Mines DI, Novelli L. The risk of upper gastrointestinal tract bleeding associated with mefenamic acid in women of reproductive age. Poster presented at the 2004 20th ICPE International Conference on Pharmacoepidemiology & Therapeutic Risk Management; August 2004. Bordeaux, France. [abstract] Pharmacoepidemiol Drug Saf. 2004 Sep 23; 13(Suppl 1):S54-5. doi: 10.1002/pds.987.


Background: Mefenamic acid is a non-steroidal antiinflammatory drug (NSAID) that is commonly prescribed to treat menorrhagia and dysmenorrhea. As a class, prescription-strength non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of upper gastrointestinal bleeding (UGIB) 3-fold above baseline. However, the risk of UGIB associated with mefenamic acid use is not known. We conducted a study to evaluate the safety of mefenamic acid for a potential over-the-counter (OTC) conversion in the UK.

Objective: To determine the risk of UGIB associated with the proposed OTC-strength use of mefenamic acid (1500 mg/day) in women of reproductive age and to compare it with the risk associated with OTC-strength ibuprofen (1200 mg/ day).

Methods: All women in the General Practice Research Database (GPRD) who received a prescription for mefenamic acid 1500 mg/day or ibuprofen 1200 mg/day between 1988–2002 were eligible for this retrospective cohort study if they were between 11 and 50 years old on the date of the first prescription for either drug (‘index date’). Daily dose was calculated from the pill strength and dosage instructions. To simulate short-term NSAID use, we excluded patients who had received another NSAID prescription in the period 6 months before through 1 month after the index date.We calculated the absolute risk of UGIB in the 14 days following the index date for each treatment group as well as a relative risk (RR) comparing mefenamic acid with ibuprofen. We tested for confounding and effect modification with a stratified Mantel-Haenszel approach.

Results: The study population included 53 067 mefenamic acid users and 157 023 ibuprofen users. Within 14 days of the index date, 3 cases of UGIB occurred in mefenamic acid users (risk per 100 000: 5.7; 95% CI: 1.2, 16.5) and 2 cases occurred in ibuprofen users (risk per 100 000: 1.3; 95% CI: 0.2, 4.6). The relative risk was 4.4 (95% CI: 0.7, 26.6); the risk difference was 4.4 per 100 000 persons (95% CI: 2.3, 11.0). Assuming that the observed risk difference was not due to chance, 22 728 women would need to be treated with mefenamic acid instead of ibuprofen in order to incur 1 additional UGIB within 14 days of prescription.We did not identify any confounding or effect modification. Results did not differ substantially with longer risk windows.

Conclusion: In women of reproductive age, the risk of UGIB associated with OTC-strength mefenamic acid is low and does not differ statistically from the risk associated with ibuprofen. Even if the observed risk difference is real, any excess risk would be quite small.

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