Benazepril

證據等級: L5

預測適應症: 5 個

Benazepril: From Hypertension to Malignant Renovascular Hypertension

One-Sentence Summary

Benazepril is an angiotensin-converting enzyme (ACE) inhibitor originally used to treat hypertension and chronic kidney disease by blocking the renin-angiotensin system (RAS). The TxGNN model predicts it may have activity against Malignant Renovascular Hypertension, with a prediction score of 99.65%. However, no clinical trials and no targeted publications currently support this repurposing direction, placing this prediction at the lowest evidence level (L5).

Quick Overview

Item	Content
Original Indication	Hypertension (ACE inhibitor class)
Predicted New Indication	Malignant Renovascular Hypertension
TxGNN Prediction Score	99.65%
Evidence Level	L5
India Market Status	✗ Not Marketed
Number of Registrations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available from the Evidence Pack. Based on known pharmacology, Benazepril is a prodrug ACE inhibitor (converted to active benazeprilat) that blocks the conversion of angiotensin I to angiotensin II (Ang II). This reduces systemic vascular resistance, lowers aldosterone secretion, and promotes natriuresis — making it effective in systemic hypertension and renal-protective in chronic kidney disease.

The mechanistic link to malignant renovascular hypertension is biologically plausible but carries significant clinical risk. In renovascular hypertension, the kidneys downstream of a stenotic artery rely heavily on Ang II-mediated efferent arteriolar constriction to maintain glomerular filtration pressure. Blocking ACE in this context can precipitously drop renal perfusion, potentially triggering acute kidney injury — particularly in bilateral renal artery stenosis. The TxGNN model likely detected the shared “hypertension” node in the knowledge graph, but the mechanistic picture is more nuanced than a simple match.

The high TxGNN prediction score (99.65%) reflects a strong computational signal, most likely derived from Benazepril’s established antihypertensive activity and its existing connections to renal vascular biology in the knowledge graph. However, this is a case where the model score and the clinical risk are in tension: the same mechanism that makes ACE inhibitors useful for hypertension is precisely the reason they are considered a relative or absolute contraindication in certain forms of renovascular hypertension.

Clinical Trial Evidence

Currently no related clinical trials registered for Benazepril in malignant renovascular hypertension.

Literature Evidence

Currently no related literature available specifically targeting Benazepril in malignant renovascular hypertension.

India Market Information

Benazepril currently has no registered licenses in India. There are no approved products on record.

Safety Considerations

Drug-Drug Interactions (169 interactions identified):

The following are notable moderate-level interactions identified from DDInter:

Interacting Drug	Interaction Level	Clinical Relevance
Hydrocortisone	Moderate	Corticosteroids may antagonize antihypertensive effect; sodium/water retention risk
Insulin human	Moderate	ACE inhibitors may enhance hypoglycaemic effect; monitor blood glucose
Insulin glargine	Moderate	Same class risk — enhanced hypoglycaemia with insulin analogues
Insulin detemir	Moderate	Enhanced hypoglycaemic risk
Insulin aspart	Moderate	Enhanced hypoglycaemic risk
Insulin degludec	Moderate	Enhanced hypoglycaemic risk
Insulin glulisine	Moderate	Enhanced hypoglycaemic risk
Insulin lispro	Moderate	Enhanced hypoglycaemic risk
Glimepiride	Moderate	Sulfonylurea + ACE inhibitor: potentiated glucose-lowering effect
Glipizide	Moderate	Same risk as glimepiride
Glyburide	Moderate	Same risk as glimepiride
Alogliptin	Moderate	DPP-4 inhibitor: increased risk of angioedema with concurrent ACE inhibitor use
Dapagliflozin	Moderate	SGLT-2 inhibitor: additive blood pressure and renal effects
Exenatide	Moderate	GLP-1 agonist: potential pharmacodynamic interaction
Acetohexamide	Moderate	First-generation sulfonylurea: enhanced hypoglycaemia risk
Chlorpropamide	Moderate	First-generation sulfonylurea: enhanced hypoglycaemia risk
Glycerin	Moderate	Osmotic agent: additive renal and blood pressure effects

Note: 169 total drug interactions were identified. Listing above represents the most clinically significant categories. For a complete interaction profile, please refer to the full DDInter data and the prescribing information.

For key warnings and contraindications, please refer to the package insert, as this data was not available in the current Evidence Pack.

Conclusion and Next Steps

Decision: Hold

Rationale: This prediction is entirely model-generated (L5 evidence) with no supporting clinical trials or targeted literature. More critically, the predicted indication — malignant renovascular hypertension — carries a well-established mechanistic contraindication risk for ACE inhibitors: Ang II blockade in the setting of renal artery stenosis can precipitate acute renal failure, meaning the drug’s known mechanism is a potential hazard rather than a therapeutic advantage for this specific disease subtype.

To proceed, the following is needed:

MOA documentation: Retrieve full mechanism of action from DrugBank (currently marked as Data Gap DG002)
Safety label review: Download and parse the prescribing information to extract key warnings and contraindications (Data Gap DG001 — Blocking severity)
Literature search refinement: Conduct targeted searches combining “benazepril OR ACE inhibitor” with “renovascular hypertension” to assess whether any indirect evidence exists
Clinical risk assessment: Consult a nephrologist or hypertension specialist to formally evaluate whether this indication represents a contraindication rather than a repurposing opportunity
Regulatory review: Assess whether Benazepril is currently contraindicated in bilateral renal artery stenosis per approved labelling in any jurisdiction
India registration strategy: If pursuing this market, a full registration dossier would be required given current zero-licence status in India
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.