Abstract / Summary
Abstract Purpose To evaluate the impact of CYP2C19 genetic polymorphisms on voriconazole exposure and the occurrence of adverse drug reactions in a Uruguayan hematology-oncology population treated with voriconazole. Methods Oncohematologic patients treated at a university hospital in Uruguay were enrolled between December 2021 and December 2024. CYP2C19 genotyping classified patients as normal, intermediate, or rapid metabolizers. Trough concentrations, clinical and paraclinical outcomes, including adverse drug reactions, were analyzed. Results Nearly half (46%) of trough concentrations fell outside the recommended therapeutic range: 27% were subtherapeutic and 19% were supratherapeutic. Genotypic distribution was 60% normal, 28% intermediate and 12% rapid metabolizers. Rapid metabolizers showed lower voriconazole exposure than normal metabolizers. While exposure did not differ significantly between intermediate and normal metabolizers, dose-dependent adverse events, including hallucinations and arthralgia, occurred in intermediate metabolizers. Elevated liver enzymes were observed in 60% of patients but were generally mild and frequently influenced by co-administration of other hepatotoxic agents. Conclusion CYP2C19 genetic polymorphisms significantly influence VCZ plasma levels and the risk of toxicity. CYP2C19 genotyping enables early identification of patients at risk of suboptimal drug exposure and adverse effects but is insufficient as a standalone strategy. Integrating preemptive genotyping with routine therapeutic drug monitoring is essential to personalize treatment, particularly in high-risk patients and complex clinical scenarios involving significant drug-drug interactions. Careful liver function monitoring remains crucial, especially in patients receiving other hepatotoxic agents.