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IBS vs coeliac disease workup — UKMLA MCQ

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HardGastroenterologyIBS vs coeliac disease workupUKMLAMRCGP AKTPARAMRCP Part 1

A 56-year-old is due to start adjuvant capecitabine. Pretreatment genotyping identifies a pathogenic DPYD variant that the accredited laboratory classifies as causing partial, rather than complete, dihydropyrimidine-dehydrogenase deficiency. Which prescribing plan best follows current UK drug-safety advice?

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Correct answer: A — Start reduced-dose capecitabine with close monitoring and cautiously escalate if tolerated

The best answer is “Start reduced-dose capecitabine with close monitoring and cautiously escalate if tolerated”. Partial DPD deficiency increases the risk of early severe or fatal fluoropyrimidine toxicity, but it is not the absolute contraindication that applies to complete deficiency. MHRA advice is to consider a reduced starting dose, monitor particularly carefully during the first cycle and after dose increases, and consider cautious escalation when serious toxicity is absent. Changing to systemic fluorouracil does not remove the DPD-dependent risk, while folinic acid is not prophylaxis for fluoropyrimidine toxicity.

Reference: MHRA Drug Safety Update, DPD testing before systemic fluoropyrimidines: https://www.gov.uk/drug-safety-update/5-fluorouracil-intravenous-capecitabine-tegafur-dpd-testing-recommended-before-initiation-to-identify-patients-at-increased-risk-of-severe-and-fatal-toxicity