Leflunomide is currently licensed for the treatment of rheumatoid and psoriatic arthritis. Its use is generally contraindicated during pregnancy due to teratogenicity in several animal models.
The active metabolite of leflunomide is highly protein bound and undergoes extensive enterohepatic recycling, prolonging the half-life of the drug. The manufacturer currently recommends a two-year waiting period after discontinuation of leflunomide before attempting to conceive. If a woman becomes pregnant while taking leflunomide, or within two years of discontinuation, the manufacturer recommends an 11-day washout protocol using colestyramine or activated charcoal to enhance drug elimination.
The available human data comprise a case-control study, a small prospective cohort study, and several case reports/series that collectively describe the outcomes of approximately 500 unique pregnancies exposed to leflunomide. In almost all cases, leflunomide was discontinued upon recognition of pregnancy, usually early in the first trimester. In the majority of exposures, a washout procedure was carried out which potentially limits the level and duration of exposure. Data on miscarriage, low infant birth weight, and preterm delivery following exposure are limited but are currently reassuring.
Leflunomide does not appear to be a major human teratogen if the drug is discontinued and a drug washout procedure is carried out. While malformations have been observed in some exposed pregnancies, there is no obvious pattern suggestive of a specific embryopathy. However, the teratogenicity of leflunomide in humans is undetermined. If in utero exposure to leflunomide has occurred, washout treatment to enhance drug elimination and a detailed structural fetal ultrasound are advised.
This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to NHS health care professionals who are logged in.
If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.
If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.