Captopril
| Evidence Level: L5 | Predicted Indications: 3 |
Table of Contents
Captopril: From Hypertension to Malignant Hypertensive Renal Disease
One-Sentence Summary
Captopril is an ACE inhibitor originally used for hypertension and diabetic nephropathy. The TxGNN model predicts it may be effective for malignant hypertensive renal disease, but there are no registered clinical trials and only 1 publication (a diagnostic case report), so the evidence is essentially limited to model prediction and mechanistic plausibility.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Hypertension, hypertensive disorder, diabetic nephropathy (the licence records compiled for this report contain no indication text) |
| Predicted New Indication | Malignant hypertensive renal disease |
| TxGNN Prediction Score | 0.9928 |
| Evidence Level | L5 |
| Canada Market Status | Marketed (marketed DINs: 9 of 9) |
| Number of DINs | 9 (marketed: 9) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available in the data compiled for this report. Based on known information, captopril belongs to the ACE inhibitor class. It reduces angiotensin II-mediated vasoconstriction and aldosterone release, and its efficacy in hypertension and diabetic nephropathy is established.
Malignant hypertension with renal involvement is a condition in which activation of the renin-angiotensin-aldosterone system (RAAS) is a key driver. This makes ACE inhibition mechanistically plausible. However, this predicted indication largely overlaps with captopril’s existing hypertension and kidney-related use. It is better viewed as an extension of an existing indication than as a distinct repurposing opportunity.
Other high-scoring predictions follow similar logic:
- Malignant renovascular hypertension (score 0.9928): strongly angiotensin II-dependent, so ACE inhibition is coherent. The supporting literature is mostly old case reports, reviews and diagnostic papers.
- Pulmonary hypertension (two subtypes) (score 0.9915): supported only by the model score and tangential mechanistic data. ACE inhibitors have not shown reliable benefit in pulmonary arterial hypertension.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 28902735 | 2017 | Case report | Clinical Nuclear Medicine | A positive captopril renography was found in a patient without renal artery stenosis but with a large chromophobe renal cell carcinoma. Renin-dependent hypertension resolved after nephrectomy. This is a diagnostic use, not evidence of therapeutic benefit. |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 01942964 | TEVA-CAPTOPRIL | Not specified | Not specified |
| 00893595 | APO-CAPTO TAB 12.5MG | Not specified | Not specified |
| 01942980 | TEVA-CAPTOPRIL | Not specified | Not specified |
| 00893625 | APO-CAPTO TAB 100MG | Not specified | Not specified |
| 00893617 | APO-CAPTO TAB 50MG | Not specified | Not specified |
Nine single-ingredient licences are valid in total. The five above are shown; the others include NOYADA (two licences) and further TEVA-CAPTOPRIL strengths.
Safety Considerations
- Contraindication-related conditions (from the knowledge graph, not label text): kidney disease, liver disease, pancreatitis, gallbladder disease, angioedema (including hereditary and ACE inhibitor-induced forms), systemic lupus erythematosus, diabetes mellitus and diabetic ketoacidosis, neutropenia and agranulocytosis, aortic stenosis and aortic valve disease, hypotensive disorder, hyperparathyroidism, hepatic coma/encephalopathy, connective tissue disease, bone disease, potassium deficiency and hyperuricemia.
- Drug Interactions: The interaction query returned 100 records. Those listed first are mostly Moderate, including:
- Corticosteroids (hydrocortisone, dexamethasone, betamethasone, triamcinolone, budesonide)
- Antidiabetic agents (metformin, alogliptin, canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, exenatide, chlorpropamide, acetohexamide)
- Others (bupropion, morphine, acetylsalicylic acid, dronabinol)
- Minor interactions: aluminum hydroxide and calcium carbonate
- Disease-specific caution: ACE inhibitors can precipitate acute renal failure in bilateral renal artery stenosis or stenosis of a solitary kidney. This is relevant to the renovascular predictions.
Please refer to the package insert for the official warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is high (0.9928) and the mechanism is plausible, but there are no clinical trials and the only publication is a diagnostic case report. The indication also largely overlaps with captopril’s existing hypertension and nephropathy use, so it offers little distinct repurposing value.
To proceed, the following is needed:
- Package insert warnings and contraindications from Health Canada, which is a blocking gap for safety screening
- Detailed mechanism of action data
- Therapeutic clinical evidence (trials or cohort studies) in malignant hypertension with renal involvement
- A clear determination of whether this indication is already covered by existing labeling
- A renal safety plan, including renal artery stenosis screening, renal function and potassium monitoring
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.