Pharmacokinetic Interaction Between Isavuconazole and Rifabutin in a Real‐World Setting

TL;DR

This study examines how the antifungal drug isavuconazole interacts with rifabutin in real-world patients, finding that drug levels remain effective but require monitoring.

Contribution

The study provides real-world pharmacokinetic data on isavuconazole and rifabutin co-administration, which is under-researched.

Findings

Isavuconazole trough concentrations remained above 1 mg/L in 86% of patients on rifabutin.

Median corrected 24-h steady-state isavuconazole was 2.7 mg/L with a wide range of variability.

Therapeutic drug monitoring is essential when these drugs are used together.

Abstract

Since rifabutin has less severe drug interactions, it is preferred over rifampin when administered concomitantly with azole antifungals. However, limited data exist to evaluate this interaction.

This was a single‐centre study of hospitalised patients who received concomitant isavuconazole and rifabutin prior to plasma isavuconazole therapeutic drug monitoring. Isavuconazole was administered at a standard dose of isavuconazonium sulphate 372 mg every 8 h for six doses followed by 372 mg every 24 h.

Of the seven patients included, the median age (range) was 53 years (33–67), 71% (5/7) were solid organ transplant recipients and no patients had underlying cirrhosis. The median (range) corrected 24‐h steady‐state isavuconazole was 2.7 mg/L (0.7–3.7) and 86% (6/7) had an isavuconazole level > 1 mg/L. The median (range) area under the curve (AUC 24), half‐life (T
½) and clearance (Cl) were 85 mg/L h (33–112), 13.1 h (6.8–17.8) and 4 L/h (3.1–10.7), respectively.

This study demonstrates that isavuconazole trough concentrations are often maintained above 1 mg/L despite patients being on concomitant rifabutin. However, therapeutic drug monitoring is mandatory in this setting. Further research is warranted to confirm these results.