|Trade names||Sabril, Vigadrone, Kigabeq, others|
|Side effects||Permanent vision problems, headache, tiredness, abdominal pain, swelling|
|Typical dose||0.5 to 1.5 grams BID (adults)|
|Elimination half-life||5–8 hours in young adults, 12–13 hours in the elderly.|
|Chemical and physical data|
|Molar mass||129.159 g·mol−1|
|3D model (JSmol)|
|Melting point||171 to 177 °C (340 to 351 °F)|
Vigabatrin, sold under the brand name Sabril, is a medication used to treat epilepsy. Specifically it is used for complex partial seizures that are uncontrolled with other measures or for infantile spasms. It is taken by mouth.
Common side effects include headache, tiredness, abdominal pain, vision problems, and swelling. Permanent vision problems occur in about a third of people; with an onset of a month to years after starting treatment. It is believed to work by decreasing the breakdown of γ-aminobutyric acid (GABA).
Vigabatrin was approved for medical use in the United States in 2009. It became available as a generic medication in 2019. In the United Kingdom a hundred tablets of 500 mg costs the NHS about £45 as of 2021. In the United States this amount costs about 10,600 USD. In Canada this amount costs about 96 CAD.
In Canada, vigabatrin is approved for use with other medications in treatment resistant epilepsy, complex partial seizures, secondary generalized seizures, and for monotherapy use in infantile spasms in West syndrome.
As of 2003, vigabatrin is approved in Mexico for the treatment of epilepsy that is not satisfactorily controlled by conventional therapy (adjunctive or monotherapy) or in recently diagnosed patients who have not tried other agents (monotherapy).
In the USA it is indicated as monotherapy for children one month to two years of age with infantile spasms for whom the potential benefits outweigh the potential risk of vision loss, and as add-on therapy for adults with refractory complex partial seizures (CPS) who have inadequately responded to several alternative treatments and for whom the potential benefits outweigh the risk of vision loss.
Vigabatrin is also used to treat seizures in succinic semialdehyde dehydrogenase deficiency (SSADHD), which is an inborn GABA metabolism defect that causes intellectual disability, hypotonia, seizures, speech disturbance, and ataxia through the accumulation of γ-Hydroxybutyric acid (GHB). Vigabatrin helps lower GHB levels through GABA transaminase inhibition. However, this is in the brain only; it has no effect on peripheral GABA transaminase, so the GHB keeps building up and eventually reaches the brain.
Central nervous system
Sleepiness (12.5%), headache (3.8%), dizziness (3.8%), nervousness (2.7%), depression (2.5%), memory disturbances (2.3%), diplopia (2.2%), aggression (2.0%), ataxia (1.9%), vertigo (1.9%), hyperactivity (1.8%), vision loss (1.6%) (See below), confusion (1.4%), insomnia (1.3%), impaired concentration (1.2%), personality issues (1.1%). Out of 299 children, 33 (11%) became hyperactive.
Some patients develop psychosis during the course of vigabatrin therapy, which is more common in adults than in children. This can happen even in patients with no prior history of psychosis. Other rare CNS side effects include anxiety, emotional lability, irritability, tremor, abnormal gait, and speech disorder.
Body as a whole
A teratology study conducted in rabbits found that a dose of 150 mg/kg/day caused cleft palate in 2% of pups and a dose of 200 mg/kg/day caused it in 9%. This may be due to a decrease in methionine levels, according to a study published in March 2001. In 2005, a study conducted at the University of Catania was published stating that rats whose mothers had consumed 250–1000 mg/kg/day had poorer performance in the water maze and open-field tasks, rats in the 750-mg group were underweight at birth and did not catch up to the control group, and rats in the 1000 mg group did not survive pregnancy.
There is no controlled teratology data in humans to date.
In 2003, vigabatrin was shown by Frisén and Malmgren to cause irreversible diffuse atrophy of the retinal nerve fiber layer in a retrospective study of 25 patients. This has the most effect on the outer area (as opposed to the macular, or central area) of the retina. Visual field defects had been reported as early as 1997 by Tom Eke and others, in the UK. Some authors, including Comaish et al. believe that visual field loss and electrophysiological changes may be demonstrable in up to 50% of Vigabatrin users.
In 1984, Drs Rimmer and Richens at the University of Wales reported that administering vigabatrin with phenytoin lowered the serum phenytoin concentration in patients with treatment-resistant epilepsy. Five years later, the same two scientists reported a fall in concentration of phenytoin of 23% within five weeks in a paper describing their failed attempt at elucidating the mechanism behind this interaction.
Vigabatrin is an irreversible mechanism-based inhibitor of gamma-aminobutyric acid aminotransferase (GABA-AT), the enzyme responsible for the catabolism of GABA. Inhibition of GABA-AT results in increased levels of GABA in the brain. Vigabatrin is a racemic compound, and its [S]-enantiomer is pharmacologically active.,
With most drugs, elimination half-life is a useful predictor of dosing schedules and the time needed to reach steady state concentrations. In the case of vigabatrin, however, it has been found that the half-life of biologic activity is far longer than the elimination half-life.
For vigabatrin, there is no range of target concentrations because researchers found no difference between the serum concentration levels of responders and those of non-responders. Instead, the duration of action is believed to be more a function of the GABA-T resynthesis rate; levels of GABA-T do not usually return to their normal state until six days after stopping the medication.
Vigabatrin was developed in the 1980s with the specific goal of increasing GABA concentrations in the brain in order to stop an epileptic seizure. To do this, the drug was designed to irreversibly inhibit the GABA transaminase, which degrades the GABA substrate.
It was approved for treatment in the United Kingdom in 1989, and the United States in 2009. It was delayed in the US in 1983 because animal trials produced intramyelinic edema, however, the effects were not apparent in human trials so the drug design continued. In 1997, the trials were temporarily suspended because it was linked to peripheral visual field defects.
Society and culture
Vigabatrin is sold as Sabril in Canada, Mexico, and the United Kingdom. The brand name in Denmark is Sabrilex. Sabril was approved in the United States on August 21, 2009 and is marketed in the U.S. by Lundbeck Inc., which acquired Ovation Pharmaceuticals, the U.S. sponsor in March 2009.
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