The Food and Drug Administration (FDA) is requiring that a new warning be added to the labeling of lamotrigine (Lamictal) stating that in rare situations the drug can cause a serious immune disorder called hemophagocytic lymphohistiocytosis (HLH). Lamotrigine is used to treat seizures and bipolar disorder. The warning is for both generic and trade-name versions of the drug.
In HLH, the immune system becomes uncontrollably hyperactive. Symptoms usually begin with a fever above 101[degrees]F and a rash, and the immune disorder may lead to severe problems of the liver, kidneys, lungs, or blood cells. The FDA has identified eight cases worldwide of confirmed or suspected HLH. These were identified in the literature and in the FDA Adverse Event Reporting System database between 1994, the year lamotrigine was approved, and September 2017. All cases required hospitalization and one resulted in death. In all cases, the patients developed HLH within eight to 24 days of starting lamotrigine therapy and had positive bone marrow biopsies consistent with hemophagocytosis.
A diagnosis of HLH can be established if a patient has at least five of the known signs or symptoms of the disorder (see International Diagnostic Criteria for HLH). Because the early symptoms of fever and rash are nonspecific, it can be difficult to identify HLH when it first occurs. Nurses should instruct patients starting lamotrigine to immediately report the following adverse effects to their provider: high persistent fever, signs of liver damage (pain or swelling in the upper right abdomen, jaundice, unusual bleeding), swollen lymph nodes, or nervous system problems (visual disturbances, difficulty walking, seizures). If a patient recently began lamotrigine and presents with any of these symptoms, HLH should be considered and laboratory tests and other diagnostic studies conducted. NPs should refer patients thought to be experiencing HLH to a hematologist.
To read the FDA Drug Safety Communication regarding lamotrigine, see http://www.fda.gov/Drugs/DrugSafety/ucm605470.htm.