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

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.