Cheplapharm — Xeloda EMA EPAR variation assessment report (EMEA/H/C/000316, 2001)
Cheplapharm · 2001 · EMA EPAR variation assessment report
Report summary
This report summarizes the EMA's assessment of fluorouracil and related substances, prompted by concerns over severe toxicity in DPD-deficient patients. The referral, triggered by France, aimed to establish EU-level action for detecting DPD deficiency. The report details the drugs' pharmacokinetics, pharmacogenetics, and mechanism, emphasizing DPD's role in metabolism and toxicity. It highlights the incidence of severe and lethal toxicities, linking them to specific DPYD variants. Various DPD deficiency screening methods (genotyping and phenotyping) are discussed, along with their limitations and utility in routine practice. The PRAC recommended mandatory pre-treatment DPD testing, contraindicating treatment in complete DPD deficiency, and dose adjustments for partial deficiency. Therapeutic drug monitoring for 5-fluorouracil was also advised to enhance safety and efficacy.
Key findings — cited to the page
| Lethal toxicities, grade 5 | 0.1% - 1% | · p.13 |
| Severe toxicities, grade ≥ 4 | 3% - 5% | · p.13 |
| Severe toxicities, grade ≥ 4 | 6.7% | PHRC FUSAFE (section 1) · p.13 |
| Severe toxicities, grade ≥ 4 | 2% | PHRC FUSAFE (section 2) · p.13 |
| Overall toxicities, grade ≥ 3 | 24% | PHRC FUSAFE (section 1) · p.13 |
| Overall toxicities, grade ≥ 3 | 43% | PHRC FUSAFE (section 2) · p.13 |
| Overall toxicities, grade ≥ 3 | 20% - 25% | · p.13 |
| Overall toxicities, grade ≥ 3 | 6% - 57% | · p.13 |
| Overall toxicities, grade ≥ 3 | 10% - 30% | · p.13 |
| Overall toxicities, grade ≥ 3 | 25% | · p.13 |
| Overall toxicities, grade ≥ 3 | 25% - 50% | · p.13 |
| Lethal toxicities, grade 5 | 0.05% | PHRC FUSAFE (section 1) · p.13 |
Source: Cheplapharm ↗ · License: EMA - reuse permitted with acknowledgement. Summary and findings are extracted from the published document; every figure cites its page. Informational only — not investment advice. Explore the Oncology library →