Elsevier

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Jul.16.2020

Elsevier Drug Monographs

Methylprednisolone

Indications/Dosage

Labeled

  • acute lymphocytic leukemia (ALL)
  • acute respiratory distress syndrome (ARDS)
  • Addison's disease
  • adrenocortical insufficiency
  • adrenogenital syndrome
  • allergic conjunctivitis
  • allergic rhinitis
  • alopecia
  • anaphylaxis
  • angioedema
  • ankylosing spondylitis
  • anterior segment inflammation
  • asthma
  • atopic dermatitis
  • berylliosis
  • bursitis
  • chorioretinitis
  • chronic lymphocytic leukemia (CLL)
  • chronic obstructive pulmonary disease (COPD)
  • congenital adrenal hyperplasia
  • contact dermatitis
  • corneal ulcer
  • Crohn's disease
  • dermatitis herpetiformis
  • dermatomyositis
  • discoid lupus erythematosus
  • eczema
  • eosinophilic pneumonia
  • epicondylitis
  • erythema multiforme
  • erythroblastopenia
  • exfoliative dermatitis
  • food allergy
  • gouty arthritis
  • granuloma annulare
  • Graves' ophthalmopathy
  • hemolytic anemia
  • herpes zoster ocular infection
  • Hodgkin lymphoma
  • hypercalcemia
  • hypoplastic anemia
  • immune thrombocytopenic purpura (ITP)
  • insect bites or stings
  • iritis
  • juvenile rheumatoid arthritis (JRA)/juvenile idiopathic arthritis (JIA)
  • keloids
  • keratitis
  • kidney transplant rejection
  • lichen planus
  • lichen simplex
  • Loeffler's syndrome
  • lupus nephritis
  • multiple sclerosis
  • myasthenia gravis
  • mycosis fungoides
  • necrobiosis lipoidica diabeticorum
  • nephrotic syndrome
  • non-Hodgkin's lymphoma (NHL)
  • optic neuritis
  • osteoarthritis
  • pemphigus
  • perennial allergies
  • pneumonitis
  • polymyositis
  • postoperative ocular inflammation
  • proteinuria
  • pruritus
  • psoriasis
  • psoriatic arthritis
  • rheumatic carditis
  • sarcoidosis
  • seasonal allergies
  • seborrheic dermatitis
  • serum sickness
  • status asthmaticus
  • Stevens-Johnson syndrome
  • systemic lupus erythematosus (SLE)
  • temporal arteritis
  • tenosynovitis
  • thrombocytopenia
  • thyroiditis
  • trichinosis
  • tuberculosis infection
  • ulcerative colitis
  • urticaria
  • uveitis
  • vernal keratoconjunctivitis

Off-Label

  • acute interstitial nephritis (AIN)
  • carpal tunnel syndrome
  • Churg-Strauss syndrome
  • endophthalmitis
  • graft-versus-host disease (GVHD)
  • heart transplant rejection
  • Kawasaki disease
  • laryngotracheobronchitis (croup)
  • mixed connective tissue disease
  • multiple myeloma
  • multisystem inflammatory syndrome in children (MIS-C)
  • Pneumocystis pneumonia (PCP)
  • polyarteritis nodosa
  • polychondritis
  • pseudogout
  • pulmonary edema
  • pulmonary fibrosis
  • severe acute respiratory syndrome (SARS)
  • spinal cord injury
  • Wegener's granulomatosis
  • fat embolism syndrome prophylaxis
† Off-label indication

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.[33558]

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).[54288] Some experts recommend 0.5 to 1 mg/kg/dose IV every 4 to 6 hours.[59746]

For the treatment of asthma

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.[23999] 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.[25077]

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 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.[26496]

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.[25160] 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 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.[44772] 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.[56027] [59648]

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.[55710] [55705] [55709] [50683]

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.[50733] [55608] [62699] 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.[64393] [64397]

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.[54978] [55494] [55495] [55499] [55716] 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.[55498] 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.[64393] [64397]

Oral dosage

Adults

4 to 48 mg PO per day, administered in 4 divided doses is the general FDA-approved dose range.[30015] 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.[50733] [55608] [62699] 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.[64393] [64397]

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.[54978] [55494] [55495] [55499] [55716] Usual pediatric dose range: 0.5 to 1.7 mg/kg/day PO given in divided doses.[52618] [62697] 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.[64393] [64397]

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 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 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).[30015]

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 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.[30015]

Children and Adolescents

0.5 to 1.7 mg/kg/day PO, given in divided doses every 6 to 12 hours.[52618] [62697]

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.[41362]

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.[41362]

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.[41361] [52618] [62697]

Intramuscular dosage (methylprednisolone acetate injection suspension)

Adults

10 to 120 mg IM. Subsequent doses may be given determined by patient response and condition.[41362]

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.[41362]

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 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.[30015]

Children

0.5 to 1.7 mg/kg/day PO, given in divided doses every 6 to 12 hours.[52618] [62697]

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.[41361]

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.[41361] [52618] [62697]

Intramuscular dosage (methylprednisolone acetate injection suspension)

Adults

10 to 120 mg IM. Subsequent doses are determined by patient response and condition.[41362]

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.[41362]

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.[30015]

Children

0.5 to 1.7 mg/kg/day PO, given in divided doses every 6 to 12 hours.[52618] [62697]

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.[41361]

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.[41361] [52618] [62697]

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.[30015]

Children

0.5 to 1.7 mg/kg/day PO, given in divided doses every 6 to 12 hours.[52618] [62697] 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.[41361]

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.[30015] 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.[33275] [34362] 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.[55862] 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.[55862]

Children and Adolescents

0.5 to 1.7 mg/kg/day PO, given in divided doses every 6 to 12 hours.[52618] [62697]

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.[41361] 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.[33275] [34362] 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.[55862] 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.[55862]

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.[41361] [52618] [62697]

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.[41362] 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.[33275] [34362] Trials have mostly involved use of oral or intravenous dose forms, using oral dosing for 4 weeks or intravenous administration for 5 days.[55862] 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.[55862]

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.[41362]

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 Pneumocystis pneumonia (PCP)†

Intravenous dosage (methylprednisolone sodium succinate injection)

Adults

30 to 45 mg IV 2 to 3 times daily; taper dose after 5 to 7 days over 1 to 2 weeks. A suggested taper is 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. Start therapy as early as possible and within 72 hours after starting specific PCP therapy. Recommended for patients with moderate to severe infection, defined by a PaO2 less than 70 mmHg at room air or an alveolar-arterial DO2 gradient of 35 mmHg or more. The benefits of starting corticosteroids after 72 hours are unclear.[34362] [64856] [64858] [64860] [64862] [64907]

Adolescents

30 to 45 mg IV 2 to 3 times daily; taper dose after 5 to 7 days over 1 to 2 weeks. A suggested taper is 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. Start therapy as early as possible and within 72 hours after starting specific PCP therapy. Recommended for patients with moderate to severe infection, defined by a PaO2 less than 70 mmHg at room air or an alveolar-arterial DO2 gradient of 35 mmHg or more. The benefits of starting corticosteroids after 72 hours are unclear.[34362] [64856] [64858] [64860] [64862] [64907]

Infants and Children

1 mg/kg/dose IV every 6 hours on days 1 to 7; then 1 mg/kg/dose IV twice daily on days 8 to 9; then 0.5 mg/kg/dose twice daily on days 10 to 11; then 1 mg/kg/dose IV once daily on days 12 to 16. Start therapy as early as possible and within 72 hours after starting specific PCP therapy. Recommended for patients with moderate to severe infection, defined by a PaO2 less than 70 mmHg at room air or an alveolar-arterial DO2 gradient more than 35 mmHg.[34361] [64856] [64858] [64860] [64862] [64907]

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.[27413] 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).[27341] 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.[27413]

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 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.[32123]

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 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.[51730] [51731]

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.[25089]

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.[51803]

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.[30015]

Children

0.5 to 1.7 mg/kg/day PO, given in divided doses every 6 to 12 hours.[52618] [62697]

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.[41361]

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.[41361] [52618] [62697]

Intramuscular dosage (methylprednisolone acetate injection suspension)

Adults

10 to 120 mg IM. Subsequent doses are determined by response and condition.[41362]

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.[41362]

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.[55690] [55691] [55692] [55693] [61950] 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.[61950] 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.[55690] [55692] [55693] A reduction in the frequency and severity of coronary artery lesions has also been reported with pulse dose methylprednisolone treatment.[55690] [55691] [55693]

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.[58690] [58691] [58692]

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

Oral dosage

Adults

4 to 48 mg, depending on disease treated, PO per day administered in 4 divided doses.[30015]

Children and Adolescents

0.5 to 1.7 mg/kg/day PO, given in divided doses every 6 to 12 hours.[52618] [62697]

Intravenous or Intramuscular dosage

Adults

Initially, 10 to 40 mg IV or IM. Subsequent IV/IM doses are determined by response and condition.[41361]

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.[41361] [52618] [62697]

Intramuscular dosage (methylprednisolone acetate injection suspension)

Adults

10 to 120 mg IM. Frequency of dosing varies with the condition being treated and patient response.[41362]

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.[41362]

For the management of multisystem inflammatory syndrome in children (MIS-C) post SARS-CoV-2 exposure†

Intravenous dosage

Infants, Children, and Adolescents

Available data are limited, and efficacy has not been established. 2 to 30 mg/kg/day IV has been reported, depending on the severity of illness, and is being used in combination with IVIG with or without aspirin. A 3-week at-home taper has been recommended.[65545] [65546] [65547] [65577] [65706] [65720] In 1 institutional protocol, methylprednisolone 3-day pulse dosing is recommended in high-risk patients (infants, Kawasaki disease shock syndrome, CRP more than 130 g/dL, admission echo Z score more than 2.5 or aneurysms, or Asian race) in combination with IVIG.[65577] Other dosing strategies that have been recommended for patients with symptoms of severe Kawasaki disease (KD), defined by fever or persistent inflammation for 48 hours or more after IVIG, Kobayashi score of 5 or more, features of secondary hemophagocytic lymphohistiocytosis (SHLH), shock, age younger than 1 year, or coronary or peripheral aneurysms at the time of diagnosis include methylprednisolone 0.8 mg/kg/dose IV twice daily for 5 to 7 days or until CRP normalizes followed by oral prednisone/prednisolone 2 mg/kg/day tapered over 2 to 3 weeks and methylprednisolone 10 to 30 mg/kg/dose IV daily for 3 days followed by oral prednisone/prednisolone 2 mg/kg/day until day 7 or until CRP normalizes and then tapered over 2 to 3 weeks. A dosing strategy for patients with signs and symptoms of SHLH includes methylprednisolone 30 mg/kg/dose IV daily for 3 doses followed by 1 mg/kg/dose IV every 12 hours then tapered.[65706] In a prospective observational study (n = 21, age 3 to 16 years), 7 patients received corticosteroids 2 to 10 mg/kg/day. All patients were discharged home after a median hospital stay of 8 days (range 5 to 17 days).[65546] In retrospective studies and case series (n = 6 to 186), 34% to 100% of patients received steroids.[65545] [65547] [65712] [65713] [65714]

Therapeutic Drug Monitoring

Maximum Dosage Limits

    Patients with Hepatic Impairment Dosing

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

    Patients with Renal Impairment Dosing

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

    † Off-label indication
    Revision Date: 07/16/2020, 06:35:48 PM

    References

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Pneumocystis jiroveci in solid organ transplantation: guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant 2019;9:e13587.64934 - Shenoi RP, Timm N, AAP Committee on Drugs, AAP Committee on Emergency Medicine. Drugs used to treat pediatric emergencies. Pediatrics 2020;145:e20193450.65545 - Verdoni L, Mazza A, Gervasoni A, et al. An outbreak of severe Kawasaki-like disease at the Italian epicenter of the SARS-CoV-2 epidemic: an observational cohort study. Lancet 2020; 395 (10239): 1771-1778.65546 - Toubiana J, Poirault C, Corsia A, et al. Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: prospective observational study. BMJ 2020; 369m2094. Published 2020 Jun 3. doi: 10.1135/bmj.m209465547 - Chiotos K, Bassiri H, Behrens EM, et al. Multisystem inflammatory syndrome in children during the COVID-19 pandemic: a case series [published online ahead of print, 2020 May 28]. J Pediatric Infect Dis Soc. 2020; piaa069. doi:10.1093/jpids/piaa06965577 - Hennon TR, Penque MD, Abdul-Aziz R, et al. COVID-19 associated multisystem inflammatory syndrome in children (MIS-C) guidelines; a western New York approach. Prog Pediatric Cardiol 2020 May 23.65706 - Nakra NA, Blumberg DA, Herrera-Guerra A, Lakshminrusimha S. Multisystem inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection: review of clinical presentation, hypothetical pathogenesis, and proposed management. Children 2020; 7(7): 69.65712 - Belhadjer Z, Meot M, Bajolle F, et al. Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic. Circulation 2020 [Epub ahead of print]65713 - Feldstein LR, Rose EB, Horwitz SM, et al. Multisystem inflammatory syndrome in U.S. children and adolescents. [Epub ahead of print, 2020 June 29]. N Engl J Med.65714 - Dufort EM, Koumans EH, Chow EJ, et al. Multisystem inflammatory syndrome in children in New York State. [Epub ahead of print, 2020 June 29]. N Engl J Med.65720 - American Academy of Pediatrics (AAP). Multisystem inflammatory syndrome in children (MIS-C) interim guidance. Accessed July 17, 2020. Available at on the World Wide Web at: https://services.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/clinical-guidance/multisystem-inflammatory-syndrome-in-children-mis-c-interim-guidance/

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    Methylprednisolone Sodium Succinate Powder for solution for injection

    Methylprednisolone Sodium Succinate 1g Powder for Injection (55390-0219) (Bedford Laboratories, a Hikma Company) (off market)

    Methylprednisolone Sodium Succinate Powder for solution for injection

    Methylprednisolone Sodium Succinate 1g Powder for Injection (55390-0259) (Bedford Laboratories, a Hikma Company) (off market)

    Methylprednisolone Sodium Succinate Powder for solution for injection

    Methylprednisolone Sodium Succinate 1g Powder for Injection (63323-0265) (Fresenius Kabi USA, LLC) null

    Methylprednisolone Sodium Succinate Powder for solution for injection

    Methylprednisolone Sodium Succinate 1g Powder for Injection (00143-9851) (Hikma Pharmaceuticals USA inc.) null

    Methylprednisolone Sodium Succinate Powder for solution for injection

    Methylprednisolone Sodium Succinate 1g Powder for Injection (25021-0810) (Sagent Pharmaceuticals) null

    Methylprednisolone Sodium Succinate Powder for solution for injection

    Solu-Medrol 1g Powder for Injection (00009-3389) (Pfizer Inc.) (off market)Solu-Medrol 1g Powder for Injection package photo

    Methylprednisolone Sodium Succinate Powder for solution for injection

    Solu-Medrol 1g Powder for Injection (00009-0698) (Pfizer Inc.) null

    Methylprednisolone Sodium Succinate Powder for solution for injection

    Solu-Medrol 1g Powder for Injection (00009-0018) (Pfizer Inc.) null

    Methylprednisolone Sodium Succinate Powder for solution for injection

    Solu-Medrol 1g Powder for Injection (PREMIER ProRX) (00009-0698) (Pfizer Inc.) null

    Methylprednisolone Sodium Succinate Powder for solution for injection

    Solu-Medrol 2g Powder for Injection (00009-0796) (Pfizer Inc.) (off market)

    Methylprednisolone Sodium Succinate Powder for solution for injection

    Solu-Medrol 2g Powder for Injection (00009-0850) (Pfizer Inc.) null

    Methylprednisolone Sodium Succinate Powder for solution for injection

    A-Methapred 40mg Powder for Injection (00409-5684) (Hospira Worldwide, Inc., a Pfizer Company) null

    Methylprednisolone Sodium Succinate Powder for solution for injection

    A-Methapred 40mg Powder for Injection (00074-5684) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

    Methylprednisolone Sodium Succinate Powder for solution for injection

    A-Methapred 40mg Powder for Injection (00409-3217) (Hospira Worldwide, Inc., a Pfizer Company) null

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    A-Methapred 40mg Powder for Injection (00409-5684) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

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    Methylprednisolone Sodium Succinate 40mg Powder for Injection (70121-1000) (Amneal Biosciences) null

    Methylprednisolone Sodium Succinate Powder for solution for injection

    Methylprednisolone Sodium Succinate 40mg Powder for Injection (55390-0209) (Bedford Laboratories, a Hikma Company) (off market)

    Methylprednisolone Sodium Succinate Powder for solution for injection

    Methylprednisolone Sodium Succinate 40mg Powder for Injection (63323-0255) (Fresenius Kabi USA, LLC) null

    Methylprednisolone Sodium Succinate Powder for solution for injection

    Methylprednisolone Sodium Succinate 40mg Powder for Injection (25021-0807) (Sagent Pharmaceuticals) null

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    Solu-Medrol 40mg Powder for Injection (00009-0113) (Pfizer Inc.) (off market)Solu-Medrol 40mg Powder for Injection package photo

    Methylprednisolone Sodium Succinate Powder for solution for injection

    Solu-Medrol 40mg Powder for Injection (00009-0039) (Pfizer Inc.) nullSolu-Medrol 40mg Powder for Injection package photo

    Methylprednisolone Sodium Succinate Powder for solution for injection

    Solu-Medrol 40mg Powder for Injection (NOVAPLUS) (00009-0039) (Pfizer Inc.) null

    Methylprednisolone Sodium Succinate Powder for solution for injection

    Solu-Medrol 40mg Powder for Injection (PREMIER ProRx) (00009-0039) (Pfizer Inc.) null

    Methylprednisolone Sodium Succinate Powder for solution for injection

    A-Methapred 125mg Powder for Injection (00074-5685) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

    Methylprednisolone Sodium Succinate Powder for solution for injection

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    Methylprednisolone Sodium Succinate Powder for solution for injection

    A-Methapred 125mg Powder for Injection (00409-5685) (Hospira Worldwide, Inc., a Pfizer Company) null

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    A-Methapred 125mg Powder for Injection (00409-5685) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

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    Methylprednisolone Sodium Succinate 125mg Powder for Injection (70121-1001) (Amneal Biosciences) null

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    Methylprednisolone Sodium Succinate 125mg Powder for Injection (55390-0210) (Bedford Laboratories, a Hikma Company) (off market)

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    Methylprednisolone Sodium Succinate Powder for solution for injection

    Methylprednisolone Sodium Succinate 125mg Powder for Injection (25021-0808) (Sagent Pharmaceuticals) null

    Methylprednisolone Sodium Succinate Powder for solution for injection

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    Methylprednisolone Sodium Succinate Powder for solution for injection

    Solu-Medrol 125mg Powder for Injection (00009-0047) (Pfizer Inc.) nullSolu-Medrol 125mg Powder for Injection package photo

    Methylprednisolone Sodium Succinate Powder for solution for injection

    Solu-Medrol 125mg Powder for Injection (NOVAPLUS) (00009-0047) (Pfizer Inc.) null

    Methylprednisolone Sodium Succinate Powder for solution for injection

    Solu-Medrol 125mg Powder for Injection (PREMIER ProRx) (00009-0047) (Pfizer Inc.) null

    Methylprednisolone Sodium Succinate Powder for solution for injection

    A-Methapred 500mg Powder for Injection (00074-5630) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

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    Methylprednisolone Sodium Succinate 500mg Powder for Injection (55390-0218) (Bedford Laboratories, a Hikma Company) (off market)

    Methylprednisolone Sodium Succinate Powder for solution for injection

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    Methylprednisolone Sodium Succinate 500mg Powder for Injection (00143-9850) (Hikma Pharmaceuticals USA inc.) null

    Methylprednisolone Sodium Succinate Powder for solution for injection

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    Solu-Medrol 500mg Powder for Injection (00009-0887) (Pfizer Inc.) (off market)

    Methylprednisolone Sodium Succinate Powder for solution for injection

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    Methylprednisolone Sodium Succinate Powder for solution for injection

    Solu-Medrol 500mg Powder for Injection (00009-0003) (Pfizer Inc.) null

    Methylprednisolone Sodium Succinate Powder for solution for injection

    A-Methapred 1000mg Powder for Injection (00074-5631) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

    Description/Classification

    Description

    Methylprednisolone and its derivatives, methylprednisolone sodium succinate and methylprednisolone acetate, are synthetic glucocorticoids used orally or parenterally as antiinflammatory or immunosuppressive agents. Methylprednisolone is used in many conditions in adult and pediatric patients, including many allergic, dermatologic, and inflammatory states when systemic treatment is medically necessary. The drug is commonly used parenterally when a patient cannot take oral prednisone. Methylprednisolone has very little mineralocorticoid activity and is therefore not used to manage adrenal insufficiency unless a more potent mineralocorticoid is administered concomitantly. Systemic corticosteroids may be added to other long-term maintenance medications in the management of uncontrolled severe persistent asthma. Once stabilization of asthma is achieved, regular attempts should be made to reduce or eliminate the use of systemic corticosteroids due to the side effects associated with chronic administration.[64807] Short courses of treatment may be used in moderate to severe exacerbations of asthma or COPD.[62784][63765][64807] If long-term therapy is required, the lowest possible effective dose should be used.

    Classifications

    • Systemic Hormonal Agents (excluding Sex Hormones)
      • Systemic Corticosteroids
        • Systemic Corticosteroids, Plain
    Revision Date: 05/29/2020, 01:34:50 PM

    References

    62784 - Leuppi JD, Schuetz P, Bingisser R, et al. Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial. JAMA. 2013;309:2223-2231.63765 - Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2019. Retrieved 11/19/2018. Available on the World Wide Web at https://goldcopd.org/wp-content/uploads/2018/11/GOLD-2019-v1.7-FINAL-14Nov2018-WMS.pdf64807 - Global Strategy for Asthma Management and Prevention. Global Initiative for Asthma (GINA) 2020. Available from: http://www.ginasthma.org. Accessed May 20th, 2020.

    Administration Information

    General Administration Information

    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.

     

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

    Route-Specific Administration

    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).

    Clinical Pharmaceutics Information

    From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database

    Methylprednisolone acetate

    pH Range
    pH 3.5 to 7
    ReferencesAnon. Manufacturer's information and labeling. (Package insert).
    Stability
    Methylprednisolone acetate injectable suspension in intact vials stored as directed by the manufacturer is stable until the labeled expiration date.
    ReferencesAnon. Manufacturer's information and labeling. (Package insert).
    Other Information
    Other drugs: The manufacturer indicates that methylprednisolone acetate should not be mixed with other drugs because of the potential for incompatibilities.
    ReferencesAnon. Manufacturer's information and labeling. (Package insert).
    Stability Max
    Maximum reported stability period: Combined with ropivacaine hydrochloride - 30 days refrigerated and at room temperature with and without light exposure.
    ReferencesRobustelli della Cuna FS, Mella M, Magistrali G, et al. Stability and compatibility of methylprednisolone acetate and ropivacaine hydrochloride in polypropylene syringes for epidural administration. Am J Health-Syst Pharm. 2001; 58

    Methylprednisolone sodium succinate

    pH Range
    pH 7 to 8
    ReferencesSolu-Medrol (methylprednisolone sodium succinate) injection package insert. New York, NY. Pharmacia & Upjohn Co. 2018; Jul
    Sodium Content
    Methylprednisolone sodium succinate 1 g provides 2.01 mEq of sodium.
    ReferencesRaymond G, Day P, Rabb M. Sodium content of commonly administered intravenous drugs. Hosp Pharm. 1982; 17
    Osmolality/Osmolarity
    The manufacturer indicates that the osmolarities of the various concentrations of reconstituted methylprednisolone sodium succinate are as noted: 40 mg/mL is 500 mOsm/L; 62.5 mg/mL is 400 mOsm/L; 65.4 mg/mL is 420 mOsm/L; and 125 mg/mL is 440 mOsm/L The calculated osmolalities of methylprednisolone sodium succinate 20 mg/mL in dextrose 5% or sodium chloride 0.9% are 318 mOsm/kg and 345 mOsm/kg, respectively. The calculated osmolalities of methylprednisolone sodium succinate 10 mg/mL in dextrose 5% or sodium chloride 0.9% are 291 mOsm/kg and 318 mOsm/kg, respectively. The calculated osmolalities of methylprednisolone sodium succinate 5 mg/mL in dextrose 5% or sodium chloride 0.9% are 275 mOsm/kg and 301 mOsm/kg, respectively.
    ReferencesAnon. Manufacturer's information and labeling. (Package insert).
    ReferencesWermeling DP, Rapp RP, DeLuca PP, et al. Osmolality of small-volume intravenous admixtures. Am J Hosp Pharm. 1986; 42
    Stability
    The containers should not be autoclaved to sterilize the exterior of the containers because of heat sensitivity of the drug. The manufacturer indicates that reconstituted methylprednisolone sodium succinate is stable for 48 hours at room temperature. It is subject to ester hydrolysis resulting in the formation of decomposition products that include less soluble free methylprednisolone and precipitate formation. The reconstituted injection should be clear and should be discarded if not free of particulates. Nahata et al. reported that Upjohn methylprednisolone sodium succinate reconstituted with sterile water for injection to a concentration of 4 mg/mL packaged in glass vials was stable for 24 hours at room temperature and 7 days refrigerated. HPLC analysis found 10% drug loss in 24 hours at 22 degrees C and 6% loss in 7 days at 4 degrees C. The loss increased to 17% in 14 days under refrigeration. Infusion Solutions: The manufacturer recommends dilution of methylprednisolone sodium succinate in dextrose 5%, dextrose 5% in sodium chloride 0.9%, or in sodium chloride 0.9% for intravenous infusion. Methylprednisolone sodium succinate may appear hazy upon dilution, although improvements in manufacturing have substantially reduced the amount of haze compared to the past. The haziness may be higher in dextrose 5% than in sodium chloride 0.9%. Pyter et al. reported that increasing drug concentration also played a role in increasing haze. In addition, they noted that simple ester hydrolysis did not explain differences in observed haze. Instead, they suggested that the solubility of free methylprednisolone in various concentrations of methylprednisolone sodium succinate may be important. The solubility of free methylprednisolone increases with increasing concentrations of methylprednisolone sodium succinate reducing haze and precipitation in concentrations over 10 mg/mL. Differences between dextrose 5% and sodium chloride 0.9% were attributed to the pH of the dextrose and the electrolyte content of the sodium chloride 0.9%. Packaged in Syringes: Gupta reported that Pharmacia & Upjohn methylprednisolone sodium succinate 10 mg/mL in sodium chloride 0.9% packaged in Becton Dickinson and Monoject polypropylene syringes remained clear and stable for 7 days at room temperature and at least 21 days refrigerated. HPLC analysis found about 10% loss occurred in 7 days at 25 degrees C and about 4% loss occurred in 21 days at 5 degrees C. Intrathecal Solutions D'Hondt et al. reported the stability of a 3-drug intrathecal combination in 0.9% sodium chloride. The 3-drug combination contained cytarabine 3.85 mg/mL, methotrexate sodium 1.54 mg/mL, and methylprednisolone sodium succinate 0.51 mg/mL. The 3-drug mixture was packaged in plastic syringes (PhaSeal, Carmel Pharma) and Type I brown glass vials. Samples were stored refrigerated at 5 degrees C, room temperature of 25 degrees C, and elevated temperature of 40 degrees C all protected from exposure to light. The samples were evaluated for physical and chemical stability over 48 hours. All of the samples were found to be physically compatible throughout the study period. Stability-indicating HPLC analysis found cytarabine and methotrexate were both chemically stable for 48 hours at all three temperature in both containers. However, methylprednisolone sodium succinate proved to be the least stable component exhibiting losses of about 6 to 7% in 48 hours at 5 degrees C, 5% and 10 to 14% losses in 8 and 24 hours, respectively, at 25 degrees C , and 10% or more in 4 hours at 40 degrees C . In addition, if exposed to intense ultraviolet or visible light, substantial losses of methotrexate sodium occurred. The authors concluded that the 3-drug mixture was only stable for 12 hours if refrigerated and protected from exposure to light.
    ReferencesD'Hondt M, Vangheluwe E, Van Dorpe S, et al. Stability of extemporaneously prepared cytarabine, methotrexate sodium, and methylprednisolone sodium succinate. Am J Health-Syst Pharm. 2012; 69
    ReferencesGupta VD. Chemical stability of methylprednisolone sodium succinate after reconstitution in 0.9% sodium chloride injection and storage in polypropylene syringes. Int J Pharmaceut Compound. 2001; 5
    ReferencesNahata MC, Morosco RS, Hipple TF. Stability of diluted methylprednisolone sodium succinate injection at two temperatures. Am J Hosp Pharm. 1994; 51
    ReferencesPyter RA, Hsu LCC, Buddenhagen JD. Stability of methylprednisolone sodium succinate in 5% dextrose and0.9% sodium chloride injections. Am J Hosp Pharm. 1983; 40
    ReferencesUlsaker G, Teien G. Degradation of methylprednisolone sodium succinate in a diluent-containing vial. Am J Health-Syst Pharm. 2002; 59
    ReferencesSolu-Medrol (methylprednisolone sodium succinate) injection package insert. New York, NY. Pharmacia & Upjohn Co. 2018; Jul
    pH Effects
    The pH exhibiting the minimum rate of ester hydrolysis is pH 3.5. Between pH 3.4 and 7.4 acyl migration is the principal route of decomposition.
    ReferencesAnderson BD, Taphouse V. Initial rate studies of hydrolysis and acyl migration in methylprednisolone 21-hemisuccinate and 17-hemisuccinate. J Pharm Sci. 1981; 70
    Light Exposure
    Methylprednisolone sodium succinate should be protected from exposure to light during long-term storage. D'Hondt et al. evaluated the stability of methylprednisolone sodium succinate 0.51 mg/mL in a 3-drug intrathecal injection exposed to intense ultraviolet and visible light at 25 degrees C. Stability-indicating HPLC analysis found little change in the methylprednisolone sodium succinate concentration after 48 hours exposed to ultraviolet light and 192 hours exposed to visible light.
    ReferencesD'Hondt M, Vangheluwe E, Van Dorpe S, et al. Stability of extemporaneously prepared cytarabine, methotrexate sodium, and methylprednisolone sodium succinate. Am J Health-Syst Pharm. 2012; 69
    ReferencesSolu-Medrol (methylprednisolone sodium succinate) injection package insert. New York, NY. Pharmacia & Upjohn Co. 2018; Jul
    Freezing
    Ho and Goeman reported that reconstituted methylprednisolone sodium succinate 62.5 mg/mL was stable when frozen exhibiting no loss of drug for 4 weeks frozen at -20 degrees C. Sewell and Palmer reported that methylprednisolone sodium succinate 4.6 mg/mL (500 mg/108 mL) in sodium chloride 0.9% frozen at -20 degrees C was physically and chemically stable. No visible particulates or increase in microparticles occurred, and HPLC analysis found no loss of drug in 12 months of frozen storage with microwave thawing.
    ReferencesHo NFH, Goeman JA. Prediction of pharmaceutical stability of parenteral solutions. Drug Intell Clin Pharm. 1970; 4
    ReferencesSewell GJ, Palmer AJ. The chemical and physical stability of three intravenous infusions subjected to fozen storage and microwave thawing. Int J Pharm. 1991; 72
    Filtration
    Pall reported that methylprednisolone sodium succinate 4 mg/mL underwent little or no loss due to filtration through a Supor membrane filter.
    ReferencesAnon. Pall Medical Supor-membrane IV filter device drug-adsorption data. Data on file. 2004; 8
    Sorption Leaching
    Methylprednisolone sodium succinate has not been found to undergo substantial sorption to polyvinyl chloride (PVC), polyethylene, ethylene vinyl acetate (EVA), polypropylene (in syringes), or glass containers, or to elastomeric pump reservoirs. In addition, Xu et al. reported no sorption occurred to a polyurethane central catheter from Arrow International as well as no leaching of the chlorhexidine antimicrobial in it.
    ReferencesAnon. Guidelines for the administration of drugs using the Homepump Eclipse and C-Series disposable elastomeric infusion systems. Lake Forest, CA: I-Flow Corporation. 2004;
    ReferencesGupta VD. Chemical stability of methylprednisolone sodium succinate after reconstitution in 0.9% sodium chloride injection and storage in polypropylene syringes. Int J Pharmaceut Compound. 2001; 5
    ReferencesStewart JT, Warren FW, King AD. Stability of ranitidine hydrochloride and seven medications. Am J Hosp Pharm. 1994; 51
    ReferencesTrissel LA, Zhang Y. Stability of methylprednisolone sodium succinate in AutoDose infusion system bags. J Am Pharm Assoc. 2002; 42
    ReferencesXu QA, Zhang Y, Trissel LA, et al. Adequacy of a new chlorhexidine-bearing polyurethane central catheter for administration of 82 selected parenteral drugs. Ann Pharmacother. 2000; 34
    ReferencesZeidler C, Dettmering D, Schrammer W, et al. Compatibility of various drugs used in intensive care medicine in polyethylene, PVC, and glass infusion containers. Eur Hosp Pharm. 1999; 5
    Other Information
    Other Drugs: Amphotericin B is compatible with limited concentrations of methylprednisolone sodium succinate but precipitation may appear at higher concentrations. Irinotecan mixed with methylprednisolone sodium succinate resulted in an admixture pH over 6.5; 10% loss of irinotecan will occur in about 3 hours at this pH.
    ReferencesMcEvoy GK (ed). AHFS Drug Information (current edition). Bethesda, MD: American Society of Health-System Pharmacists.
    ReferencesTanque N, Ueda H, Moriyama Y, et al. Compatibility of irinotecan hydrochloride injection with other injections. Jpn J Hosp Pharm. 1996; 22
    ReferencesTrissel LA, Leissing NC. Trissel's Tables of Physical Compatibility. Lake Forest, IL: MultiMatrix, Inc. 1996;
    Stability Max
    Maximum reported stability periods: Reconstituted solution- 48 hours at room temperature. In D5W- 48 hours at room temperature. In NS- 48 hours at room temperature and 30 days refrigerated.
    ReferencesAnon. Manufacturer's information and labeling. (Package insert).
    ReferencesStewart JT, Warren FW, King AD. Stability of ranitidine hydrochloride and seven medications. Am J Hosp Pharm. 1994; 51
    ReferencesTrissel LA, Zhang Y. Stability of methylprednisolone sodium succinate in AutoDose infusion system bags. J Am Pharm Assoc. 2002; 42
    • [object Object]
    Revision Date: 09/18/2018, 08:16:15 AMCopyright 2004-2020 by Lawrence A. Trissel. All Rights Reserved.

    References

    Adverse Reactions

    Mild

    • abdominal pain
    • acne vulgaris
    • alopecia
    • amenorrhea
    • anorexia
    • anxiety
    • appetite stimulation
    • arthralgia
    • arthropathy
    • diaphoresis
    • diarrhea
    • dysmenorrhea
    • ecchymosis
    • emotional lability
    • fever
    • headache
    • hiccups
    • hirsutism
    • hypertrichosis
    • infection
    • injection site reaction
    • insomnia
    • lactose intolerance
    • lethargy
    • leukocytosis
    • malaise
    • menstrual irregularity
    • myalgia
    • nausea
    • paresthesias
    • petechiae
    • rash
    • restlessness
    • skin hyperpigmentation
    • skin hypopigmentation
    • striae
    • syncope
    • urinary urgency
    • urticaria
    • vertigo
    • vomiting
    • weakness
    • weight gain
    • xerosis

    Moderate

    • adrenocortical insufficiency
    • cataracts
    • constipation
    • Cushing's syndrome
    • depression
    • diabetes mellitus
    • edema
    • EEG changes
    • elevated hepatic enzymes
    • erythema
    • euphoria
    • exophthalmos
    • fluid retention
    • gastritis
    • glycosuria
    • growth inhibition
    • hepatitis
    • hepatomegaly
    • hypercholesterolemia
    • hyperglycemia
    • hypernatremia
    • hypertension
    • hypocalcemia
    • hypokalemia
    • hypotension
    • hypothalamic-pituitary-adrenal (HPA) suppression
    • immunosuppression
    • impaired wound healing
    • metabolic alkalosis
    • myopathy
    • neuritis
    • ocular infection
    • osteoporosis
    • palpitations
    • peripheral neuropathy
    • phlebitis
    • physiological dependence
    • pseudotumor cerebri
    • psychosis
    • scleroderma renal crisis
    • sinus tachycardia
    • sodium retention
    • urinary incontinence
    • withdrawal

    Severe

    • anaphylactoid reactions
    • angioedema
    • arrhythmia exacerbation
    • avascular necrosis
    • bone fractures
    • bradycardia
    • cardiac arrest
    • cardiomyopathy
    • esophageal ulceration
    • exfoliative dermatitis
    • GI perforation
    • heart failure
    • increased intracranial pressure
    • ocular hypertension
    • optic neuritis
    • pancreatitis
    • papilledema
    • peptic ulcer
    • pulmonary edema
    • retinopathy
    • seizures
    • skin atrophy
    • tendon rupture
    • thromboembolism
    • thrombosis
    • vasculitis
    • visual impairment

    Glucocorticoids are responsible for protein metabolism, and prolonged therapy can result in various musculoskeletal manifestations, including: myopathy (myalgia, muscle wasting, muscle weakness, quadriparesis), impaired wound healing, bone matrix atrophy (osteoporosis), bone fractures such as vertebral compression fractures or fractures of long bones, and avascular necrosis of femoral or humoral heads. These effects are more likely to occur in older or debilitated patients. Glucocorticoids interact with calcium metabolism at many sites, including: calcinosis, decreasing the synthesis by osteoblasts of the principle proteins of bone matrix, malabsorption of calcium in both the nephron and the gut, and reduction of sex hormone concentrations. Although all of these actions probably contribute to glucocorticoid-induced osteoporosis, the actions on osteoblasts is most important. Glucocorticoids do not modify vitamin D metabolism.[24837] Postmenopausal women, in particular, should be monitored for signs of osteoporosis during methylprednisolone therapy. Because of retardation of bone growth, children receiving prolonged corticosteroid therapy may have growth inhibition. Intra-articular injections of corticosteroids can cause Charcot-like arthropathy and postinjection flare. Atrophy at the site of injection has been reported following administration of soluble glucocorticoids. Tendon rupture has also been reported.[30015] [41361] [41362]

    Methylprednisolone can mask the symptoms of infection and should be avoided during an acute viral, fungal, or bacterial infection; as well, patients receiving corticosteroids are more susceptible to infections than are healthy individuals. Leukocytosis has been reported and is a common physiologic effect of systemic corticosteroid therapy and may need to be differentiated from the leukocytosis that occurs with inflammatory or infectious processes.[30943] [65096] [65097] Immunosuppression is most likely to occur in patients receiving high-dose (e.g., equivalent to 1 mg/kg or more of prednisone daily), systemic corticosteroid therapy for any period of time, particularly in conjunction with corticosteroid-sparing drugs (e.g., troleandomycin) and/or concomitant immunosuppressant agents; however, patients receiving moderate dosages of systemic corticosteroids for short periods or low dosages for prolonged periods also may be at risk. Corticosteroids can reactivate tuberculosis and should not be used in patients with a history of active tuberculosis except when chemoprophylaxis is instituted concomitantly. Patients receiving immunosuppressive doses of corticosteroids should be advised to avoid exposure to measles or varicella (chickenpox) and, if exposed to these diseases, to seek medical advice immediately.[30015] [41361] [41362]

    Corticosteroids are divided into two classes: mineralocorticoids and glucocorticoids. Methylprednisolone is a glucocorticoid with minimal mineralocorticoid activity. Mineralocorticoids alter electrolyte and fluid balance by facilitating sodium retention and hydrogen and potassium excretion at the level of the distal renal tubule, resulting in increased plasma volume. Although the incidence of effects with this medication are not well elicited, mineralocorticoid properties can cause fluid retention; electrolyte disturbances (hypokalemia, hypokalemic metabolic alkalosis, hypernatremia, hypocalcemia); and edema. In a review of 93 studies of corticosteroid use, hypertension was found to develop approximately 4 times as often in steroid recipients compared to control groups.[24362] As a result of the steroid-induced edema and elevated blood pressure, congestive heart failure can occur in susceptible patients. Dietary salt restriction and potassium supplementation may be needed in persons receiving treatment with methylprednisolone.[30015] [41361] [41362]

    Cardiovascular adverse events have been reported during and/or after treatment with parenteral methylprednisolone. These adverse events include bradycardia, cardiac arrest, cardiac arrhythmia exacerbation, cardiac failure, cardiomegaly, fat (lipid) emboli, hypertrophic cardiomyopathy (in premature infants), pulmonary edema, sinus tachycardia, syncope, and vasculitis. Additionally, corticosteroid therapy has also been associated with ruptures of the left ventricular free wall in persons having recently experienced a myocardial infarction; thus, caution is advised when prescribing methylprednisolone to these patients.[41361] [41362]

    Although corticosteroids are used to treat Graves' ophthalmopathy, ocular effects, such as exophthalmos, posterior subcapsular cataracts, retinopathy, or ocular hypertension, can result from prolonged use of methylprednisolone and could result in glaucoma or ocular nerve damage including optic neuritis. Temporary or permanent visual impairment, including blindness, has been reported with glucocorticoid administration by several routes of administration including intranasal and ophthalmic administration. Secondary bacterial, fungal, and viral ocular infection can be exacerbated by corticosteroid therapy. Corneal perforation may occur if corticosteroids are administered to patients with ocular herpes simplex and, thus, should not be used during active ocular herpes simplex infection.[30015] [41361] [41362]

    Prolonged therapy of methylprednisolone can adversely affect the endocrine system, resulting in hypercorticism (Cushing's syndrome), menstrual irregularity including amenorrhea or dysmenorrhea, hyperglycemia, glycosuria, and aggravation of diabetes mellitus in susceptible patients.[30015] [41361] [41362] In a published review of 93 studies of corticosteroid use, the development of diabetes mellitus was determined to occur 4 times more frequently in steroid recipients compared to control groups.[24362] Insulin or oral hypoglycemic dosages may require adjustment.

    Adverse GI effects associated with long-term corticosteroid administration include nausea, vomiting, and anorexia. Appetite stimulation with weight gain, diarrhea, constipation, abdominal pain and distention, esophageal ulceration, gastritis, GI perforation, and pancreatitis also have been reported. A few patients receiving prolonged corticosteroid administration have experienced production, reactivation, perforation, or delayed healing of peptic ulcer disease. Although it was once believed that corticosteroids like methylprednisolone contributed to the development of peptic ulcer disease, in a published review of 93 studies of corticosteroid use, the incidence of peptic ulcer disease was not found to be higher in steroid recipients compared to control groups.[24362] Cases of hepatomegaly and elevated hepatic enzymes (reversible upon discontinuation) have been associated with the use of methylprednisolone.[30015] [41361] [41362] Rarely, high doses of cyclically pulsed IV methylprednisolone can induce a toxic form of acute hepatitis. This may occur several weeks after exposure and resolution has been observed after treatment is discontinued. However, serious liver injury may occur, which could result in acute hepatic failure and death. Discontinue IV methylprednisolone if toxic hepatitis occurs. Avoid future use of high dose IV methylprednisolone in patients with toxic hepatitis caused by methylprednisolone.[41361]

    Adverse neurologic effects have been reported during prolonged corticosteroid administration and include headache, insomnia, vertigo, restlessness, ischemic peripheral neuropathy, neuritis, seizures or convulsions, and EEG changes. Mental disturbances, including depression, anxiety, euphoria, personality changes, and psychosis, have also been reported; emotional lability and psychotic problems can be exacerbated by methylprednisolone therapy.[30015] [41361] [41362]

    Various adverse dermatologic effects reported during corticosteroid therapy include rash (unspecified), skin atrophy, dry skin or xerosis, acne vulgaris, alopecia or thinning scalp hair, diaphoresis, impaired wound healing, facial erythema, striae, petechiae, hirsutism or hypertrichosis, ecchymosis, and easy bruising. Hypersensitivity reactions may manifest as allergic dermatitis, urticaria, anaphylactoid reactions, and/or angioedema.[30015] Paresthesias (burning or tingling) in the perineal area may occur following IV injection of corticosteroids like methylprednisolone. Parenteral corticosteroid therapy has also produced skin hypopigmentation, skin hyperpigmentation, scarring, and other types of injection site reaction (e.g., induration, delayed pain or soreness, subcutaneous and cutaneous atrophy, and sterile abscesses); use via incorrect route of administration and/or excessive doses may increase risk of such effects.[41361] [41362]

    Pharmacologic doses of methylprednisolone administered for prolonged periods can result in physiological dependence due to hypothalamic-pituitary-adrenal (HPA) suppression. Exogenous corticosteroids exert negative feedback on the pituitary, inhibiting the secretion of adrenocorticotropin (ACTH). This inhibition decreases ACTH-mediated synthesis of endogenous corticosteroids and androgens by the adrenal cortex. The severity of glucocorticoid-induced secondary adrenocortical insufficiency varies among individuals and is dependent on the dose, frequency, time of administration, and duration of therapy. Administering the drug on alternate days may help to alleviate this adverse effect. Patients with HPA suppression will require increased doses of corticosteroids during periods of physiologic stress. Acute adrenal insufficiency and even death can occur if sudden withdrawal of the drugs is undertaken. 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. A non-HAP withdrawal syndrome can occur following abrupt discontinuance of corticosteroid therapy and is apparently unrelated to adrenocortical insufficiency. This syndrome includes symptoms such as anorexia, lethargy, nausea, vomiting, headache, fever, arthralgia, myalgia, exfoliative dermatitis, weight loss, and hypotension. These effects are believed to be due to the sudden change in glucocorticoid concentration rather than to low corticosteroid levels. Increased intracranial pressure with papilledema (i.e., pseudotumor cerebri) has also been reported with withdrawal of glucocorticoid therapy.[30015] [41361] [41362]

    Hypercholesterolemia, atherosclerosis, fat (lipid) emboli, thrombosis, thromboembolism, and phlebitis, specifically, thrombophlebitis have been associated with corticosteroid therapy. Other adverse events reported during treatment with corticosteroids include abnormal fat deposits (moon face), hiccups, malaise, and changes (increase or decrease) in the motility and number of spermatozoa. Palpitations, glossitis, stomatitis, urinary incontinence, and urinary urgency have been rarely reported. Corticosteroids like methylprednisolone may also decrease serum concentrations of vitamin C (ascorbic acid) and vitamin A which may rarely produce symptoms of vitamin A deficiency or vitamin C deficiency.[30015] [41361] [41362]

    The Solu-Medrol 40 mg presentation contains lactose monohydrate produced from cow's milk. In situations where allergic symptoms worsen or new allergic symptoms occur after administration of this preparation, consider the potential for hypersensitivity reactions to cow's milk ingredients. Additionally, lactose intolerance symptoms such as nausea/vomiting, bloating, abdominal pain (cramps), and flatulence may occur. Use appropriate precautions when administering to patients with a cow's milk sensitivity or lactose intolerance. If hypersensitivity reactions occur with the Solu-Medrol 40 mg presentation, consider discontinuing treatments and using alternative treatments, including corticosteroid formulations that do not contain ingredients produced from cow's milk.[41361]

    An increased incidence of scleroderma renal crisis (SRC) has been observed in patients with systemic sclerosis (systemic scleroderma) treated with corticosteroids. SRC is characterized by malignant hypertension and acute renal failure (unspecified) that may be accompanied by oliguria or anuria.[30015] [41361] [41362]

    Revision Date: 03/09/2020, 05:38:39 PM

    References

    24362 - Conn HO, Poynard T. Corticosteroids and peptic ulcer: meta-analysis of adverse events during steroid therapy. J Intern Med 1994;236:619-32.24837 - Reid IR. Preventing glucocorticoid-induced osteoporosis. N Engl J Med 1997;337:420-1.30015 - Medrol (methylprednisolone) package insert. New York, NY: Pharmacia and Upjohn Company; 2018 July.30943 - Schimmer B, Parker K. Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Hardman JG, Limbird LE, Molinoff PB, et al., eds. Goodman and Gilman's the Pharmacological Basis of Therapeutics, 10th edition. New York: McGraw Hill, 2001;1649-1674.41361 - Solu-Medrol (methylprednisolone sodium succinate for injection) package insert. New York, NY: Pharmacia and Upjohn Co; 2018 July.41362 - Depo-Medrol (methylprednisolone acetate for injection, suspension) package insert. New York, NY: Pharmacia and Upjohn Company; 2018 July.65096 - Abramson N, Melton B. Leukocytosis: basic of clinical assessment. Am Fam Physician 2000;62:2053-60.65097 - Shoenfeld Y, Gurewich Y, Gallant LA, et al. Prednisone-induced leukocytosis. Influenced of dosage, method and duration of administration on the degree of leukocytosis. Am J Med 1981;71:773-8.

    Contraindications/Precautions

    Absolute contraindications are italicized.

    • corticosteroid hypersensitivity
    • intrathecal administration
    • abrupt discontinuation
    • breast-feeding
    • cataracts
    • children
    • coagulopathy
    • Cushing's syndrome
    • diabetes mellitus
    • diverticulitis
    • epidural administration
    • fungal infection
    • geriatric
    • GI perforation
    • glaucoma
    • growth inhibition
    • head trauma
    • heart failure
    • hepatic disease
    • herpes infection
    • hypertension
    • hyperthyroidism
    • hypothalamic-pituitary-adrenal (HPA) suppression
    • hypothyroidism
    • immune thrombocytopenic purpura (ITP)
    • immunosuppression
    • increased intracranial pressure
    • increased intraocular pressure
    • infants
    • infection
    • intravenous administration
    • measles
    • myasthenia gravis
    • mycobacterial infection
    • myocardial infarction
    • neonates
    • neurologic events
    • osteoporosis
    • peptic ulcer disease
    • pregnancy
    • premature neonates
    • psychosis
    • renal disease
    • scleroderma
    • seizure disorder
    • sepsis
    • surgery
    • thromboembolic disease
    • thyroid disease
    • tuberculosis
    • ulcerative colitis
    • vaccination
    • varicella
    • viral infection
    • visual disturbance

    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.[41361]

    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.[41361] [41362] Do not give methylprednisolone acetate (e.g., Depo-Medrol) via intravenous administration.[41362] Do not administer any form of parenteral methylprednisolone into the deltoid muscle as subcutaneous atrophy occurs with high frequency following such use.[41361] [41362] 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.[41361] [57053]

    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 [41362] or when the sodium succinate parenteral solution (e.g., Solu-Medrol) or oral formulations are used to control drug reactions.[41361] 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.[41361] Do not administer parenteral methylprednisolone intra-articularly, intrabursally, or for intratendinous use for local effect in the presence of an acute infection [41361] [41362]; further, local administration of methylprednisolone acetate into a previously infected site is not usually recommended.[41362] 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.[30015] [41361] [41362]

    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.

    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.

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

    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.

    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.[30015] [41361] [41362]

    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.

    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.[30015] [41361] [41362]

    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]

    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.[41361] [41362]

    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.[41361] 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.[33727] [33728] In one of the reports, 2 babies had normal blood cell counts, no increase in infections, and above average growth rates.[33728] 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.[27500] 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.

    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.[41361] 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.[51792] [58998] 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.[41361]

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

    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).

    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.[41361] [41362]

    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.[27642] It is advisable that patients who have a hypersensitivity reaction to any corticosteroid undergo skin testing, which, although not a conclusive predictor, may help to determine if hypersensitivity to another corticosteroid exists. Such patients should be carefully monitored during and following the administration of any corticosteroid.[27616]

    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.[30015] [41361] [41362]

    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.[63923] 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.[60742]

    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.[41361]

    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.

    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.[41361]

    Revision Date: 11/06/2019, 03:30:06 PM

    References

    27500 - American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.27616 - Butani L. Corticosteroid-induced hypersensitivity reactions. Ann Allergy Asthma Immunol 2002;89(5):439-445.27642 - Kamm GL, Hagmeyer KO. Allergic-type reactions to corticosteroids. Ann Pharmacother 1999;33(4):451-460.30015 - Medrol (methylprednisolone) package insert. New York, NY: Pharmacia and Upjohn Company; 2018 July.33727 - Coulam CB, Moyer TP, Jiang N-S, et al. Breast-feeding after renal transplantation. Transplant Proc 1982;13:605-9.33728 - Grekas DM, Vasiliou SS, Lazarides AN. Immunosuppresive therapy and breast-feeding after renal transplantation. Nephron 1984;37:68. Letter.41361 - Solu-Medrol (methylprednisolone sodium succinate for injection) package insert. New York, NY: Pharmacia and Upjohn Co; 2018 July.41362 - Depo-Medrol (methylprednisolone acetate for injection, suspension) package insert. New York, NY: Pharmacia and Upjohn Company; 2018 July.51792 - Patradoon-Ho P, Gunasekera H, Ryan MM. Inhaled corticosteroids, adrenal suppression and benign intracranial hypertension. Med J Aust 2006;185:279-28057053 - Food and Drug Administration (US FDA) Drug Medwatch-FDA requires label changes to warn of rare but serious neurologic problems after epidural corticosteroid injections for pain. Retrieved April 23, 2014. Available on the World Wide Web at http://www.fda.gov/downloads/Drugs/DrugSafety/UCM394286.pdf.58998 - Neville BG, Wilson J. Benign intracranial hypertension following corticosteroid withdrawal in childhood. Br Med J 1970;3:554-556.60742 - Health Care Financing Administration. Interpretive Guidelines for Long-term Care Facilities. Title 42 CFR 483.25(l) F329: Unnecessary Drugs. Revised 2015.63923 - The American Geriatrics Society 2019 Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2019;00:1-21.

    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.

    Revision Date: 01/11/2018, 11:43:25 AM

    References

    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.[41361][41362][30943]

     

    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.[41361]

    Route-Specific Pharmacokinetics

    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.[41361]

    Intramuscular Route

    Systemic absorption is rapid following IM administration of methylprednisolone sodium succinate.[41361]

    Other Route(s)

    Intra-articular Route

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

    Revision Date: 09/04/2018, 03:57:33 PM

    References

    30943 - Schimmer B, Parker K. Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Hardman JG, Limbird LE, Molinoff PB, et al., eds. Goodman and Gilman's the Pharmacological Basis of Therapeutics, 10th edition. New York: McGraw Hill, 2001;1649-1674.41361 - Solu-Medrol (methylprednisolone sodium succinate for injection) package insert. New York, NY: Pharmacia and Upjohn Co; 2018 July.41362 - Depo-Medrol (methylprednisolone acetate for injection, suspension) package insert. New York, NY: Pharmacia and Upjohn Company; 2018 July.

    Pregnancy/Breast-feeding

    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.[41361] [41362]

    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.[41361] 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.[33727] [33728] In one of the reports, 2 babies had normal blood cell counts, no increase in infections, and above average growth rates.[33728] 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.[27500] 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.

    Revision Date: 04/03/2018, 03:12:12 PM

    References

    27500 - American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.33727 - Coulam CB, Moyer TP, Jiang N-S, et al. Breast-feeding after renal transplantation. Transplant Proc 1982;13:605-9.33728 - Grekas DM, Vasiliou SS, Lazarides AN. Immunosuppresive therapy and breast-feeding after renal transplantation. Nephron 1984;37:68. Letter.41361 - Solu-Medrol (methylprednisolone sodium succinate for injection) package insert. New York, NY: Pharmacia and Upjohn Co; 2018 July.41362 - Depo-Medrol (methylprednisolone acetate for injection, suspension) package insert. New York, NY: Pharmacia and Upjohn Company; 2018 July.

    Interactions

    Level 1 (Severe)

    • Alefacept
    • Iopamidol
    • Live Vaccines
    • Metyrapone

    Level 2 (Major)

    • Amiodarone
    • Boceprevir
    • Conivaptan
    • Desmopressin
    • Dofetilide
    • Efalizumab
    • Halofantrine
    • Hylan G-F 20
    • Idelalisib
    • Iohexol
    • Levomethadyl
    • Macimorelin
    • Mifepristone
    • Muromonab-CD3
    • Natalizumab
    • Penicillamine
    • Ritodrine
    • Sargramostim, GM-CSF
    • Sipuleucel-T
    • Tacrolimus
    • Telaprevir
    • Vigabatrin

    Level 3 (Moderate)

    • Abatacept
    • Acetaminophen; Aspirin, ASA; Caffeine
    • Acetaminophen; Butalbital
    • Acetaminophen; Butalbital; Caffeine
    • Acetaminophen; Butalbital; Caffeine; Codeine
    • Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine
    • Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide
    • Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine
    • Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine
    • Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine
    • Acetaminophen; Dextromethorphan; Phenylephrine
    • Acetaminophen; Guaifenesin; Phenylephrine
    • Acetazolamide
    • Acetohexamide
    • Adalimumab
    • Albiglutide
    • Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ
    • Aliskiren; Hydrochlorothiazide, HCTZ
    • Alogliptin; Metformin
    • Alpha-glucosidase Inhibitors
    • Ambenonium Chloride
    • Amifampridine
    • Amiloride; Hydrochlorothiazide, HCTZ
    • Aminosalicylate sodium, Aminosalicylic acid
    • Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan
    • Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan
    • Amphotericin B
    • Amphotericin B cholesteryl sulfate complex (ABCD)
    • Amphotericin B lipid complex (ABLC)
    • Amphotericin B liposomal (LAmB)
    • Antithymocyte Globulin
    • Aprepitant, Fosaprepitant
    • Argatroban
    • Arsenic Trioxide
    • Asparaginase Erwinia chrysanthemi
    • Aspirin, ASA
    • Aspirin, ASA; Butalbital; Caffeine
    • Aspirin, ASA; Butalbital; Caffeine; Codeine
    • Aspirin, ASA; Caffeine; Dihydrocodeine
    • Aspirin, ASA; Caffeine; Orphenadrine
    • Aspirin, ASA; Carisoprodol
    • Aspirin, ASA; Carisoprodol; Codeine
    • Aspirin, ASA; Citric Acid; Sodium Bicarbonate
    • Aspirin, ASA; Dipyridamole
    • Aspirin, ASA; Omeprazole
    • Aspirin, ASA; Oxycodone
    • Aspirin, ASA; Pravastatin
    • Atazanavir
    • Atazanavir; Cobicistat
    • Atenolol; Chlorthalidone
    • Atracurium
    • Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
    • Atropine; Hyoscyamine; Phenobarbital; Scopolamine
    • Azilsartan; Chlorthalidone
    • Belladonna Alkaloids; Ergotamine; Phenobarbital
    • Benazepril; Hydrochlorothiazide, HCTZ
    • Bendroflumethiazide; Nadolol
    • Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
    • Bepridil
    • Bismuth Subsalicylate
    • Bismuth Subsalicylate; Metronidazole; Tetracycline
    • Bisoprolol; Hydrochlorothiazide, HCTZ
    • Bivalirudin
    • Brompheniramine; Carbetapentane; Phenylephrine
    • Brompheniramine; Dextromethorphan; Phenylephrine
    • Bupropion
    • Bupropion; Naltrexone
    • Butabarbital
    • Calcium Carbonate
    • Calcium Carbonate; Magnesium Hydroxide
    • Calcium Carbonate; Risedronate
    • Calcium Carbonate; Simethicone
    • Canagliflozin
    • Canagliflozin; Metformin
    • Candesartan; Hydrochlorothiazide, HCTZ
    • Captopril; Hydrochlorothiazide, HCTZ
    • Carbamazepine
    • Carbetapentane; Chlorpheniramine; Phenylephrine
    • Carbetapentane; Diphenhydramine; Phenylephrine
    • Carbetapentane; Guaifenesin; Phenylephrine
    • Carbetapentane; Phenylephrine
    • Carbetapentane; Phenylephrine; Pyrilamine
    • Carbinoxamine; Hydrocodone; Phenylephrine
    • Carbinoxamine; Phenylephrine
    • Ceritinib
    • Certolizumab pegol
    • Chlophedianol; Guaifenesin; Phenylephrine
    • Chlorothiazide
    • Chlorpheniramine; Dextromethorphan; Phenylephrine
    • Chlorpheniramine; Dihydrocodeine; Phenylephrine
    • Chlorpheniramine; Hydrocodone; Phenylephrine
    • Chlorpheniramine; Phenylephrine
    • Chlorpropamide
    • Chlorthalidone
    • Chlorthalidone; Clonidine
    • Cholestyramine
    • Choline Salicylate; Magnesium Salicylate
    • Cimetidine
    • Cisatracurium
    • Citalopram
    • Clindamycin
    • Cobicistat
    • Codeine; Phenylephrine; Promethazine
    • Cyclosporine
    • Dapagliflozin
    • Dapagliflozin; Metformin
    • Dapagliflozin; Saxagliptin
    • Darunavir
    • Darunavir; Cobicistat
    • Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
    • Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
    • Deferasirox
    • Denosumab
    • Dextran
    • Dextromethorphan; Diphenhydramine; Phenylephrine
    • Dextromethorphan; Guaifenesin; Phenylephrine
    • Digoxin
    • Diltiazem
    • Dipeptidyl Peptidase-4 Inhibitors
    • Diphenhydramine; Hydrocodone; Phenylephrine
    • Diphenhydramine; Phenylephrine
    • Doxacurium
    • Dronedarone
    • Droperidol
    • Dulaglutide
    • Echinacea
    • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
    • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
    • Empagliflozin
    • Empagliflozin; Linagliptin
    • Empagliflozin; Linagliptin; Metformin
    • Empagliflozin; Metformin
    • Enalapril; Hydrochlorothiazide, HCTZ
    • Ephedrine
    • Eprosartan; Hydrochlorothiazide, HCTZ
    • Erlotinib
    • Ertugliflozin
    • Ertugliflozin; Metformin
    • Ertugliflozin; Sitagliptin
    • Estrogens
    • Etravirine
    • Exenatide
    • Fluconazole
    • Fluoxymesterone
    • Fosamprenavir
    • Fosinopril; Hydrochlorothiazide, HCTZ
    • Gallium Ga 68 Dotatate
    • Gemcitabine
    • Gentamicin
    • Glimepiride
    • Glimepiride; Pioglitazone
    • Glimepiride; Rosiglitazone
    • Glipizide
    • Glipizide; Metformin
    • Glyburide
    • Glyburide; Metformin
    • Glycerol Phenylbutyrate
    • Golimumab
    • grapefruit juice
    • Guaifenesin; Phenylephrine
    • Haloperidol
    • Hemin
    • Heparin
    • Hetastarch
    • Hydantoins
    • Hydralazine; Hydrochlorothiazide, HCTZ
    • Hydrochlorothiazide, HCTZ
    • Hydrochlorothiazide, HCTZ; Irbesartan
    • Hydrochlorothiazide, HCTZ; Lisinopril
    • Hydrochlorothiazide, HCTZ; Losartan
    • Hydrochlorothiazide, HCTZ; Methyldopa
    • Hydrochlorothiazide, HCTZ; Metoprolol
    • Hydrochlorothiazide, HCTZ; Moexipril
    • Hydrochlorothiazide, HCTZ; Olmesartan
    • Hydrochlorothiazide, HCTZ; Propranolol
    • Hydrochlorothiazide, HCTZ; Quinapril
    • Hydrochlorothiazide, HCTZ; Spironolactone
    • Hydrochlorothiazide, HCTZ; Telmisartan
    • Hydrochlorothiazide, HCTZ; Triamterene
    • Hydrochlorothiazide, HCTZ; Valsartan
    • Hydrocodone; Phenylephrine
    • Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate
    • Ibritumomab Tiuxetan
    • Incretin Mimetics
    • Indapamide
    • Inebilizumab
    • Infliximab
    • Insulin Degludec; Liraglutide
    • Insulin Glargine; Lixisenatide
    • Insulins
    • Isavuconazonium
    • Isoniazid, INH; Pyrazinamide, PZA; Rifampin
    • Isoniazid, INH; Rifampin
    • Isoproterenol
    • Itraconazole
    • Ketoconazole
    • L-Asparaginase Escherichia coli
    • Letermovir
    • Levetiracetam
    • Linagliptin; Metformin
    • Liraglutide
    • Lixisenatide
    • Loop diuretics
    • Lopinavir; Ritonavir
    • Lumacaftor; Ivacaftor
    • Lumacaftor; Ivacaftor
    • Magnesium Salicylate
    • Mannitol
    • Mecasermin rinfabate
    • Mecasermin, Recombinant, rh-IGF-1
    • Meglitinides
    • Mephobarbital
    • Metformin
    • Metformin; Pioglitazone
    • Metformin; Repaglinide
    • Metformin; Rosiglitazone
    • Metformin; Saxagliptin
    • Metformin; Sitagliptin
    • Methazolamide
    • Methenamine; Sodium Acid Phosphate
    • Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine
    • Methyclothiazide
    • Metolazone
    • Micafungin
    • Mitotane
    • Mivacurium
    • Moxifloxacin
    • Nateglinide
    • Nefazodone
    • Neostigmine
    • Neuromuscular blockers
    • Nicardipine
    • Nonsteroidal antiinflammatory drugs
    • Ocrelizumab
    • Ombitasvir; Paritaprevir; Ritonavir
    • Omeprazole; Amoxicillin; Rifabutin
    • Ondansetron
    • Oxymetholone
    • Ozanimod
    • Pancuronium
    • Pazopanib
    • Pegaspargase
    • Peginterferon Alfa-2a
    • Phenobarbital
    • Phenylephrine
    • Phenylephrine; Promethazine
    • Physostigmine
    • Pimozide
    • Posaconazole
    • Potassium
    • Potassium Chloride
    • Potassium Phosphate; Sodium Phosphate
    • Pramlintide
    • Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements)
    • Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved)
    • Primidone
    • Propranolol
    • Propylthiouracil, PTU
    • Pyridostigmine
    • Quetiapine
    • Quinolones
    • Rapacuronium
    • Regular Insulin
    • Repaglinide
    • Rifabutin
    • Rifampin
    • Rifamycins
    • Rifapentine
    • Rilonacept
    • Ritonavir
    • Rituximab
    • Rituximab; Hyaluronidase
    • Rocuronium
    • Salicylates
    • Salsalate
    • Saquinavir
    • Semaglutide
    • SGLT2 Inhibitors
    • Siponimod
    • Sodium Benzoate; Sodium Phenylacetate
    • Sodium Chloride
    • Sodium Phenylbutyrate
    • Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous
    • Somatropin, rh-GH
    • Succinylcholine
    • Sulfonylureas
    • Telbivudine
    • Telithromycin
    • Telotristat Ethyl
    • Testosterone
    • Thiazide diuretics
    • Thiazolidinediones
    • Thyroid hormones
    • Tobramycin
    • Tolazamide
    • Tolbutamide
    • Trandolapril; Verapamil
    • Tranexamic Acid
    • Tuberculin Purified Protein Derivative, PPD
    • Tubocurarine
    • Tucatinib
    • Vancomycin
    • Vecuronium
    • Verapamil
    • Vincristine Liposomal
    • Voriconazole
    • Vorinostat
    • Warfarin

    Level 4 (Minor)

    • Aldesleukin, IL-2
    • Alemtuzumab
    • Altretamine
    • Aminolevulinic Acid
    • Amoxicillin; Clarithromycin; Lansoprazole
    • Amoxicillin; Clarithromycin; Omeprazole
    • Antitumor antibiotics
    • Azathioprine
    • Basiliximab
    • Bexarotene
    • Bortezomib
    • Bosentan
    • Carmustine, BCNU
    • Chlorambucil
    • Clarithromycin
    • Clofarabine
    • Denileukin Diftitox
    • Drospirenone; Ethinyl Estradiol; Levomefolate
    • Econazole
    • Erythromycin
    • Erythromycin; Sulfisoxazole
    • Estramustine
    • Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate
    • Hydroxyurea
    • Interferon Alfa-2a
    • Interferon Alfa-2b
    • Interferon Alfa-2b; Ribavirin
    • Isoniazid, INH
    • Isotretinoin
    • Levomefolate
    • Lomustine, CCNU
    • Melphalan
    • Mepenzolate
    • Methoxsalen
    • Mitoxantrone
    • Nelarabine
    • Oritavancin
    • Photosensitizing agents (topical)
    • Potassium-sparing diuretics
    • Purine analogs
    • Tositumomab
    • Tretinoin, ATRA
    • Zafirlukast
    Abatacept: (Moderate) Concomitant use of immunosuppressives, as well as long-term corticosteroids, may potentially increase the risk of serious infection in abatacept treated patients. Advise patients taking abatacept to seek immediate medical advice if they develop signs and symptoms suggestive of infection. [8565] Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Acetaminophen; 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. [28001] 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. [28001] 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. [28001] Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Acetazolamide: (Moderate) Corticosteroids may increase the risk of hypokalemia if used concurrently with acetazolamide. Hypokalemia may be especially severe with prolonged use of corticotropin, ACTH. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy. [26417] [28267] Acetohexamide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Adalimumab: (Moderate) Closely monitor for the development of signs and symptoms of infection if coadministration of a corticosteroid with adalimumab is necessary. Adalimumab treatment increases the risk for serious infections that may lead to hospitalization or death. Patients taking concomitant immunosuppressants including corticosteroids may be at greater risk of infection. [27939] Albiglutide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Aldesleukin, IL-2: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [41853] [7592] [7714] 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. [4657] 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. [7714] Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Alogliptin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] Alpha-glucosidase Inhibitors: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Altretamine: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects. [4661] [7714] Ambenonium Chloride: (Moderate) Concomitant use of anticholinesterase agents, such as ambenonium chloride, and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents used to treat myasthenia should be withdrawn at least 24 hours before initiating corticosteroid therapy. [29779] [30015] [30028] [42863] [56146] [64165] Amifampridine: (Moderate) Carefully consider the need for concomitant treatment with systemic corticosteroids and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Systemic corticosteroids may increase the risk of seizures in some patients. [45339] [63790] Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Aminolevulinic Acid: (Minor) Corticosteroids administered prior to or concomitantly with photosensitizing agents used in photodynamic therapy may decrease the efficacy of the treatment. [6625] Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Amiodarone: (Major) Use caution when coadministering amiodarone with drugs which may induce hypokalemia and, or hypomagnesemia, including corticosteroids. Since antiarrhythmic drugs may be ineffective or may be arrhythmogenic in patients with hypokalemia, any potassium or magnesium deficiency should be corrected before instituting and during amiodarone therapy. [26417] [28224] [29377] Amlodipine; 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. [26417] [54246] 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. [26417] [54246] 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. [28238] [30016] 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. [28238] [30016] Amphotericin B cholesteryl sulfate complex (ABCD): (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly. [30011] [40134] Amphotericin B lipid complex (ABLC): (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly. [30011] [40134] Amphotericin B liposomal (LAmB): (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly. [30011] [40134] Amphotericin B: (Moderate) The potassium-wasting effects of corticosteroid therapy can be exacerbated by concomitant administration of other potassium-depleting drugs including amphotericin B. Serum potassium levels should be monitored in patients receiving these drugs concomitantly. [30011] [40134] Antithymocyte Globulin: (Moderate) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [6303] [7714] 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. [7714] 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. [30676] [40027] Argatroban: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Arsenic Trioxide: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide. [26417] [59438] Asparaginase Erwinia chrysanthemi: (Moderate) Concomitant use of L-asparaginase with corticosteroids can result in additive hyperglycemia. L-Asparaginase transiently inhibits insulin production contributing to hyperglycemia seen during concurrent corticosteroid therapy. Insulin therapy may be required in some cases. Administration of L-asparaginase after rather than before corticosteroids reportedly has produced fewer hypersensitivity reactions. [55362] Aspirin, ASA: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Butalbital; Caffeine: (Moderate) Coadministration may result in decreased exposure to methylprednisolone. Butalbital is a CYP3A4 inducer; methylprednisolone is a CYP3A4 substrate. Monitor for decreased response to methylprednisolone during concurrent use. [28001] (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Coadministration may result in decreased exposure to methylprednisolone. Butalbital is a CYP3A4 inducer; methylprednisolone is a CYP3A4 substrate. Monitor for decreased response to methylprednisolone during concurrent use. [28001] (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Carisoprodol: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Dipyridamole: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Omeprazole: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Oxycodone: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Aspirin, ASA; Pravastatin: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Atazanavir: (Moderate) Coadministration of 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. [28142] [30676] [34482] [58000] 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. [28142] [30676] [34482] [58000] (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. [30015] [41361] [41362] [51664] [58000] [58763] Atenolol; Chlorthalidone: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Atracurium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] 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. [28001] Azathioprine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [4710] [7714] Azilsartan; Chlorthalidone: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Basiliximab: (Minor) Because systemically administered corticosteroids have immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives. [4746] Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Coadministration may result in decreased exposure to methylprednisolone. Phenobarbital is a CYP3A4 inducer; methylprednisolone is a CYP3A4 substrate. Monitor for decreased response to methylprednisolone during concurrent use. [28001] Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Bendroflumethiazide; Nadolol: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Bepridil: (Moderate) Hypokalemia-producing agents, including corticosteroids, may increase the risk of bepridil-induced arrhythmias and should therefore be administered cautiously in patients receiving bepridil therapy. [3085] [4953] Bexarotene: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents, such as bexarotene. [30943] Bismuth Subsalicylate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Bivalirudin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Boceprevir: (Major) 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. [30015] [44314] Bortezomib: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Bosentan: (Minor) A dose adjustment of 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. [28496] Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Bupropion: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Bupropion; Naltrexone: (Moderate) Because bupropion is associated with a dose-related risk of seizures, extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as systemic corticosteroids. Low initial dosing and slow dosage titration of bupropion is recommended if these combinations must be used; the patient should be closely monitored. [41057] [41086] Butabarbital: (Moderate) Coadministration may result in decreased exposure to methylprednisolone. Butabarbital is a CYP3A4 inducer; methylprednisolone is a CYP3A4 substrate. Monitor for decreased response to methylprednisolone during concurrent use. [28001] 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. [31468] 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. [31468] 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. [31468] 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. [31468] Canagliflozin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Canagliflozin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Carbamazepine: (Moderate) Hepatic microsomal enzyme inducers, including carbamazepine, can increase the metabolism of methylprednisolone. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted when carbamazepine is used with methylprednisolone. [41237] Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Carbetapentane; Guaifenesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Carbetapentane; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Carbinoxamine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Carmustine, BCNU: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [5946] [7714] [7944] 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. [30016] [57094] 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. [10783] Chlophedianol; Guaifenesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Chlorambucil: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [4757] [7714] Chlorothiazide: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Chlorpheniramine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Chlorpropamide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Chlorthalidone: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Chlorthalidone; Clonidine: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] 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. [30288] [41362] [61778] Choline Salicylate; Magnesium Salicylate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Cimetidine: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Cisatracurium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] Citalopram: (Moderate) Caution is advisable during concurrent use of citalopram and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with citalopram. [26417] [28269] Clarithromycin: (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. [28238] [30016] Clindamycin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Clofarabine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7557] [7714] Cobicistat: (Moderate) 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. [30015] [41361] [41362] [51664] [58000] [58763] Codeine; Phenylephrine; Promethazine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Conivaptan: (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. [30015] [31764] 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. [36319] [41361] Dapagliflozin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Dapagliflozin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Dapagliflozin; Saxagliptin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Darunavir: (Moderate) Coadministration of 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. [30015] [32432] 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. [30015] [41361] [41362] [51664] [58000] [58763] (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. [30015] [32432] 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. [30015] [41361] [41362] [51664] [58000] [58763] (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. [30015] [32432] 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. [30015] [47165] [58664] Deferasirox: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including corticosteroids. [31807] Denileukin Diftitox: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Denosumab: (Moderate) The safety and efficacy of denosumab use in patients with immunosuppression have not been evaluated. Patients receiving immunosuppressives along with denosumab may be at a greater risk of developing an infection. [40862] Desmopressin: (Major) Desmopressin, when used in the treatment of nocturia is contraindicated with corticosteroids because of the risk of severe hyponatremia. Desmopressin can be started or resumed 3 days or 5 half-lives after the corticosteroid is discontinued, whichever is longer. [61806] Dextran: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Digoxin: (Moderate) Hypokalemia, hypomagnesemia, or hypercalcemia increase digoxin's effect. Corticosteroids can precipitate digoxin toxicity via their effect on electrolyte balance. It is recommended that serum potassium, magnesium, and calcium be monitored regularly in patients receiving digoxin. [28272] [29377] Diltiazem: (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. [4718] [5654] Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Diphenhydramine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Dofetilide: (Major) Corticosteroids can cause increases in blood pressure, sodium and water retention, and hypokalemia, predisposing patients to interactions with certain other medications. Corticosteroid-induced hypokalemia could also enhance the proarrhythmic effects of dofetilide. [49489] Doxacurium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] Dronedarone: (Moderate) 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. [30015] [36101] Droperidol: (Moderate) Caution is advised when using droperidol in combination with corticosteroids which may lead to electrolyte abnormalities, especially hypokalemia or hypomagnesemia, as such abnormalities may increase the risk for QT prolongation or cardiac arrhythmias. [5468] 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. [35581] [42117] Dulaglutide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Echinacea: (Moderate) Echinacea possesses immunostimulatory activity and may theoretically reduce the response to immunosuppressant drugs like corticosteroids. For some patients who are using corticosteroids for serious illness, such as cancer or organ transplant, this potential interaction may result in the preferable avoidance of Echinacea. Although documentation is lacking, coadministration of echinacea with immunosuppressants is not recommended by some resources. [25398] [32073] [61902] [61905] Econazole: (Minor) In vitro studies indicate that corticosteroids inhibit the antifungal activity of econazole against C. albicans in a concentration-dependent manner. When the concentration of the corticosteroid was equal to or greater than that of econazole on a weight basis, the antifungal activity of econazole was substantially inhibited. When the corticosteroid concentration was one-tenth that of econazole, no inhibition of antifungal activity was observed. [6968] Efalizumab: (Major) Patients receiving immunosuppressives should not receive concurrent therapy with efalizumab because of the possibility of increased infections and malignancies. [7127] [7714] 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. [30015] [41361] [41362] [51664] [58000] [58763] 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. [30015] [41361] [41362] [51664] [58000] [58763] Empagliflozin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Empagliflozin; Linagliptin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Empagliflozin; Linagliptin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Empagliflozin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Ephedrine: (Moderate) Ephedrine may enhance the metabolic clearance of corticosteroids. Decreased blood concentrations and lessened physiologic activity may necessitate an increase in corticosteroid dosage. [8844] Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Erlotinib: (Moderate) Monitor for symptoms of gastrointestinal (GI) perforation (e.g., severe abdominal pain, fever, nausea, and vomiting) if coadministration of erlotinib with 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. [30555] Ertugliflozin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Ertugliflozin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Ertugliflozin; Sitagliptin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Erythromycin: (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. [6764] 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. [6764] Estramustine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [4744] [7714] Estrogens: (Moderate) Estrogens have been associated with elevated serum concentrations of corticosteroid binding globulin (CBG), leading to increased total circulating corticosteroids, although the free concentrations of these hormones may be lower; the clinical significance is not known. Estrogens are CYP3A4 substrates and dexamethasone is a CYP3A4 inducer; concomitant use may decrease the clinical efficacy of estrogens. Patients should be monitored for signs of decreased clinical effects of estrogens (e.g., breakthrough bleeding), oral contraceptives, or non-oral combination contraceptives if these drugs are used together. [4718] [4744] [6395] 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. [35581] [42117] 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. [33718] [41361] Exenatide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] 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. [54506] Fluoxymesterone: (Moderate) Coadministration of corticosteroids and fluoxymesterone may increase the risk of edema, especially in patients with underlying cardiac or hepatic disease. Corticosteroids with greater mineralocorticoid activity, such as fludrocortisone, may be more likely to cause edema. Administer these drugs in combination with caution. [11342] 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. [29012] [30015] Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Gallium Ga 68 Dotatate: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia. Also, corticotropin may cause calcium loss and sodium and fluid retention. Mannitol itself can cause hypernatremia. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly. [6524] Gemcitabine: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Gentamicin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Glimepiride: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Glimepiride; 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. [28032] [30585] [51002] [62853] Glimepiride; Rosiglitazone: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Glipizide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Glipizide; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Glyburide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Glyburide; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Glycerol Phenylbutyrate: (Moderate) Corticosteroids may induce elevated blood ammonia concentrations. Corticosteroids should be used with caution in patients receiving glycerol phenylbutyrate. Monitor ammonia concentrations closely. [53022] 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. [35501] 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. [6770] Guaifenesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Halofantrine: (Major) Due to the risks of cardiac toxicity of halofantrine in patients with hypokalemia and/or hypomagnesemia, the use of halofantrine should be avoided in combination with agents that may lead to electrolyte losses, such as corticosteroids. [4968] Haloperidol: (Moderate) Caution is advisable during concurrent use of haloperidol and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with haloperidol. [28307] Hemin: (Moderate) Hemin works by inhibiting aminolevulinic acid synthetase. Corticosteroids increase the activity of this enzyme should not be used with hemin. [6702] Heparin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Hetastarch: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Hydantoins: (Moderate) Hydantoin anticonvulsants induce hepatic microsomal enzymes and may increase the metabolism of 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. [28001] [28771] Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Hydrochlorothiazide, HCTZ: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Hydrochlorothiazide, HCTZ; 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. [26417] [54246] 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. [26417] [54246] 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. [26417] [54246] Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Hydrochlorothiazide, HCTZ; 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. [26417] [54246] Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] 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. [26417] [54246] 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. [26417] [54246] (Moderate) Patients receiving corticosteroids during propranolol therapy may be at increased risk of hypoglycemia due to the loss of counter-regulatory cortisol response. This effect may be more pronounced in infants and young children. If concurrent use is necessary, carefully monitor vital signs and blood glucose concentrations as clinically indicated. [56853] 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. [26417] [54246] 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. [26417] [54246] 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. [26417] [54246] 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. [26417] [54246] 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. [26417] [54246] Hydrocodone; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Hydroxyurea: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] 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). [45238] [45239] Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia. [57713] [57714] [57715] Ibritumomab Tiuxetan: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia. [57713] [57714] [57715] (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with 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. [41361] [57675] Incretin Mimetics: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Indapamide: (Moderate) Additive hypokalemia may occur when indapamide is coadministered with other drugs with a significant risk of hypokalemia such as systemic corticosteroids. Coadminister with caution and careful monitoring. [26417] Inebilizumab: (Moderate) Concomitant usage of inebilizumab with immunosuppressant drugs, including systemic corticosteroids, may increase the risk of infection. Consider the risk of additive immune system effects when coadministering therapies that cause immunosuppression with inebilizumab. [65576] 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. [27994] Insulin Degludec; Liraglutide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Insulin Glargine; Lixisenatide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Insulins: (Moderate) Monitor patients receiving insulin closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Interferon Alfa-2a: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Interferon Alfa-2b: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Interferon Alfa-2b; Ribavirin: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] 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. [28963] [57053] 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. [5442] 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. [30015] [41361] [41362] [59042] 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. [29847] [41362] 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. [28483] [28818] [29210] [34482] (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. [29847] [41362] 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. [28483] [28818] [29210] [34482] (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. [29847] [41362] Isoproterenol: (Moderate) The risk of cardiac toxicity with isoproterenol in asthma patients appears to be increased with the coadministration of corticosteroids. Intravenous infusions of isoproterenol in refractory asthmatic children at rates of 0.05 to 2.7 mcg/kg/min have caused clinical deterioration, myocardial infarction (necrosis), congestive heart failure and death. [28004] Isotretinoin: (Minor) Both isotretinoin and corticosteroids can cause osteoporosis during chronic use. Patients receiving systemic corticosteroids should receive isotretinoin therapy with caution. [5283] Itraconazole: (Moderate) 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. [27983] [40233] 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. [27982] [28001] [28279] [28761] [34535] L-Asparaginase Escherichia coli: (Moderate) Concomitant use of L-asparaginase with corticosteroids can result in additive hyperglycemia. L-Asparaginase transiently inhibits insulin production contributing to hyperglycemia seen during concurrent corticosteroid therapy. Insulin therapy may be required in some cases. Administration of L-asparaginase after rather than before corticosteroids reportedly has produced fewer hypersensitivity reactions. [55362] 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). [30016] [62611] Levetiracetam: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] 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. [35581] [42117] Levomethadyl: (Major) Caution is advised when using levomethadyl in combination with other agents, such as corticosteroids, that may lead to electrolyte abnormalities, especially hypokalemia or hypomagnesemia. [3085] Linagliptin; Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] Liraglutide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] 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. [41361] [43236] Lixisenatide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Lomustine, CCNU: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [5946] [7714] [7944] Loop diuretics: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia and/or hypomagnesemia. While glucocorticoids with mineralocorticoid activity (e.g., cortisone, hydrocortisone) can cause sodium and fluid retention. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly. [26417] [28429] [29779] Lopinavir; Ritonavir: (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. [30015] [47165] [58664] 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. [30015] [59891] 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. [30015] [59891] Macimorelin: (Major) Avoid use of macimorelin with drugs that directly affect pituitary growth hormone secretion, such as corticosteroids. Healthcare providers are advised to discontinue corticosteroid therapy and observe a sufficient washout period before administering macimorelin. Use of these medications together may impact the accuracy of the macimorelin growth hormone test. [62723] Magnesium Salicylate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Mannitol: (Moderate) Corticosteroids may accentuate the electrolyte loss associated with diuretic therapy resulting in hypokalemia. Also, corticotropin may cause calcium loss and sodium and fluid retention. Mannitol itself can cause hypernatremia. Close monitoring of electrolytes should occur in patients receiving these drugs concomitantly. [6524] Mecasermin rinfabate: (Moderate) Additional monitoring may be required when coadministering systemic or inhaled corticosteroids and mecasermin, recombinant, rh-IGF-1. In animal studies, corticosteroids impair the growth-stimulating effects of growth hormone (GH) through interference with the physiological stimulation of epiphyseal chondrocyte proliferation exerted by GH and IGF-1. Dexamethasone administration on long bone tissue in vitro resulted in a decrease of local synthesis of IGF-1. Similar counteractive effects are expected in humans. If systemic or inhaled glucocorticoid therapy is required, the steroid dose should be carefully adjusted and growth rate monitored. [8314] [8315] Mecasermin, Recombinant, rh-IGF-1: (Moderate) Additional monitoring may be required when coadministering systemic or inhaled corticosteroids and mecasermin, recombinant, rh-IGF-1. In animal studies, corticosteroids impair the growth-stimulating effects of growth hormone (GH) through interference with the physiological stimulation of epiphyseal chondrocyte proliferation exerted by GH and IGF-1. Dexamethasone administration on long bone tissue in vitro resulted in a decrease of local synthesis of IGF-1. Similar counteractive effects are expected in humans. If systemic or inhaled glucocorticoid therapy is required, the steroid dose should be carefully adjusted and growth rate monitored. [8314] [8315] Meglitinides: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] 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. [7714] [7943] [7944] Mepenzolate: (Minor) Anticholinergics, such as mepenzolate, antagonize the effects of antiglaucoma agents. Mepenzolate is contraindicated in patients with glaucoma and therefore should not be coadministered with medications being prescribed for the treatment of glaucoma. In addition, anticholinergic drugs taken concurrently with corticosteroids in the presence of increased intraocular pressure may be hazardous. [42281] Mephobarbital: (Moderate) Coadministration may result in decreased exposure to methylprednisolone. Mephobarbital is a CYP3A4 inducer; methylprednisolone is a CYP3A4 substrate. Monitor for decreased response to methylprednisolone during concurrent use. [28001] Metformin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] Metformin; 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. [28032] [28550] [30585] [51002] [62853] Metformin; Repaglinide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Metformin; Rosiglitazone: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] Metformin; Saxagliptin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] Metformin; Sitagliptin: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [28550] [30585] [51002] [62853] Methazolamide: (Moderate) Corticosteroids may increase the risk of hypokalemia if used concurrently with methazolamide. Hypokalemia may be especially severe with prolonged use of corticotropin, ACTH. Monitor serum potassium levels to determine the need for potassium supplementation and/or alteration in drug therapy. The chronic use of corticosteroids may augment calcium excretion with methazolamide leading to increased risk for hypocalcemia and/or osteoporosis. [5023] Methenamine; Sodium Acid Phosphate: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia. [57713] [57714] [57715] Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia. [57713] [57714] [57715] Methoxsalen: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Methyclothiazide: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Metolazone: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] 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. [33528] Micafungin: (Moderate) Leukopenia, neutropenia, anemia, and thrombocytopenia have been associated with micafungin. Patients who are taking immunosuppressives such as the corticosteroids with micafungin concomitantly may have additive risks for infection or other side effects. In a pharmacokinetic trial, micafungin had no effect on the pharmacokinetics of prednisolone. Acute intravascular hemolysis and hemoglobinuria was seen in a healthy volunteer during infusion of micafungin (200 mg) and oral prednisolone (20 mg). This reaction was transient, and the subject did not develop significant anemia. [44913] Mifepristone: (Major) Mifepristone for termination of pregnancy is contraindicated in patients on long-term corticosteroid therapy and mifepristone for Cushing's disease or other chronic conditions is contraindicated in patients who require concomitant treatment with systemic corticosteroids for life-saving purposes, such as serious medical conditions or illnesses (e.g., immunosuppression after organ transplantation). For other situations where corticosteroids are used for treating non-life threatening conditions, mifepristone may lead to reduced corticosteroid efficacy and exacerbation or deterioration of such conditions. This is because mifepristone exhibits antiglucocorticoid activity that may antagonize corticosteroid therapy and the stabilization of the underlying corticosteroid-treated illness. Mifepristone may also cause adrenal insufficiency, so patients receiving corticosteroids for non life-threatening illness require close monitoring. Because serum cortisol levels remain elevated and may even increase during treatment with mifepristone, serum cortisol levels do not provide an accurate assessment of hypoadrenalism. Patients should be closely monitored for signs and symptoms of adrenal insufficiency, If adrenal insufficiency occurs, stop mifepristone treatment and administer systemic glucocorticoids without delay; high doses may be needed to treat these events. Factors considered in deciding on the duration of glucocorticoid treatment should include the long half-life of mifepristone (85 hours). [28003] [48697] Mitotane: (Moderate) Use caution if mitotane and 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. [34482] [41934] Mitoxantrone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Mivacurium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] Moxifloxacin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] 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. [7714] Natalizumab: (Major) Ordinarily, patients receiving chronic immunosuppressant therapy should not be treated with natalizumab. Treatment recommendations for combined corticosteroid therapy are dependent on the underlying indication for natalizumab therapy. Corticosteroids should be tapered in those patients with Crohn's disease who are on chronic corticosteroids when they start natalizumab therapy, as soon as a therapeutic benefit has occurred. If the patient cannot discontinue systemic corticosteroids within 6 months, discontinue natalizumab. The concomitant use of natalizumab and corticosteroids may further increase the risk of serious infections, including progressive multifocal leukoencephalopathy, over the risk observed with use of natalizumab alone. In multiple sclerosis (MS) clinical trials, an increase in infections was seen in patients concurrently receiving short courses of corticosteroids. However, the increase in infections in natalizumab-treated patients who received steroids was similar to the increase in placebo-treated patients who received steroids. Short courses of steroid use during natalizumab, such as when they are needed for MS relapse treatment, appear to be acceptable for use concurrently. [30470] [62264] Nateglinide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Nefazodone: (Moderate) 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. [4591] Nelarabine: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Neostigmine: (Moderate) Concomitant use of anticholinesterase agents, such as neostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating systemic corticosteroid therapy. [29779] [30015] [30028] [31123] [54891] [56146] [64165] Neuromuscular blockers: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] Nicardipine: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Nonsteroidal antiinflammatory drugs: (Moderate) Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged concomitant administration should be avoided. Concomitant use of corticosteroids appears to increase the risk of adverse GI events due to NSAIDs. Corticosteroids can have profound effects on sodium-potassium balance; NSAIDs also can affect sodium and fluid balance. Monitor serum potassium concentrations; potassium supplementation may be necessary. In addition, NSAIDs may mask fever, pain, swelling and other signs and symptoms of an infection; use NSAIDs with caution in patients receiving immunosuppressant dosages of corticosteroids. The Beers criteria recommends that this drug combination be avoided in older adults; if coadministration cannot be avoided, provide gastrointestinal protection. [24574] [29890] [63923] 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. [61838] 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. [30015] [47165] [58664] Omeprazole; Amoxicillin; 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. [28483] [28818] [29210] [34482] Ondansetron: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Oritavancin: (Minor) 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. [30676] [57741] Oxymetholone: (Moderate) Concomitant use of oxymetholone with corticosteroids or corticotropin, ACTH may cause increased edema. Manage edema with diuretic and/or digitalis therapy. [48342] Ozanimod: (Moderate) Concomitant use of ozanimod with methylprednisolone may increase the risk of immunosuppression. Monitor patients carefully for signs and symptoms of infection. Ozanimod 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. [65169] Pancuronium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] 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. [30676] [37098] [7714] Pegaspargase: (Moderate) Concomitant use of pegaspargase with corticosteroids can result in additive hyperglycemia. Insulin therapy may be required in some cases. [55362] 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. [29421] Penicillamine: (Major) Agents such as immunosuppressives have adverse reactions similar to those of penicillamine. Concomitant use of penicillamine with these agents is contraindicated because of the increased risk of developing severe hematologic and renal toxicity. [5567] Phenobarbital: (Moderate) Coadministration may result in decreased exposure to methylprednisolone. Phenobarbital is a CYP3A4 inducer; methylprednisolone is a CYP3A4 substrate. Monitor for decreased response to methylprednisolone during concurrent use. [28001] Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Phenylephrine; Promethazine: (Moderate) The therapeutic effect of phenylephrine may be increased in patient receiving corticosteroids, such as hydrocortisone. Monitor patients for increased pressor effect if these agents are administered concomitantly. [54374] [57578] Photosensitizing agents (topical): (Minor) Corticosteroids administered prior to or concomitantly with photosensitizing agents used in photodynamic therapy may decrease the efficacy of the treatment. [6625] Physostigmine: (Moderate) Concomitant use of anticholinesterase agents. such as physostigmine, and systemic corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase inhibitors at least 24 hours before initiating corticosteroid therapy. [29779] [30015] [30028] [31123] [56146] [64165] Pimozide: (Moderate) According to the manufacturer of pimozide, the drug should not be coadministered with drugs known to cause electrolyte imbalances, such as high-dose, systemic corticosteroid therapy. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), and electrolyte imbalances (e.g., hypokalemia, hypocalcemia, hypomagnesemia) may increase the risk of life-threatening arrhythmias. Pimozide is contraindicated in patients with known hypokalemia or hypomagnesemia. Topical corticosteroids are less likely to interact. [28225] [43463] 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. [30015] [32723] Potassium Chloride: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Potassium Phosphate; Sodium Phosphate: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia. [57713] [57714] [57715] Potassium: (Moderate) Corticotropin can cause alterations in serum potassium levels. The use of potassium salts or supplements would be expected to alter the effects of corticotropin on serum potassium levels. Also, there have been reports of generalized tonic-clonic seizures and/or loss of consciousness associated with use of bowel preparation products in patients with no prior history of seizure disorder. Therefore, magnesium sulfate; potassium sulfate; sodium sulfate should be administered with caution during concurrent use of medications that lower the seizure threshold such as systemic corticosteroids. [30015] [41573] Potassium-sparing diuretics: (Minor) The manufacturer of spironolactone lists corticosteroids as a potential drug that interacts with spironolactone. Intensified electrolyte depletion, particularly hypokalemia, may occur. However, potassium-sparing diuretics such as spironolactone do not induce hypokalemia. In fact, hypokalemia is one of the indications for potassium-sparing diuretic therapy. Therefore, drugs that induce potassium loss, such as corticosteroids, could counter the hyperkalemic effects of potassium-sparing diuretics. [26417] [29016] [30011] Pramlintide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Moderate) Corticosteroids blunt the adrenal secretion of endogenous DHEA and DHEAS, resulting in reduced DHEA and DHEAS serum concentrations. [2460] Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Moderate) Corticosteroids blunt the adrenal secretion of endogenous DHEA and DHEAS, resulting in reduced DHEA and DHEAS serum concentrations. [2460] 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. [28001] Propranolol: (Moderate) Patients receiving corticosteroids during propranolol therapy may be at increased risk of hypoglycemia due to the loss of counter-regulatory cortisol response. This effect may be more pronounced in infants and young children. If concurrent use is necessary, carefully monitor vital signs and blood glucose concentrations as clinically indicated. [56853] 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. [6763] Purine analogs: (Minor) Concurrent use of purine analogs with other agents which cause bone marrow or immune suppression such as other antineoplastic agents or immunosuppressives may result in additive effects. [5504] Pyridostigmine: (Moderate) Concomitant use of anticholinesterase agents. such as pyridostigmine, and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating corticosteroid therapy. [29779] [30015] [30028] [31123] [34253] [56146] [64002] [64165] Quetiapine: (Moderate) Use caution when administering quetiapine with corticosteroids. QT prolongation has occurred during concurrent use of quetiapine and medications known to cause electrolyte imbalance (i.e. corticosteroids). [26417] [29118] Quinolones: (Moderate) Quinolones have been associated with an increased risk of tendon rupture requiring surgical repair or resulting in prolonged disability; this risk is further increased in those receiving concomitant corticosteroids. Discontinue quinolone therapy at the first sign of tendon inflammation or tendon pain, as these are symptoms that may precede rupture of the tendon. [28423] [28424] [28764] [29818] [30738] [62028] [65562] Rapacuronium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] Regular Insulin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Repaglinide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] 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. [28483] [28818] [29210] [34482] 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. [28483] [28818] [29210] [34482] 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. [28483] [28818] [29210] [34482] 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. [28483] [28818] [29210] [34482] Rilonacept: (Moderate) Patients receiving immunosuppressives along with rilonacept may be at a greater risk of developing an infection. [10690] Ritodrine: (Major) Ritodrine has caused maternal pulmonary edema, which appears more often in patients treated concomitantly with corticosteroids. Patients so treated should be closely monitored in the hospital. [7110] [7111] [7572] Ritonavir: (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. [30015] [47165] [58664] Rituximab: (Moderate) Rituximab and corticosteroids are commonly used together; however, monitor the patient for immunosuppression and signs and symptoms of infection during combined chronic therapy. [30943] [49773] [56233] Rituximab; Hyaluronidase: (Moderate) Rituximab and corticosteroids are commonly used together; however, monitor the patient for immunosuppression and signs and symptoms of infection during combined chronic therapy. [30943] [49773] [56233] Rocuronium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] Salicylates: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Salsalate: (Moderate) Salicylates or NSAIDs should be used cautiously in patients receiving corticosteroids. While there is controversy regarding the ulcerogenic potential of corticosteroids alone, concomitant administration of corticosteroids with aspirin may increase the GI toxicity of aspirin and other non-acetylated salicylates. Withdrawal of corticosteroids can result in increased plasma concentrations of salicylate and possible toxicity. Concomitant use of corticosteroids may increase the risk of adverse GI events due to NSAIDs. Although some patients may need to be given corticosteroids and NSAIDs concomitantly, which can be done successfully for short periods of time without sequelae, prolonged coadministration should be avoided. [24574] [28502] Saquinavir: (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. [28995] [30015] Sargramostim, GM-CSF: (Major) Avoid the concomitant use of sargramostim and systemic corticosteroid agents due to the risk of additive myeloproliferative effects. If coadministration of these drugs is required, frequently monitor patients for clinical and laboratory signs of excess myeloproliferative effects (e.g., leukocytosis). Sargramostim is a recombinant human granulocyte-macrophage colony-stimulating factor that works by promoting proliferation and differentiation of hematopoietic progenitor cells. [61087] Semaglutide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] SGLT2 Inhibitors: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] 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. [64031] 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. [40277] Sodium Benzoate; Sodium Phenylacetate: (Moderate) Corticosteroids may cause protein breakdown, which could lead to elevated blood ammonia concentrations, especially in patients with an impaired ability to form urea. Corticosteroids should be used with caution in patients receiving treatment for hyperammonemia. [8083] Sodium Chloride: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Sodium Phenylbutyrate: (Moderate) The concurrent use of corticosteroids with sodium phenylbutyrate may increase plasma ammonia levels (hyperammonemia) by causing the breakdown of body protein. Patients with urea cycle disorders being treated with sodium phenylbutyrate usually should not receive regular treatment with corticosteroids. [57685] Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia. [57713] [57714] [57715] Somatropin, rh-GH: (Moderate) Corticosteroids can retard bone growth and therefore, can inhibit the growth-promoting effects of somatropin. If corticosteroid therapy is required, the corticosteroid dose should be carefully adjusted. [6807] Succinylcholine: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] Sulfonylureas: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] 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. [11365] [28611] 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. [30015] [44393] Telbivudine: (Moderate) The risk of myopathy may be increased if corticosteroids are coadministered with telbivudine. Monitor patients for any signs or symptoms of unexplained muscle pain, tenderness, or weakness, particularly during periods of upward dosage titration. [9671] Telithromycin: (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. [28156] 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. [34482] [61795] Testosterone: (Moderate) Coadministration of corticosteroids and testosterone may increase the risk of edema, especially in patients with underlying cardiac or hepatic disease. Corticosteroids with greater mineralocorticoid activity, such as fludrocortisone, may be more likely to cause edema. Administer these drugs in combination with caution. [33698] Thiazide diuretics: (Moderate) Additive hypokalemia may occur when non-potassium sparing diuretics, including thiazide diuretics, are coadministered with other drugs with a significant risk of hypokalemia, such as corticosteroids. Monitoring serum potassium levels and cardiac function is advised, and potassium supplementation may be required. [26417] [54246] Thiazolidinediones: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Thyroid hormones: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents. [29779] [30015] [43942] Tobramycin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Tolazamide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Tolbutamide: (Moderate) Monitor patients receiving antidiabetic agents closely for worsening glycemic control when corticosteroids are instituted and for signs of hypoglycemia when corticosteroids are discontinued. Systemic and inhaled corticosteroids are known to increase blood glucose and worsen glycemic control in patients taking antidiabetic agents. The main risk factors for impaired glucose tolerance due to corticosteroids are the dose of steroid and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells. [28032] [30585] [51002] [62853] Tositumomab: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Trandolapril; Verapamil: (Moderate) 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. [28001] [28920] Tranexamic Acid: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Tretinoin, ATRA: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. [7714] Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy. [43298] [43299] Tubocurarine: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] Tucatinib: (Moderate) Monitor for steroid-related adverse reactions if coadministration of methylprednisolone with tucatinib is necessary, due to increased methylprednisolone exposure; Cushings syndrome and adrenal suppression could potentially occur with long-term use. Methylprednisolone is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor. 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. [30015] [30016] [65295] Vancomycin: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together. [54506] Vecuronium: (Moderate) Limit the period of use of neuromuscular blockers and corticosteroids and only use when the specific advantages of the drugs outweigh the risks for acute myopathy. An acute myopathy has been observed with the use of high doses of corticosteroids in patients receiving concomitant long-term therapy with neuromuscular blockers. Clinical improvement or recovery after stopping therapy may require weeks to years. [41361] [41961] [42031] [43319] [54278] [60760] [61750] [61937] 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. [28001] [28920] Vigabatrin: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks. [36250] Vincristine Liposomal: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia. [57713] [57714] [57715] Voriconazole: (Moderate) 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. [30015] Vorinostat: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary. [26417] [32789] Warfarin: (Moderate) 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. [28549] [29779] Zafirlukast: (Minor) Zafirlukast inhibits the CYP3A4 isoenzymes and should be used cautiously in patients stabilized on drugs metabolized by CYP3A4, such as corticosteroids. [4718] [4948]
    Revision Date: 08/07/2020, 02:26:00 AM

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    Monitoring Parameters

    • blood glucose
    • blood pressure
    • growth rate
    • pulmonary function tests (PFTs)
    • serum potassium
    • weight

    US Drug Names

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

    Global Drug names

    Argentina

    • Advantan - (Bayer)
    • Cipridanol - (Richmond)
    • Corticel - (Serono)
    • Cortisolona - (Klonal)
    • Proavenal M - (Panalab)
    • Rontamida - (Lafedar)
    • Solu-Medrol - (Pfizer)
    • Totalsolona - (Paylos)

    Australia

    • Advantan - (Bayer)
    • Depo-Medrol - (Pfizer)
    • Depo-Nisolone - (Pfizer)
    • Medrol - (Pharmacia)
    • Medrol Acne Lotion - (Upjohn)
    • Methylpred - (Alphapharm)
    • Solu-Medrol - (Pfizer)

    Austria

    • Advantan - (Bayer)
    • Depo-Medrol - (Pfizer)
    • Metasol - (Dermapharm)
    • Promedrol - (Pharmacia Upjohn)
    • Solu-Medrol - (Pfizer)
    • Urbason - (Sanofi-Aventis)

    Belgium

    • Advantan - (Bayer)
    • Depo-Medrol - (Pfizer)
    • Medrol - (Pfizer)
    • Solu-Medrol - (Pfizer)

    Brazil

    • Advantan - (Bayer)
    • Alergolon - (Biolab)
    • Depo-Medrol - (Pfizer)
    • Predi-Medrol - (Uniao Quimica)
    • Predmetil - (Eurofarma)
    • Solu-Medrol - (Pfizer)
    • Solu-Pred - (Cellofarm)
    • Solupren - (Bergamo)
    • Unimedrol - (Uniao Quimica)

    Canada

    • Depo-Medrol - (Pfizer)
    • Medrol - (Pfizer)
    • Medrol Acne Lotion - (Pfizer)
    • Medrol Veriderm - (Pharmacia Upjohn)
    • Solu-Medrol - (Pfizer)

    Chile

    • Depo-Medrol - (Pfizer)
    • Medrol - (Pfizer)
    • Solu-Medrol - (Pfizer)

    China

    • Medrol - (Pfizer)
    • Mi Le Song - (TianJin)
    • Solu-Medrol - (Pfizer)
    • You Jin - (Tian Yao)

    Czech Republic

    • Advantan - (Bayer)
    • Depo-Medrol - (Pfizer)
    • Medrol - (Pfizer)
    • Metypred - (Orion)
    • Solu-Medrol - (Pfizer)
    • Urbason - (Aventis)

    Denmark

    • Depo-Medrol - (Pfizer)
    • Medrol - (Pfizer)
    • Solu-Medrol - (Pfizer)

    Finland

    • Advantan - (Bayer)
    • Depo-Medrol - (Pfizer)
    • Medrol - (Pfizer)
    • Solomet - (Orion)
    • Solu-Medrol - (Pfizer)

    France

    • Dépo-Médrol - (Pfizer)
    • Médrol - (Pfizer)
    • Solpredone - (France Labo)
    • Solu-Médrol - (Pfizer)
    • Veriderm Medrol - (Upjohn)

    Germany

    • Advantan - (Jenapharm)
    • Depo-Medrate - (Pharmacia)
    • Medrate - (Pharmacia)
    • Medrate Akne-Lotio - (Upjohn)
    • Methylprednisolut - (Mibe)
    • Metypred - (Galen)
    • Metysolon - (Dermapharm)
    • M-PredniHexal - (Hexal)
    • Predni M - (Winthrop)
    • Urbason - (Sanofi-Aventis)
    • Urbason Depot - (Hoechst)

    Greece

    • Advantan - (Bayer)
    • Depo-Medrol - (Pfizer)
    • Depo-Medrone - (IFET)
    • Fodier - (Verisfield)
    • Lyo-drol - (Vianex (Βιανεξ))
    • Medrol - (Pfizer)
    • Medrol Acne Lotion - (Pfizer)
    • Solu-Medrol - (Pfizer)
    • Veriderm Medrol - (Pfizer)

    Hong Kong

    • Advantan - (Bayer)
    • Depo-Medrol - (Pfizer)
    • Medason - (I & C)
    • Medrol - (Pfizer)
    • Solu-Medrol - (Pfizer)

    Hungary

    • Advantan - (Bayer)
    • Depo-Medrol - (Pfizer)
    • Medrol - (Pfizer)
    • Metypred - (Orion)
    • Solu-Medrol - (Pfizer)

    India

    • Acto-Pred - (Ferring)
    • Aricort M - (Arika)
    • Avpred - (Arvincare)
    • Biolone - (Ind Biosciences)
    • Cecort - (Comed)
    • Depomax - (Biomax)
    • Depo-Medrol - (Pfizer)
    • Depopred - (Sun)
    • Deposet - (VHB)
    • Dispred - (JB Chemicals)
    • Elpred M - (Lancer)
    • Geopred - (Geo)
    • Happisone - (Mission Happiness)
    • Hosicort - (Hos & Ins)
    • Ivepred - (Sun)
    • Lumi-M - (Aronex)
    • Lupus - (Biosciences Pharmakon)
    • MB Sole - (Health Biotech)
    • Medicort - (Trumac)
    • Medrol - (Pharmacia Upjohn)
    • Mega-Pred - (Venus)
    • Melpred - (Cipla)
    • Melsone - (Psychotropics)
    • Mepred - (Nitro Organics)
    • Meprosol - (Esma)
    • Mepsonate - (Gland)
    • Methyl-Pred - (Shreshtha)
    • MPA - (Chandra Bhagat)
    • MPSS - (Chandra Bhagat)
    • MSLone - (Elfin)
    • Mypred - (Samarth)
    • Nayapred - (BMW)
    • Neo-Drol - (Neon)
    • Neodrol-AS - (Neon)
    • Nicord - (Evershine)
    • Nicort - (Abbott)
    • Nispred - (Neiss)
    • Omnacortil - (Macleods)
    • Solu-Medrol - (Pfizer)
    • Unidrol - (Unichem)

    Indonesia

    • Advantan - (Bayer)
    • Comedrol - (Berlico Mulia)
    • Depo-Medrol - (Pfizer)
    • Ersolon - (Erlimpex)
    • Flameson - (Graha)
    • Flason - (Ikapharmindo)
    • Fumethyl - (Futamed)
    • Gamesolone - (Galenium)
    • Glomeson - (Global Health)
    • Hexilon - (Kalbe)
    • Iflaz - (Kalbe)
    • Intidrol - (Interbat)
    • Inxilon - (Hexpharm)
    • Konixon - (Konimex)
    • Lameson - (Lapi)
    • Lexcomet - (Molex Ayus)
    • Medixon - (Ferron)
    • Medrol - (Pfizer)
    • Meprilon - (Mugi)
    • Meproson - (Meprofarm)
    • Mesol - (Gracia)
    • Metcor - (Pharmacore)
    • Methylon - (Bernofarm)
    • Metidrol - (Medikon)
    • Metisol - (Hexpharm)
    • Metrison - (Dexa)
    • Nichomedson - (Nicholas)
    • Phadilon - (Phapros)
    • Prednicort - (Otto)
    • Prednox - (Pyridam)
    • Pretilon - (Sandoz)
    • Prolon 8 - (Promed)
    • Rhemafar - (Ifars)
    • Sanexon - (Sanbe)
    • Simdrol - (Simex)
    • Solu-Medrol - (Pfizer)
    • Somerol - (Ethica)
    • Sonicor - (GMP)
    • Stenirol - (Guardian)
    • Thimelon - (Ethica)
    • Tisolon - (Exeltis)
    • Tison - (Landson)
    • Toras - (Pharos)
    • Tropidrol - (Tropica Mas)
    • Urbason - (Sanofi-Aventis)
    • Xilon - (Mahakam Beta)
    • Yalone - (Yarindo)

    Ireland

    • Advantan - (Bayer)
    • Depo-Medrone - (Pfizer)
    • Medrone - (Pharmacia Upjohn)
    • Solu-Medrone - (Pfizer)

    Israel

    • A-Methapred - (Abbott)
    • Depo-Medrol - (Pfizer)
    • Medrol - (Pfizer)
    • Solu-Medrol - (Pfizer)
    • Vanderm - (Agis)

    Italy

    • Advantan - (Intendis)
    • Asmacortone - (NCSN)
    • Avancort - (Intendis)
    • Caberdelta M - (Caber)
    • Depo-Medrol - (Pfizer)
    • Emmetipi - (Sicor)
    • Esametone - (Lisapharma)
    • Firmacort - (FIRMA)
    • Medrol - (Pfizer)
    • Medrol Lozione Antiacne - (Pharmacia)
    • Medrol Veriderm - (Pharmacia Upjohn)
    • Mega-Star - (Lenza)
    • Metilbetasone Solubile - (SoSe)
    • Prednilen - (Lenza)
    • Reactenol - (Lafare)
    • Sieropresol - (Herdel)
    • Solu-Medrol - (Pfizer)
    • Summicort - (Benvegna)
    • Supresol - (Hospira)
    • Urbason - (Sanofi-Aventis)

    Japan

    • Medrol - (Pfizer)

    Malaysia

    • Depo-Medrol - (Pfizer)
    • Medixon - (Bernofarm)
    • Solu-Medrol - (Pfizer)
    • Solu-Pred - (DHA)

    Mexico

    • Advantan - (Bayer)
    • Cryosolona - (Cryopharma)
    • Depo-Medrol - (Pfizer)
    • Metisona - (Precimex)
    • Prednilem - (Teva)
    • Radilem - (Teva)
    • Rumaxoi - (Interlab)
    • Solipred - (Aspen)
    • Solsolona - (Cryopharma)
    • Solu-Medrol - (Pfizer)

    Netherlands

    • Depo-Medrol - (Pfizer)
    • Medrol - (Pharmacia)
    • Metypresol - (Pharmachemie)
    • Solu-Medrol - (Pfizer)

    New Zealand

    • Advantan - (CSL)
    • Depo-Medrol - (Pfizer)
    • Medrol - (Pfizer)
    • Solu-Medrol - (Pfizer)

    Norway

    • Depo-Medrol - (Pfizer)
    • Medrol - (Pfizer)
    • Solu-Medrol - (Pfizer)

    Philippines

    • Adrena - (Teva)
    • Advantan - (Bayer)
    • Depo-Medrol - (Pfizer)
    • Medixon - (Glorious Dexa)
    • Medrol - (Pfizer)
    • Mepresone - (Dexa)
    • Metcort - (Unilab)
    • Methylpred - (Lyka)
    • Prednivex - (Vexxa)
    • Prednox - (Pyridam)
    • Solucin - (Swiss Parenterals)
    • Solu-Medrol - (Pfizer)
    • Solu-Ped - (Huons)

    Poland

    • Advantan - (Bayer)
    • Depo-Medrol - (Pfizer)
    • Medrol - (Pfizer)
    • Meprelon - (Sun-Farm)
    • Metypred - (Orion)
    • Solu-Medrol - (Pfizer)

    Portugal

    • Advantan - (Bayer)
    • Depo-Medrol - (Pfizer)
    • Medrol - (Pfizer)
    • Metilpren - (Mayne)
    • Solu-Medrol - (Pfizer)

    Russian Federation

    • Advantan - (Bayer)
    • Depo-Medrol - (Pfizer)
    • Ivepred - (Sun)
    • Komfoderm - (Akrikhin)
    • Lemod - (Hemofarm)
    • Medrol - (Pfizer)
    • Metypred - (Orion)
    • Solu-Medrol - (Pfizer)

    Singapore

    • Solu-Medrol - (Pfizer)

    South Africa

    • Advantan - (Bayer)
    • AP Methylpred - (Aspen)
    • Depo-Medrol - (Pfizer)
    • Medrol - (Pfizer)
    • Metypresol - (Intramed)
    • Solu-Medrol - (Pfizer)

    Spain

    • Adventan - (Bayer)
    • Depo Moderin - (Pharmacia)
    • Lexxema - (Italfarmaco)
    • Moderin Acne - (Pharmacia)
    • Solu-Moderin - (Pfizer)
    • Urbason - (Sanofi-Aventis)
    • Urbason Depot - (Hoechst)

    Sweden

    • Depo-Medrol - (Pfizer)
    • Depo-Medrone - (Upjohn)
    • Medrol - (Pfizer)
    • Medrone - (Upjohn)
    • Solu-Medrol - (Pfizer)
    • Solu-Medrone - (Upjohn)

    Switzerland

    • Advantan - (Bayer)
    • Depo-Medrol - (Pfizer)
    • Medrol - (Pfizer)
    • Promedrol - (Pharmacia Upjohn)
    • Solu-Medrol - (Pfizer)
    • Urbason - (Hoechst Marion Roussel)

    Thailand

    • Depo-Medrol - (Pfizer)
    • Solu-Medrol - (Pfizer)

    Turkey

    • Advantan - (Intendis)
    • Depo-Medrol - (Eczacibasi)
    • Depometikort - (Ulagay)
    • Ectopix - (Abdi)
    • Exenate - (Pharmactive)
    • Precort - (Kocak)
    • Precort-Liyo - (Kocak)
    • Prednol - (Nevzat)
    • Urbason - (Sanofi-Aventis)

    Ukraine

    • Advantan - (Bayer)
    • Depo-Medrol - (Pfizer)
    • Medrol - (Pfizer)
    • Metypred - (Orion)
    • Solu-Medrol - (Pfizer)
    • Sterocort - (Phytopharm)

    United Kingdom

    • Depo-Medrone - (Pfizer)
    • Medrone - (Pfizer)
    • Medrone Acne Lotion - (Upjohn)
    • Solu-Medrone - (Pfizer)

    Venezuela

    • Advantan - (Schering)
    • Depo-Medrol - (Pfizer)
    • Medrol - (Pfizer)
    • Novacort - (Pediatrics)
    • Prednicort - (Behrens)
    • Solu-Medrol - (Pfizer)