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Vigabatrin is an anticonvulsant that inhibits the catabolism of GABA. It is an analog of GABA, but it is not a receptor agonist.
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Mechanism of action
Vigabatrin is an irreversible inhibitor of gamma-aminobutyric acid transaminase (GABA-T), the enzyme responsible for the catabolism of GABA, which increases the level of GABA in the synapses.
Vigabatrin is a racemic compound, and its S-enantiomer is pharmacologically active.
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Pharmacokinetics
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.•
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Canada
In Canada, vigabatrin is approved for use as an adjunctive treatment (with other drugs) in treatment resistant epilepsy, complex partial seizures, secondary generalized seizures, and for monotherapy use in infantile spasms in West syndrome.
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Mexico
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).
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Unapproved/Investigational
In November of 2001, a team of scientists lead by Peter Zwanzger of the University of Munich reported that vigabatrin reduced cholecystokinin tetrapeptide-induced symptoms of panic disorder, in addition to elevated cortisol and ACTH levels, in healthy volunteers.•
In 1994, Feucht and Brantner-Inthaler reported that vigabatrin reduced seizures by 50-100% in 85% of children with Lennox-Gastaut syndrome who had poor results with a valproate.•
In 1984, a double-blind crossover-study of six Huntington's disease patients—five of them on antipsychotics—reported that vigabatrin did little, if anything, to improve hyperkinetic movements, the ability to carry out daily activities, or normalize motor function.•
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Common
Out of 2,081 subjects, somnolence (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 abnormalities (1.6%), confusion (1.4%), insomnia (1.3%), impaired concentration (1.2%), personality disorder (1.1%).
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Rare
Some patients develop psychosis during the course of vigabatrin therapy,•
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Common
Abdominal pain (1.6%), constipation (1.4%), vomiting (1.4%), and nausea (1.4%).
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Rare
Dyspepsia and increased appetite occurred in less than 1% of subjects in clinical trials.[
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Common
Fatigue (9.2%), weight gain (5.0%), asthenia (1.1%).
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Teratogenicity
A teratology study conducted in rabbits found that a dose of 150mg/kg/day caused cleft palate in 2% of pups and a dose of 200 mg/kg/day caused it in 9%.
There is no controlled teratology data in humans to date.
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More on "abnormal vision"
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.•
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Drug interactions
A study published in 2002 found that vigabatrin causes a statistically significant increase in plasma clearance of carbamazepine.•
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.• The concentration of phenytoin falls to 23% within five weeks, according to an experiment published in 1989 by the same two scientists that tried and failed to elucidate the mechanism behind this interaction.•
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Brand names
Vigabatrin is sold as Sabril® in Canada,
and the United Kingdom.
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