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. 2016 Oct 12;6(10):e012991.
doi: 10.1136/bmjopen-2016-012991.

Evaluating the safety and dosing of drugs in patients with liver cirrhosis by literature review and expert opinion

Rianne A Weersink  1 , Margriet Bouma  2 , David M Burger  3 , Joost P H Drenth  4 , Nicole G M Hunfeld  5 , Minke Kranenborg  6 , Margje H Monster-Simons  7 , Sandra A W van Putten  8 , Herold J Metselaar  9 , Katja Taxis  10 , Sander D Borgsteede  11
Affiliations

Evaluating the safety and dosing of drugs in patients with liver cirrhosis by literature review and expert opinion

Rianne A Weersink et al. BMJ Open. .

Abstract

Introduction: Liver cirrhosis can have a major impact on drug pharmacokinetics and pharmacodynamics. Patients with cirrhosis often suffer from potentially preventable adverse drug reactions. Guidelines on safe prescribing for these patients are lacking. The aim of this study is to develop a systematic method for evaluating the safety and optimal dosage of drugs in patients with liver cirrhosis.

Methods and analysis: For each drug, a six-step evaluation process will be followed. (1) Available evidence on the pharmacokinetics and safety of a drug in patients with liver cirrhosis will be collected from the Summary of Product Characteristics (SmPC) and a systematic literature review will be performed. (2) Data regarding two outcomes, namely pharmacokinetics and safety, will be extracted and presented in a standardised assessment report. (3) A safety classification and dosage suggestion will be proposed for each drug. (4) An expert panel will discuss the validity and clinical relevance of this suggested advice. (5) Advices will be implemented in all relevant Clinical Decision Support Systems in the Netherlands and published on a website for patients and healthcare professionals. (6) The continuity of the advices will be guaranteed by a yearly check of new literature and comments on the advices. This protocol will be applied in the evaluation of a selection of drugs: (A) drugs used to treat (complications of) liver cirrhosis, and (B) drugs frequently prescribed to the general population.

Ethics and dissemination: Since this study does not directly involve human participants, it does not require ethical clearance. Besides implementation on a website and in clinical decision support systems, we aim to publish the generated advices of one or two drug classes in a peer-reviewed journal and at conference meetings.

Keywords: drug safety; expert opinion; literature review; liver cirrhosis; practice guideline.

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Conflict of interest statement

DB has received research grants from BMS, MSD and ViiV and has performed teaching for Abbvie, BMS, Gilead, MSD and ViiV, outside the submitted work. JD has received research grants from Abbvie and Janssen and has been a member of advisory boards of AbbVie, BMS, Gilead, Janssen, and Merck, outside the submitted work. HM has received research grants from AbbVie, Astellas, Novartis and Gilead and has been a member of advisory boards of AbbVie, Astellas and Novartis, outside the submitted work.

Figures

Figure 1
Figure 1
Flow chart of the six-step process used per drug for evaluating the safety and optimal dosage in liver cirrhosis.
See this image and copyright information in PMC

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