MYCOPHENOLIC ACID tablet, delayed release

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

MYCOPHENOLATE SODIUM (UNII: WX877SQI1G) (MYCOPHENOLIC ACID - UNII:HU9DX48N0T)

Available from:

CONCORD BIOTECH LIMITED

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

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. 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. Mycophenolic acid delayed-release tablets are contraindicated in patients with a hypersensitivity to mycophenolate sodium, mycophenolic acid (MPA), mycophenolate mofetil, or to any of its excipients. Reactions like rash, pruritus, hypotension, and chest pain have been observed in clinical trials and post marketing reports [see Adverse Reactions (6) ]. 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 mycophenolic acid delayed-release tablets treatment. To report a pregnancy or obtain information about the registry, visit www.mycophenolateREMS.com or call 1-800-617-8191. 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. 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 delayed-release tablets 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. 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). Patients must use acceptable birth control during entire mycophenolic acid delayed-release tablets therapy, and for 6 weeks after stopping mycophenolic acid delayed-release tablets, unless the patient chooses abstinence (she chooses to avoid heterosexual intercourse completely). Patients should be aware that mycophenolic acid delayed-release tablets reduces blood levels of the hormones in the oral contraceptive pill and could theoretically reduce its effectiveness [see Patient Counseling Information (17), Drug Interactions (7.8) ]. Male Patients Genotoxic effects have been observed in animal studies at exposures exceeding the human therapeutic exposures by approximately 2.5 times. Thus, the risk of genotoxic effects on sperm cells cannot be excluded. Based on this potential risk, sexually active male patients and/or their female partners are recommended to use effective contraception during treatment of the male patient and for at least 90 days after cessation of treatment. Also, based on the potential risk of genotoxic effects, male patients should not donate sperm during treatment with mycophenolic acid delayed-release tablets and for at least 90 days after cessation of treatment [see Use in Specific Populations (8.1), Nonclinical Toxicology (13.1), Patient Counseling Information (17)] . The safety and effectiveness of mycophenolic acid delayed-release tablets have been established in pediatric kidney transplant patients 5 to 16 years of age who were initiated on mycophenolic acid delayed-release tablets at least 6 months post-transplant. Use of mycophenolic acid delayed-release tablets in this age group is supported by evidence from adequate and well-controlled studies of mycophenolic acid delayed-release tablets in a similar population of adult kidney transplant patients with additional pharmacokinetic data in pediatric kidney transplant patients [see Dosage and Administration (2.2, 2.3), Clinical Pharmacology (12.3) ]. Pediatric doses for patients with BSA <1.19 m2 cannot be accurately administered using currently available formulations of mycophenolic acid delayed-release tablets. The safety and effectiveness of mycophenolic acid delayed-release tablets in de novo pediatric kidney transplant patients and in pediatric kidney transplant patients below the age of 5 years have not been established. Clinical studies of mycophenolic acid delayed-release tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Of the 372 patients treated with mycophenolic acid delayed-release tablets in the clinical trials, 6% (N=21) were 65 years of age and older and 0.3% (N=1) were 75 years of age and older. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Product summary:

360 mg tablet: Pink to light pink colored, enteric coated, ovaloid biconvex tablet, debossed with "C2" on one side and plain on other side, containing 360 mg mycophenolic acid (MPA) as mycophenolate sodium. Bottles of 120 with child resistance closure, NDC 68254-5002-1 Bottles of 500, NDC 68254-5002-2 180 mg tablet: Lime green colored, enteric coated, round biconvex tablet, debossed with "C1" on one side and plain on other side, containing 180 mg mycophenolic acid (MPA) as mycophenolate sodium. Bottles of 120 with child resistance closure, NDC 68254-5001-1 Bottles of 1000, NDC 68254-5001-2 Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 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 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.

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

MYCOPHENOLIC ACID- MYCOPHENOLIC ACID TABLET, DELAYED RELEASE
CONCORD BIOTECH LIMITED
----------
MEDICATION GUIDE
Mycophenolic Acid Delayed-Release Tablets
(mye" koe fe nol′ ik as′ id)
Read the Medication Guide that comes with mycophenolic acid
delayed-release tablets before you start
taking it and each time you get a refill. There may be new
information. This Medication Guide does not
take the place of talking with your healthcare provider about your
medical condition or treatment. If you
have any questions about mycophenolic acid delayed-release tablets,
ask your doctor.
What is the most important information I should know about
Mycophenolic acid delayed-release tablets?
Mycophenolic acid delayed-release tablets can cause serious side
effects, including:
•
Increased risk of loss of pregnancy (miscarriage) and higher risk of
birth defects. Females who
take mycophenolic acid delayed-release tablets during pregnancy, have
a higher risk of
miscarriage during the first 3 months (first trimester), and a higher
risk that their baby will be born
with birth defects.
•
If you are a female who can become pregnant:
•
Your doctor must talk with you about acceptable birth control methods
(contraceptive counseling) while taking mycophenolic acid
delayed-release tablets.
•
You should have a pregnancy test immediately before starting
mycophenolic acid
delayed-release tablets and another pregnancy test 8 to 10 days later.
Pregnancy
tests should be repeated during routine follow-up visits with your
doctor. Talk to
your doctor about the results of all of your pregnancy tests.
•
You must use acceptable birth control during your entire mycophenolic
acid
delayed-release tablets therapy and for 6 weeks after stopping
mycophenolic acid
delayed-release tablets, unless at any time you choose to avoid sexual
intercourse
(abstinence) with a man completely. Mycophenolic acid delayed-release
tablets
decreases blood levels of the hormones in birth control pills that you
take by mouth.
Birth control pills may not work as well whil

Summary of Product characteristics

MYCOPHENOLIC ACID- MYCOPHENOLIC ACID TABLET, DELAYED RELEASE
CONCORD BIOTECH LIMITED
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
MYCOPHENOLIC ACID
DELAYED-RELEASE TABLETS SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING
INFORMATION FOR
MYCOPHENOLIC ACID DELAYED-RELEASE TABLETS.
MYCOPHENOLIC ACID DELAYED-RELEASE TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2004
WARNING: EMBRYO-FETAL TOXICITY, MALIGNANCIES, AND SERIOUS INFECTIONS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING_
USE DURING PREGNANCY IS ASSOCIATED WITH INCREASED RISKS OF PREGNANCY
LOSS AND
CONGENITAL MALFORMATIONS. AVOID IF SAFER TREATMENT OPTIONS ARE
AVAILABLE.FEMALES OF
REPRODUCTIVE POTENTIAL MUST BE COUNSELED REGARDING PREGNANCY
PREVENTION AND
PLANNING. (5.1, 8.1, 8.3)
ONLY PHYSICIANS EXPERIENCED IN IMMUNOSUPPRESSIVE THERAPY AND
MANAGEMENT OF
ORGAN TRANSPLANT PATIENTS SHOULD PRESCRIBE MYCOPHENOLIC ACID
DELAYED-RELEASE
TABLETS. (5.2)
INCREASED RISK OF DEVELOPMENT OF LYMPHOMA AND OTHER MALIGNANCIES,
PARTICULARLY OF
THE SKIN, DUE TO IMMUNOSUPPRESSION. (5.3)
INCREASED SUSCEPTIBILITY TO BACTERIAL, VIRAL, FUNGAL, AND PROTOZOAL
INFECTIONS, INCLUDING
OPPORTUNISTIC INFECTIONS. (5.4, 5.5)
RECENT MAJOR CHANGES
Warnings and Precautions, New or Reactivated Viral Infections (5.5)
3/2022
Warnings and Precautions, Acute Inflammatory Syndrome Associated with
Mycophenolate Products (5.7)
3/2022
INDICATIONS AND USAGE
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)
DOSAGE AND ADMINISTRATION
In adults: 720 mg by mouth, twice daily (1,440 mg