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Clinical calculator summary

DPYD Activity Score Interpreter

DPYD activity score summarizes predicted DPD enzyme activity and fluoropyrimidine toxicity risk.

Evidence-based context for fast calculator use

Purpose:
Support pretreatment fluoropyrimidine pharmacogenomic dose discussion
Population:
Patients being considered for systemic fluoropyrimidine therapy with a laboratory-reported DPYD activity score
Factors:
Laboratory-reported DPYD activity score, Drug context, Guideline-specific recommendation
Reference:
CPIC fluoropyrimidine-DPYD guideline and 2018 dosing update; DPWG DPYD-fluoropyrimidine guideline
HomeDPYD / DPD Fluoropyrimidine Activity Score
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DPYD / DPD Fluoropyrimidine Activity Score

Clinical Context & Background

DPYD encodes dihydropyrimidine dehydrogenase (DPD), the main enzyme responsible for fluoropyrimidine catabolism. Reduced DPD activity increases the risk of severe or fatal toxicity from 5-fluorouracil and capecitabine.
This tool interprets, but does not calculate, the activity score reported by a validated pharmacogenomic assay or clinical laboratory. The 2024 joint laboratory consensus recommends a seven-variant Tier 1 DPYD panel; laboratories may test additional variants and must account for assay nomenclature, phase, and uncertain findings. Use the laboratory phenotype when available.
Current published CPIC guidance is used for 5-FU and capecitabine, while DPWG guidance is used for tegafur because CPIC does not provide tegafur dosing recommendations. CPIC announced a future HapB3-specific score of 1.75 and 75% cycle-one dose in July 2026, but stated that this change remains pending publication and is therefore not implemented here.
Formula Logic
Interpret the laboratory-reported DPYD activity score. When a genotype is translated to a score, CPIC uses the two variants with the lowest activity values; phase and uncertain variants may require laboratory or pharmacogenomics review.

Reference Data

Activity ScorePredicted Phenotype5-FU / Capecitabine Guidance
2Normal metabolizerStandard starting dose; routine monitoring
1 or 1.5Intermediate metabolizerStart at 50%, then titrate
0.5Poor metabolizerAvoid; specialist dosing and early monitoring if unavoidable
0Poor metabolizerAvoid fluoropyrimidines

Clinical Workflow

Use, Interpret, And Continue The Patient Pathway

Expand for workflow guidance, limitations, examples, and related next steps.

When To Use

  • Use before starting 5-FU or capecitabine when a validated DPYD result is available.
  • Use only when the patient and clinical setting match the population described for DPYD / DPD Activity Score.

How To Interpret

  • Lower activity scores indicate reduced DPD function and greater risk of severe fluoropyrimidine toxicity.
  • Interpret thresholds with the entered units, current clinical status, and local guideline context.

What To Do Next

  • Verify the laboratory phenotype, planned regimen, starting-dose guidance, and capacity for early toxicity or pharmacokinetic monitoring.
  • Document the inputs, result, clinical judgment, and any reason for deviating from the model-guided pathway.

Limitations

  • Do not infer an activity score from an unvalidated variant or use genotype to exclude all non-genetic toxicity risk.
  • This calculator supports clinical assessment and does not independently prescribe treatment.

Validated Population

Patients with an interpretable clinical DPYD genotype or laboratory-reported activity score before 5-FU or capecitabine

Clinical example

A reported activity score of 1.0 supports an intermediate-metabolizer pathway with a reduced starting-dose discussion and careful titration rather than automatic standard dosing.

Calculation verification history

Verified
  1. : Production browser revalidation

    • Five source-backed DPYD cases were exercised on the public production route through visible browser controls; 5/5 expected activity-score interpretations matched across normal, intermediate, poor, and tegafur-specific branches.
    • No unexpected N/A, literal undefined value, stale control, or browser-console error was observed.
    Download latest production check (Excel)

    Case-level evidence is retained in validation/browser-revalidation/dpyd-fluoropyrimidine-activity-score-2026-08-03.json.

  2. : Production browser validation

    • Ten source-backed cases were exercised on the public production route through visible browser controls; 10/10 case records passed their expected-versus-observed assertions across 11 visible submissions.
    • Overall browser status: failed-console. medium: Production emitted minified React error #418 during route loads/reloads used by this run.
    • Case-level inputs, expected and observed results, reset/repeat behavior, failure reproductions, and console evidence are retained in the production-browser evidence record.

    Case-level production evidence is retained in validation/browser-production/dpyd-fluoropyrimidine-activity-score.json.

  3. : Full validation test

    • Checked all five currently published activity scores across 5-FU, capecitabine, and tegafur, plus phenotype and invalid-input handling.
  4. : Correction

    • Separated CPIC 5-FU/capecitabine recommendations from DPWG tegafur recommendations.
    • Removed contradictory tegafur advice and rejected missing or unsupported drug and activity-score values.
    • Clarified that this tool interprets a laboratory-reported score and that the announced 2026 HapB3 score change remains pending publication.

    Included in the current validation report.

Verification confirms the calculator implementation against the cited model; it is not independent clinical validation, regulatory approval, or medical advice.

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Frequently Asked Questions

Can this calculator replace a DPYD laboratory report?

No. It interprets a score from a validated clinical laboratory. Use the laboratory phenotype and seek pharmacogenomics review for uncertain variants, phase ambiguity, or discordant results.

Why is activity score 1.75 not available?

CPIC announced a pending HapB3-specific change in July 2026, but stated it will not update the guideline or database until publication. This calculator will be revalidated when the final guideline is published.

Does a normal DPYD activity score eliminate fluoropyrimidine toxicity risk?

No. A normal score does not exclude risk from untested variants, other genetic factors, organ dysfunction, interactions, regimen, or patient-specific factors.

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