Vigabatrin Prescribing Information
- Vigabatrin can cause permanent bilateral concentric visual field constriction, including tunnel vision that can result in disability. In some cases, vigabatrin also can damage the central retina and may decrease visual acuity[see Warnings and Precautions (.)]5.1 Permanent Vision Loss
Vigabatrin can cause permanent vision loss. Because of this risk and because, when it is effective, vigabatrin provides an observable symptomatic benefit; patient response and continued need for treatment should be periodically assessed.
Based upon adult studies, 30 percent or more of patients can be affected with bilateral concentric visual field constriction ranging in severity from mild to severe. Severe cases may be characterized by tunnel vision to within 10 degrees of visual fixation, which can result in disability. In some cases, vigabatrin also can damage the central retina and may decrease visual acuity. Symptoms of vision loss from vigabatrin are unlikely to be recognized by patients or caregivers before vision loss is severe. Vision loss of milder severity, while often unrecognized by the patient or caregiver, can still adversely affect function.
Because assessing vision may be difficult in children, the frequency and extent of vision loss is poorly characterized in these patients. For this reason, the understanding of the risk is primarily based on the adult experience. The possibility that vision loss from vigabatrin may be more common, more severe, or have more severe functional consequences in children than in adults cannot be excluded.
The onset of vision loss from vigabatrin is unpredictable and can occur within weeks of starting treatment or sooner, or at any time after starting treatment, even after months or years.
The risk of vision loss increases with increasing dose and cumulative exposure, but there is no dose or exposure known to be free of risk of vision loss.
In patients with refractory complex partial seizures, vigabatrin should be withdrawn if a substantial clinical benefit is not observed within 3 months of initiating treatment. If, in the clinical judgment of the prescriber, evidence of treatment failure becomes obvious earlier than 3 months, treatment should be discontinued at that time
[see Dosage and Administration and Warnings and Precautions ].Vigabatrin should not be used in patients with, or at high risk of, other types of irreversible vision loss unless the benefits of treatment clearly outweigh the risks. The interaction of other types of irreversible vision damage with vision damage from vigabatrin has not been well-characterized, but is likely adverse.
Vigabatrin should not be used with other drugs associated with serious adverse ophthalmic effects such as retinopathy or glaucoma unless the benefits clearly outweigh the risks.
Monitoring of VisionMonitoring of vision by an ophthalmic professional with expertise in visual field interpretation and the ability to perform dilated indirect ophthalmoscopy of the retina is recommended
[see Warnings and Precautions ].For patients receiving vigabatrin, vision assessment is recommended at baseline (no later than 4 weeks after starting vigabatrin), at least every 3 months while on therapy, and about 3 to 6 months after the discontinuation of therapy. The diagnostic approach should be individualized for the patient and clinical situation.In adults and cooperative pediatric patients, perimetry is recommended, preferably by automated threshold visual field testing. Additional testing may also include electrophysiology (e.g., electroretinography [ERG]), retinal imaging (e.g., optical coherence tomography [OCT]), and/or other methods appropriate for the patient. In patients who cannot be tested, treatment may continue according to clinical judgment, with appropriate patient counseling. Because of variability, results from ophthalmic monitoring must be interpreted with caution, and repeat assessment is recommended if results are abnormal or uninterpretable. Repeat assessment in the first few weeks of treatment is recommended to establish if, and to what degree, reproducible results can be obtained, and to guide selection of appropriate ongoing monitoring for the patient.
The onset and progression of vision loss from vigabatrin is unpredictable, and it may occur or worsen precipitously between assessments. Once detected, vision loss due to vigabatrin is not reversible. It is expected that even with frequent monitoring, some vigabatrin patients will develop severe vision loss. Consider drug discontinuation, balancing benefit and risk, if vision loss is documented. It is possible that vision loss can worsen despite discontinuation of vigabatrin.
- The onset of vision loss from vigabatrin is unpredictable, and can occur within weeks of starting treatment or sooner, or at any time after starting treatment, even after months or years.
- Symptoms of vision loss from vigabatrin are unlikely to be recognized by patients or caregivers before vision loss is severe. Vision loss of milder severity, while often unrecognized by the patient or caregiver, can still adversely affect function.
- The risk of vision loss increases with increasing dose and cumulative exposure, but there is no dose or exposure known to be free of risk of vision loss.
- Vision assessment is recommended at baseline (no later than 4 weeks after starting vigabatrin), at least every 3 months during therapy, and about 3 to 6 months after the discontinuation of therapy.
- Once detected, vision loss due to vigabatrin is not reversible. It is expected that, even with frequent monitoring, some patients will develop severe vision loss.
- Consider drug discontinuation, balancing benefit and risk, if vision loss is documented.
- Risk of new or worsening vision loss continues as long as vigabatrin is used. It is possible that vision loss can worsen despite discontinuation of vigabatrin.
- Because of the risk of vision loss, vigabatrin should be withdrawn from patients with refractory complex partial seizures who fail to show substantial clinical benefit within 3 months of initiation and within 2 to 4 weeks of initiation for patients with infantile spasms, or sooner if treatment failure becomes obvious. Patient response to and continued need for vigabatrin should be periodically reassessed.
- Vigabatrin should not be used in patients with, or at high risk of, other types of irreversible vision loss unless the benefits of treatment clearly outweigh the risks.
- Vigabatrin should not be used with other drugs associated with serious adverse ophthalmic effects such as retinopathy or glaucoma unless the benefits clearly outweigh the risks.
- Use the lowest dosage and shortest exposure to vigabatrin consistent with clinical objectives[see Dosage and Administration (.)]2.1 Important Dosing and Administration InstructionsDosing
Use the lowest dosage and shortest exposure to vigabatrin tablets consistent with clinical objectives
[see Warnings and Precautions ].The vigabatrin dosing regimen depends on the indication, age group, weight, and dosage form (tablets or for oral solution)
[see Dosage and Administration ]. Patients with impaired renal function require dose adjustment[see Dosage and Administration ].Monitoring of vigabatrin plasma concentrations to optimize therapy is not helpful.
AdministrationVigabatrin tablets are given orally with or without food.
If a decision is made to discontinue vigabatrin tablets, the dose should be gradually reduced
[see Dosage and Administration and Warnings and Precautions ].
Vigabatrin tablets are available only through a restricted distribution program called the Vigabatrin REMS Program, because of the risk of permanent vision loss.
Notable requirements of the Vigabatrin REMS Program include the following:
- Prescribers must be certified by enrolling in the program, agreeing to counsel patients on the risk of vision loss and the need for periodic monitoring of vision, and reporting any event suggestive of vision loss to Vigabatrin REMS Program.
- Patients must enroll in the program.
- Pharmacies must be certified and must only dispense to patients authorized to receive vigabatrin tablets.
Further information is available at
Vigabatrin tablets are indicated for the treatment of:
- Refractory Complex Partial Seizures as adjunctive therapy in patients 2 years of age and older who have responded inadequately to several alternative treatments; Vigabatrin tablets are not indicated as a first line agent ()1.1 Refractory Complex Partial Seizures (CPS)
Vigabatrin tablets are indicated as adjunctive therapy for adults and pediatric patients 2 years of age and older with refractory complex partial seizures who have inadequately responded to several alternative treatments and for whom the potential benefits outweigh the risk of vision loss
[see Warnings and Precautions ]. Vigabatrin tablets are not indicated as a first line agent for complex partial seizures.
- Adults (17 years of age and older): Initiate at 1,000 mg/day (500 mg twice daily); increase total daily dose weekly in 500 mg/day increments, to the recommended dose of 3,000 mg/day (1,500 mg twice daily) ()2.2 Refractory Complex Partial SeizuresAdults (Patients 17 Years of Age and Older)
Treatment should be initiated at 1,000 mg/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 vigabatrin tablets in adults is 3,000 mg/day (1,500 mg twice daily). A 6,000 mg/day dose has not been shown to confer additional benefit compared to the 3,000 mg/day dose and is associated with an increased incidence of adverse events.
In controlled clinical studies in adults with complex partial seizures, vigabatrin was tapered by decreasing the daily dose 1,000 mg/day on a weekly basis until discontinued
[see Warnings and Precautions ].Pediatric (Patients 2 to 16 Years of Age)The recommended dosage is based on body weight and administered as two divided doses, as shown in Table 1. The dosage may be increased in weekly intervals to the total daily maintenance dosage, depending on response.
Pediatric patients weighing more than 60 kg should be dosed according to adult recommendations.
Table 1. CPS Dosing Recommendations for Pediatric Patients Weighing 10 kg up to 60 kg†† Body Weight
[kg]Total Daily* Starting Dose
[mg/day]Total Daily* Maintenance Dose†
[mg/day]10 kg to 15 kg 350 mg 1,050 mg Greater than 15 kg to 20 kg 450 mg 1,300 mg Greater than 20 kg to 25 kg 500 mg 1,500 mg Greater than 25 kg to 60 kg 500 mg 2,000 mg *Administered in two divided doses
†Maintenance dose is based on 3,000 mg/day adult-equivalent dose
††Patients weighing more than 60 kg should be dosed according to adult recommendations
In patients with refractory complex partial seizures, vigabatrin tablets should be withdrawn if a substantial clinical benefit is not observed within 3 months of initiating treatment. If, in the clinical judgment of the prescriber, evidence of treatment failure becomes obvious earlier than 3 months, treatment should be discontinued at that time
[see Warnings and Precautions ].In a controlled study in pediatric patients with complex partial seizures, vigabatrin was tapered by decreasing the daily dose by one third every week for three weeks
[see Warnings and Precautions ]. - Pediatric (2 to 16 years of age): The recommended dosage is based on body weight and administered as two divided doses ()2.2 Refractory Complex Partial SeizuresAdults (Patients 17 Years of Age and Older)
Treatment should be initiated at 1,000 mg/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 vigabatrin tablets in adults is 3,000 mg/day (1,500 mg twice daily). A 6,000 mg/day dose has not been shown to confer additional benefit compared to the 3,000 mg/day dose and is associated with an increased incidence of adverse events.
In controlled clinical studies in adults with complex partial seizures, vigabatrin was tapered by decreasing the daily dose 1,000 mg/day on a weekly basis until discontinued
[see Warnings and Precautions ].Pediatric (Patients 2 to 16 Years of Age)The recommended dosage is based on body weight and administered as two divided doses, as shown in Table 1. The dosage may be increased in weekly intervals to the total daily maintenance dosage, depending on response.
Pediatric patients weighing more than 60 kg should be dosed according to adult recommendations.
Table 1. CPS Dosing Recommendations for Pediatric Patients Weighing 10 kg up to 60 kg†† Body Weight
[kg]Total Daily* Starting Dose
[mg/day]Total Daily* Maintenance Dose†
[mg/day]10 kg to 15 kg 350 mg 1,050 mg Greater than 15 kg to 20 kg 450 mg 1,300 mg Greater than 20 kg to 25 kg 500 mg 1,500 mg Greater than 25 kg to 60 kg 500 mg 2,000 mg *Administered in two divided doses
†Maintenance dose is based on 3,000 mg/day adult-equivalent dose
††Patients weighing more than 60 kg should be dosed according to adult recommendations
In patients with refractory complex partial seizures, vigabatrin tablets should be withdrawn if a substantial clinical benefit is not observed within 3 months of initiating treatment. If, in the clinical judgment of the prescriber, evidence of treatment failure becomes obvious earlier than 3 months, treatment should be discontinued at that time
[see Warnings and Precautions ].In a controlled study in pediatric patients with complex partial seizures, vigabatrin was tapered by decreasing the daily dose by one third every week for three weeks
[see Warnings and Precautions ]. - The dosage may be increased in weekly intervals, depending on response ()2.2 Refractory Complex Partial SeizuresAdults (Patients 17 Years of Age and Older)
Treatment should be initiated at 1,000 mg/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 vigabatrin tablets in adults is 3,000 mg/day (1,500 mg twice daily). A 6,000 mg/day dose has not been shown to confer additional benefit compared to the 3,000 mg/day dose and is associated with an increased incidence of adverse events.
In controlled clinical studies in adults with complex partial seizures, vigabatrin was tapered by decreasing the daily dose 1,000 mg/day on a weekly basis until discontinued
[see Warnings and Precautions ].Pediatric (Patients 2 to 16 Years of Age)The recommended dosage is based on body weight and administered as two divided doses, as shown in Table 1. The dosage may be increased in weekly intervals to the total daily maintenance dosage, depending on response.
Pediatric patients weighing more than 60 kg should be dosed according to adult recommendations.
Table 1. CPS Dosing Recommendations for Pediatric Patients Weighing 10 kg up to 60 kg†† Body Weight
[kg]Total Daily* Starting Dose
[mg/day]Total Daily* Maintenance Dose†
[mg/day]10 kg to 15 kg 350 mg 1,050 mg Greater than 15 kg to 20 kg 450 mg 1,300 mg Greater than 20 kg to 25 kg 500 mg 1,500 mg Greater than 25 kg to 60 kg 500 mg 2,000 mg *Administered in two divided doses
†Maintenance dose is based on 3,000 mg/day adult-equivalent dose
††Patients weighing more than 60 kg should be dosed according to adult recommendations
In patients with refractory complex partial seizures, vigabatrin tablets should be withdrawn if a substantial clinical benefit is not observed within 3 months of initiating treatment. If, in the clinical judgment of the prescriber, evidence of treatment failure becomes obvious earlier than 3 months, treatment should be discontinued at that time
[see Warnings and Precautions ].In a controlled study in pediatric patients with complex partial seizures, vigabatrin was tapered by decreasing the daily dose by one third every week for three weeks
[see Warnings and Precautions ]. - Dose patients weighing more than 60 kg according to adult recommendations ()2.2 Refractory Complex Partial SeizuresAdults (Patients 17 Years of Age and Older)
Treatment should be initiated at 1,000 mg/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 vigabatrin tablets in adults is 3,000 mg/day (1,500 mg twice daily). A 6,000 mg/day dose has not been shown to confer additional benefit compared to the 3,000 mg/day dose and is associated with an increased incidence of adverse events.
In controlled clinical studies in adults with complex partial seizures, vigabatrin was tapered by decreasing the daily dose 1,000 mg/day on a weekly basis until discontinued
[see Warnings and Precautions ].Pediatric (Patients 2 to 16 Years of Age)The recommended dosage is based on body weight and administered as two divided doses, as shown in Table 1. The dosage may be increased in weekly intervals to the total daily maintenance dosage, depending on response.
Pediatric patients weighing more than 60 kg should be dosed according to adult recommendations.
Table 1. CPS Dosing Recommendations for Pediatric Patients Weighing 10 kg up to 60 kg†† Body Weight
[kg]Total Daily* Starting Dose
[mg/day]Total Daily* Maintenance Dose†
[mg/day]10 kg to 15 kg 350 mg 1,050 mg Greater than 15 kg to 20 kg 450 mg 1,300 mg Greater than 20 kg to 25 kg 500 mg 1,500 mg Greater than 25 kg to 60 kg 500 mg 2,000 mg *Administered in two divided doses
†Maintenance dose is based on 3,000 mg/day adult-equivalent dose
††Patients weighing more than 60 kg should be dosed according to adult recommendations
In patients with refractory complex partial seizures, vigabatrin tablets should be withdrawn if a substantial clinical benefit is not observed within 3 months of initiating treatment. If, in the clinical judgment of the prescriber, evidence of treatment failure becomes obvious earlier than 3 months, treatment should be discontinued at that time
[see Warnings and Precautions ].In a controlled study in pediatric patients with complex partial seizures, vigabatrin was tapered by decreasing the daily dose by one third every week for three weeks
[see Warnings and Precautions ].
Vigabatrin is primarily eliminated through the kidney.
- Mild renal impairment (CLcr >50 to 80 mL/min): dose should be decreased by 25%
- Moderate renal impairment (CLcr >30 to 50 mL/min): dose should be decreased by 50%
- Severe renal impairment (CLcr >10 to 30 mL/min): dose should be decreased by 75%
CLcr in mL/min may be estimated from serum creatinine (mg/dL) using the following formulas:
- Patients 2 to <12 years old: CLcr (mL/min/1.73 m2) = (K × Ht) / Scr height (Ht) in cm; serum creatinine (Scr) in mg/dL K (proportionality constant): Female Child (<12 years): K=0.55; Male Child (<12 years): K=0.70
- Adult and pediatric patients 12 years or older: CLcr (mL/min) = [140-age(years)] ×weight(kg) /[72 ×serum creatinine(mg/dL)] (× 0.85for female patients)
The effect of dialysis on vigabatrin clearance has not been adequately studied
Clinical studies of vigabatrin did not include sufficient numbers of patients aged 65 and over to determine whether they responded differently from younger patients.
Vigabatrin is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
Oral administration of a single dose of 1.5 g of vigabatrin to elderly (≥65 years) patients with reduced creatinine clearance (<50 mL/min) was associated with moderate to severe sedation and confusion in 4 of 5 patients, lasting up to 5 days. The renal clearance of vigabatrin was 36% lower in healthy elderly subjects (≥65 years) than in young healthy males. Adjustment of dose or frequency of administration should be considered. Such patients may respond to a lower maintenance dose
Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
Dose adjustment, including initiating treatment with a lower dose, is necessary in pediatric patients 2 years of age and older and adults with mild (creatinine clearance >50 to 80 mL/min), moderate (creatinine clearance >30 to 50 mL/min) and severe (creatinine clearance >10 to 30 mL/min) renal impairment
Vigabatrin Tablet USP, 500 mg: white to off white, oval shaped, biconvex, film coated scored tablets de bossed with '87' on one side and '1' and '2' on either side of score line on the other side.
- Pregnancy: Based on animal data, may cause fetal harm ()
8.1 PregnancyPregnancy Exposure RegistryThere is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, including vigabatrin, during pregnancy. Encourage women who are taking vigabatrin during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll-free number 1-888-233-2334 or visiting the website,
http://www.aedpregnancyregistry.org/. This must be done by the patient herself.Risk SummaryThere are no adequate data on the developmental risk associated with the use of vigabatrin in pregnant women. Limited available data from case reports and cohort studies pertaining to vigabatrin use in pregnant women have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. However, based on animal data, vigabatrin use in pregnant women may result in fetal harm.
When administered to pregnant animals, vigabatrin produced developmental toxicity, including an increase in fetal malformations and offspring neurobehavioral and neurohistopathological effects, at clinically relevant doses. In addition, developmental neurotoxicity was observed in rats treated with vigabatrin during a period of postnatal development corresponding to the third trimester of human pregnancy
(see Data).In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.
DataAnimal DataAdministration of vigabatrin (oral doses of 50 to 200 mg/kg/day) to pregnant rabbits throughout the period of organogenesis was associated with an increased incidence of malformations (cleft palate) and embryofetal death; these findings were observed in two separate studies. The no-effect dose for adverse effects on embryofetal development in rabbits (100 mg/kg/day) is approximately 1/2 the maximum recommended human dose (MRHD) of 3 g/day on a body surface area (mg/m2) basis. In rats, oral administration of vigabatrin (50, 100, or 150 mg/kg/day) throughout organogenesis resulted in decreased fetal body weights and increased incidences of fetal anatomic variations. The no-effect dose for adverse effects on embryo-fetal development in rats (50 mg/kg/day) is approximately 1/5 the MRHD on a mg/m2basis. Oral administration of vigabatrin (50, 100, 150 mg/kg/day) to rats from the latter part of pregnancy through weaning produced long-term neurohistopathological (hippocampal vacuolation) and neurobehavioral (convulsions) abnormalities in the offspring. A no-effect dose for developmental neurotoxicity in rats was not established; the low-effect dose (50 mg/kg/day) is approximately 1/5 the MRHD on a mg/m2basis.
In a published study, vigabatrin (300 or 450 mg/kg) was administered by intraperitoneal injection to a mutant mouse strain on a single day during organogenesis (day 7, 8, 9, 10, 11, or 12). An increase in fetal malformations (including cleft palate) was observed at both doses.
Oral administration of vigabatrin (5, 15, or 50 mg/kg/day) to young rats during the neonatal and juvenile periods of development (postnatal days 4 to 65) produced neurobehavioral (convulsions, neuromotor impairment, learning deficits) and neurohistopathological (brain vacuolation, decreased myelination, and retinal dysplasia) abnormalities in treated animals. The early postnatal period in rats is generally thought to correspond to late pregnancy in humans in terms of brain development. The no-effect dose for developmental neurotoxicity in juvenile rats (5 mg/kg/day) was associated with plasma vigabatrin exposures (AUC) less than 1/30 of those measured in pediatric patients receiving an oral dose of 50 mg/kg.
- Lactation: Vigabatrin is excreted in human milk ()8.2 LactationRisk Summary
Vigabatrin is excreted in human milk. The effects of vigabatrin on the breastfed infant and on milk production are unknown. Because of the potential for serious adverse reactions from vigabatrin in nursing infants, breastfeeding is not recommended. If exposing a breastfed infant to vigabatrin, observe for any potential adverse effects
[see Warnings and Precautions ].
None.