Cytisinicline is a naturally occurring plant-based alkaloid compound that is derived from laburnum and cytisus. It has been commercially available over the counter in Europe for decades. This medication is used as a smoking cessation agent. In the United States, it is currently in phase 3 clinical trials and could provide a new option for smoking cessation in the near future.
Clinical Trial Data
A phase 3 clinical study was conducted in 2023 called “Cytisinicline for Smoking Cessation: A Randomized Clinical Trial”. Cytisinicline was compared to placebo to test smoking cessation efficacy. Participants in the study were assigned randomly in 1:1:1 ratio of either cytisinicline 3 mg three times daily for 6 weeks, cytisinicline 3 mg three times daily for 12 weeks, or placebo. The authors of the study found that at both 6 and 12 weeks of cytisinicline treatment compared to placebo, there was a significant difference in smoking abstinence rate. At 6 weeks the smoking abstinence rates were 25.3% vs 4.4% (95% CI, P<0.001). At 12 weeks, the smoking abstinence rates were 32.6% vs 7.0% (95% CI, P<0.001). Overall, at 6 and 12 weeks, cytisinicline was found to be effective in smoking cessation. The most common side effects of cytisinicline in the study were insomnia and abnormal dreams, but overall well tolerated.
Comparison to Varenicline
Varenicline has a half-life of 24 hours, while cytisinicline’s half-life is 4.8 hours. Due to the shorter half-life of in the study above, it was dosed three times daily, and the European manufacturer recommended 6 times daily dosing, compared to varenicline’s two times daily dosing. Varenicline may be better for patient adherence due to less frequent dosing. The side effect profile for both of the medications are very similar. Abnormal dreams and insomnia are two common adverse effects of varenicline that may come up on your board exam. In a noninferiority trial conducted in Australia in 2021 comparing cytisinicline to varenicline, cytisinicline failed to demonstrate noninferiority. This indicates that varenicline may be more effective in smoking cessation compared to cytisinicline. Another finding in this trial was that cytisinicline was associated with fewer reported adverse effects. This indicates that it may be more tolerable than varenicline. While cytisinicline is not commercially available in the United States, in Europe it costs around 150 euros for a month’s supply. If approved by the FDA, it will be interesting to see what the retail price is set at.
Place in Therapy
Overall, cytisinicline has been shown to be effective in smoking cessation in phase 3 trials. It appears to have a potentially lower incidence of adverse effects than varenicline, however, current trials have not shown it to be as effective as varenicline. Frequent dosing may be a significant downside compared to varenicline. If FDA approval happens, I envision this medication being a solid consideration in those who haven’t tolerated varenicline or who have failed other smoking cessation options.
This article was written by Hunter Backholm, PharmD, Candidate in collaboration with Eric Christianon, PharmD, BCPS, BCGP.
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