Fluorouracil (5-FU)

SETTING: initial treatment should be given in hospital, and fluorouracil should be given only by or under the strict supervision of a qualified physician conversant with the use of potent antimetabolites. WEIGHT BASIS: it is customary to calculate the dose using the patient's actual bodyweight unless there is obesity, oedema or some form of abnormal fluid retention such as ascites, in which case ideal weight is used. OTHER SINGLE-AGENT REGIMENS FROM THE SAME SPC — Intravenous injection: 12 mg/kg bodyweight, but not more than the recommended 1 g daily dose, may be given daily for 3 days and then, if there is no evidence of toxicity, 6 mg/kg on alternate days for 3 further doses; an alternative regimen is 15 mg/kg as a single intravenous injection once a week throughout the course. Intra-arterial infusion: 5/7.5 mg/kg bodyweight daily may be given by 24-hour continuous intra-arterial infusion. MAINTENANCE THERAPY: an initial intensive course may be followed by maintenance therapy provided there are no significant toxic effects, and toxic side effects must disappear before maintenance is started. The initial course can be repeated after an interval of 4 to 6 weeks from the last dose, or treatment continued with intravenous injections of 5 to 15 mg/kg bodyweight at weekly intervals. Some patients have received up to 30 g at a maximum rate of 1 g daily. A more recent alternative is 15 mg/kg IV once a week throughout the course, which obviates the need for an initial period of daily administration. WITH IRRADIATION: the standard dose of fluorouracil should be used. WITH LEUCOVORIN: fluorouracil is often given concomitantly with leucovorin, which may potentiate its therapeutic effects and may therefore increase toxicity, especially gastrointestinal and haematologic — monitor carefully and consider decreasing the fluorouracil dose based on current guidelines. DOSE REDUCTION SITUATIONS: reduce the initial dose by one-third to one-half in cachexia, major surgery within the preceding 30 days, reduced bone marrow function, or impaired hepatic or renal function. BLOOD COUNT TABLE: leucocytes above 3.5 x 10^9/l with thrombocytes above 125 x 10^9/l — recommended dose; leucocytes 2.5 to 3.5 x 10^9/l with thrombocytes 75 to 125 x 10^9/l — 50% of the recommended dose; leucocytes below 2.5 x 10^9/l or thrombocytes below 75 x 10^9/l — suspend treatment for one week, and resume if the blood count normalises. HEPATIC: if plasma bilirubin exceeds 5 mg/dl, treatment should be discontinued. STOPPING RULES (section 4.4): stop treatment if platelets fall below 100,000 per mm3 or the white cell count falls below 3,500 per mm3, and at the first sign of oral ulceration or of stomatitis, diarrhoea, gastrointestinal bleeding, haemorrhage at any site, oesophagopharyngitis or intractable vomiting. CHILDREN: the SPC states 'No recommendations are made regarding the use of fluorouracil in children.' ELDERLY: use with caution; female gender and age 70 years or older are reported as independent risk factors for severe toxicity from fluorouracil-based chemotherapy, and decreased kidney function with age makes a dose decrease necessary. SOURCE CAVEATS: the fetched UK SPC (Fluorouracil 25 mg/ml Injection) sections 4.4 and 4.8 were truncated at the source-fetch limit and section 4.5 (interactions) was not retrieved. The openFDA fallback in this bundle is a topical fluorouracil CREAM label (actinic keratosis and superficial basal cell carcinoma) — a different route and indication — and was deliberately NOT used for dosing.