MIGARD

Indications

• Acute migraine treatment
• Menstrual migraine prophylaxis (not licensed for this indication)

Dosage

Adults: For acute migraine treatment, 2.5 mg to be taken as soon as possible after onset, followed by an additional 2.5 mg after at least 4 hours if required, with a

Mechanism of action

Frovatriptan acts as a selective agonist for serotonin (5-HT) type 1B and 1D receptors. Its mechanism of action involves three key pharmacological actions: (1) stimulation of presynaptic 5-HT1D receptors, which inhibits dural vasodilation and inflammation; (2) direct inhibition of trigeminal nucleus cell excitability through 5-HT1B/1D receptor agonism in the brainstem; and (3) vasoconstriction of meningeal and cerebral vessels due to vascular 5-HT1B receptor agonism. This combination of actions helps in reducing the severity of migraine attacks by constricting dilated blood vessels in the brain.

Pharmacodynamics

Frovatriptan demonstrates high affinity for 5-HT1B and 5-HT1D receptors, making it effective in the management of migraine. It does not significantly affect GABAA-mediated channel activity and shows no affinity for benzodiazepine binding sites. Its ability to inhibit excessive dilation of extracerebral and intracranial arteries is crucial in mitigating migraine symptoms, as the condition often involves the swelling of these vessels.

Pharmacokinetics

Frovatriptan is rapidly absorbed following oral administration, with peak plasma concentrations occurring within 2 to 4 hours. It has a long half-life, which allows for prolonged therapeutic effects. The drug is metabolized primarily in the liver through cytochrome P450 enzymes, and its elimination occurs mainly via renal pathways. The pharmacokinetic profile supports its use in acute migraine treatment, providing sustained relief.

Contra-indications

• Coronary vasospasm
• Ischaemic heart disease
• Peripheral vascular disease
• Previous cerebrovascular accident
• Previous myocardial infarction
• Previous transient ischaemic attack
• Prinzmetal’s angina
• Severe hypertension
• Uncontrolled hypertension

Adverse effects

• Anxiety
• Arrhythmias
• Arthralgia
• Confusion
• Dehydration
• Dizziness
• Fatigue
• Nausea
• Vomiting
• Chest pain
• Myocardial infarction
• Hypersensitivity reactions
• Tremor
• Hyperacusis
• Hiccups
• Episaxis
• Constipation
• Breast tenderness
• Fever

Interactions

• Fluvoxamine (increases concentration of frovatriptan)

Precautions

• Conditions which predispose to coronary artery disease
• Elderly patients

Pregnancy

Frovatriptan should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Data on use in pregnancy are limited.

Breast-feeding

It is not known whether frovatriptan is excreted in human milk. Caution should be exercised when administering to breastfeeding women.

Storage

Store in a well-closed container at room temperature, away from moisture and heat.

Formulations

• Frovatriptan 2.5 mg tablets (Migard, Mylatrip)

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. Frovatriptan is believed to act on extracerebral, intracranial arteries and to inhibit excessive dilation of these vessels in migraine. In anesthetized dogs and cats, intravenous administration of frovatriptan produced selective constriction of the carotid vascular bed and had no effect on blood pressure (both species) or coronary resistance (in dogs). Frovatriptan succinate is a selective agonist of serotonin (5-hydroxytryptamine; 5-HT) type 1B and 1D receptors. Frovatriptan is structurally distinct from, but pharmacologically related to, other selective 5-HT1B/1D receptor agonists (e.g., almotriptan, naratriptan, rizatriptan, sumatriptan). Because the mechanisms involved in the pathogenesis of migraine are not clearly understood, the precise mechanism of action of 5-HT1 receptor agonists in the management of migraine has yet to be established. However, current data suggest that 5-HT1 receptor agonists, including frovatriptan, may ameliorate migraine through selective constriction of certain intracranial blood vessels, inhibition of neuropeptide release, and/or reduced transmission in the trigeminal pain pathway. Frovatriptan has no significant effects on GABAA mediated channel activity and has not 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.

Pharmacodynamics

Frovatriptan is a second generation triptan 5-HT receptor agonist that binds with high affinity for 5-HT_1B and 5-HT_1D receptors. It is structurally distinct from, but pharmacologically related to other selective 5-HT_1B/1D receptor agonists. 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.