Impact of special patient populations on the pharmacokinetics of echinocandins

Abstract

Echinocandins belong to the class of antifungal agents. Currently, three echinocandin drugs are licensed for intravenous treatment of invasive fungal infections: anidulafungin, caspofungin and micafungin. While their antifungal activity overlaps, there are substantial differences in pharmacokinetics (PK). Numerous factors may account for variability in PK of echinocandins including age (pediatrics vs adults), body surface area and body composition (normal weight vs obesity), disease status (e.g., critically ill and burn patients) and organ dysfunction (kidney and liver impairment). Subsequent effects of altered exposure might impact efficacy and safety. Knowledge of PK behavior is crucial in optimal clinical utilization of echinocandin in a specific patient or patient population. This review provides up-to-date information on PK data of anidulafungin, caspofungin and micafungin in special patient populations. Patient populations addressed are neonates, children and adolescents, obese patients, patients with hepatic or renal impairment, critically ill patients (including burn patients) and patients with hematological diseases.

Keywords:

• anidulafungin
• caspofungin
• critically ill
• hematology
• invasive fungal infection
• micafungin
• obesity
• organ dysfunction
• pediatrics
• pharmacokinetics

Financial & competing interests disclosure

RJM Brüggemann has served as a consultant to and has received grants from Astellas, Gilead Sciences, Merck Sharpe and Dohme Corp. and Pfizer Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Echinocandins are widely used in many different patient populations for the prevention and treatment of Candida infections.

• There are profound pharmacokinetic (PK) differences between the three echinocandins.

• Dose adjustments should take into account specific patient characteristics and associated PK parameters and are different for each echinocandin.

• Therapeutic drug monitoring should be considered for those patients in whom PK is unpredictable, or yet unknown.