Mycophenolate Mofetil (Page 5 of 10)

8 USE IN SPECIFIC POPULATIONS

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 mycophenolate mofetil for oral suspension treatment. To report a pregnancy or obtain information about the registry, visit www.mycophenolateREMS.com or call 1-800-617-8191.

Risk Summary

Use of mycophenolate mofetil 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 (0.02 to 0.1 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 mycophenolate mofetil for oral suspension should be discussed with the pregnant woman.

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 mycophenolate mofetil 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 mycophenolate mofetil 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 mycophenolate mofetil 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 0.03 and 0.02 times the recommended human doses for renal and cardiac transplant patients, respectively, when corrected for BSA. Oral administration of mycophenolate mofetil 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 0.1 and 0.06 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 mycophenolate mofetil 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 mycophenolate mofetil and any potential adverse effects on the breastfed infant from mycophenolate mofetil 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 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 patients who are considering pregnancy, consider alternative immunosuppressants with less potential for embryofetal toxicity whenever possible. Risks and benefits of mycophenolate mofetil 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 mIU/mL immediately before starting mycophenolate mofetil for oral suspension. 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 mycophenolate mofetil for oral suspension must receive contraceptive counseling and use acceptable contraception (see Table 7 for acceptable contraception methods). Patients must use acceptable birth control during the entire mycophenolate mofetil for oral suspension therapy, and for 6 weeks after stopping mycophenolate mofetil for oral suspension, unless the patient chooses abstinence.

Patients should be aware that mycophenolate mofetil reduces blood levels of the hormones from the oral contraceptive pill and could theoretically reduce its effectiveness [see Drug Interactions (7.2)].

Table 7: Acceptable Contraception Methods For Females of Reproductive Potential Pick from the following birth control options:

Option 1

Methods to

Use Alone

  • Intrauterine devices (IUDs)
  • Tubal sterilization
  • Patient’s partner vasectomy

OR

Option 2

Hormone Methods

choose 1

Barrier Methods

choose 1

Choose One Hormone Method AND

One Barrier

Method

Estrogen and Progesterone

  • Oral Contraceptive Pill
  • Transdermal patch
  • Vaginal ring

Progesterone-only

  • Injection
  • Implant

AND

  • Diaphragm with spermicide
  • Cervical cap with spermicide
  • Contraceptive sponge
  • Male condom
  • Female condom

OR

Option 3

Barrier Methods

choose 1

Barrier Methods

choose 1

Choose One Barrier Method from each column (must choose two methods)

  • Diaphragm with spermicide
  • Cervical cap with spermicide
  • Contraceptive sponge

AND

  • Male condom
  • Female condom

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 mycophenolate mofetil for oral suspension and for at least 90 days after cessation of treatment [see Use in Special Populations (8.1), Nonclinical Toxicology (13.1), Patient Counseling Information (17.9)].

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