Varenicline (Chantix)


  • Tobacco Addiction (see Tobacco, [[Tobacco]])
    • Meta-Analysis Examining Efficacy of Nicotine Partial Receptor Agonist in Tobacco Cessation (2012) [MEDLINE]
      • Cytisine increased the chances of quitting, although absolute quit rates were modest
      • Varenicline (at standard dose) increased the chances of successful long-term smoking cessation between 2-3x compared with pharmacologically-unassisted quit attempts
      • More participants quit successfully with varenicline than with bupropion
      • Limited evidence suggests that varenicline may have a role to play in relapse prevention


  • Partial Neuronal α4β2 Nicotinic Receptor Agonist
    • Also binds to 5-HT3 Receptor with moderate affinity: unclear significance
    • Also stimulates dopamine activity (but to a much smaller degree than nicotine does), resulting in decreased craving and withdrawal symptoms


  • Elimination Half-Life: 24 hrs


  • Minimal: <10% of clearance is via metabolism


  • Initial (PO)
    • Days 1-3: 0.5 mg qday
    • Days 4-7: 0.5 mg BID
  • Maintenance (PO): 1 mg BID x 12 wks

Dose Adjustment

  • Hepatic: no dose adjustment
  • Renal
    • CrCl ≥30 mL/min: no dose adjustment
    • CrCl <30 mL/min: start 0.5 mg PO qday (with maximum dose: 0.5 mg BID)

Adverse Effects

Allergic Adverse Effects

Dermatologic Adverse Effects

Cardiovascular Adverse Effects

Serious Cardiovascular Events

  • Studies: probably no increased risk of cardiovascular events with varenicline use, based on studies below
    • Systematic Review and Meta-Analysis of 14 Trials (2011) [MEDLINE]: this analysis used the Peto odds ratio (which can overestimate differences with extremely rare events) -> findings suggested an increased risk of cardiovascular events with varenicline use
    • Meta-Analysis of 22 Trials (2012) [MEDLINE]: this analysis did not find an increased risk of cardiovascular events with varenicline, refuting the results of the prior analysis

Gastrointestinal Adverse Effects

  • Nausea (see Nausea and Vomiting, [[Nausea and Vomiting]]): occurs in 16-40% of cases
    • Tends to subside over time

Neurologic Adverse Effects

  • Abnormal Dreams: occur in 9%-13% of cases
    • Nightmares: occur in 1-2% of cases
  • Agitation: occurs in 7% of cases
  • Central Nervous System Depression
  • Depression/Suicidal Ideation (see Depression, [[Depression]]): depression occurs in 4-11% of cases
  • Headache (see Headache, [[Headache]]): occurs in 15-19% of cases
  • irritability: occurs in 11% of cases
  • Seizures (see Seizures, [[Seizures]]): reported in patients with/without a history of seizures


  • Placebo-controlled trial of cytisine for smoking cessation. N Engl J Med 2011;365:1193-1200 [MEDLINE]
  • Risk of serious adverse cardiovascular events associated with varenicline: a systematic review and meta-analysis. CMAJ 2011;183(12): 1359-1366 [MEDLINE]
  • Risk of cardiovascular serious adverse events associated with varenicline use for tobacco cessation: systematic review and meta-analysis. BMJ 2012; 344:e2856 [MEDLINE]
  • Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev 2012;4:CD006103 [MEDLINE]
  • Efficacy of cytisine in helping smokers quit: systematic review and meta-analysis. Thorax 2013;68:1037-1042 [MEDLINE]
  • Cytisine versus nicotine for smoking cessation. N Engl J Med 2014;371:2353-2362 [MEDLINE]
  • Cytisine—a tobacco treatment hiding in plain sight. N Engl J Med 2014;371:2420-2421 [MEDLINE]