Felodipine
| Evidence Level: L5 | Predicted Indications: 5 |
Table of Contents
- Felodipine
- Pharmacist Assessment Report
- Felodipine: 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
- India Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Felodipine: From Hypertension to Pulmonary Hypertension Owing to Lung Disease and/or Hypoxia
One-Sentence Summary
Felodipine is a dihydropyridine calcium channel blocker, and hypertension is its original use. The TxGNN model predicts it may be effective for pulmonary hypertension owing to lung disease and/or hypoxia, but there are no clinical trials and only 9 publications, all of them indirect preclinical studies. This is essentially a model prediction with little direct support.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Hypertension (relation recorded in the knowledge graph; no indication text appears in the local licence records) |
| Predicted New Indication | Pulmonary hypertension owing to lung disease and/or hypoxia |
| TxGNN Prediction Score | 0.9991 |
| Evidence Level | L5 |
| India Market Status | Listed in a compiled Indian medicine price dataset (5 of 5) – CDSCO approval status is not included in this data |
| Number of Listed Products | 5 (valid: 5) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Felodipine is, however, a known dihydropyridine L-type calcium channel blocker with vasodilatory activity. Its use in hypertension is recorded in the knowledge graph.
In theory, a vasodilator could counter hypoxic pulmonary vasoconstriction, the key mechanism in pulmonary hypertension due to lung disease. This is the basis of the TxGNN prediction.
The link is weak, though. None of the retrieved publications studied the pulmonary vasculature or pulmonary hypertension. They cover hypoxia or anoxia effects in rat kidney tubules, human atrial muscle, cerebral vessels, and neurons. Calcium channel blockers are also generally not recommended for this type of pulmonary hypertension, because they can inhibit hypoxic vasoconstriction and worsen ventilation-perfusion matching and gas exchange. The evidence level is therefore L5, because no cited study directly addresses this disease.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
All studies below are preclinical and concern hypoxia or anoxia in other tissues. None address pulmonary hypertension directly.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 8584414 | 1995 | Preclinical (rat proximal tubules) | Pflugers Arch | Felodipine protected rat kidney tubules from hypoxic injury through a calcium-independent mechanism |
| 9431863 | 1997 | Preclinical (human atrial muscle, ex vivo) | Int J Cardiol | Felodipine pretreatment protected atrial muscle from hypoxia-reoxygenation dysfunction |
| 8394565 | 1993 | Preclinical (cultured cells) | Pflugers Arch | L-type calcium channel blockers, including felodipine, affected anoxia-induced rises in intracellular calcium in kidney tubule cells |
| 3961832 | 1986 | Preclinical (rat cerebral blood flow) | Stroke | Dihydropyridines, including felodipine, reduced the anoxia-induced increase in cerebral blood flow |
| 3343292 | 1988 | Preclinical (rat cerebral cortex) | J Cereb Blood Flow Metab | Felodipine and nifedipine suppressed hypoxia-evoked adenosine and inosine release |
| 8110031 | 1993 | Preclinical (animal behaviour) | Arch Int Pharmacodyn Ther | Effects of three calcium channel blockers on passive avoidance in normal and hypoxia-exposed rats |
| 8160846 | 1994 | Preclinical (rat aortic rings) | Am J Physiol | A prior anoxia episode attenuated vasorelaxation on a subsequent anoxia episode |
| 3142891 | 1988 | Preclinical (dog cerebral arteries) | J Cereb Blood Flow Metab | Reoxygenation and calcium-induced contractions were modified by vasodilator agents |
| 9864178 | 1999 | Preclinical (rat polymorphonuclear cells) | Blood | Nitric oxide augmented free radical generation after hypoxia-reoxygenation |
India Market Information
All five licences are valid single-ingredient products. The records contain no approved indication text.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 88740 | Felogard 10 Tablet ER (Cipla Ltd) | Strip of 10 extended-release tablets | Not stated in the records |
| 90866 | Felogard 2.5 Tablet ER (Cipla Ltd) | Strip of 10 extended-release tablets | Not stated in the records |
| 87278 | Felogard 5mg Tablet ER (Cipla Ltd) | Strip of 10 extended-release tablets | Not stated in the records |
| 177770 | Plendil 2.5mg Tablet ER (AstraZeneca) | Strip of 10 extended-release tablets | Not stated in the records |
| 177359 | Plendil 10mg Tablet (AstraZeneca) | Strip of 10 tablets | Not stated in the records |
Safety Considerations
- Contraindications recorded in the knowledge graph (not label text): kidney disease, liver disease, gallbladder disease, angioedema (including hereditary and acquired forms), neutropenia, agranulocytosis, aortic stenosis, hypotensive disorder, hypertrophic cardiomyopathy, renal artery obstruction, myocardial infarction, coronary artery disease, and atherosclerosis. These should be checked against the actual package insert.
- Drug Interactions: 246 interactions were recorded. Examples include one Major interaction (dolasetron) and Moderate interactions with several corticosteroids (hydrocortisone, dexamethasone, betamethasone, budesonide, triamcinolone), cimetidine, clarithromycin, aprepitant, bupropion, morphine, aspirin, and the SGLT2 inhibitors canagliflozin, dapagliflozin, and empagliflozin.
Package insert warnings and contraindications were not available. Please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests only on a high model score. There are no clinical trials and no study of felodipine in pulmonary hypertension. The literature is indirect preclinical work, and calcium channel blockers are generally not recommended for pulmonary hypertension due to lung disease because of the risk of worsened gas exchange.
Other predicted indications are no stronger:
- Pulmonary hypertension with unclear multifactorial mechanism, malignant hypertensive renal disease, and Braddock syndrome have no trials or literature (L5).
- Chronic pulmonary heart disease has three older, small, indirect hemodynamic studies, including one in severe COPD (PMID 2838319). None of them shows a clinical outcome benefit, so evidence for this disease also remains at L5 under the rule that requires direct study of the disease itself.
To proceed, the following is needed:
- Retrieve the package insert warnings and contraindications (currently a blocking data gap).
- Obtain mechanism of action data.
- Run preclinical studies in pulmonary vascular models of hypoxic pulmonary hypertension.
- Review the safety of worsened gas exchange and ventilation-perfusion mismatch before any clinical study.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.