Varenicline is a drug used for smoking cessation that is a partial agonist of the nicotinic acetylcholine receptor. It was approved by the FDA in 2006 and works to reduce cravings and withdrawal symptoms from smoking. Studies have shown varenicline is more effective for smoking cessation than placebo, nicotine patches, or bupropion. Common side effects include nausea, abnormal dreams, insomnia, and neuropsychiatric issues. The recommended dosing regimen is 0.5 mg daily for the first week, then 0.5 mg twice daily for a week, followed by the maintenance dose of 1 mg twice daily for at least 12 weeks.

1. VARENICLINE
Dr. Subodh Sharma
Resident (First Year)
Department of Psychiatry
NMCTH, Birgunj , Nepal

2. Introduction
 It is a high-affinity partial agonist for the α4β2 nicotinic
acetylcholine receptor subtype (nACh)
 Used as pharmacotherapeutic agent for smoking cessation.
 Non nicotine drugs for smoking.

3.  Approved by FDA in 2006
 Use of Cytisus plants as a smoking substitutes during World War
II led to extraction of cytisine.
 Cytisine analogs led to varenicline at Pfizer.

4. Available options for Smoking Cessation
 Non pharmacological
Behavior therapy (individual / group/ telephone quit line)
Clinical counselling
 Pharmacological
Nicotine replacement (patches/ gums/lozenges)
Bupropion
Varenicline

5. Studies on Varenicline
 A meta-analysis of randomized trials found that varenicline was more
effective for smoking cessation than placebo (RR 2.27, 95% CI 2.02-2.55)
 Cahill K, Stevens S, Perera R, Lancaster T. Pharmacological interventions for smoking
cessation: an overview and network meta-analysis. Cochrane Database Syst Rev 2013;
:CD009329.
 In another meta-analysis of randomized controlled trials, more patients were
abstinent at 24 weeks with varenicline compared with both placebo
and nicotine patch (RR 2.24, 95% CI 2.06-2.43; and RR 1.25, 95% CI 1.14-
1.37 respectively)
 Cahill K, Lindson-Hawley N, Thomas KH, et al. Nicotine receptor partial agonists for
smoking cessation. Cochrane Database Syst Rev 2016; :CD006103.

6.  Head-to-head double-blinded randomized controlled trial comparing
multiple agents (varenicline, bupropion, nicotine patch) and placebo,
varenicline was more effective in producing six months of tobacco
abstinence than other drugs or placebo.
Anthenelli RM, Benowitz NL, West R, et al. Neuropsychiatric safety and efficacy of
varenicline, bupropion, and nicotine patch in smokers with and without psychiatric
disorders (EAGLES): a double-blind, randomized, placebo-controlled clinical trial
.
 Varenicline is safe for use by tobacco users with chronic obstructive
pulmonary disease (COPD)
Tashkin DP, Rennard S, Hays JT, et al. Effects of varenicline on smoking cessation in
patients with mild to moderate COPD: a randomized controlled trial. Chest 2011;
139:591.

7. Nonpharmacologic methods
Method
Versus minimal or usual care unless otherwise
noted
Risk ratio (95% CI)
Behavioral counseling
Individual counseling 1.57 (1.40-1.77)
Group counseling 1.88 (1.52-2.33)
Telephone quit line counseling 1.38 (1.19-1.61)
Clinician counseling
Brief advice 1.66 (1.42-1.94)
Brief counseling 1.86 (1.60-2.15)
Brief counseling (versus brief advice) 1.37 (1.20-1.56)

8. Pharmacologic methods
Method
(number of trials)
Versus placebo unless otherwise noted
Risk ratio (95% CI)
First-line pharmacotherapies
*
Nicotine replacement
[5]
All types combined 1.55 (1.49-1.61)
Combination [versus individual products] 1.25 (1.15-1.36)
Patch (43) 1.64 (1.53-1.75)
Gum (56) 1.49 (1.40-1.60)
Lozenge (7) 1.52 (1.32-1.74)
Inhaler (4) 1.90 (1.36-2.67)
Nasal spray (4) 2.02 (1.49-2.73)
Varenicline (27) 2.24 (2.06-2.43)
Bupropion SR (46) 1.64 (1.52-1.77)

9. Mechanism of Action
It is a high-affinity partial agonist for the
α4β2 nicotinic acetylcholine receptor subtype
(nACh)
Release of the neurotransmitter dopamine in
the nucleus accumbens, reward center of the
brain when activated
Reduce the feelings of craving and withdrawal
caused by smoking cessation.

10. Pharmacokinetics and Pharmacodynamics
Absorption
• Completely absorbed
• Bioavailability: high
• Peak plasma time: 3-4hrs
Distribution
• Protien bound <20%
Metabolism
• Minimal metabolism, Hepatic
Excretion: urine (92%)
Half life :24hrs

11. Dosing
 Initial:
Days 1 to 3: 0.5 mg once daily. (after food)
Days 4 to 7: 0.5 mg twice daily.
 Maintenance (day 8 and later): 1 mg twice daily; may consider a
temporary or permanent dose reduction if usual dose is not tolerated.
 Duration: Continue maintenance dose for at least 11 weeks (for a total of
at least 12 weeks of treatment).
 May consider extended maintenance therapy based on individual patient
risk : benefit; evidence suggests relapse prevention benefits with
continuing therapy for up to 1 year.

12. Adverse effects
 Nausea: Dose-dependent nausea may occur; both transient and
persistent nausea has been reported. Dosage reduction may be
considered for intolerable nausea
 Neuropsychiatric effects: Post marketing cases of serious
neuropsychiatric events (including depression, suicidal thoughts, and
suicide) have been reported in patients with or without preexisting
psychiatric disease
 Somnambulism: Cases of somnambulism, involving harmful
behavior to self, others, or property, have been reported. Discontinue
treatment if somnambulism occurs

13. Side effects
 Cardiovascular: Angina pectoris (4%), chest pain (3%), peripheral
edema (2%)
 Central nervous system: Headache (12% to 19%), insomnia (9% to
19%), abnormal dreams (8% to 13%), irritability (11%), suicidal ideation
(11%), depression (4% to 11%) Anxiety (8%), sleep disorder (3% to 5%)
 Gastrointestinal: Nausea (16% to 40%), vomiting (5% to 11%)
Flatulence (6% to 9%), constipation (5% to 8%), diarrhea (6%),
increased appetite (3% to 4%)

14. Use in Pregnancy
 FDA Category C
 Available data have not suggested increased risk for major birth
defects as compared with women who smoke
 Studies are not conclusive of whether quitting smoking with
varenicline reduses the risk of birth defects which are the result of
smoking.

15. Cost
 A one-month supply of varenicline will cost approximately $120 for
the maintenance dose.
 Not available in Nepal
 Used and available in India as Varni 0.5mg tablet

16. References
 T. Varenicline. Drugs Jiménez-Ruiz, C., Berlin, I. & Hering
 Effect of Maintenance Therapy With Varenicline on Smoking
CessationA Randomized Controlled Trial Serena Tonstad, MD,
PhD; Philip Tønnesen, MD, PhD
 Varenicline ; A Review of its Use as an Aid to Smoking Cessation
Therapy Gillian M. Keating & M. Asif A. Siddiqui
 Varenicline for Tobacco Dependence J. Taylor Hays, M.D., and Jon
O. Ebbert, M.D.
 UpToDate

17. Thank You !