Sumatriptan

Chemical structure of sumatriptan Source:Wikimedia Commons

Sumatriptan is a medicine that acts by constricting the blood vessels in the brain to relieve the pain of migraine headache. It is available in nasal spray, tablet, and injectible forms. Sumatriptan is available only by prescription in the United States and Canada, whereas the tablets are sold over-the-counter in the United Kingdom.

Other Names

• Imitrex
• Imigran
• Imigran Recovery

Uses

Sumatriptan is used for the short-term treatment of most types of migraine attacks, with or without aura, in adults. It is not used to prevent migraines, or to decrease the number of migraine attacks. Sumatriptan has been shown to be effective in the treatment of cluster headaches, but it is not approved for this condition.^[1]

How Sumatriptan is Taken

Sumatriptan is taken daily as needed to relieve migraine pain. It is available in a nasal spray, tablet, or injectable form. Nasal sprays contain 5 mg or 20 mg sumatriptan in 0.1 ml of solution. Tablets are available in doses of 25 mg, 50 mg, or 100 mg. Daily doses of the tablet should not exceed 200 mg. Injectable forms are available at a concentration of 6 mg/0.5mL and are injected underneath the skin (subcutaneous). No more than 2 injections should be used in a 24-hour period, and injections should be separated by at least 1 hour.

How Sumatriptan Works

A migraine is caused, at least in part, by the dilation (widening) of certain blood vessels in the brain. Serotonin, which is also called 5-hydroxytryptamine, is a neurotransmitter that constricts blood vessels. Neurotransmitters are chemicals that send messages from one neuron (brain cell) to another, or from a neuron to a tissue (such as blood vessels). Sumatriptan is called a serotonin-agonist because it acts like serotonin, activating serotonin receptors on the blood vessels. Activation of these receptors constricts the blood vessels which relieves the pain of migraines. Sumatriptan also reduces substances in the body that can trigger headaches and relieve other migraine symptoms, including nausea and sensitivity to light and sound.

The injectable and nasal spray forms of sumatriptan take effect quicker than the oral form, but their effects do not last as long.

Sumatriptan is metabolized, or modified, by enzymes in the liver called monoamine oxidases. The injected and nasal spray forms of sumatriptan are metabolized to a lesser extent than is the oral form. The time required for the concentration in the blood to be reduced by half, the half-life, is approximately 2.5 hours. Sumatriptan is excreted from the body through both the urine and stool. Liver damage can slow the elimination of sumatriptan.

Side Effects

Some common side effects of sumatriptan include the following:

• Dizziness
• Fatigue
• Tingling
• Flushing (hot flashes)

Rarely, sumatriptan can cause allergic reactions. The signs of an allergic reaction include shortness of breath, wheezing, heart throbbing, swelling of eyelids, face, or lips, a skin rash, lumps, and hives.

Risks

Precautions

Sumatriptan should not be used in individuals with the following conditions:

• Uncontrolled high blood pressure
• Heart disease or a history of heart disease
• Hemiplegic or basilar migraine
• Stroke
• Circulation problems to the arms, legs, and bowels
• Severe liver disease

Sumatriptan is also not taken with other migraine medications. These include medications in the same drug class as sumatriptan, drugs that inhibit monoamine oxidase (Monoamine Oxidase Inhibitor|monoamine oxidase inhibitors), or ergot derivatives (e.g., ergotamine, dihydroergotamine (Migranal), or methylsergide). Sumatriptan can be used if the monoamine oxidase inhibitor was taken at least two weeks before taking sumatriptan, or if sumatriptan is taken at least 24 hours before or after taking an ergot derivative.

Sumatriptan is used with caution in individuals with risk factors for heart disease. These factors include high cholesterol, high blood pressure, diabetes, and obesity.

Caution is used when sumatriptan is taken with other drugs that elevate levels of serotonin, such as the selective serotonin reuptake inhibitors (e.g., fluoxetine (Prozac)), or the serotonin-norepinephrine reuptake inhibitors (e.g., venlafaxine (Effexor)).

Interactions

Sumatriptan can interact with other drugs. While other medications may affect how sumatriptan works, sumatriptan can also influence how other drugs work.

Interactions are more likely with drugs that elevate levels of serotonin. Drugs that inhibit the enzyme monoamine oxidase, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors increase serotonin levels. The most serious result of elevated serotonin is the serotonin syndrome. This syndrome, which can be life-threatening, is more likely to occur when starting combinations of these drugs, or when the dose of any of these drugs is elevated during the co-administration. Below are some symptoms of the serotonin syndrome:

• Restlessness
• Hallucinations
• Loss of coordination
• Rapid heart beat
• Increased body temperature
• Fast changes in blood pressure
• Overactive reflexes
• Diarrhea
• Nausea and vomiting

Other serious manifestations of the syndrome include pain, pressure or tightness of the chest or throat.

Overdose

Single oral doses of 140 to 400 mg have been given without significant adverse effects. However, long-term, high-dose sumatriptan can result in a condition characterized by daily bleed of dark green blood. This condition, called sulfhemoglobinemia, is caused by the integration of the sulfur atom in sumatriptan into the hemoglobin molecule of blood. Once the drug is discontinued, the blood will return to the normal color in a few weeks.

History

Discovery

Sumatriptan was discovered in the 1970s by a team from the pharmaceutical company Glaxo. One of the lead researchers, Dr. Patrick Humphrey recently wrote a retrospective article about the way the medicine was developed. ^[2] Dr. Humphrey states that it has been long known that vasodilators (like alcohol) make migrane headaches worse, and that vasoconstrictors (like ergotamine) improve migrane symptoms. Using the ear artery of a dog, the team was able to isolate the compound GR43175, which was later named sumatriptan. The compound, a selective vasoconstrictor, only had effect on the carotid arteries in the head, thus decreasing side effects while maximizing improvement of migrane symptoms. Sumatriptan has had a positive effect on the treatment of migrane headache as it has focused attention on the condition and has lead to the discovery of several new medicines to treat migranes.

Name

The name sumatriptan derives from triptan, reflecting the action on the tryptamine receptors and suma for the 5-sulfonamide group of the chemical structure.

Manufacturer

GlaxoSmithKline was the first to market sumatriptan in 1991. Since then, Mylan Laboratories has been given the approval to market sumatriptan tablets, and Spectrum Pharmaceuticals has filed for permission to market the injectable form.

Research

Recent discoveries

All three forms of sumatriptan have proven effective in reducing pain two hours after dosing. Some clinical results are presented below.

• The effectiveness of sumatriptan nasal spray was examined over a six month period in patients with moderate to severe migraine pain.^[3] Between 44% and 60% of patients taking the nasal spray had pain relief two hours after taking the drug, the response being dependent on the dose. About one-third of patients receiving the placebo had pain relief. An analysis was performed on six clinical trials of oral sumatriptan for the relief of mild pain associated with the onset of a migraine.^[4] The study found that 49% and 58% of patients taking either 50 mg or 100 mg sumatriptan, respectively, had complete pain relief after two hours. Only 24% of patients taking a placebo had relief at that time. In a clinical trial of 577 patients with moderate to severe migraine, 70% of patients had complete pain relief two hours after injecting sumatriptan. ^[5] Only 24% of patients given a placebo had pain relief at that time.

• In addition, a study published in JAMA in 2007 describes research done by the Nashville Neuroscience group, who found that sumatriptan 85 mg, in combination with naproxen sodium 500 mg, relieved symptoms of a migrane headache better than either medicine alone. ^[6]

Clinical Trials

There are several ongoing clinical trials involving sumatriptan. Most involve Trexima, a combination of sumatriptan and naproxen sodium. Information is available at ClinicalTrials.gov.

• Sumatriptan 4 mg Statdose in the Acute Treatment of Cluster Headache: [1]
• Efficacy of Combination Product (Sumatriptan Succinate/Naproxen Sodium) in Eletriptan Non-Responders: [2]
• TREXIMA™ (Sumatriptan + Naproxen Sodium) Versus Butalbital-Containing Combination Medications (BCM) for the Acute Treatment of Migraine: [3]
• A Randomized Trial to Optimize Discharge From the ED After Treatment for Headache (HEDNet2): [4]
• Long-Term Safety of Trexima for Migraine in Adolescents: [5]
• TREXIMA Versus Butalbital-Containing Combination Medications for the Acute Treatment of Migraine in Adults: [6]

References

1. ↑ Beck E, Sieber WJ, Trejo R. Management of cluster headache.Am Fam Physician. 2005 Feb 15;71(4):717-24.Abstract
2. ↑ Humpfrey P. The discovery of a new drug class for the acute treatment of migraine. Headache. 2007 Apr;47 Suppl 1:S10-9. Abstract | PDF
3. ↑ Diamond S, Elkind A, Jackson RT, Ryan R, DeBussey S, Asgharnejad M. Multiple-attack efficacy and tolerability of sumatriptan nasal spray in the treatment of migraine. Arch Fam Med. 1998 May-Jun; 7(3):234-40. Abstract | PDF
4. ↑ Winner P, Landy S, Richardson M, Ames M. Early intervention in migraine with sumatriptan tablets 50 mg versus 100 mg: a pooled analysis of data from six clinical trials. Clin Ther. 2005 Nov; 27(11):1785-94. Abstract
5. ↑ Wendt J, Cady R, Singer R et al., A randomized, double-blind, placebo-controlled trial of the efficacy and tolerability of a 4-mg dose of subcutaneous sumatriptan for the treatment of acute migraine attacks in adults. Clin Ther. 2006 Apr; 28(4):517-26. Abstract
6. ↑ Brandes J, Kudrow D, Stark S, O'Carroll C, Adelman J, O'Donnell F, et al. Sumatriptan-naproxen for acute treatment of migraine: a randomized trial. JAMA. 2007 Apr 4;297(13):1443-54. Abstract | Full Text

External Links

• The Migraine Relief Center