Methotrexate is teratogenic and is contraindicated during pregnancy and breast-feeding. Prior to attempting pregnancy, women should wait at least one menstrual cycle and men at least 3 months after discontinuing this drug. Additional contraindications to methotrexate administration include kidney, liver, and lung disease; moderate to high alcohol use; immunodeficiency; blood dyscrasias; and hypersensitivity. Elderly persons may be at increased risk for toxicity because of decreased renal and hepatic function.
Methotrexate clearance can be decreased by the coadministration of NSAIDs; however, this not usually a problem with the low doses of methotrexate used to treat arthritis. Methotrexate can be displaced from plasma protein binding sites by phenylbutazone, pheny-toin, sulfonylureas, and sulfonamides and certain other antibiotics. The antifolate effects of methotrexate are additive with those of other folate-inhibitory drugs, such as trimethoprim.
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