A new member has been born into the triptan family for the treatment of Migraine disease and Cluster Headaches - Frova® (frovatriptan) from the Élan Corporation.
The April, 2002, issue of the journal Headache is dedicated almost entirely to articles on Frova®. This "second generation" triptan is meant to deliver the desirable effects of previous triptans without the negatives:
"...The molecule was selected for development based upon its distinctive pharmacologic characteristics, which suggested that it would have the clinical potential for a long duration of action and a low likelihood of side effects and drug interactions."1
As we've discussed before, triptans are selective 5-HT1 (serotonin) receptor agonists. The targeted cells have multiple 5-HT1 receptors. Being selective receptor agonists means that the triptans work on specific receptors. The difference between the different triptans is the receptors on which they work and to what degree:
"As with other triptans, frovatriptan has a moderate affinity for the 5-HT1A and 5-HT1F receptor subtypes, but in contrast to most other triptans, frovatriptan has a moderate affinity for the 5-HT7 receptor."2
A concern with triptans is that they would work not only on cerebral blood vessels, but also on coronary vessels. Trials indicate that Frova has overcome that concern:
"Studies of frovatriptan in isolated human arteries demonstrated a lower threshold for constriction of cerebral than coronary vasculature and a bell-shaped dose-response curve was apparent in the coronary arteries. In anesthetized dogs, frovatriptan administration produced no measurable effect on cardiac function or on blood pressure. Frovatriptan had no effects on coronary blood flow following transient coronary artery occlusion, whereas sumatriptan (Imitrex/Imigran) produced a prolonged and significant decrease in coronary blood flow."2
The need to eat when taking triptans, adjust dosage in older patients, the use of oral contraceptives, renal impairment, and recurrence of Migraine have been factors in treatment with triptans. The current research on Frova® indicates:
"Frovatriptan can be taken without regard for food intake, and because of the large therapeutic margin and shallow dose-response curve, there is no need for dosage adjustment in the elderly, in women taking a combined oral contraceptive, in patients with mild-to-severe renal impairment, mild-to-moderate hepatic impairment, or according to gender. The long duration of exposure may reduce the likelihood of early migraine recurrence."3
A major concern with any medication is always possible interaction with other medications. Clinical trials of Frova® brought researchers to the conclusion:
"...it is unlikely that frovatriptan will alter the pharmacokinetics of concomitantly administered drugs. Frovatriptan, therefore, appears to have a low risk of interaction with other drugs, and adjustments of dose are unlikely to be required when it is coadministered with other agents."4
Another concern for any patient is possible side effects of medications. As was planned and hoped, trials showed Frova® to be well tolerated:
"Short- and long-term use of frovatriptan 2.5 mg was well tolerated by a wide variety of patients. Frovatriptan treatment produced an adverse events profile similar to that of placebo, and in a direct comparison study was better tolerated than sumatriptan 100 mg."5
Since Imitrex® (sumatriptan), the first triptan, was introduced in
the early 1990's, the triptans have significantly improved Migraine and Cluster
Headache treatment. If Frova® lives up to it's pre-marketing clinical
trial results, it will add an invaluable tool to the arsenal of Migraine and
Cluster abortives.
