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.
- liver cirrhosis
- drug safety
- practice guideline
- expert opinion
- literature review
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Acknowledgements The authors thank Corine Colijn, Jan-Kees Huyts, Peter Mol, José Willemse, Froukje Harkes-Idzinga and Marleen Journée-Gillissen for their contribution towards study funding.
Contributors RW and SB wrote and drafted the protocol. MB, JD, NH, HM and SB contributed to the application for study funding. All authors contributed to the development of the study protocol and read and approved the final manuscript.
Funding This work was supported by ZonMw GGG-STIP grant number 836044009. ZonMw is the Dutch national organisation for health research and healthcare innovation. ZonMw's main commissioning organisations are the Ministry of Health, Welfare and Sport and the Netherlands Organisation for Scientific Research. ZonMw did not influence the content of the guideline.
Competing interests 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.
Provenance and peer review Not commissioned; externally peer reviewed.