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  • CLASSES

    Systemic Corticosteroids, Plain

    DEA CLASS

    Rx

    DESCRIPTION

    Oral and parenteral synthetic glucocorticoid; little mineralocorticoid activity; similar potency to prednisone; commonly used parenterally when patient cannot take oral prednisone.

    COMMON BRAND NAMES

    A-Methapred, Depmedalone-40, Depmedalone-80, Depo-Medrol, Medrol, Medrol Dosepak, Solu-Medrol

    HOW SUPPLIED

    A-Methapred/Methylprednisolone/Methylprednisolone Sodium Succinate/Solu-Medrol Intramuscular Inj Pwd F/Sol: 1g, 2g, 40mg, 125mg, 500mg
    A-Methapred/Methylprednisolone/Methylprednisolone Sodium Succinate/Solu-Medrol Intravenous Inj Pwd F/Sol: 1g, 2g, 40mg, 125mg, 500mg
    Depmedalone-40/Depmedalone-80/Depo-Medrol/Methylprednisolone/Methylprednisolone Acetate Intralesional Inj Susp: 1mL, 40mg, 80mg
    Depmedalone-40/Depmedalone-80/Depo-Medrol/Methylprednisolone/Methylprednisolone Acetate Intramuscular Inj Susp: 1mL, 20mg, 40mg, 80mg
    Depmedalone-40/Depmedalone-80/Depo-Medrol/Methylprednisolone/Methylprednisolone Acetate Intrasynovial Inj Susp: 1mL, 20mg, 40mg, 80mg
    Depmedalone-40/Depmedalone-80/Depo-Medrol/Methylprednisolone/Methylprednisolone Acetate Soft Tissue Inj Susp: 1mL, 40mg, 80mg
    Depo-Medrol Intra-Articular Inj Susp: 1mL, 40mg, 80mg
    Medrol/Medrol Dosepak/Methylprednisolone Oral Tab: 2mg, 4mg, 8mg, 16mg, 32mg

    DOSAGE & INDICATIONS

    For the treatment of status asthmaticus.
    Intravenous or Intramuscular dosage (methylprednisolone sodium succinate)
    Adults

    40 to 80 mg/day IV or IM in 1 to 2 divided doses until peak expiratory flow is 70% of predicted or personal best is recommended by the current National Asthma Education and Prevention Program (NAEPP) guidelines.

    Infants, Children, and Adolescents

    2 mg/kg IV or IM load (Max: 60 mg/dose), then 0.5 mg/kg/dose IV every 6 hours or 1 mg/kg/dose IV every 12 hours (Max: 120 mg/day). Some experts recommend 0.5 to 1 mg/kg/dose IV every 4 to 6 hours.

    For the treatment of asthma.
    For a moderate to severe asthma exacerbation in the emergency department or the hospital.
    Oral dosage
    Adults, Adolescents, and Children 12 years and older

    40 mg PO once daily in the morning for 5 to 7 days is adequate for most patients. Alternatively, 40 to 80 mg/day PO or IV in 1 to 2 divided doses until peak expiratory flow is 70% of predicted or personal best may be used. Total course of treatment may range from 3 to 10 days.

    Infants and Children 11 years and younger

    1 to 2 mg/kg/day PO in 2 divided doses (Max: 40 to 60 mg/day) for 3 to 5 days is usually sufficient. Continue until peak expiratory flow is 70% of predicted or personal best.

    Intravenous or Intramuscular dosage (methylprednisolone sodium succinate)
    Adults, Adolescents, and Children 12 years and older

    40 mg IV or IM once daily in the morning for 5 to 7 days is adequate for most patients. Alternatively, 40 to 80 mg/day IV or IM in 1 to 2 divided doses until peak expiratory flow is 70% of predicted or personal best is recommended by the National Asthma Education and Prevention Program (NAEPP) guidelines. Change to oral therapy as soon as feasible. Oral administration of corticosteroids has been shown to have equivalent efficacy to that of parenteral methylprednisolone and is preferred because it is less invasive.

    Infants and Children 11 years and younger

    1 to 2 mg/kg/day IV or IM in 2 divided doses (Max: 60 mg/day) until peak expiratory flow is 70% of predicted or personal best is recommended by the current National Asthma Education and Prevention Program (NAEPP) guidelines. However, both the current Global Initiative for Asthma (GINA) and previous NAEPP guidelines recommended 1 mg/kg/dose every 6 hours for the first 24 and 48 hours, respectively, and this regimen is still commonly used in clinical practice. Change to oral therapy as soon as feasible. Oral administration of corticosteroids has been shown to have equivalent efficacy to that of parenteral methylprednisolone and is preferred because it is less invasive.

    For an acute asthma exacerbation on an outpatient basis.
    Oral dosage
    Adults, Adolescents, and Children 12 years and older

    40 to 60 mg/day PO in 1 to 2 divided doses for 5 to 10 days.

    Infants and Children 11 years and younger

    1 to 2 mg/kg/day PO in 1 to 2 divided doses (Max: 60 mg/day) for 3 to 10 days or until patient achieves peak expiratory flow of 80% or personal best or symptoms resolve; a 3 to 5 day course is usually sufficient.

    Intramuscular dosage (methylprednisolone acetate injection suspension, e.g., Depo-Medrol)
    Adults, Adolescents, and Children 5 years and older

    240 mg IM once may be used in place of a short burst of oral steroids for patients who are vomiting or if compliance is an issue.

    Infants and Children 4 years and younger

    7.5 mg/kg IM once (Max: 240 mg/dose) may be used in place of a short burst of oral steroids for patients who are vomiting or if compliance is an issue.

    For long-term prevention of symptoms in severe persistent asthma.
    Oral dosage
    Adults, Adolescents, and Children 12 years and older

    7.5 to 60 mg PO administered once daily in the morning or as alternate-day therapy as needed for symptom control.

    Infants and Children 11 years and younger

    0.25 to 2 mg/kg/day PO administered once daily in the morning or as alternate-day therapy as needed for symptom control (Max: 60 mg/day).

    For the treatment of the acute respiratory distress syndrome (ARDS).
    Intravenous (methylprednisolone sodium succinate injection) and Oral dosage
    Adults

    Corticosteroid use in ARDS is controversial. If there are no signs of improvement 7 to 14 days after ARDS onset, 1.6 to 3.2 mg/kg/day IV in divided doses for 7 to 14 days has been recommended. Alternatively, a tapered dosage (2 mg/kg/day on days 1 to 14; 1 mg/kg/day on days 15 to 21; 0.5 mg/kg/day on days 22 to 28; 0.25 mg/kg/day on days 29 to 30; 0.125 mg/kg/day on days 31 to 32) is used. Initiate with the IV route, given in 4 divided doses; PO doses are administered as a single daily dose.

    For the management of symptomatic sarcoidosis.
    Oral dosage
    Adults

    Initially, 24 to 32 mg PO per day. Alternatively, 40 to 48 mg PO every other day has also been used. Taper after several weeks to the lowest effective maintenance dose (often 8 to 12 mg PO every other day). Treatment with corticosteroids is usually indicated only if elevated calcium is present or if there is a decline in the function of a vital organ (lungs, kidneys, eyes, heart, or CNS).

    Intravenous dosage (methylprednisolone sodium succinate)
    Adults

    A dose of 30 mg/kg IV once a week for 6 weeks, with or without oral maintenance corticosteroid therapy, has been used. Therapy produced immediate improvement in all patients, however, 66% relapsed 1 year later. One patient without oral maintenance corticosteroids and 3 patients with oral maintenance corticosteroids showed persistent improvement. Treatment with corticosteroids is usually indicated only if elevated calcium is present or if there is a decline in the function of a vital organ (lungs, kidneys, eyes, heart, or CNS).

    For the treatment of a critical period of regional enteritis (Crohn's disease) or ulcerative colitis.
    Intravenous or Intramuscular dosage (methylprednisolone sodium succinate injection)
    Adults

    0.75 to 1 mg/kg/day IV (Max: 60 to 80 mg/day IV). Maximum recommended duration at full dose is 2 weeks; switch to oral therapy once a response is achieved, then taper over 8 to 12 weeks. Systemic corticosteroids are helpful to induce remission. Because of the potential complications of steroid use, steroids should be used selectively and in the lowest dose possible for the shortest duration as possible.

    Children and Adolescents

    1 to 1.5 mg/kg/day (Max: 60 mg/day) IV or IM in 1 to 2 divided doses for 2 to 4 weeks; transition to oral corticosteroids as soon as feasible and slowly taper over several weeks after response achieved. Pulse methylprednisolone therapy (20 to 30 mg/kg/day [Max: 1 gram/day] IV for 3 days) has also been used successfully to induce remission in children with moderate to severe ulcerative colitis. Because of the potential complications of steroid use, steroids should be used selectively and in the lowest dose possible for the shortest duration as possible.

    Oral dosage
    Adults

    4 to 48 mg PO per day, administered in 4 divided doses is the general FDA-approved dose range. A methylprednisolone dose of 48 mg/day PO in divided doses, once response is achieved with IV, is suggested. Maximum recommended duration at full dose is 2 weeks. Thereafter, tapering by 4 to 8 mg/week until complete discontinuation within 8 to 12 weeks is recommended. Systemic corticosteroids are helpful to induce remission. Because of the potential complications of steroid use, steroids should be used selectively and in the lowest dose possible for the shortest duration as possible.

    Children and Adolescents

    1 to 1.5 mg/kg/day (Max: 60 mg/day) PO in 1 to 2 divided doses for 2 to 4 weeks, followed by a slow taper over several weeks after response achieved, has been suggested for inflammatory bowel disease in pediatrics. Usual pediatric dose range: 0.5 to 1.7 mg/kg/day PO given in divided doses. Because of the potential complications of steroid use, steroids should be used selectively and in the lowest dose possible for the shortest duration as possible.

    For the treatment of allergic disorders including anaphylaxis or anaphylactoid reactions, angioedema, acute noninfectious laryngeal edema, hypersensitivity reactions (drug or food allergy), urticaria, serum sickness, and severe perennial allergies or seasonal allergies, including allergic rhinitis.
    For non-emergent treatment of hypersensitivity or allergic conditions.
    Oral dosage
    Adults

    4 to 48 mg, depending on disease treated, PO per day administered in 4 divided doses.

    Infants, Children, and Adolescents

    0.11 to 2 mg/kg/day PO, IV, or IM in 1 to 4 divided doses is the general initial dose range for methylprednisolone.

    Intramuscular dosage (methylprednisolone acetate injection suspension)
    Adults

    10 to 120 mg IM. Subsequent IM doses are determined by response and condition.

    Children and Adolescents

    0.5 to 1.7 mg/kg/day IM (a single injection during each 24-hour period equal to the total daily oral dose is usually sufficient). Determine need for repeat IM doses based on condition and patient response.

    For the urgent treatment of severe conditions like anaphylaxis, angioedema, or urticarial transfusion-related reactions.
    Intravenous dosage (methylprednisolone sodium succinate)
    Adults

    For anaphylaxis, 1 to 2 mg/kg/dose IV (Max: 125 mg/dose). The general dosage range in the FDA-approved product label is 10 to 40 mg IV infused over several minutes. Subsequent doses are determined by response and condition. Corticosteroids are not indicated as initial treatment for anaphylaxis, but can be given as adjunctive therapy after the administration of epinephrine. For drug-induced angioedema failing to respond to epinephrine or H1-blockers, short courses of 40 to 120 mg/day IV can be given for the late phase of an acute reaction.

    Infants, Children, and Adolescents

    1 to 2 mg/kg/dose IV (Max: 125 mg/dose). Corticosteroids are not indicated as initial treatment for anaphylaxis, but can be given as adjunctive therapy after the administration of epinephrine.

    For the treatment of corticosteroid-responsive dermatologic disorders (e.g., alopecia areata, atopic dermatitis, bullous dermatitis herpetiformis, contact dermatitis including Rhus dermatitis due to poison ivy, poison oak, poison sumac, discoid lupus erythematosus, eczema, exfoliative dermatitis, insect bites or stings, granuloma annulare, keloids, lichen striatus, lichen planus, lichen simplex, mycosis fungoides, necrobiosis lipoidica diabeticorum, pemphigus, pityriasis rosea, polymorphous light eruption, pruritus, psoriasis, seborrheic dermatitis, or xerosis).
    For mild-moderate corticosteroid responsive dermatoses.
    Oral dosage
    Adults

    4 to 48 mg, depending on disease treated, PO per day administered in 4 divided doses.

    Children and Adolescents

    0.5 to 1.7 mg/kg/day PO, given in divided doses every 6 to 12 hours.

    For severe inflammatory dermatoses, like exfoliative dermatitis, erythema multiforme or Stevens-Johnson syndrome, or psoriasis not responding to topical therapy.
    Intramuscular or Intravenous dosage (methylprednisolone sodium succinate injection)
    Adults

    Initially, 10 to 40 mg IV or IM. Subsequent IV/IM doses are determined by response and condition.

    Children and Adolescents

    In pediatric patients, the initial dose range is 0.11 to 1.6 mg/kg/day IV or IM in 3 or 4 divided doses (3.2 to 48 mg/m2/day). Adjust to patient condition and response.

    Intramuscular dosage (methylprednisolone acetate injection suspension)
    Adults

    10 to 120 mg IM. Subsequent doses may be given determined by patient response and condition.

    Children and Adolescents

    0.5 to 1.7 mg/kg/day IM (a single injection during each 24-hour period equal to the total daily oral dose is usually sufficient). Determine need for repeat IM doses based on condition and patient response.

    For the treatment of acute exacerbations of multiple sclerosis.
    Oral dosage
    Adults

    Methylprednisolone based regimen is 160 mg PO per day for 1 week, followed by 64 mg PO every other day for 1 month (dosing is determined by converting the effective prednisolone dose to methylprednisolone; each 4 mg of methylprednisolone is equivalent to 5 mg of prednisolone).

    For the treatment of myasthenia gravis in patients who are poorly controlled with cholinesterase inhibitor therapy.
    Oral dosage
    Adults and Adolescents

    Initially, 12 to 20 mg PO per day. Increase, as needed, by 4 mg PO every 2 to 3 days until there is marked clinical improvement or to a maximum of 40 mg/day PO. Dose is usually continued for 1 to 3 months and then is gradually tapered to an alternate-day dosage. Some clinicians use initial dosages of 48 to 64 mg PO per day with gradual tapering. Although higher initial dosages may provide more rapid benefit, early exacerbations of myasthenic weakness may be more common than with lower initial dosages. The methylprednisolone dosage listed is based on a recommended prednisone dose converted to an equivalent methylprednisolone dose.

    For the treatment of hypercalcemia associated with certain types of cancer.
    Oral dosage
    Adults

    32 to 80 mg PO per day is usually effective for hypercalcemia due to hematologic cancers. 12 to 24 mg PO per day may be sufficient for other tumors (e.g., breast cancer). The dosage listed is based on a recommended prednisone dose converted to an equivalent methylprednisolone dose.

    For the treatment of non-neoplastic hematologic disorders including immune thrombocytopenic purpura (ITP), secondary thrombocytopenia in adults, acquired (autoimmune) hemolytic anemia, erythroblastopenia (RBC anemia), and congenital hypoplastic anemia.
    Oral dosage
    Adults

    4 to 48 mg/day PO, administered in 4 divided doses. Adjust to severity of condition and patient response.

    Children

    0.5 to 1.7 mg/kg/day PO, given in divided doses every 6 to 12 hours.

    Intravenous or Intramuscular dosage (methylprednisolone sodium succinate injection)
    Adults

    Initially, 10 to 40 mg IV or IM. Subsequent IV/IM doses are determined by response and condition. IM administration is contraindicated in patients with ITP.

    Children

    In pediatric patients, the initial dose range is 0.11 to 1.6 mg/kg/day IV or IM in 3 or 4 divided doses (3.2 to 48 mg/m2/day). Adjust to patient condition and response. IM administration is contraindicated in ITP.

    For the treatment of adrenocortical function abnormalities, such as adrenocortical insufficiency, congenital adrenal hyperplasia (CAH), chronic primary (Addison's disease) or secondary adrenocortical insufficiency, or adrenogenital syndrome.
    Oral dosage
    Adults

    4 to 48 mg/day PO, administered in 4 divided doses. Adjust depending on severity of the condition treated and patient response. Hydrocortisone and cortisone are the preferred drugs; methylprednisolone has little to no mineralocorticoid properties. For acute conditions, parenteral therapy is recommended. Dosing is highly variable.

    Children

    0.5 to 1.7 mg/kg/day PO, given in divided doses every 6 to 12 hours. Hydrocortisone and cortisone are the preferred drugs; methylprednisolone has little to no mineralocorticoid properties. For acute conditions, parenteral therapy is recommended. Dosing is highly variable.

    Intravenous or intramuscular dosage (methylprednisolone sodium succinate injection)
    Adults

    Initially, 10 to 40 mg IV. Subsequent IV/IM doses are determined by response and condition. Hydrocortisone and cortisone are the preferred drugs; methylprednisolone has little to no mineralocorticoid properties. For acute conditions, parenteral therapy is recommended. Dosing is highly variable.

    Children

    In pediatric patients, the initial dose range is 0.11 to 1.6 mg/kg/day IV or IM in 3 or 4 divided doses (3.2 to 48 mg/m2/day). Hydrocortisone and cortisone are the preferred drugs; methylprednisolone has little to no mineralocorticoid properties. For acute conditions, parenteral therapy is recommended. Dosing is highly variable.

    For the treatment of complicated or disseminated pulmonary tuberculosis infection (i.e., tuberculous meningitis and pericarditis) as adjunctive therapy in combination with antituberculous therapy.
    Oral dosage
    Adults

    FDA-approved initial dose is 4 to 48 mg/day PO in divided doses. Adjunctive corticosteroid therapy has been shown to improve survival for patients with tuberculosis involving the CNS and pericardium, but has not been universally recommended by guidelines for all forms of tuberculosis. Initial doses in clinical trials for tuberculosis in general use the following doses: 48 mg/day PO daily for 4 weeks or 20 mg/kg/day IV for weight of 50 kg or less or 1 gram/day IV for weight greater than 50 kg for 5 days; many trials were prior to the use of rifampin, which may decrease bioavailability and increase plasma clearance of corticosteroids. A meta-analysis suggests that steroid use may reduce mortality in all forms of tuberculosis, which may be influenced by genetic variation at the LTA4H gene.

    Children and Adolescents

    0.5 to 1.7 mg/kg/day PO, given in divided doses every 6 to 12 hours.

    Intramuscular or Intravenous dosage (methylprednisolone sodium succinate injection)
    Adults

    FDA-approved initial dose is 10 to 40 mg IM or IV, with subsequent doses and adjustments depending upon the disease being treated. When high-dose therapy is desired, the recommended dose is 30 mg/kg administered IV over at least 30 minutes. This dose may be repeated every 4 to 6 hours for 48 hours. Adjunctive corticosteroid therapy has been shown to improve survival for patients with tuberculosis involving the CNS and pericardium, but has not been universally recommended by guidelines for all forms of tuberculosis. Initial doses in clinical trials for tuberculosis in general use the following doses: 48 mg/day PO daily for 4 weeks or 20 mg/kg/day IV for weight of 50 kg or less or 1 gram/day IV for weight greater than 50 kg for 5 days; many trials were prior to the use of rifampin, which may decrease bioavailability and increase plasma clearance of corticosteroids. A meta-analysis suggests that steroid use may reduce mortality in all forms of tuberculosis, which may be influenced by genetic variation at the LTA4H gene.

    Children and Adolescents

    In pediatric patients, the initial dose range is 0.11 to 1.6 mg/kg/day IV or IM in 3 or 4 divided doses (3.2 to 48 mg/m2/day). Adjust to patient condition and response.

    Intramuscular dosage (methylprednisolone acetate injection suspension)
    Adults

    The FDA-approved dose is 4 to 120 mg IM per day, depending upon the disease being treated. Adjunctive corticosteroid therapy has been shown to improve survival for patients with tuberculosis involving the CNS and pericardium, but has not been universally recommended by guidelines for all forms of tuberculosis. Trials have mostly involved use of oral or intravenous dose forms, using oral dosing for 4 weeks or intravenous administration for 5 days. A meta-analysis suggests that steroid use may reduce mortality in all forms of tuberculosis, which may be influenced by genetic variation at the LTA4H gene.

    Children and Adolescents

    0.5 to 1.7 mg/kg/day IM (a single injection during each 24-hour period equal to the total daily oral dose is usually sufficient). Determine need for repeat IM doses based on condition and patient response.

    For the treatment of trichinosis with neurologic or myocardial involvement.
    Oral or Intravenous dosage
    Adults

    The optimal dosage has not been established; critically-ill patients may require high doses (e.g., 48 mg PO or IV per day) for 2 or more weeks. The dosage listed is based on a recommended prednisone dose converted to an equivalent methylprednisolone dose.

    For the treatment of nonsuppurative thyroiditis.
    Oral dosage
    Adults

    Glucocorticoids are reserved for severe cases. Although prednisone is commonly used, a methylprednisolone dosage of 16 to 32 mg/day PO has similar potency.

    For the treatment of acute kidney transplant rejection.
    Intravenous dosage (methylprednisolone sodium succinate injection)
    Adults, Adolescents and Children

    250 to 1,000 mg IV given once daily or on alternate days for 3 to 5 doses. Renal transplant guidelines recommend corticosteroids for the initial treatment of acute rejection.

    For the treatment of proteinuria to induce diuresis or promote remission in the nephrotic syndrome, without uremia, of the idiopathic type or due to lupus nephritis.
    For induction treatment of lupus nephritis.
    Intravenous dosage (methylprednisolone sodium succinate injection)
    Adults

    Guidelines suggest methylprednisolone 500 to 1,000 mg/day IV for 3 doses, followed by 0.5 to 1 mg/kg/day PO prednisone which is then tapered after a few weeks to lowest effective dose that controls the disease. Used in combination with other induction agents, depending on the severity of the disease.

    Oral dosage
    Adults

    4 to 48 mg, depending on disease treated, PO per day administered in 4 divided doses.

    Children and Adolescents

    0.5 to 1.7 mg/kg/day PO, given in divided doses every 6 to 12 hours.

    Intravenous or Intramuscular dosage
    Adults

    Initially, 10 to 40 mg IV or IM. Subsequent IV/IM doses are determined by response and condition.

    Children

    In pediatric patients, the initial dose range is 0.11 to 1.6 mg/kg/day IV or IM in 3 or 4 divided doses (3.2 to 48 mg/m2/day). Adjust to patient condition and response.

    Intramuscular dosage (methylprednisolone acetate injection suspension)
    Adults

    10 to 120 mg IM. Frequency of dosing varies with the condition being treated and patient response.

    Children

    0.5 to 1.7 mg/kg/day IM (a single injection during each 24-hour period equal to the total daily oral dose is usually sufficient). Determine need for repeat IM doses based on condition and patient response.

    For the treatment of respiratory conditions including airway-obstructing hemangioma† in infants, aspiration pneumonitis, eosinophilic pneumonia, berylliosis, chronic obstructive pulmonary disease (COPD), Loeffler's syndrome, or noncardiogenic pulmonary edema†.
    For chronic oral management of non-asthmatic respiratory conditions.
    Oral dosage
    Adults

    4 to 48 mg, depending on disease treated, PO per day administered in 4 divided doses.

    Children and Adolescents

    0.5 to 1.7 mg/kg/day PO, given in divided doses every 6 to 12 hours.

    For parenteral management of non-asthmatic respiratory conditions when oral dosing not feasible or severity or compromised airway warrants.
    Intramuscular or Intravenous dosage (methylprednisolone sodium succinate injection)
    Adults

    Initially, 10 to 40 mg IV or IM. Subsequent IV/IM doses are determined by response and condition.

    Children and Adolescents

    In pediatric patients, the initial dose range is 0.11 to 1.6 mg/kg/day IV or IM in 3 or 4 divided doses (3.2 to 48 mg/m2/day). Adjust to patient condition and response.

    Intramuscular dosage (methylprednisolone acetate injection suspension)
    Adults

    10 to 120 mg IM. Frequency of dosing varies with the condition being treated and patient response.

    Children and Adolescents

    0.5 to 1.7 mg/kg/day IM (a single injection during each 24-hour period equal to the total daily oral dose is usually sufficient). Determine need for repeat IM doses based on condition and patient response.

    For chronic maintenance therapy for idiopathic pulmonary fibrosis†.
    Intravenous dosage (methylprednisolone sodium succinate injection)
    Adults

    High-dose (pulse doses) of 1 to 2 grams IV once weekly or every other week; however, there is no proven advantage over oral corticosteroids.

    For the treatment of laryngotracheobronchitis (croup)†.
    Intravenous or Intramuscular dosage (methylprednisolone sodium succinate)
    Infants and Children

    1 to 2 mg/kg/dose IV or IM as an initial dose. Continued or maximum dosing is not specified; however, continued corticosteroid dosing may be warranted to ensure a sustained effect on airway patency. Of note, prednisolone has a similar biological half-life as methylprednisolone and, when prescribed for mild to moderate croup, is often continued for a total of 2 to 3 days.

    For the treatment of acute spinal cord injury†.
    Intravenous infusion dosage (methylprednisolone sodium succinate)
    Adults, Adolescents, and Children

    30 mg/kg IV given over 15 minutes, followed 45 minutes later by 5.4 mg/kg/hour IV infusion given for 23 hours. Although not widely employed or recommended, the continuous infusion has been repeated for an additional 23 hours in selected patients. Use has been controversial, as small benefits in mortality, motor function, or sensation have not translated to clinically relevant outcomes for long-term recovery, and treatment may result in an increased risk for adverse events such as embolus, hyperglycemia, or infection.

    For adjunctive therapy in the treatment of rheumatic disorders including acute gouty arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis (JRA)/juvenile idiopathic arthritis (JIA), post-traumatic osteoarthritis, pseudogout†, psoriatic arthritis, or rheumatoid arthritis, or for the treatment of acute episodes or exacerbation of nonrheumatic inflammatory conditions including acute and subacute bursitis, epicondylitis, and acute non-specific tenosynovitis.
    Oral dosage
    Adults

    4 to 48 mg/day PO, administered in 4 divided doses. Adjust to response and severity of condition.

    Children and Adolescents

    0.5 to 1.7 mg/kg/day PO, given in divided doses every 6 to 12 hours.

    Intra-articular injection or Intra-lesional dosage (methylprednisolone acetate injection suspension)
    Adults

    10 to 80 mg at the appropriate site, depending upon degree of inflammation and size and location of affected area. Repeat doses are not usually required for 1 to 5 weeks. Dosage ranges for specific joints: large joints: 20 to 80 mg; medium joints: 10 to 40 mg; small joints: 4 to 10 mg. Suggested intralesional dosage range is 20 to 60 mg.

    Intramuscular or Intravenous dosage (methylprednisolone sodium succinate injection)
    Adults

    Initially, 10 to 40 mg IV or IM. Subsequent IV/IM doses are determined by response and condition.

    Children and Adolescents

    In pediatric patients, the initial dose range is 0.11 to 1.6 mg/kg/day IV or IM in 3 or 4 divided doses (3.2 to 48 mg/m2/day). Adjust to patient condition and response.

    Intramuscular dosage (methylprednisolone acetate injection suspension)
    Adults

    10 to 120 mg IM. Subsequent doses may be given determined by patient response and condition.

    Children and Adolescents

    0.5 to 1.7 mg/kg/day IM (a single injection during each 24-hour period equal to the total daily oral dose is usually sufficient). Determine need for repeat IM doses based on condition and patient response.

    For the treatment of selected cases of acute rheumatic carditis, systemic dermatomyositis (polymyositis), systemic lupus erythematosus (SLE), temporal arteritis, Churg-Strauss syndrome†, mixed connective tissue disease†, polyarteritis nodosa†, relapsing polychondritis†, polymyalgia rheumatica†, vasculitis†, or Wegener's granulomatosis†.
    For routine treatment.
    Oral dosage
    Adults

    4 to 48 mg/day PO, administered in 4 divided doses. Adjust to response and severity of condition.

    Children

    0.5 to 1.7 mg/kg/day PO, given in divided doses every 6 to 12 hours.

    Intramuscular or Intravenous dosage (methylprednisolone sodium succinate injection)
    Adults

    Initially, 10 to 40 mg IV or IM. Subsequent IV/IM doses are determined by response and condition.

    Children

    In pediatric patients, the initial dose range is 0.11 to 1.6 mg/kg/day IV or IM in 3 or 4 divided doses (3.2 to 48 mg/m2/day). Adjust to patient condition and response.

    Intramuscular dosage (methylprednisolone acetate injection suspension)
    Adults

    10 to 120 mg IM. Frequency of dosing varies with the condition and response.

    Children

    0.5 to 1.7 mg/kg/day IM (a single injection during each 24-hour period equal to the total daily oral dose is usually sufficient). Determine need for repeat IM doses based on condition and patient response.

    For the palliative management of leukemia and lymphoma in adults and acute leukemias of childhood including acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), Hodgkin lymphoma, non-Hodgkin's lymphoma (NHL), or multiple myeloma†.
    Oral dosage
    Adults

    4 to 48 mg/day PO, administered in 4 divided doses. Adjust to severity of condition and patient response.

    Children

    0.5 to 1.7 mg/kg/day PO, given in divided doses every 6 to 12 hours.

    Intramuscular or Intravenous dosage (methylprednisolone sodium succinate injection)
    Adults

    Initially, 10 to 40 mg IV or IM. Subsequent IV/IM doses are determined by response and condition.

    Children

    In pediatric patients, the initial dose range is 0.11 to 1.6 mg/kg/day IV or IM in 3 or 4 divided doses (3.2 to 48 mg/m2/day). Adjust to patient condition and response.

    Intramuscular dosage (methylprednisolone acetate injection suspension)
    Adults

    10 to 120 mg IM. Subsequent doses are determined by patient response and condition.

    Children

    0.5 to 1.7 mg/kg/day IM (a single injection during each 24-hour period equal to the total daily oral dose is usually sufficient). Determine need for repeat IM doses based on condition and patient response.

    For the treatment of Pneumocystis pneumonia (PCP)† in HIV patients as adjunctive therapy.
    Intravenous dosage (methylprednisolone sodium succinate injection)
    Adults and Adolescents

    30 mg IV twice daily on days 1 to 5; then 30 mg IV once daily on days 6 to 10; then 15 mg IV once daily on days 11 to 21. Begin therapy as early as possible and within 72 hours of PCP therapy. Corticosteroids are recommended in patients with a PaO2 of less than 70 mmHg at room air or with an alveolar-arterial O2 gradient greater than 35 mmHg. The benefits of corticosteroid therapy started after 72 hours of PCP therapy is unknown, but some clinicians may recommend for moderate-to-severe PCP.

    For the treatment of Severe Acute Respiratory Syndrome (SARS)†.
    Intravenous dosage
    Adults

    A treatment protocol based on the treatment of 31 patients with probable SARS (diagnosed according to WHO criteria) in Hong Kong, suggests methylprednisolone 1 mg/kg IV every 8 hours for 5 days, followed by 1 mg/kg IV every 12 hours for 5 days, in conjunction with ribavirin, and followed by prednisolone PO to complete a 21-day corticosteroid regimen. Another regimen used ribavirin IV with methylprednisolone 240 to 320 mg daily IV in divided doses or hydrocortisone IV (4 mg/kg every 8 hours, tapered to 200 mg every 8 hours). Other than supportive care, there is no established treatment for SARS. Due to lack of efficacy data, ribavirin and methylprednisolone combination therapy should be reserved for patients with the following: extensive or bilateral chest radiographic involvement; persistent chest radiographic involvement and persistent high fever for 2 days; clinical, chest radiographic, or laboratory findings suggestive of worsening; or oxygen saturation less than 95% on room air.

    For the treatment of acute interstitial nephritis (AIN)†.
    Intravenous dosage (methylprednisolone sodium succinate injection)
    Adults

    There is variation in the literature with regard to dosage regimens. Methylprednisolone 125 mg IV every 6 hours for a few days, followed by prednisone or prednisolone tapered over 3 to 6 weeks is commonly reported. Following biopsy to confirm diagnosis, corticosteroids are usually instituted soon afterward. Corticosteroid use is an adjunctive measure; removal of the suspected offending agent /cause is the primary treatment. While many case reports suggest a possible net benefit to the use of corticosteroids for AIN, some experts advocate for more prospective study of their value.

    Children

    There is variation in the literature with regard to dosage regimens. Methylprednisolone 1 mg/kg IV every 6 hours for a few days, followed by oral prednisone or prednisolone tapered over 3 to 6 weeks has been reported.

    For the treatment of acute graft-versus-host disease (GVHD)†.
    Intravenous dosage (methylprednisolone sodium succinate injection)
    Adults, Adolescents and Children

    2 to 2.5 mg/kg/day IV, tapered slowly over 2 to 3 weeks. Initial doses of 10 mg/kg/day IV have also been used; although there is no definitive data that higher doses are more effective than lower doses. For GVHD limited to the skin, an initial dose of 1 mg/kg/day IV may be used. One study indicated that a cumulative methylprednisolone dose of 2,000 mg/m2 (or roughly 50 mg/kg) is required for complete resolution of acute graft-versus-host disease in most patients.

    For the treatment of heart transplant rejection†.
    Intravenous dosage (methylprednisolone sodium succinate injection)
    Adults

    According to guidelines, 250 to 1,000 mg/day IV for 3 days is first line for symptomatic acute cellular rejection irrespective of ISHLT endomyocardial biopsy grade. The regimen should also be used for asymptomatic severe (ISHLT 3R) acute cellular rejection and can be used for for asymptomatic moderate acute cellular rejection (ISHLT 2R). Also consider for hyperacute rejection and for antibody-mediated rejection. A taper can be considered.

    For the systemic treatment of ophthalmic disorders including allergic conjunctivitis, allergic marginal corneal ulcer, anterior segment inflammation, chorioretinitis, endophthalmitis†, Graves' ophthalmopathy, herpes zoster ocular infection (herpes zoster ophthalmicus), iritis, keratitis, postoperative ocular inflammation, optic neuritis, diffuse posterior uveitis, or vernal keratoconjunctivitis.
    Oral dosage
    Adults

    4 to 48 mg/day PO, administered in 4 divided doses. Adjust to condition severity and response.

    Children

    0.5 to 1.7 mg/kg/day PO, given in divided doses every 6 to 12 hours.

    Intramuscular or Intravenous dosage (methylprednisolone sodium succinate)
    Adults

    Initially, 10 to 40 mg IV or IM. Subsequent IV/IM doses are determined by response and condition.

    Children

    In pediatric patients, the initial dose range is 0.11 to 1.6 mg/kg/day IV or IM in 3 or 4 divided doses (3.2 to 48 mg/m2/day). Adjust to patient condition and response.

    Intramuscular dosage (methylprednisolone acetate injection suspension)
    Adults

    10 to 120 mg IM. Subsequent doses are determined by response and condition.

    Children

    0.5 to 1.7 mg/kg/day IM (a single injection during each 24-hour period equal to the total daily oral dose is usually sufficient). Determine need for repeat IM doses based on condition and patient response.

    For adjunctive therapy in the treatment of carpal tunnel syndrome†.
    Local injection (methylprednisolone acetate injection suspension)
    Adults

    40 to 80 mg as a single injection adjacent to the carpal tunnel. Reassess at 6 to 8 weeks. To avoid median-nerve injury, use specialized administration techniques. Use of 2 or more repeat injections is not advised; local tendon damage may occur. The definitive treatment for median-nerve entrapment is surgery. Corticosteroids are temporary measures; patients who have intermittent pain and paresthesias without any fixed motor-sensory deficits may respond to conservative therapy.

    For the treatment of IVIG-refractory Kawasaki disease†.
    Intravenous or Intramuscular dosage (methylprednisolone sodium succinate injection)
    Infants, Children, and Adolescents

    30 mg/kg/dose (Max: 1 gram/dose) IV or IM once daily for 1 to 3 days. High-dose pulse steroids may be considered as an alternative to a second infusion of IVIG or for retreatment of patients who have had recurrent or recrudescent fever after additional IVIG, but should not be used as routine primary therapy with IVIG in patients with Kawasaki disease. Corticosteroid treatment has been shown to shorten the duration of fever in patients with IVIG-refractory Kawasaki disease or patients at high risk for IVIG-refractory disease. A reduction in the frequency and severity of coronary artery lesions has also been reported with pulse dose methylprednisolone treatment.

    For fat embolism syndrome prophylaxis†.
    Intravenous dosage
    Adults

    Dosage not established. 1 or 1.5 mg/kg IV every 8 hours for 6 doses or 30 mg/kg IV every 4 hours for 2 doses has been used.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Corticosteroid dosage must be individualized and is highly variable depending on the nature and severity of the disease, route of treatment, and on patient response.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Systemic dosage may need adjustment depending on the degree of hepatic insufficiency, but quantitative recommendations are not available.

    Renal Impairment

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

    ADMINISTRATION

    NOTE: Dosage must be individualized and is very variable depending on the nature and severity of the disease, and on the patients response. If therapy is continued for more than a few days, withdrawal must be gradual.
     

    Oral Administration

    Administer methylprednisolone with meals to minimize indigestion or GI irritation. If given once daily or every other day, administer in the morning to coincide with the body's normal cortisol secretion.
    For 'Dose-Packs': Follow the administration and dose titration schedule as indicated on the package.

    Injectable Administration

    NOTE: Only methylprednisolone sodium succinate (Solu-Medrol) may be administered intravenously. NEVER administer methylprednisolone acetate suspension (Depo-Medrol, Sano-Drol, Methacort, Cortimed, and others) intravenously.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Direct intravenous injection:
    Use only methylprednisolone sodium succinate.
    Reconstitute with provided diluent or add 2 ml of bacteriostatic water (with benzyl alcohol) for injection.
    May be administered undiluted.
    Administer directly into a vein over 3—15 minutes. Doses >= 2 mg/kg or 250 mg should be given by intermittent infusion (see below), unless the potential benefits of direct IV injection outweigh the potential risks (e.g., life-threatening shock).
     
    Intermittent intravenous infusion:
    Use only methylprednisolone sodium succinate.
    Dilute in D5W, 0.9% Sodium Chloride (NS), or D5NS injection. Haze may form upon dilution.
    Infuse over 15—60 minutes. Large doses (e.g., >= 500 mg) should be administered over at least 30—60 minutes.

    Intramuscular Administration

    Intramuscular injection:
    Use methylprednisolone acetate or sodium succinate.
    Shake suspension well before withdrawing into the syringe.
    Inject deeply into a well-developed muscle. Rotate sites of injection.

    Other Injectable Administration

    Intra-articular injection:
    Use only methylprednisolone acetate.
    Using sterile technique, attach a 20—24 gauge needle to an empty syringe and insert the needle into the synovial cavity. Withdraw a few drops of synovial fluid to confirm that the needle is in the joint. With the needle still in place, exchange the aspirating syringe with the syringe containing methylprednisolone and inject the drug into the joint.
     
    Intralesional injection:
    Use only methylprednisolone acetate.
    Using a tuberculin syringe with a 25-gauge, 0.5-inch needle, inject methylprednisolone intradermally (not subcutaneously).

    STORAGE

    A-Methapred:
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Use within 48 hours after mixing
    Depmedalone-40:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Depmedalone-80 :
    - Discard unused portion. Do not store for later use.
    - Store between 68 to 77 degrees F
    Depo-Medrol:
    - Discard unused portion. Do not store for later use.
    - Store between 68 to 77 degrees F
    Medrol:
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Medrol Dosepak:
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Solu-Medrol:
    - Discard unused portion. Do not store for later use.
    - Protect from light
    - Store unreconstituted product at 68 to 77 degrees F
    - Use within 48 hours after mixing

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Increased dosages of rapid-acting corticosteroids may be necessary for patients undergoing physiologic stress such as major surgical procedure, acute infection, or blood loss. Methylprednisolone should be administered before, during, and after the stressful situation.
     
    The Solu-Medrol 40 mg presentation contains lactose monohydrate produced from cow's milk and is contraindicated in patients with a known or suspected hypersensitivity to cow's milk or it's components or other dairy products.

    Epidural administration, intrathecal administration, intravenous administration, neurologic events

    Severe medical events have occurred following administration of parenteral methylprednisolone via an incorrect route; to minimize the incidence of adverse events, care must be taken to administer the drug as intended and to not exceed recommended doses in each injection. Use of methylprednisolone is contraindicated for intrathecal administration. Do not give methylprednisolone acetate (e.g., Depo-Medrol) via intravenous administration. Do not administer any form of parenteral methylprednisolone into the deltoid muscle as subcutaneous atrophy occurs with high frequency following such use. Epidural administration of corticosteroids should be used with great caution. Rare, but serious neurologic events, including cortical blindness, stroke, spinal cord infarction, paralysis, seizures, nerve injury, brain edema, and death have been associated with epidural administration of injectable corticosteroids. These events have been reported with and without the use of fluoroscopy. Many cases were temporally associated with the corticosteroid injection; reactions occurred within minutes to 48 hours after injection. Some cases were confirmed through magnetic resonance imaging (MRI) or computed tomography (CT) scan. Many patients did not recover from the reported adverse effects. Discuss the benefits and risks of epidural corticosteroid injections with the patient before treatment. If a decision is made to proceed with corticosteroid epidural administration, counsel patients to seek emergency medical attention if they experience symptoms after injection such as vision changes, tingling in the arms or legs, dizziness, severe headache, seizures, or sudden weakness or numbness of face, arm, or leg.

    Fungal infection, infection, measles, mycobacterial infection, sepsis, tuberculosis, varicella, viral infection

    Corticosteroid therapy can mask the symptoms of infection, reactivate latent infection, exacerbate concurrent infection, and/or result in the development of secondary infection. Regardless of the dosage formulation, use of methylprednisolone is contraindicated in patients with systemic fungal infection, except when the acetate parenteral suspension (e.g., Depo-Medrol) is administered as an intra-articular injection for a localized joint condition or when the sodium succinate parenteral solution (e.g., Solu-Medrol) or oral formulations are used to control drug reactions. Further, use of any methylprednisolone formulation is not advised in cases of viral infection or bacterial infections that are not adequately controlled by antiinfective agents. The safety and efficacy of methylprednisolone sodium succinate in patients with sepsis syndrome and septic shock have not been established; study suggests that such use may increase the risk of mortality in patients with elevated serum creatinine levels and in those who develop secondary infections after methylprednisolone use. Do not administer parenteral methylprednisolone intra-articularly, intrabursally, or for intratendinous use for local effect in the presence of an acute infection ; further, local administration of methylprednisolone acetate into a previously infected site is not usually recommended. Use methylprednisolone with caution, if at all, in patients with intercurrent infections due to pathogens (e.g., amoeba, candida, cryptococcus, nocardia, pneumocystis, toxoplasma, or mycobacterial infection), known or suspected Strongyloides (threadworm) infestation, or a history of active tuberculosis except when chemoprophylaxis is instituted concomitantly. Patients receiving immunosuppressive doses of methylprednisolone should be advised to avoid exposure to measles or varicella and, if exposed to these diseases, to seek medical advice immediately.

    Surgery

    Patients should be instructed to notify their physician immediately if signs of infection or injury occur, both during treatment or up to 12 months following cessation of therapy with methylprednisolone. Dosages should be adjusted, or glucocorticoid therapy reintroduced, if required. If surgery is needed, patients should advise the attending physician of the corticosteroid they have received within the last 12 months and the disease for which they were being treated. Identification cards that include the name of the patient's disease, the currently administered type and dose of corticosteroid, and the patient's physician should be carried with the patient at all times.

    Myocardial infarction

    Corticosteroid therapy has been associated with left ventricular free-wall rupture in patients with recent myocardial infarction and methylprednisolone should therefore be used cautiously in these patients.

    Heart failure, hypertension

    Corticosteroids cause edema, which can exacerbate congestive heart failure or hypertension. Methylprednisolone should be used with caution in these patients.

    Cataracts, glaucoma, increased intraocular pressure, visual disturbance

    Corticosteroids should be used cautiously in patients with glaucoma or other visual disturbance. Corticosteroids are well known to cause cataracts and increased intraocular pressure and can exacerbate glaucoma during long-term administration. Patients receiving methylprednisolone chronically should be periodically assessed for cataract formation.

    Diabetes mellitus, herpes infection, osteoporosis, psychosis, renal disease, scleroderma, seizure disorder

    Methylprednisolone should be used with extreme caution in patients with psychosis, emotional instability, herpes infection (especially ocular herpes simplex infections), osteoporosis, diabetes mellitus, renal disease or seizure disorder because corticosteroids can exacerbate these conditions. Caution should also be used when treating patients with systemic sclerosis (scleroderma); an increased incidence of scleroderma renal crisis has been observed with the use of corticosteroids, including methylprednisolone.

    Myasthenia gravis

    Methylprednisolone should be used with caution in patients with myasthenia gravis who are being treated with anticholinesterase agents (see Interactions). Muscle weakness can be transiently increased during the initiation of glucocorticoid therapy in patients with myasthenia gravis, necessitating respiratory support.

    Diverticulitis, GI perforation, hepatic disease, peptic ulcer disease, ulcerative colitis

    Systemic corticosteroids should be used with caution in patients with active or latent peptic ulcer disease, diverticulitis, fresh intestinal anastomoses, and nonspecific ulcerative colitis, since steroids may increase the risk of a gastrointestinal (GI) perforation. Signs of peritoneal irritation following GI perforation in patients receiving corticosteroids may be minimal or absent. Corticosteroids should not be used in patients where there is a possibility of impending GI perforation, abscess, or pyogenic infection. There is an enhanced effect due to decreased metabolism of corticosteroids in patients with severe hepatic disease with cirrhosis.

    Coagulopathy, idiopathic thrombocytopenic purpura (ITP), thromboembolic disease

    Glucocorticoids rarely can increase blood coagulability and cause intravascular thrombosis, thrombophlebitis, and thromboembolism. Therefore, methylprednisolone should be used with caution in patients with coagulopathy and/or thromboembolic disease. It is important to note that corticosteroid use via intramuscular administration for immune thrombocytopenic purpura (ITP) is contraindicated, though intravascular and oral administration of methylprednisolone are utilized for this condition.[41361] [41362]

    Pregnancy

    There are no adequate or well controlled studies of the use of methylprednisolone in pregnant women. Complications, including cleft palate, stillbirth, and premature abortion, have been reported when corticosteroids were administered during pregnancy in animals. If these drugs must be used during pregnancy, the potential risks should be discussed with the patient. Babies born to women receiving large doses of corticosteroids during pregnancy should be monitored for signs of adrenal insufficiency, and appropriate therapy should be initiated, if necessary. Corticosteroids have been shown to impair fertility in male rats.

    Breast-feeding

    Corticosteroids distribute into breast milk, and the manufacturer states that because of the potential for serious adverse reactions in nursing babies, a decision should be made whether to discontinue nursing or to discontinue the drug. However, there have been reports of breast-feeding in 3 babies who were breast-fed from birth during maternal use of methylprednisolone (6 to 8 mg PO daily) with no reported adverse effects up to 3 months. In one of the reports, 2 babies had normal blood cell counts, no increase in infections, and above average growth rates. At higher daily methylprednisolone doses, avoidance of breast-feeding during times of peak milk concentrations (usually until 3 to 4 hours following a dose) can help limit infant exposure. While the American Academy of Pediatrics does not comment on the use of methylprednisolone during breast-feeding, it does consider other corticosteroids (prednisone and prednisolone) to be usually compatible with breast-feeding. 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.

    Children, growth inhibition, increased intracranial pressure, infants

    Pediatric-specific issues should be considered prior to treatment initiation with systemic corticosteroids, such as methylprednisolone. The potential for growth inhibition should be monitored during prolonged therapy in infants, children, and adolescents, and the potential for growth effects should be weighed against the clinical benefit obtained and the availability of other treatment alternatives. Administration of corticosteroids to pediatric patients should be limited to the least amount compatible with an effective therapeutic regimen. Pediatric patients may be more susceptible to developing systemic toxicity; adrenal suppression and increased intracranial pressure have been reported with the use and/or withdrawal of various corticosteroid formulations in young patients.  Further, children receiving corticosteroids are immunosuppressed and are therefore more susceptible to infection. Normally innocuous infections can become fatal in children receiving systemic corticosteroids, so care should be taken to avoid exposure to patients with infectious diseases, particularly those with chicken pox or measles.

    Cushing's syndrome

    Glucocorticoids can produce or aggravate Cushing's syndrome, thus methylprednisolone should be avoided in patients with Cushing's disease.

    Abrupt discontinuation, hypothalamic-pituitary-adrenal (HPA) suppression

    Pharmacologic doses of methylprednisolone administered for prolonged periods may result in hypothalamic-pituitary-adrenal (HPA) suppression. Acute adrenal insufficiency and even death may occur following abrupt discontinuation. Withdrawal from prolonged oral corticosteroid therapy should be gradual; HPA suppression can last for up to 12 months following cessation of therapy, and patients may need supplemental corticosteroid treatment during periods of physiologic stress, such as surgery, acute blood loss, or infection, even after the drug has been discontinued. Also, a non-HPA withdrawal syndrome may occur following abrupt discontinuation of corticosteroid therapy, and is apparently unrelated to adrenocortical insufficiency. These effects are thought to be due to the sudden change in glucocorticoid concentration rather than to low corticosteroid levels (see Adverse Reactions).

    Neonates, premature neonates

    Although all forms of methylprednisolone should be used with caution in newborns due to potential for drug-induced growth inhibition and immunosuppression, several commercial formulations of parenteral methylprednisolone are contraindicated in premature neonates and should be avoided in neonates because these products contain benzyl alcohol. Administration of benzyl alcohol to neonates can result in 'gasping syndrome,' which is a potentially fatal condition characterized by metabolic acidosis and CNS, respiratory, circulatory, and renal dysfunction; it is also characterized by high concentrations of benzyl alcohol and its metabolites in the blood and urine. While the minimum amount of benzyl alcohol at which toxicity may occur is not known, 'gasping syndrome' has been associated with benzyl alcohol dosages >99 mg/kg/day in neonates and low-birth-weight neonates. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic failure, renal failure, hypotension, bradycardia, and cardiovascular collapse. Rare cases of death, primarily in preterm infants, have been reported. Further, an increased incidence of kernicterus, especially in small, preterm infants has been reported. Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all sources. Premature infants, infants with a low birth weight, and patients who receive a high dose may be more likely to develop toxicity.

    Corticosteroid hypersensitivity

    True corticosteroid hypersensitivity reactions are rare. The use of methylprednisolone products in a patient who has previously experienced a hypersensitivity reaction to that product is contraindicated. While a hypersensitivity reaction could be to a specific salt of the corticosteroid (i.e., methylprednisolone sodium succinate), patients who have demonstrated a prior hypersensitivity reaction to methylprednisolone should receive any form of methylprednisolone with extreme caution. It is possible, though also rare, that such patients will display cross-hypersensitivity to other corticosteroids; there have been reports that a cross-sensitivity between hydrocortisone and methylprednisolone may exist. 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.

    Hyperthyroidism, hypothyroidism, thyroid disease

    Additional monitoring and/or periodic methylprednisolone dosage adjustments may been needed in patients with thyroid disease, as corticosteroid metabolic clearance is affected by thyroid function. Patients with hyperthyroidism have an increased rate of methylprednisolone elimination and may have a less than expected drug-effect; while those with hypothyroidism have decreased corticosteroid clearance and can have an exaggerated drug response.

    Geriatric

    Use systemic corticosteroids with caution in the geriatric patient; the risks and benefits of therapy should be considered for any individual patient. According to the Beers Criteria, systemic corticosteroids are considered potentially inappropriate medications (PIMs) for use in geriatric patients with delirium or at high risk for delirium and should be avoided in these patient populations due to the possibility of new-onset delirium or exacerbation of the current condition. The Beers expert panel notes that oral and parenteral corticosteroids may be required for conditions such as exacerbation of chronic obstructive pulmonary disease (COPD) but should be prescribed in the lowest effective dose and for the shortest possible duration. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities. According to the OBRA guidelines, the need for continued use of a glucocorticoid, with the exception of topical or inhaled formulations, should be documented, along with monitoring for and management of adverse consequences. Intermediate or longer-term use may cause hyperglycemia, psychosis, edema, insomnia, hypertension, osteoporosis, mood lability, or depression.

    Immunosuppression

    Patients receiving high-dose systemic corticosteroid therapy, such as methylprednisolone, for any period of time are at risk to develop immunosuppression; patients receiving moderate dosages of systemic corticosteroids for short periods or low doses for prolonged periods also may be at risk. When given in combination with other immunosuppressive agents, there is a risk of significant immunosuppression.

    Vaccination

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

    Head trauma

    Results from one multicenter, randomized, placebo-controlled study with methylprednisolone hemisuccinate, an IV corticosteroid, showed an increase in early (at 2 weeks) and late (at 6 months) mortality in patients with head trauma who were determined not to have other clear indications for corticosteroid treatment. High doses of systemic corticosteroids, including methylprednisolone, should not be used for the treatment of traumatic brain injury.

    ADVERSE REACTIONS

    Severe

    tendon rupture / Delayed / Incidence not known
    bone fractures / Delayed / Incidence not known
    avascular necrosis / Delayed / Incidence not known
    heart failure / Delayed / Incidence not known
    bradycardia / Rapid / Incidence not known
    arrhythmia exacerbation / Early / Incidence not known
    cardiomyopathy / Delayed / Incidence not known
    cardiac arrest / Early / Incidence not known
    vasculitis / Delayed / Incidence not known
    pulmonary edema / Early / Incidence not known
    retinopathy / Delayed / Incidence not known
    optic neuritis / Delayed / Incidence not known
    visual impairment / Early / Incidence not known
    ocular hypertension / Delayed / Incidence not known
    esophageal ulceration / Delayed / Incidence not known
    peptic ulcer / Delayed / Incidence not known
    pancreatitis / Delayed / Incidence not known
    GI perforation / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    skin atrophy / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    papilledema / Delayed / Incidence not known
    exfoliative dermatitis / Delayed / Incidence not known
    increased intracranial pressure / Early / Incidence not known
    thromboembolism / Delayed / Incidence not known
    thrombosis / Delayed / Incidence not known

    Moderate

    growth inhibition / Delayed / Incidence not known
    osteoporosis / Delayed / Incidence not known
    impaired wound healing / Delayed / Incidence not known
    myopathy / Delayed / Incidence not known
    immunosuppression / Delayed / Incidence not known
    metabolic alkalosis / Delayed / Incidence not known
    hypokalemia / Delayed / Incidence not known
    hypocalcemia / Delayed / Incidence not known
    sodium retention / Delayed / Incidence not known
    hypernatremia / Delayed / Incidence not known
    fluid retention / Delayed / Incidence not known
    edema / Delayed / Incidence not known
    hypertension / Early / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    exophthalmos / Delayed / Incidence not known
    ocular infection / Delayed / Incidence not known
    cataracts / Delayed / Incidence not known
    diabetes mellitus / Delayed / Incidence not known
    hyperglycemia / Delayed / Incidence not known
    Cushing's syndrome / Delayed / Incidence not known
    glycosuria / Early / Incidence not known
    constipation / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    hepatomegaly / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    gastritis / Delayed / Incidence not known
    EEG changes / Delayed / Incidence not known
    peripheral neuropathy / Delayed / Incidence not known
    euphoria / Early / Incidence not known
    neuritis / Delayed / Incidence not known
    psychosis / Early / Incidence not known
    depression / Delayed / Incidence not known
    erythema / Early / Incidence not known
    pseudotumor cerebri / Delayed / Incidence not known
    physiological dependence / Delayed / Incidence not known
    adrenocortical insufficiency / Delayed / Incidence not known
    withdrawal / Early / Incidence not known
    hypotension / Rapid / Incidence not known
    hypothalamic-pituitary-adrenal (HPA) suppression / Delayed / Incidence not known
    phlebitis / Rapid / Incidence not known
    hypercholesterolemia / Delayed / Incidence not known
    urinary incontinence / Early / Incidence not known
    palpitations / Early / Incidence not known
    scleroderma renal crisis / Early / Incidence not known

    Mild

    myalgia / Early / Incidence not known
    weakness / Early / Incidence not known
    arthropathy / Delayed / Incidence not known
    infection / Delayed / Incidence not known
    leukocytosis / Delayed / Incidence not known
    syncope / Early / Incidence not known
    amenorrhea / Delayed / Incidence not known
    dysmenorrhea / Delayed / Incidence not known
    menstrual irregularity / Delayed / Incidence not known
    abdominal pain / Early / Incidence not known
    nausea / Early / Incidence not known
    vomiting / Early / Incidence not known
    anorexia / Delayed / Incidence not known
    appetite stimulation / Delayed / Incidence not known
    weight gain / Delayed / Incidence not known
    diarrhea / Early / Incidence not known
    emotional lability / Early / Incidence not known
    anxiety / Delayed / Incidence not known
    restlessness / Early / Incidence not known
    headache / Early / Incidence not known
    vertigo / Early / Incidence not known
    insomnia / Early / Incidence not known
    hirsutism / Delayed / Incidence not known
    skin hyperpigmentation / Delayed / Incidence not known
    ecchymosis / Delayed / Incidence not known
    striae / Delayed / Incidence not known
    diaphoresis / Early / Incidence not known
    acne vulgaris / Delayed / Incidence not known
    xerosis / Delayed / Incidence not known
    rash / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    alopecia / Delayed / Incidence not known
    hypertrichosis / Delayed / Incidence not known
    petechiae / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    injection site reaction / Rapid / Incidence not known
    skin hypopigmentation / Delayed / Incidence not known
    arthralgia / Delayed / Incidence not known
    fever / Early / Incidence not known
    lethargy / Early / Incidence not known
    malaise / Early / Incidence not known
    hiccups / Early / Incidence not known
    urinary urgency / Early / Incidence not known
    lactose intolerance / Early / 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 methylprednisolone. Butalbital is a CYP3A4 inducer; methylprednisolone is a CYP3A4 substrate. Monitor for decreased response to methylprednisolone during concurrent use.
    Acetaminophen; Butalbital; Caffeine: (Moderate) Coadministration may result in decreased exposure to methylprednisolone. Butalbital is a CYP3A4 inducer; methylprednisolone is a CYP3A4 substrate. Monitor for decreased response to methylprednisolone during concurrent use.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) Coadministration may result in decreased exposure to methylprednisolone. Butalbital is a CYP3A4 inducer; methylprednisolone is a CYP3A4 substrate. Monitor for decreased response to methylprednisolone 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.
    Alefacept: (Severe) Patients receiving other immunosuppressives should not receive concurrent therapy with alefacept; there is the possibility of excessive immunosuppression and subsequent risks of infection and other serious side effects.
    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.
    Amiodarone: (Major) Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia, including corticosteroids. Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy.
    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: (Minor) Postmarketing reports of interactions with coadministration of clarithromycin and methylprednisolone have been noted. Clarithromycin is a CYP3A4 inhibitor and may decrease the clearance of methylprednisolone if coadministered.
    Amoxicillin; Clarithromycin; Omeprazole: (Minor) Postmarketing reports of interactions with coadministration of clarithromycin and methylprednisolone have been noted. Clarithromycin is a CYP3A4 inhibitor and may decrease the clearance of methylprednisolone if coadministered.
    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.
    Aprepitant, Fosaprepitant: (Moderate) When coadministered with a single dose of fosaprepitant 150 mg IV, reduce the dose of intravenous methylprednisolone by 25% or oral methylprednisolone by 50% on days 1 and 2 for patients receiving highly emetogenic chemotherapy (HEC) and on day 1 for patients receiving moderately emetogenic chemotherapy (MEC); the manufacturer also makes a general recommendation of a 25% (IV) or 50% (PO) methylprednisolone dose reduction (time frame not specified) when coadministered with an oral aprepitant regimen (125 mg/80 mg/80 mg). Methylprednisolone is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of methylprednisolone. A 3-day regimen of oral aprepitant (125 mg/80 mg/80 mg) increased the AUC of methylprednisolone (125 mg IV/40 mg PO/40 mg PO) by 1.34-fold on day 1 and by 2.5-fold on day 3; the effect of other aprepitant, fosaprepitant doses on methylprednisolone pharmacokinetics has not been reported. However, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
    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 methylprednisolone. Butalbital is a CYP3A4 inducer; methylprednisolone is a CYP3A4 substrate. Monitor for decreased response to methylprednisolone 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 methylprednisolone. Butalbital is a CYP3A4 inducer; methylprednisolone is a CYP3A4 substrate. Monitor for decreased response to methylprednisolone 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: (Moderate) Coadministration of methylprednisolone with atazanavir may cause elevated methylprednisolone serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Methylprednisolone is a CYP3A4 substrate; atazanavir is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
    Atazanavir; Cobicistat: (Moderate) Coadministration of methylprednisolone with atazanavir may cause elevated methylprednisolone serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Methylprednisolone is a CYP3A4 substrate; atazanavir is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. (Moderate) Coadministration of methylprednisolone with cobicistat may cause elevated methylprednisolone serum concentrations, potentially resulting in Cushing's syndrome or adrenal suppression. Cobicistat is a CYP3A4 inhibitor, while methylprednisolone is a CYP3A4 substrate. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
    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 methylprednisolone. Phenobarbital is a CYP3A4 inducer; methylprednisolone is a CYP3A4 substrate. Monitor for decreased response to methylprednisolone 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 methylprednisolone. Phenobarbital is a CYP3A4 inducer; methylprednisolone is a CYP3A4 substrate. Monitor for decreased response to methylprednisolone 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.
    Bexarotene: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents, such as bexarotene.
    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.
    Boceprevir: (Major) Concomitant use of systemic methylprednisolone with boceprevir may result in increased plasma concentrations of methylprednisolone, resulting in significantly reduced serum cortisol concentrations. Avoid coadministration if possible, particularly for extended durations. Methylprednisolone is a CYP3A4 substrate; boceprevir is a strong inhibitor of CYP3A4. Coadministration may result in elevated methylprednisolone plasma concentrations. For long-term use, consider an alternative corticosteroid, such as beclomethasone or prednisolone, if appropriate. whose concentrations are less affected by strong CYP3A4 inhibitors.
    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.
    Bosentan: (Minor) A dose adjustment of methylprednisolone may be necessary if bosentan is initiated or withdrawn during therapy. Bosentan may increase the metabolism of methylprednisolone resulting in decreased exposure. Bosentan is an inducer of CYP3A4; methylprednisolone is a CYP3A4 substrate.
    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 methylprednisolone. Butabarbital is a CYP3A4 inducer; methylprednisolone is a CYP3A4 substrate. Monitor for decreased response to methylprednisolone during concurrent use.
    Calcium Carbonate: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function.
    Calcium Carbonate; Magnesium Hydroxide: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function.
    Calcium Carbonate; Risedronate: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function.
    Calcium Carbonate; Simethicone: (Moderate) Calcium absorption is reduced when calcium carbonate is taken concomitantly with systemic corticosteroids. Systemic corticosteroids induce a negative calcium balance by inhibiting intestinal calcium absorption as well as by increasing renal calcium losses. The mechanism by which these drugs inhibit calcium absorption in the intestine is likely to involve a direct inhibition of absorptive cell function.
    Canagliflozin: (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 methylprednisolone. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with methylprednisolone.
    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: (Moderate) Monitor for steroid-related adverse reactions if coadministration of ceritinib with methylprednisolone is necessary, due to increased methylprednisolone exposure; Cushings syndrome and adrenal suppression could potentially occur with long-term use. Ceritinib is a strong CYP3A4 inhibitor and methylprednisolone is a CYP3A4 substrate. Another strong CYP3A4 inhibitor has been reported to decrease the metabolism of certain corticosteroids by up to 60%, leading to increased risk of corticosteroid side effects.
    Certolizumab pegol: (Moderate) The safety and efficacy of certolizumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with certolizumab may be at a greater risk of developing an infection. Many of the serious infections occurred in patients on immunosuppressive therapy who received certolizumab.
    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.
    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.
    Cholestyramine: (Moderate) The absorption of oral corticosteroids, such as methylprednisolone, may be reduced during concurrent administration with cholestyramine. In a study of 10 healthy subjects, reductions in plasma cortisol concentrations and delays in peak concentrations were observed when cholestyramine 4 g was given prior to a single dose of another corticosteroid. When given with cholestyramine, the AUC of the corticosteroid decreased by approximately one-third and time to peak plasma cortisol concentrations was reached 50 +/- 22 minutes later than controls. It is recommended that other drugs be taken at least 1 hour before or 4 to 6 hours after cholestyramine (or as great an interval as possible) to avoid absorption interference.
    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: (Minor) Postmarketing reports of interactions with coadministration of clarithromycin and methylprednisolone have been noted. Clarithromycin is a CYP3A4 inhibitor and may decrease the clearance of methylprednisolone if coadministered.
    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: (Moderate) Coadministration of methylprednisolone with cobicistat may cause elevated methylprednisolone serum concentrations, potentially resulting in Cushing's syndrome or adrenal suppression. Cobicistat is a CYP3A4 inhibitor, while methylprednisolone is a CYP3A4 substrate. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
    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) Avoid coadministration of conivaptan, a CYP3A4 inhibitor and methylprednisolone, a CYP3A4 substrate. Concurrent use may result in elevated methylprednisolone serum concentrations. According to the manufacturer of conivaptan, concomitant use of conivaptan, a strong CYP3A4 inhibitor, and CYP3A substrates, such as methylprednisolone, should be avoided. Coadministration of conivaptan with other CYP3A substrates has resulted in increased mean AUC values (2 to 3 times). Similar pharmacokinetic effects could be seen with methylprednisolone. Treatment with methylprednisolone may be initiated no sooner than 1 week after completion of conivaptan therapy. In addition, conivaptan has been associated with hypokalemia (9.8%). Although not studied, consider the potential for additive hypokalemic effects if conivaptan is coadministered with drugs known to induce hypokalemia, such as corticosteroids.
    Cyclosporine: (Moderate) Convulsions have been reported during concurrent use of cyclosporine and high dose methylprednisolone. In addition, mutual inhibition of metabolism occurs with concurrent use of cyclosporine and methylprednisolone; therefore, the potential for adverse events associated with either drug may be increased. Coadministration should be approached with caution.
    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: (Moderate) Coadministration of methylprednisolone with darunavir may cause elevated methylprednisolone serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Monitor closely. For long-term use, consider an alternative corticosteroid, such as beclomethasone and prednisolone, if appropriate. whose concentrations are less affected by strong CYP3A4 inhibitors. Methylprednisolone is a CYP3A4 substrate and darunavir is a strong inhibitor of CYP3A4.
    Darunavir; Cobicistat: (Moderate) Coadministration of methylprednisolone with cobicistat may cause elevated methylprednisolone serum concentrations, potentially resulting in Cushing's syndrome or adrenal suppression. Cobicistat is a CYP3A4 inhibitor, while methylprednisolone is a CYP3A4 substrate. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. (Moderate) Coadministration of methylprednisolone with darunavir may cause elevated methylprednisolone serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Monitor closely. For long-term use, consider an alternative corticosteroid, such as beclomethasone and prednisolone, if appropriate. whose concentrations are less affected by strong CYP3A4 inhibitors. Methylprednisolone is a CYP3A4 substrate and darunavir is a strong inhibitor of CYP3A4.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Coadministration of methylprednisolone with cobicistat may cause elevated methylprednisolone serum concentrations, potentially resulting in Cushing's syndrome or adrenal suppression. Cobicistat is a CYP3A4 inhibitor, while methylprednisolone is a CYP3A4 substrate. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use. (Moderate) Coadministration of methylprednisolone with darunavir may cause elevated methylprednisolone serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Monitor closely. For long-term use, consider an alternative corticosteroid, such as beclomethasone and prednisolone, if appropriate. whose concentrations are less affected by strong CYP3A4 inhibitors. Methylprednisolone is a CYP3A4 substrate and darunavir is a strong inhibitor of CYP3A4.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Coadministration of methylprednisolone with ritonavir may cause elevated methylprednisolone serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Monitor closely. For long-term use, consider an alternative corticosteroid, such as beclomethasone and prednisolone, if appropriate. whose concentrations are less affected by strong CYP3A4 inhibitors. Methylprednisolone is a CYP3A4 substrate and ritonavir is a strong inhibitor of CYP3A4.
    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.
    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.
    Diltiazem: (Moderate) Diltiazem may decrease the metabolism of methylprednisolone via inhibition of the CYP3A4 isoenzyme, with the potential for increased corticosteroid effects. Oral coadministration of diltiazem and methylprednisolone has been shown to increase the AUC of methylprednisolone by about 2.6-fold and increase the half-life 1.9-fold.
    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.
    Dronedarone: (Moderate) Coadministration of methylprednisolone with dronedarone may cause elevated methylprednisolone serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Monitor closely. Methylprednisolone is a CYP3A4 substrate and dronedarone is an inhibitor of CYP3A4.
    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.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) L-methylfolate and methylprednisolone should be used together cautiously. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with methylprednisolone. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together.
    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.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Coadministration of methylprednisolone with cobicistat may cause elevated methylprednisolone serum concentrations, potentially resulting in Cushing's syndrome or adrenal suppression. Cobicistat is a CYP3A4 inhibitor, while methylprednisolone is a CYP3A4 substrate. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of methylprednisolone with cobicistat may cause elevated methylprednisolone serum concentrations, potentially resulting in Cushing's syndrome or adrenal suppression. Cobicistat is a CYP3A4 inhibitor, while methylprednisolone is a CYP3A4 substrate. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
    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.
    Erlotinib: (Moderate) Monitor for symptoms of gastrointestinal (GI) perforation (e.g., severe abdominal pain, fever, nausea, and vomiting) if coadministration of erlotinib with methylprednisolone is necessary. Permanently discontinue erlotinib in patients who develop GI perforation. The pooled incidence of GI perforation clinical trials of erlotinib ranged from 0.1% to 0.4%, including fatal cases; patients receiving concomitant methylprednisolone may be at increased risk.
    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.
    Erythromycin: (Minor) Erythromycin decreases the clearance of methylprednisolone. The clinical implications of these pharmacokinetic interactions are uncertain, but some studies have used the interaction to dose-reduce methylprednisolone in acutely asthmatic patients without compromising steroid efficacy.
    Erythromycin; Sulfisoxazole: (Minor) Erythromycin decreases the clearance of methylprednisolone. The clinical implications of these pharmacokinetic interactions are uncertain, but some studies have used the interaction to dose-reduce methylprednisolone in acutely asthmatic patients without compromising steroid efficacy.
    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.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Minor) L-methylfolate and methylprednisolone should be used together cautiously. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with methylprednisolone. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together.
    Etravirine: (Moderate) Monitor for decreased efficacy of methylprednisolone if coadministration with etravirine is necessary; plasma concentrations of methylprednisolone may decrease. Methylprednisolone is a CYP3A substrate and etravirine induces CYP3A.
    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: (Moderate) Concomitant use of methylprednisolone and fosamprenavir may result in altered methylprednisolone plasma concentrations. Monitor closely. Methylprednisolone is a substrate of CYP3A4. Amprenavir, the active metabolite of fosamprenavir, is a potent inhibitor of CYP3A4, but may also induce this enzyme to some degree. The net effect is likely increased methylprednisolone exposure.
    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.
    Golimumab: (Moderate) The safety and efficacy of golimumab in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with golimumab may be at a greater risk of developing an infection.
    Grapefruit juice: (Moderate) Grapefruit juice may enhance steroid effects if taken with oral methylprednisolone. Grapefruit juice contains a compound that inhibits CYP3A4 in enterocytes; decreased methylprednisolone metabolism is the probable mechanism. Methylprednisolone peak concentrations and AUC increased and the half-life of methylprednisolone was prolonged in one study of the interaction. The clinical significance of the interaction is uncertain. Patients should be advised to not significantly alter their grapefruit juice ingestion.
    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 methylprednisolone, 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.
    Hylan G-F 20: (Major) The safety and efficacy of hylan G-F 20 given concomitantly with other intra-articular injectables have not been established. Other intra-articular injections may include intra-articular steroids (betamethasone, dexamethasone, hydrocortisone, prednisolone, methylprednisolone, and triamcinolone).
    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) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with methylprednisolone, a CYP3A substrate, as methylprednisolone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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.
    Infliximab: (Moderate) Many serious infections during infliximab therapy have occurred in patients who received concurrent immunosuppressives that, in addition to their underlying Crohn's disease or rheumatoid arthritis, predisposed patients to infections. The impact of concurrent infliximab therapy and immunosuppression on the development of malignancies is unknown. In clinical trials, the use of concomitant immunosuppressant agents appeared to reduce the frequency of antibodies to infliximab and appeared to reduce infusion reactions.
    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.
    Iohexol: (Major) Serious adverse events, including death, have been observed during intrathecal administration of both corticosteroids (i.e., methylprednisolone) and radiopaque contrast agents (i.e., iohexol); therefore, concurrent use of these medications via the intrathecal route is contraindicated. Cases of cortical blindness, stroke, spinal cord infarction, paralysis, seizures, nerve injury, brain edema, and death have been temporally associated (i.e., within minutes to 48 hours after injection) with epidural administration of injectable corticosteroids. In addition, patients inadvertently administered iohexol formulations not indicated for intrathecal use have experienced seizures, convulsions, cerebral hemorrhages, brain edema, and death. Administering these medications together via the intrathecal route may increase the risk for serious adverse events.
    Iopamidol: (Severe) Because both intrathecal corticosteroids (i.e., methylprednisolone) and intrathecal radiopaque contrast agents (i.e., iopamidoll) can increase the risk of seizures, the intrathecal administration of corticosteroids with intrathecal radiopaque contrast agents is contraindicated.
    Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with methylprednisolone may result in increased serum concentrations of methylprednisolone. Methylprednisolone is a substrate of CYP3A4 and isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4. Caution and close monitoring for adverse effects, such as corticosteroid-related adverse effects, are advised if these drugs are used together.
    Isoniazid, INH: (Minor) Corticosteroids, such as methylprednisolone, may decrease serum concentrations of isoniazid. Isoniazid serum concentrations decreased by 25% and 40% in slow and rapid acetylators, respectively, when isoniazid (10 mg/kg) was co-administered with another corticosteroid. The exact mechanism of action of the interaction is unknown. The decrease in plasma concentrations may be caused by enhanced acetylation or renal clearance of isoniazid or by an increase in total body water.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) A dose adjustment of methylprednisolone may be necessary when administered concurrently with rifamycins, due to the potential for decreased exposure of methylprednisolone. Rifamycins are inducers of CYP3A4; methylprednisolone is a CYP3A4 substrate. (Minor) Corticosteroids, such as methylprednisolone, may decrease serum concentrations of isoniazid. Isoniazid serum concentrations decreased by 25% and 40% in slow and rapid acetylators, respectively, when isoniazid (10 mg/kg) was co-administered with another corticosteroid. The exact mechanism of action of the interaction is unknown. The decrease in plasma concentrations may be caused by enhanced acetylation or renal clearance of isoniazid or by an increase in total body water.
    Isoniazid, INH; Rifampin: (Moderate) A dose adjustment of methylprednisolone may be necessary when administered concurrently with rifamycins, due to the potential for decreased exposure of methylprednisolone. Rifamycins are inducers of CYP3A4; methylprednisolone is a CYP3A4 substrate. (Minor) Corticosteroids, such as methylprednisolone, may decrease serum concentrations of isoniazid. Isoniazid serum concentrations decreased by 25% and 40% in slow and rapid acetylators, respectively, when isoniazid (10 mg/kg) was co-administered with another corticosteroid. The exact mechanism of action of the interaction is unknown. The decrease in plasma concentrations may be caused by enhanced acetylation or renal clearance of isoniazid or by an increase in total body water.
    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: (Moderate) Itraconazole may inhibit the metabolism of methylprednisolone via hepatic CYP3A4 inhibition. Several published reports note that itraconazole decreases the clearance and increases the elimination half-life of methylprednisolone, resulting in increased exposure to methylprednisolone. The interaction can result in enhanced adrenal suppression.
    Ketoconazole: (Moderate) Ketoconazole can decrease the hepatic clearance of methylprednisolone, resulting in increased plasma concentrations. The interaction may be due to the inhibition of CYP3A4 by ketoconazole, and subsequent decreases in corticosteroid metabolism by the same isoenzyme. Prednisolone and prednisone pharmacokinetics appear less susceptible than methylprednisolone to CYP3A4 inhibitory interactions. Ketoconazole also can enhance the adrenal suppressive effects of corticosteroids.
    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) An increase in the plasma concentration of methylprednisolone may occur if given with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. Methylprednisolone is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. In a drug interaction study, concurrent administration of certain corticosteroids with another potent CYP3A4 inhibitor significantly decreased the corticosteroid metabolism (up to 60% reduction).
    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.
    Levomefolate: (Minor) L-methylfolate and methylprednisolone should be used together cautiously. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with methylprednisolone. Monitor patients for decreased efficacy of L-methylfolate if these agents are 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.
    Live Vaccines: (Severe) Live vaccines should generally not be administered to an immunosuppressed patient. Live vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system. The immunosuppressive effects of steroid treatment differ, but many clinicians consider a dose equivalent to either 2 mg/kg/day or 20 mg/day of prednisone as sufficiently immunosuppressive to raise concern about the safety of immunization with live vaccines. Patients on corticosteroid treatment for 2 weeks or more may be vaccinated after steroid therapy has been discontinued for at least 3 months in accordance with general recommendations for the use of live vaccines. The CDC has stated that discontinuation of steroids for 1 month prior to live vaccine administration may be sufficient. Live vaccines should not be given to individuals who are considered to be immunocompromised until more information is available.
    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: (Moderate) Coadministration of methylprednisolone with ritonavir may cause elevated methylprednisolone serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Monitor closely. For long-term use, consider an alternative corticosteroid, such as beclomethasone and prednisolone, if appropriate. whose concentrations are less affected by strong CYP3A4 inhibitors. Methylprednisolone is a CYP3A4 substrate and ritonavir is a strong inhibitor of CYP3A4.
    Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may reduce the efficacy of methylprednisolone by decreasing systemic exposure of the corticosteroid. If used together, a higher systemic corticosteroid dose may be required to obtain the desired therapeutic effect. Methylprednisolone is a CYP3A4 substrate. Lumacaftor is a strong CYP3A inducer.
    Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may reduce the efficacy of methylprednisolone by decreasing systemic exposure of the corticosteroid. If used together, a higher systemic corticosteroid dose may be required to obtain the desired therapeutic effect. Methylprednisolone is a CYP3A4 substrate. Lumacaftor is a strong CYP3A inducer.
    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 methylprednisolone. Mephobarbital is a CYP3A4 inducer; methylprednisolone is a CYP3A4 substrate. Monitor for decreased response to methylprednisolone 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: (Severe) 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.
    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 methylprednisolone are used concomitantly, and monitor for decreased efficacy of methylprednisolone and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and methylprednisolone is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of methylprednisolone.
    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: (Moderate) It appears that nefazodone inhibits the metabolism of methylprednisolone. In addition, concomitant nefazodone prolongs the duration of methylprednisolone induced cortisol suppression. If nefazodone and methylprednisolone are to be coadministered, care should be taken with regards to the potential for prolonged corticosteroid exposure.
    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.
    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.
    Ocrelizumab: (Moderate) Ocrelizumab has not been studied in combination with other immunosuppressive or immune modulating therapies used for the treatment of multiple sclerosis, including immunosuppressant doses of corticosteroids. Concomitant use of ocrelizumab with any of these therapies may increase the risk of immunosuppression. Monitor patients carefully for signs and symptoms of infection.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Coadministration of methylprednisolone with ritonavir may cause elevated methylprednisolone serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Monitor closely. For long-term use, consider an alternative corticosteroid, such as beclomethasone and prednisolone, if appropriate. whose concentrations are less affected by strong CYP3A4 inhibitors. Methylprednisolone is a CYP3A4 substrate and ritonavir is a strong inhibitor of CYP3A4.
    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.
    Oritavancin: (Minor) Methylprednisolone is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of methylprednisolone may be reduced if these drugs are administered concurrently.
    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.
    Pazopanib: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and methylprednisolone, a CYP3A4 substrate, may cause an increase in systemic concentrations of methylprednisolone. Use caution when administering these drugs concomitantly. In addition, concomitant administration may predispose the patient to over-immunosuppression resulting in an increased risk for the development of severe infections.
    Pegaspargase: (Moderate) Concomitant use of pegaspargase with corticosteroids can result in additive hyperglycemia. Insulin therapy may be required in some cases.
    Peginterferon Alfa-2a: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
    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 methylprednisolone. Phenobarbital is a CYP3A4 inducer; methylprednisolone is a CYP3A4 substrate. Monitor for decreased response to methylprednisolone 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: (Moderate) Coadministration of methylprednisolone with posaconazole may cause elevated methylprednisolone serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Monitor closely. For long-term use, consider an alternative corticosteroid, such as beclomethasone and prednisolone, if appropriate. whose concentrations are less affected by strong CYP3A4 inhibitors. Methylprednisolone is a CYP3A4 substrate and posaconazole is a strong inhibitor of CYP3A4.
    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 methylprednisolone. Primidone is a CYP3A4 inducer; methylprednisolone is a CYP3A4 substrate. Monitor for decreased response to methylprednisolone 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.
    Propylthiouracil, PTU: (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.
    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.
    Rifabutin: (Moderate) A dose adjustment of methylprednisolone may be necessary when administered concurrently with rifamycins, due to the potential for decreased exposure of methylprednisolone. Rifamycins are inducers of CYP3A4; methylprednisolone is a CYP3A4 substrate.
    Rifampin: (Moderate) A dose adjustment of methylprednisolone may be necessary when administered concurrently with rifamycins, due to the potential for decreased exposure of methylprednisolone. Rifamycins are inducers of CYP3A4; methylprednisolone is a CYP3A4 substrate.
    Rifamycins: (Moderate) A dose adjustment of methylprednisolone may be necessary when administered concurrently with rifamycins, due to the potential for decreased exposure of methylprednisolone. Rifamycins are inducers of CYP3A4; methylprednisolone is a CYP3A4 substrate.
    Rifapentine: (Moderate) A dose adjustment of methylprednisolone may be necessary when administered concurrently with rifamycins, due to the potential for decreased exposure of methylprednisolone. Rifamycins are inducers of CYP3A4; methylprednisolone is a CYP3A4 substrate.
    Rilonacept: (Moderate) Patients receiving immunosuppressives along with rilonacept may be at a greater risk of developing an infection.
    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: (Moderate) Coadministration of methylprednisolone with ritonavir may cause elevated methylprednisolone serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Monitor closely. For long-term use, consider an alternative corticosteroid, such as beclomethasone and prednisolone, if appropriate. whose concentrations are less affected by strong CYP3A4 inhibitors. Methylprednisolone is a CYP3A4 substrate and ritonavir is a strong inhibitor of CYP3A4.
    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: (Moderate) Saquinavir may inhibit CYP3A4 metabolism of methylprednisolone, resulting in increased plasma methylprednisolone concentrations and reduced serum cortisol concentrations. There have been reports of clinically significant drug interactions in patients receiving ritonavir with other corticosteroids, resulting in systemic corticosteroid effects including Cushing syndrome and adrenal suppression. Similar results are expected with saquinavir. Consider using an alternative treatment to methylprednisolone, such as a corticosteroid not metabolized by CYP3A4 (i.e., beclomethasone or prednisolone). If corticosteroid therapy is to be discontinued, consider tapering the dose over a period of time to decrease the potential for withdrawal.
    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.
    Siponimod: (Moderate) Monitor patients carefully for signs and symptoms of infection during coadministration of siponimod and methylprednisolone. Concomitant use may increase the risk of immunosuppression. Siponimod has not been studied in combination with other immunosuppressive therapies used for the treatment of multiple sclerosis, including immunosuppressant doses of corticosteroids.
    Sipuleucel-T: (Major) Concomitant use of sipuleucel-T and immunosuppressives should be avoided. Concurrent administration of immunosuppressives with the leukapheresis procedure that occurs prior to sipuleucel-T infusion has not been studied. Sipuleucel-T stimulates the immune system and patients receiving immunosuppressives may have a diminished response to sipuleucel-T. When appropriate, consider discontinuing or reducing the dose of immunosuppressives prior to initiating therapy with sipuleucel-T.
    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.
    Tacrolimus: (Major) Patients receiving tacrolimus and systemic corticosteroids concomitantly should be carefully monitored for alterations in tacrolimus whole blood concentrations. According to the manufacturer of tacrolimus, methylprednisolone may increase tacrolimus blood concentrations. The mechanism of the interaction is unclear. Tacrolimus is a CYP3A4 substrate, but methylprednisolone does not appear to have an inhibitory effect on CYP3A4 activity. For example, the pharmacokinetics and pharmacodynamics of the CYP3A4 substrate triazolam were determined in a three-phase cross-over study; the three treatment periods were placebo, methylprednisolone 32 mg PO 1 hour before triazolam 0.25 mg PO, and methylprednisolone 8 mg PO daily for 9 days before triazolam 0.25 mg PO. The single methylprednisolone dose did not significantly affect CYP3A4 activity. Methylprednisolone receipt for 9 days led to slightly reduced maximum triazolam concentrations, which may have been due to an inducing effect on the CYP3A4-mediated first-pass metabolism of triazolam.
    Telaprevir: (Major) Concomitant use of systemic methylprednisolone with telaprevir may result in increased plasma concentrations of methylprednisolone, resulting in significantly reduced serum cortisol concentrations. Avoid coadministration if possible, particularly for extended durations. Methylprednisolone is a CYP3A4 substrate; telaprevir is a strong inhibitor of CYP3A4. Coadministration may result in elevated methylprednisolone plasma concentrations. For long-term use, consider an alternative corticosteroid, such as beclomethasone or prednisolone, if appropriate. whose concentrations are less affected by strong CYP3A4 inhibitors.
    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: (Moderate) Concurrent administration of methylprednisolone with telithromycin may result in elevated methylprednisolone plasma concentrations. Use caution and monitor for corticosteroid-related side effects if these drugs are administered together. Methylprednisolone is metabolized by the hepatic isoenzyme CYP3A4; telithromycin is a strong CYP3A4 inhibitor.
    Telotristat Ethyl: (Moderate) Use caution if coadministration of telotristat ethyl and methylprednisolone is necessary, as the systemic exposure of methylprednisolone may be decreased resulting in reduced efficacy. If these drugs are used together, monitor patients for suboptimal efficacy of methylprednisolone; consider increasing the dose of methylprednisolone if necessary. Methylprednisolone is a CYP3A4 substrate. 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.
    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.
    Tocilizumab: (Moderate) Closely observe patients for signs of infection. Most patients taking tocilizumab who developed serious infections were taking concomitant immunosuppressives such as systemic corticosteroids.
    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.
    Trandolapril; Verapamil: (Moderate) Verapamil may decrease the metabolism of methylprednisolone via inhibition of the CYP3A4 isoenzyme, with the potential for increased corticosteroid effects. Verapamil is a moderate CYP3A4 inhibitor and methylprednisolone is a CYP3A4 substrate. Oral coadministration of another moderate CYP3A4 inhibitor and methylprednisolone has been shown to increase the AUC of methylprednisolone by about 2.6-fold and increase the half-life 1.9-fold.
    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.
    Verapamil: (Moderate) Verapamil may decrease the metabolism of methylprednisolone via inhibition of the CYP3A4 isoenzyme, with the potential for increased corticosteroid effects. Verapamil is a moderate CYP3A4 inhibitor and methylprednisolone is a CYP3A4 substrate. Oral coadministration of another moderate CYP3A4 inhibitor and methylprednisolone has been shown to increase the AUC of methylprednisolone by about 2.6-fold and increase the half-life 1.9-fold.
    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: (Moderate) Coadministration of methylprednisolone with voriconazole may cause elevated methylprednisolone serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Monitor closely. For long-term use, consider an alternative corticosteroid, such as beclomethasone and prednisolone, if appropriate. whose concentrations are less affected by CYP3A4 inhibitors. Methylprednisolone is a CYP3A4 substrate and voriconazole is an inhibitor of CYP3A4.
    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 adequate or well controlled studies of the use of methylprednisolone in pregnant women. Complications, including cleft palate, stillbirth, and premature abortion, have been reported when corticosteroids were administered during pregnancy in animals. If these drugs must be used during pregnancy, the potential risks should be discussed with the patient. Babies born to women receiving large doses of corticosteroids during pregnancy should be monitored for signs of adrenal insufficiency, and appropriate therapy should be initiated, if necessary. Corticosteroids have been shown to impair fertility in male rats.

    Corticosteroids distribute into breast milk, and the manufacturer states that because of the potential for serious adverse reactions in nursing babies, a decision should be made whether to discontinue nursing or to discontinue the drug. However, there have been reports of breast-feeding in 3 babies who were breast-fed from birth during maternal use of methylprednisolone (6 to 8 mg PO daily) with no reported adverse effects up to 3 months. In one of the reports, 2 babies had normal blood cell counts, no increase in infections, and above average growth rates. At higher daily methylprednisolone doses, avoidance of breast-feeding during times of peak milk concentrations (usually until 3 to 4 hours following a dose) can help limit infant exposure. While the American Academy of Pediatrics does not comment on the use of methylprednisolone during breast-feeding, it does consider other corticosteroids (prednisone and prednisolone) to be usually compatible with breast-feeding. 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

    Glucocorticoids are naturally occurring hormones that prevent or suppress inflammation and immune responses when administered at pharmacological doses. At the molecular level, unbound glucocorticoids readily cross cell membranes and bind with high affinity to specific cytoplasmic receptors. This binding induces a response by modifying transcription and, ultimately, protein synthesis to achieve the steroid's intended action. Such actions can include: inhibition of leukocyte infiltration at the site of inflammation, interference in the function of mediators of inflammatory response, and suppression of humoral immune responses. Some of the net effects include reduction in edema or scar tissue as well as a general suppression in immune response. The degree of clinical effect is normally related to the dose administered. The antiinflammatory actions of corticosteroids are thought to involve phospholipase A2 inhibitory proteins, collectively called lipocortins. Lipocortins, in turn, control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of the precursor molecule arachidonic acid. Likewise, the numerous adverse effects related to corticosteroid use are usually related to the dose administered and the duration of therapy.

    PHARMACOKINETICS

    Methylprednisolone is administered orally; methylprednisolone sodium succinate solution is administered by IM and IV injection, and by IV infusion; methylprednisolone acetate suspension is administered by IM, intra-articular, intralesional, or soft tissue injection. The onset and duration of action of parenteral methylprednisolone are dependent on the route of administration, the site of administration, and, if the drug is administered by intra-articular or IM injection, the extent of the local blood supply. As with other corticosteroids, once in systemic circulation, methylprednisolone is quickly distributed into the kidneys, intestines, skin, liver, and muscle. Corticosteroids distribute into breast milk and cross the placenta. Methylprednisolone is metabolized by the liver to inactive metabolites. These inactive metabolites, as well as a small portion of unchanged drug, are excreted in the urine. The biological half-life of methylprednisolone is 18 to 36 hours.
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4
    Methylprednisolone is a substrate of both CYP3A4, and may exhibit drug interactions with CYP3A4 inducers or inhibitors.

    Oral Route

    Methylprednisolone is rapidly absorbed following an oral dose. Peak effects following oral administration occur within 1—2 hours.

    Intravenous Route

    Following IV administration of methylprednisolone sodium succinate, effects occur within 1 hour and excretion is almost complete within 12 hours. Repeat dosing is needed every 4 to 6 hours if continuously high plasma levels of methylprednisolone are required.

    Intramuscular Route

    Systemic absorption is rapid following IM administration of methylprednisolone sodium succinate.

    Other Route(s)

    Intra-articular Route
    Absorption of methylprednisolone from an intra-articular injection site can be very slow, continuing over about 7 days.