Concomitant Azole Initiation Decreases Time to Stable Goal Sirolimus Concentrations in Pediatric Allogeneic Transplant Recipients

Variability of sirolimus pharmacokinetics, often compounded by interactions with azole antifungal therapy, leads to concentrations outside the goal range and increased risk of related complications. We assessed the time to initial attainment of stable goal sirolimus concentrations in patients who either concomitantly initiated azole therapy and sirolimus (concomitant group) or initiated an azole after sirolimus initiation (delayed group). The median time to attainment of stable goal sirolimus concentrations was 8.0 days in the delayed group versus 6.0 days in the concomitant group. Patients in the concomitant group reached stable goal concentrations earlier than those in the delayed group (hazard ratio: 0.27, 95% CI: 0.14-0.5, P<0.001), after adjusting for age, sex, and race. The delayed group was estimated to have concentrations outside of goal range at almost 2 times the rate in the concomitant group (P<0.001), after adjusting for age, sex, and race. Thus, we conclude that concomitant initiation of sirolimus and azoles may facilitate the achievement of stable goal sirolimus concentrations sooner after allogeneic cell transplant.