Review article: prescribing medications in patients with cirrhosis - a practical guide.

BACKGROUND: Most drugs have not been well studied in cirrhosis; recommendations on safe use are based largely on experience and/or expert opinion, with dosing recommendations often based on pharmacokinetic (PK) changes.

AIM: To provide a practical approach to prescribing medications for cirrhotic patients.

METHODS: An indexed MEDLINE search was conducted using keywords cirrhosis, drug-induced liver injury, pharmacodynamics (PDs), PKs, drug disposition and adverse drug reactions. Unpublished information from the Food and Drug Administration and industry was also reviewed.

RESULTS: Most medications have not been adequately studied in cirrhosis, and specific prescribing information is often lacking. Lower doses are generally recommended based on PK changes, but data are limited in terms of correlating PD effects with the degree of liver impairment. Very few drugs have been documented to have their hepatotoxicity potential enhanced by cirrhosis; most of these involve antituberculosis or antiretroviral agents used for HIV or viral hepatitis. Paracetamol can be used safely when prescribed in relatively small doses (2-3 g or less/day) for short durations, and is recommended as first-line treatment of pain. In contrast, NSAIDs should be used cautiously (or not at all) in advanced cirrhosis. Proton pump inhibitors have been linked to an increased risk of spontaneous bacterial peritonitis (SBP) in cirrhosis and should be used with care.

CONCLUSIONS: Most drugs can be used safely in cirrhosis, including those that are potentially hepatotoxic, but lower doses or reduced dosing frequency is often recommended, due to altered PKs. Drugs that can precipitate renal failure, gastrointestinal bleeding, SBP and encephalopathy should be identified and avoided.