PMID- 19393839
OWN - NLM
STAT- MEDLINE
DCOM- 20090611
LR  - 20171116
IS  - 0149-2918 (Print)
IS  - 0149-2918 (Linking)
VI  - 31
IP  - 3
DP  - 2009 Mar
TI  - Varenicline: a first-line treatment option for smoking cessation.
PG  - 463-91
LID - 10.1016/j.clinthera.2009.03.021 [doi]
AB  - BACKGROUND: Varenicline acts as a partial agonist/antagonist with affinity and 
      selectivity for alpha(4) beta(2) nicotinic acetylcholine receptors. This activity 
      at the nicotine-receptor level may help patients achieve smoking cessation by 
      reducing cravings/withdrawal symptoms and smoking satisfaction. OBJECTIVE: This 
      article reviews the literature on the pharmacologic properties, therapeutic 
      efficacy, and tolerability of varenicline for smoking cessation. METHODS: 
      Pertinent controlled clinical trials, meta-analyses, meeting abstracts, case 
      reports, and review articles published in English between 1966 and May 2008 were 
      identified through searches of MEDLINE and OVID using the terms varenicline, 
      smoking, tobacco cessation, and CP 526555. RESULTS: Eight clinical trials were 
      identified that compared <or=12 weeks of varenicline treatment with placebo 
      and/or bupropion sustained release (SR); one of the trials reported follow-up 
      data to 24 weeks, and the remainder reported data to 52 weeks. During treatment 
      with oral varenicline titrated to 1 mg BID, CO-confirmed 4-week continuous quit 
      rates/continuous abstinence rates (CQRs/CARs) in weeks 9 through 12 ranged from 
      43.9% (odds ratio [OR] = 3.85 [95% CI, 2.69-5.50; P < 0.001 vs placebo]; OR = 
      1.90 [95% CI, 1.38-2.62; P < 0.001 vs bupropion SR]) to 65.4% (OR = 2.98 [95% CI, 
      1.78-4.99; P < 0.001 vs placebo]). In 4 of these trials, varenicline 1 mg BID was 
      associated with significantly higher CQRs/CARs compared with placebo at week-52 
      follow-up, ranging from 21.9% (P < 0.001) to 34.6% (P = 0.036). One trial 
      reported a significantly higher CAR at 52 weeks with varenicline compared with 
      bupropion SR (23.0% vs 14.6%, respectively; P = 0.004), and another reported a 
      significantly higher CAR at 52 weeks with varenicline compared with nicotine 
      replacement therapy (25.9% vs 19.8%, respectively; P = 0.040). In a 
      relapse-prevention study that included a 12-week extension period for 
      participants who were abstinent after the initial 12 weeks of treatment, CARs 
      were significantly improved at 24 weeks with varenicline relative to placebo 
      (70.5% vs 49.6%, respectively; OR = 2.48; 95% CI, 1.95-3.16; P < 0.001). 
      Treatment with varenicline was generally well tolerated in study populations with 
      no major comorbidities. In a pooled analysis of 2 Phase III trials, the most 
      commonly reported adverse events (AEs) with varenicline, bupropion SR, and 
      placebo were nausea (28.8%, 9.9%, and 9.1%, respectively), insomnia (14.2%, 
      21.5%, and 12.6%), and headache (14.2%, 11.1%, and 12.4%). In a pooled analysis 
      of 2 identically designed Phase III trials, bupropion SR was associated with the 
      highest overall rates of discontinuation due to all-cause AEs compared with 
      varenicline and placebo (13.9%, 9.5%, and 8.2%, respectively) and due to AEs 
      considered related to study drug (12.1%, 7.9%, and 6.4%). In double-blind 
      clinical trials of varenicline, nausea was the most frequently reported AE 
      (16.3%-41.9%). Varenicline treatment should begin 7 days before the proposed 
      smoking quit date; dose titration is recommended to minimize dose-related nausea. 
      Based on postmarketing reports of serious AEs in vareniclinetreated patients, 
      caution is recommended when operating vehicles or heavy machinery. Patient 
      education and monitoring for potential AEs are also recommended, particularly in 
      patients with a history of psychiatric illness. CONCLUSIONS: Varenicline has a 
      unique mechanism of action compared with other first-line options for smoking 
      cessation. Available clinical-trial data support its use as an effective and 
      generally well-tolerated therapy for smoking cessation in healthy adult smokers, 
      although there is a need for further efficacy and safety evaluation in the 
      general population, particularly those with comorbid conditions.
FAU - Garrison, Gina Daubney
AU  - Garrison GD
AD  - Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, 
      Albany, New York 12208-3492, USA. gina.garrison@acphs.edu
FAU - Dugan, Sara E
AU  - Dugan SE
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Benzazepines)
RN  - 0 (Nicotinic Agonists)
RN  - 0 (Quinoxalines)
RN  - 0 (Receptors, Nicotinic)
RN  - 0 (nicotinic receptor alpha4beta2)
RN  - 01ZG3TPX31 (Bupropion)
RN  - W6HS99O8ZO (Varenicline)
SB  - IM
MH  - Benzazepines/administration & dosage/adverse 
      effects/economics/pharmacokinetics/*therapeutic use
MH  - Bupropion/therapeutic use
MH  - Cost-Benefit Analysis
MH  - Drug Costs
MH  - Drug Interactions
MH  - Drug Partial Agonism
MH  - Humans
MH  - Nicotinic Agonists/administration & dosage/adverse 
      effects/economics/pharmacokinetics/*therapeutic use
MH  - Quinoxalines/administration & dosage/adverse 
      effects/economics/pharmacokinetics/*therapeutic use
MH  - Receptors, Nicotinic/*drug effects/metabolism
MH  - Recurrence
MH  - Smoking/metabolism
MH  - Smoking Cessation/economics/*methods
MH  - *Smoking Prevention
MH  - Tobacco Use Disorder/*drug therapy/metabolism
MH  - Treatment Outcome
MH  - Varenicline
RF  - 50
EDAT- 2009/04/28 09:00
MHDA- 2009/06/12 09:00
CRDT- 2009/04/28 09:00
PHST- 2008/10/15 00:00 [accepted]
PHST- 2009/04/28 09:00 [entrez]
PHST- 2009/04/28 09:00 [pubmed]
PHST- 2009/06/12 09:00 [medline]
AID - S0149-2918(09)00096-4 [pii]
AID - 10.1016/j.clinthera.2009.03.021 [doi]
PST - ppublish
SO  - Clin Ther. 2009 Mar;31(3):463-91. doi: 10.1016/j.clinthera.2009.03.021.