FDA Drug Safety Communication

Based on a U.S. Food and Drug Administration (FDA) review of a large clinical trial that we required the drug companies to conduct, we have determined the risk of serious side effects on mood, behavior, or thinking with the stop-smoking medicines Chantix (varenicline) and Zyban (bupropion)* is lower than previously suspected. The risk of these mental health side effects is still present, especially in those currently being treated for mental illnesses such as depression, anxiety disorders, or schizophrenia, or who have been treated for mental illnesses in the past. However, most people who had these side effects did not have serious consequences such as hospitalization. The results of the trial confirm that the benefits of stopping smoking outweigh the risks of these medicines.

As a result of our review of the large clinical trial, we are removing the Boxed Warning, FDA's most prominent warning, for serious mental health side effects from the Chantix drug label. The language describing the serious mental health side effects seen in patients quitting smoking will also be removed from the Boxed Warning in the Zyban label.** We are also updating the existing warning section in both labels that describes the side effects on mood, behavior, or thinking to include the results from the clinical trial. This decision is consistent with the recommendations of external experts at a September 2016 FDA Advisory Committee meeting. The patient Medication Guide that explains the risks associated with the use of the medicines will continue to be provided with every patient prescription; however, the risk evaluation and mitigation strategy (REMS) that formally required the Medication Guide will be removed.

Our review of the clinical trial results also confirmed that Chantix, Zyban, and nicotine replacement patches were all more effective for helping people quit smoking than was an inactive treatment called a placebo. These medicines were found to better help people quit smoking regardless of whether or not they had a history of mental illness.

Health care professionals should counsel patients about the benefits of stopping smoking and how they can get help to quit, and discuss the benefits and risks of using medicines to help them quit smoking.

FDA continues to evaluate the safety and effectiveness of drugs after they go on the market. In the case of Chantix and Zyban, we received and assessed case reports of serious changes in mood and behavior in patients taking the medicines, which led us to require that a Boxed Warning be added to the labels in 2009. At the time, we required the drug companies to conduct a large clinical trial to evaluate these side effects, and we have now reviewed the findings. Based on these results, we now have a better idea about the frequency and severity of these side effects on mood, behavior, or thinking, and have confirmed that the benefits of taking Chantix or Zyban to help quit smoking outweigh these risks.

*There are other bupropion products that are approved for psychiatric disorders, including major depressive disorder. The language concerning serious side effects on mood, behavior, or thinking in people taking bupropion for stopping smoking will be removed from the Boxed Warning of those products' labels as well.

**The active ingredient in Zyban is in the antidepressant class; therefore the label carries the class Boxed Warning for suicidality and antidepressant drugs. This language will remain in a Boxed Warning in the labels for Zyban and other bupropion products.

View the full FDA Drug Safety Communication on FDA.gov