Participant of Mycophenolate REMS
See Important Safety Information below.
Click for Full Prescribing Information, including Black Box Warning.
See below for full indication and Important Safety Information.
WARNING: EMBRYOFETAL TOXICITY, MALIGNANCIES, and SERIOUS INFECTIONS
Handling and Disposal: Mycophenolate mofetil (MMF) has demonstrated teratogenic effects in humans. Wearing disposable gloves is recommended when wiping the outer surface of the bottle and or the bottle cap. Avoid direct contact of MYHIBBIN with skin or mucous membranes. Follow applicable special handling and disposal procedures according to OSHA Hazardous Drugs. Do not use after 60 days of first opening the bottle.
Hypersensitivity to mycophenolate mofetil, mycophenolic acid, polysorbate 80, or any other component of the drug product.
Embryofetal Toxicity
Use of MMF during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of congenital malformations, especially external ear and other facial abnormalities including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, kidney, and nervous system. Females of reproductive potential must be made aware of these risks and must be counseled regarding pregnancy prevention and planning. Avoid use of MYHIBBIN during pregnancy if safer treatment options are available.
Lymphoma and Other Malignancies
Patients receiving immunosuppressants, including MYHIBBIN, are at increased risk of developing lymphomas and other malignancies, particularly of the skin. The risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any specific agent. For patients with increased risk for skin cancer, exposure to sunlight and UV light should be limited by wearing protective clothing and using a broad-spectrum sunscreen with a high protection factor.
Post-transplant lymphoproliferative disorder(PTLD) developed in 0.4% to 1% of patients receiving MMF (2 g or 3 g) with other immunosuppressive agents in controlled clinical trials of kidney, heart, and liver transplant patients. The majority of PTLD cases appear to be related to Epstein-Barr Virus (EBV) infection. The risk of PTLD appears greatest in those individuals who are EBV seronegative, a population which includes many young children. In pediatric patients, no other malignancies besides PTLD were observed in clinical trials.
Serious Infections
Patients receiving immunosuppressants, including MYHIBBIN, are at increased risk of developing bacterial, fungal, protozoal, and new or reactivated viral infections, including opportunistic infections. The risk increases with the total immunosuppressive load. These infections may lead to serious outcomes, including hospitalizations and death.
Consider dose reduction or discontinuation of MYHIBBIN in patients who develop new infections or reactivate viral infections, weighing the risk that reduced immunosuppression represents to the functioning allograft.
Blood Dyscrasias: Neutropenia and Pure Red Cell Aplasia (PRCA)
Severe neutropenia [absolute neutrophil count (ANC) <0.5 x 103/µL] developed in transplant patients receiving MMF 3 g daily. Patients receiving MYHIBBIN should be monitored for neutropenia. Neutropenia has been observed most frequently in the period from 31 to 180 days post-transplant in patients treated for prevention of kidney, heart,and liver rejection. The development of neutropenia may be related to MYHIBBIN itself, concomitant medications, viral infections, or a combination of these causes. If neutropenia develops (ANC <1.3 x 103/µL), dosing with MYHIBBIN should be interrupted or the dose reduced, appropriate diagnostic tests performed, and the patient managed appropriately.
Consider monitoring with complete blood counts weekly for the first month, twice monthly for the second and third months, and monthly for the remainder of the first year.
Gastrointestinal Complications
Gastrointestinal bleeding requiring hospitalization, ulceration, and perforations were observed in clinical trials. Physicians should be aware of these serious adverse effects particularly when administering MYHIBBIN to patients with a gastrointestinal disease.
Patients With Hypoxanthine-Guanine Phosphoribosyltransferase (HGPRT) Deficiency
Mycophenolate mofetil is an inosine monophosphate dehydrogenase (IMPDH) inhibitor; therefore, it should be avoided in patients with hereditary deficiencies of HGPRT, such as Lesch-Nyhan and Kelley-Seegmiller syndromes, because it may cause an exacerbation of disease symptoms characterized by the overproduction and accumulation of uric acid leading to symptoms associated with gout, such as acute arthritis, tophi, nephrolithiasis or urolithiasis, and renal disease including renal failure.
Acute Inflammatory Syndrome Associated With Mycophenolate Products
Acute inflammatory syndrome (AIS) has been reported with the use of MMF and mycophenolate products, and some cases have resulted in hospitalization. AIS is a paradoxical pro-inflammatory reaction characterized by fever, arthralgias, arthritis, muscle pain, and elevated inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate, without evidence of infection or underlying disease recurrence. Symptoms occur within weeks to months of initiation of treatment or a dose increase. After discontinuation, improvement of symptoms and inflammatory markers are usually observed within 24 to 48 hours.
Monitor patients for symptoms and laboratory parameters of AIS when starting treatment with mycophenolate products or when increasing the dosage. Discontinue treatment and consider other treatment alternatives based on the risk and benefit for the patient.
Immunizations
During treatment with MYHIBBIN, the use of live attenuated vaccines should be avoided (e.g., intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines) and patients should be advised that vaccinations may be less effective. Advise patients to discuss with a physician before seeking any immunizations.
Blood Donation
Patients should not donate blood during therapy and for at least 6 weeks following discontinuation of MYHIBBIN because their blood or blood products might be administered to a female of reproductive potential or a pregnant woman.
Semen Donation
Based on animal data, men should not donate semen during therapy and for 90 days following discontinuation of MYHIBBIN.
Effect of Concomitant Medications on Mycophenolic Acid Concentrations
A variety of drugs have the potential to alter systemic MPA exposure when co-administered with MYHIBBIN. Therefore, determination of MPA concentrations in plasma before and after making any changes to immunosuppressive therapy, or when adding or discontinuing concomitant medications, may be appropriate to ensure MPA concentrations remain stable.
Potential Impairment of Ability to Drive or Operate Machinery
MYHIBBIN may impact the ability to drive and use machines. Patients should avoid driving or using machines if they experience somnolence, confusion, dizziness, tremors, or hypotension during treatment with MYHIBBIN.
The most common adverse reactions in clinical trials (≥20%) include diarrhea, leukopenia, infection, and vomiting, and there is evidence of a higher frequency of certain types of infections (e.g., opportunistic infection).
See full prescribing information for drugs that may interfere with systemic exposure and reduce MYHIBBIN efficacy: antacids with magnesium or aluminum hydroxide, proton pump inhibitors, drugs that interfere with enterohepatic recirculation, telmisartan, calcium-free phosphate binders.
MYHIBBIN may reduce the effectiveness of oral contraceptives. Use of additional barrier contraceptive methods is recommended.
See full prescribing information for other important drug interactions.
Pregnancy
Use of MMF during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of multiple congenital malformations in multiple organ systems (see Human Data). Oral administration of mycophenolate to rats and rabbits during the period of organogenesis produced congenital malformations and pregnancy loss at doses less than the recommended clinical dose (0.01 to 0.05 times the recommended clinical doses in kidney and heart transplant patients).
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to mycophenolate during pregnancy and those becoming pregnant within 6 weeks of discontinuing MYHIBBIN treatment. To report a pregnancy or obtain information about the registry, visit the Mycophenolate Pregnancy Registry at www.mycophenolateREMS.com or call 1-800-617-8191.
Females and Males of Reproductive Potential
Females of reproductive potential must be made aware of the increased risk of first trimester pregnancy loss and congenital malformations and must be counseled regarding pregnancy prevention and planning.
Pregnancy Planning
For patients who are considering pregnancy, consider alternative immunosuppressants with less potential for embryofetal toxicity whenever possible. Risks and benefits of MYHIBBIN should be discussed with the patient.
Pregnancy Testing
To prevent unplanned exposure during pregnancy, all females of reproductive potential should have a serum or urine pregnancy test with a sensitivity of at least 25 mlU/mL immediately before starting MYHIBBIN. Another pregnancy test with the same sensitivity should be done 8 to 10 days later. Repeat pregnancy tests should be performed during routine follow-up visits. Results of all pregnancy tests should be discussed with the patient. In the event of a positive pregnancy test, consider alternative immunosuppressants with less potential for embryofetal toxicity whenever possible.
Contraception
Female Patients
Females of reproductive potential taking MYHIBBIN must receive contraceptive counseling and use acceptable contraception. Patients must use acceptable birth control during the entire MYHIBBIN therapy, and for 6 weeks after stopping MYHIBBIN, unless the patient chooses abstinence.
Patients should be aware that MYHIBBIN reduces blood levels of the hormones from the oral contraceptive pill and could theoretically reduce its effectiveness.
Male Patients
Genotoxic effects have been observed in animal studies at exposures exceeding the human therapeutic exposures by approximately 1.25 times. Thus, the risk of genotoxic effects on sperm cells cannot be excluded. Based on this potential risk, sexually active male patients and/or their female partners are recommended to use effective contraception during treatment of the male patient and for at least 90 days after cessation of treatment. Also, based on the potential risk of genotoxic effects, male patients should not donate sperm during treatment with MYHIBBIN and for at least 90 days after cessation of treatment.
The Important Safety Information does not include all the information needed to use MYHIBBIN safely and effectively. Please see the full Prescribing Information for MYHIBBIN.
To Report SUSPECTED ADVERSE REACTIONS, contact Azurity Pharmaceuticals, Inc. at 1-800-461-7449, or FDA at 1-800-FDA-1088 or www.fda.gov/MedWatch.
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