LAMICTAL can cause serious rashes requiring hospitalization and discontinuation of treatment. The incidence of these rashes, which have included Stevens-Johnson syndrome, is approximately 0.8 percent (8 per 1,000) in pediatric patients (2 to 16 years of age) receiving LAMICTAL as adjunctive therapy for epilepsy and 0.3 percent (3 per 1,000) in adults on adjunctive therapy for epilepsy. In clinical trials of bipolar and other mood...
LAMICTAL can cause serious rashes requiring hospitalization and discontinuation of treatment. The incidence of these rashes, which have included Stevens-Johnson syndrome, is approximately 0.8 percent (8 per 1,000) in pediatric patients (2 to 16 years of age) receiving LAMICTAL as adjunctive therapy for epilepsy and 0.3 percent (3 per 1,000) in adults on adjunctive therapy for epilepsy. In clinical trials of bipolar and other mood disorders, the rate of serious rash was 0.08 percent (0.8 per 1,000) in adult patients receiving LAMICTAL as initial monotherapy and 0.13 percent (1.3 per 1,000) in adult patients receiving LAMICTAL as adjunctive therapy. In a prospectively followed cohort of 1,983 pediatric patients (2 to 16 years of age) with epilepsy taking adjunctive LAMICTAL, there was 1 rash-related death. In worldwide postmarketing experience, rare cases of toxic epidermal necrolysis and/or rash-related death have been reported in adult and pediatric patients, but their numbers are too few to permit a precise estimate of the rate.
Other than age, there are as of yet no factors identified that are known to predict the risk of occurrence or the severity of rash caused by LAMICTAL. There are suggestions, yet to be proven, that the risk of rash may also be increased by (1) coadministration of LAMICTAL with valproate (includes valproic acid and divalproex sodium), (2) exceeding the recommended initial dose of LAMICTAL, or (3) exceeding the recommended dose escalation for LAMICTAL. However, cases have occurred in the absence of these factors.
Nearly all cases of life-threatening rashes caused by LAMICTAL have occurred within two to eight weeks of treatment initiation. However, isolated cases have occurred after prolonged treatment (e.g., six months). Accordingly, duration of therapy cannot be relied upon as means to predict the potential risk heralded by the first appearance of a rash.
Although benign rashes are also caused by LAMICTAL, it is not possible to predict reliably which rashes will prove to be serious or life-threatening. Accordingly, LAMICTAL should ordinarily be discontinued at the first sign of rash, unless the rash is clearly not drug-related. Discontinuation of treatment may not prevent a rash from becoming life-threatening or permanently disabling or disfiguring.
The Food and Drug Administration (FDA) issued a public warning on Aug. 12, 2010, about the risk of developing aseptic meningitis with the use of lamotrigine (LAMICTAL).
Lamotrigine was approved by the FDA in 1994 for seizure control and in 2003 for bipolar disorder. In 2009, the total number of lamotrigine and LAMICTAL prescriptions dispensed in the U.S. was more than 8.8 million.
The FDA’s decision to issue this serious warning for lamotrigine was based on a review of the drug’s adverse event reports submitted from December 1994 through November 2009. A total of 40 cases of aseptic meningitis were identified in pediatric and adult patients taking lamotrigine.
Forty meningitis cases may sound insignificant, but only 1 to 10 percent of serious adverse drug reactions are reported to the FDA. The true number of cases of aseptic meningitis experienced by patients taking lamotrigine since 1994 is between 400 and 4,000, or perhaps even higher.
Meningitis is an inflammation of the meninges, the thin tissue that surrounds the brain and spinal cord. Aseptic meningitis appears similar to bacterial meningitis; however, bacteria do not grow in cultures of the fluid around the brain and spinal cord.
In the 40 reported cases, meningitis symptoms including headache, fever, nausea, vomiting, neck pain, rash, sensitivity to light and muscle pain were reported. Symptoms developed one to 42 days after starting lamotrigine, or within 16 days on average. There was one reported death, but the link to aseptic meningitis in that case was uncertain. Thirty-five out of the 40 cases required hospitalization.
Most of the time, the symptoms disappeared after the patient stopped taking lamotrigine. In 15 cases, there was a rapid return of symptoms after a patient again started taking lamotrigine. In the cases where was restarted, the symptoms recurred within 30 minutes and up to 24 hours after restarting the drug, and frequently became more severe than they previously had been.
Some patients who developed aseptic meningitis after taking lamotrigine had underlying diseases such as systemic lupus erythematosus or other autoimmune disorders. In addition, some patients had side effects involving other organs, such as the liver and kidney, indicating that some of the cases of lamotrigine-associated meningitis may have been caused by hypersensitivity or general drug reactions.
FDA-approved patient information for lamotrigine
Since 2006, lamotrigine has been required to display a black-box warning (see above) in its professional product label about an increased risk of serious skin reactions with use of the drug.
A black box is the strongest type of safety warning that the FDA can require in a drug’s professional product label or package insert, and is reserved for products that can cause serious harm or death to patients.
Lamotrigine also is among a growing list of drugs that are required to be dispensed with an FDA-approved Medication Guide written specifically for consumers. The FDA has the authority to require Medication Guides for drugs that present serious public health concerns.
The Medication Guide for lamotrigine can be obtained on the FDA’s website at www.fda.gov or by asking a pharmacist.
What You Can Do
It is important to quickly diagnose the cause of meningitis so that treatment can be started as early as possible, especially if the meningitis is found to be bacterial. Although lamotrigine has been associated with aseptic (nonbacterial) meningitis, people who are using the drug could also, coincidentally, have bacterial meningitis, which needs to be promptly diagnosed and treated with antibiotics. Contact your health care professional right away if you experience headache, fever, chills, nausea, vomiting, stiff neck, rash, abnormal sensitivity to light, drowsiness or confusion while taking lamotrigine.
Read the Medication Guide given to you each time you receive a prescription for lamotrigine. It will explain the risks and benefits of the drug.
Consumers may report serious adverse events with lamotrigine or other product-quality problems to the FDA’s MedWatch Adverse Event Reporting program online or by regular mail, fax or phone.
Regular Mail: Use postage-paid FDA form 3500 and mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787
Fax: (800) FDA-0178
Phone: (800) FDA-1088