Folate antagonist — inhibits DHFR → reduces tetrahydrofolate → impairs thymidine + purine synthesis. Low-dose immunosuppressive mechanism is AICAR accumulation → adenosine release → anti-inflammatory. Leucovorin (folinic acid) is the antidote for overdose.
Half-Life (t½)
PO: 8h, IV: 8h
Dosing Guidelines
PO: Typical 13.3 mg (Range: 7.5–25 mg)
SC: Typical 13.3 mg (Range: 7.5–25 mg)
IM: Typical 13.3 mg (Range: 7.5–25 mg)
IV: Typical 13.3 mg (Range: 7.5–25 mg)
Target Organ Systems
immune-hematologic
Interactions
Folic Acid (caution): Antagonises MTX therapeutic effect in oncology; necessary adjunct in rheumatologic use for side-effect reduction. Oncology uses leucovorin (folinic acid / 5-formyl-THF) — which bypasses DHFR — as the rescue agent after high-dose MTX, titrated to plasma MTX. [Howard 2016]