Vigabatrin is a GABA derivative that is used in combination with other agents as therapy of refractory complex partial seizures and as monotherapy for infantile spasms. Vigabatrin is associated with a paradoxical decrease in serum enzyme levels during therapy, explained by its direct inhibition of aminotransferase activity. Vigabatrin has not been convincingly linked to cases of clinically apparent liver injury, but was linked to a fatal case of Reye syndrome in a child with severe developmental delay.


Vigabatrin (vye ga' ba trin) is a vinyl derivative of gamma-aminobutyric acid (GABA) that acts as a competitive inhibitor of GABA transaminase. Vigabatrin prevents the breakdown of GABA and thus may increase GABAergic, neuroinhibitory activity. Vigabatrin has been shown to be effective in reducing seizure activity as add on therapy in patients with refractory partial onset seizures. It was available in other countries for more than a decade before it was approved for use in the United States in 2009. Current indications include as adjuvant therapy in patients with refractory complex partial seizures and as monotherapy for infantile spasms in children ages 1 month to 2 years. Vigabatrin is available in tablets of 500 mg and as a powder for oral solution generically and under the brand name Sabril. The typical initial dose is 500 mg twice daily, with subsequent increases to a recommended average dose of 3000 mg daily in adults and 2000 mg in children 10 to 16 years of age. Doses for children with infantile spasms are weight based. Side effects may include fatigue, somnolence, nystagmus, tremor, blurred vision, memory impairment, mood changes, confusion and weight gain. Rare, but severe adverse events include visual loss, visual field constriction and retinal dysfunction, for which reason vigabatrin is available only through a restricted program that requires prospective ophthalmologic monitoring.


In controlled clinical trials, addition of vigabatrin to standard anticonvulsant therapy was reported to cause an immediate and marked decrease in serum enzyme levels that could be reproduced by simply mixing vigabatrin with plasma. In some instances, markedly raised serum ALT levels were found to rapidly fall into the normal range with treatment. Vigabatrin inhibits GABA transaminase and is thus suspected of also being an inhibitor of alanine and aspartate aminotransferase, accounting for its unusual effects on liver associated enzymes. In prelicensure clinical trials, there were no reports of serum enzyme elevations during treatment and no instances of clinically apparent liver injury. After its general availability, however, there have been isolated case reports of severe liver injury and hepatitis associated with vigabatrin use. The onset of injury was 3 to 10 months after starting vigabatrin and was largely hepatocellular. One case resulted in rapid death from liver failure and a second worsened despite stopping and ultimately required a course of immunosuppression with prednisone and azathioprine (Case 1). Thus, clinically apparent liver injury from vigabatrin may occur and can be severe, but is rare.

Likelihood score: D (possible rare cause of clinically apparent liver injury).

Mechanism of Injury

Vigabatrin is an amino acid derivative and is metabolized by many tissues in the body. It is unlikely to be directly hepatotoxic and is not reported to cause drug-drug interactions. Instances of liver injury from vigabatrin are likely to be due to hypersensitivity.

Outcome and Management

Patients who have developed serious hypersensitivity reactions to aromatic anticonvulsants such as phenytoin, carbamazepine and lamotrigine have later tolerated therapy with vigabatrin without recurrence. The structure of vigabatrin would suggest that it does not share sensitivity to other anticonvulsant agents.

Drug Class: Anticonvulsants


Case 1. Acute hepatitis attributed to vigabatrin.(1)

A 25 year old woman was found to have abnormal liver tests 10 months after starting vigabatrin for partial onset seizures. The serum bilirubin was minimally raised (2.0 mg/dL), but ALT values were 10 times and AST 8 times the upper limit of normal (Table). Vigabatrin was continued, but several weeks later she developed symptoms of fatigue and nausea and repeat blood testing showed persistence of the liver test abnormalities. Vigabatrin was stopped and she was referred for further evaluation. She denied a history of liver disease, alcohol abuse or risk factors for viral hepatitis. She was not taking other medications and denied use of over-the-counter drugs or herbal supplements. Physical examination was unremarkable and showed no fever or rash. Tests for acute hepatitis A, B and C were negative as were tests for EBV and CMV infection. Autoantibodies were not detected. Imaging of the liver by ultrasound was normal. A liver biopsy showed panlobular hepatitis with hepatocellular necrosis and inflammatory infiltrates of lymphocytes and eosinophils. Plasma cells and neutrophils were not prominent and there was no fat or fibrosis. Despite stopping vigabatrin, she continued to worsen and serum bilirubin rose to 4.1 mg/dL and prothrombin index fell to 54%. Because of the worsening and the possibility of autoimmune liver injury, prednisone and azathioprine were started, but blood tests had already showed evidence of improvement. Thereafter, she improved rapidly, and she was asymptomatic and all tests were normal one month later. The immunosuppressive therapy was gradually tapered and was stopped after 4 months. In follow up 8 months later, all liver tests remained normal.

Key Points

Laboratory Values


A woman with partial onset seizures developed evidence of acute hepatitis 10 months after starting vigabatrin. She was taking no other medications and had no risk factors for viral hepatitis. Medical evaluation revealed no evidence for other forms of liver disease, and a liver biopsy was compatible with drug induced liver injury. Because of concerns over the severity of the injury and the possibility of an early autoimmune hepatitis, prednisone and azathioprine were started, but blood tests showed evidence of improvement even before these medications was started. In follow up, she was able to stop the immunosuppressive regimen without recurrence of injury, strong evidence against autoimmune hepatitis. This was a fairly convincing case of vigabatrin induced liver injury. The absence of other reports may merely reflect the fact that the drug is rarely used, particularly as monotherapy. Vigabatrin is approved in the United States, only as adjunctive therapy to be used with other anticonvulsant agents for partial seizures in adults. Its serious adverse events (particularly retinal) have limited it more wide scale use. Why a simple GABA derivative would cause liver toxicity is unclear. Despite the absence of signs of hypersensitivity, the most likely explanation is immunologic.



Vigabatrin – Generic, Sabril®




Product labeling at DailyMed, National Library of Medicine, NIH



Locher C, Zafrani ES, Dhumeaux D, Mallat A. Gastroenterol Clin Biol. 2001;25:556–7. [Vigabatrin-induced cytolytic hepatitis] French. [PubMed: 11521114]


References updated: 31 July 2020

Abbreviations used: SJS/TEN, Stevens-Johnson syndrome and toxic epidermal necrolysis.

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    (In a 16 month old boy with Alpers syndrome, severe developmental delay and liver disease, addition of vigabatrin to standard anticonvulsant therapy was followed by day 15 by a 91% decrease in ALT [247 to 18 U/L] and 19% decrease in Alk P levels [into the normal range], effects that could be reproduced in vitro, by addition of vigabatrin to plasma).
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  • Locher C, Zafrani ES, Dhumeaux D, Mallat A. Gastroenterol Clin Biol. 2001;25:556–7. [Vigabatrin-induced cytolytic hepatitis] French. [PubMed: 11521114]
    (25 year old woman with partial onset seizures developed acute hepatitis 10 months after starting vigabatrin [bilirubin 2.0 rising to 4.1 mg/dL, ALT 10 rising to 45 times ULN, Alk P 1.5 times ULN), ultimately treated with prednisone and azathioprine and improving rapidly, but able to stop all immunosuppression several months later without relapse: Case 1).
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    (Concise review of indications and side effects of anticonvulsants; vigabatrin is approved as add on therapy of Lennox-Gastaut syndrome in children and adults; discussion of adverse effects does not mention hepatotoxicity, but mentions that vigabatrin is a mild inducer of CYP 3A4).
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    (Review of adverse event reports to the FDA between 2014 and 2018 identified ~2.9 million reports, 1034 for SJS/TEN, the most common class of drugs being anticonvulsants with 17 of 34 having at least one report, those most frequently linked being lamotrigine [n=106], carbamazepine [22], levetiracetam [14], phenytoin [14], valproate [9], clonazepam [8] and zonisamide [7]; no mention of vigabatrin).
  • Somoza EC, Winship D, Gorodetzky CW, Lewis D, Ciraulo DA, Galloway GP, Segal SD, et al. A multisite, double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of vigabatrin for treating cocaine dependence. JAMA Psychiatry. 2013;70:630–7. [PubMed: 23575810]
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