1537. Multicenter Study with Therapeutic Drug Monitoring (TDM) of Voriconazole (VRCZ) in Japanese Patients

Abstract

BackgroundTDM of VRCZ might be useful, especially in Asian people because of CYP2C19 genetic polymorphisms. However, limited data are available because of the small sample size.MethodsPatients who received VRCZ and had TDM were reviewed retrospectively at five institutions. Adequate VRCZ dosage was defined as a loading dose of 5–6 ± 0.5 mg/kg twice daily followed by a maintenance dose of 3–4 ± 0.5 mg/kg twice daily. For prophylaxis, the loading dose was left to the physician’s discretion. Optimal timing of TDM was defined as 4–7 days after starting therapy. Patients with adequate dosing and optimal timing of TDM were evaluated for analysis of trough levels (Cmin). Target Cmin was set at 1–5 µg/mL.ResultsThe study included 584 patients (treatment: 402; prophylaxis: 182). TDM was conducted on days 4–7 in 66.5% of patients (>7, 30.2%). A low adequate dosage (44.5%) was observed for treatment mainly because of a low performance of the loading dose (46.8%). Achievement of target Cmin was obtained in 62.7% (>5 µg/mL, 32.2%) in the treatment group and in 67.6% (11.0%) in the prophylaxis group. Seventy-one of 81 (81.7%) patients who required a dose reduction reached target Cmin by the second TDM. In 38 patients whose dose was not altered at oral switching, Cmin was significantly reduced from 2.5 ± 1.6 to 1.2 ± 1.3 μg/mL (P = 0.002), which indicated the necessity of TDM after oral switching. Hepatotoxicity occurred in 4.6% and visual symptoms in 7.9% of patients. Visual symptoms resolved without discontinuation of VRCZ in 73.9% of patients. Because of dosage adjustment based on TDM, high Cmin did not cause hepatotoxicity. However, the incidence of visual symptoms was significantly higher in patients with a high Cmin (12.7% vs. 5.4%, P = 0.002).ConclusionOne-third of Japanese patients who underwent VRCZ treatment with a loading dose showed high Cmin. Occurrence of hepatotoxicity was prevented with alteration of dosage in these patients (AMED, JP18fk0108045).Disclosures All authors: No reported disclosures.