Patients with reduced dihydropyrimidine dehydrogenase (DPD) activity cannot clear fluoropyrimidines normally, and can develop severe or fatal mucositis, diarrhoea and neutropenia from standard doses. Partial deficiency is not rare.
The European Medicines Agency recommends testing before starting 5-FU or capecitabine, by genotyping DPYD variants or measuring uracil levels. A reduced dose, titrated up if tolerated, is standard for intermediate metabolisers. Where testing is unavailable, a severe reaction in the first cycle should prompt consideration of DPD deficiency.
- Order DPYD genotyping or uracil levels before the first fluoropyrimidine dose where available
- Reduce the starting dose for partial deficiency
- Avoid fluoropyrimidines in complete deficiency
- Treat early severe toxicity as a possible DPD deficiency, and stop the drug
Why it matters
A pre-treatment test can prevent a rare but often fatal first-cycle toxicity.
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