Is leflunomide (LEF) safe for pregnant women with rheumatoid arthritis (RA)?

Updated: May 11, 2018
  • Author: Katherine K Temprano, MD; Chief Editor: Christine Isaacs, MD  more...
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Leflunomide (LEF), a pyrimidine synthesis inhibitor, is also a category X medication; it is extremely teratogenic and is absolutely contraindicated in pregnancy. Its half-life is 14-15 days, but the active metabolite undergoes extensive enterohepatic circulation; thus, the drug takes up to 2 years to be undetectable in plasma. Consequently, discontinuation of the drug before conception is insufficient. The drug needs to be eliminated with administration of cholestyramine (8 g tid for 11 d). Plasma levels of less than 0.02 mg/L should be verified with 2 separate tests at least 2 weeks apart. [26] If unacceptably high levels persist, additional cholestyramine may be given.

A study by Chambers et al of 64 women who became pregnant while taking leflunomide and underwent cholestyramine treatment found no significant increase in adverse pregnancy outcomes. These authors suggested that although the sample size was small, the findings can provide some reassurance to women in this situation. [27]

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