Varenicline Adherence Research Articles

Identifying determinants of varenicline adherence using the Theoretical Domains framework: a rapid review

BackgroundAdhering to varenicline has been shown to significantly improve the chances of successfully quitting smoking, with studies indicating a twofold increase in 6-month quit rates. However, despite its potential benefits, many individuals struggle with maintaining good adherence to varenicline; thus there is a need to develop scalable strategies to help people adhere. As a first step to inform the development of an intervention to improve adherence to varenicline, we conducted a rapid literature review to identify: 1) modifiable barriers and facilitators to varenicline adherence, and 2) behaviour change techniques associated with increased adherence to varenicline.MethodsWe searched MEDLINE, Embase, APA PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials for relevant studies published between 2006 and 2022. Search terms included “varenicline,” “smoking cessation,” and "adherence," and their respective subject headings and synonyms. We screened and included studies reporting modifiable determinants of adherence to varenicline and then assessed quality, extracted modifiable determinants and mapped them to the Theoretical Domains Framework version 2 and the Behaviour Change Technique Taxonomy version 1.ResultsA total of 1,221 titles were identified through the database searches; 61 met the eligibility criteria. Most of the studies were randomized controlled trials and predominantly focused on barriers to varenicline. Only nine studies explicitly mentioned behaviour change techniques used to help varenicline adherence. Eight domains were identified as barriers to varenicline adherence (behavioural regulation, memory, goals, intentions, beliefs about capabilities, beliefs about consequences, optimism/pessimism, and environmental context) and five as facilitators (knowledge, behavioural regulation, beliefs about capabilities, social influences, and environmental context).ConclusionsThis study identifies barriers and facilitators that should be addressed when developing a complex adherence intervention tailored to patients’ needs based on modifiable determinants of medication adherence, some of which are under- used by existing adherence interventions. The findings from this review will inform the design of a theory-based healthbot planned to improve varenicline adherence in people undergoing smoking cessation treatment.Systematic review registrationThis study was registered with PROSPERO (# CRD42022321838).

AI Conversational Agent to Improve Varenicline Adherence: Protocol for a Mixed Methods Feasibility Study.

Varenicline is a pharmacological intervention for tobacco dependence that is safe and effective in facilitating smoking cessation. Enhanced adherence to varenicline augments the probability of prolonged smoking abstinence. However, research has shown that one-third of people who use varenicline are nonadherent by the second week. There is evidence showing that behavioral support helps with medication adherence. We have designed an artificial intelligence (AI) conversational agent or health bot, called "ChatV," based on evidence of what works as well as what varenicline is, that can provide these supports. ChatV is an evidence-based, patient- and health care provider-informed health bot to improve adherence to varenicline. ChatV has been programmed to provide medication reminders, answer questions about varenicline and smoking cessation, and track medication intake and the number of cigarettes. This study aims to explore the feasibility of the ChatV health bot, to examine if it is used as intended, and to determine the appropriateness of proceeding with a randomized controlled trial. We will conduct a mixed methods feasibility study where we will pilot-test ChatV with 40 participants. Participants will be provided with a standard 12-week varenicline regimen and access to ChatV. Passive data collection will include adoption measures (how often participants use the chatbot, what features they used, when did they use it, etc). In addition, participants will complete questionnaires (at 1, 4, 8, and 12 weeks) assessing self-reported smoking status and varenicline adherence, as well as questions regarding the acceptability, appropriateness, and usability of the chatbot, and participate in an interview assessing acceptability, appropriateness, fidelity, and adoption. We will use "stop, amend, and go" progression criteria for pilot studies to decide if a randomized controlled trial is a reasonable next step and what modifications are required. A health equity lens will be adopted during participant recruitment and data analysis to understand and address the differences in uptake and use of this digital health solution among diverse sociodemographic groups. The taxonomy of implementation outcomes will be used to assess feasibility, that is, acceptability, appropriateness, fidelity, adoption, and usability. In addition, medication adherence and smoking cessation will be measured to assess the preliminary treatment effect. Interview data will be analyzed using the framework analysis method. Participant enrollment for the study will begin in January 2024. By using predetermined progression criteria, the results of this preliminary study will inform the determination of whether to advance toward a larger randomized controlled trial to test the effectiveness of the health bot. Additionally, this study will explore the acceptability, appropriateness, fidelity, adoption, and usability of the health bot. These insights will be instrumental in refining the intervention and the health bot. ClinicalTrials.gov NCT05997901; https://classic.clinicaltrials.gov/ct2/show/NCT05997901. PRR1-10.2196/53556.

Varenicline Combined With Oral Nicotine Replacement Therapy and Smartphone-Based Medication Reminders for Smoking Cessation: Feasibility Randomized Controlled Trial.

Varenicline and oral nicotine replacement therapy (NRT) have each been shown to increase the likelihood of smoking cessation, but their combination has not been studied. In addition, smoking cessation medication adherence is often poor, thus, challenging the ability to evaluate medication efficacy. This study examined the effects of combined varenicline and oral NRT and smartphone medication reminders on pharmacotherapy adherence and smoking abstinence among adults enrolled in smoking cessation treatment. A 2×2 factorial design was used. Participants (N=34) were randomized to (1) varenicline + oral NRT (VAR+NRT) or varenicline alone (VAR) and (2) smartphone medication reminder messages (REM) or no reminder messages (NREM) over 13 weeks. Participants assigned to VAR+REM received varenicline reminder prompts, and those assigned to VAR+NRT+REM also received reminders to use oral NRT. The other 2 groups (VAR+NREM and VAR+NRT+NREM) did not receive medication reminders. Participants were not blinded to intervention groups. All participants received tobacco cessation counseling. Smartphone assessments of smoking as well as varenicline and NRT use (if applicable) were prompted daily through the first 12 weeks after a scheduled quit date. Descriptive statistics were generated to characterize the relations between medication and reminder group assignments with daily smoking, daily varenicline adherence, and daily quantity of oral NRT used. Participants completed follow-up assessments for 26 weeks after the quit date. Participants were predominantly White (71%), and half were female (50%). On average, participants were 54.2 (SD 9.4) years of age, they smoked an average of 19.0 (SD 9.0) cigarettes per day and had smoked for 34.6 (SD 12.7) years. Descriptively, participants assigned to VAR+NRT reported more days of smoking abstinence compared to VAR (29.3 vs 26.3 days). Participants assigned to REM reported more days of smoking abstinence than those assigned to NREM (40.5 vs 21.8 days). Participants assigned to REM were adherent to varenicline on more days compared to those assigned to NREM (58.6 vs 40.5 days), and participants assigned to VAR were adherent to varenicline on more days than those assigned to VAR + NRT (50.7 vs 43.3 days). In the subsample of participants assigned to VAR+NRT, participants assigned to REM reported more days where ≥5 pieces of NRT were used than NREM (14.0 vs 7.4 days). Average overall medication adherence (assessed via the Medication Adherence Questionnaire) showed the same pattern as the daily smartphone-based adherence assessments. Preliminary findings indicated that smoking cessation interventions may benefit from incorporating medication reminders and combining varenicline with oral NRT, though combining medications may be associated with poorer adherence. Further study is warranted. ClinicalTrials.gov NCT03722966; https://classic.clinicaltrials.gov/ct2/show/NCT03722966.

Effectiveness of the Brief Guided Self-Change Therapy Combined with Varenicline under “Real-Life” Conditions and Mediators for Smoking Cessation

Background : Brief therapies have proven to reduce tobacco cost-effectively, however, unsuccessful quit attempts remain notable in real-life conditions, and the underlying mechanisms of treatment success are still unclear. Objectives : We aimed to analyze the effectiveness of the Guided Self-Change (GSC) therapy combined with varenicline (VAR+T) in public health services against varenicline alone (VAR), and to identify mediators of treatment outcomes. We conducted a two-arm quasi-experimental study with 126 treatment-seeking smokers (age=57.3±9.1 years; 59.5% women). Before treatment, and at weeks 12 and 24, we assessed tobacco use and five potential mediators: withdrawal, craving, motivation to quit, anxiety, and depression. Results : Only 25% of participants adhered to varenicline prescription, and 54% to GSC therapy. VAR+T group showed a greater proportion of abstainers compared to VAR group at week 12 (75% vs 57.4%; φc=0.21) and week 24 (62.9% vs 52.5%; φc=0.10). When controlling for weeks taking varenicline, motivation showed a significant indirect effect over abstinence rates in VAR+T compared with VAR (a1b1=1.34; 95%CI=0.04, 5.03). Conclusions : The GSC effectiveness seems to increase motivation which in turn contributes to reducing tobacco use. The implementation of GSC therapy in public health services could minimize treatment duration and increase smoking abstinence in ‘real-life’ conditions where varenicline adherence remains low.

Experiences of hospitalized smokers initiated on varenicline as part of a pragmatic smoking cessation trial

Varenicline is an effective monotherapy for smoking cessation, but adherence is often suboptimal. This qualitative study explored the experiences of varenicline treatment among participants enrolled in a randomized controlled trial, who self-reported being adherent or nonadherent to varenicline treatment (n = 15). Individual interviews were conducted using a semi-structured interview guide. Data were analyzed using thematic framework approach. An environment of forced abstinence played a key role in motivating quit attempts. The main barriers to varenicline adherence were medicine-related side effects, relapse to smoking, and a belief that the medication was not working if abstinence was not achieved by the target quit date. Participants adherent to treatment adopted a reduce-to-quit approach and noticed a gradual reduction in cigarette cravings. When asked about their preferences for support while on varenicline treatment, participants expressed the need for proactive follow-up by health professionals and more active behavioral support to assist them in adhering to treatment. Prescribers should encourage varenicline users to persist with treatment, even if abstinence is not achieved by the target quit date. Further research is needed to explore the awareness and acceptability of the reduce-to-quit method among prescribers and patients and its impact on varenicline adherence and in term long-term abstinence.

Timing of smoking cessation treatment integrated into outpatient treatment with medications for opioid use disorder: Feasibility trial

IntroductionCigarette smoking rates among individuals with opioid use disorder (OUD) are notoriously high and may be improved by considering the timing of treatment integration for these two substances. The current study examined the feasibility of a method for assessing the timing of integrating smoking cessation pharmacotherapy within three different phases of outpatient treatment with medication for OUD (MOUD). MethodsSeventy-four buprenorphine-maintained smokers were enrolled in a quasi-experimental study across three MOUD treatment phases: 0–90 (Phase 1), 91–365 (Phase 2), and > 365 days of MOUD treatment (Phase 3). During a 12-week varenicline-based intervention, the study assessed outcomes daily via text messages (cigarette smoking, varenicline adherence, side effects) or monthly at in-person visits (quit motivation and carbon monoxide levels). ResultsThirty-five participants completed the study, with a lower retention rate in Phase 1 (37.5%) relative to Phases 2 (53.5%) or 3 (57.1%). A trend occurred for Phase 1 participants to report aversive side effects (e.g., abnormal dreams, gastrointestinal distress) on more study days. Among completers, adherence to text messaging and varenicline use was high and independent of MOUD treatment phase. Participants in all phases reported declines in cigarette smoking and increases in quit motivation over time; the study observed biochemically verified tobacco abstinence among only a few participants from Phases 2 or 3. ConclusionsThis feasibility study demonstrates a method to evaluate the timing of treatment integration for cigarette smoking and MOUD. Method strengths include a study schedule that coincided with the MOUD clinic schedule and use of text messaging to encourage varenicline adherence and evaluate outcomes regularly.

Effect of varenicline directly observed therapy versus varenicline self-administered therapy on varenicline adherence and smoking cessation in methadone-maintained smokers: a randomized controlled trial.

Level of adherence to tobacco cessation medication regimens is believed to be causally related to medication effectiveness. This study aimed to evaluate the efficacy of varenicline directly observed therapy (DOT) on varenicline adherence and smoking cessation rates among smokers with opioid use disorder (OUD) receiving methadone treatment. Multicenter, parallel-group two-arm randomized controlled trial. Urban opioid treatment program (OTP) in the Bronx, New York, USA. Daily smokers of ≥5 cigarettes/day, interested in quitting (ladder of change score 6-8), in methadone treatment for ≥3months, attending OTP≥3days/week. Participants' mean age was 49years, 56% were male, 44% Latino, 30% Black, and they smoked a median of 10 cigarettes/day. Individual, block, random assignment to 12weeks of varenicline, either directly observed with methadone (DOT, n=50) or via unsupervised self-administered treatment (SAT, n=50). The primary outcome was adherence measured by pill count. The secondary outcome was 7-day point prevalence tobacco abstinence verified by expired carbon monoxide (CO)<8 parts per million. Retention at 24weeks was 92%. Mean adherence was 78.5% [95% confidence interval (CI)=71.8-85.2%] in the DOT group versus 61.8% in the SAT group (95% CI=55.0-68.6%); differences were driven by DOT effects in the first 6weeks. CO-verified abstinence did not differ between groups during the intervention (P=0.26), but was higher in the DOT than the SAT group at intervention end (DOT=18% versus SAT=10%, difference=8%, 95% CI=-13, 28); this difference was not significant (P=0.39) and was not sustained at 24-week follow-up. Among daily smokers attending opioid treatment programs, opioid treatment program-based varenicline directly observed therapy was associated with early increases in varenicline adherence compared with self-administered treatment, but findings were inconclusive as to whether directly observed therapy was associated with a difference in tobacco abstinence.

Medication adherence and rate of nicotine metabolism are associated with response to treatment with varenicline among smokers with HIV

IntroductionPLWHA who smoke have shown lower cessation rates within placebo-controlled randomized trials of varenicline. Adherence and rate of nicotine metabolism may be associated with quit rates in such clinical trials. MethodsThis secondary analysis of a randomized placebo-controlled trial of varenicline for smoking among PLWHA (N = 179) examined the relationship between varenicline adherence (pill count, ≥80% of pills), nicotine metabolism (based on the nicotine metabolite ratio; NMR) and end-of-treatment smoking cessation (self-reported 7-day point prevalence abstinence, confirmed with carbon monoxide of ≤ 8 ppm, at the end of treatment; EOT). ResultsCombining varenicline and placebo arms, greater adherence (OR = 1.011, 95% CI:1.00–1.02, p = 0.051) and faster nicotine metabolism (OR = 3.08, 95% CI:1.01–9.37, p = 0.047) were related to higher quit rates. In separate models, adherence (OR = 1.009, 95% CI:1.004–1.01, p < 0.001) and nicotine metabolism rate (OR = 2.04, 95% CI:1.19–3.49, p = 0.009) interacted with treatment arm to effect quit rates. The quit rate for varenicline vs. placebo was higher for both non-adherent (19% vs. 5%; χ2[1] = 2.80, p = 0.09) and adherent (35% vs. 15%; χ2[1] = 6.51, p = 0.01) participants, but the difference between treatment arms was statistically significant only for adherent participants. Likewise, among slow metabolizers (NMR < 0.31), the varenicline quit rate was not significantly higher vs. placebo (14% vs. 5%; χ2[1] = 1.17, p = 0.28) but, among fast metabolizers (NMR ≥ 0.31), the quit rate for varenicline was significantly higher vs. placebo (33% vs. 14%; χ2[1] = 4.43, p = 0.04). ConclusionsIncreasing varenicline adherence and ensuring that fast nicotine metabolizers receive varenicline may increase quit rates for PLWHA.

Correlates of varenicline adherence among smokers with HIV and its association with smoking cessation

IntroductionWith medical advances, the life expectancy of people living with HIV/AIDS (PLWHA) has improved; however, tobacco use remains a prominent risk for mortality. Although studies have examined the efficacy of varenicline for treating smoking among PLWHA, the relationship between varenicline adherence and cessation and correlates of varenicline adherence remain under-studied. MethodsWe conducted secondary analyses from a randomized placebo-controlled trial of varenicline for smoking among PLWHA, using data from participants who received varenicline (N = 89). The relationship between varenicline adherence (based on pill count) and end-of-treatment smoking cessation was assessed, as were correlates of varenicline adherence. ResultsThose who were abstinent took an average of 137.1 pills (SD = 39.3), or 83% of pills prescribed, vs. 105.3 pills (SD = 64.1), or 64%, for those who were smoking (OR = 1.01, 95% CI: 1.001–1.021, p = 0.03); 52/89 (58%) participants were adherent based on taking ≥80% of pills. The quit rate for adherent participants was 35% (18/52) vs. 19% (7/37) for non-adherent participants. Adherent participants were older, smoked fewer cigarettes each day, started smoking at an older age, and had lower baseline creatinine vs. non-adherent participants (p < 0.05). There was a significant time-by-group interaction effect for anxiety (F[1,72] = 6.24, p = 0.02), depression (F[1,72] = 4.2, p = 0.04), and insomnia (F[1,72] = 7.73, p = 0.007), indicating that adherent participants had less depression, anxiety, and insomnia during the initial weeks of treatment, vs. non-adherent participants. ConclusionsOur findings underscore the importance of varenicline adherence for determining cessation and highlight the role of early changes in anxiety, depression, and insomnia determining varenicline adherence.

Different measures of varenicline adherence, nicotine metabolite ratio and smoking abstinence

Different measures of varenicline adherence, nicotine metabolite ratio and smoking abstinence

The association between self-reported varenicline adherence and varenicline blood levels in a sample of cancer patients receiving treatment for tobacco dependence

IntroductionThe degree to which smokers quit successfully with varenicline is strongly associated with their adherence to the medication regimen. Thus, measuring varenicline adherence to identify smokers needing additional intervention is a priority. Few studies, however, have examined the validity of self-reported varenicline adherence, using a biological assessment of adherence as a reference. No study has examined this issue among cancer patients trying to quit smoking, who may show unique patterns of adherence given their medical comorbidity. MethodsThis study used data from 76 cancer patients who received varenicline and provided self-reported varenicline adherence data (pill count) and a blood sample to determine varenicline metabolites 4 weeks after initiating varenicline. ResultsReceiver operating characteristic (ROC) curve analyses of plasma varenicline levels showed that 4 ng/ml was the optimal cut-point for differentiating adherence with significant (p's < 0.04) area under the curve values, ranging from 0.73–0.80 for 3-day, 7-day, and 4-week self-reported pill count; specificity values ranged from 0.63–0.78 and sensitivity values ranged from 0.82–0.94. Using this cut-point, adherence was high (88%). However, plasma varenicline levels were weakly correlated with 3-day and 4-week pill count and total pill count (12 weeks) was not correlated with plasma varenicline levels. Patients with head and neck cancer, gastrointestinal cancer, and more advanced disease showed lower varenicline adherence and lower plasma varenicline. ConclusionsUsing the 4 ng/ml cut-point, this study suggests validity of short-term self-reported varenicline adherence among cancer patients undergoing tobacco dependence treatment in contrast to studies in the general population, which supported 12-week pill count.

Predictors of Varenicline Adherence Among Cancer Patients Treated for Tobacco Dependence and its Association With Smoking Cessation.

The degree to which smokers adhere to pharmacotherapy predicts treatment success. The development of interventions to increase adherence requires identification of predictors of treatment adherence, particularly among specific clinical populations. Using data from a 12-week open-label phase of a clinical trial of varenicline for tobacco dependence among cancer patients (N = 207), we examined: (1) the relationship between self-reported varenicline adherence and verified smoking cessation and (2) demographic and disease-related variables, and early changes in cognition, affect, withdrawal, the reinforcing effects of smoking, and medication side effects, as correlates of varenicline adherence. At the end of 12 weeks, 35% of the sample had quit smoking and 52% reported taking ≥80% of varenicline. Varenicline adherence was associated with cessation (p < .001): 58% of participants who were adherent had quit smoking versus 11% of those who were not. Participants who experienced early reductions in depressed mood and satisfaction from smoking and experienced an increase in the toxic effects of smoking, showed greater varenicline adherence (p < .05); the relationship between greater adherence and improved cognition, reduced craving, and reduced sleep problems and vomiting approached significance (p < .10). Among cancer patients treated for tobacco dependence with varenicline, adherence is associated with smoking cessation. Initial changes in depressed mood and the reinforcing effects of smoking are predictive of adherence. The benefits of varenicline for treating tobacco dependence among cancer patients may depend upon boosting adherence by addressing early signs of depression and reducing the reinforcing dimensions of cigarettes.

Predicting smoking abstinence with biological and self-report measures of adherence to varenicline: Impact on pharmacogenetic trial outcomes

IntroductionAdherence to pharmacotherapies for tobacco dependence, such as varenicline, is necessary for effective treatment. The relationship between varenicline adherence, determined by commonly used indirect (i.e., self-reported pill counts) and infrequently used direct (i.e., varenicline levels) methods, and abstinence outcomes have not been previously examined, nor has their impact on the outcomes of a genetically randomized clinical trial been assessed. MethodsAt Week 1 following target quit date, self-reported pill count and salivary varenicline levels were obtained from participants (N = 376) in a smoking cessation clinical trial (NCT01314001). Point-prevalence abstinence was biochemically-verified by salivary cotinine at Week 1 and by exhaled carbon monoxide at Week 1, end-of-treatment, 6 and 12 months following treatment. Blood nicotine metabolite ratio (NMR) was obtained at baseline. ResultsAdherent individuals based on varenicline levels were significantly more likely to be abstinent than non-adherent individuals at Week 1 (odds ratios [ORs] 1.92–3.16, p’s≤0.006), end-of-treatment (OR = 2.53, p = .004), and six months following treatment (OR = 2.30, p = .03). In contrast, pill counts did not consistently predict abstinence. Including direct measures of adherence enhanced the association between rate of nicotine metabolism (NMR) and end-of-treatment abstinence; normal metabolizers (NMR ≥ 0.31) were significantly more likely than slow metabolizers (NMR < 0.31) to be abstinent at end-of-treatment (OR = 2.00, p = .005). ConclusionAdherence based on salivary varenicline, rather than on pill counts, is predictive of Week 1 abstinence, irrespective of the biomarker of abstinence assessed, and of long-term abstinence. Direct measures of adherence enhance the ability to assess the impact of a biomarker or genetic marker on abstinence outcomes.

Improvement of the association between self-reported pill count and varenicline levels following exclusion of participants with misreported pill count: A commentary on Peng et al. (2017)

IntroductionWe previously reported poor associations between salivary varenicline and pill counts, and a substantial overestimation of adherence by pill counts in “Measures and predictors of varenicline adherence in the treatment of nicotine dependence” (Peng et al., 2017). We have since conducted supplementary analyses characterizing, and then excluding, individuals with established inaccurate pill count recall. MethodsBased on published varenicline pharmacokinetics (including drug levels, and the long half-life) and our detection limits, conservatively we should be able to detect varenicline in anyone who took at least one pill during the 48h prior to saliva collection; thus, those reporting 1 or more pills in this time frame but who had undetectable salivary varenicline were deemed to have inaccurate pill count recall. Correlations between pill counts and salivary varenicline, and Receiver Operating Characteristics curve analyses were conducted following exclusion of participants with inaccurate pill count recall. ResultsNearly 20% of our participants (N=67/376) had inaccurate self-reported pill counts. These participants were younger, non-white, lower income, and unmarried (evaluated using chi-square or Mann-Whitney U test). Following exclusion of these individuals, the correlations between salivary varenicline and pill count improved and the area under the curve (AUC) of pill counts for discriminating adherence improved modestly. ConclusionWhen the 20% of individuals with inaccurate pill count recall were excluded, an improved association between self-reported pill count and salivary varenicline was observed, albeit still weak. A substantial overestimation of adherence by pill counts relative to salivary varenicline is still observed even after exclusion of almost 20% of the group having established inaccurate reporting suggesting that these individuals, with identifiable inaccuracies, were only part of the overestimation of adherence.

Measures and predictors of varenicline adherence in the treatment of nicotine dependence

IntroductionWhile adherence to medication in smoking cessation clinical trials is strongly associated with clinical outcome, very few studies have evaluated the validity of pill count as a measure of adherence relative to a biological assay, and evaluated a broad range of correlates of adherence. MethodsIn a smoking cessation clinical trial of varenicline, we compared pill counts collected over 4 different time periods to varenicline salivary levels taken after 2weeks of treatment, as well as evaluated predictors of adherence to varenicline. ResultsUsing a binary measure of adherence based on salivary varenicline levels, adherence was higher among older, white, and more educated participants. Relative to 3, 7, and 14-day pill count, 12-week pill count was the only significant measure able to discriminate adherence as defined by salivary varenicline levels (assessed by area under the receiver operating characteristic curve; AUC=0.59, p=0.004). Seventy-two percent of participants who indicated adherence on 12-week pill count were classified as adherent based on varenicline saliva levels (sensitivity=0.80; specificity=0.40). There was modest variability in the relationship between 12-week pill count and varenicline levels across race and rate of nicotine metabolism. Lastly, General Estimating Equation models demonstrated that longitudinal changes in withdrawal, craving, negative and positive affect, and side effect count and severity were not related to adherence based on salivary varenicline levels. ConclusionsThese results indicate that 12-week pill count was the best, albeit a relatively weak, measure of varenicline adherence; additional factors associated with treatment adherence need to be identified.

Addressing varenicline adherence through repackaging in a dose administration aid.

BackgroundEnsuring 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.ObjectiveTo 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.MethodsVarenicline 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.ResultsWeight, 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.ConclusionRepackaging 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.

Combining Text Messaging and Telephone Counseling to Increase Varenicline Adherence and Smoking Abstinence Among Cigarette Smokers Living with HIV: A Randomized Controlled Study.

Smoking represents an important health risk for people living with HIV (PLHIV). Low adherence to smoking cessation pharmacotherapy may limit treatment effectiveness. In this study, 158 participants recruited from three HIV care centers in New York City were randomized to receive 12-weeks of varenicline (Chantix) either alone as standard care (SC) or in combination with text message (TM) support or TM plus cell phone-delivered adherence-focused motivational and behavioral therapy (ABT). Generalized linear mixed-effect models found a significant decline in varenicline adherence from week 1-12 across treatment groups. At 12-weeks, the probability of smoking abstinence was significantly higher in SC+TM+ABT than in SC. The study demonstrates the feasibility of delivering adherence-focused interventions to PLHIV who smoke. Findings suggest intensive behavioral support is an important component of an effective smoking cessation intervention for this population, and a focus on improving adherence self-efficacy may lead to more consistent adherence and higher smoking abstinence.

Correlates of Adherence to Varenicline Among HIV+ Smokers.

Low rates of adherence to smoking cessation pharmacotherapy may limit the effectiveness of treatment. However, few studies have examined adherence in smoking cessation trials thus, there is a limited understanding of factors that influence adherence behaviors. This brief report analyzes correlates of adherence to varenicline among people living with HIV/AIDS. Study participants were recruited from three HIV care centers in New York City and enrolled in a three-arm randomized controlled pilot study in which all subjects received varenicline. At the 1-month study visit, there were no significant differences in adherence by study condition, therefore we combined treatment arms to examine correlates of adherence (n = 127). We used pill counts to assess varenicline adherence, defined as taking at least 80% of the prescribed dose. We conducted a multivariate path analysis to assess factors proposed by the information-motivation-behavioral skills model to predict adherence. Only 56% of smokers were at least 80% adherent to varenicline at 1 month. Adherence-related information, self-efficacy, a college degree, and non-Hispanic white race/ethnicity were associated with increased varenicline adherence. In path analysis, information and motivation were associated with increased adherence self-efficacy, and adherence self-efficacy was associated with increased adherence, but with marginal significance. These associations with adherence were no longer significant after controlling for race/ethnicity and education. Further exploration of the role of a modifiable correlates of adherence, such as adherence-related information, motivation and self-efficacy is warranted. Interventions are needed that can address disparities in these and other psychosocial factors that may mediate poor medication adherence.

Formative Evaluation of a Text Messaging Intervention to Promote Varenicline Adherence Among Tobacco-Dependent Persons with HIV

Few published studies describe processes in the development of mobile health interventions. This study reports data from a formative evaluation of a text messaging intervention being developed to increase adherence to smoking cessation medication (varenicline) among tobacco-dependent persons with HIV/AIDS. Four focus groups were conducted (N = 29) using a mixed-methods approach to assess: (a) beliefs and preferences regarding the use of varenicline, (b) preferences for receiving tobacco-related texts, and (c) the acceptability of draft text messages. Themes that emerged from the focus groups were that (a) participants were cautious and wanted to discuss varenicline carefully with health care providers, (b) participants preferred simple messages that were positive and encouraging, (c) messages should emphasize tobacco cessation and not varenicline adherence, and (d) texts would serve as a reminder about goals and foster support and connectedness with the health care team. Overall, 47 out of the 100 messages received a grade of C or less (rated on a 5-point grade scale: A, B, C, D, or F), the majority of which focused on medication adherence. All participants reported that they were likely to read the messages. The majority (64%) indicated that they preferred receiving 2 or more messages per day. Gathering systematic participant feedback provides critical input in intervention planning.

Association of out-of-pocket pharmacy costs with adherence to varenicline.

Varenicline, a nicotinic acetylcholine receptor partial agonist, is a pharmacotherapy indicated for smoking cessation treatment. To date, no research has examined the relationship between out-of-pocket (OOP) expense and varenicline adherence among Medicare beneficiaries. To (a) characterize medication utilization patterns of varenicline among Medicare members newly initiated on varenicline and (b) examine the relationship between member OOP expense and varenicline medication adherence. In this retrospective cohort study, pharmacy claims data were used to identify Medicare Advantage Prescription Drug Plan (MAPD) members newly initiated on varenicline. Demographic and clinical characteristics, varenicline medication utilization patterns, and pharmacy costs (total and varenicline-specific) were determined for members included in the study. Varenicline adherence was measured by calculating the proportion of days covered (PDC) over a period of 84 days (12 weeks) after initiation. Multiple regression analysis was used to examine the relationship between varenicline OOP cost and varenicline medication utilization, while controlling for sociodemographic characteristics, clinical factors, and nonvarenicline pharmacy costs. A total of 15,452 MAPD members were included in the analysis. Mean (SD) subject age was 62.6 (10.0) years; 21.1% (n = 3,256) were dual eligible; and 33.0% (n = 5,106) received a low-income subsidy. Mean (SD) initial varenicline treatment episode duration was 50.8 (37.8) days, with a mean (SD) varenicline days' supply of 47.8 (32.6) obtained by members during the initial treatment episode. Mean (SD) PDC was 0.51 (0.24), and 14.9% (n = 2,302) of members were classified as adherent to treatment (PDC ≥ 0.80). Greater varenicline OOP expense was significantly associated with lower PDC (regression coefficient = -0.058, P less than 0.001) and significantly associated with lower odds of receiving a refill for varenicline (odds ratio 0.594, 95% CI: 0.540-0.655, P less than 0.001). Among Medicare beneficiaries newly initiated on varenicline, medication adherence was suboptimal, and greater OOP cost was associated with lower adherence and lower odds of refilling varenicline.