DEPO-MEDROL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DEPO-MEDROL (DEPO-MEDROL).
Methylprednisolone acetate is a synthetic glucocorticoid receptor agonist that modulates gene expression to suppress inflammation, immune responses, and adrenal function by inhibiting phospholipase A2, reducing prostaglandin and leukotriene synthesis, and decreasing cytokine production.
| Metabolism | Primarily hepatic metabolism via CYP3A4-mediated hydroxylation; also conjugated to glucuronides and sulfates. Metabolites are inactive. |
| Excretion | Primarily hepatic metabolism; renal excretion of metabolites (<10% unchanged). Fecal excretion is minor (<5%). |
| Half-life | Plasma terminal elimination half-life: 2.5-4.0 hours (methylprednisolone acetate formulation). Duration of adrenal suppression correlates with tissue esterase hydrolysis and prolonged tissue retention. |
| Protein binding | Approximately 77% bound to corticosteroid-binding globulin (CBG, transcortin) and albumin. |
| Volume of Distribution | Vd: 0.7-1.1 L/kg (methylprednisolone). Distributes widely into tissues, with high intracellular concentrations. |
| Bioavailability | IM: 100% but gradual absorption (depot); Intra-articular: 100% locally but limited systemic absorption (dose-dependent). Not available orally in this formulation. |
| Onset of Action | IM: 6-48 hours (gradual release from depot); Intra-articular: within 24-48 hours. IV: immediate (for methylprednisolone sodium succinate, but not applicable to DEPO-MEDROL). |
| Duration of Action | IM: 1-4 weeks (depends on dose and injection site); Intra-articular: 1-5 weeks; Depot effect due to slow microcrystal dissolution. |
| Action Class | Glucocorticoids |
| Brand Substitutes | Mepresso D 80mg Injection, Deposet 80mg Injection, Stalen 80mg Injection, Sirolon 80mg Injection, Predshot 80mg Injection |
IV: 10-40 mg every 1-2 weeks; IM: 40-120 mg every 1-4 weeks; Intra-articular/soft tissue: 4-80 mg per injection, repeat every 1-5 weeks as needed.
| Dosage form | INJECTABLE |
| Renal impairment | No specific GFR-based dose adjustments recommended; use with caution in severe renal impairment due to increased risk of fluid retention. |
| Liver impairment | Child-Pugh A: No adjustment; Child-Pugh B: Reduce dose by 50%; Child-Pugh C: Avoid use or reduce dose by 75% due to impaired metabolism. |
| Pediatric use | Intra-articular/soft tissue: 4-40 mg per injection, repeat every 1-5 weeks; IM/IV: 0.5-1.5 mg/kg every 1-4 weeks; maximum 80 mg per dose. |
| Geriatric use | Start at lower end of dosing range (e.g., IM 40 mg every 2-4 weeks); monitor for fluid retention, osteoporosis, and hyperglycemia; use minimum effective duration. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DEPO-MEDROL (DEPO-MEDROL).
| Breastfeeding | Methylprednisolone excreted into breast milk; M/P ratio 0.14-0.66. Low doses (< 40 mg/day) considered compatible with breastfeeding. Higher doses may cause infant adrenal suppression; monitor infant for growth and development. |
| Teratogenic Risk | First trimester: Increased risk of cleft palate (odds ratio 3.35), preterm birth, and low birth weight. Second trimester: Risk of fetal adrenal suppression, intrauterine growth restriction. Third trimester: Neonatal adrenal insufficiency, hypoglycemia, and premature closure of ductus arteriosus. |
■ FDA Black Box Warning
Intrathecal or epidural administration of methylprednisolone acetate (Depo-Medrol) is contraindicated and may result in severe adverse events including arachnoiditis, meningitis, paraparesis/paraplegia, sensory disturbances, bowel/bladder dysfunction, and visual impairment/loss. Do not inject into epidural or intrathecal space.
| Serious Effects |
["Systemic fungal infections","Intrathecal or epidural administration (black box warning)","Hypersensitivity to methylprednisolone or any component of the formulation","Idiopathic thrombocytopenic purpura (IM use is contraindicated)","Concurrent live or live attenuated vaccines"]
| Precautions | ["Immunosuppression: increased susceptibility to infections, reactivation of latent infections (e.g., tuberculosis, hepatitis B)","Hypothalamic-pituitary-adrenal (HPA) axis suppression: adrenal insufficiency upon withdrawal, especially after prolonged use","Osteoporosis: risk of bone loss with long-term use","Gastrointestinal perforation: peptic ulcer disease, diverticulitis, anastomotic leaks","Ocular effects: cataracts, glaucoma, central serous chorioretinopathy","Cardiovascular: hypertension, fluid retention, electrolyte disturbances, increased risk of thromboembolism","Psychiatric disturbances: euphoria, insomnia, mood swings, psychosis","Growth suppression in children","Cushing's syndrome with chronic use","Exacerbation of fungal infections; avoid use in systemic fungal infections except for emergency therapy","Live or live attenuated vaccines are contraindicated during high-dose therapy"] |
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| Fetal Monitoring |
| Monitor maternal blood pressure, blood glucose, signs of infection, and fluid balance. Assess fetal growth by ultrasound and amniotic fluid volume. Monitor for preterm labor. Evaluate neonatal adrenal function at birth if used in late pregnancy. |
| Fertility Effects | May cause menstrual irregularities and ovulatory dysfunction due to hormonal interference. Reversible upon discontinuation. No permanent effect on fertility reported in animal studies. |