Varenicline: The Newest Agent for Smoking Cessation

Lisa A. Potts; Candice L. Garwood


Am J Health Syst Pharm. 2007;64(13):1381-1384. 

In This Article

Abstract and Introduction


Purpose: The pharmacology, pharmacokinetics, clinical efficacy, safety, dosage and administration, and place in therapy of varenicline are reviewed.
Summary: Varenicline is the newest therapy approved by the Food and Drug Administration for smoking cessation and the first in its class targeting the neurobiology of nicotine addiction. Varenicline is selective for the α4ß2 acetylcholine-receptor subtype as a partial agonist, thus conferring its effect in limiting the reinforcing aspect of the addictive nicotine molecule. Varenicline is completely absorbed orally and not affected by food. Steady state is reached within four days of administration. Three Phase III clinical trials of varenicline have been published. Two studies compared varenicline with bupropion in patients over age 18 years who smoked more than 10 cigarettes daily. When the data of the two trials were pooled, varenicline use was associated with significant improvements in the four-week carbon-monoxide-confirmed continuous quit rate (44.2% at weeks 9-12 compared with bupropion (29.7%) and placebo (17.7%) (p < 0.0001 for each comparison). The third trial found that continuous quit rates were also significantly higher in patients treated with varenicline versus placebo. Varenicline is generally well tolerated. Varenicline has been administered concurrently with warfarin, digoxin, transdermal nicotine, bupropion, cimetidine, and metformin without any clinically significant drug interactions.
Conclusion: Varenicline, a newly approved agent for smoking cessation, offers a new option to patients who cannot tolerate the adverse effects associated with nicotine-replacement therapy and bupropion. It is also an alternative to consider in patients with contraindications to such therapies.


More than a third of the world's adult population smokes cigarettes.[1] Tobacco smoke is a leading cause of death from heart attack, stroke, chronic obstructive pulmonary disease, and cancer.[2] Current guidelines emphasize the importance of tobacco cessation and outline a variety of interventions. Several firstline agents are available to patients who are willing to quit. These include extended-release bupropion and nicotine-replacement therapy (NRT) with gum, lozenge, inhaler, nasal spray, or patch. Clonidine and nortiptyline may be offered as secondline therapies if firstline therapies fail.[3] Varenicline is the first nonnicotine drug therapy developed specifically for use in smoking cessation.

Early research found that cytisine, an alkaloid plant product found in Cytisus laburnum L., or golden rain tree, is a partial agonist of the α4ß2 nicotinic acetylcholine receptors. During World War II, the leaves of the golden rain tree were substituted for tobacco, as they were found to curb the craving for nicotine. For decades, cytisine has been used in Eastern Europe as an aid for smoking cessation and has been marketed under the trade name Tabex (Sopharma AD, Sofia, Bulgaria). Despite cytisine's use for smoking cessation, there is little documentation of its efficacy, and most studies evaluating its use were poorly designed.[4] Cytisine has served as a prototype and vehicle for discovery of new drug entities to be used for smoking cessation. This is the case for varenicline (Chantix, Pfizer). This agent was derived from the cytisine compound to have greater bioavailability and selectivity for α4ß2 receptors as a partial agonist.[5]


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