ould resolve following drug withdrawal. General supportive measures and symptomatic treatment should be followed in all cases of overdosage. Cyclosporine is not dialyzable to any great extent, nor is it cleared well by charcoal hemoperfusion. The oral dosage at which half of experimental animals are estimated to die is 31 times, 39 times and > 54 times the human maintenance dose for transplant patients (6 mg/kg; corrections based on body surface area) in mice, rats, and rabbits.
DOSAGE AND ADMINISTRATION
Gengraf (cyclosporine oral solution, USP [MODIFIED]) has increased bioavailability in comparison to Sandimmune®. Gengraf and Sandimmune® are not bioequivalent and cannot be used interchangeably without physician supervision.
The daily dose of Gengraf (cyclosporine oral solution, USP [MODIFIED]) should always be given in two divided doses (BID). It is recommended that Gengraf 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.
Newly Transplanted Patients
The initial oral dose of Gengraf (cyclosporine oral solution, USP [MODIFIED]) can be given 4-12 hours prior to transplantation or be given postoperatively. The initial dose of Gengraf varies depending on the transplanted organ and the other immunosuppressive agents included in the immunosuppressive protocol. In newly transplanted patients, the initial oral dose of Gengraf is the same as the initial oral dose of Sandimmune®. Suggested initial doses are available from the results of a 1994 survey of the use of Sandimmune® in U.S. transplant centers. The mean ± SD initial doses were 9 ± 3 mg/kg/day for renal transplant patients (75 centers), 8 ± 4 mg/kg/day for liver transplant patients (30 centers), and 7 ± 3 mg/kg/day for heart transplant patients (24 centers). Total daily doses were divided into two equal daily doses. The Gengraf dose is subsequently adjusted to achieve a pre-defined cyclosporine blood concentration (see DOSAGE AND ADMINISTRATION -Blood Concentration Monitoring in Transplant Patients, below). If cyclosporine trough blood concentrations are used, the target range is the same for Gengraf as for Sandimmune®. Using the same trough concentration target range for Gengraf as for Sandimmune® results in greater cyclosporine exposure when Gengraf is administered (see CLINICAL PHARMACOLOGY -Pharmacokinetics, Absorption). Dosing should be titrated based on clinical assessments of rejection and tolerability. Lower Gengraf doses may be sufficient as maintenance therapy.
Adjunct therapy with adrenal corticosteroids is recommended initially. Different tapering dosage schedules of prednisone appear to achieve similar results. A representative dosage schedule based on the patient's weight started with 2 mg/kg/day for the first 4 days tapered to 1 mg/kg/day by 1 week, 0.6 mg/kg/day by 2 weeks, 0.3 mg/kg/day by 1 month, and 0.15 mg/kg/day by 2 months and thereafter as a maintenance dose. Steroid doses may be further tapered on an individualized basis depending on status of patient and function of graft. Adjustments in dosage of prednisone must be made according to the clinical situation.
Conversion From Sandimmune®* (Cyclosporine Oral Solution) To Gengraf (Cyclosporine Oral S
