Safe use of medication in patients with cirrhosis: pharmacokinetic and pharmacodynamic considerations

ABSTRACT

Introduction: The global burden of cirrhosis is rising, and clinicians increasingly face the challenge of safely prescribing medicines for complications of hepatic disease and comorbidities. Prescribing in patients with cirrhosis is complicated by alterations that can occur in the pharmacology of medicines.

Areas covered: This paper provides an overview of current knowledge on the pharmacokinetics and pharmacodynamics of medicines in patients with cirrhosis. We describe the pathophysiological changes that occur and their consequences on pharmacokinetic parameters. We explain that the influence of cirrhosis on the pharmacokinetics depends on several drug and patient characteristics. Patients with cirrhosis also have an increased susceptibility to some toxicological effects of medicines, such as renal impairment and hematological toxicity, which we describe in detail. In addition, we discuss approaches to apply this knowledge in practice and improve safe medication use in patients with cirrhosis.

Expert opinion: Tailored pharmacotherapy is needed to ensure safe and appropriate use of medicines in patients with cirrhosis. Clinicians are supported by freely available recommendations on safe drug use in cirrhosis published on a website. In addition, a regular evaluation of medication use in patients with cirrhosis could resolve and prevent medication-related problems.

KEYWORDS:

• Cirrhosis
• hepatic impairment
• hepatology
• medication safety
• pharmacology
• pharmacokinetics
• pharmacodynamics

Article highlights

• Cirrhosis may affect all pharmacokinetic parameters, which can result in an increased plasma drug concentration. The extent of increase depends on both drug (e.g. pharmacokinetic properties and the administration route) and patient characteristics (e.g. the etiology and severity of cirrhosis).

• Patients with cirrhosis may have an increased susceptibility to the toxicological effects of medicines due to pathophysiological changes.

• Health-care professionals should anticipate these pharmacokinetic and pharmacodynamic changes and can be supported by recommendations for safe prescribing in cirrhosis.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

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Funding

This paper was not funded.