Increased trough concentration of venetoclax when combined with itraconazole for acute myeloid leukemia

Ann Hematol. 2024 Nov;103(11):4497-4502. doi: 10.1007/s00277-024-05845-2. Epub 2024 Sep 27.

Abstract

The administration of venetoclax (Ven) with azacitidine (Aza) was used as induction or salvage therapy for 34 patients with acute myeloid leukemia (AML) in our institute. An itraconazole oral solution (ITCZ-OS) was administered to 17 patients (50%) as antifungal prophylaxis. The trough concentration of Ven was significantly higher in patients treated with ITCZ than in those who were not (median values, 1.31 μg/mL vs. 0.64 μg/mL; p = 0.0072). Ven concentrations were > 3 μg/mL in some patients treated with ITCZ and the patient with the highest Ven concentration (5.58 μg/mL) expired after grade 4 neutropenia persisted for more than 50 days after the 1st cycle of Ven/Aza. It was also found that the group with concentrations equal to or above 1.29 μg/mL showed a significantly higher rate of achieving CR or CRi (p = 0.039). In conclusion, the measurement of Ven concentrations in AML cases is essential in daily clinical practice, particularly in those receiving antifungal prophylaxis.

Keywords: AML; CR or CRi; Itraconazole; Venetoclax.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / pharmacokinetics
  • Antifungal Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Azacitidine / administration & dosage
  • Azacitidine / therapeutic use
  • Bridged Bicyclo Compounds, Heterocyclic* / administration & dosage
  • Bridged Bicyclo Compounds, Heterocyclic* / pharmacokinetics
  • Bridged Bicyclo Compounds, Heterocyclic* / therapeutic use
  • Female
  • Humans
  • Itraconazole* / administration & dosage
  • Itraconazole* / therapeutic use
  • Leukemia, Myeloid, Acute* / blood
  • Leukemia, Myeloid, Acute* / drug therapy
  • Male
  • Middle Aged
  • Retrospective Studies
  • Sulfonamides* / administration & dosage
  • Sulfonamides* / pharmacokinetics
  • Sulfonamides* / therapeutic use

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Sulfonamides
  • venetoclax
  • Itraconazole
  • Azacitidine
  • Antifungal Agents