 mg/day inhaled via jet nebulizer either once daily or divided into 2 doses. The maximum manufacturer recommended total dose is 1 mg/day. The National Asthma Education and Prevention Program Expert Panel defines low dose therapy for budesonide inhalation suspension as 0.25—0.5 mg/day, medium dose therapy as > 0.5— 1 mg/day, and high dose therapy as > 1 mg/day for children ages 1—4 years. Titrate to the lowest effective dose once asthma stability is achieved. Prolonged use of high doses, i.e. > 1 mg/day, may be associated with additional adverse effects.

    Infants >=6 months† and Children 12 months†

    Clinical studies have not been published; however, limited data suggest 0.25—1 mg per day given by oral inhalation once daily or in 2 divided doses may be used as general guidance. Titrate to the lowest effective dose once asthma stability is achieved.

    Oral inhalation dosage (Pulmicort Turbuhaler inhalation powder 200 mcg/dose)
    Adults

    NOTE: This product is discontinued in the US. 400—800 mcg (2—4 puffs) twice daily by oral inhalation. The maximum recommended dose is 800 mcg twice daily. Titrate to the lowest effective dose once asthma stability is achieved.

    Children > = 6 years

    NOTE: This product is discontinued in the US. 200—400 mcg (1—2 puffs) twice daily by oral inhalation. The maximum manufacturer recommended dose is 400 mcg twice daily. The National Asthma Education and Prevention Program Expert Panel defines low dose therapy for budesonide dry powder inhalers as 180—400 mcg/day, medium dose therapy as > 400—800 mcg/day, and high dose therapy as > 800 mcg/day for children ages 5—11 years. Titrate down to the lowest effective dose once asthma stability is achieved. Prolonged use of high doses, i.e. > 800 mcg/day, may be associated with additional adverse effects.

    Children 5 years†

    NOTE: This product is discontinued in the US. 200—400 mcg (1—2 puffs) twice daily by oral inhalation. The usual maximum recommended dose is 400 mcg twice daily. The National Asthma Education and Prevention Program Expert Panel defines low dose therapy for budesonide dry powder inhalers as 180—400 mcg/day, medium dose therapy as > 400—800 mcg/day, and high dose therapy as > 800 mcg/day for children ages 5—11 years. Titrate down to the lowest effective dose once asthma stability is achieved. Prolonged use of high doses, i.e. > 800 mcg/day, may be associated with additional adverse effects.

    For mild to moderate Crohn's disease involving the ileum and/or ascending colon.
    For active disease in patients not previously receiving oral prednisolone.
    Oral dosage (Entocort EC)
    Adults

    9 mg PO once daily in the morning for up to 8 weeks. Dosing may be tapered 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. Consider reduced doses for elderly based on hepatic function.

    Children and Adolescents 8 years and older

    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.

    For active disease in patients previously receiving oral prednisolone.
    Oral dosage (Entocort EC)
    Adults

    Do not abruptly stop prednisolone. Taper prednisolone downward with the initiation of oral budesonide treatment. Give 9 mg budesonide 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. Consider reduced doses for elderly based on hepatic function. In clinical trials, patients were switched from oral prednisolone to oral budesonide with no reports of adrenal insufficiency. Comparative efficacy was favorable for budesonide.

    Children and Adolescents 8 years and older

    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. Do not abruptly stop prednisolone. Taper prednisolone downward with the initiation of oral budesonide treatment.

    For maintenance of clinical remission for up to 3 months.
    NOTE: A Crohn’s Disease Activity Index (CDAI) < 150 after 8 weeks of treatment for active disease is recommended before maintenance treatment is initiated.
    Oral dosage (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.

    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 with or without food for up to 8 weeks.

    Rectal dosage (rectal foam)

    NOTE: Budesonide rectal foam is indicated for active mild to moderate distal ulcerative colitis extending up to 40 cm from the anal verge.

    Adults

    2 mg (1 metered dose) rectally twice daily (once in the morning and once in the evening) for 2 weeks followed by 2 mg (1 metered dose) rectally once daily (in the evening) for 4 weeks. When applied in the evening, rectal foam should be used immediately prior to bedtime.

    For the improvement of symptoms of mild to moderate acute laryngotracheobronchitis (croup)†.
    Nebulized dosage (Pulmicort Respules inhalation suspension for nebulization)
    Infants > = 3 months to Children < = 5 years

    2 mg inhaled via nebulizer as a single dose was used in one study. Disease severity score was less in the budesonide group and patients receiving budesonide were discharged from the ER sooner and were less likely to be admitted versus placebo. In another study, a single 4 mg nebulized dose was used and was superior to placebo but inferior to IM dexamethasone.

    For the treatment of collagenous colitis† (a form of microscopic colitis).
    Oral dosage (Entocort EC)
    Adults

    9 mg PO once daily or on a tapering schedule for 8 weeks has been used in clinical trials. 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 of the lamina propria infiltrates in the budesonide group (p < 0.001). Another controlled trial (n = 20) studied a 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 compared to 2 patients in the placebo group (p < 0.001). Patients receiving budesonide reported reduced stool weight and frequency; histological inflammation was also significantly improved. Limited data on long-term safety and efficacy along with improved 'quality-of-life' appear positive.

    For exercise-induced bronchospasm prophylaxis†.
    Oral inhalation dosage
    Adults

    A dose of 800 mcg inhaled twice daily has been used; the maximum recommended dose is 720 mcg twice daily. A starting dose of 360 mcg twice daily may be appropriate. Titrate to the lowest effective dose. The American Thoracic Society recommends daily administration of an inhaled corticosteroid (ICS) such as budesonide in patients who continue to have EIB symptoms despite using an inhaled short-acting beta-2 agonist (SABA) before exercise, or in those who require daily (or more frequent) SABA use. In clinical practice, ICSs may be a first-line choice for a controller agent to be added to SABAs; leukotriene receptor antagonists may also be used. The choice between the 2 classes must be made on an individual basis considering patient preferences and baseline lung function. Patients with EIB associated with greater airway inflammation (e.g., asthma) may benefit more from ICS therapy. The efficacy of budesonide in the treatment of EIB was examined in a double-blind, placebo-controlled trial in which 40 adult subjects with asthma received inhaled budesonide or placebo for 6 weeks. Subjects refrained from the use of any medications other than the study drug and an inhaled beta-2 agonist used as needed. For exercise assessment, the maximum percentage fall from pre-exercise baseline FEV1 was obtained following a 6 minute treadmill challenge, with FEV1 assessed before exercise and up to 20 minutes after. After budesonide treatment, the median percent fall in FEV1 decreased from 23.5% to 6.7%, vs. 25.6% to 22.1% with placebo (difference of 13.3%, 95% CI 3.5—27.5, p < 0.01). Bronchial reactivity to histamine and hyperventilation also decreased with active drug.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    Maximum dose dependent on indication and specific drug formulation administered.

    Elderly

    Maximum dose dependent on indication and specific drug formulation administered.

    Adolescents

    Maximum dose dependent on indication and specific drug formulation administered.

    Children

    5—11 years: Maximum dose dependent on indication and specific drug formulation administered; oral inhalation doses up to and > 800 mcg/day of the inhalation powder and up to 2 mg of the inhalation suspension have been recommended by the NAEPP.
    1—4 years: Maximum dose dependent on indication and specific drug formulation administered; oral inhalation doses up to and > 1 mg of the inhalation suspension have been recommended by the NAEPP.

    Infants

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available for inhaled budesonide; it appears that no dosage adjustments are needed. For oral budesonide (i.e., Entocort EC), consider a reduced dose of 3 mg once daily in patients with moderate hepatic impairment (Child-Pugh Class B); avoid use in patients with severe hepatic impairment (Child-Pugh Class C). Monitor the patient for signs/symptoms of hypercorticism. Consider drug discontinuation in cases of hypercorticism.

    Renal Impairment

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

    ADMINISTRATION

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

    Oral Administration
    Oral Solid Formulations

    Gastro-resistant Capsules or Extended-release tablets:
    Administer whole; do not chew, break, or crush.
    Administer the total daily dose in the morning, with or without food.
    Do not administer with grapefruit juice; patient should avoid consumption of grapefruit juice for the duration of therapy.

    Inhalation Administration
    Oral Inhalation Administration

    Dry powder for inhalation (Pulmicort Flexhaler):
    NOTE: Most children < 4 years of age may not generate sufficient inspiratory flow to activate dry powder inhalers.
    Instruct patient on proper administration technique.
    A new inhaler should be primed before use, per the priming instructions that come with the device. While priming the inhaler and loading the dose, the inhaler should always be held in an upright position. To load the dose on a primed inhaler, 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 one 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 one time each week with a dry tissue.The inhaler should not be used if it has been damage 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.
     
    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 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 has not been studied.
    The choice of using a mouthpiece versus a face mask must be made based on the skills and understanding of each individual patient.
    Using 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 has not been adequately assessed; administer budesonide inhalation suspension separately in the nebulizer.
    Storage: Store inhalation suspension upright at controlled room temperature and protected from light. When the envelope has been opened, the shelf life of the unused Respules is 2 weeks; return unused Respules to the aluminum foil envelope to protect from light. Any opened Respule should be used promptly.

    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 one person.

    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.

    STORAGE

    Entocort EC:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Pulmicort:
    - After opening the foil pouch, product should be used within 2 weeks
    - After opening the foil pouch, store unused product in the foil pouch to protect it from light
    - Do not freeze
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store upright
    Rhinocort:
    - Do not freeze
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Rhinocort Aqua:
    - Do not freeze
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    UCERIS:
    - Do not refrigerate
    - Protect from direct sunlight
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    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.

    Acute bronchospasm, milk protein hypersensitivity, status asthmaticus

    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. 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. Additionally, budesonide is contraindicated for use in any patient with a known hypersensitivity to budesonide or any ingredient in the formulation. 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.

    Fungal infection, herpes infection, immunosuppression, infection, ocular infection, tuberculosis, viral infection

    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.

    Vaccination

    Corticosteroid therapy, such as with budesonide use, usually does not contraindicate vaccination with live-virus vaccines when such therapy is: short-term (< 2 weeks); low to moderate dose; long-term alternate day treatment with short-acting preparations; maintenance physiologic doses (replacement therapy); or administered topically (skin or eye), by aerosol, or by intra-articular, bursal, or tendon injection. The immunosuppressive effects of steroid treatment differ, but many clinicians consider a dose equivalent to either 2 mg/kg or a total dose equivalent to 20 mg/day of prednisone as sufficiently immunosuppressive to raise concern about the safety of immunization with live-virus vaccines. In general, patients with severe immunosuppression due to large doses of corticosteroids should not receive vaccination with live-virus vaccines. When cancer chemotherapy or immunosuppressive therapy is being considered (e.g., for patients with Hodgkin's disease or organ transplantation), vaccination should precede the initiation of chemotherapy or immunotherapy by >= 2 weeks. Patients vaccinated while on immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated at least 3 months after discontinuation of therapy. In patients who have received high-dose, systemic corticosteroids for >= 2 weeks, it is recommended to wait at least 3 months after discontinuation of therapy before administering a live-virus vaccine.

    Measles, varicella

    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.

    Growth inhibition, infants, neonates

    Many dosage formulations of budesonide have been evaluated for safety and efficacy in children of varying ages, but the efficacy and safety of budesonide are not established for infants or neonates. For nebulizer inhalation (Pulmicort Respules), safety has been studied in infants as young as 6 months of age; however, efficacy has not been established for infants. The safety and efficacy of budesonide aerosol powder for inhalation (Pulmicort Flexhaler) has not been determined for pediatric patients < 6 years of age. Budesonide nasal inhalations (Rhinocort Aqua, Rhinocort Allergy) are safe and effective in children 6 years of age and older. The safety and efficacy of oral budesonide (e.g., Entocort EC, Uceris) in pediatric patients has not been determined. Of particular concern in pediatric patients, budesonide, like other corticosteroids, may interfere with growth patterns, regardless of route of administration. Children and adolescents 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, the lowest effective dose should be used and growth should be routinely monitored during use.

    Pregnancy

    Budesonide inhalation powder (Pulmicort Turbuhaler and Flexhaler), budesonide inhalation solution (Pulmicort Respules), and budesonide nasal inhalation solution (Rhinocort Aqua) are classified as FDA pregnancy risk category B. A review of Swedish registries indicated that in over 2000 births there was no increased risk for congenital malformations during early pregnancy with the inhalation powder or solution. A position statement by the American College of Allergy, Asthma and Immunology notes that budesonide is a good choice for pregnant women requiring high doses of inhaled steroids for effective asthma management. Despite adverse effects in animal studies, fetal harm appears remote. Low-dose inhaled corticosteroids are considered first line therapy for control of mild persistent asthma during pregnancy according to the 2004 guidelines of the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group. 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. Inhaled budesonide (FDA pregnancy category B) is preferred over other inhaled corticosteroids due to availability of more safety information during pregnancy. 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. 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. Oral budesonide products (e.g., Entocort EC, Uceris) are classified as FDA pregnancy risk category C. As with other corticosteroids, these budesonide products 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, 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.

    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. Low-dose inhaled corticosteroids are considered first line therapy for control of mild persistent asthma during pregnancy and lactation according to the 2004 guidelines of the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group. However, due to greater availability of data in pregnancy, budesonide is the preferred agent in this population. The amount of inhaled budesonide excreted in breast-milk is minute, and infant exposure is negligible. Reviewers and an expert panel consider inhaled corticosteroids acceptable to use during breast-feeding. . 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. According to the manufacturer of oral budesonide (e.g., Entocort EC, 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. Budesonide rectal foam (e.g., Uceris Rectal) is likely to result in budesonide in human milk as budesonide delivered by inhalation from a dry powder inhaler is present in human milk at low concentrations. Although the American Academy of Pediatrics (AAP) has not has not evaluated the use of budesonide during breast-feeding, the AAP considers other corticosteroids, such as prednisone, to be usually compatible with lactation. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Abrupt discontinuation, adrenal insufficiency, corticosteroid withdrawal, hypothalamic-pituitary-adrenal (HPA) suppression, increased intracranial pressure

    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 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.

    Gastroenteritis, surgery, trauma

    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.

    Cushing's syndrome, hypercortisolism

    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.

    Nasal septal perforation, nasal surgery, nasal trauma

    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.

    Malnutrition, osteoporosis, tobacco smoking

    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.

    Edema, heart failure, hypertension

    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. Congestive heart failure can occur in susceptible patients.

    Diabetes mellitus, hyperglycemia, hyperthyroidism, hypothyroidism, psychosis, renal disease, seizure disorder, thyroid disease

    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. 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.

    Children, diverticulitis, GI disease, GI perforation, hepatic disease, peptic ulcer disease

    Systemic corticosteroids, including oral budesonide, should be used with caution in patients with GI disease, diverticulitis, intestinal anastomosis (because of the possibility of perforation), or severe hepatic disease. Increased systemic availability of oral budesonide has been demonstrated in children with Crohn's disease and patients with hepatic cirrhosis. 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. Monitor these patients for signs and symptoms of hypercorticism. Consideration of oral budesonide dose reduction is warranted in patients with moderate hepatic impairment (Child-Pugh Class B); avoid use in patients with severe hepatic impairment (Child-Pugh Class C). Corticosteroids should not be used in patients when there is a possibility of impending GI perforation, abscess, or pyogenic infection. Systemic corticosteroids should not be used in patients with peptic ulcer disease except under life-threatening circumstances.

    Cataracts, glaucoma, increased intraocular pressure, visual disturbance

    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.

    Myasthenia gravis

    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.

    Corticosteroid hypersensitivity

    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.

    Geriatric

    There is no special precaution needed for the use of inhaled or nasal budesonide in older adults. Studies have not determined if geriatric patients respond differently to systemic budesonide treatment than younger adults. 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. 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 and parenteral corticosteroids may be required for conditions such as exacerbation of chronic obstructive pulmonary disease (COPD) but should be prescribed in the lowest effective dose and for the shortest possible duration.

    ADVERSE REACTIONS

    Severe

    visual impairment / Early / 0-5.0
    GI obstruction / Delayed / 0-5.0
    gastrointestinal fistula / Delayed / 0-5.0
    bronchospasm / Rapid / 0-2.0
    angioedema / Rapid / 0-1.0
    anaphylactoid reactions / Rapid / 0-1.0
    avascular necrosis / Delayed / 0-1.0
    Churg-Strauss syndrome / Delayed / 0-1.0
    vasculitis / Delayed / 0-1.0
    nasal septum perforation / Delayed / Incidence not known
    ocular hypertension / Delayed / Incidence not known
    skeletal changes / Delayed / Incidence not known
    increased intracranial pressure / Early / Incidence not known
    pancreatitis / Delayed / Incidence not known

    Moderate

    Cushing's syndrome / Delayed / 0-11.0
    candidiasis / Delayed / 0-5.0
    confusion / Early / 0-5.0
    atopic dermatitis / Delayed / 0-5.0
    contact dermatitis / Delayed / 0-5.0
    glossitis / Early / 0-5.0
    constipation / Delayed / 1.0-5.0
    hemorrhoids / Delayed / 0-5.0
    palpitations / Early / 0-5.0
    chest pain (unspecified) / Early / 0-5.0
    sinus tachycardia / Rapid / 0-5.0
    hypertension / Early / 0-5.0
    hypokalemia / Delayed / 1.0-4.9
    dysphonia / Delayed / 1.0-3.0
    migraine / Early / 1.0-3.0
    fluid retention / Delayed / 1.0-3.0
    hypertonia / Delayed / 1.0-3.0
    ocular infection / Delayed / 1.0-2.9
    psychosis / Early / 0-1.0
    depression / Delayed / 0-1.0
    cataracts / Delayed / 0-1.0
    hyperglycemia / Delayed / 0-1.0
    eosinophilia / Delayed / 0-1.0
    pyuria / Delayed / 1.0
    anemia / Delayed / 1.0
    hematuria / Delayed / 1.0
    hypothalamic-pituitary-adrenal (HPA) suppression / Delayed / Incidence not known
    adrenocortical insufficiency / Delayed / Incidence not known
    withdrawal / Early / Incidence not known
    growth inhibition / Delayed / Incidence not known
    osteoporosis / Delayed / Incidence not known
    osteopenia / Delayed / Incidence not known
    edema / Delayed / Incidence not known

    Mild

    headache / Early / 3.0-37.0
    acne vulgaris / Delayed / 0-15.0
    nausea / Early / 1.8-13.0
    rhinitis / Early / 2.1-12.0
    emotional lability / Early / 4.0-10.0
    abdominal pain / Early / 1.0-10.0
    diarrhea / Early / 2.0-10.0
    cough / Delayed / 2.0-9.0
    epistaxis / Delayed / 2.0-8.0
    fatigue / Early / 1.0-8.0
    flatulence / Early / 6.0-8.0
    dizziness / Early / 7.0-7.0
    insomnia / Early / 0-6.0
    dyspepsia / Early / 6.0-6.0
    vomiting / Early / 1.0-6.0
    infection / Delayed / 2.0-5.0
    drowsiness / Early / 0-5.0
    tremor / Early / 0-5.0
    agitation / Early / 0-5.0
    hyperkinesis / Delayed / 0-5.0
    paresthesias / Delayed / 0-5.0
    vertigo / Early / 0-5.0
    diaphoresis / Early / 0-5.0
    alopecia / Delayed / 0-5.0
    purpura / Delayed / 0-5.0
    arthralgia / Delayed / 5.0-5.0
    hirsutism / Delayed / 1.0-5.0
    weight gain / Delayed / 1.0-5.0
    appetite stimulation / Delayed / 0-5.0
    asthenia / Delayed / 0-5.0
    malaise / Early / 0-5.0
    flushing / Rapid / 1.0-4.9
    myalgia / Early / 1.0-4.9
    leukocytosis / Delayed / 1.0-4.9
    rash (unspecified) / Early / 0-4.0
    hoarseness / Early / 1.0-3.0
    ecchymosis / Delayed / 1.0-3.0
    pruritus / Rapid / 1.0-3.0
    xerostomia / Early / 1.0-3.0
    dysgeusia / Early / 1.0-3.0
    syncope / Early / 1.0-3.0
    otalgia / Early / 1.0-2.9
    anorexia / Delayed / 1.0-2.9
    nasal congestion / Early / 2.7-2.7
    nasal irritation / Early / 2.0-2.0
    anxiety / Delayed / 0-1.0
    irritability / Delayed / 0-1.0
    urticaria / Rapid / 0-1.0
    pharyngitis / Delayed / 3.0
    fever / Early / 2.0
    sinusitis / Delayed / 3.0
    back pain / Delayed / 3.0
    throat irritation / Early / Incidence not known
    dysosmia / Delayed / Incidence not known
    maculopapular rash / Early / Incidence not known

    DRUG INTERACTIONS

    Abatacept: 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.
    Acetaminophen; Aspirin, ASA; Caffeine: 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.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: 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.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: 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.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: 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.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: 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.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: 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.
    Acetaminophen; Dextromethorphan; Phenylephrine: 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.
    Acetaminophen; Guaifenesin; Phenylephrine: 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.
    Acetazolamide: 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.
    Acetohexamide: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Albiglutide: When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia and cause blood glucose concentrations to rise. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Aldesleukin, IL-2: 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.
    Alemtuzumab: 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.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: 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.
    Aliskiren; Hydrochlorothiazide, HCTZ: 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.
    Alogliptin: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Alogliptin; Metformin: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. In addition, blood lactate concentrations and the lactate to pyruvate ratio increase when metformin is coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with increased morbidity rates. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted. Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Alogliptin; Pioglitazone: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Alpha-glucosidase Inhibitors: Systemic corticosteroids increase blood glucose levels. Because of this action, a potential pharmacodynamic interaction exists between corticosteroids and acarbose. Patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of acarbose.
    Altretamine: Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
    Aluminum Hydroxide: 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.
    Aluminum Hydroxide; Magnesium Carbonate: 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.
    Aluminum Hydroxide; Magnesium Hydroxide: 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.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: 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.
    Aluminum Hydroxide; Magnesium Trisilicate: 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.
    Ambenonium Chloride: Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
    Amiloride; Hydrochlorothiazide, HCTZ: 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.
    Aminosalicylate sodium, Aminosalicylic acid: 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.
    Amiodarone: 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. Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia including corticosteroids.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: 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.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: 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.
    Amoxicillin; Clarithromycin; Lansoprazole: Clarithromycin 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. 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.
    Amoxicillin; Clarithromycin; Omeprazole: Clarithromycin 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. 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.
    Amphotericin B cholesteryl sulfate complex (ABCD): 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.
    Amphotericin B lipid complex (ABLC): 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.
    Amphotericin B liposomal (LAmB): 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.
    Amphotericin B: 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.
    Antacids: 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.
    Anthracyclines: 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. Also, dexamethasone is a CYP3A4 inducer and doxorubicin is a major substrate of CYP3A4. However, these drugs are commonly used together in treatment
    Antithymocyte Globulin: 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.
    Antitumor antibiotics: 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.
    Aprepitant, Fosaprepitant: 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.
    Argatroban: 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.
    Arsenic Trioxide: Because electrolyte abnormalities increase the risk of QT interval prolongation and serious arrhythmias, avoid the concomitant use of arsenic trioxide with drugs that may cause electrolyte abnormalities, particularly hypokalemia and hypomagnesemia. Examples of drugs that may cause electrolyte abnormalities include corticosteroids. If concomitant drug use is unavoidable, frequently monitor serum electrolytes (and replace as necessary) and electrocardiograms.
    Asparaginase Erwinia chrysanthemi: 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.
    Aspirin, ASA: 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.
    Aspirin, ASA; Butalbital; Caffeine: 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.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: 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.
    Aspirin, ASA; Caffeine; Dihydrocodeine: 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.
    Aspirin, ASA; Carisoprodol: 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.
    Aspirin, ASA; Carisoprodol; Codeine: 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.
    Aspirin, ASA; Dipyridamole: 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.
    Aspirin, ASA; Omeprazole: 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. 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.
    Aspirin, ASA; Oxycodone: 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.
    Aspirin, ASA; Pravastatin: 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.
    Atazanavir: Due to atazanavir-induced inhibition of CYP3A4 isoenzymes, atazanavir may inhibit the metabolism and thus, increase the serum concentrations of drugs that are largely metabolized via CYP3A4, including budesonide.
    Atazanavir; Cobicistat: Due to atazanavir-induced inhibition of CYP3A4 isoenzymes, atazanavir may inhibit the metabolism and thus, increase the serum concentrations of drugs that are largely metabolized via CYP3A4, including budesonide. Plasma concentrations of orally administered budesonide may increase during coadministration with CYP3A4 and p-glycoprotein (P-gp) inhibitors such as cobicistat. A budesonide dose reduction should be considered. Toxicity may occur, particularly excessive HPA-axis suppression. Theoretically, inhibition of CYP3A4 may also be clinically significant for inhaled forms of budesonide, including budesonide nasal spray.
    Atenolol; Chlorthalidone: 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.
    Atracurium: Corticosteroids cause hypokalemia, which potentiates neuromuscular blockade with nondepolarizing neuromuscular blockers.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: 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.
    Azacitidine: 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.
    Azathioprine: 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.
    Azilsartan; Chlorthalidone: 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.
    Azithromycin: Both budesonide and azithromycin are P-glycoprotein (PGP) inhibitors and substrates, so coadministration may lead to increased concentrations of either agent. Monitor patients for increased side effects if these drugs are given together.
    Bacillus Calmette-Guerin Vaccine, BCG: Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system. Children who are receiving high doses of systemic corticosteroids (i.e., greater than or equal to 2 mg/kg prednisone orally per day) for 2 weeks or more may be vaccinated after steroid therapy has been discontinued for at least 3 months in accordance with general recommendations for the use of live-virus vaccines. The CDC has stated that discontinuation of steroids for 1 month prior to varicella virus vaccine live administration may be sufficient. Budesonide may affect the immunogenicity of live vaccines. An open-label study examined the immune responsiveness to varicella vaccine in 243 pediatric asthma patients who were treated with budesonide inhalation suspension 0.251 mg daily (n = 151) or non-corticosteroid asthma therapy (n = 92). The percentage of patients developing a seroprotective antibody titer of at least 5 (gpELISA value) in response to the vaccination was slightly lower in patients treated with budesonide compared to patients treated with non-corticosteroid asthma therapy (85% vs. 90%). Even though no patient treated with budesonide inhalation suspension developed chicken pox because of vaccination, live-virus vaccines should not be given to individuals who are considered to be immunocompromised until more information is available.
    Barbiturates: The effects of corticosteroids can be decreased during concomitant treatment with barbiturates. Barbiturates have been shown to affect the clinical response to prednisone in asthmatics and to affect the pharmacokinetics of dexamethasone, methylprednisolone, and prednisolone. It is likely that barbiturates affect all corticosteroids similarly. Dose adjustments may be necessary.
    Basiliximab: 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.
    Benazepril; Hydrochlorothiazide, HCTZ: 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.
    Bendroflumethiazide; Nadolol: 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.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: 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.
    Bepridil: Hypokalemia-producing agents, including corticosteroids, may increase the risk of bepridil-induced arrhythmias and should therefore be administered cautiously in patients receiving bepridil therapy.
    Bevacizumab: 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.
    Bexarotene: 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.
    Bismuth Subsalicylate: 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.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: 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.
    Bisoprolol; Hydrochlorothiazide, HCTZ: 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.
    Boceprevir: 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, re-adjust 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.
    Bortezomib: 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.
    Bosentan: Hepatic microsomal enzyme inducers, including bosentan, can increase the metabolism of glucocorticoids. Dosages of systemic betamethasone may require adjustment if bosentan is initiated or withdrawn during corticosteroid therapy.
    Brompheniramine; Carbetapentane; Phenylephrine: 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.
    Bupropion: 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. The manufacturer recommends low initial dosing and slow dosage titration if these combinations must be used; the patient should be closely monitored.
    Bupropion; Naltrexone: 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. The manufacturer recommends low initial dosing and slow dosage titration if these combinations must be used; the patient should be closely monitored.
    Cabozantinib: Monitor for an increase in budesonide-related adverse events if concomitant use with cabozantinib is necessary, as plasma concentrations of budesonide may be increased. Cabozantinib is a P-glycoprotein (P-gp) inhibitor and budesonide is a substrate of P-gp; the clinical relevance of this finding is unknown.
    Calcium Carbonate: 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.
    Calcium Carbonate; Magnesium Hydroxide: 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. 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.
    Calcium Carbonate; Risedronate: 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.
    Calcium; Vitamin D: 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.
    Canagliflozin: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Canagliflozin; Metformin: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. In addition, blood lactate concentrations and the lactate to pyruvate ratio increase when metformin is coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with increased morbidity rates. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted. Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Candesartan; Hydrochlorothiazide, HCTZ: 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.
    Capecitabine: 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.
    Captopril; Hydrochlorothiazide, HCTZ: 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.
    Carbamazepine: Hepatic microsomal enzyme inducers, including carbamazepine, can increase the metabolism of corticosteroids. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with corticosteroids.
    Carbetapentane; Chlorpheniramine; Phenylephrine: 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.
    Carbetapentane; Diphenhydramine; Phenylephrine: 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.
    Carbetapentane; Guaifenesin; Phenylephrine: 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.
    Carbetapentane; Phenylephrine: 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.
    Carbetapentane; Phenylephrine; Pyrilamine: 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.
    Carbinoxamine; Hydrocodone; Phenylephrine: 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.
    Carbinoxamine; Phenylephrine: 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.
    Carmustine, BCNU: 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.
    Carvedilol: 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.
    Chlophedianol; Guaifenesin; Phenylephrine: 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.
    Chlorambucil: 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.
    Chlorothiazide: 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.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: 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.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: 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.
    Chlorpheniramine; Hydrocodone; Phenylephrine: 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.
    Chlorpheniramine; Phenylephrine: 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.
    Chlorpropamide: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Chlorthalidone: 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.
    Chlorthalidone; Clonidine: 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.
    Choline Salicylate; Magnesium Salicylate: 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.
    Cimetidine: 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. In general, it may be prudent to avoid drugs such as H2-blockers in combination with oral budesonide. 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.
    Ciprofloxacin: 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.
    Cisatracurium: Corticosteroids cause hypokalemia, which potentiates neuromuscular blockade with nondepolarizing neuromuscular blockers.
    Citalopram: Citalopram causes dose-dependent QT interval prolongation. Concurrent use of citalopram and medications known to cause electrolyte imbalance may increase the risk of developing QT prolongation. Therefore, caution is advisable during concurrent use of citalopram and corticosteroids. It should be noted that CYP3A4 is one of the isoenzymes involved in the metabolism of citalopram, and dexamethasone is an inducer of this isoenzyme. In theory, decreased efficacy of citalopram is possible during combined use with dexamethasone; however, because citalopram is metabolized by multiple enzyme systems, induction of one pathway may not appreciably increase citalopram clearance.
    Clarithromycin: Clarithromycin 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.
    Clofarabine: 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.
    Cobicistat: Plasma concentrations of orally administered budesonide may increase during coadministration with CYP3A4 and p-glycoprotein (P-gp) inhibitors such as cobicistat. A budesonide dose reduction should be considered. Toxicity may occur, particularly excessive HPA-axis suppression. Theoretically, inhibition of CYP3A4 may also be clinically significant for inhaled forms of budesonide, including budesonide nasal spray.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: Plasma concentrations of orally administered budesonide may increase during coadministration with CYP3A4 and p-glycoprotein (P-gp) inhibitors such as cobicistat. A budesonide dose reduction should be considered. Toxicity may occur, particularly excessive HPA-axis suppression. Theoretically, inhibition of CYP3A4 may also be clinically significant for inhaled forms of budesonide, including budesonide nasal spray.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: Plasma concentrations of orally administered budesonide may increase during coadministration with CYP3A4 and p-glycoprotein (P-gp) inhibitors such as cobicistat. A budesonide dose reduction should be considered. Toxicity may occur, particularly excessive HPA-axis suppression. Theoretically, inhibition of CYP3A4 may also be clinically significant for inhaled forms of budesonide, including budesonide nasal spray.
    Cod Liver Oil: A relationship of functional antagonism exists between vitamin D analogs, which promote calcium absorption, and corticosteroids, which inhibit calcium absorption. Therapeutic effect of cod liver oil should be monitored when used concomitantly with corticosteroids.
    Codeine; Phenylephrine; Promethazine: 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.
    Conivaptan: Coadministration of conivaptan, a CYP3A4 and P-glycoprotein (P-gp) inhibitor with budesonide, a CYP3A and P-gp substrate, can increase budesonide exposure leading to increased or prolonged therapeutic effects and adverse events. According to the manufacturer of conivaptan, concomitant use of conivaptan and CYP3A substrates should be avoided. Treatment with budesonide may be initiated no sooner than 1 week after completion of conivaptan therapy. Theoretically, inhibition of CYP3A4 may also be clinically significant for inhaled forms of budesonide, including budesonide nasal spray. In addition, conivaptan has been associated with hypokalemia (9.8%). Although not studied, consider the potential for additive hypokalemic effects if conivaptan is coadministered with drugs known to induce hypokalemia, such as corticosteroids.
    Crizotinib: Concomitant use of crizotinib and budesonide may result in increased concentrations of both agents. Crizotinib is a CYP3A4 and P-glycoprotein (PGP) substrate/inhibitor, while budesonide is a CYP3A4 substrate and PGP substrate/inhibitor. Monitor patients for toxicity with coadministration.
    Cyclosporine: 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 like cyclosporine. While therapy is designed to take advantage of this effect, patients may be predisposed to over-immunosuppression resulting in an increased risk for the development of severe infections. In addition, increased activity of both cyclosporine and corticosteroids may occur when the two are used concurrently.
    Cytarabine, ARA-C: 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.
    Daclatasvir: 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.
    Danazol: Danazol may increase plasma concentrations of oral budesonide due to inhibition of the CYP3A4 isoenzyme, and can enhance the cortisol suppression associated with budesonide administered via inhalation. Use caution when budesonide is coadministered with drugs that inhibit CYP3A enzymes and consider dose reduction. Toxicity may occur, particularly excessive HPA-axis suppression.
    Dapagliflozin: Systemic corticosteroids increase blood glucose levels; a potential pharmacodynamic interaction exists between corticosteroids and all antidiabetic agents. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent. Blood lactate concentrations and the lactate to pyruvate ratio increased when metformin was coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with an increased risk of lactic acidosis, so patients on metformin concurrently with systemic steroids should be monitored closely.
    Dapagliflozin; Metformin: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. In addition, blood lactate concentrations and the lactate to pyruvate ratio increase when metformin is coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with increased morbidity rates. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted. Systemic corticosteroids increase blood glucose levels; a potential pharmacodynamic interaction exists between corticosteroids and all antidiabetic agents. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent. Blood lactate concentrations and the lactate to pyruvate ratio increased when metformin was coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with an increased risk of lactic acidosis, so patients on metformin concurrently with systemic steroids should be monitored closely.
    Darunavir: The plasma concentrations of budesonide may be elevated when administered concurrently with darunavir. An alternative corticosteroid should be considered, particularly for long-term use. If these drugs are coadministered, clinical monitoring for adverse effects, such as corticosteroid-related side effects, is recommended. Darunavir is a CYP3A4 and P-glycoprotein (P-gp) inhibitor, while budesonide is a CYP3A4 and P-gp substrate.
    Darunavir; Cobicistat: The plasma concentrations of budesonide may be elevated when administered concurrently with darunavir. An alternative corticosteroid should be considered, particularly for long-term use. If these drugs are coadministered, clinical monitoring for adverse effects, such as corticosteroid-related side effects, is recommended. Darunavir is a CYP3A4 and P-glycoprotein (P-gp) inhibitor, while budesonide is a CYP3A4 and P-gp substrate. Plasma concentrations of orally administered budesonide may increase during coadministration with CYP3A4 and p-glycoprotein (P-gp) inhibitors such as cobicistat. A budesonide dose reduction should be considered. Toxicity may occur, particularly excessive HPA-axis suppression. Theoretically, inhibition of CYP3A4 may also be clinically significant for inhaled forms of budesonide, including budesonide nasal spray.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: Via inhibition of CYP3A4, ritonavir significantly increases plasma concentrations of budesonide, resulting in significantly reduced serum cortisol concentrations. During post-marketing use, there have been reports of clinically significant drug interactions in patients receiving budesonide with ritonavir, resulting in systemic corticosteroid effects including Cushing's syndrome and adrenal suppression. Therefore, coadministration of budesonide and ritonavir (or ritonavir-containing products or treatment regimens) is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects.
    Decitabine: 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.
    Deferasirox: 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.
    Delavirdine: Delavirdine may increase plasma concentrations of oral budesonide due to inhibition of the CYP3A4 isoenzyme and can enhance the cortisol suppression associated with budesonide administered via inhalation. Use caution when budesonide is coadministered with drugs that inhibit CYP3A enzymes, such as delavirdine, and consider dose reduction. Toxicity may occur, particularly excessive HPA-axis suppression.
    Denileukin Diftitox: 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.
    Denosumab: 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.
    Dexamethasone: 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.
    Dexlansoprazole: 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.
    Dextran: 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.
    Dextromethorphan; Diphenhydramine; Phenylephrine: 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.
    Dextromethorphan; Guaifenesin; Phenylephrine: 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.
    Dextromethorphan; Quinidine: Plasma concentrations of orally administered budesonide may increase during coadministration with CYP3A4 inhibitors, such as quinidine; a budesonide dose reduction should be considered. Toxicity may occur, particularly excessive HPA-axis suppression. Theoretically, inhibition of CYP3A4 may be clinically significant for inhaled forms of budesonide, including budesonide nasal spray.
    Digoxin: 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.
    Diltiazem: 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.
    Diphenhydramine; Hydrocodone; Phenylephrine: 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.
    Diphenhydramine; Phenylephrine: 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.
    Dofetilide: 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.
    Doxacurium: Corticosteroids cause hypokalemia, which potentiates neuromuscular blockade with nondepolarizing neuromuscular blockers.
    Dronedarone: 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.
    Droperidol: 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.
    Dulaglutide: When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia and cause blood glucose concentrations to rise. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Echinacea: The pharmacologic actions of echinacea could potentially result in pharmacodynamic interactions with drugs that alter immune system activity. The German Commission E considers the use of echinacea contraindicated for use in patients undergoing treatments for severe, chronic progressive disease. Avoid the use of echinacea in patients who are taking corticosteroids.
    Econazole: 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.
    Efalizumab: Patients receiving immunosuppressives should not receive concurrent therapy with efalizumab because of the possibility of increased infections and malignancies.
    Elbasvir; Grazoprevir: 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.
    Eliglustat: 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.
    Empagliflozin: Systemic corticosteroids increase blood glucose levels. Because of this action, a potential pharmacodynamic interaction exists between corticosteroids and all antidiabetic agents. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Empagliflozin; Linagliptin: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents, such as linagliptin, should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted. Systemic corticosteroids increase blood glucose levels. Because of this action, a potential pharmacodynamic interaction exists between corticosteroids and all antidiabetic agents. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Empagliflozin; Metformin: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. In addition, blood lactate concentrations and the lactate to pyruvate ratio increase when metformin is coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with increased morbidity rates. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted. Systemic corticosteroids increase blood glucose levels. Because of this action, a potential pharmacodynamic interaction exists between corticosteroids and all antidiabetic agents. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Enalapril; Hydrochlorothiazide, HCTZ: 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.
    Ephedrine: Ephedrine may enhance the metabolic clearance of corticosteroids. Decreased blood concentrations and lessened physiologic activity may necessitate an increase in corticosteroid dosage.
    Eprosartan; Hydrochlorothiazide, HCTZ: 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.
    Erythromycin: Erythromycin may increase plasma concentrations of oral budesonide due to inhibition of the CYP3A4, and can enhance the cortisol suppression associated with budesonide administered via inhalation. Use caution when budesonide is coadministered with drugs that inhibit CYP3A enzymes and consider dose reduction.
    Erythromycin; Sulfisoxazole: Erythromycin may increase plasma concentrations of oral budesonide due to inhibition of the CYP3A4, and can enhance the cortisol suppression associated with budesonide administered via inhalation. Use caution when budesonide is coadministered with drugs that inhibit CYP3A enzymes and consider dose reduction.
    Esomeprazole: 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.
    Esomeprazole; Naproxen: 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.
    Estramustine: 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.
    Estrogens: 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.
    Etravirine: 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.
    Exenatide: When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia and cause blood glucose concentrations to rise. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Famotidine: 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. In general, it may be prudent to avoid drugs such as H2-blockers in combination with oral budesonide.
    Famotidine; Ibuprofen: 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. In general, it may be prudent to avoid drugs such as H2-blockers in combination with oral budesonide.
    Floxuridine: 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.
    Fluconazole: 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. Use caution when budesonide is coadministered with drugs that inhibit CYP3A enzymes, such as fluconazole, and consider dose reduction. Toxicity may occur, particularly excessive HPA-axis suppression. Inhibition of CYP3A4 may be clinically significant for inhaled forms of budesonide as well.
    Fluorouracil, 5-FU: 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.
    Fluoxetine: Use caution when budesonide is coadministered with drugs that inhibit CYP3A enzymes, such as fluoxetine, and consider dose reduction. Toxicity may occur, particularly excessive HPA-axis suppression. Inhibition of CYP3A4 may be clinically significant for inhaled forms of budesonide as well.
    Fluoxetine; Olanzapine: Use caution when budesonide is coadministered with drugs that inhibit CYP3A enzymes, such as fluoxetine, and consider dose reduction. Toxicity may occur, particularly excessive HPA-axis suppression. Inhibition of CYP3A4 may be clinically significant for inhaled forms of budesonide as well.
    Fluoxymesterone: 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.
    Fluvoxamine: Fluvoxamine may increase plasma concentrations of oral budesonide due to inhibition of the CYP3A4 isoenzyme. Use caution when budesonide is coadministered with drugs that inhibit CYP3A enzymes and consider dose reduction. Toxicity may occur, particularly excessive HPA-axis suppression.
    Fosamprenavir: 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.
    Fosinopril; Hydrochlorothiazide, HCTZ: 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.
    Gallium Ga 68 Dotatate: 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.
    Gemcitabine: 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.
    Gemifloxacin: 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.
    Gemtuzumab Ozogamicin: 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.
    Gentamicin: 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.
    Glimepiride: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Glimepiride; Pioglitazone: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Glimepiride; Rosiglitazone: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Glipizide: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Glipizide; Metformin: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. In addition, blood lactate concentrations and the lactate to pyruvate ratio increase when metformin is coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with increased morbidity rates. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted. Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Glyburide: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Glyburide; Metformin: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. In addition, blood lactate concentrations and the lactate to pyruvate ratio increase when metformin is coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with increased morbidity rates. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted. Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Glycerol Phenylbutyrate: Corticosteroids may induce elevated blood ammonia concentrations. Corticosteroids should be used with caution in patients receiving glycerol phenylbutyrate. Monitor ammonia concentrations closely.
    Grapefruit juice: 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.
    Griseofulvin: Theoretically, induction of the cytochrome P450 3A4 isoenzyme by griseofulvin may result in a lowering of budesonide plasma concentrations, reducing the clinical effect.
    Guaifenesin; Phenylephrine: 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.
    H2-blockers: 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. In general, it may be prudent to avoid drugs such as H2-blockers in combination with oral budesonide.
    Halofantrine: 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.
    Haloperidol: QT prolongation has been observed during haloperidol treatment. Use of haloperidol and medications known to cause electrolyte imbalance may increase the risk of QT prolongation. Therefore, caution is advisable during concurrent use of haloperidol and corticosteroids. Topical corticosteroids are less likely to interact.
    Hemin: Hemin works by inhibiting aminolevulinic acid synthetase. Corticosteroids increase the activity of this enzyme should not be used with hemin.
    Heparin: 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.
    Hetastarch: 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.
    Hydantoins: Hydantoin anticonvulsants induce hepatic microsomal enzymes and may increase the metabolism of other drugs, leading to reduced efficacy of the concomitant medication. Medications that may be affected include the corticosteroids. Depending on the individual clinical situation and the indication for the interacting medication, enzyme-induction interactions may not always produce reductions in treatment efficacy.
    Hydralazine; Hydrochlorothiazide, HCTZ: 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.
    Hydrochlorothiazide, HCTZ: 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.
    Hydrochlorothiazide, HCTZ; Irbesartan: 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.
    Hydrochlorothiazide, HCTZ; Lisinopril: 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.
    Hydrochlorothiazide, HCTZ; Losartan: 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.
    Hydrochlorothiazide, HCTZ; Methyldopa: 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.
    Hydrochlorothiazide, HCTZ; Metoprolol: 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.
    Hydrochlorothiazide, HCTZ; Moexipril: 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.
    Hydrochlorothiazide, HCTZ; Olmesartan: 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.
    Hydrochlorothiazide, HCTZ; Propranolol: 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. 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.
    Hydrochlorothiazide, HCTZ; Quinapril: 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.
    Hydrochlorothiazide, HCTZ; Spironolactone: 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.
    Hydrochlorothiazide, HCTZ; Telmisartan: 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.
    Hydrochlorothiazide, HCTZ; Triamterene: 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.
    Hydrochlorothiazide, HCTZ; Valsartan: 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.
    Hydrocodone; Phenylephrine: 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.
    Hydroxyurea: 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.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: 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. Use potassium phosphate; sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
    Ibritumomab Tiuxetan: 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. Use potassium phosphate; sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia. 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.
    Ibuprofen lysine: Increased adverse gastrointestinal effects are possible if ibuprofen lysine is used with corticosteroids. 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.
    Idelalisib: 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.
    Ifosfamide: 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.
    Incretin Mimetics: When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia and cause blood glucose concentrations to rise. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Indapamide: 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.
    Indinavir: 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.
    Insulin Degludec; Liraglutide: When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia and cause blood glucose concentrations to rise. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Insulins: Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Endogenous counter-regulatory hormones are released in response to hypoglycemia. When released, blood glucose concentrations rise. When these hormones or their derivatives (e.g., corticosteroids) are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of insulin.
    Interferon Alfa-2a: 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.
    Interferon Alfa-2b: 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.
    Interferon Alfa-2b; Ribavirin: 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.
    Intranasal Influenza Vaccine: Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system. Children who are receiving high doses of systemic corticosteroids (i.e., greater than or equal to 2 mg/kg prednisone orally per day) for 2 weeks or more may be vaccinated after steroid therapy has been discontinued for at least 3 months in accordance with general recommendations for the use of live-virus vaccines. The CDC has stated that discontinuation of steroids for 1 month prior to varicella virus vaccine live administration may be sufficient. Budesonide may affect the immunogenicity of live vaccines. An open-label study examined the immune responsiveness to varicella vaccine in 243 pediatric asthma patients who were treated with budesonide inhalation suspension 0.251 mg daily (n = 151) or non-corticosteroid asthma therapy (n = 92). The percentage of patients developing a seroprotective antibody titer of at least 5 (gpELISA value) in response to the vaccination was slightly lower in patients treated with budesonide compared to patients treated with non-corticosteroid asthma therapy (85% vs. 90%). Even though no patient treated with budesonide inhalation suspension developed chicken pox because of vaccination, live-virus vaccines should not be given to individuals who are considered to be immunocompromised until more information is available.
    Isavuconazonium: 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.
    Isoniazid, INH: Isoniazid inhibits the metabolism of CYP3A4, and therefore may inhibit the hepatic metabolism of certain corticosteroids including budesonide.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: Isoniazid inhibits the metabolism of CYP3A4, and therefore may inhibit the hepatic metabolism of certain corticosteroids including budesonide.
    Isoniazid, INH; Rifampin: Isoniazid inhibits the metabolism of CYP3A4, and therefore may inhibit the hepatic metabolism of certain corticosteroids including budesonide.
    Isoproterenol: 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.
    Isotretinoin: Both isotretinoin and corticosteroids can cause osteoporosis during chronic use. Patients receiving systemic corticosteroids should receive isotretinoin therapy with caution.
    Itraconazole: Due to itraconazole-induced inhibition of cytochrome P450 3A4, interactions are possible with agents that are substrates of this enzyme including budesonide.
    Ivacaftor: 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.
    Ixabepilone: Ixabepilone is a weak inhibitor of P-glycoprotein (Pgp). 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.
    Japanese Encephalitis Virus Vaccine: Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system. Children who are receiving high doses of systemic corticosteroids (i.e., greater than or equal to 2 mg/kg prednisone orally per day) for 2 weeks or more may be vaccinated after steroid therapy has been discontinued for at least 3 months in accordance with general recommendations for the use of live-virus vaccines. The CDC has stated that discontinuation of steroids for 1 month prior to varicella virus vaccine live administration may be sufficient. Budesonide may affect the immunogenicity of live vaccines. An open-label study examined the immune responsiveness to varicella vaccine in 243 pediatric asthma patients who were treated with budesonide inhalation suspension 0.251 mg daily (n = 151) or non-corticosteroid asthma therapy (n = 92). The percentage of patients developing a seroprotective antibody titer of at least 5 (gpELISA value) in response to the vaccination was slightly lower in patients treated with budesonide compared to patients treated with non-corticosteroid asthma therapy (85% vs. 90%). Even though no patient treated with budesonide inhalation suspension developed chicken pox because of vaccination, live-virus vaccines should not be given to individuals who are considered to be immunocompromised until more information is available.
    Ketoconazole: Ketoconazole can decrease the hepatic clearance of corticosteroids, resulting in increased plasma concentrations. The interaction may be due to the inhibition of cytochrome P-450 3A4 isoenzyme by ketoconazole, and subsequent decreases in corticosteroid metabolism by the same isoenzyme. Prednisone is metabolized by the liver to the active metabolite prednisolone. Prednisolone is formed through the 11b-hydroxydehydrogenase enzyme, which is not part of the CYP system, but prednisolone is metabolized by the CYP3A4-mediated 6b-hydroxylase enzyme to inactive compounds. Prednisolone and prednisone pharmacokinetics appear less susceptible than methylprednisolone to CYP3A4 inhibitory interactions. Ketoconazole also can enhance the adrenal suppressive effects of corticosteroids. 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. Inhaled ciclesonide and its active metabolite des-ciclesonide may be similarly affected. In a drug interaction study, orally inhaled ciclesonide coadministered with oral ketoconazole increased the AUC of des-ciclesonide by approximately 3.6-fold at steady state, while levels of ciclesonide remained unchanged.
    Lansoprazole: 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.
    Lansoprazole; Naproxen: 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.
    L-Asparaginase Escherichia coli: 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.
    Ledipasvir; Sofosbuvir: 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.
    Levetiracetam: 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.
    Levofloxacin: 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.
    Levomethadyl: Caution is advised when using levomethadyl in combination with other agents, such as corticosteroids, that may lead to electrolyte abnormalities, especially hypokalemia or hypomagnesemia.
    Linagliptin: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents, such as linagliptin, should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Linagliptin; Metformin: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. In addition, blood lactate concentrations and the lactate to pyruvate ratio increase when metformin is coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with increased morbidity rates. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted. Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents, such as linagliptin, should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Liraglutide: When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia and cause blood glucose concentrations to rise. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Lisdexamfetamine: The amphetamines may interfere with laboratory tests for the determination of corticosteroids. Plasma cortisol concentrations may be increased, especially during evening hours. Amphetamines may also interfere with urinary steroid determinations.
    Live Vaccines: Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system. Children who are receiving high doses of systemic corticosteroids (i.e., greater than or equal to 2 mg/kg prednisone orally per day) for 2 weeks or more may be vaccinated after steroid therapy has been discontinued for at least 3 months in accordance with general recommendations for the use of live-virus vaccines. The CDC has stated that discontinuation of steroids for 1 month prior to varicella virus vaccine live administration may be sufficient. Budesonide may affect the immunogenicity of live vaccines. An open-label study examined the immune responsiveness to varicella vaccine in 243 pediatric asthma patients who were treated with budesonide inhalation suspension 0.251 mg daily (n = 151) or non-corticosteroid asthma therapy (n = 92). The percentage of patients developing a seroprotective antibody titer of at least 5 (gpELISA value) in response to the vaccination was slightly lower in patients treated with budesonide compared to patients treated with non-corticosteroid asthma therapy (85% vs. 90%). Even though no patient treated with budesonide inhalation suspension developed chicken pox because of vaccination, live-virus vaccines should not be given to individuals who are considered to be immunocompromised until more information is available.
    Lomustine, CCNU: 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.
    Loop diuretics: 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.
    Lopinavir; Ritonavir: Decreased lopinavir plasma concentrations have been observed when systemic budesonide and lopinavir; ritonavir are coadministered, increasing the risk for HIV treatment failure. Additionally, inhibition of CYP3A4 by lopinavir; ritonavir increases plasma exposure of budesonide, resulting in significantly reduced serum cortisol concentrations. During post-marketing use, there have been reports of clinically significant drug interactions in patients receiving inhaled or intranasally administered budesonide with ritonavir, resulting in systemic corticosteroid effects including Cushing syndrome and adrenal suppression. Therefore, coadministration of budesonide (or budesonide-containing products) and ritonavir (or ritonavir-containing products or treatment regimens) is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects. If concurrent use if required, caution and carefully monitor of HIV treatment status and adverse effects are recommended. Via inhibition of CYP3A4, ritonavir significantly increases plasma concentrations of budesonide, resulting in significantly reduced serum cortisol concentrations. During post-marketing use, there have been reports of clinically significant drug interactions in patients receiving budesonide with ritonavir, resulting in systemic corticosteroid effects including Cushing's syndrome and adrenal suppression. Therefore, coadministration of budesonide and ritonavir (or ritonavir-containing products or treatment regimens) is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects.
    Luliconazole: Theoretically, luliconazole may increase the side effects of budesonide, which is a CYP3A4 substrate. Monitor patients for adverse effects of budesonide, such as excessive HPA-axis suppression. In vitro, therapeutic doses of luliconazole inhibit the activity of CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole.
    Lumacaftor; Ivacaftor: 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.
    Lumacaftor; Ivacaftor: 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.
    Magnesium Hydroxide: 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.
    Magnesium Salicylate: 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.
    Mannitol: 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.
    Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system. Children who are receiving high doses of systemic corticosteroids (i.e., greater than or equal to 2 mg/kg prednisone orally per day) for 2 weeks or more may be vaccinated after steroid therapy has been discontinued for at least 3 months in accordance with general recommendations for the use of live-virus vaccines. The CDC has stated that discontinuation of steroids for 1 month prior to varicella virus vaccine live administration may be sufficient. Budesonide may affect the immunogenicity of live vaccines. An open-label study examined the immune responsiveness to varicella vaccine in 243 pediatric asthma patients who were treated with budesonide inhalation suspension 0.251 mg daily (n = 151) or non-corticosteroid asthma therapy (n = 92). The percentage of patients developing a seroprotective antibody titer of at least 5 (gpELISA value) in response to the vaccination was slightly lower in patients treated with budesonide compared to patients treated with non-corticosteroid asthma therapy (85% vs. 90%). Even though no patient treated with budesonide inhalation suspension developed chicken pox because of vaccination, live-virus vaccines should not be given to individuals who are considered to be immunocompromised until more information is available.
    Measles/Mumps/Rubella Vaccines, MMR: Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system. Children who are receiving high doses of systemic corticosteroids (i.e., greater than or equal to 2 mg/kg prednisone orally per day) for 2 weeks or more may be vaccinated after steroid therapy has been discontinued for at least 3 months in accordance with general recommendations for the use of live-virus vaccines. The CDC has stated that discontinuation of steroids for 1 month prior to varicella virus vaccine live administration may be sufficient. Budesonide may affect the immunogenicity of live vaccines. An open-label study examined the immune responsiveness to varicella vaccine in 243 pediatric asthma patients who were treated with budesonide inhalation suspension 0.251 mg daily (n = 151) or non-corticosteroid asthma therapy (n = 92). The percentage of patients developing a seroprotective antibody titer of at least 5 (gpELISA value) in response to the vaccination was slightly lower in patients treated with budesonide compared to patients treated with non-corticosteroid asthma therapy (85% vs. 90%). Even though no patient treated with budesonide inhalation suspension developed chicken pox because of vaccination, live-virus vaccines should not be given to individuals who are considered to be immunocompromised until more information is available.
    Mecasermin rinfabate: 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.
    Mecasermin, Recombinant, rh-IGF-1: 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.
    Meglitinides: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Melphalan: 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.
    Mepenzolate: 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.
    Metformin: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. In addition, blood lactate concentrations and the lactate to pyruvate ratio increase when metformin is coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with increased morbidity rates. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Metformin; Pioglitazone: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. In addition, blood lactate concentrations and the lactate to pyruvate ratio increase when metformin is coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with increased morbidity rates. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Metformin; Repaglinide: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent. Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. In addition, blood lactate concentrations and the lactate to pyruvate ratio increase when metformin is coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with increased morbidity rates. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Metformin; Rosiglitazone: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. In addition, blood lactate concentrations and the lactate to pyruvate ratio increase when metformin is coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with increased morbidity rates. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Metformin; Saxagliptin: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. In addition, blood lactate concentrations and the lactate to pyruvate ratio increase when metformin is coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with increased morbidity rates. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted. Systemic corticosteroids increase blood glucose levels. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Metformin; Sitagliptin: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. In addition, blood lactate concentrations and the lactate to pyruvate ratio increase when metformin is coadministered with corticosteroids (e.g., hydrocortisone). Elevated lactic acid concentrations are associated with increased morbidity rates. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted. Systemic corticosteroids increase blood glucose levels. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Methazolamide: 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.
    Methenamine; Sodium Acid Phosphate: Use potassium phosphate; sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: Use potassium phosphate; sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
    Methotrexate: 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.
    Methoxsalen: 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.
    Methyclothiazide: 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.
    Metolazone: 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.
    Metyrapone: 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 topical or inhaled corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Micafungin: 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.
    Mifepristone, RU-486: Mifepristone, RU-486 (Mifeprex) and Mifepristone (Korlym) both exhibit antiglucocorticoid activity that may antagonize corticosteroids. In rats, the activity of dexamethasone was inhibited by oral mifepristone doses of 10 to 25 mg/kg. A mifepristone dose of 4.5 mg/kg in humans resulted in compensatory increases in ACTH and cortisol. Mifepristone (Mifeprex) is contraindicated in patients on long-term corticosteroid therapy and Korlym is contraindicated in patients who require concomitant treatment with systemic corticosteroids for serious medical conditions or illnesses (e.g., immunosuppression after organ transplantation).
    Mitotane: 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.
    Mitoxantrone: 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.
    Mivacurium: Corticosteroids cause hypokalemia, which potentiates neuromuscular blockade with nondepolarizing neuromuscular blockers.
    Modafinil: Theoretically, induction of the cytochrome P450 3A4 isoenzyme by modafinil may result in a lowering of budesonide plasma concentrations, reducing the clinical effect.
    Moxifloxacin: 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. 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.
    Muromonab-CD3: 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. While therapy is designed to take advantage of this effect, patients may be predisposed to over-immunosuppression resulting in an increased risk for the development of severe infections. Close clinical monitoring is advised with concurrent use; in the presence of serious infections, continuation of the corticosteroid or immunosuppressive agent may be necessary but should be accompanied by appropriate antimicrobial therapies as indicated.
    Nafcillin: Theoretically, induction of the cytochrome P450 3A4 isoenzyme, such as nafcillin, may result in a lowering of budesonide plasma concentrations, reducing the clinical effect.
    Natalizumab: The concomitant use of natalizumab and immunosuppressives such as the corticosteroids may further increase the risk of infections over the risk observed with use of natalizumab alone. The safety and efficacy of natalizumab in combination with immunosuppressants has not been evaluated. Patients receiving chronic immunosuppressant therapy should not ordinarily be treated with natalizumab. In patients with Crohn's disease who start natalizumab while on chronic corticosteroids, commence steroid withdrawal as soon as a therapeutic benefit with natalizumab has occurred. Discontinue natalizumab if the patient cannot discontinue oral corticosteroids within 6 months. Ordinarily, patients with multiple sclerosis receiving chronic immunosuppressant therapy should not be treated with natalizumab.
    Nateglinide: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Nefazodone: Use caution when budesonide is coadministered with drugs that inhibit CYP3A enzymes, such as nefazodone, and consider dose reduction. Toxicity may occur, particularly excessive HPA-axis suppression.
    Nelarabine: 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.
    Nelfinavir: Nelfinavir 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.
    Neostigmine: Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
    Neuromuscular blockers: Corticosteroids cause hypokalemia, which potentiates neuromuscular blockade with nondepolarizing neuromuscular blockers.
    Nevirapine: Theoretically, induction of the cytochrome P450 3A4 isoenzyme by nevirapine may result in a lowering of budesonide plasma concentrations, reducing the clinical effect.
    Nicardipine: 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.
    Nizatidine: 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. In general, it may be prudent to avoid drugs such as H2-blockers in combination with oral budesonide.
    Nonsteroidal antiinflammatory drugs: 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.
    Norfloxacin: 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.
    Ofloxacin: 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.
    Olaparib: Use caution if coadministration of olaparib with budesonide is necessary, due to an increased risk of budesonide-related adverse reactions. Budesonide is primarily metabolized by CYP3A4, but is also a P-glycoprotein (P-gp) substrate. Olaparib is an in vitro P-gp inhibitor, although the clinical relevance is unknown.
    Ombitasvir; Paritaprevir; Ritonavir: Via inhibition of CYP3A4, ritonavir significantly increases plasma concentrations of budesonide, resulting in significantly reduced serum cortisol concentrations. During post-marketing use, there have been reports of clinically significant drug interactions in patients receiving budesonide with ritonavir, resulting in systemic corticosteroid effects including Cushing's syndrome and adrenal suppression. Therefore, coadministration of budesonide and ritonavir (or ritonavir-containing products or treatment regimens) is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects.
    Omeprazole: 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.
    Omeprazole; Sodium Bicarbonate: 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. 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.
    Ondansetron: 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.
    Oritavancin: 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.
    Oxymetholone: Concomitant use of oxymetholone with corticosteroids or corticotropin, ACTH may cause increased edema. Manage edema with diuretic and/or digitalis therapy.
    Pancuronium: Corticosteroids cause hypokalemia, which potentiates neuromuscular blockade with nondepolarizing neuromuscular blockers.
    Pantoprazole: 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.
    Pazopanib: 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.
    Pegaspargase: Concomitant use of pegaspargase with corticosteroids can result in additive hyperglycemia. Insulin therapy may be required in some cases.
    Pemetrexed: Additive effects may be seen when pemetrexed is given with other immunosuppressives or antineoplastic agents.
    Penicillamine: 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.
    Phenylephrine: 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.
    Phenylephrine; Promethazine: 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.
    Phosphorus Salts: Use potassium phosphate; sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
    Photosensitizing agents: Corticosteroids administered systemically prior to or concomitantly with photosensitizing agents may decrease the efficacy of photodynamic therapy.
    Physostigmine: Corticosteroids may interact with cholinesterase inhibitors, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
    Pimozide: Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Use of pimozide and medications known to cause electrolyte imbalance may increase the risk of QT prolongation. Therefore, caution is advisable during concurrent use of pimozide and corticosteroids. Topical corticosteroids are less likely to interact. According to the manufacturer, potassium deficiencies should be correctly prior to treatment with pimozide and normalized potassium levels should be maintained during treatment.
    Platinum compounds: 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.
    Posaconazole: Posaconazole and budesonide should be coadministered with caution due to an increased potential for adverse events. 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.
    Potassium Phosphate; Sodium Phosphate: Use potassium phosphate; sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
    Potassium Salts: 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.
    Potassium: 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.
    Potassium-sparing diuretics: 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.
    Pramlintide: Systemic corticosteroids increase blood glucose levels. Because of this action, a potential pharmacodynamic interaction exists between corticosteroids and all antidiabetic agents. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): Corticosteroids blunt the adrenal secretion of endogenous DHEA and DHEAS, resulting in reduced DHEA and DHEAS serum concentrations.
    Propranolol: 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.
    Proton pump inhibitors: 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.
    Purine analogs: 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.
    Pyridostigmine: Corticosteroids may interact with cholinesterase inhibitors including ambenonium, neostigmine, and pyridostigmine, occasionally causing severe muscle weakness in patients with myasthenia gravis. Glucocorticoids are occasionally used therapeutically, however, in the treatment of some patients with myasthenia gravis. In such patients, it is recommended that corticosteroid therapy be initiated at low dosages and with close clinical monitoring. The dosage should be increased gradually as tolerated, with continued careful monitoring of the patient's clinical status.
    Pyrimidine analogs: 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.
    Quetiapine: QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance. Therefore, caution is advisable during concurrent use of quetiapine and corticosteroids.
    Quinidine: Plasma concentrations of orally administered budesonide may increase during coadministration with CYP3A4 inhibitors, such as quinidine; a budesonide dose reduction should be considered. Toxicity may occur, particularly excessive HPA-axis suppression. Theoretically, inhibition of CYP3A4 may be clinically significant for inhaled forms of budesonide, including budesonide nasal spray.
    Quinolones: 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.
    Rabeprazole: 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.
    Ranitidine: 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. In general, it may be prudent to avoid drugs such as H2-blockers in combination with oral budesonide.
    Rapacuronium: Corticosteroids cause hypokalemia, which potentiates neuromuscular blockade with nondepolarizing neuromuscular blockers.
    Repaglinide: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Rifamycins: Rifamycins are inducers of the cytochrome P450 hepatic enzyme system. Drugs metabolized by CYP enzymes, including corticosteroids, may require dosage adjustments when administered concurrently with rifamycins.
    Ritodrine: 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.
    Ritonavir: Via inhibition of CYP3A4, ritonavir significantly increases plasma concentrations of budesonide, resulting in significantly reduced serum cortisol concentrations. During post-marketing use, there have been reports of clinically significant drug interactions in patients receiving budesonide with ritonavir, resulting in systemic corticosteroid effects including Cushing's syndrome and adrenal suppression. Therefore, coadministration of budesonide and ritonavir (or ritonavir-containing products or treatment regimens) is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects.
    Rituximab: 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.
    Rocuronium: Corticosteroids cause hypokalemia, which potentiates neuromuscular blockade with nondepolarizing neuromuscular blockers.
    Rotavirus Vaccine: Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system. Children who are receiving high doses of systemic corticosteroids (i.e., greater than or equal to 2 mg/kg prednisone orally per day) for 2 weeks or more may be vaccinated after steroid therapy has been discontinued for at least 3 months in accordance with general recommendations for the use of live-virus vaccines. The CDC has stated that discontinuation of steroids for 1 month prior to varicella virus vaccine live administration may be sufficient. Budesonide may affect the immunogenicity of live vaccines. An open-label study examined the immune responsiveness to varicella vaccine in 243 pediatric asthma patients who were treated with budesonide inhalation suspension 0.251 mg daily (n = 151) or non-corticosteroid asthma therapy (n = 92). The percentage of patients developing a seroprotective antibody titer of at least 5 (gpELISA value) in response to the vaccination was slightly lower in patients treated with budesonide compared to patients treated with non-corticosteroid asthma therapy (85% vs. 90%). Even though no patient treated with budesonide inhalation suspension developed chicken pox because of vaccination, live-virus vaccines should not be given to individuals who are considered to be immunocompromised until more information is available.
    Rubella Virus Vaccine Live: Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system. Children who are receiving high doses of systemic corticosteroids (i.e., greater than or equal to 2 mg/kg prednisone orally per day) for 2 weeks or more may be vaccinated after steroid therapy has been discontinued for at least 3 months in accordance with general recommendations for the use of live-virus vaccines. The CDC has stated that discontinuation of steroids for 1 month prior to varicella virus vaccine live administration may be sufficient. Budesonide may affect the immunogenicity of live vaccines. An open-label study examined the immune responsiveness to varicella vaccine in 243 pediatric asthma patients who were treated with budesonide inhalation suspension 0.251 mg daily (n = 151) or non-corticosteroid asthma therapy (n = 92). The percentage of patients developing a seroprotective antibody titer of at least 5 (gpELISA value) in response to the vaccination was slightly lower in patients treated with budesonide compared to patients treated with non-corticosteroid asthma therapy (85% vs. 90%). Even though no patient treated with budesonide inhalation suspension developed chicken pox because of vaccination, live-virus vaccines should not be given to individuals who are considered to be immunocompromised until more information is available.
    Salicylates: 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.
    Salsalate: 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.
    Sapropterin: Caution is advised with the concomitant use of sapropterin and budesonide as coadministration may result in increased systemic exposure of budesonide. Budesonide is a substrate for the drug transporter P-glycoprotein (P-gp); in vitro data show that sapropterin may inhibit P-gp. If these drugs are used together, closely monitor for increased side effects of budesonide.
    Saquinavir: Plasma concentrations of orally administered budesonide may increase during coadministration with CYP3A4 inhibitors like saquinavir; a budesonide dose reduction should be considered. Toxicity may occur, particularly excessive HPA-axis suppression. Theoretically, inhibition of CYP3A4 may be clinically significant for inhaled forms of budesonide, including budesonide nasal spray.
    Saxagliptin: Systemic corticosteroids increase blood glucose levels. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Simeprevir: 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.
    Simvastatin; Sitagliptin: Systemic corticosteroids increase blood glucose levels. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Sitagliptin: Systemic corticosteroids increase blood glucose levels. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Smallpox Vaccine, Vaccinia Vaccine: Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system. Children who are receiving high doses of systemic corticosteroids (i.e., greater than or equal to 2 mg/kg prednisone orally per day) for 2 weeks or more may be vaccinated after steroid therapy has been discontinued for at least 3 months in accordance with general recommendations for the use of live-virus vaccines. The CDC has stated that discontinuation of steroids for 1 month prior to varicella virus vaccine live administration may be sufficient. Budesonide may affect the immunogenicity of live vaccines. An open-label study examined the immune responsiveness to varicella vaccine in 243 pediatric asthma patients who were treated with budesonide inhalation suspension 0.251 mg daily (n = 151) or non-corticosteroid asthma therapy (n = 92). The percentage of patients developing a seroprotective antibody titer of at least 5 (gpELISA value) in response to the vaccination was slightly lower in patients treated with budesonide compared to patients treated with non-corticosteroid asthma therapy (85% vs. 90%). Even though no patient treated with budesonide inhalation suspension developed chicken pox because of vaccination, live-virus vaccines should not be given to individuals who are considered to be immunocompromised until more information is available.
    Sodium Benzoate; Sodium Phenylacetate: 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.
    Sodium Bicarbonate: 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.
    Sodium Chloride: 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.
    Sodium Phenylbutyrate: 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.
    Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: Use potassium phosphate; sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
    Somatropin, rh-GH: 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.
    St. John's Wort, Hypericum perforatum: 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.
    Succinylcholine: Corticosteroids cause hypokalemia, which potentiates neuromuscular blockade with nondepolarizing neuromuscular blockers.
    Sulfonylureas: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Taxanes: 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. In addition, Cabazitaxel is a CYP3A4 substrate and concomitant use with strong CYP3A4 inducers such as dexamethasone may lead to reduced concentrations of cabazitaxel. Avoid concomitant use of cabazitaxel and strong CYP3A4 inducers. Consider alternative therapies with low enzyme induction potential.
    Telaprevir: 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.
    Telbivudine: 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.
    Telithromycin: 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.
    Temsirolimus: Use caution if coadministration of temsirolimus with budesonide is necessary, and monitor for an increase in budesonide-related adverse reactions. Temsirolimus is a P-glycoprotein (P-gp) inhibitor in vitro, and budesonide is a P-gp substrate. Pharmacokinetic data are not available for concomitant use of temsirolimus with P-gp substrates, but exposure to budesonide is likely to increase.
    Testosterone: 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.
    Thiazide diuretics: 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.
    Thiazolidinediones: Drugs which may cause hyperglycemia, including corticosteroids, may cause temporary loss of glycemic control. Diabetic patients who are administered systemic corticosteroid therapy may require an adjustment in the dosing of the antidiabetic agent.
    Thyroid hormones: 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.
    Tobramycin: 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.
    Tolazamide: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Tolbutamide: Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia. When released, blood glucose concentrations rise. When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Tositumomab: 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.
    Trandolapril; Verapamil: Plasma concentrations of orally administered budesonide may increase during coadministration with CYP3A4 inhibitors like verapamil. A budesonide dose reduction should be considered.
    Trastuzumab: 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.
    Tretinoin, ATRA: 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.
    Tuberculin Purified Protein Derivative, PPD: 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.
    Tubocurarine: Corticosteroids cause hypokalemia, which potentiates neuromuscular blockade with nondepolarizing neuromuscular blockers.
    Typhoid Vaccine: Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system. Children who are receiving high doses of systemic corticosteroids (i.e., greater than or equal to 2 mg/kg prednisone orally per day) for 2 weeks or more may be vaccinated after steroid therapy has been discontinued for at least 3 months in accordance with general recommendations for the use of live-virus vaccines. The CDC has stated that discontinuation of steroids for 1 month prior to varicella virus vaccine live administration may be sufficient. Budesonide may affect the immunogenicity of live vaccines. An open-label study examined the immune responsiveness to varicella vaccine in 243 pediatric asthma patients who were treated with budesonide inhalation suspension 0.251 mg daily (n = 151) or non-corticosteroid asthma therapy (n = 92). The percentage of patients developing a seroprotective antibody titer of at least 5 (gpELISA value) in response to the vaccination was slightly lower in patients treated with budesonide compared to patients treated with non-corticosteroid asthma therapy (85% vs. 90%). Even though no patient treated with budesonide inhalation suspension developed chicken pox because of vaccination, live-virus vaccines should not be given to individuals who are considered to be immunocompromised until more information is available.
    Ulipristal: In vitro data indicate that ulipristal may be an inhibitor of P-glycoprotein (P-gp) at clinically relevant concentrations. Thus, co-administration of ulipristal and P-gp substrates such as budesonide may increase budesonide concentrations. With single doses of ulipristal for emergency contraception it is not clear this interaction will have clinical consequence. In the absence of clinical data, co-administration of ulipristal (when given daily) and P-gp substrates is not recommended.
    Vandetanib: Use caution if coadministration of vandetanib with budesonide is necessary, due to a possible increase in budesonide-related adverse reactions. Budesonide is primarily metabolized by CYP3A4, but it is also a substrate of P-glycoprotein (P-gp). Coadministration with vandetanib increased the Cmax and AUC of digoxin, another P-gp substrate, by 29% and 23%, respectively.
    Varicella-Zoster Virus Vaccine, Live: Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system. Children who are receiving high doses of systemic corticosteroids (i.e., greater than or equal to 2 mg/kg prednisone orally per day) for 2 weeks or more may be vaccinated after steroid therapy has been discontinued for at least 3 months in accordance with general recommendations for the use of live-virus vaccines. The CDC has stated that discontinuation of steroids for 1 month prior to varicella virus vaccine live administration may be sufficient. Budesonide may affect the immunogenicity of live vaccines. An open-label study examined the immune responsiveness to varicella vaccine in 243 pediatric asthma patients who were treated with budesonide inhalation suspension 0.251 mg daily (n = 151) or non-corticosteroid asthma therapy (n = 92). The percentage of patients developing a seroprotective antibody titer of at least 5 (gpELISA value) in response to the vaccination was slightly lower in patients treated with budesonide compared to patients treated with non-corticosteroid asthma therapy (85% vs. 90%). Even though no patient treated with budesonide inhalation suspension developed chicken pox because of vaccination, live-virus vaccines should not be given to individuals who are considered to be immunocompromised until more information is available.
    Vecuronium: Corticosteroids cause hypokalemia, which potentiates neuromuscular blockade with nondepolarizing neuromuscular blockers.
    Vemurafenib: 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.
    Verapamil: Plasma concentrations of orally administered budesonide may increase during coadministration with CYP3A4 inhibitors like verapamil. A budesonide dose reduction should be considered.
    Vigabatrin: 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.
    Vinblastine: Use caution when administering vinblastine concurrently with a CYP3A4 inducer such as dexamethasone. Vinblastine is metabolized by CYP3A4 and dexamethasone may decrease vinblastine plasma concentrations. In addition, because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with antineoplastic agents. While therapy is designed to take advantage of this effect, patients may be predisposed to over-immunosuppression resulting in an increased risk for the development of severe infections. Close clinical monitoring is advised with concurrent use; in the presence of serious infections, continuation of the corticosteroid or immunosuppressive agent may be necessary but should be accompanied by appropriate antimicrobial therapies as indicated.
    Vincristine Liposomal: Use potassium phosphate; sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
    Voriconazole: Voriconazole is an inhibitor of CYP3A4 isoenzyme. Budesonide is a substrate for CYP3A4, and when combined with voriconazole, may theoretically have reduced metabolism, and therefore higher serum concentrations resulting in toxicity.
    Vorinostat: 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.
    Warfarin: The effect of corticosteroids on oral anticoagulants (e.g., 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. Thus corticosteroids should be used cautiously and with appropriate clinical monitoring in patients receiving oral anticoagulants; coagulation indices (e.g., INR, etc.) should be monitored to maintain the desired anticoagulant effect. During high-dose corticosteroid administration, daily laboratory monitoring may be desirable.
    Yellow Fever Vaccine, Live: Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system. Children who are receiving high doses of systemic corticosteroids (i.e., greater than or equal to 2 mg/kg prednisone orally per day) for 2 weeks or more may be vaccinated after steroid therapy has been discontinued for at least 3 months in accordance with general recommendations for the use of live-virus vaccines. The CDC has stated that discontinuation of steroids for 1 month prior to varicella virus vaccine live administration may be sufficient. Budesonide may affect the immunogenicity of live vaccines. An open-label study examined the immune responsiveness to varicella vaccine in 243 pediatric asthma patients who were treated with budesonide inhalation suspension 0.251 mg daily (n = 151) or non-corticosteroid asthma therapy (n = 92). The percentage of patients developing a seroprotective antibody titer of at least 5 (gpELISA value) in response to the vaccination was slightly lower in patients treated with budesonide compared to patients treated with non-corticosteroid asthma therapy (85% vs. 90%). Even though no patient treated with budesonide inhalation suspension developed chicken pox because of vaccination, live-virus vaccines should not be given to individuals who are considered to be immunocompromised until more information is available.
    Zafirlukast: Zafirlukast inhibits the CYP3A4 isoenzymes and should be used cautiously in patients stabilized on drugs metabolized by CYP3A4, such as corticosteroids.
    Zileuton: Zileuton is metabolized by the cytochrome P450 isoenzyme 3A4. Although administration of zileuton with other drugs metabolized by CYP3A4 has not been studied, zileuton may inhibit CYP3A4 isoenzymes. Zileuton could potentially compete with other CYP3A4 substrates.
    Zonisamide: 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.

    PREGNANCY AND LACTATION

    Pregnancy

    Budesonide inhalation powder (Pulmicort Turbuhaler and Flexhaler), budesonide inhalation solution (Pulmicort Respules), and budesonide nasal inhalation solution (Rhinocort Aqua) are classified as FDA pregnancy risk category B. A review of Swedish registries indicated that in over 2000 births there was no increased risk for congenital malformations during early pregnancy with the inhalation powder or solution. A position statement by the American College of Allergy, Asthma and Immunology notes that budesonide is a good choice for pregnant women requiring high doses of inhaled steroids for effective asthma management. Despite adverse effects in animal studies, fetal harm appears remote. Low-dose inhaled corticosteroids are considered first line therapy for control of mild persistent asthma during pregnancy according to the 2004 guidelines of the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group. 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. Inhaled budesonide (FDA pregnancy category B) is preferred over other inhaled corticosteroids due to availability of more safety information during pregnancy. 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. 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. Oral budesonide products (e.g., Entocort EC, Uceris) are classified as FDA pregnancy risk category C. As with other corticosteroids, these budesonide products 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, 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.

    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. Low-dose inhaled corticosteroids are considered first line therapy for control of mild persistent asthma during pregnancy and lactation according to the 2004 guidelines of the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group. However, due to greater availability of data in pregnancy, budesonide is the preferred agent in this population. The amount of inhaled budesonide excreted in breast-milk is minute, and infant exposure is negligible. Reviewers and an expert panel consider inhaled corticosteroids acceptable to use during breast-feeding. . 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. According to the manufacturer of oral budesonide (e.g., Entocort EC, 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. Budesonide rectal foam (e.g., Uceris Rectal) is likely to result in budesonide in human milk as budesonide delivered by inhalation from a dry powder inhaler is present in human milk at low concentrations. Although the American Academy of Pediatrics (AAP) has not has not evaluated the use of budesonide during breast-feeding, the AAP considers other corticosteroids, such as prednisone, to be usually compatible with lactation. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    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.
     
    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.
     
    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.

    PHARMACOKINETICS

    Budesonide is administered by nasal inhalation, oral inhalation, and by mouth. 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.
     
    Affected cytochrome P450 isoenzymes and drug transporters: P-glycoprotein (P-gp), CYP3A4
    In vitro data show that metabolism of budesonide occurs primarily by CYP3A4. Budesonide is also a substrate and inhibitor of P-glycoprotein transport.

    Oral Route

    Gastro-resistant capsules (Entocort EC): Oral budesonide capsules are a coated formulation that resists dissolution in acidic gastric contents but dissolves in the duodenum at a pH > 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 patients and in healthy subjects, demonstrating a high first-pass elimination of the drug. A high-fat meal has been shown to delay peak concentrations by 2.3 hours with no changes in AUC. Following oral administration of 9 mg once daily in patients with active Crohn's disease, the Cmax and AUC were 4 +/- 2.1 nmol/L and 35 +/- 19.8 nmol x hour/L, respectively. Following repeated administration of 3 to 15 mg, budesonide pharmacokinetics were dose-proportional and no accumulation was observed. In Crohn's disease, onset of therapeutic effect with oral budesonide typically occurs by week 2 of treatment with peak remission rates at 8 weeks.
    Extended-release tablets (Uceris): Following oral administration, 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. No accumulation was observed following 7 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%.

    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.
    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.

    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.
     
    Rectal Route
    In a population PK analysis in patients with distal ulcerative colitis, the estimated AUC0-12 following administration of budesonide rectal foam (Uceris) 2 mg PR twice daily was 4.31 ng x hour/mL with a CV of 64% in the target patient population.