Active ingredient: Frovatriptan - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Anti-migraine Agents
• Vasoconstrictor Agents
• Anti-inflammatory Agents

Dosage Forms

• Tablet

Brands / Synonyms

Frova; Miguard

Indications

For the acute treatment of migraine attacks with or without aura in adults.

Pharmacology

Frovatriptan is a second generation triptan 5-HT receptor agonist that binds with high affinity for 5-HT_1B and 5-HT_1D receptors. Frovatriptan has no significant effects on GABA_A mediated channel activity and has no significant affinity for benzodiazepine binding sites. Frovatriptan is believed to act on extracerebral, intracranial arteries and to inhibit excessive dilation of these vessels in migraine. Research has shown that migraine can be caused by the swelling of blood vessels around the brain. Frovatriptan eases the pain associated with migraine by narrowing these blood vessels. Frovatriptan has one of the highest affinities for the 5-HT_1B of the second-generation triptan agonists.

Mechanism of Action

Three distinct pharmacological actions have been implicated in the antimigraine effect of the triptans: (1) stimulation of presynaptic 5-HT_1D receptors, which serves to inhibit both dural vasodilation and inflammation; (2) direct inhibition of trigeminal nuclei cell excitability via 5-HT_1B/1D receptor agonism in the brainstem and (3) vasoconstriction of meningeal, dural, cerebral or pial vessels as a result of vascular 5-HT_1B receptor agonism.

Absorption

Frovatriptan is rapidly absorbed from the duodenum, but has low oral bioavailability.

Toxicity

There is no direct experience of any patient taking an overdose of Frovatriptan. The maximum single dose of frovatriptan given to male and female patients with migraine was 40 mg (16 times the clinical dose) and the maximum single dose given to healthy male subjects was 100 mg (40 times the clinical dose) without significant adverse events.

Biotrnasformation / Drug Metabolism

In vitro, cytochrome P450 1A2 appears to be the principal enzyme involved in the metabolism of frovatriptan to several metabolites including hydroxylated frovatriptan, N-acetyl desmethyl frovatriptan, hydroxylated N-acetyl desmethyl frovatriptan and desmethyl frovatriptan, and several other minor metabolites. Desmethyl frovatriptan has lower affinity for 5-HT_1B/1D receptors compared to the parent compound. The N-acetyl desmethyl metabolite has no significant affinity for 5-HT receptors. The activity of the other metabolites is unknown.

Contraindications

FROVA should not be given to patients with ischemic heart disease (e.g. angina pectoris, history of myocardial infarction, or documented silent ischemia), or to patients who have symptoms or findings consistent with ischemic heart disease, coronary artery vasospasm, including Prinzmetalís variant angina or other significant underlying cardiovascular disease.

FROVA should not be given to patients with cerebrovascular syndromes including (but not limited to) strokes of any type as well as transient ischemic attacks.

FROVA should not be given to patients with peripheral vascular disease including (but is not limited to) ischemic bowel disease.

FROVA should not be given to patients with uncontrolled hypertension . FROVA should not be administered to patients with hemiplegic or basilar migraine.

FROVA should not be used within 24 hours of treatment with another 5-HT₁ agonist, an ergotamine containing or ergot-type medication such as dihydroergotamine (DHE) or methysergide.

FROVA is contraindicated in patients who are hypersensitive to frovatriptan or any of the inactive ingredients in the tablets.

Drug Interactions

Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Due to a theoretical risk of a pharmacodynamic interaction, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and FROVA within 24 hours of each other should be avoided (see CONTRAINDICATIONS).

Concomitant use of other 5-HT_1B/1D agonists within 24 hours of FROVA treatment is not recommended.

Selective serotonin reuptake inhibitors (SSRIs) (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline) have been reported, rarely, to cause weakness, hyperreflexia, and incoordination when coadministered with 5-HT₁ agonists. If concomitant treatment with frovatriptan and an SSRI is clinically warranted, appropriate observation of the patient is advised.

Drug/Laboratory Test Interactions

FROVA is not known to interfere with commonly employed clinical laboratory tests.