ADVERSE REACTIONS
The incidence of adverse events for Myfortic® (mycophenolic acid) was determined in randomized, comparative, active-controlled, double-blind, double-dummy trials in prevention of acute rejection in de novo and maintenance kidney transplant patients.
The principal adverse reactions associated with the administration of Myfortic include constipation, nausea, and urinary tract infection in de novo patients and nausea, diarrhea and nasopharyngitis in maintenance patients.
Adverse events reported in ≥20% of patients receiving Myfortic or mycophenolate mofetil in the 12-month de novo renal study and maintenance renal study, when used in combination with cyclosporine, USP (MODIFIED) and corticosteroids, are listed in Table 4. Adverse event rates were similar between Myfortic and mycophenolate mofetil in both de novo and maintenance patients.
Table 4 Adverse Events (%) in Controlled de novo and Maintenance Renal Studies Reported in ≥20% of Patients
| de novo Renal Study | Maintenance Renal Study |
| Myfortic®
1.44 g/day
(n=213) | mycophenolate mofetil
2 g/day
(n=210) | Myfortic®
1.44 g/day
(n=159) | mycophenolate mofetil
2 g/day
(n=163) |
| Blood and Lymphatic System Disorders | | | | |
| Anemia | 21.6 | 21.9 | – | – |
| Leukopenia | 19.2 | 20.5 | – | – |
| Gastrointestinal System Disorders | | | | |
| Constipation | 38.0 | 39.5 | – | – |
| Nausea | 29.1 | 27.1 | 24.5 | 19.0 |
| Diarrhea | 23.5 | 24.8 | 21.4 | 24.5 |
| Vomiting | 23.0 | 20.0 | – | – |
| Dyspepsia | 22.5 | 19.0 | – | – |
| Infections and Infestations | | | | |
| Urinary Tract Infection | 29.1 | 33.3 | – | – |
| CMV Infection | 20.2 | 18.1 | – | – |
| Nervous System Disorder | | | | |
| Insomnia | 23.5 | 23.8 | – | – |
| Surgical and Medical Procedure | | | | |
| Post-Operative Pain | 23.9 | 18.6 | – | – |
Table 5 summarizes the incidence of opportunistic infections in de novo and maintenance transplant patients, which were similar in both treatment groups.
Table 5 Viral and Fungal Infections (%) Reported Over 0-12 Months
| de novo Renal Study | Maintenance Renal Study |
| Myfortic®
1.44 g/day
(n = 213) | mycophenolate mofetil
2 g/day
(n = 210) | Myfortic®
1.44 g/day
(n = 159) | mycophenolate mofetil
2 g/day
(n = 163) |
| (%) | (%) | (%) | (%) |
| Any Cytomegalovirus | 21.6 | 20.5 | 1.9 | 1.8 |
| - Cytomegalovirus Disease | 4.7 | 4.3 | 0 | 0.6 |
| Herpes Simplex | 8.0 | 6.2 | 1.3 | 2.5 |
| Herpes Zoster | 4.7 | 3.8 | 1.9 | 3.1 |
| Any Fungal Infection | 10.8 | 11.9 | 2.5 | 1.8 |
| - Candida NOS | 5.6 | 6.2 | 0 | 1.8 |
| - Candida Albicans | 2.3 | 3.8 | 0.6 | 0 |
The following opportunistic infections occurred rarely in the above controlled trials: aspergillus and cryptococcus.
The incidence of malignancies and lymphoma is consistent with that reported in the literature for this patient population. Lymphoma developed in 2 de novo patients (0.9%), (one diagnosed 9 days after treatment initiation) and in 2 maintenance patients (1.3%) (one was AIDS-related), receiving Myfortic with other immunosuppressive agents in the 12-month controlled clinical trials. Non-melanoma skin carcinoma occurred in 0.9% de novo and 1.8% maintenance patients. Other types of malignancy occurred in 0.5% de novo and 0.6% maintenance patients.
The following adverse events were reported between 3% to <20% incidence in de novo and maintenance patients treated with Myfortic in combination with cyclosporine and corticosteroids are listed in Table 6.
Table 6 Adverse Events Reported in 3% to <20% of Patients Treated with Myfortic® in Combination with Cyclosporine* and Corticosteroids
| de novo Renal Study | Maintenance Renal Study |
| Blood and Lymphatic Disorders | Lymphocele, thrombocytopenia | Leukopenia, anemia |
| Cardiac Disorder | Tachycardia | – |
| Eye Disorder | Vision blurred | – |
| Endocrine Disorders | Cushingoid, hirsutism | – |
| Gastrointestinal Disorders | Abdominal pain upper, flatulence, abdominal distension, sore throat, abdominal pain lower, abdominal pain, gingival hyperplasia, loose stool | Vomiting, dyspepsia, abdominal pain, constipation, gastroesophageal reflux disease, loose stool, flatulence, abdominal pain upper |
| General Disorders and Administration Site Conditions | Edema, edema lower limb, pyrexia, pain, fatigue, edema peripheral, chest pain | Fatigue, pyrexia, edema, chest pain, peripheral edema |
| Infections and Infestations | Nasopharyngitis, herpes simplex, upper respiratory tract infection, oral candidiasis, herpes zoster, sinusitis, wound infection, implant infection, pneumonia | Nasopharyngitis, upper respiratory tract infection, urinary tract infection, influenza, sinusitis |
| Injury, Poisoning, and Procedural Complications | Drug toxicity | Postprocedural pain |
| Investigations | Blood creatinine increased hemoglobin decrease, blood pressure increased, liver function tests abnormal | Blood creatinine increase, weight increase |
| Metabolism and Nutrition Disorders | Hypocalcemia, hyperuricemia, hyperlipidemia, hypokalemia, hypophosphatemia hypercholesterolemia, hyperkalemia, hypomagnesemia, diabetes mellitus, hyperphosphatemia, dehydration, fluid overload, hyperglycemia, hypercalcemia | Dehydration, hypokalemia, hypercholesterolemia |
| Musculoskeletal and Connective Tissue Disorders | Back pain, arthralgia, pain in limb, muscle cramps, myalgia | Arthralgia, pain in limb, back pain, muscle cramps, peripheral swelling, myalgia |
| Nervous System Disorders | Tremor, headache, dizziness (excluding vertigo) | Headache, dizziness |
| Psychiatric Disorders | Anxiety | Insomnia, depression |
| Renal and Urinary Disorders | Renal tubular necrosis, renal impairment, dysuria, hematuria, hydronephrosis, bladder spasm, urinary retention | – |
| Respiratory, Thoracic and Mediastinal Disorders | Cough, dyspnea, dyspnea exertional | Cough, dyspnea, pharyngolaryngeal pain, sinus congestion |
| Skin and Subcutaneous Tissue Disorders | Acne, pruritus | Rash, contusion |
| Surgical and Medical Procedures | Complications of transplant surgery, postoperative complications, postoperative wound complication | – |
| Vascular Disorders | Hypertension, hypertension aggravated, hypotension | Hypertension |
* USP (MODIFIED)
The following additional adverse reactions have been associated with the exposure to MPA when administered as a sodium salt or as mofetil ester:
Gastrointestinal: Colitis (sometimes caused by CMV), pancreatitis, esophagitis, intestinal perforation, gastrointestinal hemorrhage, gastric ulcers, duodenal ulcers, and ileus (see PRECAUTIONS).
Resistance Mechanism Disorders : 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 serious infections such as tuberculosis and atypical mycobacterial infection.
Respiratory: Interstitial lung disorders, including fatal pulmonary fibrosis, have been reported rarely with MPA administration and should be considered in the differential diagnosis of pulmonary symptoms ranging from dyspnea to respiratory failure in post-transplant patients receiving MPA derivatives.
Postmarketing Experience
Cases of progressive multifocal leukoencephalopathy (PML), sometimes fatal, have been reported in patients treated with mycophenolate mofetil (MMF). Mycophenolate mofetil (MMF) is metabolized to mycophenolic acid (MPA), the active ingredient in Myfortic and the active form of the drug (see WARNINGS, Progressive Multifocal Leukoencephalopathy).
|
REPORTS OF SUSPECTED MYFORTIC SIDE EFFECTS / ADVERSE REACTIONS
Below is a sample of reports where side effects / adverse reactions may be related to Myfortic. The information is not vetted and should not be considered as verified clinical evidence.
Possible Myfortic side effects / adverse reactions in 70 year old male
Reported by a physician from Austria on 2011-10-04
Patient: 70 year old male weighing 72.0 kg (158.4 pounds)
Reactions: Pneumonia, Cardiac Failure, Bronchopneumonia, Circulatory Collapse, Enteritis, Septic Shock, Leukopenia
Adverse event resulted in: death
Suspect drug(s):
Myfortic
Dosage: 360 mg
Administration route: Oral
Indication: Immunosuppression
Start date: 2010-11-14
Myfortic
Dosage: 720 mg, unk
Administration route: Oral
Start date: 2010-11-15
End date: 2010-12-04
Myfortic
Dosage: 720 mg, unk
Administration route: Oral
Start date: 2011-01-07
End date: 2011-01-09
Myfortic
Dosage: 360 mg, unk
Administration route: Oral
Start date: 2011-01-05
End date: 2011-01-06
Other drugs received by patient: Pantoprazole Sodium; Insulin Novo; Yomogi; CAL-D-Vita; Urosin; Prograf; Sodium Polystyrene Sulfonate; Tamsulosin HCL; Aprednislon; Lovenox
Possible Myfortic side effects / adverse reactions in 47 year old male
Reported by a individual with unspecified qualification from United States on 2011-10-12
Patient: 47 year old male weighing 74.0 kg (162.8 pounds)
Reactions: Blood Creatine Phosphokinase Increased, Vomiting, Nausea, Pancreatitis, Kidney Transplant Rejection, Gastric Ulcer
Adverse event resulted in: hospitalization
Suspect drug(s):
Myfortic
Other drugs received by patient: Wellbutrin XL; Soriatane; Zofran; Cymbalta; Prednisone; Abilify; Lamictal; Protonix; Norvasc; Adderall XR 10; Adderall 5; Diazepam; Atenolol; Temazepam; Prograf
Possible Myfortic side effects / adverse reactions in 61 year old male
Reported by a physician from United States on 2011-10-18
Patient: 61 year old male weighing 84.0 kg (184.8 pounds)
Reactions: Squamous Cell Carcinoma of Skin
Suspect drug(s):
Myfortic
Dosage: 720 mg
Administration route: Oral
Indication: Immunosuppression
Start date: 2009-09-16
End date: 2009-10-06
Study Drug
Dosage: 10 mg
Administration route: Oral
Indication: Kidney Transplant Rejection
Start date: 2009-12-18
Prednisone
Dosage: 5 mg
Administration route: Oral
Indication: Immunosuppression
Start date: 2009-01-04
Myfortic
Dosage: 360 mg
Administration route: Oral
Start date: 2010-10-07
End date: 2010-12-23
Myfortic
Dosage: 180 mg
Administration route: Oral
Start date: 2010-12-24
Other drugs received by patient: Simvastatin; Norvasc; Multi-Vitamins; Lovaza; Vitamin D; Bactrim; Calcium Carbonate
|
