CRESEMBA (isavuconazonium sulfate) is a water soluble produg of the active triazole, isavuconazole, recently approved by the FDA for the treatment of invasive aspergillosis and invasive mucormycosis. The objective of this study was to evaluate the effect of renal impairment (mild, moderate, severe and end stage renal disease [ESRD]) on the pharmacokinetics of isavuconazole relative to the pharmacokinetics in healthy subjects with normal renal function.
This was a 2-part open-label, single-dose, parallel group study in male and female subjects. Subjects were enrolled on the basis of their renal function as assessed by estimation of creatinine clearance based on the Cockcroft-Gault formula (CLcr) adjusted for body surface area in subjects with ESRD and requiring hemodialysis (CLcr < 15 mL/min/1.73m2), mild (CLcr 50 80 mL/min/1.73m2), moderate (CLcr 30 < 50 mL/min/1.73m2) and severe impairment (CLcr < 30 mL/min/1.73m2) or healthy subjects (CLcr > 80 mL/min/1.73m2) matched overall by age, sex, weight and smoking status. Each subject received a single 1h intravenous dose of 372 mg of isavuconazonium sulfate (200 mg eq. isavuconazole) on day 1 (approximately 1-h after completion of routine hemodialysis procedures in ESRD subjects). ESRD subjects received an additional dose just prior to dialysis on day 15.
Isavuconazole was highly protein bound (>99%) regardless of renal function group. Renal excretion of isavuconazole itself was less than 1% of the dose administered. Compared with healthy subjects, plasma isavuconazole AUC values were not significantly different in subjects with renal impairment. Hemodialysis did not significantly clear isavuconazole from plasma (mean CLD = 292 mL/h).
Total isavuconazole AUC and Cmax values were not affected to a clinically meaningful extent in subjects with mild to severe renal impairment or in patients with ESRD compared to healthy subjects. A dose adjustment is not warranted in patients with renal impairment or in patients with ESRD.
- ICAAC 55th (2015)