Should tacrolimus dose be reduced upon posaconazole initiation in transplant patients?

A recent study has proven the feasibility of an empiric 50-percent dose reduction of oral tacrolimus to 0.03 mg/kg/day when used together with posaconazole to achieve therapeutic levels in patients receiving an allogeneic stem cell transplant.

This retrospective chart review at an academic medical centre sought to determine whether tacrolimus doses should be reduced upon initiation of posaconazole in allogeneic stem cell transplant patients. All transplant recipients who were treated with concomitant posaconazole and tacrolimus from February 2016 through December 2017 were included in the analysis.

An internal electronic database was used to identify 79 patients. Those who did not receive an empiric dose reduction had significantly longer median time to therapeutic tacrolimus concentration (dose reduction: 0 percent, 10 d; 1–30 percent, 4 d; 31–65 percent, 5 d; >65 percent, 4 d; p=0.0395).

Patients who did not receive an empiric dose reduction also had the highest rate of supratherapeutic levels, which was found to be substantial compared to those receiving 31–65-percent dose reduction (p<0.001).

Posaconazole lowers the risk of invasive Aspergillus in transplant recipients, according to the investigators. However, it also significantly inhibits tacrolimus metabolism.

“One study demonstrated that a threefold dose reduction of tacrolimus was required to obtain therapeutic concentrations when used with posaconazole,” they said. “However, with empiric dose reduction, there is a risk of subtherapeutic tacrolimus levels and subsequent graft failure or graft-versus-host disease.”