What are the differences in side effects between prednisolone and methylprednisolone?

Side Effects: Prednisolone vs Methylprednisolone

There is a lack of convincing evidence showing significantly fewer side effects with methylprednisolone compared to prednisolone, with the exception of weight gain, which appears to be reduced with intramuscular methylprednisolone. 1

Key Evidence on Side Effect Differences

Limited Clinical Differentiation

The 2015 EULAR/ACR guidelines explicitly acknowledge that there is insufficient evidence demonstrating a meaningful difference in adverse events between these two corticosteroids 1. The guideline panel reviewed available evidence and found:

• Weight gain was the only side effect shown to be reduced with intramuscular methylprednisolone compared to oral prednisolone 1
• No statistically significant reduction in other glucocorticoid-related adverse events was demonstrated 1
• Long-term safety benefits of methylprednisolone over prednisolone remain unknown 1

Shared Glucocorticoid Side Effect Profile

Both medications carry the same class-wide risks, including 1, 2:

• Metabolic effects: Hyperglycemia, diabetes, weight gain, dyslipidemia 1, 3
• Musculoskeletal effects: Osteoporosis, fractures, myopathy 1
• Cardiovascular effects: Hypertension, cardiovascular disease 1
• Ophthalmologic effects: Cataracts, glaucoma 1
• Gastrointestinal effects: Peptic ulcer disease 1
• Infectious complications: Immunosuppression with increased risk of bacterial, viral, fungal, and opportunistic infections 2
• Psychiatric effects: Mood changes, psychosis, insomnia 2

Pharmacokinetic Considerations

Methylprednisolone demonstrates more predictable pharmacokinetics than prednisolone 4:

• Methylprednisolone shows linear, dose-proportional pharmacokinetics with no time dependency 4
• Prednisolone exhibits dose-dependent and time-dependent pharmacokinetics due to saturable protein binding 4
• Prednisolone's complicated pharmacokinetic properties make dose adjustments less predictable 4

Tissue Penetration Differences

Methylprednisolone achieves higher bronchoalveolar penetration than prednisolone at equivalent plasma concentrations 5:

• At plasma concentrations >800 ng/ml, methylprednisolone bronchoalveolar fluid concentrations increase exponentially 5
• At plasma concentrations around 2000 ng/ml, methylprednisolone bronchoalveolar levels are five times higher than prednisolone 5
• This difference may be clinically relevant for inflammatory lung diseases but does not necessarily translate to fewer systemic side effects 5

Clinical Context for Drug Selection

When to Consider Intramuscular Methylprednisolone

The EULAR/ACR guidelines suggest intramuscular methylprednisolone may be considered in specific scenarios 1:

• Female patients with difficult-to-control comorbidities requiring lower cumulative glucocorticoid exposure 1
• Patients with hypertension, diabetes, osteoporosis, or glaucoma where minimizing weight gain is particularly important 1
• Situations where a lower cumulative dose is desirable 1

Potency Equivalence

Methylprednisolone and prednisolone have similar potency 6:

• Both are intermediate-acting corticosteroids 6
• Both are approximately 4-5 times more potent than hydrocortisone 6
• The standard Medrol dose pack (84 mg methylprednisolone over 6 days) is equivalent to approximately 105 mg of prednisone 3

Important Clinical Caveats

Common Pitfalls to Avoid

• Do not assume methylprednisolone is inherently safer based on route of administration alone—the evidence does not support this 1
• Monitor for the same side effects regardless of which agent is chosen, as the glucocorticoid class effects are shared 2
• Screen for latent infections (tuberculosis, hepatitis B, strongyloides) before initiating either medication 2
• Assess baseline risk factors for glucocorticoid toxicity including diabetes, hypertension, osteoporosis, glaucoma, and peptic ulcer disease 1

Monitoring Recommendations

Both medications require identical monitoring for 2:

• Blood glucose and diabetes development 3, 2
• Blood pressure 1
• Bone density and fracture risk 1
• Ophthalmologic complications 1
• Signs of infection or immunosuppression 2