Interaksi Posakonazol dan Takrolimus

Nephrotoxicity and leukoencephalopathy (including deaths) have been reported in clinical efficacy studies in patients with elevated cyclosporine or tacrolimus concentrations.

Frequent monitoring of tacrolimus or cyclosporine whole blood trough concentrations should be performed during and at discontinuation of Noxafil treatment and the tacrolimus or cyclosporine dose adjusted accordingly.

Tacrolimus • At initiation of posaconazole treatment, reduce the tacrolimus dosage to approximately one-third of the original tacrolimus dosage.

• Frequent monitoring of tacrolimus whole blood trough concentrations should be performed during and at discontinuation of posaconazole treatment and the tacrolimus dosage should be modified accordingly [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3) ] .

Calcineurin-Inhibitor Toxicity : Noxafil increases concentrations of cyclosporine or tacrolimus; reduce dose of cyclosporine and tacrolimus and monitor concentrations frequently.

Reduce ASTAGRAF XL dose (for voriconazole and posaconazole, give one-third of the original dose) and adjust dose based on tacrolimus whole blood trough concentrations [see Dosage and Administration ( 2.3 , 2.4 ) and Clinical Pharmacology ( 12.3 )].

The risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors).

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection.

In contrast, the concomitant use of strong CYP3A inhibitors may decrease the metabolism of tacrolimus, leading to higher whole blood trough concentrations and greater risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and Precautions ( 5.7 , 5.11 )] .

Therefore, adjust ASTAGRAF XL dose and monitor tacrolimus whole blood trough concentrations when co-administering ASTAGRAF XL with strong CYP3A inhibitors (e.g., including, but not limited to, telaprevir, boceprevir, ritonavir, ketoconazole, itraconazole, voriconazole, clarithromycin) or strong CYP3A inducers (e.g., including, but not limited to, rifampin, rifabutin)…