Myfortic Adverse Reactions

Summary of the safety profile: The following undesirable effects cover adverse drug reactions from two controlled clinical trials. The trials evaluated the safety of Myfortic and mycophenolate mofetil in 423 de novo and in 322 maintenance renal transplant patients (randomized 1:1); the incidence of adverse events was similar between treatments in each population.
The very common (≥10%) adverse drug reactions associated with Myfortic in combination with ciclosporin for microemulsion and corticosteroids include leukopenia and diarrhoea.
Malignancies: Patient receiving immunosuppressive regimens involving combinations of drugs, including MPA, are at increased risk of developing lymphomas and other malignancies, particularly of the skin (see Precautions). Overall rates of malignancies observed in Myfortic clinical trials are as follows: lymphoproliferative disease or lymphoma developed in 2 de novo patients (0.9%) and in 2 maintenance patients (1.3%) receiving Myfortic for up to 1 year; non-melanoma skin carcinomas occurred in 0.9% of de novo and 1.8% of maintenance patients receiving Myfortic for up to 1 year; other types of malignancy occurred in 0.5% of de novo and 0.6% of maintenance patients.
Opportunistic infections: 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 de novo renal transplant patients receiving Myfortic with other immunosuppressants in controlled clinical trials of renal transplant patients followed for 1 year were CMV (cytomegalovirus), candidiasis and herpes simplex. The overall rate of CMV infections (serology, viremia or disease) observed in Myfortic clinical trials was reported in 21.6% of de novo and in 1.9% of maintenance renal transplant patients.
Tabulated summary of adverse drug reactions from clinical trials: Adverse drug reactions (Table 4) are ranked by frequency, with the most frequent first, using the following convention: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000) very rare (<1/10,000), including isolated reports. Within each frequency grouping, adverse reactions are ranked in order of decreasing seriousness.
Table 4 as follows contains adverse drug reactions possibly or probably related to Myfortic reported in the two phase III randomized, double blind, controlled, multi-center trials: 1 in de novo kidney transplant patients and 1 in maintenance kidney transplant patients, in which Myfortic was administered at a dose of 1,440 mg /day for 12 months together with ciclosporin microemulsion and corticosteroids. It is compiled according to MedDRA system organ class. (See Table 4.)

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Note: Renal transplant patients were treated with 1,440 mg Myfortic daily for up to one year. A similar profile was seen in the de novo and maintenance transplant population although the incidence tended to be lower in the maintenance patients.
Listing of adverse drug reactions from post-marketing experience: The following adverse drug reactions have been derived from post-marketing experience with Myfortic via spontaneous case reports and literature cases. As these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency which is therefore categorized as not known. Adverse drug reactions are listed according to MedDRA system organ class. Within each system organ class, ADRs are presented in order of decreasing seriousness.
Immune system disorders: Hypersensitivity reactions (including anaphylaxis).
Skin and subcutaneous tissue disorders: Rash has been identified as an adverse drug reaction from post-approval clinical trials, post marketing surveillance and spontaneous reports.
General disorders and administration site conditions: de novo purine synthesis inhibitors-associated acute inflammatory syndrome.
The following adverse reactions are attributed to MPA derivatives as a class effect: Infections and infestations: Serious, sometimes life-threatening infections, including meningitis, infectious endocarditis, tuberculosis, and atypical mycobacterial infection. Polyomavirus associated nephropathy (PVAN), especially due to BK virus infection. Cases of progressive multifocal leukoencephalopathy (PML), sometimes fatal, have been reported (see Precautions).
Blood and lymphatic system disorders: Agranulocytosis, neutropenia, pancytopenia. Cases of pure red cell aplasia (PRCA) have been reported in patients treated with MPA derivatives in combination with other immunosuppressants (see Precautions).
Gastrointestinal disorders: Colitis, oesophagitis (including CMV-colitis and -oesophagitis), CMV gastritis, pancreatitis, intestinal perforation, gastrointestinal haemorrhage, gastric ulcers, duodenal ulcers, ileus.
Pregnancy, puerperium and perinatal conditions: Cases of spontaneous abortion have been reported in patients exposed to mycophenolate mainly in the first trimester (see Use in Pregnancy & Lactation).
Congenital disorders: Congenital malformations have been observed post-marketing in children of patients exposed to mycophenolate in combination with other immunosuppressants (see Use in Pregnancy & Lactation).
Geriatric population (65 years of age or older): Geriatric patients may generally be at increased risk of adverse drug reactions due to immunosuppression. Geriatric patients receiving Myfortic as part of a combination immunosuppressive regimen, did not show an increased risk of adverse reactions, compared to younger individuals in the Myfortic clinical trials.