Hints for individualization of TAC dosage
One TAC trough level adaption step is defined as 2 ng/mL (investigators are allowed to target a range of ± 1 ng/mL; thus one step might be within a minimum of 1 ng/mL and a maximum of 3 ng/mL). This allows for additional individualization and accounts for limited granularity of TAC dosage formulation. Additional individualization might be necessary in the following clinical scenarios: Absolute changes in TAC dose might have different effect sizes on the TTV load. A change >20% in TAC dose is expected to show significant changes in the TTV load. Thus the upper range of 3 ng/mL might be targeted in case of high TAC intake and the lower range of 1 ng/ml in case of low TAC intake. Significant changes in TTV load are expected 6 weeks (= 1 visit) after a significant change in immunosuppression has been performed. However, the full effect might take up to 12 weeks (= 2 visits). If a change in the TAC target has been performed at the visit before and another TAC change in the same direction is suggested at the current visit, the lower TAC step range of 1 ng/mL might be targeted. Simultaneous relevant changes in immunosuppression other than TAC might influence the subsequent TTV load and the risk of infection/rejection, e.g. if mycophenolic acid has to be stopped and the TTV load indicates a TAC decrease, a TAC target change of 1 ng/mL might be performed. The peak TTV level is at month 3 to 4 post-transplantation; thereafter, the TTV load shows a gentle decline towards month 12 post-transplantation. If the TTV load indicates a reduction in the TAC target at visit 1, but the TAC level is within the local centre range, a TAC target reduction of 1 ng/mL might be performed.