Dose adjustment in patients with liver cirrhosis: impact on adverse drug reactions and hospitalizations

Abstract

Aim and background To assess drug-related problems in patients with liver cirrhosis by investigating the prevalence of inadequately dosed drugs and their association with adverse drug reactions (ADRs) and hospitalizations. Methods This was a cross-sectional retrospective study assessing the dose adequacy of drug treatment of 400 cirrhotic patients at hospital admission based on the authors' own previous studies and standard literature. The prevalence of total and preventable ADRs and of hospitalizations due to preventable ADRs was determined. Results Of all 1653 drugs prescribed (median 4 per patient), 336 (20 %) drugs were inadequately dosed in 184 patients. Overall, 210 ADRs (78 % preventable) occurred in 120 patients. Sixty-nine ADRs (33 % of all ADRs) were associated with inadequate drug dosing in 46 patients, of which 68 % were preventable. Nonsteroidal anti-inflammatory drugs and psycholeptics in particular frequently caused preventable ADRs associated with inadequate drug dosing. Inadequate drug dosing was more frequently associated with ADRs than adequate drug dosing, and patients receiving inadequately dosed drugs were more frequently admitted to the hospital due to ADRs. Hospitalization of patients receiving inadequately dosed drugs that caused preventable ADRs resulted in 94 additional hospital days. ConclusionIn this retrospective study, inadequate drug dosing was associated with an increased frequency of ADRs, hospital admissions and hospital days in cirrhotic patients. We therefore conclude that the careful dosing of critical drugs is important in patients with liver cirrhosis.

A Study of the Relationship between Serum Bile Acids and Propranolol Pharmacokinetics and Pharmacodynamics in Patients with Liver Cirrhosis and in Healthy Controls

“…In patients with liver cirrhosis, the bioavailability of such drugs can reach 100% due to intra- and extrahepatic porto-systemic shunts [1], [5], [6]. High-extraction drugs must therefore be dosed very carefully in this population to avoid dose-dependent adverse reactions [7].…”

A Prediction Model of Drug Exposure in Cirrhotic Patients According to Child–Pugh Classification

“…Loop diuretics (furosemide and torsemide) and potassium-sparing diuretics (spironolactone) are the most widely used drugs (59 % on admission) in cirrhotic patients with ascites [8]. They are also the class of drugs most frequently associated with an adverse drug reaction such as metabolic disorder (hyperkalemia or hyponatremia) or worsening renal function [9].…”

Discrepancies in Liver Disease Labeling in the Package Inserts of Commonly Prescribed Medications

“…The authors also lamented that, by adding a label of exercising COMMENTARIES caution for use in patients with liver disease, the "problem is shifted to the prescriber." 12 In summary, a large number of widely prescribed drugs carry liver disease-related labeling in their official package inserts, and there is substantial discrepancy in the labeling by US and European agencies. It would be important for the regulatory authorities and Pharma to reevaluate the process by which package inserts are developed and consider a universal package insert wherever feasible.…”

“…11 The same group of researchers also found that 20% of drug prescriptions to patients with cirrhosis were inappropriate, mostly owing to inaccurate doses or prescribing otherwise contraindicated drugs. 12 Patients with inadequately dosed drugs were more frequently hospitalized owing to adverse drug reactions. 12 As the authors pointed out, in contrast with impaired renal function, no generally accepted dose recommendations exist for patients with impaired liver function.…”

“…12 Patients with inadequately dosed drugs were more frequently hospitalized owing to adverse drug reactions. 12 As the authors pointed out, in contrast with impaired renal function, no generally accepted dose recommendations exist for patients with impaired liver function. 9 This lack might be owing to the fact that there may not be any generally accepted definition of impaired liver function, unlike what we have for renal function with creatinine.…”