Frovatriptan
| Evidence Level: L5 | Predicted Indications: 2 |
Table of Contents
Frovatriptan: Atrophoderma vermiculata
One-Sentence Summary
Frovatriptan is a triptan originally used for the acute treatment of migraine, with or without aura. There are currently no registered clinical trials and 18 publications on frovatriptan in migraine generally, but none specific to the brainstem aura subtype.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Atrophoderma vermiculata |
| TxGNN Prediction Score | 0.9973 |
| Evidence Level | L5 |
| Canada Market Status | Marketed (marketed DINs: 5 of 6; cancelled: 1) |
| Number of DINs | 6 (marketed: 5) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on the published literature, frovatriptan is a second-generation triptan that acts as a 5-HT1B/1D receptor agonist. It is thought to work by constricting cranial blood vessels and inhibiting the release of trigeminal neuropeptides. It has a long elimination half-life (about 26 hours) and a relatively low rate of headache recurrence.
Migraine with brainstem aura is a subtype of migraine with aura, so the pharmacology overlaps with frovatriptan’s approved use. Several studies support frovatriptan in migraine with aura in general, including a pooled analysis and a subgroup analysis against zolmitriptan. However, no data specific to the brainstem aura subtype were found.
There is also a safety caveat. Triptans have historically been used cautiously in brainstem aura (formerly called basilar-type migraine) because of theoretical vasoconstriction concerns. The link described here rests on general knowledge of the drug class, and the safety question needs separate evaluation.
The two other predictions (atrophoderma vermiculata and ulerythema ophryogenesis) have high scores (0.9973 and 0.9945) but no plausible mechanistic link, no clinical trials, and no literature. They are computational predictions only and are not pursued here.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
The publications below concern frovatriptan in migraine or migraine with aura generally, not specifically brainstem aura.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 24363238 | 2014 | RCT | Cephalalgia | Frovatriptan plus dexketoprofen compared with frovatriptan alone for migraine attacks with or without aura |
| 24867846 | 2014 | RCT | Neurol Sci | Early vs. late use of frovatriptan plus dexketoprofen vs. frovatriptan alone in migraine with or without aura |
| 21437714 | 2011 | RCT | J Headache Pain | Double-blind crossover study of patient preference, frovatriptan vs. almotriptan, in 133 migraineurs |
| 25916333 | 2015 | Pooled analysis | J Headache Pain | Meta-analysis comparing frovatriptan with rizatriptan, zolmitriptan and almotriptan in migraine with aura |
| 22644173 | 2012 | Subgroup analysis of RCT | Neurol Sci | Frovatriptan vs. zolmitriptan in 18 patients with migraine with aura |
| 25600718 | 2015 | Guideline | Headache | American Headache Society evidence assessment of acute migraine pharmacotherapies |
| 12028324 | 2002 | Placebo-controlled studies | Headache | Confirmed the clinical efficacy of frovatriptan 2.5 mg |
| 27757013 | 2016 | Review | Drug Des Devel Ther | Review of frovatriptan efficacy, including crossover preference studies against other triptans |
| 22900951 | 2012 | Review | CNS Drugs | Review of frovatriptan pharmacology, efficacy and tolerability |
| 18457529 | 2008 | Review | Expert Rev Neurother | Frovatriptan for acute migraine and prevention of predictable menstrual migraine |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02257084 | FROVA | Not specified | Not specified |
| 02415844 | TEVA-FROVATRIPTAN | Not specified | Not specified |
| 02426471 | APO-FROVATRIPTAN | Not specified | Not specified |
| 02497131 | JAMP FROVATRIPTAN | Not specified | Not specified |
| 02509687 | MINT-FROVATRIPTAN | Not specified | Not specified |
A sixth authorization (DIN 02535475, FROVATRIPTAN) is also valid.
Safety Considerations
- Contraindications flagged in the knowledge graph (not taken from label text):
- Cardiovascular and cerebrovascular: coronary artery disease, myocardial ischemia, Prinzmetal angina, coronary vasospasm, stroke, cerebral infarction, transient ischemic attack, vertebrobasilar insufficiency, sudden cardiac arrest, heart conduction disease, peripheral vascular disease and peripheral arterial disease, intermittent claudication, Raynaud disease, ischemic bowel disease.
- Blood pressure and metabolic: hypertension, diabetes mellitus, diabetic ketoacidosis, obesity.
- Other: serotonin syndrome, familial or sporadic hemiplegic migraine.
- Relevance to the new indication: The vascular and cerebrovascular contraindications, together with vertebrobasilar insufficiency and hemiplegic migraine, are particularly important for brainstem aura.
- Drug interactions: 31 interactions were identified. Major interactions include:
- 5-HT3 antagonists: dolasetron, palonosetron, ondansetron, granisetron.
- Serotonergic or anorectic agents: lorcaserin, fenfluramine, dexfenfluramine, sibutramine.
- Methylene blue.
- Moderate interactions include morphine, codeine, hydrocodone and deferasirox.
Please refer to the package insert for label warnings and contraindications, which were not available in the data compiled for this report.
Conclusion and Next Steps
Decision: Hold
Rationale: Frovatriptan is well established in migraine with or without aura, and the mechanism is plausible for the brainstem aura subtype. However, no trials or literature address brainstem aura specifically, and triptans carry a theoretical vasoconstriction concern in this subtype. The strength of the evidence is L3, and the recommendation is a research question, not a development step.
To proceed, the following is needed:
- Health Canada package insert warnings, contraindications and approved indication text, which are currently missing and block safety screening
- Detailed mechanism of action data from DrugBank
- A focused literature review and safety assessment of triptan use in brainstem aura, including vertebrobasilar and cerebrovascular risk
- Dosage form and route information for the Canadian products
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.