The Food and Drug Administration (FDA) has issued warning regarding the use of lamotrigine and the possibility of hemophagocytic lymphohistiocytosis (HLH), a rare but serious immune system reaction. The FDA is requiring that a new warning be added to the prescribing information for all lamotrigine products to alert of this possible side effect.
Lamotrigine is indicated for the treatment of seizure disorders as well as bipolar I disorder.
According to the FDA, 8 cases of confirmed or suspected HLH associated with lamotrigine have been reported worldwide (2 in the US). All cases were reported to have serious outcomes. All eight reported hospitalization, three reported other serious important medical events, two reported the outcome as being lifethreatening, and one reported death. All cases had a plausible temporal relationship with lamotrigine, occurring within 24 days of starting lamotrigine treatment. Doses ranged from 25 mg every other day to 250 mg once daily in the six cases that reported this information. In seven cases, HLH improved after treatment and discontinuation of Lamictal, and one case did not improve and had a fatal outcome.
In all but one case, HLH had improved after treatment (i.e., steroids, intravenous immunoglobulin, blood products, chemotherapy) and discontinuation of lamotrigine. While all 8 cases reported concomitant medications, none of these medications were associated with HLH.
As per the FDA communication, a diagnosis of HLH can be made if a patient has ≥5 of the following symptoms:
Fever and rashes, Splenomegaly, Cytopenias affecting ≥2 of 3 lineages in the peripheral blood (hemoglobin <90g/L [in infants <4 weeks: hemoglobin <100g/L; platelets <100 x 109/L; neutrophils <1.0 x 109/L), Hypertriglyceridemia (fasting triglycerides ≥265mg/dL) and/or hypofibrinogenemia (≤1.5g/L), High levels of blood ferritin (≥500µg/L), Hemophagocytosis identified through bone marrow, spleen, or lymph node biopsy, Decreased or absent Natural Killer Cell activity, Elevated blood levels of CD25 showing prolonged immune cell activation (≥2400 U/mL)
Patients should be counseled on the symptoms associated with HLH and should be advised to seek medical attention immediately if they experience these symptoms while on lamotrigine therapy.
