Myfortic Adverse Reactions

Summary of the Safety Profile: The following undesirable effects cover adverse drug reactions from 2 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 the administration of Myfortic in combination with ciclosporin for microemulsion and corticosteroids include leucopenia and diarrhea.
Malignancies: Patients receiving immunosuppressive therapy 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 following: Lymphoproliferative disease or lymphoma developed in 2 de novo (0.9%) patients and in 2 maintenance patients (1.3%) receiving Myfortic for up to 1 year; non-melanoma skin carcinomas occurred in 0.9% de novo and 1.8% maintenance patients receiving Myfortic for up to 1 year; other types of malignancy occurred in 0.5% de novo and 0.6% 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 cytomegalovirus (CMV), 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 reactions are ranked under heading of frequency, the most frequent first, using the following convention: Very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10,000, <1/1000) very rare (<1/10,000), including isolated reports. Within each frequency grouping, adverse reactions are ranked in order of decreasing seriousness.
Listed as follows are adverse drug reactions possibly or probably related to Myfortic reported in the 2 phase III randomized, double blind, controlled, multicenter trials: 1 in de novo kidney transplant patients and 1 in maintenance kidney transplant patients, in which Myfortic was administered at a dose of 1440 mg daily for 12 months together with ciclosporin microemulsion and corticosteroids. It is compiled according to MedDRA system organ class.
Adverse Drug Reactions Possibly or Probably Related to Myfortic Reported in the 2 Phase III Pivotal Trials: Infections and Infestations: Very Common: Viral, bacterial and fungal infections. Common: Upper respiratory tract infections, pneumonia. Uncommon: Wound infection, sepsis*, osteomyelitis*.
Benign and Malignant Neoplasms: Uncommon: Skin papilloma*, basal cell and squamous cell carcinomas*, kaposi's sarcoma*, lymphoproliferative disorder.
Blood and Lymphatic System Disorders: Very Common: Leukopenia. Common: Anemia, thrombocytopenia. Uncommon: Lymphocele*, lymphopenia*, neutropenia*, lymphadenopathy*.
Metabolism and Nutrition Disorders: Very Common: Hypocalcemia, hypokalemia, hyperuricemia. Common: Hyperkalemia, hypomagnesemia. Uncommon: Anorexia, hyperlipidaemia, diabetes mellitus*, hypercholesterolaemia*, hypophosphataemia.
Psychiatric Disorders: Common: Anxiety. Uncommon: Delusional perception*.
Nervous System Disorders: Common: Dizziness, headache. Uncommon: Tremor, insomnia*.
Eye Disorders: Uncommon: Conjunctivitis*, blurred vision*.
Cardiac Disorders: Uncommon: Tachycardia, pulmonary oedema*.
Vascular Disorders: Very Common: Hypertension, hypotension. Common: Aggravated hypertension.
Respiratory, Thoracic and Mediastinal Disorders: Common: Cough, dyspnea, dyspnea exertional. Uncommon: Interstitial lung disease including fatal pulmonary fibrosis and congestion*, wheezing*.
Gastrointestinal Disorders: Very Common: Diarrhea. Common: Abdominal distension and pain, constipation, dyspepsia, flatulence, gastritis, loose stools, nausea, vomiting. Uncommon: Abdominal tenderness, pancreatitis, eructation, halitosis*, ileus*, esophagitis*, peptic ulcer*, subileus*, gastrointestinal hemorrhage, dry mouth*, lip ulceration*, parotid duct obstruction*, gastro-esophageal reflux disease*, gingival hyperplasia*, peritonitis*.
Hepatobiliary Disorders: Common: Abnormal hepatic function tests.
Skin and Subcutaneous Tissue Disorders: Uncommon: Alopecia, contusion*, acne.
Musculoskeletal, Connective Tissue Disorders: Common: Arthralgia, asthenia, myalgia. Uncommon: Back pain*, muscle cramps.
Renal and Urinary Disorders: Common: Increased blood creatinine. Uncommon: Hematuria*, renal tubular necrosis*, urethral stricture.
General Disorders and Administration Site Conditions: Common: Fatigue, peripheral edema, pyrexia. Uncommon: Influenza-like illness, lower limb oedema*, pain, rigors*, weakness*.
*Event reported in a single patient (out of 372) only.
Note: Renal transplant patients were treated with Myfortic 1440 mg daily up to 1 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. Because 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 (ADRs) are listed according to system organ classes in MedDRA. Within each system organ class, ADRs are presented in order of decreasing seriousness.
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.
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 immunosuppressive agents (see Precautions).
Gastrointestinal Disorders: Colitis, esophagitis (including CMV-colitis and -esophagitis), CMV gastritis, pancreatitis, intestinal perforation, gastrointestinal hemorrhage, gastric ulcers, duodenal ulcers, ileus.
Geriatric Population: Elderly patients may generally be at increased risk of adverse drug reactions due to immunosuppression. Elderly 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.