sumatriptan

Sumatriptan is effective for ending or relieving the intensity of migraine and cluster headaches. It is most effective when taken early after the start of the pain.{{cite journal | vauthors = Derry CJ, Derry S, Moore RA | title = Sumatriptan (all routes of administration) for acute migraine attacks in adults - overview of Cochrane reviews | journal = The Cochrane Database of Systematic Reviews | volume = 2014 | issue = 5 | pages = CD009108 | date = May 2014 | pmid = 24865446 | pmc = 6469574 | doi = 10.1002/14651858.CD009108.pub2 }} Injected sumatriptan is more effective than other formulations.{{cite journal | vauthors = Dahlöf CG | title = Sumatriptan: pharmacological basis and clinical results | journal = Current Medical Research and Opinion | volume = 17 | pages = s35–s45 | year = 2001 | issue = Suppl 1 | pmid = 12463276 | doi = 10.1185/0300799039117010 | url = http://www.medscape.com/viewarticle/429671_4 | access-date = 16 July 2016 | url-status = live | s2cid = 2355125 | df = dmy-all | archive-url = https://web.archive.org/web/20170217060845/http://www.medscape.com/viewarticle/429671_4 | archive-date = 17 February 2017 | url-access = subscription }}

Oral sumatriptan can be used also in the treatment of post-dural puncture headache.{{cite journal| vauthors = Shaat AM, Abdalgaleil MM |date=1 January 2021|title=Is theophylline more effective than sumatriptan in the treatment of post-dural puncture headache? A randomized clinical trial|journal=Egyptian Journal of Anaesthesia|volume=37|issue=1|pages=310–316|doi=10.1080/11101849.2021.1949195|issn=1110-1849|doi-access=free}}

Overdose of sumatriptan can cause sulfhemoglobinemia, a rare condition in which the blood changes from red to green, due to the integration of sulfur into the hemoglobin molecule. If sumatriptan is discontinued, the condition reverses within a few weeks.{{cite news |date=8 June 2007 |title=Patient bleeds dark green blood |url=http://news.bbc.co.uk/2/hi/health/6733203.stm |url-status=live |archive-url=https://web.archive.org/web/20100805042210/http://news.bbc.co.uk/2/hi/health/6733203.stm |archive-date=5 August 2010 |access-date=6 March 2010 |work=BBC News |df=dmy-all}}

Serious cardiac events, including some that have been fatal, have occurred following the use of sumatriptan injection or tablets. Events reported have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation.{{cite journal | vauthors = Kelly KM | title = Cardiac arrest following use of sumatriptan | journal = Neurology | volume = 45 | issue = 6 | pages = 1211–1213 | date = June 1995 | pmid = 7783891 | doi = 10.1212/wnl.45.6.1211 | s2cid = 35168945 }} There are reports of Takotsubo cardiomyopathy and transient amnesia after sumatriptan use.{{Cite journal | vauthors = Chohan A |date=2023-03-07 |title=Sumatriptan-Induced Takotsubo Cardiomyopathy |url=https://linkinghub.elsevier.com/retrieve/pii/S0735109723039426 |journal=Journal of the American College of Cardiology |series=ACC.23 |volume=81 |issue=8, Supplement |pages=3498 |doi=10.1016/S0735-1097(23)03942-6 |issn=0735-1097}}

The most common side effects{{cite web |url = https://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4180b_09_05_Imitrex%20label%20tablet%2012-04%20Sponsor.pdfsumatriptan |title = Tablets |website = fda.gov |access-date = 19 February 2018 }}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}} 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 (including chest 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 low abuse potential;{{cite journal | vauthors = Sullivan JT, Preston KL, Testa MP, Busch M, Jasinski DR | title = Psychoactivity and abuse potential of sumatriptan | journal = Clinical Pharmacology and Therapeutics | volume = 52 | issue = 6 | pages = 635–642 | date = December 1992 | pmid = 1333934 | doi = 10.1038/clpt.1992.202 }} however overuse is associated with medication overuse headache.{{Cite web |title=TGA eBS - Product and Consumer Medicine Information |url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=pi&q=sumatriptan |access-date=2025-03-03 |website=www.ebs.tga.gov.au}} Moreover, prolonged sumatriptan use is associated with pronociceptive effects, resulting in allodynia. 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.{{Cite journal | vauthors = Chiarugi A, Buonvicino D |date=2025-01-01 |title=Critical reflections on medication overuse headache in patients with migraine: An unsolved riddle in nociception |journal=Neurobiology of Pain |volume=17 |pages=100179 |doi=10.1016/j.ynpai.2025.100179 |pmid=40040782 |issn=2452-073X|pmc=11876746 }}

Concurrent use with other triptans or ergot-containing medications (e.g., ergotamine, dihydroergotamine) within 24 hours can result in additive vasoconstriction.{{Cite web |title=DailyMed - SUMATRIPTAN- sumatriptan succinate tablet tablet |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2abc46d5-1810-469d-8d31-fafa7312421c |access-date=2024-05-03 |website=dailymed.nlm.nih.gov}}{{Cite journal |title=Drugs for Migraine | journal = The Medical Letter on Drugs and Therapeutics | date = June 2023 | volume = 65 | issue = 678 | pages = 89–96| publisher = The Medical Letter Inc. | doi = 10.58347/tml.2023.1678a |url=https://secure.medicalletter.org/TML-article-1678a#:~:text=Subcutaneous%20sumatriptan%20is%20the%20most,in%20patients%20with%20vascular%20disease. |access-date=2024-05-03 |language=en}} Increased systemic exposure to sumatriptan can occur if used within 2 weeks after a monoamine oxidase inhibitor (MAOI). Cases of serotonin syndrome have been reported with co-administration of triptans and serotonin reuptake inhibitors.

{{Further|Serotonin receptor agonist|Triptan#Mechanism_of_action}}

Sumatriptan is molecularly similar to serotonin (5-HT), and is a 5-HT receptor (types 5-HT_1D and 5-HT_1B

{{cite journal | vauthors = Razzaque Z, Heald MA, Pickard JD, Maskell L, Beer MS, Hill RG, Longmore J | title = Vasoconstriction in human isolated middle meningeal arteries: determining the contribution of 5-HT1B- and 5-HT1F-receptor activation | journal = British Journal of Clinical Pharmacology | volume = 47 | issue = 1 | pages = 75–82 | date = January 1999 | pmid = 10073743 | pmc = 2014192 | doi = 10.1046/j.1365-2125.1999.00851.x }}) agonist. Sumatriptan's primary therapeutic effect is related in its inhibition of the release of calcitonin gene-related peptide (CGRP), likely through its 5-HT_1D/1B receptor agonist action.{{cite journal | vauthors = Juhasz G, Zsombok T, Jakab B, Nemeth J, Szolcsanyi J, Bagdy G | title = Sumatriptan causes parallel decrease in plasma calcitonin gene-related peptide (CGRP) concentration and migraine headache during nitroglycerin induced migraine attack | journal = Cephalalgia | volume = 25 | issue = 3 | pages = 179–183 | date = March 2005 | pmid = 15689192 | doi = 10.1111/j.1468-2982.2005.00836.x | s2cid = 13007101 }} This has been substantiated by the efficacy of more recently developed CGRP targeting drugs and antibodies developed for the preventive treatment of migraine.{{cite journal | vauthors = Tso AR, Goadsby PJ | title = Anti-CGRP Monoclonal Antibodies: the Next Era of Migraine Prevention? | journal = Current Treatment Options in Neurology | volume = 19 | issue = 8 | pages = 27 | date = August 2017 | pmid = 28653227 | pmc = 5486583 | doi = 10.1007/s11940-017-0463-4 }} How agonism of the 5-HT_1D/1B receptors inhibits CGRP release is not fully understood. CGRP is believed to cause sensitization of trigeminal nociceptive neurons, contributing to the pain experienced in migraine.{{cite journal | vauthors = Giniatullin R, Nistri A, Fabbretti E | title = Molecular mechanisms of sensitization of pain-transducing P2X3 receptors by the migraine mediators CGRP and NGF | journal = Molecular Neurobiology | volume = 37 | issue = 1 | pages = 83–90 | date = February 2008 | pmid = 18459072 | doi = 10.1007/s12035-008-8020-5 | s2cid = 25689799 }}

Sumatriptan is also shown to decrease the activity of the trigeminal 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.{{cite journal | vauthors = Ekbom K, Waldenlind E, Richard L, Andersson B, Boivie J, Dizdar N, etal | title = Treatment of acute cluster headache with sumatriptan | journal = The New England Journal of Medicine | volume = 325 | issue = 5 | pages = 322–326 | date = August 1991 | pmid = 1647496 | doi = 10.1056/NEJM199108013250505 | collaboration = Sumatriptan Cluster Headache Study Group | doi-access = free }}

Sumatriptan is administered in several forms: tablets, subcutaneous injection, and nasal spray. Oral administration (as succinate salt) has low bioavailability, partly due to presystemic metabolism—some of it gets broken down in the stomach and bloodstream before it reaches the target arteries. A rapid-release tablet formulation with the same bioavailability but a high concentration can achieve therapeutic effects on average 10–15 minutes earlier than other oral formulations.{{Cite web |title=Sumatriptan |url=https://go.drugbank.com/drugs/DB00669 |access-date=2025-03-04 |website=go.drugbank.com |language=en}} When injected, sumatriptan is faster-acting (usually within 10 minutes), but the effect lasts for a shorter time.{{Citation needed|date=March 2025}}

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.{{cite journal |vauthors=Fox AW |date=February 2004 |title=Onset of effect of 5-HT1B/1D agonists: a model with pharmacokinetic validation |journal=Headache |volume=44 |issue=2 |pages=142–147 |doi=10.1111/j.1526-4610.2004.04030.x |pmid=14756852 |s2cid=25587940}}{{cite journal |vauthors=Freidank-Mueschenborn E, Fox AW |date=June 2005 |title=Resolution of concentration-response differences in onset of effect between subcutaneous and oral sumatriptan |journal=Headache |volume=45 |issue=6 |pages=632–637 |doi=10.1111/j.1526-4610.2005.05129a.x |pmid=15953294 |s2cid=20755695}}

Sumatriptan is metabolised primarily by monoamine oxidase A into indol-3-yl-acetaldehyde and then into corresponding carboxylic acid. It is further modified by UDP-glucuronosyltransferase into a conjugate with glucuronic acid. Other pathways are mediated by cytochrome P450 isoenzymes, which give an N-oxide derivative, and N-desmethyl and N,N-didesmethyl forms (the latter can be converted into the aldehyde by monoamine oxidase A). N-desmethyl derivative can also undergo a reaction with D-cysteine.{{cite journal | vauthors = Pöstges T, Lehr M | title = Metabolism of sumatriptan revisited | journal = Pharmacology Research & Perspectives | volume = 11 | issue = 1 | pages = e01051 | date = February 2023 | pmid = 36655303 | pmc = 9849828 | doi = 10.1002/prp2.1051 }}

These metabolites are excreted in the urine and bile. Only about 3% of the active drug may be recovered unchanged.

File:Sumatriptan metabolism pathway.png

File:Sumatriptan vails 100 5509.jpg

In 1991, Glaxo received approval for sumatriptan, which was the first available triptan.{{Citation needed|date=March 2025}}

In July 2009, the US Food and Drug Administration (FDA) approved a single-use jet 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.{{cite journal | vauthors = Brandes JL, Cady RK, Freitag FG, Smith TR, Chandler P, Fox AW, Linn L, Farr SJ | title = Needle-free subcutaneous sumatriptan (Sumavel DosePro): bioequivalence and ease of use | journal = Headache | volume = 49 | issue = 10 | pages = 1435–1444 | year = 2009 | pmid = 19849720 | doi = 10.1111/j.1526-4610.2009.01530.x | s2cid = 25696109 }}

Phase III studies with an iontophoretic transdermal patch (Zelrix/Zecuity) started in July 2008.{{ClinicalTrialsGov|NCT00724815|The Efficacy and Tolerability of NP101 Patch in the Treatment of Acute Migraine (NP101-007)}} This patch uses low voltage controlled by a pre-programmed microchip to deliver a single dose of sumatriptan through the skin within 30 minutes.{{cite web |url = http://www.nupathe.com/description.php?secid=3&subsecid=7#_ELECTRONIC_DRUG |title = SmartRelief -electronically assisted drug delivery (iontophoresis) |website = nupathe.com |access-date = 19 February 2018 |url-status = live |archive-url = https://web.archive.org/web/20160107062814/http://www.nupathe.com/description.php?secid=3&subsecid=7#_ELECTRONIC_DRUG |archive-date = 7 January 2016 |df = dmy-all }}{{cite journal | vauthors = Pierce M, Marbury T, O'Neill C, Siegel S, Du W, Sebree T | title = Zelrix: a novel transdermal formulation of sumatriptan | journal = Headache | volume = 49 | issue = 6 | pages = 817–825 | date = June 2009 | pmid = 19438727 | doi = 10.1111/j.1526-4610.2009.01437.x | s2cid = 205683188 | doi-access = free }} Zecuity was approved by the FDA in January 2013.{{cite web |url = http://ir.nupathe.com/press-releases/nupathe-s-zecuity-approved-by-the-fda-for-the-acut-nasdaq-path-975802NuPathe's |title = Zecuity Approved by the FDA for the Acute Treatment of Migraine |website = nupathe.com |access-date = 19 February 2018 |url-status = live |archive-url = https://web.archive.org/web/20160107062814/http://ir.nupathe.com/press-releases/nupathe-s-zecuity-approved-by-the-fda-for-the-acut-nasdaq-path-975802NuPathe's |archive-date = 7 January 2016 |df = dmy-all }} Sales of Zecuity have been stopped following reports of skin burns and irritation.{{cite web|url=http://www.fiercepharma.com/pharma/teva-pulls-migraine-patch-zecuity-reports-burning-scarring|title=Teva pulls migraine patch Zecuity on reports of burning, scarring |website=FiercePharma |date=13 June 2016 |access-date=10 April 2017|url-status=live|archive-url=https://web.archive.org/web/20170321022606/http://www.fiercepharma.com/pharma/teva-pulls-migraine-patch-zecuity-reports-burning-scarring|archive-date=21 March 2017}}

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.{{cite web |title = Poisons Standard June 2017 |url = https://www.legislation.gov.au/Details/F2017L00605/Html/Text#_Toc471222305 |access-date = 22 July 2017 |date = 18 May 2017 |url-status = live |archive-url = https://web.archive.org/web/20170731114704/https://www.legislation.gov.au/Details/F2017L00605/Html/Text#_Toc471222305 |archive-date = 31 July 2017 |df = dmy-all }} However, it can be bought over the counter in the UK{{cite web |title = Press release: First Over The Counter (OTC) migraine pill made available |url = http://www.mhra.gov.uk/NewsCentre/Pressreleases/CON2023768 |publisher = Medicines and Healthcare Products Regulatory Agency |access-date = 28 January 2015 |archive-url = http://webarchive.nationalarchives.gov.uk/20141205150130/http://www.mhra.gov.uk/NewsCentre/Pressreleases/CON2023768 |archive-date = 5 December 2014 }} and Sweden.{{cite web |author1 = European Medicines Agency |author-link1 = European Medicines Agency |title = Assessment Report: Sumatriptan Galpharm 50 mg Tablets |url = http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002140/WC500122862.pdf |publisher = European Medicines Agency |access-date = 28 January 2015 |page = 20 |date = 23 November 2011 |url-status = live |archive-url = https://web.archive.org/web/20160107062816/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002140/WC500122862.pdf |archive-date = 7 January 2016 |df = dmy-all }}

In Russia, versions of sumatriptan which are not registered in the State Register of Medicines may be regarded as narcotic drugs (derivatives of dimethyltryptamine).{{cite web|url=http://base.garant.ru/12112176/|title=Постановление Правительства РФ от 30 июня 1998 г. N 681 "Об утверждении перечня наркотических средств, психотропных веществ и их прекурсоров, подлежащих контролю в Российской Федерации" (с изменениями и дополнениями)|quote=ДМТ (диметилтриптамин) и его производные, за исключением производных, включенных в качестве самостоятельных позиций в перечень|publisher=Гарант|access-date=28 April 2019|language=ru}}

Glaxo patents for sumatriptan expired in February 2009. At that time, Imitrex sold for about $25 a pill.{{cite web |title=GlaxoSmithKline sets out to dupe migraine sufferers with Treximet smoke and mirrors |date=24 April 2008 |publisher=Community Catalyst |url=https://www.communitycatalyst.org/blog/glaxosmithkline-sets-out-to-dupe-migraine-sufferers-with-treximet-smoke-and-mirrors-pal |access-date=22 March 2019}} 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.{{cite news |title = Par Pharmaceutical begins shipment of sumatriptan injection |url = http://www.parpharm.com/media/NR_20081106.jsp |archive-url = https://web.archive.org/web/20081210132734/http://www.parpharm.com/media/NR_20081106.jsp |url-status = dead |archive-date = 10 December 2008 |work = Par Pharmaceutical |date = 6 November 2008 |access-date = 25 November 2008 |df = dmy-all }}

Mylan Laboratories Inc., Ranbaxy Laboratories, Sandoz (a subsidiary of Novartis), 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 U.S. 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.{{cite news | vauthors = LaMattina J |title = If You 'Want To Make A Good Drug Great' Cost Must Be Factored In |url = https://www.forbes.com/sites/johnlamattina/2015/03/03/if-you-want-to-make-a-good-drug-great-cost-must-be-factored-in/ |access-date = 13 February 2017 |work = Forbes |date = 2 March 2015 |url-status = live |archive-url = https://web.archive.org/web/20170214105140/http://www.forbes.com/sites/johnlamattina/2015/03/03/if-you-want-to-make-a-good-drug-great-cost-must-be-factored-in/ |archive-date = 14 February 2017 |df = dmy-all }}

According to the American Headache Society, "Patients frequently state that they have difficulty accessing triptans prescribed to them."{{Citation | vauthors=((Minen, M. T.)), ((Lindberg, K.)), ((Langford, A.)), ((Loder, E.)) | year=2017 | title=Variation in Prescription Drug Coverage for Triptans: Analysis of Insurance Formularies | journal=Headache: The Journal of Head and Face Pain | volume=57 | issue=8 | pages=1243–1251 | publisher=Wiley | doi=10.1111/head.13134 | pmid=28691382 | s2cid=42239120 | url=http://dx.doi.org/10.1111/head.13134| url-access=subscription }} In the U.S. triptans cost from $12 to $120 each, and more than 80% of U.S. health insurance plans place a limit on the amount of pills available to a patient per month, which has been called "arbitrary and unfair."{{citation |title=Practice Matters Wide Variation in Triptan Coverage Across Commercial and Government Health Plans | vauthors = Bender E |date=7 September 2017 |journal=Neurology Today |volume=17 |issue=17 |page=7 |publisher=American Academy of Neurology |doi=10.1097/01.NT.0000524839.20893.03 |s2cid=80167113 |url=https://journals.lww.com/neurotodayonline/fulltext/2017/09070/Practice_Matters__Wide_Variation_in_Triptan.4.aspx |access-date=26 June 2022|url-access=subscription }}

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