Update on the Teratogenicity of Maternal Mycophenolate Mofetil

Abstract

Mycophenolic acid (MPA) products, namely mycophenolate mofetil and mycophenolate sodium, are immunosuppressive medications used to prevent rejection in solid organ transplant recipients and to treat various autoimmune disorders. Mycophenolate therapy is considered to be teratogenic based on observational studies of pregnancies exposed to MPA, which demonstrated an increased incidence of miscarriages in pregnancies exposed to MPA during their first trimester and a pattern of birth defects in the offspring of some pregnancies exposed to MPA. Herein, we have detailed case and series reports in a comprehensive literature review summarizing what is known to date regarding fetal exposure to MPA. Based on evidence from the literature, results of postmarketing surveillance, and information from registries such as the National Transplantation Pregnancy Registry in the United States, it is advised that pregnancy be avoided by women taking MPA. Preconception planning offers the opportunity to explore the alternatives to protect the mother, her transplanted organ, and minimize fetal risk. How to proceed in cases of unplanned pregnancies exposed to MPA in transplant recipients is a complex issue. Research involving large epidemiological studies is expected to be sparse as women heed the warnings about becoming pregnant on MPA. Published recommendations for managing MPA in women of childbearing potential include discontinuing the medication prior to conception, switching the MPA to another medication, or discontinuing the MPA when the pregnancy is discovered.

Management of Juvenile Myasthenia Gravis

“…Common side-effects include nausea, vomiting, diarrhea, and less frequently leukopenia. Mycophenolate has been shown to be teratogenic and use is generally avoided in females of childbearing age as a long term option ( 48 ).…”

Fetal Toxicity of Immunosuppressive Drugs in Pregnancy

“…The FDA classifies these drugs as Category D., i.e., with positive evidence of human fetal risk. It is recommended that pregnancy be avoided by women taking MPA [42]. Women being considered for treatment with MPA should always have a negative pregnancy test and should employ at least two methods of contraception during its use [43,44].…”

Stratifying management of rheumatic disease for pregnancy and breastfeeding

“…Given that leflunomide was teratogenic in animal studies and has a long half-life, a cholestyramine washout to eliminate the drug from the body should be completed pre-conception, despite reassuring data from accidental exposures in human pregnancies 90 . Mycophenolate mofetil is teratogenic and should be stopped 6 weeks before conception 91 . Cyclophosphamide is teratogenic and should be stopped at least 3 months before conception 92 .…”