EMA has recommended that patients should be tested for the lack of the enzyme dihydropyrimidine dehydrogenase (DPD) before starting cancer treatment with fluorouracil given by injection or infusion (drip) or with the related medicines, capecitabine and tegafur.
As treatment for severe fungal infections with flucytosine (another medicine related to fluorouracil) should not be delayed, testing patients for DPD deficiency before they start treatment is not required
Patient who completely lack DPD must not be given any fluorouracil medicines. For patients with partial deficiency, the doctor may consider starting cancer treatment at lower doses than normal or stopping flucytosine treatment if severe side effects occur.
These recommendations do not apply to fluorouracil medicines used on the skin for conditions such as actinic keratosis and warts, as only very low levels of the medicine are absorbed through the skin.
A significant proportion of the general population has a deficiency of DPD, which is needed to break down fluorouracil and the related medicines capecitabine, tegafur and flucytosine. As a result, following treatment with these medicines, fluorouracil can build up in their blood, leading to severe and life-threatening side effects such as neutropenia (low levels of neutrophils, a type of white blood cells needed to fight infection), neurotoxicity (damage to the nervous system), severe diarrhoea and stomatitis (inflammation of the lining of the mouth).
Patients can be tested for DPD deficiency by measuring the level of uracil (a substance broken down by DPD) in the blood, or by checking for the presence of certain mutations (changes) in the gene for DPD. Relevant clinical guidelines should be taken into consideration.