Mould-active azoles: pharmacokinetics, drug interactions in neutropenic patients

Mould-active azoles are used to treat systemic mycoses in neutropenic patients because of their broad spectrum activity, their availability as intravenous or oral formulations, and their safety. These agents exhibit complex pharmacokinetics and interact with many drugs, however, which can make their use in neutropenic patients challenging. With the addition of two mould-active azoles to the marketplace in the past several years, this paper will provide an overview of the pharmacokinetics and drug-drug interaction profiles of these azoles and will review the issues surrounding the therapeutic drug monitoring of these agents.

New mould-active azoles have sparked interest in correlating their serum concentrations to efficacy and toxicity. Efforts to establish such correlations have, however, generally proved unsuccessful. All mould-active azoles interact significantly with calcineurin inhibitors.

When used in combination with mould-active azoles, calcineurin inhibitor doses should be reduced by at least 50% and their blood or serum concentrations should be closely monitored.