Back to Search
Start Over
Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction of DPYD and fluoropyrimidines
- Source :
- European Journal of Human Genetics, 28, 508-517, European Journal of Human Genetics, 28, 4, pp. 508-517, European Journal of Human Genetics, European Journal of Human Genetics, 28, 508-517. Nature Publishing Group, European Journal of Human Genetics, 28(4), 508-517. NATURE PUBLISHING GROUP, European Journal of Human Genetics, 28, 508. Nature Publishing Group, EJHG, 28(4). Nature Publishing Group
- Publication Year :
- 2020
-
Abstract
- Despite advances in the field of pharmacogenetics (PGx), clinical acceptance has remained limited. The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate PGx implementation by developing evidence-based pharmacogenetics guidelines to optimize pharmacotherapy. This guideline describes the starting dose optimization of three anti-cancer drugs (fluoropyrimidines: 5-fluorouracil, capecitabine and tegafur) to decrease the risk of severe, potentially fatal, toxicity (such as diarrhoea, hand-foot syndrome, mucositis or myelosuppression). Dihydropyrimidine dehydrogenase (DPD, encoded by theDPYDgene) enzyme deficiency increases risk of fluoropyrimidine-induced toxicity. TheDPYD-gene activity score, determined by fourDPYDvariants, predicts DPD activity and can be used to optimize an individual’s starting dose. The gene activity score ranges from 0 (no DPD activity) to 2 (normal DPD activity). In case it is not possible to calculate the gene activity score based onDPYDgenotype, we recommend to determine the DPD activity and adjust the initial dose based on available data. For patients initiating 5-fluorouracil or capecitabine: subjects with a gene activity score of 0 are recommended to avoid systemic and cutaneous 5-fluorouracil or capecitabine; subjects with a gene activity score of 1 or 1.5 are recommended to initiate therapy with 50% the standard dose of 5-fluorouracil or capecitabine. For subjects initiating tegafur: subjects with a gene activity score of 0, 1 or 1.5 are recommended to avoid tegafur. Subjects with a gene activity score of 2 (reference) should receive a standard dose. Based on the DPWG clinical implication score,DPYDgenotyping is considered “essential”, therefore directingDPYDtesting prior to initiating fluoropyrimidines.
- Subjects :
- Oncology
Antimetabolites, Antineoplastic
medicine.medical_specialty
Drug-Related Side Effects and Adverse Reactions
Pharmacogenomic Variants
Vascular damage Radboud Institute for Health Sciences [Radboudumc 16]
Tegafur
Article
Capecitabine
Prognostic markers
03 medical and health sciences
0302 clinical medicine
Pharmacotherapy
All institutes and research themes of the Radboud University Medical Center
Drug Therapy
Internal medicine
Dihydropyrimidine dehydrogenase
medicine
Mucositis
Genetics
Humans
Chemotherapy
Genetics(clinical)
Genetic Testing
Dihydrouracil Dehydrogenase (NADP)
Genetics (clinical)
030304 developmental biology
0303 health sciences
business.industry
Guideline
medicine.disease
3. Good health
Haplotypes
030220 oncology & carcinogenesis
Practice Guidelines as Topic
DPYD
Fluorouracil
business
Pharmacogenetics
medicine.drug
Subjects
Details
- ISSN :
- 10184813
- Database :
- OpenAIRE
- Journal :
- European Journal of Human Genetics, 28, 508-517, European Journal of Human Genetics, 28, 4, pp. 508-517, European Journal of Human Genetics, European Journal of Human Genetics, 28, 508-517. Nature Publishing Group, European Journal of Human Genetics, 28(4), 508-517. NATURE PUBLISHING GROUP, European Journal of Human Genetics, 28, 508. Nature Publishing Group, EJHG, 28(4). Nature Publishing Group
- Accession number :
- edsair.doi.dedup.....8474b9021c322be9257cacb4a8dc9311