Clinical consequences of varenicline shortage: A study on the French national pharmacovigilance database

Varenicline is a smoking cessation therapy included in the World Health Organization (WHO) model list of essential medicines. In May 2021, the presence of N-nitroso-varenicline, a carcinogenic agent, was detected in varenicline tablets above the limits determined by the European Medicine Agency (EMA), leading to batches being recalled and causing a shortage of this drug. The aim of this study was to use pharmacovigilance data to evaluate the clinical consequences of the shortage of varenicline.

Data were extracted from the French PharmacoVigilance Database using the following terms: "varenicline (tartrate of)", "varenicline" and "tartrate of varenicline" as the suspected, interactive, or concomitant medication from 4 April 2021 to 17 March 2023. Each case was reviewed by a pharmacovigilance expert to select only cases that involved a varenicline shortage.

Among the 32 included cases, the reported adverse effects were: smoking relapse (n=21), tobacco cessation failure (n=7) and tobacco withdrawal syndrome (n=2). Most of the patients presented a high level of tobacco dependence. Before the introduction of varenicline, these smokers consumed a median of 20 cigarettes per day. They did not smoke while receiving varenicline. After the shortage, the daily cigarette consumption went up to 10 in all patients treated with nicotine replacement therapy (NRT) and up to 20 when NRT was not used.

In the context of a varenicline shortage, the pharmacovigilance data confirmed the risk of smoking relapse and/or cessation failure in patients with a strong addiction to cigarettes. Given the role of smoking exposure in respiratory, cancer and cardiovascular risk, it is vitally important that the availability of this medicine is ensured. Solutions, such as the importation of alternatives produced by other brands that pass the tests for impurity quantification, may prevent the risk in this context.