Drug-interactions of azole antifungals with selected immunosuppressants in transplant patients: strategies for optimal management in clinical practice

• Azole antifungals can increase blood concentrations of immunosuppressants.
• Tools to assess interactions between azoles and immunosuppressants are presented.
• A stepwise approach is included to systematically assess drug–drug interactions.
• Management options to circumvent or manage drug–drug interactions are provided.
• Ideally, drug–drug interactions are guided by means of therapeutic drug monitoring (TDM).

The management of drug–drug interactions (DDIs) between azole antifungals (fluconazole, itraconazole, posaconazole and voriconazole) and immunosuppressants (cyclosporine, tacrolimus, everolimus and sirolimus) in transplant patients remains challenging, as the impact of altered immunosuppressant concentrations puts the patient at high risk for either toxicity or transplant rejection. As a result, it is a complex task for the clinician to maintain immunosuppressant concentrations within the desired therapeutic range and this requires a highly individualized patient approach. We provide important tools for adequate assessment of the drug interactions that cause this pharmacokinetic variability of immunosuppressants. A stepwise approach for the evaluation and subsequent management options, including a decision flow chart, are provided for optimal handling of these clinically relevant DDIs.