Safety Of Varenicline Research Articles

Stopping smokeless tobacco with varenicline: randomised double blind placebo controlled trial

Objective To assess the efficacy and safety of varenicline (a licensed cigarette smoking cessation aid) in helping users of smokeless tobacco to quit.Design Double blind, placebo controlled, parallel group, multicentre,...

Safety and Effectiveness of Varenicline in a Veteran Population with a High Prevalence of Mental Illness

Varenicline is a selective nicotinic receptor partial agonist used to aid in the process of smoking cessation. Research on varenicline's approval for marketing demonstrated that after 12 weeks of treatment, at least 44% of patients successfully quit smoking and, on average, 13% of individuals discontinued therapy due to an adverse drug event (ADE). Growing postmarketing data linked varenicline to an increase in neuropsychiatric symptoms. To evaluate the safety profile, specifically psychiatric symptoms, and effectiveness of varenicline in a veteran population and to determine whether there is an association among specific baseline demographics and success rate. The study was a retrospective review of a prospective performance measure involving veterans initiated on varenicline. Patients were contacted via telephone throughout treatment and at week 12 for effectiveness follow-up. Smoking history was obtained and medication counseling was provided. The primary endpoint was tobacco cessation between weeks 9 and 12 of therapy. Varenicline's safety profile and discontinuation rates due to ADEs were also analyzed. Of the 50 patients included in the study, 30% (n = 15) successfully quit smoking and 70% (n = 35) failed therapy (lack of effectiveness, n = 22; intolerability, n = 13). Prevalence of underlying mental illness in the success group (4/15; 27%) versus failure group (20/35; 57%) was statistically significant (p < 0.001). All patients who discontinued therapy due to an increase in mood and behavioral changes (n = 4) had an underlying psychiatric illness. The study results demonstrate a lower success rate and a higher incidence of discontinuation due to an ADE in our veteran population compared with premarketing data. An inverse association was shown between psychiatric disorders and success. Cautious treatment initiation and close monitoring of veterans initiated on varenicline are warranted. Furthermore, the results from this study demonstrate the need for prospective effectiveness trials to determine the clinical significance of the results.

A Preliminary Benefit-Risk Assessment of Varenicline in Smoking Cessation

Varenicline is a recently developed medication for smoking cessation, which has been available on prescription since 2006. It is a selective nicotinic acetylcholine receptor partial agonist, and is designed to reduce withdrawal symptoms and to lessen the rewards of continued smoking. Our objective in this article is to assess the efficacy of varenicline as an aid to smoking cessation and to weigh the potential benefits against the possible risks. We identified ten randomized controlled trials and one cohort study with historical controls. In total there were 7999 participants, 5112 of whom received varenicline. Eight of the trials compared varenicline with placebo for cessation, two compared it with nicotine replacement therapy and one tested extended use for relapse prevention. Three of the varenicline/placebo trials also included a bupropion arm. The recommended dosage of varenicline 1 mg twice daily more than doubled the chances of quitting at 6 months or longer, with a relative risk (RR) compared with placebo of 2.38 (95% CI 2.00, 2.84). It also outperformed bupropion (RR 1.52 [95% CI 1.22, 1.88]) and nicotine replacement (RR 1.31 [95% CI 1.01, 1.71]). A reduced dosage regimen of 1 mg daily also increased cessation (RR 1.88 [95% CI 1.35, 2.60]). In the trials, varenicline significantly reduced craving and other withdrawal symptoms. The most frequent adverse event was nausea, occurring in 30-40% of varenicline users. However, this was generally reported at mild to moderate levels, diminished over time and was associated with attributable discontinuation rates of between 0.6% and 7.6%. Other commonly occurring adverse events included insomnia, abnormal dreams and headache. Serious adverse events were rare, with no treatment-related deaths during the treatment or follow-up phases. Postmarketing surveillance has raised new questions about the safety of varenicline. In February 2008, the US FDA issued a public health advisory note, reporting a possible association between varenicline and an increased risk of behaviour change, agitation, depressed mood, and suicidal ideation and behaviour. They have required the manufacturers to revise the labelling of varenicline and the Summary of Product Characteristics, and to issue a medication guide. It is arguable that much of the reported behavioural and mood changes may be associated with nicotine withdrawal, although some effects occurred in people who continued to smoke while taking the medication. In view of the potential, if unproven, risk that varenicline may be associated with serious neuropsychiatric adverse outcomes, patients attempting to quit smoking with varenicline, and their families and caregivers, should be alerted about the need to monitor for neuropsychiatric symptoms, including changes in behaviour, agitation, depressed mood, suicidal ideation and suicidal behaviour, and to report such symptoms immediately to the patient's healthcare provider.

Vareniclin – medikamentöse Therapie der Tabakabhängigkeit

Every year about 1.2 million deaths attributable to smoking occur in Europe. Effective smoking cessation, therefore, is essential. Varenicline is the first medication specifically developed for smoking cessation. The efficacy of varenicline in smoking cessation is due to its role as a partial agonist/antagonist at the alpha4beta2 nicotine receptors. This dual action causes a reduction in cigarette craving as well as withdrawal symptoms; moreover, it decreases the pleasurable and reinforcing effects of smoking. This article discusses the current clinical data regarding efficacy and safety of varenicline and its role in smoking cessation.

Varenicline safety under review

Varenicline safety under review

Varenicline safety under review

Varenicline safety under review

Varenicline: A review of the literature and place in therapy

Evidence regarding the health consequences of smoking is undeniable, yet 21% of the American population continues to smoke. In addition to behavioral modifications, first-line treatment options include nicotine replacement therapies and bupropion SR. Varenicline, which was recently approved by the Food and Drug Administration (FDA), offers a novel mechanism of action for smoking cessation. This article reviews current first-line smoking cessation aids and evaluates the clinical trials pertaining to the efficacy and safety of varenicline. Additionally, the authors attempt to establish the role of varenicline in smoking cessation therapy and determine whether varenicline should be used prior to other first-line smoking cessation aids, particularly considering the lower costs of generic alternatives. At present, clinical studies have not established the efficacy of varenicline after repeated courses, following bupropion failures, or in various unstudied populations. Relatively poor study outcomes emphasize the need to provide patients with behavioral counseling throughout each quit attempt and for 1 year past the quit date.

Oral Varenicline for Smoking Cessation

To review the pharmacology, pharmacokinetics, efficacy, and safety of varenicline and provide a review of relevant clinical data. A MEDLINE search (2001-December 2006) was conducted using the key words varenicline and nicotine replacement therapy for clinical trials limited to human subjects and published in English. All available human trials of varenicline were selected for review. References cited in identified articles were used for additional citations. Varenicline selectively targets the alpha4beta2 nicotine receptors in the brain that are responsible for cravings and withdrawal associated with nicotine use and dependence. Maximal plasma concentration occurs within 3-4 hours after administration and, after multiple doses, a steady-state concentration is reached within 4 days. Varenicline has a half-life of 24 hours. Oral bioavailability is not affected by food or time of administration. It exhibits linear pharmacokinetics and low plasma protein binding (< or =20%) regardless of a patient's age and renal status. It can be administered once daily. Dosage adjustments are not required in patients with hepatic insufficiency, but adjustments may be necessary in patients with severe renal insufficiency. Clinically significant drug-drug interactions have not been observed with varenicline or co-inhibitors of the human organic cation transporter, which mediates renal secretion of varenicline. Substrates such as warfarin, digoxin, cimetidine, metformin, bupropion, and transdermal nicotine do not alter pharmacokinetic parameters when coadministered with varenicline. In vitro studies have not demonstrated alterations in cytochrome P450 enzyme parameters. Varenicline's safety with coadministration of nicotine replacement products has not been well established. Varenicline is an effective oral agent for smoking cessation.

Varenicline: A Novel Nicotinic Receptor Partial Agonist for Smoking Cessation

Objective: To review the pharmacology, pharmacokinetics, clinical efficacy, and safety of varenicline, a selective partial nicotinic receptor agonist for smoking cessation. Data Sources: Primary literature and review articles were obtained via a MEDLINE search (1966–January 2007) using the key terms smoking cessation, nicotinic receptor, tobacco, and varenicline. Additional studies and abstracts were identified from the bibliographies of reviewed literature. Study Selection and Data Extraction: Available English-language literature, including abstracts, preclinical and clinical trials, and review articles were identified. Six randomized, placebo-controlled trials were evaluated to determine varenicline's efficacy for smoking cessation. Data Synthesis: Varenicline is a partial agonist selective for the α4β2 nicotinic receptor. Varenicline has been compared with placebo and sustained-release (SR) bupropion in randomized, double-blind, controlled trials. These trials found varenicline to have more successful 4 week continuous quit rates compared with both placebo and bupropion SR. One study reported a significantly increased continuous abstinence rate with varenicline versus bupropion SR; however, 2 other studies found no difference between varenicline and bupropion SR. To date, dose-dependent nausea is the most frequent adverse effect associated with varenicline; this may be limited with proper dosage titration. Conclusions: Increased cessation rates in comparison with placebo and, possibly, bupropion SR, as well as limited safety concerns, suggest that varenicline may have a role as another first-line therapy for smoking cessation.

Smoking Cessation Efficacy and Safety of Varenicline, an α4β2 Nicotinic Receptor Partial Agonist

Varenicline, an alpha4beta2 nicotinic receptor partial agonist, has the potential to relieve nicotine craving and withdrawal symptoms while reducing the reinforcing effects of nicotine. Phase 3 studies have evaluated the effects of varenicline on inducing smoking cessation and maintaining smoking abstinence. Two identically designed randomized, double-blind, smoking cessation studies recruited smokers of 10 or more cigarettes daily who were motivated to quit. Treatment with varenicline 1 mg twice daily was compared with treatment with bupropion 150 mg twice daily or matching placebo for 12 weeks, followed by a 40-week nontreatment observation period. In a third study that investigated maintenance of abstinence, smokers were treated with 12 weeks of open-label varenicline 1 mg twice daily. Subjects who did not smoke during the last week of treatment were eligible to be randomized to varenicline or placebo for an additional 12 weeks, followed by a 28-week nontreatment observation period. Brief smoking cessation counseling was given at clinic visits or telephone contacts scheduled regularly during the entire duration of the 3 studies. Measurement of carbon monoxide in expired breath was used to verify the subjects' reports of nonsmoking. In the 2 smoking cessation studies, varenicline significantly increased the 4-week continuous abstinence rate during weeks 9 to 12 relative to placebo and bupropion. The continuous abstinence rate during weeks 9 to 52 was also increased compared with placebo and with bupropion (statistically significant in one of the studies). In the maintenance study, smokers who quit after an initial course of open-label varenicline had greater long-term efficacy when they received an additional 12 weeks of varenicline than when they received placebo. In all 3 studies, varenicline was safe and well tolerated, with overall treatment discontinuation rates similar to that of placebo. Nausea was the adverse event that occurred more frequently in subjects receiving varenicline but was mostly mild in intensity. The results of these studies demonstrate a new order of efficacy in medical therapy for smoking cessation. Varenicline proved to be more effective than bupropion in inducing cessation. Furthermore, varenicline prevented relapse in smokers who had progressed toward cessation by quitting for at least 1 week.

Varenicline: For smoking cessation

Varenicline, a partial agonist of alpha4beta2 nicotinic acetylcholine receptor (nAChR), is the most recently approved drug for smoking cessation. Despite the availability of effective treatments for smoking cessation, such as nicotine replacement therapy and Bupropion sustained-release, abstinence rates remain less than optimal. As a nAChR partial agonist, Varenicline attenuates the craving and withdrawal symptoms that occur with abstinence from nicotine and also reduces the rewarding effects of nicotine obtained from smoking in patients who lapse. Clinical trials have demonstrated superior efficacy of this drug over Bupropion-SR for achieving abstinence from smoking, and Varenicline has also been shown to significantly delay smoking relapse. As the latest agent approved for smoking cessation, the mechanism of action, efficacy, and safety of Varenicline has been reviewed in this paper.