General Information

CellCept (mycophenolate mofetil) is an antimetabolite immunosuppressant.

CellCept is specifically indicated for the prophylaxis of organ rejection in recipients of allogeneic kidney, heart or liver transplants, and should be used in combination with other immunosuppressants.

CellCept is supplied as capsules, tablets and an oral suspension. 

CellCept oral dosage forms (capsules, tablets or oral suspension)

CellCept 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 CellCept 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 CellCept should be given as soon as possible following kidney, heart or liver transplant. It is recommended that CellCept be administered on an empty stomach. In stable transplant patients, however, CellCept may be administered with food if necessary. Once reconstituted, CellCept Oral Suspension must not be mixed with any liquids prior to dose administration. If needed, CellCept 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 CellCept at the usual times.

CellCept Intravenous

CellCept Intravenous is recommended for patients unable to take oral CellCept . 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 CellCept as soon as they can tolerate oral medication. CellCept Intravenous must be reconstituted before use. CellCept Intravenous is incompatible with other intravenous infusion solutions and should not be mixed or administered concurrently via the same infusion catheter with other intravenous drugs or infusion admixtures. CellCept Intravenous must not be administered as a bolus. Following reconstitution, CellCept Intravenous must be administered by slow intravenous infusion over a period of no less than 2 hours by either peripheral or central vein, as rapid infusion increases the risk of local adverse reactions such as phlebitis and thrombosis.

Dosing for Kidney Transplant Patients:

Adults and Pediatrics

• Adults: The recommended dose for adult kidney transplant patients is 1 g orally or intravenously infused over no less than 2 hours, twice daily (daily dose of 2 g). Pediatrics (3 months and older) Pediatric dosing is based on body surface area (BSA). The recommended dose of CellCept oral suspension for pediatric kidney transplant patients 3 months and older is 600 mg/m2 , administered twice daily (maximum daily dose of 2g or 10 mL of the oral suspension).
• Pediatric patients with BSA ≥ 1.25 m2 may be dosed with capsules or tablets as follows:

Dosing for Heart Transplant Patients:

Adults: The recommended dose of CellCept for adult heart transplant patients is 1.5 g orally or intravenously infused over no less than 2 hours administered twice daily (daily dose of 3 g).

Dosing for Liver Transplant Patients:

Adults: The recommended dose of CellCept for adult liver transplant patients is 1.5 g administered orally twice daily (daily dose of 3 g) or 1 g infused intravenously over no less than 2 hours, twice daily (daily dose of 2 g).

Mechanism of Action

CellCept (mycophenolate mofetil) is an antimetabolite immunosuppressant. Mycophenolate mofetil (MMF) is absorbed following oral administration and hydrolyzed to mycophenolic acid (MPA), the active metabolite. MPA is a selective, uncompetitive, and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), and therefore inhibits the de novo pathway of guanosine nucleotide synthesis without incorporation into DNA. Because T- and B-lymphocytes are critically dependent for their proliferation on de novo synthesis of purines, whereas other cell types can utilize salvage pathways, MPA has potent cytostatic effects on lymphocytes. MPA inhibits proliferative responses of T- and B-lymphocytes to both mitogenic and allospecific stimulation. Addition of guanosine or deoxyguanosine reverses the cytostatic effects of MPA on lymphocytes. MPA also suppresses antibody formation by B-lymphocytes. MPA prevents the glycosylation of lymphocyte and monocyte glycoproteins that are involved in intercellular adhesion to endothelial cells and may inhibit recruitment of leukocytes into sites of inflammation and graft rejection. MMF did not inhibit early events in the activation of human peripheral blood mononuclear cells, such as the production of interleukin-1 (IL-1) and interleukin-2 (IL-2), but did block the coupling of these events to DNA synthesis and proliferation.

Side Effects

Adverse effects associated with the use of CellCept may include, but are not limited to, the following:

• diarrhea
• leukopenia
• infection
• vomiting
• higher frequency of certain types of infections e.g., opportunistic infection

The CellCept drug label comes with the following Black Box Warning: 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. Increased susceptibility to infections, including opportunistic infections and severe infections with fatal outcomes.

Clinical Trial Results

Kidney Transplant: Adults

The three de novo kidney transplantation studies compared two dose levels of oral CellCept (1 g twice daily and 1.5 g twice daily) with azathioprine (2 studies) or placebo (1 study) to prevent acute rejection episodes. One of the two studies with azathioprine (AZA) control arm also included anti-thymocyte globulin (ATGAM) induction therapy. In all three de novo kidney transplantation studies, the primary efficacy endpoint was the proportion of patients in each treatment group who experienced treatment failure within the first 6 months after transplantation. Treatment failure was defined as biopsy-proven acute rejection on treatment or the occurrence of death, graft loss or early termination from the study for any reason without prior biopsy-proven rejection. CellCept, in combination with corticosteroids and cyclosporine, reduced (statistically significant at 0.05 level) the incidence of treatment failure within the first 6 months following transplantation.

Pediatrics- De Novo Kidney transplantation PK Study with Long Term Follow-Up

One open-label, safety and pharmacokinetic study of CellCept oral suspension 600 mg/m2 twice daily (up to 1 g twice daily) in combination with cyclosporine and corticosteroids was performed at centers in the United States (9), Europe (5) and Australia (1) in 100 pediatric patients (3 months to 18 years of age) for the prevention of renal allograft rejection. CellCept was well tolerated in pediatric patients and the pharmacokinetics profile was similar to that seen in adult patients dosed with 1 g twice daily CellCept capsules. The rate of biopsy-proven rejection was similar across the age groups (3 months to <6 years, 6 years to <12 years, 12 years to 18 years). The overall biopsy proven rejection rate at 6 months was comparable to adults. The combined incidence of graft loss (5%) and patient death (2%) at 12 months post-transplant was similar to that observed in adult kidney transplant patients.

Heart Transplantation

A double-blind, randomized, comparative, parallel-group, multicenter study in primary de novo heart transplant recipients was performed at centers in the United States (20), in Canada (1), in Europe (5) and in Australia (2). The total number of patients enrolled (ITT population) was 650; 72 never received study drug and 578 received study drug (Safety Population). Patients received CellCept 1.5 g twice daily (n=289) or AZA 1.5 to 3 mg/kg/day (n=289), in combination with cyclosporine (Sandimmune or Neoral ) and corticosteroids as maintenance immunosuppressive therapy. The two primary efficacy endpoints were: (1) the proportion of patients who, after transplantation, had at least one endomyocardial biopsy-proven rejection with hemodynamic compromise, or were re-transplanted or died, within the first 6 months, and (2) the proportion of patients who died or were re-transplanted during the first 12 months following transplantation. Patients who prematurely discontinued treatment were followed for the occurrence of allograft rejection for up to 6 months and for the occurrence of death for 1 year. The analyses of the endpoints showed: Rejection: No difference was established between CellCept and AZA with respect to biopsy-proven rejection with hemodynamic compromise. Survival: CellCept was shown to be at least as effective as AZA in preventing death or re-transplantation at 1 year. 

Liver Transplant

A double-blind, randomized, comparative, parallel-group, multicenter study in primary hepatic transplant recipients was performed at centers in the United States (16), in Canada (2), in Europe (4) and in Australia (1). The total number of patients enrolled was 565. Per protocol, patients received CellCept 1 g twice daily intravenously for up to 14 days followed by CellCept 1.5 g twice daily orally or AZA 1 to 2 mg/kg/day intravenously followed by AZA 1 to 2 mg/kg/day orally, in combination with cyclosporine (Neoral ) and corticosteroids as maintenance immunosuppressive therapy. The actual median oral dose of AZA on study was 1.5 mg/kg/day (range of 0.3 to 3.8 mg/kg/day) initially and 1.26 mg/kg/day (range of 0.3 to 3.8 mg/kg/day) at 12 months. The two primary endpoints were: (1) the proportion of patients who experienced, in the first 6 months post-transplantation, one or more episodes of biopsy-proven and treated rejection or death or retransplantation, and (2) the proportion of patients who experienced graft loss (death or re-transplantation) during the first 12 months post-transplantation. Patients who prematurely discontinued treatment were followed for the occurrence of allograft rejection and for the occurrence of graft loss (death or re-transplantation) for 1 year. In combination with corticosteroids and cyclosporine, CellCept demonstrated a lower rate of acute rejection at 6 months and a similar rate of death or re-transplantation at 1 year compared to AZA.