Losartan
| Evidence Level: L4 | Predicted Indications: 8 |
Table of Contents
Losartan: From Hypertension to Malignant Hypertensive Renal Disease
One-Sentence Summary
Losartan is a marketed angiotensin II receptor blocker (ARB) that is used as an antihypertensive. The TxGNN model predicts it may be effective for malignant hypertensive renal disease. Support is thin: 0 clinical trials and 1 preclinical publication (a rat model).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Hypertension (from general pharmacology; the license records provided contain no indication text) |
| Predicted New Indication | Malignant hypertensive renal disease |
| TxGNN Prediction Score | 99.73% |
| Evidence Level | L4 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 20 licenses (the listed examples are generic ANDAs) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the source record. Based on general pharmacology, losartan blocks the angiotensin II type 1 (AT1) receptor, and its efficacy in hypertension is well established. Mechanistically, it may be applicable to hypertension-driven kidney injury.
Malignant hypertensive renal disease (malignant hypertensive nephrosclerosis) combines severe blood pressure elevation with progressive kidney damage. The one supporting paper is a rat model in which angiotensin II and NF-κB signalling play a pathogenic role in malignant hypertensive nephrosclerosis. That fits the logic of AT1 blockade.
This link is inferred only. No trial in the pack tests losartan in this condition, and the score is a model prediction. Losartan is already marketed with a known safety profile, so a safety-focused first review is feasible.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 30809002 | 2019 | Preclinical animal model | Hypertens Res | In a rat model of malignant hypertensive nephrosclerosis (uninephrectomy plus salt overload), angiotensin II and the NF-κB system have a pathogenic role. The abstract excerpt does not show whether losartan itself was tested. |
US Market Information
The records provided contain no approved-indication text. Examples of the 20 listed licenses:
| Authorization Number | Product Name | Dosage Form | Manufacturer |
|---|---|---|---|
| ANDA203835 | Losartan Potassium | Tablet, film coated | PD-Rx Pharmaceuticals, Inc. |
| ANDA203835 | Losartan Potassium | Tablet, film coated | Proficient Rx LP |
| ANDA078243 | Losartan Potassium | Tablet, film coated | Zydus Lifesciences Limited |
| ANDA078243 | Losartan Potassium | Tablet, film coated | American Health Packaging |
| ANDA078243 | Losartan Potassium | Tablet, film coated | AvPAK |
All listed products are oral tablets.
Safety Considerations
Please refer to the package insert for safety information. The Evidence Pack has no warnings or contraindications, and its drug-interaction query returned no results.
Conclusion and Next Steps
Decision: Hold
Rationale: The only support is a preclinical rat model and a model prediction. There are no clinical trials, and the mechanistic link is inferred rather than tested with losartan. The package-insert safety data are missing, which blocks the safety screening stage.
To proceed, the following is needed:
- Package insert warnings and contraindications from the FDA label (the current blocking gap)
- Mechanism of action data from DrugBank
- Losartan-specific preclinical or clinical evidence in malignant hypertensive nephrosclerosis, such as ARB studies or registry data in severe hypertension with renal injury
- A safety plan for patients with severe renal impairment, covering renal function and potassium monitoring
This report is for research reference only and is not medical advice. Repurposing candidates require clinical validation before use.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.