What are the differences between methylprednisolone, prednisolone, and dexamethasone in terms of their characteristics and uses?

Key Differences Between Methylprednisolone, Prednisolone, and Dexamethasone

Potency and Equivalency

Dexamethasone is approximately 25 times more potent than hydrocortisone, methylprednisolone is 5 times more potent, and prednisolone is 4 times more potent than hydrocortisone. 1, 2, 3

The equivalent anti-inflammatory doses are:

• Dexamethasone 10 mg = Methylprednisolone 48 mg = Prednisolone 60 mg 1, 2
• This potency difference is critical to avoid underdosing—for example, the commonly prescribed methylprednisolone dose pack (84 mg total over 6 days) provides only the equivalent of 105 mg prednisone, compared to 540 mg prednisone over 14 days using standard dosing 1, 2

Pharmacological Properties

Dexamethasone has superior blood-brain barrier penetration and longer duration of action compared to methylprednisolone and prednisolone, making it the preferred choice for CNS conditions. 2, 4, 5

Key pharmacological distinctions:

• Dexamethasone is a long-acting corticosteroid with minimal sodium-retaining properties and enhanced CNS penetration 5, 3
• Methylprednisolone is an intermediate-acting product with rapid onset when given IV, suitable for acute severe inflammatory conditions and IgE-mediated reactions 4, 6, 3
• Prednisolone is an intermediate-acting product readily absorbed from the GI tract, commonly used for oral systemic therapy 1, 3

Clinical Applications by Condition

CNS and Antiemetic Indications

Dexamethasone is the preferred corticosteroid for conditions requiring CNS penetration, including chemotherapy-induced nausea and CNS malignancies. 2, 4

• The American Society of Clinical Oncology recommends dexamethasone for antiemetic regimens across all emetic risk categories 2
• For immune effector cell-associated neurotoxicity grade 2, dexamethasone 10 mg IV is recommended 2

Acute Inflammatory and Allergic Conditions

Methylprednisolone is the standard corticosteroid for IgE-mediated infusion reactions and acute severe inflammatory conditions requiring rapid high-dose IV therapy. 4

• The European Society for Medical Oncology recommends methylprednisolone 100 mg IV for premedication and management of IgE-mediated reactions 4
• For grade 3 neurotoxicity, methylprednisolone 1 mg/kg IV is recommended over dexamethasone 2

Sudden Sensorineural Hearing Loss

Both dexamethasone and methylprednisolone are considered equivalent in safety and efficacy for sudden hearing loss, though dexamethasone may yield better outcomes for intratympanic administration. 1, 2

• Recommended doses: dexamethasone 10 mg/day or methylprednisolone 48 mg/day for 7-14 days, then taper 1
• Single daily doses are preferred for both medications 1, 2

Pediatric Acute Lymphoblastic Leukemia

Dexamethasone shows improved outcomes during induction in patients younger than 10 years of age but carries higher osteonecrosis risk in patients 10 years or older. 1, 2

• Dexamethasone significantly decreases isolated CNS relapse risk and improves event-free survival compared to prednisone 1
• Age-based selection is critical: use dexamethasone in younger children, consider prednisolone/prednisone in adolescents 1, 2

Autoimmune Conditions (Pemphigus Vulgaris)

Prednisolone at 1-2 mg/kg/day is the standard initial treatment for pemphigus vulgaris, with pulsed IV methylprednisolone (10-20 mg/kg or 250-1000 mg) reserved for recalcitrant cases. 1

• Oral dexamethasone pulses showed no additional benefit and more adverse effects compared to conventional oral prednisolone with azathioprine 1
• Pulsed IV methylprednisolone may achieve more rapid disease control but has not conclusively demonstrated long-term benefits 1

Route of Administration

All three corticosteroids can be administered via multiple routes:

• Oral, intravenous, or intratympanic administration is possible depending on clinical scenario 1, 2, 4
• At biologically equivalent doses, oral formulations are equally effective as intravenous for both dexamethasone and methylprednisolone 2
• IV route is preferred when oral absorption is compromised, rapid onset is needed, or severe malabsorption is present 7

Common Pitfalls and Caveats

Underdosing

The most common error is underdosing due to failure to account for potency differences. 1, 2

• Always calculate equivalent doses: 60 mg prednisolone = 48 mg methylprednisolone = 10 mg dexamethasone 1, 2
• Avoid pre-packaged methylprednisolone dose packs for conditions requiring adequate corticosteroid dosing 1, 2

Age Considerations

In pediatric patients, age significantly impacts corticosteroid selection due to differential toxicity profiles. 1, 2

• Dexamethasone: better outcomes in children <10 years but higher osteonecrosis risk in those ≥10 years 1, 2
• Consider switching to prednisolone in older pediatric patients to reduce osteonecrosis risk 1

Toxicity Profile

Dexamethasone carries higher risks of osteonecrosis and infection compared to prednisolone, though all corticosteroids share common adverse effects. 1

• Most serious side effects occur with chronic use; short 10-14 day courses have acceptable and manageable adverse events 1
• Add proton pump inhibitor for GI prophylaxis when prescribing >30 mg prednisone equivalent/day for >3 weeks 7
• Monitor and treat hyperglycemia, hypernatremia, and hypokalemia with all corticosteroids 7

Clinical Context Matters

For severe COVID-19, recent evidence suggests dexamethasone may be associated with lower mortality compared to methylprednisolone, though earlier studies showed conflicting results. 8, 9

• A 2025 retrospective study showed dexamethasone associated with lower in-hospital mortality (adjusted OR: 0.24) and shorter hospital stay compared to methylprednisolone 8
• However, a 2021 randomized trial showed methylprednisolone 2 mg/kg/day demonstrated better clinical outcomes than dexamethasone 6 mg/day 9
• The conflicting evidence highlights the importance of dose equivalency—the methylprednisolone dose in the positive trial was substantially higher than the dexamethasone equivalent 10, 9