Tolerability of isavuconazole after posaconazole toxicity in leukaemia patients

Mycoses. 2019 Jan;62(1):81-86. doi: 10.1111/myc.12851. Epub 2018 Oct 24.

Abstract

Background: Posaconazole (PCZ) is widely used for prophylaxis or treatment of invasive fungal infections (IFIs) in leukaemia patients. However, issues with PCZ tolerability can result in treatment interruption. Isavuconazole (ISA) has a similar broad spectrum of activity to PCZ; however, real-world data regarding the tolerability of ISA after PCZ toxicity are lacking.

Objectives: To describe the tolerability of ISA after PCZ toxicity in leukaemia patients.

Patients/methods: We retrospectively assessed tolerability of ISA after PCZ toxicity in adult leukaemia patients (March 2015 to November 2017). We included all patients who received ≥7 days of ISA within 48 hours of PCZ discontinuation. Laboratory markers for liver toxicity were collected at three time points: prior to PCZ, at switch to ISA and after ISA therapy.

Results: We identified 23 such patients. Increased liver function tests (LFTs) were noted in 20 patients on PCZ, while three patients had Grade 3/4 QTc prolongation. No patient discontinued subsequent ISA due to toxicity. Grade 3/4 elevations in LFTs were decreased after changing to ISA (30% after PCZ vs 5% after ISA). No patient had significant QTc prolongation after switching to ISA.

Conclusions: Isavuconazole was well-tolerated in patients discontinuing PCZ due to toxicity, with no patient discontinuing ISA due to toxicity.

Keywords: invasive fungal infections; isavuconazole; leukaemia; neutropenia; posaconazole; toxicity.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Chemical and Drug Induced Liver Injury / epidemiology*
  • Chemical and Drug Induced Liver Injury / pathology
  • Drug-Related Side Effects and Adverse Reactions / epidemiology*
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Female
  • Humans
  • Leukemia / complications*
  • Liver Function Tests
  • Male
  • Middle Aged
  • Mycoses / drug therapy*
  • Mycoses / prevention & control*
  • Nitriles / administration & dosage
  • Nitriles / adverse effects*
  • Pyridines / administration & dosage
  • Pyridines / adverse effects*
  • Retrospective Studies
  • Triazoles / administration & dosage
  • Triazoles / adverse effects*
  • Young Adult

Substances

  • Nitriles
  • Pyridines
  • Triazoles
  • isavuconazole
  • posaconazole