Pharmacogenomics · CPIC Level A · Fluoropyrimidines (oral)

DPYD genotype-guided dosing for capecitabine

CPIC-aligned reference. Educational use only — not a substitute for clinical pharmacology consultation.

TL;DR

Capecitabine is an oral 5-FU prodrug. DPYD-deficient patients face the same severe (potentially fatal) toxicity as with intravenous 5-FU. CPIC Level A pre-treatment genotyping for DPYD *2A, *13, c.2846A>T, HapB3. The biology and dosing recommendations are identical to DPYD + 5-FU; this page focuses on the practical rollout in colorectal, breast, gastric, and pancreatic oncology where capecitabine is first-line.

Variants tested

See the four actionable DPYD variants documented on the DPYD + 5-FU page. Same panel, same activity score mapping.

Phenotype mapping

  • Normal metabolizer: standard capecitabine dose (e.g., 1250 mg/m² BID days 1-14 of 21-day cycle for colorectal monotherapy).
  • Intermediate metabolizer (activity 1-1.5): 50% starting dose, titrate by toxicity.
  • Poor metabolizer (activity 0-0.5): avoid capecitabine; alternative regimen or markedly reduced dose with intensive monitoring.

Dosing recommendation

Pre-treatment DPYD genotyping is recommended for all patients starting capecitabine. The most consequential indications:

  • Colorectal cancer: capecitabine in CAPOX, CAPIRI, CAPEOX, monotherapy maintenance. High toxicity burden in DPD-deficient.
  • Breast cancer: capecitabine alone or with tucatinib + trastuzumab (HER2CLIMB regimen for HER2+ mBC).
  • Gastric / esophageal: CAPOX or CAPECITABINE backbone.
  • Pancreatic: capecitabine + gemcitabine in selected adjuvant settings.

Uridine triacetate (Vistogard) is the antidote for life-threatening capecitabine toxicity within 96 hours of the dose.

Evidence

Same evidence base as the DPYD + 5-FU page: Henricks 2018 demonstrated genotype-guided dosing reduces severe toxicity from ~73% to ~28% in DPYD heterozygotes. The EMA endorsed mandatory pre-treatment testing in 2020 for capecitabine and 5-FU.

Frequently asked questions

Why a separate page for capecitabine?
Practical rollout. Capecitabine is the more commonly prescribed fluoropyrimidine in modern oncology (oral, outpatient-friendly) and the SEO query patterns are distinct. The biology and dosing recommendations are identical to 5-FU.
Are there capecitabine-specific dose-modification tables?
CPIC tables provide percentage reductions; specific mg/m² targets depend on the regimen (capecitabine monotherapy vs CAPOX vs HER2CLIMB) and other components. Pharmacy or clinical pharmacology should translate the activity score to a specific starting dose for the regimen at hand.
Is hand-foot syndrome more DPYD-driven or capecitabine-specific?
Capecitabine has a stronger hand-foot syndrome signal than IV 5-FU due to skin-level enzymatic activation. DPYD genotype influences total exposure but doesn't predict hand-foot syndrome uniquely. Cold-compresses, urea-based emollients, and dose modification remain the standard management.

Citations