Varenicline: the newest agent for smoking cessation.

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 alpha4beta2 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.