varenicline
Nicotinic receptor partial agonist· Brands: Champix, ChantixPO
Mechanism of action
Varenicline is a partial agonist at the alpha4beta2 nicotinic acetylcholine receptor. It binds with high affinity and selectivity, stimulating dopamine release to a lesser extent than nicotine, which reduces craving and withdrawal symptoms. It also blocks the binding of nicotine to these receptors, thereby diminishing the rewarding effects of smoking.
Pharmacokinetics
Varenicline is well absorbed after oral administration with a bioavailability of approximately 90%. Peak plasma concentrations occur within 3 to 4 hours. The elimination half-life is about 24 hours, allowing twice-daily dosing. It is predominantly excreted unchanged in the urine, with minimal metabolism. No significant dose adjustment is required in mild to moderate renal impairment, but severe renal impairment may necessitate dose reduction.
Indications & dosing
Smoking cessation
Start with 0.5 mg once daily for days 1-3, then 0.5 mg twice daily for days 4-7, then 1 mg twice daily. Duration 12 weeks, may continue for another 12 weeks if needed.
- adult · PO: 1 mg twice daily · Start with 0.5 mg once daily for days 1-3, then 0.5 mg twice daily for days 4-7, then 1 mg twice daily. Duration 12 weeks, may continue for another 12 weeks if needed.
Alcohol use disorderoff-label
Off-label use. Limited evidence; consult specialist.
- adult · PO: 1 mg twice daily · Off-label use. Limited evidence; consult specialist.
Contraindications & precautions
- Known hypersensitivity to varenicline or any component · Anaphylaxis, angioedema, and skin reactions have been reported.
- Severe renal impairment (eGFR < 30 mL/min) · Dose reduction is required; use only if benefits outweigh risks.
- Pregnancy · Use only if potential benefit justifies risk to fetus.
- Monitor for changes in behaviour, mood, or suicidal ideation during treatment.
- Dose adjustment is needed for severe renal impairment.
- Use caution in patients with a history of psychiatric illness.
- Use caution in patients with cardiovascular disease.
- Advise patients to stop treatment and seek medical help if angioedema or severe skin reactions occur.
Adverse effects
- Nausea
- Insomnia
- Abnormal dreams
- Headache
- Vomiting
- Neuropsychiatric symptoms (depression, suicidal ideation)serious
- Angioedemaserious
- Severe skin reactions (e.g., Stevens-Johnson syndrome)serious
- Cardiovascular events (e.g., myocardial infarction)serious
Renal & hepatic adjustment
- eGFR 0–30: In severe renal impairment (eGFR <30 mL/min), reduce the starting dose to 0.5 mg once daily, then increase to 0.5 mg twice daily after 4 days.
Monitoring, pregnancy & toxicity
- Neuropsychiatric symptoms (e.g., mood change, suicidal ideation) · Before and during treatment
- Cardiovascular symptoms (e.g., chest pain, dyspnoea, palpitations) · During treatment
- Treatment response (smoking cessation) · At follow-up
- Pregnancy: Not recommended during pregnancy. If pregnancy is confirmed, consider stopping varenicline and discussing alternative smoking cessation strategies.
- Toxicity: Nausea, vomiting, insomnia, and abnormal dreams · Symptomatic treatment; these effects are common and often self-limiting.
- Toxicity: Overdose may cause agitation, confusion, or seizures · Supportive care, monitor vital signs, and consider the need for activated charcoal if recent large ingestion.
Clinical notes
Varenicline is used as an aid to smoking cessation. Treatment should be started one week before the target quit date, with a dose titration over the first week. Common adverse effects include nausea, insomnia, headache, and abnormal dreams. There have been reports of neuropsychiatric symptoms, but evidence suggests the risk is low, particularly in patients without a history of psychiatric illness. Advise patients to seek medical help if they experience mood changes or suicidal thoughts. Also consider the potential for interactions with nicotine replacement therapy.
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BNF; local formulary