Quinapril
| Evidence Level: L5 | Predicted Indications: 5 |
Table of Contents
Quinapril: From Hypertension to Malignant Renovascular Hypertension
One-Sentence Summary
Quinapril is an ACE inhibitor originally used to treat hypertension. The TxGNN model predicts it may be effective for malignant renovascular hypertension, but no clinical trials and no publications currently support this specific prediction, so it rests on the model score alone.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Hypertension (hypertensive disorder) |
| Predicted New Indication | Malignant renovascular hypertension |
| TxGNN Prediction Score | 99.86% |
| Evidence Level | L5 |
| US Market Status | Cancelled only (no currently valid authorizations) |
| Number of NDAs | 5 (all ANDAs, all cancelled) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on known information, quinapril is an angiotensin-converting enzyme (ACE) inhibitor. Its efficacy in hypertension is established, and mechanistically it may be applicable to malignant renovascular hypertension, which is strongly driven by activation of the renin-angiotensin system.
The new indication is closely related to the original one. It is largely an extension of the hypertension indication rather than a distinct repurposing opportunity. There is also a notable caution: ACE inhibitors carry a known risk of acute renal failure in patients with bilateral renal artery stenosis, a common cause of renovascular hypertension, so any use would require careful caution.
Other predicted indications (for reference):
| Predicted Indication | Score | Evidence Level | Note |
|---|---|---|---|
| Malignant hypertensive renal disease | 99.86% | L5 | Plausible link through reduced angiotensin II-mediated vascular injury and glomerular hypertension, but prediction-only |
| Pulmonary hypertension owing to lung disease and/or hypoxia | 99.85% | L4 | Two animal studies, including one showing reduced hypoxic pulmonary hypertension in rats; no human data (Research Question) |
| Pulmonary hypertension with unclear multifactorial mechanism | 99.85% | L5 | Only indirect extrapolation; prediction-only |
| Braddock syndrome | 99.79% | L5 | No clear mechanistic link; may reflect a knowledge-graph artifact |
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available for malignant renovascular hypertension.
For the closest related prediction (pulmonary hypertension owing to lung disease and/or hypoxia), the following preclinical studies were found:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 8873672 | 1996 | Animal study | Circulation | Inhibiting tissue ACE with quinapril reduced hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats |
| 8720418 | 1996 | Animal study | J Cardiovasc Pharmacol | Quinapril preserved left ventricular function and energy metabolism in rats after myocardial infarction (indirect relevance) |
US Market Information
All five US authorizations are cancelled; no valid authorization currently exists.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ANDA078457 (Cipla USA) | Quinapril | Tablet | Not available (cancelled) |
| ANDA077690 (Lupin) | Quinapril | Tablet | Not available (cancelled) |
| ANDA205823 (Solco Healthcare) | Quinapril | Tablet | Not available (cancelled) |
| ANDA202725 (Aurobindo) | Quinapril | Tablet, film coated | Not available (cancelled) |
| ANDA076803 (Chartwell RX) | Quinapril | Tablet, film coated | Not available (cancelled) |
Safety Considerations
Package insert warnings and contraindications were not available in the data compiled for this report; please refer to the package insert for label safety information.
- Disease contraindications from the knowledge graph (not label text): kidney disease, angioedema (including hereditary, acquired, and RAAS-blocker-induced forms), pancreatitis, liver disease, hepatic coma/encephalopathy, gallbladder disease, systemic lupus erythematosus, diabetes mellitus and diabetic ketoacidosis, potassium deficiency, hypotensive disorder, neutropenia/agranulocytosis, hyperparathyroidism, connective tissue disease, gout, anuria, and neonatal jaundice.
- Drug Interactions: 100 interactions were identified. The one rated Major is potassium citrate (risk of hyperkalaemia). Many others are rated Moderate, including metformin, canagliflozin, dapagliflozin, chlorpropamide, acetylsalicylic acid, corticosteroids (hydrocortisone, dexamethasone, betamethasone, budesonide, triamcinolone), tetracyclines (doxycycline, tetracycline), bupropion, morphine, and atropine.
- Indication-specific cautions: risk of acute renal failure in bilateral renal artery stenosis; renal function and potassium monitoring needed; possible systemic hypotension if considered for pulmonary hypertension.
Conclusion and Next Steps
Decision: Hold
Rationale: The 99.86% TxGNN score is not backed by any clinical trial or publication, and the new indication largely overlaps with the original hypertension indication. All US authorizations are cancelled, and the kidney-related safety signals are directly relevant to this setting.
To proceed, the following is needed:
- FDA package insert warnings and contraindications (a blocking gap for safety screening)
- Mechanism of action data (for example from DrugBank)
- Clinical or observational evidence of quinapril in renovascular or malignant hypertension, especially renal safety in renal artery stenosis
- Clarification of why US authorizations were cancelled, and the route and formulation requirements
- If pursuing the pulmonary hypertension direction, human data to supplement the animal-only evidence
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.