- Medicines and Healthcare products Regulatory Agency
- 14 December 2015
- Last updated:
- 14 December 2015, see all updates
- Therapeutic area:
- Immunosuppression and transplantation and Obstetrics, gynaecology and fertility
Mycophenolate mofetil and its active metabolite mycophenolic acid are associated with a high rate of serious birth defects and increased risk of spontaneous abortion.
Key updated safety advice for healthcare professionals:
- Mycophenolate mofetil or mycophenolic acid should not be used in pregnancy unless there is no suitable alternative treatment to prevent transplant rejection
- Physicians should ensure that women and men taking mycophenolate mofetil and mycophenolic acid understand: the risk of harm to a baby; the need for effective contraception; the need to plan for pregnancy and change treatment as necessary; and the need to immediately consult a physician if there is a possibility of pregnancy
- Mycophenolate mofetil or mycophenolic acid treatment should only be initiated in women of child bearing potential when there is a negative pregnancy test result to rule out unintended use in pregnancy
- Mycophenolate mofetil or mycophenolic acid should only be given to women of childbearing potential who are using highly effective contraception
- Women should use 2 forms of effective contraception during treatment and for 6 weeks after stopping treatment
- Men (including those who have had a vasectomy) should use condoms during treatment and for at least 90 days after stopping treatment. This advice is a precautionary measure due to the genotoxicity of these products
- Female partners of male patients treated with mycophenolate mofetil or mycophenolic acid should use highly effective contraception during treatment and for 90 days after the last dose
Mycophenolate mofetil (CellCept, a prodrug of mycophenolic acid1) is an immunosuppressive agent used in combination with ciclosporin and corticosteroids for the prevention of acute transplant rejection in patients who have received kidney, heart, or liver transplants.
Risk of birth defects and spontaneous abortion
Mycophenolate mofetil is a known teratogen; the most frequently reported congenital malformation is that of the ear. A review of worldwide cases of congenital malformations after exposure during pregnancy has confirmed mycophenolate mofetil as a powerful human teratogen, and showed evidence of an increased rate of congenital malformations and spontaneous abortions compared with other immunosuppressants:
- spontaneous abortions have been reported in 45–49% of pregnant women exposed to mycophenolate mofetil, compared with 12–33% with other immunosuppressants
- based on literature reports,2 3 4 malformations occurred in 23–27% of live births in women exposed to mycophenolate mofetil during pregnancy (compared with 2–3% of live births in the overall worldwide population, and with approximately 4–5% of live births in transplant recipients treated with other immunosuppressants).
- previously only ear malformations had been recognised, but prospectively gathered data have now identified a range of disorders The following other malformations (including multiple malformations) were most frequently reported:
- congenital heart disease, such as atrial and ventricular septal defects
- facial malformations, including cleft lip and cleft palate, micrognathia, and hypertelorism of the orbits
- eye abnormalities
- finger malformations
- tracheo-oesophageal malformations
- nervous system malformations, such as spina bifida
- renal abnormalities
Updated advice on pregnancy testing
Before starting mycophenolate mofetil treatment, women of childbearing potential should have a negative pregnancy test result to exclude unintended exposure of the embryo to mycophenolate.
Two serum or urine pregnancy tests with a sensitivity of at least 25 mIU/mL are recommended. The second test should be done 8–10 days after the first one and immediately before starting mycophenolate mofetil. Pregnancy tests should be repeated as clinically required (eg, after any gap in contraception is reported). Results of all pregnancy tests should be discussed with the patient.
Patients should be instructed not to stop treatment but to consult their physician immediately should pregnancy occur.
Reporting of suspected adverse reactions
Suspected adverse reactions to mycophenolate mofetil, including adverse pregnancy outcomes, should be reported to us on a Yellow Card.
Letter sent to healthcare professionals 10 November 2015
This advice has been implemented as a result of a review of CellCept. Product information for other mycophenolate mofetil and mycophenolic acid products will be updated accordingly in due course. ↩
Sifontis NM, et al. Pregnancy outcomes in solid organ transplant recipients with exposure to mycophenolate mofetil or sirolimus. Transplantation 2006; 82: 1698–702. ↩
Coscia LA, et al. Report from the National Transplantation Pregnancy Registry (NTPR): outcomes of pregnancy after transplantation. Cos Clin Transpl 2009: 103–22. ↩
Hoeltzenbein M, et al. Teratogenicity of mycophenolate confirmed in a prospective study of the European Network of Teratology Information Services. Am J Med Genet A 2012; 158A: 588–96. ↩
Published: 14 December 2015
Updated: 14 December 2015
- Mycophenolate mofetil, mycophenolic acid: new pregnancy-prevention advice for women and men
- First published.