Evidence-Based Recommendations to Improve the Safe Use of Drugs in Patients with Liver Cirrhosis.

INTRODUCTION: The presence of liver cirrhosis can have a major impact on pharmacodynamics and pharmacokinetics, but guidance for prescribing is lacking.

OBJECTIVE: The aim of this study is to provide an overview of evidence-based recommendations developed for the safe use of drugs in liver cirrhosis.

METHODS: Recommendations were based on a systematic literature search combined with expert opinion from a panel of 10 experts. The safety of each drug was classified as safe, no additional risks known, additional risks known, unsafe, unknown or the safety class was dependent on the severity of liver cirrhosis (Child-Pugh classification). If applicable, drug-specific dosing advice was provided. All recommendations were implemented in clinical decision support systems and on a website.

RESULTS: We formulated 218 recommendations for a total of 209 drugs. For nine drugs, two recommendations were formulated for different administration routes or indications. Drugs were classified as 'safe' in 29 recommendations (13.3%), 'no additional risks known' in 60 (27.5%), 'additional risks known' in 3 (1.4%), and 'unsafe' in 30 (13.8%). In 57 (26.1%) of the recommendations, safety depended on the severity of liver cirrhosis and was 'unknown' in 39 (17.9%) recommendations. Large alterations in pharmacodynamics were the main reason for classifying a drug as 'unsafe'. For 67 drugs (31%), a dose adjustment was needed.

CONCLUSIONS: Over 200 recommendations were developed for the safe use of drugs in patients with liver cirrhosis. Implementing these recommendations into clinical practice can possibly enhance medication safety in this vulnerable patient group.