Sumatriptan isindicated for the acute treatment of migraine with or without aura in adults; or the acute treatment of cluster headache in adults.[1]
Sumatriptan is effective for ending or relieving the intensity ofmigraine andcluster headaches.[14] Injected sumatriptan is more effective than other formulations.[15]
Oral sumatriptan can be used also in the treatment of post-dural puncture headache.[16]
The most common side effects[1] reported by at least 2% of patients in controlled trials of sumatriptan (25-, 50-, and 100-mg tablets) for migraine are atypical sensations (paresthesia and warm/cold sensations) reported by 4% in the placebo group and 5–6% in the sumatriptan groups, pain and other pressure sensations (includingchest pain) reported by 4% in the placebo group and 6–8% in the sumatriptan groups, neurological events (vertigo) reported by less than 1% in the placebo group and less than 1% to 2% in the sumatriptan groups.Malaise/fatigue occurred in less than 1% of the placebo group and 2–3% of the sumatriptan groups.Sleep disturbance occurred in less than 1% in the placebo group to 2% in the sumatriptan group.
Sumatriptan has a lowabuse potential;[19] however overuse is associated withmedication overuse headache.[20] Moreover, prolonged sumatriptan use is associated with pronociceptive effects, resulting inallodynia. This effect's association with medication overuse headache, however, is controversial, due to the fact that animal-model studies are not consistent with typical presentation of this disorder.[21]
Overdose of sumatriptan can causesulfhemoglobinemia, a rare condition in which the blood changes from red to green, due to the integration ofsulfur into thehemoglobin molecule. If sumatriptan is discontinued, the condition reverses within a few weeks.[22]
Sumatriptan is structurally similar to theneurotransmitterserotonin (5-HT) and acts as anagonist of the serotonin5-HT1B,5-HT1D, and5-HT1F receptors.[6] Sumatriptan's primary therapeutic effect is related in its inhibition of the release ofcalcitonin gene-related peptide (CGRP), likely through its 5-HT1D/1B receptor agonist action.[45] This has been substantiated by the efficacy of more recently developed CGRP targeting drugs and antibodies developed for the preventive treatment of migraine.[46] How agonism of the 5-HT1D/1B receptors inhibits CGRP release is not fully understood. CGRP is believed to cause sensitization of trigeminalnociceptive neurons, contributing to the pain experienced in migraine.[47]
Sumatriptan is also shown to decrease the activity of thetrigeminal nerve, which presumably accounts for sumatriptan's efficacy in treating cluster headaches. The injectable form of the drug has been shown to abort a cluster headache within 30 minutes in 77% of cases.[48]
Sumatriptan is administered in several forms: tablets,subcutaneous injection, and nasal spray. Oral administration (assuccinate salt) has lowbioavailability, partly due topresystemic metabolism—some of it gets broken down in the stomach and bloodstream before it reaches the target arteries. There is no simple, direct relationship between sumatriptan concentration (pharmacokinetics) per se in the blood and its anti-migraine effect (pharmacodynamics). This paradox has, to some extent, been resolved by comparing the rates of absorption of the various sumatriptan formulations, rather than the absolute amounts of drug that they deliver.[49][50]
A 2010literature review concluded that sumatriptan can enter thebrain to some minor extent in both animals and humans but that this minor penetration is nonetheless sufficient to causepharmacological effects.[51] Subsequent research has found sumatriptan given during migraine attacks decreases brainserotonin5-HT1B receptorbinding in humans, with a correspondingreceptor occupancy of 16%.[52][53] However, this apparent occupancy could alternatively be due to increased serotonin release during migraine attacks.[52] In contrast toreceptor antagonists, it is notable thatagonists like sumatriptan require only a low fractional receptor occupancy to produce central effects.[51] It is notable in this regard that the possible occupancy with sumatriptan was comparable to that with centrally actingopioids.[53] Besides the clinical findings, further animal studies have found that sumatriptan rapidly enters the brain in spite of its poorlipophilicity and was able to do so more quickly than thebenzodiazepineoxazepam.[53][54]
In 1991, Glaxo received approval for sumatriptan, which was the first availabletriptan.[citation needed]
In July 2009, the USFood and Drug Administration (FDA) approved a single-usejet injector formulation of sumatriptan. The device delivers a subcutaneous injection of sumatriptan, without the use of a needle.Autoinjectors with needles have been previously available in Europe and North America.[58]
Phase III studies with aniontophoretictransdermal patch (Zelrix/Zecuity) started in July 2008.[59] This patch uses lowvoltage controlled by a pre-programmedmicrochip to deliver a single dose of sumatriptan through the skin within 30 minutes.[60][61] Zecuity was approved by the FDA in January 2013.[62] Sales of Zecuity have been stopped following reports of skin burns and irritation.[63]
In the United States, it is available only by medical prescription. It is available over the counter in many states in Australia. The product requires labelling by a pharmacist and is only available in packs of two without a medical prescription.[64] However, it can be bought over the counter in the UK[65] and Sweden.[66]
In Russia, versions of sumatriptan which are not registered in the State Register of Medicines may be regarded as narcotic drugs (derivatives ofdimethyltryptamine).[67]
Glaxo patents for sumatriptan expired in February 2009. At that time, Imitrex sold for about $25 a pill.[68]Par Pharmaceutical then introduced generic versions of sumatriptan injection (sumatriptan succinate injection) 4- and 6-mg starter kits and 4- and 6-mg filled syringe cartridges, and 6-mg vials soon after.[69]
Mylan Laboratories Inc.,Sun Pharma, Sandoz (a subsidiary ofNovartis),Dr. Reddy's Laboratories, and other companies have been producing generic versions of sumatriptan tablets in 25-, 50-, and 100-mg doses. Generic forms of the drug are available in US and European markets after Glaxo's patent protections expired in the respective countries. A nasal spray form of sumatriptan known as AVP-825 has been developed by Avanir and is generically available in some countries.[70]
According to theAmerican Headache Society, "Patients frequently state that they have difficulty accessing triptans prescribed to them."[71] In the US, triptans cost from $12 to $120 each, and more than 80% of US health insurance plans place a limit on the amount of pills available to a patient per month, which has been called "arbitrary and unfair."[72]
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^Nelson DL, Phebus LA, Johnson KW, Wainscott DB, Cohen ML, Calligaro DO, et al. (October 2010). "Preclinical pharmacological profile of the selective 5-HT1F receptor agonist lasmiditan".Cephalalgia.30 (10):1159–1169.doi:10.1177/0333102410370873.PMID20855361.
^Rubio-Beltrán E, Labastida-Ramírez A, Haanes KA, van den Bogaerdt A, Bogers AJ, Zanelli E, et al. (December 2019)."Characterization of binding, functional activity, and contractile responses of the selective 5-HT1F receptor agonist lasmiditan".British Journal of Pharmacology.176 (24):4681–4695.doi:10.1111/bph.14832.PMC6965684.PMID31418454.TABLE 1 Summary of pIC50 (negative logarithm of the molar concentration of these compounds at which 50% of the radioligand is displaced) and pKi (negative logarithm of the molar concentration of the Ki ) values of individual antimigraine drugs at 5‐HT receptors [...] TABLE 2 Summary of pEC50 values of cAMP (5‐HT1A/B/E/F and 5‐HT7), GTPγS (5‐HT1A/B/D/E/F), and IP (5‐HT2) assays of individual antimigraine drugs at 5‐HT receptors [...]
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^Clinical trial numberNCT00724815 for "The Efficacy and Tolerability of NP101 Patch in the Treatment of Acute Migraine (NP101-007)" atClinicalTrials.gov
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