An updated label for the smoking cessation drug varenicline that includes new safety data involving people with cardiovascular disease has been approved by the Food and Drug Administration, the agency has announced.
Also added to the label is information on the use of varenicline in patients with chronic obstructive pulmonary disease (COPD) and alternative directions for selecting a date to quit smoking, according to the July 22 announcement. Varenicline, a nicotinic receptor partial agonist, was approved in 2006 for use as an aid to smoking cessation treatment; it is marketed by Pfizer as Chantix.
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Smokers with heart disease should weigh the risks of taking smoking cessation drug varenicline.
The cardiovascular safety information summarizes the results of a randomized study of 700 smokers with stable cardiovascular disease who received 1 mg of varenicline twice a day or placebo for 12 weeks and who were followed for an additional 40 weeks. The study found that those on varenicline had twice the chance of staying abstinent from smoking for as long as 12 months, compared to those on placebo. But it also found that treatment "may be associated with a small increased risk of certain cardiovascular adverse events in these patients."
Health care professionals are advised to "always weigh the potential benefits of Chantix against its potential risks when deciding to use the drug in patients with cardiovascular disease."
In a safety alert issued by the FDA, the agency stated that over 52 weeks, there were more reports of certain cardiovascular events among those on varenicline compared with those on placebo. Those events included nonfatal myocardial infarction (2% vs. 0.9%) and the need for coronary vascularization (2.3% vs. 0.9%).
The information on patients with COPD summarizes the results of a 52-week study of 460 patients, aged 35 years and older with mild to moderate COPD, that found that treatment with varenicline, 1 mg twice daily for 12 weeks, was more effective in helping these patients quit smoking and stay abstinent for as long as one year, when compared to placebo.
The varenicline label has advised that patients select a date to quit smoking and start taking varenicline 7 days before that date. The label still includes that recommendation, but now states that as an alternative, patients can start taking varenicline "and then quit smoking between days 8 and 35 of treatment."
That recommendation is based on the results of a randomized study of otherwise healthy smokers that found the alternative dosing schedule was more effective than placebo in helping patients quit smoking and remain abstinent for as long as 24 weeks. No new safety issues were identified in the study and adverse events were similar to those in the clinical trial described on the original drug label.
The Cardiovascular Risks of Varenicline
Earlier in July, the potential cardiovascular risks associated with varenicline received widespread media coverage with the online publication of a meta-analysis of 14 studies comparing the drug to placebo (Can. Med. Assoc. J. 2011 July 4 [doi:10.1503/cmaj.110218]).
The studies enrolled more than 8,000 patients, including almost 5,000 on varenicline (most were taking the 1 mg twice a day dose), treated from 7 to 52 weeks. Patients with cardiovascular disease were included in the trials, however all but one excluded those with unstable cardiovascular disease. The rate of serious cardiovascular events was significantly higher among those on varenicline compared with placebo (1.06% vs. 0.82%), which represented a 72% increased risk.
While the study had some limitations, it did raise safety concerns" about the potential for these events in people treated with the drug and follow-up safety studies should be conducted, the authors concluded.
In an accompanying editorial, Dr. J. Taylor Hays, of the Mayo Clinic, Rochester, Minn., wrote that "although their results suggest that a measure of caution should be taken in prescribing varenicline for the treatment of tobacco dependence, the small absolute risk of cardiovascular events associated with taking varenicline is outweighed by the enormous benefit of reducing cardiovascular morbidity and mortality that can be achieved with successful abstinence from smoking" (Can. Med. Assoc. J. 2011 July 4 [doi:10.1503/cmaj.110804]).
Dr. Hays has received grant funding from Pfizer to conduct a varenicline study. The lead author of the meta-analysis, Dr. Sonal Singh, of Johns Hopkins University, Baltimore, was supported with a grant from the National Center for Research Resources, a component of the National Institutes of Health. A coauthor, Dr. Curt Furberg, of Wake Forest University, Winston-Salem, N.C., who supervised the study, has been paid by plaintiffs for expert testimony on Pfizer’s COX-2 inhibitors.