Page 111 - Personalised medicine of fluoropyrimidines using DPYD pharmacogenetics Carin Lunenburg

Supplement
ref. 41 – FU SPC Carac (fluorouracil) cream 16-12- 03 (USA).
Level of evidence score: 0
gene act. 0: CTC- AE 4
patients with partial DPD activity as measured by any specific test.
Contraindications: Carac should not be used in patients with dihydropyrimidine dehydrogenase (DPD) deficiency. DPD deficiency may lead to 5-FU entering the anabolic route, resulting in cytotoxic activity and possible toxicity.
Warning: Patients should discontinue treatment with
Carac if symptoms of DPD deficiency develop.
Rare, unexpected systemic toxicity (e.g. stomatitis, 4 diarrhoea, neutropenia and neurotoxicity) associated
with parenteral administration of 5-FU has been
attributed to DPD deficiency. A case of life-
threatening systemic toxicity has been reported
following topical use of 5% 5-FU by a patient with
fully non-functional DPD. Symptoms included severe
abdominal pain, haemorrhagic diarrhoea, vomiting,
fever and chills. Physical examination showed
stomatitis, erythematous rash, neutropenia,
thrombocytopenia, inflammation of the oesophagus,
stomach and small intestine. Although this patient
had used 5% 5-FU cream, it is not known whether
patients with severe DPD deficiency develop systemic
toxicity in response to lower concentrations of
topically administered 5-FU.
# For studies that did not show significant differences for intermediate metabolizers (IM) or poor metabolizers (PM) due to very low numbers of IM or PM in the study (<4), the effect for IM or PM was scored as if this concerned a case. This was indicated by placing the case code (2) behind the score.
a SPC Xeloda (capecitabine) 14-12-16 (USA).
Abbreviations: 5-FU: 5-fluorouracil; 95% CI: 95% confidence interval; CAP: capecitabine; Cl: clearance; comb: combination therapy (≥ 2 oncolytic drugs), Css: steady-state plasma concentration; DPD: dihydropyrimidine dehydrogenase; gene act.: gene activity score; gene activity score 2: two fully functional alleles (extensive metaboliser); gene activity score 1.5: one fully functional and one partially functional allele; gene activity score 1: one fully functional and one non-functional allele or two partially functional alleles; gene activity score 0.5: one non-functional and one partially functional allele; gene activity score 0: two non-functional alleles; mono: monotherapy (one oncolytic drug); NS: non-significant; RR: relative risk; S: significant; SNP: single nucleotide polymorphism.
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