Sumatriptan, sold under the brand name Imitrex among others, is a

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

used to treat

migraine headaches Migraine (, ) is a complex neurological disorder characterized by episodes of moderate-to-severe headache, most often unilateral and generally associated with nausea, and light and sound sensitivity. Other characterizing symptoms may inc ...

and

cluster headaches Cluster headache is a neurological disorder characterized by recurrent severe headaches on one side of the head, typically around the eye(s). There is often accompanying eye watering, nasal congestion, or swelling around the eye on the affecte ...

. It is taken orally,

intranasally Nasal administration, popularly known as snorting, is a route of administration in which drugs are insufflated through the nose. It can be a form of either topical administration or systemic administration, as the drugs thus locally delivered ca ...

, or by subcutaneous

injection Injection or injected may refer to: Science and technology * Injective function, a mathematical function mapping distinct arguments to distinct values * Injection (medicine), insertion of liquid into the body with a syringe * Injection, in broadca ...

. Therapeutic effects generally occur within three hours. Its primary effect as a serotonin 5-HT_1B/ 5-HT_1D receptor agonist can create common side effects such as

chest pressure Chest pain is pain or discomfort in the chest, typically the front of the chest. It may be described as sharp, dull, pressure, heaviness or squeezing. Associated symptoms may include pain in the shoulder, arm, upper abdomen, or jaw, along with na ...

, fatigue, vomiting, tingling, and

vertigo Vertigo is a condition in which a person has the sensation that they are moving, or that objects around them are moving, when they are not. Often it feels like a spinning or swaying movement. It may be associated with nausea, vomiting, perspira ...

. Serious side effects may include

serotonin syndrome Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain Serotonin, serotonergic medications or Recreational drug use, drugs. The symptoms can range from mild to severe, and are potentially fatal. Symptoms in mild c ...

heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

, and

seizure A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

s. With excessive use,

medication overuse headache A medication overuse headache (MOH), also known as a rebound headache, usually occurs when painkillers are taken frequently to relieve headaches. These cases are often referred to as painkiller headaches. Rebound headaches frequently occur daily, ...

s may occur. It is unclear if use during

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

breastfeeding Breastfeeding, also known as nursing, is the process where breast milk is fed to a child. Infants may suck the milk directly from the breast, or milk may be extracted with a Breast pump, pump and then fed to the infant. The World Health Orga ...

is safe. The mechanism of action is not entirely clear. It is in the

triptan Triptans are a family of tryptamine-based medication, drugs used as abortive medication in the treatment of migraines and cluster headaches. This drug class was first commercially introduced in the 1990s. While effective at treating individual h ...

class of medications. Sumatriptan was patented in 1982 and approved for medical use in 1991. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

. In 2022, it was the 95th most commonly prescribed medication in the United States, with more than 6million prescriptions. It is also available as the combination product

sumatriptan/naproxen Sumatriptan/naproxen, sold under the brand name Treximet among others, is a fixed-dose combination medication used to treat migraines. It is taken by mouth. It contains sumatriptan, as the succinate, a serotonin 5-hydroxytryptamine (5-HT) 1b/1d ...

Medical uses

Sumatriptan is effective for ending or relieving the intensity of

migraine Migraine (, ) is a complex neurological disorder characterized by episodes of moderate-to-severe headache, most often unilateral and generally associated with nausea, and light and sound sensitivity. Other characterizing symptoms may includ ...

and

cluster headache Cluster headache is a neurological disorder characterized by recurrent severe headaches on one side of the head, typically around the eye, eye(s). There is often accompanying eye watering, nasal congestion, or swelling around the eye on the aff ...

s. It is most effective when taken early after the start of the pain. Injected sumatriptan is more effective than other formulations. Oral sumatriptan can be used also in the treatment of post-dural puncture headache.

Adverse effects

Overdose of sumatriptan can cause

sulfhemoglobinemia Sulfhemoglobinemia is a rare condition in which there is excess sulfhemoglobin (SulfHb) in the blood. The pigment is a greenish derivative of hemoglobin which cannot be converted back to normal, functional hemoglobin. It causes cyanosis even at ...

, a rare condition in which the blood changes from red to green, due to the integration of

sulfur Sulfur ( American spelling and the preferred IUPAC name) or sulphur ( Commonwealth spelling) is a chemical element; it has symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms ...

into the

hemoglobin Hemoglobin (haemoglobin, Hb or Hgb) is a protein containing iron that facilitates the transportation of oxygen in red blood cells. Almost all vertebrates contain hemoglobin, with the sole exception of the fish family Channichthyidae. Hemoglobin ...

molecule. If sumatriptan is discontinued, the condition reverses within a few weeks. 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 Coronary vasospasm refers to when a coronary artery suddenly undergoes either complete or sub-total temporary occlusion. In 1959, Prinzmetal et al. described a type of chest pain resulting from coronary vasospasm, referring to it as a variant for ...

, transient myocardial ischemia,

myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...

ventricular tachycardia Ventricular tachycardia (V-tach or VT) is a cardiovascular disorder in which fast heart rate occurs in the ventricles of the heart. Although a few seconds of VT may not result in permanent problems, longer periods are dangerous; and multiple ...

, and

ventricular fibrillation Ventricular fibrillation (V-fib or VF) is an abnormal heart rhythm in which the Ventricle (heart), ventricles of the heart Fibrillation, quiver. It is due to disorganized electrical conduction system of the heart, electrical activity. Ventricula ...

. There are reports of Takotsubo cardiomyopathy and transient

amnesia Amnesia is a deficit in memory caused by brain damage or brain diseases,Gazzaniga, M., Ivry, R., & Mangun, G. (2009) Cognitive Neuroscience: The biology of the mind. New York: W.W. Norton & Company. but it can also be temporarily caused by t ...

after sumatriptan use. The most common side effects reported by at least 2% of patients in controlled trials of sumatriptan (25-, 50-, and 100-mg tablets) for migraine are atypical sensations (

paresthesia Paresthesia is a sensation of the skin that may feel like numbness (''hypoesthesia''), tingling, pricking, chilling, or burning. It can be temporary or Chronic condition, chronic and has many possible underlying causes. Paresthesia is usually p ...

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 Chest pain is pain or discomfort in the chest, typically the front of the chest. It may be described as sharp, dull, pressure, heaviness or squeezing. Associated symptoms may include pain in the shoulder, arm, upper abdomen, or jaw, along with n ...

) reported by 4% in the placebo group and 6–8% in the sumatriptan groups, neurological events (

) reported by less than 1% in the placebo group and less than 1% to 2% in the sumatriptan groups.

Malaise In medicine, malaise is a feeling of general discomfort, uneasiness or lack of wellbeing and often the first sign of an infection or other disease. It is considered a vague termdescribing the state of simply not feeling well. The word has exist ...

fatigue Fatigue is a state of tiredness (which is not sleepiness), exhaustion or loss of energy. It is a signs and symptoms, symptom of any of various diseases; it is not a disease in itself. Fatigue (in the medical sense) is sometimes associated wit ...

occurred in less than 1% of the placebo group and 2–3% of the sumatriptan groups.

Sleep disturbance A sleep disorder, or somnipathy, is a medical disorder affecting an individual's sleep patterns, sometimes impacting physical, mental, social, and emotional functioning. Polysomnography and actigraphy are tests commonly ordered for diagnosing s ...

occurred in less than 1% in the placebo group to 2% in the sumatriptan group. Sumatriptan has a low

abuse potential Substance misuse, also known as drug misuse or, in older vernacular, substance abuse, is the use of a drug in amounts or by methods that are harmful to the individual or others. It is a form of substance-related disorder, differing definitions ...

; however overuse is associated with

. Moreover, prolonged sumatriptan use is associated with pronociceptive effects, resulting in

allodynia Allodynia is a condition in which pain is caused by a stimulus that does not normally elicit pain. For example, sunburn can cause temporary allodynia, so that usually painless stimuli, such as wearing clothing or running cold or warm water over ...

. 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.

Interactions

Concurrent use with other

triptans Triptans are a family of tryptamine-based drugs used as abortive medication in the treatment of migraines and cluster headaches. This drug class was first commercially introduced in the 1990s. While effective at treating individual headaches, t ...

or ergot-containing medications (e.g.,

ergotamine Ergotamine, sold under the brand name Ergomar among others, is an ergopeptine and part of the ergot family of alkaloids; it is structurally and biochemically closely related to ergoline. It is structurally similar to several neurotransmitter ...

dihydroergotamine Dihydroergotamine (DHE), sold under the brand names D.H.E. 45 and Migranal among others, is an ergot alkaloid used to treat migraines. It is a derivative of ergotamine. It is administered as a nasal spray or injection and has an efficacy simila ...

) within 24 hours can result in additive

vasoconstriction Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vesse ...

. Increased systemic exposure to sumatriptan can occur if used within 2 weeks after a

monoamine oxidase inhibitor Monoamine oxidase inhibitors (MAOIs) are a drug class, class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressa ...

(MAOI). Cases of

have been reported with co-administration of triptans and

serotonin reuptake inhibitors A serotonin reuptake inhibitor (SRI) is a type of drug which acts as a reuptake inhibitor of the neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) by blocking the action of the serotonin transporter (SERT). This in turn leads to increa ...

Pharmacology

Mechanism of action

Sumatriptan is molecularly similar to

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

(5-HT), and is a

5-HT receptor 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in multiple tissues including the Central nervous system, central and peripheral nervous systems ...

(types 5-HT_1D and 5-HT_1B)

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

. Sumatriptan's primary therapeutic effect is related in its inhibition of the release of

calcitonin gene-related peptide Calcitonin gene-related peptide (CGRP) is a neuropeptide that belongs to the calcitonin family. Human CGRP consists of two Protein isoform, isoforms, CGRP alpha (α-CGRP, also known as CGRP I) and CGRP beta (β-CGRP, also known as CGRP II). α-C ...

(CGRP), likely through its 5-HT_1D/1B receptor agonist action. This has been substantiated by the efficacy of more recently developed CGRP targeting drugs and antibodies developed for the preventive treatment of migraine. 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 In physiology, nociception , also nocioception; ) is the sensory nervous system's process of encoding noxious stimuli. It deals with a series of events and processes required for an organism to receive a painful stimulus, convert it to a molecular ...

neurons, contributing to the pain experienced in migraine. Sumatriptan is also shown to decrease the activity of the

trigeminal nerve In neuroanatomy, the trigeminal nerve (literal translation, lit. ''triplet'' nerve), also known as the fifth cranial nerve, cranial nerve V, or simply CN V, is a cranial nerve responsible for Sense, sensation in the face and motor functions ...

, 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.

Pharmacokinetics

Sumatriptan is administered in several forms: tablets,

subcutaneous injection Subcutaneous administration is the insertion of medications beneath the skin either by injection or infusion. A subcutaneous injection is administered as a bolus (medicine), bolus into the subcutis, the layer of skin directly below the dermis and ...

, and nasal spray. Oral administration (as

succinate Succinic acid () is a dicarboxylic acid with the chemical formula (CH2)2(CO2H)2. In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological roles as a metabolic intermediate being converted into Fuma ...

salt) has low

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

, 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. When injected, sumatriptan is faster-acting (usually within 10 minutes), but the effect lasts for a shorter time. 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.

Metabolism

Sumatriptan is metabolised primarily by

monoamine oxidase A Monoamine oxidase A, also known as MAO-A, is an enzyme ( E.C. 1.4.3.4) that in humans is encoded by the ''MAOA'' gene. This gene is one of two neighboring gene family members that encode mitochondrial enzymes which catalyze the oxidative dea ...

into indol-3-yl-acetaldehyde and then into corresponding carboxylic acid. It is further modified by

UDP-glucuronosyltransferase Uridine 5'-diphospho-glucuronosyltransferase ( UDP-glucuronosyltransferase, UDPGT or UGT) is a microsomal glycosyltransferase () that catalyzes the transfer of the glucuronic acid component of UDP-glucuronic acid to a small hydrophobic molecu ...

into a conjugate with

glucuronic acid Glucuronic acid (GCA, from ) is a uronic acid that was first isolated from urine (hence the name "uronic acid"). It is found in many natural gum, gums such as gum arabic ( 18%), xanthan, and kombucha tea and is important for the metabolism of ...

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

History

In 1991, Glaxo received approval for sumatriptan, which was the first available

. In July 2009, the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) approved a single-use

jet injector A jet injector is a type of medical injecting syringe device used for a method of drug delivery known as jet injection. A narrow, high-pressure stream of liquid is made to penetrate the outermost layer of the skin (stratum corneum) to deliver me ...

formulation of sumatriptan. The device delivers a subcutaneous injection of sumatriptan, without the use of a needle.

Autoinjector An autoinjector (or auto-injector) is a medical device for injection of a premeasured dose of a particular drug. Most autoinjectors are one-use, disposable, spring-loaded syringes (prefilled syringes). By design, autoinjectors are easy to use an ...

s with needles have been previously available in Europe and North America. Phase III studies with an

iontophoretic Iontophoresis is a process of transdermal drug delivery by use of a voltage gradient on the skin. Molecules are transported across the stratum corneum by electrophoresis and electroosmosis and the electric field can also increase the permeability ...

transdermal patch A transdermal patch is a medicated adhesive patch that is placed on the skin to deliver a specific Dose (biochemistry), dose of medication through the skin and into the bloodstream. An advantage of a transdermal drug delivery route over ot ...

(Zelrix/Zecuity) started in July 2008. This patch uses low

voltage Voltage, also known as (electrical) potential difference, electric pressure, or electric tension, is the difference in electric potential between two points. In a Electrostatics, static electric field, it corresponds to the Work (electrical), ...

controlled by a pre-programmed

microchip An integrated circuit (IC), also known as a microchip or simply chip, is a set of electronic circuits, consisting of various electronic components (such as transistors, resistors, and capacitors) and their interconnections. These components a ...

to deliver a single dose of sumatriptan through the skin within 30 minutes. Zecuity was approved by the FDA in January 2013. Sales of Zecuity have been stopped following reports of skin burns and irritation.

Society and culture

Legal status

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. However, it can be bought over the counter in the UK and Sweden. In Russia, versions of sumatriptan which are not registered in the State Register of Medicines may be regarded as narcotic drugs (derivatives of

dimethyltryptamine Dimethyltryptamine (DMT), also known as ''N'',''N''-dimethyltryptamine (''N'',''N''-DMT), is a Psychedelic drug, serotonergic hallucinogen and Investigational New Drug, investigational drug of the substituted tryptamine, tryptamine family tha ...

Generics

Glaxo patents for sumatriptan expired in February 2009. At that time, Imitrex sold for about $25 a pill. 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. Mylan Laboratories Inc.,

Ranbaxy Laboratories Ranbaxy Laboratories Limited was an Indian multinational pharmaceutical company that was incorporated in India in 1961 and remained an entity until 2014. The company went public in 1973. Ownership of Ranbaxy changed twice over the course of its ...

, Sandoz (a subsidiary of

Novartis Novartis AG is a Swiss multinational corporation, multinational pharmaceutical company, pharmaceutical corporation based in Basel, Switzerland. Novartis is one of the largest pharmaceutical companies in the world and was the eighth largest by re ...

Dr. Reddy's Laboratories Dr. Reddy's Laboratories Ltd. is an Indian multinational Pharmaceutical industry, pharmaceutical company based in Hyderabad. The company was founded by Kallam Anji Reddy, who previously worked in the mentor institute Indian Drugs and Pharmace ...

, 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.

Controversy

According to the

American Headache Society ''Headache: The Journal of Head and Face Pain'' is a peer-reviewed medical journal covering all aspects of head and face pain. It is the official journal of the American Headache Society (https://americanheadachesociety.org). It was established in ...

, "Patients frequently state that they have difficulty accessing triptans prescribed to them." 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."

References

{{Portal bar , Medicine 5-HT1B agonists 5-HT1D agonists 5-HT1F agonists N,N-Dialkyltryptamines Dimethylamino compounds Drugs developed by Pfizer Drugs developed by GSK plc Sulfonamides Triptans World Health Organization essential medicines Wikipedia medicine articles ready to translate