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 Mycophenolate mofetil (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 Mycophenolate mofetil (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 Mycophenolate mofetil (CellCept) demonstrated an overall better safety profile than patients receiving 3 g Mycophenolate mofetil (CellCept). The safety profile of Mycophenolate mofetil (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 leukopenia, followed by anemia, nausea, abdominal pain, sepsis, nausea and vomiting, and dyspepsia were the predominant adverse events reported more frequently in patients receiving Mycophenolate mofetil (CellCept) in comparison to patients receiving i.v. corticosteroids.
The adverse event profile associated with the administration of Mycophenolate mofetil (CellCept) i.v. has been shown to be similar to that observed after oral administration.
Tabulated summary of adverse drug reactions from clinical trials: Adverse drug reactions from clinical trials (Tables 7a and 7b) 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 increases with total immunosuppressive load (see Precautions). The most serious infections were sepsis and peritonitis. The most common opportunistic infections in patients receiving Mycophenolate mofetil (CellCept) with other immunosuppressants were mucocutaneous candida, CMV viremia/syndrome, and herpes simplex. The proportion of patients with CMV viremia/syndrome was 13.5%.
Malignancies: Patients receiving Mycophenolate mofetil (CellCept) as part of an immunosuppressive regimen 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 Mycophenolate mofetil (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 Mycophenolate mofetil (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: Children (aged 3 months to 18 years): The type and frequency of adverse drug reactions in a clinical study of 100 pediatric patients aged 3 months to 18 years given 600 mg/m² mycophenolate mofetil orally twice daily, were generally similar to those observed in adult patients given 1 g Mycophenolate mofetil (CellCept) twice daily. However, the following treatment-related adverse events occurred with a frequency of ≥ 10 % in children and were more frequent in the pediatric population, particularly in children under 6 years of age, when the frequency of treatment-related adverse events were compared to adults: diarrhea, leukopenia, sepsis, infection, and anemia.
Elderly patients (≥65 years): Elderly patients, particularly those who are receiving Mycophenolate mofetil (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 Mycophenolate mofetil (CellCept) treated patients (see Precautions).
Congenital disorders and Pregnancy, puerperium, and perinatal conditions: See Pregnancy for further information under Use in Pregnancy & Lactation.
General disorders and administration site conditions: De novo purine synthesis inhibitors-associated acute inflammatory syndrome is a newly described paradoxical pro-inflammatory reaction associated with mycophenolate and other purine synthesis inhibitors, characterized by fever, arthralgias, arthritis, muscle pain and elevated inflammatory markers. Anecdotal literature reports showed rapid improvements following discontinuation of the drug.