Gastrointestinal bleeding (requiring hospitalization) has been observed in approximately 3% of renal, in 1.7% of cardiac, and in 5.4% of hepatic transplant patients treated with CellCept 3 g daily. In pediatric renal transplant patients, 5/148 cases of gastrointestinal bleeding (requiring hospitalization) were observed.

Gastrointestinal perforations have rarely been observed. Most patients receiving CellCept were also receiving other drugs known to be associated with these complications. Patients with active peptic ulcer disease were excluded from enrollment in studies with mycophenolate mofetil. Because CellCept has been associated with an increased incidence of digestive system adverse events, including infrequent cases of gastrointestinal tract ulceration, hemorrhage, and perforation, CellCept should be administered with caution in patients with active serious digestive system disease.

Subjects with severe chronic renal impairment (GFR <25 mL/min/1.73 m2) who have received single doses of CellCept showed higher plasma MPA and MPAG AUCs relative to subjects with lesser degrees of renal impairment or normal healthy volunteers. No data are available on the safety of long-term exposure to these levels of MPAG. Doses of CellCept greater than 1 g administered twice a day to renal transplant patients should be avoided and they should be carefully observed (see CLINICAL PHARMACOLOGY: Pharmacokinetics and DOSAGE AND ADMINISTRATION).

No data are available for cardiac or hepatic transplant patients with severe chronic renal impairment. CellCept may be used for cardiac or hepatic transplant patients with severe chronic renal impairment if the potential benefits outweigh the potential risks.

In patients with delayed renal graft function posttransplant, mean MPA AUC(0-12h) was comparable, but MPAG AUC(0-12h) was 2-fold to 3-fold higher, compared to that seen in posttransplant patients without delayed renal graft function. In the three controlled studies of prevention of renal rejection, there were 298 of 1483 patients (20%) with delayed graft function. Although patients with delayed graft function have a higher incidence of certain adverse events (anemia, thrombocytopenia, hyperkalemia) than patients without delayed graft function, these events were not more frequent in patients receiving CellCept than azathioprine or placebo. No dose adjustment is recommended for these patients; however, they should be carefully observed (see CLINICAL PHARMACOLOGY: Pharmacokinetics and DOSAGE AND ADMINISTRATION).

In cardiac transplant patients, the overall incidence of opportunistic infections was approximately 10% higher in patients treated with CellCept than in those receiving azathioprine therapy, but this difference was not associated with excess mortality due to infection/sepsis among patients treated with CellCept (see ADVERSE REACTIONS).

There were more herpes virus (H. simplex, H. zoster, and cytomegalovirus) infections in cardiac transplant patients treated with CellCept compared to those treated with azathioprine (see ADVERSE REACTIONS).

It is recommended that CellCept not be administered concomitantly with azathioprine because both have the potential to cause bone marrow suppression and such concomitant administration has not been studied clinically.

In view of the significant reduction in the AUC of MPA by cholestyramine, caution should be used in the concomitant administration of CellCept with drugs that interfere with enterohepatic recirculation because of the potential to reduce the efficacy of CellCept (see PRECAUTIONS: Drug Interactions).

On theoretical grounds, because CellCept is an IMPDH (inosine monophosphate dehydrogenase) inhibitor, it should be avoided in patients with rare hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndrome.

During treatment with CellCept, the use of live attenuated vaccines should be avoided and patients should be advised that vaccinations may be less effective (see PRECAUTIONS: Drug Interactions: Live Vaccines).