WASHINGTON (Reuters) - Widely used epilepsy drugs must carry a warning that the medicines increase the chances of suicidal thoughts or actions, U.S. officials said on Tuesday.
Manufacturers also need to develop pamphlets to alert patients to the risks of the medicines, which include Pfizer Inc’s (PFE.N) Lyrica and Neurontin, GlaxoSmithKline PLC’s (GSK.L) Lamictal and Johnson & Johnson’s (JNJ.N) Topamax.
The FDA action followed recommendations from a panel of outside experts who met in July. The advisers agreed the drugs needed a warning but urged against a strong “black box” that could scare patients from effective treatment.
In a public health advisory, the FDA said it found people “who took one of the antiepileptic drugs, either alone or as part of a combination, had almost twice the risk of having suicidal thoughts or behaviors compared with patients who did not take one of the drugs.”
The increase represented about one additional case of suicidal thinking or behavior for every 530 patients treated with one of the medicines, the FDA said. The chances were about 0.4 percent for each person with an antiepileptic drug, and 0.2 percent without it.
The findings were based on an FDA analysis of 199 clinical trials involving 11 anti-epileptic drugs. The risk of suicidal thoughts or behavior was “generally consistent” among all of the drugs and was seen if patients were treated for epilepsy, psychiatric disorders or other conditions.
Sales of epilepsy drugs topped $10 billion in 2007, according to health-care information company IMS Health. Both Lamictal and Topamax saw roughly $2.1 billion sales, while Lyrica reached nearly $1.1 billion.
Epilepsy drugs aim to prevent seizures, and roughly 11 million patients take them, according to FDA data. Some of the medicines also are approved for depression, migraines or other conditions.
The FDA said its action applied to all anti-epileptic drugs. It listed 21 different medicines sold under various brand and generic names.
Pfizer had argued to the FDA panel meeting in July that Lyrica and Neurontin did not increase the risk of suicidal behavior and should be exempt from tougher warnings.
On Tuesday, Pfizer spokesman Jack Cox said the company would work with the FDA to update the drug labels. He said Lyrica and Neurontin “are important medicines that have helped millions of patients with serious conditions.”
The FDA said it was using powers it received earlier this year to order the drugmakers to add the warnings. Companies may appeal the ruling. Some of the medicines already included information about suicidal behavior.
Patients and caregivers should contact a doctor if they notice unusual changes in mood, behavior or actions, the FDA advised. “Patients who are currently taking an antiepileptic medicine should not make any treatment changes” without talking to a doctor, Russell Katz, director of neurology drugs at the FDA, said in a statement.
Before the panel meeting in July, FDA staff had advocated a black-box warning about the risk of suicidal behavior. The warning ordered by the FDA on Tuesday will be less prominent.
Doctors have voiced concern that patients will stop taking the drugs and risk seizures. “The risk of suicide possibly associated with (epilepsy drugs) is extremely small compared to the potential danger of leaving patients untreated,” the American Epilepsy Society said in a statement last week.
Glaxo believes the findings of the FDA analysis should be added to the labels of epilepsy drugs, company spokeswoman Sarah Alspach said, adding Glaxo would review the FDA action.
The company “remains confident in the overall safety and efficacy profile of Lamictal,” she said.
Abbott spokeswoman Laureen Cassidy said the company would comply with the request for its drug, Depakote, even though the FDA analysis “did not detect a signal” for the medicine.
Topamax already includes information about suicidal behavior in its prescribing instructions, said Tricia Geoghegan, a spokeswoman for J&J unit Ortho-McNeil Neurologics Inc. “We will continue to work with the FDA to make sure any changes they request are in there,” she said.
UCB SA (UCB.BR) will add the warning to its drug Keppra, spokeswoman Andrea Levin said. Another UCB drug, Vimpat, already includes the warning, she said.
Reporting by Lisa Richwine; editing by Maureen Bavdek and Carol Bishopric