Inhibits dihydrofolate reductase → ↓ purine/pyrimidine synthesis (antiproliferative and immunomodulatory).
Black Box Warning
Embryo-fetal toxicity (contraindicated in pregnancy for non-cancer use), severe hypersensitivity/anaphylaxis, serious reactions of bone marrow, GI tract, liver, lungs, skin and kidneys, and fatal medication errors from daily instead of WEEKLY dosing.
Clinical Notes
RA, psoriasis, ectopic pregnancy (off-label), chemotherapy. Dose WEEKLY (not daily) for RA; supplement folic acid; leucovorin rescue with high-dose therapy. Avoid in pregnancy.