Mycophenolatedosage

­ADULTS DOSAGE Kidney Transplant 1 g twice daily, orally Heart Transplant 1.5 g twice daily orally Liver Transplant 1.5 g twice daily orally PEDIATRICS Kidney Transplant 600 mg/m 2 orally twice daily, up to maximum of 2 g daily Heart Transplant 600 mg/m 2 orally twice daily (starting dose) up to a maximum of 900 mg/m 2 twice daily (3 g or 15 mL of oral suspension) Liver Transplant 600 mg/m 2 orally twice daily (starting dose) up to a maximum of 900 mg/m 2 twice daily (3 g or 15 mL of oral suspension) CELLCEPT Intravenous is an alternative when patients cannot tolerate oral medication. Administer within 24 hours following transplantation, until patients can tolerate oral medication, up to 14 days. Reduce or interrupt dosing in the event of neutropenia. See full prescribing information (FPI) for: adjustments for renal impairment and neutropenia, preparation of oral suspension.

2.1 Important

Administration Instructions Mycophenolate mofetil for oral suspension should not be used without the supervision of a physician with experience in immunosuppressive therapy. Mycophenolate mofetil for Oral Suspension Mycophenolate mofetil oral dosage forms (capsules, tablets or oral suspension) should not be used interchangeably with mycophenolic acid delayed-release tablets without supervision of a physician with experience in immunosuppressive therapy because the rates of absorption following the administration of mycophenolate mofetil oral dosage forms and mycophenolic acid delayed-release tablets are not equivalent. CELLCEPT tablets should not be crushed and CELLCEPT capsules should not be opened or crushed. Patients should avoid inhalation or contact of the skin or mucous membranes with the powder contained in CELLCEPT capsules and oral suspension. If such contact occurs, they must wash the area of contact thoroughly with soap and water. In case of ocular contact, rinse eyes with plain water. The initial oral dose of mycophenolate mofetil for oral suspension should be given as soon as possible following kidney, heart or liver transplant. It is recommended that mycophenolate mofetil for oral suspension be administered on an empty stomach. In stable transplant patients, however, mycophenolate mofetil for oral suspension may be administered with food if necessary. Once reconstituted, mycophenolate mofetil for oral suspension must not be mixed with any liquids prior to dose administration. If needed, mycophenolate mofetil for oral suspension can be administered via a nasogastric tube with a minimum size of 8 French (minimum 1.7 mm interior diameter). Patients should be instructed to take a missed dose as soon as they remember, except if it is closer than 2 hours to the next scheduled dose; in this case, they should continue to take mycophenolate mofetil for oral suspension at the usual times. CELLCEPT Intravenous CELLCEPT Intravenous is recommended for patients unable to take oral mycophenolate mofetil. CELLCEPT Intravenous should be administered within 24 hours following transplant. CELLCEPT Intravenous can be administered for up to 14 days; however, patients should be switched to oral mycophenolate mofetil as soon as they can tolerate oral medication.

2.2 Dosage Recommendations for

Kidney Transplant Patients Adults The recommended dosage for adult kidney transplant patients is 1 g orally, twice daily (total daily dose of 2 g). Pediatrics (3 months and older) Pediatric dosing is based on body surface area (BSA). The recommended dosage of mycophenolate mofetil for oral suspension for pediatric kidney transplant patients 3 months and older is 600 mg/m 2, administered twice daily (maximum total daily dose of 2 g or 10 mL of the oral suspension). Pediatric patients with BSA ≥ 1.25 m 2 may be dosed with capsules or tablets as follows: Table 1 Pediatric Kidney Transplant: Dosage Using Capsules or Tablets Body Surface Area Dosage 1.25 m 2 to ˂1.5 m 2 CELLCEPT capsule 750 mg twice daily (1.5 g total daily dose) ≥ 1.5 m 2 CELLCEPT capsules or tablets 1 g twice daily (2 g total daily dose)

2.3 Dosage Recommendations for

Heart Transplant Patients Adults The recommended dosage of mycophenolate mofetil for oral suspension for adult heart transplant patients is 1.5 g orally administered twice daily (total daily dose of 3 g). Pediatrics (3 months and older) The recommended starting dosage of mycophenolate mofetil for oral suspension for pediatric heart transplant patients 3 months and older is 600 mg/m 2, administered twice daily. If well tolerated, the dose can be increased to a maintenance dosage of 900 mg/m 2 twice daily (maximum total daily dose of 3 g or 15 mL of the oral suspension). The dose may be individualized based on clinical assessment. Pediatric patients with BSA ≥1.25 m 2 may be started on therapy with capsules or tablets as follows: Table 2 Pediatric Heart Transplant: Pediatric Starting Dosage Using Capsules or Tablets * Maximum maintenance dose: 3 g total daily. Body Surface Area Starting Dosage * 1.25 m 2 to ˂1.5 m 2 CELLCEPT capsule 750 mg twice daily (1.5 g total daily dose) ≥ 1.5 m 2 CELLCEPT capsules or tablets 1 g twice daily (2 g total daily dose)

2.4 Dosage Recommendations for

Liver Transplant Patients Adults The recommended dosage of mycophenolate mofetil for oral suspension for adult liver transplant patients is 1.5 g administered orally twice daily (total daily dose of 3 g). Pediatrics (3 months and older) The recommended starting dosage of mycophenolate mofetil for oral suspension for pediatric liver transplant patients 3 months of age and older is 600 mg/m 2, administered twice daily. If well tolerated, the dose can be increased to a maintenance dosage of 900 mg/m 2 twice daily (maximum total daily dose of 3 g or 15 mL of the oral suspension). The dose may be individualized based on clinical assessment. Pediatric patients with BSA ≥1.25 m 2 may be started on therapy with capsules or tablets as follows: Table 3 Pediatric Liver Transplant: Pediatric Starting Dosage Using Capsules or Tablets * Maximum maintenance dose: 3 g total daily. Body Surface Area Starting Dosage * 1.25 m 2 to ˂1.5 m 2 CELLCEPT capsule 750 mg twice daily (1.5 g total daily dose) ≥ 1.5 m 2 CELLCEPT capsules or tablets 1 g twice daily (2 g total daily dose)

2.5 Dosage Modifications:

Patients with Renal Impairment, Neutropenia Renal Impairment No dosage modifications are needed in kidney transplant patients with delayed graft function postoperatively. In kidney transplant patients with severe chronic impairment of the graft (GFR <25 mL/min/1.73 m 2 ), do not administer doses of mycophenolate mofetil for oral suspension greater than 1 g twice a day. These patients should be carefully monitored. Neutropenia If neutropenia develops (ANC <1.3 x 10 3 /μL), dosing with mycophenolate mofetil for oral suspension should be interrupted or reduced, appropriate diagnostic tests performed, and the patient managed appropriately.

2.6 Preparation

Instructions of Oral Suspension for Pharmacists General Preparation Instructions Before Handling the Formulations Mycophenolate mofetil (MMF) has demonstrated teratogenic effects in humans. Follow applicable special handling and disposal procedures 1. Care should be taken to avoid inhalation or direct contact with skin or mucous membranes of the dry powder or the constituted suspension because MMF has demonstrated teratogenic effects in humans. Wearing disposable gloves is recommended during reconstitution and when wiping the outer surface of the bottle/cap and the table surface after reconstitution. If such contact occurs, wash hands thoroughly with soap and water; rinse eyes with water. Alert patients that they and others should also avoid inhalation or contact of the skin or mucous membranes with the oral suspension. Advise them to wash the area thoroughly with soap and water if such contact occurs; if ocular contact occurs, rinse eyes with plain water. Mycophenolate Mofetil for Oral Suspension Mycophenolate mofetil for oral suspension must be reconstituted by the pharmacist prior to dispensing to the patient. Mycophenolate mofetil for oral suspension should not be mixed with any other medication. After reconstitution, the oral suspension contains 200 mg/mL MMF. Before proceeding with the reconstitution steps read the general preparation instructions above. The following are the steps for reconstitution: Tap the closed bottle several times to loosen the powder. Measure 94 mL of water in a graduated cylinder. Add approximately half the total amount of water for reconstitution to the bottle and shake the closed bottle well for about 1 minute. Add the remainder of water and shake the closed bottle well for about 1 minute. Remove the child-resistant cap and push bottle adapter into neck of bottle. Close bottle with child-resistant cap tightly. This will assure the proper seating of the bottle adapter in the bottle and child-resistant status of the cap. Write the date of expiration of the constituted suspension on the bottle label. (The shelf-life of the constituted suspension is 60 days.) Dispense with the “Instruction for Use” and oral dispensers. Alert patients to read the important handling information described in the instructions for use. Store reconstituted suspension at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Storage in a refrigerator at 2°C to 8°C (36°F to 46°F) is acceptable. Do not freeze. Discard any unused portion 60 days after constitution.