A post-marketing evaluation of posaconazole plasma concentrations in neutropenic patients with haematological malignancy receiving posaconazole prophylaxis

Int J Antimicrob Agents. 2011 Mar;37(3):266-9. doi: 10.1016/j.ijantimicag.2010.11.021. Epub 2011 Jan 13.

Abstract

This is one of the first studies to report on therapeutic drug monitoring (TDM) of posaconazole (PCZ) for antifungal prophylaxis in patients with acute myelogenous leukaemia or myelodysplastic syndrome outside of the rigours of clinical licencing trials. A number of factors have been identified or proposed as causing poor oral absorption of PCZ. Putative PCZ concentrations have been recommended for TDM (0.5 μg/mL or 0.7 μg/mL). In this study, 19 (90.5%) of 21 patients failed to reach the higher putative target of 0.7 μg/mL, and 16 patients (76.2%) failed to reach the lower target of 0.5 μg/mL. Increasing the dose did not help four of six patients reach target concentrations. Three of the patients developed 'proven' or 'possible' fungal infections, all with PCZ concentrations <0.5 μg/mL. Use of acid-suppressing agents appears to explain some of the poor absorption. TDM of PCZ is warranted in patients receiving this orally administered agent.

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / blood*
  • Antifungal Agents / pharmacokinetics
  • Antifungal Agents / therapeutic use
  • Drug Monitoring
  • Female
  • Humans
  • Immunocompromised Host
  • Leukemia, Myeloid, Acute / drug therapy*
  • Male
  • Middle Aged
  • Mycoses / prevention & control*
  • Myelodysplastic Syndromes / drug therapy*
  • Neutropenia* / chemically induced
  • Retrospective Studies
  • Triazoles / administration & dosage
  • Triazoles / blood*
  • Triazoles / pharmacokinetics
  • Triazoles / therapeutic use

Substances

  • Antifungal Agents
  • Triazoles
  • posaconazole