The enzyme dihydropyrimidine dehydrogenase (DPD) plays an important role for the degradation of 5-FU. Nucleoside analogues, such as brivudine and sorivudine, may lead to a drastic increase in the plasma concentrations of 5-FU or other fluoropyrimidines and thus to an accompanying increase in toxicity.
For this reason, an interval of at least 4 weeks should be kept between intake of 5-FU and brivudine, sorivudine and analogues.
If necessary, determination of the DPD enzyme activity is indicated prior to therapy with 5-fluoropyrimidines. In case of inadvertent administration of brivudine to patients treated with fluorouracil, effective measures to reduce fluorouracil toxicity should be taken. Immediate hospitalisation is recommended. All measures to prevent systemic infections and dehydration should be initiated.
Patients taking phenytoin concomitantly with fluorouracil should be examined at regular intervals for an elevated phenytoin plasma level.
Damage to intestinal wall requires symptomatic treatment according to the degree of severity, e.g. fluid substitution. Mild diarrhoea may respond to antidiarrhoeals. However, they are not sufficient in moderate to severe diarrhoea.
Prior to and during therapy with fluorouracil, the subsequent examinations are recommended: daily inspection of oral cavity and pharynx in view of mucosal alterations; blood count including differential blood count and thrombocytes prior to each administration of fluorouracil; retention values; hepatic values.
In concurrent use of fluorouracil and oral anticoagulants, the Quick's value is closely to be monitored.
Patients should be advised additionally about the possible occurrence of stomatitis/mucositis, diarrhoea and bleeding (in particular from the gastrointestinal tract). Patients should be advised to consult the attending physician if first signs occur.
For injectable products containing FM27 in rubber material, e.g. in removable needle shields or tip caps: Latex-sensitive individuals: The [name of the affected part of the product, e.g. removable needle shield] of 5-Fluorouracil Ebewe contains a derivative of natural rubber latex. Although no natural rubber latex is detected in the [name of the affected part of the product], the safe use of 5-Fluorouracil Ebewe in latex-sensitive individuals has not been studied.
Effects on ability to drive and use machines: Fluorouracil may cause nausea and vomiting and thus indirectly lead to impaired ability to drive or to operate machinery. For this reason, driving and operating machinery should be refrained from during treatment with fluorouracil.
Use in Pregnancy: Pregnant personnel is to be excluded from handling with fluorouracil.
Use in Lactation: Due to the potentially mutagenic and carcinogenic effect, increased safety rules apply to nursing personnel and physicians. When handling with fluorouracil, any contact with skin and mucosae is to be avoided. Preparation must be performed by means of an absolutely aseptic technique. Use of a workbench with laminar air flow (LAF) is recommended. When handling with fluorouracil, protective clothing must be worn.
Use in Children: No sufficient experience is available regarding efficacy and safety of fluorouracil in children.