Methotrexate toxicity: Difference between revisions
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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- | *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]] | ||
* | *[[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== | ||
== | ==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" /> | ||
** | **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 | ||
** | **[[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]
- 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.