FDA: Boxed Warning Removed from Smoking Cessation Treatment

The FDA determined the benefits of this smoking cessation therapy outweighed the potential risks.

The Food and Drug Administration (FDA) has approved updated labeling for Chantix (varenicline; Pfizer) and Zyban (bupropion; GlaxoSmithKline) that removes the boxed warning regarding serious neuropsychiatric events. 

The removal of the boxed warning is supported by data from the EAGLES (Evaluating Adverse Events in a Global Smoking Cessation Study) study (n=8,144) , the largest smoking cessation clinical trial in patients with and without a history of psychiatric disorder. This decision was also in line with the recent recommendation by the FDA Psychopharmacologic Drugs and Drug Safety and Risk Management Advisory Committees. 

The EAGLES study found that in the group of patients without a history of psychiatric disorder, Chantix was not associated with a higher incidence of clinically significant neuropsychiatric adverse events in a composite endpoint comprising of anxiety, depression, feeling abnormal, hostility, agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, and irritability. Among those with a history of psychiatric disorder, there were more events reported in each treatment group vs. the non-psychiatric group.  

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Although there is still a risk of neuropsychiatric adverse events associated with Chantix and Zyban, most patients who experienced changes in mood, behavior or thinking did not have serious consequences. Thus, the FDA determined the benefits of these smoking cessation treatments outweigh the risk of neuropsychiatric adverse events. 

The updated labeling now states that postmarketing reports of serious or clinically significant neuropsychiatric adverse events in patients treated with Chantix include changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide. Patients receiving Chantix should be observed for the occurrence of such symptoms and should discontinue treatment if they experience such symptoms. 

The Medication Guide that contains the risks associated with the use of the medicines will still be issued with every patient prescription but the risk evaluation and mitigation strategy (REMS) that formally required the Medication Guide will be lifted.  

Other revisions based on the EAGLES study include updates to the corresponding warning regarding neuropsychiatric safety and the addition of information on the superior efficacy of Chantix vs. bupropion or nicotine patch. 

“As healthcare providers work on the front lines to help people who are struggling to quit smoking, this new labeling provides clinically relevant information on the safety and efficacy of CHANTIX to help them and their patients make informed decisions about smoking cessation treatment,” said Dr. A. Eden Evins, director, Massachusetts General Hospital Center for Addiction Medicine and William Cox Family Associate Professor of Psychiatry in the Field of Addiction Medicine, Harvard Medical School.

Chantix, an alpha4-beta2 nicotinic acetylcholine receptor partial agonist, was initially approved by the FDA in May 2006 to aid adults aged ≥18 years in smoking cessation along with support.

For more information call (888) 463-6332 or visit FDA.gov.