How it works
Varenicline binds with subnanomolar affinity to α4β2 nAChRs, where it acts as a partial agonist: it stimulates dopamine release in the mesolimbic reward pathway at approximately 40–60% of the maximal effect of nicotine, relieving craving and withdrawal symptoms. At the same time, by occupying the same binding sites, it competitively blocks nicotine from inhaled smoke, blunting the reinforcing effect of a lapse. Varenicline is also a full agonist at α7 nAChRs and a partial agonist at α3β4 and α6β2* nAChRs, though the clinical relevance of these additional actions is less well defined. (PMID 16820546; PMID 16820547)Clinical evidence
Two pivotal phase 3 trials, each randomising approximately 1,000 generally healthy smokers, compared varenicline (titrated to 1 mg twice daily) with placebo and sustained-release bupropion over 12 weeks of treatment with 40 weeks of nondrug follow-up. In the first trial (NCT00141206), the carbon monoxide–confirmed continuous abstinence rate for weeks 9–12 was 44.0% for varenicline versus 17.7% for placebo (OR 3.85; 95% CI 2.70–5.50) and 29.5% for bupropion (OR 1.93; 95% CI 1.40–2.68). The continuous abstinence rate for weeks 9–52 was 21.9% for varenicline versus 8.4% for placebo (OR 3.09; 95% CI 1.95–4.91). The second trial (NCT00143364) reported consistent results: 43.9% varenicline versus 17.6% placebo at weeks 9–12 (OR 3.85; 95% CI 2.69–5.50). Nausea was the most common adverse event, occurring in 28–29% of participants in the varenicline groups. (PMID 16820546; PMID 16820547)Renal impairment
Varenicline is eliminated predominantly by renal glomerular filtration and active tubular secretion. Exposure is unchanged in mild impairment but increased 1.5-fold in moderate impairment (CrCl 30–50 mL/min) and 2.1-fold in severe impairment (CrCl <30 mL/min). For severe renal impairment, the recommended dose is 0.5 mg once daily initially, titrated to a maximum of 0.5 mg twice daily if tolerated. Treatment is not recommended in end-stage renal disease due to insufficient clinical experience. (EMA Champix product information)Hepatic impairment and pregnancy
No dosage adjustment is needed in hepatic impairment. Varenicline undergoes minimal hepatic metabolism and is primarily renally cleared. (EMA Champix SmPC 4.2) Varenicline should be avoided during pregnancy as a precautionary measure. A moderate amount of pregnancy-exposure registry data has not identified a malformative or fetotoxic signal, but animal studies showed reproductive toxicity at clinically relevant exposures. It is not known whether varenicline is excreted in human breast milk. (EMA Champix SmPC 4.6) The only contraindication is hypersensitivity to the active substance or any excipient. (EMA Champix SmPC 4.3)How to use
Two things run in parallel from day one: how the tablet is taken, and the quit plan it is meant to support.Swallow after food with water
Take each tablet whole after food with a full glass of water to reduce nausea. Use the starter pack in order, and don’t combine it with another quit-smoking medicine unless the prescriber has planned it.
Pair tablets with a quit plan
Set the agreed target quit date, usually 1–2 weeks after starting, and use behavioural support for triggers and cravings. A flexible quit date within the first 5 weeks may be agreed in some cases.
Dose schedule
This gradual start improves tolerance. Kidney function or side effects may require a lower dose, and a further course is considered individually.
What has been reported
Contact your doctor if
- Thoughts of self-harm, severe agitation, psychosis, a seizure, chest pain, or stroke symptoms — seek urgent help
- A severe skin reaction, facial or throat swelling, or breathing difficulty
- Nausea, insomnia, mood effects, or kidney-related concerns make it hard to continue, or smoking has not stopped as planned