Dual toxicity of voriconazole in a CYP2C19 poor metabolizer: A case analysis of Life-threatening neutropenia and hepatocellular injury

Voriconazole, a first-line therapy for invasive aspergillosis, exhibits variable pharmacokinetics due to CYP2C19 polymorphisms. However, severe hematological toxicity, particularly life-threatening neutropenia, remains under-recognized. The concomitant occurrence of dual severe organ toxicities in CYP2C19 poor metabolizers (PMs) poses a significant clinical challenge. Here, we report a case of a 71-year-old Chinese male with invasive pulmonary aspergillosis. After approximately 40 days of oral voriconazole therapy (400 mg q12h loading dose, then 200 mg q12h maintenance), he sequentially developed grade 4 neutropenia (absolute neutrophil count nadir 0.02×10 9 /L) with fever and grade 3 hepatocellular liver injury (alanine aminotransferase peak 738 U/L). Pharmacogenomic testing revealed a CYP2C19 *2/*3 PM genotype. Causality assessments using the Naranjo and RUCAM scales rated both events as ”probable” in relation to voriconazole. Following discontinuation of voriconazole and a switch to alternative antifungals (isavuconazole, then liposomal amphotericin B), along with granulocyte colony-stimulating factor and hepatoprotective therapy, his neutrophil count and liver function recovered. The patient was discharged in stable condition. This case underscores the necessity of pre-emptive pharmacogenomic testing, vigilant monitoring of complete blood counts alongside liver function, and therapeutic drug monitoring in patients requiring long-term voriconazole therapy, especially the elderly, to enable early intervention and improve safety outcomes.