mycophenolic acid
Tablet, Delayed Release · Oral
Uses
Mycophenolic acid delayed-release tablets are an antimetabolite immunosuppressant indicated for prophylaxis of organ rejection in adult patients receiving kidney transplants and in pediatric patients at least 5 years of age and older who are at least 6 months post kidney transplant. ( 1.1 ) Use in combination with cyclosporine and corticosteroids. ( 1.1 ) Limitations of Use: Mycophenolic acid delayed release tablets and mycophenolate mofetil tablets and capsules should not be used interchangeably. ( 1.2 ) 1.1 Prophylaxis of Organ Rejection in Kidney Transplant Mycophenolic acid delayed-release tablets are indicated for the prophylaxis of organ rejection in adult patients receiving a kidney transplant. Mycophenolic acid delayed-release tablets are indicated for the prophylaxis of organ rejection in pediatric patients 5 years of age and older who are at least 6 months post kidney transplant. Mycophenolic acid delayed-release tablets are to be used in combination with cyclosporine and corticosteroids. 1.2 Limitations of Use Mycophenolic acid delayed-release tablets and mycophenolate mofetil (MMF) tablets and capsules should not be used interchangeably without physician supervision because the rate of absorption following the administration of these two products is not equivalent.
Dosage and administration
In adults: 720 mg by mouth, twice daily (1,440 mg total daily dose) on an empty stomach, 1 hour before or 2 hours after food intake. ( 2.1 ) In children: 5 years of age and older (who are at least 6 months post kidney transplant), 400 mg/m 2 by mouth, twice daily (up to a maximum of 720 mg twice daily). ( 2.2 ) Do not crush, chew, or cut tablet prior to ingestion. ( 2.3 ) 2.1 Dosage in Adult Kidney Transplant Patients The recommended dose of mycophenolic acid delayed-release tablets are 720 mg administered twice daily (1,440 mg total daily dose). 2.2 Dosage in Pediatric Kidney Transplant Patients The recommended dose of mycophenolic acid in conversion (at least 6 months post-transplant) pediatric patients age 5 years and older is 400 mg/m 2 body surface area (BSA) administered twice daily (up to a maximum dose of 720 mg administered twice daily). 2.3 Administration Mycophenolic acid delayed-release tablets should be taken on an empty stomach, 1 hour before or 2 hours after food intake [see Clinical Pharmacology ( 12.3 ) ] . Mycophenolic acid delayed-release tablets should not be crushed, chewed, or cut prior to ingesting. The tablets should be swallowed whole in order to maintain the integrity of the enteric coating. Pediatric patients with a BSA of 1.19 m 2 to 1.58 m 2 may be dosed either with three mycophenolic acid 180 mg tablets, or one 180 mg tablet plus one 360 mg tablet twice daily (1,080 mg daily dose). Patients with a BSA of > 1.58 m 2 may be dosed either with four mycophenolic acid 180 mg tablets, or two mycophenolic acid 360 mg tablets twice daily (1,440 mg daily dose). Pediatric doses for patients with BSA < 1.19 m 2 cannot be accurately administered using currently available formulations of mycophenolic acid tablets.
Dosage forms and strengths
Mycophenolic acid delayed-release tablets, USP are available as 180 mg and 360 mg tablets. Table 1: Description of Mycophenolic Acid Delayed-Release Tablets, USP Dosage strength 180 mg tablet 360 mg tablet Active ingredient mycophenolic acid as mycophenolate sodium mycophenolic acid as mycophenolate sodium Appearance Light green, round, slightly biconvex bevelled edge enteric coated tablet Light pink, oval, biconvex enteric coated tablet Imprint Engraved “MYC” over “180” on one side, “APO” on the other side Engraved “MYC 360” on one side, “APO” on the other side Mycophenolic acid are available as 180 mg and 360 mg tablets. ( 3 )
Contraindications
Mycophenolic acid delayed-release tablets are contraindicated in patients with history of hypersensitivity, including anaphylaxis, to mycophenolate sodium, mycophenolic acid (MPA), mycophenolate mofetil, or to any of its excipients [see Warnings and Precautions ( 5.9 ), Adverse Reactions ( 6.2 )]. History of hypersensitivity, including anaphylaxis, to mycophenolate sodium, mycophenolic acid (MPA), mycophenolate mofetil, or to any of its excipients. ( 4 )
Warnings and precautions
New or Reactivated Viral Infections: Consider reducing immunosuppression. ( 5.5 ) Blood Dyscrasias, including Pure Red Cell Aplasia (PRCA): Monitor for neutropenia or anemia; consider treatment interruption or dose reduction. ( 5.6 ) Serious GI Tract Complications (gastrointestinal bleeding, perforations and ulcers): Administer with caution to patients with active digestive system disease. ( 5.7 ) Hypersensitivity Reactions: Discontinue mycophenolic acid delayed-release tablets; treat and monitor until signs and symptoms resolve. ( 5.9 ) Immunizations: Avoid live attenuated vaccines. ( 5.10 ) Patients with Hereditary Deficiency of Hypoxanthine-guanine Phosphoribosyl-transferase (HGPRT): May cause exacerbation of disease symptoms; avoid use. ( 5.11 ) Blood Donation: Avoid during therapy and for 6 weeks thereafter. ( 5.12 ) Semen Donation: Avoid during therapy and for 90 days thereafter. ( 5.13 ) 5.1 Embryo-Fetal Toxicity Use of mycophenolic acid delayed-release tablets 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 aware of these risks and must be counseled regarding pregnancy prevention and planning. Avoid use of mycophenolic acid delayed-release tablets during pregnancy if safer treatment options are available [see Use in Specific Populations ( 8.1 , 8.3 )]. 5.2 Management of Immunosuppression Only physicians experienced in immunosuppressive therapy and management of organ transplant patients should prescribe mycophenolic acid delayed-release tablets. Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physicians responsible for maintenance therapy should have complete information requisite for the follow-up of the patient [see Boxed Warning ] . 5.3 Lymphoma and Other Malignancies Patients receiving immunosuppressants, including mycophenolic acid delayed-release tablets, are at increased risk of developing lymphomas and other malignancies, particularly of the skin [see Adverse Reactions ( 6 ) ] . The risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any specific agent. As usual 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) has been reported in immunosuppressed organ transplant recipients. The majority of PTLD events appear 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. 5.4 Serious Infections Patients receiving immunosuppressants, including mycophenolic acid delayed-release tablets, are at increased risk of developing bacterial, viral, fungal, and protozoal infections, and new or reactivated viral infections, including opportunistic infections [see Warnings and Precautions ( 5.5 ) ] . These infections may lead to serious, including fatal outcomes. Because of the danger of oversuppression of the immune system which can increase susceptibility to infection, combination immunosuppressant therapy should be used with caution. 5.5 New or Reactivated Viral Infections Polyomavirus associated nephropathy (PVAN), JC virus-associated progressive multifocal leukoencephalopathy (PML), cytomegalovirus (CMV) infections, reactivation of hepatitis B (HBV) or hepatitis C (HCV), SARS-CoV-2 infection, have been reported in patients treated with immunosuppressants, including MPA derivatives mycophenolic acid delayed-release tablets and MMF. Reduction in immunosuppression should be considered for patients who develop evidence of new or reactivated viral infections. Physicians should also consider 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. 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. Risk factors for PML include treatment with immunosuppressant therapies and impairment of immune function. In immunosuppressed patients, physicians should consider PML in the differential diagnosis in patients reporting neurological symptoms and consultation with a neurologist should be considered as clinically indicated. 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 [see Adverse Reactions ( 6.1 )] . 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. 5.6 Blood Dyscrasias, Including Pure Red Cell Aplasia Cases of pure red cell aplasia (PRCA) have been reported in patients treated with MPA derivatives in combination with other immunosuppressive agents. The mechanism for MPA derivatives induced PRCA is unknown; the relative contribution of other immunosuppressants and their combinations in an immunosuppressive regimen is also unknown. In some cases, PRCA was found to be reversible with dose reduction or cessation of therapy with MPA derivatives. In transplant patients, however, reduced immunosuppression may place the graft at risk.
Side effects
The following adverse reactions are discussed in greater detail in other sections of the label. Embryo-Fetal Toxicity [see Boxed Warning, Warnings and Precautions ( 5.1 ) ] Lymphomas and Other Malignancies [see Boxed Warning, Warnings and Precautions ( 5.3 ) ] Serious Infections [see Boxed Warning, Warnings and Precautions ( 5.4 ) ] New or Reactivated Viral Infections [see Warnings and Precautions ( 5.5 ) ] Blood Dyscrasias, Including Pure Red Cell Aplasia [see Warnings and Precautions ( 5.6) ] Serious GI Tract Complications [see Warnings and Precautions ( 5.7 ) ] Acute Inflammatory Syndrome Associated with Mycophenolate Products [see Warnings and Precautions ( 5.8 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.9 )] Rare Hereditary Deficiencies [see Warnings and Precautions ( 5.11 )] Most common adverse reactions ( ≥ 20%): anemia, leukopenia, constipation, nausea, diarrhea, vomiting, dyspepsia, urinary tract infection, CMV infection, insomnia, and postoperative pain. ( 6.2 ) To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at 1-800-706-5575 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below derive from two randomized, comparative, active-controlled, double-blind, double-dummy trials in prevention of acute rejection in de novo and converted stable kidney transplant patients. In the de novo trial, patients were administered either mycophenolic acid delayed-release tablets 1.44 grams per day (N = 213) or MMF 2 grams per day (N = 210) within 48 hours post-transplant for 12 months in combination with cyclosporine, USP MODIFIED and corticosteroids. Forty-one percent of patients also received antibody therapy as induction treatment. In the conversion trial, renal transplant patients who were at least 6 months post-transplant and receiving 2 grams per day MMF in combination with cyclosporine USP MODIFIED, with or without corticosteroids for at least two weeks prior to entry in the trial were randomized to mycophenolic acid delayed-release tablets 1.44 grams per day (N = 159) or MMF 2 grams per day (N = 163) for 12 months. The average age of patients in both studies was 47 years and 48 years ( de novo study and conversion study, respectively), ranging from 22 to 75 years. Approximately 66% of patients were male; 82% were white, 12% were black, and 6% other races. About 40% of patients were from the United States and 60% from other countries. In the de novo trial, the overall incidence of discontinuation due to adverse reactions was 18% (39/213) and 17% (35/210) in the mycophenolic acid delayed-release tablets and MMF arms, respectively . The most common adverse reactions leading to discontinuation in the mycophenolic acid delayed-release tablets arm were graft loss (2%), diarrhea (2%), vomiting (1%), renal impairment (1%), CMV infection (1%), and leukopenia (1%). The overall incidence of patients reporting dose reduction at least once during the 0- to 12-month study period was 59% and 60% in the mycophenolic acid delayed-release tablets and MMF arms, respectively. The most frequent reasons for dose reduction in the mycophenolic acid delayed-release tablets arm were adverse reactions (44%), dose reductions according to protocol guidelines (17%), dosing errors (11%) and missing data (2%). The most common adverse reactions (≥ 20%) associated with the administration of mycophenolic acid delayed-release tablets were anemia, leukopenia, constipation, nausea, diarrhea, vomiting, dyspepsia, urinary tract infection, CMV infection, insomnia, and postoperative pain. The adverse reactions reported in ≥ 10% of patients in the de novo trial are presented in Table 2 below. Table 2: Adverse Reactions (%) Reported in ≥ 10% of De novo Kidney Transplant Patients in Either Treatment Group De novo Renal Trial ** System organ class adverse drug reactions Mycophenolic acid delayed-release tablets 1.44 grams per day (n = 213) (%) Mycophenolate mofetil (MMF) 2 gr ams per day (n = 210) (%) Blood and lymphatic system disorders Anemia 22 22 Leukopenia 19 21 Gastrointestinal system disorders Constipation 38 40 Nausea 29 27 Diarrhea 24 25 Vomiting 23 20 Dyspepsia 23 19 Abdominal pain upper 14 14 Flatulence 10 13 General and administrative site disorders Edema 17 18 Edema lower limb 16 17 Pyrexia 13 19 Investigations Increased blood creatinine 15 10 Infections and infestations Urinary tract infection 29 33 CMV infection 20 18 Metabolism and nutrition disorders Hypocalcemia 11 15 Hyperuricemia 13 13 Hyperlipidemia 12 10 Hypokalemia 13 9 Hypophosphatemia 11 9 Musculoskeletal, connective tissue and bone disorders Back pain 12 6 Arthralgia 7 11 Nervous system disorder Insomnia 24 24 Tremor 12 14 Headache 13 11 Vascular disorders Hypertension 18 18 **The trial was not designed to support comparative claims for mycophenolic acid for the adverse reactions reported in this table. Table 3 summarizes the incidence of opportunistic infections in de novo transplant patients. Table 3: Viral and Fungal Infections (%) Reported Over 0 to 12 Months De novo Renal Trial Mycophenolic acid delayed-release tablets 1.44 grams per day (n = 213) (%) Mycophenolate mofetil (MMF) 2 grams per day (n = 210) (%) Any cytomegalovirus 22 21 -Cytomegalovirus disease 5 4 Herpes simplex 8 6 Herpes zoster 5 4 Any fungal infection 11 12 - Candida NOS 6 6 - Candida albicans 2 4 Lymphoma developed in 2 de novo patients (1%), (1 diagnosed 9 days after treatment initiation) and in 2 conversion patients (1%) receiving mycophenolic acid delayed-release tablets with other immunosuppressive agents in the 12-month controlled clinical trials. Nonmelanoma skin carcinoma occurred in 1% de novo and 12% conversion patients.
Drug interactions
Antacids with Magnesium and Aluminum Hydroxides: Decreases concentrations of MPA; concomitant use is not recommended. ( 7.1 ) Azathioprine: Competition for purine metabolism; concomitant administration is not recommended. ( 7.2 ) Cholestyramine, Bile Acid Sequestrates, Oral Activated Charcoal, and Other Drugs that Interfere with Enterohepatic Recirculation: May decrease MPA concentrations; concomitant use is not recommended. ( 7.3 ) Sevelamer: May decrease MPA concentrations; concomitant use is not recommended. ( 7.4 ) Cyclosporine: May decrease MPA concentrations; exercise caution when switching from cyclosporine to other drugs or from other drugs to cyclosporine. ( 7.5 ) Norfloxacin and Metronidazole: May decrease MPA concentrations; concomitant use with both drugs is not recommended. ( 7.6 ) Rifampin: May decrease MPA concentrations; concomitant use is not recommended unless the benefit outweighs the risk. ( 7.7 ) Hormonal Contraceptives: May reduce the effectiveness of oral contraceptives. Additional barrier contraceptive methods must be used. ( 5.2 , 7.8 ) Acyclovir, Valacyclovir, Ganciclovir, Valganciclovir, and Other Drugs that Undergo Renal Tubular Secretion: May increase concentrations of mycophenolic acid glucuronide (MPAG) and coadministered drug; monitor blood cell counts. ( 7.9 ) 7.1 Antacids With Magnesium and Aluminum Hydroxides Concomitant use of mycophenolic acid delayed-release tablets and antacids decreased plasma concentrations of mycophenolic acid (MPA). It is recommended that mycophenolic acid delayed-release tablets and antacids not be administered simultaneously [see Clinical Pharmacology ( 12.3 ) ] . 7.2 Azathioprine Given that azathioprine and MMF inhibit purine metabolism, it is recommended that mycophenolic acid delayed-release tablets not be administered concomitantly with azathioprine or MMF. 7.3 Cholestyramine, Bile Acid Sequestrates, Oral Activated Charcoal and Other Drugs That Interfere With Enterohepatic Recirculation Drugs that interrupt enterohepatic recirculation may decrease MPA plasma concentrations when coadministered with MMF. Therefore, do not administer mycophenolic acid delayed-release tablets with cholestyramine or other agents that may interfere with enterohepatic recirculation or drugs that may bind bile acids, e.g., bile acid sequestrates or oral activated charcoal, because of the potential to reduce the efficacy of mycophenolic acid delayed-release tablets [see Clinical Pharmacology ( 12.3 ) ] . 7.4 Sevelamer Concomitant administration of sevelamer and MMF may decrease MPA plasma concentrations. Sevelamer and other calcium-free phosphate binders should not be administered simultaneously with mycophenolic acid delayed-release tablets [see Clinical Pharmacology ( 12.3 ) ] . 7.5 Cyclosporine Cyclosporine inhibits the enterohepatic recirculation of MPA, and therefore, MPA plasma concentrations may be decreased when mycophenolic acid delayed-release tablets are coadministered with cyclosporine. Clinicians should be aware that there is also a potential change of MPA plasma concentrations after switching from cyclosporine to other immunosuppressive drugs or from other immunosuppressive drugs to cyclosporine in patients concomitantly receiving mycophenolic acid delayed-release tablets [see Clinical Pharmacology ( 12.3 ) ] . 7.6 Norfloxacin and Metronidazole MPA plasma concentrations may be decreased when MMF is administrated with norfloxacin and metronidazole. Therefore, mycophenolic acid delayed-release tablets are not recommended to be given with the combination of norfloxacin and metronidazole. Although there will be no effect on MPA plasma concentrations when mycophenolic acid delayed-release tablets are concomitantly administered with norfloxacin or metronidazole when given separately [see Clinical Pharmacology ( 12.3 ) ] . 7.7 Rifampin The concomitant administration of MMF and rifampin may decrease MPA plasma concentrations. Therefore, mycophenolic acid delayed-release tablets are not recommended to be given with rifampin concomitantly unless the benefit outweighs the risk [see Clinical Pharmacology ( 12.3 ) ] . 7.8 Hormonal Contraceptives In a drug interaction study, mean levonorgestrel AUC was decreased by 15% when coadministered with MMF. Although mycophenolic acid delayed-release tablets may not have any influence on the ovulation-suppressing action of oral contraceptives, additional barrier contraceptive methods must be used when mycophenolic acid delayed-release tablets are coadministered with hormonal contraceptives (e.g., birth control pill, transdermal patch, vaginal ring, injection, and implant) [see Warnings and Precautions ( 5.1 ), Use in Specific Populations ( 8.3 ), Clinical Pharmacology ( 12.3 )]. 7.9 Acyclovir (Valacyclovir), Ganciclovir (Valganciclovir), and Other Drugs That Undergo Renal Tubular Secretion The coadministration of MMF and acyclovir or ganciclovir may increase plasma concentrations of mycophenolic acid glucuronide (MPAG) and acyclovir/valacyclovir/ganciclovir/valganciclovir as their coexistence competes for tubular secretion. Both acyclovir/valacyclovir/ganciclovir/valganciclovir and MPAG concentrations will be also increased in the presence of renal impairment. Acyclovir/valacyclovir/ganciclovir/valganciclovir may be taken with mycophenolic acid; however, during the period of treatment, physicians should monitor blood cell counts [see Clinical Pharmacology ( 12.3 ) ] . 7.10 Ciprofloxacin, Amoxicillin Plus Clavulanic Acid and Other Drugs That Alter the Gastrointestinal Flora Drugs that alter the gastrointestinal flora, such as ciprofloxacin or amoxicillin plus clavulanic acid may interact with MMF by disrupting enterohepatic recirculation. Interference of MPAG hydrolysis may lead to less MPA available for absorption when mycophenolic acid delayed-release tablet is concomitantly administered with ciprofloxacin or amoxicillin plus clavulanic acid.
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 Risk Summary Following oral or intravenous (IV) administration, MMF is metabolized to mycophenolic acid (MPA), the active ingredient in mycophenolic acid delayed-release tablets and the active form of the drug. Use of MMF during pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of multiple congenital malformations in multiple organ systems (see Human Data) . Oral administration of mycophenolate to rats and rabbits during the period of organogenesis produced congenital malformations and pregnancy loss at doses less than the recommended clinical dose (0.05 and 1.1 times exposure at the recommended clinical doses in kidney transplant patients for rats and rabbits, respectively) (see Animal Data). Risks and benefits of mycophenolic acid delayed-release tablets should be discussed with the patient. When appropriate, consider alternative immunosuppressants with less potential for embryo-fetal toxicity. The estimated 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, congenital malformations and pregnancy loss occurred when pregnant rats and rabbits received mycophenolate at dose multiples equivalent to and less than the recommended human dose. Oral administration of mycophenolate sodium to pregnant rats from Gestational Day 7 to Day 16 at a dose as low as 1 mg per kg resulted in malformations including anophthalmia, exencephaly, and umbilical hernia. The systemic exposure at this dose represents 0.05 times the clinical exposure at the human dose of 1,440 mg per day of mycophenolic acid delayed-release tablets. Oral administration of mycophenolate to pregnant rabbits from Gestational Day 7 to Day 19 resulted in embryofetal lethality and malformations, including ectopia cordis, ectopic kidneys, diaphragmatic hernia, and umbilical hernia at doses equal to or greater than 80 mg per kg per day, in the absence of maternal toxicity. This corresponds to about 1.1 times the recommended clinical dose based on 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 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 mycophenolic acid delayed-release tablets and any potential adverse effects on the breastfed infant from mycophenolic acid or from the underlying maternal condition. Because available data are limited, it is not possible to exclude potential risks to a breastfeeding infant. 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 to 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 female patients taking mycophenolic acid delayed-release tablets who are considering pregnancy, consider alternative immunosuppressants with less potential for embryo-fetal toxicity. Risks and benefits of mycophenolic acid delayed-release tablets should be discussed with the patient. Pregnancy Testing To prevent unplanned exposure during pregnancy, females of reproductive potential should have a serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL immediately before starting mycophenolic acid delayed-release tablets. 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 embryo-fetal toxicity whenever possible. Contraception Female Patients Females of reproductive potential taking mycophenolic acid delayed-release tablets must receive contraceptive counseling and use acceptable contraception (see Table 5 for Acceptable Contraception Methods).
Overdosage
Signs and Symptoms There have been anecdotal reports of deliberate or accidental overdoses with mycophenolic acid delayed-release tablets, whereas not all patients experienced related adverse reactions. In those overdose cases in which adverse reactions were reported, the reactions fall within the known safety profile of the class. Accordingly, an overdose of mycophenolic acid delayed-release tablets could possibly result in oversuppression of the immune system and may increase the susceptibility to infection, including opportunistic infections, fatal infections and sepsis. If blood dyscrasias occur (e.g., neutropenia with absolute neutrophil count < 1.5 x 10 3 /mcL or anemia), it may be appropriate to interrupt or discontinue mycophenolic acid delayed-release tablets. Possible signs and symptoms of acute overdose could include the following: hematological abnormalities, such as leukopenia and neutropenia, and gastrointestinal symptoms, such as abdominal pain, diarrhea, nausea and vomiting, and dyspepsia. Treatment and Management General supportive measures and symptomatic treatment should be followed in all cases of overdosage. Although dialysis may be used to remove the inactive metabolite mycophenolic acid glucuronide (MPAG), it would not be expected to remove clinically significant amounts of the active moiety, mycophenolic acid, due to the 98% plasma protein binding of mycophenolic acid. By interfering with enterohepatic circulation of mycophenolic acid, activated charcoal or bile sequestrates, such as cholestyramine, may reduce the systemic mycophenolic acid exposure.
Description
Mycophenolic acid delayed-release tablets, USP are an enteric formulation of mycophenolate sodium that delivers the active moiety mycophenolic acid (MPA). Mycophenolic acid is an immunosuppressive agent. As the sodium salt, MPA is chemically designated as ( E )-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4-enoic acid sodium salt. Its molecular formula is C 17 H 19 O 6 Na. The molecular weight is 342.32 g/mol and the structural formula is : Mycophenolic acid, as the sodium salt, is a white to off-white powder and is highly soluble in aqueous media at physiological pH and practically insoluble in 0.1N hydrochloric acid. Mycophenolic acid is available for oral use as delayed-release tablets containing either 180 mg or 360 mg of mycophenolic acid. Inactive ingredients include colloidal silicon dioxide, hypromellose, methylcellulose, polyethylene glycol, sodium lauryl sulfate and stearic acid. The enteric coating of the tablet consists of ferric oxide red (360 mg), ferric oxide yellow, indigotine al lake (180 mg), methacrylic acid and ethyl acrylate copolymer dispersion, talc, titanium dioxide, and triethyl citrate. mycophenolic figure.jpg
How supplied
Mycophenolic acid delayed-release tablets, USP are supplied as: 180 mg tablet: Light green, round, slightly biconvex bevelled edge enteric coated tablet. Engraved “MYC” over “180” on one side, “APO” on the other side, containing 180 mg mycophenolic acid (MPA) as mycophenolate sodium. Bottles of 30……………………………………………………NDC 60505-2965-3 Bottles of 60……………………………………………………NDC 60505-2965-6 Bottles of 90……………………………………………………NDC 60505-2965-9 Bottles of 100………………………………………….……… NDC 60505-2965-1 Bottles of 120……………………………………………….… NDC 60505-2965-7 Bottles of 500…………………………………………………. NDC 60505-2965-5 Bottles of 1,000……………………………………………...… NDC 60505-2965-8 360 mg tablet: Light pink, oval, biconvex enteric coated tablet. Engraved “MYC 360” on one side, “APO” on the other side, containing 360 mg mycophenolic acid (MPA) as mycophenolate sodium. Bottles of 30……………………………………………………NDC 60505-2966-3 Bottles of 60……………………………………………………NDC 60505-2966-6 Bottles of 90……………………………………………………NDC 60505-2966-9 Bottles of 100………………………………………….……… NDC 60505-2966-1 Bottles of 120……………………………………………….… NDC 60505-2966-7 Bottles of 500…………………………………………………. NDC 60505-2966-5 Bottles of 1,000……………………………………………...… NDC 60505-2966-8 Storage Store at 20 °C to 25°C ( 68 °F to 77°F); excursions permitted from 15° C to 30°C (59° F to 86°F) [see USP Controlled Room Temperature]. Protect from moisture. Dispense in a tight container (USP). Handling Keep out of reach and sight of children. Mycophenolic acid delayed-release tablets, USP should not be crushed or cut in order to maintain the integrity of the enteric coating [see Dosage and Administration ( 2.3 )]. Teratogenic effects have been observed with mycophenolate sodium [see Warnings and Precautions ( 5.1 )] . If for any reason the mycophenolic acid delayed-release tablets must be crushed, avoid inhalation of the powder, or direct contact of the powder, with skin or mucous membranes.
Patient information
Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Embryo-Fetal Toxicity Pregnancy loss and malformations Inform pregnant women and females of reproductive potential that use of mycophenolic acid delayed-release tablets in pregnancy is associated with an increased risk of first trimester pregnancy loss and an increased risk of congenital malformations. Advise patients that they must use an acceptable form of contraception [see Warnings and Precautions ( 5.1 ), Use in Specific Populations ( 8.1 , 8.3 )]. 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 acceptable form of birth control during the entire mycophenolic acid delayed-release tablets therapy and for 6 weeks after stopping mycophenolic acid delayed-release tablets, unless the patient chooses to avoid heterosexual sexual intercourse completely (abstinence). Mycophenolic acid delayed-release tablets 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 embryo-fetal toxicity. Risks and benefits of mycophenolic acid delayed-release tablets should be discussed with the patient [see Use in Specific Populations ( 8.3 )]. 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. Development of Lymphoma and Other Malignancies Inform patients they are at increased risk of developing lymphomas and other malignancies, particularly of the skin, due to immunosuppression [see Warnings and Precautions ( 5.3 )]. Advise patients to limit exposure to sunlight and ultraviolet (UV) light by wearing protective clothing and use a broad-spectrum sunscreen with a high protection factor [see Warnings and Precautions ( 5.3 )]. Increased Risk of Infection Inform patients they are at increased risk of developing a variety of infections, including opportunistic infections, due to immunosuppression and to contact their physician if they develop any symptoms of infection as explained in the Medication Guide [see Warnings and Precautions ( 5.4 , 5.5 )] . Blood Dyscrasias Inform patients they are at increased risk for developing blood dyscrasias (e.g., neutropenia or anemia) and to immediately contact their healthcare provider if they experience any evidence of infection, unexpected bruising, bleeding, or any other manifestation of bone marrow suppression [see Warnings and Precautions ( 5.6 )]. Gastrointestinal Tract Complications Inform patients that mycophenolic acid delayed-release tablets 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 ( 5.7 )]. Acute Inflammatory Syndrome Inform patients that acute inflammatory reactions have been reported in some patients who received mycophenolate products. 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 ( 5.8 )] . Hypersensitivity Reactions Inform patients of the potential risk of hypersensitivity reactions. Advise patients to stop taking mycophenolic acid delayed-release tablets 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 ( 5.9 )]. Immunizations Inform patients that mycophenolic acid delayed-release tablets can interfere with the usual response to immunizations and that they should avoid live vaccines. Before seeking vaccines on their own, advise patients to discuss first with their physician [see Warnings and Precautions ( 5.10 )]. Administration Instructions Advise patients to swallow mycophenolic acid delayed-release tablets whole, and not to crush, chew, or cut the tablets. Inform patients to take mycophenolic acid delayed-release tablets on an empty stomach, 1 hour before or 2 hours after food intake. Blood Donation Advise patients not to donate blood during therapy and for at least 6 weeks following discontinuation of mycophenolic acid delayed-release tablets [see Warnings and Precautions ( 5.12 )]. Semen Donation Advise males of childbearing potential not to donate semen during therapy and for 90 days following discontinuation of mycophenolic acid delayed-release tablets [see Warnings and Precautions ( 5.13 )]. Drug Interactions Patients should be advised to report to their doctor the use of any other medications while taking mycophenolic acid delayed-release tablets. The simultaneous administration of any of the following drugs with mycophenolic acid delayed-release tablets may result in clinically significant adverse reactions: Antacids with magnesium and aluminum hydroxides [see Drug Interactions ( 7.1 )], Clinical Pharmacology ( 12.3 )] Azathioprine [see Drug Interactions ( 7.2 )] Cholestyramine [see Drug Interactions ( 7.3 ), Clinical Pharmacology ( 12.3 )] Hormonal Contraceptives (e.g., birth control pill, transdermal patch, vaginal ring, injection, and implant) [ see Warnings and Precautions ( 5.2 ), Drug Interactions ( 7.8 )] APOTEX INC. MY COPHENOLIC ACID DELAYED-RELEASE TABLETS , USP 180 mg and 360 mg Manufactured by Manufactured for Apotex Inc. Apotex Corp. Toronto, Ontario Weston, Florida Canada M9L 1T9 33326 Revision: 21
Label text from the FDA structured product label by Apotex Corp (revised Sep 2, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Mycophenolate Sodium in 39 products
- Mycophenolic Acid in 2 products
mycophenolic acid NDC products (41)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 50090-6492 | Mycophenolate Sodium 360 mg/1 Tablet, Delayed Release | A-S Medication Solutions | ANDA |
| 16729-189 | Mycophenolate Sodium 360 mg/1 Tablet, Delayed Release | Accord Healthcare Inc. | ANDA |
| 16729-261 | Mycophenolate Sodium 180 mg/1 Tablet, Delayed Release | Accord Healthcare Inc. | ANDA |
| 72888-200 | Mycophenolate Sodium 360 mg/1 Tablet, Delayed Release | Advagen Pharma Limited | ANDA |
| 72888-199 | Mycophenolate Sodium 180 mg/1 Tablet, Delayed Release | Advagen Pharma Limited | ANDA |
| 68084-918 | Mycophenolate Sodium 360 mg/1 Tablet, Delayed Release | American Health Packaging | ANDA |
| 68084-907 | Mycophenolate Sodium 180 mg/1 Tablet, Delayed Release | American Health Packaging | ANDA |
| 60505-2966 | Mycophenolate Sodium 360 mg/1 Tablet, Delayed Release | Apotex Corp | ANDA |
| 60505-2965 | Mycophenolate Sodium 180 mg/1 Tablet, Delayed Release | Apotex Corp | ANDA |
| 72819-156 | Mycophenolic Acid 360 mg/1 Tablet, Delayed Release | Archis Pharma LLC | ANDA |
| 72819-155 | Mycophenolic Acid 180 mg/1 Tablet, Delayed Release | Archis Pharma LLC | ANDA |
| 67877-929 | Mycophenolate Sodium 360 mg/1 Tablet, Delayed Release | Ascend Laboratories, LLC | ANDA |
| 67877-426 | Mycophenolate Sodium 180 mg/1 Tablet, Delayed Release | Ascend Laboratories, LLC | ANDA |
| 67877-427 | Mycophenolate Sodium 360 mg/1 Tablet, Delayed Release | Ascend Laboratories, LLC | ANDA |
| 67877-928 | Mycophenolate Sodium 180 mg/1 Tablet, Delayed Release | Ascend Laboratories, LLC | ANDA |
| 59651-622 | Mycophenolate Sodium 360 mg/1 Tablet, Delayed Release | Aurobindo Pharma Limited | ANDA |
| 59651-621 | Mycophenolate Sodium 180 mg/1 Tablet, Delayed Release | Aurobindo Pharma Limited | ANDA |
| 70377-040 | Mycophenolate Sodium 360 mg/1 Tablet, Delayed Release | Biocon Pharma Inc. | ANDA |
| 70377-039 | Mycophenolate Sodium 180 mg/1 Tablet, Delayed Release | Biocon Pharma Inc. | ANDA |
| 70377-126 | Mycophenolate Sodium 180 mg/1 Tablet, Delayed Release | Biocon Pharma Inc. | ANDA |
| 70377-127 | Mycophenolate Sodium 360 mg/1 Tablet, Delayed Release | Biocon Pharma Inc. | ANDA |
| 68254-5001 | Mycophenolate Sodium 180 mg/1 Tablet, Delayed Release | CONCORD BIOTECH LIMITED | ANDA |
| 68254-5002 | Mycophenolate Sodium 360 mg/1 Tablet, Delayed Release | CONCORD BIOTECH LIMITED | ANDA |
| 60429-017 | Mycophenolate Sodium 360 mg/1 Tablet, Delayed Release | Golden State Medical Supply, Inc. | ANDA |
| 60429-016 | Mycophenolate Sodium 180 mg/1 Tablet, Delayed Release | Golden State Medical Supply, Inc. | ANDA |
| 0904-6786 | Mycophenolate Sodium 360 mg/1 Tablet, Delayed Release | Major Pharmaceuticals | ANDA |
| 0904-7372 | Mycophenolate Sodium 360 mg/1 Tablet, Delayed Release | Major Pharmaceuticals | ANDA |
| 0904-6785 | Mycophenolate Sodium 180 mg/1 Tablet, Delayed Release | Major Pharmaceuticals | ANDA |
| 82293-012 | Mycophenolate Sodium 180 mg/1 Tablet, Delayed Release | Novugen Pharma (USA) LLC. | ANDA |
| 82293-013 | Mycophenolate Sodium 360 mg/1 Tablet, Delayed Release | Novugen Pharma (USA) LLC. | ANDA |
| 72789-246 | Mycophenolate Sodium 360 mg/1 Tablet, Delayed Release | PD-Rx Pharmaceuticals, Inc. | ANDA |
| 72789-247 | Mycophenolate Sodium 180 mg/1 Tablet, Delayed Release | PD-Rx Pharmaceuticals, Inc. | ANDA |
| 70518-4391 | Mycophenolate Sodium 360 mg/1 Tablet, Delayed Release | REMEDYREPACK INC. | ANDA |
| 70436-172 | Mycophenolate Sodium 180 mg/1 Tablet, Delayed Release | Slate Run Pharmaceuticals, LLC | ANDA |
| 70436-173 | Mycophenolate Sodium 360 mg/1 Tablet, Delayed Release | Slate Run Pharmaceuticals, LLC | ANDA |
| 85972-161 | Mycophenolate Sodium 180 mg/1 Tablet, Delayed Release | Stellon Biotech Inc. | ANDA |
| 85972-162 | Mycophenolate Sodium 360 mg/1 Tablet, Delayed Release | Stellon Biotech Inc. | ANDA |
| 24979-161 | Mycophenolate Sodium 360 mg/1 Tablet, Delayed Release | Upsher-Smith Laboratories, LLC | ANDA |
| 24979-160 | Mycophenolate Sodium 180 mg/1 Tablet, Delayed Release | Upsher-Smith Laboratories, LLC | ANDA |
| 66828-0296 | Mycophenolate Sodium 360 mg/1 Tablet, Delayed Release | Novartis Pharma Produktions GmbH | DRUG FOR FURTHER PROCESSING |
| 66828-0289 | Mycophenolate Sodium 180 mg/1 Tablet, Delayed Release | Novartis Pharma Produktions GmbH | DRUG FOR FURTHER PROCESSING |
mycophenolic acid recalls
- D-0668-2024 Oct 2, 2024 · Class II · Ongoing
Failed Dissolution Specifications
Frequently asked questions
What is mycophenolic acid used for?
Mycophenolic acid delayed-release tablets are an antimetabolite immunosuppressant indicated for prophylaxis of organ rejection in adult patients receiving kidney transplants and in pediatric patients at least 5 years of age and older who are at least 6 months post kidney transplant. ( 1.1 ) Use in combination with cyclosporine and corticosteroids. ( 1.1 ) Limitations of Use: Mycophenolic acid…
What are the side effects of mycophenolic acid?
The following adverse reactions are discussed in greater detail in other sections of the label. Embryo-Fetal Toxicity [see Boxed Warning, Warnings and Precautions ( 5.1 ) ] Lymphomas and Other Malignancies [see Boxed Warning, Warnings and Precautions ( 5.3 ) ] Serious Infections [see Boxed Warning, Warnings and Precautions ( 5.4 ) ] New or Reactivated Viral Infections [see Warnings and… See the full label for the complete list.
Who makes mycophenolic acid?
mycophenolic acid is listed by 19 labelers in the FDA NDC directory, including A-S Medication Solutions, Accord Healthcare Inc., Advagen Pharma Limited, American Health Packaging.
Has mycophenolic acid been recalled?
The FDA enforcement database lists 1 recall for mycophenolic acid, most recently D-0668-2024 (class ii): Failed Dissolution Specifications