Recent alert from U.S. Food and Drug Administration (FDA) related to lamotrigine (market as Lamictal from GlaxoSmithKline included orally disintegrating tablet; Lamictal ODT, a chewable, dispersible tablet; Lamictal CD, and extended release product; Lamictal XR), as approvement treatment for epilepsy in children 2 years and older, also for bipolar disorder in adults, said that this drug can cause aseptic meningitis, an inflammation in the layers lining the brain (meninges).

According to the U.S. FDA safety announcement, the FDA revise the Warnings and Precautions section of the drug labels and the patient Medication Guide to include information about the risk of aseptic meningitis, based on FDA’s review of adverse event reports submitted between first approved of this drug in December 1994 and November 2009.

During above period, more than 46 million prescriptions were dispensed, and total cases of aseptic meningitis identified was 40 cases, both in pediatric and adult patients who is taking the drug.

Of 40 cases, the FDA noted included fever, headache, vomiting, nausea, nuchal rigidity, photophobia, myalgias, and rash.

According to the FDA, the symptoms of aseptic meningitis occurred in 1 – 42 days after starting the drug (the mean days is 16). 1 patient reported death, although the death was not thought to be the result of aseptic meningitis, and 35 of 40 patients required hospitalization.

According to the FDA statement, most symptoms resolved after lamotrigine was withdrawn. However, 15 patients reported a rapid return of symptoms after reinitiation of the drug use; after reinitiation, the symptoms recurred within 30 minutes to 24 hours with a mean hours was 5.
The statement notes, “In these re-challenge cases, symptoms were frequently more severe after re-exposure.”

Of reported cases, they note 25 contained data on cerebrospinal fluid (CSF) findings. CSF analysis showed a mild to moderate pleocytosis, normal glucose levels, and mild to moderate increase in protein.
In addition, although a predominance of lymphocytes was reported in approximately one-third, cerebrospinal fluid white blood cell count differentials showed a predominance of neutrophils in most cases.

Some of the patients treated with lamotrigine who developed aseptic meningitis had underlying diagnoses of systemic lupus erythematosus or other autoimmune diseases.
The FDA document states, “In addition, some patients also had new onset of signs and symptoms of involvement of other organs (predominantly hepatic and renal involvement), which may suggest that some of the cases of meningitis associated with lamotrigine were part of a hypersensitivity or generalized drug reaction.”

A director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, Russell Katz, MD, in press release said, “Aseptic meningitis is a rare but serious side effect of Lamictal use. Patients that experience symptoms should consult their healthcare professional immediately.”

Any adverse event due to lamotrigine use can report and contact to Medwatich by telephone at 1-800-1088 or fax at 1-800-FDA-0178, or mail to MedWatch, FDA, 5600 Fisher Lane, Rockville, MD 20857 (use postage-paid FDA form 3500).