chapter  4
6 Pages


WithJames L. Schardein, Orest T. Macina

Methotrexate is an antimetabolite antineoplastic and immunosuppressant drug. It is a methyl derivative of aminopterin, and it is used therapeutically in treating trophoblastic neoplasms, leukemias, psoriasis, and rheumatoid arthritis. It has largely replaced aminopterin in this therapeutic category; low dose therapy is indicated, however, as the drug, like aminopterin, has abortifacient properties. Animal effect levels were generally higher than human therapeutic levels. In humans, methotrexate has been shown, from at least 18 case reports, to be an active teratogen and developmental toxicant. For further information on methotrexate developmental toxicity, see the literature. Methotrexate is teratogenic in animals when given by parenteral or oral routes of administration. Dogs were said to be resistant to the induction of malformations by methotrexate, but details of the study were incompletely reported, and further details were unobtainable.