Leflunomide (Arava) and Pregnancy

Leflunomide (available as Arava / Lefno / Lefumide / Rumalef) is a powerful DMARD used for Rheumatoid Arthritis.

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.

References:
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)

Download the ebook: Successful pregnancy with Rheumatoid Arthritis.

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8 Responses to Leflunomide (Arava) and Pregnancy

  1. Raghuvir K Trifale says:

    Cholestyramine is also used in cases of Hypercholesterolemia.Will this treatment cause Hypocholesterolemia.Is lower than average cholesterol level is harmful?

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  2. Hi there it’s me, I am also visiting this website on a regular basis, this web site is truly pleasant and the viewers are really sharing nice thoughts.

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  3. Leslie says:

    Can you talk about what medications are safe or that you use for your RA patients who would like to become pregnant? Or to use during their pregnacy?

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  4. Dr. Akerkar,
    Thank you for this detailed information. Can you please address the following:
    I discontinued use of Arava specifically so that I can plan for pregnancy. My rheumatologist did not prescribe the Cholestyramine course. Is this something I should request?
    My doctor advised me that I need to wait for 2 years after discontinuing use of Arava before trying to conceive. If I complete the Cholestyramine course and my levels are tested for adequate washout, would it be considered safe to attempt conception before the 2 year waiting period (assuming I have all other areas of health/medications addressed)?
    Thank you,
    Rebecca

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    • Yes. Take the chloestyramine course & check the Arava levels twice. The levels should be less than 0.02 mg/L on two occasions 2 weeks apart.
      Though waiting for 2 years remains the best option, this option is considered quite safe to consider conception.

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  5. Vickie feane says:

    Unfortunatly my attempt at taking the ‘wash out’ had to be stopped after one ay as I was diagnosed with gallstones, I am currently not in a healthy enough state do recommence the washout, I have been off arava for 2months but have just taken my second dose of humira. Without the washout when is the soonest I can begin trying to conceive? I have been told different times by different doctors, anything from 6months to 2years…. Would the washout affect the humira I am now taking? Would the humira affect my plasma levels when i do get them checked? Many thanks in advance for your reply.

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