Ranolazine
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Ranolazine: From Chronic Angina to Nephrogenic Syndrome of Inappropriate Antidiuresis
One-Sentence Summary
Ranolazine is an extended-release oral drug marketed in Singapore, and it is known as a second-line treatment for chronic angina. The TxGNN model predicts it may be effective for nephrogenic syndrome of inappropriate antidiuresis, but this is a graph-based prediction only. There are currently 0 clinical trials and 0 publications supporting this specific direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the Singapore licence records compiled for this report (the literature describes use in chronic angina) |
| Predicted New Indication | Nephrogenic syndrome of inappropriate antidiuresis |
| TxGNN Prediction Score | 99.65% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 3 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Ranolazine is generally known to inhibit the late sodium current and partially inhibit fatty acid oxidation, and its efficacy in chronic angina is established.
Nephrogenic syndrome of inappropriate antidiuresis is caused by gain-of-function changes in the vasopressin V2 receptor pathway. Ranolazine's known actions have no evident connection to this pathway. The high score (0.996) most likely reflects relationships in the knowledge graph rather than a pharmacological rationale, so the prediction should be treated as a hypothesis only.
For context, other top-ranked predictions are also unsupported by trials. The only ones with any related literature are the headache disorder prediction (rank 9; one 2016 case report on migraine in a patient with microvascular angina and atrial fibrillation) and a Cochrane review on myotonia, which concerns sodium channel pharmacology rather than headache.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available for nephrogenic syndrome of inappropriate antidiuresis.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN14861P | Ranexa Prolonged-Release Tablet 375 mg | Tablet, film coated, extended release | Not stated in the licence record |
| SIN14862P | Ranexa Prolonged-Release Tablet 500 mg | Tablet, film coated, extended release | Not stated in the licence record |
| SIN14863P | Ranexa Prolonged-Release Tablet 750 mg | Tablet, film coated, extended release | Not stated in the licence record |
All three licences are valid single-ingredient products from Menarini-Von Heyden GmbH, administered orally.
Safety Considerations
- Disease contraindications from the knowledge graph (derived from the TxGNN knowledge graph, not from label text): long QT syndrome, familial long QT syndrome, torsades de pointes, kidney disease, pyoureter, cirrhosis of liver.
- Drug Interactions: 100 interactions were identified. Those rated Major include:
- Aprepitant
- Dexamethasone
- Clarithromycin
- Dolasetron
- Eliglustat
Moderate interactions include famotidine, metformin, loperamide, budesonide, canagliflozin, dapagliflozin and empagliflozin, among others. Minor interactions include bupropion, lorcaserin and cimetidine.
Please refer to the package insert for warnings and contraindications from the label.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests only on a knowledge-graph score. No clinical trials or publications support it, and the known pharmacology of ranolazine has no clear link to the disease mechanism. The knowledge-graph contraindications (QT prolongation, kidney disease and liver cirrhosis) add further caution.
To proceed, the following is needed:
- Mechanism of action data to assess any plausible biological link
- Package insert warnings and contraindications from the Singapore regulator, plus the approved indication text
- Preclinical or mechanistic studies testing ranolazine in V2 receptor gain-of-function models
- A safety review of QT risk and renal and hepatic impairment in the target population
- A review of the higher-ranked alternatives, such as headache disorder, where limited indirect literature exists
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.