MYCOPHENOLATE MOFETIL

Fetal Risk Summary

Mycophenolate mofetil is a purine synthesis inhibitor that is used as an immunosuppressant agent in the prophylaxis of organ rejection in patients receiving allogeneic renal and liver transplants (1). Following oral administration, the drug undergoes rapid and complete hydrolysis to mycophenolic acid, the active moiety.

Reproductive studies have been conducted in rats and rabbits (2). In both species, in the absence of maternal toxicity, fetal resorptions and malformations (type not specified) were observed at doses of 6 mg/kg/day (0.03 times the recommended human dose based on body surface area basis [RHD]) in rats and 90 mg/kg/day (0.92 times the RHD) in rabbits. In rats, a dose of 4.5 mg/kg/day (0.02 times the RHD) produced malformations, principally of the head and eyes (2).

It is not known if mycophenolate mofetil or the active metabolite, mycophenolic acid, crosses the human placenta to the fetus. The molecular weight of the prodrug (about 434), however, is low enough that transfer to the fetus probably occurs. The animal data cited above support this assessment.

No reports describing the use of mycophenolate mofetil during human pregnancy have been located. A 1998 review was also unable to locate reports on the use of the immunosuppressant during pregnancy (1). Because of the potential for congenital defects, use of the drug during pregnancy may represent a high risk to the fetus. Women of childbearing potential who are prescribed this agent should be informed of this risk. The manufacturer recommends these women use effective contraception before and during therapy and for 6 weeks after therapy is stopped (2).

Breast Feeding Summary

Mycophenolate mofetil is excreted into the milk of lactating rats (2). Reports of human use during lactation have not been found. The molecular weight of the drug (about 434) is low enough, however, that passage into human milk should be expected. Mycophenolate mofetil is rapidly and completely hydrolyzed to mycophenolic acid upon absorption. Because of the potential for serious adverse effects in a nursing infant, including an increased frequency of certain infections and the possible development of lymphoma observed in adults (2), mycophenolate mofetil should be considered contraindicated during breast feeding.

References

1. Casele HL, Laifer SA. Pregnancy after liver transplantation. Semin Perinatol 1998;22:149–55.
2. Product information. CellCept. Roche Pharmaceuticals, 1998.