Methylprednisolone

Pharmacologic Category

Corticosteroid, Systemic

Dosing: Adult

Note:

Dosing: Evidence to support an optimal dose and duration are lacking for most indications; recommendations provided are general guidelines only and primarily based on expert opinion. In general, glucocorticoid dosing should be individualized and the minimum effective dose/duration should be used. For select indications with weight-based dosing, consider using ideal body weight in obese patients, especially with longer durations of therapy (Erstad 2004; Furst 2019a). Hypothalamic-pituitary-adrenal suppression: Although some patients may become hypothalamic-pituitary-adrenal (HPA) suppressed with lower doses or briefer exposure, some experts consider HPA-axis suppression likely in any adult receiving >16 mg/day (daytime dosing) or ≥4 mg per 24 hours (evening or night dosing) for >3 weeks, or with Cushingoid appearance (Furst 2019b; Joseph 2016); do not abruptly discontinue treatment in these patients; dose tapering may be necessary (Cooper 2003). Safety: Only the methylprednisolone succinate formulation (Solu-Medrol) may be given IV. Methylprednisolone acetate suspension (Depo-Medrol) is intended for IM or intra-articular administration only; do not administer the acetate preparation IV (Grissinger 2007; ISMP 2016).

Usual dosage range:

IV (succinate): 40 to 125 mg/day given in a single daily dose or in divided doses; rarely, for certain conditions, may go up to 1 to 2 mg/kg/day.

Initial high-dose “pulse” therapy for select indications (eg, severe systemic rheumatic disorders): 7 to 15 mg/kg/dose (or 500 mg to 1 g/dose) given once daily for 3 to 5 days.

Oral: 16 to 64 mg/day once daily or in divided doses.

The following dosing is from the commercially available tapered-dosage product (eg, dose-pack containing 21 × 4 mg tablets):

Day 1: 24 mg on day 1 administered as 8 mg (2 tablets) before breakfast, 4 mg (1 tablet) after lunch, 4 mg (1 tablet) after supper, and 8 mg (2 tablets) at bedtime or 24 mg (6 tablets) as a single dose or divided into 2 or 3 doses upon initiation (regardless of time of day).

Day 2: 20 mg on day 2 administered as 4 mg (1 tablet) before breakfast, 4 mg (1 tablet) after lunch, 4 mg (1 tablet) after supper, and 8 mg (2 tablets) at bedtime.

Day 3: 16 mg on day 3 administered as 4 mg (1 tablet) before breakfast, 4 mg (1 tablet) after lunch, 4 mg (1 tablet) after supper, and 4 mg (1 tablet) at bedtime.

Day 4: 12 mg on day 4 administered as 4 mg (1 tablet) before breakfast, 4 mg (1 tablet) after lunch, and 4 mg (1 tablet) at bedtime.

Day 5: 8 mg on day 5 administered as 4 mg (1 tablet) before breakfast and 4 mg (1 tablet) at bedtime.

Day 6: 4 mg on day 6 administered as 4 mg (1 tablet) before breakfast.

IM (acetate or succinate): 40 to 60 mg as a single dose.

Intra-articular (acetate suspension): Note: Dose ranges per manufacturer's labeling. Specific dose is determined based upon joint size, severity of inflammation, amount of articular fluid present, and clinician judgment.

Larger joint (eg, knee, shoulder, hip): 20 to 80 mg.

Medium joint (eg, wrist, ankle, elbow): 10 to 40 mg.

Small joint (eg, toe, finger): 4 to 10 mg.

Intralesional (acetate): 20 to 60 mg; for large lesions, it may be necessary to distribute doses ranging from 20 to 40 mg by repeated local injections; 1 to 4 injections are usually employed with intervals between injections varying with the type of lesion being treated and clinical response.

Indication-specific dosing:

Acute respiratory distress syndrome, moderate to severe (off-label use): Note: Some experts recommend against routine use but will consider on a case-by-case basis (eg, in patients refractory to other therapeutic strategies; glucocorticoids may have a mortality benefit if administered within 14 day of onset) (Siegel 2019). Use ideal body weight to calculate dose. If patient is extubated between days 1 to 14, advance to day 15 of therapy and taper according to the following schedule. Do not abruptly discontinue since this may cause deterioration due to inflammatory response (Meduri 2007; SCCM/ESICM [Annane 2017]; Steinberg 2006).

IV (succinate): Loading dose of 1 mg/kg over 30 minutes, followed by a gradual taper:

Days 1 to 14: 1 mg/kg/day in divided doses or as a continuous infusion.

Days 15 to 21: 0.5 mg/kg/day in divided doses or as a continuous infusion.

Days 22 to 25: 0.25 mg/kg/day in divided doses or as a continuous infusion.

Days 26 to 28: 0.125 mg/kg/day in divided doses or as a continuous infusion.

Allergic conditions:

Anaphylaxis (adjunct to epinephrine for prevention of late-phase/biphasic reaction): Note: Do not use for initial or sole treatment of anaphylaxis because corticosteroids do not result in the prompt relief of upper or lower airway obstruction or shock (AAAAI [Lieberman 2015]; EAACI [Muraro 2014]; WAO [Simons 2011]; WAO [Simons 2015]). Some experts limit use to patients with severe or persistent steroid-responsive symptoms (eg, bronchospasm in patients with asthma) (Campbell 2019).

IV (succinate): 1 to 2 mg/kg (Campbell 2014) or 50 to 125 mg as a single dose (Campbell 2019; WAO [Simons 2011]).

Angioedema (acute allergic) and/or urticaria (acute): Note: For moderate to severe symptoms without signs of anaphylaxis. Use epinephrine if anaphylaxis symptoms (eg, risk of airway or cardiovascular compromise) are present (Cicardi 2014; Zuraw 2019). In patients with acute urticaria, consider reserving use for patients with significant angioedema or whose symptoms are unresponsive to antihistamines (Asero 2020; Barniol 2018; Bernstein 2014; EAACI [Zuberbier 2018]; Powell 2015). The optimal dosing strategy has not been defined (Bernstein 2014; EAACI [Zuberbier 2018]; James 2017; Powell 2015).

IV (succinate): Initial: 60 to 80 mg; switch to an oral corticosteroid as soon as possible, tapering the dose for a total treatment duration of ≤10 days (EAACI [Zuberbier 2018]; Zuraw 2019).

Oral: Initial: 16 to 32 mg/day in 1 to 2 divided doses for 3 to 4 days (Barniol 2018; Powell 2015; Zuraw 2019); may consider tapering the dose for a total treatment duration of ≤10 days (EAACI [Zuberbier 2018]; Zuraw 2019).

Asthma, acute exacerbation: Note: For moderate to severe exacerbations or in patients who do not respond promptly and completely to short-acting beta agonists; administer within 1 hour of presentation to emergency department (GINA 2018; NAEPP 2007).

Oral (preferred route), IV (succinate): 40 to 60 mg/day in 1 or 2 divided doses for 3 to 10 days (GINA 2018; NAEPP 2007); doses up to 60 to 80 mg every 6 to 12 hours have been used in critically ill patients (Fanta 2019). If symptoms do not resolve and peak expiratory flow is not at least 70% of personal best, then longer treatment may be required (GINA 2018; NAEPP 2007).

Chronic obstructive pulmonary disease, acute exacerbation (off-label use): Note: In patients with severe but not life-threatening exacerbations, oral regimens are recommended. Use IV route in patients who cannot tolerate oral therapy (eg, shock, mechanically ventilated) (GOLD 2019; Stoller 2019).

Oral; IV (succinate): 40 to 60 mg daily for 5 to 14 days (GOLD 2019; Stoller 2019). Doses up to 60 mg every 6 hours have been used in critically ill patients, although outcome data are limited. Note: Dose is based on an equivalent dose of prednisone; optimal dose has not been established. If patient improves with therapy, may discontinue without taper. If patient does not improve, a longer duration of therapy may be indicated (Stoller 2019).

Deceased organ donor management (hormonal resuscitation for the deceased organ donor) (off-label use): Note: Data supporting benefit are conflicting; if given, it should be administered after blood has been collected for tissue typing (Dupuis 2014; SCCM/ACCP/AOPO [Kotloff 2015]).

IV (succinate): Regimens include: 1 g (as an IV infusion) or 15 mg/kg (as an IV infusion) or 250 mg (as an IV bolus) followed by a continuous infusion at 100 mg/hour; usually given as part of combination hormone therapy (SCCM/ACCP/AOPO [Kotloff 2015]).

Giant cell arteritis, treatment: Note: Due to the rapidly progressive nature of the disease, start treatment immediately once diagnosis is highly suspected (Dasgupta 2010). In patients presenting without threatened/evolving vision loss, an oral glucocorticoid is suggested as initial therapy rather than IV methylprednisolone (Docken 2019).

Initial pulse therapy in patients presenting with threatened/evolving vision loss: IV (succinate): 500 mg to 1 g daily for 3 days, followed by an oral glucocorticoid (eg, prednisone) (Dasgupta 2010).

Gout, acute flare: Oral: 24 to 32 mg/day in 1 or 2 divided doses until symptom improvement, followed by a 7- to 10-day taper (or 14- to 21-day taper in patients with multiple prior flares) (Becker 2019). A tapered (6-day) dose pack may be sufficient in some patients (ACR [Khanna 2012]).

Unable to take orally, 1 to 2 joints affected, and no possibility of joint infection: Note: Clinicians must have sufficient expertise to perform arthrocentesis and injection.

Intra-articular (acetate): Usual dose: Larger joint (eg, knee): 40 mg; Medium joint (eg, wrist, ankle, elbow): 30 mg; Small joint (eg, toe, finger): 10 mg; a range of doses may be used based on patient factors and clinician judgment, see note at top of adult dosing section regarding intra-articular injection (ACR [Khanna 2012]; Becker 2019); may mix the glucocorticoid with an equal volume of local anesthetic (Cardone 2002; Roberts 2019).

Unable to take orally and/or not an appropriate candidate for intra-articular injection:

IM (acetate or succinate): Initial: 40 to 60 mg as a single dose; may repeat once or twice at ≥48-hour intervals if benefit fades or there is no flare resolution (ACR [Khanna 2012]; Becker 2019).

Hospitalized patients: IV (succinate): 20 mg twice daily until clinical improvement, followed by stepwise reduction in each dose by 50% until 5 mg twice daily; then maintain a dose of ≥4 mg (or oral equivalent) twice daily for 5 days (ACR [Khanna 2012]; Becker 2019).

Graft-vs-host disease, acute, treatment (off-label use): Note: For grade ≥2 acute graft-versus-host disease. An optimal regimen has not been identified; refer to institutional protocols as variations exist. Treatment is dependent on the severity and the rate of progression (ASBMT [Martin 2012]; EBMT/ELN [Ruutu 2014]).

IV (succinate): Initial: 2 mg/kg/day in 2 divided doses; dose may vary based on organ involvement and severity. Continue for several weeks, then taper over several months (ASBMT [Martin 2012]; Chao 2019; EBMT/ELN [Ruutu 2014]).

Immune thrombocytopenia (initial therapy): Note: Goal of therapy is to provide a safe platelet count to prevent clinically important bleeding rather than normalization of the platelet count (Arnold 2019).

Patients with severe bleeding (in combination with other treatments): IV (succinate): 1 g once daily for 3 doses (Arnold 2019; von dem Borne 1988). Note: Due to the short-term response, maintenance therapy with an oral glucocorticoid (eg, prednisone) may be required (Provan 2010).

Inflammatory bowel disease:

Crohn disease, acute (eg, severe/fulminant disease and/or unable to take oral) (adjunctive agent): Note: Not for long-term use (ACG [Lichtenstein 2018]). In patients with localized peritonitis, some experts recommend against initiating corticosteroids due to the potential of masking further clinical deterioration; however, if already receiving corticosteroids, continued use may be appropriate (Hashash 2019).

IV (succinate): 40 to 60 mg/day (ACG [Lichtenstein 2018]).

Note: For patients who have been receiving chronic treatment with a corticosteroid, a small increase in their daily dose may be required during an acute exacerbation (Hashash 2019). Steroid-sparing agents (eg, biologic agents, immunomodulators) should be introduced with a goal of discontinuing corticosteroid therapy as soon as possible (ACG [Lichtenstein 2018]).

Ulcerative colitis, acute (severe or fulminant): Note: Not for long-term use.

IV (succinate): 60 mg/day in 1 to 3 divided doses. If response to treatment is inadequate after 5 days (severe) or 3 days (fulminant), second-line therapy is initiated (ACG [Rubin 2019]; Peppercorn 2019).

Iodinated contrast media allergic-like reaction, prevention: Note: Generally for patients with a prior allergic-like or unknown-type iodinated contrast reaction who will be receiving another iodinated contrast agent. Nonurgent premedication with an oral corticosteroid is generally preferred when contrast administration is scheduled to begin in ≥12 hours; however, consider an urgent (accelerated) regimen with an IV corticosteroid for those requiring contrast in <12 hours (ACR 2018).

Nonurgent regimen:

Oral: 32 mg administered 12 hours and 2 hours before contrast medium administration in combination with oral diphenhydramine 50 mg (administered 1 hour prior to contrast) (ACR 2018; Davenport 2019).

Urgent (accelerated) regimen:

IV (succinate): 40 mg every 4 hours until contrast medium administration in combination with IV diphenhydramine 50 mg (administered 1 hour prior to contrast) (ACR 2018).

Multiple sclerosis, acute exacerbation: Note: For patients with an acute exacerbation resulting in neurologic symptoms and increased disability or impairments in vision, strength, or cerebellar function (Olek 2019).

Initial pulse therapy: IV (succinate): 500 mg to 1 g daily for 3 to 7 days (5 days typically), either alone or followed by an oral taper with prednisone (Goodin 2014; Le Page 2015; Myhr 2009; NICE 2014; Olek 2019).

Myopathies (dermatomyositis/polymyositis), treatment:

Initial pulse therapy in patients presenting with severe systemic involvement or profound weakness: IV (succinate): 1 g daily for 3 to 5 days, followed by oral prednisone (Dalakas 2011; Findlay 2015).

Nausea and vomiting of pregnancy, severe/refractory (off-label use): Note: Reserve use as an add-on therapy when all other pharmacologic regimens have failed.

IV (succinate): 16 mg every 8 hours for 3 days. If no response within 3 days, discontinue treatment. If symptoms improve, complete 3-day course of treatment, then taper dose over 2 weeks (ACOG 189 2018; Safari 1998).

Pneumocystis pneumonia, adjunctive therapy for moderate to severe disease (off-label use): Note: Recommended when on room air PaO₂ <70 mm Hg or PAO₂-PaO₂ ≥35 mm Hg. Dosing is based on an equivalent dose of prednisone.

IV (succinate): 30 mg twice daily on days 1 to 5 beginning as early as possible, followed by 30 mg once daily on days 6 to 10, then 15 mg once daily on days 11 to 21 (AST [Martin 2013]; HHS [OI adult 2019]; Sax 2020; Thomas 2019).

Prostate cancer, metastatic, castration-resistant (off-label use): Oral: 4 mg twice daily (in combination with micronized abiraterone acetate) (Stein 2018).

Systemic rheumatic disorders (eg, antineutrophil cytoplasmic antibody-associated vasculitis, mixed cryoglobulinemia syndrome, polyarteritis nodosa, rheumatoid arthritis, systemic lupus erythematosus), organ-threatening or life-threatening: Note: The following dosage ranges are for guidance only; dosing should be highly individualized, taking into account disease severity, the specific disorder, and disease manifestations.

Initial pulse therapy (optional): IV (succinate): 7 to 15 mg/kg/day (maximum dose: 500 mg to 1 g/day) typically for up to 3 days, followed by an oral glucocorticoid (eg, prednisone); may be given as part of an appropriate combination regimen. Lower doses (eg, 250 mg/day) may be appropriate in some patients (eg, less severe manifestations) (Fervenza 2019; Forbess 2015; Merkel 2019a; Merkel 2020; Muchtar 2017).

Warm autoimmune hemolytic anemia:

IV (succinate): 250 mg to 1 g daily for 1 to 3 days, followed by an oral glucocorticoid (eg, prednisone) (Barros 2010; Zanella 2014); a clinician experienced with the treatment of hemolytic anemia should be involved with therapy.

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

Dosing: Chemotherapy Regimens

Leukemia, acute lymphocytic: Hyper-CVAD (Leukemia, Acute Lymphocytic)

Lymphoma, Hodgkin:

ESHAP (Hodgkin)

MINE-ESHAP (Hodgkin)

Lymphoma, non-Hodgkin: ESHAP

Lymphoma, non-Hodgkin (DLBCL): R-ESHAP (NHL-DLBCL)

Prostate cancer: Abiraterone-Methylprednisolone (Prostate)

Dosing: Pediatric

Note: Adjust dose depending upon condition being treated and response of patient. The lowest possible dose should be used to control the condition; when dose reduction is possible, the dose should be reduced gradually. In life-threatening situations, parenteral doses larger than the oral dose may be needed. Only sodium succinate salt may be given IV

Asthma, exacerbation:

Acute, short-course “burst” (NAEPP 2007):

Infants and Children <12 years:

Oral: 1 to 2 mg/kg/day in divided doses once or twice daily for 3 to 10 days; maximum daily dose: 60 mg/day; Note: Burst should be continued until symptoms resolve or patient achieves peak expiratory flow 80% of personal best; usually requires 3 to 10 days of treatment (~5 days on average); longer treatment may be required

IM (acetate): Note: This may be given in place of short-course “burst” of oral steroids in patients who are vomiting or if compliance is a problem.

Children ≤4 years: 7.5 mg/kg as a one-time dose; maximum dose: 240 mg

Children 5 to 11 years: 240 mg as a one-time dose

Children ≥12 years and Adolescents:

Oral: 40 to 60 mg/day in divided doses once or twice daily for 3 to 10 days; Note: Burst should be continued until symptoms resolve and peak expiratory flow is at least 80% of personal best; usually requires 3 to 10 days of treatment (~5 days on average); longer treatment may be required

IM (acetate): 240 mg as a one-time dose; Note: This may be given in place of short-course “burst” of oral steroids in patients who are vomiting or if compliance is a problem

Hospital/emergency medical care doses:

Infants and Children <12 years: Oral, IV: 1 to 2 mg/kg/day in 2 divided doses; maximum daily dose: 60 mg/day; continue until peak expiratory flow is 70% of predicted or personal best

Children ≥12 years and Adolescents: Oral, IV: 40 to 80 mg/day in divided doses once or twice daily until peak expiratory flow is 70% of predicted or personal best

Status asthmaticus (previous NAEPP guidelines; still used by some clinicians): Children: IV: Loading dose: 2 mg/kg/dose, then 0.5 to 1 mg/kg/dose every 6 hours; Note: See NAEPP 2007 guidelines for asthma exacerbations (emergency medical care or hospital doses) listed above

Asthma, long-term treatment (maintenance) (NAEPP 2007):

Infants and Children <12 years: Oral: 0.25 to 2 mg/kg/day once daily in the morning or every other day as needed for asthma control; maximum daily dose: 60 mg/day

Children ≥12 years and Adolescents: Oral: 7.5 to 60 mg daily once daily in the morning or every other day as needed for asthma control

General dosing; anti-inflammatory or immunosuppressive: Infants, Children, and Adolescents: Note: Dosing range variable; individualize dose for disease state and patient response; Oral, IM (acetate or succinate), IV (succinate): Initial: 0.11 to 1.6 mg/kg/day or 3.2 to 48 mg/m²/day; usual range: 0.5 to 1.7 mg/kg/day (Kliegman 2015); for oral, IM (succinate) and IV (succinate) administer in divided doses every 6 to 12 hours; for IM (acetate) administer as a single daily dose

“Pulse” therapy: IV (succinate): 15 to 30 mg/kg/dose once daily for 3 days; maximum dose: 1,000 mg

Long-acting: IM (acetate): 4 to 80 mg every 1 to 2 weeks

Kawasaki disease: Limited data available; optimal regimen not established; efficacy variable.

Primary treatment, patients at high risk for coronary artery aneurysms:

Pulse dosing: Infants and Children: IV: 30 mg/kg/dose as a single dose in combination with IVIG and aspirin (AHA [McCrindle 2017]; Ogata 2012; Okada 2009)

Taper dosing: Infants and Children: IV: 1.6 mg/kg/day in divided doses every 8 hours for 5 days or until afebrile, then transition to oral prednisolone; maximum daily dose: 48 mg/day; give in combination with aspirin and an additional dose of IVIG (AHA [McCrindle 2017]; Kobayashi 2012). Note: Dosing based on use of IV prednisolone product (2 mg/kg/day) which is not available in US; dosing converted to equivalent methylprednisolone dosing; however, clinical necessity of conversion is unknown.

Treatment, refractory/resistant disease: Note: Reserve use for patients who remain febrile after initial IVIG dose:

Pulse dosing: Infants and Children: IV: 30 mg/kg/dose once daily for 1 or 3 days; may be given in combination with additional IVIG dose (AHA [McCrindle 2017]; Ebato 2017; Miura 2008).

Taper dosing: Infants and Children: IV: 1.6 mg/kg/day in divided doses every 8 hours for 5 days or until afebrile, then transition to oral prednisolone; maximum daily dose: 48 mg/day; give in combination with aspirin and an additional dose of IVIG (AHA [McCrindle 2017]; Kobayashi 2012; Kobayashi 2013). Note: Dosing based on use of IV prednisolone product (2 mg/kg/day) which is not available in US; dosing converted to equivalent methylprednisolone dosing; however, clinical necessity of conversion is unknown.

Lupus nephritis: Children and Adolescents: IV (succinate): High-dose "pulse" therapy: 30 mg/kg/dose or 600 to 1,000 mg/m²/dose once daily for 3 days; maximum dose: 1,000 mg (Adams 2006; Marks 2010)

Spinal cord injury, acute: Limited data available: Children and Adolescents: IV (succinate): 30 mg/kg over 15 minutes followed in 45 minutes by a continuous infusion of 5.4 mg/kg/hour for 23 hours (Bracken 1992; Jaffe 1991); Note: Due to insufficient evidence of clinical efficacy (ie, preserving or improving spinal cord function), the routine use of methylprednisolone in the treatment of acute spinal cord injury is no longer recommended. If used in this setting, methylprednisolone should not be initiated >8 hours after the injury; not effective in penetrating trauma (eg, gunshot) (Consortium for Spinal Cord Medicine 2008).

Pneumocystis pneumonia; moderate or severe infection: Note: Initiate therapy within 72 hours of diagnosis, if possible.

Infants and Children: IV (succinate): 1 mg/kg/dose every 6 hours on days 1 to 7, then 1 mg/kg/dose twice daily on days 8 to 9, then 0.5 mg/kg/dose twice daily on days 10 and 11, and 1 mg/kg/dose once daily on days 12 to 16 (CDC 2009)

Adolescents: IV (succinate): 30 mg twice daily on days 1 to 5, then 30 mg once daily on days 6 to 10, then 15 mg once daily on days 11 to 21 (CDC 2009a)

Graft-versus-host disease, acute (GVHD): Infants, Children and Adolescents: IV (succinate): 1 to 2 mg/kg/dose once daily; if using low dose (1 mg/kg) and no improvement after 3 days, increase dose to 2 mg/kg. Continue therapy for 5 to 7 days; if improvement observed, may taper by 10% of starting dose every 4 days; if no improvement, then considered steroid-refractory GVHD and additional agents should be considered (Carpenter 2010)

Dosing: Renal Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; use with caution; slightly dialyzable (5% to 20%); administer dose posthemodialysis

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Calculations

• Body Surface Area (Mosteller Method)
• Corticosteroid Conversion (Glucocorticoid Effect)

Use: Labeled Indications

Oral, IM (acetate or succinate), and IV (succinate only) administration: Anti-inflammatory or immunosuppressant agent in the treatment of a variety of diseases, including those of hematologic (eg, immune thrombocytopenia, warm autoimmune hemolytic anemia), allergic, gastrointestinal (eg, Crohn disease, ulcerative colitis), inflammatory, neoplastic, neurologic (eg, multiple sclerosis), rheumatic (eg, antineutrophil cytoplasmic antibody-associated vasculitis, dermatomyositis/polymyositis, giant-cell arteritis, gout [acute flare], giant cell arteritis, mixed cryoglobulinemia syndrome, polyarteritis nodosa, rheumatoid arthritis, systemic lupus erythematosus), and/or autoimmune origin.

Intra-articular or soft tissue administration (acetate only): Gout (acute flare), acute and subacute bursitis, acute nonspecific tenosynovitis, epicondylitis, rheumatoid arthritis, and/or synovitis of osteoarthritis.

Intralesional administration (acetate only): Alopecia areata; discoid lupus erythematosus; keloids; localized hypertrophic, infiltrated, inflammatory lesions of granuloma annulare, lichen planus, lichen simplex chronicus (neurodermatitis), and psoriatic plaques; and necrobiosis lipoidica diabeticorum. May be useful in cystic tumor of an aponeurosis or tendon (ganglia).

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

Acute respiratory distress syndrome, moderate to severeLevel of Evidence [G]

Based on the Society of Critical Care Medicine/European Society of Intensive Care Medicine guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency in critically ill patients, methylprednisolone may be considered as an option in hospitalized patients with early moderate to severe acute respiratory distress syndrome (PaO₂/FiO₂ <200 and within 14 days of onset). Corticosteroids blunt the febrile response; therefore, infection surveillance is recommended. Some experts are not in favor of routine use of methylprednisolone for this indication until further data become available from adequately powered, randomized, controlled trials displaying a clear benefit ^Ref.

Cardiac transplant: Acute cellular rejection (treatment)Level of Evidence [G]

Based on the International Society for Heart and Lung Transplantation (ISHLT) guidelines for the care of heart transplant recipients, high-dose IV corticosteroids (methylprednisolone) are effective and recommended in the treatment of symptomatic acute cellular rejection (irrespective of ISHLT endomyocardial biopsy grade) and asymptomatic severe acute cellular rejection (ISHLT 3R) of the cardiac allograft. IV methylprednisolone is also an option for asymptomatic moderate acute cellular rejection (ISHLT 2R). There are currently no large randomized trials evaluating treatments for acute cellular rejection in cardiac transplantation; recommendations are based on consensus. Dosing is varied, refer to institutional protocol.

Cardiac transplant: Antibody-mediated rejection (treatment)Level of Evidence [G]

Based on the American Heart Association (AHA) scientific statement on antibody-mediated rejection in cardiac transplantation and the ISHLT guidelines for the care of heart transplant recipients, IV methylprednisolone, typically in combination with other immune therapies, may be a reasonable option for the primary treatment of patients with antibody-mediated rejection of the cardiac allograft. ISHLT guidelines state that high-dose corticosteroids (IV methylprednisolone) may be used to disrupt the immune-mediated injury of the heart allograft and reduce the risk of recurrent rejection. There are currently no large randomized trials evaluating treatments for antibody-mediated rejection in cardiac transplantation; recommendations are based on consensus. Dosing is varied, refer to institutional protocol.

Chronic obstructive pulmonary disease (acute exacerbation)Level of Evidence [G]

Based on the Global Initiative for Chronic Obstructive Lung Disease’s 2019 global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease, methylprednisolone (systemic) is recommended for acute exacerbations of chronic obstructive pulmonary disease. Short-term treatment with systemic corticosteroids has been shown to reduce recovery time, risk of early relapse, treatment failure, and length of hospital stay, as well as improve lung function. However, long-term use is associated with significant adverse effects.

Deceased organ donor management (hormonal resuscitation for the deceased organ donor)Level of Evidence [C, G]

Data from retrospective cohort studies of brain-dead donors who successfully donated organs suggest that the use of IV methylprednisolone given concomitantly with vasopressin, levothyroxine (or liothyronine), and a continuous infusion of insulin (goal blood glucose: 120 to 180 mg/dL) may be beneficial for hemodynamically unstable brain-dead donors to increase the quantity and quality of organs available for transplantation ^Ref; however, data supporting benefit are conflicting ^Ref.

Based on a Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations consensus statement, the use of methylprednisolone (in combination with levothyroxine [or liothyronine], vasopressin, and insulin) should be considered for hemodynamically unstable donors or potential cardiac donors with reduced left ventricular ejection fraction (<45%) ^Ref.

Graft-vs-host disease, acuteLevel of Evidence [C, G]

Data from a review by the American Society of Blood and Marrow Transplantation support the use of methylprednisolone for acute graft-vs-host disease (GVHD) ^Ref.

Based on the European Group for Blood and Marrow Transplantation/European LeukemiaNet working group guidelines, methylprednisolone is recommended for the treatment of acute GVHD (grade II or higher) ^Ref.

In-hospital cardiac arrestLevel of Evidence [C, G]

Data from 2 randomized controlled trials of patients experiencing in-hospital cardiac arrest suggest that the combination of vasopressin, epinephrine (standard dose), and methylprednisolone administered during cardiac arrest followed by hydrocortisone given after return of spontaneous circulation may be beneficial for the treatment of patients in this setting ^Ref. Additional trials are necessary to further define the role of this regimen and of hydrocortisone (post-arrest) for the treatment of patients who experience in-hospital cardiac arrest.

Based on the 2015 AHA guidelines for cardiopulmonary resuscitation and emergency cardiovascular care, the intra-arrest use of methylprednisolone (in combination with epinephrine and vasopressin) in patients with in-hospital cardiac arrest followed by hydrocortisone given after return of spontaneous circulation may be considered (based on limited evidence); however, further studies are warranted before routine administration of this combination can be recommended.

Nausea and vomiting of pregnancy, severe/refractoryLevel of Evidence [C, G]

Data from a limited number of patients studied in a randomized, double-blind, active-control study suggest that methylprednisolone may be beneficial for preventing rehospitalization in the treatment of hyperemesis gravidarum ^Ref.

Based on the American College of Obstetricians and Gynecologists practice bulletin on nausea and vomiting of pregnancy, use of methylprednisolone may be considered for adjunctive treatment of severe nausea and vomiting in pregnant women. Due to risks of adverse fetal events associated with first trimester exposure, use is reserved for refractory cases in women with dehydration.

Pneumocystis pneumonia, adjunctive therapy for moderate to severe diseaseLevel of Evidence [C, G]

Data from a small, retrospective, single-center study evaluating the use of corticosteroids in adults with severe non-HIV-related Pneumocystis carinii pneumonia suggest that high-dose corticosteroid therapy, as an adjunct to antimicrobial therapy, shortens mechanical ventilation duration, ICU stay, and supplemental oxygen duration ^Ref.

Based on the US Department of Health and Human Services guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV, IV methylprednisolone is an effective and recommended alternative to prednisone when parenteral administration is necessary for adjunctive treatment of Pneumocystis pneumonia in HIV-infected patients.

Prostate cancer, metastatic, castration-resistantLevel of Evidence [B]

Data from a multicenter, randomized, open-label, active-controlled, phase 2 trial support the use of methylprednisolone (in combination with micronized abiraterone acetate) for the treatment of metastatic castration-resistant prostate cancer ^Ref.

Level of Evidence Definitions

Level of Evidence Scale

Use: Unsupported: Adult

Acute spinal cord injury

Although older studies supported the use of methylprednisolone for the treatment of acute spinal cord injury, more complications (eg, wound infections, severe pneumonia, sepsis) occurred with methylprednisolone administration compared to placebo and other treatments ^Ref. The use of methylprednisolone in this setting remains controversial. According to the Congress of Neurological Surgeons guidelines for the management of acute cervical spine and spinal cord injuries, the use of methylprednisolone for the treatment of acute spinal cord injury is not recommended.

Class and Related Monographs

Glucocorticoids

Clinical Practice Guidelines

Alcoholic liver disease:

ACG, “American College of Gastroenterology Clinical Guideline, Alcoholic Liver Disease,” January 2018

Asthma:

GINA, "Global Strategy for Asthma Management and Prevention," 2018 Update

NHLBI and NAEPP, "Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma," Full Report 2007

Bronchiolitis Obliterans Syndrome:

International Society for Heart and Lung Transplantation, American Thoracic Society, and European Respiratory Society (ISHLT/STS/ERS), "An International ISHLT/ATS/ERS Clinical Practice Guideline: Diagnosis and Management of Bronchiolitis Obliterans Syndrome," August 2014

Cardiac Transplantation:

AHA, "Antibody-Mediated Rejection in Cardiac Transplantation: Emerging Knowledge in Diagnosis and Management," April 2015

ISHLT, "Care of Heart Transplant Recipients," 2010

Congenital Adrenal Hyperplasia:

The Endocrine Society, Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency, November 2018

COPD:

ACCP/CTS, "Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease: American College of Chest Physicians and Canadian Thoracic Society Guideline," 2014

Canadian Thoracic Society Recommendations for Management of Chronic Obstructive Pulmonary Disease, 2007 Update

GOLD, "Global Strategy for Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (GOLD)," 2019

Critical Illness-Related Corticosteroid Insufficiency:

Society of Critical Care Medicine/European Society of Intensive Care Medicine, “Guidelines for the Diagnosis and Management of Critical Illness-Related Corticosteroid Insufficiency in Critically Ill Patients,” December 2017

Crohn Disease:

American College of Gastroenterology (ACG), “Management of Crohn's Disease in Adults,” March 2018

Gout:

3e Initiative, Guidelines for the Management of Gout, 2014

American College of Rheumatology (ACR), Guideline for the Management of Acute Gout, 2012

BSR/BHPR, Guideline for the Management of Gout, 2007

Hypopituitarism:

Endocrine Society, “Hormonal Replacement in Hypopituitarism in Adults,” 2016

Juvenile Idiopathic Arthritis:

American College of Rheumatology, "2013 Update of the 2011 American College of Rheumatology Recommendations for the Treatment of Juvenile Idiopathic Arthritis," 2013

Lupus Nephritis:

EULAR/ERA-EDTA, Management of Adult and Paediatric Lupus Nephritis, November 2012

Opportunistic Infections:

HHS, Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV-Exposed and HIV-Infected Children, November 2013

HHS, Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, September 2015

Osteoarthritis:

American College of Rheumatology, "Recommendations for the Use of Nonpharmacologic and Pharmacologic Therapies in Osteoarthritis of the Hand, Hip, and Knee," 2012

Polymyalgia Rheumatica:

European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR), "2015 Recommendations for the Management of Polymyalgia Rheumatica," 2015

Spinal Cord Injury:

"Early Acute Management in Adults with Spinal Cord Injury," May 2008

Ulcerative Colitis:

American College of Gastroenterology, "Ulcerative Colitis in Adults," March 2019

Administration: IM

IM (acetate, succinate): Avoid injection into the deltoid muscle due to a high incidence of subcutaneous atrophy. Avoid injection or leakage into the dermis. Do not inject into areas that have evidence of acute local infection.

Administration: IV

IV (succinate): Rate dependent upon dose and severity of condition; typically, intermittent infusion is administered over 15 to 60 minutes. Administer large doses over at least 30 to 60 minutes; do not administer large doses as IV push; severe adverse effects, including hypotension, cardiac arrhythmia, and sudden death, have been reported in patients receiving methylprednisolone doses ≥250 mg administered over <30 minutes (Ditzian-Kadanoff 1987, Erstad 1989, Guillén 1998, Lucas 1993). Note: In some spinal cord injury trials, bolus doses (30 mg/kg) have been administered over 15 minutes. Do not administer acetate form IV.

Administration: Injectable Detail

pH: Succinate: 7 to 8 (adjusted with sodium hydroxide); Acetate: 3 to 7 (adjusted with sodium hydroxide)

Administration: Oral

Administer tablets after meals or with food or milk to decrease GI upset. If prescribed once daily, administer in the morning.

Administration: Other

Intra-articular or soft tissue (acetate): See manufacturer’s labeling for details.

Intralesional: Inject directly into the lesion. For large lesions, administer multiple small injections (20 to 40 mg) into the area of the lesion. Avoid injection of sufficient material to cause blanching because this may be followed by a small slough.

Administration: Pediatric

Oral: Administer after meals or with food or milk; if prescribed once daily, administer dose in the early morning to mimic the normal diurnal variation of endogenous cortisol

Parenteral:

IM: Acetate, Succinate: Avoid injection into the deltoid muscle due to a high incidence of subcutaneous atrophy. Do not inject into areas that have evidence of acute local infection. Discard contents of single-dose vial after use.

IV: Succinate: Rate dependent upon dose and severity of condition; typically intermittent infusion is administered over 15 to 60 minutes. Administer large doses over at least 30 to 60 minutes; do not administer large dose as IV push; severe adverse effects, including hypotension, cardiac arrhythmia, and sudden death, have been reported in patients receiving methylprednisolone doses ≥250 mg administered over <30 minutes (Ditzian-Kadanoff 1987; Erstad 1989; Guillén 1998; Lucas 1993). Note: In some spinal cord injury trials, bolus doses (30 mg/kg) have been administered over 15 minutes. Do not administer acetate form IV.

Dietary Considerations

Take tablets with meals to decrease GI upset; need diet rich in pyridoxine, vitamin C, vitamin D, folate, calcium, phosphorus, and protein.

Storage/Stability

Methylprednisolone acetate injection and tablets: Store at 20°C to 25°C (68°F to 77°F). Do not autoclave vials.

Methylprednisolone sodium succinate injection: Store intact vials at 20°C to 25°C (68°F to 77°F). Protect from light. Do not autoclave. Store reconstituted solutions at 20°C to 25°C (68°F to 77°F) and use within 48 hours.

Preparation for Administration: Adult

Methylprednisolone sodium succinate injection: Reconstitute vials only with provided diluent or bacteriostatic water with benzyl alcohol (see manufacturer's labeling for details). For IV infusion, dilute reconstituted dose in D5W, NS, or D5NS. Formulations containing benzyl alcohol should not be used in neonates. Neonates should only receive doses reconstituted with preservative free SWFI.

Preparation for Administration: Pediatric

Parenteral: Reconstitute vials with provided diluent or bacteriostatic water (see manufacturer's labeling for details). Act-O-Vial (self-contained powder for injection plus diluent [preservative-free SWFI or bacteriostatic water]) may be reconstituted by pressing the activator to force diluent into the powder compartment. Following gentle agitation, solution may be withdrawn via syringe through a needle inserted into the center of the stopper. Neonates should only receive doses reconstituted with preservative free SWFI.

IV infusion: Dilute reconstituted dose in D5W, NS or D5NS. Limited published information is available regarding dilution in pediatric patients; in one case series, pediatric patients with rheumatic diseases received a pulse dose of 30 mg/kg up to 1,000 mg added to 100 mL of diluent (NS or D5¹/₄NS) (Akikusa 2007); in another rheumatic disease trial, a pulse dose of 30 mg/kg up to 2,000 mg was added to 100 mL of diluent (D5W) (Miller 1980).

Compatibility

See Trissel’s IV Compatibility Database

Open Trissel's IV Compatibility

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used for many health problems like allergy signs, asthma, adrenal gland problems, blood problems, skin rashes, or swelling problems.

• This is not a list of all health problems that this drug may be used for. Talk with the doctor.

Frequently reported side effects of this drug

• Nausea

• Vomiting

• Trouble sleeping

• Agitation

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Infection

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin

• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit

• Low potassium like muscle pain or weakness, muscle cramps, or an abnormal heartbeat

• Cushing syndrome like weight gain in upper back or abdomen; moon face; severe headache; or slow healing

• Adrenal gland problems like severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss

• Pancreatitis like severe abdominal pain, severe back pain, severe nausea, or vomiting

• Skin changes like acne, stretch marks, slow healing, or hair growth

• Severe loss of strength and energy

• Irritability

• Tremors

• Fast heartbeat

• Confusion

• Severe headache

• Passing out

• Dizziness

• Sweating a lot

• Shortness of breath

• Excessive weight gain

• Swelling of arms or legs

• Chest pain

• Menstrual changes

• Bone pain

• Joint pain

• Vision changes

• Behavioral changes

• Mood changes

• Seizures

• Burning or numbness feeling

• Bruising

• Bleeding

• Severe abdominal pain

• Vomiting blood

• Black, tarry, or bloody stools

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Medication Safety Issues

Sound-alike/look-alike issues:

International issues:

Contraindications

Hypersensitivity to methylprednisolone or any component of the formulation; systemic fungal infection (except intra-articular injection for localized joint conditions); intrathecal administration; live or attenuated virus vaccines (with immunosuppressive doses of corticosteroids); use in premature infants (formulations containing benzyl alcohol preservative only); immune thrombocytopenia (formerly known as idiopathic thrombocytopenic purpura) (IM administration only)

Additional contraindication: Methylprednisolone sodium succinate 40 mg vial only: Hypersensitivity to cow's milk or its components or other dairy products which may contain trace amounts of milk ingredients (known or suspected).

Canadian labeling: Additional contraindications (not in US labeling):

Methylprednisolone tablets: Herpes simplex of the eye, vaccinia and varicella (except for short-term or emergency therapy)

Methylprednisolone acetate injection: Epidural or intravascular administration; intra-articular injections in unstable joints; herpes simplex of the eye, vaccinia and varicella (except for short-term or emergency therapy)

Methylprednisolone sodium succinate: Epidural administration; herpes simplex keratitis, vaccinia and varicella, arrested tuberculosis, acute psychoses, Cushing syndrome, peptic ulcer, markedly elevated serum creatinine (except for short-term or emergency therapy)

Documentation of allergenic cross-reactivity for corticosteroids is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Warnings/Precautions

Concerns related to adverse effects:

• Adrenal suppression: May cause hypercortisolism or suppression of hypothalamic-pituitary-adrenal (HPA) axis, particularly in younger children or in patients receiving high doses for prolonged periods. HPA axis suppression may lead to adrenal crisis. Withdrawal and discontinuation of a corticosteroid should be done slowly and carefully. Particular care is required when patients are transferred from systemic corticosteroids to inhaled products due to possible adrenal insufficiency or withdrawal from steroids, including an increase in allergic symptoms. Adult patients receiving >20 mg per day of prednisone (or equivalent) may be most susceptible. Fatalities have occurred due to adrenal insufficiency in asthmatic patients during and after transfer from systemic corticosteroids to aerosol steroids; aerosol steroids do not provide the systemic steroid needed to treat patients having trauma, surgery, or infections.

• Anaphylactoid reactions: Rare cases of anaphylactoid reactions have been observed in patients receiving corticosteroids.

• Dermal changes: Avoid injection or leakage into the dermis; dermal and/or subdermal skin depression may occur at the site of injection. Avoid deltoid muscle injection; subcutaneous atrophy may occur.

• Hepatic effects: High doses of methylprednisolone IV (usually doses of 1 g/day in adults) may induce a toxic form of acute hepatitis (rare); serious hepatic injury may occur, resulting in acute liver failure and death. Time to onset can be several weeks or longer; resolution has been observed after discontinuation of therapy. Discontinue methylprednisolone if toxic hepatitis occurs. Avoid use of high doses in patients with a history of methylprednisone-induced toxic hepatitis.

• Immunosuppression: Prolonged use of corticosteroids may increase the incidence of secondary infection, cause activation of latent infections, mask acute infection (including fungal infections), prolong or exacerbate viral or parasitic infections, or limit response to killed or inactivated vaccines. Exposure to chickenpox or measles should be avoided; corticosteroids should not be used to treat ocular herpes simplex. Corticosteroids should not be used for cerebral malaria, fungal infections, or viral hepatitis. Close observation is required in patients with latent tuberculosis and/or TB reactivity; restrict use in active TB (only fulminating or disseminated TB in conjunction with antituberculosis treatment). Amebiasis should be ruled out in any patient with recent travel to tropic climates or unexplained diarrhea prior to initiation of corticosteroids. Use with extreme caution in patients with Strongyloides infections; hyperinfection, dissemination and fatalities have occurred.

• Kaposi sarcoma: Prolonged treatment with corticosteroids has been associated with the development of Kaposi sarcoma (case reports); discontinuation may result in clinical improvement (Goedert 2002).

• Myopathy: Acute myopathy has been reported with high dose corticosteroids, usually in patients with neuromuscular transmission disorders; may involve ocular and/or respiratory muscles; monitor creatine kinase; recovery may be delayed.

• Psychiatric disturbances: Corticosteroid use may cause psychiatric disturbances, including euphoria, insomnia, mood swings, personality changes, severe depression, or psychotic manifestations. Preexisting psychiatric conditions may be exacerbated by corticosteroid use.

• Septic arthritis: May occur as a complication to parenteral therapy; institute appropriate antimicrobial therapy as required.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with heart failure (HF) and/or hypertension; use has been associated with fluid retention, electrolyte disturbances, and hypertension. Use with caution following acute myocardial infarction (MI); corticosteroids have been associated with myocardial rupture.

• Diabetes: Use corticosteroids with caution in patients with diabetes mellitus; may alter glucose production/regulation leading to hyperglycemia.

• Gastrointestinal disease: Use with caution in patients with GI diseases (diverticulitis, fresh intestinal anastomoses, active or latent peptic ulcer, ulcerative colitis, abscess or other pyogenic infection) due to perforation risk.

• Head injury: Increased mortality was observed in patients receiving high-dose IV methylprednisolone; high-dose corticosteroids should not be used for the management of head injury.

• Hepatic impairment: Use with caution in patients with hepatic impairment, including cirrhosis; long-term use has been associated with fluid retention.

• Myasthenia gravis: Use with caution in patients with myasthenia gravis; exacerbation of symptoms has occurred especially during initial treatment with corticosteroids.

• Ocular disease: Use with caution in patients with cataracts and/or glaucoma; increased intraocular pressure, open-angle glaucoma, and cataracts have occurred with prolonged use. Not recommended for the treatment of optic neuritis; may increase frequency of new episodes. Use with caution in patients with a history of ocular herpes simplex; corneal perforation has occurred; do not use in active ocular herpes simplex. Consider routine eye exams in chronic users.

• Osteoporosis: Use with caution in patients with osteoporosis; high doses and/or long-term use of corticosteroids have been associated with increased bone loss and osteoporotic fractures.

• Renal impairment: Use with caution in patients with renal impairment; fluid retention may occur.

• Seizure disorders: Use corticosteroids with caution in patients with a history of seizure disorder; seizures have been reported with adrenal crisis.

• Septic shock or sepsis syndrome: Corticosteroids should not be administered for the treatment of sepsis in the absence of shock (SCCM/ESICM [Annane 2017]). A study has failed to demonstrate efficacy in septic shock or sepsis syndrome treatment; use may increase mortality in some populations (eg, patients with elevated serum creatinine, patients who develop secondary infections after use).

• Systemic sclerosis (scleroderma): Use of higher dose corticosteroid therapy (in adults, ≥15 mg/day of prednisone or equivalent) in patients with systemic sclerosis may increase the risk of scleroderma renal crisis; avoid use when possible (Steen 1998; Trang 2012).

• Thyroid disease: Changes in thyroid status may necessitate dosage adjustments; metabolic clearance of corticosteroids increases in hyperthyroid patients and decreases in hypothyroid ones.

Concurrent drug therapy issues

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Use with caution in the elderly with the smallest possible effective dose for the shortest duration.

• Pediatric: May affect growth velocity; growth should be routinely monitored in pediatric patients.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Methylprednisolone acetate IM injection (multiple-dose vial) and the diluent for methylprednisolone sodium succinate injection may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997], CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. Additionally, benzyl alcohol may also be toxic to neural tissue when administered locally (eg, intra-articular, intralesional). See manufacturer's labeling.

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Other warnings/precautions:

• Discontinuation of therapy: Withdraw therapy with gradual tapering of dose.

• Epidural injection: Corticosteroids are not approved for epidural injection. Serious neurologic events (eg, spinal cord infarction, paraplegia, quadriplegia, cortical blindness, stroke), some resulting in death, have been reported with epidural injection of corticosteroids, with and without use of fluoroscopy.

• Stress: Patients may require higher doses when subject to stress (ie, trauma, surgery, severe infection).

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

Because of the risk of adverse effects, systemic corticosteroids should be used cautiously in the elderly, in the smallest possible dose, and for the shortest possible time.

Warnings: Additional Pediatric Considerations

May cause osteoporosis (at any age) or inhibition of bone growth in pediatric patients. Use with caution in patients with osteoporosis. In a population-based study of children, risk of fracture was shown to be increased with >4 courses of corticosteroids; underlying clinical condition may also impact bone health and osteoporotic effect of corticosteroids (Leonard, 2007). Increased IOP may occur, especially with prolonged use; in children, increased IOP has been shown to be dose dependent and produce a greater IOP in children <6 years than older children treated with ophthalmic dexamethasone (Lam, 2005). Hypertrophic cardiomyopathy has been reported in premature neonates.

Pregnancy Considerations

Methylprednisolone crosses the placenta (Anderson 1981). Some studies have shown an association between first trimester systemic corticosteroid use and oral clefts or decreased birth weight; however, information is conflicting and may be influenced by maternal dose/indication for use (Lunghi 2010; Park-Wyllie 2000; Pradat 2003). Hypoadrenalism may occur in newborns following maternal use of corticosteroids in pregnancy; monitor.

When systemic corticosteroids are needed in pregnancy for rheumatic disorders, it is generally recommended to use the lowest effective dose for the shortest duration of time, avoiding high doses during the first trimester (Götestam Skorpen 2016; Makol 2011; Østensen 2009).

For dermatologic disorders in pregnant women, systemic corticosteroids are generally not preferred for initial therapy; should be avoided during the first trimester; and used during the second or third trimester at the lowest effective dose (Bae 2012; Leachman 2006).

Pregnant women with poorly controlled asthma or asthma exacerbations may have a greater fetal/maternal risk than what is associated with appropriately used medications. Uncontrolled asthma is associated with an increased risk of perinatal mortality, preeclampsia, preterm birth, and low birth weight infants. Inhaled corticosteroids are recommended for the treatment of asthma during pregnancy; however, systemic corticosteroids should be used to control acute exacerbations or treat severe persistent asthma (ACOG 2008; GINA 2018; Namazy 2016).

Methylprednisolone may be considered for adjunctive treatment of severe nausea and vomiting in pregnant women. Due to risks of adverse fetal events associated with first trimester exposure, use is reserved for refractory cases in women with dehydration (ACOG 189 2018).

The Transplant Pregnancy Registry International (TPR) is a registry that follows pregnancies that occur in maternal transplant recipients or those fathered by male transplant recipients. The TPR encourages reporting of pregnancies following solid organ transplant by contacting them at 1-877-955-6877 or https://www.transplantpregnancyregistry.org.

Breast-Feeding Considerations

Methylprednisolone is present in breast milk (Cooper 2015; Strijbos 2015).

The relative infant dose (RID) of methylprednisolone is 2.8% to 5.6% when calculated using the highest breast milk concentration located and compared to a weight-adjusted infant dose of 15 to 30 mg/kg/day. In general, breastfeeding is considered acceptable when the RID is <10%; when an RID is >25% breastfeeding should generally be avoided (Anderson 2016; Ito 2000). Using the highest milk concentration (5.55 mcg/mL), the estimated daily infant dose via breast milk is 0.8325 mg/kg/day. This milk concentration was obtained following maternal administration of methylprednisolone 1,000 mg IV infused over 2 hours. The maximum milk concentration occurred 1 hour after the maternal dose and methylprednisolone was below the limits of quantification 12 hours after the dose (Cooper 2015).

The manufacturer notes that when used systemically, maternal use of corticosteroids have the potential to cause adverse events in a breastfeeding infant (eg, growth suppression, interfere with endogenous corticosteroid production) and therefore recommends a decision be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of treatment to the mother.

Corticosteroids are generally considered acceptable in breastfeeding women when used in usual doses (Götestam Skorpen 2016; WHO 2002); however, monitoring of the nursing infant is recommended (WHO 2002). If there is concern about exposure to the infant, some guidelines recommend waiting 4 hours after the maternal dose of an oral systemic corticosteroid before breastfeeding in order to decrease potential exposure to the breastfeeding infant (based on a study using prednisolone) (Bae 2012; Butler 2014; Götestam Skorpen 2016; Leachman 2006; Makol 2011; Ost 1985).

Adverse Reactions

Frequency not defined:

Cardiovascular: Bradycardia, cardiac arrest, cardiac arrhythmia, cardiac failure, cardiomegaly, circulatory shock, edema, embolism (fat), hypertension, hypertrophic cardiomyopathy (in neonates), myocardial rupture (post MI), syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis

Central nervous system: Arachnoiditis, depression, emotional lability, euphoria, headache, increased intracranial pressure, insomnia, malaise, meningitis, myasthenia, neuritis, neuropathy, paraplegia, paresthesia, personality changes, psychic disorders, pseudotumor cerebri (usually following discontinuation), seizure, sensory disturbance, vertigo

Dermatologic: Acne vulgaris, allergic dermatitis, alopecia, atrophic striae, diaphoresis, ecchymoses, epidermal thinning, erythema, exfoliation of skin, facial erythema, hyperpigmentation, hypertrichosis, hypopigmentation, skin atrophy, skin rash, suppression of skin test reaction, thinning hair, urticaria, xeroderma

Endocrine & metabolic: Adrenal suppression, calcinosis, cushingoid state, Cushing syndrome, decreased glucose tolerance, diabetes mellitus, fluid retention, glycosuria, growth suppression (children), hirsutism, HPA-axis suppression, hyperglycemia, hyperlipidemia, hypokalemia, hypokalemic alkalosis, insulin resistance (increased requirements for insulin or oral hypoglycemic agents in diabetes), menstrual disease, moon face, negative nitrogen balance, protein catabolism, sodium retention, weight gain

Gastrointestinal: Abdominal distention, bladder dysfunction (after intrathecal administration, including bowel dysfunction), carbohydrate intolerance (increased), gastrointestinal hemorrhage, gastrointestinal perforation, hiccups, increased appetite, intestinal perforation (of both of the small and large intestines; especially in patients with inflammatory bowel disease), nausea, pancreatitis, peptic ulcer, spermatozoa disorder (decreased motility and number of spermatozoa), ulcerative esophagitis

Hematologic: Leukocytosis (transient), malignant neoplasm (secondary), petechia

Hepatic: Hepatomegaly, increased liver enzymes, increased serum transaminases

Hypersensitivity: Anaphylactoid reaction, anaphylaxis, angioedema, hypersensitivity reaction

Infection: Increased susceptibility to infection, infection (ophthalmic), sterile abscess

Local: Injection site infection

Neuromuscular & skeletal: Amyotrophy, arthropathy, aseptic necrosis of femoral head, aseptic necrosis of humoral head, bone fracture, Charcot-like arthropathy, lipotrophy, osteoporosis, rupture of tendon, steroid myopathy, vertebral compression fracture

Ophthalmic: Blindness, exophthalmoses, glaucoma, increased intraocular pressure, ophthalmic inflammation (ophthalmic), subcapsular posterior cataract, visual impairment

Respiratory: Pulmonary edema, rhinitis

Miscellaneous: Anaphylactoid reaction, anaphylaxis, angioedema, hypersensitivity reactions, tissue sloughing (residue or slough at injection site), wound healing impairment

<1%, postmarketing, and/or case reports: Venous thrombosis (Johannesdottir 2013)

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• Corticosteroid Allergy

Metabolism/Transport Effects

Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions Open Interactions

Acetylcholinesterase Inhibitors: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur. Risk C: Monitor therapy

Aldesleukin: Corticosteroids may diminish the antineoplastic effect of Aldesleukin. Risk X: Avoid combination

Amphotericin B: Corticosteroids (Systemic) may enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy

Androgens: Corticosteroids (Systemic) may enhance the fluid-retaining effect of Androgens. Risk C: Monitor therapy

Antacids: May decrease the bioavailability of Corticosteroids (Oral). Management: Consider separating doses by 2 or more hours. Budesonide enteric coated tablets could dissolve prematurely if given with drugs that lower gastric acid, with unknown impact on budesonide therapeutic effects. Risk D: Consider therapy modification

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Aprepitant: May increase the serum concentration of Corticosteroids (Systemic). Management: No dose adjustment is needed for single 40 mg aprepitant doses. For other regimens, reduce oral dexamethasone or methylprednisolone doses by 50%, and IV methylprednisolone doses by 25%. Antiemetic regimens containing dexamethasone reflect this adjustment. Risk D: Consider therapy modification

Axicabtagene Ciloleucel: Corticosteroids (Systemic) may diminish the therapeutic effect of Axicabtagene Ciloleucel. Management: Avoid use of corticosteroids as premedication before axicabtagene ciloleucel. Corticosteroids may, however, be required for treatment of cytokine release syndrome or neurologic toxicity. Risk D: Consider therapy modification

Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Risk D: Consider therapy modification

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

Bile Acid Sequestrants: May decrease the absorption of Corticosteroids (Oral). Risk C: Monitor therapy

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Calcitriol (Systemic): Corticosteroids (Systemic) may diminish the therapeutic effect of Calcitriol (Systemic). Risk C: Monitor therapy

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Risk X: Avoid combination

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Risk C: Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Corticorelin: Corticosteroids may diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy. Risk C: Monitor therapy

Cosyntropin: Corticosteroids (Systemic) may diminish the diagnostic effect of Cosyntropin. Risk C: Monitor therapy

CycloSPORINE (Systemic): May increase the serum concentration of MethylPREDNISolone. MethylPREDNISolone may increase the serum concentration of CycloSPORINE (Systemic). MethylPREDNISolone may decrease the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of MethylPREDNISolone. Management: Consider methylprednisolone dose increases in patients receiving strong CYP3A4 inducers and monitor closely for reduced steroid efficacy. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of MethylPREDNISolone. Management: Consider methylprednisolone dose reduction in patients receiving strong CYP3A4 inhibitors and monitor for increased steroid related adverse effects. Risk D: Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Risk D: Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Deferasirox: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor therapy

Deferasirox: Corticosteroids may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor therapy

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Risk C: Monitor therapy

Desirudin: Corticosteroids (Systemic) may enhance the anticoagulant effect of Desirudin. More specifically, corticosteroids may increase hemorrhagic risk during desirudin treatment. Management: Discontinue treatment with systemic corticosteroids prior to desirudin initiation. If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation. Risk D: Consider therapy modification

Desmopressin: Corticosteroids (Systemic) may enhance the hyponatremic effect of Desmopressin. Risk X: Avoid combination

DilTIAZem: May increase the serum concentration of Corticosteroids (Systemic). Risk C: Monitor therapy

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Risk D: Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Estrogen Derivatives: May increase the serum concentration of Corticosteroids (Systemic). Risk C: Monitor therapy

Fexinidazole [INT]: Corticosteroids (Systemic) may enhance the arrhythmogenic effect of Fexinidazole [INT]. Risk X: Avoid combination

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Risk D: Consider therapy modification

Fosaprepitant: May increase the serum concentration of Corticosteroids (Systemic). The active metabolite aprepitant is likely responsible for this effect. Risk D: Consider therapy modification

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Hyaluronidase: Corticosteroids may diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving corticosteroids (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Risk D: Consider therapy modification

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Indacaterol: May enhance the hypokalemic effect of Corticosteroids (Systemic). Risk C: Monitor therapy

Indium 111 Capromab Pendetide: Corticosteroids (Systemic) may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Risk X: Avoid combination

Isoniazid: Corticosteroids (Systemic) may decrease the serum concentration of Isoniazid. Risk C: Monitor therapy

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification

Loop Diuretics: Corticosteroids (Systemic) may enhance the hypokalemic effect of Loop Diuretics. Risk C: Monitor therapy

Macimorelin: Corticosteroids (Systemic) may diminish the diagnostic effect of Macimorelin. Risk X: Avoid combination

Mifamurtide: Corticosteroids (Systemic) may diminish the therapeutic effect of Mifamurtide. Risk X: Avoid combination

MiFEPRIStone: May diminish the therapeutic effect of Corticosteroids (Systemic). MiFEPRIStone may increase the serum concentration of Corticosteroids (Systemic). Management: Avoid mifepristone in patients who require long-term corticosteroid treatment of serious illnesses or conditions (e.g., for immunosuppression following transplantation). Corticosteroid effects may be reduced by mifepristone treatment. Risk X: Avoid combination

Mitotane: May decrease the serum concentration of Corticosteroids (Systemic). Risk D: Consider therapy modification

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Risk D: Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Neuromuscular-Blocking Agents (Nondepolarizing): May enhance the adverse neuromuscular effect of Corticosteroids (Systemic). Increased muscle weakness, possibly progressing to polyneuropathies and myopathies, may occur. Risk D: Consider therapy modification

Nicorandil: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Nicorandil. Gastrointestinal perforation has been reported in association with this combination. Risk C: Monitor therapy

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Risk D: Consider therapy modification

Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (Nonselective): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor therapy

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Risk C: Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination

Quinolones: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Quinolones. Specifically, the risk of tendonitis and tendon rupture may be increased. Risk C: Monitor therapy

Ritodrine: Corticosteroids may enhance the adverse/toxic effect of Ritodrine. Risk C: Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Risk D: Consider therapy modification

Salicylates: May enhance the adverse/toxic effect of Corticosteroids (Systemic). These specifically include gastrointestinal ulceration and bleeding. Corticosteroids (Systemic) may decrease the serum concentration of Salicylates. Withdrawal of corticosteroids may result in salicylate toxicity. Risk C: Monitor therapy

Sargramostim: Corticosteroids (Systemic) may enhance the therapeutic effect of Sargramostim. Specifically, corticosteroids may enhance the myeloproliferative effects of sargramostim. Risk C: Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Risk C: Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Somatropin: Corticosteroids (Systemic) may diminish the therapeutic effect of Somatropin. Risk C: Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Risk D: Consider therapy modification

Tacrolimus (Systemic): Corticosteroids (Systemic) may decrease the serum concentration of Tacrolimus (Systemic). Conversely, when discontinuing corticosteroid therapy, tacrolimus concentrations may increase. Risk C: Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Risk C: Monitor therapy

Thiazide and Thiazide-Like Diuretics: Corticosteroids (Systemic) may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Tisagenlecleucel: Corticosteroids (Systemic) may diminish the therapeutic effect of Tisagenlecleucel. Management: Avoid use of corticosteroids as premedication or at any time during treatment with tisagenlecleucel, except in the case of life-threatening emergency (such as resistant cytokine release syndrome). Risk D: Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Risk D: Consider therapy modification

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy

Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Urea Cycle Disorder Agents: Corticosteroids (Systemic) may diminish the therapeutic effect of Urea Cycle Disorder Agents. More specifically, Corticosteroids (Systemic) may increase protein catabolism and plasma ammonia concentrations, thereby increasing the doses of Urea Cycle Disorder Agents needed to maintain these concentrations in the target range. Risk C: Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Risk D: Consider therapy modification

Vaccines (Live): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Vaccines (Live). Corticosteroids (Systemic) may diminish the therapeutic effect of Vaccines (Live). Management: Doses equivalent to less than 2 mg/kg or 20 mg per day of prednisone administered for less than 2 weeks are not considered sufficiently immunosuppressive to create vaccine safety concerns. Higher doses and longer durations should be avoided. Risk D: Consider therapy modification

Warfarin: Corticosteroids (Systemic) may enhance the anticoagulant effect of Warfarin. Risk C: Monitor therapy

Test Interactions

Decreased response to skin tests

Genes of Interest

• Cytochrome P450 3A4

Monitoring Parameters

Blood pressure, blood glucose, electrolytes; weight; intraocular pressure (use >6 weeks); bone mineral density; growth and development in children; HPA axis suppression

Advanced Practitioners Physical Assessment/Monitoring

Obtain blood glucose and electrolytes. Monitor blood pressure, weight, and intraocular pressure (if using >6 months). Obtain bone mineral density test. Monitor growth in children. Assess for HPA axis suppression or signs of infection.

Nursing Physical Assessment/Monitoring

Check ordered labs and tests and report abnormalities. Monitor for signs and symptoms of infection and adrenal crisis (nausea, vomiting, dizziness, syncope, weakness, mood changes, weight loss); instruct patient to report. Instruct patients with diabetes to monitor serum glucose levels closely.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Kit, Injection, as acetate:

P-Care D40: 40 mg/mL [contains polyethylene glycol]

P-Care D80: 40 mg/mL [contains polyethylene glycol]

ReadySharp methylPREDNISolone: 80 mg/mL [DSC] [contains polyethylene glycol]

Solution Reconstituted, Injection, as sodium succinate [strength expressed as base]:

SOLU-Medrol: 500 mg (1 ea)

SOLU-Medrol: 2 g (1 ea [DSC]) [contains benzyl alcohol]

Generic: 40 mg (1 ea); 125 mg (1 ea); 500 mg (1 ea); 1000 mg (1 ea)

Solution Reconstituted, Injection, as sodium succinate [strength expressed as base, preservative free]:

SOLU-Medrol: 40 mg (1 ea) [contains lactose]

SOLU-Medrol: 125 mg (1 ea); 500 mg (1 ea); 1000 mg (1 ea); 2 g (1 ea)

Suspension, Injection, as acetate:

DEPO-Medrol: 20 mg/mL (5 mL); 40 mg/mL (5 mL, 10 mL) [contains benzyl alcohol, polyethylene glycol, polysorbate 80]

DEPO-Medrol: 40 mg/mL (1 mL) [contains polyethylene glycol]

DEPO-Medrol: 80 mg/mL (5 mL) [contains benzyl alcohol, polyethylene glycol, polysorbate 80]

DEPO-Medrol: 80 mg/mL (1 mL) [contains polyethylene glycol]

Generic: 40 mg/mL (1 mL, 5 mL, 10 mL); 80 mg/mL (1 mL, 5 mL)

Suspension, Injection, as acetate [preservative free]:

DEPO-Medrol: 40 mg/mL (1 mL) [contains polyethylene glycol]

Tablet, Oral:

Medrol: 2 mg, 8 mg, 16 mg, 32 mg, 4 mg [scored]

Generic: 8 mg, 16 mg, 32 mg, 4 mg

Tablet Therapy Pack, Oral:

Medrol: 4 mg (21 ea) [scored]

Generic: 4 mg (21 ea)

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Injection, as sodium succinate [strength expressed as base]:

SOLU-medrol: 40 mg (1 ea) [contains benzyl alcohol, lactose]

Solu-MEDROL: 125 mg (1 ea) [contains benzyl alcohol]

Solu-MEDROL: 500 mg (1 ea)

Solu-MEDROL: 500 mg (1 ea) [contains benzyl alcohol]

Solu-MEDROL: 1000 mg (1 ea)

Generic: 40 mg (1 ea); 125 mg (1 ea); 500 mg (1 ea); 1000 mg (1 ea)

Suspension, Injection, as acetate:

Depo-Medrol: 20 mg/mL (5 mL) [contains benzyl alcohol]

Depo-Medrol: 40 mg/mL (1 mL)

Depo-Medrol: 40 mg/mL (2 mL, 5 mL) [contains benzyl alcohol]

Depo-Medrol: 80 mg/mL (1 mL)

Depo-Medrol: 80 mg/mL (5 mL) [contains benzyl alcohol]

Generic: 40 mg/mL (1 mL, 2 mL, 5 mL); 80 mg/mL (1 mL, 5 mL)

Tablet, Oral:

Medrol: 16 mg, 4 mg

Anatomic Therapeutic Chemical (ATC) Classification

• D07AA01
• H02AB04

Generic Available (US)

Yes

Pricing: US

Solution (reconstituted) (methylPREDNISolone Sodium Succ Injection)

40 mg (per each): $5.52 - $7.30

125 mg (per each): $9.36 - $13.98

500 mg (per each): $27.74

1000 mg (per each): $36.00 - $50.27

Solution (reconstituted) (SOLU-Medrol Injection)

2 g (per each): $99.73

40 mg (per each): $7.22

125 mg (per each): $11.63

500 mg (per each): $27.74

1000 mg (per each): $50.27

Suspension (DEPO-Medrol Injection)

20 mg/mL (per mL): $7.93

40 mg/mL (per mL): $12.68

80 mg/mL (per mL): $22.01

Suspension (methylPREDNISolone Acetate Injection)

40 mg/mL (per mL): $10.44

80 mg/mL (per mL): $17.16

Tablet Therapy Pack (Medrol Oral)

4 mg (per each): $0.36

Tablet Therapy Pack (methylPREDNISolone Oral)

4 mg (per each): $1.43 - $1.65

Tablets (Medrol Oral)

2 mg (per each): $1.94

4 mg (per each): $0.36

8 mg (per each): $2.11

16 mg (per each): $3.40

32 mg (per each): $11.86

Tablets (methylPREDNISolone Oral)

4 mg (per each): $1.43 - $2.23

8 mg (per each): $2.01

16 mg (per each): $3.11 - $3.54

32 mg (per each): $4.62 - $5.18

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

In a tissue-specific manner, corticosteroids regulate gene expression subsequent to binding specific intracellular receptors and translocation into the nucleus. Corticosteroids exert a wide array of physiologic effects including modulation of carbohydrate, protein, and lipid metabolism and maintenance of fluid and electrolyte homeostasis. Moreover cardiovascular, immunologic, musculoskeletal, endocrine, and neurologic physiology are influenced by corticosteroids. Decreases inflammation by suppression of migration of polymorphonuclear leukocytes and reversal of increased capillary permeability.

Pharmacodynamics/Kinetics

Onset of action: IV (succinate): Within 1 hour; Intra-articular (acetate): 1 week

Duration: Intra-articular (acetate): 1 to 5 weeks

Absorption: Oral: Well absorbed (Czock 2005)

Bioavailability: Oral: 88% ± 23% (Czock 2005)

Distribution: V_d: IV (succinate): 24 L ± 6 L (Czock 2005)

Metabolism: Hepatic to metabolites (Czock 2005)

Half-life elimination:

Adolescents: IV: 1.9 ± 0.7 hours (age range: 12 to 20 years; Rouster-Stevens 2008)

Adults: Oral: 2.5 ± 1.2 hours (Czock 2005); IV (succinate): 0.25 ± 0.1 hour (Czock 2005)

Time to peak, plasma:

Oral: 2.1 ± 0.7 hours (Czock 2005)

IV (succinate): 0.8 hours (Czock 2005)

Excretion: Urine (1.3% [oral], 9.2% [IV succinate] as unchanged drug) (Czock 2005)

Pharmacodynamics/Kinetics: Additional Considerations

Geriatric: Decreased clearance and increased half-life (Czock 2005)

Obesity: Decreased clearance and increased half-life (Czock 2005)

Dental Use

Treatment of a variety of oral diseases of allergic, inflammatory, or autoimmune origin

* See Uses in AHFS Essentials for additional information.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Ulcerative esophagitis.

Effects on Bleeding

No information available to require special precautions

Dental Usual Dosing

Anti-inflammatory or immunosuppressive: Adults: Oral: 2 to 60 mg/day in 1 to 4 divided doses to start, followed by gradual reduction in dosage to the lowest possible level consistent with maintaining an adequate clinical response.

Related Information

• Beers Criteria 2019: Potentially Inappropriate Medication Use in Older Adults ≥65 Years of Age
• Corticosteroids Systemic Equivalencies
• Management of Chemotherapy-Induced Nausea and Vomiting in Adults
• Relative Infant Dose
• Stress Replacement of Corticosteroids

Pharmacotherapy Pearls

Sodium content of 1 g sodium succinate injection: 2.01 mEq; 53 mg of sodium succinate salt is equivalent to 40 mg of methylprednisolone base

Methylprednisolone acetate: Depo-Medrol

Methylprednisolone sodium succinate: Solu-Medrol

Index Terms

6-α-Methylprednisolone; A-Methapred; Medrol Dose Pack; Methylprednisolone Acetate; Methylprednisolone Sodium Succinate; Solumedrol

FDA Approval Date

October 24, 2000

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Brand Names: International

Adrelan (PH); Advantan (MX); Adventan (ES); Cipridanol (PY); Comedrol (ID); Cryosolona (MX); Depo Medrol (AE, BH, JO, KW, LB, QA, SA); Depo-Medrol (BB, EG, ET, IS, LU, LV, MX, NO, SI, SK, UA, VN, ZW); Depo-Medrone (IE, MT); Epizolone-Depot (ET); Flason (ID); Flumethyl (ID); Lexcomet (ID); Lexxema (ES); M-Nisol (LK); M-Prednihexal (DE); Madomed (TH); Meapron (KR); Medason (HK); Medexa (VN); Medisolu (KR); Medixon (ID, MY, PH); Medlon (VN); Mednin (TW); Medrate (DE); Medrol (AE, BB, BE, BH, BM, BS, BZ, CH, CL, CN, CO, CR, CY, CZ, DE, DK, DO, EC, EE, ES, FI, FR, GB, GR, GT, GY, HN, HR, ID, IE, IL, IN, IQ, IR, IT, JM, JO, KR, KW, LT, LU, LV, LY, MT, NI, NL, NO, NZ, OM, PA, PE, PH, PL, PT, QA, RO, RU, SA, SE, SI, SK, SR, SV, SY, TR, TT, UA, VE, YE, ZA); Medrone (GB); Melone 16 (TW); Melsone (IN); Menisone (TW); Meprednisona All Pro (AR); Mepresone (PH); Mesolone (KR); Metcor (ID); Metcort (PH); Methylon (KR); Methylpred (AU); Methylprednisolone David Bull (LU); Methysol (KR); Metrite (LK); Metypred (UA); Neo-Drol (LK); Nisolon-M (KR); Predlitem (MX); Prednivex (LK, PH); Prednol (TR); Prednox (PH); Prena (KR); Pretilon (ID); Prolon (ID); Sanexon (ID, LK); Sol-U-Pred (LK); Sologen (KR); Solomet (FI); Solu Medrol (BF, BJ, CI, ET, GH, GM, GN, KE, LK, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW); Solu-Medon (VN); Solu-Medrol (AE, AU, BB, BG, BH, CL, CN, CR, CY, DO, EG, GT, HK, HN, HR, IS, JO, JP, KW, LB, LT, LU, LV, MX, MY, NI, PA, PK, QA, RO, SA, SI, SK, SV, TH, TR, UA, UY); Solu-Medrone (IE, MT); Solu-Moderin (ES); Solu-Pred (MY); Somidex (TH); Sonicor (ID); Thimelon (ID); Thylmedi (VN); Tisolon-4 (ID); Tropidrol (ID); Urbason (AT, CZ, DE, EG, ES, HR, NL); Urbason Retard (IT); Yalone (ID)

Last Updated 3/5/20