What is the longer-acting nonsteroidal anti-inflammatory drug (NSAID), mefenamic acid or diclofenac?

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Last updated: April 17, 2025View editorial policy

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From the Research

Diclofenac is the longer-acting NSAID compared to mefenamic acid, with its therapeutic effects lasting 8-12 hours, making it more convenient for patients requiring pain relief throughout the day. The difference in duration of action between diclofenac and mefenamic acid is due to their pharmacokinetic profiles, with diclofenac having better tissue penetration and accumulation at sites of inflammation 1. Diclofenac's half-life is approximately 1-2 hours, but its effects last longer, allowing for twice-daily dosing regimens, whereas mefenamic acid has a similar half-life but its therapeutic effects generally last only 6 hours, requiring more frequent dosing (usually three to four times daily) 2, 3.

The extended duration of diclofenac is partly due to its ability to persist in synovial fluid, which is the proposed site of action for NSAIDs, allowing for more sustained anti-inflammatory and analgesic effects with less frequent dosing 2. Both medications work by inhibiting cyclooxygenase enzymes to reduce prostaglandin synthesis, but diclofenac's pharmacokinetic profile makes it a more convenient option for patients requiring pain relief throughout the day.

Some key points to consider when choosing between diclofenac and mefenamic acid include:

  • Diclofenac has a faster onset of action and longer duration of action compared to mefenamic acid 3
  • Diclofenac has better tissue penetration and accumulation at sites of inflammation, making it more effective for patients with inflammatory conditions 1
  • Mefenamic acid may have a higher risk of cardiovascular events compared to diclofenac, as shown in a population-based cohort study 4
  • Diclofenac is generally well-tolerated and has a similar safety profile to other NSAIDs, with the most frequent adverse effects being gastrointestinal 2, 3

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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