Pharmacology Update
Varenicline Tartrate Tablets (Chantix™)
By William T. Elliott, MD, FACP, and James Chan, PhD, PharmD, Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationships to this field of study.
The FDA has approved a new agent for smoking cessation. Varenicline is a partial agonist of the α4β2 subtype of nicotinic receptors. It blocks the action of nicotine but provides a lower level of stimulation of dopamine release to reduce craving and withdrawal symptoms. Chemically and pharmacologically, varenicline is similar to cytosine, a plant alkaloid used in Eastern Europe. It is marketed by Pfizer Labs as Chantix™.
Indications
Varenicline is indicated as an aid to smoking cessation treatment.1
Dosage
The recommended dose is 1 mg twice daily with a full glass of water after eating. This should be titrated from 0.5 mg once daily for 3 days, 0.5 mg twice daily for 4 days, then 1 mg twice daily thereafter. Treatment should start one week before the 'stop smoking date' and continue for 12 weeks. For those who have successfully stopped smoking at the end of the period, an additional 12 weeks of treatment is recommended. For patients with severe renal impairment, the recommended dose is 0.5 mg twice daily and for those with end-stage renal disease on hemodialysis, a maximum dose of 0.5 mg daily is recommended.1 Varenicline is supplied as 0.5 mg and 1 mg tablets.
Potential Advantages
Varenicline appears to be more effective than bupropion.1-3 No drug-drug interaction has been demonstrated.
Potential Disadvantages
Nausea and insomnia are the most common side effects. Nausea is generally mild or moderate in severity and usually transient. However it may persist in some patients. Abrupt discontinuation of varenicline results in irritability and/or sleep disturbance in 3% of patients.1
Comments
Nicotine activates the α4β2 subtype of nicotinic receptors in the brain resulting in dopamine release. Repeated exposure to nicotine and dopamine response is believed to be associated with reinforcement and addictive properties of nicotine.2 Varenicline acts as a partial agonist thus blocking the nicotine receptor to nicotine but providing moderate levels of dopamine release to reduce withdrawal and craving. Efficacy was shown in 6 clinical trials. Typical subjects used an average of 21 cigarettes per day for an average of 25 years. Abstinence was self-reported and verified by exhaled carbon monoxide measurements. In patients randomized to 1 mg twice daily, continuous abstinence rates (weeks 9- 52) were 23% compared to 4% for placebo. In two comparative trials (n = 1022,1023), continuous abstinence was 21%-22% for varenicline, 14-16% for bupropion SR (150 mg twice daily), and 8-10% for placebo. An additional 12 weeks of treatment in subjects who had successfully quit smoking at week 12 resulted in 54% with continuous abstinence at week 52 (40 weeks post treatment) compared to 39% with only 12 weeks of treatment. Varenicline appears to be well tolerated with nausea (30%) the most common adverse event. Discontinuation of treatment during placebo-controlled trials was 12% for varenicline compared to 10% for placebo. The wholesale cost for varenicline is $269 for a 12-week course.
Clinical Implications
Smoking is implicated in increases risks of several types of cancer and chronic diseases. The CDC estimates that there are 44.5 million smokers in the United States and 8.6% have chronic disease directly related to smoking. Approximately 50% of long-term smokers die prematurely from the effects of smoking.4 Most smokers are addicted to nicotine and have difficulty quitting. There are currently several available effective pharmacotherapies for smoking cessation.5 These include nicotine replacement, bupropion, nortriptyline, and clonidine. Abstinence rates have been generally disappointing, ranging from 15-25% at 6-12 months compared to 9-12% for placebo.2 Varenicline provides a drug with a different mechanism of action and may be marginally better than bupropion.
References
1. Chantix Product Information. Pfizer Labs. May 2006.
2. Foulds J. The neurobiological basis for partial agonist treatment of nicotine dependence: varenicline. Int J Clin Pract. 2006;60:571-576.
3. Fagerstrom K, Balfour DJK. Neuropharmacology and potential efficacy of new treatments for tobacco dependence. Expert Opin Investig Drugs. 2006;15:107-116.
4. Henningfield JB, et al. Pharmacotherapy for nicotine dependence. CA Cancer J Clin. 2005;55:281-299.
5. Foulds J, et al. Developments in pharmacotherapy for tobacco dependence: past, present and future. Drug Alcohol Rev. 2006;25:59-71.
The FDA has approved a new agent for smoking cessation. Varenicline blocks the action of nicotine but provides a lower level of stimulation of dopamine release to reduce craving and withdrawal symptoms.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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