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

ABSTRACT Background 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. Methods 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. Results 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. Conclusion 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.