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The following adverse reactions are discussed in greater detail in other sections of the label.
- Embryofetal Toxicity [see BOXED WARNING, WARNINGS AND PRECAUTIONS]
- Lymphomas and Other Malignancies [see BOXED WARNING, WARNINGS AND PRECAUTIONS]
- Serious Infections [see BOXED WARNING, WARNINGS AND PRECAUTIONS]
- New or Reactivated Viral Infections [see WARNINGS AND PRECAUTIONS]
- Blood Dyscrasias Including Pure Red Cell Aplasia [see WARNINGS AND PRECAUTIONS]
- Serious GI Tract Complications [see WARNINGS AND PRECAUTIONS]
- Rare Hereditary Deficiencies [see WARNINGS AND PRECAUTIONS]
Clinical Studies Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described below derive from two randomized, comparative, active-controlled, double-blind, double-dummy trials in prevention of acute rejection in de novo and converted stable kidney transplant patients.
In the de novo trial, patients were administered either Myfortic 1.44 grams per day (N=213) or MMF 2 grams per day (N=210) within 48 hours post-transplant for 12 months in combination with cyclosporine, USP MODIFIED and corticosteroids. Forty-one percent of patients also received antibody therapy as induction treatment. In the conversion trial, renal transplant patients who were at least 6 months post-transplant and receiving 2 grams per day MMF in combination with cyclosporine USP MODIFIED, with or without corticosteroids for at least two weeks prior to entry in the trial were randomized to Myfortic 1.44 grams per day (N=159) or MMF 2 grams per day (N=163) for 12 months.
The average age of patients in both studies was 47 years and 48 years (de novo study and conversion study, respectively), ranging from 22 to 75 years. Approximately 66% of patients were male; 82% were white, 12% were black, and 6% other races. About 40% of patients were from the United States and 60% from other countries.
In the de novo trial, the overall incidence of discontinuation due to adverse reactions was 18% (39/213) and 17% (35/210) in the Myfortic and MMF arms, respectively. The most common adverse reactions leading to discontinuation in the Myfortic arm were graft loss (2%), diarrhea (2%), vomiting (1%), renal impairment (1%), CMV infection (1%), and leukopenia (1%). The overall incidence of patients reporting dose reduction at least once during the 0 to 12 month study period was 59% and 60% in the Myfortic and MMF arms, respectively. The most frequent reasons for dose reduction in the Myfortic arm were adverse reactions (44%), dose reductions according to protocol guidelines (17%), dosing errors (11%) and missing data (2%).
The most common adverse reactions ( ≥ 20%) associated with the administration of Myfortic were anemia, leukopenia, constipation, nausea, diarrhea, vomiting, dyspepsia, urinary tract infection, CMV infection, insomnia, and postoperative pain.
The adverse reactions reported in ≥ 10% of patients in the de novo trial are presented in Table 2 below.
Table 2: Adverse Reactions (%) Reported in ≥ 10%
of de novo Kidney Transplant Patients in Either Treatment Group
|System organ class Adverse drug reactions||de novo Renal Trial|
|Myfortic1.44 grams per day
|mycophenolate mofetil (MMF) 2 grams per day
|Blood and Lymphatic System Disorders|
|Gastrointestinal System Disorders|
|Abdominal pain upper||14||14|
|General and Administrative Site Disorders|
|Edema lower limb||16||17|
|Increased blood creatinine||15||10|
|Infections and Infestations|
|Urinary Tract Infection||29||33|
|Metabolism and Nutrition Disorders|
|Musculoskeletal, Connective Tissue and Bone Disorders|
|Nervous System Disorder|
|**The trial was not designed to support comparative claims for Myfortic for the adverse reactions reported in this table.|
Table 3 summarizes the incidence of opportunistic infections in de novo transplant patients.
Table 3: Viral and Fungal Infections (%) Reported Over
0 to 12 Months
|de novo Renal Trial|
|Myfortic 1.44 grams per day
|mycophenolate mofetil (MMF) 2 grams per day
|Any Fungal Infection||11||12|
Lymphoma developed in 2 de novo patients (1%), (1 diagnosed 9 days after treatment initiation) and in 2 conversion patients (1%) receiving Myfortic with other immunosuppressive agents in the 12-month controlled clinical trials.
The adverse reactions reported in < 10% of de novo or conversion patients treated with Myfortic in combination with cyclosporine and corticosteroids are listed in Table 4.
Table 4: Adverse Reactions
Reported in < 10% of Patients Treated with Myfortic in Combination with
Cyclosporine* and Corticosteroids
|Blood and Lymphatic Disorders||Lymphocele, thrombocytopenia|
|Eye Disorder||Vision blurred|
|Gastrointestinal Disorders||Abdominal pain, abdominal distension, gastroesophageal reflux disease, gingival hyperplasia|
|General Disorders and Administration Site Conditions||Fatigue, peripheral edema|
|Infections and Infestations||Nasopharyngitis, herpes simplex, upper respiratory infection, oral candidiasis, herpes zoster, sinusitis, influenza, wound infection, implant infection, pneumonia, sepsis|
|Investigations||Hemoglobin decrease, liver function tests abnormal|
|Metabolism and Nutrition Disorders||Hypercholesterolemia, hyperkalemia, hypomagnesemia, diabetes mellitus, hyperglycemia|
|Musculoskeletal and Connective Tissue Disorders||Arthralgia, pain in limb, peripheral swelling, muscle cramps, myalgia|
|Nervous System Disorders||Dizziness (excluding vertigo)|
|Renal and Urinary Disorders||Renal tubular necrosis, renal impairment, hematuria, urinary retention|
|Respiratory, Thoracic and Mediastinal Disorders||Cough, dyspnea, dyspnea exertional|
|Skin and Subcutaneous Tissue Disorders||Acne, pruritus, rash|
|Vascular Disorders||Hypertension aggravated, hypotension|
The following additional adverse reactions have been associated with the exposure to mycophenolic acid (MPA) when administered as a sodium salt or as mofetil ester:
Gastrointestinal: Intestinal perforation, gastrointestinal hemorrhage, gastric ulcers, duodenal ulcers [see WARNINGS AND PRECAUTIONS], colitis (including CMV colitis), pancreatitis, esophagitis, and ileus.
The following adverse reactions have been identified during post-approval use of Myfortic or other MPA derivatives. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- Congenital malformations including ear, facial, cardiac and nervous system malformations and an increased incidence of first trimester pregnancy loss have been reported following exposure to MMF during pregnancy [see BOXED WARNING, WARNINGS AND PRECAUTIONS].
- Infections [see WARNINGS
- Cases of progressive multifocal leukoencephalopathy (PML), sometimes fatal.
- Polyomavirus associated nephropathy (PVAN), especially due to BK virus infection, associated with serious outcomes, including deteriorating renal function and renal graft loss.
- Viral reactivation in patients infected with HBV or HCV.
- Cases of pure red cell aplasia (PRCA) have been reported in patients treated with MPA derivatives in combination with other immunosuppressive agents [see WARNINGS AND PRECAUTIONS].
The following additional adverse reactions have been identified during postapproval use of Myfortic: agranulocytosis, asthenia, osteomyelitis, lymphadenopathy, lymphopenia, wheezing, dry mouth, gastritis, peritonitis, anorexia, alopecia, pulmonary edema, Kaposi's sarcoma.
Read the Myfortic (mycophenolic acid) Side Effects Center for a complete guide to possible side effects
Antacids With Magnesium And Aluminum Hydroxides
Concomitant use of Myfortic and antacids decreased plasma concentrations of mycophenolic acid (MPA). It is recommended that Myfortic and antacids not be administered simultaneously [see CLINICAL PHARMACOLOGY].
Cholestyramine, Bile Acid Sequestrates, Oral Activated Charcoal And Other Drugs That Interfere With Enterohepatic Recirculation
Drugs that interrupt enterohepatic recirculation may decrease MPA plasma concentrations when coadministered with MMF. Therefore, do not administer Myfortic with cholestyramine or other agents that may interfere with enterohepatic recirculation or drugs that may bind bile acids, e.g., bile acid sequestrates or oral activated charcoal, because of the potential to reduce the efficacy of Myfortic [see CLINICAL PHARMACOLOGY].
Concomitant administration of sevelamer and MMF may decrease MPA plasma concentrations. Sevelamer and other calcium free phosphate binders should not be administered simultaneously with Myfortic [see CLINICAL PHARMACOLOGY].
Cyclosporine inhibits the enterohepatic recirculation of MPA, and therefore, MPA plasma concentrations may be decreased when Myfortic is coadministered with cyclosporine. Clinicians should be aware that there is also a potential change of MPA plasma concentrations after switching from cyclosporine to other immunosuppressive drugs or from other immunosuppressive drugs to cyclosporine in patients concomitantly receiving Myfortic [see CLINICAL PHARMACOLOGY].
Norfloxacin And Metronidazole
MPA plasma concentrations may be decreased when MMF is administrated with norfloxacin and metronidazole. Therefore, Myfortic is not recommended to be given with the combination of norfloxacin and metronidazole. Although there will be no effect on MPA plasma concentrations when Myfortic is concomitantly administered with norfloxacin or metronidazole when given separately [see CLINICAL PHARMACOLOGY].
The concomitant administration of MMF and rifampin may decrease MPA plasma concentrations. Therefore, Myfortic is not recommended to be given with rifampin concomitantly unless the benefit outweighs the risk [see CLINICAL PHARMACOLOGY].
In a drug interaction study, mean levonorgestrel AUC was decreased by 15% when coadministered with MMF. Although Myfortic may not have any influence on the ovulation-suppressing action of oral contraceptives, it is recommended to coadminister Myfortic with hormonal contraceptives (e.g., birth control pill, transdermal patch, vaginal ring, injection, and implant) with caution, and additional barrier contraceptive methods must be used [see WARNINGS AND PRECAUTIONS, Use in Specific Populations, and CLINICAL PHARMACOLOGY].
Acyclovir (Valacyclovir), Ganciclovir (Valganciclovir), And Other Drugs That Undergo Renal Tubular Secretion
The coadministration of MMF and acyclovir or ganciclovir may increase plasma concentrations of mycophenolic acid glucuronide (MPAG) and acyclovir/valacyclovir/ganciclovir/valganciclovir as their coexistence competes for tubular secretion. Both acyclovir/valacyclovir/ganciclovir/valganciclovir and MPAG concentrations will be also increased in the presence of renal impairment. Acyclovir/valacyclovir/ganciclovir/ valganciclovir may be taken with Myfortic; however, during the period of treatment, physicians should monitor blood cell counts [see CLINICAL PHARMACOLOGY].
Ciprofloxacin, Amoxicillin Plus Clavulanic Acid And Other Drugs That Alter The Gastrointestinal Flora
Drugs that alter the gastrointestinal flora such as ciprofloxacin or amoxicillin plus clavulanic acid may interact with MMF by disrupting enterohepatic recirculation. Interference of MPAG hydrolysis may lead to less MPA available for absorption when Myfortic is concomitantly administered with ciprofloxacin or amoxicillin plus clavulanic acid. The clinical relevance of this interaction is unclear; however, no dose adjustment of Myfortic is needed when coadministered with these drugs [see CLINICAL PHARMACOLOGY].
Administration of a pantoprazole at a dose of 40 mg twice daily for 4 days to healthy volunteers did not alter the pharmacokinetics of a single dose of Myfortic [see CLINICAL PHARMACOLOGY].
Read the Myfortic Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 11/5/2015
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