title: Evaluating the safety and dosing of drugs in patients with liver cirrhosis by literature review and expert opinion.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Health Base Foundation, Houten, The Netherlands Department of Pharmacy, Unit of Pharmacotherapy, -Epidemiology & -Economics, University of Groningen, Groningen, The Netherlands.
authors.forename: Rianne A
authors.initials: RA
authors.lastname: Weersink
authors.affiliation: Department of Guideline Development, Dutch College of General Practice, Utrecht, The Netherlands.
authors.forename: Margriet
authors.initials: M
authors.lastname: Bouma
authors.affiliation: Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
authors.affiliation: Department of Gastroenterology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Joost P H
authors.initials: JP
authors.lastname: Drenth
authors.affiliation: Department of Pharmacy and Department of Intensive Care, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Nicole G M
authors.initials: NG
authors.lastname: Hunfeld
authors.affiliation: Centre for Information on Medicines, Royal Dutch Pharmacists Association (KNMP), The Hague, The Netherlands.
authors.forename: Minke
authors.initials: M
authors.lastname: Kranenborg
authors.affiliation: Dutch Medicines Evaluation Board, Utrecht, The Netherlands.
authors.forename: Margje H
authors.initials: MH
authors.lastname: Monster-Simons
authors.affiliation: De Brug Pharmacy, Almere, The Netherlands.
authors.forename: Sandra A W
authors.initials: SA
authors.lastname: van Putten
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Herold J
authors.initials: HJ
authors.lastname: Metselaar
authors.affiliation: Department of Pharmacy, Unit of Pharmacotherapy, -Epidemiology & -Economics, University of Groningen, Groningen, The Netherlands.
authors.forename: Katja
authors.initials: K
authors.lastname: Taxis
authors.affiliation: Health Base Foundation, Houten, The Netherlands SIR Institute for Pharmacy Practice and Policy, Leiden, The Netherlands.
authors.forename: Sander D
authors.initials: SD
authors.lastname: Borgsteede
mesh_terms: D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D004347:Drug Interactions; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy*; D009426:Netherlands / Q000453:epidemiology; D061214:Patient Safety; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D017410:Practice Guidelines as Topic; D055553:Prescription Drugs / Q000008:administration & dosage*
chemical_list: D004364:Pharmaceutical Preparations; D055553:Prescription Drugs
keywords: drug safety; expert opinion; literature review; liver cirrhosis; practice guideline