Varenicline (Chantix) is a selective alpha4-beta2 neuronal nicotinic acetylcholine receptor partial agonist approved as an aid to smoking cessation therapy. This receptor is believed to play a significant role in reinforcing the effects of nicotine and in maintaining smoking behaviors. The agonist effect of varenicline at the nicotinic receptor is approximately half that of nicotine, which may lessen craving and withdrawal without inducing dependence. In theory, stimulation of the nicotinic receptor by a partial agonist could provide enough stimulation to reduce craving and withdrawal while competitively blocking the binding of smoked nicotine.1,2 Varenicline represents a new approach to smoking cessation by mitigating some of the satisfying and reinforcing aspects of smoking.
|Approximate monthly cost*
|0.5 mg once daily for three days, followed by 0.5 mg twice daily for four days, then 1 mg twice daily for 12 weeks
|0.5-mg or 1-mg tablets; available in a monthly blister package
|$114 for the starting dosage; $120 for the maintenance dose
Studies of more than 4,500 patients have established a favorable safety profile for varenicline, and there have been no reports of abuse or serious safety issues. Because varenicline is excreted by the kidney, the manufacturer recommends reducing the dosage in patients with impaired renal function. There are currently no known drug interactions, and the safety of varenicline used in combination with other smoking cessation therapies has not been established. Because smoking may alter the metabolism of some medications (e.g., warfarin [Coumadin], theophylline), dosing adjustments of other drugs the patient is receiving may need to be made upon smoking cessation.2 Varenicline is U.S. Food and Drug Administration pregnancy category C.
The most common adverse effect associated with varenicline is nausea, which occurs in about 30 percent of patients taking the maintenance dose. Although the nausea is not typically severe, it may persist for the duration of treatment in a small number of persons. Other common adverse effects that occur in more than 10 percent of patients include headache, insomnia, abnormal dreams, and flatulence. The rate of discontinuation because of side effects was 12 percent for patients receiving varenicline compared with 10 percent for patients receiving placebo.2
Varenicline has been compared with placebo in five studies3–7 and with sustained-release bupropion (Wellbutrin SR) in three studies of healthy persons highly motivated to quit smoking.5–7 On average, patients had been smokers for 20 to 25 years and reported smoking approximately one pack per day. Most patients (approximately 90 percent) had tried to quit at least once.3–7 Based on these studies, about 20 percent of patients taking varenicline will be continuously abstinent from smoking one year after treatment compared with less than 10 percent of patients taking placebo. In other words, for approximately every nine patients treated with varenicline instead of placebo, one additional patient will remain abstinent for one year.3–7
Varenicline treatment seems to be as effective or more effective than treatment with sustained-release bupropion. Two studies found that treatment with varenicline had similar results to treatment with bupropion,5,7 and one study found better abstinence rates with varenicline at one year compared with bupropion (23.0 versus 14.6 percent, respectively).6
Varenicline has not been compared with nicotine replacement therapy or for use in combination with other smoking cessation therapies. Also, varenicline has not been studied in patients who use tobacco products other than cigarettes or in patients who have significant cardiopulmonary disease or psychological disorders.
A one-month supply of varenicline will cost approximately $120 for the maintenance dose. This is more than the cost of generic sustained-release bupropion ($116) but less than the cost of Wellbutrin SR ($150). Patients who smoke one pack per day will spend an average of $130 per month on cigarettes.8
Varenicline is taken with a full glass of water twice daily after a meal. The initial dose is 0.5 mg once daily starting one week before the quit date and increased to 0.5 mg twice daily after three days. At the start of the second week, the dose is increased to 1 mg twice daily and continued for 12 weeks. If a patient relapses during the 12 weeks of therapy or after therapy is completed, he or she should be encouraged to make another attempt to quit once contributing factors have been identified and addressed. Patients unable to tolerate the side effects at the maintenance dose should have the dose lowered temporarily or permanently. Patients with pronounced renal dysfunction (creatinine clearance less than 30 mL per minute [0.5 mL per second]) should take half the usual dose.2
For every nine highly-motivated patients who use varenicline instead of placebo, one will not be smoking one year later. Although the cost of therapy is a limitation (total cost is approximately $360 for a three-month course), the easy dosage titration, lack of drug interactions, and favorable side-effect profile make varenicline an appealing alternative to sustained-release bupropion for smoking cessation.