Abstract
The aim of this study was to determine the influence of different CYP2C19 genotypes on selected liver function parameters, and ADR occurrence during VCZ prophylaxis in adult patients after allo-HSCT (allogeneic hematopoietic stem cell transplantation). CYP2C19 mutations were determined in a cohort of 30 adults using PCR-RFLP methods established by Sim et al. and Goldstein and Blaisdell. The patients’ protocol included biometrical and biochemical data, information on the underlying disease, chemotherapy, molds infections occurring during VCZ treatment, adverse drug reactions typical for the use of voriconazole, and probable drug - drug interactions. The observation and reporting of ADR took place from the −1 until the +20th day of VCZ therapy. For statistical analysis the χ2 test was used (p < 0.05). Among the examined patients 23 suffered from at least one side effect during VCZ therapy. Most frequent ADR were gastrointestinal disturbances (n = 15), nervous system (n = 11) and skin (n = 7) disorders. Patients with at least one loss of function allele (*2) were more likely to experience adverse drug reactions than those, with different genotypes. Due to the limited number of patients the result could not be proven with a statistical significance. Previous determination of CYP2C19 genotype may be a useful tool for prevention of adverse drug reactions during VCZ prophylaxis among patients after allo-HSCT.
Highlights
IntroductionFor patients classified as those at highest risk of developing invasive fungal infections (IFIs)
Antifungal prophylaxis is crucial for the success of each hematologic treatment
In a previously published article, we describe 4 patients with CYP2C19*2/*17 genotype experiencing more often side effects of voriconazole others treated with the same protocols [15]
Summary
For patients classified as those at highest risk of developing invasive fungal infections (IFIs) These are patients receiving intensive chemotherapy for acute myeloid leukemia and myelodysplastic syndrome, as well as corticosteroid therapy for graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (alloHSCT) [1]. In this group of patients, IFIs are mainly caused by Aspergillus spp. and Candida spp. One of the new generation triazol antifungal agents with broad-spectrum activity is voriconazole (VCZ) It is indicated for treatment of invasive aspergillosis, candidemia in nonneutropenic patients, fluconazole-resistant serious invasive Candida spp. infections and serious fungal infections caused by Scedosporium spp. and Fusarium spp. The liver metabolism is primarily conducted by the hepatic cytochrome P450
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