CELLCEPT Powder for concentrate for solution for infusion Ref.[8145] Active ingredients: Mycophenolate mofetil

Treatment with CellCept should be initiated and maintained by appropriately qualified transplant specialists.

CAUTION: CELLCEPT I.V. SOLUTION MUST NOT BE ADMINISTERED BY RAPID OR BOLUS INTRAVENOUS INJECTION.

Posology

CellCept 500 mg powder for concentrate for solution for infusion is an alternative dosage form to CellCept oral forms (capsules, tablets and powder for oral suspension) that may be administered for up to 14 days. The initial dose of CellCept 500 mg powder for concentrate for solution for infusion should be given within 24 hours following transplantation.

Renal transplant

The recommended dose in renal transplant patients is 1 g administered twice daily (2 g daily dose).

Hepatic transplant

The recommended dose of CellCept for infusion in hepatic transplant patients is 1 g administered twice daily (2 g daily dose). IV CellCept should continue for the first 4 days following hepatic transplant, with oral CellCept initiated as soon after this as it can be tolerated. The recommended dose of oral CellCept in hepatic transplant patients is 1.5 g administered twice daily (3 g daily dose).

Use in special populations

Paediatric population

Safety and efficacy of CellCept for infusion in paediatric patients have not been established. No pharmacokinetic data with CellCept for infusion are available for paediatric renal transplant patients. No pharmacokinetic data are available for paediatric patients following hepatic transplants.

Elderly

The recommended dose of 1 g administered twice a day for renal or hepatic transplant patients is appropriate for the elderly.

Renal impairment

In renal transplant patients with severe chronic renal impairment (glomerular filtration rate <25 mL/min/1.73 m²), outside the immediate post-transplant period, doses greater than 1 g administered twice a day should be avoided. These patients should also be carefully observed. No dose adjustments are needed in patients experiencing delayed renal graft function post-operatively (see section 5.2). No data are available for hepatic transplant patients with severe chronic renal impairment.

Severe hepatic impairment

No dose adjustments are needed for renal transplant patients with severe hepatic parenchymal disease. Treatment during rejection episodes

Mycophenolic acid (MPA) is the active metabolite of mycophenolate mofetil. Renal transplant rejection does not lead to changes in MPA pharmacokinetics; dosage reduction or interruption of CellCept is not required. No pharmacokinetic data are available during hepatic transplant rejection.

Paediatric population

No data are available for treatment of first or refractory rejection in paediatric transplant patients.

Method of administration

Following reconstitution to a concentration of 6 mg/mL, CellCept 500 mg powder for concentrate for solution for infusion must be administered by slow intravenous infusion over a period of 2 hours by either a peripheral or a central vein (see section 6.6).

Precautions to be taken before handling or administering the medicinal product Because mycophenolate mofetil has demonstrated teratogenic effects in rats and rabbits, avoid direct contact of the dry powder or prepared solutions of CellCept 500 mg powder for concentrate for solution for infusion with skin or mucous membranes. If such contact occurs, wash thoroughly with soap and water; rinse eyes with plain water.

For instructions on reconstitution and dilution of the medicinal product before administration, see section 6.6.

Reports of overdoses with mycophenolate mofetil have been received from clinical trials and during post-marketing experience. In many of these cases, no adverse events were reported. In those overdose cases in which adverse events were reported, the events fall within the known safety profile of the medicinal product.

It is expected that an overdose of mycophenolate mofetil could possibly result in over suppression of the immune system and increase susceptibility to infections and bone marrow suppression (see section 4.4). If neutropenia develops, dosing with CellCept should be interrupted or the dose reduced (see section 4.4).

Haemodialysis would not be expected to remove clinically significant amounts of MPA or MPAG. Bile acid sequestrants, such as cholestyramine, can remove MPA by decreasing the enterohepatic recirculation of the drug (see section 5.2).

Powder for concentrate for solution for infusion: 3 years.

Reconstituted solution and infusion solution: If the infusion solution is not prepared immediately prior to administration, the commencement of administration of the infusion solution should be within 3 hours from reconstitution and dilution of the medicinal product.

Powder for concentrate for solution for infusion: Do not store above 30°C.

Reconstituted solution and infusion solution: Store at 15–30°C.

20 mL type I clear glass vials with grey butyl rubber stopper and aluminium seals with plastic flip-off caps. CellCept 500 mg powder for concentrate for solution for infusion is available in packs containing 4 vials.

Preparation of Infusion Solution (6 mg/mL)

CellCept 500 mg powder for concentrate for solution for infusion does not contain an antibacterial preservative; therefore, reconstitution and dilution of the product must be performed under aseptic conditions.

CellCept 500 mg powder for concentrate for solution for infusion must be prepared in two steps: the first step is a reconstitution step with glucose intravenous infusion 5% and the second step is a dilution step with glucose intravenous infusion 5%. A detailed description of the preparation is given below:

Step 1:

a. Two vials of CellCept 500 mg powder for concentrate for solution for infusion are used for preparing each 1 g dose. Reconstitute the content of each vial by injecting 14 mL of glucose intravenous infusion 5%.
b. Gently shake the vial to dissolve the medicinal product yielding a slightly yellow solution.
c. Inspect the resulting solution for particulate matter and discoloration prior to further dilution. Discard the vial if particulate matter or discoloration is observed.

Step 2:

a. Further dilute the content of the two reconstituted vials (approx. 2 × 15 mL) into 140 mL of glucose intravenous infusion 5%. The final concentration of the solution is 6 mg/mL mycophenolate mofetil.
b. Inspect the infusion solution for particulate matter or discoloration. Discard the infusion solution if particulate matter or discoloration is observed.

If the infusion solution is not prepared immediately prior to administration, the commencement of administration of the infusion solution should be within 3 hours from reconstitution and dilution of the medicinal product. Keep solutions at 15 – 30°C.

Any unused product or waste material should be disposed of in accordance with local requirements.