Mycophenolate

CELLCEPT [mycophenolate mofetil (MMF)] is indicated for the prophylaxis of organ rejection, in adult and pediatric recipients 3 months of age and older of allogeneic kidney, heart or liver transplants, in combination with other immunosuppressants. CELLCEPT is an antimetabolite immunosuppressant indicated for the prophylaxis of organ rejection in adult and pediatric recipients 3 months of age and older of allogeneic kidney, heart or liver transplants, in combination with other immunosuppressants.

Mycophenolate mofetil (MMF) is absorbed following oral administration and hydrolyzed to mycophenolic acid (MPA), the active metabolite. MPA is a selective uncompetitive inhibitor of the two isoforms (type I and type II) of inosine monophosphate dehydrogenase (IMPDH) leading to inhibition of the de novo pathway of guanosine nucleotide synthesis and blocks DNA synthesis. The mechanism of action of MPA is multifaceted and includes effects on cellular checkpoints responsible for metabolic programming of lymphocytes. MPA shifts transcriptional activities in lymphocytes from a proliferative state to catabolic processes.

ADULTS DOSAGE Kidney Transplant 1 g twice daily, orally or intravenously (IV) over no less than 2 h. Heart Transplant 1.5 g twice daily orally or IV, over no less than 2 h. Liver Transplant 1.5 g twice daily orally or 1g twice daily IV over no less than 2 h. 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.

CELLCEPT is contraindicated in patients with a history of hypersensitivity, including anaphylaxis, to mycophenolate mofetil (MMF), mycophenolic acid (MPA) or any component of the drug product. CELLCEPT Intravenous is contraindicated in patients who are allergic to Polysorbate 80 (TWEEN). History of hypersensitivity, including anaphylaxis, to mycophenolate mofetil, mycophenolic acid or any component of the drug product. Patients allergic to Polysorbate 80 (present in CELLCEPT IV)

Boxed warning (embryofetal toxicity, malignancies and serious infections): Use during pregnancy is associated with increased risks of first trimester pregnancy loss and congenital malformations. Avoid if safer treatment options are available. Females of reproductive potential must be counseled regarding pregnancy prevention and planning. Increased risk of development of lymphoma and other malignancies, particularly of the skin. Blood Dyscrasias (Neutropenia, Red Blood Cell Aplasia): Monitor with blood tests, consider treatment interruption or dose reduction. Gastrointestinal Complications: Monitor for complications such as bleeding, ulceration and perforations, particularly in patients with underlying gastrointestinal disorders. Hypoxanthine-Guanine Phosphoribosyl-Transferase Deficiency: Avoid use of CELLCEPT.

The following adverse reactions are discussed in greater detail in other sections of the label: Embryofetal Toxicity Lymphomas and Other Malignancies Serious Infections Blood Dyscrasias: Neutropenia, Pure Red Cell Aplasia Gastrointestinal Complications Acute Inflammatory Syndrome Associated with Mycophenolate Products Hypersensitivity Reactions The most common adverse reactions in clinical trials (20 % or greater) include diarrhea, leukopenia, infection, vomiting, and there is evidence of a higher frequency of certain types of infections e.g., opportunistic infection. com

See FPI for drugs that may interfere with systemic exposure and reduce CELLCEPT efficacy: antacids with magnesium or aluminum hydroxide, proton pump inhibitors, drugs that interfere with enterohepatic recirculation, telmisartan, calcium-free phosphate binders. CELLCEPT may reduce effectiveness of oral contraceptives. Use of additional barrier contraceptive methods is recommended. See FPI for other important drug interactions.

Storage Store at 25°C (77°F), excursions permitted to 15°C to 30°C (59°F to 86°F) CELLCEPT (mycophenolate mofetil tablets) 500 mg Tablets Lavender-colored, caplet-shaped, film-coated tablets engraved with "CELLCEPT 500" on one side and "Roche" on the other Sizes Bottle of 100 NDC 0004-0260-01 Bottle of 500 NDC 0004-0260-43 Storage and Dispensing Information: Store at 25°C (77°F), excursions permitted to 15°C to 30°C (59°F to 86°F).