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Risk factors for subtherapeutic levels of posaconazole tablet

Laura A Tang1, Bernard L Marini1, Lydia Benitez1

  • 1Department of Pharmacy, University of Michigan Health System, Ann Arbor, MI, USA.

The Journal of Antimicrobial Chemotherapy
|November 2, 2017
PubMed
Abstract

Insights

Subtherapeutic posaconazole levels in patients taking the tablet formulation were linked to diarrhea, proton pump inhibitor use, and higher weight. Therapeutic drug monitoring may be needed for specific high-risk patients to ensure effective antifungal prophylaxis.

Area of Science:

  • Pharmacology
  • Infectious Diseases
  • Hematology

Background:

  • Posaconazole is a key antifungal for patients with hematological malignancies at high risk of invasive fungal infections (IFIs).
  • Subtherapeutic posaconazole concentrations are linked to breakthrough IFIs, with known risk factors for the suspension formulation.
  • Risk factors for subtherapeutic troughs with the posaconazole tablet formulation in a large patient population remain unevaluated.

Purpose of the Study:

  • To identify risk factors associated with subtherapeutic posaconazole troughs in patients using the tablet formulation for IFIs prophylaxis.

Main Methods:

  • A retrospective analysis of 157 patients receiving posaconazole tablets for prophylaxis was conducted.
  • Patients included those with hematological malignancies undergoing induction therapy and stem cell transplant recipients with graft-versus-host disease.
  • Serum trough concentrations were evaluated from February 2013 to March 2015.

Main Results:

  • Overall, 18% (28/157) of patients exhibited subtherapeutic posaconazole troughs (<700 ng/mL).
  • Higher likelihood of subtherapeutic troughs was associated with concurrent diarrhea (83%), proton pump inhibitor use (93%), and body weight exceeding 90 kg (48%).

Conclusions:

  • The posaconazole tablet offers more consistent concentrations than the suspension formulation.
  • Therapeutic drug monitoring (TDM) may still be valuable for identifying subtherapeutic troughs in specific patient populations.
  • These findings can guide the selection of patients who would benefit most from TDM for posaconazole therapy.

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