Sumatriptan
Encyclopedia
Sumatriptan is a triptan
sulfa
drug
containing a sulfonamide
group. It is used for the treatment of migraine
headache
s. Sumatriptan is produced and marketed by various drug manufacturers with many different trade names such as Sumatriptan, Imitrex, Imigran, Imigran recovery.
s, solution for injection
, and nasal inhaler
s.
On April 15, 2008, the US FDA approved a combination of sumatriptan and naproxen
, an NSAID. This combination has shown a benefit over either medicine used separately.
In July 2009, the US FDA approved a single-use jet injector
formulation of sumatriptan. The device delivers a subcutaneous injection of 6 mg sumatriptan. A similar application has been filed in Europe.
Phase III studies with a iontophoretic transdermal patch
(Zelrix) started in July 2008. This patch uses low voltage
controlled by a pre-programmed microchip
to deliver a single dose of sumatriptan through the skin within 30 minutes.
(5HT), and is a 5-HT (types 5-HT1D and 5-HT1B) agonist
. The specific receptor
subtypes it activates are present on the cranial arteries and veins. Acting as an agonist at these receptors, Sumatriptan reduces the vascular inflammation associated with migraine.
The specific receptor
subtype it activates is present in the cranial and basilar arteries
. Activation of these receptors causes vasoconstriction
of those dilated arteries. Sumatriptan is also shown to decrease the activity of the trigeminal nerve
, which, it is presumed, accounts for sumatriptan's efficacy in treating cluster headaches
. The injectable form of the drug has been shown to abort a cluster headache within fifteen minutes in 96% of cases.
, and nasal spray. Oral administration (as succinate) suffers from poor bioavailability
, partly due to presystemic metabolism
—some of it gets broken down in the stomach and bloodstream before it reaches the target arteries. A new rapid-release tablet formulation has the same bioavailability, but the maximum concentration is achieved on average 10–15 minutes earlier. When injected, sumatriptan is faster-acting (usually within 10 minutes), but the effect lasts for a shorter time. Sumatriptan is metabolised primarily by monoamine oxidase A
into an indole acetic acid analogue, part of which is further conjugated with glucuronic acid
. These metabolites are excreted in the urine and bile. Only about 3% of the active drug may be recovered unchanged.
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.
, a rare condition in which the blood changes from red to greenish-black, due to the integration of sulfur
into the 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 Imitrex Injection or Tablets. Events reported have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation.
The most common side-effects reported by at least 2% of patients in controlled trials of Imitrex (25, 50, and 100 mg tablets) for migraine are atypical sensations (paresthesias and warm/cold sensations) reported by 4% in the placebo group and 5-6% in the Imitrex groups, pain and other pressure sensations (including chest pain) reported by 4% in the placebo group and 6-8% in the Imitrex groups, neurological events (vertigo
) reported by less than 1% in the placebo group and less than 1% to 2% in the Imitrex groups. Malaise/fatigue occurred in less than 1% of the placebo group and 2-3% of the Imitrex groups.
announced that it would begin shipping generic versions of Imitrex Injection (sumatriptan succinate injection) 4 mg and 6 mg starter kits and 4 mg and 6 mg pre-filled syringe cartridges to the trade immediately. In addition, Par anticipates launching the 6 mg vials early in 2009.
Mylan Laboratories Inc. has received FDA approval for its generic version of Imitrex tablets in 25-, 50-, and 100-milligram doses. The drug will soon be available, or is already available, in European markets, since Glaxo's patent protections have expired in those jurisdictions. However, sales of the generic drug are still restricted in the U.S., since Glaxo won an extension on their patent until 2009. A generic version of the drug in tablet form became available December 2008 in the United States and is distributed by Ranbaxy.
See also Sumavel DosePro (above).
Triptan
Triptans are a family of tryptamine-based drugs used as abortive medication in the treatment of migraines and cluster headaches. They were first introduced in the 1990s...
sulfa
SULFA
SULFA, short for Surrendered ULFA, i.e. members of the United Liberation Front of Asom that surrendered to the government.Beginning with 1990, the Government of India has attempted to wean away members of ULFA. In 1992 a large section of second rank leaders and members surrendered to government...
drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
containing a sulfonamide
Sulfonamide (chemistry)
In chemistry, the sulfonamide functional group is -S2-NH2, a sulfonyl group connected to an amine group.A sulfonamide is a compound that contains this group. The general formula is RSO2NH2, where R is some organic group. For example, "methanesulfonamide" is CH3SO2NH2...
group. It is used for the treatment of migraine
Migraine
Migraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...
headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
s. Sumatriptan is produced and marketed by various drug manufacturers with many different trade names such as Sumatriptan, Imitrex, Imigran, Imigran recovery.
Approval and availability
Sumatriptan was the first clinically available triptan (in 1991). In the United States and most developed countries, it is available only by medical prescription. Several dosage forms for sumatriptan have been approved, including tabletTablet
A tablet is a pharmaceutical dosage form. It comprises a mixture of active substances and excipients, usually in powder form, pressed or compacted from a powder into a solid dose...
s, solution for injection
Injection (medicine)
An injection is an infusion method of putting fluid into the body, usually with a hollow needle and a syringe which is pierced through the skin to a sufficient depth for the material to be forced into the body...
, and nasal inhaler
Inhaler
An inhaler or puffer is a medical device used for delivering medication into the body via the lungs. It is mainly used in the treatment of asthma and Chronic Obstructive Pulmonary Disease . Zanamivir , used to treat influenza, must be administered via inhaler...
s.
On April 15, 2008, the US FDA approved a combination of sumatriptan and naproxen
Naproxen
Naproxen sodium is a nonsteroidal anti-inflammatory drug commonly used for the reduction of pain, fever, inflammation and stiffness caused by conditions such as:...
, an NSAID. This combination has shown a benefit over either medicine used separately.
In July 2009, the US FDA approved a single-use jet injector
Jet injector
A jet injector is a type of medical injecting syringe that uses a high-pressure narrow jet of the injection liquid instead of a hypodermic needle to penetrate the epidermis...
formulation of sumatriptan. The device delivers a subcutaneous injection of 6 mg sumatriptan. A similar application has been filed in Europe.
Phase III studies with a iontophoretic transdermal patch
Transdermal patch
A transdermal patch is a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and into the bloodstream. Often, this promotes healing to an injured area of the body. An advantage of a transdermal drug delivery route over other types of...
(Zelrix) started in July 2008. This patch uses low voltage
Voltage
Voltage, otherwise known as electrical potential difference or electric tension is the difference in electric potential between two points — or the difference in electric potential energy per unit charge between two points...
controlled by a pre-programmed microchip
Microchip
Microchip can also refer to:* Integrated circuit, a set of electronic components on a single unit.* Microchip Technology, a company that makes popular 8, 16 and 32-bit microcontroller lines.* Microchip implant , a microchip implanted into animals....
to deliver a single dose of sumatriptan through the skin within 30 minutes.
Mode of action
Sumatriptan is structurally similar to serotoninSerotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
(5HT), and is a 5-HT (types 5-HT1D and 5-HT1B) agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
. The specific receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
subtypes it activates are present on the cranial arteries and veins. Acting as an agonist at these receptors, Sumatriptan reduces the vascular inflammation associated with migraine.
The specific receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
subtype it activates is present in the cranial and basilar arteries
Artery
Arteries are blood vessels that carry blood away from the heart. This blood is normally oxygenated, exceptions made for the pulmonary and umbilical arteries....
. Activation of these receptors causes vasoconstriction
Vasoconstriction
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, particularly the large arteries, small arterioles and veins. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in...
of those dilated arteries. Sumatriptan is also shown to decrease the activity of the trigeminal nerve
Trigeminal nerve
The trigeminal nerve contains both sensory and motor fibres. It is responsible for sensation in the face and certain motor functions such as biting, chewing, and swallowing. Sensory information from the face and body is processed by parallel pathways in the central nervous system...
, which, it is presumed, accounts for sumatriptan's efficacy in treating cluster headaches
Cluster headache
Cluster headache, nicknamed "suicide headache", is a neurological disease that involves, as its most prominent feature, an immense degree of pain in the head. Cluster headaches occur periodically: spontaneous remissions interrupt active periods of pain. The cause of the disease is currently unknown...
. The injectable form of the drug has been shown to abort a cluster headache within fifteen minutes in 96% of cases.
Pharmacokinetics
Sumatriptan is administered in several forms; tablets, subcutaneous injectionSubcutaneous injection
A subcutaneous injection is administered as a bolus into the subcutis, the layer of skin directly below the dermis and epidermis, collectively referred to as the...
, and nasal spray. Oral administration (as succinate) suffers from poor bioavailability
Bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...
, partly due to presystemic metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
—some of it gets broken down in the stomach and bloodstream before it reaches the target arteries. A new rapid-release tablet formulation has the same bioavailability, but the maximum concentration is achieved on average 10–15 minutes earlier. When injected, sumatriptan is faster-acting (usually within 10 minutes), but the effect lasts for a shorter time. Sumatriptan is metabolised primarily by monoamine oxidase A
Monoamine oxidase
L-Monoamine oxidases are a family of enzymes that catalyze the oxidation of monoamines. They are found bound to the outer membrane of mitochondria in most cell types in the body. The enzyme was originally discovered by Mary Bernheim in the liver and was named tyramine oxidase...
into an indole acetic acid analogue, part of which is further conjugated with glucuronic acid
Glucuronic acid
Glucuronic acid is a carboxylic acid. Its structure is similar to that of glucose. However, glucuronic acid's sixth carbon is oxidized to a carboxylic acid...
. These metabolites are excreted in the urine and bile. Only about 3% of the active drug may be recovered unchanged.
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.
Side-effects
Large doses of sumatriptan (200 mg/day) can cause sulfhemoglobinemiaSulfhemoglobinemia
Sulfhemoglobinemia is a rare condition in which there is excess sulfhemoglobin in the blood. The pigment is a greenish derivative of hemoglobin which cannot be converted back to normal, functional hemoglobin...
, a rare condition in which the blood changes from red to greenish-black, due to the integration of sulfur
Sulfur
Sulfur or sulphur is the chemical element with atomic number 16. In the periodic table it is represented by the symbol S. It is an abundant, multivalent non-metal. Under normal conditions, sulfur atoms form cyclic octatomic molecules with chemical formula S8. Elemental sulfur is a bright yellow...
into the hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
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 Imitrex Injection or Tablets. Events reported have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation.
The most common side-effects reported by at least 2% of patients in controlled trials of Imitrex (25, 50, and 100 mg tablets) for migraine are atypical sensations (paresthesias and warm/cold sensations) reported by 4% in the placebo group and 5-6% in the Imitrex groups, pain and other pressure sensations (including chest pain) reported by 4% in the placebo group and 6-8% in the Imitrex groups, neurological events (vertigo
Vertigo
Vertigo is a form of dizziness.Vertigo may also refer to:* Vertigo , a 1958 film by Alfred Hitchcock**Vertigo , its soundtrack** Vertigo effect, or Dolly zoom, a special effect in film, named after the movie...
) reported by less than 1% in the placebo group and less than 1% to 2% in the Imitrex groups. Malaise/fatigue occurred in less than 1% of the placebo group and 2-3% of the Imitrex groups.
Generics
On November 6, 2008, Par PharmaceuticalPar Pharmaceutical
Par Pharmaceutical develops, manufactures and markets generic and branded specialty pharmaceuticals. Par was founded in 1978 and initially traded on the New York Stock Exchange in 1987...
announced that it would begin shipping generic versions of Imitrex Injection (sumatriptan succinate injection) 4 mg and 6 mg starter kits and 4 mg and 6 mg pre-filled syringe cartridges to the trade immediately. In addition, Par anticipates launching the 6 mg vials early in 2009.
Mylan Laboratories Inc. has received FDA approval for its generic version of Imitrex tablets in 25-, 50-, and 100-milligram doses. The drug will soon be available, or is already available, in European markets, since Glaxo's patent protections have expired in those jurisdictions. However, sales of the generic drug are still restricted in the U.S., since Glaxo won an extension on their patent until 2009. A generic version of the drug in tablet form became available December 2008 in the United States and is distributed by Ranbaxy.
See also Sumavel DosePro (above).