Rash and Liver Dysfunction Related to Lamotrigine Therapy

Abstract

An 81-year-old female with a 50 year history of bipolar disorder and no known history of liver dysfunction LEA RC SERWETMAN PharmD, at time of writing, Clinical Rotation in Acute Care, Advanced Pharmacy Experiential Program, Objective: To report a case of rash and liver dysfunction associated with lamotrigine treatment.Case Summary: An 81-year-old woman with a history of bipolar disorder presented to the emergency department with complaints of fever, chills, nausea, and headache. Two weeks prior to presentation, liver enzymes were normal. Lamotrigine 50 mg/day and sustained-release bupropion 200 mg/day were started after discontinuation of citalopram. The patient had previous exposure to bupropion and documented rash with exposure to penicillin and sulfa. On admission, laboratory tests revealed slightly elevated liver enzymes and slightly low serum albumin. All medications were continued. On hospital day 3, a diffuse maculopapular rash developed on the patient's chest, abdomen, neck, and upper extremities, which was pruritic and warm to the touch. Both lamotrigine and bupropion were discontinued. Liver enzymes increased to more than 3 times the upper limit of normal, and serum albumin decreased. Liver function tests improved on day 6, and the rash resolved. Discussion:Predictive risk factors associated with lamotrigine-induced rash and liver dysfunction include rapid dose titration, previously reported rash with other medications, age, and concurrent interacting medications. More serious adverse effects, such as Stevens-Johnson syndrome and fulminant hepatic failure, have also been associated with lamotrigine treatment. If rash appears at any time during treatment, lamotrigine must be discontinued. According to the Naranjo probability scale, an association between lamotrigine and rash and liver dysfunction could be considered probable in this case. Conclusions:A faster than recommended dose titration may lead to lamotrigine-induced adverse effects such as rash and liver dysfunction in patients with risk factors.

Lamotrigine-Related Severe Cutaneous Adverse Reaction in Patient with Epilepsy

“…Many patients showed improvement after stopping AEDs. Furthermore, combined treatment with VPA and LTG was observed to cause hepatotoxicity through decreased clearance of LTG [8,11].…”

“…Furthermore, LTG has rare adverse severe skin reactions such as: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms (DRESS), and anticonvulsant hypersensitivity syndrome, which may lead to terminating LTG treatment [9][10][11]. Slow introduction and titration of LTG dosage may reduce or eliminate these adverse symptoms [9].…”

“…Additionally, LTG was also used to treat bipolar I disorder and as adjunctive therapy for the management of seizures associated with Lennox-Gastaut syndrome [9][10][11].…”

Lamotrigine–dextran conjugates-synthesis, characterization, and biological evaluation

“…Patients receiving chronic treatment with LTG in the form of single or polytherapy are at a high risk of elevation of hepatic enzymes without clinical signs or symptoms of hepatic dysfunctions to fatal hepatotoxicity (May et al, 1996;Meshkibaf et al, 2006;Fayad et al, 2000). A study with different dose of LTG showed that at therapeutic level there was a significant increase in the levels of alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin (Serwetman et al, 2008;Overstreat et al, 2002;Moeller 2008;Makin et al, 1995;Sauve et al, 2000).…”