# 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.

## Key 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.