Difference between revisions of "Methotrexate toxicity"

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==Background==
 
==Background==
 
*Methotrexate blocks dihydrofolate reductase (DHFR) → blocks conversion of folate to folinic acid
 
*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
+
*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<ref name="Weidmann" />
 
*Folate supplementation is often given with methotrexate, and ↓ risk of toxicity<ref name="Weidmann" />
 
*Absorbed by saturable transporter in GI tract<ref name="Schmiegelow">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.</ref>
 
*Absorbed by saturable transporter in GI tract<ref name="Schmiegelow">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.</ref>
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==Management==
 
==Management==
 
+
''Early initiation of therapy is important, so begin treatment once MTX toxicity is strongly suspected''
 +
*'''Folinic Acid (Leucovorin)'''<ref name="Weidmann" />
 +
**20 mg IV or IM q6h until MTX serum level <10<sup>−8</sup> 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==
 
==Disposition==

Revision as of 09:02, 17 July 2015

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. 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.