Sumatriptan

295.4

295.40

8R78F6L9VO

DTXSID4023628

C1240

N02CC01|N - Nervous system

2935904000

73.6

0.93

Solid

1.1778 (rough estimate)

169-171 °C

497.7±55.0 °C(Predicted)

254.8±31.5 °C

1.6740 (estimate)

H2O: 21.4 mg/mL;40.3 [ug/mL]

Sumatriptan succinate injection and tablets and sumatriptan nasal spray should be protected from light and stored at 2-30 deg C.

7.05X10-9 mm Hg at 25 deg C (est)

4.9None

Henry's Law constant = 4.47X10-14 atm-cu m/mol at 25 °C (est)

4.9|pKa = 10.4 (est) (amide)

162.1 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]

MW: 413.49; mp 165-166 °C /Sumatriptan succinate/

UN 3261 8/PG 2

3

36/37/38

26

NL9482200

Xi

P201, P202, P264, P273, P280, P281, P305+P351+P338, P308+P313, P337+P313, P405, P501

H319

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl sumatriptan, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.|The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl sumatriptan succinate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Sumatriptan succinate/

|Warning|H319 (40%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]|P201, P202, P264, P273, P280, P281, P305+P351+P338, P308+P313, P337+P313, P405, and P501|Aggregated GHS information provided by 5 companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Symptoms of overdose include convulsions, tremor, paralysis, inactivity, ptosis, erythema of the extremities, abnormal respiration, cyanosis, ataxia, mydriasis, salivation, and lacrimation. Overdoses may be fatal and patients should be monitored for 3-5 half lives or while symptoms persist.

In large prospective controlled trials, the different triptans have not been associated with serum enzyme elevations or hepatotoxicity; however, the frequency of monitoring in most studies was limited and rates of ALT elevations not reported. There have been rare individual reports of cholestatic hepatitis after the use of triptans, largely associated with zolmitriptan. Typically, the onset of injury was within 1 to 2 weeks of taking several doses of the zolmitriptan for a protracted and severe migraine attack. Recurrent jaundice with intermittent therapy has also been reported (Case 1). The pattern of serum enzyme elevations was mixed or cholestatic, and recovery was complete within 1 to 2 months. Allergic manifestations (rash, fever, eosinophilia) were not present and autoantibodies did not develop.

Alcohol consumed 30 minutes prior to sumatriptan ingestion had no effect on the pharmacokinetics of sumatriptan.|Due to gut and hepatic metabolic first-pass effects, the increase of systemic exposure after coadministration of an MAO-A inhibitor with oral sumatriptan is greater than after coadministration of the monoamine oxidase inhibitors (MAOI) with subcutaneous sumatriptan. In a study of 14 healthy females, pretreatment with an MAO-A inhibitor decreased the clearance of subcutaneous sumatriptan. Under the conditions of this experiment, the result was a 2-fold increase in the area under the sumatriptan plasma concentration x time curve (AUC), corresponding to a 40% increase in elimination half-life. This interaction was not evident with an MAO-B inhibitor. A small study evaluating the effect of pretreatment with an MAO-A inhibitor on the bioavailability from a 25-mg oral sumatriptan tablet resulted in an approximately 7-fold increase in systemic exposure.|Sumatriptan tablets and any ergotamine-containing or ergot-type medication (like dihydroergotamine or methysergide) should not be used within 24 hours of each other, nor should sumatriptan and another 5-HT1 agonists.|A 65-year-old woman was referred with confusion, strange behavior, sinus tachycardia, hypertension and hyperthermia. She had been taking sumatriptan and paroxetine and recovered completely after discontinuation of these agents. The diagnosis was 'serotonin syndrome', a result of overstimulation of 5-HT(1A) receptors in the raphe nuclei of the brainstem. It is a complication of the use of serotonergic agents and is associated with the rapid onset of mental, autonomic and neurological symptoms. Treatment consists of discontinuation of the suspected medication and, in severe cases, providing symptomatic relief. ...

Sumatriptan is 14%-21% bound to protein in circulation.

Sumatriptan's production and use as a migraine medication(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 80(SRC), determined from a log Kow of 0.93(2) and a regression-derived equation(3), indicates that sumatriptan is expected to have high mobility in soil(SRC). However, aromatic amines are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group(4,5), suggesting that mobility may be much lower in some soils. Volatilization of sumatriptan from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4.5X10-14 atm-cu m/mole(SRC), using a fragment constant estimation method(6). Sumatriptan is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 7.1X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(7). Biodegradation data were not available(SRC, 2009).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 80(SRC), determined from a log Kow of 0.93(2) and a regression-derived equation(3), indicates that sumatriptan is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 4.5X10-14 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2009).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), sumatriptan, which has an estimated vapor pressure of 7.1X10-8 mm Hg at 25 °C is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase sumatriptan may be removed from the air by wet or dry deposition(SRC). Sumatriptan does not contain chromophores that absorb at wavelengths >290 nm(4) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Sumatriptan is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Sumatriptan does not contain chromophores that absorb at wavelengths >290 nm(1) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3 was calculated in fish for sumatriptan(SRC), using a log Kow of 0.93(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Koc of sumatriptan is estimated as 80(SRC), using a log Kow of 0.93(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that sumatriptan is expected to have high mobility in soil. However, aromatic amines are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group(4,5), suggesting that mobility may be much lower in some soils(SRC).

The Henry's Law constant for sumatriptan is estimated as 4.5X10-14 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that sumatriptan is expected to be essentially nonvolatile from water surfaces(2). Sumatriptan is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 7.0X10-9 mm Hg(SRC), determined from a fragment constant method(3).

While data specific to sumatriptan were not located(SRC, 2009), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2).

Sumatriptan is distributed into milk in humans and animals; in animals, sumatriptan concentrations are eight-fold higher than concurrent maternal plasma concentrations. In a limited number of healthy lactating women, the total recovery of sumatriptan in breast milk averaged 0.24% of a single 6-mg subcutaneous dose, corresponding to an average infant exposure of 3.5% of the maternal dose on a weight-adjusted basis.|The excretion of a 6 mg subcutaneous dose of sumatriptan in breast milk was studied in five lactating volunteer subjects with a mean age of 27.6 years and a mean body weight of 75 kg. Drug concentrations in milk and plasma over the ensuing 8 hr were measured by high-performance liquid chromatography. The mean milk:plasma ratio estimated from the areas under the milk and plasma concentration-time curves (AUC) was 4.9 (95% CI 4.1-5.7), indicating a significant transfer of sumatriptan into the milk compartment. The mean total recovery of drug in milk was estimated to be only 14.4 ug (95% CI 6.1-22.7 ug), or 0.24% of the 6 mg administered dose. On a weight-adjusted basis this corresponded to a mean infant exposure of 3.5% of the maternal dose (95% CI 0.3-6.7%). If oral bioavailability in the infant is similar to that in adults (14%), the weight-adjusted infant dose is reduced to 0.49%. Furthermore, allowance for reduced clearance in the infant predicts an infant exposure varying from 4.9% in a very premature neonate to 0.7% in a 30 week old infant. Since sumatriptan is usually administered as a single dose at infrequent intervals, the low level of excretion in breast milk suggests that continued breast feeding following its use will not pose a significant risk to the suckling infant. Even this minor exposure could be largely avoided by expressing and discarding all milk for 8 hr after the dose.

Occupational exposure to sumatriptan may occur through inhalation and dermal contact with this compound at workplaces where sumatriptan is produced or used. Use data indicate that exposure may be limited to those administered this drug in the treatment of migraines. (SRC)

A combination sumatriptan and [naproxen] tablet is indicated for the treatment of migraines with or without auras in patients 12 years of age and older. Sumatriptan nasal powder, nasal spray, subcutaneous injection, and tablets are indicated to treat migraines with or without auras in adults. One of the subcutaneous formulations of sumatriptan is also indicated to treat cluster headaches in adults, while the other subcutaneous formulation is not.

The triptans are a group of serotonin receptor agonists that are useful in the therapy of vascular headaches and migraine. The triptans are generally used in low doses for a limited period of time and have not been associated with serum enzyme elevations, but some have been implicated in rare instances of clinically apparent, acute cholestatic hepatitis.

Migraine Headache Agents

Serotonin Agonists; Vasoconstrictor Agents|Sumatriptan tablets are indicated for the acute treatment of migraine attacks with or without aura in adults. /Included in US product label/|Sumatriptan tablets are NOT intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine. Safety and effectiveness of sumatriptan tablets have not been established for cluster headache, which is present in an older, predominantly male population. /Included in US product label/|/EXPTL Ther:/ To determine the impact of sumatriptan prophylaxis on acute mountain sickness (AMS) and altitude headache development within 24 hours of ascent, we designed a double-blind, randomized, clinical trial. A prospective, double-blind, randomized, placebo-controlled trial was conducted in Tochal Mountain Hotel at an altitude of 3,500 meters above sea level during October 2006 to November 2006. A total of 102 Iranian adults were assigned to receive either sumatriptan succinate (50mg) or placebo within 1 hour of ascent. AMS incidence was measured by Lake Louise AMS score > or = 3 with headache and one other symptom. Secondary outcome measures included severity of syndrome (Lake Louise scores > or = 5), incidence of headache, and severity of headache. Based on intention-to-treat analysis, AMS was more prevalent in placebo group (n = 23 [45.1%]) than sumatriptan group (n = 12 [23.5%]; p = 0.02). Headache also had a greater rate for placebo users (placebo vs sumatriptan group: 29 [56.9%] vs 17 [33.3%]; p = 0.02). No association was detected between sumatriptan prophylaxis and AMS or altitude headache severity. Sumatriptan prophylaxis is effective to prevent AMS development. Furthermore, our findings confirm cerebral vasodilative and edematous mechanisms of AMS progression, whereas sumatriptan is a selective 5-hydroxytryptamine(1) receptor subtype agonist and a selective cerebral vasoconstrictor as a result|/EXPTL Ther:/ ... A patient with a 4-year history of cyclic vomiting was treated for an episode of nausea, vomiting, and abdominal pain. This patient had been hospitalized numerous times for cyclic vomiting over the previous 4 years, each hospitalization lasting from 3 to 11 days. Following a single subcutaneous injection of sumatriptan 6 mg, the patient ceased vomiting and was discharged 40 hours from the time of admission. The efficacy of sumatriptan in migraine headache appears to be mediated through its agonist activity at the serotonin1D receptor, resulting in constriction of dural blood vessels. According to published reports, therapeutic attempts at controlling cyclic vomiting often have included antimigraine therapies. Consistent with these reports, sumatriptan also appears effective in the treatment of cyclic vomiting. The pathogenesis of cyclic vomiting appears to share similarities with classic migraine, both of which may respond to sumatriptan therapy according to this report and previous work. Further study of the use of sumatriptan in the treatment of cyclic vomiting appears warranted.

Most adverse effects associated with sumatriptan are well defined, transient, and mild to moderate in intensity, although serious cardiac events (coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, ventricular fibrillation) have been reported rarely in patients receiving the drug subcutaneously or orally. Adverse effects associated with the drug usually occur within 1 hour after subcutaneous or oral administration of sumatriptan and generally resolve within 10-30 minutes (subcutaneous) or 1 hour (oral). The incidence of adverse effects associated with sumatriptan generally remains unchanged or decreases with repeated use of the drug. However, the incidence of adverse effects appears to increase with higher than recommended doses of the drug. In addition, the overall incidence of adverse effects among patients receiving sumatriptan injection for the treatment of cluster headache is lower than that in patients being treated with the drug for migraine.|The most frequently reported adverse effects associated with subcutaneous sumatriptan succinate therapy are injection site reaction (eg, minor pain, edema, tingling at the site of injection, burning, transient erythema), tingling, dizziness or vertigo, and sensations of warmth or heat. Common adverse effects reported in patients receiving oral sumatriptan for the treatment of migraine or cluster headache include malaise or fatigue, nausea or vomiting, dizziness or vertigo, tingling, and nasal discomfort. Since some adverse effects noted with sumatriptan therapy (eg, nausea or gastric symptoms, tingling, photophobia, visual disturbances, headache, numbness, neck pain, drowsiness/sedation, asthenia, fatigue) also are symptoms associated with migraine attacks and/or the postdromal period, it may be difficult to distinguish the effects of underlying disease processes from drug-induced effects. The most frequently reported adverse effects associated with intranasal sumatriptan include disturbances of taste, nausea or vomiting, and disease of nasal cavity or sinuses. For adverse effects reported with sumatriptan therapy in the Cautions section, a causal relationship to the drug has not always been established. In addition, the incidence of adverse effects reported in clinical trials may not predict precisely the likelihood of encountering these effects under usual medical practice where patient characteristics and other factors differ from those prevailing in the trials.|Pooled data from controlled studies indicate that the most frequently reported adverse effect associated with subcutaneous sumatriptan succinate therapy is injection site reaction, consisting of minor pain, edema, induration, swelling, contusions, subcutaneous bleeding, stinging or tingling at the site of injection, burning, and/or transient erythema. Lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue) has been reported in less than 0.1% of patients receiving the drug subcutaneously. Injection site reactions occurred in 58.7% of patients receiving the drug subcutaneously in controlled trials; this effect occurred with less frequency in patients using an auto-injector to administer the drug.|Nasal and/or throat irritation were reported in approximately 5% of patients receiving 5-, 10-, or 20-mg doses of intranasal sumatriptan on 1 or 2 occasions in controlled clinical studies. Transient irritative symptoms (eg, burning, numbness, paresthesia, discharge, pain or soreness) were reported to be severe in about 1% of patients receiving intranasal sumatriptan; these symptoms generally resolved in less than 2 hours. Limited examination of the nose and throat did not reveal clinically noticeable injury in these patients. In addition, an increased incidence of local irritation has not been observed in patients receiving intranasal sumatriptan repeatedly for up to 1 year. However, epithelial hyperplasia (with and without keratinization) and squamous metaplasia were observed in the larynx of rats receiving inhaled sumatriptan daily for 1 month at dosages as low as one-half the maximum daily human exposure (based on dose per surface area of nasal cavity). In addition, evidence of epithelial hyperplasia, focal squamous metaplasia, granulomata, bronchitis, and fibrosing alveolitis was observed in the respiratory and nasal mucosa in dogs administered various formulations of sumatriptan by intranasal instillation daily for up to 13 weeks, at exposure rates of 2-4 times the maximum daily human exposure (based on dose per surface area of nasal cavity). The changes observed in both species are not considered to be signs of preneoplastic or neoplastic transformation. Local effects on nasal and respiratory tissues after chronic, repeated intranasal administration of sumatriptan have not been studied in animals or humans.|For more Drug Warnings (Complete) data for Sumatriptan (42 total), please visit the HSDB record page.

Sumatriptan constricts cranial blood vessels and prevents the release of vasoactive peptides. The dose of sumatriptan varies widely by route of administration and in most cases, no more than 2 doses should be given daily. Medication overuse headaches may occur in patients who use sumatriptan frequently.

Drugs used to cause constriction of the blood vessels. (See all compounds classified as Vasoconstrictor Agents.)|Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT1 RECEPTORS. Included under this heading are agonists for one or more of the specific 5-HT1 receptor subtypes. (See all compounds classified as Serotonin 5-HT1 Receptor Agonists.)

A 6mg subcutaneous injection of sumatriptan reaches a C_max of 69.5ng/mL (95% CI of 62.8-76.9ng/mL) with a T_max of 0.17h (95% CI of 0.08-0.33h), an AUC of 9.0h\*ng/mL (95% CI of 7.5-10.9h\*ng/mL), and a bioavailability of 100%. A 25mg oral dose of sumatriptan reaches a C_max of 16.5ng/mL (95% CI of 13.5-20.1ng/mL) with a T_max of 1.50h (95% CI of 0.50-2.00h), an AUC of 8.7h\*ng/mL (95% CI of 6.1-12.5h\*ng/mL), and a bioavailability of 14.3% (95% CI of 11.4-17.9%). A 20mg intranasal dose of sumatriptan reaches a C_max of 12.9ng/mL (95% CI of 10.5-15.9ng/mL) with a T_max of 1.50h (95% CI of 0.25-3.00h), an AUC of 7.4h\*ng/mL (95% CI of 5.0-10.8h\*ng/mL), and a bioavailability of 15.8% (95% CI of 12.6-19.8%). A 25mg rectal dose of sumatriptan reaches a C_max of 22.9ng/mL (95% CI of 18.4-28.6ng/mL) with a T_max of 1.00h (95% CI of 0.75-3.00h), an AUC of 14.6h\*ng/mL (95% CI of 11.3-18.8h\*ng/mL), and a bioavailability of 19.2% (95% CI of 15.3-24.1%).|22±4% is excreted in the urine as unchanged sumatriptan and 38±7% in urine as indole acetic acid approximately 40% is excreted in the feces.|Sumatriptan has a volume of distribution of 50±8L for a 6mg subcutaneous dose, or 2.7L/kg.|Subcutaneous sumatriptan has a clearance of 0.22L/min (95% CI of 0.19-0.25L/min). Oral sumatriptan has a clearance of 0.17L/min (95% CI of 0.14-0.21L/min). Rectal sumatriptan has a clearance of 0.17L/min (95% CI of 0.14-0.21L/min). Intrsnasal sumatriptan has a clearance of 0.21L/min (95% CI of 0.18-0.25L/min). Total plasma clearance of sumatriptan is approximately 1200mL/min.|Sumatriptan is rapidly absorbed following subcutaneous or oral administration; oral absorption appears to occur in the small intestine. The drug also is absorbed rapidly following intranasal administration. The bioavailability of sumatriptan given subcutaneously is almost complete, averaging about 97% of that obtained with iv administration of the drug. The bioavailability of sumatriptan following oral or intranasal administration averages only about 15 or 17%, respectively, principally because of presystemic metabolism of the drug and in part because of incomplete absorption. The area under the plasma concentration-time curve (AUC) and peak serum concentration of sumatriptan increase linearly with single subcutaneous doses of 1-16 mg. The extent of sumatriptan absorption (AUC) also is dose-proportional following single oral doses of 25-200 mg; however, peak plasma concentrations after a 100-mg oral dose of sumatriptan are approximately 25% less than those predicted from a 25-mg oral dose.|Interindividual variability in the absorption of sumatriptan after oral administration results in multiple peaks in plasma concentration, possibly because of differences in the rates of gastric emptying, small-bowel transit, and/or presystemic metabolism; however, 75-80% of the final peak plasma concentration is reached within 45 minutes after dosing. Administration of higher than recommended single oral doses of sumatriptan (ie, 200-400 mg) is associated with a decrease in the rate of absorption.|Oral absorption of the drug does not appear to be affected appreciably by gastric stasis that may occur during a migraine attack; however, the time to peak concentration is prolonged by about 30 minutes. The pharmacokinetics of sumatriptan following subcutaneous injection reportedly are similar during migraine attacks and pain-free periods. Absorption of subcutaneous sumatriptan is not affected by race or gender.|A food effect study involving administration of sumatriptan tablets to healthy volunteers under fasting conditions and with a high-fat meal indicated that the Cmax and AUC were increased by 15% and 12%, respectively, when administered in the fed state.|For more Absorption, Distribution and Excretion (Complete) data for Sumatriptan (17 total), please visit the HSDB record page.

Sumatriptan is predominantly metabolized by monoamine oxidase A. The main metabolites are the inactive indole acetic acid and indole acetic acid glucuronide.|The principal metabolite of sumatriptan is its inactive indole acetic acid analog, which is formed by oxidative N-deamination of the N-dimethyl side chain. The indole acetic acid metabolite of sumatriptan achieves plasma concentrations 6-7 times higher than those of sumatriptan but has a half-life similar to that of the parent compound, suggesting that clearance of this metabolite is formation-rate limited. Other minor metabolites of sumatriptan, an ester glucuronide of the indole acetic acid derivative and an indole ethyl alcohol derivative, also have been identified.|Metabolism is the principal clearance process for sumatriptan. Sumatriptan is metabolized in the liver and possibly in the GI tract and is eliminated in urine and feces. In vitro studies suggest that sumatriptan is metabolized by monoamine oxidase (MAO), principally the A isoenzyme (MAO-A); inhibitors of this enzyme may increase systemic exposure to sumatriptan.

Subcutaneous sumatriptan has a half life of 1.9h (95% CI of 1.7-2.0h). Oral sumatriptan has a half life of 1.7h (95% CI of 1.4-1.9h). Rectal sumatriptan has a half life of 1.8h (95% CI of 1.6-2.2h). Intrsnasal sumatriptan has a half life of 1.8h (95% CI of 1.7-2.0h).|Following single subcutaneous or oral doses of sumatriptan in healthy individuals, the terminal elimination half-life of the drug is 1.5-2.6 hours.|Following single-dose oral administration of large doses of sumatriptan or repeated administration of smaller doses, a second terminal elimination phase has been observed but not characterized. The prolonged elimination half-life with multiple dosing or administration of large single doses may indicate enterohepatic recycling or prolonged oral absorption and does not appear to affect substantially the disposition of the drug. Most of a dose of sumatriptan is excreted within 10-24 hours.|Following intranasal administration of sumatriptan, the elimination half-life reportedly is about 2 hours.

Sumatriptan is an agonist of 5-HT_1B and 5-HT_1D. This agonism leads to constriction of cranial blood vessels and inhibits the release of pro-inflammatory neuropeptides. Sumatriptan decreases carotid arterial blood flow, but increases blood flow velocity in the internal carotid artery and middle cerebral artery.[A179734 Agonism of the 5-HT_1B and 5-HT_1D receptors also inhibits sensory neurons, preventing the release of vasoactive peptides.[A179734 Sumatriptan does not cross the blood brain barrier.|Sumatriptan and other currently available drugs that are effective for acute migraine, including dihydroergotamine and ergotamine, have binding affinity for serotonin type 1 (5-HT1) receptors, particularly the 5-HT1D (also called 5-HT1Dalpha) and 5-HT1B (also called 5-HT1Dbeta) subtypes located on trigeminal sensory neurons innervating dural blood vessels. The 5-HT1B and 5-HT1D receptors function as autoreceptors, activation of which leads to inhibition of firing of serotonin neurons and a reduction in the synthesis and release of serotonin. Upon binding to these 5-HT1 receptor subtypes, sumatriptan inhibits adenylate cyclase activity via regulatory G proteins, increases intracellular calcium, and affects other intracellular events that lead to vasoconstriction and inhibition of sensory nociceptive (trigeminal) nerve firing and vasoactive neuropeptide release. Sumatriptan has the highest affinity for the 5-HT1D receptor, the most common serotonin receptor subtype in the brain, and a 2- to 17-fold lower affinity for 5-HT1A receptors; agonist activity at 5-HT1A and other serotonin receptors may be responsible for some of the adverse effects noted with administration of serotonin or serotonergic antimigraine drugs (eg, ergotamine, dihydroergotamine). Sumatriptan has essentially no affinity for (based on standard radioligand binding assays) nor pharmacologic activity at other serotonin receptors (eg, 5-HT2, 5-HT3) or at receptors of the dopamine1, dopamine2, muscarinic, histamine, benzodiazepine, or alpha1-, alpha2-, or beta-adrenergic type.|Sumatriptan is a selective agonist of vascular serotonin (5-hydroxytryptamine; 5-HT) type 1-like receptors, probably the 5-HT1D and 5-HT1B subtypes. The mechanisms involved in the pathogenesis of migraine and cluster headache are not clearly understood; consequently, the precise mechanism of action of sumatriptan in the management of these disorders has not been established. However, current data suggest that sumatriptan may ameliorate migraine and cluster headache through selective constriction of certain large cranial blood vessels and/or inhibition of neurogenic inflammatory processes in the CNS. While some features of migraine clearly reflect effects on cerebral blood vessels, neurogenic mechanisms involving activation of the trigeminovascular system also have been implicated; current evidence suggests that both mechanisms may be involved.|The vascular 5-HT1 receptor subtype that sumatriptan activates is present on cranial arteries in both dog and primate, on the human basilar artery, and in the vasculature of human dura mater and mediates vasoconstriction. This action in humans correlates with the relief of migraine headache. In addition to causing vasoconstriction, experimental data from animal studies show that sumatriptan also activates 5-HT1 receptors on peripheral terminals of the trigeminal nerve innervating cranial blood vessels. Such an action may also contribute to the antimigrainous effect of sumatriptan in humans.|Sumatriptan selectively reduces carotid arterial blood flow and/or constricts carotid arteriovenous anastomoses in anesthetized animals without appreciable effects on arterial blood pressure or total peripheral resistance. The drug produces contraction of vascular smooth muscle in vitro in saphenous veins in dogs and humans, but such contractions are weaker than those produced by serotonin or ergot alkaloids (eg, methysergide).|For more Mechanism of Action (Complete) data for Sumatriptan (9 total), please visit the HSDB record page.

[3-[2-(dimethylamino)ethyl]]-2-[[3-[2-(dimethylamino)ethanyl]]-1H-indol-5-yl]]-N-methylmethane-sulphonamide|N-methyl[3-]-2-(methylamino)ethyl]-1H-indol-5-yl]methanesulphonamide|[3-[2-(dimethylamino)ethyl]-1-(hydroxymethyl)-1H-indol-5-yl]-N-methylmethanesulphonamide|N,N-dimethyl-2-[5-[(methylsulphamoyl)methyl]-1H-indol-3-yl]ethanamine N-oxide|For more Impurities (Complete) data for Sumatriptan (8 total), please visit the HSDB record page.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/|In case of acute overdosage, establish and maintain an airway and ensure adequate oxygenation and ventilation. Intravenous access should be established and gastric lavage (after intubation, if patient is unconscious) and administration of activated charcoal together with a laxative should be considered. The possibility of obtundation, seizure, or dystonic reaction of the head and neck following overdose may create a risk of aspiration with induced emesis. Cardiovascular monitoring should commence immediately and should include continuous electrocardiographic monitoring to detect possible arrhythmias. If antiarrhythmic therapy is administered, disopyramide, procainamide, and quinidine carry a theoretical hazard of additive QT-prolonging effects that might be additive to those of ziprasidone. Hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluids. If sympathomimetic agents are used for vascular support, epinephrine and dopamine should not be used, since beta stimulation combined with a1 antagonism associated with ziprasidone may worsen hypotension. Similarly, it is reasonable to expect that the alpha-adrenergic-blocking properties of bretylium might be additive to those of ziprasidone, resulting in problematic hypotension. In cases of severe extrapyramidal symptoms, anticholinergic medication should be administered. There is no specific antidote to ziprasidone, and it is not dialyzable. The possibility of multiple drug involvement should be considered. Close medical supervision and monitoring should continue until the patient recovers.

/HUMAN EXPOSURE STUDIES/ The excretion of a 6 mg subcutaneous dose of sumatriptan in breast milk was studied in five lactating volunteer subjects with a mean age of 27.6 years and a mean body weight of 75 kg. Drug concentrations in milk and plasma over the ensuing 8 hr were measured by high-performance liquid chromatography. The mean milk:plasma ratio estimated from the areas under the milk and plasma concentration-time curves (AUC) was 4.9 (95% CI 4.1-5.7), indicating a significant transfer of sumatriptan into the milk compartment. The mean total recovery of drug in milk was estimated to be only 14.4 ug (95% CI 6.1-22.7 ug), or 0.24% of the 6 mg administered dose. On a weight-adjusted basis this corresponded to a mean infant exposure of 3.5% of the maternal dose (95% CI 0.3-6.7%). If oral bioavailability in the infant is similar to that in adults (14%), the weight-adjusted infant dose is reduced to 0.49%. Furthermore, allowance for reduced clearance in the infant predicts an infant exposure varying from 4.9% in a very premature neonate to 0.7% in a 30 week old infant. Since sumatriptan is usually administered as a single dose at infrequent intervals, the low level of excretion in breast milk suggests that continued breast feeding following its use will not pose a significant risk to the suckling infant. Even this minor exposure could be largely avoided by expressing and discarding all milk for 8 hr after the dose.|/HUMAN EXPOSURE STUDIES/ Patients (N = 670) have received single oral doses of 140 to 300 mg without significant adverse effects. Volunteers (N = 174) have received single oral doses of 140 to 400 mg without serious adverse events.|/SIGNS AND SYMPTOMS/ Cerebral angiopathy of the postpartum period is a rare entity, sometimes promoted by vasoconstrictives drug prescription. Its clinical presentation includes headaches, seizures and focal neurological deficits, which develop shortly after a normal pregnancy. The diagnosis is based on clinical findings and angiography, showing multiple narrowing of the intracranial cerebral arteries. This neurological feature is reversible and the clinical outcome is good. We report a case of benign cerebral angiopathy in a 20-year-old woman in the postpartum period, occurring after administration of sumatriptan and ergot derivates.|/SIGNS AND SYMPTOMS/ Other arrhythmias or ECG abnormalities reported infrequently in patients receiving sumatriptan therapy include bradycardia, tachycardia, nonspecific ST or T wave changes, prolongation of PR or QTC intervals, sinus arrhythmias, abnormal P waves with nodal rhythm, QRS/T-axis deviations, nonsustained ventricular premature complexes, isolated junctional ectopic beats, atrial ectopic beats, and delayed activation of the right ventricle.|For more Human Toxicity Excerpts (Complete) data for Sumatriptan (21 total), please visit the HSDB record page.

3-(2-(Dimethylamino)ethyl)-N-methyl-1H-indole-5-methanesulfonamide

Formulations: (AHFS, 2009)

Analyte: sumatriptan; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards|Analyte: sumatriptan; matrix: chemical identification: retention time of the major peak of the liquid chromatogram with comparison to standards|Analyte: sumatriptan; matrix: chemical purity; procedure: liquid chromatography with ultraviolet detection at 282 nm and comparison with standards|Analyte: sumatriptan; matrix: pharmaceutical preparation (nasal spray); procedure: infrared absorption spectrophotometry with comparison to standards (chemical identification)|For more Analytic Laboratory Methods (Complete) data for Sumatriptan (8 total), please visit the HSDB record page.

Analyte: sumatriptan; matrix: pharmaceutical preparation; procedure: capillary electrophoresis with ultraviolet detection at 214 nm and comparison to standards|Analyte: sumatriptan; matrix: pharmaceutical preparation; procedure: capillary electrophoresis with UV detection at 214 nm; limit of detection: 25 ng/mL|Analyte: sumatriptan; matrix: blood (plasma); procedure: high-performance liquid chromatography with mass spectrometry detection; limit of quantitation: 2ng/mL|Analyte: sumatriptan; matrix: blood (plasma), urine; procedure: high-performance liquid chromatography with electrochemical detection; limit of quantitation: 1 ng/mL (blood), 200 ng/mL (urine)

Human drugs -> Sumatriptan Galpharm -> EMA Drug Category|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals