Relationship between Early-onset Adverse Events and Drug Plasma Concentrations in Patients Receiving Oral Voriconazole
Year: 2024
Type: article
Study design: Observational Study
Abstract: Neuropathy, visual impairment, and hepatic dysfunction are common adverse events in voriconazole therapy. Therapeutic drug monitoring (TDM) is useful for improving treatment efficacy and preventing drug-related adverse events. This study was designed to prospectively examine the relationship between adverse events and drug plasma concentrations that occur early during treatment in patients receiving regular oral voriconazole. Patients kept a diary of their medication and blood collection times, neurological symptoms, and visual symptoms. Plasma concentrations of VRCZ were measured on days 4 and 7 after administration of VRCZ in hospitalized patients (26 patients) who received a loading dose of VRCZ at our hospital. The incidence of neurological, visual, and hepatic dysfunction was 34.6％, 50.0％, and 26.9％, respectively. The median timing and duration of adverse events were neuropathy after 3 and 5 days, visual impairment after 1 and 3 days, and hepatic dysfunction after 9 and 5 days. The mean VRCZ plasma concentrations in patients with adverse events were considerably higher than those in patients without adverse events. The cutoff values of VRCZ plasma concentration for predicting adverse events were 4.02, 3.61, and 5.14 µg/mL for neuropathy, visual impairment, and liver dysfunction, respectively. In addition, half of the patients spontaneously recovered from adverse events, whereas others recovered with dose reductions. These results indicate that early TDM intervention (VRCZ plasma concentration: < 4 µg/mL) on days 4 and 7 of oral VRCZ administration is expected to contribute to early recovery from early adverse events and to avoid severe events.
Authors: Takanori Miura, Hirofumi Awata, Keisuke Sugiyama, Taketo Asano, Misaki Kakimoto, Yoichi Hasegawa, Masashi Sawa
Institutions: Anjo Kosei Hospital, Meijo University
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4406203159