Isavuconazole Prophylaxis (Isa Px) Among Solid Organ Transplant (Sot) Patients (Pts): Preliminary Impressions on Dosing and Interactions with Tacrolimus

R. M. Rivosecchi1 , C. N. J. Clancy1 , R. K. Shields1 , L. Clark1 , A. Humar1 , C. R. Ensor1 , B. A. Falcione1 , R. Venkataramanan2 , M-H. Nguyen1

Author address: 

1 UPMC Presbyterian, Pittsburgh, PA, 2 Univ. of Pittsburgh Sch. of Pharmacy, Pittsburgh, PA


: ISA is approved for treatment of invasive aspergillosis and mucormycosis (IM). The use of ISA as px has not been evaluated. Our SOT program began universal ISA px following a cluster of IM cases among pts receiving voriconazole (VOR) px. There are no definitive recommendations for FK dosing among pts receiving ISA. We describe our preliminary experience using FK in SOT pts receiving ISA. Methods: This was a retrospective review of SOT pts from Sept. to Dec. 2015. Pts received ISA 372 mg Q 8h for 6 doses, then 372 mg Qd. Px duration was 4 mos for lung (Lu) and 1 mo for other SOT. FK dose was at the discretion of the treating physician with titrations based on daily monitoring during the early post-transplant period. Results: 95 SOT pts have received primary ISA px. We describe 41 pts who received ISA and FK (Kidney (K) transplant, 18; Liver (Li), 10; Lu, 10; Heart (H), 2; Li-K, 1), and who were followed for ≥2 mos post-SOT. Median age was 59 yrs, and 66% were men. 5 pts had received VOR and 2 fluconazole previously. Among the remaining 34 pts, median times to first therapeutic FK levels were 6d (K), 6d (Lu), 5d (Li) and 2.5d (H). Median (SD) FK concentration/dose (C/D) ratios, in (ng/mL)/(mg/kg), were 110 (±85) at d7 and 110 (±216) at d14. In 26% (9/34) of pts, there was a downward trend in C/D over 21d. C/D was highest during the first 2d (median 175) and lower on d3 (104, p=.002) and d4 (127, p=.0002), likely reflecting ISA loading doses. 85% of pts exhibited consistent C/D from d3 to d21, and 15% exhibited an upward trend. Median FK C/D during ISA px was 27% higher than after stopping px (p=.04). Of note, 1 pt developed invasive fungal infection (IFI) on ISA px. VOR and posaconazole levels were sub-therapeutic during subsequent treatment, suggesting poor absorption or high clearance in this pt (genetic studies pending). Conclusions: Our preliminary data suggest that ISA increases FK levels in SOT pts by 27%. Clinicians should be aware that FK levels during ISA loading may be higher than at later time points, and that there is inter-pt variability in the effect of ISA on FK levels. Inter-pt variability and occurrence of a IFI suggest a potential role for ISA therapeutic drug monitoring in guiding management.

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Full conference title: 

ASM Microbe 2016
    • ASM microbe 1st (2016)