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Therapeutic drug monitoring in the treatment of invasive aspergillosis with voriconazole in cancer patients—an evidence-based approach

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Abstract

Invasive aspergillosis (IA) is a life-threatening complication in hematological cancer patients. Voriconazole (VCZ) is the established first-line treatment of IA. VCZ has a nonlinear pharmacokinetic profile and exhibits considerable variability of drug exposure. Therefore, therapeutic drug monitoring (TDM) of VCZ may help to improve treatment results in IA patients, but evidence-based data on the clinical use of TDM in patients treated with VCZ for IA are scarce. Evidence-based guidance is needed to support decisions on the use of TDM in routine VCZ therapy of IA. Our present analysis assessed published studies for evidence-based criteria for TDM of VCZ to improve efficacy and safety of IA therapy in cancer patients. Literature searches of MEDLINE and Cochrane database were performed. We identified 27 clinical studies reporting on the use of plasma level monitoring and/or TDM for VCZ. For each study, strength of recommendation and quality of evidence were categorized according to predefined criteria. A number of studies were published on plasma level monitoring (PLM) and TDM in VCZ therapy of IA. Across studies, VCZ levels >5–5.5 mg/L were found to be associated with toxicity, while reaching minimum levels of >1–2 mg/L appeared to improve efficacy. Timing, frequency, and intervention thresholds and dosage increments of VCZ for adjustment of plasma levels remain to be established. Currently, there is still no conclusive evidence for recommendations in routine clinical practice. More data from prospective randomized studies with TDM are desirable to provide a solid evidence basis for these approaches.

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Acknowledgments

This work was supported by an unrestricted grant by Pfizer Inc. Editorial support was provided by M. Fischer (Fischer BioMedical, Homburg, Germany).

Disclosures

M.K.: Advisory board for Pfizer, MSD, Gilead, Astellas.

T.L.: Speaker’s bureau of Astellas, Gilead Sciences, GlaxoSmithKline, Merck/MSD, and Pfizer; research grant from Gilead Sciences; consultant to Astellas, Gilead Sciences, and Merck/MSD.

D.B.: Consultations for Gilead, research support from Gilead and Pfizer, speakers bureau of Astellaa, Gilead, and Pfizer, MSD; travel grants from Astellas, MSD, and Pfizer

H.-P. L.: Speaker’s bureau of Astellas, Gilead Sciences, Merck/MSD, and Pfizer; advisory board for Astellas, Gilead Sciences, Merck/MSD, and Pfizer.

S.K.: Speaker’s bureau of Astellas, Gilead Sciences, MSD and Pfizer, research grant from Pfizer, advisory board for Astellas, Gilead Sciences, MSD and Pfizer.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Medical Clinic IV, Hematology and Oncology, Neuperlach Hospital, Munich, Germany

    Meinolf Karthaus

  2. Pediatric Hematology and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany

    Thomas Lehrnbecher

  3. Hospital Pharmacy, University Hospital Tübingen, Tübingen, Germany

    Hans-Peter Lipp

  4. Intensive Care Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany

    Stefan Kluge

  5. Department of Hematology and Oncology, Mannheim University Hospital, University of Heidelberg, Mannheim, Germany

    Dieter Buchheidt

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  1. Meinolf Karthaus
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  2. Thomas Lehrnbecher
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Correspondence to Meinolf Karthaus.

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Karthaus, M., Lehrnbecher, T., Lipp, HP. et al. Therapeutic drug monitoring in the treatment of invasive aspergillosis with voriconazole in cancer patients—an evidence-based approach. Ann Hematol 94, 547–556 (2015). https://doi.org/10.1007/s00277-015-2333-z

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