REMS: FDA approved a REMS for vigabatrin to ensure that the benefits outweigh the risks. The REMS may apply to one or more preparations of vigabatrin and consists of the following: elements to assure safe use and implementation system. See the FDA REMS page ([Web]). |
Vigabatrin, an irreversible inhibitor of gamma-aminobutyric acid transaminase (GABA-T), is an anticonvulsant.1
Refractory Complex Partial Seizures
Vigabatrin is used orally in combination with other anticonvulsant agents in the management of refractory complex partial seizures (CPS) in adults and pediatric patients 2 years of age and older who have not responded adequately to several alternative treatments.1, 16, 17, 25 However, because of the risk of severe and potentially disabling visual field defects, vigabatrin should be used only in patients in whom the potential benefits outweigh the risk of vision loss.1, 3 Vigabatrin should not be used as first-line therapy for CPS.1
Efficacy of vigabatrin as adjunctive therapy in adults with CPS was established in the US in 2 multicenter, double-blind, placebo-controlled clinical studies; 357 adults (18-60 years of age) with refractory CPS with or without secondary generalization were enrolled.1, 16, 17, 22 Patients were required to be on an adequate and stable dosage regimen of 1-2 other anticonvulsant agents and to have a history of failure on an adequate regimen of carbamazepine or phenytoin.1, 16, 17 Patients had a history of about 8 seizures (median) per month for a median of about 20 years prior to entering the studies.1, 16, 17 The studies were similarly designed with an 8-week baseline period followed by a 16- or 18-week titration and treatment phase with either vigabatrin or placebo.1, 16, 17 In study 1, patients were randomized to receive vigabatrin (1, 3, or 6 g daily) or placebo; in study 2, patients were randomized to receive vigabatrin 3 g daily or placebo.1, 16, 17 The primary efficacy measure in both studies was the reduction in average monthly (28-day) seizure frequency at the end of the study compared with baseline.1, 16, 17 Patients receiving the 3-g daily dosage of vigabatrin in both studies experienced a substantially greater reduction in 28-day seizure frequency than did patients receiving placebo.1, 16, 17 Although the 6-g daily dosage of vigabatrin in the first study reduced seizure frequency to a greater extent than placebo, the higher dosage was not found to be superior to the 3-g daily dosage and was associated with a higher incidence of adverse effects.1, 16 In these studies, therapeutic success (defined as a reduction in seizure frequency of 50% or more) was attained in a higher percentage of patients receiving vigabatrin dosages of 3 or 6 g daily (39-51% or 53%, respectively) compared with those receiving placebo (9-21%).1 For both studies, there was no difference in the effectiveness of vigabatrin between male and female patients; analyses of age and race were not possible.1
Efficacy of vigabatrin as adjunctive therapy in pediatric patients 3-16 years of age with CPS was evaluated in 3 multicenter, randomized, double-blind, placebo-controlled, parallel-group studies.1 The studies enrolled patients 3 to 16 years of age with refractory CPS with or without secondary generalization, and the study period included a 6- to 10-week baseline period followed by a 14- to 17-week treatment phase (titration and maintenance period) with either vigabatrin or placebo.1 Because no individual study was adequately powered to determine efficacy of vigabatrin in patients 3 years of age and older, data from the 3 pediatric studies were pooled and used in a pharmacometric bridging analysis using weight-normalized dosages to establish efficacy and determine the appropriate dosage regimen of vigabatrin in pediatric patients 2 to 16 years of age.1
Vigabatrin has been shown in a number of controlled clinical trials to be more effective than placebo in reducing seizure frequency in patients with difficult to control CPS.1, 16, 17, 18, 19, 20, 22 In a meta-analysis of 11 short-term, randomized, double-blind, placebo-controlled trials in adults and pediatric patients 10-64 years of age with refractory partial epilepsy, patients receiving vigabatrin in addition to other anticonvulsant therapy were 2- to 3-times more likely to obtain a 50% or greater reduction in seizure frequency compared with those who received placebo in addition to other anticonvulsant therapy.18 However, patients receiving vigabatrin in these studies also were more likely to have treatment withdrawn and experience adverse effects (e.g., fatigue, drowsiness) than were those receiving placebo.18
Guidelines from the American Academy of Neurology (AAN) and the American Epilepsy Society (AES) provide recommendations on management of treatment-resistant focal epilepsy in adults.940 Pregabalin and perampanel have Level A evidence supporting their use as effective agents to reduce seizure frequency in adults with treatment-resistant focal epilepsy.940 Vigabatrin is also recommended for management of treatment-resistant focal epilepsy; however, it should not be used as a first-line agent.940 The guideline authors note that the benefits of vigabatrin must be weighed against its risks, especially the risk of irreversible retinopathy, prior to initiation.940, 940
Vigabatrin is used orally as monotherapy for the management of infantile spasms (IS) in pediatric patients 1 month to 2 years of age for whom the potential benefits outweigh the risk of vision loss.1, 2, 3, 5, 6, 7, 25, 58 Vigabatrin is designated an orphan drug by FDA for use in this condition.5
Efficacy of vigabatrin as monotherapy for the treatment of IS was established in the US in 2 multicenter controlled studies; both studies were similar in terms of disease characteristics and prior treatments and enrolled infants with a confirmed diagnosis of IS.1, 6, 7, 2 Study 1, which was initiated as a compassionate-use program, was a large randomized study comparing low-dosage (18-36 mg/kg daily) and high-dosage (100-148 mg/kg daily with initial dosage titration during the first 7 days) vigabatrin therapy in 221 infants under 2 years of age with newly diagnosed, previously untreated IS.1, 2, 6 Patients with both symptomatic and cryptogenic etiologies were included.1, 2 The study was conducted in 2 phases, with an initial 14- to 21-day, partially blinded phase in which vigabatrin was administered in a fixed dosage (low-dosage group) or titrated for up to 7 days to the target dosage (high-dosage group) and then a constant dosage of the drug was given for 7 days.1, 2, 6 Patients then entered the flexible-dosing phase, at which time patients who were initially randomized to the low-dosage group were switched to the high-dosage regimen if they continued to have IS.6 If spasms still were present in either group after 7 days, further titration of the dosage was allowed until patients became spasm-free, reached a maximum tolerated dosage, or received the maximum allowable dosage of 200 mg/kg daily.6 The primary efficacy end point of the study was the proportion of patients achieving complete cessation of spasms for 7 consecutive days beginning within the first 14 days of treatment.1, 6 Spasm freedom was achieved in more patients in the high-dosage group versus the low-dosage vigabatrin group (15.9 and 7%, respectively).1, 2 Patients in the study could then enter an open-label, dose-ranging extension study for up to 3 years.55 Over the 3-year follow-up period, approximately 23% of the patients who became spasm-free for 7 consecutive days relapsed and 72% of those subsequently regained freedom from spasms; about 79% of the patients who regained freedom from spasms remained spasm-free for the rest of the follow-up period.55 Vigabatrin was found to be particularly effective in treating IS associated with tuberous sclerosis.6, 55
In study 2, which was a multicenter, double-blind, placebo-controlled study, 40 infants between 1 and 20 months of age with newly diagnosed IS were randomized to receive either vigabatrin (50 mg/kg daily initially with subsequent titration up to a maximum dosage of 150 mg/kg daily) or placebo for 5 days after an initial pretreatment period of 2 or 3 days.1, 7, 2 None of the patients in this study had tuberous sclerosis.7 Following the double-blind treatment phase, patients entered a 6-month, open-label extension phase.7 The primary efficacy end point of the study was the average percent change in daily spasm frequency from baseline to the end of the blinded treatment period; spasm frequency was assessed during a predefined and consistent 2-hour window of observation.1, 2, 7 No significant difference in average spasm frequency was observed in patients receiving vigabatrin versus placebo using the 2-hour observation window.1, 2, 7, 23 However, when results were reanalyzed using a 24-hour window of observation, a statistically significant difference in the overall percentage of reductions in spasms was seen between the vigabatrin group and the placebo group (68.9 and 17%, respectively).1, 2, 23 Among the 36 patients who entered the open-label extension phase, 42% were spasm-free with vigabatrin monotherapy at the end of the 24-week follow-up period.7
Duration of vigabatrin therapy was evaluated in a post hoc analysis of a Canadian Pediatric Epilepsy Network (CPEN) study of developmental outcomes in patients with IS.1 The 38 out of 68 infants who responded to vigabatrin in this study (i.e., complete cessation of spasms and hypsarrhythmia) continued to receive vigabatrin therapy for a total duration of 6 months.1, 2 These infants were then followed for an additional 18 months after discontinuance of the drug to determine their clinical outcome.1, 2 A post hoc analysis of patient outcomes indicated no observed recurrence of IS in any of these infants.1, 2
Infantile spasms (also known as West's syndrome) is a syndrome that consists of a peculiar type of epileptic seizure and a typical electroencephalogram (EEG) abnormality, which often is called hypsarrhythmia; psychomotor retardation frequently is observed upon follow-up.8, 58, 62 Onset of seizures generally occurs within the first year of life, with a peak age of onset of 3 to 5 months.8, 58
A guideline published by the AAN in 2012, which was reaffirmed in 2021 and then retired in 2024, recommended low-dose adrenocorticotropic hormone (ACTH) or vigabatrin for short-term treatment of IS.941 The authors stated that ACTH is preferred over vigabatrin, except when used to treat tuberous sclerosis complex.941 At the time the guideline was published, the authors noted insufficient evidence to support other agents as monotherapy or combination therapy for short-term treatment of IS.941
Dispensing and Administration Precautions
Vigabatrin is available orally as tablets, a powder for oral solution with a final concentration of 50 mg/mL, and a concentrated 100 mg/mL oral solution that does not require reconstitution or dilution prior to administration.1, 2 Vigabatrin is administered orally and may be given without regard to meals.1, 2, 25
When using the powder for oral solution, clinicians should review and discuss the medication guide and instructions on proper reconstitution, administration, and dosing procedures with the patient or caregiver(s) and confirm their understanding.1 When using the concentrated 100 mg/mL oral solution, verify the strength and dose of the product before prescribing, dispensing, and administering the product.2
Vigabatrin powder for oral solution should be prepared and administered according to the manufacturer's directions.1, 4 The manufacturer states that only water should be used to dissolve the powder.1, 3, 4
To prepare the oral solution, the entire contents of the appropriate number of packets of vigabatrin powder for oral solution (500 mg/packet) should be emptied into a clean cup and dissolved with 10 mL of cold or room-temperature water per packet; resultant solutions have a final concentration of 50 mg/mL.1, 4 For doses between 0 and 500 mg, 1 packet of vigabatrin powder should be dissolved with 10 mL of water; for doses between 501 mg and 1 g, 2 packets of vigabatrin powder should be dissolved with 20 mL of water; and for doses between 1 and 1.5 g, 3 packets of vigabatrin powder should be dissolved with 30 mL of water.1, 4 The solution should be mixed thoroughly with a small spoon or other clean utensil until the powder has completely dissolved and the solution is clear.4 The resulting solution should be discarded if it is not clear (or free of particles) and colorless.1 Each dose of vigabatrin oral solution should be administered immediately following preparation.1, 4
Depending on the dose to be administered, a 3-mL or 10-mL oral syringe supplied by the pharmacy should be used to withdraw the specific volume of solution that will provide the appropriate dose and any remaining solution should be discarded.1, 4 A calibrated measuring device should be used to measure and deliver the dose of vigabatrin powder for oral solution or oral solution; a household teaspoon or tablespoon is not an appropriate measuring device.1, 2
Store vigabatrin tablets and powder for oral solution at 20-25°C.1
Store unopened bottles of vigabatrin 100 mg/mL oral solution between 20-25°C (excursions permitted to 15-30°C).2 After opening vigabatrin 100 mg/mL oral solution, store at room temperature or in a refrigerator, between 2-30°C; discard any unused medication within 90 days after first opening.2
Since there is no direct correlation between plasma vigabatrin concentrations and efficacy, therapeutic drug monitoring of vigabatrin is not useful.1, 2
The manufacturer states that the lowest dosage and shortest duration of therapy with vigabatrin consistent with clinical objectives should be used.1, 2
The dosage regimen of vigabatrin depends on the indication, age group, weight, and dosage form (tablets or powder for oral solution).1
If therapy is to be discontinued, vigabatrin should be withdrawn gradually.1, 2
Refractory Complex Partial Seizures
The initial oral dosage of vigabatrin for adjunctive treatment of refractory complex partial seizures (CPS) in adults and pediatric patients 17 years of age and older is 1 g daily (given as 500 mg twice daily).1 The total daily dosage may be increased in 500-mg increments at weekly intervals up to the recommended maintenance dosage of 3 g daily (given as 1.5 g twice daily) based on patient response.1 A dosage of 6 g daily has not been shown to produce additional therapeutic benefit compared with a dosage of 3 g daily and was associated with an increased incidence of adverse effects.1
The manufacturer states that patient response and the continued need for vigabatrin therapy should be periodically reassessed.1 Because of the risk of permanent vision loss, vigabatrin therapy should be withdrawn in patients with refractory CPS who do not demonstrate substantial clinical benefit within 3 months of therapy initiation.1 If treatment failure is evident earlier than 3 months, vigabatrin should be discontinued at that time.1
If a decision is made to discontinue vigabatrin, dosage should be reduced gradually.1 In controlled clinical studies, vigabatrin was tapered in adults with CPS by decreasing the daily dosage by 1 g on a weekly basis until the drug was discontinued.1
Refractory Complex Partial Seizures
The oral dosage of vigabatrin for adjunctive treatment of refractory CPS in pediatric patients who are 17 years of age or older or who weigh >60 kg is the same as for adults .1 The initial dose is 1 g daily (given as 500 mg twice daily).1 The total daily dosage may be increased in 500-mg increments at weekly intervals up to the recommended maintenance dosage of 3 g daily (given as 1.5 g twice daily) based on patient response.1
In pediatric patients 2-16 years of age, the initial oral dosage of vigabatrin for adjunctive treatment of refractory CPS should be based on body weight; the dose should be administered as 2 divided doses.1 (See Table 1) The total daily dosage may be increased at weekly intervals up to the recommended maintenance dosage, depending on response.1 The manufacturer states that patients 2 to 16 years of age weighing more than 60 kg should be dosed according to the adult dosage recommendations.1
Weight (kg) | Starting Dosage (Total Daily Doseb) | |
|---|---|---|
10-15 | 350 mg daily | 1050 mg daily |
>15-20 | 450 mg daily | 1300 mg daily |
>20-25 | 500 mg daily | 1500 mg daily |
>25-60 | 500 mg daily | 2000 mg daily |
aPatients weighing >60 kg should be dosed according to adult recommendations.
bAdministered in 2 divided doses.
cMaintenance dose is based on 3000 mg per day adult-equivalent dose.
The manufacturer states that patient response and the continued need for vigabatrin therapy should be periodically reassessed.1 Because of the risk of permanent vision loss, vigabatrin therapy should be withdrawn in patients with refractory CPS who do not demonstrate substantial clinical benefit within 3 months of therapy initiation.1 If treatment failure is evident earlier than 3 months, vigabatrin should be discontinued at that time.1
If a decision is made to discontinue vigabatrin, dosage should be reduced gradually.1 In a controlled study in pediatric patients with CPS, vigabatrin was tapered by decreasing the daily dosage by one-third every week for 3 weeks.1
The initial oral dosage of vigabatrin as monotherapy for infantile spasms (IS) in children 1 month to 2 years of age is 50 mg/kg daily, administered in 2 divided doses (given as 25 mg/kg twice daily).1, 2 Dosage may be increased in increments of 25-50 mg/kg daily every 3 days up to a maximum dosage of 150 mg/kg daily, administered in 2 divided doses (given as 75 mg/kg twice daily).1, 2
Weight (kg) | Starting Dosage (50 mg/kg daily)a | Maximum Dosage (150 mg/kg daily)a |
|---|---|---|
3 | 75 mg twice daily | 225 mg twice daily |
4 | 100 mg twice daily | 300 mg twice daily |
5 | 125 mg twice daily | 375 mg twice daily |
6 | 150 mg twice daily | 450 mg twice daily |
7 | 175 mg twice daily | 525 mg twice daily |
8 | 200 mg twice daily | 600 mg twice daily |
9 | 225 mg twice daily | 675 mg twice daily |
10 | 250 mg twice daily | 750 mg twice daily |
11 | 275 mg twice daily | 825 mg twice daily |
12 | 300 mg twice daily | 900 mg twice daily |
13 | 325 mg twice daily | 975 mg twice daily |
14 | 350 mg twice daily | 1050 mg twice daily |
15 | 375 mg twice daily | 1125 mg twice daily |
16 | 400 mg twice daily | 1200 mg twice daily |
aThe volume of solution required per dose varies depending on the specific product used; consult the product prescribing information for details.
The manufacturer states that patient response and the continued need for vigabatrin therapy should be periodically reassessed.1, 2 Because of the risk of permanent vision loss, vigabatrin therapy should be withdrawn in patients with IS who do not demonstrate substantial clinical benefit within 2-4 weeks of therapy initiation.1, 2 If treatment failure is evident earlier than 2-4 weeks, vigabatrin should be discontinued at that time.1, 2
If a decision is made to discontinue vigabatrin, dosage should be reduced gradually.1, 2 In a controlled clinical study in patients with IS, vigabatrin was tapered at a rate of 25-50 mg/kg daily every 3 or 4 days until the drug was discontinued.1, 2
The manufacturer does not provide specific dosage recommendations for vigabatrin in patients with hepatic impairment.1, 2
Dosage of vigabatrin should be reduced in adults and pediatric patients 2 years of age and older with renal impairment.1 In adults and pediatric patients 2 years of age and older with mild renal impairment (creatinine clearance (ClCr) greater than 50 up to 80 mL/minute), dosage should be decreased by 25%; in adults and pediatric patients 2 years of age and older with moderate renal impairment (ClCr greater than 30 up to 50 mL/minute), dosage should be decreased by 50%; and in adults and pediatric patients 2 years of age and older with severe renal impairment (ClCr greater than 10 up to 30 mL/minute), dosage should be decreased by 75%.1
In pediatric patients 2 years of age to less than 12 years of age, Clcr can be estimated by using the following formula:1
Clcr = [K × height (in cm)] / serum creatinine (in mg/dL)
K for female child (<12 years) = 0.55
K for male child (<12 years) = 0.70
In pediatric patients 12 years of age or older and adults, Clcr can be estimated by using the following formula:1
Clcr male = [(140 - age) × weight (in kg)] / [72 × serum creatinine (in mg/dL)]
Clcr female = 0.85 × Clcr male
The manufacturer states that information about how to adjust the dosage of vigabatrin in infants with renal impairment is unavailable.1, 2
The manufacturer states that the effect of hemodialysis on vigabatrin clearance has not been adequately studied and does not provide specific dosage recommendations for vigabatrin in patients undergoing hemodialysis.1
Because of the possibility of decreased renal function in geriatric patients, careful dosage selection is recommended.1 Adjusting the dosage or frequency of administration should be considered in geriatric patients; such patients may respond to a lower maintenance dosage.1
Vigabatrin 100 mg/mL oral solution is not approved for use in adults.2
A boxed warning about the risk of permanent vision loss is included in the prescribing information for vigabatrin.1, 2 Because of this risk and because vigabatrin, when effective, provides an observable symptomatic benefit, patient response and continued need for treatment with the drug should be periodically assessed.1, 2
Visual field defects, including permanent vision loss, have been reported in infants, children, and adults receiving vigabatrin.1, 2 Based on clinical studies in adults, bilateral concentric visual field constriction ranging in severity from mild to severe may occur in 30% or more of patients receiving the drug.1, 2 Severe cases may be characterized by tunnel vision to within 10 degrees of visual fixation, which can lead to disability.1, 2 In some cases, vigabatrin can also damage the central retina and decrease visual acuity.1, 2 Because vision assessment may be difficult in infants and children, the frequency and extent of vision loss is poorly characterized in such patients; therefore, the understanding of the risk is mainly based on adult experience with the drug.1, 2 The possibility that vigabatrin-induced vision loss may be more common, more severe, or have more functional consequences in infants and children than in adults cannot be excluded.1, 2
The onset and progression of vision loss with vigabatrin are unpredictable and can occur within weeks of beginning treatment or sooner or at any time after starting therapy, even after months or years.1, 2 In addition, vision loss may develop or worsen precipitously between vision assessments.1, 2 Symptoms of vigabatrin-associated vision loss are unlikely to be recognized by patients or caregivers before the impairment is severe.1, 2 Vision loss of milder severity that is often unrecognized by the patient or caregiver can still adversely affect function.1, 2 Once detected, vigabatrin-induced visual field defects are irreversible and will not improve even after the drug is discontinued.1, 2 In addition, it is possible that further impairment of vision may occur following drug discontinuance.1, 2 Risk of vision loss increases with increasing dosages and cumulative exposure to vigabatrin; however, no dosage or exposure to the drug is known to be free of the risk of vision loss.1, 2
In patients with refractory complex partial seizures, vigabatrin therapy should be withdrawn if a substantial clinical benefit is not observed within 3 months of initiating the drug.1 If, in the clinical judgment of the prescribing clinician, evidence of treatment failure becomes obvious earlier than 3 months, vigabatrin treatment should be discontinued at that time.1
In patients with infantile spasms (IS), vigabatrin therapy should be withdrawn if a substantial clinical benefit is not observed within 2 to 4 weeks of initiating the drug.1, 2 If, in the clinical judgment of the prescribing clinician, evidence of treatment failure becomes obvious earlier than 2 to 4 weeks, vigabatrin treatment should be discontinued at that time.1, 2
Monitoring 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 in patients receiving vigabatrin.1, 2 Because such vision testing in infants is difficult, vigabatrin-induced vision loss may not be detected until it is severe.1, 2 In patients receiving vigabatrin, vision testing is recommended at baseline (no later than 4 weeks after start of therapy), at least every 3 months during treatment, and about 3 to 6 months following cessation of therapy.1, 2
The diagnostic approach for vision loss should be individualized for the patient and clinical situation.1, 2 In adults and cooperative pediatric patients, perimetry testing is recommended, preferably by automated threshold visual field testing1, 2 ; however, perimetry testing in children younger than 9 years of age usually is not possible.1 Additional vision testing may include electrophysiology (e.g., electroretinography [ERG]), retinal imaging (e.g., optical coherence tomography [OCT]), and/or other methods appropriate for the patient.1, 2 In patients who cannot be tested, vigabatrin therapy may continue according to clinical judgment, with appropriate patient counseling.1, 2 Because of variability, results of ophthalmic monitoring should be interpreted with caution; the manufacturer states that any abnormal or uninterpretable findings should be verified by a repeat test.1, 2 Repeat assessment in the first few weeks of therapy is recommended to establish if and to what degree reproducible results can be obtained and also to guide selection of appropriate ongoing vision monitoring in the patient.1
Unless the benefits clearly outweigh the risks, vigabatrin should not be used in patients with, or at high risk of, other types of irreversible vision loss.1, 2 The interaction of other types of irreversible vision damage with vigabatrin-associated vision damage has not been well characterized, but is expected to be adverse.1, 2 In addition, vigabatrin should not be used concurrently with other drugs associated with serious adverse ophthalmic effects (e.g., retinopathy, glaucoma) unless the benefits clearly outweigh the risks.1, 2
It is expected that, even with frequent vision monitoring, some patients receiving vigabatrin will develop severe vision loss.1, 2 If vision loss is documented in a patient receiving vigabatrin, discontinuance of the drug should be considered, balancing the benefit and risk of continued therapy.1, 2
Other Warnings and Precautions
Magnetic Resonance Imaging Abnormalities in Infants
Abnormal magnetic resonance imaging (MRI) signal changes characterized by increased T2 signal and restricted diffusion in a symmetric pattern involving deep gray matter areas of the brain (thalamus, basal ganglia, brain stem, cerebellum) have been reported in some infants receiving vigabatrin for IS.1, 2 Results of a retrospective, multicenter review of MRI data from 205 infants with IS showed a higher prevalence of MRI abnormalities among patients treated with vigabatrin compared with those receiving other therapies (22% versus 4%, respectively).1, 2
Vigabatrin-induced MRI abnormalities generally are transient and resolve upon drug discontinuance.1, 2 In a few patients, the abnormalities resolved despite continued use.1, 2 Coincident motor abnormalities have been reported in some infants; however, a causal relationship to the drug has not been established and the potential for long-term clinical sequelae is unclear.1, 2
Neurotoxicity (brain histopathology and neurobehavioral abnormalities) has been observed in rats exposed to vigabatrin during late gestation and the neonatal and juvenile periods of development; neurotoxicity (brain histopathology) also has been observed in dogs exposed to the drug during the juvenile period of development.1, 2 The relationship between these findings and the MRI abnormalities observed in infants treated with vigabatrin for IS is unknown .1, 2
The specific pattern of MRI signal abnormalities observed in vigabatrin-treated IS patients was not observed in older pediatric patients (3 years of age or older) or adults treated with the drug for refractory complex partial seizures (CPS).1, 23, 25, 30, 31
For adults treated with vigabatrin, the manufacturer states that routine MRI surveillance is unnecessary since there is no evidence that vigabatrin causes MRI changes in this population.1
Intramyelinic edema (IME) has been reported upon postmortem examination of infants who received vigabatrin for treatment of IS.1, 2 Abnormal MRI signal changes characterized by increased T2 signal and restricted diffusion in a symmetric pattern involving deep gray matter areas of the brain (thalamus, basal ganglia, brain stem, cerebellum) have been reported in some infants receiving vigabatrin for IS.1, 2 Studies evaluating the effects of vigabatrin on MRI and evoked potentials in adult patients with epilepsy have not demonstrated clear-cut abnormalities.1
Vigabatrin has been shown to produce vacuolation in brain white matter tracts in animal studies.1, 2 Vacuolation, characterized by fluid accumulation and separation of the outer layers of myelin (IME), was observed in multiple species of animals including adult and juvenile rats, adult mice, dogs, and possibly monkeys following vigabatrin administration at dosages within the human therapeutic range.1, 2 Such lesions were correlated with changes in MRI (high T2-weighted signals) and visual and somatosensory evoked potentials, and were reversible in some, but not all, animal species studied following drug discontinuance.1, 2
Studies in vigabatrin-treated rats during the neonatal and juvenile periods of development have revealed vacuolar changes that occurred in gray matter areas of the brain (e.g., thalamus, midbrain, deep cerebellar nuclei, substantia nigra, hippocampus, forebrain) and are considered distinct from the IME observed in adult animals receiving the drug.1, 2 Decreased myelination and evidence of oligodendrocyte injury also were observed following vigabatrin administration in the brains of vigabatrin-treated rats.1, 2 Long-term neurobehavioral abnormalities (e.g., convulsions, neuromotor impairment, learning deficits) also were reported following vigabatrin treatment of young rats.1, 2, 2 In addition, vacuolar changes in gray matter areas of the brain (including the septic nuclei, hippocampus, hypothalamus, thalamus, cerebellum, and globus pallidus) have been reported after vigabatrin administration to juvenile dogs; neurobehavioral effects of the drug in the juvenile dog were not assessed in these studies.1, 2 The neurotoxic effects occurred in young animals at dosages lower than those producing neurotoxicity in adult animals and were associated with plasma drug concentrations substantially lower than those achieved clinically in infants and children.1, 2 In another animal study, apoptotic neurodegeneration occurred in the brain of young rats exposed to postnatal intraperitoneal injections of vigabatrin (200 and 400 mg/kg daily).1, 2 Administration of vigabatrin to female rats during pregnancy and lactation at doses lower than those used clinically has resulted in hippocampal vacuolation and convulsions in the mature offspring.1
Suicidal Behavior and Ideation
Suicidal behavior and ideation have been reported in patients receiving anticonvulsants, including vigabatrin.1 Vigabatrin 100 mg/mL oral solution is approved for use in patients 1 month to 2 years of age, and is not approved for use in adolescents or adults; anticonvulsants increase the risk of suicidal thoughts or behavior in adolescents and adults.2 A pooled analysis of suicidality reports from 199 placebo-controlled studies involving 11 anticonvulsants in patients with epilepsy, psychiatric disorders, and other conditions found that patients receiving anticonvulsants had approximately twice the risk of suicidal behavior or ideation (0.43%) compared with patients receiving placebo (0.24%).1, 2 This increased suicidality risk was observed as early as 1 week after beginning therapy and continued through 24 weeks.1, 2, 2 Although patients treated with an anticonvulsant for epilepsy, psychiatric disorders, and other conditions were all found to have an increased suicidality risk compared with those receiving placebo1, 2 , the relative suicidality risk was higher for patients with epilepsy compared with those receiving anticonvulsants for other conditions.1
Clinicians should inform patients, their families, and caregivers of the potential for an increased risk of suicidality with anticonvulsant therapy and that all patients currently receiving or beginning therapy with any anticonvulsant be closely monitored for notable changes that may indicate the emergence or worsening of suicidal thoughts or behavior or depression.1 Any concerning behavior should be reported to a clinician immediately.1
Clinicians who prescribe vigabatrin or any other anticonvulsant should balance the risk of suicidality with the clinical need for the drug and the risk associated with untreated illness.1 Epilepsy and many other illnesses for which anticonvulsants are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior.1 If suicidal thoughts or behavior emerge during anticonvulsant therapy, the clinician should consider whether these symptoms may be related to the illness being treated.1
Withdrawal of Antiepileptic Drugs
As with all anticonvulsant agents, vigabatrin therapy should be withdrawn gradually.1, 2 However, prompt withdrawal may be considered if discontinuance of therapy is necessary because of a serious adverse effect.1, 2
In North American controlled studies, 6% of vigabatrin-treated patients and 2% of placebo recipients had adverse effects of anemia and/or met criteria for potentially clinically important hematology changes involving hemoglobin, hematocrit, and/or red blood cell indices.1 In controlled clinical studies in the US, vigabatrin-treated patients experienced a mean decrease in hemoglobin and hematocrit of approximately 3 and 1%, respectively, compared with no change and a 1% increase, respectively, in those receiving placebo.1, 2
Vigabatrin causes somnolence and fatigue.1, 2 Somnolence and fatigue were reported in 24 and 28%, respectively, of adults receiving vigabatrin in 2 controlled studies compared with 10 and 15%, respectively, of those receiving placebo.1, 2 In controlled studies in pediatric patients, somnolence and fatigue were reported in 6 and 10% of patients receiving vigabatrin, respectively, compared with 5 and 7% of those receiving placebo, respectively.1, 2 Somnolence and fatigue each caused patient discontinuance from clinical trials in about 1% of vigabatrin-treated adults; there were no discontinuances due to somnolence or fatigue in the pediatric clinical trials.1, 2
Vigabatrin may impair mental and/or physical abilities required to perform potentially hazardous tasks such as driving or operating machinery.1
Vigabatrin causes symptoms of peripheral neuropathy in adults.1, 2 In controlled and uncontrolled studies conducted in North America, signs and/or symptoms of peripheral neuropathy were reported in 4.2% of patients receiving vigabatrin.1, 2 In North American controlled trials, 1.4% of vigabatrin-treated patients and none of the placebo recipients developed signs and/or symptoms of peripheral neuropathy.1, 2 These studies were not designed to systematically evaluate peripheral neuropathy; therefore, it is not known whether these signs and symptoms are related to duration of treatment or cumulative dosage, or if the findings are completely reversible upon drug discontinuance.1, 2 Initial manifestations in these studies included symptoms of numbness or tingling in the toes or feet, signs of reduced distal lower limb vibration or position sensation, and/or progressive loss of reflexes starting at the ankles.1, 2
Studies in pediatric patients were not designed to assess symptoms of peripheral neuropathy;1, 2 however, the observed incidence of such symptoms in controlled pediatric studies appeared to be similar for pediatric patients who received vigabatrin or placebo.1, 2
Vigabatrin causes weight gain in adults and pediatric patients.1, 2
In randomized, controlled trials in adults, 17% of vigabatrin-treated patients gained 7% or more of their baseline body weight compared with 8% of those who received placebo; vigabatrin-treated patients experienced a mean weight gain of 3.5 kg compared with 1.6 kg in placebo recipients.1 In randomized, controlled trials in pediatric patients with refractory CPS, 47% of vigabatrin-treated patients gained 7% or more of their baseline body weight compared with 19% of those who received placebo.1, 2 In all epilepsy trials, 0.6% of vigabatrin-treated patients discontinued the drug because of weight gain.1, 2
Weight gain did not appear to be related to the occurrence of edema .1, 2 The long-term effects of such weight gain are not known.1, 2
Vigabatrin causes edema in adults.1, 2 Studies in pediatric patients were not designed to assess edema; however, the observed incidence of edema (based on pooled data from controlled pediatric studies) appeared similar with vigabatrin and placebo.1, 2
Pooled data from clinical studies demonstrated an increased risk of peripheral edema and edema in patients receiving vigabatrin (2 and 1%, respectively) compared with those receiving placebo (1 and 0%, respectively).1, 2 There was no apparent association between edema and adverse cardiovascular effects such as hypertension or congestive heart failure in adults.1 Edema also was not associated with laboratory changes suggesting deterioration of renal or hepatic function.1, 2
There are no adequate data on the developmental risk associated with use of vigabatrin in pregnant patients.1, 2 Limited data from case reports and cohort studies in pregnant patients have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.1, 2 However, animal data suggest use of vigabatrin in pregnancy may result in fetal harm.1, 2
Vigabatrin produced developmental toxicity, including teratogenic, neurobehavioral, and neurohistopathologic effects, when administered to pregnant animals in clinically relevant dosages.1, 2 Developmental neurotoxicity was observed in animals given vigabatrin during a period of postnatal development corresponding to the third trimester of human pregnancy.1, 2
The North American Antiepileptic Drug (NAAED) Pregnancy Registry may be contacted at 888-233-2334 (for patients); NAAED registry information also is available on the website [Web].1, 2
Vigabatrin distributes into milk; the effects on the breast-fed infant and on milk production are not known1, 2 Because of the potential for serious adverse reactions to vigabatrin in nursing infants , the manufacturer recommends against breast-feeding while taking vigabatrin.1, 2 In the event that a decision is made to continue breastfeeding during vigabatrin therapy, the nursing infant should be monitored for potential adverse effects.1, 2
Safety and efficacy of vigabatrin tablets and powder for oral solution, as adjunctive therapy for refractory CPS in pediatric patients 2 to 16 years of age have been established.1 The drug is indicated as adjunctive therapy for refractory CPS in pediatric patients 2 years of age and older who have not responded adequately to several alternative treatments.1 The dosage recommendation in this population depends on the age group and is based on weight .1 Adverse effects in this pediatric population are similar to those observed in adults.1
Safety and efficacy of vigabatrin have not been established in pediatric patients younger than 2 years with refractory CPS.1
Safety and efficacy of vigabatrin (all formulations) as monotherapy for IS have been established in pediatric patients 1 month to 2 years of age, and the drug is indicated in such patients when the potential benefits of vigabatrin therapy outweigh the potential risk of developing permanent vision loss.1, 2 Safety and efficacy of the drug have not been established in patients with IS outside this age group.1, 2
Abnormal MRI signal changes and IME have been observed in infants and young children treated with vigabatrin.1, 2
The elimination half-life of vigabatrin is approximately 5.7 hours in infants (5 months to 2 years of age)1, 2 , 6.8 hours for children (3 to 9 years of age), 9.5 hours in children and adolescents 10 to 16 years of age, and 10.5 hours in adults.1
Clinical studies of vigabatrin did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adults.1, 2
Vigabatrin is known to be substantially excreted by the kidney, and the risk of toxic reactions to the drug may be greater in patients with impaired renal function.1, 2 Because geriatric patients are more likely to have reduced renal function, careful dosage selection is advised and renal function monitoring may be useful.1, 2
Administration of single oral doses of vigabatrin to 5 patients older than 65 years of age with reduced renal function (creatinine clearance [ClCr] less than 50 mL/minute) resulted in moderate to severe sedation and confusion in 4 out of 5 patients lasting up to 5 days.1, 2
Renal clearance of vigabatrin is reduced by 36% in healthy individuals 65 years of age or older compared with healthy younger individuals; an adjustment in vigabatrin dosage or frequency of administration should be considered in patients in this age group.1, 2
Other reported clinical experience has not identified differences in responses to vigabatrin between geriatric and younger patients.1, 2
Vigabatrin is not substantially metabolized.1, 2 The pharmacokinetics of vigabatrin in patients with hepatic impairment have not been evaluated.1, 2
Vigabatrin has been shown to suppress ALT and AST activity, which may preclude use of these enzyme concentrations, particularly ALT, to detect early hepatic injury.1, 2
Since vigabatrin is principally eliminated by the kidneys, caution should be exercised when using the drug in patients with renal impairment.1
Systemic exposure to vigabatrin is increased by approximately 30%, 2-fold, or 4.5-fold in adults with mild renal impairment (ClCr greater than 50 up to 80 mL/minute), moderate renal impairment (ClCr greater than 30 up to 50 mL/minute), or severe renal impairment (ClCr greater than 10 up to 30 mL/minute), respectively.1, 2 In addition, terminal half-life of vigabatrin is increased by 55%, 2-fold, or 3.5-fold in adults with mild, moderate, or severe renal impairment, respectively.1, 2
The effect of hemodialysis on vigabatrin clearance has not been adequately studied.1, 2 However, in isolated case reports in renal failure patients receiving therapeutic dosages of vigabatrin, hemodialysis reduced plasma concentrations of the drug by 40-60%.1, 2
Dosage of vigabatrin should be adjusted in pediatric patients 2 years of age or older and adults with mild, moderate, or severe renal impairment, and such patients should be monitored closely for any dose-related adverse effects.1
The manufacturer states that information about how to adjust vigabatrin dosage in infants with renal impairment is not available.1, 2
Studies specifically evaluating race-related differences in the pharmacokinetics of vigabatrin have not been conducted.2, 1, 2 Limited data from a cross-study comparison of Caucasian and Japanese adult patients suggest that mean renal clearance of vigabatrin may be lower in Japanese than in Caucasian populations.1, 2
Vigabatrin causes permanent damage to vision in a high percentage of patients.1
The most common adverse effects reported (incidence ≥5% over placebo) in adolescents and adults ≥16 years of age with refractory CPS included blurred vision, somnolence, dizziness, abnormal coordination, tremor, and fatigue.1
In controlled clinical studies in pediatric patients 3 to 16 years of age with refractory CPS receiving vigabatrin, adverse effects occurring at an incidence ≥5% over placebo included weight gain.1
In a placebo-controlled study in pediatric patients with IS, adverse effects occurring in >5% of vigabatrin-treated patients and more frequently than in placebo recipients included somnolence, bronchitis, ear infection, and acute otitis media.1, 2
Vigabatrin is not extensively metabolized by hepatic cytochrome P450 (CYP) isoenzymes.1, 2 Vigabatrin induces CYP2C9, but does not appear to induce other hepatic CYP isoenzymes.1, 2
Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes
Vigabatrin potentially may interact with drugs that are extensively metabolized by CYP2C9; clinically important drug interactions mediated by other CYP450 isoenzymes are considered unlikely.1, 2
Drugs associated with Serious Adverse Ophthalmic Effects
Because of the risk of vision loss, vigabatrin should not be used concurrently with other drugs associated with serious adverse ophthalmic effects such as retinopathy (e.g., chloroquine, hydroxychloroquine, phenothiazines) or glaucoma (e.g., adrenergic agents, anticholinergic agents) unless the benefits clearly outweigh the risks.1, 2
Concurrent administration of ethanol 0.6 g/kg and vigabatrin 1.5 g twice daily did not result in any pharmacokinetic interaction.1, 2
Based on population pharmacokinetics, no clinically significant pharmacokinetic interactions are expected when vigabatrin is used concomitantly with phenobarbital, carbamazepine, clorazepate, primidone, or sodium valproate.1, 2 .1
In a study in healthy individuals, concomitant administration of vigabatrin (1.5 g twice daily) with clonazepam (0.5 mg) did not affect plasma concentrations of vigabatrin; however, mean peak plasma clonazepam concentrations increased by 30% and mean time to peak clonazepam concentrations decreased by 45%, which may increase the risk of clonazepam-associated adverse effects.1, 2
In controlled clinical studies, concomitant administration of phenytoin and vigabatrin resulted in moderate reductions (averaging 16-20%) in total plasma phenytoin concentrations, probably due to induction of CYP2C.1, 2 Such reductions may be of little clinical importance, and phenytoin dosage adjustments are not routinely required; however, phenytoin dosage adjustment should be considered if clinically indicated.1, 2
In a double-blind, placebo-controlled study in healthy individuals receiving a fixed combination oral contraceptive (ethinyl estradiol and levonorgestrel), administration of vigabatrin (3 g daily) did not substantially interfere with CYP3A-mediated metabolism of the contraceptive.1 Based on this study, vigabatrin is unlikely to affect the efficacy of steroid oral contraceptives.1 In addition, no significant changes were observed in the pharmacokinetic parameters of vigabatrin following concurrent administration.1
Urine Tests for Metabolic Disorders
Vigabatrin may increase the amount of amino acids in the urine, possibly resulting in a false positive test for certain rare genetic metabolic disorders (e.g., alpha aminoadipic aciduria).1, 2
Vigabatrin is a structural analog of gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system (CNS).17, 18, 20, 22 Although the exact mechanism of vigabatrin's antiseizure effect is unknown, it is thought to be related to the drug's action as a preferential and irreversible inhibitor of GABA transaminase (GABA-T), which is the enzyme responsible for the degradation of GABA and the resultant increase in GABA concentrations in the CNS.1, 6, 16, 17, 18, 19, 20, 22, 25 Vigabatrin is commercially available as a racemic mixture of 2 enantiomers; the S enantiomer is pharmacologically active and the R enantiomer is inactive.44, 57
Following oral administration of vigabatrin, CNS and blood concentrations of GABA increase in a dose-related manner; however, there is no direct correlation between plasma concentrations and efficacy of the drug.1, 2
Vigabatrin is rapidly and essentially completely absorbed following oral administration.1, 2 Following oral administration, peak plasma concentrations of vigabatrin generally occur within approximately 2.5 hours in infants (5 months to 2 years of age) and approximately 1 hour in children and adolescents (3-16 years of age), as well as adults.1, 2 Vigabatrin exhibits linear pharmacokinetics following single oral doses of 500 mg to 4 g and multiple doses of 500 mg to 2 g twice daily.1, 2 Little accumulation of the drug occurs with multiple dosing in adult and pediatric patients.1, 2 Administration of vigabatrin with food in healthy individuals decreased peak plasma concentrations of the drug by 33% and increased time to peak concentration, but did not affect systemic exposure to the drug.1, 2
Vigabatrin is widely distributed throughout the body, does not bind to plasma proteins, and is not extensively metabolized.1, 2 Elimination occurs principally via renal excretion; studies with radiolabeled drug indicate that 95% of an orally administered dose is recovered in urine over 72 hours with unchanged drug accounting for the majority of the recovered dose.1, 2 The elimination half-life of vigabatrin is about 10.5 hours in adults, 9.5 hours in pediatric patients 10 to 16 years of age, 6.8 hours in pediatric patients 3 to 9 years of age, and 5.7 hours in pediatric patients 5 months to 2 years of age.1, 2
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Distribution of vigabatrin is restricted.1, 2, 71
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Powder for oral solution | 500 mg | Sabril® (available in packets) | |
500 mg | Vigadrone® (available in packets) | |||
500 mg | Vigpoder™ (available in packets) | |||
Tablets, film-coated | 500 mg | Sabril® (scored) | Lundbeck | |
500 mg | Vigadrone® (scored) | |||
Oral Solution | 100 mg/mL | Vigafyde™ |
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions May 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Lundbeck LLC. Sabril® (vigabatrin) tablets and powder for oral solution prescribing information. Deerfield, IL; 2021 Oct. [Web]
2. Upsher-Smith Laboratories LLC. Vigafyde™ (vigabatrin) oral solution prescribing information. Parsippany, NJ; 2024 Nov. [Web]
3. Lundbeck. Sabril® (vigabatrin) tablets and powder for oral solution medication guide. Deerfield, IL; 2021 Oct.
4. Lundbeck. Sabril® (vigabatrin) powder for oral solution instructions for use. Deerfield, IL; 2021 Oct.
5. US Food and Drug Administration. Search orphan drug designations and approvals. From FDA web site. Accessed 2025 Jan 6. [Web]
6. Elterman RD, Shields WD, Mansfield KA and the US Infantile Spasms Vigabatrin Study Group et al. Randomized trial of vigabatrin in patients with infantile spasms. Neurology . 2001; 57:1416-21. [PubMed 11673582]
7. Appleton RE, Peters ACB, Mumford JP et al. Randomised, placebo-controlled study of vigabatrin as first-line treatment of infantile spasms. Epilepsia . 1999; 40:1627-33. [PubMed 10565592]
8. Hancock EC, Osborne JP, Edwards SW. Treatment of infantile spasms. Cochrane Database Syst Rev 2008, Issue 4. Art. No.: CD001770. DOI: 10.1002/14651858.CD001770.pub2.
10. US Food and Drug Administration. FDA Alert: Information for healthcare professionals: suicidal behavior and ideation and antiepileptic drugs. Rockville, MD; 2008 Jan 31; updated 2008 Dec 16. From the FDA website. Accessed 2010 Mar 5. [Web]
11. US Food and Drug Administration. FDA News: FDA alerts health care providers to risk of suicidal thoughts and behavior with antiepileptic medications. Rockville, MD; 2008 Jan 31. From the FDA website. Accessed 2010 Mar 12. [Web]
12. US Food and Drug Administration. Suicidal behavior and ideation and antiepileptic drugs: update 5/5/2009. Rockville, MD; 2009 May 5. From the FDA website. Accessed 2010 Mar 12. [Web]
14. Mackay MT, Weiss SK, Adams-Webber T et al. Practice parameter: medical treatment of infantile spasms: report of the American Academy of Neurology and the Child Neurology Society. Neurology . 2004; 62:1668-81. [PubMed 15159460]
15. National Collaborating Centre for Primary Care. The diagnosis and management of the epilepsies in adults and children in primary and secondary care. London, UK: Royal College of General Practitioners; 2004 Oct. Available from website. Accessed 2010 March 20. [Web]
16. Dean C, Mosier M, Penry K. Dose-response study of vigabatrin as add-on therapy in patients with uncontrolled complex partial seizures. Epilepsia . 1999; 40:74-82. [PubMed 9924905]
17. French JA, Mosier M, Walker S and the Vigabatrin Protocol 024 Investigative Cohort et al. A double-blind, placebo-controlled study of vigabatrin three g/day in patients with uncontrolled complex partial seizures. Neurology . 1996; 46:54-61. [PubMed 8559421]
18. Bresnahan R, Gianatsi M, Maguire MJ, Tudur Smith C, Marson AG. Vigabatrin add-on therapy for drug-resistant focal epilepsy. Cochrane Database Syst Rev . 2020;7(7):CD007302. doi:10.1002/14651858.CD007302.pub3
19. Bruni J, Guberman A, Vachon L et al. Vigabatrin as add-on therapy for adult complex partial seizures: a double-blind, placebo-controlled multicentre study. The Canadian Vigabatrin Study Group. Seizure . 2000; 9:224-32. [PubMed 10777431]
20. Beran RG, Berkovic SF, Buchanan N et al. A double-blind, placebo-controlled crossover study of vigabatrin 2 g/day and 3 g/day in uncontrolled partial seizures. Seizure . 1996; 5:259-65. [PubMed 8952010]
22. Tolman JA, Faulkner MA. Vigabatrin: a comprehensive review of drug properties including clinical updates following recent FDA approval. Expert Opin Pharmacother . 2009; 10:3077-89. [PubMed 19954276]
23. Food and Drug Administration. Center for Drug Evaluation and Research: Application number 20-427: Summary Review. From FDA website. [Web]
25. Anon. Vigabatrin (Sabril) for epilepsy. Med Lett Drugs Ther. 2010; 52:14-6.
27. Vigevano F, Cilio MR. Vigabatrin versus ACTH as first-line treatment for infantile spasms: a randomized, prospective study. Epilepsia . 1997; 38:1270-4. [PubMed 9578521]
28. Granström ML, Gaily E, Liukkonen E. Treatment of infantile spasms: results of a population-based study with vigabatrin as the first drug for spasms. Epilepsia . 1999; 40:950-7. [PubMed 10403219]
29. Chiron C, Dumas C, Jambaqué I et al. Randomized trial comparing vigabatrin and hydrocortisone in infantile spasms due to tuberous sclerosis. Epilepsy Res . 1997; 26:389-95. [PubMed 9095401]
30. Milh M, Villeneuve N, Chapon F et al. Transient brain magnetic resonance imaging hyperintensity in basal ganglia and brain stem of epileptic infants treated with vigabatrin. J Child Neurol . 2009; 24:305-15. [PubMed 19258289]
31. Wheless JW, Carmant L, Bebin M et al. Magnetic resonance imaging abnormalities associated with vigabatrin in patients with epilepsy. Epilepsia . 2009; 50:195-205. [PubMed 19054414]
32. Pearl PL, Vezina LG, Saneto RP et al. Cerebral MRI abnormalities associated with vigabatrin therapy. Epilepsia . 2009; 50:184-94. [PubMed 18783433]
33. Cohen JA, Fisher RS, Brigell MG et al. The potential for vigabatrin-induced intramyelinic edema in humans. Epilepsia . 2000; 41:148-57. [PubMed 10691111]
34. Wild JM, Ahn HS, Baulac M et al. Vigabatrin and epilepsy: lessons learned. Epilepsia . 2007; 48:1318-27. [PubMed 17635558]
35. Eke T, Talbot JF, Lawden MC. Severe persistent visual field constriction associated with vigabatrin. BMJ . 1997; 314:180-1. [PubMed 9022432]
36. Gaily E, Jonsson H, Lappi M. Visual fields at school-age in children treated with vigabatrin in infancy. Epilepsia . 2009; 50:206-16. [PubMed 19215279]
37. Wild JM, Chiron C, Ahn H et al. Visual field loss in patients with refractory partial epilepsy treated with vigabatrin: final results from an open-label, observational, multicentre study. CNS Drugs . 2009; 23:965-82. [PubMed 19845417]
40. Levinson DF, Devinsky O. Psychiatric adverse events during vigabatrin therapy. Neurology . 1999; 53:1503-11. [PubMed 10534259]
41. Rimmer EM, Richens A. Interaction between vigabatrin and phenytoin. Br J Clin Pharmacol . 1989; 27 (Suppl. 1):27S-33S. [PubMed 2757906][Web]
42. Richens A. Pharmacokinetic and pharmacodynamic drug interactions during treatment with vigabatrin. Acta Neurol Scand . 1995; 162:43-6.
43. Perucca E, Cloyd J, Critchley D et al. Rufinamide: clinical pharmacokinetics and concentration-response relationships in patients with epilepsy. Epilepsia . 2008; 49:1123-41. [PubMed 18503564]
44. Tran A, O'Mahoney T, Rey E et al. Vigabatrin: placental transfer in vivo and excretion into breast milk of the enantiomers. Br J Clin Pharmacol . 1998; 45:409-11. [PubMed 9578192]
45. Bar-Oz B, Nulman I, Koren G et al. Anticonvulsants and breast-feeding: a critical review. Paediatr Drugs . 2000; 2:113-26. [PubMed 10937463]
46. Sánchez-Alcaraz A, Quintana MB, Lopez E et al. Effect of vigabatrin on the pharmacokinetics of carbamazepine. J Clin Pharm Ther . 2002; 27:427-30. [PubMed 12472982]
47. Perucca E, Cloyd J, Critchley D et al. Rufinamide: clinical pharmacokinetics and concentration-response relationships in patients with epilepsy. Epilepsia . 2008; 49:1123-41. [PubMed 18503564]
48. Jedrzejczak J, Dlawichowska E, Owczarek K et al. Effect of vigabatrin on carbamazepine blood serum levels in patients with epilepsy. Epilepsy Res . 2000; 39:115-20. [PubMed 10759299]
49. Baxter K, ed. Carbamazepine + vigabatrin. Stockley's Drug Interactions. [online] London: The Pharmaceutical Press; updated 2009 Dec 2. From the Medicines Complete website. Accessed 2010 Apr 20. [Web]
50. Bartoli A, Gatti G, Cipolla G et al. A double-blind, placebo-controlled study on the effect of vigabatrin on in vivo parameters of hepatic microsomal enzyme induction and on the kinetics of steroid oral contraceptives in healthy female volunteers. Epilepsia . 1997; 38:702-7. [PubMed 9186253]
51. Dracopoulos A, Widjaja E, Raybaud C et al. Vigabatrin-associated reversible MRI signal changes in patients with infantile spasms. Epilepsia . 2010; 51:1297-304. [PubMed 20384718]
53. Bachmann D, Ritz R, Wad N et al. Vigabatrin dosing during hemodialysis. Seizure . 1996; 5:239-42. [PubMed 8902928]
54. Li J, Tripathi RC, Tripathi BJ. Drug-induced ocular disorders. Drug Saf . 2008; 31:127-41. [PubMed 18217789]
55. Elterman RD, Shields WD, Bittman RM et al. Vigabatrin for the treatment of infantile spasms: final report of a randomized trial. J Child Neurol . 2010; :Apr 19 [epub ahead of print]. [PubMed 20404353]
56. Lahat E, Ben-Zeev B, Zlotnik J et al. Aminoaciduria resulting from vigabatrin administration in children with epilepsy. Pediatr Neurol . 1999; 21:460-3. [PubMed 10428431]
57. Jacqz-Aigrain E, Guillonneau M, Rey E et al. Pharmacokinetics of the S(+) and R(-) enantiomers of vigabatrin during chronic dosing in a patient with renal failure. Br J Clin Pharmacol . 1997; 44:183-5. [PubMed 9278207]
58. Kossoff EH. Infantile spasms. The Neurologist . 2010; 16:69-75. [PubMed 20220440]
59. Reidenberg P, Glue P, Banfield C et al. Pharmacokinetic interaction studies between felbamate and vigabatrin. Br J Clin Pharmacol . 1995; 40:157-60. [PubMed 8562299]
60. Baxter K, ed. Vigabatrin + felbamate. Stockley's Drug Interactions. [online] London: The Pharmaceutical Press; updated 2009 Oct 12. From the Medicines Complete website. Accessed 2010 Apr 20. [Web]
61. Yang T, Pruthi S, Geyer JR et al. MRI changes associated with vigabatrin treatment mimicking tumor progression. Pediatr Blood Cancer . 2010; :Jun 8 [epub ahead of print]. [PubMed 20533524]
62. Pellock JM, Hrachovy R, Shinnar S et al. Infantile spasms: A U.S. consensus report. Epilepsia . 2010; :.
63. Sergott RC, Wheless JW, Smith MC et al. Evidence-based review of recommendations for visual function testing in patients treated with vigabatrin. Neuro-Ophthalmology . 2010; 34:20-35.
64. Miller NR, Johnson MA, Paul SR et al. Visual dysfunction in patients receiving vigabatrin: clinical and electrophysiologic findings. Neurology . 1999; 53:2082-7. [PubMed 10599785]
65. Malmgren K, Ben-Menachem E, Frisén L. Vigabatrin visual toxicity: evolution and dose dependence. Epilepsia . 2001; 42:609-15. [PubMed 11380567]
66. Dalla Bernardina B, Fontana E, Vigevano F et al. Efficacy and tolerability of vigabatrin in children with refractory partial seizures: a single-blind dose-increasing study. Epilepsia . 1995; 36:687-91. [PubMed 7555986]
67. Luna D, Dulac O, Pajot N et al. Vigabatrin in the treatment of childhood epilepsies: a single-blind placebo-controlled study. Epilepsia . 1989 Jul-Aug; 30:430-7.
68. Walker SD, Kälviäinen R. Non-vision adverse events with vigabatrin therapy. Acta Neurol Scand Suppl . 2011; :72-82. [PubMed 22061182]
71. US Food and Drug Administration. Vigabatrin REMS program risk evaluation and mitigation strategy (REMS). Last modified/revised 2024 Sep. From FDA website. [Web]
72. National Institute for Occupational Safety and Health. NIOSH list of hazardous drugs in healthcare settings, 2024. From CDC web site. Accessed 2025 Jan 6. [Web]
940. Kanner AM, Ashman E, Gloss D, et al. Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs II: Treatment-resistant epilepsy: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology . 2018;91(2):82-90. doi:10.1212/WNL.0000000000005756
941. Go CY, Mackay MT, Weiss SK, et al. Evidence-based guideline update: medical treatment of infantile spasms. Report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology . 2012;78(24):1974-1980. doi:10.1212/WNL.0b013e318259e2cf