Drug Evaluation


, Volume 43, Issue 5, pp 776-798

First online:


A Review of its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Efficacy in the Acute Treatment of Migraine and Cluster Headache
  • Kerry L. DechantAffiliated withAdis International Limited
  • , Stephen P. ClissoldAffiliated withAdis International Limited

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Sumatriptan is a serotonin1 (5-HT1) receptor agonist, which is effective in the acute treatment of migraine headache. Its antimigraine activity is believed to derive from selective vasoconstriction of cranial blood vessels which are dilated and distended during migraine headache and/or from inhibition of neurogenically mediated inflammation in the dura mater.

In placebo-controlled comparative studies, sumatriptan reduced migraine headache from ‘moderate or severe’ to ‘mild or none’ within 2 hours in 50 to 73% of patients following oral administration of 100 or 200mg, and within 1 hour in 70 to 80% of patients following subcutaneous doses of 6 to 8mg or intranasal doses 20mg into each nostril. In addition, sumatriptan alleviated the accompanying symptoms of nausea, vomiting, and photophobia/phonophobia more effectively than placebo, and permitted higher percentages of patients to resume normal daily activities. Sumatriptan 100mg orally was more effective in the acute treatment of migraine than oral combination therapy consisting of ergotamine 2mg plus caffeine 200mg or aspirin 900mg plus metoclopramide 10mg. Pooled data from nearly 5000 patients treated with either oral or subcutaneous sumatriptan in clinical trials indicate that it is well tolerated.

However, migraine recurrence within 24 or 48 hours of initial symptom resolution developed in approximately 40% of patients treated with sumatriptan, irrespective of route of administration. It is likely that migraine recurrence is related to the short half-life of the drug (approximately 2 hours). Future studies should attempt to ascertain whether additional doses of sumatriptan will help prevent migraine recurrence in patients with attacks of long duration and if so, should determine the optimum interval between dosages.

In conclusion, sumatriptan is an important addition to the range of drugs currently available for acute treatment of migraine. It provides rapid relief from debilitating symptoms in a high percentage of patients, particularly after subcutaneous administration. At this stage in its development a number of questions remain to be answered — most notably whether repeat doses will help prevent recurrent attacks and which patients are most likely to respond to therapy. Nevertheless, sumatriptan presently offers a combination of efficacy and tolerability that is unique in this particular clinical setting.

Pharmacodynamic Properties

The pathophysiology of migraine remains uncertain; however, it is believed that migraine pain arises from excessive dilatation of cerebral blood vessels, particularly those in the dura mater, and/or an accompanying localised sterile inflammatory response mediated by release of vaso-active neuropeptides from sensory fibres innervating these blood vessels. Although evidence to date remains circumstantial, it appears that serotonin is involved in the pathogenesis of migraine. Sumatriptan is a highly selective agonist at a serotoninergic 5-HT1 receptor subtype which mediates constriction of certain cranial blood vessels, and at a prejunctional 5-HT1 receptor subtype which mediates inhibition of neuropeptide release by sensory pain fibres in dura mater. Sumatriptan is virtually devoid of activity at the 5-HT1 receptor mediating cranial vascular smooth muscle relaxation, and at 5-HT2 and 5-HT3 receptors, but has a weak vasoconstrictor effect in the coronary arteries mediated by 5-HT1-like receptors.

Studies in anaesthetised animals have shown that sumatriptan decreases blood flow through carotid arteriovenous anastomoses; however, it is not yet known whether this activity corresponds to the mechanism of action of sumatriptan in humans. In animal species, sumatriptan blocked plasma protein extravasation within the dura mater induced by electrical stimulation of the trigeminal nerve, by inhibiting release of the vasoactive substance, calcitonin gene-related peptide (CGRP). In patients with migraine, elevated CGRP levels were normalised following successful treatment with sumatriptan.

Pharmacokinetic Properties

Maximum plasma concentrations of sumatriptan were achieved at a median of 10 min (range 5 to 20 min) after a single 6mg subcutaneous dose, and at a median of 1.5 hours (range 0.5 to 4.5 hours) after a 100mg oral dose. In healthy volunteers, mean peak plasma concentrations of sumatriptan were 72 μg/L after 6mg subcutaneously, 77 μg/L after 3mg intravenously, and 54 μg/Ltg/L after 100mg orally. The mean bioavailability of sumatriptan was 96% after subcutaneous administration, but only 14% after oral administration, primarily because of extensive presystemic metabolism.

In humans, sumatriptan is 14 to 21% bound to plasma proteins and has a mean apparent volume of distribution of 170L.

Sumatriptan is cleared predominantly by hepatic metabolism, with the major metabolite being the inactive indoleacetic acid analogue. In healthy volunteers, total plasma clearance of sumatriptan following intravenous administration was 72 L/h and renal clearance was 16 L/h. Sumatriptan is excreted predominantly in the urine following subcutaneous administration, but after oral administration, faecal excretion of sumatriptan is increased. Sumatriptan has a mean terminal elimination half-life of approximately 2 hours.

Therapeutic use

Comparative studies have demonstrated that sumatriptan is effective in the acute treatment of migraine with or without aura. A single oral dose of 100 or 200mg produced complete or almost complete relief of headache in 50 to 73% of attacks within 2 hours of treatment. Oral sumatriptan 100mg was significantly more effective in the treatment of migraine than were the oral combination regimens of ergotamine 2mg plus caffeine 200mg, and aspirin 900mg plus metoclopramide 10mg. Subcutaneous sumatriptan 6mg relieved headache in 70 to 77% of patients within 1 hour of treatment, and a 75% response rate at 2 hours was observed in patients treated with intranasal sumatriptan (20mg insufflation into each nostril 15 minutes apart). Compared with placebo, sumatriptan more effectively alleviated the associated symptoms of nausea, vomiting, and photophobia/phonophobia in the majority of patients. However, migraine recurred within 24 to 48 hours of initial resolution in approximately 40% of patients treated with sumatriptan. It is possible that patients with migraine attacks of long duration may benefit from additional doses of sumatriptan, although this awaits confirmation in future studies.

Sumatriptan is also effective in patients with cluster headache. A randomised crossover study reported that subcutaneous sumatriptan 6mg produced significant reduction in headache at 10 and at 15 minutes after administration. At 15 minutes, headache severity was decreased in 74% of attacks treated with sumatriptan compared with 26% of attacks treated with placebo.


Sumatriptan was well tolerated in clinical trials. Adverse events were generally mild and transient and were related to the route of administration. Nausea/vomiting and taste disturbances were the most common adverse events reported by patients after oral administration, although these were partly related to the unpleasant taste of the dispersible tablet used in clinical studies. The dispersible tablet has since been replaced with a film-coated tablet. Brief episodes of mild pain and redness at the site of injection were reported by 40% of patients treated with subcutaneous sumatriptan, and this formulation was associated with higher incidences of tingling, flushing, burning and warm/hot sensations than placebo. Sumatriptan caused feelings of heaviness, and pressure or tightness in the chest and neck, particularly after subcutaneous administration, but the mechanism for these effects is presently unknown. Serious adverse events were rare, although a single case of possible myocardial ischaemia was reported with intravenously administered sumatriptan.

Dosage and Administration

The recommended dosage of subcutaneous sumatriptan in the treatment of migraine is 6mg, administered at the onset of symptoms. If symptoms recur, a repeat 6mg dose may be administered at least 1 hour after the first dose. The maximum recommended dosage of subcutaneous sumatriptan is 12mg during 24 hours. The recommended oral dosage of sumatriptan in the treatment of migraine is 100mg, administered at the onset of symptoms. If symptoms recur, up to 2 additional 100mg doses may be taken during a 24-hour period. The maximum recommended oral dosage is 300mg in 24 hours.