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Review
. 2019 Nov;114(11):1951-1969.
doi: 10.1111/add.14721. Epub 2019 Jul 19.

Cytisine for nicotine addiction treatment: a review of pharmacology, therapeutics and an update of clinical trial evidence for smoking cessation

Piotr Tutka  1   2   3 , Denis Vinnikov  4   5 , Ryan J Courtney  3 , Neal L Benowitz  6   7
Affiliations
Review

Cytisine for nicotine addiction treatment: a review of pharmacology, therapeutics and an update of clinical trial evidence for smoking cessation

Piotr Tutka et al. Addiction. 2019 Nov.

Abstract

Aims: To review cytisine's history of use, pre-clinical evidence, clinical pharmacokinetics, efficacy, adverse reactions (ARs) and safety for smoking cessation.

Methods: A synoptic review of the use of cytisine as a smoking cessation medication, mechanism of action, pharmacokinetics and safety. Relevant literature on data included in these sections were identified through a search of 11 databases with additional literature obtained from reports and monographs. Three databases (PubMed, EMBASE and www.elibrary.ru) were systematically searched for studies published from 2012 to August 2018 in any language to provide an updated meta-analysis of cytisine's efficacy and ARs for smoking cessation compared with placebo. We pooled the relative risks (RR) of abstinence in the efficacy analysis and RR of ARs, either reported by the authors or calculated from the reports.

Results: Cytisine has been in use since 1964 and is currently marketed in 18 countries. Systemic bioavailability from oral ingestion is high and clearance is primarily renal, with minimal or no metabolism. Brain uptake in animal models is moderate. The plasma half-life averages 4.8 hours. Eight studies were included for meta-analysis of efficacy. With heterogeneous results, the overall RR versus placebo of successful continuous abstinence at the longest follow-up was 1.74 [95% confidence interval (CI) = 1.38-2.19]. Nausea, vomiting, dyspepsia, upper abdominal pain and dry mouth that were mild or moderate were the most common ARs, with RR versus placebo 1.10 (95% CI = 0.95-1.28). The cost of cytisine in eastern and central Europe is several-fold less than that of other smoking cessation medications.

Conclusions: Cytisine is a low-cost medication found to increase the likelihood of smoking cessation. The most frequently reported ARs of cytisine involve gastrointestinal symptoms that are mostly reported as either mild or moderate in severity.

Keywords: Addiction; cessation; cytisine; low-/middle-income country; nicotine; nicotinic receptor partial agonist.

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References

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