FLUOROURACILE IKMA 50 mg/ml Roztwór do wstrzykiwań lub infuzji

Treść ulotki

1. Fluorouracile Hikma
   1. What is Fluorouracile Hikma and what is it used for
   2. What you need to know before you use Fluorouracile Hikma
   3. How to use Fluorouracile Hikma
   4. Possible side effects
   5. How to store Fluorouracile Hikma
   6. Package Contents and Other Information

Fluorouracile Hikma

50 mg/ml
Solution for injection/infusion
Generic medicine

because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse
• If any side effects occur, including any not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet

• 1. What Fluorouracile Hikma is and what it is used for
• 2. What you need to know before you use Fluorouracile Hikma
• 3. How to use Fluorouracile Hikma
• 4. Possible side effects
• 5. How to store Fluorouracile Hikma
• 6. Contents of the pack and other information

1. What is Fluorouracile Hikma and what is it used for

Fluorouracile Hikma contains the active ingredient fluorouracil. It is an antineoplastic drug.
Fluorouracile Hikma is used to treat many common tumors, in particular tumors
of the colon, esophagus, pancreas, stomach, head, neck and breast. It can
be used in combination with other antineoplastic drugs and with radiotherapy.

2. What you need to know before you use Fluorouracile Hikma

Do not use Fluorouracile Hikma:

• if you are allergic to fluorouracil or to any of the other ingredients of this medicine (listed in section 6).
• if you have serious infections (e.g. Herpes zoster, chickenpox).
• if your tumor is non-malignant.
• if you are very debilitated following a long illness.
• if your bone marrow has been damaged by other treatments (including radiotherapy).
• if you are taking brivudine, sorivudine and analogues (an antiviral drug).
• if you are pregnant or breastfeeding
• if you have severe impairment of your liver function
• if you are homozygous for the dihydropyrimidine dehydrogenase (DPD) enzyme

Warnings and precautions
Talk to your doctor or nurse before using Fluorouracile Hikma.
Pay particular attention with Fluorouracile Hikma:

• if the number of cells in your blood drops too low (you must have blood tests to check these values).
• if you suffer from mouth ulcers, fever or bleeding anywhere or if you feel weak (these symptoms may be the consequence of a very low number of cells in your blood).
• if you suffer from kidney problems.
• if you suffer from liver problems including jaundice (yellowing of the skin).
• if you suffer from heart problems. Tell your doctor if you feel chest pain during treatment.
• if you suffer from reduced activity or a deficiency of the DPD (dihydropyrimidine dehydrogenase) enzyme.
• if you have received high-dose pelvic radiation.
• if you suffer from gastrointestinal disorders (stomatitis, diarrhea, bleeding of the gastrointestinal tract) or bleeding at any site.

Other medicines and Fluorouracile Hikma
Tell your doctor if you are taking, have recently taken or may take any
other medicines.
The medicines listed below affect the effect of fluorouracil:

• Methotrexate (an antineoplastic medicine)
• Metronidazole (an antibiotic)
• Calcium leucovorin (also called calcium folinate - used to reduce the harmful effects of antineoplastic medicines)
• Allopurinol (used to treat gout)
• Cimetidine (used to treat stomach ulcers)
• Warfarin (used for the treatment of platelets)
• Interferon alfa 2a; brivudine, sorivudine and analogues (an antiviral drug)
• Cisplatin (an antineoplastic medicine)
• Phenytoin (used to control epilepsy/seizures and an irregular heartbeat)
• Vaccines
• Vinorelbine (an antineoplastic drug)
• Cyclophosphamide (an antineoplastic drug)
• Levamisole (medicine used to treat worm infections)
• Tamoxifen (an antineoplastic drug)

Pregnancy, breastfeeding and fertility
You must not take this medicine if you are pregnant or planning a
pregnancy. If you are a woman of childbearing potential you must use an effective method of contraception
while taking this medicine and for at least 6 months after taking it. If pregnancy occurs during
treatment, you should inform your doctor and undergo genetic counseling.
Since it is not known whether fluorouracil passes into breast milk, breastfeeding must
be discontinued if the mother is being treated with Fluorouracile Hikma.
If you are a man, you should avoid procreation during and up to 6 months after stopping
treatment with Fluorouracile Hikma. It is recommended to evaluate sperm preservation
before treatment for the possibility of irreversible infertility following therapy with
Fluorouracile Hikma.
Ask your doctor for advice before taking any medicine.

Driving and operating machinery
Do not drive or operate machinery because fluorouracil can produce undesirable effects such as nausea
and vomiting. It can also produce adverse events on your nervous system and changes in vision. If
you experience any of these effects, do not drive or use tools or machinery, as this may
compromise your ability to drive or operate machinery.

Fluorouracile Hikma contains sodium
This medicinal product contains less than 1 mmol of sodium (23 mg) per millilitre, i.e.
it is practically “sodium-free”.

3. How to use Fluorouracile Hikma

The dose of medication that will be administered to you will depend on your medical condition, your
body weight, whether you have recently undergone surgery, and how well your kidneys and liver
are working. It will also depend on the results of your blood tests.
The first part of your treatment will be administered daily or at weekly intervals.
Further administrations may occur depending on your response to treatment. You may
also receive treatment in combination with radiotherapy.
The medication may be diluted with a glucose or sodium chloride solution before it is
administered to you. It will be administered into a vein either as a normal injection or
as a slow infusion via an intravenous drip (infusion).

If you take more Fluorouracile Hikma than you should
Since this medication will be administered to you while you are in hospital, it is
unlikely that you will be given too little or too much medication, however, tell your
doctor or pharmacist if you have any doubts.
You will need to undergo blood tests during and after treatment with
Fluorouracile Hikma to monitor the levels of your blood cells.
Treatment must be stopped if the level of your white blood cells drops too low.
Nausea, vomiting, diarrhea, severe mucositis and gastrointestinal ulceration may occur if
you are given too much Fluorouracile Hikma. If you have any doubts about the use of this
product, please consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

If any of the following effects occur, tell your doctor immediately:

• severe allergic reaction - you may experience sudden itching (urticaria), swelling of the hands, feet, ankles, face, lips, mouth or throat (which can cause difficulty swallowing or breathing), and you may feel like you are going to faint,
• chest pain,
• your stools are stained with blood or black,
• your mouth becomes painful or develops ulcers,
• numbness, tingling or tremors in your hands or feet,
• increased heart rate and shortness of breath,
• feeling confused or unsteady on your feet, problems with coordination of arms and legs, difficulty with thinking / speaking, problems with vision / memory

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

Very common side effects (more than 1 in 10 people):

• ischemic abnormalities on ECG (insufficient blood supply to an organ, generally following blockage of an artery)
• Neutropenia (an abnormally low level of neutrophils in the blood)
• Leukopenia (an abnormally low number of white blood cells in the blood)
• Anemia (a condition in which the mass of red blood cells in the blood is insufficient)
• Pancytopenia (a disorder in which the bone marrow greatly reduces or blocks the production of blood cells).
• Reduction in the production of blood cells
• High fever and a sharp drop in circulating white blood cells
• Inflammation of the lining of the mouth and digestive tract
• Pharyngitis (inflammation of the mucous membranes of the pharynx)
• Inflammation of the rectum or anus
• Loss of appetite
• Watery diarrhea
• Nausea
• Vomiting
• Hair loss
• Hand-foot syndrome which is a toxic skin reaction.
• Delayed wound healing
• Nosebleeds
• Fatigue
• General weakness
• Tiredness
• Lack of energy
• Inflammation of the lining of the mucosa of any structure of the mouth
• Esophagitis (inflammation of the esophagus)
• Increased uric acid in the blood

Common side effects (less than 1 in 10 people):

• Angina pectoris (Severe chest pain associated with insufficient blood supply to the heart)

Uncommon side effects (less than 1 in 100 people):

• Abnormal heart rhythm
• Heart attack
• Myocardial ischemia (loss of oxygen from the heart muscle)
• Myocarditis (inflammatory disease of the heart muscle)
• Heart failure
• Dilated cardiomyopathy (a type of heart disease in which the heart muscle is abnormally dilated, thickened and/or stiffened)
• Cardiac shock
• Low blood pressure
• Drowsiness
• Dehydration
• Bacterial infection in the bloodstream or body tissues
• Gastrointestinal ulcers and bleeding, skin loss
• rhythmic eye movements
• Headache
• Feeling of imbalance and instability
• Symptoms of Parkinson's disease (a progressive movement disorder marked by tremors, rigidity and slow movements)
• Pyramidal symptoms
• feeling sick
• Skin inflammation
• skin changes such as dry skin, cracks, erosion, skin redness, itchy maculopapular rash (rash that originated from the lower extremities and progressed to the arms and then to the chest)
• a rash that accompanies some infectious diseases
• Appearance of itchy bruises on the skin
• Photosensitivity
• Hyperpigmentation of the skin
• Striped or depigmentation hyperpigmentation near the veins
• changes in nails (e.g., diffuse superficial blue pigmentation, hyperpigmentation; nail dystrophy, pain and thickening of the nail bed.
• Paronychia (inflammation of the tissue surrounding the nail)
• Inflammation of the nail matrix with pus formation and nail shedding
• disorders in sperm or egg production
• tearing
• blurred vision,
• inflammation or redness of the lining of the white part of the eye and the lower eyelid.
• Eye movement disorder
• Optic neuritis (a visual disturbance characterized by inflammation of the optic nerve)
• Double vision
• reduced visual acuity
• Excessive sensitivity to light and discomfort in sunlight or well-lit places
• eye disorder characterized by chronic inflammation of the lower eyelid
• Lower eyelid turning outward
• blocked tear ducts
• A layer or mass of dead tissue separated from the surrounding living tissue, such as in a wound, sore, or inflammation.
• Liver cell damage

Rare side effects (more than 1 in 10,000 but less than 1 in 1,000):

• Generalized allergic reaction
• Insufficient blood flow to the brain, intestines and peripheral organs
• Discoloration of the fingers of the hands, toes, and occasionally other areas
• Development of a blood clot inside blood vessels, can occur in both arteries and veins
• Swelling (inflammation) of a vein caused by a blood clot
• Severe allergic reaction involving the whole body (anaphylaxis)
• Systemic vasodilation (dilation of blood vessels) leading to low blood pressure
• Confusion
• Increased T4 (total thyroxine), increased T3 (total triiodothyronine)

Very rare side effects (less than 1 in 10,000):

• Cardiac arrest (sudden cessation of heartbeat and cardiac function)
• Sudden cardiac death (unexpected death due to heart problems)
• Symptoms of leukoencephalopathy (diseases affecting the white matter of the brain) including ataxia (loss of the ability to coordinate muscle movement)
• Difficulty articulating words
• Confusion
• Confused mental state or altered awareness especially regarding time, place or identity
• Abnormal muscle weakness or fatigue
• Acute cerebellar syndrome
• Partial or total loss of the ability to communicate verbally or using written words.
• Convulsion or coma in patients who have received high doses of 5-fluorouracil and in patients with dihydropyrimidine dehydrogenase deficiency
• Kidney failure
• Liver cell damage (cases with fatal outcome)
• Inflammation of the gallbladder
• Slow and progressive destruction of the small bile ducts

Not known (frequency cannot be estimated):

• Fever
• Numbness or weakness of the arms and legs

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor or nurse. You can also report side effects directly through the national reporting system at:
http://www.agenziafarmaco.gov.it/it/responsabili .
By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Fluorouracile Hikma

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and on the packaging after
EXP.
Store at a temperature below 25°C. Do not refrigerate or freeze.
Keep the container in the outer packaging to protect the medicine from light.
For single use only. Discard any unused portion of the medicine.
Do not use the product if the solution appears brown or dark yellow.
Do not use this medicine if you notice that the container is damaged or if particles or
crystals are visible.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist
how to dispose of medicines you no longer use. This will help protect the environment.

6. Package Contents and Other Information

What Fluorouracile Hikma Contains

• The active ingredient is fluorouracil.
• The other ingredients are trometamol, sodium hydroxide and water for injections

Description of the Appearance of Fluorouracile Hikma and Package Contents
Fluorouracile Hikma, 50 mg/ml, solution for injection or for infusion is a clear,
colourless to almost colourless solution in a type I glass vial closed with a stopper.
1 ml of solution contains 50 mg of fluorouracil (as sodium salt formed in situ).
Each 5ml vial contains 250 mg of fluorouracil.
Each 10ml vial contains 500 mg of fluorouracil.
Each 20ml vial contains 1000 mg of fluorouracil.
Each 100ml vial contains 5000 mg of fluorouracil.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Hikma Farmacêutica (Portugal), S.A.
Estrada do Rio da Mó, 8, 8A e 8B – Fervença
2705-906 Terrugem SNT
Portugal
Manufacturer
Thymoorgan Pharmazie GmbH
Schiffgraben 23
38690 Goslar
Germany

This medicinal product is authorised in the Member States of the European Economic Area with
the following denominations::
Italy: Fluorouracile Hikma
Portugal: Fluorouracilo Hikma, 50 mg/ml, Solução injetável ou para perfusão
United Kingdom: Fluorouracil 50 mg/ml, Solution for injection/infusion
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The following information is intended only for healthcare professionals:

INSTRUCTIONS FOR USE/HANDLING, PREPARATION AND GUIDANCE
FOR THE DISPOSAL OF FLUOROURACIL INJECTION
Guidelines on handling cytotoxic substances
Fluorouracile Hikma must only be administered under the supervision of qualified physicians
experienced in the use of anti-cancer drugs.

Preparation (guidelines):
Contamination
If contact with skin or eyes occurs, the affected area should be washed with plenty of
water or normal saline. A cream with 1% hydrocortisone can be used to treat transient skin burning. In the event of eye contact or if the
preparation is inhaled or ingested, medical advice should be sought.
In case of spillage, operators should wear gloves, mask, goggles and disposable apron and absorb the spilled product with absorbent material stored in the area for this
purpose. The area should then be cleaned and all contaminated material transferred to a cytotoxic spill bag or drum and sealed for incineration.

First Aid
Eye contact: wash immediately with water and consult a doctor.
Skin contact: wash thoroughly with water and soap and remove contaminated clothing.
Inhalation, Ingestion: consult a doctor.

Disposal
Syringes, containers, absorbent materials, solution and any other contaminated material
must be placed in a thick plastic bag or other waterproof container,
labelled as cytotoxic material and incinerated at at least 700°C.
Chemical inactivation can be achieved using a 5% sodium hypochlorite solution
within 24 hours.
a) Chemotherapeutic agents must be prepared for administration only by adequately qualified medical personnel in the safe use of preparation.
b) Operations such as reconstitution of the powder and transfer to syringes should only take place
in specially designated areas.
c) Personnel performing these procedures must be adequately protected with
special clothing, two pairs of latex gloves, one in PVC (latex should be worn under the PVC), this covers the different permeability of the various antineoplastic agents, and eye protection. Luerlock syringes and fittings should always be used both in the preparation of
cytotoxic products and for their administration.

• (d) Pregnant personnel should be warned not to handle chemotherapeutic agents.
• (e) Refer to local guidelines before starting.

Instructions for Use
Fluorouracile Hikma can be administered by intravenous injection or infusion or
intra-arterial.

Incompatibilities
Fluorouracil is incompatible with folinic acid, carboplatin, cisplatin, cytarabine, diazepam,
doxorubicin, droperidol, filgrastim, gallium nitrate, methotrexate, metoclopramide, morphine,
ondansetron, parenteral nutrition, vinorelbine, and other anthracyclines.
Formulated solutions are alkaline and it is recommended to avoid mixtures with acidic drugs or
acidic preparations. In the absence of compatibility studies, this medicinal product should not
be mixed with other medicinal products.

Shelf Life and Storage Conditions
Shelf life of unopened vial:
18 months
Shelf life after dilution

During Use: Chemical and physical stability during use has been demonstrated for 24 hours at 25°C
with 5% glucose or 0.9% sodium chloride solutions at concentrations of 0.6 mg/ml and 4.0 mg/ml of
Fluorouracile Hikma.
From a microbiological point of view, the product must be used immediately. If not used
immediately, the storage times during use and the conditions before use are
under the responsibility of the user and should normally not be longer than 24 hours at

• 2 – 8°C, unless the dilution has taken place in a controlled environment and validated aseptic conditions.