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
- Australia Market Information
- Safety Considerations
- Conclusion and Next Steps
- Other Predicted Indications Worth Noting
- Disclaimer
Felodipine: From Hypertension to Pulmonary Hypertension Owing to Lung Disease and/or Hypoxia
One-Sentence Summary
Felodipine is a dihydropyridine calcium channel blocker, 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 supporting evidence is weak: there are no registered clinical trials and only 9 publications, all preclinical or ex vivo studies that do not address pulmonary hypertension directly.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Hypertension (hypertensive disorder); no approved indication text is available for the ARTG entry |
| Predicted New Indication | Pulmonary hypertension owing to lung disease and/or hypoxia |
| TxGNN Prediction Score | 0.9991 |
| Evidence Level | L5 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, felodipine is a dihydropyridine L-type calcium channel blocker. Its efficacy in hypertension is established, and mechanistically it may be applicable to pulmonary hypertension through vascular smooth muscle relaxation, which could counter hypoxic pulmonary vasoconstriction.
The link between systemic hypertension and pulmonary hypertension is mainly the shared target of vascular tone. However, the retrieved literature covers hypoxia and anoxia models in rat kidney tubules, human atrial muscle, cerebral arteries and neutrophils. None of it examines the pulmonary circulation. Dihydropyridine calcium channel blockers may also worsen ventilation-perfusion matching and cause hypoxaemia in patients with lung disease. The high TxGNN score is therefore not supported by direct clinical evidence.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
All nine publications retrieved are preclinical, animal or ex vivo studies.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 9431863 | 1997 | Ex vivo (human atrial muscle) | Int J Cardiol | Felodipine pretreatment protected human atrial muscle from hypoxia-reoxygenation dysfunction in a stunning model |
| 8584414 | 1995 | Preclinical (rat renal tubules) | Pflugers Arch | Felodipine protected proximal tubules from hypoxic injury via a calcium-independent mechanism |
| 8394565 | 1993 | Preclinical (cultured cells) | Pflugers Arch | Effect of L-type calcium channel blockers on anoxia-induced rises in intracellular calcium in rabbit proximal tubule cells |
| 8160846 | 1994 | Preclinical (rat aorta) | Am J Physiol | A prior anoxic episode attenuated vasorelaxation to a subsequent anoxic episode |
| 8110031 | 1993 | Animal (behaviour) | Arch Int Pharmacodyn Ther | Effects of nicardipine, felodipine and nifedipine on learning and hypoxia-induced retention deficits in rats |
| 3961832 | 1986 | Animal (cerebral blood flow) | Stroke | Dihydropyridines depressed the rise in cerebral blood flow elicited by anoxia in rats |
| 3343292 | 1988 | Animal (rat cerebral cortex) | J Cereb Blood Flow Metab | Nifedipine and felodipine suppressed hypoxia-evoked adenosine and inosine release |
| 3142891 | 1988 | Preclinical (cerebral arteries) | J Cereb Blood Flow Metab | Reoxygenation and calcium-induced cerebroarterial contractions as affected by vasodilator agents |
| 9864178 | 1999 | Preclinical (neutrophils) | Blood | Nitric oxide augmented free radical generation in rat neutrophils after hypoxia-reoxygenation |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 13377C | Felodil XR 2.5 | Tablet 2.5 mg (extended release) | Not available in the data compiled for this report |
Safety Considerations
Formal warnings and contraindications were not available in the data compiled for this report. Please refer to the TGA-approved Product Information (PI) for full safety information.
- Disease associations flagged as contraindications in the knowledge graph (not label text): kidney disease, liver disease, gallbladder disease, angioedema (including hereditary and acquired forms), neutropenia and agranulocytosis, aortic stenosis, hypotensive disorders, hypertrophic cardiomyopathy, renal artery obstruction, myocardial infarction, coronary artery disease, and atherosclerosis. These should be verified against the PI.
- Drug interactions: 100 interactions were recorded. The only Major interaction among those listed is with dolasetron. Examples of Moderate interactions include clarithromycin, cimetidine, aprepitant, bupropion, morphine, acetylsalicylic acid, corticosteroids (hydrocortisone, dexamethasone, betamethasone, budesonide, triamcinolone), SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin), magnesium sulfate, dronabinol and nabilone.
- Indication-specific concerns: in patients with lung disease, dihydropyridine calcium channel blockers may impair hypoxic vasoconstriction and worsen hypoxaemia, and may cause reflex tachycardia.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests on a high model score without any clinical trials or pulmonary-specific studies. The retrieved literature is entirely preclinical, and there is a plausible safety concern (worsened hypoxaemia) in this population. Calcium channel blockers are appropriate only for a small subset of vasoreactive pulmonary arterial hypertension patients.
To proceed, the following is needed:
- Pulmonary-specific preclinical or haemodynamic data, such as pulmonary vascular resistance studies in hypoxic pulmonary hypertension
- Safety assessment of gas exchange and oxygenation in patients with chronic lung disease
- Mechanism of action data and the TGA Product Information (warnings, contraindications and approved indication text) for the ARTG entry
Other Predicted Indications Worth Noting
Other predictions with some evidence were considered. They may be better research questions than the top-ranked prediction, although none changes the Hold decision for the primary indication.
| Predicted Indication | Evidence Level | Comment |
|---|---|---|
| Prinzmetal angina | L3 | Small clinical studies (for example PMIDs 8013514 and 1746458) showed activity against provoked ischaemia and comparability with nifedipine. Calcium channel blockers are already standard therapy, so the incremental novelty is limited. |
| Cerebrovascular disorder | L1 | The FEVER trial (16269957) showed fewer cardiovascular events including stroke, but the benefit is attributable to blood pressure lowering in hypertension, not a distinct cerebrovascular effect. |
| Chronic pulmonary heart disease | L3 | Small 1980s haemodynamic studies in severe COPD (2838319) showed reduced pulmonary and systemic vascular resistance, with no outcome data. |
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.