Effect of variations in treatment regimen and liver cirrhosis on exposure to benzodiazepines during treatment of alcohol withdrawal syndrome

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Abstract

Purpose: Benzodiazepines (BDZs) are the drugs of choice to prevent the symptoms of alcohol withdrawal syndrome (AWS). Various treatment protocols are published and have been shown to be effective in both office-managed and facility-managed treatment of AWS. The aim of this scientific commentary is to demonstrate the differences in the expected exposure to BDZs during AWS treatment using different treatment regimens available in the literature, in patients with or without alcoholic liver cirrhosis.

Methods: Diazepam and lorazepam AWS protocols were examined and reviewed in the literature, and blood plasma levels were examined and compared, respectively.

Results: Considerable variation in the blood levels with the different dosing schedules was found. Because the drugs are metabolized differently, we have also shown that liver disease affects the blood levels of diazepam, but not of lorazepam.

Conclusions: Differences in treatment regimens, the choice of BDZ, as well as the presence of liver cirrhosis can substantially alter the exposure of patients to drugs used for AWS treatment. Outpatient treatment of AWS has been shown to be relatively safe and effective for the treatment of AWS but patients should be carefully monitored.

Keywords: benzodiazepines, alcohol withdrawal, cirrhosis, pharmacokinetics, clearance, area under curve, metabolism, outpatients.

Abbreviations: AUC, area under the curve; AWS, alcohol withdrawal syndrome; BCMA, British Columbia Medical Association; BDZ, benzodiazepine.

Citation: Gershkovich P, Wasan KM, Ribeyre C, Ibrahim F, McNeill JH. Effect of variations in treatment regimen and liver cirrhosis on exposure to benzodiazepines during treatment of alcohol withdrawal syndrome. Drugs in Context 2015; 4: 212287. DOI: 10.7573/dic.212287

Contributions: PG performed and analyzed the pharmacokinetic modeling and contributed to writing of the first draft of the manuscript. KMW participated in data analysis and the writing of the manuscript. CR participated in modeling and data analysis. FI performed the pharmacokinetic modeling. JHM coordinated and supervised the project and contributed to writing of the first draft of the manuscript.

Potential conflicts of interest: The International Committee of Medical Journal Editors’ (ICMJE) Potential Conflicts of Interests forms for the authors are available for download at: https://www.drugsincontext.com/wp-content/uploads/2015/08/dic.212287-COI.pdf. The authors declare no conflict of interest.

Funding declaration: No dedicated funding has been obtained for this project.

Copyright: Copyright © 2015 Gershkovich P, Wasan KM, Ribeyre C, Ibrahim F, McNeill JH. Distributed under the terms of the Creative Commons License Deed CC BY 3.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below.

Correct attribution: Copyright © 2015 Gershkovich P, Wasan KM, Ribeyre C, Ibrahim F, McNeill JH. http://dx.doi.org/10.7573/dic.212287. Published by Drugs in Context under Creative Commons License Deed CC BY 3.0.

Article URL: https://www.drugsincontext.com/effect-of-variations-in-treatment-regimen-and-liver-cirrhosis-on-exposure-to-benzodiazepines-during-treatment-of-alcohol-withdrawal-syndrome/

Correspondence: John H McNeill, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada. jmcneill@mail.ubc.ca

Provenance: Submitted; externally peer reviewed

Submitted: 17 July 2015; Peer review comments to author: 21 July 2015; Published: 7 August 2015

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