5. Men who inseminate their spouse while taking leflunomide are not at increased risk for parenting a child with birth defects or genetic disease, since leflunomide and its metabolites are not mutagenic or cytotoxic. The very small quantitiy of TFMA, which has mutagenic potential, is present in such small quantities that it can be disregarded. While it would have been less anxiety-provoking for the family if cholestyramine washout had been performed, this non-measurable risk would not warrant an interruption of a wanted pregnancy.
Acknowledgment: Basic science data, animal studies and pharmacokinetic studies performed and presented by scientists from Hoechst-Marion-Roussell (Aventis) at the August 1998 FDA hearing has been utilized for preparing portions of this commentary. The author was a consultant to Hoechst-Marion-Roussell (Renamed Aventis because of a merger) to evaluate the reproductive and teratogenic risks of leflunomide and assist in preparing the package labeling.
Epilogue: Since the drug has been approved almost all of the pregnant women exposed to AravaTM have been referred to the Clinical and Environmental Laboratories at the duPont Hospital for Children and the author has personally counseled rheumatologists, mothers, other family members, the family’s obstetrician or perinatologist. As of December 15, 1999 all referrals will be directed to the California Teratogen Service under the direction of Dr. Kenneth Lyon Jones at the University of California at San Diego. Aventis has awarded a contract to the California Teratogen Service to assume major responsibility for counseling these patients, examining any infants that are delivered, reviewing ultrasounds that may have been taken before pregnancy interruption and following surviving children for developmental evaluation. In other words Dr. Jones and his staff will be prospectively following these pregnancies to determine whether there is a teratogenic risk from therapeutic levels of leflunomide in human pregnancies. The telephone number of the California Teratogen Service is 1-877-311-6811.