Nifedipine
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
Nifedipine: From Hypertension to Migraine with Brainstem Aura
One-Sentence Summary
Nifedipine is a calcium channel blocker, originally used to treat hypertension and Prinzmetal angina. The TxGNN model predicts it may be effective for migraine with brainstem aura, but the evidence is thin: no clinical trials and 2 publications are linked to this exact subtype. The broader migraine indication has 1 registered trial (not efficacy-focused) and about 20 publications, and the available evidence is mixed.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Hypertension, hypertensive disorder, Prinzmetal angina (the registration records for Singapore list no indication text) |
| Predicted New Indication | Migraine with brainstem aura |
| TxGNN Prediction Score | 92.63% |
| Evidence Level | L3 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 11 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available. Based on known information, nifedipine is a dihydropyridine L-type calcium channel blocker. Its efficacy in hypertension and angina is established, and it acts by relaxing vascular smooth muscle.
Calcium channel blockade is plausibly relevant to migraine, through cortical spreading depression and cerebrovascular tone. Migraine prophylaxis with calcium channel blockers has been studied for decades. However, nifedipine has limited CNS selectivity, and the literature gathered for this report is not specific to the brainstem aura subtype. Any support is extrapolated from migraine in general.
The evidence for nifedipine in migraine is not encouraging:
- A double-blind study found nifedipine increased headache intensity when used to treat acute attacks of migraine with aura.
- A crossover placebo-controlled study in classic migraine prophylaxis (24 patients) found no difference in headache frequency, with significantly more side effects on nifedipine (54% vs 8%).
- A small crossover study in India reported a satisfactory response in 71.4% of migraine patients (28 patients), so results are mixed.
Clinical Trial Evidence
Currently no clinical trials are registered for migraine with brainstem aura.
For the broader indication of migraine disorder (rank 2 prediction, score 91.80%), one trial is linked:
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01431326 | N/A | Completed | 3520 | Pharmacokinetics of understudied drugs given to children as standard of care; no migraine efficacy endpoint, so only marginally relevant |
Literature Evidence
Migraine with brainstem aura (2 publications):
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 1423566 | 1992 | RCT | Cephalalgia | Nifedipine increased headache intensity versus vehicle in acute attacks of migraine with aura; not useful as abortive treatment |
| 1353873 | 1992 | Review | Pathologie-biologie | Effectiveness of verapamil, diltiazem and nifedipine for migraine prevention cannot be considered firmly demonstrated |
Broader migraine disorder (selected):
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 42673559 | 2026 | Systematic review / guideline | Neurology | AAN/AHS review of pharmacologic migraine prevention; conclusions on nifedipine not available in the data compiled |
| 40580307 | 2025 | Systematic review | Naunyn-Schmiedeberg's Arch Pharmacol | Efficacy and safety of calcium channel blockers in migraine |
| 2644581 | 1989 | Placebo-controlled crossover | Neurology | No significant difference in headache frequency vs placebo; more side effects with nifedipine |
| 8773038 | 1995 | Randomised double-blind crossover | J Assoc Physicians India | Satisfactory response in 71.4% of migraineurs in a 28-patient study |
| 8349477 | 1993 | Comparative clinical study | Headache | Flunarizine vs nifedipine in migraine prophylaxis |
| 2036669 | 1991 | Clinical study | Cephalalgia | Responder and non-responder rates for metoprolol, propranolol and nifedipine (58 patients) |
| 1970289 | 1990 | Review | Drugs | Beta-blockers and calcium antagonists in migraine prophylaxis |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN07710P | ADALAT LA 30 TABLET 30 mg | Tablet, film coated | Not specified in the data |
| SIN11671P | NIFEDIPINE LA TABLET 30 mg | Tablet, film coated | Not specified in the data |
| SIN08776P | AA PHARMA NIFEDIPINE CAPSULE 10MG | Capsule | Not specified in the data |
| SIN07228P | NIFELAT TABLET 10 mg | Tablet, film coated | Not specified in the data |
| SIN11117P | DEPIN-E RETARD TABLETS 20 mg | Tablet | Not specified in the data |
There are 11 valid single-ingredient registrations in total, all oral (tablet, film-coated tablet and capsule).
Safety Considerations
- Contraindications / risk conditions (from the knowledge graph, not label text): porphyria (including inherited porphyria and porphyrin metabolism disease), kidney disease, liver disease (including cirrhosis), gallbladder disease, hypotensive disorder, acute coronary syndrome, myocardial infarction, coronary thrombosis, hemoglobinopathy, pyloric stenosis, heart failure, intestinal obstruction, pyoureter.
- Drug Interactions: 100 interactions were found. Notable ones include:
- Major: cisapride
- Moderate: clarithromycin, cimetidine, aprepitant, bupropion, acetylsalicylic acid, canagliflozin, corticosteroids (betamethasone, budesonide), and calcium salts (acetate, carbonate, chloride, citrate, gluconate, lactate and others)
- Minor: ranitidine
- Migraine-specific tolerability: nifedipine causes vasodilatory headache, and the literature shows a higher rate of side effects than placebo in migraine prophylaxis.
- Grapefruit juice may increase oral bioavailability through CYP3A4 inhibition.
Please refer to the package insert for full warnings. The label warnings and contraindications have not yet been retrieved.
Conclusion and Next Steps
Decision: Hold
Rationale: The TxGNN score is high, but no trials target migraine with brainstem aura, and the available migraine studies are old, small and inconsistent. Two studies showed no benefit or worsening headache, and nifedipine is not a standard migraine agent. Brainstem aura evidence is extrapolated from general migraine.
To proceed, the following is needed:
- Retrieval of the HSA package insert warnings and contraindications (a blocking gap for safety screening)
- Mechanism of action data from DrugBank
- Review of the 2026 AAN/AHS migraine prevention guideline for its conclusions on nifedipine
- Evidence specific to the brainstem aura subtype, or a well-designed prospective trial
- Comparison against established migraine preventives (beta-blockers, flunarizine, and others)
Other predictions noted: The "common cold" prediction appears to be driven by the term "cold". The supporting literature actually concerns Raynaud's phenomenon, for which calcium channel blockers have Cochrane-level support. Raynaud's phenomenon could be assessed separately as a distinct indication.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.