Is prednisone or methylprednisolone better?

Prednisone and Methylprednisolone Are Clinically Equivalent for Most Indications

For the vast majority of clinical situations, prednisone and methylprednisolone are interchangeable when dosed appropriately, with prednisone being the preferred choice due to lower cost, simpler dosing, and more predictable pharmacokinetics.

Pharmacologic Equivalence and Dosing

The key principle is that 4 mg of methylprednisolone equals 5 mg of prednisone in anti-inflammatory potency 1, 2. Both are intermediate-acting corticosteroids that are approximately 4-5 times more potent than hydrocortisone 3.

Route of Administration Considerations

• Oral prednisone and oral methylprednisolone are therapeutically equivalent when dose-adjusted 1.
• In hospitalized children with acute asthma, oral prednisone (2 mg/kg/dose twice daily) showed no difference in length of stay compared to intravenous methylprednisolone (1 mg/kg/dose four times daily), but oral prednisone resulted in significantly shorter duration of supplemental oxygen requirement (30 vs 52 hours, P=0.04) 4.
• Oral prednisone is approximately 10 times less expensive than intravenous methylprednisolone while providing equivalent clinical outcomes 4.

Pharmacokinetic Advantages of Prednisone

Prednisone has more predictable pharmacokinetics, making it easier to dose accurately:

• Methylprednisolone demonstrates linear pharmacokinetics with no dose or time dependency 5.
• Prednisolone (the active metabolite of prednisone) shows dose-dependent pharmacokinetics due to saturable protein binding, but the unbound clearance and volume of distribution remain consistent 5.
• Methylprednisolone concentrations are directly proportional to dose without requiring plasma protein binding determinations 5.
• Despite prednisolone's complicated protein binding, prednisone remains the standard choice in clinical practice because its pharmacokinetics are well-established and dosing guidelines are more extensively validated 1.

Clinical Guideline Recommendations

Autoimmune Hepatitis

• The American Association for the Study of Liver Diseases recommends prednisone/prednisolone (40 mg daily tapered to 10 mg daily) combined with azathioprine as first-line treatment for patients without cirrhosis or acute severe disease 1.
• For acute severe autoimmune hepatitis, prednisone or prednisolone alone at 0.5-1 mg/kg daily (up to 2 mg/kg in children) is recommended 1.

Graft-Versus-Host Disease

• The NCCN guidelines state that methylprednisolone and prednisone are interchangeable when using dose equivalents 1.
• For grade II acute GVHD: 0.5-1 mg/kg/day of methylprednisolone or prednisone dose equivalent 1.
• For grade III-IV acute GVHD: 1-2 mg/kg/day of methylprednisolone or prednisone dose equivalent 1.
• There is no role for escalation of methylprednisolone above 2 mg/kg/day 1.

Bullous Pemphigoid

• The British Association of Dermatologists recommends prednisone or prednisolone as bioequivalent options 1.
• Dosing: 0.75-1 mg/kg for severe disease, 0.5 mg/kg for mild/localized disease, 0.3 mg/kg for moderate disease 1.
• High-dose intravenous methylprednisolone (1 g daily or 15 mg/kg daily for 3 days) showed rapid response but was associated with high mortality (4 of 8 patients died within 4.5 months) 1.

Ulcerative Colitis

• The Toronto Consensus recommends oral corticosteroids (typically prednisone 40-60 mg/day) as first-line therapy for moderate to severe active disease 1.
• Oral corticosteroids are strongly recommended against for maintenance therapy due to ineffectiveness and significant adverse effects with prolonged use 1.

When Methylprednisolone May Be Preferred

Intravenous methylprednisolone is indicated when:

• Oral administration is not feasible (severe nausea, vomiting, altered mental status, NPO status) 2.
• Rapid onset of action is critical in life-threatening situations 2.
• However, even in these situations, once the patient can tolerate oral intake, transition to oral prednisone is appropriate 4.

Common Pitfalls to Avoid

• Do not use the standard methylprednisolone dose pack for conditions requiring adequate steroid dosing - it provides significantly less than the recommended total dose (e.g., only provides ~150 mg total vs. 540 mg prednisone over 14 days for a 60-kg adult) 6.
• Avoid doses of prednisolone >40 mg daily in elderly patients with bullous pemphigoid - mortality during the first year is significantly higher with high-dose systemic corticosteroids 1.
• Do not escalate methylprednisolone above 2 mg/kg/day - there is no additional benefit and significantly increased toxicity 1.
• Never use oral corticosteroids for maintenance therapy in ulcerative colitis - they are ineffective and associated with increased serious infections (HR 1.57) and mortality (HR 2.14) 1.

Practical Recommendation

Choose prednisone as the default oral corticosteroid for cost-effectiveness, established dosing guidelines, and equivalent efficacy. Reserve methylprednisolone for situations requiring intravenous administration or when institutional protocols specifically mandate its use 4, 3.