التداخل بين دارونافير وكوبيسيستات وتاكروليموس

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)…

A rapid, sharp rise in tacrolimus levels has been reported after co-administration with a strong CYP3A4 inhibitor, clarithromycin, despite an initial reduction of tacrolimus dose.

Therapeutic drug monitoring is recommended with concomitant use Immunosuppressant /neoplastic: everolimus ↑ immunosuppressants Co-administration of everolimus and PREZCOBIX or PREZCOBIX PED is not recommended. irinotecan Discontinue PREZCOBIX or PREZCOBIX PED at least 1 week prior to starting irinotecan therapy.

Immunosuppressants: cyclosporine, sirolimus, tacrolimus ↑ immunosuppressants These immunosuppressant agents are metabolized by CYP3A.