Sumatriptan

Article Author:
Yudhveer Brar
Article Editor:
Abdolreza Saadabadi
Updated:
10/17/2019 3:14:41 PM
PubMed Link:
Sumatriptan

Indications

Sumatriptan is FDA approved as an abortive treatment for migraine attacks with or without aura in adults. Acute treatment of cluster headache episodes can be relieved by administration of subcutaneous treatment. According to the clinical studies, sumatriptan is an effective and well-tolerated treatment for a migraine when given intravenously, subcutaneously, or orally. It relieves photophobia, nausea, headache and functional disability. Non FDA-approved indications of sumatriptan include treatment of a migraine in children and adolescents.[1][2][3]

Mechanism of Action

Serotonin (5-hydroxytryptamine) has a central role in the pathophysiology of a migraine. Its metabolism is abnormal in patients with a migraine, and intravenous administration of 5-hydroxytryptamine can alleviate migraine attacks. Antimigraine drugs share the ability to activate 5-hydroxytryptamine receptors. Headaches, a prominent feature of a migraine, are believed to result from the following: excessive dilatation of extracerebral cranial (dural or meningeal) arteries, arteriovenous shunts, or both; neurogenic dural plasma extravasation; or a combination of these mechanisms. Sumatriptan (3-[2-(dimethylamino)ethyl]-N-methylindole-5-methanesulfonamide) is a selective agonist of 5–hydroxytryptamine1—like receptors that blocks plasma leakage from the dura and venous sinuses. This is stimulated by perivascular trigeminal fibers that release substance P, calcitonin G-related peptide, and neurokinin A. This pain mechanism may provide the final common pathway for other cephalgias and migraines, which explains the overlap and similarities between different headache syndromes. Subcutaneous administration of sumatriptan, however, results in rapid attainment of peak plasma levels.

Sumatriptan 5-HT1B/1D receptor agonist leads to vasoconstriction in the basilar artery and the blood vessels of the dura mater. It decreases peripheral nociception either by a selective cranial vasoconstriction or an effect on trigeminovascular nerves. A peripheral effect on trigeminal vascular nerves was indicated by the blocking effect of sumatriptan of neurogenically mediated plasma extravasation. Sumatriptan inhibits the presynaptic terminal of the trigeminal nucleus caudalis which leads to the reversal of facial allodynia. Triptans not only decrease transmission of the pain impulses to the trigeminal nucleus caudalis but also release inflammatory mediators from trigeminal nerves, therefore reducing calcitonin gene-related peptide-mediated vasodilation. Migraine pain is associated with middle cerebral artery dilatation which leads to the lower velocity of regional cerebral blood flow. Sumatriptan reverses the dilatation of MCA which suggests that the 5-HT receptor system has a role in the pathogenesis of a migraine.[4][5][6][7]

An acute dose of sumatriptan (100 micrograms/kg) decreases the 5-HT synthesis rate in many brain regions including the dorsal raphe nucleus. Chronically, sumatriptan (300 micrograms/kg per day) induced significant increases in the 5-HT synthesis rate in many projection areas but did not affect the dorsal raphe nucleus.

Administration

Sumatriptan can be administered orally (Imitrex, Imigran, and an ingredient in Treximet), intranasally (Imitrex), via subcutaneous injection (Imitrex, Alsuma, Sumavel), rectally, and more recently, as a transdermal patch (Zelrix/Zecuity). The sumatriptan nasal powder system has faster improvement in migraine-related disability and migraine pain intensity at early time points as compared to the oral sumatriptan. Sumatriptan (25 mg) administered rectally is an effective treatment for acute migraine attacks and leads to a significant reduction in symptoms within two hours. Individuals with nausea and vomiting can be administered a subcutaneous injection as compared to oral; however, subcutaneous administration is associated with increased adverse events. Subcutaneous administration also has been considered the most efficacious treatment in the acute phase of a migraine, both on pain as well as on associated autonomic symptoms. Oral sumatriptan has been shown to be an effective drug for the treatment of a single acute attack of a migraine. Absorption of sumatriptan is rapid after oral and subcutaneous administration. However, the bioavailability of oral sumatriptan is just 14% as compared to the subcutaneous administration which is nearly 100%. Elimination of sumatriptan is primarily by metabolism to a nonactive indoleacetic acid analog. The pharmacokinetic and pharmacodynamic variables of sumatriptan are not altered by the presence of alcohol, food, prophylactic migraine treatments, or dihydroergotamine.

Adverse Effects

Sumatriptan can cause adverse central nervous system events outside migraine attacks. It can cause mild sedative effects such as sleepiness or fatigue. It also causes a significant increase in the EEG alpha power as compared with the placebo. In a study measured by the Yale-Brown Scale, sumatriptan worsened the symptoms of patients with obsessive-compulsive disorder (OCD).  Sumatriptan also can cause a transient rise in blood pressure, but the rise of blood pressure is the same as would be anticipated during moderate exercise. Subcutaneous injection administered by the physician results in transient stinging at the site of injection in most subjects; however, toleration is better when the subjects use the auto-injector. Sumatriptan can induce angle-closure glaucoma, but this is a rare event and should be treated correctly and promptly to prevent visual loss. A common adverse drug reaction of subcutaneous sumatriptan includes injection site reaction (bleeding, bruising, erythema). Intranasal sumatriptan leads to dysgeusia and nasal discomfort. Sumatriptan works earlier and more completely as compared to a combination of caffeine and ergotamine, but sumatriptan is associated with a higher rate of recurrent headaches. Rothner et al. reported a case of facial nerve palsy in a teenager using sumatriptan nasal spray. Hossein et al. described a recurrent paresis of the superior division of the oculomotor nerve occurring after subcutaneous administration of the drug. A thorough evaluation should be done of the patients who present with acute onset of a severe headache, and sumatriptan should be administered carefully since it could precipitate RCVS (Reversible cerebral vasoconstriction syndrome) or aggravate cerebral vasoconstriction. Vascular imaging should be performed after several days if sumatriptan-induced reversible vasoconstriction syndrome is suspected.

Contraindications

Oral, intranasal, and subcutaneous routes of sumatriptan administration are contraindicated in patients with severe hepatic treatment. It is also contradicted in patients receiving concurrent MAO type A inhibitors or within two weeks of discontinuing an MAO type A inhibitor. Patients with signs and symptoms of ischemic heart disease are relatively C/I. Ischemic heart disease includes coronary artery vasospasm, MI, Prinzmetal angina, and Angina pectoris. Sumatriptan also is contraindicated in patients who use ergotamine and another 5-HT1 agonist concurrently. Patients with peripheral vascular disease (also, Ischemic bowel disease), cerebrovascular syndromes, or uncontrolled hypertension have a contraindication to Sumatriptan as well.

Monitoring

The elimination half-life of sumatriptan is 1 to 4 hours, and the therapeutic plasma drug concentrations range from 0.013 to 0.095 mg/L.  Sumatriptan daily doses in adults should not exceed 300 mg orally, 40 mg intranasally, 12 mg parenterally and 13 mg transdermally (two patches).

Enhancing Healthcare Team Outcomes

Patients with migraine are usually managed with an interprofessional team that consists of a neurologist, nurse practitioner, primary care provider, pharmacist, and the emergency department physician. When patients present with an acute migraine attack, one of the drugs to abort the attack is sumatriptan. The drug is an effective and well-tolerated treatment for a migraine when given intravenously, subcutaneously, or orally. However, when prescribers of sumatriptan must be fully aware of its CNS adverse effects. It can cause mild sedative effects such as sleepiness or fatigue. Sumatriptan can alter blood pressure and the subcutaneous injection results in transient stinging at the site of injection. Sumatriptan is also associated with a high rate of recurrent headaches and precipitate the reversible cerebral vasoconstriction syndrome. To be on the safe side, it is important to start at the lowest dose and administer it orally. [8][9][10](Level V)


References

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[7] Landy S,Munjal S,Brand-Schieber E,Rapoport AM, Efficacy and safety of DFN-11 (sumatriptan injection, 3 mg) in adults with episodic migraine: an 8-week open-label extension study. The journal of headache and pain. 2018 Aug 15;     [PubMed PMID: 30112725]
[8] Loder EW,Rayhill M,Burch RC, Safety Problems With a Transdermal Patch for Migraine: Lessons From the Development, Approval, and Marketing Process. Headache. 2018 Nov;     [PubMed PMID: 30367818]
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