Mefenamic Acid
| Evidence Level: L2 | Predicted Indications: 6 |
Table of Contents
Mefenamic Acid: Headache disorder
One-Sentence Summary
Mefenamic acid is a non-steroidal anti-inflammatory drug (NSAID) that blocks prostaglandin synthesis. The TxGNN model predicts it may be effective for headache disorder, and the literature includes 3 small randomized double-blind trials in migraine (a subtype of headache disorder) and several reviews and guidelines, but no registered clinical trials for the broad category. The evidence level is L2.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Headache disorder |
| TxGNN Prediction Score | 0.9964 |
| Evidence Level | L2 |
| Canada Market Status | Marketed (marketed DINs: 1 of 1) |
| Number of DINs | 1 (marketed: 1) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data are not available in the data compiled for this report. Based on what is known about the drug class, mefenamic acid inhibits cyclooxygenase (COX) and so reduces prostaglandin synthesis. Prostaglandins contribute to vasodilation, sensitization of trigeminovascular pain fibres and neurogenic inflammation, which are processes involved in headache.
Headache disorder is a broad category. The supporting studies are mostly in migraine, with the strongest signal in menstrually related migraine, where perimenstrual prostaglandin surges are a plausible driver. Three double-blind randomized trials support this: one against acetaminophen (1983, 40 patients), one against propranolol and placebo for prophylaxis (1986, 29 patients), and one against placebo in menstrual migraine (2000, 24 patients). These trials are small and old, there is no phase 3 programme, and no headache-specific trials are registered. Long-term use also carries a risk of enteropathy and medication-overuse headache.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 10799353 | 2000 | RCT | European Journal of Medical Research | Double-blind placebo-controlled study of mefenamic acid in acute menstrual migraine (24 patients, 2 cycles) |
| 3524092 | 1986 | RCT | Acta Neurologica Scandinavica | Mefenamic acid and propranolol both reduced attack frequency and total duration vs placebo in prophylaxis (29 patients, 17 completed) |
| 6347393 | 1983 | RCT | Cephalalgia | Double-blind crossover comparison of mefenamic acid 500 mg with paracetamol 500 mg in 40 migraine patients |
| 22529203 | 2012 | Guideline | Neurology | AAN/AHS evidence-based update on NSAIDs and complementary treatments for episodic migraine prevention |
| 18427072 | 2008 | Review | Neurology | Evidence-based review and meta-analysis of acute and short-term preventive treatment of menstrually related migraine |
| 20836574 | 2010 | Review | Drugs | Prevention and treatment of menstrual migraine |
| 1495823 | 1992 | Review | Pathologie-biologie | Review of controlled NSAID studies in acute and prophylactic migraine treatment, including mefenamic acid |
| 8749241 | 1995 | Review | Cephalalgia | Analgesics and NSAIDs in acute migraine attacks, usually combined with an antiemetic |
| 29095288 | 2017 | Case series | Medicine | Severe enteropathy with villous atrophy in prolonged mefenamic acid users (safety signal) |
| 38812640 | 2024 | Preclinical | Turkish Journal of Medical Sciences | Leaky gut and inflammatory biomarkers in a rat model of medication-overuse headache |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02229452 | MEFENAMIC | Not specified | Not specified |
Safety Considerations
- Drug Interactions: 100 interactions were found in the interaction database. Those listed here include moderate-level interactions with acetylsalicylic acid, metformin, chlorpropamide, and the corticosteroids hydrocortisone, dexamethasone, betamethasone, budesonide and triamcinolone. Other moderate interactions include aprepitant, mesalazine, balsalazide, and the potassium citrate and bicarbonate salts. Minor interactions include famotidine, ranitidine, cimetidine and dapagliflozin.
- Literature-based safety signals: prolonged use has been linked to enteropathy with villous atrophy, and analgesic overuse has been linked to chronic renal disease and medication-overuse headache in headache patients.
Please refer to the package insert for full warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Small randomized double-blind trials in migraine support efficacy, which gives an evidence level of L2. However, they are old, small and not specific to the broader headache disorder category, and long-term use carries gastrointestinal, renal and medication-overuse risks.
To proceed, the following is needed:
- The Health Canada package insert, to confirm warnings and contraindications
- Detailed mechanism-of-action data
- Larger, modern controlled trials in a defined headache population (for example menstrually related migraine)
- A plan to limit treatment duration and monitor gastrointestinal and renal safety
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.