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Initial U.S. Approval: 2009
SABRIL (vigabatrin) is available as a white, film-coated tablet for oral administration. Each tablet contains 500 mg vigabatrin. Tablets also contain as inactive ingredients: hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycols, povidone, sodium starch glycolate, and titanium dioxide. Vigabatrin is an oral antiepileptic drug with the chemical name (±) 4-amino-5-hexenoic acid. It is a racemate consisting of two enantiomers. The molecular formula is C6H11NO2 and the molecular weight is 129.16.
Vigabatrin is a white to off-white powder which is freely soluble in water, slightly soluble in methyl alcohol, very slightly soluble in ethyl alcohol and chloroform, and insoluble in toluene and hexane. The pH of a 1% aqueous solution is about 6.9. The n-octanol/water partition coefficient of vigabatrin is about 0.011 (log P=-1.96) at physiologic pH. Vigabatrin melts with decomposition in a 3-degree range within the temperature interval of 171°C to 176°C. The dissociation constants (pKa) of vigabatrin are 4 and 9.7 at room temperature (25°C).
Mechanism of Action
The precise mechanism of vigabatrin's anti-seizure effect is unknown, but it is believed to be the result of its action as an irreversible inhibitor of y-aminobutyric acid transaminase (GABA-T), the enzyme responsible for the metabolism of the inhibitory neurotransmitter GABA. This action results in increased levels of GABA in the central nervous system.
No direct correlation between plasma concentration and efficacy has been established. The duration of drug effect is presumed to be dependent on the rate of enzyme re-synthesis rather than on the rate of elimination of the drug from the systemic circulation
INDICATIONS AND USAGE
Refractory Complex Partial Seizures in Adults
SABRIL® is indicated as adjunctive therapy for adult patients 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 [see WARNINGS AND PRECAUTIONS, Vision Loss]. SABRIL is not indicated as a first line agent for complex partial seizures.
USE IN SPECIFIC POPULATIONS
Pregnancy: Based on animal data, may cause fetal harm. Pregnancy registry available.
Nursing Mothers: SABRIL is excreted in human milk.
Renal Impairment: Dose adjustment recommended.
WARNINGS AND PRECAUTIONS
Decreased phenytoin plasma levels have been reported.
Most common adverse reactions (change of
placebo) in addition to permanent vision loss in adult
controlled trials with vigabatrin were fatigue, somnolence,
nystagmus, tremor, vision blurred, memory impairment, weight
gain, arthralgia, abnormal coordination, and confusional state.
To report SUSPECTED ADVERSE REACTIONS, contact Lundbeck Inc. at 1-800-455-1141 or www.lundbeckinc.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DOSAGE AND ADMINISTRATION
Refractory Complex Partial Seizures in Adults
SABRIL 500 mg tablets should be given as twice daily oral administration with or without food. Therapy should be initiated at 1 g/day (500 mg twice daily). Total daily dose may be increased in 500 mg increments at weekly intervals depending on response. The recommended dose of SABRIL in adults is 3 g/day (1.5 g twice daily). A 6 g/day dose has not been shown to confer additional benefit compared to the 3 g/day dose and is associated with an increased incidence of adverse events.
Patients with Renal Impairment
SABRIL is primarily eliminated through the kidney. In patients with renal impairment, dose adjustments should be made as follows:
In patients with mild renal impairment (CLcr >50 to 80 mL/min), the dose should be decreased by 25%; in patients with moderate renal impairment (CLcr >30 to 50 mL/min), the dose should be decreased by 50%; and in patients with severe renal impairment (CLcr >10 to <30 mL/min), the dose should be decreased by 75%.
CLcr in mL/min may be estimated from a serum creatinine (mg/dL) determination using the following formula:
CLcr *= [140-age (years)]× weight (kg)/72× serum creatinine (mg/dL)]
*[× 0.85 for female patients]
The effect of dialysis on SABRIL clearance has not been adequately studied.
General Dosing Considerations
SABRIL should be withdrawn gradually. In controlled clinical studies in adults with CPS, vigabatrin was tapered by decreasing the daily dose 1 g/day on a weekly basis until discontinued [see WARNINGS AND PRECAUTIONS, Withdrawal of Antiepileptic Drugs (AEDs)].
HOW SUPPLIED/STORAGE AND HANDLING
Each SABRIL film-coated tablet contains 500 mg vigabatrin and is white, film-coated, oval, biconvex, scored on one side, and debossed with OV 111 on the other.
NDC 67386-111-01: Bottles of 100.
Store at 20-25°C (68-77°F). See USP controlled room temperature
Package Insert data:
Marketed by: Lundbeck Inc., Deerfield, IL 60015, U.S.A.
® Trademark of Lundbeck Inc.
Revised: September 2010
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