Effects of routes, concentrations and genetic polymorphisms on posaconazole-tacrolimus interactions in allogeneic haematopoietic cell transplantation.

There is no prospective research on factors influencing posaconazole (PSCZ)-tacrolimus (TAC) interactions. This prospective observational study analysed 30 allogeneic haematopoietic cell transplantation recipients: 19 started PSCZ while receiving oral (n = 10) or intravenous (IV) TAC (n = 9) and 11 switched from IV to oral TAC during PSCZ administration. Following PSCZ initiation, the median TAC dose reductions were 45% for oral and 39% for IV TAC. Oral TAC concentration-to-dose ratios (C/D) significantly increased over 2 weeks (P < .01) and correlated with PSCZ concentrations (ρ = 0.92, P < .01), whereas IV TAC C/D showed no significant changes or correlations. The median IV to oral TAC conversion ratio was 2.86. Linear regression analyses revealed significant associations between PSCZ concentrations and oral TAC C/D changes, CYP3A5 polymorphisms and IV TAC C/D changes, and CYP3A5 polymorphisms and TAC conversion ratios. TAC route, PSCZ concentrations and genetic polymorphisms may influence PSCZ-TAC interactions.