Which has fewer side effects, naproxen (nonsteroidal anti-inflammatory drug) or mefenamic acid (nonsteroidal anti-inflammatory drug)?

Naproxen Has Fewer Side Effects Than Mefenamic Acid

Naproxen generally has fewer side effects than mefenamic acid, particularly regarding gastrointestinal tolerability in long-term use. 1

Comparative Side Effect Profiles

Gastrointestinal Side Effects

• Naproxen has been shown to have better gastrointestinal tolerability compared to many NSAIDs, though it still carries risk of GI adverse events 2
• In clinical studies with patients with rheumatoid arthritis, osteoarthritis, and juvenile arthritis, naproxen demonstrated a lower frequency and severity of gastrointestinal side effects (nausea, dyspepsia, heartburn) compared to other NSAIDs 1
• Mefenamic acid is associated with higher rates of gastrointestinal side effects, including diarrhea and abdominal pain 2, 3
• FDA data indicates that naproxen has been specifically studied for gastric bleeding and erosion, showing statistically significantly less gastric bleeding and erosion than aspirin 1

Cardiovascular Risk

• Both medications carry cardiovascular risks as NSAIDs
• Naproxen may have a slightly more favorable cardiovascular risk profile compared to some other NSAIDs 2
• The American Geriatrics Society recommends avoiding high-risk NSAIDs in elderly patients, with naproxen often preferred over other options for its relatively balanced risk profile 2

Renal Effects

• Both drugs can affect renal function
• Comparative studies have shown that naproxen may cause less significant increases in serum creatinine and urea compared to some other NSAIDs 4

Specific Patient Populations

• In elderly patients, naproxen has been studied specifically for long-term hepatic and renal tolerability, with transient laboratory abnormalities noted but generally acceptable safety 1
• For menorrhagia treatment, a randomized trial showed that mefenamic acid reduced blood loss by 20-39% while naproxen reduced it by only 12%, suggesting that for this specific indication, mefenamic acid may be more effective despite potentially more side effects 5

Dosing Considerations

• Naproxen is typically dosed twice daily (375-500 mg twice daily), which may improve adherence compared to mefenamic acid's more frequent dosing requirements 2, 1
• Mefenamic acid is typically dosed three times daily (500 mg three times daily) 2
• Lower dosing frequency may contribute to better adherence and potentially fewer side effects with naproxen

Special Considerations

• For short-term use (such as fever or acute pain), the side effect profiles may be more comparable 6
• For chronic conditions requiring long-term NSAID therapy, naproxen's better GI tolerability profile makes it preferable 2, 1
• In patients with high GI risk, either medication should be used with gastroprotection (proton pump inhibitor) 2

Clinical Recommendations

• For most patients requiring NSAID therapy, naproxen is preferable due to its better overall side effect profile
• In specific cases where mefenamic acid has demonstrated superior efficacy (such as menorrhagia), the benefit may outweigh the increased side effect risk
• For elderly patients, naproxen at the lowest effective dose with appropriate gastroprotection is generally safer 2
• Patients with a history of GI bleeding should avoid both drugs if possible, but naproxen with PPI protection would be preferable if an NSAID is necessary 2

The evidence clearly demonstrates that naproxen has a more favorable side effect profile, particularly regarding gastrointestinal tolerability, which is the most common adverse effect limiting NSAID use.