Depo-Medrol (Methylprednisolone Injection): Uses, Dosage, and Side Effects

1. DISCLAIMER

IMPORTANT NOTICE: This monograph is intended for healthcare professionals and is provided strictly for educational and scientific purposes. It is based on a critical integration of historical product leaflets, current FDA/EMA-approved prescribing information, and contemporary clinical guidelines available up to late 2025. Some historical indications, routes, or practices described in older sources are now considered obsolete, discouraged, or unsafe.

We do not guarantee the accuracy, completeness, or currency of all information presented. Official and current prescribing information from the manufacturer and relevant regulatory authorities must always be consulted before making clinical decisions. By using this material, the reader assumes full professional responsibility for interpretation and application.

⚠️ Intrathecal and epidural administration of Depo-Medrol® are NOT approved and are associated with serious neurologic risks.

2. SUMMARY

Depo-Medrol® is a depot injectable suspension containing methylprednisolone acetate, a long-acting synthetic glucocorticoid with potent anti-inflammatory and immunosuppressive properties. The acetate ester and low aqueous solubility result in slow absorption and prolonged local or systemic effects lasting from days to weeks, depending on dose and route.

In modern practice, its use is restricted and adjunctive, favored mainly for selected intra-articular, intralesional, soft tissue, or intramuscular indications when oral or topical therapy is not feasible or ineffective. Increasing awareness of safety risks—particularly with repeated injections and non-approved routes—necessitates cautious, guideline-aligned use.

3. BRAND NAME

Depo-Medrol® (methylprednisolone acetate injectable suspension)

4. CATEGORY

• Pharmacological Class: Synthetic glucocorticoid (corticosteroid)
• Therapeutic Class: Anti-inflammatory, immunosuppressant
• ATC Code: H02AB04

5. ACTIVE INGREDIENT

Methylprednisolone Acetate

• 6α-methyl derivative of prednisolone
• Approximately 5× anti-inflammatory potency of hydrocortisone
• Minimal mineralocorticoid activity
• Formulated as a micronized crystalline suspension to achieve a depot effect

Steroid equivalence (approximate): 4 mg methylprednisolone ≈ 5 mg prednisolone ≈ 20 mg hydrocortisone

6. PHARMACEUTICAL FORM & STRENGTH

• Form: Sterile aqueous suspension for injection
• Available strengths: 20 mg/mL, 40 mg/mL, 80 mg/mL (region-dependent)
• Appearance: White to off-white suspension (must be shaken well)
• Excipients (may vary): polyethylene glycol, polysorbate 80, sodium phosphate buffers, sodium chloride, benzyl alcohol (in some multidose vials), water for injection

7. MANUFACTURER & MARKETING AUTHORIZATION

• Original developer: Upjohn
• Current global manufacturer: Pfizer Inc.
• Local Manufacturer (Egypt): Egyptian International Pharmaceutical Industries Co. (EIPICO)

Note: Regionally manufactured or licensed versions may exist and should be confirmed with local regulatory authorities.

8. MECHANISM OF ACTION

Methylprednisolone binds to intracellular glucocorticoid receptors, forming a complex that translocates to the nucleus and modulates gene transcription. This results in:

• Inhibition of phospholipase A₂ → ↓ prostaglandins and leukotrienes
• Suppression of pro-inflammatory cytokines (IL-1, IL-6, TNF-α)
• Reduced leukocyte migration and capillary permeability
• Stabilization of lysosomal membranes

9. THERAPEUTIC SCOPE (NOT AN ANTIMICROBIAL)

Depo-Medrol® has no antimicrobial activity. Its clinical effects are anti-inflammatory and immunosuppressive.

10. PHARMACOKINETICS

• Absorption: Slow after IM or local injection due to low solubility
• Onset: 4–8 hours
• Peak effect: 24–48 hours
• Duration: 1–4 weeks (dose-, site-, and condition-dependent)
• Protein binding: ~75–80%
• Metabolism: Hepatic (CYP3A4)
• Elimination: Renal (metabolites)
• Biological half-life: ~18–36 hours

11. INDICATIONS (MODERN, GUIDELINE-ALIGNED)

Adjunctive short-term therapy only:

Intra-articular / Soft Tissue

• Acute flares of rheumatoid arthritis or osteoarthritis
• Bursitis, tendinitis, tenosynovitis
• Epicondylitis
• Ganglion cysts

Intralesional (Dermatology)

• Keloids and hypertrophic scars
• Alopecia areata
• Discoid lupus erythematosus
• Localized lichen planus, psoriatic plaques

Intramuscular (Systemic effect)

• Severe allergic or inflammatory conditions when oral therapy is not feasible
• Selected asthma or dermatitis exacerbations

Not indicated for chronic maintenance therapy or as monotherapy for degenerative joint disease.

12. ADMINISTRATION & HANDLING

• Ready-to-use suspension; do not dilute or mix
• Shake vigorously before each use
• Strict aseptic technique required
• NOT for IV, intrathecal, or epidural use

13. CONTRAINDICATIONS

• Hypersensitivity to methylprednisolone or excipients
• Systemic fungal infections (unless adequately treated)
• Idiopathic thrombocytopenic purpura (IM route)
• Live vaccines during immunosuppressive dosing
• Intrathecal or epidural administration
• Infected joints or local infection at injection site

14. WARNINGS & PRECAUTIONS

• Increased risk of infection and masking of symptoms
• HPA axis suppression with repeated or high-dose use
• Hyperglycemia, hypertension, fluid retention
• Osteoporosis, avascular necrosis with repeated exposure
• Psychiatric disturbances
• Skin and subcutaneous atrophy at injection sites

Repeated intra-articular injections should be limited (≤3–4 per joint per year).

15. DRUG INTERACTIONS

• CYP3A4 inhibitors: ↑ steroid exposure
• CYP3A4 inducers: ↓ efficacy
• NSAIDs: ↑ GI bleeding risk
• Antidiabetics: ↓ glycemic control
• Diuretics: ↑ hypokalemia
• Vaccines: Reduced response to vaccines

16. ADVERSE EFFECTS

Common: Injection site pain, transient flare, weight gain, mood changes

Serious (dose/duration-related):

• Cushingoid features
• Adrenal suppression or crisis
• Osteoporosis and fractures
• Hyperglycemia, hypertension
• Cataracts, glaucoma
• Severe infections

17. USE IN SPECIAL POPULATIONS

• Pregnancy: Use only if benefit outweighs risk; avoid first trimester when possible
• Lactation: Small amounts excreted in milk; caution advised
• Pediatrics: Risk of growth suppression; use lowest effective dose
• Elderly: Increased susceptibility to metabolic and bone effects
• Renal/Hepatic impairment: Use with caution due to reduced clearance.

18. STORAGE CONDITIONS

• Store at controlled room temperature 20–25°C
• Protect from light and freezing
• Single-use vials: discard after use
• Multidose vials: follow manufacturer guidance

19. FREQUENTLY ASKED QUESTIONS (FAQ)

Q: Can Depo-Medrol be given IV or epidural? A: No. These routes are not approved and carry serious risks.

Q: How long does one injection last? A: Typically 1–4 weeks, depending on dose and site.

Q: Is it the same as Solu-Medrol®? A: No. Solu-Medrol® is a soluble formulation for IV/IM use with a rapid onset and short duration.

20. REFERENCES

1. Pfizer Prescribing Information: Depo-Medrol® (updated 2024–2025)
2. FDA Drug Safety Communications on epidural corticosteroid injections
3. UpToDate / Lexicomp: Methylprednisolone drug monographs
4. WHO Model List of Essential Medicines (2023)