Background and Objectives The presence of liver cirrhosis affects the selection and dosing of drugs metabolised by the liver as doses have to be adjusted to the remaining liver function. This is a major challenge in clinical practice as specific guidelines are lacking. The aim of this study was to identify drugs for which recommendations on selection and dose adjustments for patients with cirrhosis exist by assessing the literature according to certain quality standards, paying particular attention to the suitability of these recommendations for clinical practice. Methods A systematic literature review included peer-reviewed publications that were published by October 2020 in PubMed in the English language and aimed to generate recommendations on dose adjustment in patients with liver cirrhosis. Subsequently, the identified publications were checked for reporting quality against the relevant reporting guidelines and the Oxford Centre for Evidence-Based Medicine Levels of Evidence. Finally, all specific dose recommendations were extracted, compared with the specifications of the Summaries of Product Characteristics and mapped according to the Anatomical Therapeutic Chemical/Defined Daily Dose Index. Results Eighteen publications covering a total of 1145 dose recommendations for 481 active substances were identified. There were 706 recommendations for 316 substances sufficiently specific for application in clinical practice. For 22 active substances, the specific recommendations were consistent across multiple publications, of which only six were also consistent with the respective Summaries of Product Characteristics. Conclusions As the majority of dose recommendations were not sufficiently specific or even contradictory, there is an urgent need for the definition of standard parameters for a uniform assessment of drugs in liver cirrhosis. In addition, dose recommendations should be aligned by suitable methods.

(1) Adverse drug events (ADEs) are a common cause of emergency department visits and occur frequently during hospitalisation. Instruments that facilitate the detection of the most relevant ADEs could lead to a more targeted and efficient use of limited resources in research and practice. (2) We conducted two consensus processes based on the RAND/UCLA appropriateness method, in order to prioritise ADEs leading to hospital admission (panel 1) and occurring during hospital stay (panel 2) for inclusion in future ADE measurement instruments. In each panel, the experts were asked to assess the “overall importance” of each ADE on a four-point Likert scale (1 = not important to 4 = very important). ADEs with a median rating of ≥3 without disagreement were defined as “prioritised“. (3) The 13 experts in panel 1 prioritised 38 out of 65 ADEs, while the 12 experts in panel 2 prioritised 34 out of 63 ADEs. The highest rated events were acute kidney injury and hypoglycaemia (both panels), as well as Stevens–Johnson syndrome in panel 1 and rhabdomyolysis in panel 2. (4) The survey led to a set of ADEs for which there was consensus that they were of particular importance as presentations of acute medication-related harm, thereby providing a focus for further medication safety research and clinical practice.

Background and Objectives Liver cirrhosis profoundly alters pharmacokinetics and is frequently associated with medication-related problems. Stage-specific dosing guidance remains inconsistent, and prescribing information often lacks clarity. As a result, treatment decisions rely on individual clinical judgement and may differ between professional groups. This study assessed drug-selection and dose-adjustment practices among hepatologists, clinical pharmacologists, and clinical pharmacists, quantified consensus across Child-Pugh stages, and evaluated alignment with prescribing information as a basis for harmonised dosing guidance. Methods Twelve experts from hepatology, clinical pharmacology, and clinical pharmacy evaluated prioritised drugs for patients with liver cirrhosis across Child-Pugh stages A–C in a structured survey. For each drug, experts indicated whether they would apply no dose adjustment, modify the dose, or avoid administration. Consensus was defined as at least 75% agreement, and interrater agreement was assessed by pairwise percentage agreement. Consensus recommendations were compared with the dosing information provided in each drug’s Summary of Product Characteristics. Results Consensus or strong consensus was achieved for only 20% of 177 recommendations, mainly for no dose adjustment or avoidance. Agreement decreased with disease severity (Child-Pugh A 83%; B 47%; C 41%). Of 36 consensus recommendations, 18 matched the summary of product characteristics, while six diverged from it. Pharmacists and clinical pharmacologists more often recommended dose adjustments, especially in Child-Pugh B and C, whereas hepatologists preferred standard dosing or avoidance. Conclusions Expert recommendations for dosing in cirrhosis showed marked variability and limited concordance with prescribing information, underscoring the need for harmonised interdisciplinary guidance integrating pharmacokinetic evidence and clinical feasibility.

Background: Liver cirrhosis leads to an impaired liver function with reduced metabolic capacity, which affects the pharmacokinetics of several drugs, requiring dose adjustments. Although limited literature provides guidance on appropriate administration of drugs in cirrhosis, no guidelines currently exist for dose selection or adjustment. Objective: The objective of this study is to provide guidance on the selection, dosing, and appropriate use of drugs in patients with liver cirrhosis and evaluate the clinical application of these recommendations. Methods: Three steps are planned to establish dose recommendations for patients with liver cirrhosis. First, a systematic literature search will be conducted to identify specific recommendations for drug selection and dosing in cirrhosis, and the literature will be assessed for reporting quality and evidence level. Subsequently, the resulting recommendations will undergo an internal preassessment procedure for relevance of the covered drugs with regard to availability, the clinical impact of adverse drug reactions, the frequency of use, and the expected benefit of dose adjustment. Second, a modified Delphi procedure will be conducted to (1) analyze the clinical handling of the identified drugs by experts in clinical practice in a first round and (2) parse changes resulting from the inclusion of medication-related information and further harmonize differing dose recommendations in a second round. Finally, the adopted dose recommendations will be implemented in a clinical study involving patients with liver cirrhosis to analyze the impact of the recommendations on patient safety. Results: The planned clinical validation phase started in January 2025 and is currently underway. As of May 2026, 121 patients have been enrolled. Statistical analyses will be conducted in accordance with the predefined analysis plan. Findings from the literature review, the Delphi consensus process, and the clinical validation phase will be reported in subsequent publications. Final study results and data analysis are anticipated in August 2026. Conclusions: This protocol outlines a structured approach combining a systematic literature review of specific dose recommendations in patients with cirrhosis that integrates a quality assessment to ensure the inclusion of only high-quality evidence, expert opinions through a Delphi consensus aligning differing recommendations, and a clinical validation to support safer drug therapy in patients with liver cirrhosis.

BACKGROUND Liver cirrhosis leads to an impaired liver function with reduced metabolisation capacity which affects the pharmacokinetics of several drugs requiring dose adjustments. Although limited literature provides guidance on appropriate administration of drugs in cirrhosis, no guidelines currently existfor dose selection or adjustment. OBJECTIVE The objective of this study is to provide guidance on the selection, dosing and appropriate use of drugs in patients with liver cirrhosis and to evaluate the clinical application of these recommendations. METHODS Three steps are planned to establish dose recommendations for patients with liver cirrhosis: (1) A systematic literature search will be conducted to identify specific recommendations for drug selection and dosing in cirrhosis and assessed for reporting quality and evidence level. Subsequently, the resulting recommendations will be undergo an internal pre-assessment procedure for relevance of the covered drugs with regard to availability, the clinical impact of adverse drug reactions, the frequency of use and the expected benefit of dose adjustment. (2) A modified Delphi procedure will be conducted to (a) analyze the clinical handling of the identified drugs by experts in clinical practice in a first round and (b) harmonize differing dose recommendations in a second round. (3) Finally, the adopted dose recommendations will be implemented in a clinical study involving patients with liver cirrhosis to analyze their impact on the patients´ safety. RESULTS The study has been registered in the German Registry of Clinical Trials (DRKS00033779), and the planned clinical validation phase is currently underway. CONCLUSIONS This protocol outlines a structured approach combining a systematic literature review of specific dose recommendations in patients with cirrhosis integrating a quality assessment to ensure the inclusion of only high-quality evidence, expert opinions by a Delphi consensus aligning differing recommendations and a clinical validation to support safer drug therapy in patients with liver cirrhosis. CLINICALTRIAL This study was registered in the German Registry of Clinical Trials (DRKS) on 2024-12-27 with code number DRKS00033779 (https://www.drks.de/search/de/trial/DRKS00033779 ).