Medrol - Drug Monograph

Introduction

Medrol (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 a significant position in the therapeutic armamentarium for managing various inflammatory, allergic, and autoimmune conditions. This monograph provides a comprehensive overview of Medrol's pharmacology, clinical applications, and safety considerations.

Mechanism of Action

Methylprednisolone exerts its effects primarily through genomic mechanisms. 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:

• Anti-inflammatory effects: Suppresses transcription of genes encoding pro-inflammatory cytokines (IL-1, IL-2, IL-6, TNF-α) while enhancing transcription of anti-inflammatory proteins
• Immunosuppressive effects: Reduces lymphocyte proliferation and migration, decreases immunoglobulin production, and inhibits macrophage and neutrophil function
• Metabolic effects: Influences carbohydrate, protein, and lipid metabolism through various genomic pathways

Non-genomic mechanisms involving membrane-bound receptors may contribute to rapid effects observed with high-dose therapy.

Indications

• Endocrine disorders: Primary or secondary adrenocortical insufficiency
• Rheumatic disorders: Rheumatoid arthritis, acute gouty arthritis
• Collagen diseases: Systemic lupus erythematosus, acute rheumatic carditis
• Dermatologic diseases: Pemphigus, severe psoriasis, exfoliative dermatitis
• Allergic states: Severe seasonal or perennial allergic rhinitis, bronchial asthma
• Ophthalmic diseases: Severe acute and chronic allergic and inflammatory processes
• Respiratory diseases: Symptomatic sarcoidosis, berylliosis, aspiration pneumonitis
• Hematologic disorders: Idiopathic thrombocytopenic purpura, acquired hemolytic anemia
• Neoplastic diseases: Palliative management of leukemias and lymphomas
• Edematous states: To induce diuresis in nephrotic syndrome
• Gastrointestinal diseases: Ulcerative colitis, regional enteritis
• Nervous system: Acute exacerbations of multiple sclerosis

• Adjunct in severe Pneumocystis jirovecii pneumonia
• Acute spinal cord injury (high-dose therapy)
• Organ transplantation rejection prophylaxis and treatment
• Severe COVID-19 with systemic inflammation

Dosage and Administration

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

• Initial dosage: 4-48 mg daily, depending on disease severity
• Maintenance dosage: Gradually reduce to lowest effective dose
• Pulse therapy: 1000 mg IV daily for 3-5 days (e.g., for MS exacerbations)

• Hepatic impairment: Reduce dosage; impaired metabolism may require adjustment
• Renal impairment: No specific dosage adjustment required
• Elderly: Use lower doses due to increased risk of adverse effects
• Pediatric: Dosing based on severity of disease, not body weight (typically 0.5-2 mg/kg/day)

• Oral: Administer with food to reduce gastrointestinal irritation
• IV: Administer methylprednisolone sodium succinate formulation over at least 30 minutes
• IM: Use methylprednisolone acetate for depot formulation

Pharmacokinetics

• Oral: Rapid and nearly complete (bioavailability 82-89%)
• Peak plasma concentrations: 1-2 hours after oral administration

• Volume of distribution: Approximately 1.2-1.5 L/kg
• Protein binding: 40-60% to albumin and transcortin
• Crosses placenta and appears in breast milk

• Primarily hepatic via CYP3A4-mediated metabolism
• Forms inactive metabolites including 20α-hydroxymethylprednisolone and 20β-hydroxymethylprednisolone

• Half-life: 2.5-4 hours (plasma), 18-36 hours (biological)
• Excretion: Primarily renal (unchanged drug <5%)
• Clearance: Reduced in hepatic impairment and elderly patients

Contraindications

• Systemic fungal infections
• Known hypersensitivity to methylprednisolone or components
• Live virus vaccinations during immunosuppressive therapy
• Absolute contraindications:

- Untreated systemic infections - Idiopathic thrombocytopenic purpura (IM administration) - Cerebral malaria

Warnings and Precautions

• Increased mortality in patients with COVID-19 receiving mechanical ventilation
• Serious and fatal infections due to immunosuppression

• Adrenal suppression: May occur with prolonged therapy; requires gradual withdrawal
• Immunosuppression: Increased susceptibility to infections, including opportunistic infections
• Hyperglycemia: May exacerbate diabetes mellitus
• Cardiovascular risk: Hypertension, fluid retention, congestive heart failure
• Psychiatric effects: May cause euphoria, insomnia, mood swings, depression, or psychosis
• Osteoporosis: Increased risk with long-term therapy
• Ophthalmic effects: Cataracts, glaucoma, corneal perforation
• Gastrointestinal effects: Peptic ulcer disease, pancreatitis

Drug Interactions

• Strong CYP3A4 inhibitors (ketoconazole, clarithromycin): Increase methylprednisolone exposure
• Strong CYP3A4 inducers (rifampin, carbamazepine): Decrease methylprednisolone exposure
• Anticoagulants: Altered response to warfarin
• Antidiabetic agents: Reduced hypoglycemic effect
• NSAIDs: Increased risk of GI ulceration
• Diuretics: Enhanced potassium-wasting effects
• Vaccines: Reduced immune response to vaccines
• Live vaccines: Risk of disseminated infection

Adverse Effects

• Insomnia
• Increased appetite
• Weight gain
• Fluid retention
• Mood changes
• Hyperglycemia
• Hypertension
• Indigestion

• Severe infections
• Osteoporosis and fractures
• Avascular necrosis
• Peptic ulcer disease
• Adrenal insufficiency
• Cushing's syndrome
• Posterior subcapsular cataracts
• Anaphylaxis
• Psychotic episodes

Monitoring Parameters

• Complete blood count
• Blood glucose levels
• Electrolytes (especially potassium)
• Blood pressure
• Bone density scan (if long-term therapy anticipated)
• Ophthalmologic examination

• Blood glucose (regularly during therapy)
• Blood pressure (at each visit)
• Weight (weekly initially)
• Signs of infection
• Growth velocity in children
• Bone density (annually with long-term therapy)
• Ophthalmologic exams (annually with long-term therapy)
• Adrenal function tests when tapering or discontinuing

Patient Education

• Take exactly as prescribed; do not stop abruptly
• Take with food to reduce stomach upset
• Report any signs of infection (fever, sore throat)
• Monitor for weight gain, swelling, or mood changes
• Inform all healthcare providers about corticosteroid use
• Carry medical alert identification
• Avoid exposure to infections when possible
• Report vision changes or eye pain
• Be aware of potential for increased blood sugar
• Discuss bone health protection strategies with provider
• Do not receive live vaccines while on therapy
• Notify provider if surgery is planned

• Maintain balanced diet with adequate calcium and vitamin D
• Engage in weight-bearing exercise as tolerated
• Practice good hygiene to prevent infections
• Limit alcohol consumption

References

1. Lexicomp Online. Methylprednisolone: Drug Information. Wolters Kluwer Clinical Drug Information, 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, et al. Corticosteroid-induced clinical adverse events: incidence, risk factors and patient's opinion. Br J Dermatol. 2007;157(1):142-148. 6. American Diabetes Association. Diabetes Care in the Hospital: Standards of Medical Care in Diabetes—2023. Diabetes Care. 2023;46(Suppl 1):S267-S278. 7. Buckley L, et al. 2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Rheumatol. 2017;69(8):1521-1537. 8. Medrol [package insert]. New York, NY: Pfizer Inc; 2022.