Posaconazole liquid vs tablet formulation in lung transplant recipients

Mycoses. 2018 Mar;61(3):186-194. doi: 10.1111/myc.12724. Epub 2017 Nov 22.

Abstract

Posaconazole is an extended-spectrum triazole antifungal used in the treatment and prophylaxis of Aspergillus infections. It is available as oral suspension (POS-Liq) and delayed-release tablets (POS-Tab). The aim of this longitudinal, retrospective study was to compare the clinical effectiveness, toxicity and pharmacokinetics of POS-Liq vs POS-Tab in lung transplant recipients (LTx-recipients), who were treated with both formulations subsequently. Twenty-four consecutive LTx-recipients with 191 documented posaconazole trough levels (PTLs) for POS-Liq or POS-Tab were included. The administered daily doses were 300 mg for POS-Tab and 600 mg (prophylaxis) or 800 mg (therapy) for POS-Liq. Target PTLs were ≥700 ng/mL (prophylaxis) and ≥1250 ng/mL (therapy). The overall prophylactic and therapeutic response rates were 78% and 67%, respectively. No cases of hepatotoxicity or QT-prolongation were observed with either formulation. The achieved target PTLs were tripled under POS-Tab compared to POS-Liq with fewer risk factors for sub-therapeutic PTLs. Concomitant administration of POS-Tab significantly reduced the tacrolimus concentration-to-dose ratio (P = .001). We suggest the use of POS-Tab is appropriate for prophylaxis and therapy of Aspergillus infections in LTx-recipients, since POS-Tab displayed more reliable PTLs with no added adverse events. However, we recommend regular drug monitoring for POS-Liq and for therapy with POS-Tab and that immunosuppressant levels are monitored closely when the posaconazole formulation is switched.

Keywords: antifungal agents; dosage form; invasive fungal infection; lung transplantation; posaconazole; therapeutic drug monitoring.

Publication types

  • Comparative Study
  • Observational Study

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antifungal Agents / administration & dosage*
  • Antifungal Agents / pharmacokinetics*
  • Antifungal Agents / therapeutic use
  • Aspergillosis / blood
  • Aspergillosis / drug therapy
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / therapeutic use
  • Drug Monitoring / methods
  • Female
  • Humans
  • Invasive Fungal Infections / drug therapy
  • Longitudinal Studies
  • Lung Transplantation*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Suspensions
  • Tablets
  • Transplant Recipients*
  • Triazoles / administration & dosage*
  • Triazoles / pharmacokinetics*
  • Triazoles / therapeutic use
  • Young Adult

Substances

  • Antifungal Agents
  • Delayed-Action Preparations
  • Suspensions
  • Tablets
  • Triazoles
  • posaconazole