Methotrexate toxicity: Difference between revisions

(/* Clinical FeaturesWeidmann 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-...)
 
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==Clinical Features<ref name="Weidmann">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.</ref>==
==Clinical Features<ref name="Weidmann">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.</ref>==
*[[Nausea/vomiting]]
*[[Nausea/vomiting]]
*[[Folic acid deficiency]]
*[[Folate deficiency]]
*Myelosuppression
*Myelosuppression, [[pancytopenia]]
*Hepatotoxicity
*[[Hepatotoxicity]]
**Acutely - transaminitis
**Acutely - transaminitis
**Chronic - [[cirrhosis]]/fibrosis
**Chronic - [[cirrhosis]]/fibrosis
*Pulmonary toxicity
*Pulmonary toxicity
*Renal injury (ATN) secondary to precipitation of methotrexate crystals<ref name="Schmiegelow" />
*[[acute kidney injury|Renal injury]] (ATN) secondary to precipitation of methotrexate crystals<ref name="Schmiegelow" />
*Cutaneous injury (stomatitis, mucositis, ulcerations, SJS and [[TEN]], etc.)
*Cutaneous injury (stomatitis, mucositis, ulcerations, [[SJS]] and [[TEN]], etc.)


==Differential Diagnosis==
==Differential Diagnosis==

Latest revision as of 15:59, 30 January 2019

Background

  • 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[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]

Differential Diagnosis

Evaluation

Management

Early initiation of therapy is important, so begin treatment once MTX toxicity is strongly suspected

  • Folinic Acid (Leucovorin)[1]
    • 20mg IV or IM q6h until MTX serum level <10−8 M
  • Glucarpidase
    • Works by enzymatic cleaving of MTX into metabolites
  • Hydration and urine alkalinization
    • Bicarbonate drip at 1.5-2x maintenance rate to maintain urine pH of >7.5
    • MTX is excreted renally

Disposition

  • Admit

See Also

References

  1. 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. 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.