How to manage medications in the setting of liver disease with the application of six questions

Summary Objective: Reviewing the current literature to guide clinicians managing medications in the setting of liver disease. Literature sources: Using the terms liver disease, medication management, and therapeutic monitoring, a literature review was conducted to identify peer‐reviewed articles in MEDLINE (1966–April 2009). Reference citations were reviewed as an additional resource. Published English‐language literatures, articles and trials were reviewed. Emphasis was placed on prospective, randomised, double‐blind, placebo‐controlled clinical trials. Question synthesis: An informed decision on how to manage medications in the setting of liver disease should account for changes that transpire in a medication’s first‐pass metabolism, protein binding, volume of distribution, clearance and pharmacodynamic interactions. To incorporate these issues within one’s thought process, clinicians can utilise the following six questions to evaluate a medication use: (i) Is the patient experiencing acute or chronic liver failure? (ii) Does the drug have high hepatic first‐pass metabolism? (iii) Is the medication highly protein‐bound? (iv) Is there a change in the volume of distribution for the medication? (v) Is the clearance of the medication significantly altered? and (vi) Is there a pharmacodynamic interaction with the medication? Conclusions: The introduction and use of six clinically relevant questions in the setting of liver disease can serve as a guide to clinicians who manage patients with liver disease.