Methylprednisolone - Drug Monograph

Introduction

Methylprednisolone is a synthetic glucocorticoid corticosteroid medication widely used in clinical practice for its potent anti-inflammatory and immunosuppressive properties. As an intermediate-acting corticosteroid, it occupies an important therapeutic position between shorter-acting hydrocortisone and longer-acting dexamethasone. Methylprednisolone is available in various formulations including oral tablets, intravenous and intramuscular injections, and topical preparations, making it versatile for numerous clinical scenarios.

Mechanism of Action

Methylprednisolone exerts its effects through genomic and non-genomic mechanisms. Primarily, it diffuses across cell membranes and binds to intracellular glucocorticoid receptors, forming a complex that translocates to the nucleus. This complex binds to glucocorticoid response elements on DNA, modulating gene transcription. The drug:

• Inhibits phospholipase A2, reducing prostaglandin and leukotriene synthesis
• Suppresses cytokine production (IL-1, IL-2, IL-6, TNF-α, IFN-γ)
• Decreases inflammatory cell migration and activation
• Stabilizes lysosomal membranes
• Reduces capillary permeability

These actions collectively result in potent anti-inflammatory, immunosuppressive, antiproliferative, and vasoconstrictive effects.

Indications

• Endocrine disorders: Primary and secondary adrenal insufficiency
• Rheumatic disorders: Rheumatoid arthritis, acute gouty arthritis
• Collagen diseases: Systemic lupus erythematosus, acute rheumatic carditis
• Dermatologic conditions: Pemphigus, severe psoriasis, exfoliative dermatitis
• Allergic states: Seasonal or perennial allergic rhinitis, bronchial asthma
• Ophthalmic diseases: Allergic conjunctivitis, keratitis
• Respiratory diseases: Symptomatic sarcoidosis, berylliosis
• Hematologic disorders: Idiopathic thrombocytopenic purpura, acquired hemolytic anemia
• Neoplastic diseases: Leukemias and lymphomas in adults
• Edematous states: Nephrotic syndrome
• Gastrointestinal diseases: Ulcerative colitis
• Nervous system: Acute exacerbations of multiple sclerosis

• Spinal cord injury (high-dose pulse therapy)
• Organ transplantation rejection prophylaxis
• Severe COVID-19 pneumonia
• Autoimmune hepatitis
• Cerebral edema

Dosage and Administration

• Use the lowest effective dose for shortest duration possible
• Taper gradually when discontinuing chronic therapy

• Oral: 4-48 mg daily in divided doses
• IV/IM: 10-250 mg every 4-6 hours

• Anti-inflammatory: 4-48 mg daily
• Multiple sclerosis: 200 mg daily for 7 days, then 80 mg every other day for 1 month
• Spinal cord injury: 30 mg/kg IV bolus over 15 min, then 5.4 mg/kg/hour for 23 hours
• Pulse therapy: 500-1000 mg IV daily for 3-5 days
• Adrenal insufficiency: 4-8 mg daily in divided doses

• Hepatic impairment: Dose reduction may be necessary
• Renal impairment: No adjustment typically needed
• Elderly: Use lowest effective dose; increased fracture risk
• Pediatric: 0.5-1.7 mg/kg/day in divided doses

Pharmacokinetics

• Oral: Rapid and nearly complete (bioavailability 82-99%)
• Peak plasma concentration: 1-2 hours post oral administration
• Food does not significantly affect absorption

• Volume of distribution: 1.2-1.5 L/kg
• Protein binding: 77%
• Crosses placenta and enters breast milk

• Primarily hepatic via CYP3A4
• Converted to inactive metabolites
• Half-life: 2.3-4 hours (plasma); 18-36 hours (biological)

• Renal excretion (mainly as metabolites)
• Clearance: 5.0-5.6 mL/min/kg
• Dialysis: Not significantly removed

Contraindications

• Systemic fungal infections
• Known hypersensitivity to methylprednisolone or components
• Live or attenuated virus vaccinations during immunosuppressive therapy
• Active untreated infections (unless concomitant anti-infective therapy)
• Recent myocardial infarction (relative contraindication)

Warnings and Precautions

• Corticosteroids can cause serious and fatal infections
• May exacerbate hypertension, diabetes, glaucoma, and peptic ulcer disease
• Can cause psychiatric reactions including euphoria, insomnia, mood swings, and depression

• Adrenal suppression with long-term use
• Increased infection risk (viral, bacterial, fungal, parasitic)
• Gastrointestinal perforation risk in patients with GI disorders
• Ocular effects: cataracts, glaucoma
• Skeletal effects: osteoporosis, avascular necrosis
• Fluid and electrolyte disturbances
• Impaired wound healing
• Growth suppression in children
• Kaposi's sarcoma in immunocompromised patients

Drug Interactions

• Anticoagulants: Altered anticoagulant effect
• Antidiabetic agents: Reduced hypoglycemic effect
• CYP3A4 inducers (phenytoin, rifampin): Reduced methylprednisolone efficacy
• CYP3A4 inhibitors (ketoconazole): Increased methylprednisolone levels
• Diuretics: Enhanced potassium wasting
• NSAIDs: Increased GI ulcer risk
• Vaccines: Reduced vaccine efficacy; live vaccine complications
• Cardiac glycosides: Increased digitalis toxicity risk

Adverse Effects

• Insomnia
• Increased appetite
• Weight gain
• Fluid retention
• Mood changes
• Hyperglycemia
• Dyspepsia
• Acne
• Hirsutism

• Adrenal suppression and crisis
• Severe infections
• Osteoporosis and fractures
• Avascular necrosis
• Peptic ulcer disease with perforation
• Pancreatitis
• Psychiatric disorders
• Ocular hypertension and cataracts
• Hypersensitivity reactions
• Cardiovascular events

Monitoring Parameters

• Complete medical history and physical examination
• Blood pressure, weight, height (pediatrics)
• CBC with differential
• Electrolytes, glucose, lipids
• Bone density scan (if long-term therapy anticipated)
• Tuberculosis screening
• Ophthalmologic examination

• Blood glucose (regularly during therapy)
• Blood pressure (at each visit)
• Weight (monthly)
• Electrolytes (periodically)
• Growth velocity (pediatric patients)
• Bone density (annually if long-term therapy)
• Signs of infection
• Ophthalmologic exams (every 6-12 months)
• Adrenal function tests when tapering

Patient Education

• Take exactly as prescribed; do not stop abruptly
• Report any signs of infection (fever, sore throat)
• Monitor blood sugar if diabetic
• Report mood changes, vision changes, or unusual swelling
• Avoid contact with people who have infections
• Inform all healthcare providers about corticosteroid use
• Carry medical alert identification
• Take with food to minimize GI upset
• Do not receive live vaccines while on therapy
• Importance of regular follow-up appointments
• Calcium and vitamin D supplementation recommended
• Lifestyle modifications: weight-bearing exercise, smoking cessation

• Single daily doses should be taken in the morning
• Do not double dose if missed
• Store at room temperature away from moisture
• Report any abdominal pain or black stools immediately

References

1. Lexicomp Online. Methylprednisolone: Drug Information. Wolters Kluwer Clinical Drug Information, Inc. 2023. 2. Micromedex Solutions. Methylprednisolone. IBM Watson Health. 2023. 3. Liu D, et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol. 2013;9(1):30. 4. Coutinho AE, Chapman KE. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol. 2011;335(1):2-13. 5. Fardet L, Petersen I, Nazareth I. Suicidal behavior and severe neuropsychiatric disorders following glucocorticoid therapy in primary care. Am J Psychiatry. 2012;169(5):491-497. 6. American Society of Health-System Pharmacists. AHFS Drug Information. Bethesda, MD. 2023. 7. National Institutes of Health. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Methylprednisolone. 2023. 8. Streck WF, Lockwood DH. Pituitary adrenal recovery following short-term suppression with corticosteroids. Am J Med. 1979;66(6):910-914.