Varenicline

• Smoking Cessation
• Nicotine Dependence
• Tobacco Use Disorder

Varenicline is a nicotinic receptor partial agonist used as an aid to smoking cessation treatment. It works by reducing cravings and withdrawal symptoms while blocking the rewarding effects of nicotine.

Mechanism of Action

Varenicline targets nicotinic acetylcholine receptors:

• Alpha-4 beta-2 nicotinic receptor partial agonism: Binds with high affinity to these receptors
• Partial agonist effect: Provides moderate dopamine release, reducing cravings and withdrawal
• Antagonist effect: Blocks nicotine from binding, reducing rewarding effects of smoking
• High receptor selectivity: Selective for alpha-4 beta-2 subtype
• Sustained receptor occupancy: Long half-life provides continuous receptor blockade

This dual mechanism makes it effective for both withdrawal relief and relapse prevention.

Available Formulations

Varenicline is available as tablets:

• 0.5 mg, 1 mg tablets (Chantix)
• Starting Month Pak (dose escalation package)
• Continuing Month Pak (maintenance)

Medical Uses

FDA-Approved Indication:

• Aid to smoking cessation treatment in adults

Varenicline is typically used as part of a comprehensive smoking cessation program including counseling.

Dosing Guidelines

Adults:

• Days 1-3: 0.5 mg once daily
• Days 4-7: 0.5 mg twice daily
• Day 8 through end of treatment: 1 mg twice daily
• Duration: 12 weeks (may extend additional 12 weeks for maintenance)

Set a quit date:

• Start varenicline 1-2 weeks before target quit date, OR
• Start and quit when ready between days 8-35 of treatment

Renal Impairment:

• CrCl <30 mL/min: Start 0.5 mg once daily; max 0.5 mg twice daily
• End-stage renal disease: 0.5 mg once daily

Important Safety Information

Boxed Warning (Updated 2016):

• Risk of serious mental health events including changes in behavior, hostility, agitation, depressed mood, suicidal thoughts and behavior was removed after large safety studies

Warnings and Precautions:

• Neuropsychiatric symptoms: Monitor for mood and behavior changes; discontinue if severe symptoms occur
• History of psychiatric disorders: Use with caution; benefits vs risks
• Seizures: Cases reported; use with caution in patients with seizure history
• Cardiovascular events: Some studies showed increased CV events; weigh risks
• Sleepwalking: Cases reported; discontinue if occurs
• Hypersensitivity reactions: Angioedema and severe skin reactions reported

Drug Interactions

• Nicotine replacement therapy: Increased adverse effects (nausea, headache, dizziness); use combination with caution
• Alcohol: May increase intoxicating effects of alcohol; some patients report decreased alcohol tolerance
• Insulin: Smoking cessation may increase insulin sensitivity; monitor blood glucose
• Theophylline, warfarin: Smoking affects metabolism; monitor when quitting

Special Populations

• Hepatic Impairment: No adjustment needed
• Renal Impairment: Dose adjustment for severe impairment and ESRD
• Pregnancy: Use only if benefit outweighs risk (NRT may be preferred)
• Lactation: Present in milk; consider risk vs benefit
• Elderly: No adjustment; may be more sensitive to adverse effects
• Adolescents: Not FDA-approved for patients <18 years