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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.

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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].

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Last Update: January 27, 2014.



Oxcarbazepine is a keto analogue of carbamazepine and, like the parent drug, is a potent anticonvulsant used alone or in combination with other agents in the therapy of poartial seizures. Oxcarbazepine has been linked to rare instances of clinically apparent acute drug induced liver injury which resembles carbamazepine hepatotoxicity.


Oxcarbazepine (ox" kar baz' e peen) is a keto analog of carbamazepine and functions as a prodrug being rapidly converted to 10-hydroxycarbazepine. Oxcarbazepine and carbamazepine are iminostilbenes related chemically to the tricyclic antidepresants and unrelated in structure to most other anticonvulsants. They appear to act by suppression of spread of seizure activity by reduction in the posttetanic potentiation of synaptic transmission. Oxcarbazepine was approved for use in epilepsy in the United States in 2000 and remains in common use. Oxcarbazepine is indicated for prevention and management of partial, complex, mixed and generalized seizures and is commonly used alone or in combination with other anticonvulsants. It is used off-label to treat bipolar disorder. Oxcarbazepine is available as tablets of 150, 300 and 600 mg generically and under the commercial name of Trileptal and as an extended release form under the name Oxtellar XR. Oral formulations for use in children are also available. The recommended starting dose in adults is 300 mg twice daily followed by increases at weekly intervals based upon clinical response, the usual final dose being 600 mg twice daily. Frequent side effects include drowsiness, sedation, ataxia, blurred vision, nausea, vomiting, and skin rash.


Chronic therapy with oxcarbazepine is associated with elevations in serum aminotransferase levels in a small proportion of patients. These elevations are rarely clinically significant and do not usually require dose modification. Clinically apparent hepatotoxicity from oxcarbazepine is uncommon but described, and is probably less common than occurs with carbemazepine. Oxcarbazepine hepatotoxicity can occur in the setting of anticonvulsant hypersensitivity syndrome with onset of fever, followed by rash, facial edema, lymphadenopathy, elevations in white count and eosinophilia 2 to 8 weeks after starting therapy. The liver involvement ranges from a mild and transient elevation in serum enzymes to abrupt onset of an acute hepatitis-like syndrome, that can be severe and even fatal. The typical enzyme elevations are usually mixed, but can be either hepatocellular or cholestatic. Liver biopsy shows mixed necroinflammatory-cholestatic injury with prominence of eosinophils and occasionally granulomas.

Mechanism of Injury

The mechanism of oxcarbazepine hepatotoxicity appears to be hypersensitivity or an immunological response to a metabolically generated drug-protein complex. Oxcarbazepine like other aromatic anticonvulsants may also trigger acute porphyria by inducing delta- aminolevulinic acid (ALA) synthetase activity. It also induces CYP 3A4 and inhibits CYP 2C19 and can cause drug-drug interactions particularly with other drugs used for epilepsy that induce CYP 3A4 such as phenytoin and phenobarbital.

Outcome and Management

Oxcarbazepine and carbamazepine hepatotoxicity is usually rapidly reversible with stopping therapy, improvements beginning within days. In cases of severe injury, progression to acute liver failure and death can occur. Corticosteroids have been used but with uncertain effectiveness. Cross reactivity with other aromatic anticonvulsants (carbamazepine, phenytoin, phenobarbital, primidone, and lamotrigine) is common, but not invariable. Patients with severe hypersensitivity to oxcarbazepine should avoid exposure to other aromatic anticonvulsants and be switched instead to agents such as a benzodiazepine, valproate, levetiracetam, gabapentin or pregabalin.

Drug Class: Anticonvulsants; see also Carbamazepine



Oxcarbazepine – Generic, Trileptal®




Product labeling at DailyMed, National Library of Medicine, NIH


Oxcarbazepine chemical structure


References updated: 27 January 2014

See also references for Carbamazepine.

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    oxcarbazepine undergoes less oxidative metabolism that carbamazepine and is a less potent P450 enzyme inducer; cross reactivity between the 2 drugs is estimated to be 25%).
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    (Review of clinical features, major causes and suspected pathogenesis of DRESS; major causes are aromatic anticonvulsants, abacavir, azathioprine, and sulfonamides).
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    (4 year old developed necrotizing rash and fever 4 months after starting carbamazepine [bilirubin 4.0 mg/dL, ALT 673 U/L, Alk P 481 U/L, GGT 613 U/L], Stevens-Johnson syndrome; biopsy showing “early” vanishing bile duct syndrome, treated with corticosteroids with rapid response but slow decline in GGT and cholesterol at the time of 6 week follow up).
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  • Bosdure E, Cano A, Roquelaure B, Reynaud R, Boyer M, Viard L, Sarles J. [Oxcarbazepine and DRESS syndrome: a paediatric cause of acute liver failure]. Arch Pediatr 2004; 11: 1073-7. French. [PubMed: 15350998]
    (11 year old girl developed rash, fever and eosinophilia 43 days after starting oxcarbazepine [bilirubin not given, ALT 25 times ULN, Alk P not given, factor V 15%], progressing to hepatic failure, but eventually improving spontaneously and resolving completely within 6 weeks).
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    Anti-HHV-6 testing of 100 patients with drug induced hypersensitivity syndrome [34% with hepatitis] found rise in IgG levels in 62 patients, largely in more severe cases; HHV-6 DNA detected in 18; drugs included carbamazepine, phenobarbital, phenytoin, allopurinol, sulfasalazine and mexiletine).
  • Ganeva M, Gancheva T, Lazarova R, et al. Carbamazepine-induced drug reaction with eosinophilia and systemic symptoms(DRESS) syndrome: report of four cases and brief review. Int J Dermatol 2008; 47: 853-60. (Review of carbamazepine induced hypersensitivity syndromes and 4 case reports; onset after 3-4 weeks of starting carbamazepine with rash, fever and eosinophilia, 2 with liver involvement and 1 with jaundice, all treated with corticosteroids and all resolved without recurrence, 3 taking valproate). [PubMed: 18717872]
  • Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J; Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 2008; 135: 1924-34. [PMC free article: PMC3654244] [PubMed: 18955056]
    (Among 300 cases of drug induced liver disease in the US collected between 2004 and 2008, valproate accounted for 6, lamotrigine 5, phenytoin 5, gabapentin and topiramate 1 each; none due to oxcarbazepine).
  • Björnsson E. Hepatotoxicity associated with antiepileptic drugs. Acta Neurol Scan 2008; 118: 281-90. [PubMed: 18341684]
    (Review of all anticonvulsants including 60 cases of carbamazepine usually part of hypersensitivity syndrome, typically mixed enzyme pattern, 27% with eosinophilia, mean onset at 5 weeks, 17% mortality more common in children, with hepatocellular pattern of enzymes and with longer latency to onset; mentions oxcabazepine has been linked to a few cases reports showing mild-to-moderate liver test elevations).
  • Franzoni E, Gentile V, Pellicciari A, Garone C, Iero L, Gualandi S, Cordelli DM, et al. Prospective study on long-term treatment with oxcarbazepine in pediatric epilepsy. J Neurol 2009; 256: 1527-32. [PubMed: 19597919]
    (Among 36 children with epilepsy treated with oxcarbazepine for up to 3 years, “no hepatic dysfunctions were reported”).
  • Buggy Y, Layton D, Fogg C, Shakir SA. Safety profile of oxcarbazepine: results from a prescription-event monitoring study. Epilepsia 2010; 51: 818-29. ( [PubMed: 20132298]
    Results of mail survey of 2243 patients given a prescription for oxcarbazepine by physicians in England between 2000 and 2003, mostly for seizures but also trigeminal neuralgia and neuropathic pain; 40% as monotherapy, most common side effects were sedation, nausea, malaise and dizziness; no mention of liver injury or ALT elevations).
  • Hsu HF, Huang SY. Severe hepatitis associated with administration of oxcarbazepine. Pediatr Int 2010; 52: 677-8. [PubMed: 20958883]
    (8 year old girl with partial seizures developed malaise, fever and pharyngitis without rash 12 days after starting oxcarbazepine [bilirubin 0.6 mg/dL, ALT 1258 U/L, ALk P 128 U/L], resolving rapidly upon stopping and then tolerating levetiracetam).
  • Drugs for epilepsy. Treat Guidel Med Lett 2013; 11: 9-18. [PubMed: 23348233]
    (Concise review of drugs of choice for epilepsy; oxcarbazepine alone or in combination is useful for treatment of partial seizures; adverse events include somnolence, dizziness, diplopia, ataxia, nausea and vomiting; liver injury is not mentioned).


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