Increasing the Dose of Varenicline in Patients Who Do Not Respond to the Standard Dose

Jiménez-Ruíz, Carlos A.; Peña, S.M.; Cicero, Ana; Mayayo, M. Paz Marco; Cristóbal, Maribel; Perera, Lidia

doi:10.1016/j.mayocp.2013.08.015

Cited by 16 publications

(19 citation statements)

References 2 publications

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“…Similarly, no new adverse effects other than nausea were observed in a cohort of smokers who received a varenicline tartrate dosage of 3 mg/d. 9 A case report describes a teenager who ingested thirty 0.5-mg tablets of varenicline tartrate. 10 Apart from vomiting, she experienced no other symptoms, and her physical examination after ingestion was unremarkable.…”

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confidence: 99%

Increasing Varenicline Dose in Smokers Who Do Not Respond to the Standard Dosage

et al. 2015

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confidence: 99%

Increasing Varenicline Dose in Smokers Who Do Not Respond to the Standard Dosage

et al. 2015

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“…Despite the weak proportion of variability in the varenicline concentrations separately explained by BW (14%) or UGT2B7 rs7439366 polymorphism (9%), Figure 2 highlighted a 4-times variation in varenicline exposure between the two extreme groups of BW and UGT2B7 rs7439366 polymorphism already proposed for nonresponders to the standard dose in a clinical experience [52]. We acknowledge that in the present study the effect of UGT2B7 rs7439366 polymorphism observed on varenicline concentrations is more important than expected based on the data published by Obach et al [4].…”

Section: Discussionmentioning

confidence: 91%

Influence of body weight and UGT2B7 polymorphism on varenicline exposure in a cohort of smokers from the general population

Glatard

Guidi

Dobrinas

et al. 2019

Eur J Clin Pharmacol

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The abstinence rate to tobacco after varenicline treatment is moderate and might be partially affected by variability in varenicline concentrations. This study aimed at characterizing the sources of variability in varenicline pharmacokinetics and to relate varenicline exposure to abstinence. Methods: The population pharmacokinetic analysis (NONMEM®) included 121 varenicline concentrations from 82 individuals and tested the influence of genetic and non-genetic characteristics on apparent clearance (CL/F) and volume of distribution (V/F). Model-based average concentrations over 24 h (Cav) were used to test the impact of varenicline exposure on the input rate (Kin) expressed as a function of the number of cigarettes per day in a turnover model of 373 expired carbon monoxide levels. Results: A one-compartment model with first order absorption and elimination appropriately described varenicline concentrations. CL/F was 8.5 L/h (coefficient of variation, 26%), V/F was 228 L and the absorption rate (ka) was fixed to 0.98 h-1. CL/F increased by 46% in 100-kg individuals compared to 60kg individuals and was found to be 21% higher in UGT2B7 rs7439366 TT individuals. These covariates explained 14% and 9% of the inter-individual variability in CL/F, respectively. No influence of varenicline Cav was found on Kin in addition to the number of cigarettes. Conclusions: Body weight mostly and to a smaller extent genetic polymorphisms of UGT2B7 can influence varenicline exposure. Dose adjustment based on body weight and, if available, on UGT2B7 genotype might be useful to improve clinical efficacy and tolerability of varenicline.

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“…9 These studies have reassured patients and providers regarding the safety profile of varenicline and have encouraged researchers to explore novel ways of maximizing its effectiveness, including combining it with other medications 10 or using it in higher doses. 11 …”

Section: Introductionmentioning

confidence: 99%

“…The first was a retrospective case series study that showed increasing varenicline from 2 mg/day to 3 mg/day resulted in a 50% increase in abstinence rate among 52 smokers who were “favorable responders” but had not quit after 8 weeks of 2 mg/day varenicline. 11 The second study was a randomized placebo-controlled trial involving 200 smokers initially treated for 2 weeks with 2 mg/day of varenicline, who were “nonresponders” as they did not quit and did not reduce smoking by half or more at 2 weeks. They were then randomized to varenicline 3 mg/day or varenicline 2 mg plus a placebo pill as a control.…”

Section: Introductionmentioning

confidence: 99%

Improvement of Smoking Abstinence Rates With Increased Varenicline Dosage

Karam‐Hage¹,

Kypriotakis²,

Robinson³

et al. 2018

J Clin Psychopharmacol

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Purpose/Background It is unclear whether increasing the dose of varenicline beyond the standard dose of 2 mg/day would improve smoking abstinence. Methods/Procedures We examined the effect of 3 mg/day of varenicline on smoking abstinence among smokers who had reduced their smoking by 50% or more in response to 2 mg/day for at least 6 weeks but had not quit smoking. Of 2833 patients treated with varenicline, a subset of 73 smokers were increased to 3 mg/day after 6 weeks. We used a propensity score analysis involving multiple baseline covariates to create a comparative sample of 356 smokers who remained on 2 mg/day. All smokers received concurrent and similar smoking-cessation counseling. Findings/Results At 3 months, we found higher 7-day PPA rate in the 3-mg group (26%) than in the 2-mg group (11.5%; χ2=10.60; p<0.001; Risk Ratio (RR)= 2.3 [95% confidence interval, 1.4–3.6]). The difference in abstinence rates remained significant at the 6 months (p<0.001; RR= 2.6 [95% confidence interval, 1.6–3.9]) and 9 months follow-up (p<0.001; RR= 2.2 [95% confidence interval, 1.4–3.3]). Implications/Conclusions We conclude that a relatively small increase in the daily dose of varenicline seems to offer a benefit for those who are not able to achieve total abstinence after ~6 weeks of 2 mg/day.

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Increasing the Dose of Varenicline in Patients Who Do Not Respond to the Standard Dose

Cited by 16 publications

References 2 publications

Increasing Varenicline Dose in Smokers Who Do Not Respond to the Standard Dosage

Increasing Varenicline Dose in Smokers Who Do Not Respond to the Standard Dosage

Influence of body weight and UGT2B7 polymorphism on varenicline exposure in a cohort of smokers from the general population

Improvement of Smoking Abstinence Rates With Increased Varenicline Dosage

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