Volume 51, Number 9

Ann L. Parke, MD
Division of Rheumatology
University of Connecticut Health Center,
School of Medicine
Farmington, CT

Methotrexate is an antimetabolite and interferes with folic acid metabolism and purine synthesis. Fifty percent of fetuses exposed to methotrexate may be abnormal with multiple cranial abnormalities, particularly with exposure during the first trimester. This drug is also an abortofactant and should not be used by women attempting to become pregnant. Methotrexate is widely distributed throughout body tissues with reports of persistence of this drug in the liver up to 116 days after exposure. Because of concerns about the potential for abnormalities in ova and spermatoza, we recommend that patients taking methotrexate discontinue this drug 4 months prior to conception.

Methotrexate is contraindicated during lactation.

Leflunomide inhibits pyrimidine synthesis and is an immune modulator by inhibiting T cell proliferation and activation, as well as DNA synthesis.

Animal studies have shown that leflunomide is embryotoxic. The current recommendations are that leflunomide should not be used in pregnancy, and any patient taking this drug and wishing to become pregnant should be treated with cholestyra-mine (8 grams three times daily for 11 days) or charcoal to reduce the blood level to 0.03 mg/litre which is considered to be the safe human level. The current recommendations are to treat with cholestyramine and then wait for three cycles before attempting pregnancy. Patients who become pregnant unexpectedly need to understand that even if cholestyramine is used as soon as the pregnancy is known, the fetus will be exposed to leflunomide during organogenesis. The most dangerous time for neural development is between 8 and 15 weeks of gestation.

The concern for men taking leflunomide during conception is less because the drug is not mutogenic (6). Human experience with this drug is limited, but it is recommended that men discontinue this medication prior to fertilization.

Leflunomide is considered to be incompatible with breast feeding, but little is known about the pharmacokinetics of this drug in breast milk.

Sulfasalazine (5-aminosalicyclic acid and sulfapyridine) and some of its metabolites cross the placenta but this drug is considered safe in pregnancy. Men planning to start a family should be advised that this drug is known to affect spermatogenesis. It also interferes with folic acid metabolism. Sulfapyridine is excreted in breast milk but current recommendations are that it can be used with caution in lactating women.