Drug dosage recommendations in patients with chronic liver disease

Abstract

Chronic liver diseases (CLD) alter the kinetics of drugs. Despite dosage adjustment is based on Child-Pugh scores, there are no available recommendations and/or algorithms of reference to facilitate dosage regimens.A literature review about dose adjustment of the drugs from the hospital guide -which are included in the list of the WHO recommended drugs to be avoided or used with caution in patients with liver disease-was carried out. The therapeutic novelties from the last few years were also included. In order to do so, the summary of product characteristics (SPC), the database DrugDexMicromedex, the WHO recommendations and the review articles from the last 10 years in Medline were reviewed. Moreover, the kinetic parameters of each drug were calculated with the aim of establishing a theoretical recommendation based on the proposal of Delcò and Huet.Recommendations for 186 drugs are presented according to the SPC (49.5%), DrugDex-Micromedex (26.3%) and WHO (18.8%) indications; six recommendations were based on specific publications; the theoretical recommendation based on pharmacokinetic parameters was proposed in four drugs.The final recommendations for clinical management were: dosage modification (26.9%), hepatic/analytical monitoring of the patient (8.6%), contraindication (18.8%), use with caution (19.3%) and no adjustment required (26.3%).In this review, specific recommendations for the practical management of patients with chronic liver disease are presented. It has been elaborated through a synthesis of the published bibliography and completed by following a theoretical methodology.

Dosage adjustment for hepatic dysfunction

“…Hepatic extraction ratio (E) was < 0.3 in 19 drugs (31.6 % of drugs with E data available). These data coincide with those obtained by Periáñez-Párraga L et al (1). In 60 drugs (30.8 %), E was obtained through the bibliography, while Periañez-Párraga L et al…”

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

“…Specific recommendations for dose adjustment based on Child-Pugh classification are often vague, imprecise, or lacking [76,77]. For drugs with a narrow therapeutic index, it is sometimes recommended that both initial and maintenance doses should be reduced by at least 50 %; however, this kind of recommendation is totally empirical [2].…”

Changes in Pharmacokinetic Properties of Antibacterial Drugs in Critically Ill Patients

“…© Farm Pol, 2020, 76 (1): [33][34][35][36][37][38][39][40][41][42][43][44][45][46] ciała, a także towarzyszące zmiany patologiczne w organizmie chorego (np. stopień niewydolności funkcji nerek, wątroby, współtowarzyszące choroby), które odpowiedzialne są za obserwowane różnice międzyosobnicze w wielkości oznaczanych stężeń leku, po podaniu zastosowanych dawek.…”

“…W praktyce klinicznej powszechnie stosowana skala Child-Pugh jest narzędziem służącym do diagnozowania stopnia niewydolności wątroby, ale także do dostosowania dawkowania leku do stopnia jej uszkodzenia u pacjentów w stanie krytycznym. Warto zauważyć, że jedynymi lekami przeciwdrobnoustrojowymi, dla których zaleca się zmniejszenie dawki u pacjentów z ostrym wirusowym zapaleniem wątroby typu C są metronidazol, tygecyklina i kaspofungina [40]. Niewydolność wątroby jest również związana ze zmniejszonym wytwarzaniem albuminy, co prowadzi do hipoproteinemii i jej konsekwencji opisanych wyżej.…”