Cyclosporine

Only physicians experienced in management of systemic immunosuppressive therapy for the indicated disease should prescribe cyclosporine capsules, USP MODIFIED. At doses used in solid organ transplantation, only physicians experienced in immunosuppressive therapy and management of organ transplant recipients should prescribe cyclosporine capsules, USP MODIFIED. Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient.

Cyclosporine capsules, USP MODIFIED, a systemic immunosuppressant, may increase the susceptibility to infection and the development of neoplasia. In kidney, liver, and heart transplant patients cyclosporine capsules, USP MODIFIED may be administered with other immunosuppressive agents. Increased susceptibility to infection and the possible development of lymphoma and other neoplasms may result from the increase in the degree of immunosuppression in transplant patients.

Cyclosporine capsules, USP MODIFIED have increased bioavailability in comparison to Sandimmune^® (cyclosporine capsules, USP). Cyclosporine capsules, USP MODIFIED and Sandimmune (cyclosporine capsules, USP) are not bioequivalent and cannot be used interchangeably without physician supervision. For a given trough concentration, cyclosporine exposure will be greater with cyclosporine capsules, USP MODIFIED than with Sandimmune (cyclosporine capsules, USP). If a patient who is receiving exceptionally high doses of Sandimmune (cyclosporine capsules, USP) is converted to cyclosporine capsules, USP MODIFIED, particular caution should be exercised. Cyclosporine blood concentrations should be monitored in transplant and rheumatoid arthritis patients taking cyclosporine capsules, USP MODIFIED to avoid toxicity due to high concentrations. Dose adjustments should be made in transplant patients to minimize possible organ rejection due to low concentrations. Comparison of blood concentrations in the published literature with blood concentrations obtained using current assays must be done with detailed knowledge of the assay methods employed (see

Cyclosporine capsules, USP MODIFIED are indicated for the prophylaxis of organ rejection in kidney, liver, and heart allogeneic transplants. Cyclosporine capsules, USP MODIFIED have been used in combination with azathioprine and corticosteroids.

The daily dose of cyclosporine capsules, USP MODIFIED should always be given in two divided doses (BID). It is recommended that cyclosporine capsules, USP MODIFIED be administered on a consistent schedule with regard to time of day and relation to meals. Grapefruit and grapefruit juice affect metabolism, increasing blood concentration of cyclosporine, thus should be avoided.

In a study performed in 4 subjects with end-stage renal disease (creatinine clearance < 5 mL/min), an intravenous infusion of 3.5 mg/kg of cyclosporine over 4 hours administered at the end of a hemodialysis session resulted in a mean volume of distribution (Vdss) of 3.49 L/kg and systemic clearance (CL) of 0.369 L/hr/kg. This systemic CL (0.369 L/hr/kg) was approximately two thirds of the mean systemic CL (0.56 L/hr/kg) of cyclosporine in historical control subjects with normal renal function. In 5 liver transplant patients, the mean clearance of cyclosporine on and off hemodialysis was 463 mL/min and 398 mL/min, respectively. Less than 1% of the dose of cyclosporine was recovered in the dialysate.

The principal adverse reactions of cyclosporine therapy are renal dysfunction, tremor, hirsutism, hypertension, and gum hyperplasia.