Almotriptan: a review of its use in migraine.
Authors: Keam SJ , Goa KL , Figgitt DP 
Published: December 2004

Drugs. 2002;62(2):387‐414

Almotriptan is a selective serotonin 5‐HT(1B/1D) receptor agonist (‘triptan’). Its efficacy and tolerability have been assessed in a number of randomised, controlled trials in over 4800 adults with moderate or severe attacks of migraine. Oral almotriptan has a rapid onset of action (significant headache relief is observed 0.5 hours after administration of a 12.5mg dose) and efficacy is sustained in most patients who respond by 2 hours. The drug is significantly more effective than placebo as measured by a number of parameters including 2‐hour headache response and pain‐free response rates. Other symptoms of migraine, including nausea, photophobia and phonophobia, are also alleviated by almotriptan. The efficacy of oral almotriptan appears to be maintained over repeated doses for multiple attacks of migraine treated over a long period (up to 1 year). High headache response rates were reported over all attacks without tachyphylaxis. For the relief of single attacks of migraine, oral almotriptan 12.5mg had similar efficacy to oral sumatriptan 50mg. Patients given almotriptan report less concern with adverse effects than patients given sumatriptan. The lower incidence of chest pain following treatment with almotriptan than with sumatriptan may lead to a reduction in direct costs, with fewer patients requiring management of chest pain. Almotriptan is well tolerated. Most adverse events were of mild or moderate intensity, transient, and generally resolved without intervention or the need for treatment withdrawal. The most common adverse events associated with oral almotriptan 12.5mg treatment were dizziness, paraesthesia, nausea, fatigue, headache, somnolence, skeletal pain, vomiting and chest symptoms. The incidence of adverse events did not differ from placebo and decreased in the longer term. Almotriptan can be coadministered with drugs that share a common hepatic metabolic path; in addition, dosage reduction is required only in the presence of severe renal or hepatic impairment. CONCLUSIONS: Almotriptan is an effective drug for the acute treatment of moderate or severe attacks of migraine in adults. An oral dose of almotriptan 12.5mg has shown greater efficacy than placebo; current data indicate that efficacy is similar to that of oral sumatriptan 50mg, and is maintained in the long term (<or=1 year). Almotriptan has a good adverse event profile and a generally similar overall tolerability profile to sumatriptan; of note, almotriptan is associated with a significantly lower incidence of chest pain than sumatriptan. However, further clinical experience is required to clearly define the place of almotriptan among the other currently available triptans. Nevertheless, because triptans have an important place in various management regimens, and because the nature of individual patient response to triptans is idiosyncratic, almotriptan is likely to become a useful treatment option in the management of adults with moderate or severe migraine headaches.

Comment: Why does almotriptan buck the trend compared with other triptans and show placebolike tolerability, and yet efficacy and time to onset of effect comparable to sumatriptan? Does this represent truly different pharmacology or are there subtle differences in the trial populations/methodologies used to collect adverse events (AEs) in the almotriptan trial program? One possible reason for diminished AEs in the almotriptan users in this study might be the higher smoking prevalence in southern Europe and hence hepatic enzyme induction resulting in more rapid metabolism of almotriptan. It would be interesting to query the databases on other triptan studies in North America and Europe to check for differences in AE reporting for other triptans vis a vis smoking.

Naratriptan also has very low AEs reported, and this has always been attributed to a low dose, since efficacy was correspondingly lower as well. Was hepatic induction an issue in the naratriptan population as well, or are these two triptans demonstrably better tolerated clinically? DSM and SJT