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  • CLASSES

    Plain Topical Corticosteroids
    Respiratory Corticosteroids
    Topical Nasal Corticosteroids

    DEA CLASS

    Rx, OTC

    DESCRIPTION

    Synthetic corticosteroid; used topically, intranasally, and by oral inhalation
    Medium-potency topical products are used for corticosteroid-responsive dermatoses, including atopic dermatitis, in adults and pediatric patients 3 months and older
    Used via oral inhalation for maintenance treatment of asthma or COPD; used intranasally for allergic / non-allergic rhinitis and for nasal polyps

    COMMON BRAND NAMES

    ARMONAIR RESPICLICK, ARNUITY ELLIPTA, ClariSpray, Cutivate, Flonase, Flonase Allergy Relief, Flonase Sensimist, Flovent Diskus, Flovent HFA, XHANCE

    HOW SUPPLIED

    ARNUITY ELLIPTA Respiratory (Inhalation) Inhalant: 1actuation, 50mcg, 100mcg, 200mcg
    ClariSpray/Flonase/Flonase Allergy Relief/Flonase Sensimist/Fluticasone Propionate Nasal Spray Met: 1actuation, 27.5mcg, 50mcg
    Cutivate/Fluticasone Propionate Topical Cream: 0.05%
    Cutivate/Fluticasone Propionate Topical Lotion: 0.05%
    Cutivate/Fluticasone Propionate Topical Ointment: 0.005%
    Flovent Diskus Respiratory (Inhalation) Pwd: 1actuation, 50mcg, 100mcg, 250mcg
    Flovent HFA Respiratory (Inhalation) Aer Met: 1actuation, 44mcg, 110mcg, 220mcg
    XHANCE Intrasinal Spray Met: 1actuation, 93mcg

    DOSAGE & INDICATIONS

    For the treatment of pruritus and topical inflammation associated with moderate to severe corticosteroid-responsive dermatoses, including the treatment of alopecia areata, discoid lupus erythematosus, generalized exfoliative dermatitis, cutaneous lichen planus, lichen simplex chronicus, lichen striatus, nodular prurigo, pompholyx (dyshidrosis), pemphigus, polymorphous light eruption, psoriasis, seborrheic dermatitis, severe contact dermatitis, severe Rhus dermatitis (due to plants like poison ivy), and xerosis.
    Topical dosage (cream or ointment)
    Adults

    Apply sparingly to the affected area(s) twice daily. Rub in gently. In the treatment of psoriasis, studies suggest that patients respond preferentially to the 0.005% ointment. Therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary.

    Topical dosage (cream only)
    Infants 3 months and older, Children, and Adolescents

    Apply sparingly to affected area(s) twice daily. Application in the diaper area is not recommended; diapers and plastic pants are considered occlusive dressings and may increase systemic absorption. Discontinue therapy when control is achieved. If no improvement is seen within 2 weeks, reassessment may be necessary. Safety and efficacy in pediatric patients for more than 4 weeks has not been established.

    For the treatment of eczema, including atopic dermatitis.
    Topical dosage (cream)
    Adults, Adolescents, Children, and Infants 3 months and older

    Apply sparingly to affected area(s) once or twice daily. Application in the diaper area is not recommended; diapers and plastic pants are considered occlusive dressings and may increase systemic absorption. Discontinue therapy when control is achieved. If no improvement is seen within 2 weeks, reassessment may be necessary. Safety and efficacy for use in pediatric patients for more than 4 weeks have not been established.

    Topical dosage (lotion)
    Adults, Adolescents, Children, and Infants 3 months and older

    Apply sparingly to affected area(s) once daily. Application in the diaper area is not recommended; diapers and plastic pants are considered occlusive dressings and may increase systemic absorption. Discontinue therapy when control is achieved. If improvement is not seen within 2 weeks, reassessment may be necessary. Safety and efficacy for use in pediatric patients for more than 4 weeks have not been established.

    Topical dosage (ointment)
    Adults

    Apply sparingly to affected area(s) twice daily. Use with occlusive dressings is not recommended.

    For the management of symptoms associated with seasonal allergies or perennial allergies, including allergic rhinitis and allergic conjunctivitis.
    Nasal dosage (fluticasone furoate 27.5 mcg/spray; e.g., OTC Flonase Sensimist)
    Adults

    2 sprays per nostril once daily (110 mcg/day) during week 1. After 1 week, 1 to 2 sprays per nostril once daily (55 to 110 mcg/day) may be used as needed. For OTC products: after 6 months of use, a healthcare professional should be consulted.

    Children and Adolescents 12 years and older

    2 sprays per nostril once daily (110 mcg/day) during week 1. After 1 week, 1 to 2 sprays per nostril once daily (55 to 110 mcg/day) may be used as needed. For OTC products: after 6 months of use, a healthcare professional should be consulted.

    Children 2 to 11 years

    1 spray per nostril once daily (55 mcg/day). Use for the shortest amount of time necessary to achieve symptom relief. For OTC products: after 2 months of daily use per year, a healthcare professional should be consulted.

    Nasal dosage (fluticasone propionate 50 mcg/spray; e.g., OTC Flonase Allergy Relief)
    Adults

    2 sprays per nostril once daily (200 mcg/day) initially. After 1 week, 1 to 2 sprays per nostril once daily (100 to 200 mcg/day) may be used as needed. For OTC products: after 6 months of use, a healthcare professional should be consulted.

    Children and Adolescents 12 years and older

    2 sprays per nostril once daily (200 mcg/day) initially. After 1 week, 1 to 2 sprays per nostril once daily (100 to 200 mcg/day) may be used as needed. For OTC products: after 6 months of use, a healthcare professional should be consulted.

    Children 4 to 11 years

    1 spray per nostril once daily (100 mcg/day). Use for the shortest amount of time necessary to achieve symptom relief. Max: 1 spray per nostril daily (100 mcg/day). For OTC products: after 2 months of daily use per year, a healthcare professional should be consulted.

    For the management of nasal symptoms associated with vasomotor rhinitis (perennial nonallergic rhinitis).
    Nasal inhalation dosage (fluticasone propionate 50 mcg/spray; RX Flonase)
    Adults

    2 sprays per nostril once daily (200 mcg/day). May also administer as 1 spray per nostril twice daily (200 mcg/day). When adequate response achieved, reduce to 1 spray per nostril once daily (100 mcg/day). Max: 2 sprays per nostril daily (200 mcg/day).

    Children and Adolescents 4 years and older

    1 spray per nostril once daily (100 mcg/day). May increase to 2 sprays per nostril once daily (200 mcg/day). When adequate response achieved, reduce to 1 spray per nostril once daily (100 mcg/day). Max: 2 sprays per nostril daily (200 mcg/day).

    For the maintenance treatment of asthma.
    Oral inhalation aerosol dosage (i.e., Flovent HFA)
    Adults

    Initially, 88 mcg via oral inhalation twice daily, approximately 12 hours apart for patients not currently on an inhalational corticosteroid. The starting dosage is based on previous asthma therapy and asthma severity, including consideration of the current control of asthma symptoms and risk of future exacerbation. Maximum benefit may not be seen for 1 to 2 weeks. May titrate after 2 weeks if patient response is not adequate. Max: 880 mcg twice daily. If symptoms arise between doses, an inhaled short-acting beta-2 agonist (SABA) should be used for immediate relief. If a dosage regimen fails to provide adequate control of asthma, the therapeutic regimen should be re-evaluated and additional therapeutic options (e.g., replacing the current strength with a higher strength, initiating an inhaled corticosteroid and long-acting beta-2 agonist (LABA) combination product or oral corticosteroids) should be considered. After asthma stability has been achieved, titrate to the lowest effective dosage to reduce the possibility of adverse reactions.

    Children and Adolescents 12 years and older

    Initially, 88 mcg via oral inhalation twice daily, approximately 12 hours apart for patients not currently on an inhalational corticosteroid. The starting dosage is based on previous asthma therapy and asthma severity, including consideration of the current control of asthma symptoms and risk of future exacerbation. Maximum benefit may not be seen for 1 to 2 weeks. May titrate after 2 weeks if patient response is not adequate. Max: 880 mcg twice daily. If symptoms arise between doses, an inhaled short-acting beta-2 agonist (SABA) should be used for immediate relief. If a dosage regimen fails to provide adequate control of asthma, the therapeutic regimen should be re-evaluated and additional therapeutic options (e.g., replacing the current strength with a higher strength or initiating oral corticosteroids) should be considered. After asthma stability has been achieved, titrate to the lowest effective dosage to reduce the possibility of side effects. The National Asthma Education and Prevention Program Expert Panel (NAEPP) defines low dose therapy as 88 to 264 mcg/day, medium dose as more than 264 to 440 mcg/day, and high dose therapy as more than 440 mcg/day for children 12 years and older. The Global Initiative for Asthma (GINA) guidelines define low dose therapy as 100 to 250 mcg/day, medium dose as more than 250 to 500 mcg/day, and high dose therapy as more than 500 mcg/day in this age group.

    Children 6 to 11 years

    88 mcg via oral inhalation twice daily, approximately 12 hours apart is recommended by FDA-approved labeling. If symptoms arise between doses, an inhaled short-acting beta-2 agonist (SABA) should be used for immediate relief. If a dosage regimen fails to provide adequate control of asthma, the therapeutic regimen should be re-evaluated and additional therapeutic options (e.g., replacing the current strength with a higher strength or initiating oral corticosteroids) should be considered. After asthma stability has been achieved, titrate to the lowest effective dosage to reduce the possibility of side effects. The National Asthma Education and Prevention Program Expert Panel (NAEPP) defines low dose therapy as 88 to 176 mcg/day, medium dose therapy as more than 176 to 352 mcg/day, and high dose therapy as more than 352 mcg/day for children ages 6 to 11 years. The Global Initiative for Asthma (GINA) guidelines define low dose therapy as 100 to 200 mcg/day, medium dose as more than 200 to 500 mcg/day, and high dose as more than 500 mcg/day in this age group. Prolonged use of high doses (i.e., more than 352 mcg/day) may be associated with additional adverse reactions.

    Children 5 years

    88 mcg via oral inhalation twice daily, approximately 12 hours apart is recommended by FDA-approved labeling. If symptoms arise between doses, an inhaled short-acting beta-2 agonist (SABA) should be used for immediate relief. If a dosage regimen fails to provide adequate control of asthma, the therapeutic regimen should be re-evaluated and additional therapeutic options (e.g., replacing the current strength with a higher strength or initiating oral corticosteroids) should be considered. After asthma stability has been achieved, titrate to the lowest effective dosage to reduce the possibility of side effects. The National Asthma Education and Prevention Program Expert Panel (NAEPP) defines low dose therapy as 88 to 176 mcg/day, medium dose therapy as more than 176 to 352 mcg/day, and high dose therapy as more than 352 mcg/day for children 5 years of age. The Global Initiative for Asthma (GINA) guidelines define low dose therapy as 100 mcg/day in this age group. Prolonged use of high doses (i.e., more than 352 mcg/day), may be associated with additional adverse reactions.

    Children 4 years

    88 mcg via oral inhalation twice daily, approximately 12 hours apart is recommended by FDA-approved labeling. If symptoms arise between doses, an inhaled short-acting beta-2 agonist (SABA) should be used for immediate relief. If a dosage regimen fails to provide adequate control of asthma, the therapeutic regimen should be re-evaluated and additional therapeutic options (e.g., replacing the current strength with a higher strength or initiating oral corticosteroids) should be considered. After asthma stability has been achieved, titrate to the lowest effective dosage to reduce the possibility of side effects. The National Asthma Education and Prevention Program Expert Panel (NAEPP) defines low dose therapy as 176 mcg/day, medium dose therapy as more than 176 to 352 mcg/day, and high dose therapy as more than 352 mcg/day for children ages 1 to 4 years. The Global Initiative for Asthma (GINA) guidelines define low dose therapy as 100 mcg/day in this age group. Per the NAEPP, the definition of low dose therapy for children 4 years or younger is higher than that for children 5 to 11 years due to a lower dose delivered via face mask and efficacy data in young children. Titrate to the lowest effective dose once asthma stability is achieved. Prolonged use of high doses (i.e., more than 352 mcg/day) may be associated with additional adverse reactions.

    Oral inhalation powder dosage (i.e., Flovent Diskus)
    Adults

    Initially, 100 mcg via oral inhalation twice daily, approximately 12 hours apart. Maximum benefit may not be seen for 1 to 2 weeks. May titrate after 2 weeks if patient response is not adequate. Max: 1,000 mcg twice daily. Titrate to lowest effective dose once stable.

    Children and Adolescents 12 years and older

    Initially, 100 mcg via oral inhalation twice daily, approximately 12 hours apart. Maximum benefit may not be seen for 1 to 2 weeks. May titrate after 2 weeks if patient response is not adequate. Max: 1,000 mcg twice daily. The National Asthma Education and Prevention Program (NAEPP) Expert Panel defines low dose therapy as 100 to 300 mcg/day, medium dose as more than 300 to 500 mcg/day, and high dose therapy as more than 500 mcg/day for children 12 years and older. The Global Initiative for Asthma (GINA) guidelines define low dose therapy as 100 to 250 mcg/day, medium dose as more than 250 to 500 mcg/day, and high dose therapy as more than 500 mcg/day in this age group. Titrate to the lowest effective dose once asthma stability is achieved. Prolonged use of high doses (i.e., more than 1,000 mcg/day) may be associated with additional adverse reactions.

    Children 6 to 11 years

    50 mcg via oral inhalation twice daily, approximately 12 hours apart is recommended by FDA-approved labeling. Larger initial doses may be considered for patients with poor asthma control or who have previously required high doses of inhaled corticosteroids. Max: 100 mcg twice daily. The National Asthma Education and Prevention Program Expert Panel (NAEPP) defines low dose therapy as 100 to 200 mcg/day, medium dose therapy as more than 200 to 400 mcg/day, and high dose therapy as more than 400 mcg/day for children 6 to 11 years of age. The Global Initiative for Asthma guidelines define low dose therapy as 100 to 200 mcg/day, medium dose as more than 200 to 400 mcg/day, and high dose therapy as more than 400 mcg/day in this age group. Titrate to the lowest effective dose once asthma stability is achieved. Prolonged use of high doses (i.e., more than 400 mcg/day) may be associated with additional adverse reactions.

    Children 5 years

    50 mcg via oral inhalation twice daily, approximately 12 hours apart, is recommended by FDA-approved labeling. Larger initial doses may be considered for patients with poor asthma control or who have previously required high doses of inhaled corticosteroids. Max: 100 mcg twice daily. The National Asthma Education and Prevention Program Expert Panel (NAEPP) defines low dose therapy as 100 to 200 mcg/day, medium dose therapy as more than 200 to 400 mcg/day, and high dose therapy as more than 400 mcg/day for children 5 years of age. Titrate to the lowest effective dose once asthma stability is achieved. Prolonged use of high doses (i.e., more than 400 mcg/day) may be associated with additional adverse reactions.

    Children 4 years

    Initially, 50 mcg via oral inhalation twice daily, approximately 12 hours apart. Larger initial doses may be considered for patients with poor asthma control or who have previously required high doses of inhaled corticosteroids. Max: 100 mcg twice daily. Titrate to the lowest effective dose once asthma stability is achieved. Prolonged use of high doses may be associated with additional adverse reactions.

    Oral inhalation powder dosage (i.e., Arnuity Ellipta)
    Adults

    Initial dose based on previous asthma drug therapy and disease severity; 100 mcg via oral inhalation once daily is the usual recommended starting dose for patients not on an inhaled corticosteroid. After 2 weeks of therapy, if asthma symptoms are uncontrolled, increase dose to 200 mcg via oral inhalation once daily. Max: 200 mcg once daily. Administer at the same time each day. The maximum beneficial effect may not be achieved for up to 2 weeks or longer after starting treatment. Titrate to the lowest effective dose once asthma stability is achieved.

    Children and Adolescents 12 years and older

    Initial dose based on previous asthma drug therapy and disease severity; 100 mcg via oral inhalation once daily is the usual recommended starting dose for patients not on an inhaled corticosteroid. After 2 weeks of therapy, if asthma symptoms are uncontrolled, increase dose to 200 mcg via oral inhalation once daily. Max: 200 mcg once daily. Administer at the same time each day. The maximum beneficial effect may not be achieved for up to 2 weeks or longer after starting treatment. Titrate to the lowest effective dose once asthma stability is achieved.

    Children 5 to 11 years

    50 mcg via oral inhalation once daily. Administer at the same time each day. The maximum beneficial effect may not be achieved for up to 2 weeks or longer after starting treatment.

    Oral inhalation powder dosage (i.e., Armonair Respiclick)
    Adults

    The starting dosage is based on the severity of asthma. An initial dosage of 55 mcg via oral inhalation twice daily is the usual recommended dose for patients NOT on an inhaled corticosteroid. For those who remain uncontrolled after 2 weeks of therapy, increase to 113 mcg via oral inhalation twice daily. Max: 232 mcg twice daily. For other patients, the starting dose should be based on previous asthma drug therapy and disease severity. Administer at the same time each day. Maximum benefit may not be achieved for up to 2 weeks or longer. Titrate to the lowest effective dose once asthma stability is achieved to reduce the possibility of adverse reactions.

    Children and Adolescents 12 years and older

    The starting dosage is based on the severity of asthma. An initial dosage of 55 mcg via oral inhalation twice daily is the usual recommended dose for patients NOT on an inhaled corticosteroid. For those who remain uncontrolled after 2 weeks of therapy, increase to 113 mcg via oral inhalation twice daily. Max: 232 mcg twice daily. For other patients, the starting dose should be based on previous asthma drug therapy and disease severity. Administer at the same time each day. Maximum benefit may not be achieved for up to 2 weeks or longer. Titrate to the lowest effective dose once asthma stability is achieved to reduce the possibility of adverse reactions.

    For the treatment of nasal polyps.
    Nasal inhalation dosage ( fluticasone propionate nasal spray 93 mcg/spray; i.e., Xhance)
    Adults

    1 spray (93 mcg of fluticasone propionate per spray) in each nostril twice daily (total daily dose, 372 mcg/day). A dose of 2 sprays in each nostril twice daily may also be effective in some patients. Max: 2 sprays in each nostril twice daily (total daily dose, 744 mcg/day). Effectiveness depends on regular use; patient should use at regular intervals. Individual patients will experience a variable time to onset and different degrees of symptom relief.

    For the maintenance treatment of chronic obstructive pulmonary disease (COPD)†, including chronic bronchitis† and emphysema†.
    Oral inhalation dosage (fluticasone propionate powder for inhalation or pressurized inhalation suspension)
    Adults

    The optimal dose for COPD is not established, although inhaled corticosteroids (ICS) are well-accepted treatments for patients at risk for exacerbation per COPD guidelines. Typical doses range from 50 mcg to 500 mcg inhaled orally twice daily depending on the formulation used and patient response. Do not use fluticasone for the relief of acute bronchospasm; use a short-acting beta-2 agonist (SABA). According to the Global Initiative for Chronic Lung Disease (GOLD) guidelines, ICS may be used in combination with an inhaled long-acting beta-2 agonist (LABA) as initial therapy in group D (those with a high risk of exacerbation). Combination of a LABA with an ICS has the greatest likelihood of reducing exacerbations in patients with blood eosinophil counts of 200 cells/microL or more. An ICS combined with a LABA is more effective than the individual components in improving lung function and health status and reducing exacerbations in patients with exacerbations and moderate to very severe COPD; however clinical trials failed to demonstrate a statistically significant effect on survival. At follow-up, if the patient is still experiencing dyspnea, consider switching inhaler device and investigate for other causes of dyspnea. If the patient has exacerbations, consider triple therapy with a long-acting muscarinic antagonist (LAMA), a LABA, and an inhaled corticosteroid (ICS).

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

    A suggested adult dose is not available; use of typical initial doses for asthma may be considered. The American Thoracic Society recommends daily administration of an inhaled corticosteroid (ICS) such as fluticasone in patients who continue to have exercise-induced bronchospasm (EIB) despite using an inhaled short-acting beta-2 agonist (SABA) before exercise, or in those who require daily (or more frequent) SABA use. Specific studies evaluating the optimal dose of fluticasone for EIB prevention in adults are not available; however, doses of 100 mcg and 250 mcg twice daily were evaluated in 37 asthmatic children with a mean age 10.3 years. During the placebo-controlled, parallel group study, EIB severity decreased significantly with fluticasone compared to placebo in both treatment arms, and reductions did not differ significantly between fluticasone dosage groups. 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.

    Children and Adolescents 6 years and older

    Optimal dosing not well established; use of typical initial daily doses for asthma may be considered. Fluticasone 100 mcg and 250 mcg via oral inhalation twice daily significantly decreased the severity of exercise-induced bronchospasm (EIB) compared to placebo within 3 weeks of initiation in a placebo-controlled, parallel group study of children with asthma (n = 37; mean age: 10.3 years). Reductions in EIB severity did not differ significantly between the dosage groups and were sustained throughout 24 weeks of treatment; the mean % fall in FEV1 after exercise decreased from 34.1% to 9.9% in the 100 mcg/dose group and from 35.9% to 7.6% in the 250 mcg/dose group. Maximal improvement may be seen 2 to 4 weeks after inhaled corticosteroid (ICS) initiation. American Thoracic Society guidelines recommend daily administration of an ICS in patients with EIB who continue to have symptoms despite use of an inhaled short-acting beta-agonist (SABA) before exercise, or in those who develop SABA tolerance due to regular (e.g., daily) use. ICSs are considered the most effective anti-inflammatory agents for EIB; they are preferred controller agents in patients with below normal baseline lung function and/or asthma. Use of an ICS as an 'as needed' treatment only before exercise is NOT recommended.

    †Indicates off-label use

    MAXIMUM DOSAGE

    In general, corticosteroid dosage must be individualized and is highly variable depending on the nature and severity of the disease, route and product of administration, and on patient age and response. For some products maximum dosage limits have not been specified.

    Adults

    Topical: Twice daily application for cream/ointment; once daily application for lotion.
    Intranasal: 110 mcg/day intranasally for fluticasone furoate (e.g., Flonase Sensimist); 200 mcg/day intranasally for fluticasone propionate (e.g., Flonase, Flonase Allergy); 744 mcg/day intranasally for fluticasone propionate for nasal polyps (Xhance).
    Inhaler maximum dosages: 2,000 mcg/day via fluticasone propionate dry powder inhaler (DPI) (Flovent Diskus); 464 mcg/day via fluticasone propionate DPI (Armonair Respiclick); 200 mcg/day via fluticasone furoate DPI (Arnuity Ellipta); 1,760 mcg/day via fluticasone propionate MDI (Flovent HFA).

    Geriatric

    Topical: Twice daily application for cream/ointment; once daily application for lotion.
    Intranasal: 110 mcg/day intranasally for fluticasone furoate (e.g., Flonase Sensimist); 200 mcg/day intranasally for fluticasone propionate (e.g., Flonase, Flonase Allergy); 744 mcg/day intranasally for fluticasone propionate for nasal polyps (Xhance). 
    Inhaler maximum dosages: 2,000 mcg/day via fluticasone propionate dry powder inhaler (DPI) (Flovent Diskus); 464 mcg/day via fluticasone propionate DPI (Armonair Respiclick); 200 mcg/day via fluticasone furoate DPI (Arnuity Ellipta); 1,760 mcg/day via fluticasone propionate MDI (Flovent HFA).

    Adolescents

    Topical: Twice daily application for cream/ointment; once daily application for lotion.
    Intranasal: 110 mcg/day intranasally for fluticasone furoate (e.g., Flonase Sensimist); 200 mcg/day intranasally for fluticasone propionate (e.g., Flonase, Flonase Allergy). Safety and efficacy not established for fluticasone propionate for nasal polyps (Xhance).
    Inhaler maximum dosages: 2,000 mcg/day via fluticasone propionate dry powder inhaler (DPI) (Flovent Diskus); 464 mcg/day via fluticasone propionate DPI (Armonair Respiclick); 200 mcg/day via fluticasone furoate DPI (Arnuity Ellipta); 1,760 mcg/day via fluticasone propionate MDI (Flovent HFA).

    Children

    12 years:
    Topical: Twice daily application for cream/ointment; once daily application for lotion.
    Intranasal: 110 mcg/day intranasally for fluticasone furoate (e.g., Flonase Sensimist); 200 mcg/day intranasally for fluticasone propionate (e.g., Flonase, Flonase Allergy). Safety and efficacy not established for fluticasone propionate for nasal polyps (Xhance).
    Inhaler maximum dosages: 2,000 mcg/day via fluticasone propionate dry powder inhaler (DPI) (Flovent Diskus); 464 mcg/day via fluticasone propionate DPI (Armonair Respiclick); 200 mcg/day via fluticasone furoate DPI (Arnuity Ellipta); 1,760 mcg/day via fluticasone propionate MDI (Flovent HFA).
     
    5 to 11 years:
    Topical: Twice daily application for cream/ointment; once daily application for lotion.
    Intranasal: 55 mcg/day intranasally for fluticasone furoate (e.g., Flonase Sensimist); 200 mcg/day intranasally for fluticasone propionate (e.g., Flonase, Flonase Allergy). Safety and efficacy not established for fluticasone propionate for nasal polyps (Xhance).
    Inhaler maximum dosages: 200 mcg/day via fluticasone propionate dry powder inhaler (DPI) (Flovent Diskus), however doses of up to 400 mcg/day off-label have been used for asthma; 176 mcg/day via fluticasone propionate MDI (Flovent HFA) per FDA-approved labeling, however, doses of 352 mcg/day or more have been used off-label for asthma; 50 mcg/day via fluticasone furoate DPI (Arnuity Ellipta). Safety and efficacy of the fluticasone propionate DPI (Armonair Respiclick) has not been established.
     
    4 years: Topical: Twice daily application for cream; once daily application for lotion. Intranasal: 55 mcg/day intranasally for fluticasone furoate (e.g., Flonase Sensimist); 200 mcg/day intranasally for fluticasone propionate (e.g., Flonase, Flonase Allergy). Safety and efficacy not established for fluticasone propionate for nasal polyps (Xhance). Inhaled: 200 mcg/day via fluticasone propionate dry powder inhaler (DPI) (Flovent Diskus); 176 mcg/day via fluticasone propionate MDI (Flovent HFA) per FDA-approved labeling, however, doses of 352 mcg/day or more have been used off-label for asthma. Safety and efficacy of the fluticasone furoate DPI (Arnuity Ellipta) or the fluticasone propionate DPI (Armonair Respiclick) have not been established.
     
    2 to 3 years: Twice daily application for cream; once daily application for lotion; 55 mcg/day intranasally for fluticasone furoate (Flonase Sensimist). Fluticasone propionate MDI (Flovent HFA) has been used off-label in treatment of asthma. Safety and efficacy have not been established for other formulations.
     
    1 year: Twice daily application for cream; once daily application for lotion. Fluticasone propionate MDI (Flovent HFA) has been used off-label in treatment of asthma. Safety and efficacy have not been established for other formulations.

    Infants

    3 months and older: Twice daily application for cream; once daily application for lotion. Safety and efficacy have not been established for other formulations.
    1 to 2 months: Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; however, caution is recommended in those with moderate or severe hepatic impairment. Patients with hepatic disease who are receiving fluticasone propionate for nasal polyps should be closely monitored.

    Renal Impairment

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

    ADMINISTRATION

    Topical Administration

    For topical dermatologic use only. Not for ophthalmic, oral, or intravaginal use.
    Patients who fail to respond to topical fluticasone treatment after 1 to 4 weeks should be re-evaluated.
    Once control of the treated condition has been achieved, discontinue fluticasone treatment. Intermittent application may be needed to maintain remission or control of the condition in some cases. The lowest effective maintenance application should be used. Other options include changing to a less potent topical corticosteroid for maintenance and control of inflammation and symptoms.
    Fluticasone propionate preparations generally should not be used with occlusive dressings. Instruct patients not to bandage, cover, or wrap area in any way that may be occlusive.

    Cream/Ointment/Lotion Formulations

    Wash hands before and after fluticasone application. Use gloves if required by universal precautions. Apply sparingly in a thin film and rub gently into affected area. Restrict application to the active lesions or affected areas and try to avoid normal surrounding skin.
    The amount of cream or ointment needed to cover a certain area can be calculated. A 1 gram application of cream covers 100 cm2 of skin. The entire skin surface of the average size adult will be covered by 30 grams of topical steroid cream.

    Inhalation Administration
    Oral Inhalation Administration

    Oral inhalation aerosol (Flovent HFA):
    NOTE: The metered-dose inhalers deliver either 44 mcg/spray, 110 mcg/spray, or 220 mcg/spray depending on the formulation selected.
    Instruct patient to shake the canister well before administering.
    Instruct patient on proper inhalation technique.
    Flovent HFA should be primed prior to the initial use by releasing 4 sprays into the air, away from the face and other people. Shake the inhaler well before each use. The inhaler should also be primed by releasing 1 spray into the air if it has not been used for 7 days or longer. The canister contains a dose counter. The inhaler should be discarded after the counter reads 000. Although the canister is still operational and may contain medication, the accuracy of medication delivery cannot be assured. Patients should be instructed to contact the pharmacist or provider regarding a refill when the counter reads 020.
    Each canister is supplied with a dark orange oral actuator along with patient instructions.
    For patients of any age unable to coordinate inhalation and actuation, a spacer or valved holding chamber (VHC) may be beneficial.
    The choice of using a mouthpiece versus a face mask with a spacer/VHC device must be made based on the skills and understanding of each individual patient. However, in general, children < 4 years require administration with a tight fitting face mask and spacer/VHC device to achieve optimal delivery. If a face mask is used, allow 3—5 inhalations per actuation. Administration of fluticasone HFA via the AeroChamber Plus VHC with face mask has been shown to result in higher systemic exposure in patients ages 6 months to 3 years compared to children 4—11 years of age who receive the same dose without the VHC or face mask.
    Following administration, instruct patient to rinse mouth thoroughly with water or mouthwash to remove fluticasone deposited in the mouth and to minimize dry mouth or throat, throat irritation, and hoarseness.
    The inhaler must be cleaned daily. Remove the canister and cap from the inhaler. Rinse the inhaler with warm water and dry thoroughly.
    To avoid the spread of infection, do not use the inhaler for more than one person.
     
    Powder for oral inhalation (Flovent Diskus):
    Prior to initial use, instruct the patient to remove the diskus device from the moisture-protective foil pouch and to safely throw away the foil pouch. The diskus device will be in the closed position. The patient should fill in the “Pouch opened” and “Use by” dates in the blank lines on the label. The “Use by” date for Flovent Diskus 50 mcg is 6 weeks from the date the pouch is opened. The “Use by” date for Flovent Diskus 100 mcg and 250 mcg devices is 2 months from the date the pouch is opened.
    Open the diskus device by holding the device in one hand and using the thumb of the other hand to push the thumbgrip away as far as it will go until the mouthpiece shows and snaps into place.
    Instruct the patient to hold the diskus device in a level, flat position with the mouthpiece towards them and to slide the lever away from them as far as it will go until it clicks. The number on the dose counter will count down by 1; the diskus device is now ready to use.
    To avoid releasing a dose by mistake before the patient is ready to inhale, warn the patient not to close or tilt the diskus device, not to play with the lever, and not to slide the lever more than once.
    Before inhaling the dose, have the patient breathe out as far as they can while holding the diskus device level and away from their mouth. They should never breathe out into the diskus mouthpiece.
    Instruct the patient to put the mouthpiece to their lips and breathe in through the mouth quickly and deeply through the diskus device. Remove the diskus device from the mouth, hold breath for about 10 seconds, or for as long as is comfortable, and then breathe out slowly.
    After taking a dose, the patient should close the diskus device by sliding the thumbgrip it back towards them far as it will go. The diskus device will click shut. The lever will automatically return to its original position.
    The counter displays how many doses are left. The counter number will count down each time the patient uses the diskus device. After 55 doses (23 doses from the sample pack), the patient will see numbers 5 to 0 in red to warn that there are only a few doses left.
    After administration, instruct patient to rinse mouth with water and spit out the water; they should not swallow it.
    To avoid the spread of infection, do not use the inhaler for more than one person.
     
    Powder for oral inhalation (Arnuity Ellipta):
    Administer via oral inhalation.
    Instruct the patient to open and prepare mouthpiece of the fluticasone inhaler and slide the cover down to activate the first dose (see package instructions). The counter counts down by 1 each time the patient opens the cover.
    Holding the inhaler mouthpiece level to, but away from, the mouth, the patient should exhale. Then, put the mouthpiece to the lips and have patient breathe in the dose deeply and slowly. Remove the inhaler from the mouth, hold breath for about 3 to 4 seconds, and then exhale slowly. Instruct patient to close the inhaler.
    If the cover is opened and closed without inhaling the medicine, the dose will be lost. The lost dose will be held in the inhaler, but it will no longer be available to be inhaled. It is not possible to accidentally take a double dose or an extra dose in one inhalation.
    Following administration, instruct patient to rinse mouth with water to minimize dry mouth and systemic side effects. Do not swallow the water.
    Routine cleaning of the inhaler is not required; the patient can clean the mouthpiece if needed, using a dry tissue, before the cover is closed.
    Discard inhaler after 30 sprays or when the counter reads "0", or when the expiration date has passed.
     
    Powder for Oral Inhalation (Armonair Respiclick, fluticasone furoate dry powder inhaler [DPI]):
    Each canister is supplied with a white inhaler with the mouthpiece, green cap that covers the mouthpiece, and patient instructions.
    Do not use the DPI with a spacer or valve holding chamber (VHC) device.
    Priming is not necessary.
    Instruct the patient to hold the inhaler upright and open the green cap all the way back until it "clicks" immediately prior to use. The inhaler does not need to be shaken. If a "click" is not heard then the inhaler may not be activated to give the dose of medicine.
    Before inhaling the dose, have the patient breathe out as far as they can while holding the DPI device level and away from their mouth. They should never breathe out into the DPI mouthpiece.
    Instruct the patient to put the mouthpiece to their lips and breathe in through the mouth quickly and deeply through the DPI device without blocking the vent above the mouthpiece. Remove the DPI device from the mouth, hold breath for about 10 seconds, and then breathe out slowly.
    After taking a dose, the patient should close the cap; the cap should not be opened until the patient is ready for the next dose.
    The canister contains a dose counter. The inhaler contains 60 doses (inhalations) and will change to red when 20 doses are left. Patients should be instructed to request a refill when the counter reads 20. The inhaler should be discarded after the counter reads "0".
    After administration, instruct patient to rinse mouth thoroughly with water to remove fluticasone deposited in the mouth and minimize dry mouth or throat, throat irritation, hoarseness, and local infection. Water should be spit out and not swallowed.
    To avoid the spread of infection, do not use the inhaler for more than one person.
    Instruct the patient to safely dispose of the device by the specified "use by" date or when the counter reads "0", whichever comes first.

    Intranasal Inhalation Administration

    NOTE: Different nasal formulations are available; the fluticasone propionate nasal sprays (Flonase delivers 50 mcg/spray and Xhance delivers 93 mcg/spray); fluticasone furoate nasal spray (Flonase Sensimist delivers 27.5 mcg/spray).
     
    General Nasal Administration Information
    Instruct patient on the proper use of the nasal spray.
    Ensure that the proper product has been selected.
    Before using for the first time the unit must be primed. Keep the sprayer pointed away from patient, other people, and pets.
    To avoid the spread of infection, do not use the sprayer for more than one person.
     
    For fluticasone propionate (e.g., Flonase products): Shake well before each use. Before first use, pump the activator 6 times until a fine wide spray appears. If the unit has not been used for 7 days, re-prime the unit. After administration, wipe the nasal applicator with a clean tissue and replace the cap. The nasal applicator should be cleaned at least 1 time each week. To clean, rinse the applicator with warm tap water, taking care not to suck water into the bottle, and allow to dry at room temperature before replacing the cap.
     
    For fluticasone propionate (e.g., Xhance): Shake well before each use. Before first use, prime the unit by first gently shaking and then pressing the bottle 7 times or until a fine mist appears; direct the spray into the air, away from the face. If the unit has not been used for 7 days, re-prime the unit by shaking and releasing 2 sprays, in the same manner. Fluticasone propionate is delivered into the nose by actuating the pump spray into 1 nostril while simultaneously blowing (exhaling) into the mouthpiece of the device. To administer, insert the tapered tip of the cone-shaped nosepiece deep into 1 nostril and form a tight seal between the nosepiece and the nostril. Next, place the flexible mouthpiece into the mouth, bending it as necessary to maintain a tight seal. Blow into the mouthpiece, and while continuing to blow, push the bottle up to actuate the spray pump. Continuing to blow through the mouth, but not inhaling or exhaling through the nose, at the time of actuation is important to achieve intended drug deposition. Repeat the process in the other nostril for a full dose. After administration, wipe the nasal applicator with a clean tissue and replace the cap. The nasal applicator should be cleaned at least 1 time each week. To clean, rinse the applicator with warm tap water, taking care not to suck water into the bottle, and allow to dry at room temperature before replacing the cap.
     
    For fluticasone furoate (e.g., Flonase Sensimist): Shake well before each use. Before first use, release 6 test sprays into the air away from face. If the cap has been left off the bottle for at least 5 days, or spray has not been used for more than 30 days, prime the pump again until a fine mist appears. After administration, wipe the nozzle with a clean, try tissue. Do not use water to clean the nozzle. Clean the inside of the cap with a clean, dry tissue once weekly. Discard after 120 sprays, even if the bottle is not empty.

    STORAGE

    ARMONAIR RESPICLICK:
    - Avoid excessive humidity
    - Discard 30 days after first use
    - Store away from excessive heat and cold
    - Store between 59 to 77 degrees F, excursions permitted to 59 to 86 degrees F
    - Store in a dry place
    - Store in original package until time of use
    ARNUITY ELLIPTA:
    - Avoid direct heat and sunlight
    - Product should always be stored in the blister and only removed immediately before use
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store in a dry place
    ClariSpray:
    - Store between 39 to 86 degrees F
    Cutivate:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Flonase:
    - Store between 39 to 86 degrees F
    Flonase Allergy Relief:
    - Store between 39 to 86 degrees F
    Flonase Sensimist :
    - Do not freeze
    - Do not refrigerate
    - Store at room temperature (between 59 to 86 degrees F)
    Flovent Diskus :
    - Avoid direct heat and sunlight
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store in a dry place
    Flovent HFA:
    - Exposure to temperatures above 120 degrees F may cause bursting
    - For best results, product should be at room temperature before use
    - Keep away from heat and flame
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store inhaler with mouthpiece down
    Veramyst:
    - Do not refrigerate
    - Protect from freezing
    - Store at room temperature (between 59 to 86 degrees F)
    - Store upright
    XHANCE:
    - Protect from light
    - Store away from excessive heat and cold
    - Store between 59 to 77 degrees F, excursions permitted to 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Use of fluticasone does 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.

    Corticosteroid hypersensitivity, milk protein hypersensitivity

    Fluticasone is contraindicated for use in anyone who is hypersensitive to the medication or any components of the respective products. Although true corticosteroid hypersensitivity is rare, patients who have demonstrated a prior hypersensitivity reaction to fluticasone should not receive any form of fluticasone. 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. Fluticasone inhalation powders (Flovent Diskus, Armonair Respiclick, and Arnuity Ellipta) are contraindicated in patients with severe milk protein hypersensitivity; these formulations contain lactose and have been associated, rarely, with anaphylactoid reactions.

    Acute bronchospasm, status asthmaticus

    Inhaled formulations of fluticasone are contraindicated for the primary treatment of patients with status asthmaticus or other types of acute bronchospasm for which intensive therapy is warranted. Patients should be advised that fluticasone 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.

    Cushing's syndrome, hypothalamic-pituitary-adrenal (HPA) suppression, occlusive dressing, skin abrasion, surgery

    Systemic absorption of topical or inhaled corticosteroids, like fluticasone, has produced reversible hypothalamic-pituitary-adrenal (HPA) suppression, manifestations of Cushing's syndrome, hyperglycemia, and glycosuria in some patients. Use fluticasone with caution in patients with underlying Cushing's syndrome. Conditions which increase systemic absorption of topical corticosteroids include use over large surface areas, prolonged use, use in areas where the epidermal barrier is disrupted (i.e., skin abrasion), and the use of an occlusive dressing. Patients receiving large doses of a potent topical corticosteroid applied to a large surface area or under an occlusive dressing should be evaluated periodically for evidence of HPA axis suppression. Recovery of HPA axis function is generally prompt and complete upon discontinuation of the topical corticosteroid. Use of intranasal corticosteroids in susceptible individuals or in excess of recommended dosing may result in hypercorticism and adrenal suppression. In the event of such complications, the drug should be slowly discontinued. Although the risk of developing HPA suppression is very low with orally inhaled fluticasone, patients should, nevertheless, be monitored for this possibility. If HPA suppression occurs, patients will require systemic corticosteroids during periods of physiologic stress. If surgery is required, patients should notify all health care providers that they have received inhaled corticosteroids within the last 12 months. Infrequently, signs and symptoms of corticosteroid withdrawal may occur, requiring supplemental systemic corticosteroids. Fluticasone should not be substituted for systemic corticosteroid administration because the amount of inhaled fluticasone that reaches the systemic circulation is insufficient to replace orally administered corticosteroids. Deaths due to adrenal insufficiency have been reported in asthma patients during and following such a transfer.

    Diabetes mellitus

    Topical and inhaled corticosteroids, such as fluticasone, should be used with caution in patients with diabetes mellitus. Exacerbation of diabetes may occur with systemic absorption of the topical corticosteroid. Use of topical corticosteroids may further delay healing of skin ulcers in diabetic patients.

    Nasal septal perforation, nasal surgery, nasal trauma

    As with any long-term topical treatment of the nasal cavity, patients using fluticasone intranasally over several months or longer should be examined periodically for possible changes in the nasal mucosa. Further, because of the inhibitory effect of corticosteroids on wound healing, patients who have experienced recent nasal septal perforation or ulcer, nasal surgery, or nasal trauma should not use a nasal corticosteroid until healing has occurred. Patients receiving fluticasone nasal sprays should avoid spraying the inhaler directly on the septum (center of the nose).

    Fungal infection, herpes infection, infection, measles, tuberculosis, varicella, viral infection

    The incidence or course of acute viral or bacterial infection is probably minimally affected by inhaled corticosteroids in most immunocompetent individuals. However, the use of inhaled or application of topical fluticasone in the presence of infection, including tuberculosis of the skin, active or latent tuberculosis of the respiratory tract, fungal infection, systemic parasitic infection, ocular herpes simplex, and cutaneous or systemic viral infection (e.g., herpes infection, measles, or varicella), should be initiated or continued cautiously, if at all. Because of the potential for worsening infection, fluticasone therapy may need to be interrupted during some active infections. Chickenpox and measles can have a more serious or even fatal course in susceptible children using corticosteroids; the exact risk associated with inhaled or topical fluticasone is unclear. If an unimmunized patient is exposed to chickenpox or measles, proper prophylaxis may be indicated. Corticosteroid therapy can reactivate tuberculosis and should not be used except when chemoprophylaxis is instituted concomitantly. The use of nasal or orally inhaled fluticasone may result in localized fungal infection of the nose, mouth, and pharynx with Candida albicans. Instruct patients to rinse their mouth after each use of orally inhaled fluticasone to minimize risk. If oropharyngeal candidiasis develops, it should be treated with appropriate local or systemic antifungal therapy while still continuing fluticasone therapy; temporary interruption of respiratory inhaler use should only be done under close medical supervision. Patients using fluticasone nasal sprays for extended periods (i.e., months) should be examined periodically for evidence of infection or other adverse effects on the nasal mucosa.

    Malnutrition, osteoporosis, tobacco smoking

    Detrimental effects on bone metabolism are expected to be much lower with inhaled compared to systemically-administered corticosteroids. A 2-year study of fluticasone (inhalation aerosol 88 or 440 mcg twice daily) in asthma patients found no statistically significant changes in bone mineral density (BMD) via dual-energy x-ray absorptiometry (DEXA) at the lumbar spine. However, some data suggest that high-dose inhaled steroids may also decrease bone formation and increase resorption, and decreases in bone mineral density have been reported in patients receiving long-term therapy of inhaled corticosteroids. Patients receiving inhaled respiratory steroids, such as fluticasone, may be at increased risk of bone loss compared to healthy individuals; compounding risk factors include preexisting osteopenia, prolonged immobilization, family history of osteoporosis, postmenopausal status, advanced age, tobacco smoking, malnutrition, and use of other medications that may reduce bone mass. Patients with these risk factors should be monitored and treated with established standards of care. Due to a systemic absorption of less than 2% after appropriate use, adverse effects on bone are not as likely with intranasal fluticasone therapy; however, assess for decrease in bone mineral density initially and periodically thereafter as per standards of care.

    Geriatric

    Reported clinical experience with fluticasone administered intranasal or via oral respiratory inhalation has not identified differences in responses between geriatric and younger patients, but greater sensitivity of some older individuals cannot be ruled out. No dosage adjustments are needed based on geriatric age alone. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). The OBRA guidelines caution that orally inhaled corticosteroids, such as fluticasone, can cause throat irritation and oral candidiasis, particularly if the mouth is not rinsed after administration.

    Hepatic disease

    Pharmacokinetic studies have shown that following intranasal and respiratory inhalation administration of fluticasone, most of the drug is absorbed after being swallowed and undergoes extensive first-pass metabolism through the liver. Hepatic impairment may lead to accumulation of fluticasone in plasma. Therefore, patients with hepatic disease should be closely monitored when receiving nasal or orally inhaled fluticasone.

    Acne rosacea, acne vulgaris, perioral dermatitis, peripheral vascular disease, skin atrophy

    As with other potent fluorinated topical corticosteroids, fluticasone creams and ointments should not be used to treat acne vulgaris, acne rosacea, or perioral dermatitis. Fluticasone may aggravate these conditions. Fluticasone topical preparations are not recommended to be applied to the face. Topical corticosteroids should be used for brief periods or under close medical supervision in patients with evidence of pre-existing skin atrophy, especially the elderly. Purpura and skin lacerations that may raise the skin and subcutaneous tissue from deep fascia may be more likely to occur with the use of topical corticosteroids in geriatric patients. Use fluticasone preparations cautiously in patients with markedly impaired circulation or peripheral vascular disease due to the potential for skin ulcer. Use of lower potency topical corticosteroids may be necessary in some patients.

    Cataracts, glaucoma, increased intraocular pressure, ocular exposure

    Care should be taken to avoid ocular exposure and use of any fluticasone product (topical, nasal, or inhaled) around the eyes as cases of visual impairment and ocular hypertension have been reported with topical and inhaled corticosteroids. Take care during administration not to expose the eyes. Also, glaucoma, increased intraocular pressure, and cataracts have been reported with long-term use of nasal and inhaled corticosteroids. Patients with a change in vision or a history of increased intraocular pressure, glaucoma, or cataracts should be closely monitored during corticosteroid therapy. Consider referral to an ophthalmologist in patients who develop ocular symptoms or who use fluticasone long term.[40475] [43972] [51761] [58740]

    Formaldehyde hypersensitivity

    Fluticasone lotion and cream should not be used in individuals with formaldehyde hypersensitivity. In these patients, the use of fluticasone may prevent healing or worsen dermatitis. The lotion and cream formulations contain the excipient imidurea, which releases formaldehyde as a breakdown product. Formaldehyde may cause allergic sensitization or irritation upon contact with the skin.

    Children, growth inhibition, increased intracranial pressure, infants

    The safety and efficacy of orally inhaled fluticasone has not been established for infants and children less than 4 years of age; specific nasal and oral inhalation product labels should be consulted prior to use in children as some products are not FDA-approved for certain populations and/or ages of pediatric patients. The safety and efficacy of intranasal fluticasone furoate (i.e., Flonase Sensimist) has not been established for pediatric patients less than 2 years of age and fluticasone propionate intranasal is not recommended for non-prescription use in children under 4 years of age. The safety and efficacy of intranasal fluticasone propionate (Xhance) has not been established in pediatric patients under the age of 18 years. Growth inhibition has been observed in some children following therapy with high-dose fluticasone propionate inhalations. Children receiving fluticasone respiratory inhalations should be monitored closely for growth inhibition; the effect of fluticasone on final adult height is not known. There is some evidence indicating that intranasal corticosteroids may also cause reduced growth velocity in children. However, data from a 1-year, placebo-controlled trial in children (3 to 9 years of age) with allergic rhinitis receiving fluticasone propionate nasal spray (Flonase) showed no statistically significant adverse effect on growth; no evidence of clinically significant effects on HPA axis function or bone mineral density were observed. Data from a 1-year, placebo-controlled growth study in children (5 years to 8.5 years of age) showed a lower mean growth velocity in the patients receiving fluticasone furoate nasal spray (Veramyst) compared with placebo (mean treatment difference -0.27 cm/year [CI -0.48 to -0.06]). Routine monitoring of growth in children receiving intranasal corticosteroids as well as using the lowest effective dose to minimize systemic effects is recommended. Topical fluticasone preparations are generally not recommended in pediatric patients except where the benefits of treatment would outweigh the potential risks of therapy. Fluticasone ointment (e.g., Cutivate ointment) is recommended only for adult patients; in a study of 35 children with atopic dermatitis treated with fluticasone ointment, subnormal adrenal function was observed with cosyntropin stimulation testing and the FDA has denied approval of this dosage form for use in pediatric patients. Children and infants may absorb proportionally larger amounts of topical corticosteroids due to a larger skin surface area to body weight ratio, and therefore are more susceptible to developing systemic toxicity, especially with high-potency products. Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing's syndrome, and increased intracranial pressure have been reported in children receiving topical corticosteroid creams and ointments. Adrenal suppression and increased intracranial pressure have also been reported with the use and/or withdrawal of other formulations of corticosteroids in pediatric patients.

    Pregnancy

    There are no randomized clinical studies of fluticasone during pregnancy; there are clinical considerations with the use of fluticasone in pregnant women. Fluticasone should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. Infants born to mothers taking substantial corticosteroid doses during pregnancy should be monitored for signs of hypoadrenalism. Available data from published literature on the use of inhaled or intranasal fluticasone propionate in pregnant women have not reported a clear association with adverse developmental outcomes. Fetal abnormalities have been reported in the off-spring of mice, rats, and rabbits exposed to the medications during gestation. Teratogenicity characteristic of corticosteroids, decreased fetal body weight, and skeletal variations was noted in the off-spring of mice, rats, and rabbits exposed to subcutaneous fluticasone at doses less than the maximum recommended human daily inhaled dose (MRHDID) on a mg/m2 basis. When inhaled fluticasone propionate was administered to rats, fetal body weight was decreased, but teratogenicity was not induced at a maternal toxic dose approximately 0.13 times the MRHDID (on a mg/m2 basis with a maternal inhalation dose of 25.7 mcg/kg/day). Experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroid exposure than are humans. Inhaled corticosteroids are often preferred over systemic corticosteroids when use cannot be avoided for the management of asthma during pregnancy. 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 during pregnancy are limited. However, dose titration may be considered for those with moderate to severe persistent asthma, preferably using budesonide. Due to the availability of safety information during pregnancy, budesonide is preferred over other inhaled corticosteroids. 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. Similarly, other fluticasone formulations, such as intranasal fluticasone, should be avoided unless the potential therapeutic benefit justifies the added risk to the fetus. Fluorinated topical corticosteroid creams and ointments, like fluticasone, are not recommended for use in pregnancy. Lower potency topical corticosteroids are usually used, if needed.

    Breast-feeding

    Fluticasone via inhalation typically results in low systemic concentrations; therefore, the amount excreted into breast-milk after inhalation or nasal use is expected to be very low. Reviewers and an expert panel consider inhaled and oral corticosteroids acceptable to use during breast-feeding. Low-dose inhaled corticosteroids are considered first line therapy for control of mild persistent asthma during lactation. Due to greater availability of data, budesonide is the preferred agent in this population. 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. It is not known whether topical administration of fluticasone could result in sufficient systemic absorption to produce detectable quantities in breast milk. However, most dermatologists stress that topical corticosteroids can be safely used during lactation and breast-feeding. If applied topically, care should be used to ensure the infant will not come into direct contact with the area of application, such as the breast. Increased blood pressure has been reported in an infant whose mother applied a high potency topical corticosteroid ointment directly to the nipples. 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 ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Sunlight (UV) exposure

    Patients that apply topical fluticasone to exposed portions of the body should avoid excessive sunlight (UV) exposure from either natural or artificial sources (e.g., tanning booths, sun lamps, etc.).

    ADVERSE REACTIONS

    Severe

    ocular hypertension / Delayed / 1.0-2.9
    nasal septum perforation / Delayed / 0.3-0.3
    increased intracranial pressure / Early / Incidence not known
    keratitis / Delayed / Incidence not known
    visual impairment / Early / Incidence not known
    skin atrophy / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    Churg-Strauss syndrome / Delayed / Incidence not known
    vasculitis / Delayed / Incidence not known
    muscle paralysis / Delayed / Incidence not known
    bronchospasm / Rapid / Incidence not known
    cholecystitis / Delayed / Incidence not known

    Moderate

    dysphonia / Delayed / 2.0-19.0
    conjunctivitis / Delayed / 1.0-3.0
    contact dermatitis / Delayed / 1.0-3.0
    migraine / Early / 1.0-3.0
    cataracts / Delayed / 1.2-1.2
    withdrawal / Early / Incidence not known
    hypothalamic-pituitary-adrenal (HPA) suppression / Delayed / Incidence not known
    adrenocortical insufficiency / Delayed / Incidence not known
    Cushing's syndrome / Delayed / Incidence not known
    growth inhibition / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    blurred vision / Early / Incidence not known
    hematoma / Early / Incidence not known
    erythema / Early / Incidence not known
    skin ulcer / Delayed / Incidence not known
    impaired wound healing / Delayed / Incidence not known
    hypotension / Rapid / Incidence not known
    eosinophilia / Delayed / Incidence not known
    osteopenia / Delayed / Incidence not known
    osteoporosis / Delayed / Incidence not known
    depression / Delayed / Incidence not known
    wheezing / Rapid / Incidence not known
    dyspnea / Early / Incidence not known
    palpitations / Early / Incidence not known
    glycosuria / Early / Incidence not known
    oral ulceration / Delayed / Incidence not known
    hyperglycemia / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    bleeding / Early / Incidence not known
    tolerance / Delayed / Incidence not known

    Mild

    headache / Early / 1.0-34.0
    sinusitis / Delayed / 0-33.0
    fatigue / Early / 16.0-28.0
    malaise / Early / 16.0-28.0
    pharyngitis / Delayed / 1.0-25.0
    nasal congestion / Early / 4.0-22.0
    throat irritation / Early / 3.0-22.0
    arthralgia / Delayed / 17.0-17.0
    insomnia / Early / 3.0-13.0
    rhinitis / Early / 0-13.0
    musculoskeletal pain / Early / 1.0-12.0
    hoarseness / Early / 2.0-9.0
    cough / Delayed / 1.0-9.0
    rash / Early / 1.0-8.0
    xerosis / Delayed / 7.0-7.0
    fever / Early / 1.0-7.0
    epistaxis / Delayed / 1.0-6.9
    pruritus / Rapid / 1.0-6.0
    skin irritation / Early / 2.0-5.0
    back pain / Delayed / 1.0-4.0
    nasal irritation / Early / 2.4-3.2
    ocular irritation / Rapid / 1.0-3.0
    dizziness / Early / 1.0-3.0
    laryngitis / Delayed / 1.0-3.0
    rhinorrhea / Early / 1.0-3.0
    sneezing / Early / 1.0-3.0
    dysmenorrhea / Delayed / 1.0-3.0
    otalgia / Early / 1.0-3.0
    dental pain / Delayed / 3.0-3.0
    menstrual irregularity / Delayed / 1.0-3.0
    folliculitis / Delayed / 0-1.0
    xerophthalmia / Early / Incidence not known
    urticaria / Rapid / Incidence not known
    striae / Delayed / Incidence not known
    acneiform rash / Delayed / Incidence not known
    telangiectasia / Delayed / Incidence not known
    skin hypopigmentation / Delayed / Incidence not known
    vesicular rash / Delayed / Incidence not known
    miliaria / Delayed / Incidence not known
    purpura / Delayed / Incidence not known
    acne vulgaris / Delayed / Incidence not known
    hypertrichosis / Delayed / Incidence not known
    ecchymosis / Delayed / Incidence not known
    flushing / Rapid / Incidence not known
    restlessness / Early / Incidence not known
    irritability / Delayed / Incidence not known
    agitation / Early / Incidence not known
    anxiety / Delayed / Incidence not known
    muscle cramps / Delayed / Incidence not known
    rhinalgia / Early / Incidence not known
    anosmia / Delayed / Incidence not known
    nasal dryness / Early / Incidence not known
    weight gain / Delayed / Incidence not known

    DRUG INTERACTIONS

    Abatacept: (Moderate) Concomitant use of immunosuppressives, as well as long-term corticosteroids, may potentially increase the risk of serious infection in abatacept treated patients. Advise patients taking abatacept to seek immediate medical advice if they develop signs and symptoms suggestive of infection.
    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Acetaminophen; Butalbital: (Moderate) Coadministration may result in decreased exposure to fluticasone. Butalbital is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone during concurrent use.
    Acetaminophen; Butalbital; Caffeine: (Moderate) Coadministration may result in decreased exposure to fluticasone. Butalbital is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone during concurrent use.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) Coadministration may result in decreased exposure to fluticasone. Butalbital is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone during concurrent use.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Acetazolamide: (Moderate) Corticosteroids may increase the risk of hypokalemia if used concurrently with acetazolamide. Hypokalemia may be especially severe with prolonged use of corticotropin, ACTH. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy.
    Acetohexamide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Adalimumab: (Moderate) Closely monitor for the development of signs and symptoms of infection if coadministration of a corticosteroid with adalimumab is necessary. Adalimumab treatment increases the risk for serious infections that may lead to hospitalization or death. Patients taking concomitant immunosuppressants including corticosteroids may be at greater risk of infection.
    Albiglutide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Aldesleukin, IL-2: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Alemtuzumab: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Alogliptin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Alpha-glucosidase Inhibitors: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Altretamine: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
    Ambenonium Chloride: (Minor) 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.
    Amifampridine: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients.
    Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Aminolevulinic Acid: (Minor) Corticosteroids administered prior to or concomitantly with photosensitizing agents used in photodynamic therapy may decrease the efficacy of the treatment.
    Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Coadministration of inhaled fluticasone propionate and clarithromycin is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Coadministration of inhaled fluticasone propionate and clarithromycin is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Amphotericin B cholesteryl sulfate complex (ABCD): (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
    Amphotericin B lipid complex (ABLC): (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
    Amphotericin B liposomal (LAmB): (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
    Amphotericin B: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly.
    Antithymocyte Globulin: (Moderate) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Antitumor antibiotics: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Argatroban: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Arsenic Trioxide: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
    Asparaginase Erwinia chrysanthemi: (Moderate) Concomitant use of L-asparaginase with corticosteroids can result in additive hyperglycemia. L-Asparaginase transiently inhibits insulin production contributing to hyperglycemia seen during concurrent corticosteroid therapy. Insulin therapy may be required in some cases. Administration of L-asparaginase after rather than before corticosteroids reportedly has produced fewer hypersensitivity reactions.
    Aspirin, ASA: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Coadministration may result in decreased exposure to fluticasone. Butalbital is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone during concurrent use. (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Coadministration may result in decreased exposure to fluticasone. Butalbital is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone during concurrent use. (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Aspirin, ASA; Carisoprodol: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Aspirin, ASA; Dipyridamole: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Aspirin, ASA; Omeprazole: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Aspirin, ASA; Oxycodone: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Aspirin, ASA; Pravastatin: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Atazanavir: (Major) Coadministration of inhaled fluticasone propionate and atazanavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Atazanavir; Cobicistat: (Major) Coadministration of inhaled fluticasone propionate and atazanavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; atazanavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate. (Major) Coadministration of inhaled fluticasone propionate and cobicistat is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Atenolol; Chlorthalidone: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Atracurium: (Moderate) Caution and close monitoring are advised if corticosteroids and neuromuscular blockers are used together, particularly for long periods, due to enhanced neuromuscular blocking effects. In such patients, a peripheral nerve stimulator may be of value in monitoring the response. Concurrent use may increase the risk of acute myopathy. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Moderate) Coadministration may result in decreased exposure to fluticasone. Phenobarbital is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone during concurrent use.
    Azathioprine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Azilsartan; Chlorthalidone: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Basiliximab: (Minor) Because systemically administered corticosteroids have immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Coadministration may result in decreased exposure to fluticasone. Phenobarbital is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone during concurrent use.
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Bendroflumethiazide; Nadolol: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Bepridil: (Moderate) Hypokalemia-producing agents, including corticosteroids, may increase the risk of bepridil-induced arrhythmias and should therefore be administered cautiously in patients receiving bepridil therapy.
    Bismuth Subsalicylate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Bivalirudin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Bortezomib: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Bupropion: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored.
    Bupropion; Naltrexone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored.
    Butabarbital: (Moderate) Coadministration may result in decreased exposure to fluticasone. Butabarbital is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone during concurrent use.
    Calcium Carbonate: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids.
    Calcium Carbonate; Magnesium Hydroxide: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids.
    Calcium Carbonate; Risedronate: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids.
    Calcium Carbonate; Simethicone: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids.
    Canagliflozin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Canagliflozin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Carbamazepine: (Moderate) Hepatic microsomal enzyme inducers, including carbamazepine, can increase the metabolism of fluticasone. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with fluticasone.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Carbetapentane; Guaifenesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Carbetapentane; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Carbinoxamine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Carmustine, BCNU: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Ceritinib: (Major) Coadministration of inhaled fluticasone propionate and ceritinib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Chlophedianol; Guaifenesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Chlorambucil: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Chloramphenicol: (Major) Coadministration of inhaled fluticasone propionate and chloramphenicol is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Chlorothiazide: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Chlorpheniramine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Chlorpropamide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Chlorthalidone: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Chlorthalidone; Clonidine: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Choline Salicylate; Magnesium Salicylate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Cimetidine: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Cisatracurium: (Moderate) Caution and close monitoring are advised if corticosteroids and neuromuscular blockers are used together, particularly for long periods, due to enhanced neuromuscular blocking effects. In such patients, a peripheral nerve stimulator may be of value in monitoring the response. Concurrent use may increase the risk of acute myopathy. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
    Citalopram: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram.
    Clarithromycin: (Major) Coadministration of inhaled fluticasone propionate and clarithromycin is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; clarithromycin is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Clindamycin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Clofarabine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Cobicistat: (Major) Coadministration of inhaled fluticasone propionate and cobicistat is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Codeine; Phenylephrine; Promethazine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Conivaptan: (Major) Coadministration of inhaled fluticasone propionate and conivaptan is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; conivaptan is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate. Additionally, 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.
    Dapagliflozin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Dapagliflozin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Dapagliflozin; Saxagliptin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Darunavir: (Major) Coadministration of inhaled fluticasone propionate and darunavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Darunavir; Cobicistat: (Major) Coadministration of inhaled fluticasone propionate and cobicistat is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate. (Major) Coadministration of inhaled fluticasone propionate and darunavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Coadministration of inhaled fluticasone propionate and cobicistat is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate. (Major) Coadministration of inhaled fluticasone propionate and darunavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; darunavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Coadministration of inhaled fluticasone propionate and ritonavir is not recommended; use caution with inhaled fluticasone furoate. During post-marketing use, there have been reports of clinically significant drug interactions in patients receiving inhaled fluticasone propionate with ritonavir, resulting in systemic corticosteroid effects including Cushing's syndrome and adrenal suppression. Fluticasone is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with ritonavir increased plasma fluticasone propionate exposure resulting in an 86% decrease in serum cortisol AUC. Another strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Deferasirox: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including corticosteroids.
    Delavirdine: (Major) Coadministration of inhaled fluticasone propionate and delavirdine is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; delavirdine is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Denileukin Diftitox: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Denosumab: (Moderate) The safety and efficacy of denosumab use in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with denosumab may be at a greater risk of developing an infection.
    Desmopressin: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer.
    Dextran: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Digoxin: (Moderate) Hypokalemia, hypomagnesemia, or hypercalcemia increase digoxin's effect. Corticosteroids can precipitate digoxin toxicity via their effect on electrolyte balance. It is recommended that serum potassium, magnesium, and calcium be monitored regularly in patients receiving digoxin.
    Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Diphenhydramine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Dofetilide: (Major) Corticosteroids can cause increases in blood pressure, sodium and water retention, and hypokalemia, predisposing patients to interactions with certain other medications. Corticosteroid-induced hypokalemia could also enhance the proarrhythmic effects of dofetilide.
    Doxacurium: (Moderate) Caution and close monitoring are advised if corticosteroids and neuromuscular blockers are used together, particularly for long periods, due to enhanced neuromuscular blocking effects. In such patients, a peripheral nerve stimulator may be of value in monitoring the response. Concurrent use may increase the risk of acute myopathy. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
    Droperidol: (Moderate) Caution is advised when using droperidol in combination with corticosteroids which may lead to electrolyte abnormalities, especially hypokalemia or hypomagnesemia, as such abnormalities may increase the risk for QT prolongation or cardiac arrhythmias.
    Dulaglutide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Echinacea: (Moderate) Echinacea possesses immunostimulatory activity and may theoretically reduce the response to immunosuppressant drugs like corticosteroids. For some patients who are using corticosteroids for serious illness, such as cancer or organ transplant, this potential interaction may result in the preferable avoidance of Echinacea. Although documentation is lacking, coadministration of echinacea with immunosuppressants is not recommended by some resources.
    Econazole: (Minor) In vitro studies indicate that corticosteroids inhibit the antifungal activity of econazole against C. albicans in a concentration-dependent manner. When the concentration of the corticosteroid was equal to or greater than that of econazole on a weight basis, the antifungal activity of econazole was substantially inhibited. When the corticosteroid concentration was one-tenth that of econazole, no inhibition of antifungal activity was observed.
    Efalizumab: (Major) Patients receiving immunosuppressives should not receive concurrent therapy with efalizumab because of the possibility of increased infections and malignancies.
    Elbasvir; Grazoprevir: (Moderate) Administering fluticasone with elbasvir; grazoprevir may result in elevated fluticasone plasma concentrations. Fluticasone is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Coadministration of inhaled fluticasone propionate and cobicistat is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of inhaled fluticasone propionate and cobicistat is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; cobicistat is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Empagliflozin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Empagliflozin; Linagliptin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Empagliflozin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Ephedrine: (Moderate) 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: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Ertugliflozin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Ertugliflozin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Ertugliflozin; Sitagliptin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Estramustine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Estrogens: (Moderate) Estrogens have been associated with elevated serum concentrations of corticosteroid binding globulin (CBG), leading to increased total circulating corticosteroids, although the free concentrations of these hormones may be lower; the clinical significance is not known. Estrogens are CYP3A4 substrates and dexamethasone is a CYP3A4 inducer; concomitant use may decrease the clinical efficacy of estrogens. Patients should be monitored for signs of decreased clinical effects of estrogens (e.g., breakthrough bleeding), oral contraceptives, or non-oral combination contraceptives if these drugs are used together.
    Exenatide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Fluconazole: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Fluoxymesterone: (Moderate) Coadministration of corticosteroids and fluoxymesterone may increase the risk of edema, especially in patients with underlying cardiac or hepatic disease. Corticosteroids with greater mineralocorticoid activity, such as fludrocortisone, may be more likely to cause edema. Administer these drugs in combination with caution.
    Fosamprenavir: (Major) Coadministration of inhaled fluticasone propionate and fosamprenavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; fosamprenavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Gallium Ga 68 Dotatate: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia. Also, corticotropin may cause calcium loss and sodium and fluid retention. Mannitol itself can cause hypernatremia. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    Gemcitabine: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Gentamicin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Glimepiride: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Glimepiride; Pioglitazone: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Glimepiride; Rosiglitazone: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Glipizide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Glipizide; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Glyburide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Glyburide; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Glycerol Phenylbutyrate: (Moderate) Corticosteroids may induce elevated blood ammonia concentrations. Corticosteroids should be used with caution in patients receiving glycerol phenylbutyrate. Monitor ammonia concentrations closely.
    Grapefruit juice: (Major) Instruct patients using inhaled fluticasone propionate products to avoid grapefruit juice. Patients using fluticasone furoate products should be aware of the potential for increased adverse effects if they regularly consume grapefruit juice. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; grapefruit juice is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Guaifenesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Halofantrine: (Major) Due to the risks of cardiac toxicity of halofantrine in patients with hypokalemia and/or hypomagnesemia, the use of halofantrine should be avoided in combination with agents that may lead to electrolyte losses, such as corticosteroids.
    Haloperidol: (Moderate) Caution is advisable during concurrent use of haloperidol and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with haloperidol.
    Hemin: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Corticosteroids increase the activity of this enzyme should not be used with hemin.
    Heparin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Hetastarch: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Hydantoins: (Moderate) Hydantoin anticonvulsants induce hepatic microsomal enzymes and may increase the metabolism of fluticasone, leading to reduced efficacy. Depending on the individual clinical situation and the indication for the interacting medication, enzyme-induction interactions may not always produce reductions in treatment efficacy.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrochlorothiazide, HCTZ; Irbesartan: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrochlorothiazide, HCTZ; Lisinopril: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrochlorothiazide, HCTZ; Losartan: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrochlorothiazide, HCTZ; Propranolol: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. (Moderate) Patients receiving corticosteroids during propranolol therapy may be at increased risk of hypoglycemia due to the loss of counter-regulatory cortisol response. This effect may be more pronounced in infants and young children. If concurrent use is necessary, carefully monitor vital signs and blood glucose concentrations as clinically indicated.
    Hydrochlorothiazide, HCTZ; Quinapril: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrochlorothiazide, HCTZ; Spironolactone: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrochlorothiazide, HCTZ; Telmisartan: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrochlorothiazide, HCTZ; Triamterene: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Hydrocodone; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Hydroxyurea: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
    Ibritumomab Tiuxetan: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia. (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Idelalisib: (Major) Coadministration of inhaled fluticasone propionate and idelalisib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Incretin Mimetics: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Indapamide: (Moderate) Additive hypokalemia may occur when indapamide is coadministered with other drugs with a significant risk of hypokalemia such as systemic corticosteroids. Coadminister with caution and careful monitoring.
    Indinavir: (Major) Coadministration of inhaled fluticasone propionate and indinavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; indinavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Insulin Degludec; Liraglutide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Insulin Glargine; Lixisenatide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Insulins: (Moderate) Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Interferon Alfa-2a: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Interferon Alfa-2b: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Interferon Alfa-2b; Ribavirin: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) A dose adjustment of fluticasone may be necessary when administered concurrently with rifamycins. Fluticasone, although given by topical or inhalation routes, may be systemically absorbed resulting in a potential for decreased systemic exposure. Rifamycins are inducers of CYP3A4; fluticasone is a substrate of CYP3A4.
    Isoniazid, INH; Rifampin: (Moderate) A dose adjustment of fluticasone may be necessary when administered concurrently with rifamycins. Fluticasone, although given by topical or inhalation routes, may be systemically absorbed resulting in a potential for decreased systemic exposure. Rifamycins are inducers of CYP3A4; fluticasone is a substrate of CYP3A4.
    Isoproterenol: (Moderate) The risk of cardiac toxicity with isoproterenol in asthma patients appears to be increased with the coadministration of corticosteroids. Intravenous infusions of isoproterenol in refractory asthmatic children at rates of 0.05 to 2.7 mcg/kg/min have caused clinical deterioration, myocardial infarction (necrosis), congestive heart failure and death.
    Isotretinoin: (Minor) Both isotretinoin and corticosteroids can cause osteoporosis during chronic use. Patients receiving systemic corticosteroids should receive isotretinoin therapy with caution.
    Itraconazole: (Major) Coadministration of inhaled fluticasone propionate and itraconazole is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; itraconazole is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Ketoconazole: (Major) Coadministration of inhaled fluticasone propionate and ketoconazole is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; ketoconazole is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with ketoconazole increased plasma fluticasone exposure by 1.9-fold with a 45% decrease in plasma cortisol AUC, but had no effect on urinary excretion of cortisol. Ketoconazole increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    L-Asparaginase Escherichia coli: (Moderate) Concomitant use of L-asparaginase with corticosteroids can result in additive hyperglycemia. L-Asparaginase transiently inhibits insulin production contributing to hyperglycemia seen during concurrent corticosteroid therapy. Insulin therapy may be required in some cases. Administration of L-asparaginase after rather than before corticosteroids reportedly has produced fewer hypersensitivity reactions.
    Letermovir: (Moderate) A clinically relevant increase in the plasma concentration of fluticasone may occur if given with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. Concurrent use of all 3 drugs together is not recommended because increased systemic corticosteroid adverse events may develop. Fluticasone is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates is similar to a strong CYP3A4 inhibitor. In a drug interaction study, use of fluticasone with another strong CYP3A4 inhibitor resulted in a 1.9-fold increase in plasma fluticasone exposure and a 45% decrease in plasma cortisol exposure, but had no effect on urinary excretion of cortisol.
    Levetiracetam: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Levomethadyl: (Major) Caution is advised when using levomethadyl in combination with other agents, such as corticosteroids, that may lead to electrolyte abnormalities, especially hypokalemia or hypomagnesemia.
    Linagliptin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Liraglutide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Lixisenatide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Lomustine, CCNU: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Loop diuretics: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    Lopinavir; Ritonavir: (Major) Coadministration of inhaled fluticasone propionate and lopinavir; ritonavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; lopinavir; ritonavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate. (Major) Coadministration of inhaled fluticasone propionate and ritonavir is not recommended; use caution with inhaled fluticasone furoate. During post-marketing use, there have been reports of clinically significant drug interactions in patients receiving inhaled fluticasone propionate with ritonavir, resulting in systemic corticosteroid effects including Cushing's syndrome and adrenal suppression. Fluticasone is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with ritonavir increased plasma fluticasone propionate exposure resulting in an 86% decrease in serum cortisol AUC. Another strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Macimorelin: (Major) Avoid use of macimorelin with drugs that directly affect pituitary growth hormone secretion, such as corticosteroids. Healthcare providers are advised to discontinue corticosteroid therapy and observe a sufficient washout period before administering macimorelin. Use of these medications together may impact the accuracy of the macimorelin growth hormone test.
    Magnesium Salicylate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Mannitol: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia. Also, corticotropin may cause calcium loss and sodium and fluid retention. Mannitol itself can cause hypernatremia. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly.
    Mecasermin rinfabate: (Moderate) Additional monitoring may be required when coadministering systemic or inhaled corticosteroids and mecasermin, recombinant, rh-IGF-1. In animal studies, corticosteroids impair the growth-stimulating effects of growth hormone (GH) through interference with the physiological stimulation of epiphyseal chondrocyte proliferation exerted by GH and IGF-1. Dexamethasone administration on long bone tissue in vitro resulted in a decrease of local synthesis of IGF-1. Similar counteractive effects are expected in humans. If systemic or inhaled glucocorticoid therapy is required, the steroid dose should be carefully adjusted and growth rate monitored.
    Mecasermin, Recombinant, rh-IGF-1: (Moderate) Additional monitoring may be required when coadministering systemic or inhaled corticosteroids and mecasermin, recombinant, rh-IGF-1. In animal studies, corticosteroids impair the growth-stimulating effects of growth hormone (GH) through interference with the physiological stimulation of epiphyseal chondrocyte proliferation exerted by GH and IGF-1. Dexamethasone administration on long bone tissue in vitro resulted in a decrease of local synthesis of IGF-1. Similar counteractive effects are expected in humans. If systemic or inhaled glucocorticoid therapy is required, the steroid dose should be carefully adjusted and growth rate monitored.
    Meglitinides: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Melphalan: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Mepenzolate: (Minor) Anticholinergics, such as mepenzolate, antagonize the effects of antiglaucoma agents. Mepenzolate is contraindicated in patients with glaucoma and therefore should not be coadministered with medications being prescribed for the treatment of glaucoma. In addition, anticholinergic drugs taken concurrently with corticosteroids in the presence of increased intraocular pressure may be hazardous.
    Mephobarbital: (Moderate) Coadministration may result in decreased exposure to fluticasone. Mephobarbital is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone during concurrent use.
    Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Metformin; Pioglitazone: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Metformin; Repaglinide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Metformin; Rosiglitazone: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Metformin; Saxagliptin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Metformin; Sitagliptin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Methacholine: (Moderate) Regular use of oral or inhaled corticosteroids may acutely decrease bronchial responsiveness to methacholine; however, corticosteroids may be continued with methacholine use.
    Methazolamide: (Moderate) Corticosteroids may increase the risk of hypokalemia if used concurrently with methazolamide. Hypokalemia may be especially severe with prolonged use of corticotropin, ACTH. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy. The chronic use of corticosteroids may augment calcium excretion with methazolamide leading to increased risk for hypocalcemia and/or osteoporosis.
    Methenamine; Sodium Acid Phosphate: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
    Methoxsalen: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Methyclothiazide: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Metolazone: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Metyrapone: (Major) 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 corticosteroids is minimal, temporary discontinuation of these products should be considered if possible to reduce the potential for interference with the test results.
    Micafungin: (Moderate) Leukopenia, neutropenia, anemia, and thrombocytopenia have been associated with micafungin. Patients who are taking immunosuppressives such as the corticosteroids with micafungin concomitantly may have additive risks for infection or other side effects. In a pharmacokinetic trial, micafungin had no effect on the pharmacokinetics of prednisolone. Acute intravascular hemolysis and hemoglobinuria was seen in a healthy volunteer during infusion of micafungin (200 mg) and oral prednisolone (20 mg). This reaction was transient, and the subject did not develop significant anemia.
    Mifepristone: (Major) Mifepristone for termination of pregnancy is contraindicated in patients on long-term corticosteroid therapy and mifepristone for Cushing's disease or other chronic conditions is contraindicated in patients who require concomitant treatment with systemic corticosteroids for life-saving purposes, such as serious medical conditions or illnesses (e.g., immunosuppression after organ transplantation). For other situations where corticosteroids are used for treating non-life threatening conditions, mifepristone may lead to reduced corticosteroid efficacy and exacerbation or deterioration of such conditions. This is because mifepristone exhibits antiglucocorticoid activity that may antagonize corticosteroid therapy and the stabilization of the underlying corticosteroid-treated illness. Mifepristone may also cause adrenal insufficiency, so patients receiving corticosteroids for non life-threatening illness require close monitoring. Because serum cortisol levels remain elevated and may even increase during treatment with mifepristone, serum cortisol levels do not provide an accurate assessment of hypoadrenalism. Patients should be closely monitored for signs and symptoms of adrenal insufficiency, If adrenal insufficiency occurs, stop mifepristone treatment and administer systemic glucocorticoids without delay; high doses may be needed to treat these events. Factors considered in deciding on the duration of glucocorticoid treatment should include the long half-life of mifepristone (85 hours).
    Mitotane: (Moderate) Use caution if mitotane and fluticasone are used concomitantly, and monitor for decreased efficacy of fluticasone and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and fluticasone is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of fluticasone.
    Mitoxantrone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Mivacurium: (Moderate) Caution and close monitoring are advised if corticosteroids and neuromuscular blockers are used together, particularly for long periods, due to enhanced neuromuscular blocking effects. In such patients, a peripheral nerve stimulator may be of value in monitoring the response. Concurrent use may increase the risk of acute myopathy. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
    Moxifloxacin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Muromonab-CD3: (Major) 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.
    Natalizumab: (Major) Ordinarily, patients receiving chronic immunosuppressant therapy should not be treated with natalizumab. Treatment recommendations for combined corticosteroid therapy are dependent on the underlying indication for natalizumab therapy. Corticosteroids should be tapered in those patients with Crohn's disease who are on chronic corticosteroids when they start natalizumab therapy, as soon as a therapeutic benefit has occurred. If the patient cannot discontinue systemic corticosteroids within 6 months, discontinue natalizumab. The concomitant use of natalizumab and corticosteroids may further increase the risk of serious infections, including progressive multifocal leukoencephalopathy, over the risk observed with use of natalizumab alone. In multiple sclerosis (MS) clinical trials, an increase in infections was seen in patients concurrently receiving short courses of corticosteroids. However, the increase in infections in natalizumab-treated patients who received steroids was similar to the increase in placebo-treated patients who received steroids. Short courses of steroid use during natalizumab, such as when they are needed for MS relapse treatment, appear to be acceptable for use concurrently.
    Nateglinide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Nefazodone: (Major) Coadministration of inhaled fluticasone propionate and nefazodone is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; nefazodone is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Nelarabine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Nelfinavir: (Major) Coadministration of inhaled fluticasone propionate and nelfinavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; nelfinavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Neostigmine: (Minor) 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: (Moderate) Caution and close monitoring are advised if corticosteroids and neuromuscular blockers are used together, particularly for long periods, due to enhanced neuromuscular blocking effects. In such patients, a peripheral nerve stimulator may be of value in monitoring the response. Concurrent use may increase the risk of acute myopathy. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
    Nonsteroidal antiinflammatory drugs: (Moderate) Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged concomitant administration should be avoided. Concomitant use of corticosteroids appears to increase the risk of adverse GI events due to NSAIDs. Corticosteroids can have profound effects on sodium-potassium balance; NSAIDs also can affect sodium and fluid balance. Monitor serum potassium concentrations; potassium supplementation may be necessary. In addition, NSAIDs may mask fever, pain, swelling and other signs and symptoms of an infection; use NSAIDs with caution in patients receiving immunosuppressant dosages of corticosteroids. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) Coadministration of inhaled fluticasone propionate and ritonavir is not recommended; use caution with inhaled fluticasone furoate. During post-marketing use, there have been reports of clinically significant drug interactions in patients receiving inhaled fluticasone propionate with ritonavir, resulting in systemic corticosteroid effects including Cushing's syndrome and adrenal suppression. Fluticasone is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with ritonavir increased plasma fluticasone propionate exposure resulting in an 86% decrease in serum cortisol AUC. Another strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Ondansetron: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Oxymetholone: (Moderate) Concomitant use of oxymetholone with corticosteroids or corticotropin, ACTH may cause increased edema. Manage edema with diuretic and/or digitalis therapy.
    Pancuronium: (Moderate) Caution and close monitoring are advised if corticosteroids and neuromuscular blockers are used together, particularly for long periods, due to enhanced neuromuscular blocking effects. In such patients, a peripheral nerve stimulator may be of value in monitoring the response. Concurrent use may increase the risk of acute myopathy. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
    Pegaspargase: (Moderate) Concomitant use of pegaspargase with corticosteroids can result in additive hyperglycemia. Insulin therapy may be required in some cases.
    Penicillamine: (Major) Agents such as immunosuppressives have adverse reactions similar to those of penicillamine. Concomitant use of penicillamine with these agents is contraindicated because of the increased risk of developing severe hematologic and renal toxicity.
    Phenobarbital: (Moderate) Coadministration may result in decreased exposure to fluticasone. Phenobarbital is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone during concurrent use.
    Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Phenylephrine; Promethazine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly.
    Photosensitizing agents (topical): (Minor) Corticosteroids administered prior to or concomitantly with photosensitizing agents used in photodynamic therapy may decrease the efficacy of the treatment.
    Photosensitizing agents: (Minor) Corticosteroids administered systemically prior to or concomitantly with photosensitizing agents may decrease the efficacy of photodynamic therapy.
    Physostigmine: (Minor) 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: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact.
    Posaconazole: (Major) Coadministration of inhaled fluticasone propionate and posaconazole is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; posaconazole is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Potassium Chloride: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Potassium Phosphate; Sodium Phosphate: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
    Potassium: (Moderate) Corticotropin can cause alterations in serum potassium levels. The use of potassium salts or supplements would be expected to alter the effects of corticotropin on serum potassium levels. Also, there have been reports of generalized tonic-clonic seizures and/or loss of consciousness associated with use of bowel preparation products in patients with no prior history of seizure disorder. Therefore, magnesium sulfate; potassium sulfate; sodium sulfate should be administered with caution during concurrent use of medications that lower the seizure threshold such as systemic corticosteroids.
    Potassium-sparing diuretics: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics.
    Pramlintide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Moderate) Corticosteroids blunt the adrenal secretion of endogenous DHEA and DHEAS, resulting in reduced DHEA and DHEAS serum concentrations.
    Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Moderate) Corticosteroids blunt the adrenal secretion of endogenous DHEA and DHEAS, resulting in reduced DHEA and DHEAS serum concentrations.
    Primidone: (Moderate) Coadministration may result in decreased exposure to fluticasone. Primidone is a CYP3A4 inducer; fluticasone is a CYP3A4 substrate. Monitor for decreased response to fluticasone during concurrent use.
    Propranolol: (Moderate) Patients receiving corticosteroids during propranolol therapy may be at increased risk of hypoglycemia due to the loss of counter-regulatory cortisol response. This effect may be more pronounced in infants and young children. If concurrent use is necessary, carefully monitor vital signs and blood glucose concentrations as clinically indicated.
    Purine analogs: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects.
    Pyridostigmine: (Minor) 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.
    Quetiapine: (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids).
    Quinolones: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon.
    Rapacuronium: (Moderate) Caution and close monitoring are advised if corticosteroids and neuromuscular blockers are used together, particularly for long periods, due to enhanced neuromuscular blocking effects. In such patients, a peripheral nerve stimulator may be of value in monitoring the response. Concurrent use may increase the risk of acute myopathy. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
    Regular Insulin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Repaglinide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Ribociclib: (Major) Coadministration of inhaled fluticasone propionate and ribociclib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; ribociclib is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Ribociclib; Letrozole: (Major) Coadministration of inhaled fluticasone propionate and ribociclib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; ribociclib is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Rifabutin: (Moderate) A dose adjustment of fluticasone may be necessary when administered concurrently with rifamycins. Fluticasone, although given by topical or inhalation routes, may be systemically absorbed resulting in a potential for decreased systemic exposure. Rifamycins are inducers of CYP3A4; fluticasone is a substrate of CYP3A4.
    Rifampin: (Moderate) A dose adjustment of fluticasone may be necessary when administered concurrently with rifamycins. Fluticasone, although given by topical or inhalation routes, may be systemically absorbed resulting in a potential for decreased systemic exposure. Rifamycins are inducers of CYP3A4; fluticasone is a substrate of CYP3A4.
    Rifamycins: (Moderate) A dose adjustment of fluticasone may be necessary when administered concurrently with rifamycins. Fluticasone, although given by topical or inhalation routes, may be systemically absorbed resulting in a potential for decreased systemic exposure. Rifamycins are inducers of CYP3A4; fluticasone is a substrate of CYP3A4.
    Rifapentine: (Moderate) A dose adjustment of fluticasone may be necessary when administered concurrently with rifamycins. Fluticasone, although given by topical or inhalation routes, may be systemically absorbed resulting in a potential for decreased systemic exposure. Rifamycins are inducers of CYP3A4; fluticasone is a substrate of CYP3A4.
    Ritodrine: (Major) Ritodrine has caused maternal pulmonary edema, which appears more often in patients treated concomitantly with corticosteroids. Patients so treated should be closely monitored in the hospital.
    Ritonavir: (Major) Coadministration of inhaled fluticasone propionate and ritonavir is not recommended; use caution with inhaled fluticasone furoate. During post-marketing use, there have been reports of clinically significant drug interactions in patients receiving inhaled fluticasone propionate with ritonavir, resulting in systemic corticosteroid effects including Cushing's syndrome and adrenal suppression. Fluticasone is a CYP3A4 substrate; ritonavir is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with ritonavir increased plasma fluticasone propionate exposure resulting in an 86% decrease in serum cortisol AUC. Another strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Rituximab: (Moderate) Rituximab and corticosteroids are commonly used together; however, monitor the patient for immunosuppression and signs and symptoms of infection during combined chronic therapy.
    Rituximab; Hyaluronidase: (Moderate) Rituximab and corticosteroids are commonly used together; however, monitor the patient for immunosuppression and signs and symptoms of infection during combined chronic therapy.
    Rocuronium: (Moderate) Caution and close monitoring are advised if corticosteroids and neuromuscular blockers are used together, particularly for long periods, due to enhanced neuromuscular blocking effects. In such patients, a peripheral nerve stimulator may be of value in monitoring the response. Concurrent use may increase the risk of acute myopathy. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
    Salicylates: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Salsalate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided.
    Saquinavir: (Major) Coadministration of inhaled fluticasone propionate and saquinavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; saquinavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Sargramostim, GM-CSF: (Major) Avoid the concomitant use of sargramostim and systemic corticosteroid agents due to the risk of additive myeloproliferative effects. If coadministration of these drugs is required, frequently monitor patients for clinical and laboratory signs of excess myeloproliferative effects (e.g., leukocytosis). Sargramostim is a recombinant human granulocyte-macrophage colony-stimulating factor that works by promoting proliferation and differentiation of hematopoietic progenitor cells.
    Semaglutide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    SGLT2 Inhibitors: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Sodium Benzoate; Sodium Phenylacetate: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia.
    Sodium Chloride: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Sodium Phenylbutyrate: (Moderate) The concurrent use of corticosteroids with sodium phenylbutyrate may increase plasma ammonia levels (hyperammonemia) by causing the breakdown of body protein. Patients with urea cycle disorders being treated with sodium phenylbutyrate usually should not receive regular treatment with corticosteroids.
    Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
    Somatropin, rh-GH: (Moderate) Corticosteroids can retard bone growth and therefore, can inhibit the growth-promoting effects of somatropin. If corticosteroid therapy is required, the corticosteroid dose should be carefully adjusted.
    Succinylcholine: (Moderate) Caution and close monitoring are advised if corticosteroids and neuromuscular blockers are used together, particularly for long periods, due to enhanced neuromuscular blocking effects. In such patients, a peripheral nerve stimulator may be of value in monitoring the response. Concurrent use may increase the risk of acute myopathy. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
    Sulfonylureas: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Telaprevir: (Major) Concurrent administration of fluticasone 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 fluticasone dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment.
    Telbivudine: (Moderate) The risk of myopathy may be increased if corticosteroids are coadministered with telbivudine. Monitor patients for any signs or symptoms of unexplained muscle pain, tenderness, or weakness, particularly during periods of upward dosage titration.
    Telithromycin: (Major) Coadministration of inhaled fluticasone propionate and telithromycin is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; telithromycin is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Telotristat Ethyl: (Moderate) Use caution if coadministration of telotristat ethyl and fluticasone is necessary, as the systemic exposure of fluticasone may be decreased resulting in reduced efficacy. If these drugs are used together, monitor patients for suboptimal efficacy of fluticasone; consider increasing the dose of fluticasone if necessary. Fluticasone is a CYP3A4 substrate; although given by topical or inhalation routes, may be systemically absorbed resulting in a potential for decreased systemic exposure. The mean Cmax and AUC of another sensitive CYP3A4 substrate was decreased by 25% and 48%, respectively, when coadministered with telotristat ethyl; the mechanism of this interaction appears to be that telotristat ethyl increases the glucuronidation of the CYP3A4 substrate.
    Testosterone: (Moderate) Coadministration of corticosteroids and testosterone may increase the risk of edema, especially in patients with underlying cardiac or hepatic disease. Corticosteroids with greater mineralocorticoid activity, such as fludrocortisone, may be more likely to cause edema. Administer these drugs in combination with caution.
    Thiazide diuretics: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required.
    Thiazolidinediones: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Thyroid hormones: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Tipranavir: (Major) Coadministration of inhaled fluticasone propionate and tipranavir is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; tipranavir is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Tobramycin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Tolazamide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Tolbutamide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
    Tositumomab: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Tranexamic Acid: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Tretinoin, ATRA: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents.
    Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
    Tubocurarine: (Moderate) Caution and close monitoring are advised if corticosteroids and neuromuscular blockers are used together, particularly for long periods, due to enhanced neuromuscular blocking effects. In such patients, a peripheral nerve stimulator may be of value in monitoring the response. Concurrent use may increase the risk of acute myopathy. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
    Vancomycin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Vecuronium: (Moderate) Caution and close monitoring are advised if corticosteroids and neuromuscular blockers are used together, particularly for long periods, due to enhanced neuromuscular blocking effects. In such patients, a peripheral nerve stimulator may be of value in monitoring the response. Concurrent use may increase the risk of acute myopathy. This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
    Vigabatrin: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Vinblastine: (Minor) 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: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
    Voriconazole: (Major) Coadministration of inhaled fluticasone propionate and voriconazole is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone oral inhalation is a CYP3A4 substrate and caution is warranted with coadministration of very potent CYP3A4 inhibitors, such as voriconazole. Patients may need to be observed for increased corticosteroid-related side effects. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
    Vorinostat: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
    Warfarin: (Moderate) 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.
    Zafirlukast: (Minor) Zafirlukast inhibits the CYP3A4 isoenzymes and should be used cautiously in patients stabilized on drugs metabolized by CYP3A4, such as corticosteroids.
    Zileuton: (Minor) 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.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no randomized clinical studies of fluticasone during pregnancy; there are clinical considerations with the use of fluticasone in pregnant women. Fluticasone should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. Infants born to mothers taking substantial corticosteroid doses during pregnancy should be monitored for signs of hypoadrenalism. Available data from published literature on the use of inhaled or intranasal fluticasone propionate in pregnant women have not reported a clear association with adverse developmental outcomes. Fetal abnormalities have been reported in the off-spring of mice, rats, and rabbits exposed to the medications during gestation. Teratogenicity characteristic of corticosteroids, decreased fetal body weight, and skeletal variations was noted in the off-spring of mice, rats, and rabbits exposed to subcutaneous fluticasone at doses less than the maximum recommended human daily inhaled dose (MRHDID) on a mg/m2 basis. When inhaled fluticasone propionate was administered to rats, fetal body weight was decreased, but teratogenicity was not induced at a maternal toxic dose approximately 0.13 times the MRHDID (on a mg/m2 basis with a maternal inhalation dose of 25.7 mcg/kg/day). Experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroid exposure than are humans. Inhaled corticosteroids are often preferred over systemic corticosteroids when use cannot be avoided for the management of asthma during pregnancy. 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 during pregnancy are limited. However, dose titration may be considered for those with moderate to severe persistent asthma, preferably using budesonide. Due to the availability of safety information during pregnancy, budesonide is preferred over other inhaled corticosteroids. 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. Similarly, other fluticasone formulations, such as intranasal fluticasone, should be avoided unless the potential therapeutic benefit justifies the added risk to the fetus. Fluorinated topical corticosteroid creams and ointments, like fluticasone, are not recommended for use in pregnancy. Lower potency topical corticosteroids are usually used, if needed.

    Fluticasone via inhalation typically results in low systemic concentrations; therefore, the amount excreted into breast-milk after inhalation or nasal use is expected to be very low. Reviewers and an expert panel consider inhaled and oral corticosteroids acceptable to use during breast-feeding. Low-dose inhaled corticosteroids are considered first line therapy for control of mild persistent asthma during lactation. Due to greater availability of data, budesonide is the preferred agent in this population. 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. It is not known whether topical administration of fluticasone could result in sufficient systemic absorption to produce detectable quantities in breast milk. However, most dermatologists stress that topical corticosteroids can be safely used during lactation and breast-feeding. If applied topically, care should be used to ensure the infant will not come into direct contact with the area of application, such as the breast. Increased blood pressure has been reported in an infant whose mother applied a high potency topical corticosteroid ointment directly to the nipples. 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 ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Topical corticosteroids exhibit anti-inflammatory, antipruritic, and vasoconstrictive properties. At the cellular level, corticosteroids induce peptides called lipocortins. Lipocortins antagonize phospholipase A2, an enzyme which causes the breakdown of leukocyte lysosomal membranes to release arachidonic acid. This action decreases the subsequent formation and release of endogenous inflammatory mediators including prostaglandins, kinins, histamine, liposomal enzymes and the complement system. Early anti-inflammatory effects of topical corticosteroids include the inhibition of macrophage and leukocyte movement and activity in the inflamed area by reversing vascular dilation and permeability. Later inflammatory processes such as capillary production, collagen deposition, keloid (scar) formation also are inhibited by corticosteroids. Clinically, these actions correspond to decreased edema, erythema, pruritus, plaque formation and scaling of the affected skin.
     
    In the treatment of asthma, orally inhaled corticosteroids block the late phase allergic response to allergens. Mediators involved in the pathogenesis of asthma include histamine, leukotrienes (slow releasing substance of anaphylaxis, SRS-A), eosinophil chemotactic factor of anaphylaxis (ECF-A), neutrophil chemotactic factor (NCF), cytokines, hydroxyeicosatetraenoic acids, prostaglandin-generating factor of anaphylaxis (PGF-A), prostaglandins, major basic protein, bradykinin, adenosine, peroxides, and superoxide anions. Different cell types are responsible for release of these mediators including airway epithelium, eosinophils, basophils, lung parenchyma, lymphocytes, macrophages, mast cells, neutrophils, and platelets. Corticosteroids inhibit the release of these mediators as well as inhibit IgE synthesis, attenuate mucous secretion and eicosanoid generation, up-regulate beta-receptors, promote vasoconstriction, and suppress inflammatory cell influx and inflammatory processes. Clinical effects in asthma include a reduction in bronchial hyperresponsiveness to allergens, a decreased number of asthma exacerbations, and an improvement in FEV1, peak-flow rate, and respiratory symptoms. Since corticosteroid effects take several hours to days to become clinically noticeable, they are ineffective for primary treatment of severe acute bronchospastic attacks or for status asthmaticus. Inhaled corticosteroids have no bronchodilatory properties.
     
    In the treatment of allergies, intranasal fluticasone reduces allergic responses of several cell types (e.g., mast cells and eosinophils) involved in the allergic response by the same cellular mechanism as the topical corticosteroids. Clinically, symptoms such as rhinorrhea and postnasal drip, nasal congestion, sneezing, and pharyngeal itching are reduced. In vitro studies indicate that the binding affinity of fluticasone furoate for the human glucocorticoid receptor is 1.7 and 29.9 times that of fluticasone propionate and dexamethasone, respectively. The clinical significance of these findings is currently unknown.
     
    In the treatment of nasal polyps, the precise mechanism through which intranasal fluticasone propionate affects nasal polyps and associated inflammatory symptoms is not known. Corticosteroids have been shown to have a wide range of effects on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) involved in inflammation. The anti-inflammatory action of corticosteroids contributes to their efficacy. In 7 trials in adults, fluticasone propionate nasal spray decreased nasal mucosal eosinophils in 66% of patients (35% for placebo) and basophils in 39% of patients (28% for placebo). In addition, studies suggest that carbon dioxide, which is present in the exhaled breath delivered into the nose through the device, may influence inflammatory mediator activity and neuropeptide activity, possibly through mechanisms of action that also include removal of nitric oxide, change in pH, or positive pressure. The direct relationship of these findings to long-term symptom relief is not known.

    PHARMACOKINETICS

    Fluticasone is administered by oral respiratory inhalation, intranasal spray, or by topical application to the skin. Based on studies using intravenous fluticasone propionate, the average volume of distribution (Vd) is 4.2 L/kg (range 2.3 to 16.7 L/kg) and distribution is rapid because of high lipid solubility and tissue binding. Protein binding of fluticasone is more than 90%. The drug is weakly and reversibly bound to erythrocytes and is not significantly bound to human transcortin. The only circulating metabolite of fluticasone detected in man is the 17beta-carboxylic acid derivative, which is formed through the CYP3A4 pathway; this metabolite has negligible pharmacologic activity. Excretion is primarily in the feces as parent drug and metabolites; less than 5% of a dose is excreted in the urine as metabolites. The terminal elimination half-life is approximately 7.8 hours; the half-life of intravenous fluticasone furoate averages 15 hours while half-life after oral inhalation averages 11.2 to 24 hours.
     
    Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP3A4
    The potential for fluticasone to inhibit or induce metabolic enzymes and transporter systems is negligible at low respiratory inhalation doses. However, fluticasone is a substrate of CYP3A4, and systemic exposure after oral inhalational use may increase when coadministered with strong inhibitors of CYP3A4, potentially resulting in a reduction of mean serum cortisol concentrations. Coadministration of inhaled fluticasone propionate and a strong inhibitor of CYP3A4 is not recommended; use caution with inhaled fluticasone furoate.

    Topical Route

    While systemic absorption is usually minimal, topical corticosteroids can penetrate normal intact skin; however, inflammation, skin disease, and occlusive dressing may enhance absorption. In a study of 12 healthy males, 12.5 grams of 0.05% fluticasone propionate cream twice daily for 3 weeks resulted in undetectable plasma concentrations (less than 0.05 ng/mL). In another study of 6 healthy volunteers, 25 grams of the same formulation under occlusion for 5 days yielded plasma concentrations of 0.07 to 0.39 ng/mL. When 25 grams of 0.0005% fluticasone propionate ointment was applied to healthy volunteers twice daily for 5 days under occlusion, plasma concentrations ranged from 0.08 to 0.22 ng/mL. In a rat model, 80% of radiolabeled 0.05% fluticasone propionate cream or ointment (1 g/kg over 24 hours) was recovered at the end of 7 days; 73% was found at the application site surface, less than 1% was in the skin, and approximately 5% was absorbed systemically. Skin absorption continued for the length of the trial, indicating long retention time at the application site.

    Inhalation Route

    Orally inhaled fluticasone acts locally in the lung; therefore, plasma concentrations do not predict therapeutic effect.
     
    Fluticasone propionate aerosol (e.g., Flovent HFA)
    Oral systemic bioavailability of fluticasone propionate is negligible (less than 1%), primarily due to incomplete absorption and first pass metabolism in the gut and liver. In contrast, the majority of the drug delivered to the lung is systemically absorbed. In a pharmacokinetic analysis of 215 patients receiving fluticasone metered-dose inhaler (MDI) 88 mcg twice daily, the mean peak plasma concentration (Cmax) at steady state was 20 pg/mL in patients 12 years and older; data indicated a dose-related increase in systemic exposure. Patients receiving fluticasone MDI 220 mcg (n = 15) or 440 mcg (n = 17) twice daily yielded a mean Cmax of 47.3 pg/mL and 87 pg/mL at steady state, respectively.
     
    Fluticasone propionate inhalation powder (e.g., Flovent Diskus)
    Oral systemic bioavailability of fluticasone propionate is negligible (less than 1%), primarily due to incomplete absorption and first pass metabolism in the gut and liver. In contrast, the majority of the drug delivered to the lung is systemically absorbed. The absolute bioavailability of fluticasone propionate dry powder inhaler (DPI) averages 7.8%.
     
    Fluticasone furoate inhalation powder (e.g., Arnuity Ellipta)
    Oral systemic bioavailability of fluticasone furoate is negligible (approximately 1%), primarily due to incomplete absorption and first pass metabolism in the gut and liver. The absolute bioavailability of fluticasone furoate dry powder inhaler (DPI) is 14%, primarily due to absorption of the inhaled portion of the dose delivered to the lung. Peak plasma concentrations are obtained 0.5 to 1 hour after administration. Systemic exposure (AUC) in subjects with asthma is 26% lower than observed in healthy patients. At steady state, the rate and extent of systemic exposure in children aged 5 to 11 years were comparable to that observed in adult and adolescent patients after dosing with fluticasone furoate 100 mcg monotherapy.
     
    Fluticasone propionate inhalation powder (e.g., Armonair Respiclick)
    Oral systemic bioavailability of fluticasone propionate is negligible (approximately 1%), primarily due to incomplete absorption and first pass metabolism in the gut and liver. Peak plasma concentrations are obtained 1 hour after administration.

    Other Route(s)

    Intranasal Route
    Fluticasone furoate nasal spray (e.g., Flonase Sensimist)
    The average absolute bioavailability of intranasal fluticasone fluticasone furoate is less than 0.5%. Most of an intranasal fluticasone dose is swallowed; studies using oral dosing have demonstrated systemic bioavailability is less than 1% due to incomplete absorption in the gut and first pass metabolism in the liver.
     
    Fluticasone propionate nasal spray (e.g., Flonase)
    The average absolute bioavailability of intranasal fluticasone propionate is less than 2%.
     
    Fluticasone propionate nasal spray (e.g., Xhance)
    Due to the low bioavailability by the intranasal route, the majority of the pharmacokinetic data were obtained via other routes of administration. Local exposure within the nasal cavity with this product will differ when used without exhalation through the device. The mean (SD) peak exposure (Cmax) and total exposure (AUC) following administration of fluticasone propionate 186 mcg during exhalation were 17.2 +/- 7.40 pg/mL and 111.7 +/- 49.75 pg x hours/mL, respectively, and were 25.3 +/- 10.34 pg/mL and 171.7 +/- 85.55 pg x hours/mL, respectively, following a dose of fluticasone propionate 372 mcg in healthy subjects. The Cmax and AUC following a dose of fluticasone propionate 372 mcg in patients with mild to moderate asthma were 28.7 +/- 18.72 pg/mL and 222.6 +/- 84.60 pg x hours/mL, respectively.