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
Pharmacology
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
Pharmacokinetics
Elimination Half-Life: 24 hrs
Metabolism
Minimal: <10% of clearance is via metabolism
Administration
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)
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
References
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]
