Tacrolimus is an effective immunosuppressive agent for allogeneic HSCT. It is primarily metabolized by the CYP450 3A4 isoenzyme. Voriconazole is often used to prevent fungal infections after allogeneic HSCT. It is metabolized by the CYP450 3A4, 2C9 and 2C19 isosenzymes. Studies in healthy volunteers and case reports in HSCT recipients have shown significant drug interaction between the two requiring reduction of tacrolimus dose. Ordinarily, tacrolimus prophylaxis is initiated at the dose of 0.03 mg/kg IV daily on day -1. After starting tacrolimus at this dose and having to reduce the dose substantially within 23 days in all patients receiving concomitant voriconazole 200 mg twice daily orally from day 0, we implemented a simple, pre-emptive tacrolimus dose reduction strategy to maintain steady-state levels between 5 and 15 ng/mL in patients on IV tacrolimus. As a first step, IV tacrolimus was initiated at the reduced dose of 0.022 mg/kg adjusted body weight per day. As a second step, tacrolimus dose was reduced by 3040% if the steady-state level 48 h after initiation of tacrolimus (day +1) was between 7 and 10 ng/mL, and by 4050% if the level was between 10 and 15 ng/mL. No change was made if the level was 15 ng/mL. 24 of 27 patients required dose-reduction from day 0 to day +1 based on levels. Every single patient required dose-reduction at least twice. An increase in the dose was needed in only 2 patients after initial dose-reduction. The figure below shows the minimum, maximum, and median tacrolimus doses; depicting a steady decline in the median dose.
Full conference title:
49th American Society of Haematologists Annual Meeting
- ASH 49th (2007)