It is an antiepileptic drug that inhibits the breakdown of γ-aminobutyric acid by acting as an inhibitor of the enzyme transaminase.
In Canada, vigabatrin is approved for use as an adjuvant treatment (with other drugs) in refractory epilepsy, complex partial seizures, secondary generalized seizures and for monotherapy 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 (adjuvant or monotherapy) or in newly diagnosed patients who have not tried other agents (monotherapy).
Vigabatrin is also indicated for the use of monotherapy in secondarily generalized tonic-clonic seizures, partial seizures and in infantile spasms due to West’s syndrome.
The drug is indicated as monotherapy for pediatric patients from one month to two years of age with infantile spasms for whom the potential benefits outweigh the potential risk of vision loss and as adjuvant therapy (complement) for adult patients with refractory complex partial seizures.
It has been reported that vigabatrin reduced seizures by 50-100% in 85% of children with Lennox-Gastaut syndrome who had poor results with sodium valproate.
Vigabatrin reduced the symptoms of tetracispine-induced pancreatickinin panic disorder, as well as elevated levels of cortisol and ACTH, in healthy volunteers.
It is also used to treat seizures in the deficiency of semialdehyde succinic dehydrogenase (SSADHD), which is a metabolic defect of innate that causes intellectual disability, hypotonia, seizures, speech disorders and ataxia through the accumulation of γ-hydroxybutyric acid ( GHB).
Vigabatrin helps decrease GHB levels through the inhibition of GABA transaminase. However, this is only in the brain; it has no effect on peripheral GABA transaminase, so that GHB continues to accumulate and eventually reaches the brain.
Central Nervous System:
- Drowsiness (12.5%).
- Headache (3.8%).
- Dizziness (3.8%).
- Nervousness (2.7%).
- Depression (2.5%).
- Alterations of memory (2.3%).
- Diplopía (2.2%).
- Aggression (2.0%).
- Ataxia (1.9%).
- Vertigo (1.9%).
- Hyperactivity (1.8%).
- Loss of vision (1.6%).
- Confusion (1.4%).
- Insomnia (1.3%).
- Personality problems (1.1%).
Of 299 children, 33 (11%) became hyperactive. Some patients develop psychosis during the course of therapy with vigabatrin, which is more common in adults than in children. This can happen even in patients without a history of psychosis.
Other rare side effects of the CNS include anxiety, emotional lability, irritability, tremor, abnormal gait, and speech disorder.
- Abdominal pain (1.6%).
- Constipation (1.4%).
- Vomiting (1.4%).
- Nausea (1.4%).
Dyspepsia and increased appetite occurred in less than 1% of subjects in clinical trials.
- Fatigue (9.2%).
- Weight gain (5.0%).
- Asthenia (1.1%).
In 2003, Frisén and Malmgren demonstrated that vigabatrin causes an irreversible diffuse atrophy of the retinal nerve fiber layer in a retrospective study of 25 patients.
This has the greatest effect on the external area (unlike the macular or central area) of the retina. The defects of the visual field had already been reported in 1997 by Tom Eke and others, in the United Kingdom.
Some authors, including Comaish et al. believe that loss of visual field and electrophysiological changes can be demonstrated in up to 50% of Vigabatrin users.
A study published in 2002 found that vigabatrin causes a statistically significant increase in the plasma clearance of carbamazepine.
In 1984, doctors Rimmer and Richens of the University of Wales reported that the administration of vigabatrin with phenytoin reduced the serum concentration of phenytoin in patients with refractory epilepsy.
Later the same two scientists reported a drop in phenytoin concentration of 23% in five weeks in an article describing their failed attempt to elucidate the mechanism behind this interaction.
Vigabatrin is an irreversible inhibitor of gamma-aminobutyric acid aminotransferase (GABA-AT), the enzyme responsible for the catabolism of GABA, which increases the level of GABA in the brain.
Vigabatrin is a racemic compound and its [S] -enantiomer is pharmacologically active.
Vigabatrin is sold as Sabril in Canada, Mexico, and the United Kingdom.
The brand in Denmark is Sabrilex. Sabril was approved in the United States on August 21, 2009 and is currently marketed in the US. UU For Lundbeck Inc., acquired by Ovation Pharmaceuticals, the sponsor of EE. UU