The following undesirable effects cover adverse reactions from clinical trials:
The principal adverse reactions associated with the administration of mycophenolate mofetil in combination with ciclosporin and corticosteroids include diarrhoea, leucopenia, sepsis and vomiting and there is evidence of a higher frequency of certain types of infections (see Precautions).
Patients receiving immunosuppressive regimens involving combinations of medicinal products, including mycophenolate mofetil, are at increased risk of developing lymphomas and other malignancies, particularly of the skin (see Precautions). Lymphoproliferative disease or lymphoma developed in 0.6% of patients receiving mycophenolate mofetil (2 g or 3 g daily) in combination with other immunosuppressants in controlled clinical trials of renal (2 g data), cardiac and hepatic transplant patients followed for at least 1 year. Non-melanoma skin carcinomas occurred in 3.6% of patients; other types of malignancy occurred in 1.1% of patients. Three-year safety data in renal and cardiac transplant patients did not reveal any unexpected changes in incidence of malignancy compared to the 1-year data. Hepatic transplant patients were followed for at least 1 year, but less than 3 years.
All transplant patients are at increased risk of opportunistic infections; the risk increased with total immunosuppressive load (see Precautions). The most common opportunistic infections in patients receiving mycophenolate mofetil (2 g or 3 g daily) with other immunosuppressants in controlled clinical trials of renal (2 g data), cardiac and hepatic transplant patients followed for at least 1 year were candida mucocutaneous, CMV viraemia/syndrome and Herpes simplex. The proportion of patients with CMV viraemia/syndrome was 13.5%.
Paediatric population (children and adolescents [aged 2 to 18 years]):
The type and frequency of adverse reactions in a clinical study, which recruited 92 paediatric patients aged 2 to 18 years who were given 600 mg/m2
mycophenolate mofetil orally twice daily, were generally similar to those observed in adult patients given 1 g mycophenolate mofetil twice daily. However, the following treatment-related adverse events were more frequent in the paediatric population, particularly in children under 6 years of age, when compared to adults: diarrhoea, sepsis, leucopenia, anaemia and infection.
Elderly patients (≥65 years):
Elderly patients (≥65 years) may generally be at increased risk of adverse reactions due to immunosuppression. Elderly patients receiving mycophenolate mofetil as part of a combination immunosuppressive regimen may be at increased risk of certain infections (including cytomegalovirus tissue invasive disease) and possibly gastrointestinal haemorrhage and pulmonary oedema, compared to younger individuals.
Other adverse reactions:
Adverse reactions, probably or possibly related to mycophenolate mofetil, reported in ≥1/10 and in ≥1/100 to <1/10 of patients treated with mycophenolate mofetil in the controlled clinical trials of renal (2 g data), cardiac and hepatic transplant patients are listed in the following table.
Adverse Reactions, Probably or Possibly Related to Mycophenolate mofetil, Reported in Patients Treated with Mycophenolate mofetil in Renal, Cardiac and Hepatic Clinical Trials when Used in Combination with Ciclosporin and Corticosteroids.
Within the system organ classes, undesirable effects are listed under heading of frequency, using the following categories: 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), not known (cannot be estimated from the available data).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. (See Table.)
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The following undesirable effects cover adverse reactions from post-marketing experience:
The types of adverse reactions reported during post-marketing with mycophenolate mofetil are similar to those seen in the controlled renal, cardiac and hepatic transplant studies. Additional adverse reactions reported during post-marketing are described below with the frequencies reported within brackets if known.
gingival hyperplasia (≥1/100 to <1/10), colitis including cytomegalovirus colitis (≥1/100 to <1/10), pancreatitis (≥1/100 to <1/10) and intestinal villous atrophy.
serious life-threatening infections including meningitis, endocarditis, tuberculosis and atypical mycobacterial infection. Cases of BK virus associated nephropathy, as well as cases of JC virus associated progressive multifocal leucoencephalopathy (PML), have been reported in patients treated with immunosuppressants, including mycophenolate mofetil.
Agranulocytosis (≥1/1,000 to <1/100) and neutropenia have been reported; therefore, regular monitoring of patients taking mycophenolate mofetil is advised (see Precautions). There have been reports of aplastic anaemia and bone marrow depression in patients treated with mycophenolate mofetil, some of which have been fatal.
Blood and lymphatic system disorder:
Cases of pure red cell aplasia (PRCA) have been reported in patients treated with mycophenolate mofetil (see Precautions).
Isolated cases of abnormal neutrophil morphology, including the acquired Pelger-Huet anomaly, have been observed in patients treated with mycophenolate mofetil. These changes are not associated with impaired neutrophil function. These changes may suggest a 'left shift' in the maturity of neutrophils in haematological investigations, which may be mistakenly interpreted as a sign of infection in immunosuppressed patients such as those that receive mycophenolate mofetil.
Hypersensitivity reactions, including angioneurotic oedema and anaphylactic reaction, have been reported.
Pregnancy, puerperium and perinatal conditions:
Cases of spontaneous abortions have been reported in patients exposed to mycophenolate mofetil, mainly in the first trimester, see Use in Pregnancy & Lactation.
Congenital malformations have been observed post-marketing in children of patients exposed to mycophenolate mofetil in combination with other immunosuppressants, see Use in Pregnancy & Lactation.
Respiratory, thoracic and mediastinal disorders:
There have been isolated reports of interstitial lung disease and pulmonary fibrosis in patients treated with mycophenolate mofetil in combination with other immunosuppressants, some of which have been fatal. There have also been reports of bronchiectasis in children and adults (frequency not known).
Immune system disorders:
Hypogammaglobulinaemia has been reported in patients receiving mycophenolate mofetil in combination with other immunosuppressants (frequency not known).