CellCept Adverse Reactions

The safety profile presented in this section is based on data from both clinical trials and post marketing experience and has been shown to be consistent across transplant and lupus nephritis patient populations.
Clinical trials: An estimated total of 1557 patients received CellCept during pivotal clinical trials in the prevention of acute organ rejection. Of these, 991 were included in the pooled renal studies ICM1866, MYC022, MYC023, 277 were included in the hepatic study MYC2646, and 289 were included in the cardiac study MYC1864. Patients in all study arms also received ciclosporin and corticosteroids.
Diarrhea, leukopenia, sepsis, and vomiting were among the most common and/or serious adverse drug reactions associated with the administration of CellCept in the pivotal trials. There was also evidence of a higher frequency of certain types of infection, e.g. opportunistic infections (see Precautions). In the three pivotal trials for prevention of renal transplant rejection, patients receiving 2 g per day of CellCept demonstrated an overall better safety profile than patients receiving 3 g CellCept. The safety profile of CellCept in patients treated for refractory renal transplant rejection was similar to that observed in the pivotal trials for prevention of renal rejection at doses of 3 g per day. Diarrhea and leucopenia, followed by anemia, nausea, abdominal pain, sepsis, nausea and vomiting, and dyspepsia were the predominant adverse events reported more frequently in patients receiving CellCept in comparison to patients receiving i.v. corticosteroids.
Tabulated summary of adverse drug reactions from clinical trials: Adverse drug reactions from clinical trials (Table 7) are listed by MedDRA system organ class along with their incidence. The corresponding frequency category for each adverse drug reaction is based on the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000). Due to the large differences observed in the frequency of certain ADRs across the different transplant indications, the frequency is presented separately for renal, hepatic and cardiac transplant patients. (See Tables 7a and 7b.)

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Description of selected adverse drug reactions: Infections: All patients treated with immunosuppressants are at increased risk of bacterial, viral, and fungal infections (some of which may lead to a fatal outcome), including those caused by opportunistic agents and latent viral reactivation (see Precautions). The risk increased with total immunosuppressive load (see Precautions). The most serious infections were sepsis and peritonitis. The most common opportunistic infections in patients receiving CellCept with other immunosuppressants were mucocutaneous candida, CMV viraemia/syndrome and Herpes simplex. The proportion of patients with CMV viraemia/syndrome was 13.5%.
Malignancies: Patients receiving CellCept as part of an immunosuppressive regime are at increased risk of developing lymphomas and other malignancies, particularly of the skin (see Precautions).
Three-year safety data in renal and cardiac transplant patients did not reveal any unexpected changes in the incidence of malignancy compared to the 1-year data. Hepatic transplant patients were followed for at least 1 year, but less than 3 years. In supportive clinical trials of treatment of refractory renal rejection the lymphoma rate was 3.9% at an average follow-up of 42 months.
Blood and lymphatic disorders: Cytopenias, including leukopenia, anemia, thrombocytopenia and pancytopenia, are a known risk associated with mycophenolate and may lead or contribute to the occurrence of infections and hemorrhages (see Precautions).
Gastrointestinal: The most serious gastrointestinal disorders were ulceration and hemorrhage which are known risks associated with CellCept. Mouth, esophageal, gastric, duodenal, and intestinal ulcers often complicated by hemorrhage, as well as hematemesis, melena, and hemorrhagic forms of gastritis and colitis were commonly reported during the pivotal clinical trials. The most common gastrointestinal disorders however, were diarrhea, nausea and vomiting. Endoscopic investigation of patients with CellCept-related diarrhea have revealed isolated cases of intestinal villous atrophy (see Precautions).
General disorders and administration site conditions: Edema, including peripheral, face and scrotal edema, was reported very commonly during the pivotal trials. Musculoskeletal pain such as myalgia, and neck and back pain were also very commonly reported.
Special Populations: Elderly patients (≥ 65 years): Elderly patients, particularly those who are receiving CellCept as part of a combination immunosuppressive regimen, may be at greater increased risk of certain infections (including cytomegalovirus tissue invasive disease) and possibly gastrointestinal hemorrhage and pulmonary edema, compared to younger individuals (see Precautions).
Post Marketing: Adverse drug reactions in Table 8 are listed according to system organ class in MedDRA and the corresponding frequency category estimation for each adverse drug reaction is based on the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000). (See Table 8.)

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Infections: Serious life-threatening infections such as meningitis and infectious endocarditis have been reported occasionally and there is evidence of a higher frequency of certain types of infections such as tuberculosis and atypical mycobacterial infection.
Progressive Multifocal Leukoencephalopathy (PML) and BK virus-associated nephropathy have been reported in CellCept treated patients (see Precautions).
Congenital disorders and Pregnancy, puerperium and perinatal conditions: See Use in Pregnancy & Lactation for further information.