Malignancies and Serious Infections; Kidney Graft Thrombosis; Nephrotoxicity; and Mortality in Heart Transplantation

Malignancies and Serious Infections

• Increased susceptibility to infection and the possible development of malignancies such as lymphoma and skin cancer may result from immunosuppression. [See Warnings and Precautions]
• Only physicians experienced in immunosuppression therapy and management of transplant patients should prescribe this agent.  The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient. [See Warnings and Precautions]
• Patient receiving this drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources.

Nephrotoxicity

• Increased nephrotoxicity can occur with the use of standard doses of cyclosporine in combination with everolimus. Therefore reduced doses of cyclosporine should be used in combination with everolimus in order to reduce renal dysfunction.
• It is important to monitor the cyclosporine and everolimus whole blood trough concentrations. [See Dosage and Administration, Warnings and Precautions, Clinical Pharmacology]

 Kidney Graft Thrombosis

• An increased risk of kidney arterial and venous thrombosis, resulting in graft loss, was reported, mostly within the first 30 days post-transplantation. [See Warnings and Precautions]

 Mortality in Heart Transplantation

• Increased mortality, often associated with serious infections, within the first three months post-transplantation was observed in a clinical trial of de novo heart transplant patients receiving immunosuppressive regimens with or without induction therapy. Use in heart transplantation is not recommended. [See Warnings and Precautions]