Quinidine
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
Quinidine: From Atrial Fibrillation to Nephrogenic Syndrome of Inappropriate Antidiuresis
One-Sentence Summary
Quinidine was originally used to treat atrial fibrillation and malaria. The TxGNN model predicts it may be effective for Nephrogenic Syndrome of Inappropriate Antidiuresis (NSIAD), but currently there are 0 clinical trials and 0 publications supporting this direction. The prediction rests on the model alone.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Atrial fibrillation; malaria |
| Predicted New Indication | Nephrogenic syndrome of inappropriate antidiuresis |
| TxGNN Prediction Score | 99.27% |
| Evidence Level | L5 |
| US Market Status | Cancelled only (all listed authorizations are cancelled) |
| Number of NDAs | 5 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, quinidine is a class Ia antiarrhythmic (a sodium and potassium channel blocker) and also has antimalarial activity. Its efficacy in atrial fibrillation and malaria is established.
NSIAD is caused by gain-of-function variants in the vasopressin V2 receptor gene (AVPR2) or, in some cases, GNAS. These variants cause the kidney collecting duct to reabsorb water inappropriately even when vasopressin levels are low. A possible link is that quinidine’s ion channel activity or off-target effects influence renal water handling or vasopressin signaling. This is speculative, and the data compiled for this report contain no evidence supporting it. The high score (0.993) reflects a graph-based model prediction only. The model’s rank for this prediction is 16,214.
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 |
|---|---|---|---|
| ANDA089338 | Quinidine Gluconate | Extended-release tablet | Not available (cancelled) |
| ANDA088072 | Quinidine Sulfate | Tablet | Not available (cancelled) |
| ANDA212589 | Quinidine Gluconate | Extended-release tablet | Not available (cancelled) |
| ANDA218426 | Dextromethorphan hydrobromide and quinidine sulfate | Capsule | Not available (cancelled) |
| NDA021879 | Nuedexta | Gelatin-coated capsule | Not available (cancelled) |
All five authorizations are cancelled, and no valid single-ingredient or combination authorizations remain.
Safety Considerations
- Disease associations flagged as contraindications in the knowledge graph (not label text): long QT syndrome (including familial), torsades de pointes, heart failure, atrioventricular block, progressive familial heart block, left bundle branch block, digitalis poisoning, hypotensive disorder, myasthenia gravis (including adult-onset) and other neuromuscular junction disease, kidney disease, liver disease, gallbladder disease, thrombocytopenia, potassium deficiency, psoriasis and parapsoriasis, pulmonary emphysema, and esophageal dyskinesia.
- Drug Interactions: 100 interactions were identified; the 20 retrieved include the following.
- Major: loperamide, clarithromycin, picosulfuric acid, polyethylene glycol (3350 with electrolytes), dolasetron, eliglustat, palonosetron.
- Moderate: famotidine, ranitidine, cimetidine, metformin, aprepitant, acetylsalicylic acid, bisacodyl, glycopyrronium, chlorpropamide, potassium citrate, eluxadoline, glimepiride, trospium.
Package insert warnings and contraindications were not available for this report. Please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is very high, but no clinical trials, literature, or mechanistic data support it (Evidence Level L5). All US authorizations are cancelled. Quinidine also carries significant cardiac and interaction risks, and these matter for a condition like NSIAD, which is a rare disorder.
To proceed, the following is needed:
- Mechanism of action data (MOA) and an evaluation of a plausible link to AVPR2/GNAS signaling or renal water handling
- Preclinical or in vitro evidence showing quinidine’s effect on vasopressin V2 receptor signaling or collecting duct water transport
- FDA package insert warnings and contraindications, for formal safety screening
- A literature and trial search for NSIAD treatments to confirm the absence of supporting evidence
- A risk-benefit assessment of QT prolongation and the major drug interactions in the target population
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.