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

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


Purpose: Methotrexate administration is associated with\ud frequent adverse neurological events during treatment for\ud childhood acute lymphoblastic leukemia. Here, we present\ud evidence to support the role of common drug interactions\ud and low vitamin B12 levels in potentiating methotrexate\ud neurotoxicity.\ud Methods: We review the published evidence and highlight\ud key potential drug interactions as well as present clinical\ud evidence of severe methotrexate neurotoxicity in conjunction\ud with nitrous oxide anesthesia and measurements of\ud vitamin B12 levels among pediatric leukemia patients during\ud therapy.\ud Results: We describe a very plausible mechanism for\ud methotrexate neurotoxicity in pediatric leukemia patients\ud involving reduction in methionine and consequential disruption\ud of myelin production. We provide evidence that a\ud number of commonly prescribed drugs in pediatric leukemia\ud management interact with the same folate biosynthetic\ud pathways and/or reduce functional vitamin B12 levels and\ud hence are likely to increase the toxicity of methotrexate in\ud these patients. We also present a brief case study supporting\ud out hypothesis that nitrous oxide contributes to methotrexate\ud neurotoxicity and a nutritional study, showing that \ud patients.\ud Conclusions: Use of nitrous oxide in pediatric leukemia\ud patients at the same time as methotrexate use should be\ud avoided especially as many suitable alternative anesthetic\ud agents exist. Clinicians should consider monitoring levels\ud of vitamin B12 in patients suspected of having methotrexate-\ud induced neurotoxic effects

Publisher: Springer
Year: 2016
OAI identifier:
Provided by: Enlighten

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