Myhibbin

Adults

The recommended dosage for adult kidney transplant patients is 1 g orally, administered twice daily (total daily dose of 2 g).

Warnings and Precautions, Hypersensitivity Reactions (5.8)                                   4/2025

MYHIBBIN is supplied as a white to off-white oral suspension of mycophenolate mofetil 200 mg/mL and it is supplied with a child resistant cap:

• 175 mL of suspension in 225 mL bottle.............................................. NDC 24338-018-01

Storage and Stability

• Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature].
• Do not freeze.

Possible signs and symptoms of acute overdose include hematological abnormalities such as leukopenia and neutropenia, and gastrointestinal symptoms such as abdominal pain, diarrhea, nausea, vomiting, and dyspepsia.

The experience with overdose of mycophenolate mofetil in humans is limited. The reported effects associated with overdose fall within the known safety profile of the drug. The highest dose administered to kidney transplant patients in clinical trials has been 4 g/day. In limited experience with heart and liver transplant patients in clinical trials, the highest doses used were 4 g/day or 5 g/day. At doses of 4 g/day or 5 g/day, there appears to be a higher rate, compared to the use of 3 g/day or less, of gastrointestinal intolerance (nausea, vomiting, and/or diarrhea), and occasional hematologic abnormalities, particularly neutropenia [see Warnings and Precautions (5.4)] .

1. “OSHA Hazardous Drugs.” OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html

Pregnancy Exposure Registry

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.

Risk Summary

Use of mycophenolate mofetil (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) (see Animal Data). Consider alternative immunosuppressants with less potential for embryofetal toxicity. Risks and benefits of MYHIBBIN should be discussed with the pregnant woman. The background risk of pregnancy loss and congenital malformations in organ transplant populations is not clear. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Human Data

A spectrum of congenital malformations (including multiple malformations in individual newborns) has been reported in 23 to 27% of live births in MMF exposed pregnancies, based on published data from pregnancy registries. Malformations that have been documented include external ear, eye, and other facial abnormalities including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, kidney, and nervous system.

Based on published data from pregnancy registries, the risk of first trimester pregnancy loss has been reported at 45 to 49% following MMF exposure.

Animal Data

In animal reproductive toxicology studies, there were increased rates of fetal resorptions and malformations in the absence of maternal toxicity. Oral administration of MMF to pregnant rats from Gestational Day 7 to Day 16 produced increased embryofetal lethality and fetal malformations including anophthalmia, agnathia, and hydrocephaly at doses equivalent to 0.015 and 0.01 times the recommended human doses for renal and cardiac transplant patients, respectively, when corrected for BSA. Oral administration of MMF to pregnant rabbits from Gestational Day 7 to Day 19 produced increased embryofetal lethality and fetal malformations included ectopia cordis, ectopic kidneys, diaphragmatic hernia, and umbilical hernia at dose equivalents as low as 0.05 and 0.03 times the recommended human doses for renal and cardiac transplant patients, respectively, when corrected for BSA.

MYHIBBIN (mycophenolate mofetil) is an antimetabolite immunosuppressant. It is the 2-morpholinoethyl ester of mycophenolic acid (MPA), an immunosuppressive agent; inosine monophosphate dehydrogenase (IMPDH) inhibitor.

The chemical name for mycophenolate mofetil (MMF) is 4-Hexenoic acid, 6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-,2-(4-morpholinyl) ethyl ester, (E)-. It has an empirical formula of C23H31NO7, a molecular weight of 433.49, and the following structural formula:

MMF is a white or almost white, crystalline powder. It is slightly soluble in water (43 µg/mL at pH 7.4); the solubility increases in acidic medium (4.27 mg/mL at pH 3.6).

The drug product is an oral suspension that contains 200 mg of mycophenolate mofetil/mL. The pH of suspension is between 6 and 8.

Inactive ingredients in MYHIBBIN include dibasic sodium phosphate, glycerin, methylparaben, monobasic sodium phosphate, polysorbate 80, propylparaben, purified water, raspberry flavor, simethicone emulsion, sorbitol solution, and xanthan gum.

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 the physician before seeking any immunizations.

Safety and effectiveness have been established in pediatric patients 3 months and older for the prophylaxis of organ rejection of allogenic kidney, heart or liver transplants.

Kidney Transplant

Use of MYHIBBIN in this population is supported by evidence from adequate and well-controlled studies of mycophenolate mofetil in adults with additional data from one open-label, pharmacokinetic and safety study of mycophenolate mofetil in pediatric patients after receiving allogeneic kidney transplant (100 patients, 3 months to 18 years of age) [see Dosage and Administration (2.2), Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14.1)].

Heart Transplant and Liver Transplant

Use of MYHIBBIN in pediatric heart transplant and liver transplant patients is supported by adequate and well-controlled studies and pharmacokinetic data in adult heart transplant and liver transplant patients. Additional supportive data include pharmacokinetic data in pediatric kidney transplant and pediatric liver transplant patients (8 liver transplant patients, 9 months to 5 years of age, in an open-label, pharmacokinetic and safety study) and published evidence of clinical efficacy and safety in pediatric heart transplant and pediatric liver transplant patients [see Dosage and Administration (2.3, 2.4), Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14.1)].

The combination of inactive ingredients (e.g., simethicone, sodium phosphate monobasic dihydrate, sodium phosphate dibasic dihydrate, glycerin) in MYHIBBIN have the potential to impact gastrointestinal tolerability. Monitor pediatric patients receiving MYHIBBIN for signs and symptoms of gastrointestinal intolerance.

Clinical studies of mycophenolate mofetil did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between geriatric and younger patients. In general, dose selection for a geriatric patient should take into consideration the presence of decreased hepatic, renal or cardiac function and of concomitant drug therapies. [see Adverse Reactions (6.1), Drug Interactions (7)].

Inform patients that MYHIBBIN can interfere with the usual response to immunizations. Before seeking vaccines on their own, advise patients to discuss first with their physician [see Warnings and Precautions (5.9)].

MYHIBBIN is contraindicated in patients with a history of hypersensitivity, including anaphylaxis, to mycophenolate mofetil (MMF), mycophenolic acid (MPA), polysorbate 80 (TWEEN) or any other component of the drug product  [see Warnings and Precautions (5.8)] .

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.

Based on animal data, men should not donate semen during therapy and for 90 days following discontinuation of MYHIBBIN [see Use In Specific Populations (8.3)] .

The following adverse reactions are discussed in greater detail in other sections of the label:

• Embryofetal Toxicity [see Warnings and Precautions (5.1)]

• Lymphomas and Other Malignancies [see Warnings and Precautions (5.2)]

• Serious Infections [see Warnings and Precautions (5.3)]

• Blood Dyscrasias: Neutropenia, Pure Red Cell Aplasia [see Warnings and Precautions (5.4)]

• Gastrointestinal Complications [see Warnings and Precautions (5.5)]

• Acute Inflammatory Syndrome Associated with Mycophenolate Products [see Warnings and Precautions (5.7)]

• Hypersensitivity Reactions [see Warnings and Precautions (5.8)]

• See FPI 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. ( 7.1)
• MYHIBBIN may reduce effectiveness of oral contraceptives. Use of additional barrier contraceptive methods is recommended. ( 7.2)
• See FPI for other important drug interactions. ( 7)

Advise patients not to donate blood during therapy and for at least 6 weeks following discontinuation of MYHIBBIN [see Warnings and Precautions (5.10)].

Advise males of childbearing potential not to donate semen during therapy and for 90 days following discontinuation of MYHIBBIN [see Warnings and Precautions (5.11)].

This Medication Guide has been approved by the U.S. Food and   Drug Administration                                                                                          Approved: 04/2025

MYH-MG-02

There is a lack of information regarding the pharmacodynamic effects of MMF.

Inform patients that they are at increased risk for developing blood adverse effects such as anemia or low white blood cells. Advise patients to immediately contact their healthcare provider if they experience any evidence of infection, unexpected bruising, or bleeding, or any other manifestation of bone marrow suppression [see Warnings and Precautions (5.4)].

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 [see Adverse Reactions (6.1, 6.2)].

Serious viral infections reported include:

• Polyomavirus-associated nephropathy (PVAN), especially due to BK virus infection
• JC virus-associated progressive multifocal leukoencephalopathy (PML), and
• Cytomegalovirus (CMV) infections: CMV seronegative transplant patients who receive an organ from a CMV seropositive donor are at highest risk of CMV viremia and CMV disease.
• Viral reactivation in patients infected with Hepatitis B and C
• COVID-19

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.

PVAN, especially due to BK virus infection, is associated with serious outcomes, including deteriorating renal function and renal graft loss [see Adverse Reactions (6.2)]. Patient monitoring may help detect patients at risk for PVAN.

PML, which is sometimes fatal, commonly presents with hemiparesis, apathy, confusion, cognitive deficiencies, and ataxia [see Adverse Reactions (6.2)] . In immunosuppressed patients, physicians should consider PML in the differential diagnosis in patients reporting neurological symptoms.

The risk of CMV viremia and CMV disease is highest among transplant recipients seronegative for CMV at time of transplant who receive a graft from a CMV seropositive donor. Therapeutic approaches to limiting CMV disease exist and should be routinely provided. Patient monitoring may help detect patients at risk for CMV disease.

Viral reactivation has been reported in patients infected with HBV or HCV. Monitoring infected patients for clinical and laboratory signs of active HBV or HCV infection is recommended.

MYHIBBIN is indicated for the prophylaxis of organ rejection, in adult and pediatric recipients 3 months of age and older of allogeneic kidney [see Clinical Studies (14.1)], heart [see Clinical Studies (14.2)] or liver transplants [see Clinical Studies (14.3)] , in combination with other immunosuppressants.

 Mycophenolate mofetil (MMF) is absorbed following oral administration and hydrolyzed to mycophenolic acid (MPA), the active metabolite. MPA is a selective uncompetitive inhibitor of the two isoforms (type I and type II) of inosine monophosphate dehydrogenase (IMPDH) leading to inhibition of the de novo pathway of guanosine nucleotide synthesis and blocks DNA synthesis. The mechanism of action of MPA is multifaceted and includes effects on cellular checkpoints responsible for metabolic programming of lymphocytes. MPA shifts transcriptional activities in lymphocytes from a proliferative state to catabolic processes. In vitro studies suggest that MPA modulates transcriptional activities in human CD4+ T-lymphocytes by suppressing the Akt/mTOR and STAT5 pathways that are relevant to metabolism and survival, leading to an anergic state of T-cells whereby the cells become less responsive to antigenic stimulation. Additionally, MPA enhanced the expression of negative co-stimulators such as CD70, PD-1, CTLA-4, and transcription factor FoxP3 as well as decreased the expression of positive co-stimulators CD27 and CD28.

MPA decreases proliferative responses of T- and B-lymphocytes to both mitogenic and allo-antigenic stimulation, antibody responses, as well as the production of cytokines from lymphocytes and monocytes such as GM-CSF, IFN-Ɣ, IL-17, and TNF-α. Additionally, MPA prevents the glycosylation of lymphocyte and monocyte glycoproteins that are involved in intercellular adhesion to endothelial cells and may inhibit recruitment of leukocytes into sites of inflammation and graft rejection.

Overall, the effect of MPA is cytostatic and reversible.

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 [see Use in Specific Populations (8.1, 8.3)].

Pregnancy loss and malformation

• Inform females of reproductive potential and pregnant women that use of MYHIBBIN during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of congenital malformations. Advise that they must use an acceptable form of contraception [see Warnings and Precautions (5.1), Use in Specific Populations (8.1, 8.3)].
• Encourage pregnant women to enroll in the Pregnancy Exposure Registry. This registry monitors pregnancy outcomes in women exposed to mycophenolate [see Use in Specific Populations (8.1)].

Contraception

• Discuss pregnancy testing, pregnancy prevention and planning with females of reproductive potential [see Use in Specific Populations (8.3)].
• Females of reproductive potential must use an acceptable form of birth control during the entire MYHIBBIN therapy and for 6 weeks after stopping MYHIBBIN, unless the patient chooses abstinence. MYHIBBIN may reduce effectiveness of oral contraceptives. Use of additional barrier contraceptive methods is recommended [see Use in Specific Populations (8.3)].
• For patients who are considering pregnancy, discuss appropriate alternative immunosuppressants with less potential for embryofetal toxicity. Risks and benefits of MYHIBBIN should be discussed with the patient.
• Advise sexually active male patients and/or their partners to use effective contraception during the treatment of the male patient and for at least 90 days after cessation of treatment. This recommendation is based on findings of animal studies [see Use in Specific Populations (8.3), Nonclinical Toxicology (13.1)].

A double-blind, randomized, comparative, parallel-group, multicenter study in primary de novo heart transplant recipients was performed at centers in the United States (20), in Canada (1), in Europe (5) and in Australia (2). The total number of patients enrolled (ITT population) was 650; 72 never received study drug and 578 received study drug (Safety Population). Patients received mycophenolate mofetil 1.5 g twice daily (n=289) or AZA 1.5 to 3 mg/kg/day (n=289), in combination with cyclosporine (Sandimmune ^®or Neoral ^®) and corticosteroids as maintenance immunosuppressive therapy. The two primary efficacy endpoints were: (1) the proportion of patients who, after transplantation, had at least one endomyocardial biopsy-proven rejection with hemodynamic compromise, or were re-transplanted or died, within the first 6 months, and (2) the proportion of patients who died or were re-transplanted during the first 12 months following transplantation. Patients who prematurely discontinued treatment were followed for the occurrence of allograft rejection for up to 6 months and for the occurrence of death for 1 year.

The analyses of the endpoints showed:

• Rejection: No difference was established between mycophenolate mofetil and AZA with respect to biopsy-proven rejection with hemodynamic compromise.
• Survival: Mycophenolate mofetil was shown to be at least as effective as AZA in preventing death or re-transplantation at 1 year (see Table 11 ).

^aHemodynamic compromise occurred if any of the following criteria were met: pulmonary capillary wedge pressure ≥20 mm or a 25% increase; cardiac index <2.0 L/min/m ²or a 25% decrease; ejection fraction ≤30%; pulmonary artery oxygen saturation ≤60% or a 25% decrease; presence of new S ₃gallop; fractional shortening was ≤20% or a 25% decrease; inotropic support required to manage the clinical condition.

A double-blind, randomized, comparative, parallel-group, multicenter study in primary hepatic transplant recipients was performed at centers in the United States (16), in Canada (2), in Europe (4) and in Australia (1). The total number of patients enrolled was 565. Per protocol, patients received mycophenolate mofetil 1.5 g twice daily orally or AZA 1 to 2 mg/kg/day orally, in combination with cyclosporine (Neoral ^®) and corticosteroids as maintenance immunosuppressive therapy. The actual median oral dose of AZA on study was 1.5 mg/kg/day (range of 0.3 to 3.8 mg/kg/day) initially and 1.26 mg/kg/day (range of 0.3 to 3.8 mg/kg/day) at 12 months. The two primary endpoints were: (1) the proportion of patients who experienced, in the first 6 months post-transplantation, one or more episodes of biopsy-proven and treated rejection or death or re-transplantation, and (2) the proportion of patients who experienced graft loss (death or re-transplantation) during the first 12 months post-transplantation. Patients who prematurely discontinued treatment were followed for the occurrence of allograft rejection and for the occurrence of graft loss (death or re-transplantation) for 1 year.

In combination with corticosteroids and cyclosporine, mycophenolate mofetil demonstrated a lower rate of acute rejection at 6 months and a similar rate of death or re-transplantation at 1 year compared to AZA ( Table 12 ).

• Blood Dyscrasias (Neutropenia, Red Blood Cell Aplasia): Monitor with blood tests; consider treatment interruption or dose reduction. ( 5.4)
• Gastrointestinal Complications: Monitor for complications such as bleeding, ulceration and perforations, particularly in patients with underlying gastrointestinal disorders. ( 5.5)
• Hypoxanthine-Guanine Phosphoribosyl-Transferase Deficiency: Avoid use of MYHIBBIN. ( 5.6)
• Acute Inflammatory Syndrome Associated with Mycophenolate Products: Monitor for this paradoxical inflammatory reaction. ( 5.7)
• Hypersensitivity Reactions: Discontinue MYHIBBIN; treat and monitor until signs and symptoms resolve. ( 5.8)
• Immunizations: Avoid live attenuated vaccines. ( 5.9)
• Blood Donation: Avoid during therapy and for 6 weeks thereafter. ( 5.10)
• Semen Donation: Avoid during therapy and for 90 days thereafter. ( 5.11)
• Potential Impairment on Driving and Use of Machinery: MYHIBBIN may affect ability to drive or operate machinery. ( 5.13)

• Reduce or interrupt dosing in the event of neutropenia. ( 2.5)
• See full prescribing information (FPI) for: dosage modifications for renal impairment and neutropenia ( 2.5)

Oral suspension: mycophenolate mofetil 200 mg/mL in a white to off-white suspension.

The following adverse reactions have been identified during post-approval use of mycophenolate mofetil. 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:

• Embryo-Fetal Toxicity: Congenital malformations and spontaneous abortions, mainly in the first trimester, have been reported following exposure to mycophenolate mofetil (MMF) in combination with other immunosuppressants during pregnancy [see Warnings and Precautions (5.1), and Use in Specific Populations (8.1), (8.3)]. Congenital malformations include:

- Facial malformations: cleft lip, cleft palate, micrognathia, hypertelorism of the orbits

- Abnormalities of the ear and eye: abnormally formed or absent external/middle ear, coloboma, microphthalmos

- Malformations of the fingers: polydactyly, syndactyly, brachydactyly

- Cardiac abnormalities: atrial and ventricular septal defects

- Esophageal malformations: esophageal atresia

- Nervous system malformations: such as spina bifida.

• Digestive: Colitis, pancreatitis
• Hematologic and Lymphatic: Bone marrow failure, cases of pure red cell aplasia (PRCA) and hypogammaglobulinemia have been reported in patients treated with mycophenolate mofetil in combination with other immunosuppressive agents [see Warnings and Precautions (5.4)].
• Immune: Hypersensitivity reactions, including anaphylaxis and angioedema [see Warnings and Precautions (5.8)] , hypogammaglobinemia.
• Infections: Meningitis, infectious endocarditis, tuberculosis, atypical mycobacterial infection, progressive multifocal leukoencephalopathy, BK virus infection, viral reactivation of hepatitis B and hepatitis C, protozoal infections [see Warnings and Precautions (5.3)].
• Respiratory: Bronchiectasis, interstitial lung disease, fatal pulmonary fibrosis, have been reported rarely and should be considered in the differential diagnosis of pulmonary symptoms ranging from dyspnea to respiratory failure in post-transplant patients receiving mycophenolate mofetil.
• Vascular: Lymphocele

• Male Patients: 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 (8.3)

Postmarketing cases of hypersensitivity reactions, including angioedema and anaphylaxis, have been reported with the use of MMF and mycophenolate products. These reactions generally occurred within hours to the next day after initiating MMF or mycophenolate products. If signs or symptoms of a hypersensitivity reaction occur, discontinue MYHIBBIN; treat and monitor until signs and symptoms resolve [see Contraindications (4)].

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.

An estimated total of 1557 adult patients received mycophenolate mofetil during pivotal clinical trials in the prevention of acute organ rejection. Of these, 991 were included in the three renal studies, 277 were included in one hepatic study, and 289 were included in one cardiac study. Patients in all study arms also received cyclosporine and corticosteroids.

The data described below primarily derive from five randomized, active-controlled double-blind 12-month trials of mycophenolate mofetil in de novo kidney (3) heart (1) and liver (1) transplant patients [see Clinical Studies (14.1, 14.2, and 14.3)] .

Inform patients of the potential risk of hypersensitivity reactions. Advise patients to stop taking MYHIBBIN and seek immediate medical attention if signs or symptoms of a hypersensitivity reaction occur (such as swelling of face, lips, tongue, or throat; difficulty breathing or swallowing) [see Warning and Precautions (5.8)].

Inform patients that acute inflammatory reactions have been reported in some patients who received mycophenolate mofetil. Some reactions were severe, requiring hospitalization. Advise patients to contact their physician if they develop fever, joint stiffness, joint pain or muscle pains [see Warnings and Precautions (5.7)].

• Advise patients to avoid contact of the skin or mucous membranes with MYHIBBIN. If such contact occurs, they must wash the area of contact thoroughly with soap and water. In case of ocular contact, rinse eyes with plain water.
• Advise patients to take a missed dose as soon as they remember, except if it is closer than 2 hours to the next scheduled dose; in this case they should continue to take MYHIBBIN at the usual times.

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

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 receiving immunosuppressants, including MYHIBBIN, are at increased risk of developing lymphomas and other malignancies, particularly of the skin [see Adverse Reactions (6.1)]. 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 mycophenolate mofetil (2 g or 3 g) with other immunosuppressive agents in controlled clinical trials of kidney, heart and liver transplant patients [see Adverse Reactions (6.1)]. 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 [see Adverse Reactions (6.1)].

Patients with Kidney Transplant

No dosage adjustments are recommended for kidney transplant patients with severe hepatic parenchymal disease. However, it is not known whether dosage adjustments are needed for hepatic disease with other etiologies [see Clinical Pharmacology (12.3)].

Patients with Heart Transplant

No data are available for heart transplant patients with severe hepatic parenchymal disease.

MYHIBBIN Oral Suspension, 200 mg/mL - NDC 24338-018-01 - 175 mL Carton label

MYHIBBIN Oral Suspension, 200 mg/mL - NDC 24338-018-01 - 175 mL Bottle label

Inform patients that they are at increased risk of developing a variety of infections due to immunosuppression. Instruct them to contact their physician if they develop any of the signs and symptoms of infection explained in the Medication Guide [see Warnings and Precautions (5.3)].

Inform patients that MYHIBBIN can cause gastrointestinal tract complications including bleeding, intestinal perforations, and gastric or duodenal ulcers. Advise the patient to contact their healthcare provider if they have symptoms of gastrointestinal bleeding, or sudden onset or persistent abdominal pain [see Warnings and Precautions (5.5)].

MYHIBBIN should not be used without the supervision of a physician with experience in immunosuppressive therapy.

MYHIBBIN should not be used interchangeably with mycophenolic acid delayed-release tablets without supervision of a physician with experience in immunosuppressive therapy because the rates of absorption following the administration of MYHIBBIN and mycophenolic acid delayed-release tablets are not equivalent.

Patients should avoid contact of the skin or mucous membranes with MYHIBBIN. If such contact occurs, they must wash the area of contact thoroughly with soap and water. In case of ocular contact, rinse eyes with plain water.

The initial oral dose of MYHIBBIN should be given as soon as possible following kidney, heart or liver transplant. It is recommended that MYHIBBIN be administered on an empty stomach. In stable transplant patients, however, MYHIBBIN may be administered with food if necessary [see Clinical Pharmacology (12.3)]. MYHIBBIN must not be mixed with any liquids prior to dose administration. If needed, MYHIBBIN can be administered via a nasogastric tube with a minimum size of 8 French (minimum 1.7 mm interior diameter).

Patients should be instructed to take a missed dose as soon as they remember, except if it is closer than 2 hours to the next scheduled dose; in this case, they should continue to take MYHIBBIN at the usual times.

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.

• Inform patients that they are at increased risk of developing lymphomas and other malignancies, particularly of the skin, due to immunosuppression [see Warnings and Precautions (5.2)].
• Advise patients to limit exposure to sunlight and ultraviolet (UV) light by wearing protective clothing and use of broad-spectrum sunscreen with high protection factor.

Adults

The recommended dosage for adult heart transplant patients is 1.5 g orally administered twice daily (total daily dose of 3 g).

Pediatric Patients 3 months and older

The recommended starting dosage for pediatric heart transplant patients 3 months and older is 600 mg/m², administered twice daily. If well tolerated, the dose can be increased to a maintenance dosage of 900 mg/m² administered twice daily (maximum total daily dose of 3 g or 15 mL of the oral suspension). The dose may be individualized based on clinical assessment.

Adults

The recommended dosage for adult liver transplant patients is 1.5 g administered orally twice daily (total daily dose of 3 g).

Pediatrics Patients 3 months and older

The recommended starting dosage for pediatric liver transplant patients 3 months and older is 600 mg/m², administered twice daily. If well tolerated, the dose can be increased to a maintenance dosage of 900 mg/m² administered twice daily (maximum total daily dose of 3 g or 15 mL of the oral suspension). The dose may be individualized based on clinical assessment.

Advise patients that MYHIBBIN can affect the ability to drive or operate machines. Patients should avoid driving or operating machines if they experience somnolence, confusion, dizziness, tremor or hypotension during treatment with MYHIBBIN [see Warnings and Precautions (5.13)].



Distributed by:

Azurity Pharmaceuticals, Inc. 

Woburn, MA 01801 USA



MYH-PI-02 Rev. 04/2025

In a 104-week oral carcinogenicity study in mice, MMF in daily doses up to 180 mg/kg was not tumorigenic. The highest dose tested was 0.2 times the recommended clinical dose (2 g/day) in renal transplant patients and 0.15 times the recommended clinical dose (3 g/day) in cardiac transplant patients when corrected for differences in body surface area (BSA). In a 104-week oral carcinogenicity study in rats, MMF in daily doses up to 15 mg/kg was not tumorigenic. The highest dose was 0.035 times the recommended clinical dose in kidney transplant patients and 0.025 times the recommended clinical dose in heart transplant patients when corrected for BSA. While these animal doses were lower than those given to patients, they were maximal in those species and were considered adequate to evaluate the potential for human risk [see Warnings and Precautions (5.2)].

The genotoxic potential of MMF was determined in five assays. MMF was genotoxic in the mouse lymphoma/thymidine kinase assay and the in vivo mouse micronucleus assay. MMF was not genotoxic in the bacterial mutation assay, the yeast mitotic gene conversion assay or the Chinese hamster ovary cell chromosomal aberration assay.

MMF had no effect on fertility of male rats at oral doses up to 20 mg/kg/day. This dose represents 0.05 times the recommended clinical dose in renal transplant patients and 0.03 times the recommended clinical dose in cardiac transplant patients when corrected for BSA. In a female fertility and reproduction study conducted in rats, oral doses of 4.5 mg/kg/day caused malformations (principally of the head and eyes) in the first generation offspring in the absence of maternal toxicity. This dose was 0.01 times the recommended clinical dose in renal transplant patients and 0.005 times the recommended clinical dose in cardiac transplant patients when corrected for BSA. No effects on fertility or reproductive parameters were evident in the dams or in the subsequent generation.

MYHIBBIN may impact the ability to drive and use machines. Patients should avoid driving or using machines if they experience somnolence, confusion, dizziness, tremor, or hypotension during treatment with MYHIBBIN [see Adverse Reactions (6.1)] .

Severe neutropenia [absolute neutrophil count (ANC) <0.5 x 10 ³/µL] developed in transplant patients receiving MMF 3 g daily [see Adverse Reactions (6.1)]. 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 10 ³/µL), dosing with MYHIBBIN should be interrupted or the dose reduced, appropriate diagnostic tests performed, and the patient managed appropriately [see Dosage and Administration (2.5)].

Patients receiving MYHIBBIN should be instructed to report immediately any evidence of infection, unexpected bruising, bleeding or any other manifestation of bone marrow depression.

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.

Cases of pure red cell aplasia (PRCA) have been reported in patients treated with MMF in combination with other immunosuppressive agents. In some cases, PRCA was found to be reversible with dose reduction or cessation of MMF therapy. In transplant patients, however, reduced immunosuppression may place the graft at risk.

• Use during pregnancy is associated with increased risks of first trimester pregnancy loss and congenital malformations. Avoid if safer treatment options are available. Females of reproductive potential must be counseled regarding pregnancy prevention and planning [see Warnings and Precautions (5.1), Use in Special Populations (8.1, 8.3)] .
• Increased risk of development of lymphoma and other malignancies, particularly of the skin [see Warnings and Precautions (5.2)] .
• Increased susceptibility to bacterial, viral, fungal and protozoal infections, including opportunistic infections and viral reactivation of hepatitis B and C, which may lead to hospitalizations and fatal outcomes [see Warnings and Precautions (5.3)] .

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.

A variety of drugs have 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.

Mycophenolate mofetil is an inosine monophosphate dehydrogenase (IMPDH) inhibitor; therefore it should be avoided in patients with hereditary deficiencies of hypoxanthine-guanine phosphoribosyl-transferase (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.

Adults

The recommended dosage for adult kidney transplant patients is 1 g orally, administered twice daily (total daily dose of 2 g).

Warnings and Precautions, Hypersensitivity Reactions (5.8)                                   4/2025

MYHIBBIN is supplied as a white to off-white oral suspension of mycophenolate mofetil 200 mg/mL and it is supplied with a child resistant cap:

• 175 mL of suspension in 225 mL bottle.............................................. NDC 24338-018-01

Storage and Stability

• Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature].
• Do not freeze.

Possible signs and symptoms of acute overdose include hematological abnormalities such as leukopenia and neutropenia, and gastrointestinal symptoms such as abdominal pain, diarrhea, nausea, vomiting, and dyspepsia.

The experience with overdose of mycophenolate mofetil in humans is limited. The reported effects associated with overdose fall within the known safety profile of the drug. The highest dose administered to kidney transplant patients in clinical trials has been 4 g/day. In limited experience with heart and liver transplant patients in clinical trials, the highest doses used were 4 g/day or 5 g/day. At doses of 4 g/day or 5 g/day, there appears to be a higher rate, compared to the use of 3 g/day or less, of gastrointestinal intolerance (nausea, vomiting, and/or diarrhea), and occasional hematologic abnormalities, particularly neutropenia [see Warnings and Precautions (5.4)] .

1. “OSHA Hazardous Drugs.” OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html

Pregnancy Exposure Registry

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.

Risk Summary

Use of mycophenolate mofetil (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) (see Animal Data). Consider alternative immunosuppressants with less potential for embryofetal toxicity. Risks and benefits of MYHIBBIN should be discussed with the pregnant woman. The background risk of pregnancy loss and congenital malformations in organ transplant populations is not clear. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Human Data

A spectrum of congenital malformations (including multiple malformations in individual newborns) has been reported in 23 to 27% of live births in MMF exposed pregnancies, based on published data from pregnancy registries. Malformations that have been documented include external ear, eye, and other facial abnormalities including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, kidney, and nervous system.

Based on published data from pregnancy registries, the risk of first trimester pregnancy loss has been reported at 45 to 49% following MMF exposure.

Animal Data

In animal reproductive toxicology studies, there were increased rates of fetal resorptions and malformations in the absence of maternal toxicity. Oral administration of MMF to pregnant rats from Gestational Day 7 to Day 16 produced increased embryofetal lethality and fetal malformations including anophthalmia, agnathia, and hydrocephaly at doses equivalent to 0.015 and 0.01 times the recommended human doses for renal and cardiac transplant patients, respectively, when corrected for BSA. Oral administration of MMF to pregnant rabbits from Gestational Day 7 to Day 19 produced increased embryofetal lethality and fetal malformations included ectopia cordis, ectopic kidneys, diaphragmatic hernia, and umbilical hernia at dose equivalents as low as 0.05 and 0.03 times the recommended human doses for renal and cardiac transplant patients, respectively, when corrected for BSA.

MYHIBBIN (mycophenolate mofetil) is an antimetabolite immunosuppressant. It is the 2-morpholinoethyl ester of mycophenolic acid (MPA), an immunosuppressive agent; inosine monophosphate dehydrogenase (IMPDH) inhibitor.

The chemical name for mycophenolate mofetil (MMF) is 4-Hexenoic acid, 6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-,2-(4-morpholinyl) ethyl ester, (E)-. It has an empirical formula of C23H31NO7, a molecular weight of 433.49, and the following structural formula:

MMF is a white or almost white, crystalline powder. It is slightly soluble in water (43 µg/mL at pH 7.4); the solubility increases in acidic medium (4.27 mg/mL at pH 3.6).

The drug product is an oral suspension that contains 200 mg of mycophenolate mofetil/mL. The pH of suspension is between 6 and 8.

Inactive ingredients in MYHIBBIN include dibasic sodium phosphate, glycerin, methylparaben, monobasic sodium phosphate, polysorbate 80, propylparaben, purified water, raspberry flavor, simethicone emulsion, sorbitol solution, and xanthan gum.

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 the physician before seeking any immunizations.

Safety and effectiveness have been established in pediatric patients 3 months and older for the prophylaxis of organ rejection of allogenic kidney, heart or liver transplants.

Kidney Transplant

Use of MYHIBBIN in this population is supported by evidence from adequate and well-controlled studies of mycophenolate mofetil in adults with additional data from one open-label, pharmacokinetic and safety study of mycophenolate mofetil in pediatric patients after receiving allogeneic kidney transplant (100 patients, 3 months to 18 years of age) [see Dosage and Administration (2.2), Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14.1)].

Heart Transplant and Liver Transplant

Use of MYHIBBIN in pediatric heart transplant and liver transplant patients is supported by adequate and well-controlled studies and pharmacokinetic data in adult heart transplant and liver transplant patients. Additional supportive data include pharmacokinetic data in pediatric kidney transplant and pediatric liver transplant patients (8 liver transplant patients, 9 months to 5 years of age, in an open-label, pharmacokinetic and safety study) and published evidence of clinical efficacy and safety in pediatric heart transplant and pediatric liver transplant patients [see Dosage and Administration (2.3, 2.4), Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14.1)].

The combination of inactive ingredients (e.g., simethicone, sodium phosphate monobasic dihydrate, sodium phosphate dibasic dihydrate, glycerin) in MYHIBBIN have the potential to impact gastrointestinal tolerability. Monitor pediatric patients receiving MYHIBBIN for signs and symptoms of gastrointestinal intolerance.

Clinical studies of mycophenolate mofetil did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between geriatric and younger patients. In general, dose selection for a geriatric patient should take into consideration the presence of decreased hepatic, renal or cardiac function and of concomitant drug therapies. [see Adverse Reactions (6.1), Drug Interactions (7)].

Inform patients that MYHIBBIN can interfere with the usual response to immunizations. Before seeking vaccines on their own, advise patients to discuss first with their physician [see Warnings and Precautions (5.9)].

MYHIBBIN is contraindicated in patients with a history of hypersensitivity, including anaphylaxis, to mycophenolate mofetil (MMF), mycophenolic acid (MPA), polysorbate 80 (TWEEN) or any other component of the drug product  [see Warnings and Precautions (5.8)] .

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.

Based on animal data, men should not donate semen during therapy and for 90 days following discontinuation of MYHIBBIN [see Use In Specific Populations (8.3)] .

The following adverse reactions are discussed in greater detail in other sections of the label:

• Embryofetal Toxicity [see Warnings and Precautions (5.1)]

• Lymphomas and Other Malignancies [see Warnings and Precautions (5.2)]

• Serious Infections [see Warnings and Precautions (5.3)]

• Blood Dyscrasias: Neutropenia, Pure Red Cell Aplasia [see Warnings and Precautions (5.4)]

• Gastrointestinal Complications [see Warnings and Precautions (5.5)]

• Acute Inflammatory Syndrome Associated with Mycophenolate Products [see Warnings and Precautions (5.7)]

• Hypersensitivity Reactions [see Warnings and Precautions (5.8)]

• See FPI 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. ( 7.1)
• MYHIBBIN may reduce effectiveness of oral contraceptives. Use of additional barrier contraceptive methods is recommended. ( 7.2)
• See FPI for other important drug interactions. ( 7)

Advise patients not to donate blood during therapy and for at least 6 weeks following discontinuation of MYHIBBIN [see Warnings and Precautions (5.10)].

Advise males of childbearing potential not to donate semen during therapy and for 90 days following discontinuation of MYHIBBIN [see Warnings and Precautions (5.11)].

This Medication Guide has been approved by the U.S. Food and   Drug Administration                                                                                          Approved: 04/2025

MYH-MG-02

There is a lack of information regarding the pharmacodynamic effects of MMF.

Inform patients that they are at increased risk for developing blood adverse effects such as anemia or low white blood cells. Advise patients to immediately contact their healthcare provider if they experience any evidence of infection, unexpected bruising, or bleeding, or any other manifestation of bone marrow suppression [see Warnings and Precautions (5.4)].

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 [see Adverse Reactions (6.1, 6.2)].

Serious viral infections reported include:

• Polyomavirus-associated nephropathy (PVAN), especially due to BK virus infection
• JC virus-associated progressive multifocal leukoencephalopathy (PML), and
• Cytomegalovirus (CMV) infections: CMV seronegative transplant patients who receive an organ from a CMV seropositive donor are at highest risk of CMV viremia and CMV disease.
• Viral reactivation in patients infected with Hepatitis B and C
• COVID-19

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.

PVAN, especially due to BK virus infection, is associated with serious outcomes, including deteriorating renal function and renal graft loss [see Adverse Reactions (6.2)]. Patient monitoring may help detect patients at risk for PVAN.

PML, which is sometimes fatal, commonly presents with hemiparesis, apathy, confusion, cognitive deficiencies, and ataxia [see Adverse Reactions (6.2)] . In immunosuppressed patients, physicians should consider PML in the differential diagnosis in patients reporting neurological symptoms.

The risk of CMV viremia and CMV disease is highest among transplant recipients seronegative for CMV at time of transplant who receive a graft from a CMV seropositive donor. Therapeutic approaches to limiting CMV disease exist and should be routinely provided. Patient monitoring may help detect patients at risk for CMV disease.

Viral reactivation has been reported in patients infected with HBV or HCV. Monitoring infected patients for clinical and laboratory signs of active HBV or HCV infection is recommended.

MYHIBBIN is indicated for the prophylaxis of organ rejection, in adult and pediatric recipients 3 months of age and older of allogeneic kidney [see Clinical Studies (14.1)], heart [see Clinical Studies (14.2)] or liver transplants [see Clinical Studies (14.3)] , in combination with other immunosuppressants.

 Mycophenolate mofetil (MMF) is absorbed following oral administration and hydrolyzed to mycophenolic acid (MPA), the active metabolite. MPA is a selective uncompetitive inhibitor of the two isoforms (type I and type II) of inosine monophosphate dehydrogenase (IMPDH) leading to inhibition of the de novo pathway of guanosine nucleotide synthesis and blocks DNA synthesis. The mechanism of action of MPA is multifaceted and includes effects on cellular checkpoints responsible for metabolic programming of lymphocytes. MPA shifts transcriptional activities in lymphocytes from a proliferative state to catabolic processes. In vitro studies suggest that MPA modulates transcriptional activities in human CD4+ T-lymphocytes by suppressing the Akt/mTOR and STAT5 pathways that are relevant to metabolism and survival, leading to an anergic state of T-cells whereby the cells become less responsive to antigenic stimulation. Additionally, MPA enhanced the expression of negative co-stimulators such as CD70, PD-1, CTLA-4, and transcription factor FoxP3 as well as decreased the expression of positive co-stimulators CD27 and CD28.

MPA decreases proliferative responses of T- and B-lymphocytes to both mitogenic and allo-antigenic stimulation, antibody responses, as well as the production of cytokines from lymphocytes and monocytes such as GM-CSF, IFN-Ɣ, IL-17, and TNF-α. Additionally, MPA prevents the glycosylation of lymphocyte and monocyte glycoproteins that are involved in intercellular adhesion to endothelial cells and may inhibit recruitment of leukocytes into sites of inflammation and graft rejection.

Overall, the effect of MPA is cytostatic and reversible.

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 [see Use in Specific Populations (8.1, 8.3)].

Pregnancy loss and malformation

• Inform females of reproductive potential and pregnant women that use of MYHIBBIN during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of congenital malformations. Advise that they must use an acceptable form of contraception [see Warnings and Precautions (5.1), Use in Specific Populations (8.1, 8.3)].
• Encourage pregnant women to enroll in the Pregnancy Exposure Registry. This registry monitors pregnancy outcomes in women exposed to mycophenolate [see Use in Specific Populations (8.1)].

Contraception

• Discuss pregnancy testing, pregnancy prevention and planning with females of reproductive potential [see Use in Specific Populations (8.3)].
• Females of reproductive potential must use an acceptable form of birth control during the entire MYHIBBIN therapy and for 6 weeks after stopping MYHIBBIN, unless the patient chooses abstinence. MYHIBBIN may reduce effectiveness of oral contraceptives. Use of additional barrier contraceptive methods is recommended [see Use in Specific Populations (8.3)].
• For patients who are considering pregnancy, discuss appropriate alternative immunosuppressants with less potential for embryofetal toxicity. Risks and benefits of MYHIBBIN should be discussed with the patient.
• Advise sexually active male patients and/or their partners to use effective contraception during the treatment of the male patient and for at least 90 days after cessation of treatment. This recommendation is based on findings of animal studies [see Use in Specific Populations (8.3), Nonclinical Toxicology (13.1)].

A double-blind, randomized, comparative, parallel-group, multicenter study in primary de novo heart transplant recipients was performed at centers in the United States (20), in Canada (1), in Europe (5) and in Australia (2). The total number of patients enrolled (ITT population) was 650; 72 never received study drug and 578 received study drug (Safety Population). Patients received mycophenolate mofetil 1.5 g twice daily (n=289) or AZA 1.5 to 3 mg/kg/day (n=289), in combination with cyclosporine (Sandimmune ^®or Neoral ^®) and corticosteroids as maintenance immunosuppressive therapy. The two primary efficacy endpoints were: (1) the proportion of patients who, after transplantation, had at least one endomyocardial biopsy-proven rejection with hemodynamic compromise, or were re-transplanted or died, within the first 6 months, and (2) the proportion of patients who died or were re-transplanted during the first 12 months following transplantation. Patients who prematurely discontinued treatment were followed for the occurrence of allograft rejection for up to 6 months and for the occurrence of death for 1 year.

The analyses of the endpoints showed:

• Rejection: No difference was established between mycophenolate mofetil and AZA with respect to biopsy-proven rejection with hemodynamic compromise.
• Survival: Mycophenolate mofetil was shown to be at least as effective as AZA in preventing death or re-transplantation at 1 year (see Table 11 ).

^aHemodynamic compromise occurred if any of the following criteria were met: pulmonary capillary wedge pressure ≥20 mm or a 25% increase; cardiac index <2.0 L/min/m ²or a 25% decrease; ejection fraction ≤30%; pulmonary artery oxygen saturation ≤60% or a 25% decrease; presence of new S ₃gallop; fractional shortening was ≤20% or a 25% decrease; inotropic support required to manage the clinical condition.

A double-blind, randomized, comparative, parallel-group, multicenter study in primary hepatic transplant recipients was performed at centers in the United States (16), in Canada (2), in Europe (4) and in Australia (1). The total number of patients enrolled was 565. Per protocol, patients received mycophenolate mofetil 1.5 g twice daily orally or AZA 1 to 2 mg/kg/day orally, in combination with cyclosporine (Neoral ^®) and corticosteroids as maintenance immunosuppressive therapy. The actual median oral dose of AZA on study was 1.5 mg/kg/day (range of 0.3 to 3.8 mg/kg/day) initially and 1.26 mg/kg/day (range of 0.3 to 3.8 mg/kg/day) at 12 months. The two primary endpoints were: (1) the proportion of patients who experienced, in the first 6 months post-transplantation, one or more episodes of biopsy-proven and treated rejection or death or re-transplantation, and (2) the proportion of patients who experienced graft loss (death or re-transplantation) during the first 12 months post-transplantation. Patients who prematurely discontinued treatment were followed for the occurrence of allograft rejection and for the occurrence of graft loss (death or re-transplantation) for 1 year.

In combination with corticosteroids and cyclosporine, mycophenolate mofetil demonstrated a lower rate of acute rejection at 6 months and a similar rate of death or re-transplantation at 1 year compared to AZA ( Table 12 ).

• Blood Dyscrasias (Neutropenia, Red Blood Cell Aplasia): Monitor with blood tests; consider treatment interruption or dose reduction. ( 5.4)
• Gastrointestinal Complications: Monitor for complications such as bleeding, ulceration and perforations, particularly in patients with underlying gastrointestinal disorders. ( 5.5)
• Hypoxanthine-Guanine Phosphoribosyl-Transferase Deficiency: Avoid use of MYHIBBIN. ( 5.6)
• Acute Inflammatory Syndrome Associated with Mycophenolate Products: Monitor for this paradoxical inflammatory reaction. ( 5.7)
• Hypersensitivity Reactions: Discontinue MYHIBBIN; treat and monitor until signs and symptoms resolve. ( 5.8)
• Immunizations: Avoid live attenuated vaccines. ( 5.9)
• Blood Donation: Avoid during therapy and for 6 weeks thereafter. ( 5.10)
• Semen Donation: Avoid during therapy and for 90 days thereafter. ( 5.11)
• Potential Impairment on Driving and Use of Machinery: MYHIBBIN may affect ability to drive or operate machinery. ( 5.13)

• Reduce or interrupt dosing in the event of neutropenia. ( 2.5)
• See full prescribing information (FPI) for: dosage modifications for renal impairment and neutropenia ( 2.5)

Oral suspension: mycophenolate mofetil 200 mg/mL in a white to off-white suspension.

The following adverse reactions have been identified during post-approval use of mycophenolate mofetil. 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:

• Embryo-Fetal Toxicity: Congenital malformations and spontaneous abortions, mainly in the first trimester, have been reported following exposure to mycophenolate mofetil (MMF) in combination with other immunosuppressants during pregnancy [see Warnings and Precautions (5.1), and Use in Specific Populations (8.1), (8.3)]. Congenital malformations include:

- Facial malformations: cleft lip, cleft palate, micrognathia, hypertelorism of the orbits

- Abnormalities of the ear and eye: abnormally formed or absent external/middle ear, coloboma, microphthalmos

- Malformations of the fingers: polydactyly, syndactyly, brachydactyly

- Cardiac abnormalities: atrial and ventricular septal defects

- Esophageal malformations: esophageal atresia

- Nervous system malformations: such as spina bifida.

• Digestive: Colitis, pancreatitis
• Hematologic and Lymphatic: Bone marrow failure, cases of pure red cell aplasia (PRCA) and hypogammaglobulinemia have been reported in patients treated with mycophenolate mofetil in combination with other immunosuppressive agents [see Warnings and Precautions (5.4)].
• Immune: Hypersensitivity reactions, including anaphylaxis and angioedema [see Warnings and Precautions (5.8)] , hypogammaglobinemia.
• Infections: Meningitis, infectious endocarditis, tuberculosis, atypical mycobacterial infection, progressive multifocal leukoencephalopathy, BK virus infection, viral reactivation of hepatitis B and hepatitis C, protozoal infections [see Warnings and Precautions (5.3)].
• Respiratory: Bronchiectasis, interstitial lung disease, fatal pulmonary fibrosis, have been reported rarely and should be considered in the differential diagnosis of pulmonary symptoms ranging from dyspnea to respiratory failure in post-transplant patients receiving mycophenolate mofetil.
• Vascular: Lymphocele

• Male Patients: 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 (8.3)

Postmarketing cases of hypersensitivity reactions, including angioedema and anaphylaxis, have been reported with the use of MMF and mycophenolate products. These reactions generally occurred within hours to the next day after initiating MMF or mycophenolate products. If signs or symptoms of a hypersensitivity reaction occur, discontinue MYHIBBIN; treat and monitor until signs and symptoms resolve [see Contraindications (4)].

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.

An estimated total of 1557 adult patients received mycophenolate mofetil during pivotal clinical trials in the prevention of acute organ rejection. Of these, 991 were included in the three renal studies, 277 were included in one hepatic study, and 289 were included in one cardiac study. Patients in all study arms also received cyclosporine and corticosteroids.

The data described below primarily derive from five randomized, active-controlled double-blind 12-month trials of mycophenolate mofetil in de novo kidney (3) heart (1) and liver (1) transplant patients [see Clinical Studies (14.1, 14.2, and 14.3)] .

Inform patients of the potential risk of hypersensitivity reactions. Advise patients to stop taking MYHIBBIN and seek immediate medical attention if signs or symptoms of a hypersensitivity reaction occur (such as swelling of face, lips, tongue, or throat; difficulty breathing or swallowing) [see Warning and Precautions (5.8)].

Inform patients that acute inflammatory reactions have been reported in some patients who received mycophenolate mofetil. Some reactions were severe, requiring hospitalization. Advise patients to contact their physician if they develop fever, joint stiffness, joint pain or muscle pains [see Warnings and Precautions (5.7)].

• Advise patients to avoid contact of the skin or mucous membranes with MYHIBBIN. If such contact occurs, they must wash the area of contact thoroughly with soap and water. In case of ocular contact, rinse eyes with plain water.
• Advise patients to take a missed dose as soon as they remember, except if it is closer than 2 hours to the next scheduled dose; in this case they should continue to take MYHIBBIN at the usual times.

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

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 receiving immunosuppressants, including MYHIBBIN, are at increased risk of developing lymphomas and other malignancies, particularly of the skin [see Adverse Reactions (6.1)]. 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 mycophenolate mofetil (2 g or 3 g) with other immunosuppressive agents in controlled clinical trials of kidney, heart and liver transplant patients [see Adverse Reactions (6.1)]. 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 [see Adverse Reactions (6.1)].

Patients with Kidney Transplant

No dosage adjustments are recommended for kidney transplant patients with severe hepatic parenchymal disease. However, it is not known whether dosage adjustments are needed for hepatic disease with other etiologies [see Clinical Pharmacology (12.3)].

Patients with Heart Transplant

No data are available for heart transplant patients with severe hepatic parenchymal disease.

MYHIBBIN Oral Suspension, 200 mg/mL - NDC 24338-018-01 - 175 mL Carton label

MYHIBBIN Oral Suspension, 200 mg/mL - NDC 24338-018-01 - 175 mL Bottle label

Inform patients that they are at increased risk of developing a variety of infections due to immunosuppression. Instruct them to contact their physician if they develop any of the signs and symptoms of infection explained in the Medication Guide [see Warnings and Precautions (5.3)].

Inform patients that MYHIBBIN can cause gastrointestinal tract complications including bleeding, intestinal perforations, and gastric or duodenal ulcers. Advise the patient to contact their healthcare provider if they have symptoms of gastrointestinal bleeding, or sudden onset or persistent abdominal pain [see Warnings and Precautions (5.5)].

MYHIBBIN should not be used without the supervision of a physician with experience in immunosuppressive therapy.

MYHIBBIN should not be used interchangeably with mycophenolic acid delayed-release tablets without supervision of a physician with experience in immunosuppressive therapy because the rates of absorption following the administration of MYHIBBIN and mycophenolic acid delayed-release tablets are not equivalent.

Patients should avoid contact of the skin or mucous membranes with MYHIBBIN. If such contact occurs, they must wash the area of contact thoroughly with soap and water. In case of ocular contact, rinse eyes with plain water.

The initial oral dose of MYHIBBIN should be given as soon as possible following kidney, heart or liver transplant. It is recommended that MYHIBBIN be administered on an empty stomach. In stable transplant patients, however, MYHIBBIN may be administered with food if necessary [see Clinical Pharmacology (12.3)]. MYHIBBIN must not be mixed with any liquids prior to dose administration. If needed, MYHIBBIN can be administered via a nasogastric tube with a minimum size of 8 French (minimum 1.7 mm interior diameter).

Patients should be instructed to take a missed dose as soon as they remember, except if it is closer than 2 hours to the next scheduled dose; in this case, they should continue to take MYHIBBIN at the usual times.

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.

• Inform patients that they are at increased risk of developing lymphomas and other malignancies, particularly of the skin, due to immunosuppression [see Warnings and Precautions (5.2)].
• Advise patients to limit exposure to sunlight and ultraviolet (UV) light by wearing protective clothing and use of broad-spectrum sunscreen with high protection factor.

Adults

The recommended dosage for adult heart transplant patients is 1.5 g orally administered twice daily (total daily dose of 3 g).

Pediatric Patients 3 months and older

The recommended starting dosage for pediatric heart transplant patients 3 months and older is 600 mg/m², administered twice daily. If well tolerated, the dose can be increased to a maintenance dosage of 900 mg/m² administered twice daily (maximum total daily dose of 3 g or 15 mL of the oral suspension). The dose may be individualized based on clinical assessment.

Adults

The recommended dosage for adult liver transplant patients is 1.5 g administered orally twice daily (total daily dose of 3 g).

Pediatrics Patients 3 months and older

The recommended starting dosage for pediatric liver transplant patients 3 months and older is 600 mg/m², administered twice daily. If well tolerated, the dose can be increased to a maintenance dosage of 900 mg/m² administered twice daily (maximum total daily dose of 3 g or 15 mL of the oral suspension). The dose may be individualized based on clinical assessment.

Advise patients that MYHIBBIN can affect the ability to drive or operate machines. Patients should avoid driving or operating machines if they experience somnolence, confusion, dizziness, tremor or hypotension during treatment with MYHIBBIN [see Warnings and Precautions (5.13)].



Distributed by:

Azurity Pharmaceuticals, Inc. 

Woburn, MA 01801 USA



MYH-PI-02 Rev. 04/2025

In a 104-week oral carcinogenicity study in mice, MMF in daily doses up to 180 mg/kg was not tumorigenic. The highest dose tested was 0.2 times the recommended clinical dose (2 g/day) in renal transplant patients and 0.15 times the recommended clinical dose (3 g/day) in cardiac transplant patients when corrected for differences in body surface area (BSA). In a 104-week oral carcinogenicity study in rats, MMF in daily doses up to 15 mg/kg was not tumorigenic. The highest dose was 0.035 times the recommended clinical dose in kidney transplant patients and 0.025 times the recommended clinical dose in heart transplant patients when corrected for BSA. While these animal doses were lower than those given to patients, they were maximal in those species and were considered adequate to evaluate the potential for human risk [see Warnings and Precautions (5.2)].

The genotoxic potential of MMF was determined in five assays. MMF was genotoxic in the mouse lymphoma/thymidine kinase assay and the in vivo mouse micronucleus assay. MMF was not genotoxic in the bacterial mutation assay, the yeast mitotic gene conversion assay or the Chinese hamster ovary cell chromosomal aberration assay.

MMF had no effect on fertility of male rats at oral doses up to 20 mg/kg/day. This dose represents 0.05 times the recommended clinical dose in renal transplant patients and 0.03 times the recommended clinical dose in cardiac transplant patients when corrected for BSA. In a female fertility and reproduction study conducted in rats, oral doses of 4.5 mg/kg/day caused malformations (principally of the head and eyes) in the first generation offspring in the absence of maternal toxicity. This dose was 0.01 times the recommended clinical dose in renal transplant patients and 0.005 times the recommended clinical dose in cardiac transplant patients when corrected for BSA. No effects on fertility or reproductive parameters were evident in the dams or in the subsequent generation.

MYHIBBIN may impact the ability to drive and use machines. Patients should avoid driving or using machines if they experience somnolence, confusion, dizziness, tremor, or hypotension during treatment with MYHIBBIN [see Adverse Reactions (6.1)] .

Severe neutropenia [absolute neutrophil count (ANC) <0.5 x 10 ³/µL] developed in transplant patients receiving MMF 3 g daily [see Adverse Reactions (6.1)]. 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 10 ³/µL), dosing with MYHIBBIN should be interrupted or the dose reduced, appropriate diagnostic tests performed, and the patient managed appropriately [see Dosage and Administration (2.5)].

Patients receiving MYHIBBIN should be instructed to report immediately any evidence of infection, unexpected bruising, bleeding or any other manifestation of bone marrow depression.

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.

Cases of pure red cell aplasia (PRCA) have been reported in patients treated with MMF in combination with other immunosuppressive agents. In some cases, PRCA was found to be reversible with dose reduction or cessation of MMF therapy. In transplant patients, however, reduced immunosuppression may place the graft at risk.

• Use during pregnancy is associated with increased risks of first trimester pregnancy loss and congenital malformations. Avoid if safer treatment options are available. Females of reproductive potential must be counseled regarding pregnancy prevention and planning [see Warnings and Precautions (5.1), Use in Special Populations (8.1, 8.3)] .
• Increased risk of development of lymphoma and other malignancies, particularly of the skin [see Warnings and Precautions (5.2)] .
• Increased susceptibility to bacterial, viral, fungal and protozoal infections, including opportunistic infections and viral reactivation of hepatitis B and C, which may lead to hospitalizations and fatal outcomes [see Warnings and Precautions (5.3)] .

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.

A variety of drugs have 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.

Mycophenolate mofetil is an inosine monophosphate dehydrogenase (IMPDH) inhibitor; therefore it should be avoided in patients with hereditary deficiencies of hypoxanthine-guanine phosphoribosyl-transferase (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.