Therapeutic drug monitoring of voriconazole and posaconazole for invasive aspergillosis

Abstract

Voriconazole and posaconazole are extended-spectrum triazoles recommended for treatment, prophylaxis and salvage therapy of Aspergillus diseases. Over the past decade many papers have emerged supporting the use of therapeutic drug monitoring (TDM) for azole antifungals. TDM is used to tailor the exposure of a specific drug to the individuals to optimize treatment response and minimize side effects. We reviewed the pharmacokinetics and pharmacodynamics (PK-PD) characteristics of voriconazole and posaconazole. We present the available evidence on target concentrations defining maximal efficacy and minimal toxicity. Finally we provide some practical recommendations how to best perform TDM in clinical practice.

Keywords::

• Aspergillus
• azole antifungal drugs
• pharmacodynamics
• pharmacokinetics
• therapeutic drug monitoring

Financial & competing interests disclosure

S Seyedmousavi has no conflict of interests. RJM Brüggemann, PE Verweij and JW Mouton have served as consultant to and have received research grants from Gilead Sciences, Merck, Astellas and Pfizer. 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

• • Therapeutic drug monitoring (TDM) of posaconazole and voriconazole can be recommended in the setting of prophylaxis and treatment of invasive fungal disease caused by Aspergillus fumigatus.

• • TDM may be beneficial to warrant optimal efficacy of posaconazole and voriconazole and to reduce toxicity in the case of voriconazole.

• • Controlled trials TDM versus no-TDM (specifically for posaconazole) are warranted to provide the necessary justification of the value of TDM.

• • Incorporation of MIC, disease status, genomics, other covariates will allow more thorough interpretation of the results obtained.