Mefenamic Acid
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Mefenamic Acid: From Pain and Inflammation (NSAID) to Rheumatoid Arthritis
One-Sentence Summary
Mefenamic acid is a nonsteroidal anti-inflammatory drug (NSAID) that is widely marketed in Singapore, although no approved indication text is available in the data compiled for this report. The TxGNN model predicts it may be effective for rheumatoid arthritis, supported by no registered clinical trials and 20 publications, including several older double-blind controlled trials. The evidence points to symptomatic relief only, not disease modification.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available (no approved indication text in the registration records) |
| Predicted New Indication | Rheumatoid arthritis |
| TxGNN Prediction Score | 99.73% |
| Evidence Level | L2 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 11 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the compiled data. Mefenamic acid belongs to the fenamate class of NSAIDs, which inhibit the cyclo-oxygenase enzymes (COX-1 and COX-2) and thereby reduce prostaglandin synthesis. Prostaglandins mediate pain and inflammation, which are central symptoms of rheumatoid arthritis.
Mefenamic acid is already an established analgesic and anti-inflammatory drug, so this prediction is better viewed as an established use within the NSAID class than as true repurposing. Controlled comparisons from the 1960s to 1970s against ibuprofen, sulindac, flurbiprofen, indomethacin and placebo suggest symptomatic efficacy. These studies show symptomatic benefit, not slowing of joint destruction. The drug should therefore not be seen as a disease-modifying antirheumatic agent.
Other predictions for this drug (see below) are consistent with the same mechanism, including migraine (especially menstrual migraine) and osteoarthritis.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 373989 | 1979 | RCT (double-blind crossover) | Curr Med Res Opin | In 24 patients, mefenamic acid (1500 mg/day), sulindac and flurbiprofen were all significantly better than placebo for pain, joint tenderness and morning stiffness |
| 796645 | 1976 | RCT (vs ibuprofen) | Med J Aust | Mefenamic acid 1500 mg/day compared favourably with ibuprofen 1200 mg/day; side effects mild and mostly gastrointestinal |
| 330287 | 1977 | RCT (vs ibuprofen) | J Int Med Res | In 40 patients, analgesic and anti-inflammatory effects were not significantly different from ibuprofen |
| 326491 | 1977 | Double-blind crossover | Curr Med Res Opin | In 18 patients, mefenamic acid and indomethacin were both significantly better than placebo on most parameters |
| 4294443 | 1967 | Clinical study | Ann Rheum Dis | Early clinical study of mefenamic acid in rheumatoid arthritis |
| 5920657 | 1966 | Comparative study | Br Med J | Mefenamic and flufenamic acid compared with aspirin and phenylbutazone in rheumatoid arthritis |
| 5333309 | 1966 | Review | Br Med J | Overview of mefenamic acid |
| 377958 | 1979 | Review | Am J Hosp Pharm | Review of antirheumatic drug therapy, including mefenamic acid |
| 1455792 | 1992 | Clinical study | Vopr Kurortol Fizioter Lech Fiz Kult | Electrophoresis of mefenamic acid; complete or partial response reported in 75% of 125 patients |
| 5676955 | 1968 | Case report (safety) | Br Med J | Three patients developed autoimmune haemolytic anaemia on mefenamic acid; all recovered after withdrawal |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN07726P | Pontalon Film Coated Tablet 500 mg | Film-coated tablet | Not available |
| SIN05487P | Fenagesic Capsules 250 mg | Capsule | Not available |
| SIN11071P | Melgesic Capsule 250 mg | Capsule | Not available |
| SIN08483P | Pontalon Capsule 250 mg | Capsule | Not available |
| SIN10125P | Mefril-250 Capsule 250 mg | Capsule | Not available |
A total of 11 valid single-ingredient registrations exist. Further products include Beafemic capsules, Fenagesic tablets, Fenagesic-500 tablets, Fenagesic suspension (125 mg/5 ml) and Orcigesic tablets and capsules.
Safety Considerations
- Contraindications (inferred from a drug-disease knowledge graph, not from label text): hypertension, kidney disease, liver disease, gallbladder disease, peptic ulcer disease (including active ulcer), blood coagulation disorders, myocardial infarction and other heart and cardiovascular disease, hemoglobinopathy.
- Safety signals from the literature: autoimmune haemolytic anaemia, enteropathy with villous atrophy and steatorrhoea after prolonged use, nephropathy, gastrointestinal bleeding and ulceration, and acute eosinophilic pneumonia (case reports). Caution is particularly warranted in older patients and with long-term use.
- Drug interactions: 100 interactions were identified. Those listed include:
- Moderate: acetylsalicylic acid, corticosteroids (hydrocortisone, dexamethasone, betamethasone, budesonide, triamcinolone), metformin, chlorpropamide, mesalazine, balsalazide, aprepitant, potassium citrate and bicarbonate, picosulfuric acid, polyethylene glycol with electrolytes.
- Minor: famotidine, ranitidine, cimetidine, dapagliflozin, linaclotide.
Please also refer to the package insert, as label warnings and contraindications were not available in the compiled data.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Several double-blind controlled trials show symptomatic benefit in rheumatoid arthritis comparable to other NSAIDs, and the drug is already marketed in Singapore. However, the trials are old, small, short and symptomatic only, and no trial is registered. The gastrointestinal, renal and haematological safety signals, plus a long list of interacting drugs, require careful risk control.
To proceed, the following is needed:
- Approved indication text and safety warnings from the Singapore package inserts
- Mechanism of action data confirmed from a drug database
- Confirmation of whether rheumatoid arthritis is already covered by existing labels
- Comparison against current standard rheumatoid arthritis therapy and a limit on duration of use
- Monitoring plan for gastrointestinal, renal and haematological adverse effects, especially in older patients and those with the comorbidities listed above
Other Predicted Indications (for reference)
| Predicted Indication | TxGNN Score | Evidence Level | Assessment | |------|------|------|------| | Migraine disorder / headache disorder | 99.23% / 99.64% | L2 | Double-blind trials vs acetaminophen, vs propranolol and placebo, and in menstrual migraine; best suited to short-term perimenstrual use | | Osteoarthritis | 98.73% | L2 | Older double-blind trials vs indomethacin, diclofenac and ibuprofen; a preclinical study showed no joint-protective effect | | Migraine with brainstem aura | 99.21% | L3 | Evidence indirect and extrapolated from general migraine | | Osteoarthritis susceptibility, trigeminal autonomic cephalalgia, rare genetic syndromes (colobomatous microphthalmia-rhizomelic dysplasia, brachydactyly-syndactyly, Hunter-Thompson acromesomelic dysplasia) | 98.8%–99.7% | L5 | No evidence and no plausible mechanism; likely model artifacts. Hold |
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.