The U.S. Food and Drug Administration said it will immediately require boxed warnings about the risk of serious neuropsychiatric symptoms on the packaging of two popular smoking cessation drugs -- varenicline (Chantix) and buproprion (Zyban, Wellbutrin and generics).
Reports of behavioral changes, depressed mood, agitation, hostility and suicidal thoughts and behavior associated with use of the drugs have been submitted to the FDA's adverse event reporting system.
Throughout the marketing history of the drugs, there have been 98 suicides and 188 attempted suicides in varenicline users and 14 suicides and 17 attempted suicides in buproprion users, the agency reported.
The FDA is not recommending discontinuation of the medications, which have been shown effective for quitting smoking, according to Dr. Curtis Rosebraugh, director of the agency's Office of Drug Evaluation II.
But the FDA is recommending that clinicians monitor their patients for neuropsychiatric symptoms after initiating treatment.
The FDA has been conducting a safety review of varenicline since receiving preliminary reports of problems in 2007.
Rosebraugh said it was somewhat surprising that a similar safety signal turned up for buproprion.
Because the reports of symptoms are sent to the FDA, the agency cannot make effective estimates of rates of the problems, but Rosebraugh said he thinks they are very low.
In many cases, but not all, the symptoms stopped after discontinuing treatment.
Patients who experience these symptoms while taking the drugs should be monitored, even after stopping treatment, until the symptoms resolve, Rosebraugh said.
Although some neuropsychiatric symptoms could be the result of nicotine withdrawal, there have been reports of problems in treated patients who were still smoking.
The manufacturers of the medications will be required to conduct a clinical trial to evaluate the occurrence of neuropsychiatric symptoms in patients using varenicline and buproprion to quit smoking. The study will include patients with pre-existing psychiatric disorders.
In addition to the boxed warning, information regarding allergic reactions and skin reactions, as well as updated information regarding the risk of accidental injury while driving or operating machinery, will be included in other parts of the label.