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

Abstract

Summary 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 Unpublished information from the Food and Drug Administration and industry was also reviewed.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.

Dietary Supplement Use Among Patients With Hepatocellular Carcinoma

“…[42][43][44] Reassuringly, we found no significant adverse relationship between supplement use and survival. However, our observation that milk thistle users had slightly higher overall mortality than nonusers is potentially worrisome in light of a recent study of milk thistle use among patients with advanced liver disease.…”

Review article: depression and the use of antidepressants in patients with chronic liver disease or liver transplantation

“…67,95 There are also a number of other antidepressants that are established in clinical use that may be of use in this population (see Table 1 for further details). Reboxetine has altered pharmacokinetics in those with CLD compared to healthy controls, but there are no reports of DILI in association with its use at present.…”

“…glucuronidation is often considered to be affected to a lesser extent than cytochrome P450-mediated reactions in mild cirrhosis, but may be substantially impaired in patients with advanced cirrhosis. 66,67 The aetiology of liver disease also impacts upon the degree of change in hepatic enzyme activity; acute viral hepatitis and alcohol-related liver disease tends to initially affect the pericentral region (where oxidative functions are focused), while primary biliary cirrhosis predominantly involves the periportal region. 65 To add to the complexity, changes to pharmacodynamics are also prevalent in patients with CLD; for instance, increased sensitivity is found for the central effects of opiates and benzodiazepines.…”

“…69 Part of the difficulty that clinicians face is that so few of the medications they prescribe for medical conditions that commonly co-exist with liver disease -including antidepressants -have been adequately studied in this setting, and personal experience and/or expert opinion still contributes significantly to prescription patterns within contemporary practice. Only relatively recently have formal guidelines for the evaluation of pharmacokinetics and dosing adjustments in patients with existing liver disease been proposed by both the Food and Drug Administration (FDA) 70 65,67 principally based upon their relative lack of side effects and high therapeutic index (Table 1). These are currently the most common class of antidepressants prescribed to patients with CLD.…”

Idiosyncratic drug‐induced liver injury: A short review

“…Patients with CLD are hypothesized to be at higher risk of iDILI because of the inherent altered pharmacokinetics of drugs metabolized by the liver. However, the laboratory data for this population are mixed and hindered by the competing causes of the elevation of liver biochemistries 8, 9, 10. There are no data to show that underlying CLD is a major risk factor for all‐cause iDILI, but it may increase the risk in selected drugs.…”