Methylprednisolone

Methylprednisolone is an intermediate-acting glucocorticoid with little mineralocorticoid activity, used orally for inflammatory disease and, in high-dose intravenous pulses, for severe immune-mediated organ disease. Pulse doses of 500 to 1000 mg are used for multiple sclerosis relapse, lupus nephritis, vasculitis, transplant rejection and optic neuritis. The depot acetate form is used for joint, soft tissue and intramuscular depot injection.

Classification. Glucocorticoid. Tablets 2 mg, 4 mg, 16 mg and 32 mg; intravenous and intramuscular sodium succinate 40 mg, 125 mg, 500 mg and 1 g; depot suspension (acetate) 40 mg/mL and 80 mg/mL.

Mechanism. Binds the intracellular glucocorticoid receptor, altering gene transcription: reduced cytokines, suppressed leukocyte migration and lymphocyte function, and increased gluconeogenesis, protein breakdown and lipolysis. Minimal sodium retention.

Pharmacodynamics. Anti-inflammatory potency 5 times hydrocortisone (4 mg equals hydrocortisone 20 mg and prednisolone 5 mg). Biological effect lasts 12 to 36 hours; depot acetate acts for 1 to 4 weeks.

Pharmacokinetics. Oral bioavailability about 90%; peak 1 to 2 hours; 75% protein bound; half-life 2 to 3 hours. Metabolised in the liver (CYP3A4); excreted in urine.

Oral anti-inflammatory use.

• 4 to 48 mg daily as a single morning dose or in divided doses, titrated to disease; 4 mg equals prednisolone 5 mg.

Multiple sclerosis acute relapse.

• 500 to 1000 mg intravenously once daily for 3 to 5 days, with no oral taper (or a short oral taper if the specialist prefers).

Lupus nephritis, systemic vasculitis, severe rheumatoid or other organ disease (induction).

• 500 to 1000 mg intravenously daily for 3 days (or 15 mg/kg, maximum 1000 mg), followed by oral prednisolone 0.5 to 1 mg/kg daily, tapered as disease remits.

Transplant rejection. 500 to 1000 mg intravenously daily for 3 days, with specialist direction.

Optic neuritis, giant cell arteritis with visual loss. 500 to 1000 mg intravenously daily for 3 days, then oral prednisolone.

Acute severe asthma and anaphylaxis (adjunct). 40 to 125 mg intravenously, then 40 mg every 6 to 8 hours (children 1 to 2 mg/kg every 6 hours) until oral treatment is possible.

Intra-articular or soft tissue injection (acetate).

• Large joints 20 to 80 mg, medium joints 10 to 40 mg, small joints 4 to 10 mg; repeat no more often than every 3 months. Intramuscular depot 40 to 120 mg every 1 to 4 weeks as needed.

Spinal cord injury. Not advised; high-dose regimens are not supported by current evidence.

Children.

• Oral 0.5 to 1.7 mg/kg daily in divided doses. Pulse therapy 10 to 30 mg/kg (maximum 1000 mg) intravenously daily for 3 days, in specialist care.

Adjustments.

• Kidney: no change.
• Liver: lower dose in cirrhosis; monitor.
• Older adults: use the lowest dose and add bone protection.
• Weight: dose by weight in children.

Contraindications. Systemic fungal infection; untreated sepsis or tuberculosis; live vaccines at immunosuppressive doses; hypersensitivity (including to lactose in some formulations, and to cow's milk protein in some intravenous preparations); intrathecal or epidural use of the depot acetate.

Serious adverse effects.

• With pulses: hyperglycaemia, hypertension, fluid retention, insomnia, agitation, psychosis, arrhythmia with rapid infusion, hypokalaemia, facial flushing, metallic taste, rare anaphylaxis, gastrointestinal bleeding.
• With long courses: osteoporosis, avascular necrosis, myopathy, infection (tuberculosis, hepatitis B, strongyloides, pneumocystis), cataract, glaucoma, Cushingoid features, adrenal suppression, growth suppression.
• Depot injection: skin atrophy, joint infection, tendon rupture.

Major interactions.

• Reduced effect: rifampicin, phenytoin, carbamazepine, phenobarbital.
• Increased effect or toxicity: ketoconazole, itraconazole, clarithromycin, ritonavir, grapefruit juice.
• Ciclosporin: each raises the level of the other; seizures reported.
• NSAIDs: gastrointestinal bleeding; diuretics: hypokalaemia; antidiabetic drugs: glucose rises; fluoroquinolones: tendon rupture.
• Vaccines: live vaccines are avoided.

Special groups.

• Pregnancy: used when needed; the placenta inactivates part of the dose. Monitor glucose and blood pressure.
• Breastfeeding: compatible; avoid feeding for 4 to 8 hours after high-dose pulses.
• Children: growth suppression; specialist use for pulses.
• Older adults: infection, delirium and bone loss; use pulses cautiously with cardiac disease.
• Kidney impairment: no change; liver impairment: lower dose.
• East Africa: the intravenous form is available only in referral centres; prednisolone is the practical oral equivalent (prednisolone 5 mg to methylprednisolone 4 mg). Screen for tuberculosis, hepatitis B and strongyloides before pulses and long courses, and check glucose.

Formulation and administration. Oral doses with food in the morning. Intravenous pulses of 500 to 1000 mg are given in 100 to 250 mL of 0.9% sodium chloride or 5% dextrose over at least 30 to 60 minutes (never as a fast bolus, which risks arrhythmia and cardiovascular collapse). Doses up to 250 mg can be given by injection over at least 5 minutes. Reconstitute powder with the supplied diluent and use within 24 hours. Depot acetate: shake well, use strict aseptic technique and avoid intravenous use.

Baseline. Blood pressure, glucose or HbA1c, potassium, infection screen (tuberculosis, hepatitis B, HIV), vaccination review, and bone health for courses over 3 months.

Monitoring.

• During pulses: blood pressure, heart rate, glucose and potassium, with cardiac monitoring in those with heart disease.
• During long courses: blood pressure, weight, glucose, bone density, eye pressure, growth in children.
• Mood and sleep; steroid card for courses over 3 weeks.

Dose reduction and stopping. After a pulse course of 3 to 5 days, oral therapy is either stopped or tapered as directed. For long courses, reduce by 5 to 10 mg every 1 to 2 weeks to 10 mg, then by 1 mg every 2 to 4 weeks (prednisolone equivalent).

Referral and escalation. Pulse therapy is specialist directed and given in a monitored setting. Admit suspected adrenal crisis, severe infection, psychosis, arrhythmia or hyperglycaemia with ketosis.