Varenicline’s unique mechanism involves dual action on nicotine receptors:

1. Partial Agonism at α4β2 Nicotinic Receptors:
   • Binds to the α4β2 subtype of nAChRs, the same receptors activated by nicotine (Lippincott).
   • Provides mild stimulation to reduce cravings and withdrawal symptoms, mimicking nicotine’s effects at a lower intensity (BNF).
2. Nicotine Receptor Blockade:
   • Prevents nicotine from fully binding to these receptors, reducing the reinforcing effects of smoking (Lange).
3. Dopamine Modulation:
   • Partially activates dopamine release in the brain’s reward pathways, alleviating withdrawal without the peak effects caused by nicotine (Lippincott).

Varenicline is indicated for:

1. Smoking Cessation:
   • Helps adults quit smoking by reducing cravings and withdrawal symptoms.
   • Recommended for use alongside counseling and behavioral interventions (BNF).
2. Long-Term Abstinence:
   • Shown to improve long-term success rates compared to placebo and other therapies like nicotine replacement (Lange).

Varenicline requires a titration schedule to minimize side effects. Always follow the prescribing physician’s instructions.

Standard Dosage:

• Days 1–3: 0.5 mg once daily.
• Days 4–7: 0.5 mg twice daily.
• Day 8 onward: 1 mg twice daily (BNF).

Administration Tips:

• Take tablets with food and a full glass of water to reduce nausea.
• Begin treatment 1–2 weeks before the target quit date.
• Total treatment duration is typically 12–24 weeks.

Varenicline is generally well-tolerated but may cause:

Common:

• Nausea (30% of users, often mild and transient).
• Insomnia or abnormal dreams.
• Headache, constipation, or flatulence.

Serious but Rare:

• Neuropsychiatric Effects: Mood changes, depression, suicidal ideation (requires immediate medical attention) (BNF).
• Cardiovascular Events: Increased risk in patients with pre-existing heart disease (Lippincott).
• Seizures: Rare but reported in patients with seizure history (Lange).

Before using varenicline, inform your healthcare provider if you have:

• A history of psychiatric disorders (e.g., depression, schizophrenia).
• Cardiovascular disease or kidney impairment.
• Seizure disorders or epilepsy.
• Allergies to varenicline or formulation components.

Special Populations:

• Pregnancy: Avoid unless benefits outweigh risks (limited data; BNF Category: Not formally classified).
• Breastfeeding: Safety not established; avoid.
• Renal Impairment: Dose adjustments required for severe impairment (e.g., 1 mg once daily).

Varenicline interacts with few medications but caution is advised with:

1. CNS-Acting Drugs:
   • May enhance effects of alcohol or sedatives, causing dizziness or impaired judgment (BNF).
2. Nicotine Replacement Therapy (NRT):
   • Concurrent use is not recommended due to increased nausea and headache risk (Lippincott).
3. Renally Excreted Drugs:
   • Drugs like cimetidine may reduce varenicline clearance, requiring dose adjustments (Lange).

Generic Names in Pharmacy

• Varenicline tartrate (active ingredient)
• Common brand name: Champix®