Postmarketing reports of an increased risk of first trimester loss and congenital malformations associated with the use of mycophenolate mofetil during pregnancy has prompted a pregnancy category label change for the immunosuppressant drug.
Mycophenolate mofetil, marketed as CellCept by Roche, is approved for preventing organ rejection in allogenic kidney, heart, or liver transplant recipients, and is used with cyclosporine and corticosteroids.
CellCept also has been used off-label to treat some dermatologic and rheumatologic conditions.
Based on postmarketing data from the U.S. National Transplantation Pregnancy Registry and other postmarketing data in women exposed to systemic CellCept during pregnancy, the pregnancy category label has been changed from a category C, in which the risk of fetal harm cannot be ruled out, to category D, in which there is positive evidence of fetal risk.
Exposure to CellCept during pregnancy has been associated with an increased risk of first trimester loss, and an increased risk of congenital malformations, “especially external ear and facial abnormalities, including cleft lip and palate, and anomalies of the distal limbs, heart, esophagus, and kidney,” according to Roche and the Food and Drug Administration.
The pregnancy category change was announced on the FDA's MedWatch site, and in a letter to health care professionals issued by Roche.
The letter refers to the December 2006 publication of reports from the transplant registry of 33 pregnancies in 24 female transplant patients exposed to regimens containing CellCept. Of the 33 cases, there were 15 spontaneous abortions (45%). Of the 18 live-born infants, 4 (22%) had structural malformations. There were also postmarketing reports, collected between 1995 and 2007, of 77 women exposed to systemic CellCept during pregnancy, of whom 25 (33%) had spontaneous abortions and 14 (18%) had a malformed infant or fetus.
The Roche letter advised that women of childbearing potential–including pubescent girls and perimenopausal women–should have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL 1 week before starting treatment and they should receive contraceptive counseling. Unless abstinence is chosen, women in this category should start using two contraceptive methods 4 weeks before starting treatment with CellCept, and should continue using those two methods for 6 weeks after stopping treatment. CellCept should not be used in a woman who plans to become pregnant “unless she cannot be successfully treated with other immunosuppressant drugs,” according to the letter.
Roche encourages health care professionals to register pregnant women exposed to CellCept in the transplant registry by calling 877-955-6877.
For the MedWatch announcement, Roche letter, and revised label, go to: www.fda.gov/medwatch/safety/2007/safety07.htm#CellCept2www.fda.gov/medwatch