Fluorouracil 25 mg/ml Injection
For Intravenous or Intraarterial Use
Fluorouracil is incompatible with carboplatin, cisplatin, cytarabine, diazepam, doxorubicin, other anthracyclines and possibly methotrexate.
Formulated solutions are alkaline and it is recommended that admixture with acidic drugs or preparations should be avoided.
Fluorouracil Injection may be diluted with Glucose 5% Injection or Sodium Chloride 0.9% Injection BP or Water for Injections BP immediately before parenteral use.
Dosage and Administration
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 0.8-1 gram. It is customary to calculate the dose in accordance with the patient’s actual bodyweight unless there is obesity, oedema or some form of abnormal fluid retention such as ascites. Ideal weight is used as the basis for calculation in such cases.
The initial dose should be reduced by one-third to one half in patients with any of the following:
2. Major surgery within preceding 30 days.
3. Reduced bone marrow function.
4. Impaired hepatic or renal function.
The following regimens have been recommended for use as a single agent:-
This may be in the form of an infusion or an injection, the former usually being preferred because of lesser toxicity.
15 mg/kg bodyweight but not more than 1 g per infusion, diluted in 300 – 500 ml of 5% glucose or 0.9% NaCI injection and given by intravenous infusion over 4 hours.
Alternatively the daily dose may be infused over 30 – 60 minutes or may be given as a continuous infusion over 24 hours. The infusion may be repeated daily until there is evidence of toxicity or a total dose of 12 – 15 g has been reached.
12 mg/kg bodyweight may be given daily for 3 days and then, if there is no evidence of toxicity, 6 mg/kg on alternate days for a further 3 doses.
An alternative regimen is 15 mg/kg as a single intravenous injection once a week throughout the course.
5 – 7.5 mg/kg bodyweight daily may be given by 24 hour continuous intra-arterial infusion.
An initial intensive course may be followed by maintenance therapy providing there are no significant toxic effects. In all instances, toxic side effects must disappear before maintenance therapy is started.
The initial course of fluorouracil can be repeated after an interval of 4 to 6 weeks from the last dose or, alternatively, treatment can be continued with intravenous injections of 5-15 mg/kg bodyweight at weekly intervals. This sequence constitutes a course of therapy. Some patients have received up to 30 g at a maximum rate of 1 g daily.
1. What Fluorouracil Injection is and what it is used tor
Fluorouracil Injection is an anti-cancer medicine, in the form of a solution for injection. Treatment with an anti-cancer medicine is sometimes called cancer chemotherapy.
The medicine is presented in glass containers called vials. Each ml (millilitre) of solution contains 25 mg (milligrams) of fluorouracil. The 10 ml vial contains 250 mg fluorouracil, the 20 ml vial contains 500 mg fluorouracil and the 100 ml vial contains 2.5 g fluorouracil. It is available in packs containing 5×10 ml, 10 x 20 ml or 1 x 100 ml. Not all presentations may be marketed.
Fluorouracil Injection is used to treat many common cancers, particularly cancers of the Gl tract, pancreas, large bowel, ovary, prostate and breast. It may be used in combination with other anti-cancer medicines or radiotherapy.
2. Before Fluorouracil Injection is used
Fluorouracil Injection should not be used:
• if you have shown signs of hypersensitivity (severe allergy) to fluorouracil or any of the ingredients of this medicine on previous occasions
• if you have been very much weakened by long illness
• If your bone marrow has been damaged by other treatments (including radiotherapy)
• if you are pregnant or trying for a baby
• if you are breastfeeding
• if your cancer is non-malignant
Special care will be taken:
• if the number of cells in your blood become too low (you will have blood tests to check this)
• if you have any problems with your kidneys
• if you have any problems with your liver including jaundice (yellowing of the skin)
• if you have suffered from angina or have a history of heart disease. Tell your doctor if you experience any chest pain during treatment.
• if you have reduced activity/deficiency of the enzyme DPD (dihydropyrimidine dehydrogenase).
• if you are taking certain other medicines, such as:
• methotrexate (an anti-cancer medicine)
• metronidazole (an antibiotic)
• calcium leucovorin (also called calcium folinate – used to reduce the harmful effects of anti-cancer medicines)
• allopurinol (used to treat gout)
• cimetidine (used to treat stomach ulcers)
• warfarin (used to treat blood clots)
• sorivudine (an antiviral)
Please tell your doctor if you are taking, or have recently taken, any other medicines, including ones that are not prescribed for you.
A more recent alternative method is to give 15 mg/kg intravenously once a week throughout the course of treatment. This obviates the need for an initial period of daily administration.
In Combination with Irradiation
Irradiation combined with fluorouracil has been found to be useful in the treatment of certain types of metastatic lesions in the lungs and for the relief of pain caused by recurrent, inoperable growth. The standard dose of fluorouracil should be used.
No recommendations are made regarding the use of fluorouracil in children.
Fluorouracil should be used in the elderly with similar considerations as in younger adults, I notwithstanding that incidence of concomitant medical illness is higher in the former I group.
It is recommended that Fluorouracil be given only by, or under the strict supervision of, a qualified physician who is conversant with the use of potent antimetabolites.
All patients should be admitted to hospital for initial treatment.
Adequate treatment with Fluorouracil is usually followed by leucopenia, the lowest white blood cell (W.B.C) count commonly being observed between the 7th and 14th day of the first course, but occasionally being delayed for as long as 20 days. The count usually returns to normal by the 30th day.
Daily monitoring of platelet and W.B.C count is recommended and treatment should be stopped if platelets fall below 100,000 per mm3 or the W.B.C. count falls below 3,500 per mm3. If the total count is less than 2000 mm3, and especially if there is granulocytopenia, it is recommended that the patient be placed in protective isolation in the hospital and treated with appropriate measures to prevent systemic infection.
Treatment should be stopped at the first sign of oral ulceration or if there is evidence of gastrointestinal side effects such as stomatitis, diarrhoea, bleeding from the G.I. tract or haemorrhage at any site. The ratio between effective and toxic dose is small and therapeutic response is unlikely without some degree of toxicity. Care must be taken therefore, in the selection of patients and adjustment of dosage.
Flourouracil should be used with caution in patients with reduced renal or liver function or jaundice. Isolated cases of angina, ECG abnormalities and rarely, myocardial infarction have been reported following administration of Fluorouracil. Care should therefore be exercised in treating patients who experience chest pain during courses of treatment, or patients with a history of heart disease.
The symptoms of overdose are qualitatively similar to the undesirable effects: diarrhoea, nausea and vomiting (an anti-emetic may be given for nausea and vomiting), chest pain, tachycardia, breathlessness, ECG changes and confusional state. Palmer-Plantar Erythrodysesthesia Syndrome has been reported as an unusual complication of high dose bolus or protracted continuous therapy with fluorouracil.
Do not store above 25°C. Do not refrigerate or freeze. Keep container in the outer carton.
Chemical and physical stability has been demonstrated for 5 days at 20 – 21 °C.
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 – 8°C, unless reconstitution has taken place in controlled and validated aseptic conditions.
The pH of fluorouracil injection is 8.9 and the drug has maximal stability over the pH range 8.6 to 9.0.
If a precipitate has formed as a result of exposure to low temperatures, redissolve by heating to 60°C accompanied by vigorous shaking. Allow to cool to body temperature prior to use.
The product should be discarded if it appears brown or dark yellow in solution.
Do not drive or use machines:
• if you experience any effect which may impair your ability to drive or use machines.
3. How Fluorouracil Injection is used
The dose of medicine given to you will depend on your medical condition, your body weight, if you have had recent surgery and how well your liver and kidneys are working. It will also depend on the results of your blood tests. The dose should not be more than 800 mg – 1 g per day. Your first course of treatment may be given daily or at weekly intervals. Further courses may be given according to your response to treatment. You may also receive treatment in combination with radiotherapy.
The medicine may be diluted with glucose solution, sodium chloride solution or Water for Injections before it is given to you. It will be given either into a vein or an artery. If it is given into a vein, it can either be given as a normal injection or a slow injection via a drip (infusion). If it is given into an artery, it will be given as an infusion.
As this medicine will usually be given to you whilst you are in hospital it is unlikely that you will be given too little or too much, however, tell your doctor or pharmacist if you have any concerns.
You will need to have blood tests during and after treatment with fluorouracil to check the levels of cells in your blood. Treatment may have to be stopped if the level of white blood cells drops too low.
4. Possible Side Effects
Like all medicines, fluorouracil can have side effects.
If any of the following happen, tell your doctor immediately:
• chest pains
• your bowel motions are bloodstained or black
• your mouth becomes sore or develops ulcers
• severe allergic reaction – you may experience a sudden itchy rash (hives), swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty in swallowing or breathing), and you may feel you are going to faint
• symptoms of leucoencephalopathy (disease of brain) – weakness, coordination problems in arms and legs; thinking/speech difficulties; vision/memory problems; seizures; headaches
These are very serious side effects. You may need urgent medical attention.
All of these very serious side effects are rare.
If you experience any of the following tell your doctor as soon as possible:
• feeling or being sick
• hair loss (especially in women)
• skin problems
• changes in your nails
• unsteady on your feet
• quickening of your heart rate and breathlessness
• painful and/or watering eyes, changes in vision or sensitivity to light
• feeling confused
• reddening of the palms of the hands and/or the soles of the feet
• the vein where fluorouracil is administered may become painful or discoloured
If you notice any side effects not mentioned in this leaflet, please tell your doctor or pharmacist.
5. Storing Fluorouracil Injection
Keep out of the reach of children.
The vials should not be stored above 25°C. They should not be put in the fridge or frozen.
The vials should be kept in the outer carton in order to protect from light.
This medicine should not be used after the expiry date printed on the vial label.