Other safety alerts
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| European Union: EMA recommends medicines for chemotherapy containing 5-fluorouracil: in patients with moderate or severe renal impairment, phenotyping for dihydropyrimidine dehydrogenase (DPD) deficiency by measuring blood uracil levels should be interpreted with caution |
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European Medicines Agency (EMA) announces that its safety committee, the Pharmacovigilance Risk Assessment Committee (PRAC), recommended medicines for chemotherapy containing 5-fluorouracil: in patients with moderate or severe renal impairment, phenotyping for dihydropyrimidine dehydrogenase (DPD) deficiency by measuring blood uracil levels should be interpreted with caution.
Medicines for chemotherapy containing 5-fluorouracil (5-FU) are part of the standard therapy for various cancers, including colorectal, pancreatic, gastric, breast, and head and neck cancer.
The enzyme dihydropyrimidine dehydrogenase (DPD) is made up in the liver and helps the body break down thymine and uracil. Patients with impaired DPD enzyme function are at increased risk of severe or life-threatening toxicity when treated with 5-FU or one of its prodrugs.
To identify these patients, pre-treatment testing for DPD deficiency is recommended, despite uncertainties regarding optimal testing methodology.
Patients with complete DPD deficiency are at high risk of life-threatening or fatal toxicity and must not be treated with 5-FU or other medicines of the same class (fluoropyrimidines).
Patients with partial DPD deficiency are at increased risk of severe and potentially life--threatening toxicity. To limit the risk of severe toxicity, a reduced starting dose should be considered. Subsequent doses may be increased in the absence of serious toxicity, as the efficacy of a reduced dose has not been established.
The PRAC has agreed a direct healthcare professional communication (DHPC) to inform healthcare professionals about the fact that if blood uracil levels are used to determine the DPD phenotype, the phenotype result must be interpreted with caution in patients with moderate or severe renal impairment, as renal impairment can lead to increased blood uracil levels. This could result in an incorrect diagnosis of DPD deficiency and consequently underdosing of 5-FU or other fluoropyrimidines in these patients.
Please refer to the following website in EMA for details:
http://www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-risk-assessment-committee-prac-2-5-september-2024
In Hong Kong, there are 2 registered pharmaceutical products which are fluorouracil injectable products. All products are prescription-only medicines. So far, the Department of Health (DH) has received 110 cases of adverse drug reaction related to fluorouracil, but these cases were not related to DPD deficiency.
Related news was previously issued by European Medicines Agency, the United Kingdom Medicines and Healthcare products Regulatory Agency and Australia Therapeutic Goods Administration, and was posted on the Drug Office website since 18 Mar 2019, with the latest update posted on 22 Mar 2024. Letters to inform local healthcare professionals were issued by the DH on 18 Mar 2019.
In Jun 2021, the Registration Committee of the Pharmacy and Poisons Board discussed the matter, and decided that the labelling of fluorouracil injectable products should include safety information regarding the increased risk of toxicity in patients with DPD deficiency. The DH will remain vigilant on safety update of the drug issued by other overseas drug regulatory authorities.
Ends/Saturday, Sep 7, 2024
Issued at HKT 12:15
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