Cilazapril
| Evidence Level: L5 | Predicted Indications: 3 |
Table of Contents
- Cilazapril
- Pharmacist Assessment Report
- Cilazapril: From Hypertension to Pulmonary Hypertension Owing to Lung Disease and/or Hypoxia
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Canada Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Cilazapril: From Hypertension to Pulmonary Hypertension Owing to Lung Disease and/or Hypoxia
One-Sentence Summary
Cilazapril is an ACE inhibitor originally used to treat hypertension. The TxGNN model predicts it may be effective for pulmonary hypertension owing to lung disease and/or hypoxia, but the support is limited to 4 preclinical publications (animal and cell studies) and no registered clinical trials.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Hypertension (hypertensive disorder) |
| Predicted New Indication | Pulmonary hypertension owing to lung disease and/or hypoxia |
| TxGNN Prediction Score | 0.9920 |
| Evidence Level | L5 |
| Canada Market Status | Marketed (marketed DINs: 8 of 8) |
| Number of DINs | 8 (marketed: 8) |
| 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, cilazapril is an ACE inhibitor: it blocks angiotensin-converting enzyme, reducing angiotensin II formation and the vasoconstriction it causes. Its efficacy in hypertension is established.
Hypoxic pulmonary hypertension involves pulmonary arterial ACE activity, angiotensin II-mediated vasoconstriction, and remodelling of the pulmonary vessel wall. This gives a plausible biological link to the drug’s original use, since both conditions involve the renin-angiotensin system and vascular tone.
However, all supporting evidence comes from rats or cultured cells. There is no human clinical data, and ACE inhibitors have not shown established benefit in human pulmonary hypertension. In patients with lung disease, hypotension and worsened gas exchange (from loss of hypoxic vasoconstriction) are potential concerns.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 1708054 | 1991 | Preclinical (rat) | J Cardiovasc Pharmacol | Cilazapril, a long-acting ACE inhibitor, was tested for preventing thickening of pulmonary artery walls in rats exposed to chronic hypoxia for 4 weeks |
| 7712584 | 1994 | Preclinical (rat) | Zhonghua Jie He He Hu Xi Za Zhi | Cilazapril protected against increased mean pulmonary arterial pressure and decreased PaO2 in a chronic hypoxic pulmonary hypertension model |
| 10072805 | 1997 | Preclinical (animal mechanistic) | Zhonghua Jie He He Hu Xi Za Zhi | Studied the role of local pulmonary arterial renin-angiotensin system in hypoxic pulmonary hypertension |
| 1378120 | 1992 | In vitro | J Cardiovasc Pharmacol | Cilazapril and captopril accelerated recovery from hypoxia in cultured myocardial cell aggregates |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02283794 | MYLAN-CILAZAPRIL | Not specified | Not specified |
| 01911481 | INHIBACE | Not specified | Not specified |
| 02291142 | APO-CILAZAPRIL | Not specified | Not specified |
| 02283786 | MYLAN-CILAZAPRIL | Not specified | Not specified |
| 02283778 | MYLAN-CILAZAPRIL | Not specified | Not specified |
Eight valid authorizations are on record in total; the five above are shown. The others include APO-CILAZAPRIL (02291150), INHIBACE PLUS (02181479) and APO-CILAZAPRIL/HCTZ (02284987).
Safety Considerations
- Drug Interactions: The only interaction record is the pharmacological target relationship, which confirms cilazapril acts on angiotensin-converting enzyme (ACE). No drug-drug interaction details with severity levels are available.
- Indication-specific concerns: In patients with lung disease, ACE inhibition may cause hypotension and worsen gas exchange by removing hypoxic pulmonary vasoconstriction.
For full warnings and contraindications, please refer to the package insert.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is high, but the evidence is limited to four animal or in vitro studies from the 1990s, with no human data and no registered trials. ACE inhibitors have not shown established benefit in human pulmonary hypertension, and there are physiological safety concerns in patients with lung disease.
To proceed, the following is needed:
- Human clinical data (at least a well-designed Phase 2 study in hypoxic pulmonary hypertension)
- Detailed mechanism of action data
- Health Canada package insert warnings and contraindications, reviewed for the lung disease population
- Safety plan covering blood pressure, gas exchange, renal function and potassium monitoring
Other predicted indications (for reference):
- Pulmonary hypertension with unclear multifactorial mechanism (score 0.9920): L5, no trials or literature; Hold.
- Malignant renovascular hypertension (score 0.9912): L5, mechanistically plausible but largely overlaps the existing hypertension indication; carries a risk of acute renal failure in bilateral renal artery stenosis or solitary kidney; Hold.
- Malignant hypertensive renal disease (score 0.9912): L5, prediction only, an extension of the existing indication; would need renal function and potassium monitoring; Hold.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.