Methotrexate toxicity
Background
- Methotrexate blocks dihydrofolate reductase (DHFR) → blocks conversion of folate to folinic acid
- Used in tx of Non-hodgkin lymphoma, ALL, certain other malignancies, psoriasis and other dermatological conditions, rheumatoid arthritis (as a DMARD)
- Folate supplementation is often given with methotrexate, and ↓ risk of toxicity[1]
- Absorbed by saturable transporter in GI tract[2]
- Single large oral dose will have lower bioavailability/toxicity than multiple small doses or chronic toxicity.
Clinical Features[1]
- Nausea/vomiting
- Folic acid deficiency
- Myelosuppression
- Hepatotoxicity
- Acutely - transaminitis
- Chronic - cirrhosis/fibrosis
- Pulmonary toxicity
- Renal injury (ATN) 2/2 precipitation of methotrexate crystals[2]
- Cutaneous injury (stomatitis, mucositis, ulcerations, SJS and TEN, etc.)
Differential Diagnosis
Diagnosis
Management
Early initiation of therapy is important, so begin treatment once MTX toxicity is strongly suspected
- Folinic Acid (Leucovorin)[1]
- 20 mg IV or IM q6h until MTX serum level <10−8 M
- Glucarpidase
- Works by enzymatic cleaving of MTX into metabolites
- Hydration and urine alkalinization
- Bicarb gtt at 1.5-2x maintenance rate to maintain urine pH of >7.5
- MTX is excreted renally
Disposition
- Admit
See Also
References
- ↑ 1.0 1.1 1.2 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.
- ↑ 2.0 2.1 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.