Trimetazidine
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Trimetazidine: From an Unspecified Original Indication to Endolymphatic Hydrops
One-Sentence Summary
Trimetazidine is a metabolic modulator marketed in Singapore under several brand names, but the approved indication text is not recorded in the data compiled for this report. The TxGNN model predicts it may be effective for Endolymphatic Hydrops (the condition underlying Ménière's disease), and 5 publications (including two 1990 double-blind comparisons against betahistine) are linked to this direction, with no registered clinical trials.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available in the registration data |
| Predicted New Indication | Endolymphatic hydrops (top-ranked prediction overall: mitochondrial oxidative phosphorylation disorder due to nuclear DNA anomalies, which has no supporting evidence) |
| TxGNN Prediction Score | 98.57% |
| Evidence Level | L2 (provisional; the older double-blind studies need full-text review) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 6 |
| Recommended Decision | Hold (research question; see Conclusion) |
Note: The rank 1 prediction (mitochondrial OXPHOS disorder, score 98.83%) has only a model score behind it (L5). This report focuses on endolymphatic hydrops, the highest-ranked prediction with actual supporting literature.
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on general pharmacological knowledge, trimetazidine is a partial inhibitor of long-chain 3-ketoacyl-CoA thiolase. It shifts cellular energy metabolism away from fatty acid oxidation toward glucose oxidation, which helps cells maintain energy under ischaemic stress.
It is also thought to improve cochlear and vestibular microcirculation and to protect inner-ear cells from ischaemic and oxidative stress. Endolymphatic hydrops underlies Ménière's disease, which causes recurrent vertigo, tinnitus and hearing loss. This offers a plausible link between trimetazidine's cellular-protective effects and inner-ear disorders.
The supporting studies are old (1990–1999) and their methodological quality, sample sizes and results cannot be verified from the available abstracts. The link should be considered plausible but unconfirmed.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 2240995 | 1990 | RCT (double-blind) | Ann Otolaryngol Chir Cervicofac | Trimetazidine 60 mg/day vs betahistine 36 mg/day for 2 months in 45 patients with Ménière's-type symptoms; results not visible in the abstract provided |
| 2240994 | 1990 | RCT (double-blind) | Ann Otolaryngol Chir Cervicofac | Trimetazidine 60 mg/day vs betahistine 24 mg/day for 3 months in 40 patients with peripheral vertigo (20 with Ménière's disease) |
| 10367069 | 1999 | Clinical trial synopsis | Ann Otolaryngol Chir Cervicofac | Synopsis of clinical trials of trimetazidine (Vastarel 20 mg) in vertigo; no abstract available |
| 19454061 | 2007 | Review | BMJ Clin Evid | General review of Ménière's disease; not specific to trimetazidine |
| 26208913 | 2016 | Basic/mechanistic study | Eur Arch Otorhinolaryngol | Histamine receptors in the human endolymphatic sac (rationale for betahistine); indirect relevance to trimetazidine |
Related literature for another predicted condition (recurrent vertigo): 26563011 (2015, B-ENT) studied trimetazidine, betahistine and ginkgo biloba extract for residual dizziness after successful repositioning manoeuvres for BPPV. This is a related but different condition.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN16614P | Trimezen Modified-Release Tablets 35 mg | Film-coated extended-release tablet | Not recorded |
| SIN12268P | Vastarel MR Tablet 35 mg | Film-coated tablet | Not recorded |
| SIN15092P | Maxcard Modified Release Tablets 35 mg | Film-coated extended-release tablet | Not recorded |
| SIN15877P | Vastarel XR Extended-Release Hard Capsule 80 mg | Extended-release capsule | Not recorded |
| SIN01673P | Vastarel Tablet 20 mg | Film-coated tablet | Not recorded |
A sixth authorization, SIN11607P (Metagard Tablet 20 mg), is also valid. All six are single-ingredient oral products.
Safety Considerations
Please refer to the package insert for safety information. No drug-interaction records were found in the data compiled for this report.
Conclusion and Next Steps
Decision: Hold
Rationale: Endolymphatic hydrops has the best support among the predictions, with two older double-blind comparisons against betahistine. However, their size, endpoints and results cannot be verified, no trials are registered, and the approved indications and safety information in Singapore are missing. The other predictions rest on model scores alone. The hydrops finding is best treated as a research question rather than a basis for clinical use.
To proceed, the following is needed:
- Full-text review of PMIDs 2240995, 2240994 and 10367069 to confirm design, sample size, endpoints and results
- The HSA package insert, to establish the approved indications, warnings and contraindications (this is a blocking gap for safety screening)
- Mechanism of action data from DrugBank
- A search for newer controlled trials of trimetazidine in Ménière's disease or vestibular vertigo
- A comparison with current standard treatment (e.g., betahistine)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.