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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 5/2016

Open Access 01-11-2016 | Short Communication

Drug interactions may be important risk factors for methotrexate neurotoxicity, particularly in pediatric leukemia patients

Authors: Victoria J. Forster, Frederik W. van Delft, Susan F. Baird, Shona Mair, Roderick Skinner, Christina Halsey

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2016

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Abstract

Purpose

Methotrexate administration is associated with frequent adverse neurological events during treatment for childhood acute lymphoblastic leukemia. Here, we present evidence to support the role of common drug interactions and low vitamin B12 levels in potentiating methotrexate neurotoxicity.

Methods

We review the published evidence and highlight key potential drug interactions as well as present clinical evidence of severe methotrexate neurotoxicity in conjunction with nitrous oxide anesthesia and measurements of vitamin B12 levels among pediatric leukemia patients during therapy.

Results

We describe a very plausible mechanism for methotrexate neurotoxicity in pediatric leukemia patients involving reduction in methionine and consequential disruption of myelin production. We provide evidence that a number of commonly prescribed drugs in pediatric leukemia management interact with the same folate biosynthetic pathways and/or reduce functional vitamin B12 levels and hence are likely to increase the toxicity of methotrexate in these patients. We also present a brief case study supporting out hypothesis that nitrous oxide contributes to methotrexate neurotoxicity and a nutritional study, showing that vitamin B12 deficiency is common in pediatric leukemia patients.

Conclusions

Use of nitrous oxide in pediatric leukemia patients at the same time as methotrexate use should be avoided especially as many suitable alternative anesthetic agents exist. Clinicians should consider monitoring levels of vitamin B12 in patients suspected of having methotrexate-induced neurotoxic effects.
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Metadata
Title
Drug interactions may be important risk factors for methotrexate neurotoxicity, particularly in pediatric leukemia patients
Authors
Victoria J. Forster
Frederik W. van Delft
Susan F. Baird
Shona Mair
Roderick Skinner
Christina Halsey
Publication date
01-11-2016
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 5/2016
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-016-3153-0

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