Methipred

Approved Indications:

A. Endocrine Disorders:

• Acute adrenocortical insufficiency
• Congenital adrenal hyperplasia
• Nonsuppurative thyroiditis
• Hypercalcemia associated with malignancy

B. Rheumatic Disorders:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Acute gouty arthritis
• Bursitis, synovitis, epicondylitis

C. Collagen Diseases:

• Systemic lupus erythematosus
• Systemic dermatomyositis (polymyositis)
• Acute rheumatic carditis

D. Dermatologic Diseases:

• Pemphigus
• Severe psoriasis
• Bullous dermatitis herpetiformis
• Severe erythema multiforme (Stevens-Johnson syndrome)
• Exfoliative dermatitis

E. Allergic States:

• Severe bronchial asthma
• Anaphylaxis (adjunctive)
• Drug hypersensitivity reactions
• Serum sickness
• Allergic rhinitis

F. Ophthalmic Disorders:

• Severe acute/chronic allergic and inflammatory eye conditions:
• Iritis, iridocyclitis, optic neuritis
• Allergic conjunctivitis, chorioretinitis

G. Respiratory Diseases:

• Symptomatic sarcoidosis
• Aspiration pneumonitis
• Loeffler’s syndrome
• Severe chronic obstructive pulmonary disease (COPD) exacerbations

H. Gastrointestinal Diseases:

• Ulcerative colitis
• Regional enteritis (Crohn’s disease)

I. Hematologic Disorders:

• Idiopathic thrombocytopenic purpura (in adults)
• Secondary thrombocytopenia
• Autoimmune hemolytic anemia
• Congenital (erythroid) hypoplastic anemia

J. Neoplastic Diseases:

• Palliative treatment of leukemias and lymphomas

K. Nervous System Disorders:

• Cerebral edema associated with brain tumors
• Acute spinal cord injury (high-dose protocol)
• Acute exacerbations of multiple sclerosis

L. Organ Transplantation:

• Prevention and treatment of rejection (immunosuppressive adjunct)

Off-Label / Clinically Accepted Uses:

• COVID-19-related cytokine storm (inflammatory modulation)
• Chemotherapy-induced nausea and vomiting (as adjunct)
• Septic shock (in select cases as per guidelines)

Route: Intravenous (IV), Intramuscular (IM)
Formulation: Powder for injection, requires reconstitution
Strengths: Available in 40 mg, 125 mg, 500 mg, 1 g, 2 g vials

Adults:

• General anti-inflammatory or immunosuppressive therapy:
• 10 to 500 mg IV or IM, depending on disease severity
• May be repeated every 4 to 6 hours or once daily
• Higher doses (e.g., 1–2 g/day) reserved for life-threatening conditions
• Acute spinal cord injury:
• 30 mg/kg IV bolus over 15 minutes, then after 45 minutes, continuous infusion of 5.4 mg/kg/hr for 23 hours
• MS exacerbation:
• 1 g IV once daily for 3 to 5 days
• Cerebral edema:
• 200 to 1000 mg IV daily in divided doses

Pediatrics:

• 0.5–1.7 mg/kg/day in divided IV/IM doses (not to exceed 80 mg/day)
• For severe conditions: 30 mg/kg IV once daily for 1 to 3 days under specialist care

Elderly:

• Use lowest effective dose; increased susceptibility to steroid side effects

Renal Impairment:

• No dosage adjustment necessary; monitor fluid retention, electrolytes, and blood pressure

Hepatic Impairment:

• Use with caution; impaired metabolism may prolong systemic exposure

Administration Notes:

• IV bolus should be administered over at least 5 minutes (higher doses over 30+ minutes)
• Reconstitute only with sterile bacteriostatic water or per manufacturer instructions
• Taper slowly after prolonged use to prevent adrenal crisis

Methylprednisolone Sodium Succinate is a water-soluble corticosteroid ester that, upon administration, is rapidly hydrolyzed to methylprednisolone, its active form. It binds to intracellular glucocorticoid receptors, forming a complex that enters the nucleus and alters the transcription of target genes. This leads to decreased synthesis of pro-inflammatory cytokines (e.g., IL-1, IL-6, TNF-α), reduced leukocyte infiltration, suppressed humoral immune responses, and inhibition of inflammatory mediator release. These effects collectively reduce inflammation, tissue damage, and immune hyperreactivity across multiple organ systems.

• Absorption: Complete and rapid following IV or IM injection (Sodium succinate form is more soluble than acetate)
• Bioavailability: 100% with IV administration
• Distribution: Widely distributed into tissues; crosses the placenta and is present in breast milk
• Plasma Protein Binding: ~75%
• Onset of Action: Within 1–2 hours (IV), peak effects in 1–4 hours
• Metabolism: Primarily in the liver via CYP3A4
• Half-life:
• Plasma: ~2.5–3.5 hours
• Biological: 18–36 hours (reflects anti-inflammatory duration)
• Excretion: Mostly via kidneys as inactive metabolites

• Pregnancy: Category C. Use only if benefits outweigh risks. High doses may affect fetal growth or cause adrenal suppression. Avoid chronic or high-dose therapy in pregnancy unless essential.
• Lactation: Excreted in small amounts in breast milk. Generally considered safe for short-term use; infants should be monitored for growth and adrenal effects if maternal therapy is prolonged or high-dose.

• Primary Class: Glucocorticoid (Systemic Corticosteroid)
• Subclass: Intermediate-acting corticosteroid; highly water-soluble injectable ester (Sodium Succinate)
• Formulation Purpose: Rapid onset for acute use (emergency, IV bolus, high-dose pulse therapy)

• Hypersensitivity to methylprednisolone or any component (e.g., succinate or preservatives)
• Systemic fungal infections
• Use of live or live-attenuated vaccines during immunosuppressive therapy
• Intrathecal or epidural administration (serious neurotoxicity reported)

• Immunosuppression: Increases risk for bacterial, viral, fungal, and parasitic infections; latent infections (e.g., TB) may reactivate
• Adrenal suppression: Risk with prolonged use; taper gradually
• Cardiovascular: Fluid retention, hypertension, heart failure exacerbation
• Neuropsychiatric: May induce euphoria, insomnia, psychosis, or depression
• GI: Peptic ulcers, GI bleeding, and pancreatitis possible
• Endocrine: Hyperglycemia, menstrual irregularities, Cushingoid features
• Musculoskeletal: Osteoporosis, avascular necrosis, muscle wasting
• Vaccines: Avoid live vaccines during and shortly after treatment

Common Side Effects:

• Endocrine/Metabolic: Hyperglycemia, weight gain, Cushingoid appearance
• GI: Nausea, dyspepsia, increased appetite
• CNS: Insomnia, anxiety, mood swings
• Musculoskeletal: Muscle weakness, delayed growth in children
• Dermatologic: Acne, skin thinning, delayed wound healing

Serious/Rare Adverse Effects:

• Infectious: Opportunistic infections, sepsis
• Psychiatric: Psychosis, mania, severe depression
• Cardiovascular: Arrhythmias, thromboembolism
• Hematologic: Leukocytosis
• Ophthalmic: Glaucoma, cataracts
• Others: Anaphylaxis (rare)

Timing & Severity: Risk increases with high doses and prolonged use. Serious effects may occur even after short courses in susceptible individuals.

• CYP3A4 Inhibitors (e.g., Ketoconazole, Ritonavir): Increase serum levels and risk of adverse effects
• CYP3A4 Inducers (e.g., Rifampin, Phenytoin): Decrease efficacy via increased metabolism
• NSAIDs: Additive risk of GI bleeding
• Diuretics: Enhanced risk of hypokalemia
• Vaccines (Live): Reduced efficacy; increased infection risk
• Antidiabetic Agents: Reduced effectiveness due to hyperglycemic effects

Enzyme System: Metabolized primarily by CYP3A4

• Spinal Cord Injury Protocols: Use of high-dose methylprednisolone remains controversial; some guidelines recommend against routine use due to risk of complications (e.g., infections)
• COVID-19: Included in treatment guidelines (e.g., NIH, WHO) for severe COVID-19 inflammatory syndromes in ICU patients
• Updated FDA Safety Info: Reinforced warnings regarding use with live vaccines and risk of neurotoxicity if administered via non-approved routes (e.g., epidural)

• Unreconstituted Powder Vials:
• Store at 20°C to 25°C (68°F to 77°F)
• Protect from excessive heat and light
• After Reconstitution:
• Use within prescribed time limits (usually within 48 hours at room temperature or 7 days if refrigerated, depending on the diluent used)
• Do not freeze
• Handling Precautions:
• Use aseptic technique for reconstitution and administration
• Inspect for particulate matter or discoloration before use