In animal studies, Leflunomide has been found to be toxic to the embryo. In rats; malformations of the head, rump, vertebral column, ribs, and limbs were seen; while in rabbits, malformations of the head, spine were observed.
Studies of Leflunomide in humans are obviously not possible. Hence, whatever data we have about humans is either extrapolated from the animal studies or is from the accidental pregnancies while on Leflunomide.
In view of the known fetal toxicity, Leflunomide is avoided in women of childbearing age group. If it is prescribed, reliable contraceptive measures are advised.
Leflunomide has a long half-life & tends to remain in the body for up to 2 years after stopping therapy. Hence, planning pregnancy would mean waiting for 2 years once it is stopped. There is a washout therapy though, to washout Leflunomide from the body. It consists of taking cholestyramine 8 gm thrice daily for 11 days.
Organization of Teratology Information Specialists Collaborative Research Group studied 64 pregnant women with exposure to Leflunomide during pregnancy & compared them with other pregnant ladies with Rheumatoid Arthritis as well as normal pregnant ladies. A majority of these patients did receive a Cholestyramine washout therapy. The study did not find any significant differences in the overall rate of major structural defects in the exposed group.
These numbers are small & one cannot conclude that Leflunomide is safe in pregnancy. The only conclusion we can draw from the study is that cholestyramine therapy early in cases of accidental pregnancy may avert fetal damage. The risk is least if the washout therapy is started immediately on missing a period.
Leflunomide washout therapy—
1. Cholestyramine to be taken in the dose of 8 gm thrice daily for 11 days.
2. Blood is checked for Leflunomide levels to ensure adequate washout from the body. The levels should be less than 0.02 mg/L on two occasions 2 weeks apart.
3. If the levels are higher, further Cholestyramine course is essential.
Dos & don’ts for patients on Leflunomide
1. Leflunomide is not the first drug to be used for Rheumatoid Arthritis in the childbearing age group. Your Rheumatologist will start Leflunomide therapy only if your RA is not controlled with other DMARDs & after counseling regarding the fetal toxicity.
2. Practice contraception while on Leflunomide to avoid pregnancy.
3. In case of suspected pregnancy, stop Leflunomide & consult your Rheumatologist immediately.
4. You can take a decision regarding continuation of pregnancy in consultation with your Rheumatologist. In case you wish to continue the pregnancy, washout therapy has to begin immediately.
5. Take time out & register with the Leflunomide pregnancy registries at http://otispregnancy.org/otis_study_ra.asp & http://www.uktis.org/UKTIS_reporting_form.pdf Your information will help Rheumatologists & other patients in their knowledge about this medication.
1. Birth outcomes in women who have taken Leflunomide during pregnancy. Chambers CD et al Arthritis Rheum. 2010 May; 62(5):1494-503
2. Teratogen Update: Reproductive risks of Leflunomide; A pyrimidine synthesis inhibitor: counseling women taking Leflunomide before or during pregnancy and men taking Leflunomide who are contemplating fathering a child. Brent RL Teratology 63:106–112 (2001)