Ver el código de «Methotrexate toxicity»

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

==Differential Diagnosis==


==Evaluation==


==Management==
''Early initiation of therapy is important, so begin treatment once MTX toxicity is strongly suspected''
*'''Folinic Acid ([[Leucovorin]])'''<ref name="Weidmann" />
**20mg 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
**[[Bicarbonate]] drip at 1.5-2x maintenance rate to maintain urine pH of >7.5
**MTX is excreted renally

==Disposition==
*Admit

==See Also==


==References==
<references/>

[[Category:Toxicology]]