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Journal of Pharmacy Practice Dec 2023To examine the literature pertaining to safety and efficacy of intranasal (IN) varenicline for the treatment of dry eye disease (DED). A literature search of PubMed... (Review)
Review
To examine the literature pertaining to safety and efficacy of intranasal (IN) varenicline for the treatment of dry eye disease (DED). A literature search of PubMed was performed (1985 to January 2022) using the following search terms: varenicline, OC-01, intranasal, and dry eye. Additional data were acquired from references of identified articles, prescribing information, government databases, and manufacturer website. All relevant English-language studies were included in this review. IN varenicline was FDA approved for the treatment of DED in 2021. IN varenicline has demonstrated a statistically significant improvement in outcomes related to basal tear film production as measured by a Schirmer test score (STS) in data from phase 2 and 3 clinical trials. Safety data from these trials have demonstrated that IN varenicline is generally well tolerated with minimal ocular side effects. The most common side effects reported in the trials were sneezing, coughing, along with throat and nasal irritation. Patients suffering from DED have been traditionally treated with ophthalmic preparations; however, many patients struggle with proper administration of ophthalmic products. IN varenicline stimulates nicotinic cholinergic receptors and basal tear film production through the trigeminal parasympathetic nerve pathway (TPP). There is no evidence to support the long-term remission of DED symptoms with IN varenicline as seen with anti-inflammatory modulators. IN varenicline offers an effective and novel approach to management of DED for patients who desire a non-ophthalmic preparation with a favorable side effect profile.
Topics: Humans; Varenicline; Dry Eye Syndromes; Tears
PubMed: 35703427
DOI: 10.1177/08971900221108725 -
Journal of Comparative Effectiveness... Jun 2023Herein, we report safety outcomes for varenicline solution nasal spray (VNS) within the context of clinical trial discontinuation, contrasting those with... (Randomized Controlled Trial)
Randomized Controlled Trial
Herein, we report safety outcomes for varenicline solution nasal spray (VNS) within the context of clinical trial discontinuation, contrasting those with discontinuation outcomes from topical cyclosporine and lifitegrast clinical trials. 1061 subjects were randomized across three clinical trials to receive either VNS 0.06 mg, VNS 0.03 mg, VNS 0.006 mg or vehicle control. Subjects who discontinued from treatment were noted and assigned to their appropriate categories. Despite treatment emergent adverse events, 93.5% of subjects receiving VNS completed the treatment period. By comparison, only 80% of subjects in the integrated clinical trials for cyclosporine ophthalmic emulsion and 91% of subjects in the integrated trials for lifitegrast ophthalmic solution completed the full treatment period, respectively. In clinical trials, VNS demonstrated improvements in dry eye disease signs and symptoms, was well-tolerated, and had an overall completion rate >93%. Conventional dry eye treatments (e.g., cyclosporine and lifitegrast) noted considerably higher discontinuation rates in their clinical trials.
Topics: Humans; Nasal Sprays; Varenicline; Ophthalmic Solutions; Dry Eye Syndromes; Cyclosporine; Treatment Outcome
PubMed: 37096956
DOI: 10.57264/cer-2022-0215 -
The American Journal of Psychiatry Sep 2021Pharmacological treatments that can concomitantly address cigarette smoking and heavy drinking stand to improve health care delivery for these highly prevalent... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Pharmacological treatments that can concomitantly address cigarette smoking and heavy drinking stand to improve health care delivery for these highly prevalent co-occurring conditions. This superiority trial compared the combination of varenicline and naltrexone against varenicline alone for smoking cessation and drinking reduction among heavy-drinking smokers.
METHODS
This was a phase 2 randomized double-blind clinical trial. Participants (N=165) who were daily smokers and drank heavily received either 2 mg/day of varenicline plus 50 mg/day of naltrexone or 2 mg/day of varenicline plus matched placebo pills for 12 weeks. Primary outcomes were 7-day point prevalence of nicotine abstinence (bioverified by a breath CO reading ≤5 ppm) at the 26-week follow-up and number of drinks per drinking day during the 12-week treatment phase.
RESULTS
Smoking abstinence at week 26 was significantly higher in the varenicline plus placebo condition than in the varenicline plus naltrexone condition (N=37 [45.1%] compared with N=22 [26.5%]). For drinks per drinking day, there was a medication effect favoring the combination of varenicline and naltrexone over varenicline alone across the 12-week treatment phase, although it did not meet the significance threshold.
CONCLUSIONS
These findings suggest that smoking cessation and drinking reduction can be concomitantly targeted with pharmacotherapy and that while varenicline alone may be sufficient as a smoking cessation aid in heavy-drinking smokers, the combination of varenicline and naltrexone may confer benefits with regard to drinking outcomes, particularly during the 12-week period of active medication treatment.
Topics: Adult; Alcohol Deterrents; Alcohol Drinking; Cholinergic Agonists; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Naltrexone; Narcotic Antagonists; Smoking Cessation; Smoking Cessation Agents; Varenicline
PubMed: 34080890
DOI: 10.1176/appi.ajp.2020.20070993 -
CPT: Pharmacometrics & Systems... Jul 2021Varenicline is an approved smoking cessation aid in adults. Population pharmacokinetics (popPK) and exposure-response (ER) (continuous abstinence rates [CAR] weeks 9-12...
Varenicline is an approved smoking cessation aid in adults. Population pharmacokinetics (popPK) and exposure-response (ER) (continuous abstinence rates [CAR] weeks 9-12 and nausea/vomiting incidence) for varenicline in adolescent smokers were characterized using data from two phase 1 and one phase 4 studies. A one-compartment popPK model with first-order absorption and elimination adequately fitted the observed data. The effect of female sex on apparent clearance was significant. Apparent volume of distribution increased with body weight and decreased by 24%, 15%, and 14% for black race, "other" race, and female sex, respectively. The observed range of exposure in the phase 4 study was consistent with that expected for each dose and body-weight group from the results obtained in adolescent PK studies, supporting that varenicline dose and administration were appropriate in the study. The relationship between CAR9-12 and varenicline area under the concentration-time curve (AUC) from 0 to 24 hours (AUC ) was nonsignificant (p = 0.303). Nausea/vomiting incidence increased with AUC (p < 0.001) and was higher in females. Varenicline PK and ER for tolerability in adolescent smokers were comparable with adults, while ER for efficacy confirmed the negative results reported in the phase 4 study.
Topics: Adolescent; Area Under Curve; Child; Clinical Trials, Phase I as Topic; Clinical Trials, Phase IV as Topic; Humans; Models, Biological; Racial Groups; Randomized Controlled Trials as Topic; Sex Factors; Smokers; Smoking Cessation Agents; Tissue Distribution; Varenicline; Young Adult
PubMed: 34062053
DOI: 10.1002/psp4.12645 -
Pharmacotherapy Feb 2018Tobacco use disorder is a chronic illness. With its high comorbidity rate, it is a major cause of years of life lost or years lived with disability; however, it is also... (Review)
Review
Tobacco use disorder is a chronic illness. With its high comorbidity rate, it is a major cause of years of life lost or years lived with disability; however, it is also considered the most preventable cause of death in developed countries. Since the development of nicotine replacement therapy (NRT) in 1978, treatment options have continued to evolve and expand. Despite this, currently available treatments remain insufficient, with less than 25% of smokers remaining abstinent 1 year after treatment. In this article, we review existing and emerging smoking cessation pharmacotherapies, with a special emphasis on the most promising agents that are currently being investigated. A search of the Cochrane Database of Systematic Reviews and the PubMed, Ovid, and ClinicalTrials.gov databases (August 2 to September 1, 2017) was undertaken for articles on smoking cessation pharmacotherapies, applying no language restrictions. More than 40 pharmacotherapies were reviewed including conventional pharmacotherapies-NRT, bupropion, and varenicline (all approved by the U.S. Food and Drug Administration as first-line treatment of smoking cessation)-and novel therapies: cytisine, N-acetylcysteine, cycloserine, memantine, baclofen, topiramate, galantamine, and bromocriptine. Studies of combination NRT and varenicline showed the greatest smoking cessation rates. Clonidine and nortriptyline are second-line treatments used when first-line treatments fail or are contraindicated, or by patient preference. Some novel therapies, especially acetylcholinesterase inhibitors, cytisine, and N-acetylcysteine, display promising results. Because the results of randomized clinical trials were reported using varied end points and outcome measures, direct comparisons between different pharmacotherapies cannot easily be evaluated. Additional high-quality randomized double-blind placebo-controlled trials with long-term follow-up, using validated sustained abstinence measures, are needed to find more effective smoking cessation aids.
Topics: Antidepressive Agents; Humans; Smoking Cessation; Tobacco Smoking; Tobacco Use Cessation Devices; Varenicline
PubMed: 29250815
DOI: 10.1002/phar.2073 -
Nicotine & Tobacco Research : Official... Jan 2016Conduct a systematic review and meta-analysis on the effectiveness and safety of varenicline in smokeless tobacco (SLT) cessation. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Conduct a systematic review and meta-analysis on the effectiveness and safety of varenicline in smokeless tobacco (SLT) cessation.
METHODS
PubMed, EMBASE, clinicaltrials.gov, and the Cochrane Registry were searched up to February 1, 2014, for randomized clinical trials (RCTs) comparing varenicline to placebo. Random effects Mantel-Haenszel summary relative risks (RRs), risk difference (RD), and 95% CIs were used for analysis and reporting of outcomes. Primary and secondary outcomes were the 7-day point prevalence of SLT abstinence at the end of 12 and 26 weeks, respectively. Adverse events reported include nausea, sleep disturbance, and mood disorders.
RESULTS
Three published RCTs involving 744 SLT users with a mean age of 39.7 years, of which greater than 88% were males, were randomized to varenicline (n = 370) and placebo (n = 374). Subjects in the varenicline arm had a significantly higher 7-day point prevalence of SLT abstinence at 12 weeks (48% vs. 33%; RR = 1.45, 95% CI = 1.22-1.72, p < .0001, I2 = 0%; RD = 13%, 95% CI = 4%-23%, p = .008) but not at 26 weeks (49% vs. 39%; RR = 1.38, 95% CI = 0.93-2.03, p = .11, I2 = 51%). There were no statistically significant differences in the incidences of adverse events between the 2 arms but interpretation is limited by high heterogeneity.
CONCLUSION
This pooled analysis suggests that varenicline is effective in achieving a 7-day point prevalence of SLT abstinence at 12 weeks but showed that this effect was not sustained at 26 weeks.
Topics: Humans; Nicotinic Agonists; Product Surveillance, Postmarketing; Suicide; Tobacco Use Cessation; Varenicline
PubMed: 25646351
DOI: 10.1093/ntr/ntv010 -
BMC Ophthalmology Jul 2023Dry eye disease (DED) is caused by a persistently unstable tear film leading to ocular discomfort and is treated mainly with tear supplementation. There is emerging... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dry eye disease (DED) is caused by a persistently unstable tear film leading to ocular discomfort and is treated mainly with tear supplementation. There is emerging evidence that nicotinic acetylcholine receptor (nAChR) agonists (e.g., varenicline and simpinicline) nasal sprays are effective for DED. Our systematic review and meta-analysis assessed the efficacy and safety of varenicline nasal spray (VNS) for DED treatment.
METHODS
The Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched. Only randomized controlled trials (RCTs) that evaluated the efficacy of VNS versus placebo were included. The efficacy endpoint was the mean change in the anesthetized Schirmer test score (STS), a measure of basal tear production, from baseline. The safety endpoints were serious adverse events (SAEs) and adverse events (AEs). The standardized mean difference (SMD) was used for continuous outcomes, while the risk ratio (RR) was used to demonstrate dichotomous variables. The certainty of the evidence was rated utilizing the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The risk of bias assessment was conducted using the Revised Cochrane risk of bias tool for randomized trials.
RESULTS
Three RCTs (n = 1063) met the eligibility criteria. All RCTs had a low risk of bias. The meta-analysis found a statistically significant increase in the mean STS change from baseline on day 28. The pooled analysis found no significant difference between VNS and placebo in the frequency of SAEs and ocular AEs. However, VNS had a significant effect on developing nasal cavity-related AEs.
CONCLUSION
VNS caused a highly significant improvement regarding the efficacy endpoint but caused an increased frequency of some nasal cavity-related AEs (i.e., cough and throat irritation). However, it caused neither SAEs nor ocular AEs. Included studies had a low risk of bias.
Topics: Humans; Nasal Sprays; Varenicline; Dry Eye Syndromes
PubMed: 37452334
DOI: 10.1186/s12886-023-03069-y -
Current Medical Research and Opinion May 2020Varenicline, a selective partial agonist of the α4β2 nicotinic acetylcholine receptor, is a smoking cessation pharmacotherapy that more than doubles the chance of... (Review)
Review
Varenicline, a selective partial agonist of the α4β2 nicotinic acetylcholine receptor, is a smoking cessation pharmacotherapy that more than doubles the chance of quitting smoking at 6 months compared with placebo. This article reviews salient knowledge of the discovery, pharmacological characteristics, and the efficacy and safety of varenicline in general and in specific populations of smokers and provides recommendations to support use in clinical practice.: Literature searches for varenicline were conducted using PubMed, with date limitations of 2000-2018 inclusive, using search terms covering the discovery, mechanism of action, pharmacokinetics, efficacy and safety in different populations of smokers, alternative quit approaches and combination therapy. Selection of safety and efficacy data was limited to clinical trials, meta-analyses and observational studies. Standard administration of varenicline is efficacious in helping smokers to quit, including smokers with cardiovascular disease and chronic obstructive pulmonary disease. Furthermore, varenicline efficacy may be improved with pre-loading, a gradual quitting approach for smokers unwilling or unable to quit abruptly, and extended treatment in smokers who have recently quit to help maintain abstinence. Initial concerns regarding the association of varenicline with increased risk of neuropsychiatric and cardiovascular adverse events have been disproven after extensive clinical evaluations, and the benefit-risk profile of varenicline is considered favorable. Varenicline is efficacious and safe for all adult smokers with a range of clinical characteristics. Evidence suggests that approaches offering greater flexibility in timing and duration of treatment may further extend treatment efficacy and clinical reach.
Topics: Female; Humans; Male; Nicotinic Agonists; Randomized Controlled Trials as Topic; Receptors, Nicotinic; Smoking Cessation Agents; Varenicline
PubMed: 32050807
DOI: 10.1080/03007995.2020.1729708 -
Varenicline for smoking cessation in people with schizophrenia: systematic review and meta-analysis.European Archives of Psychiatry and... Apr 2015We performed an updated meta-analysis of randomized double-blind placebo-controlled trials (RCTs) on the effects of varenicline adjuvant therapy for smoking cessation in... (Meta-Analysis)
Meta-Analysis Review
We performed an updated meta-analysis of randomized double-blind placebo-controlled trials (RCTs) on the effects of varenicline adjuvant therapy for smoking cessation in people with schizophrenia, on the basis of a previous meta-analysis (Tsoi in Cochrane Database Syst Rev 2:CD007253, 2013). We searched PubMed, the Cochrane Library databases, and PsycINFO up to August 1, 2014. RCTs comparing varenicline adjuvant therapy with placebo in schizophrenia were included. The risk ratio (RR), number needed to harm (NNH), and standardized mean differences with its 95% confidence interval (CI) were used. Seven studies (total n = 439), including 6 with only schizophrenia (total n = 352), 1 with both schizophrenia (n = 77) and bipolar disorder (n = 10), were included. Varenicline was not superior to placebo in smoking cessation (RR = 0.79, 95% CI 0.58-1.08, p = 0.14, 5 RCTs, n = 322). Varenicline failed to show its superiority to placebo for overall, positive, negative, and depressive symptoms. Moreover, there was no significant difference in the discontinuation rate due to all causes, clinical deterioration, or side effects between varenicline and placebo. Although varenicline caused less abnormal dreams/nightmares than placebo (RR = 0.47, 95% CI 0.22-0.99, p = 0.05, NNH = not significant, 4 RCTs, n = 288), it caused more nausea (RR = 1.79, 95% CI 1.20-2.67, p = 0.004, NNH = 6, p = 0.004, 6 RCTs, n = 417). We detected no significant difference in suicidal ideation and depression between varenicline and placebo. Our results suggest that although varenicline adjuvant therapy is well tolerated, varenicline is not superior to placebo for smoking cessation in people with schizophrenia. Because of the limited sample sizes of the available studies, future studies will require larger samples to ensure that these findings are generalizable.
Topics: Humans; Nicotinic Agonists; Schizophrenia; Smoking; Smoking Cessation; Varenicline
PubMed: 25283510
DOI: 10.1007/s00406-014-0551-3 -
Prescrire International Dec 2015Smoking markedly increases the risk of cardiovascular disease. Nicotine replacement therapy is available to assist in smoking cessation. To assess the cardiac adverse... (Meta-Analysis)
Meta-Analysis Review
Smoking markedly increases the risk of cardiovascular disease. Nicotine replacement therapy is available to assist in smoking cessation. To assess the cardiac adverse effects of nicotine replacement therapy, we conducted a review of the literature using the standard Prescrire methodology. A meta-analysis of 21 randomised, placebo-controlled trials published in early 2014 included a total of 11 647 patients, including 828 patients at high risk of cardiovascular events and 187 patients with acute coronary disorders. It showed that nicotine replacement therapy was associated with an increased risk of cardiac disorders, particularly palpitations, which are a known adverse effect of smoking. Among patients at high cardiovascular risk, 1.2% experienced a serious cardiovascular event, with no statistically significant difference versus placebo. Bupropion and varenicline both have serious adverse effects and have been less extensively evaluated in patients at high cardiovascular risk. In practice, when a drug is needed to assist in smoking cessation, nicotine appears to be a reasonable choice. Nicotine replacement therapy exposes patients to a risk of palpitations but rarely to serious cardiac disorders, even in individuals with a cardiovascular history. In addition, these adverse effects are better documented than those of bupropion and varenidine in such patients. Nonetheless, the cardiac effects of nicotine call for prudent use of nicotine replacement therapy: the minimum effective dose should be sought, and the goal should be total nicotine withdrawal.
Topics: Bupropion; Cardiovascular Diseases; Humans; Tobacco Use Cessation Devices; Varenicline
PubMed: 26788573
DOI: No ID Found