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Fluorouracil or Capecitabine Overdose

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Oncologic Emergency Medicine

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Abstract

5-Fluorouracil (5-FU) and its oral prodrug capecitabine are mainstays of oncologic therapy. They are fluoropyrimidine derivatives and function as antimetabolites. Fluoropyrimidines may be administered as monotherapy or in combination with other chemotherapeutic agents. They are predominantly used for the treatment of gastrointestinal, breast, and head and neck cancers. The therapeutic and toxicologic effects of 5-FU and capecitabine are attributed to their deleterious incorporation into RNA and DNA, and to their inhibition of thymidylate synthetase. Studies differ, but it is estimated that somewhere between 10% and 40% of patients on 5-FU and capecitabine develop some form of severe or life-threatening toxicity. Life-threatening toxicity may result from myelosuppression, diarrhea, mucositis, neurotoxicity, and cardiotoxicity. Hand-and-foot syndrome is also a characteristic adverse effect of 5-FU and capecitabine. Toxicity may result from intentional overdose, iatrogenic overdose, or therapeutic administration. A significant proportion severe toxicity occurs in the setting of therapeutic administration rather than acute overdose and is generally attributed to genetic polymorphisms. Treatment of toxicity is largely supportive. The antidote for fluoropyrimidine toxicity is uridine triacetate, but its indications are limited, and ideally the treating oncologist or a toxicologist should be consulted prior to its administration.

Note: Dr. Neumann performed this research at the Rocky Mountain Poison and Drug Safety, Denver Health and Hospital Authority, Denver, Colorado. She is now with the Department of Emergency Medicine, Yale University School of Medicine, New Haven, Connecticut.

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Authors and Affiliations

  1. Department of Emergency Medicine, Yale University School of Medicine, New Haven, CT, USA

    Natalie R. Neumann

  2. Rocky Mountain Poison and Drug Safety, Denver Health and Hospital Authority, Denver, CO, USA

    Christopher O. Hoyte

  3. Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, CO, USA

    Christopher O. Hoyte

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  1. Natalie R. Neumann
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  2. Christopher O. Hoyte
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Editors and Affiliations

  1. Former Professor and Founding Chair (Retired), The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Knox H. Todd

  2. Professor and Chair, Department of Radiation Medicine, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA

    Charles R. Thomas, Jr.

  3. Professor and Chair, Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Kumar Alagappan

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Neumann, N.R., Hoyte, C.O. (2021). Fluorouracil or Capecitabine Overdose. In: Todd, K.H., Thomas, Jr., C.R., Alagappan, K. (eds) Oncologic Emergency Medicine. Springer, Cham. https://doi.org/10.1007/978-3-030-67123-5_54

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