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

Forster, V. J., van Delft, F. W., Baird, S. F., Mair, S., Skinner, R. and Halsey, C. (2016) Drug interactions may be important risk factors for methotrexate neurotoxicity, particularly in pediatric leukemia patients. Cancer Chemotherapy and Pharmacology, 78(5), pp. 1093-1096. (doi: 10.1007/s00280-016-3153-0) (PMID:27659182) (PMCID:PMC5083755)

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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 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.

Item Type:Articles
Additional Information:This work was supported by the JGW Patterson Foundation, Newcastle upon Tyne, UK, (VF) and Children with Cancer UK (CH).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Halsey, Professor Chris
Authors: Forster, V. J., van Delft, F. W., Baird, S. F., Mair, S., Skinner, R., and Halsey, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Cancer Chemotherapy and Pharmacology
Publisher:Springer
ISSN:0344-5704
ISSN (Online):1432-0843
Published Online:22 September 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Cancer Chemotherapy and Pharmacology 78(5):1093-1096
Publisher Policy:Reproduced under a creative commons license

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