Methotrexate toxicity: Difference between revisions
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==Background== | ==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>== | |||
==Clinical Features== | *[[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== | ==Differential Diagnosis== | ||
== | ==Evaluation== | ||
==Management== | ==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== | ==Disposition== | ||
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<references/> | <references/> | ||
[[Category: | [[Category:Toxicology]] | ||
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]
- Nausea/vomiting
- Folate deficiency
- Myelosuppression, pancytopenia
- Hepatotoxicity
- Acutely - transaminitis
- Chronic - cirrhosis/fibrosis
- Pulmonary toxicity
- Renal injury (ATN) secondary to precipitation of methotrexate crystals[2]
- 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)[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
- ↑ 1.0 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.
- ↑ 2.0 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.