FDA Warns of Aseptic Meningitis Risk With Lamotrigine

Susan Jeffrey

Disclosures

August 12, 2010

August 12, 2010 — The US Food and Drug Administration (FDA) is warning that lamotrigine (Lamictal, GlaxoSmithKline), approved for treatment of epilepsy in children 2 years and older and for bipolar disorder in adults, can cause aseptic meningitis.

"FDA is revising the Warnings and Precautions section of the drug labels and the patient Medication Guide to include information about this risk," the FDA safety announcement notes.

Healthcare professionals are advised that if meningitis is suspected, patients should also be evaluated for other causes of meningitis and treated as indicated. "Discontinuation of Lamictal should be considered if no other clear cause of meningitis is identified," the announcement states.

40 Cases

The decision to revise the lamotrigine label is based on FDA's review of adverse event reports submitted between December 1994, when it was first approved, and November 2009. A total of 40 cases of aseptic meningitis were identified in both pediatric and adult patients taking the drug. During this same period, it is estimated more than 46 million prescriptions were dispensed.

Among the 40 cases, headache, fever, nausea, vomiting, nuchal rigidity, rash, photophobia, and myalgias were noted, the FDA notes. Symptoms occurred 1 to 42 days after starting the drug, with a mean of 16 days. There was 1 reported death, although the death was not thought to be the result of aseptic meningitis. Thirty-five of the 40 patients required hospitalization.

In most cases, symptoms resolved after lamotrigine was withdrawn.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

Of reported cases, 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, they note. In addition, cerebrospinal fluid white blood cell count differentials showed a predominance of neutrophils in most cases, although a predominance of lymphocytes was reported in approximately one-third.

Some of the patients treated with lamotrigine who developed aseptic meningitis had underlying diagnoses of systemic lupus erythematosus or other autoimmune diseases. "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," they FDA document states.

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

Lamotrigine is sold as an orally disintegrating tablet (Lamictal ODT), a chewable, dispersible tablet (Lamictal CD), and as an extended release product (Lamictal XR).

To report adverse events related to lamotrigine, contact MedWatch by telephone at 1-800-1088, by fax at 1-800-FDA-0178, MedWatch Online; or by mail to MedWatch, FDA, 5600 Fishers Lane, Rockville, MD 20857 (use postage-paid FDA Form 3500).

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