Approved August 21, 2009

VIGABATRIN
(FDA Category 1S)

SABRIL(R) (Lundbeck Inc) is an antiepileptic drug that is a synthetic derivative of gamma-aminobutyric acid (GABA).

DOSING INFORMATION: The recommended initial dose of vigabatrin for infantile spasm in children 1 month to 2 years of age is 50 mg/kg/day orally in 2 divided doses. The dose may be titrated by 25 to 50 mg/kg/day increments every 3 days up to a maximum dose of 150 mg/kg/day. Gradual tapering of the dose is recommended in epileptic patients to prevent a rebound increase in seizure frequency and possible adverse events. In clinical studies, vigabatrin was tapered by decreasing the daily dose by 25 to 50 milligrams/kilogram every 3 to 4 days until discontinued. For the treatment of refractory complex partial seizures, the recommended initial dose of vigabatrin is 500 mg orally twice daily. The total daily dose may be titrated in 500-mg increments at weekly intervals to a maximum recommended dose of 1500 mg twice daily (3 grams/day). Vigabatrin was also tapered by decreasing the daily dose by 1 gram/day on a weekly basis until discontinued to prevent a rebound increase in seizure frequency in clinical studies.

PHARMACOKINETICS: Following oral administration, vigabatrin is almost completely absorbed. Tmax is approximately 2.5 hr in infants and about 1 hr in children. The oral solution and the tablet formulation are bioequivalent. No direct correlation exists between plasma concentrations and efficacy. Vigabatrin does not bind to plasma proteins, it is widely distributed throughout the body with a mean steady-state Vd of 1.1 L/kg. Vigabatrin is not significantly metabolized. Because it is primarily renally eliminated, dose reduction in patients with renal impairment is recommended. The half-life is about 5.7 hr in infants and 7.5 hr in adults. The duration of drug effect is presumed to be dependent on the rate of enzyme resynthesis rather than on the rate of drug elimination. Vigabatrin induces CYP2C9, but does not induce other CYP450 enzyme systems.

CAUTIONS: Vigabatrin causes permanent bilateral concentric visual field constriction which increases with total dose and duration of use. Periodic vision testing is required and vigabatrin should not be used in patients at high risk for other types of irreversible vision damage. Vigabatrin is only available through a special restricted distribution program. Periodic vision testing is required for patients receiving vigabatrin therapy. Antiepileptic drugs including vigabatrin, increase the risk or suicidal thoughts and behaviors. During clinical trials in adult patients, the more frequently reported adverse events were; fatigue, somnolence, nystagmus, tremor, blurred vision, impaired memory, weight gain, arthralgia, abnormal coordination, and confusion.

FDA APPROVED INDICATIONS: Vigabatrin is indicated as monotherapy for pediatric patients (1 month to 2 years of age) with infantile spasms for whom the potential benefits outweigh the potential risk of vision loss. It is also indicated as adjunctive therapy for adult patients with refractory complex partial seizures who have responded inadequately to several alternative treatments.