Ranolazine
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
- Ranolazine
- Ranolazine: From Antianginal Therapy to Nephrogenic Syndrome of Inappropriate Antidiuresis
Ranolazine: From Antianginal Therapy to Nephrogenic Syndrome of Inappropriate Antidiuresis
One-Sentence Summary
Ranolazine is an antianginal drug that inhibits the late sodium current. The TxGNN model predicts it may be effective for nephrogenic syndrome of inappropriate antidiuresis (NSIAD), but no clinical trials and no publications currently support this direction. The prediction is based on the model alone.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the compiled US license records (the drug is generally known as an antianginal agent) |
| Predicted New Indication | Nephrogenic syndrome of inappropriate antidiuresis |
| TxGNN Prediction Score | 99.65% |
| Evidence Level | L5 |
| US Market Status | Cancelled only (no currently valid licenses) |
| Number of NDAs | 9 (all cancelled; these are ANDA generic applications) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Ranolazine is generally described as an antianginal agent that inhibits the late sodium current (INa) and, to a lesser extent, the rapid delayed rectifier potassium current (IKr).
NSIAD is caused by gain-of-function mutations in the vasopressin V2 receptor (AVPR2). These mutations cause constitutive receptor activation and unsuppressed water reabsorption, which leads to hyponatremia.
No established mechanistic link has been identified between ranolazine and this condition. No published data show that ranolazine acts on V2 receptor signaling, cAMP production, or aquaporin-2 trafficking. The very high TxGNN score is most likely driven by network-level associations in the knowledge graph (for example, ion transport or renal-related pathways). It has not been supported by any clinical or experimental evidence, so it should be read as a hypothesis only.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available.
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication | Status |
|---|---|---|---|---|
| ANDA201046 | Ranolazine (Lupin Pharmaceuticals) | Film-coated extended-release tablet | Not provided | Cancelled |
| ANDA210054 | Ranolazine (Ajanta Pharma USA) | Extended-release tablet | Not provided | Cancelled |
| ANDA210188 | Ranolazine (Vangard Labs) | Extended-release tablet | Not provided | Cancelled |
| ANDA211829 | Ranolazine (ScieGen Pharmaceuticals) | Film-coated extended-release tablet | Not provided | Cancelled |
| ANDA209953 | Ranolazine (Ascend Laboratories) | Film-coated extended-release tablet | Not provided | Cancelled |
Nine licenses are recorded in total, all cancelled. Only the first five are listed here.
Safety Considerations
- Disease contraindications from the knowledge graph (these come from the TxGNN knowledge graph, not from label text): long QT syndrome, familial long QT syndrome, torsades de pointes, kidney disease, pyoureter, and cirrhosis of liver.
- Drug Interactions: 100 interactions were found in total. Examples at the Major level include aprepitant, dexamethasone, clarithromycin, dolasetron, and eliglustat. Moderate-level examples include famotidine, metformin, loperamide, budesonide, canagliflozin, dapagliflozin, and empagliflozin. Minor-level examples include bupropion, lorcaserin, and cimetidine.
Both the QT-related contraindications and the kidney disease contraindication deserve attention for a possible renal indication such as NSIAD. Please refer to the package insert for the full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests only on a model score, with no clinical trials, no literature, and no plausible mechanistic link to the V2 receptor pathway. In addition, the drug has no currently valid US licenses, and its knowledge-graph contraindications include kidney disease and QT-related conditions.
To proceed, the following is needed:
- Mechanism of action data for ranolazine, and any experimental evidence of an effect on V2 receptor signaling, cAMP production, or aquaporin-2 trafficking
- Preclinical studies (for example, cell-based AVPR2 gain-of-function models) to test the hypothesis
- Package insert warnings and contraindications, to allow a proper safety screening, particularly for renal impairment and QT prolongation
- Clarification of the original approved indication and of the regulatory status (all licenses are currently cancelled)
- Assessment of route and formulation compatibility, which is still pending
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.