Symptoms and signs
Patients with partial or complete DPD deficiency who are treated with a standard dose of fluoropyrimidine will have increased levels of the active metabolites of fluorouracil due to the reduced DPD activity. Increased levels of the fluorouracil active metabolites are associated with an increased risk of severe or even fatal toxicity.r
DPD deficient patients will develop typical fluoropyrimidine toxicity but this typically appears much earlier and is more severe and prolonged. DPD deficiency should be considered in patients who develop severe toxicity within the first few days of therapy. An antidote is available for fluoropyrimidine overdose or overexposure and is highly effective if given within 96 hours. Read more about Fluoropyrimidine overdose or overexposure.
Investigations and diagnosis
DPD deficiency can be investigated by DPYD genotyping and measuring the DPD phenotype (dihydrouracil/uracil ratio blood levels).rr Both tests are available in Australia, however, they are currently not reimbursed and the cost and turnaround times may be limiting factors in testing upfront.
DPYD genotype test is available commercially through Douglas Hanley Moir Pathology (Sonic Pathology network) and costs $200 with a 10 business days turnaround time. Selected hospital pathology genomics laboratories also have capacity to do genotyping, also at cost to patients. Dihydrouracil/uracil ratios are available through NSW Health Pathology. The current cost is $275 with a maximum turnaround time of 2 weeks from receipt of sample.
In 2020, the Pharmacovigilance Risk Assessment Committee (PRAC) in association with the European Medicines Agency (EMA) released a statement endorsing pre-treatment DPD testing for patients undertaking treatment with fluoropyrimidines.r Updated guidelines from the European Society for Medical Oncology (ESMO) also reflect this recommendation.r Currently the US Food and Drug Administration (FDA), Therapeutics Goods Administration (TGA) and National Comprehensive Cancer Network (NCCN) do not recommend routine genetic testing prior to the administration of fluoropyrimidines.
While the product information for both capecitabine and fluorouracil warn about the potentially fatal reactions attributed to DPD deficiency, they do not recommend routine testing for DPD deficiency.