CE / CME
Pharmacists: 1.00 contact hour (0.1 CEUs)
Physician Assistants/Physician Associates: 1.00 AAPA Category 1 CME credit
Physicians: maximum of 1.00 AMA PRA Category 1 Credit™
Nurses: 1.00 Nursing contact hour of which 1.00 are eligible for pharmacology credit
Released: February 25, 2025
Expiration: May 29, 2025
Mycophenolate as Immunosuppressants: Indications
Two forms of mycophenolate are commonly used as immunosuppressants: mycophenolate mofetil and mycophenolic acid. Mycophenolate mofetil is indicated for the prophylaxis of organ rejection in adult and pediatric patients receiving an allogeneic kidney, heart, or liver transplant. It is administered in combination with other immunosuppressants and is available as an oral capsule, tablet, or suspension, or as an injection.1 Mycophenolic acid is indicated for the prophylaxis of organ rejection in adult patients with kidney transplants and in pediatric patients older than 5 years of age who are more than 6 months post kidney transplant. This agent should be used in combination with cyclosporine and corticosteroids and is available as a delayed-release tablet containing enteric-coated mycophenolate sodium.2
Mycophenolate: Immunosuppressants in Autoimmunity
In addition to its indicated use, mycophenolate has been employed for many years as an off-label therapy in the management of various autoimmune conditions, including uveitis, systemic lupus erythematosus, lupus nephritis, graft-vs-host disease, bullous pemphigoid, pemphigus vulgaris, systemic sclerosis, autoimmune hepatitis, dermatomyositis, focal segmental glomerulosclerosis, and interstitial lung disease.3
Adverse Pregnancy Outcomes Associated With Mycophenolate Use During Pregnancy
Over time, the FDA has updated its guidance to address adverse outcomes associated with the use of mycophenolate during pregnancy. Initially, warnings focused on risks during pregnancy, labor, or delivery, or for nursing mothers. Today, the warnings have expanded to include adverse outcomes related to pregnancy, lactation, and the use of mycophenolate by females and males of reproductive potential.1,2,4-6
PLLR Pregnancy and Lactation Labeling
Patients in specific populations require careful consideration when using mycophenolate, including those who are pregnant, lactating, or of reproductive potential. In these cases, it is essential to not only manage the individual’s treatment but also to educate patients on pregnancy testing, contraception, and the potential risk of infertility.
Checking Pregnancy Status Prior to Initiating Mycophenolate Therapy and Monitoring Status During Treatment
Prior to initiating mycophenolate therapy, healthcare professionals (HCPs) must confirm a female patient’s pregnancy status, and they must monitor the patient’s pregnancy status throughout treatment. The patient should undergo a high-sensitivity pregnancy test immediately before starting mycophenolate and another test 8-10 days later. Subsequently, a pregnancy test should be performed at every routine follow-up visit, and the results should be discussed with the patient.7
Pregnancy and Fetal Risks Associated With Mycophenolate Use During Pregnancy: Pregnancy Loss
The understanding of pregnancy and fetal risks associated with mycophenolate use during pregnancy has evolved over time. According to the 2006 National Transplantation Pregnancy Registry report, 24 female transplant patients reported 33 pregnancies during which they were exposed to mycophenolate. Among these, 45% resulted in spontaneous miscarriages, and 22% involved structural malformation. Postmarketing data from 77 females exposed to systemic mycophenolate treatment during pregnancy showed that 32% experienced spontaneous abortion, and 22% had a malformed fetus or infant.1,2,8
Pregnancy and Fetal Risks Associated With Mycophenolate Use During Pregnancy: Miscarriage and Birth Defects
These graphs demonstrate a significant difference in miscarriage rates when mycophenolate use is discontinued prior to conception vs after conception. A 2017 study showed that when mycophenolate was discontinued before pregnancy, the miscarriage rate was significantly lower than when it was discontinued after conception. A similar pattern was observed for birth defects, with a significantly lower risk when treatment was discontinued before conception compared with after conception.9
Mycophenolate Exposure in Female Kidney Transplant Recipients: Miscarriages
Further analysis of mycophenolate exposure in female kidney transplant recipients showed that approximately 30% of pregnancies resulted in miscarriage. Patients who discontinued mycophenolate more than 6 weeks before conception did not have a significantly different miscarriage risk compared with those who discontinued mycophenolate less than 6 weeks before conception. However, in patients who discontinued mycophenolate less than 6 weeks prior to conception, the risk of miscarriage was higher, with an odds ratio of 1.18. If treatment was discontinued during the first trimester, the risk increased further, and discontinuation in the second trimester resulted in nearly a 10-fold greater risk.9
Mycophenolate Exposure in Female Kidney Transplant Recipients: Birth Defects
The same study found that 9% of patients exposed to mycophenolate had infants with birth defects. A similar pattern emerges regarding timing. Patients who discontinued mycophenolate less than 6 weeks before conception had a notably lower risk compared with those who discontinued during the first trimester. Discontinuing the medication during the third trimester resulted in a 6-fold higher risk of birth defects.9
Pregnancy Outcomes Related to Mycophenolate Exposure in Female Kidney Transplant Recipients
This graph shows that if a patient has multiple pregnancies, the risk of birth defects increases with each additional pregnancy.9
Birth Defects Associated With Mycophenolate Use During Pregnancy
Birth defects associated with mycophenolate mofetil use during pregnancy most frequently involve the ears, orofacial structures, and eyes. Visceral, cardiac, distal limb, and central nervous system defects are also observed.9,10
Fetal Risks Associated With Mycophenolate Use During Pregnancy: Cleft Lip
This image shows an infant with a cleft lip associated with mycophenolate use during pregnancy.11
Fetal Risks Associated With Mycophenolate Use During Pregnancy: Cleft Palate
Different types of cleft palate birth defects can occur in infants exposed to mycophenolate during pregnancy.11
Fetal Risks Associated With Mycophenolate Use During Pregnancy: External Ear Abnormality
This image shows another common birth defect, an external ear abnormality in an infant who was exposed to mycophenolate mofetil during pregnancy.10
Patient Case: Lisa
Lisa, a 26-year-old woman who was diagnosed with systemic lupus erythematosus as a teenager, discusses her treatment options with her rheumatologist. Watch this brief video to learn about the decision they reached.
Pregnancy Loss and Birth Defects Associated With Mycophenolate Use During Pregnancy
Educating females of reproductive potential—including girls who have entered puberty and all women who have not passed through menopause—about the risks of mycophenolate is crucial. This education should emphasize the increased risk of first-trimester pregnancy loss and birth defects.7
Pregnancy Loss and Birth Defects Associated With Mycophenolate Use During Pregnancy: Patient Education
Regarding pregnancy loss and birth defects associated with mycophenolate, patient education is paramount. Patients should be shown the prescribing information on use in special populations and the latest data on pregnancy loss and congenital malformation risks. Education should also address pregnancy prevention and planning during mycophenolate treatment and should include discussion of acceptable contraception methods and the duration of their use. It is crucial that patients be advised to inform their HCP if they are considering pregnancy.7
Mycophenolate Risk Evaluation and Mitigation Strategy: Patient Counseling Materials
Patients can access Risk Evaluation and Mitigation Strategy (REMS) materials to learn about pregnancy risks, available contraception options, and pregnancy planning. It is important to provide alternative treatment options for patients considering pregnancy and to discuss the immunosuppressive efficacy and safety profiles of available therapies that can be used instead of mycophenolate. Through the REMS program, patients can receive brochures about mycophenolate, and HCPs can access separate materials for prescribers.7
Faculty Discussion
Jennifer Simpson, DNP:
It is very important that we discuss family planning at every visit with our patients who are being treated with mycophenolate, especially females of childbearing age. Do you agree, Dr Girnita?
Diana Girnita, MD, PhD:
Absolutely. I initiate and continue this conversation at every visit, emphasizing the medication’s potential impact on pregnancy and the alternatives available if they choose to conceive.
Jennifer Simpson, DNP:
How do you approach this sensitive topic to ensure patients feel comfortable discussing this with you?
Diana Girnita, MD, PhD:
I always ask female patients of childbearing age about any changes in their pregnancy intentions. I review the adverse effects of mycophenolate with them and remind them that there are alternatives if they are considering pregnancy.
Jennifer Simpson, DNP:
I think that it is great to highlight that there are alternatives. It reinforces that their choices are valid and supported and makes them feel more comfortable. Do you also ask them what kind of contraception they use?
Diana Girnita, MD, PhD:
Yes, I do ask them what contraception they are currently using, and I remind them about the different safety of various options, stressing the importance of reliable contraception. I also remind them to inform me immediately if they become pregnant.
Jennifer Simpson, DNP:
I agree, because if they do become pregnant, we need to get patients connected with the REMS Registry Program so they can be monitored and assessed for potential risks. Have you encountered any challenges with prescription refills because of the REMS requirements?
Diana Girnita, MD, PhD:
At this point, I have not. However, even during refill discussions, I reiterate the medication’s risk and the importance of reliable contraception when using these medications.
Jennifer Simpson, DNP:
That is great. Dr Dolin, what are your thoughts on counseling patients taking mycophenolate about contraception?
Cara D. Dolin, MD, MPH:
As a maternal–fetal medicine subspecialist, I often see patients on mycophenolate after they become pregnant or for preconception counseling. I love Dr Girnita’s approach, how she talks about this at her appointments as a rheumatologist. These discussions need to happen outside of just the OB/GYN world. I always teach my medical students to routinely inquire about pregnancy plans with patients of reproductive potential at every visit, especially with patients receiving mycophenolate. Asking “Do you plan to become pregnant in the next year?” is very important.
If the patient says no, I discuss their current contraception methods and their appropriateness. If no contraception is being used, I offer to prescribe contraception or refer the patient to a gynecologist for counseling and a prescription.
If the patient says yes, then we review their disease status, optimize preconception health, and transition them to pregnancy-compatible medications. This conversation is particularly important for patients being treated with mycophenolate, ensuring that a clear family planning strategy is in place. Given the high rate of unintended pregnancies, proactive family planning is essential, especially for patients with underlying medical conditions requiring medications that are incompatible with pregnancy.
Jennifer Simpson, DNP:
Simply asking about their plans for the next year encourages patients to consider the risks and make informed decisions for themselves and their future children.
Cara D. Dolin, MD, MPH:
Absolutely.
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