Cyclosporine and Sirolimus interaction

In kidney, liver, and heart transplant patients Neoral may be administered with other immunosuppressive agents.

For Psoriasis Patients (see also BOXED WARNING above) Psoriasis patients previously treated with PUVA and to a lesser extent, methotrexate or other immunosuppressive agents, UVB, coal tar, or radiation therapy, are at an increased risk of developing skin malignancies when taking Neoral.

Psoriasis Psoriasis patients who are treated with Neoral should not receive concomitant PUVA or UVB therapy, methotrexate or other immunosuppressive agents, coal tar or radiation therapy.

Cyclosporine may reduce the clearance of digoxin, colchicine, prednisolone, HMG-CoA reductase inhibitors (statins), aliskiren, bosentan, dabigatran, repaglinide, NSAIDs, sirolimus, etoposide, and other drugs.

Sirolimus Elevations in serum creatinine were observed in studies using sirolimus in combination with full-dose cyclosporine.

In this and another study in de novo liver transplant patients, the use of sirolimus in combination with cyclosporine or tacrolimus was associated with an increase in HAT; most cases of HAT occurred within 30 days post-transplantation and most led to graft loss or death [ see Warnings and Precautions (5.2) ].

In a multicenter clinical study, de novo renal transplant patients treated with sirolimus, mycophenolate mofetil (MMF), steroids, and an IL-2 receptor antagonist had significantly higher acute rejection rates and numerically higher death rates compared to patients treated with cyclosporine, MMF, steroids, and IL-2 receptor antagonist.

Interaction with Strong Inhibitors and Inducers of CYP3A4 and/or P-gp Avoid concomitant use of sirolimus with strong inhibitors of CYP3A4 and/or P-gp (such as ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, or clarithromycin) or strong inducers of CYP3A4 and/or P-gp (such as rifampin or rifabutin) [ see Drug Interactions (7.2) ].

• Avoid concomitant use with strong CYP3A4/P-gp inducers or strong CYP3A4/P-gp inhibitors that decrease or increase sirolimus concentrations ( 7.4 , 12.3 ).

Strong Inducers and Strong Inhibitors of CYP3A4 and P-gp Avoid concomitant use of sirolimus with strong inducers (e.g., rifampin, rifabutin) and strong inhibitors (e.g., ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, clarithromycin) of CYP3A4 and P-gp.