ABSTRACT
BACKGROUND: Ensuring adherence to prescribed smoking cessation medications, such as Champix® (varenicline), is essential during a quit attempt as non-adherence can significantly reduce the likelihood of achieving prolonged smoking abstinence. The use of dose administration aids may improve adherence, though medication stability on repackaging is not guaranteed, due to a lack of available data from manufacturers supporting this practice. OBJECTIVE: To determine the suitability for repackaging varenicline tartrate tablets into a dose administration aid, by assessing its physical and chemical stability after being repackaged and stored at ambient conditions for 6 weeks. METHODS: Varenicline tartrate (1.0 mg) tablets were repackaged into commercially available Webster-pak® blister compartments and stored for 42 days at ambient conditions characteristic of a Zone IVB climate (30 ± 2°C and 75 ± 5% relative humidity) according to the World Health Organization (WHO) guidelines on pharmaceutical stability testing. Physical and chemical tests were performed on the repackaged and control tablets, including an assessment of: tablet thickness, hardness, weight uniformity, friability, dissolution, disintegration, and content uniformity after exposure to ambient conditions and light according to International Council on Harmonisation of Technical Requirements of Pharmaceuticals for Human Use guideline Q1B. RESULTS: Weight, friability, and thickness of the tablets complied with compendial standards. A validated high performance liquid chromatography method was used to confirm that after exposure to light, and repackaging at 30°C/75% relative humidity, the tablets remained within the required 95%-105% of the stated drug content. However, tablet hardness and disintegration decreased over time, with tablets becoming softer and undergoing more rapid disintegration in water. CONCLUSION: Repackaging 1.0 mg varenicline tartrate tablets into a dose administration aid can be undertaken to improve adherence rates and therefore smoking abstinence rates. This can be performed without compromising either the physical or chemical stability of the tablets.
ABSTRACT
PURPOSE: Varenicline, the newest agent marketed for smoking cessation is regarded as effective in providing prolonged smoking abstinence. However, its adverse effect profile may cause discontinuation, potentially reducing smoking abstinence rates, thus requiring an examination of the frequency and impact of adverse effects on discontinuation. METHODS: We sought only Randomised Controlled Trials (RCTs) evaluating the effectiveness and safety of varenicline on humans, with a follow-up period of at least three months and an average Fagerstrom Test for Nicotine Dependence (FTND) score at least 5 (moderate dependence) for both the active and placebo groups. PubMed, Medscape, JCU One Search, ClinicalTrials.gov (U.S.), and the Cochrane Collaboration from January 2006 to January 2015 were searched. Fixed and random effects models were run to determine relationships between adverse effects and premature discontinuation from varenicline. RESULTS: 12 RCTs were included, involving 5 459 patients, with those receiving varenicline found to be nearly twice as likely (Odds ratio (OR) = 1.82 [1.47; 2.26]) to experience adverse effects compared to those patients on a placebo. The active group experienced nearly a 1.5 times higher (OR = 1.47 [1.19; 1.81]) rate of discontinuation. Nausea, insomnia, and headache are the most commonly reported adverse effects, with ORs of 4.40 [3.80; 5.11], 1.75 [1.48; 2.08], and 1.20 [1.02; 1.41] respectively. CONCLUSION: Adverse effects experienced during varenicline treatment appear to be associated with higher discontinuation, which are linked to lowered smoking cessation rates, suggesting a need for strategies to minimise the impacts of adverse effects, to better ensure adherence.
