Lamotrigine-associated reversible severe hepatitis: A case report

Abstract

A 43-year-old woman with a history of depression, which was being treated with oxcarbazepine twice a day (300 mg/morning and 450 mg/evening), was started on lamotrigine 2 weeks prior to her presentation, with the dose increased to 50 mg/day just prior to admission.Two weeks after starting the lamotrigine, she developed nausea and a generalized pruritic macular rash. She sought treatment in ABSTRACTIntroduction: Anticonvulsant hypersensitivity syndrome is a severe idiosyncratic reaction to antiepileptic drugs. We report a case of a woman with lamotrigine-associated hepatitis who recovered spontaneously with supportive treatment.Case Report: A 43-year-old woman was being treated with oxcarbazepine for depression and was started on lamotrigine 2 weeks prior to her presentation. The patient then developed nausea and a generalized pruritic macular rash, and was found to have elevated liver enzymes, which peaked at AST, 6079 IU/L; ALT, 6900 IU/L; total bilirubin, 3.9 mg/dL(66.7 mol/L); alkaline phosphatase, 149 IU/L; international normalized ration (INR), 1.9. The patient showed no signs of encephalopathy and her clinical examination was essentially normal except for very mild jaundice and a diffuse erythematous pruritic macular rash. The patient was hydrated and managed with supportive care. On the third day of hospitalization, her liver enzymes had improved substantially and she was discharged. At follow-up 1 month later the patient's liver enzymes were within the normal range.Discussion: We hypothesize that lamotrigine was directly responsible for the patient's rash and liver impairment given the time sequence of drug introduction and resolution of symptoms and liver enzyme abnormality once the drug was withdrawn. The patient suffered severe transaminitis when lamotrigine was added to oxcarbazepine, which resolved after termination of the medication and supportive management. We recommend monitoring the hepatic function in patients who have just been initiated on lamotrigine, especially if they develop jaundice.

Lamotrigine Associated DRESS Syndrome – a Case Report

“…Severe rashes due to lamotrigine occurr almost regularly within the fi rst 6 -8 weeks of exposure, rarely after 12 weeks and almost exclusively later (30). Several reports of lamotrigine-induced DRESS syndrome have been reported in the literature (12,27,28,29,(31)(32)(33)(34). Th e second psychoactive drug our patient was taking in combination with lamotrigine was an antipsychotic -olanzapine, an oxazepine that is prescribed to patients with schizophrenia or recurrent bipolar disorder.…”

“…Lamotrigine [6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine] is an antiepileptic drug, used in the management of a broad range of seizures in adults and children which is not an aromatic antiepileptic, thus being structurally and pharmacologically unrelated to other antiepileptic medications e.g. carbamazepine (28,29). Lamotrigine has been repoted in association with severe skin rash, multiorgan failure, DRESS syndrome, acute hepatic failure, and disseminated intravascular coagulation.…”

An Epileptic Patient with Recurrent Hyperbilirubinemia Caused by Gilbert Syndrome

“…Clarkson and Choonara [16] and Su-Yin et al [17] once reported that VPA/LTG can cause liver injury to different degrees. Hepatic injuries associated with these AEDs could be classified into two subtypes: the common type and the fulminant liver failure type.…”

A patient with epilepsy suffering from repeatedly hyperbilirubinemia caused by Gilbert Syndrome: a case report and literatures review

“…Clarkson et al [5,6] once reported that VPA/LTG can cause liver damage to various degrees, and hepatic injuries associated with these drugs can be classified to two subtypes: common type and fulminant liver failure. The former manifests temporary and reversible elevation of bilirubin and liver enzyme values, which is usually dose-dependent and the abnormality can return to normal shortly after the drug is withdrawn [24]; the latter is life-threatening and infrequent, occurring generally within 2-8 weeks (LTG) or 3 months (VPA) after initiating the use of LTG/VPA [25,26].…”

“…It has been known that certain antiepileptic drugs (AEDs) such as valproic acid (VPA) and lamotrigine (LTG) would give rise to the hepatic injury, ranging from mild and reversible abnormality of liver function tests to serious hepatotoxicity [5,6]. However, Levetiracetam (LEV), which is metabolized by enzymatic hydrolysis of the acetamide group in blood rather than liver cytochrome P450 enzymes, and excreted by the urinary system [7,8], has a minor effect on liver function.…”