Vigabatrin (Sabril, Aventis)
Vigabatrin is marketed in most major countries around the world, excluding the United States and Japan, where regulatory approval has not been forthcoming, because of effects of the drug on vision and the retina.
Vigabatrin is another "designer drug," that works by blocking metabolism of GABA, the brain's main inhibitory neurotransmitter. Accumulation of GABA inhibits seizures. Sabril is effective for partial and secondarily generalized seizures, but it also has efficacy in certain pediatric syndromes, such as infantile spasms, which are very difficult to treat with other medications. Vigabatrin has apparently good efficacy as an add-on drug for intractable partial seizures, with half of people having seizures reduced by at least 50%.
Typical side effects of vigabatrin include dizziness, unsteadiness, sleepiness, and mild thinking or memory impairment, but thinking is usually clearer than with many of the older medications. A few percent of treated patients develop depression or other serious psychiatric problems, which reverses when the medication is discontinued.
The Food and Drug Administration (FDA) in the United States has denied release of vigabatrin because of visual field changes, in up to 30% of people who take vigabatrin for more than a year. These visual field changes may or may not be noticed by the patient, as loss of peripheral vision, but specialize ophthalmological testing can disclose the inability to see in patches outside the central regions of one or both eyes.
Rarely, the visual loss involves central fields of vision, which can cause problems with reading and gross seeing. Visual field changes result from a toxic effect of vigabatrin on the retina. Visual field changes can be permanent, even after stopping vigabatrin. Therefore, use of the drug requires demonstration that no alternatives are effective for the seizures. Regular checking of visual fields by historical queries, clinical exams, and eye tests are important.
Summary Data for Vigabatrin
Pill sizes: 500 mg
Liquid for oral: none.
Injectable: none.
Typical adult dose: the manufacturer recommends 1,000 mg/d divided into two doses. I prefer to start with 500 mg at night for a week, then twice a day for a week, then 500 mg in the am and 1,000 mg in the pm for a week, then 1,000 mg twice a day for a week. Target dose is 1,000 - 3,000 mg per day divided into two daily doses. Half-life would permit daily dosing, but GI side effects might require splitting the dose.
Typical pediatric dose: I start with 250 mg per day, and increase over several weeks to 500 - 2,000 mg/d.
Metabolism: VGB irreversibly inhibits GABA-transaminase, the key enzyme for breaking down GABA. Vigabatrin is mainly cleared by the kidney.
Half-life: The relevant effect is inhibition of GABA-transaminase, which lasts about 5 days.
Serum levels: not relevant.
Pregnancy: Category C - can cause birth defects in animals, unknown in humans.
VGB decreases effects of other drugs: Can lower efficacy of Dilantin, by an unknown mechanism.
Dangerous Side Effects
Retinal toxicity, with visual loss; rare psychiatric side effects including psychosis and hallucinations; rare induction of myoclonic or nonconvulsive seizures with toxic doses. Vigabatrin causes loss of nerve linings (myelin) in animal models, a condition allied to multiple sclerosis, but no such action has been found in humans.
Common Side Effects
Sleepiness, dizziness, GI upset, blurred vision.
Other Side Effects
Headache, personality changes, rash (rare).