Important Safety Information

Sabril^® (vigabatrin) Tablets
Sabril^® (vigabatrin) for Oral Solution

Indication
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. SABRIL is not indicated as a first line agent for complex partial seizures.

SABRIL is indicated as monotherapy for pediatric patients 1 month to 2 years of age with infantile spasms (IS) for whom the potential benefits outweigh the potential risk of vision loss.

Important Safety Information

SABRIL causes permanent vision loss in infants, children, and adults. Because assessing vision loss is difficult in children, the frequency and extent of vision loss in infants and children is poorly characterized.

In adults, SABRIL causes progressive and permanent bilateral concentric visual field constriction in 30% or more of patients that ranges in severity from mild to severe, including tunnel vision to within 10° of visual fixation, and can result in disability. In some cases, SABRIL also can damage the central retina and may decrease visual acuity. The lowest dose and shortest exposure to SABRIL should be used that is consistent with clinical objectives.

Because of the risk of permanent vision loss, SABRIL should be withdrawn from a pediatric patient treated for IS (1 month to 2 years of age) who fails to show substantial clinical benefit within 2 to 4 weeks of treatment initiation, or sooner if treatment failure becomes obvious, or an adult patient treated for refractory CPS as adjunctive therapy who fails to show substantial clinical benefit within 3 months of treatment initiation, or sooner if treatment failure becomes obvious.

Vision testing for adults treated for refractory CPS as adjunctive therapy is required at baseline (no later than 4 weeks after starting SABRIL) and at least every 3 months while on therapy. Vision testing for pediatric patients treated for IS is required to the extent possible at baseline (no later than 4 weeks after starting SABRIL) and at least every 3 months while on therapy. Once detected, vision loss is not reversible. It is expected that, even with frequent monitoring, some patients will develop severe vision loss. Vision testing for adults and pediatric patients is also required about 3 to 6 months after discontinuing SABRIL therapy. The onset of vision loss from SABRIL is unpredictable and can occur within weeks of starting treatment or sooner, or at any time during treatment, even after months or years. Patient response to and continued need for SABRIL should be periodically reassessed.

Symptoms of vision loss from SABRIL are unlikely to be recognized by the patient, parent or caregiver before vision loss is severe. Vision loss of milder severity, although unrecognized by the patient, parent or caregiver may still adversely affect function. The possibility that vision loss from SABRIL may be more common or more severe, or have more severe functional consequences in infants and children than in adults, cannot be excluded.

SABRIL should not be used in patients with, or at high risk of, other types of irreversible vision loss or with other drugs associated with serious adverse ophthalmic effects such as retinopathy or glaucoma unless the benefits clearly outweigh the risks. The interaction of other types of irreversible vision damage with vision damage from SABRIL has not been well characterized, but is likely adverse.

In adult patients treated for CPS, dose adjustment, including initiating treatment with a lower dose, is necessary in patients with renal impairment. A 16% to 20% average reduction in total phenytoin plasma levels was reported in controlled clinical studies.

Abnormal MRI signal changes have been observed in some infants treated for IS with SABRIL. These changes generally resolved with discontinuation of treatment and in a few patients the lesion resolved despite continued use.

SABRIL should be discontinued gradually to avoid withdrawal seizures. In controlled clinical studies in adults with CPS, SABRIL was tapered by decreasing the daily dose at a rate of 1 g/day on a weekly basis until discontinued. In a controlled clinical study in patients with IS, vigabatrin was tapered by decreasing the daily dose at a rate of 25 to 50 mg/kg every 3 to 4 days.

Antiepileptic drugs (AEDs), including SABRIL, increase the risk of suicidal thoughts or behavior. Adult patients should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior and/or any unusual changes in mood or behavior.

SABRIL has been shown to cause neurotoxicity, anemia, somnolence, fatigue, weight gain, edema, and symptoms of peripheral neuropathy. SABRIL should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus. Vigabatrin is excreted in human milk and may cause serious adverse events in nursing infants.

The most commonly observed adverse reactions reported in 2 add-on clinical studies of adults with refractory CPS treated with SABRIL as adjunctive therapy with the recommended dose of 3 g/day (≥10% and at least 5% greater than placebo) were dizziness (SABRIL 24% vs placebo 17%), fatigue (SABRIL 23% vs placebo 16%), somnolence (SABRIL 22% vs placebo 13%), tremor (SABRIL 15% vs placebo 8%), blurred vision (SABRIL 13% vs placebo 5%), and arthralgia (SABRIL 10% vs placebo 3%). 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.

The most common adverse events reported by >5% of infants taking SABRIL for IS occurring more frequently than placebo in a randomized, placebo-controlled IS study with a 5-day double-blind treatment phase (n=40) were somnolence (SABRIL 45% vs placebo 30%), bronchitis (SABRIL 30% vs placebo 15%), ear infection (SABRIL 10% vs placebo 5%), and acute otitis media (SABRIL 10% vs placebo 0%).

Pregnancy Registry: To provide information regarding the effects of in utero exposure to SABRIL, physicians are advised to recommend that pregnant patients taking SABRIL enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll-free number 1-888-233-2334, and must be done by patients themselves. Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/.

Oral Solution: For more information, please see the full Prescribing Information including Boxed Warning, Medication Guide, and Dosing Instructions.

Solución oral: Para más información, vea por favor la información que prescribe completa incluyendo la advertencia encajonada, guía de la medicación, y las instrucciones de la dosificación.

Tablets: For more information, please see the full Prescribing Information including Boxed Warning and Medication Guide.

Tabletas: Para más información, vea por favor la información que prescribe completa incluyendo la advertencia encajonada, y guía de la medicación.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.