Myhibbin
Mycophenolate Mofetil · Suspension · Oral
Uses
1 INDICATIONS AND USAGE 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. MYHIBBIN is an antimetabolite immunosuppressant indicated for the prophylaxis of organ rejection in adult and pediatric recipients 3 months of age and older of allogeneic kidney, heart or liver transplants, in combination with other immunosuppressants. ( 1 )
Dosage and administration
Kidney Transplant 1 g orally twice daily ( 2.2 ) Heart Transplant 1.5 g orally twice daily ( 2.3 ) Liver Transplant 1.5 g orally twice daily ( 2.4 ) PEDIATRICS Kidney Transplant 600 mg/m 2 orally twice daily, up to maximum of 2 g daily ( 2.2 ) Heart Transplant 600 mg/m 2 orally twice daily (starting dose) up to a maximum of 900 mg/m 2 twice daily (maximum daily dose of 3 g or 15 mL of oral suspension) ( 2.3 ) Liver Transplant 600 mg/m 2 orally twice daily (starting dose) up to a maximum of 900 mg/m 2 twice daily (maximum daily dose of 3 g or 15 mL of oral suspension) ( 2.4 ) 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 ) 2.1 Important Administration Instructions 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. 2.2 Recommended Dosage for Kidney Transplant Patients Adults The recommended dosage for adult kidney transplant patients is 1 g orally, administered twice daily (total daily dose of 2 g). Pediatrics Patients 3 months and older Pediatric dosing is based on body surface area (BSA). The recommended dosage for pediatric kidney transplant patients 3 months and older is 600 mg/m2, administered twice daily (maximum daily dose of 2 g or 10 mL of the oral suspension). 2.3 Recommended Dosage for Heart Transplant Patients 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/m 2 , administered twice daily. If well tolerated, the dose can be increased to a maintenance dosage of 900 mg/m 2 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. 2.4 Recommended Dosage for Liver Transplant Patients 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/m 2 , administered twice daily. If well tolerated, the dose can be increased to a maintenance dosage of 900 mg/m 2 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. 2.5 Dosage Modifications: Patients with Renal Impairment, Neutropenia Renal Impairment No dosage modifications are needed in kidney transplant patients with delayed graft function postoperatively [see Clinical Pharmacology ( 12.3 )] . In kidney transplant patients with severe chronic impairment of the graft (GFR <25 mL/min/1.73 m2), do not administer doses of MYHIBBIN greater than 1 g twice a day. These patients should be carefully monitored [ see Clinical Pharmacology ( 12.3 ) ]. Neutropenia If neutropenia develops (ANC <1.3 x 103/µL), dosing with MYHIBBIN should be interrupted or reduced, appropriate diagnostic tests performed, and the patient managed appropriately [see Warnings and Precautions ( 5.4 ) and Adverse Reactions ( 6.1 )].
Dosage forms and strengths
Oral suspension: mycophenolate mofetil 200 mg/mL in a white to off-white suspension. Oral Suspension: 200 mg/mL mycophenolate mofetil.
Contraindications
4 CONTRAINDICATIONS 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 )] . History of hypersensitivity, including anaphylaxis, to mycophenolate mofetil, mycophenolic acid, polysorbate 80 or any component of the drug product ( 4 )
Warnings and precautions
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 ) 5.1 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 [see Use in Specific Populations ( 8.1 , 8.3 )]. 5.2 Lymphoma and Other Malignancies 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 )]. 5.3 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 [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. 5.4 Blood Dyscrasias: Neutropenia and Pure Red Cell Aplasia (PRCA) 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.
Side effects
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) ] The most common adverse reactions in clinical trials (20 % or greater) include diarrhea, leukopenia, infection, vomiting, and there is evidence of a higher frequency of certain types of infections e.g., opportunistic infection. ( 6.1 ) 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. 6.1 Clinical Trials 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. 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 )] . Oral Mycophenolate Mofetil The incidence of adverse reactions for mycophenolate mofetil was determined in five randomized, comparative, double- blind trials in the prevention of rejection in kidney, heart and liver transplant patients (two active- and one placebo- controlled trials, one active-controlled trial, and one active-controlled trial, respectively) [see Clinical Studies ( 14.1 , 14.2 and 14.3 )] . The three de novo kidney studies with 12-month duration compared two dose levels of oral mycophenolate mofetil (1 g twice daily and 1.5 g twice daily) with azathioprine (2 studies) or placebo (1 study) when administered in combination with cyclosporine (Sandimmune ® ) and corticosteroids to prevent acute rejection episodes. One study also included anti-thymocyte globulin (ATGAM ® ) induction therapy. In the de novo heart transplantation study with 12-month duration, patients received mycophenolate mofetil 1.5 g twice daily (n=289) or azathioprine 1.5 to 3 mg/kg/day (n=289), in combination with cyclosporine (Sandimmune ® or Neoral ® ) and corticosteroids as maintenance immunosuppressive therapy. In the de novo liver transplantation study with 12-month duration, patients received mycophenolate mofetil 1.5 g twice daily orally or azathioprine 1 to 2 mg/kg/day orally, in combination with cyclosporine (Neoral ® ) and corticosteroids as maintenance immunosuppressive therapy. The total number of patients enrolled was 565. Approximately 53% of the kidney transplant patients, 65% of the heart transplant patients, and 48% of the liver transplant patients were treated for more than 1 year. Adverse reactions reported in ≥ 20% of patients in the mycophenolate mofetil treatment groups are presented below. The safety data of three kidney transplantation studies are pooled together.
Drug interactions
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 ) 7.1 Effect of Other Drugs on MYHIBBIN Table 3 Drug Interactions with MYHIBBIN that Affect Mycophenolic Acid (MPA) Exposure Antacids with Magnesium or Aluminum Hydroxide Clinical Impact Concomitant use with an antacid containing magnesium or aluminum hydroxide decreases MPA systemic exposure [see Clinical Pharmacology ( 12.3 )] , which may reduce MYHIBBIN efficacy. Prevention or Management Administer magnesium or aluminum hydroxide containing antacids at least 2h after MYHIBBIN. Proton Pump Inhibitors (PPIs) Clinical Impact Concomitant use with PPIs decreases MPA systemic exposure [see Clinical Pharmacology ( 12.3 )] , which may reduce MYHIBBIN efficacy. Prevention or Management Monitor patients for alterations in efficacy when PPIs are co- administered with MYHIBBIN. Examples Lansoprazole, pantoprazole Drugs that Interfere with Enterohepatic Recirculation Clinical Impact Concomitant use with drugs that directly interfere with enterohepatic recirculation, or indirectly interfere with enterohepatic recirculation by altering the gastrointestinal flora, can decrease MPA systemic exposure [see Clinical Pharmacology ( 12.3 )] , which may reduce MYHIBBIN efficacy. Prevention or Management Monitor patients for alterations in efficacy or MYHIBBIN-related adverse reactions when these drugs are co-administered with MYHIBBIN. Examples Cyclosporine A, trimethoprim/sulfamethoxazole, bile acid sequestrants (cholestyramine), rifampin as well as aminoglycoside, cephalosporin, fluoroquinolone and penicillin classes of antimicrobials Drugs Modulating Glucuronidation Clinical Impact Concomitant use with drugs inducing glucuronidation decreases MPA systemic exposure, potentially reducing MYHIBBIN efficacy, while use with drugs inhibiting glucuronidation increases MPA systemic exposure [see Clinical Pharmacology (12.3)] , which may increase the risk of MYHIBBIN-related adverse reactions. Prevention or Management Monitor patients for alterations in efficacy or MYHIBBIN-related adverse reactions when these drugs are co-administered with MYHIBBIN. Examples Telmisartan (induces glucuronidation); isavuconazole (inhibits glucuronidation). Calcium Free Phosphate Binders Clinical Impact Concomitant use with calcium free phosphate binders decrease MPA systemic exposure [see Clinical Pharmacology ( 12.3 )] , which may reduce MYHIBBIN efficacy. Prevention or Management Administer calcium free phosphate binders at least 2 hours after MYHIBBIN. Examples Sevelamer 7.2 Effect of MYHIBBIN on Other Drugs Table 4 Drug Interactions with MYHIBBIN that Affect Other Drugs Drugs that Undergo Renal Tubular Secretion Clinical Impact When concomitantly used with MYHIBBIN, its metabolite MPAG, may compete with drugs eliminated by renal tubular secretion which may increase plasma concentrations and/or adverse reactions associated with these drugs. Prevention or Management Monitor for drug-related adverse reactions in patients with renal impairment. Examples Acyclovir, ganciclovir, probenecid, valacyclovir, valganciclovir Combination Oral Contraceptives Clinical Impact Concomitant use with mycophenolate mofetil decreased the systemic exposure to levonorgestrel, but did not affect the systemic exposure to ethinylestradiol [see Clinical Pharmacology ( 12.3 )] , which may result in reduced combination oral contraceptive effectiveness. Prevention or Management Use additional barrier contraceptive methods.
Use in specific populations
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 ) 8.1 Pregnancy 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. 8.2 Lactation Risk Summary There are no data on the presence of mycophenolate in human milk, or the effects on milk production. There are limited data in the National Transplantation Pregnancy Registry on the effects of mycophenolate on a breastfed child (see Data). Studies in rats treated with MMF have shown mycophenolic acid (MPA) to be present in milk. Because available data are limited, it is not possible to exclude potential risks to a breastfeeding infant. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for MYHIBBIN and any potential adverse effects on the breastfed infant from MYHIBBIN or from the underlying maternal condition. Data Limited information is available from the National Transplantation Pregnancy Registry. Of seven infants reported by the National Transplantation Pregnancy Registry to have been breastfed while the mother was taking mycophenolate, all were born at 34-40 weeks gestation, and breastfed for up to 14 months. No adverse events were reported. 8.3 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 (see Table 5 for acceptable contraception methods). 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 [see Drug Interactions ( 7.2 )].
Pregnancy
8.1 Pregnancy 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.
Pediatric use
8.4 Pediatric Use 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.
Geriatric use
8.5 Geriatric Use 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 )].
Overdosage
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 )] . Treatment and Management MPA and the phenolic glucuronide metabolite of MPA (MPAG) are usually not removed by hemodialysis. However, at high MPAG plasma concentrations (>100 µg/mL), small amounts of MPAG are removed. By increasing excretion of the drug, MPA can be removed by bile acid sequestrants, such as cholestyramine [see Clinical Pharmacology ( 12.3 )].
Description
(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. Structure
Mechanism of action
12.1 Mechanism of Action 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.
How supplied
Handling and Disposal Mycophenolate mofetil has demonstrated teratogenic effects in humans [see Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.1 )] . Wearing disposable gloves is recommended when wiping the outer surface of the bottle and or bottle cap. Avoid direct contact of MYHIBBIN with skin or mucous membranes [see Dosage and Administration ( 2.1 )]. Follow applicable special handling and disposal procedures 1 . Do not use after 60 days of first opening the bottle. 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.
Patient information
Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). 17.1 Embryofetal Toxicity 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 )] . 17.2 Development of Lymphoma and Other Malignancies 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. 17.3 Increased Risk of Serious Infections 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) ] . 17.4 Blood Dyscrasias 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 )]. 17.5 Gastrointestinal Tract Complications 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 )] . 17.6 Acute Inflammatory Syndrome 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 )] . 17.7 Hypersensitivity Reactions 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 Warnings and Precautions ( 5.8 )] . 17.8 Immunizations 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 )] . 17.9 Administration Instructions 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. 17.10 Blood Donation Advise patients not to donate blood during therapy and for at least 6 weeks following discontinuation of MYHIBBIN [see Warnings and Precautions ( 5.10 )] . 17.11 Semen Donation 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 )] . 17.12 Potential to Impair Driving and Use of Machinery 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
Label text from the FDA structured product label by Azurity Pharmaceuticals, Inc. (revised Apr 1, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Mycophenolate Mofetil in 1 product
Myhibbin NDC products (1)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 24338-018 | Mycophenolate Mofetil 200 mg/mL Suspension | Azurity Pharmaceuticals, Inc. | NDA |
Frequently asked questions
What is Myhibbin used for?
1 INDICATIONS AND USAGE 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. MYHIBBIN is an antimetabolite immunosuppressant indicated…
What are the side effects of Myhibbin?
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) ] •… See the full label for the complete list.
Who makes Myhibbin?
Myhibbin is listed by 1 labeler in the FDA NDC directory, including Azurity Pharmaceuticals, Inc..