Dose Recommendations for Common Drugs in Patients with Liver Cirrhosis: A Systematic Literature Review

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.

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.

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.

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.