FDA Removes Warnings on Smoking-Cessation Medication
Removal of the boxed warning is based on the outcomes of EAGLES (Evaluating Adverse Events in a Global Smoking Cessation Study), which is a randomized, blinded, active- and placebo-controlled clinical trial, in patients without and with a history of psychiatric disorder.
Officials with the FDA have removed a boxed warning about neuropsychiatric events from the smoking-cessation medication Chantix® (varenicline, Pfizer), according to a press release issued by Pfizer.1
Removal of the boxed warning is based on the outcomes of EAGLES (Evaluating Adverse Events in a Global Smoking Cessation Study), which is a randomized, blinded, active-and placebo-controlled clinical trial conducted by Pfizer in collaboration with GlaxoSmithKline designed in consultation with the FDA and the European Medicines Agency (EMA). It is the largest smoking cessation clinical trial in patients without and with a history of psychiatric disorder, according to the release.
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 (Zyban, GlaxoSmithKline), 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.
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, according to a Drug Safety Communication from the FDA.2
Additional labeling revisions based on EAGLES include updates to the corresponding warning regarding neuropsychiatric safety and the addition of information on Chantix compared to bupropion or nicotine patch.3,4
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, according to the FDA statement.
1. FDA Approves Removal Of Boxed Warning Regarding Serious Neuropsychiatric Events From CHANTIX® (varenicline) Labeling [news release]. Pfizer. Accessed December 16, 2016.
2. Chantix (varenicline) and Zyban (bupropion): Drug Safety Communication - Mental Health Side Effects Revised. FDA Medwatch. Accessed December 16, 2016.
3. Pfizer Laboratories Div Pfizer Inc. Chantix® (varenicline) Prescribing Information.
4. Anthenelli RM, Benowitz NL, West R, et al. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet. 2016 Apr 19: e1-e14.[Epub ahead of print].