Posaconazole oral dose and plasma levels in pediatric hematology-oncology patients

Eur J Haematol. 2018 Mar;100(3):315-322. doi: 10.1111/ejh.13017. Epub 2018 Jan 10.

Abstract

Background: Posaconazole is a triazole with limited pharmacokinetic information in children. This study assessed the correlation between posaconazole oral solution daily dosage/kg/body weight and trough plasma level.

Methods: A total of 97 hematology-oncology pediatric patients with ≥1 posaconazole plasma concentration level (PPC) assessment in the first 6 weeks after the start of posaconazole treatment were included.

Results: Posaconazole was used as prophylaxis in 84 of 97 (87%) patients and as therapy in 13 of 97 (13%). The median daily dose/kg/bw ranged from 10 to 12 mg in the prophylaxis group and 12.5 to 16.5 mg in the therapy group. The median value of PPC for the prophylaxis group was 0.9 and 0.8 μg/mL at the first and second/third determinations, respectively. Posaconazole prophylaxis failed in 4 of 84 patients (5%). The median value of PPC for the therapy group was 1.5 and 1.4 μg/mL at the first/second and the third determination, respectively. Posaconazole-related side effects were reported in 6 patients and all regressed with the suspension of the drug. In the prophylaxis group, the use of proton-pump inhibitors was significantly associated with a lower PPC, P = 0.04.

Conclusions: Posaconazole may be a valuable antifungal agent in children despite the incomplete knowledge of its pharmacokinetic characteristics.

Keywords: hematopoietic stem cell transplantation; invasive fungal infection; pediatric malignancy; posaconazole; prophylaxis; treatment.

Publication types

  • Multicenter Study

MeSH terms

  • Administration, Oral
  • Adolescent
  • Anemia, Aplastic / microbiology
  • Anemia, Aplastic / mortality
  • Anemia, Aplastic / pathology
  • Anemia, Aplastic / therapy*
  • Antifungal Agents / blood
  • Antifungal Agents / pharmacokinetics*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Child
  • Child, Preschool
  • Drug Administration Schedule
  • Drug Dosage Calculations
  • Female
  • Hematologic Neoplasms / microbiology
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / pathology
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immunologic Deficiency Syndromes / microbiology
  • Immunologic Deficiency Syndromes / mortality
  • Immunologic Deficiency Syndromes / pathology
  • Immunologic Deficiency Syndromes / therapy*
  • Infant
  • Lymphohistiocytosis, Hemophagocytic / microbiology
  • Lymphohistiocytosis, Hemophagocytic / mortality
  • Lymphohistiocytosis, Hemophagocytic / pathology
  • Lymphohistiocytosis, Hemophagocytic / therapy*
  • Male
  • Mycoses / mortality
  • Mycoses / prevention & control*
  • Remission Induction
  • Retrospective Studies
  • Survival Analysis
  • Transplantation, Homologous
  • Triazoles / blood
  • Triazoles / pharmacokinetics*

Substances

  • Antifungal Agents
  • Triazoles
  • posaconazole