Pfizer Inc's Chantix

Pfizer Inc's Chantix (varenicline tartrate),approved by the FDA in May 2006,helps cigarette smokers to quit smoking.¹

Pharmacology/Pharmacokinetics

Varenicline is a nonnicotinic drugwith a dual mechanism of action (agonistand antagonistic activity). Normally,nicotine binds to the a⁴b² neuronalnicotinic acetylcholine receptorsubunit, which stimulates the centralnervous mesolimbic dopamine system,the mechanism responsible for thereinforcement and reward experienceassociated with smoking.² Varenicline,a partial agonist, has an affinity for thea⁴b² subunit, stimulating receptor-mediatedactivity at a lower level thannicotine (agonistic activity). By bindingto the a⁴b² subunit, varenicline blocksnicotine binding, preventing stimulationof the central nervous mesolimbic dopaminesystem (antagonistic activity).²

About 92% of the drug is excretedunchanged in urine and primarily eliminatedvia glomerular filtration withactive tubular secretion via the organiccation transporter.² Dose adjustment isnot necessary for mild renal impairment(creatinine clearance of ≥50mL/min and ≤80 mL/min). There is a1.5-and 2.1-fold increase in vareniclineexposure in patients with moderate(≥30 mL/min and ≤50 mL/min) andsevere creatinine clearance (≤30mL/min), respectively. Varenicline undergoesminimal hepatic metabolism.²

Clinical Trials

The efficacy of Chantix was confirmedin 6 clinical studies all enrollingchronic cigarette smokers (10 cigarettes/day). Abstinence from smokingwas verified by patient self-report andmeasurement of exhaled carbon monoxide(CO; ≤10 ppm) at weekly visits.³

Two identical trials, both phase 3,double-blind, placebo-and active-controlled,parallel-group, multicenterstudies randomized patients to receiveChantix, bupropion SR, or placebo.^2,3Patients who had used bupropion SRpreviously were excluded. Chantix wastitrated according to the followingschedule: 0.5 mg qd for 3 days; 0.5 mgbid daily for 4 days; then 1 mg bid.Titration of bupropionSR was 150mg daily for 3 days,then 150 mg twicedaily.

Patients weretreated for 12weeks total, includingtitrationphase, and followedfor 40 weeksposttreatment. Atotal of 2045 patientswere enrolledin both studies (n = 1022 and n =1023).^4,5

In both studies, Chantix-treatedpatients had a higher superiority rate.In one study, Chantix had a CO-confirmedabstinence rate of 44% duringweeks 9 through 12, compared withthe other 2 arms (bupropion SR = 30%;placebo = 17%). Also, the Chantixgroup had a higher rate (29%) of beingcontinuously abstinent from 1 weekafter the target quit date (TQD) to theend of treatment (EOT), compared withbupropion SR (23%) and placebo(12%).^4,5 The second study also showedsimilar results where Chantix-treatedpatients had a higher superiority rateof CO-confirmed abstinence duringweeks 9 through 12 (varenicline = 44%;bupropion SR = 30%; placebo = 18%).Continuous abstinent percentage from1 week after TQD through the EOT wasalso similar to the first study (Chantix =29%; bupropion = 21%; placebo =11%).²

A study designed to assess longtermabstinence with Chantix therapyversus placebo demonstrated Chantixsuperiority rate in maintaining smokingcessation. Patients received open-labelChantix 1 mg bid for 12 weeks, thenwere randomized to active or placebofor the next 12 weeks.^2,3 The Chantixgroup had a higher continuous abstinencerate (70%) versus placebo (50%).During posttreatment follow-up, superiorityof Chantix (54%) was maintained,compared with placebo (39%).^2,3

Most frequently reported sideeffects of Chantix were nausea, insomnia,abnormal dreams, headache, dyspepsia,constipation, and flatulence.²The incidence of nausea was dose-relatedand categorized as mild tomoderate. If nausea is intolerable, alower dose should be considered.³

Conclusion

Patients should be advised to set aTQD, and treatment should begin 1week prior to that date. Dose should betitrated to 1 mg bid following a titrationschedule of 0.5 mg qd for 3 days; 0.5mg bid on days 4-7.² Chantix should betaken after a meal with a full glass ofwater. Chantix treatment should besupported with counseling and educationalmaterials on smoking cessation.²

Manufacturer recommendation forstorage is at room temperature up to77°F. Each strength, 0.5 and 1 mg, isavailable in cards and in bulk bottles of56 tablets.² Chantix is classified as inpregnancy category C and is not recommendedfor use in children underthe age of 18.

Ms. Domenici and Dr. Patel are bothpharmacists at Brigham andWomen's Hospital, Boston, Mass.

References

1. The FDA Approves New Drug for Smoking Cessation. FDA Consumer magazine.July-August 2006. Available at:www.fda.gov/fdac/features/2006/406_smoking.html. Accessed January 8, 2007.

2. Chantix [package insert]. New York, NY: Pfizer Inc; 2006.

3. Pfizer "Dear Healthcare Professional Letter" (overall safety and efficacy). January 10, 2007.