Drug interactions of tacrolimus with letermovir and azole antifungals following hematopoietic stem cell transplantation: A retrospective observational analysis

Comparison of C/D ratio of tacrolimus when co-administered with and without letermovir according to azole antifungals. Thex-andy-axes represent the categories and C/D ratios of tacrolimus, respectively. The closed circles represent the C/D ratios in patients with fluconazole. The closed squares represent the C/D ratios in patients with voriconazole. The open circles represent the C/D ratios in patients without azole antifungals. C/D ratios were compared according to co-administered letermovir by the Wilcoxon signed-rank test. ΔC/D ratios were compared by the Mann–WhitneyU test. C/D, concentration and dose-normalized by body weight, AZL, azole, LTV, letermovir. AbstractTacrolimus interacts with letermovir and azole antifungals, whereas letermovir has nonuniform effects on the pharmacokinetics of azole antifungals. We retrospectively investigated the interaction of tacrolimus (continuous infusion) with letermovir considering co-administered azole antifungals in adult hematopoietic stem cell transplantation patients. The extent of intraindividual variation in the ratio of tacrolimus concentration to dose normalized by body weight (C/D ratio) was investigated. The correlation between the C/D ratio and estimated glomerular filtration rate (eGFR) was analyzed. In 35 patients (795 points), the C/D ratio was higher in the tacrolimus plus letermovir period than in the tacrolimus alone period (1234.7 [566.2 –2721.0] ng/mL/mg/kg vs. 564.4 [245.3–1861.3] ng/mL/mg/kg,p <  .0...
Source: Pharmacology Research and Perspectives - Category: Drugs & Pharmacology Authors: Tags: ORIGINAL ARTICLE Source Type: research