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Teratogen Update: Reproductive Risks of Leflunomide (Arava™); a Pyrimidine Synthesis - page 18 / 21





18 / 21

(cholestyramine being initiated  from the 18th to the 30th postconception day).  That means that all these mothers had significant leflunomide exposure during early organogenesis.  These mothers were told that the embryo was exposed to leflunomide during early organogenesis and there was a theoretical risk of malformations to several organ systems, based on animal studies.  Without human data, we cannot be certain of the magnitude of this risk or even whether a risk exists.  Since neuronal proliferation and migration occurs later in development, if the embryo was not affected during organogenesis, an increased risk of microcephaly and mental retardation would be unlikely.  Al but three of these mothers elected to terminate their pregnancies.  Better counseling could be provided if a leflunomide level were obtained  on the day pregnancy was diagnosed, two days into the cholestyramine washout and at the end of the washout.

2. One mother had her pregnancy test at the time of the missed menstrual period and also was aware of the day of conception.  Cholestyramine was initiated on the 16th day post conception and therefore, there is a possibility that the embryo was exposed to much lower levels of leflunomide than were all the other mothers.  She elected to continue her pregnancy because of ethical considerations, not because of the lower exposure to her embryo.  

The three pregnancies that are continuing have not as yet come to term.

3.   A woman of reproductive age who was on AravaTM called to ask about the risk of pregnancy because of the fact that her ova were exposed to leflunomide.  Could leflunomide result in damage to her ova and result in damage to future pregnancies?  If the women underwent cholestyramine washout and waited for three ovulatory cycles before becoming pregnant, there would not be a measurable genetic risk from the preconception  exposure to leflunomide

4.  Men who are planning parenthood and are being treated with leflunomide should undertake cholestyramine washout and wait for at least one and possibly three spermatic cycles before inseminating their spouse.

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