- Methotrexate blocks dihydrofolate reductase (DHFR) → blocks conversion of folate to folinic acid
- Used in treatment of Non-Hodgkin's lymphoma, acute lymphocytic leukemia, certain other malignancies, psoriasis and other dermatological conditions, rheumatoid arthritis (as a DMARD)
- Folate supplementation is often given with methotrexate, and ↓ risk of toxicity
- Absorbed by saturable transporter in GI tract
- Single large oral dose will have lower bioavailability/toxicity than multiple small doses or chronic toxicity.
Early initiation of therapy is important, so begin treatment once MTX toxicity is strongly suspected
- Weidmann A, Foulkes AC, Kirkham N, Reynolds NJ. Methotrexate Toxicity During Treatment of Chronic Plaque Psoriasis: A Case Report and Review of the Literature. Dermatology and Therapy. 2014;4(2):145-156. doi:10.1007/s13555-014-0056-z.
- Schmiegelow K. Advances in individual prediction of methotrexate toxicity: a review. Br J Haematol. 2009 Sep;146(5):489-503. doi: 10.1111/j.1365-2141.2009.07765.x.