Abstract
PurposeVoriconazole (VCZ) is a new-generation triazol antifungal agent. CYP2C19 mutations have been reported to cause variability in VCZ pharmacokinetics, and thus lead to undesirable effects of pharmacotherapy. We observed four Caucasian patients who underwent allogenic hematopoietic stem cell transplantation, treated with voriconazole for prevention of fungal infections, to establish the impact of CYP2C19*2/*17 genotype on side effect occurrence.MethodsGenetic testing for CYP2C19 allele*2 and*17 was performed using two PCR-RFLP methods established by Goldstein and Blaisdell, and Sim et al. All four patients presented CYP2C19*2/*17 genotype.ResultsThe patients suffered from gastrointestinal, dermatological, neurological, hepatobiliary and renal adverse drug reactions (ADR). ADR could be best described by the use of VCZ. Other drugs potentially causing side effects were also taken into consideration. The presented complications were temporary and did not force dosage regimen adjustments or discontinuation of pharmacotherapy. After 2 months, the patients were discharged from hospital.ConclusionsDrug–drug interactions and ADR may occur even if an agent is used for prophylaxis only. We, therefore, should use any available tools for pharmacotherapy optimization—also genetic testing.
Highlights
Voriconazole (VCZ) is a new-generation triazol antifungal agent
As it is more effective in the prevention of mold infections than fluconazole (FCZ) and itraconazole, VCZ is used in prophylaxis of invasive fungal infections (IFI) among immunocompromised patients undergoing allogenic hematopoietic stem cell transplantation (Xu et al 2013)
During VCZ pharmacotherapy, we observed adverse drug reactions (ADR) in frequency that was not noticed in other patients treated with the same protocols
Summary
Voriconazole (VCZ) is a new-generation triazol antifungal agent. The drug is approved mainly for treatment of invasive aspergillosis, candidiasis and infections caused by Scedosporium spp. and Fusarium spp. (SPC Vfend 2016). The drug is approved mainly for treatment of invasive aspergillosis, candidiasis and infections caused by Scedosporium spp. and Fusarium spp. As it is more effective in the prevention of mold infections than fluconazole (FCZ) and itraconazole, VCZ is used in prophylaxis of invasive fungal infections (IFI) among immunocompromised patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) (Xu et al 2013). Mutations of the first isoenzyme have been reported to cause variability in voriconazole pharmacokinetics (Moriyama et al 2015). This is why many scientists postulate the need for CYP2C19 genotyping for therapeutic drug monitoring of VCZ (Trubiano et al 2014)
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