DPYD Genotype-Guided Fluoropyrimidine Dosing: FDA and NCCN Updates to Guide 5-FU and Capecitabine Dosing for Oncologists

A recent FDA boxed warning update on capecitabine (XELODA) and an aligned NCCN Colon Cancer guideline revision now recommends or requires pre treatment DPYD genetic testing to mitigate life threatening fluoropyrimidine toxicity. These changes leave oncologists asking: Which DPYD test should I order? How do I interpret activity scores? What if no fluoropyrimidine free regimen exists?

This presentation summarizes the new labeling and NCCN recommendations, reviews DPYD biology and variant frequencies, and provides a step-by-step framework for integrating testing into practice. It walks through fluoropyrimidine dosing guidelines, shows how to select a high-quality DPYD assay (CLIA/CAP accreditation, variant coverage, turnaround), and uses realistic cases (normal, intermediate, and poor metabolizers) to illustrate when to dose reduce, avoid fluoropyrimidines, or switch to alternative regimens. There is also guidance on recognizing early severe toxicity and using uridine triacetate.

The target audience for this presentation is medical oncologists, oncology pharmacists, and other clinicians prescribing fluoropyrimidines. By focusing on current regulatory and guideline changes, it equips clinicians to meet new compliance obligations and improve patient safety while maintaining therapeutic efficacy.

Originally published on March 2, 2026

Lecture Presenter

Ryan Nelson, PharmD Adjunct Professor Spencer Fox Eccles School of Medicine at the University of Utah Medical Director, Precision Medicine ARUP Laboratories

Ryan Nelson is a medical director of precision medicine at ARUP Laboratories and an adjunct professor with the Spencer Fox Eccles School of Medicine at the University of Utah. He received his doctorate degree in pharmacy from the University of Utah College of Pharmacy. He then completed a fellowship in personalized cancer medicine at Moffitt Cancer Center. He is a member of the American Society of Health-System Pharmacists, the American Society of Hematology, and the Clinical Pharmacogenetics Implementation Consortium. Dr. Nelson specializes in applied precision medicine with an emphasis on somatic and germline pharmacogenomics as well as pharmacoeconomics. His research interests include clinical utility and value of pharmacogenomics, gene-drug pair assessment for future implementation, and patient adherence to pharmacotherapy.

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Objectives

After this presentation, participants will be able to:

• Recognize who is at highest risk for life-threatening fluoropyrimidine toxicity due to DPD deficiency
• Choose an appropriate DPYD test (variant coverage and lab quality)
• Translate genotype to phenotype/activity score to starting dose using CPIC
• Implement a clinic workflow (including “treatment is urgent” scenarios)

Sponsored by:

Spencer Fox Eccles School of Medicine at the University of Utah, Department of Pathology,
and ARUP Laboratories