Introduction
Varenicline is a prescription medication approved by the FDA in 2006 for smoking cessation treatment. It is a selective partial agonist of the α4β2 nicotinic acetylcholine receptor specifically developed to aid in smoking cessation by reducing nicotine craving and withdrawal symptoms while decreasing the rewarding effects of smoking.
Mechanism of Action
Varenicline binds selectively to α4β2 nicotinic acetylcholine receptors in the brain, where it acts as a partial agonist. This dual mechanism:
- Produces partial stimulation of receptors, reducing nicotine craving and withdrawal symptoms
- Blocks nicotine from binding to these receptors, preventing the dopamine release that reinforces smoking behavior
This combination reduces the satisfaction obtained from smoking while alleviating withdrawal symptoms
Indications
- Smoking cessation treatment in adults
- Aid to smoking cessation in combination with behavioral support and counseling
Dosage and Administration
Standard titration regimen:- Days 1-3: 0.5 mg once daily
- Days 4-7: 0.5 mg twice daily
- Day 8 to end of treatment: 1 mg twice daily
- Renal impairment: Dose adjustment required (0.5 mg once daily in severe impairment)
- Hepatic impairment: No dose adjustment needed
- Elderly: Consider renal function before dosing
- Pregnancy: Category C - use only if potential benefit justifies risk
Pharmacokinetics
Absorption: Oral bioavailability ~100%, not affected by food Distribution: Volume of distribution ~415 L, <20% protein bound Metabolism: Minimal metabolism (<10%), primarily unchanged drug Elimination: Renal excretion (92%), half-life ~24 hours Steady state: Achieved within 4 daysContraindications
- Hypersensitivity to varenicline or any component of the formulation
- History of serious skin reactions to varenicline
Warnings and Precautions
Black Box Warning:- Serious neuropsychiatric events including depression, suicidal ideation, suicide attempt, and completed suicide
- Cardiovascular events: May increase cardiovascular risk in patients with pre-existing disease
- Seizures: Use with caution in patients with history of seizures
- Somnambulism: Reports of sleepwalking and other complex sleep behaviors
- Nausea: Most common adverse effect; dose titration helps minimize
- Accidental injury: May impair ability to drive or operate machinery
Drug Interactions
- Nicotine replacement therapy: Increased incidence of nausea, headache, and other adverse effects
- Drugs eliminated renally: Potential interaction with other renally eliminated drugs
- Alcohol: Reports of increased intoxication and unusual behavior
- Cimetidine: May increase varenicline exposure
Adverse Effects
Very common (>10%):- Nausea (30%)
- Insomnia (18%)
- Abnormal dreams (13%)
- Headache (15%)
- Constipation, flatulence, vomiting
- Sleep disorders, dysgeusia
- Fatigue, malaise
- Neuropsychiatric events (depression, suicidal ideation)
- Cardiovascular events (MI, stroke)
- Hypersensitivity reactions
- Seizures
- Erythema multiforme
Monitoring Parameters
- Smoking status and cessation progress
- Neuropsychiatric symptoms (mood, behavior, suicidal ideation)
- Renal function in patients with renal impairment
- Cardiovascular status in patients with pre-existing heart disease
- Adverse effects (particularly nausea, sleep disturbances)
- Compliance with behavioral support program
Patient Education
- Take with food and full glass of water to reduce nausea
- Continue smoking during first week of treatment while titrating dose
- Set a target quit date between days 8 and 35 of treatment
- Report any mood changes, depression, or suicidal thoughts immediately
- Avoid alcohol until effects of varenicline are known
- Use caution when driving or operating machinery
- Continue behavioral support and counseling throughout treatment
- Complete full course of treatment unless advised otherwise by healthcare provider
References
1. FDA Prescribing Information: Chantix (varenicline) tablets 2. Cahill K, et al. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2016 3. Anthenelli RM, et al. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES). Lancet. 2016 4. Rigotti NA, et al. Efficacy and safety of varenicline for smoking cessation in patients with cardiovascular disease. JAMA. 2010 5. Clinical Practice Guideline: Treating Tobacco Use and Dependence. US Department of Health and Human Services. 2008 6. Micromedex® DrugDex® Evaluations: Varenicline 7. Lexicomp® Online: Varenicline Monograph