Drug interactions between Noxafil and Prograf

ADJUST DOSE: Coadministration with posaconazole may significantly increase the plasma concentrations of tacrolimus. The proposed mechanism is posaconazole inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of tacrolimus. In healthy subjects, pretreatment with posaconazole suspension (400mg twice a day for 7 days) increased the mean peak plasma concentration (Cmax) and systemic exposure (AUC) of a single 0.05 mg/kg dose of tacrolimus by 121% and 358%, respectively. Pharmacodynamically, posaconazole and tacrolimus may have additive effects on QT interval prolongation, which can increase the risk of torsade de pointes arrhythmia. In addition, rare cases of hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and pulmonary embolus have been reported in patients receiving posaconazole and tacrolimus for management of transplant rejection or graft-versus-host disease.

MANAGEMENT: Caution is advised if tacrolimus is used in combination with posaconazole. In patients already receiving tacrolimus, the dosage should be reduced to approximately one-third of the original dosage upon initiation of posaconazole treatment. Tacrolimus blood levels should be closely monitored and the dosage adjusted accordingly, particularly following initiation or discontinuation of posaconazole therapy in patients who are stabilized on their anti-rejection regimen. Patients should be advised to seek medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, palpitations, or syncope.