Optimizing antifungal drug dosing and monitoring to avoid toxicity and improve outcomes in patients with haematological disorders

Abstract

Antifungal prophylaxis, empirical therapy and treatment of established fungal infections in the haematology population may be associated with significant toxicity or drug interactions leading to sub-therapeutic antifungal drug concentrations and poorer clinical outcomes. These risks may be minimised by clinical assessment, laboratory monitoring of biochemical or haematological indices, avoidance of particular drug combinations and dose modification in certain circumstances. Specific measures, such as the optimal timing of oral drug administration in relation to meals, use of pre-hydration and electrolyte supplementation may also be required. For certain agents, therapeutic drug monitoring (TDM) is warranted where non-compliance, non-linear pharmacokinetics, a narrow therapeutic window, suspected drug interaction or unexpected toxicity are encountered. Pharmacokinetics and pharmacodynamics of clinical relevance to the haematology population are discussed for the azole, polyene and echinocandin classes of antifungal agents. The evidence supporting an association between TDM and enhanced treatment outcomes is presented for individual antifungal drugs, and recommendations for clinical practice are provided. Further randomised study of newer antifungal agents, such as posaconazole, is required to explore the potential for improved clinical outcomes in association with TDM. © 2008 The Authors.