In the October WMSHP newsletter, Benjamin Mgboh, Pharm.D., a pharmacy practice resident at Spectrum Health, discusses a new medication to aid in smoking cessation.

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What Is New in the World of Smokers?

Benjamin Mgboh, Pharm.D.
Pharmacy Practice Resident
Spectrum Health, Grand Rapids, MI
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In the United States, over 50 million people smoke annually with estimated deaths of 438,000 per year.¹ Of current smokers, approximately 41% try to quit yearly with only 10% succeeding.² The problem that arises most times is how to achieve the goal of quitting or what regimen is best for an individual. Smoking is an addictive act that could and has caused cardiovascular diseases. Smoking increases one’s risk of lung cancer, as well as causing drug toxicity by affecting metabolism in hepatic enzymes. According to the World Health Organization, every eight seconds a person dies of a smoking-related disease.³ Smoking is the leading cause of preventable death in the world. Smoking cessation is important because of the harmful role that smoking has on life. Smoking cessation tools such as the use of nicotine replacement therapy (nicotine gums, patches, lozenges), or a dopamine/norepinephrine reuptake inhibitor (Zyban^®) are currently available. In spite of these tools, cessation is still a big issue.

Varenicline (Chantix®) is a phase III smoking cessation drug which stimulates nicotine receptors in the brain without being addictive. It is an α-4, β-2 nicotinic acetylcholine receptor partial agonist.^1,2,4 This unique mechanism of action helps to prevent withdrawal in people trying to quit smoking. Two studies were designed to compare the safety and efficacy of varenicline with bupropion SR and placebo. The studies’ (n= 1025¹ and n=1027²) results showed varenicline was significantly better for quitting smoking than placebo throughout the 52 weeks of study. The investigators also reported that varenicline was notably better for smoking cessation than bupropion SR at the end of 12 weeks of study, and 24 weeks of follow-up. The methodology of the study includes a brief counseling to participants and varenicline titrated up to 1 mg orally twice a day. Furthermore, bupropion SR was titrated to 150 mg orally twice a day or placebo for 12 weeks, with 40 weeks of non-drug follow-up.

Gonzales et al reported for weeks 9 through 12, the 4-week continuous abstinence rates was 26.3% higher for varenicline vs placebo (44% vs 17.7%). Continuous abstinence in varenicline was 14.5% higher than bupropion SR (44% vs 29.5%). For weeks 9-24 continuous abstinence rates was 8.8% higher for the Varenicline group than (29.5% vs. 20.7%) for bupropion SR. In both instances, the results were statistically and clinically significant. However, for weeks 9 through 52, the continuous abstinence rates was 13.5% higher for varenicline vs placebo but not statistically significant when compared with bupropion SR (21.9% vs 16.1%). Similarly, Jorenby et al reported that varenicline showed higher continuous abstinence than placebo at all times. For weeks 9 through 12, the 4-week continuous abstinence rate was 26.3% higher for varenicline vs placebo (43.9% vs 17.6%). Continuous abstinence in varenicline was 14.5% higher than bupropion SR (43.9% vs 29.8%). For weeks 9-24 continuous abstinence rates was 8.8% higher for the varenicline group than (29.7% vs. 20.2%) for bupropion SR. In both instances, the p value was statistically significant. However, for weeks 9 through 52, the continuous abstinence rates was 13.5% higher for varenicline vs placebo but not statistically significant when compared with bupropion SR (23% vs 14.6%).

Both studies showed that varenicline was safe and generally well tolerated when compared with bupropion SR and placebo. There were no gender differences in efficacy for varenicline.^1,2,5 Varenicline reduced craving, withdrawal symptoms, and smoking satisfaction for those who smoked during the studies.^1,2,5 Nausea (28.1%) was the most common adverse events observed in participants receiving varenicline. It was mostly mild or moderate and rarely involved discontinuation of therapy.^1,2,5 Minimal weight gain and insomnia were also associated with this treatment. However, these adverse effects were also present in the use of bupropion SR (insomnia 21.9%) or placebo.

In conclusion, both studies stated that varenicline has a better efficacy than both placebo and bupropion SR in smoking cessation. However, it should be noted that the generalization of varenicline across all age groups (mean age studied = 42 years) or populations is limited based upon the inclusion criteria. Thus it is essential for anyone intending to use this drug for smoking cessation to be well evaluated to ensure they do not fall into the category of people that were excluded in the trial studies. The current FDA dosing recommendation for varenicline use in smoking cessation is 1 mg orally twice daily. However, this regimen starts after a one week titration with 0.5 mg orally once daily on days 1, 2 & 3, then 0.5 mg twice daily on days 4, 5, 6, & 7, then 1 mg twice daily for 12 weeks (including 1 week titration).⁴ Patients are advised to begin therapy one week prior to the date set to quit smoking. Renal adjustment is required in severe renal dysfunction.⁴

References:

1. Gonzales D, Bennard SI, Nides M, et al. Varenicline, an α4β2 Nicotinic Acetylcholine Receptor Partial Agonist, vs Sustained-Release Bupropion and Placebo for smoking cessation. A Randomized controlled Trial. JAMA. 2006;296(1):47-55
2. Jorenby DE, Hays J, Taylor MD, et al. Efficacy of Varenicline, an [alpha]4[beta]2 Nicotinic Acetylcholine Receptor Partial Agonist, vs Placebo or Sustained-Release Bupropion for Smoking Cessation: A Randomized Controlled Trial. JAMA. 2006; 296(1):56-63
3. Pfizer's Varenicline Receives U.S. FDA Priority Review. http://www.pfizer.com/pfizer/are/investors_releases/2005pr/mn_2005_1221.jsp (accessed 07/16/06)
4. Klasco RK (ED): DRUGDEX® System. Thomson MICROMEDEX, Greenwood Village, Colorado (accessed 07/13/06).
5. Varenicline May Be More Effective Than Bupropion for Smoking Cessation. http://www.medscape.com/viewarticle/540203. (accessed 07/17/06)