Midostaurin drug interaction profile: a comprehensive assessment of CYP3A, CYP2B6, and CYP2C8 drug substrates, and oral contraceptives in healthy participants.

PURPOSE: Midostaurin, approved for treating FLT-3-mutated acute myeloid leukemia and advanced systemic mastocytosis, is metabolized by cytochrome P450 (CYP) 3A4 to two major metabolites, and may inhibit and/or induce CYP3A, CYP2B6, and CYP2C8. Two studies investigated the impact of midostaurin on CYP substrate drugs and oral contraceptives in healthy participants. METHODS: Using sentinel dosing for participants' safety, the effects of midostaurin at steady state following 25-day (Study 1) or 24-day (Study 2) dosing with 50 mg twice daily were evaluated on CYP substrates, midazolam (CYP3A4), bupropion (CYP2B6), and pioglitazone (CYP2C8) in Study 1; and monophasic oral contraceptives (containing ethinylestradiol [EES] and levonorgestrel [LVG]) in Study 2. RESULTS: In Study 1, midostaurin resulted in a 10% increase in midazolam peak plasma concentrations (Cmax), and 3-4% decrease in total exposures (AUC). Bupropion showed a 55% decrease in Cmax and 48-49% decrease in AUCs. Pioglitazone showed a 10% decrease in Cmax and 6% decrease in AUC. In Study 2, midostaurin resulted in a 26% increase in Cmax and 7-10% increase in AUC of EES; and a 19% increase in Cmax and 29-42% increase in AUC of LVG. Midostaurin 50 mg twice daily for 28 days ensured that steady-state concentrations of midostaurin and the active metabolites were achieved by the time of CYP substrate drugs or oral contraceptive dosing. No safety concerns were reported. CONCLUSION: Midostaurin neither inhibits nor induces CYP3A4 and CYP2C8, and weakly induces CYP2B6. Midostaurin at steady state has no clinically relevant PK interaction on hormonal contraceptives. All treatments were well tolerated.

Medication Use in the Management of Comorbidities Among Individuals With Autism Spectrum Disorder From a Large Nationwide Insurance Database.

Importance: Although there is no pharmacological treatment for autism spectrum disorder (ASD) itself, behavioral and pharmacological therapies have been used to address its symptoms and common comorbidities. A better understanding of the medications used to manage comorbid conditions in this growing population is critical; however, most previous efforts have been limited in size, duration, and lack of broad representation. Objective: To use a nationally representative database to uncover trends in the prevalence of co-occurring conditions and medication use in the management of symptoms and comorbidities over time among US individuals with ASD. Design, Setting, and Participants: This retrospective, population-based cohort study mined a nationwide, managed health plan claims database containing more than 86 million unique members. Data from January 1, 2014, to December 31, 2019, were used to analyze prescription frequency and diagnoses of comorbidities. A total of 26 722 individuals with ASD who had been prescribed at least 1 of 24 medications most commonly prescribed to treat ASD symptoms or comorbidities during the 6-year study period were included in the analysis. Exposures: Diagnosis codes for ASD based on International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. Main Outcomes and Measures: Quantitative estimates of prescription frequency for the 24 most commonly prescribed medications among the study cohort and the most common comorbidities associated with each medication in this population. Results: Among the 26 722 individuals with ASD included in the analysis (77.7% male; mean [SD] age, 14.45 [9.40] years), polypharmacy was common, ranging from 28.6% to 31.5%. Individuals' prescription regimens changed frequently within medication classes, rather than between classes. The prescription frequency of a specific medication varied considerably, depending on the coexisting diagnosis of a given comorbidity. Of the 24 medications assessed, 15 were associated with at least a 15% prevalence of a mood disorder, and 11 were associated with at least a 15% prevalence of attention-deficit/hyperactivity disorder. For patients taking antipsychotics, the 2 most common comorbidities were combined type attention-deficit/hyperactivity disorder (11.6%-17.8%) and anxiety disorder (13.1%-30.1%). Conclusions and Relevance: This study demonstrated considerable variability and transiency in the use of prescription medications by US clinicians to manage symptoms and comorbidities associated with ASD. These findings support the importance of early and ongoing surveillance of patients with ASD and co-occurring conditions and offer clinicians insight on the targeted therapies most commonly used to manage co-occurring conditions. Future research and policy efforts are critical to assess the extent to which pharmacological management of comorbidities affects quality of life and functioning in patients with ASD while continuing to optimize clinical guidelines, to ensure effective care for this growing population.

Pharmacovigilance Assessment of Cardiac Implications of Nicotine Replacement Therapy Among Smokers.

PURPOSE: The purpose of this quantitative comparative study was to examine the possible relationship between nicotine replacement therapy (NRT) and cardiac disorder risk by comparing the rates of cardiac disorder risk of NRT with cardiac disorder risk of non-replacement drugs among smokers seeking smoking cessation. METHODS: The study used retrospective quantitative design, which involved the collection of secondary data from the adverse event reporting system (FAERS) database of the U.S Food and Drug Administration (FDA). Rates of cardiac disorder were compared between the NRT group and non- NRT (varenicline and bupropion) group. Statistical analyses involved using a 2x2 contingency table and logistic regression to calculate odds ratio (reporting odds ratio (ROR)). RESULTS AND DISCUSSION: Unadjusted ROR was 0.45 (95% confidence interval [CI] 0.28, 0.70). With age and sex as confounding factors, the smokers in the NRT group still had lower odds of having cardiac disorder risk than the non-NRT group (adjusted ROR=0.44, 95% CI 0.28, 0.70). CONCLUSION: Our study findings showed lower cardiac disorder risk with the NRT group compared to the non-NRT (varenicline and bupropion) group. While the study did not aim to undermine either using NRT or non-NRT for smoking cessation therapy to prevent smoking illness, the study results offer informed findings that could potentially improve current smoking cessation management using NRT intervention among smokers and enhance smokers' health outcome. Despite the negative signal detection of cardiac disorder risk with NRT as compared to non-NRT in final findings, we still recommend further research on the causal relationship between NRT and non-NRT and cardiac disorder risk.

Stereoselective Steady-State Disposition and Bioequivalence of Brand and Generic Bupropion in Adults.

The antidepressant bupropion is stereoselectively metabolized and metabolite enantiomers have differential pharmacologic effects, but steady-state enantiomeric disposition is unknown. Controversy persists about bupropion XL 300 mg generic equivalence to brand product, and whether generics might have different stereoselective disposition leading to enantiomeric non-bioequivalence and, thus, clinical nonequivalence. This preplanned follow-on analysis of a prospective, randomized, double-blinded, crossover study of brand and 3 generic bupropion XL 300 mg products measured steady-state enantiomeric plasma and urine parent bupropion and primary and secondary metabolite concentrations and evaluated bioequivalence and pharmacokinetics. Steady-state plasma and urine bupropion disposition was markedly stereoselective, with up to 40-fold differences in plasma concentrations of the active metabolite S,S-hydroxybupropion vs. R,R,-hydroxybupropion. Urine metabolite glucuronides were prominent, but glucuronidation was metabolite-specific and enantioselective. There were no differences between any generic and brand, or between generics, in plasma enantiomer concentrations of bupropion or the major metabolites. All generic products satisfied formal bioequivalence criteria (peak plasma concentration (Cmax ) and area under the plasma concentration-time curve over 24 hours (AUC0-24 )) using enantiomers for bupropion as well as for metabolites, and generics were comparable to each other, and were considered bioequivalent, based on enantiomeric analysis. Enantiomeric bioequivalence explains the previously observed therapeutic equivalence of bupropion generics and brand in treating major depression. These results have important implications for understanding the clinical therapeutic effects of bupropion based on complex and stereoselective metabolism.

Modelling a budgetary impact analysis for funding drug-based smoking cessation therapies for patients with major depressive disorder in Spain.

BACKGROUND: Smoking is associated with high healthcare resource utilisation and cost to society. Patients with major depressive disorder (MDD) exhibit high susceptibility to nicotine dependence. Varenicline, bupropion and nicotine replacement therapy are all indicated for smoking cessation; however funding by the Spanish national health system (SNHS) is limited. We modelled a budgetary impact analysis (BIA) to estimate the impact of the SNHS funding drug-based therapies for smoking cessation in smokers with MDD. METHODS: The BIA compared the current unfunded scenario versus a funded scenario (varenicline, bupropion, nicotine replacement therapy combined with medical follow-up and counselling) using the Spanish SNHS and societal perspectives. The BIA design was a hybrid model using a decision tree algorithm (population size: smokers with MDD) and Markov chains (smoking cessation attempts) over a 5-year horizon. Smoking cessation drug efficacy was derived from clinical trials, and smoking cessation costs avoided were taken from an analysis of the Spanish National Health Survey. Results were shown as incremental cost savings. Scenarios and threshold univariate sensitivity analyses tested model robustness. RESULTS: The funded scenario resulted in an increase of 43,478 cessation attempts and 8930 fewer smokers after 5 years compared to the unfunded scenario. The cost of funding was €25.3 million and costs avoided were €26.5 million. There was a cumulative 5-year incremental cost saving of €1.2 million to Spanish society. Results were robust using alternative scenarios. CONCLUSIONS: Funding smoking cessation drugs in patients with MDD is of economic benefit to Spain and could produce net savings from the third year of implementation.

Cost-utility analysis of vortioxetine versus agomelatine, bupropion SR, sertraline and venlafaxine XR after treatment switch in major depressive disorder in Finland.

BACKGROUND: To assess the cost-utility of vortioxetine versus relevant comparators (agomelatine, bupropion SR, sertraline, and venlafaxine XR) in the finnish setting in major depressive disorder (MDD) patients with inadequate response to selective serotonin- /serotonin-norepinephrine reuptake inhibitors. METHODS: A one-year analysis was conducted using a decision tree with a Markov state transition component. The health states were remission, relapse and recovery. A Finnish healthcare payer perspective was adopted. RESULTS: Vortioxetine was less costly and more effective versus all comparators in both direct and societal perspectives. Vortioxetine reduced the average annual direct costs by 4% versus venlafaxine XR and 8% versus sertraline. The greater efficacy associated with vortioxetine was translated into a higher percentage of patients in remission and recovery. The model was most sensitive to changes in remission rates at 8 weeks. CONCLUSION: This cost-utility analysis showed vortioxetine to be a good alternative for MDD patients switching therapy in Finland.

Safety assessment of combination therapies in the treatment of obesity: focus on naltrexone/bupropion extended release and phentermine-topiramate extended release.

INTRODUCTION: Few studies on combination therapies for the treatment of obesity had been conducted until recently, when two fixed-dose combinations, bupropion-naltrexone ER fixed-dose combination and phentermine-topiramate ER titrated-dose combinations were evaluated in clinical studies that ultimately led to FDA approval. Areas covered: In this review, we discuss safety concerns about both combinations, the rationale and history of combination therapies for obesity (including phentermine plus fenfluramine), and possible future new combinations. Expert opinion: Combination therapies are a promising new area in obesity treatment, similar to what occurs with diabetes and hypertension. Safety assessment is highly important due to the high number of potential users on a chronic basis.

Trends in Use of Medications for Smoking Cessation in Medicare, 2007-2012.

INTRODUCTION: Smoking-related disease accounts for 10% of Medicare expenditures. Although clinical guidelines recommend smoking-cessation medications, they are subject to safety warnings from the U.S. Food and Drug Administration (FDA). This study investigated trends in utilization of smoking-cessation medications in Medicare from 2007 to 2012. METHODS: Data on medical claims and prescription drugs for a nationally representative sample of Medicare beneficiaries were used to study trends from 2007 to 2012 in use of smoking-cessation medications (bupropion, nicotine-replacement therapy, varenicline), among beneficiaries who used tobacco (N=205,675). Analyses were conducted in 2015. Multinomial logistic regression was used to examine differences in use of bupropion, nicotine-replacement therapy, varenicline, or more than one medication, relative to none, by beneficiaries' health and demographic characteristics. Binary logistic regression calculated average predicted probabilities of cardiovascular disease or depression among medication users before and after FDA safety warnings related to those conditions. RESULTS: Sixteen percent of tobacco users ever filled a prescription for a smoking-cessation medication. The proportion of beneficiaries who filled prescriptions for varenicline increased in 2007 but sharply declined corresponding to public warnings about adverse effects, although the same trends did not occur for bupropion or nicotine-replacement therapy. After FDA safety concerns were published, the average predicted probability of beneficiaries filling varenicline prescriptions with cardiovascular disease declined by 31%, although the average predicted probability of depression did not decline. CONCLUSIONS: Use of smoking-cessation medications among Medicare beneficiaries remains low. Health effects of Medicare policies that increase coverage for medical support for smoking cessation may be limited by low utilization of effective medications.

Homeless Clients Benefit From Smoking Cessation Treatment Delivered by a Homeless Persons' Program.

INTRODUCTION: Few homeless programs offer smoking cessation treatment. This study examined the feasibility, acceptability, and effectiveness of a smoking cessation treatment model delivered by staff of a homeless persons' program. METHODS: Fourteen nurses from Melbourne's Royal District Nursing Service Homeless Persons' Program recruited 49 clients into a 12-week program offering weekly nurse-delivered smoking cessation appointments with intermittent carbon monoxide measurements, doctor-prescribed free nicotine patch, bupropion or varenicline, and Quitline phone support. Surveys were completed at program enrolment, end of program (EoP, 3 months) and 6 months post-enrolment. RESULTS: Clients attended on average 6.7 nurse-delivered appointments. Most used pharmacotherapy (69%, n = 34) and Quitline (61%, n = 30, average 8.4 calls among users). Using all-cases analyses 29% had made a quit attempt by EoP; 24-hour point prevalence abstinence rates were 6% at EoP and 4% at 6 months (no participants achieved sustained cessation), and 29% reported 50% consumption reduction at 6 months, the latter positively associated with increased Quitline use. Tobacco consumption and money spent on tobacco halved by EoP with similar levels maintained at 6 months. Discarded butt smoking reduced. Using within-subjects analyses, all participants reported either the same or less symptoms of anxiety at EoP compared to baseline and 92% reported the same or less depressive symptoms. CONCLUSIONS: Integrating nurse support with readily accessible cessation interventions (government subsidized pharmacotherapy plus Quitline) was feasible and acceptable. While quit rates were low, treatment benefits included harm-reduction (reduced consumption and butt smoking), significant financial savings, and psychological benefits (improved or stable mood).

Race and Medication Adherence Moderate Cessation Outcomes in Criminal Justice Smokers.

INTRODUCTION: Smokers in the criminal justice system represent some of the most disadvantaged smokers in the U.S., as they have high rates of smoking (70%-80%) and are primarily uninsured, with low access to medical interventions. Few studies have examined smoking-cessation interventions in racially diverse smokers, and none have examined these characteristics among individuals supervised in the community. The purpose of this study is to determine if four sessions of standard behavioral counseling for smoking cessation would differentially aid smoking cessation for African American versus non-Hispanic white smokers under community corrections supervision. DESIGN: An RCT. SETTING/PARTICIPANTS: Five hundred smokers under community corrections supervision were recruited between 2009 and 2013 via flyers posted at the community corrections offices. INTERVENTION: All participants received 12 weeks of bupropion plus brief physician advice to quit smoking. Half of the participants received four sessions of 20-30 minutes of smoking-cessation counseling following tobacco treatment guidelines, whereas half received no additional counseling. MAIN OUTCOME MEASURES: Generalized estimating equations were used to determine factors associated with smoking abstinence across time. Analyses were conducted in 2014. RESULTS: The end-of-treatment abstinence rate across groups was 9.4%, with no significant main effects indicating group differences. However, behavioral counseling had a differential effect on cessation: whites who received counseling had higher quit rates than whites who did not receive counseling. Conversely, African Americans who did not receive counseling had higher average cessation rates than African Americans who received counseling. Overall, medication-adherent African American smokers had higher abstinence rates relative to other smokers. CONCLUSIONS: Racial disparities in smoking cessation are not evident among those who are adherent to medication. More research is needed to better understand the differential effect that behavioral counseling might have on treatment outcomes between white and African American smokers under community corrections supervision.

Geneva cocktail for cytochrome p450 and P-glycoprotein activity assessment using dried blood spots.

The suitability of the capillary dried blood spot (DBS) sampling method was assessed for simultaneous phenotyping of cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp) using a cocktail approach. Ten volunteers received an oral cocktail capsule containing low doses of the probes bupropion (CYP2B6), flurbiprofen (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), midazolam (CYP3A), and fexofenadine (P-gp) with coffee/Coke (CYP1A2) on four occasions. They received the cocktail alone (session 1), and with the CYP inhibitors fluvoxamine and voriconazole (session 2) and quinidine (session 3). In session 4, subjects received the cocktail after a 7-day pretreatment with the inducer rifampicin. The concentrations of probes/metabolites were determined in DBS and plasma using a single liquid chromatography-tandem mass spectrometry method. The pharmacokinetic profiles of the drugs were comparable in DBS and plasma. Important modulation of CYP and P-gp activities was observed in the presence of inhibitors and the inducer. Minimally invasive one- and three-point (at 2, 3, and 6 h) DBS-sampling methods were found to reliably reflect CYP and P-gp activities at each session.

General practitioner prescribing of single and combination nicotine replacement therapy in the UK: a retrospective database study.

BACKGROUND: Guidance in England and Wales recommends that nicotine replacement therapies (NRTs), varenicline or bupropion should be offered for smoking cessation support. Research on general practitioner (GP) NRT prescribing patterns for smoking cessation is lacking in the published literature. METHODS: UK primary care electronic health records were retrospectively analysed to identify the most common GP initiated NRT prescribing patterns, characterise people who receive NRT and determine whether NRTs given in a first quit attempt are different from subsequent attempts. RESULTS: The study population comprised 38,954 individuals in UK primary care data with a first ever NRT patch smoking cessation attempt for the period January 2008-December 2011. The majority (64.3%) received NRT patch monotherapy at first smoking cessation attempt, and the most common NRT was 21 mg/24 hours patch monotherapy (15.2%). Of the 35.7% first smoking cessation attempts which were NRT combination therapy, the most common combination was patch + inhalator (56.2%). The proportion of people who started a smoking cessation attempt with combination therapy increased from 25.7% in 2008 to 44.8% in 2011. The majority of the population had one recorded smoking cessation attempt but a significant minority (20.2% N = 7,868) started a second smoking cessation attempt. Second and third attempts, while predominantly patch monotherapy, also demonstrated an increasing use of NRT combinations over the study period (2ndepisode: 20.6%-38.2%; 3rdepisode: 20.0%-36.8%). However, a minority received only non-patch NRT during second and third NRT episodes. Taking into account the 39,068 people prescribed NRT patch during the study period with a history of NRT at baseline (excluded from the analysis), the total proportion of people prescribed NRT patch between 2008-2011 who had more than one NRT episode was 48.4% (46,936/96,986) and of 128,115 NRT users, only 14.7% (N = 18,838) were prescribed bupropion or varenicline prior to NRT use. CONCLUSIONS: The study findings represent new data describing GP NRT prescription patterns in the UK. Given the predominance of NRT patch monotherapy observed, health policy makers and service commissioners should ensure that GPs provide equality of access to all recommended smoking cessation pharmacotherapies.

Status and costs of smoking cessation in countries of the Eastern Mediterranean Region.

The aim of this cross-sectional observational study was to address the health care situation in regard to smoking cessation efforts and expenditure, and to provide a basis for future studies and for implementing tobacco control programmes throughout the Eastern Mediterranean Region of the World Health Organization. Information collected included methods and cost of services for tobacco cessation from all 16 participating countries. In 10 countries, cessation programmes were directed by primary physicians. In 13 countries, nicotine gum and in 14 countries nicotine patches were accessible in pharmacies. Bupropion was available at pharmacies (with a written prescription) in 6 countries and varenicline in 7 countries. However, the mean cost of each service was significantly higher than the price of a pack of cigarettes. In countries with support services for tobacco cessation, directors need to provide care at the society level that is considerably less costly and widely accessible.

State medicaid coverage for tobacco-dependence treatments --- United States, 2009.

Medicaid enrollees have nearly twice the smoking rates (37%) of the general adult population (21%), and smoking-related medical costs are responsible for 11% of Medicaid expenditures. In 2008, the Public Health Service released clinical practice guidelines recommending comprehensive coverage of effective tobacco-dependence medications and counseling by health insurers. Healthy People 2010 established a clear objective for Medicaid programs to cover all Food and Drug Administration--approved medications and counseling for tobacco cessation. To monitor progress toward that objective, the Center for Health and Public Policy Studies at the University of California, Berkeley, in collaboration with CDC, surveyed Medicaid programs in the 50 states and the District of Columbia (DC) to document their 2009 tobacco-dependence treatment coverage and found that 47 programs offered coverage. Only eight state programs offered coverage of all recommended pharmacotherapy and counseling for all Medicaid enrollees, and 16 programs reported coverage for fee-for-service enrollees that differed from that provided for Medicaid managed-care enrollees. Among the 33 programs that covered at least one combination therapy, the nicotine patch plus bupropion slow release (SR) was the one combination covered by all. The Affordable Care Act mandates Medicaid coverage of tobacco-dependence treatments for pregnant women, beginning October 1, 2010. Coverage of pharmacotherapy for all Medicaid enrollees will be enhanced by January 2014, when states no longer may exclude tobacco-dependence cessation drugs from covered benefits. Monitoring the extent to which Medicaid programs place limitations on these treatments can help in evaluating accessibility of tobacco-dependence treatments to Medicaid enrollees.

Gender, race, and education differences in abstinence rates among participants in two randomized smoking cessation trials.

INTRODUCTION: Smoking is the leading preventable cause of morbidity and mortality in the United States, but this burden is not distributed equally among smokers. Women, Blacks, and people with low socioeconomic status are especially vulnerable to the health risks of smoking and are less likely to quit. METHODS: This research examined cessation rates and treatment response among 2,850 participants (57.2% women, 11.7% Blacks, and 9.0% with less than a high school education) from two large cessation trials evaluating: nicotine patch, nicotine lozenge, bupropion, bupropion + lozenge, and nicotine patch + lozenge. RESULTS: Results revealed that women, Blacks, and smokers with less education were less likely to quit smoking successfully than men, Whites, and smokers with more education, respectively. Women did not appear to benefit more from bupropion than from nicotine replacement therapy, but women and smokers with less education benefited more from combination pharmacotherapy than from monotherapy. DISCUSSION: Women, Blacks, and smokers with less education are at elevated risk for cessation failure, and research is needed to understand this risk and develop pharmacological and psychosocial interventions to improve their long-term cessation rates.

Cost effectiveness of varenicline versus bupropion and unaided cessation for smoking cessation in a cohort of Finnish adult smokers.

OBJECTIVE: To assess the cost effectiveness of varenicline compared with bupropion or unaided cessation for smoking cessation in Finnish adult smokers. RESEARCH DESIGN AND METHODS: The BENESCO (BENEfits of Smoking Cessation on Outcomes) Markov model was used to follow a hypothetical cohort of smokers making a single quit attempt over a lifetime. Gender and age-specific data on the incidence and prevalence of five smoking-related diseases (chronic obstructive pulmonary disease [COPD], lung cancer, coronary heart disease [CHD], stroke and asthma exacerbations) were included in the model. Life-years (LYs), quality-adjusted life-years (QALYs), total treatment costs and the lifetime cumulative incidence of these parameters were the primary outcomes evaluated, and they were compared for varenicline versus bupropion and varenicline versus unaided cessation. The primary data were derived from Finnish publications and databases. Deterministic and probabilistic sensitivity analyses were performed to test the robustness of the base-case model. RESULTS: The treatment cohort comprised 229 301 smokers making a quit attempt. In the lifetime simulation, use of varenicline prevented 1965 and 5057 additional cases of smoking-related disease, and 1184 and 3047 deaths attributable to smoking, when compared with bupropion and unaided cessation, respectively. Compared with bupropion and unaided cessation varenicline treatment yielded 4392 and 11 303 additional LYs (4851 and 12 485 QALYs), respectively. Varenicline resulted in cost savings of 15 million and 43 million euros (euro) compared with bupropion and unaided cessation, respectively. In the 20-year time horizon analysis, varenicline yielded an incremental cost-effectiveness ratio (ICER) of euro8791/QALY and euro7791/QALY gained in comparison to bupropion and unaided cessation, respectively. Sensitivity analyses supported the robustness of the base-case results for varenicline. CONCLUSION: Varenicline dominated over its comparators, i.e. it was more effective and resulted in cost saving compared with bupropion and unaided cessation.

Varenicline: a pharmacoeconomic review of its use as an aid to smoking cessation.

Varenicline (Chantix, Champix) is an orally administered alpha4beta2 nicotinic acetylcholine receptor partial agonist that is indicated as an aid to smoking cessation. Well designed clinical trials indicate that varenicline is an effective aid to smoking cessation. During the last 4 weeks of treatment, carbon monoxide-confirmed continuous abstinence rates were generally significantly higher with varenicline than with placebo, bupropion sustained release (SR) or nicotine replacement therapy. Varenicline also reduced cravings, the reinforcing effects of smoking and some withdrawal symptoms. Another well designed trial demonstrated that extending varenicline therapy by an additional 12 weeks helped maintain abstinence in individuals who had quit smoking. Varenicline was generally well tolerated in clinical trials; nausea, the most commonly occurring adverse event, diminished over time. More data are needed regarding the potential for neuropsychiatric events in varenicline recipients. Some of these events may be associated with nicotine withdrawal, rather than varenicline, although neuropsychiatric events have been observed in individuals who continued to smoke whilst receiving varenicline. In modelled cost-effectiveness analyses based on data from clinical trials in participants receiving smoking cessation therapy, 12 weeks' treatment with varenicline was predicted to be cost effective from a healthcare payer perspective in numerous countries. With regard to the incremental costs per QALY or life-year gained, 12 weeks' treatment with varenicline consistently dominated bupropion SR and nicotine replacement therapy and was dominant over or considered cost effective relative to unaided cessation, regular brief counselling or nortriptyline in analyses based on Markov models. In additional modelled analyses from a healthcare payer perspective, administering varenicline for an additional 12 weeks in participants who had successfully quit smoking was estimated to have acceptable incremental costs per QALY gained relative to varenicline for 12 weeks and to dominate other smoking cessation options. Moreover, in Swedish analyses that also included societal costs for production and consumption, the incremental cost per QALY gained for varenicline versus bupropion SR, and for an additional 12 weeks of varenicline therapy versus varenicline for 12 weeks only, was below commonly accepted thresholds of cost effectiveness. A US decision-analytic model from the perspective of various US health insurance plans demonstrated that, after 2 years, varenicline was predicted to dominate bupropion SR, in terms of the incremental cost per additional smoking cessation. Varenicline was also dominant or cost effective versus nicotine replacement therapy, and cost effective versus unaided cessation. Sensitivity analyses demonstrated that the results of cost-effectiveness studies were generally robust to plausible variations in key parameters. In conclusion, varenicline is an effective aid to smoking cessation. Varenicline was generally well tolerated in clinical trials, although more data are needed regarding the potential for neuropsychiatric events. The costs associated with varenicline are offset by direct savings associated with the reduction in smoking-related diseases. Despite their limitations, available pharmacoeconomic analyses from numerous countries support the use of varenicline for 12 or 24 weeks as a cost-effective treatment relative to other smoking cessation therapies in smokers who wish to quit smoking.