Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
0.5 mg and 1 mg film-coated tablets
Approved indication: smoking cessation
Australian Medicines Handbook section 18.7
Smoking is addictive. Although many smokers try to stop, very few succeed without assistance. Some people need nicotine replacement therapy or bupropion to help them quit.1
Varenicline is a drug which binds to nicotinic receptors. It is a partial agonist so it provides some stimulation at the receptor, but also blocks nicotine. These actions may help to reduce withdrawal symptoms and the craving smokers have for nicotine.
Once someone has committed to stop smoking, they begin varenicline one or two weeks before the date they have set to quit. They gradually increase the dose from 0.5 mg daily to 1 mg twice daily which they continue until the end of the 12-week period of treatment.
The tablets are well absorbed and undergo little metabolism. Most of the dose is excreted in the urine with an elimination half-life of approximately 24 hours.
Varenicline has been compared with placebo and bupropion. In one trial, which randomised 1025 people, 44% of those given varenicline had stopped smoking by the end of the 12-week treatment period. This was significantly better than the 30% of the bupropion group and the 18% of the placebo group who stopped smoking. The patients were followed for a further 40 weeks. At the end of the year, the continuous abstinence rates were 22% for varenicline, 16% for bupropion and 8% for placebo.2
Using the same design, another trial randomised 1027 smokers. In the last month of treatment (weeks 9-12 of the study) 44% of the varenicline group, 30% of the bupropion group and 18% of the placebo group were no longer smoking. When followed up at 52 weeks the continuous abstinence rate was 23% with varenicline, 15% with bupropion and 10% with placebo.3
Many of the people who restarted smoking resumed soon after stopping treatment. Another trial therefore investigated if abstinence rates could be improved by a longer duration of treatment. People who had stopped smoking after a 12-week course were randomised to continue varenicline for another 12 weeks or take a placebo. During this maintenance phase 71% of the varenicline group did not smoke compared with 50% of the placebo group. After a year the rates were 44% and 37%.4
Many people dropped out of the smoking cessation trials.23 In the varenicline group 4-9% of people discontinued because of adverse effects. Nausea is the most common problem, affecting approximately 30% of those taking varenicline compared to approximately 10% of the placebo group. Other adverse effects which occurred more frequently with varenicline than placebo included vomiting, constipation, abnormal dreams and insomnia. Patients who cannot tolerate these adverse effects could try a reduced dose. It is not known if the elderly are more prone to adverse effects as few people over 65 years old were included in the trials of varenicline. It is not recommended for people under 18 years old. Following the marketing of varenicline in the USA, there have been reports of patients experiencing suicidal thoughts and aggressive and erratic behaviour.
Varenicline does not prevent the weight gain associated with stopping smoking. After 12 weeks of treatment, patients taking varenicline gained 2-3 kg.23 The safety of varenicline in pregnancy and breastfeeding is unknown.
All the participants had weekly counselling23 so it may not be possible to achieve the same results in routine practice. Although varenicline achieved higher rates of abstinence than bupropion, the difference was not statistically significant in the long term. There do not appear to be any published comparisons of varenicline and nicotine replacement therapy.
The Transparency Score () is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.
Notes on references
At the time the comment was prepared, information about this drug was available on the web site of the Food and Drug Administration in the USA (www.fda.gov).
At the time the comment was prepared, a scientific discussion about this drug was available on the website of the European Medicines Agency (www.emea.europa.eu).
- Litt J. What's new in smoking cessation? Aust Prescr 2005;28:73-5.
- Gonzales D, Rennard SI, Nides M, Oncken C, Azoulay S, Billing CB, et al.Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation. A randomized controlled trial. JAMA 2006;296:47-55.
- Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, et al. Efficacy of varenicline, an Î±4Î²2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation. A randomized controlled trial. JAMA 2006;296:56-63.
- Tonstad S, Tonnesen P, Hajek P, Williams KE, Billing CB, Reeves KR. Effect of maintenance therapy with varenicline on smoking cessation. A randomized controlled trial. JAMA 2006;296:64-71.