Methotrexate toxicity

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  • 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
  • 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




  • Admit

See Also


  1. 1.0 1.1 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. 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.