Almotriptan, a new anti-migraine agent: a review.

Almotriptan is a new anti-migraine agent with nanomolar affinity for human 5-HT(1B), 5-HT(1D), and 5-HT(1F) receptors, weak affinity for 5-HT(1A) and 5-HT(7) receptors and no significant affinity for more than 20 other pharmacological receptors. Almotriptan was effective in animal models predictive of anti-migraine activity in humans and had a good safety profile in animal studies. From the toxicological point of view, almotriptan has a profile similar to that of other marketed triptans. In animal studies, at levels substantially higher than required for therapeutic activity in humans, almotriptan was devoid of any oncogenic, genotoxic or teratogenic effects. Almotriptan is well absorbed orally; its absolute bioavailability in humans is 70%. Its peak plasma levels are reached at 1 to 3 h after its administration; its elimination half-life is 3 to 4 h. Almotriptan is metabolized by monoamine oxidase-mediated oxidative deamination and cytochrome P450-mediated oxidation as the major metabolic route and by flavin monooxygenase as the minor route. No dose adjustment is required for gender or age, and only in the case of severe renal impairment the dose should not exceed 12.5 mg over a 24-h period. There was no significant interaction between a single dose of almotriptan and propranolol, fluoxetine or verapamil, at multiple doses. The efficacy of almotriptan in the treatment of acute migraine was demonstrated in clinical trials on more than 3000 patients with migraine. At two h after oral administration of almotriptan, 12.5 mg, the percentages of patients showing pain relief and a pain-free score were 64 and 36%, respectively. The effects of almotriptan were significantly better than those of placebo. When almotriptan was administered in the early phase of migraine, the percentage of pain-free patients at 2 h rose to 84%. In a phase III, double-blind and placebo-controlled study, the incidence of adverse events with almotriptan was not statistically different from that of placebo. Based on the available data, it appears that almotriptan is the triptan of choice when good efficacy and high tolerability are desired.

Within-patient early versus delayed treatment of migraine attacks with almotriptan: the sooner the better.

BACKGROUND: Migraine sufferers typically have been instructed to delay triptan therapy until headache intensity is at least moderate. Recent data suggest that earlier use of triptans may be more beneficial. OBJECTIVE: To address the potential "within-patient" benefit of intervention with almotriptan 12.5 mg for migraine headache of mild intensity. METHODS: We performed a post hoc analysis of a subgroup of patients from a large, open-label, long-term clinical trial wherein 762 migraineurs used almotriptan 12.5 mg for headache attacks of any severity. Specifically, we evaluated the efficacy and safety of treatment in those patients who had treated at least 3 "mild" attacks and 3 "moderate/severe" attacks, examining rates of pain-free status, use of rescue medication, early recurrence, and adverse events for the first 3 mild and the first 3 moderate/severe attacks treated. RESULTS: There were 118 migraineurs and 708 attacks available for analysis. At 1 hour following treatment, pain-free status was achieved in 47% of mild attacks versus 14% of moderate/severe attacks (P<.001); incidences at 2 hours were 84% of mild attacks and 53% of moderate/severe attacks (P<.001). The chance of achieving pain-free status at 1 hour in at least 2 of 3 treated attacks was 45% for mild attacks and 9% for moderate/severe attacks; at 2 hours the percentages were 88% for mild attacks and 56% for moderate/severe attacks. Rescue medication was required in 8% of mild attacks and in 13% of moderate/severe attacks (P<.01). The incidence of early recurrence was 28% for mild attacks and 33% for moderate/severe attacks (P<.01). There was no difference in the incidence of adverse events for mild versus moderate/severe attacks (6% versus 7%). CONCLUSION: These results support early intervention with oral triptan therapy. When used for mild intensity head pain, almotriptan 12.5 mg produced a significantly higher incidence of pain-free status at 1 and 2 hours and lower incidences of early headache recurrence or need for rescue medication.