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Methotrexate

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Critical Care Toxicology

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Abstract

Methotrexate (amethopterin, 4-amino-10-methyl-pteroglutamic acid) has been a widely used folate antagonist, initially as an antineoplastic agent, and later on as an anti-inflammatory and immunomodulation agent. Aminopterin was the first folate antagonist successfully used for induction of temporary remission in acute leukemia in children [1]. Methotrexate, a safer related agent of aminopterin, replaced it as an antileukemic drug [2]. Since then, methotrexate has been increasingly used as a monotherapy and in combination with other antineoplastic agents for a variety of hematologic and non-hematologic malignancies in children and adults. Its anti-inflammatory and immunomodulation properties were found to be also efficacious in a broad range of dermatologic, rheumatologic, and other disease states (e.g., ectopic pregnancy, graft vs. host disease). The main clinical applications of methotrexate are shown in Table 1 [3].

The chapter of the first edition was written by Mary Beth Hines.

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Authors and Affiliations

  1. Israel Poison Information Center, Clinical Pharmacology and Toxicology Section, Rambam Health Care Campus, The Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, 9602, 31096, Haifa, Israel

    Yedidia Bentur & Yael Lurie

Authors
  1. Yedidia Bentur
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  2. Yael Lurie
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Correspondence to Yedidia Bentur .

Editor information

Editors and Affiliations

  1. Department of Medicine, Division of Clinical Pharmacology and Toxicology, University of Colorado, School of Medicine, Aurora, Colorado, USA

    Jeffrey Brent

  2. FDA, Office of New Drugs/Immediate Office, Center for Drug Evaluation and Research, Silver Spring, Maryland, USA

    Keith Burkhart

  3. Clinical Toxicology, St Thomas’ Hospital, Silver Spring, Maryland, USA

    Paul Dargan

  4. Toxicology Associates, University of Colorado, School of Medicine, Denver, Colorado, USA

    Benjamin Hatten

  5. Medical Toxicological Intensive Care Unit, Lariboisiere Hospital, Paris-Diderot University, Paris, France

    Bruno Megarbane

  6. Toxicology Associates, University of Colorado, School of Medicine, Denver, Colorado, USA

    Robert Palmer

  7. Toxinology Department, Women’s and Children’s Hospital, North Adelaide, South Australia, Australia

    Julian White

Grading System for Levels of Evidence Supporting Recommendations in Critical Care Toxicology, 2nd Edition

  1. I

    Evidence obtained from at least one properly randomized controlled trial.

  2. II-1

    Evidence obtained from well-designed controlled trials without randomization.

  3. II-2

    Evidence obtained from well-designed cohort or case–control analytic studies, preferably from more than one center or research group.

  4. II-3

    Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments (such as the results of the introduction of penicillin treatment in the 1940s) could also be regarded as this type of evidence.

  5. III

    Opinions of respected authorities, based on clinical experience, descriptive studies and case reports, or reports of expert committees.

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Bentur, Y., Lurie, Y. (2017). Methotrexate. In: Brent, J., et al. Critical Care Toxicology. Springer, Cham. https://doi.org/10.1007/978-3-319-17900-1_109

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