Mefenamic Acid
| Evidence Level: L2 | Predicted Indications: 6 |
Table of Contents
Mefenamic Acid: Headache disorder
One-Sentence Summary
Mefenamic acid is an oral non-steroidal anti-inflammatory drug (NSAID) that blocks prostaglandin synthesis. The TxGNN model predicts it may be useful for headache disorder. No clinical trials are registered for this indication, but 19 publications were compiled, including several small, older randomised double-blind studies in migraine.
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 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 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. Mefenamic acid is an NSAID that inhibits cyclooxygenase (COX) and so reduces prostaglandin synthesis.
Prostaglandins are implicated in headache and migraine pain. They are particularly implicated in menstrual migraine, where prostaglandin release is thought to be a driver. This gives a plausible mechanistic link between COX inhibition and headache relief.
The published randomised comparisons are small and mostly decades old. They cover acute migraine treatment against paracetamol, migraine prevention against propranolol and placebo, and menstrual migraine against placebo. They support the idea but do not settle it.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 6347393 | 1983 | RCT (double-blind crossover) | Cephalalgia | Mefenamic acid 500 mg compared with paracetamol 500 mg in 40 migraine patients over six attacks, with metoclopramide given in all attacks |
| 3524092 | 1986 | RCT (double-blind crossover) | Acta Neurol Scand | In 17 completers, mefenamic acid and propranolol both significantly reduced attack frequency and total duration versus placebo; no significant effect on average severity or duration |
| 10799353 | 2000 | RCT (double-blind, placebo) | Eur J Med Res | 24 women with menstrual migraine without aura were treated over two cycles, comparing mefenamic acid with placebo |
| 22529203 | 2012 | Guideline | Neurology | AAN/AHS evidence-based update on NSAIDs and other complementary treatments for episodic migraine prevention in adults |
| 18427072 | 2008 | Evidence-based review | Neurology | Systematic review and meta-analysis of therapy trials for acute and short-term preventive treatment of menstrually related migraine |
| 20836574 | 2010 | Review | Drugs | Prevention and treatment of menstrual migraine |
| 8749241 | 1995 | Review | Cephalalgia | Analgesics and NSAIDs for the acute migraine attack, usually with an antiemetic |
| 1495823 | 1992 | Review | Pathol Biol | Review of controlled NSAID studies in migraine attacks and prophylaxis, including mefenamic acid |
| 40265504 | 2025 | Review | Curr Opin Neurol | Update on the clinical course and management of migraine in women |
| 29095288 | 2017 | Case series and review (safety) | Medicine | Severe enteropathy with villous atrophy reported in prolonged mefenamic acid users |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 1824B | FEMIN | Capsule 250 mg (oral) | Not available in the data compiled for this report |
Safety Considerations
- Drug Interactions: The data compiled for this report list 100 recorded interactions. Examples:
- Moderate: corticosteroids (hydrocortisone, dexamethasone, betamethasone, triamcinolone, budesonide), metformin, acetylsalicylic acid, mesalazine, balsalazide, aprepitant, chlorpropamide, potassium citrate and potassium bicarbonate.
- Minor: famotidine, ranitidine, cimetidine and dapagliflozin.
- Literature-based safety signals:
- Severe enteropathy with villous atrophy has been reported with prolonged use.
- Analgesic-associated renal disease was documented in patients with chronic headache, with mefenamic acid among the commonly used agents.
- NSAID overuse is linked to medication-overuse headache, which is relevant to any long-term headache use.
Please refer to the TGA-approved Product Information (PI) for full warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Several randomised double-blind studies in migraine, a major headache disorder, support a benefit. They are small and dated, however, and no registered trials or Phase 3 data exist. Safety concerns with prolonged use (enteropathy, renal effects, medication-overuse headache) call for restricted, short-term use and close monitoring.
To proceed, the following is needed:
- Review of the TGA Product Information for warnings and contraindications
- Confirmation of mechanism-of-action data
- A modern, adequately powered randomised trial in a defined headache population, such as menstrual migraine
- A plan to limit treatment duration and to monitor gastrointestinal, renal and cardiovascular risk and medication-overuse headache
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.