The pharmacotherapy of cirrhosis: concerns and proposed investigations and solutions

Abstract

SUMMARYWhat is known and objective: The presence of cirrhosis has a multifaceted impact on hepatic drug metabolism. An area of concern and uncertainty in the care of patients with cirrhosis is the safe use of both prescription and over-the-counter medications. Comment: Retrospective studies indicate a high incidence of adverse drug reactions (ADRs) among patients with cirrhosis related to use of certain medication classes including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and non-steroidal anti-inflammatory drugs. Conversely, use of appropriate medications, such as statins, may be decreased in this population due to fear of precipitating hepatotoxicity. What is new and conclusion: Pharmacotherapy in cirrhosis is an area of uncertainty and heterogeneity in clinical practice. Prescribing and dosing guidelines are needed to decrease the risk of serious ADRs in this high-risk patient population. WHAT IS KNOWN AND OBJECTIVELiver cirrhosis is associated with compromised liver function, including the ability to metabolize drugs. The presence of cirrhosis has a multifaceted impact on hepatic drug metabolism. Higher plasma drug concentrations may occur due to reduced drug clearance in the setting of impaired hepatic blood flow 1,2 and altered activity of metabolizing enzymes and membrane transporters.2-4 For drugs with high protein binding and low hepatic extraction, hypo-albuminemia increases the fraction of unbound drug and can therefore heighten potential toxicity. 1,3,[5][6][7] Pharmacotherapy in cirrhosis is further complicated by the prevalence of concomitant renal dysfunction and need for multiple medications to manage the complications of cirrhosis, including varices, ascites and bacterial peritonitis. Patients with cirrhosis have tenuous physiology and are susceptible to a variety of complications. An area of concern and uncertainty in the care of patients with cirrhosis is the safe use of prescription and over-the-counter medications.3,8 Although hepatotoxicity is a common concern, patients with cirrhosis are generally at greater risk of renal failure, gastrointestinal bleeding and hepatic encephalopathy precipitated by medications. Adverse drug reactions (ADRs) constitute a significant cause of morbidity and mortality in the United States.9,10 An ADR is defined by the World Health Organization as an effect secondary to medication use which is 'noxious and unintended, and which occurs at doses used in man for prophylaxis, diagnosis or therapy '. 11 This definition is largely applied to the appropriate use of medications. More recently, the literature has focused on adverse drug events (ADEs), a more comprehensive term which refers to any injury resulting from medication use.12 ADEs and ADRs have been the focus of significant public and regulatory attention, prompting studies and guidelines aimed at decreasing their incidence. 10,12,13 Interventions and guidelines have been published for high-risk populations, including the elderly 14,15 patients with chronic kidney disease, 16 ...

Medication safety in patients with hepatic impairment: A survey of community pharmacists' knowledge level and their practice in caring for these patients

“…A barrier for pharmacists to fulfil this role was the lack of concrete prescribing recommendations for patients with hepatic impairment and deficiencies in the information for these patients in the product labels. [6][7][8][9] However, in 2018, practical guidance for safe drug use in this specific patient group was published. 10,11 In the Netherlands, the website containing all guidance (www.drugsinlivercirrhosis.…”

Evidence-Based Recommendations to Improve the Safe Use of Drugs in Patients with Liver Cirrhosis

“…Practice guidelines can support healthcare professionals in safe prescribing and can reduce the number of inappropriate drug prescriptions, as seen in other patient populations such as older people [ 8 ]. For patients with liver cirrhosis, literature regarding pharmacokinetic alterations for several drugs is available [ 5 , 9 – 12 ]; however, we were not aware of a publicly available practice guideline providing recommendations on the safe use of specific drugs in liver cirrhosis [ 13 ]. We therefore developed a systematic method to evaluate the safety and dosing of medications to provide recommendations for safe drug use in patients with liver cirrhosis [ 14 ].…”