Abstract
Pre-existing liver disease in patients with invasive fungal infections further complicates their management. Altered pharmacokinetics and tolerance issues of antifungal drugs are important concerns. Adjustment of the dosage of antifungal agents in these cases can be challenging given that current evidence to guide decision-making is limited. This comprehensive review aims to evaluate the existing evidence related to antifungal treatment in individuals with liver dysfunction. This article also provides suggestions for dosage adjustment of antifungal drugs in patients with varying degrees of hepatic impairment, after accounting for established or emerging pharmacokinetic–pharmacodynamic relationships with regard to antifungal drug efficacy in vivo.
Highlights
Invasive fungal infection (IFI) is a leading cause of morbidity and mortality among immunocompromised and critically ill patients [1,2]
The aim of the present review is to provide an overview of the safety profile of the various antifungal agents in patients with underlying liver disease
A subsequent population PK analysis concluded that a reduction of caspofungin maintenance dose in non-cirrhotic intensive-care unit (ICU) patients, who are misclassified due to hypoalbuminemia as with Child–Pugh Class B hepatic impairment, is not recommended, because it may result in significantly lower drug exposure and possible therapeutic failure [144]
Summary
Invasive fungal infection (IFI) is a leading cause of morbidity and mortality among immunocompromised and critically ill patients [1,2]. Other variables that affect PKs such as liver blood flow, biliary excretion and plasma protein binding may be altered in patients with pre-existing hepatic dysfunction [4] These patients may tolerate drug-induced liver injury (DILI) more poorly than healthy individuals [5]. The chemical properties of the agent, demographics, genetic predisposition, comorbidities including underlying hepatic disease, concomitant hepatotoxic drugs and DDIs, severity of the illness, and liver involvement by the fungal infection, all affect the possibility for hepatotoxicity [21]. Under these circumstances, it can be difficult to attribute DILI due to antifungals to only one factor. The intention is to summarize current data on the PKs of antifungals in these individuals and to increase clinical awareness of how various antifungal compounds should be used under these circumstances
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