Vegarin® (vigabatrin) is an oral antiepileptic drug (AED) approved both as a tablet and oral solution by the U.S. Food and Drug Administration (FDA) for two different epilepsies.
Each tablet contains 500 mg vigabatrin
Vegarin is indicated as monotherapy for pediatric patients one month to two years of age with infantile spasms (IS) for whom the potential benefits outweigh the potential risk of vision loss and as adjunctive (or add-on) treatment for adults 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. Vegarin is not indicated as a first line agent for adults with CPS. Vegarin causes permanent bilateral concentric visual field constriction in 30 percent or more of patients that ranges in severity from mild to severe, including tunnel vision to within 10 degrees of visual fixation and can result in disability. In some cases, Vegarin also can damage the central retina and may decrease visual acuity. Vegarin causes permanent vision loss in infants, children and adults.
The onset is unpredictable and can occur within weeks of starting treatment, or sooner, or at anytime during treatment even after months or years. Because of this risk of permanent vision loss, Vegarin approval is accompanied by an FDA-mandated Risk Evaluation and Mitigation Strategy (REMS) and is available only through a special restricted distribution program called SHARE (Support Help and Resources for Epilepsy).
Vegarin is the first and only therapy approved in the U.S. for the treatment of IS, a difficult-to-treat form of epilepsy that primarily affects infants and is characterized by spasms that typically occur in clusters of up to 100 at a time. Vegarin, as add-on therapy, is also another option for adult patients CPS who do not respond well enough to several other treatments. Vegarin should not be the first medicine used to treat CPS. In both IS and CPS, it is important that the patient and the patient’s doctor decide the possible benefit of taking Vegarin is more important than the risk of vision loss.
Vegarin was synthesized in 1975 in a deliberate attempt to find a molecule that would increase central nervous system levels of the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA). The precise mechanism of Vegarin’s antiseizure effect is unknown, but is believed to be the result of its action as an irreversible inhibitor of gamma-aminobutyric acid transaminase (GABA-T), the enzyme responsible for the metabolism of 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.
DESCRIPTION
VEGARIN® (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).
CLINICAL PHARMACOLOGY:
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
VEGARIN® 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]. VEGARIN® 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: VEGARIN® is excreted in human milk.
Renal Impairment: Dose adjustment recommended.
PRECAUTIONS
WARNINGS AND PRECAUTIONS
- VEGARIN® causes permanent vision loss
- Abnormal MRI signal changes have been reported in some infants with IS receiving VEGARIN®
- Antiepileptic drugs, including VEGARIN®, increase the risk of suicidal thoughts and behavior
- Dose should be tapered gradually to avoid withdrawal seizures
- VEGARIN® causes anemia
- VEGARIN® causes somnolence and fatigue
- VEGARIN® causes peripheral neuropathy
- VEGARIN® causes weight gain
- VEGARIN® causes edema
DRUG INTERACTIONS
Decreased phenytoin plasma levels have been reported.
ADVERSE REACTIONS
Most common adverse reactions (change of 5% over 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.
DOSAGE AND ADMINISTRATION
Refractory Complex Partial Seizures in Adults
VEGARIN® 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 VEGARIN® 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
VEGARIN® 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 VEGARIN® clearance has not been adequately studied.
General Dosing Considerations
VEGARIN® 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
VEGARIN® Tablet
Each VEGARIN® film-coated tablet contains 500 mg vigabatrin and is white, film-coated, oval, biconvex, scored on one side, and debossed with TP 111 on the other.
TPL 673SDF6-111-01: Bottles of 100.
Store at 20-25°C (68-77°F). See USP controlled room temperature
Package Insert data:
Vegarin®
(vigabatrin) Tablets
500 mg
100 Tablets