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.
General dosing; anti-inflammatory or immunosuppressive (manufacturer's labeling):
Methylprednisolone sodium succinate (immediate acting): Infants, Children, and Adolescents: Oral, IV, IM: 0.11 to 1.6 mg/kg/day in 3 to 4 divided doses.
Methylprednisolone acetate (long acting): Infants, Children, and Adolescents:
IM: 0.11 to 1.6 mg/kg/dose every 1 to 2 weeks.
Intra-articular: Dosing varies based on affected joint; general range: 4 to 80 mg every 1 to 5 weeks.
Anaphylaxis, adjunctive therapy: Limited data available:
Note: Administer epinephrine first when treating anaphylaxis. Corticosteroids are considered second- or third-line therapy and do not result in prompt resolution of airway obstruction or shock. Use of corticosteroids for anaphylaxis is controversial; they have little to no benefit on initial symptoms; typically administered to prevent biphasic or prolonged episodes of anaphylaxis (AAAAI/ACAAI [Lieberman 2015]; AAAAI/ACAAI [Shaker 2020]; EAACI [Muraro 2014]; WAO [Cardona 2020]; WAO [Simons 2011]; WAO [Simons 2015]).
Infants, Children, and Adolescents: IV, IM (succinate): 1 to 2 mg/kg/dose as a single dose; maximum dose: 125 mg/dose (AAAAI/ACAAI [Lieberman 2015]; WAO [Simons 2011]).
Asthma:
Acute exacerbation:
Outpatient management (short-course "burst") (NAEPP 2007):
Oral: 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.
Infants and Children <12 years: Oral: 1 to 2 mg/kg/day in 1 or 2 divided doses for 3 to 10 days; maximum daily dose: 60 mg/day.
Children ≥12 years and Adolescents: Oral: 40 to 60 mg/day in 1 or 2 divided doses for 3 to 10 days.
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: IM: 7.5 mg/kg as a one-time dose; maximum dose: 240 mg.
Children ≥5 years and Adolescents: IM: 240 mg as a one-time dose.
Emergency/acute care management:
Infants and Children <12 years: Oral, IV (succinate): 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 (NAEPP 2007). Some experts suggest infants and children ≤5 years may receive IV doses of 1 mg/kg/dose every 6 hours on day 1, followed by transition to oral corticosteroids to complete a 3 to 5 days course (GINA 2021)
Children ≥12 years and Adolescents: Oral, IV (succinate): 40 to 80 mg/day in 1 or 2 divided doses until peak expiratory flow is 70% of predicted or personal best (NAEPP 2007).
Status asthmaticus: Children and Adolescents: IV (succinate): Loading dose: 2 mg/kg/dose, then 0.5 to 1 mg/kg/dose every 6 hours (Carroll 2013; Giuliano 2013; Younger 1987).
Long-term treatment (non-acute), severe, persistent asthma (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 once daily in the morning or every other day as needed for asthma control.
Graft-versus-host disease, acute (GVHD): Limited data available: 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).
Immune thrombocytopenia, moderate to severe bleeding or at risk for severe bleeding: Limited data available:
Infants, Children, and Adolescents: IV (succinate): Initial: Pulse: 30 mg/kg/dose once daily for 1 to 3 doses; number of doses is determined by patient clinical status, initial and postdose platelet counts, and if used in conjunction with other therapies; maximum dose: 1,000 mg/dose; follow with oral corticosteroid therapy as clinically indicated (Ancona 2002; Gereige 2000; Provan 2019).
Juvenile idiopathic arthritis, systemic: Note: Therapy should be individualized based on disease severity and activity (CARRA [Dewitt 2012]). Limited data available:
Children and Adolescents: IV (succinate): Pulse therapy: 30 mg/kg/day once daily for 3 days; maximum dose: 1,000 mg/dose. Follow pulse therapy with oral corticosteroids; evaluate initial response at 1 to 2 weeks and then at 1 month of therapy; if condition worsens or unchanged at either time interval, may repeat methylprednisolone 30 mg/kg/dose at weekly intervals as clinically indicated (CARRA [DeWitt 2012]).
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 (succinate): 30 mg/kg/dose as a single dose in combination with intravenous immune globulin (IVIG) and aspirin (AHA [McCrindle 2017]; Ogata 2012; Okada 2009).
Taper dosing: Infants and Children: IV (succinate): 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 the United States; 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 (succinate): 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 (succinate): 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 the United States; dosing converted to equivalent methylprednisolone dosing; however, clinical necessity of conversion is unknown.
Lupus nephritis, proliferative (induction): Limited data available: Children and Adolescents: IV (succinate): Initial pulse therapy: 30 mg/kg/dose once daily for 3 doses; maximum dose: 1,000 mg/dose (CARRA [Mina 2012]; Chalhoub 2021; EULAR/ERA-EDTA [Fanouriakis 2020]; SHARE [Groot 2017]). Reported dosage range: 10 to 30 mg/kg/dose or 500 to 1,000 mg/m2/dose once daily for 3 days. Following pulse therapy transition to oral corticosteroids and taper as clinically indicated. May be given as part of an appropriate combination dosage regimen (Adams 2006; Aragon 2010; Basu 2017; Chalhoub 2021; Hogan 2018; Marks 2010).
Multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2: Limited data available, optimal regimen not established:
Note: Corticosteroids are recommended for use in combination with IVIG for management of MIS-C; evidence to determine optimal treatment regimen is limited (ACR [Henderson 2021]). Use is based on limited published experience in patients with MIS-C, extrapolation from Kawasaki disease, and expert opinion (AAP 2020; ACR [Henderson 2021]; Aronoff 2020; Belhadjer 2020; Cattalini 2021; Clouser 2020; Ouldali 2021).
Infants, Children, and Adolescents: IV (succinate): Typical dose: 2 mg/kg/day divided twice daily; doses of 0.8 to 2 mg/kg/day have been described for initial therapy; duration dependent on clinical course; may then transition to oral steroids with taper over ≥2 to 3 weeks (AAP 2020; ACR [Henderson 2021]; Belhadjer 2020; Cattalini 2021; Chiotos 2020; Clouser 2020; Ouldali 2021). In a retrospective cohort study (n=34, median age: 9 years [interquartile range: 5.1 to 12.9 years]), IVIG in combination with methylprednisolone (0.8 to 1 mg/kg/dose every 12 hours for 5 days [30 patients] or 15 to 30 mg/kg/day for 3 days [4 patients]) was compared to IVIG monotherapy; treatment with IVIG in combination with methylprednisolone was associated with greater improvement in clinical outcomes (lower risk of treatment failure, need for second-line therapy, secondary acute left ventricular dysfunction, need for hemodynamic support, and lower duration of PICU stay) (Ouldali 2021). In some patients with MIS-C and shock symptoms, or in patients who do not respond to IVIG and lower steroid doses, higher-dose methylprednisolone at 10 to 30 mg/kg/day (maximum dose: 1,000 mg/dose) for 1 to 3 days has been reported (AAP 2020; ACR [Henderson 2021]; Cattalini 2021; Chiotos 2020; Clouser 2020; Gupta 2020; Ouldali 2021).
Nephrotic syndrome, steroid resistant: Limited data available, variable regimens reported: Pulse therapy: IV (succinate): 15 to 30 mg/kg/dose or 500 mg/m2/dose once daily for 3 days; maximum dose: 1,000 mg/dose. Transition to oral corticosteroid and taper as clinically indicated (IPNA [Trautman 2020]; KDIGO 2021; Shenoy 2010; Zhang 2016). Additional pulse doses may be required; some regimens include multiple pulses over a few months until remission (Bahat 2007; Hari 2004; Mori 2004; Peña 2007).
Pneumocystis pneumonia (PCP), adjunctive therapy for moderate or severe infection: Limited data available: Note: Recommended when on room air PaO2 <70 mm Hg or PAO2-PaO2 ≥35 mm Hg. Begin as soon as possible after diagnosis and within 72 hours of PCP therapy.
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 (HHS [OI pediatric 2021]).
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 (HHS [OI adult 2021]).
Radiocontrast media reaction, prevention of rebound reaction: Limited data available: Note: If patient is experiencing anaphylaxis, administer epinephrine first. Corticosteroids may be utilized to prevent rebound reactions.
Infants, Children, and Adolescents: IV (succinate): 1 mg/kg/dose; maximum dose: 40 mg/dose (ACR 2021).
Ulcerative colitis, acute, severe: Limited data available: Children and Adolescents: IV (succinate): 1 to 1.5 mg/kg/day once daily or in divided doses 2 times daily; maximum daily dose: 60 mg/day. Higher doses should be reserved for patients with severe disease and/or who have failed oral steroids. Transition to oral therapy when clinically appropriate. If inadequate response after 3 to 5 days of IV therapy, initiate second-line therapy (ECCO/ESPGHAN [Turner 2018]).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling. The pharmacokinetic and pharmacodynamic properties of methylprednisolone in kidney impairment are not well understood (Czock 2005; Honoré 2014). Methylprednisolone clearance appears unaltered in patients with uremia (Czock 2005; Milad 1994) and it is slightly dialyzable (Czock 2005; Sherlock 1977).
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Methylprednisolone: Drug information")
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) (alternative agent): Note: Other agents (eg, triamcinolone acetonide) may be more commonly employed (Mathes 2020).
Usual dosage range: 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.
Acute respiratory distress syndrome, moderate to severe (off-label use): Note: May consider in most patients with persistent or refractory, moderate to severe acute respiratory distress syndrome, who are relatively early in the disease course (within 14 days) (Siegel 2020). 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 2021).
IV (succinate): 1 to 2 mg/kg (Campbell 2014) or 40 to 125 mg as a single dose (Campbell 2021; Castells 2021; WAO [Simons 2011]).
Angioedema (acute allergic) and/or new-onset urticaria: 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 2021). In patients with new-onset urticaria, reserve use for those with significant angioedema or with symptoms that are unresponsive to antihistamines (AAAAI/ACAAI [Bernstein 2014]; Asero 2021; EAACI [Zuberbier 2018]). The optimal dosing strategy has not been defined (AAAAI/ACAAI [Bernstein 2014]; EAACI [Zuberbier 2018]).
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 2021).
Oral: Note: Dose is based on prednisone equivalency. An example regimen is 16 to 48 mg daily initially, followed by a taper over 5 to 7 days (Asero 2021; EAACI [Zuberbier 2018]; Zuraw 2021). The total treatment duration should not exceed 10 days (EAACI [Zuberbier 2018]).
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 2021).
Oral , IV (succinate): 40 to 60 mg/day in 1 or 2 divided doses for 5 to 7 days (GINA 2021; 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 (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 2020; Stoller 2019).
Oral; IV (succinate): 40 to 60 mg daily for 5 to 14 days (GOLD 2020; 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).
COVID-19, hospitalized patients (severe or critical) (alternative agent) (off-label use):
Note: Methylprednisolone is recommended for treatment of COVID-19 in hospitalized patients requiring supplemental oxygen or ventilatory support when dexamethasone is not available or there are specific indications for methylprednisolone. Corticosteroid dosing is extrapolated from a study that used dexamethasone; the equivalent dose of methylprednisolone (or other glucocorticoid) may be substituted when dexamethasone is unavailable (IDSA [Bhimraj 2021]; NIH 2021; WHO 2020).
Oral; IV (succinate): 32 mg once daily or 16 mg twice daily for up to 10 days (or until discharge, if sooner) (IDSA [Bhimraj 2021]; NIH 2021; WHO 2020). For additional information, including use of concomitant therapies, refer to the COVID-19 dosing section of the Dexamethasone monograph.
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, treatment (acute flares):
Note: Avoid use in patients with known or suspected septic arthritis (Gaffo 2022).
Intra-articular (acetate): Note: Consider in patients with gout flare limited to 1 or 2 affected joints; clinicians must have sufficient expertise to perform arthrocentesis and injection (ACR [FitzGerald 2020]; Gaffo 2022). May mix with an equal volume of local anesthetic (Cardone 2002; Roberts 2021). Dose is individualized based on joint size, disease severity, and clinician judgment (Gaffo 2022). Typical doses are:
Large joint (eg, knee): 40 mg as a single dose (Gaffo 2022; manufacturer's labeling).
Medium joint (eg, wrist, ankle, elbow): 30 mg as a single dose (Gaffo 2022; manufacturer's labeling).
Small joint (eg, toe, finger): 10 mg as a single dose (Gaffo 2022; manufacturer's labeling).
Oral: Note: Some experts reserve use for patients who are not candidates for intra-articular glucocorticoids or when intra-articular glucocorticoid administration is not feasible (Gaffo 2022).
24 to 32 mg/day given once daily or in 2 divided doses until symptom improvement (usually 2 to 5 days), then taper gradually as tolerated (typically over 7 to 10 days); a slower taper (eg, over 14 to 21 days) may be required, particularly in patients with multiple recent flares (ACP [Qaseem 2017]; ACR [Khanna 2012]; EULAR [Richette 2017]; Gaffo 2022).
IM (acetate or succinate) (alternative route): Note: Reserve for patients who are not candidates for oral therapies or intra-articular glucocorticoid administration.
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 (Gaffo 2022).
IV (succinate) (alternative route): Note: Reserve for hospitalized patients who are not candidates for oral therapies or intra-articular glucocorticoid administration.
Initial: 20 mg twice daily until clinical improvement (usually 2 to 5 days), then reduce each dose by 50% until tapered; transition to an equivalent dose of an oral glucocorticoid (eg, prednisone) as soon as possible to complete taper (ACR [Khanna 2012]; Gaffo 2022).
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 2021).
Patients with severe bleeding (in combination with other treatments): IV (succinate): 1 g once daily for 3 doses (Arnold 2021; von dem Borne 1988). Note: Due to the short-term response, maintenance therapy with an oral glucocorticoid (eg, prednisone) may be required (Provan 2019).
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 2021).
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 2021). 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): 40 to 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]; AGA [Feuerstein 2020]; Peppercorn 2019).
Iodinated contrast media allergic-like reaction, prevention: Note: Generally reserved 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. Efficacy of premedication regimens starting <4 to 5 hours before the use of contrast has not been demonstrated (ACR 2021).
Nonurgent regimen:
Oral: 32 mg administered 12 hours and 2 hours before contrast medium administration in combination with oral or IV diphenhydramine (ACR 2021; Davenport 2021).
Urgent (accelerated) regimen:
IV (succinate): 40 mg every 4 hours until contrast medium administration in combination with IV diphenhydramine (ACR 2021). Some experts administer methylprednisolone 40 mg at 5 hours and 1 hour before contrast medium administration in combination with diphenhydramine (Davenport 2021).
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 2021).
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 2021).
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 2020; Forbess 2015; 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.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: The pharmacokinetics and pharmacodynamics of methylprednisolone in kidney impairment are not well understood (Czock 2005; Honoré 2014). Methylprednisolone clearance appears unaltered in patients with uremia (Czock 2005; Milad 1994) and it is slightly dialyzable (Czock 2005; Sherlock 1977).
Altered kidney function: No dosage adjustment necessary for any degree of kidney impairment (expert opinion).
Hemodialysis, intermittent (thrice weekly): No supplemental dose or dosage adjustment necessary (expert opinion).
Peritoneal dialysis: No dosage adjustment necessary (expert opinion).
CRRT: No dosage adjustment necessary (expert opinion).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (expert opinion).
There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.
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 [DSC] [contains polyethylene glycol]
P-Care D80: 40 mg/mL [DSC] [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]
Generic: 40 mg/mL (1 mL); 80 mg/mL (1 mL)
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)
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
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 ([DSC]); 80 mg/mL ([DSC])
Tablet, Oral:
Medrol: 16 mg, 4 mg
Oral: Administer after meals or with food or milk to decrease GI upset. 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. Avoid injection or leakage into the dermis. Do not inject into areas that have evidence of acute local infection. Discard contents of single-dose vial after use.
IV: Succinate:
IV push: May administer as a slow IV injection. Recommended rates range from over several minutes (dose not specified; US manufacturer's labeling) to over at least 5 minutes for doses ≤250 mg (Canadian manufacturer's labeling). Also refer to institution-specific policies and procedures.
Intermittent IV infusion: Rate dependent upon dose and severity of condition; typically administered as an intermittent infusion over 15 to 60 minutes. Administer doses >250 mg over at least 30 to 60 minutes; 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). Pulse doses of 15 to 30 mg/kg used in rheumatic or kidney diseases in pediatric patients have been infused over 1 to 4 hours (Hari 2004; Mori 2004; Peña 2007; Shenoy 2010; Zhang 2016). Also refer to institution-specific policies and procedures. Do not administer acetate form IV.
Oral: Administer tablets after meals or with food or milk to decrease GI upset. If prescribed once daily, administer in the morning.
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.
IV (succinate):
IV push: May administer as a slow IV injection. Recommended rates range from over several minutes (dose not specified; US manufacturer's labeling) to over at least 5 minutes for doses ≤250 mg (Canadian manufacturer's labeling). Also refer to institution-specific policies and procedures.
Intermittent IV infusion: Rate dependent upon dose and severity of condition; typically administered as an intermittent infusion over 15 to 60 minutes. Administer doses >250 mg over at least 30 to 60 minutes; 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). Also refer to institution-specific policies and procedures. Note: In some spinal cord injury trials, bolus doses (30 mg/kg) have been administered over 15 minutes. Do not administer acetate form IV.
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.
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 vials at 20°C to 25°C (68°F to 77°F) and use within 48 hours. When further diluted with D5W, NS, or D5NS, may store at ≤25°C (77°F) for up to 4 hours or at 2°C to 8°C (36°F to 46°F) for up to 24 hours.
Systemic: Oral, IM (acetate or succinate), IV (succinate only): Anti-inflammatory or immunosuppressant agent in the treatment of a variety of diseases including those of hematologic (eg, immune thrombocytopenia [oral and IV only]), allergic, inflammatory, GI (eg, ulcerative colitis), ophthalmic, neoplastic, nervous system (eg, acute exacerbations of multiple sclerosis [oral and succinate (IV/IM) only]), renal (eg, nephrotic syndrome), respiratory (eg, asthma), rheumatic (eg, rheumatoid arthritis [juvenile idiopathic arthritis], systemic lupus erythematosus), and/or autoimmune origin (FDA approved in ages >1 month and adults); has also been used for acute spinal cord injury, Pneumocystis pneumonia, and prevention and treatment of graft-versus-host disease following allogeneic bone marrow transplantation.
Local: Depot formulations (Depo-Medrol): (FDA approved in pediatric patients [age not specified] and adults).
Intra-articular (or soft tissue) (acetate only): Gout (acute flare), acute and subacute bursitis, acute nonspecific tenosynovitis, epicondylitis, rheumatoid arthritis, and/or synovitis of osteoarthritis.
Intralesional (acetate only): Alopecia areata; discoid lupus erythematosus; infiltrated, inflammatory lesions associated with granuloma annulare, lichen planus, neurodermatitis, and psoriatic plaques; keloids; necrobiosis lipoidica diabeticorum; may be helpful in cystic tumors of an aponeurosis or tendon (ganglia).
MethylPREDNISolone may be confused with medroxyPROGESTERone, methotrexate, methylTESTOSTERone, predniSONE
DEPO-Medrol may be confused with Depo-Provera, SOLU-Medrol
Medrol may be confused with Mebaral
SOLU-Medrol may be confused with salmeterol, Solu-CORTEF
Medrol [US, Canada, and multiple international markets] may be confused with Medral brand name for omeprazole [Mexico]
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
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)
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.
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 may cause transient worsening of myasthenia gravis (MG) (eg, within first 2 weeks of treatment); monitor for worsening MG (AAN [Narayanaswami 2021]).
• 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.
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).
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 intraocular pressure (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 of age than older children treated with ophthalmic dexamethasone (Lam 2005). Hypertrophic cardiomyopathy has been reported in premature neonates.
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Abrocitinib: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Abrocitinib. Management: The use of abrocitinib in combination with other immunosuppressants is not recommended. Doses equivalent to more than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks are considered immunosuppressive. Risk D: Consider therapy modification
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: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Baricitinib. Management: The use of baricitinib in combination with potent immunosuppressants is not recommended. Doses equivalent to more than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks are considered immunosuppressive. Risk D: Consider therapy modification
BCG Products: Corticosteroids (Systemic) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Bile Acid Sequestrants: May decrease the absorption of Corticosteroids (Oral). Risk C: Monitor therapy
Brincidofovir: Corticosteroids (Systemic) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Calcitriol (Systemic): Corticosteroids (Systemic) may diminish the therapeutic effect of Calcitriol (Systemic). Risk C: Monitor therapy
Cladribine: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Cladribine. 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: Corticosteroids (Systemic) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing systemic corticosteroids (dosed at 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks) several weeks prior to coccidioides immitis skin antigen testing. Risk D: Consider therapy modification
Corticorelin: Corticosteroids (Systemic) 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
COVID-19 Vaccine (Adenovirus Vector): Corticosteroids (Systemic) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: In the US, after receipt of the single dose COVID-19 adenovirus vector vaccine (Janssen), administer an additional 2nd dose using an mRNA COVID-19 vaccine, at least 28 days after the primary vaccine dose, in patients taking immunosuppressive therapies. Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Corticosteroids (Systemic) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Corticosteroids (Systemic) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Administer a 3rd dose of COVID-19 vaccine, at least 28 days after completion of the primary 2-dose series, in patients 5 years of age or older taking immunosuppressive therapies. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Corticosteroids (Systemic) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
CycloSPORINE (Systemic): May enhance the neuroexcitatory and/or seizure-potentiating effect of MethylPREDNISolone. MethylPREDNISolone may decrease the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of MethylPREDNISolone. 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 increase the serum concentration of MethylPREDNISolone. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of MethylPREDNISolone. 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
Dengue Tetravalent Vaccine (Live): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Corticosteroids (Systemic). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and systemic corticosteroids. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
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
Echinacea: May diminish the therapeutic effect of Corticosteroids (Systemic). Management: Consider avoiding echinacea in patients receiving immunosuppressants, such as systemic corticosteroids. Doses more than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks are considered immunosuppressive. 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: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fosaprepitant: May increase the serum concentration of Corticosteroids (Systemic). The active metabolite aprepitant is likely responsible for this effect. Management: Reduce the dose of corticosteroids, such as dexamethasone or oral methylprednisolone, by 50% when coadministered with fosaprepitant. Reduce intravenous methylprednisolone doses by 25% during coadministration with fosaprepitant. Risk D: Consider therapy modification
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Gallium Ga 68 Dotatate: Corticosteroids (Systemic) may diminish the diagnostic effect of Gallium Ga 68 Dotatate. Risk C: Monitor therapy
Growth Hormone Analogs: Corticosteroids (Systemic) may diminish the therapeutic effect of Growth Hormone Analogs. Growth Hormone Analogs may decrease serum concentrations of the active metabolite(s) of Corticosteroids (Systemic). Risk C: Monitor therapy
Hyaluronidase: Corticosteroids (Systemic) 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
Immune Checkpoint Inhibitors: Corticosteroids (Systemic) may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Management: Carefully consider the need for corticosteroids, at doses of a prednisone-equivalent of 10 mg or more per day, during the initiation of immune checkpoint inhibitor therapy. Use of corticosteroids to treat immune related adverse events is still recommended Risk D: Consider therapy modification
Indium 111 Capromab Pendetide: Corticosteroids (Systemic) may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Risk X: Avoid combination
Inebilizumab: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Corticosteroids (Systemic) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiation of systemic corticosteroids at immunosuppressive doses. Influenza vaccines administered less than 14 days prior to or during such therapy should be repeated 3 months after therapy. Risk D: Consider therapy modification
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
Leflunomide: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as systemic corticosteroids. Risk D: Consider therapy modification
Licorice: May increase the serum concentration of Corticosteroids (Systemic). Risk C: Monitor therapy
Loop Diuretics: Corticosteroids (Systemic) may enhance the hypokalemic effect of Loop Diuretics. Risk C: Monitor therapy
Lutetium Lu 177 Dotatate: Corticosteroids (Systemic) may diminish the therapeutic effect of Lutetium Lu 177 Dotatate. Management: Avoid repeated use of high-doses of corticosteroids during treatment with lutetium Lu 177 dotatate. Use of corticosteroids is still permitted for the treatment of neuroendocrine hormonal crisis. The effects of lower corticosteroid doses is unknown. Risk D: Consider therapy modification
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 (eg, for immunosuppression following transplantation). Corticosteroid effects may be reduced by mifepristone treatment. Risk X: Avoid combination
Natalizumab: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Neuromuscular-Blocking Agents (Nondepolarizing): May enhance the adverse neuromuscular effect of Corticosteroids (Systemic). Increased muscle weakness, possibly progressing to polyneuropathies and myopathies, may occur. Management: If concomitant therapy is required, use the lowest dose for the shortest duration to limit the risk of myopathy or neuropathy. Monitor for new onset or worsening muscle weakness, reduction or loss of deep tendon reflexes, and peripheral sensory decriments 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
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
Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the adverse/toxic effect of Corticosteroids (Systemic). Specifically, the risk of gastrointestinal bleeding, ulceration, and perforation may be increased. Risk C: Monitor therapy
Ocrelizumab: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Pidotimod: Corticosteroids (Systemic) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Corticosteroids (Systemic). Risk X: Avoid combination
Pneumococcal Vaccines: Corticosteroids (Systemic) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Polymethylmethacrylate. Specifically, the risk for hypersensitivity or implant clearance may be increased. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
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
Rabies Vaccine: Corticosteroids (Systemic) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. Risk D: Consider therapy modification
Ritodrine: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Ritodrine. Risk C: Monitor therapy
Rubella- or Varicella-Containing Live Vaccines: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Ruxolitinib (Topical): Corticosteroids (Systemic) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
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
Sipuleucel-T: Corticosteroids (Systemic) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing immunosuppressants, such as systemic corticosteroids, prior to initiating sipuleucel-T therapy. Doses equivalent to more than 2 mg/kg or 20 mg/day of prednisone given for 2 or more weeks are immunosuppressive. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Corticosteroids (Systemic). Risk C: Monitor therapy
Succinylcholine: Corticosteroids (Systemic) may enhance the neuromuscular-blocking effect of Succinylcholine. Risk C: Monitor therapy
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): Corticosteroids (Systemic) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Corticosteroids (Systemic) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
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
Tofacitinib: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Doses equivalent to more than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks are considered immunosuppressive. Risk D: Consider therapy modification
Typhoid Vaccine: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Upadacitinib: Corticosteroids (Systemic) may enhance the immunosuppressive effect of Upadacitinib. Management: Coadministration of upadacitinib with systemic corticosteroids at doses equivalent to greater than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks. Risk D: Consider therapy modification
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): Corticosteroids (Systemic) may diminish the therapeutic effect of Vaccines (Inactivated). Management: Administer vaccines at least 2 weeks prior to immunosuppressive corticosteroids if possible. If patients are vaccinated less than 14 days prior to or during such therapy, repeat vaccination at least 3 months after therapy if immunocompetence restored. Risk D: Consider therapy modification
Vaccines (Live): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Vaccines (Live). Management: Avoid live vaccines during and for 1 month after therapy with immunosuppressive doses of corticosteroids (equivalent to prednisone > 2 mg/kg or 20 mg/day in persons over 10 kg for at least 2 weeks). Give live vaccines prior to therapy whenever possible. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Corticosteroids (Systemic) may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Yellow Fever Vaccine: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Take tablets with meals to decrease GI upset; need diet rich in pyridoxine, vitamin C, vitamin D, folate, calcium, phosphorus, and protein.
Corticosteroids do not decrease fertility in patients with inflammatory bowel disease (IBD) who wish to become pregnant; however, active IBD may decrease fertility; pregnancy should be planned after a 3- to 6-month remission (Mahadevan 2019).
Methylprednisolone crosses the placenta (Anderson 1981). Some products contain benzyl alcohol, which may also cross the placenta.
Some studies have shown an association between first trimester systemic corticosteroid use and oral clefts; however, information is conflicting and may be influenced by maternal dose, duration/frequency of exposure, and indication for use. Additional data are needed to evaluate any potential risk of systemic corticosteroids and other adverse pregnancy outcomes (eg, gestational diabetes mellitus, low birth weight, preeclampsia, preterm birth) (ACOG 776 2019; Bandoli 2017; Skuladottir 2014). Hypoadrenalism may occur in newborns following maternal use of corticosteroids; monitor infants exposed to prolonged or high doses of methylprednisolone in utero (Homar 2008; Kurtoğlu 2011).
Methylprednisolone is a preferred oral corticosteroid for the treatment of maternal conditions during pregnancy because placental enzymes limit passage to the embryo (ACOG 776 2019).
When systemic corticosteroids are needed in pregnancy for rheumatic disorders, nonfluorinated corticosteroids such as methylprednisolone are preferred. Chronic high doses should be avoided (ACR [Sammaritano 2020]). Methylprednisolone may also be used to treat acute exacerbations of multiple sclerosis during pregnancy (Canibaño 2020; Dobson 2019).
Corticosteroids may be used as needed for disease flares in pregnant patients with inflammatory bowel disease; however, maintenance therapy should be avoided (Mahadevan 2019).
Uncontrolled asthma is associated with adverse events on pregnancy (increased risk of perinatal mortality, preeclampsia, preterm birth, low birth weight infants, cesarean delivery, and the development of gestational diabetes). Poorly controlled asthma or asthma exacerbations may have a greater fetal/maternal risk than what is associated with appropriately used asthma medications. Maternal treatment improves pregnancy outcomes by reducing the risk of some adverse events (eg, preterm birth, gestational diabetes). Maternal asthma symptoms should be monitored monthly during pregnancy. 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 (ERS/TSANZ [Middleton 2020]; GINA 2020).
Methylprednisolone may be considered for adjunctive treatment of severe nausea and vomiting in pregnant patients. 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).
High dose methylprednisolone may be used in the management of immune thrombocytopenia in pregnant patients refractory to oral corticosteroids; use in combination with other therapies is suggested (Provan 2019).
Systemic corticosteroids are used off label in the management of COVID-19 (NIH 2021). Methylprednisolone was not the corticosteroid evaluated in the initial study and large numbers of pregnant patients were not included (Horby 2021). However, in patients who do not require corticosteroids for other indications, or in those who have already completed a course of corticosteroids to enhance fetal lung development, equivalent doses of methylprednisolone may be preferred for use in pregnant patients with severe or critical COVID-19 due to limited placental transfer and less fetal risk. A treatment algorithm is available for pregnant patients with severe or critical COVID-19; the algorithm differentiates recommendations based on the patient's requirement for corticosteroids for fetal lung maturation. Close glucose monitoring is recommended (Saad 2020). The risk of severe illness from COVID-19 infection is increased in pregnant patients. Pregnancy is considered a high-risk medical condition by the Centers for Disease Control and Prevention (ACOG 2021). Information related to the treatment of COVID-19 during pregnancy continues to emerge; refer to current guidelines for the treatment of pregnant patients.
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.
Blood pressure, serum glucose, electrolytes, hemoglobin, occult blood loss, and clinical presence of adverse effects. Monitor intraocular pressure (if therapy >6 weeks), bone mineral density (long-term use), and weight; growth in pediatric patients (with chronic use); assess hypothalamic-pituitary-adrenal axis (HPA) suppression.
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.
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: Vd: 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)
Geriatric: Decreased clearance and increased half-life (Czock 2005)
Obesity: Decreased clearance and increased half-life (Czock 2005)
Sodium content of 1 g sodium succinate injection: 2.01 mEq; methylprednisolone sodium succinate 53 mg = methylprednisolone base 40 mg
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): $41.06 - $50.27
Solution (reconstituted) (SOLU-Medrol Injection)
2 g (per each): $113.10
40 mg (per each): $7.26
125 mg (per each): $11.69
500 mg (per each): $29.14
1000 mg (per each): $52.78
Suspension (DEPO-Medrol Injection)
20 mg/mL (per mL): $7.98
40 mg/mL (per mL): $12.74
80 mg/mL (per mL): $22.12
Suspension (methylPREDNISolone Acetate Injection)
40 mg/mL (per mL): $10.44 - $11.57
80 mg/mL (per mL): $17.16 - $19.58
Tablet Therapy Pack (Medrol Oral)
4 mg (per each): $0.37
Tablet Therapy Pack (methylPREDNISolone Oral)
4 mg (per each): $1.43 - $1.65
Tablets (Medrol Oral)
2 mg (per each): $1.97
4 mg (per each): $0.37
8 mg (per each): $2.14
16 mg (per each): $3.45
32 mg (per each): $12.04
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
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