AED class label changes
Manufacturers of antiepileptic drugs (AEDs) or anticonvulsant drugs will update product labeling to include a warning about an increased risk of suicidal thoughts or actions and will develop a Medication Guide to help patients understand this risk. These changes affect all approved AEDs except those indicated only for short-term use.
Drugs with updated labels
The approved AEDs affected by these safety label changes are Carbatrol, Celontin, Depakene, Depakote ER, Depakote sprinkles, Depakote tablets, Dilantin, Equetro, Felbatol, Gabitril, Keppra, Keppra XR, Klonopin, Lamictal, Lyrica, Mysoline, Neurontin, Peganone, Stavzor, Tegretol, Tegretol XR, Topamax, Tranxene, Tridione, Trileptal, Zarontin, Zonegran, and generics. FDA approved updated labeling for these drugs on April 23, 2009.
Drugs with Medication Guides
New comprehensive Medication Guides were approved on April 23, 2009, for Lamictal, Lyrica, Topamax, Zonegran and Keppra. Comprehensive Medication Guides are being developed for the other drugs and should be available by the end of 2009.
Advice for healthcare professionals
Epilepsy and other illnesses for which antiepileptic drugs are prescribed are associated with an increased risk of suicidal thoughts and behavior. If suicidal thoughts or behavior emerge during treatment with AEDs, the prescriber should consider whether these symptoms may be related to the illness being treated.
All patients who currently are taking or starting on any antiepileptic drug for any indication should be monitored for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.
Since issuing safety alerts on December 16, 2008 and January 31, 2008 (see below), FDA has been working with the manufacturers of drugs in this class to better understand the suicidality risk.
As described in the January 31, 2008, Information for Health Care Professionals Sheet on AEDS, eleven antiepileptic drugs were included in FDA’s original pooled analysis of placebo-controlled clinical studies in which these drugs were used to treat epilepsy as well as psychiatric disorders and other conditions.
The increased risk of suicidal thoughts or behavior was generally consistent among the eleven drugs, with varying mechanisms of action and across a range of indications. This observation suggests that the risk applies to all antiepileptic drugs used for any indication.
Valproate Information Information for Healthcare Professionals: Suicidal Behavior and Ideation and Antiepileptic Drugs[ARCHIVED]
FDA Public Health Advisory: Suicidal Thoughts and Behavior Antiepileptic Drugs[ARCHIVED]
FDA Requires Warnings about Risk of Suicidal Thoughts and Behavior for Antiepileptic Medications[ARCHIVED]
Antiepileptic Template Letter(PDF - 74KB)
Template Letter to Sponsors 12/16/2008
FDA Alerts Health Care Providers to Risk of Suicidal Thoughts and Behavior with Antiepileptic Medications[ARCHIVED]
Statistical Review and Evaluation: Antiepileptic Drugs and Suicidality(PDF - 304KB)
This is the May 23, 2008 statistical review that describes the anti-epilepsy drugs suicidality metaanalysis conducted by the Agency.
Labeling and Regulatory History from Drugs@FDA
The following is a list of antiepileptic drugs included in the analyses. Some of these drugs are also available in generic form.
Carbamazepine (marketed as Carbatrol, Equetro, Tegretol, Tegretol XR) Prescribing and Label Information Divalproex sodium (marketed as Depakote, Depakote ER) Prescribing and Label Information Felbamate (marketed as Felbatol) Prescribing and Label Information Gabapentin (marketed as Neurontin) Prescribing and Label Information Lamotrigine (marketed as Lamictal) Prescribing and Label Information Levetiracetam (marketed as Keppra) Prescribing and Label Information Oxcarbazepine (marketed as Trileptal) Prescribing and Label Information Pregabalin (marketed as Lyrica) Prescribing and Label Information Tiagabine (marketed as Gabitril) Prescribing and Label Information Topiramate (marketed as Topamax) Prescribing and Label Information Zonisamide (marketed as Zonegran) Prescribing and Label Information