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.