Losartan
| Evidence Level: L4 | Predicted Indications: 8 |
Table of Contents
Losartan: From Hypertension to Malignant Renovascular Hypertension
One-Sentence Summary
Losartan is an angiotensin II receptor blocker originally used to treat hypertension and diabetic nephropathy. The TxGNN model predicts it may be effective for malignant renovascular hypertension, but there are 0 registered clinical trials and only 2 publications (one case report and one preclinical methods review) supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Hypertension, hypertensive disorder, diabetic nephropathy (from the knowledge graph; no approved indication text in the New Zealand licence records) |
| Predicted New Indication | Malignant renovascular hypertension |
| TxGNN Prediction Score | 99.73% |
| Evidence Level | L4 |
| New Zealand Market Status | Cancelled only (no currently valid licences) |
| Number of Authorizations | 4 (all cancelled) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the compiled data. Based on known information, losartan blocks the angiotensin II type 1 (AT1) receptor (gene AGTR1) of the renin-angiotensin system. Its efficacy in hypertension and diabetic nephropathy is established, and it may be mechanistically applicable to renovascular hypertension, which is driven by the same system.
Renovascular hypertension arises when renal artery narrowing activates the renin-angiotensin system, so blocking AT1 is a logical approach. A published case report describes a patient with Takayasu's arteritis, a single kidney and malignant hypertension due to renal artery stenosis. Hypertension there was refractory to conventional treatment, and enalapril plus losartan improved blood pressure without deterioration of renal function.
There is an important caution. In bilateral renal artery stenosis or a solitary kidney, drugs of this class can precipitate acute kidney injury. The knowledge graph also lists renal artery obstruction and impaired renal function as contraindications, so safety in this exact population is a real concern.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 10667645 | 2000 | Case report | Angiology | Patient with Takayasu's arteritis, a single kidney and malignant hypertension from renal artery stenosis; enalapril plus losartan improved blood pressure without worsening renal function |
| 22294399 | 2009 | Preclinical methods review | Current Protocols in Pharmacology | Describes rat models (SHR, DOCA-salt, Goldblatt) for measuring antihypertensive activity; only indirect relevance |
New Zealand Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 2466856 | Losartan Actavis | Tab 12.5 mg | Not recorded (cancelled) |
| 2466864 | Losartan Actavis | Tab 25 mg | Not recorded (cancelled) |
| 2466872 | Losartan Actavis | Tab 50 mg | Not recorded (cancelled) |
| 2466880 | Losartan Actavis | Tab 100 mg | Not recorded (cancelled) |
Safety Considerations
- Contraindications (from the knowledge graph, not label text): pancreatitis, liver disease, gallbladder disease, systemic lupus erythematosus (including paediatric), potassium deficiency, diabetes mellitus, diabetic ketoacidosis, hyperuricaemia, hypotension, hyperparathyroidism, osteitis fibrosa, hepatic coma and encephalopathy, neonatal jaundice, anuria, gout, hypercalcaemia, nephrocalcinosis, phosphorus metabolism disease, renal artery obstruction, impaired renal function. These come from graph edges and may reflect combination products, so they need verification against the actual label.
- Population-specific risk: In bilateral renal artery stenosis or a solitary kidney, ARBs can precipitate acute kidney injury.
- Drug Interactions: No drug-drug interactions were identified. The only record is the pharmacological target, the AT1 receptor.
The package insert warnings could not be retrieved, so please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is high (99.73%), but the supporting evidence is one case report and one animal-model methods paper, with no registered trials. Losartan has no currently valid New Zealand licence, and the target population carries a recognised renal safety risk.
To proceed, the following is needed:
- Mechanism of action data confirmed from DrugBank
- Package insert warnings and contraindications from Medsafe, for safety screening
- Clinical studies in renovascular hypertension patients, with attention to renal function monitoring in renal artery stenosis
- Clarification of the New Zealand regulatory pathway, since all four licences are cancelled
- An assessment of the incremental value over the existing hypertension indication
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.