Pfizer announced that the US Food and Drug Administration (FDA) approved updates to the Chantix (varenicline) labeling, including removal of the boxed warning regarding serious neuropsychiatric events. The removal of the boxed warning is based on the outcomes of EAGLES (Evaluating Adverse Events in a Global Smoking Cessation Study), the largest smoking cessation clinical trial in patients without and with a history of psychiatric disorder, and is consistent with the recent recommendation of the FDA Psychopharmacologic Drugs and Drug Safety and Risk Management Advisory Committees. Additional labeling revisions based on EAGLES include updates to the corresponding warning regarding neuropsychiatric safety and the addition of information on the superior efficacy of Chantix compared to bupropion or nicotine patch.

“For millions who smoke, stopping smoking is one of the most important steps they can take to improve their health, and Pfizer is committed to helping smokers in their quit journey,” said Freda Lewis-Hall, M.D., DFAPA, chief medical officer and EVP, Pfizer Inc. “We are pleased with the FDA’s decision to update the Chantix labeling based on EAGLES – the largest clinical trial of smoking cessation medications - and we expect this new information may further facilitate an informed discussion about quitting with Chantix between smokers and healthcare providers.”

“While the benefits of quitting are immediate and substantial, few smokers are able to quit on their own and need the help of counseling and smoking cessation therapy,” 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. “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.”

In the US, smoking is the leading preventable cause of death, responsible for roughly 540,000 deaths each year. Stopping smoking has significant health benefits, including reducing the risk of tobacco-related diseases such as lung cancer, heart disease, stroke, chronic respiratory disease and other conditions. While smoking rates have declined overall, some segments of society have not made the same progress including people living with mental illness, Veterans, LGBTQ and other minority communities.

The updated warning in the Chantix labeling notes that postmarketing reports of serious or clinically significant neuropsychiatric adverse events in patients treated with Chantix included 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 attempting to quit smoking with Chantix should be observed for the occurrence of such symptoms and instructed to discontinue Chantix and contact a healthcare provider if they experience such symptoms.

In EAGLES, in the cohort of patients without a history of psychiatric disorder, Chantix was not associated with an increased incidence of clinically significant neuropsychiatric adverse events in a composite endpoint comprising anxiety, depression, feeling abnormal, hostility, agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, and irritability.

In the cohort of patients with a history of psychiatric disorder, there were more events reported in each treatment group compared to the non-psychiatric cohort, and the incidence of events in the composite endpoint was higher for each of the active treatments compared to placebo: Risk Differences (RDs) (95%CI) vs. placebo were 2.7% (-0.05, 5.4) for Chantix, 2.2% (-0.5, 4.9) for bupropion, and 0.4% (-2.2, 3.0) for transdermal nicotine. The neuropsychiatric events of a serious nature were reported in 0.6% of Chantix-treated patients, with 0.5% involving psychiatric hospitalization. In placebo-treated patients, serious neuropsychiatric events occurred in 0.6%, with 0.2% requiring psychiatric hospitalization.

EAGLES is a randomized, blinded, active- and placebo-controlled clinical trial, which was conducted by Pfizer in collaboration with GlaxoSmithKline at the request of and designed in consultation with the FDA and the European Medicines Agency (EMA). The trial is the first and largest to compare the safety and efficacy of Chantix, bupropion and nicotine replacement patch in approximately 8,000 smokers without and with a history of psychiatric disorder. The trial was designed to compare the risk of clinically significant neuropsychiatric adverse events in patients using Chantix, bupropion, nicotine replacement therapy or placebo as smoking cessation aids over 12 weeks of treatment, and to determine whether smokers with a history of psychiatric disorder are at a greater risk for developing clinically significant adverse events compared to smokers without a history of psychiatric disorder.

Chantix (also known as Champix in the EU and other countries) was approved by the FDA in May 2006 as a prescription medication that, along with support, helps adults 18 and over stop smoking. Chantix is approved in more than 100 countries and has been prescribed to over 20 million patients worldwide, including more than 11 million in the US. Adults who smoke may benefit from quit-smoking support programs and/or counseling during their quit attempt. It’s possible that patients might slip up and smoke while taking Chantix. If patients slip up, they can stay on Chantix and keep trying to quit.1

Chantix is contraindicated in patients with a history of serious hypersensitivity or skin reactions to Chantix.

Postmarketing reports of serious or clinically significant neuropsychiatric adverse events have been reported in patients treated with Chantix. These included 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.

The most common adverse reactions include nausea (30%), abnormal dreams, constipation, flatulence, and vomiting. Patients should be informed that they may experience vivid, unusual, or strange dreams during treatment with Chantix.