PACKAGE LEAFLET: INFORMATION FOR THE USER

Fluorouracil 50 mg/ml Injection

In this leaflet:

1.    What Fluorouracil Injection is and what it is used for

2.    Before you use Fluorouracil Injection

3.    How to use Fluorouracil Injection

4.    Possible side effects

5.    How to store Fluorouracil Injection

6.    Further information

1. WHAT FLUOROURACIL INJECTION IS AND WHAT IT IS USED FOR

Fluorouracil Injection is an anti-cancer medicine. Treatment with an anti-cancer medicine is sometimes called cancer chemotherapy.

Fluorouracil Injection is used to treat many common cancers, particularly cancers of the large bowel and breast. It may be used in combination with other anti-cancer medicines or radiotherapy.

2. BEFORE YOU USE FLUOROURACIL INJECTION

Do not use Fluorouracil Injection

•    if you have shown signs of hypersensitivity (severe allergy) to fluorouracil in the past

•    if you are in a seriously weakened state due to long illness

•    if your bone marrow has been damaged by other cancer treatments (including radiotherapy)

•    if you have a potentially serious infection

•    if your cancer is non-malignant

•    if you are pregnant or you are breast-feeding

•    if you are taking or have taken in the past 4 weeks brivudine, sorivudine and similar drugs (antivirals)

Tell your doctor if any of the above applies to you before this medicine is used. Take special care with Fluorouracil Injection

•    if your bone marrow is not producing blood cells normally (your doctor will do a blood test 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 (chest pain) or have a history of heart disease

•    if you have reduced activity/deficiency of the enzyme DPD (dihydropyrimidine dehydrogenase)

•    if you are in generally poor health and have lost a lot of weight

•    if you have had surgery within the last 30 days

•    if you are elderly

Tell your doctor if any of the above applies to you before this medicine is used. Taking/using other medicines

Special care is needed if you are taking/using other medicines as some could interact with Fluorouracil Injection, for example:

•    methotrexate, cisplatin, cytarabine, mitomycin-C, tamoxifen (anti-cancer medicines)

•    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)

•    interferon alpha 2a; brivudine, sorivudine and similar drugs (antivirals)

•    phenytoin (an anti-epilepsy medicine)

•    vaccines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Pregnancy and breast-feeding

Tell your doctor if you are pregnant, trying to become pregnant or breast-feeding.

This medicine must not be used during pregnancy and breast-feeding.

Both women of childbearing potential and men must use an effective method of contraception while taking fluorouracil and for at least 6 months afterwards.

Men are advised to seek advice on the conservation of sperm due to the possibility of irreversible infertility due to using fluorouracil.

If a pregnancy does occur during your treatment, you must inform your doctor who will advise you of the potential hazards and may recommend genetic counselling for you.

Ask your doctor or pharmacist for advice before taking any medicine. Driving and using machines

Do not drive or use machines if you experience any side effect from Fluorouracil, such as nausea and vomiting. Fluorouracil can also produce adverse events on your nervous system and cause visual changes. If you experience any of these effects, do not drive or use any tools or machines, as they may impair your ability to do so.

Important information about one of the ingredients of Fluorouracil Injection

This medicinal product contains 7 mmol (160 mg) sodium per 1 gram dose. To be taken into consideration by patients on a controlled sodium diet.

3. HOW TO USE FLUOROURACIL INJECTION

This medicine is given into a vein or an artery. If it is given into a vein, it can either be injected (using a syringe) or infused (using a drip). If it is given into an artery, it will be given as an infusion.

If it is to be given as an infusion the medicine will be diluted before use. Dose

Your doctor will work out the correct dose of Fluorouracil Injection for you and how often it must be given.

The dose of medicine given to you will depend on your medical condition, your size, if you have had recent surgery and how well your bone marrow, liver and kidneys are working.Your doctor will tell how well your bone marrow, liver and kidneys are working using blood tests.

The total daily dose should not exceed 1 gram.

If you are given too much or too little Fluorouracil Injection

This medicine will be given to you by a doctor or nurse. It is unlikely that you will be given too much or too little, however, tell your doctor or nurse if you have any concerns. If you have taken too much, your doctor will monitor you closely for at least 4 weeks.

Fluorouracil 50 mg/ml Injection

The following information is intended for medical or healthcare professionals only

Further to the information included in section 3, practical information on the preparation/handling of the medicinal product is provided here.

Incompatibilities

Fluorouracil Injection is incompatible with carboplatin, cisplatin, cytarabine, diazepam, doxorubicin, epirubicin, levamisole, other anthracyclines and possibly methotrexate.

Formulated solutions are alkaline and it is recommended that admixture with acidic drugs or preparations should be avoided.

Use and handling, and disposal

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, re-dissolve 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 colour.

Fluorouracil Injection may be diluted with Glucose 5% Injection or Sodium Chloride 0.9% Injection or Water for Injections immediately before use.

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

Chemical and physical in-use 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 not normally be longer than 24 hours at 2-8°C, unless dilution has taken place in controlled and validated aseptic conditions.

Cytotoxic Handling Guidelines

Should be administered only by, or under the direct supervision of, a qualified physician who is experienced in the use of cancer chemotherapeutic agents.

4. POSSIBLE SIDE EFFECTS

Like all medicines, fluorouracil can cause side effects, although not everybody gets them.

If any of the following happen, tell your doctor immediately:

•    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

•    chest pains (which may be due to heart problems, including having a heart attack)

•    your bowel motions are bloodstained or black

•    your mouth becomes sore or develops ulcers

•    symptoms of leucoencephalopathy (disease of brain) - extreme weakness and fatigue, staggering while walking, thinking or speech difficulties, seizures, coma.

These are very serious side effects. You may need urgent medical attention.

The frequency of possible side effects listed below is defined using the following convention:

Very common (affects more than 1 user in 10)

Common (affects 1 to 10 users in 100)

Uncommon (affects 1 to 10 users in 1,000)

Rare (affects 1 to 10 users in 10,000)

Very rare (affects less than 1 user in 10,000)

Not known (frequency cannot be estimated from the available data)

If you experience any of the following tell your doctor as soon as possible:

Very common side effects

•    abnormality in the heart's rhythm

•    anaemia

•    diarrhoea

•    feeling or being sick

•    anorexia

•    tiredness or fatigue

•    reddening of the palms of the hands and/or the soles of the feet

•    hair loss (especially in women)

•    increased chance of picking up infections and/or delayed wound healing due to low white blood cells

•    inflammation of the lining of the mouth, throat, gut, rectum or anus Uncommon side effects

•    low blood pressure (you may feel faint)

•    watering eyes, changes in vision, sensitivity to light, side-to-side movements of the eyes

•    numbness, tingling or tremor in the hands or feet

•    feeling euphoric

•    symptoms of Parkinson's disease (e.g. shaking hands)

•    headache

•    skin problems, (including dry skin, itchy weals, rash, redness, inflammation)

•    skin may appear lighter or darker

•    changes in your nails, such as changes in colour or thickening of the nails

Rare side effects

•    feeling confused

•    discolouration in your fingers and toes (Raynaud's syndrome)

•    reduced circulation to the brain, intestines and extremities (ischaemia)

•    blood clots (pain, redness or swelling of the part affected)

Very rare side effects

•    feeling unsteady on your feet

•    muscle weakness

•    sudden cardiac death Frequency unknown

•    quickening of your heart rate and breathlessness

•    fever

•    the vein where fluorouracil is administered may become painful or discoloured, which may be the sign of a blood clot

Fluorouracil may lead to changes in your blood cells. Your doctor will take blood samples to check for abnormalities (e.g. bone marrow depression which may result in low white cells, low red cells, low platelets, low gamma globulins).

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

5. HOW TO STORE FLUOROURACIL INJECTION

Keep out of the reach and sight of children Expiry

This medicine must not be used after the expiry date which is stated on the vial label and carton after ‘EXP'. Where only a month and year is stated, the expiry date refers to the last day of that month.

Storage

Keep the vials in the outer carton, in order to protect from light and store at or below 25°C. They should not be refrigerated or frozen.

Prepared infusions should be used immediately, however, if this is not possible they can be stored for up to 5 days provided they have been prepared in a way to exclude microbial contamination.

Visible signs of deterioration

The product should be discarded if it appears brown or dark yellow in colour. Disposal

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. FURTHER INFORMATION

What Fluorouracil Injection contains

The active substance is fluorouracil. Each millilitre (ml) of solution contains 50 mg of fluorouracil.

The other ingredients are sodium hydroxide and Water for Injections.

What Fluorouracil Injection looks like and contents of the pack

Fluorouracil Injection is a clear, colourless or slightly yellow solution for injection which comes in glass containers called vials.

It may be supplied in packs containing:

•    5 x 250 mg/5 ml vials

•    5 x 500 mg/10 ml vials

•    5 x 1 g/20 ml vials

•    1 or 10 x 2.5 g/50 ml vial

•    1 x 5 g/100 ml vial

•    1 x 500 mg/10 ml ONCO-VIAL™

•    1 x 1 g/20 ml ONCO-VIAL™

•    1 x 2.5 g/50 ml ONCO-VIAL™

Not all packs may be marketed.

Marketing authorisation holder and manufacturer responsible for batch release in Europe

Hospira UK Limited, Queensway, Royal Leamington Spa, Warwickshire, CV31 3RW, UK

Manufacturer

Hospira Australia Pty Ltd, Lexia Place, Mulgrave, Victoria 3170, Australia This leaflet was last revised in 12/2013

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Fluorouracil Injection should only be prepared for administration by professionals who have been trained in the safe use of the preparation. Preparation should only be carried out in an aseptic cabinet or suite dedicated for the assembly of cytotoxics.

In the event of spillage, operators should put on gloves, face mask, eye protection and disposable apron and mop up the spilled material with an absorbent material kept in the area for that purpose. The area should then be cleaned and all contaminated material transferred to a cytotoxic spillage bag or bin and sealed for incineration.

Contamination

Fluorouracil is an irritant, contact with skin and mucous membranes should be avoided.

In the event of contact with the skin or eyes, the affected area should be washed with copious amounts of water or normal saline. A bland cream may be used to treat the transient stinging of the skin. Medical advice should be sought if the eyes are affected or if the preparation is inhaled or ingested.

Please refer to the marketing authorisation holder for COSHH hazard datasheets.

Preparation Guidelines

a)    Chemotherapeutic agents should be prepared for administration only by professionals who have been trained in the safe use of the preparation.

b)    Operations such as reconstitution of powder and transfer to syringes should be carried out only under aseptic conditions in a suite or cabinet dedicated for the assembly of cytotoxics.

c)    The personnel carrying out these procedures should be adequately protected with clothing, gloves and eye shield.

d)    Pregnant personnel are advised not to handle chemotherapeutic agents. Disposal

Syringes, ONCO-VIAL™s and adaptors containing remaining solution, absorbent materials, and any other contaminated material should be placed in a thick plastic bag or other impervious container and incinerated at 700°C.

Directions for use of the ONCO-VIAL™

ONCO-VIAL™ should be used with an appropriate Hospira administration device.