Anti-Smoking Drugs Get FDA 'Black-Box' Warning

03 july 2009-- Two drugs prescribed to help people quit smoking, Chantix and Zyban, will now carry "black-box" warnings on the potential risks of psychiatric problems, including depression and suicidal thoughts, U.S. health officials said Wednesday.

The U.S. Food and Drug Administration said it was mandating the black-box warnings, the strictest possible, based on reports to the agency of these side effects and on a review of clinical trials and scientific literature.

"We are requiring the manufacturers of the smoking-cessation drugs Chantix and Zyban to add a new boxed warning highlighting the risk of serious mental health symptoms with use of these products," Dr. Curt Rosebraugh, director of the FDA's Office of Drug Evaluation II, said during a Wednesday teleconference.

The agency's review found that some people who used Chantix (varenicline) and Zyban (bupropion) experienced unusual changes in behavior, became depressed, or had their depression worsen and had thoughts of suicide or dying, the FDA said.

Rosebraugh said there were reports of 98 suicides and 188 suicide attempts involving Chantix, and 14 suicides and 17 attempts reported with Zyban.

For many users, the problems started soon after they began taking the drugs and ended when they stopped taking them. Some users, however, continued to have symptoms even after stopping the drugs. In a few cases, the problems started after the drugs were stopped, Rosebraugh said.

People taking these drugs who develop any of these symptoms should be monitored until their symptoms clear up, even if symptoms develop after stopping these drugs, Rosebraugh added.

The drugs don't contain nicotine, and some of the symptoms may be caused by nicotine withdrawal. People who stop smoking can suffer from depression, anxiety, irritability, restlessness, and sleep disturbances, the FDA noted.

Some patients who were using the drugs experienced the side effects while they were still smoking, the agency said.

Rosebraugh said the risk of using these drugs needs to be balanced with the substantial benefits of quitting smoking, and these drugs can be very effective.

"Stopping smoking is a goal we all want to work towards, and if people need medication to do it they should have access to it. So we don't want to scare people off from trying to use a medication to stop smoking; we just want them to be carefully monitored," he said.

In addition to the warning, the FDA is requesting more prescribing information in the warning section of the label, and new information in the Medication Guide for patients that discusses the risk of mental health events while using these products.

The makers of the drugs will also be required to do a clinical trial to see how often serious psychiatric symptoms occur in patients using a variety of therapies to help them quit smoking, including patients who currently have psychiatric disorders, Rosebraugh said. Results of this trial won't be known for several years, he added.

Chantix is manufactured by Pfizer Inc. Zyban is made by GlaxoSmithKline.

"The labeling update underscores the important role of health-care providers in treating smokers attempting to quit and provides specific information about Chantix and instructions that physicians and patients should follow closely," Dr. Briggs W. Morrison, senior vice president for the Primary Care Development Group at Pfizer, said in a prepared statement. "Quitting smoking is one of the best things people can do for their health, but the quitting process is both difficult and complex."

The FDA's review of consumers using nicotine patches did not find a link between patches and psychiatric side effects.

The antidepressant Wellbutrin, which contains the same active ingredient as Zyban, already carries a black-box warning.