Posology : מינונים

4.2 Posology and method of administration

Note: when using leucovorin (calcium folinate) - fluorouracil chemotherapy combination, strict caution should be exercised not to mix the 2 drugs in the same administration set because of incompatibility (see section 6.2).

Selection of an appropriate dose and treatment regime will depend upon the condition of the patient, the type of carcinoma being treated and whether fluorouracil is to be administered alone or in combination with other therapy. Initial treatment should be given in hospital and the total daily dose should not exceed 1 gram. It is customary to calculate the dose in accordance with patient's actual weight unless there is obesity, oedema or some other form of abnormal fluid retention such as ascites. In this case, ideal weight should be used as the basis for the calculation. Reduction of the dose is advisable in patients with any of the following:
1) Cachexia
2) Major surgery within preceding 30 days
3) Reduced bone marrow function
4) Impaired hepatic or renal function


Fluorouracil injection can be given by intravenous injection or intravenous infusion. Fluorouracil injection should not be mixed directly, in the same container, with other chemotherapeutic agents or intravenous additives.

Fluorouracil is applied alone and in combination with other cytostatic drugs. The fluorouracil dosage depends on the schedule opted for, the use of other cytostatic drugs, the application of radiotherapy and the method of administration. The total daily dosage will usually not exceed 1 gram.

Colorectal tumours:
The initial therapy may be given as intravenous injections or intravenous infusion. The toxicity of fluorouracil is usually higher after injection than after infusion.

As intravenous infusion, 600 mg/m² daily (with a maximum of 1 g each time) in 300 _500 ml 5% glucose solution may be given during 4 hours. This dosage is repeated daily until the first side effects occur.
Therapy should then be interrupted. After disappearance of the haematological and gastrointestinal side effects, a maintenance therapy is given.
Fluorouracil is also given as a continuous infusion. The dosage and duration of the infusion depends on the schedule chosen, the use of other cytostatic drugs and the application of radiotherapy. In a dosage up to 300 mg/m2 daily for 30-60 consecutive days, toxicity will rarely occur. In higher dosages stomatitis will be the dose-limiting side effect. A common dosage is 350 mg/m2 daily.

As injection, 480 mg/m2 daily is given intravenously on 3 consecutive days. If toxic side effects do not appear, 240 mg/m2 is given intravenously on days 5, 7 and 9, followed by a maintenance therapy. The maintenance therapy consists of injections: once a week 200-400 mg/m2 in intravenous injection.

Breast cancer:
For the treatment of breast cancer fluorouracil is given, for example, in combination with methotrexate and cyclophosphamide or in combination with doxorubicin and cyclophosphamide. The usual fluorouracil dosage in these schedules is 400-600 mg/m2, intravenously administered on days 1 and 8, in a 28-day cycle.
In some schedules fluorouracil is administered as a continuous infusion. A common dosage is 350 mg/m2/day.

Other types of administration:
Fluorouracil may be used as a continuous infusion. The dosage and duration of the infusion depends on the regimen chosen, the use of other cytostatic drugs and the application of radiotherapy. A common dosage is 350 mg/m2/day.
When fluorouracil concentrate for solution for injection is used for continuous infusion, the fact that the solution for injection has not been preserved should be taken into account.

Dosage adjustment:
The fluorouracil dose should be adjusted in accordance with the schedule below if leukocytes or thrombocytes are reduced on the first day of therapy; the lowest value determines the height of the dose.

% of dose            Leukocytes                 Thrombocytes
100                  > 3,500                    > 125,000
50                2,500-3,500                75,000-125,000
0                   < 2,500                     < 75,000

If the number of leukocytes is 2500-3500 /mm3 and/or the number of thrombocytes 75,000-125,000 /mm3, it is better not to administer cytostatic drugs for one week. When the blood count has been restored the course may be continued; if not, dose reduction may be carried out.


The administration of fluorouracil should be discontinued if a bilirubin plasma concentration over 85 micromol/L is reached. If the patient has undergone major surgery within 30 days prior to administration, the recommended dosage should be reduced by a third to a half from the very beginning.

Children
No recommendations are made regarding the use of fluorouracil in children.

Elderly
Fluorouracil should be used in the elderly with similar considerations as in younger adult dosages, notwithstanding that incidence of concomitant medical illness is higher in the former group.