Difference between revisions of "Methotrexate toxicity"

(Background)
(/* 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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==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 treatment of Non-hodgkin lymphoma, ALL, certain other malignancies, psoriasis and other dermatological conditions, rheumatoid arthritis (as a DMARD)
+
*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<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>
 
**Single large oral dose will have lower bioavailability/toxicity than multiple small doses or chronic toxicity.
 
**Single large oral dose will have lower bioavailability/toxicity than multiple small doses or chronic toxicity.
  
 
==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==
  
  
==Diagnosis==
+
==Evaluation==
  
  
 
==Management==
 
==Management==
 
''Early initiation of therapy is important, so begin treatment once MTX toxicity is strongly suspected''
 
''Early initiation of therapy is important, so begin treatment once MTX toxicity is strongly suspected''
*'''Folinic Acid (Leucovorin)'''<ref name="Weidmann" />
+
*'''Folinic Acid ([[Leucovorin]])'''<ref name="Weidmann" />
**20 mg IV or IM q6h until MTX serum level <10<sup>−8</sup> M
+
**20mg IV or IM q6h until MTX serum level <10<sup>−8</sup> M
*'''Glucarpidase'''
+
*'''[[Glucarpidase]]'''
 
**Works by enzymatic cleaving of MTX into metabolites
 
**Works by enzymatic cleaving of MTX into metabolites
 
*Hydration and urine alkalinization
 
*Hydration and urine alkalinization
**Bicarb gtt at 1.5-2x maintenance rate to maintain urine pH of >7.5
+
**[[Bicarbonate]] drip at 1.5-2x maintenance rate to maintain urine pH of >7.5
 
**MTX is excreted renally
 
**MTX is excreted renally
  

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.