Hemophagocytic lymphohistiocytosis associated with the use of lamotrigine

Objective To describe adverse event reports of hemophagocytic lymphohistiocytosis (HLH) reported in association with lamotrigine. Methods The Food and Drug Administration Adverse Event Reporting System database of spontaneous adverse event reports and medical literature databases were searched for cases of HLH reported in association with lamotrigine. Cases were included if they met the case definition of suspected or confirmed HLH and if causal association was assessed as robust or supportive. Results Eight cases met the case definition for HLH and were deemed causally associated with lamotrigine. These 8 cases of HLH had a plausible temporal relationship because they occurred within a 24-day interval from lamotrigine initiation. The doses ranged from 25 mg every other day to 250 mg once daily in the 6 cases that reported this information. Seven patients improved with drug discontinuation and one patient died after drug discontinuation and receiving an unspecified chemotherapy. Conclusions Lamotrigine is associated with immune-related adverse reactions including HLH. HLH is a potentially fatal event; prompt recognition and early therapeutic intervention to mitigate the event is important in improving patient outcomes.