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AGICIL 50 MG/ML SOLUTION FOR INJECTION /INFUSION

Active substance(s): FLUOROURACIL

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Package leaflet: Information for the user
Agicil 50 mg/ml solution for injection/infusion
Fluorouracil
Read all of this leaflet carefully before you start using this medicine because it contains
important information for you

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor, pharmacist or nurse.

This medicine has been prescribed for you only. Do not pass it on to others. It may harm
them, even if their signs of illness are the same as yours.

If you get any side effects, talk to your doctor or pharmacist or nurse. This includes any
possible side effects not listed in thisleaflet. See Section 4.
What is in this leaflet
1.
2.
3.
4.
5.
6.

What Agicil is and what it is used for
What you need to know before you use Agicil
How to use Agicil
Possible side effects
How to store Agicil
Contents of the pack and other information

1. What Agicil is and what it is used for
Agicil contains the active ingredient fluorouracil. It is an anti-cancer medicine.
This medicine is used to treat many common cancers, particularly cancers of the large bowel,
oesophagus, pancreas, stomach, head and neck and breast. It may be used in combination with
other anti-cancer medicines and radiotherapy.
2.

What you need to know before you use Agicil

Do not use Agicil
 if you are allergic to fluorouracil or any of the other ingredients of this medicine (listed in
section 6).
 if you have serious infections (e.g. Herpes zoster, chickenpox)
 if your tumour is non-malignant.
 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 taking brivudin, sorivudin and analogues (an antiviral medicine)
 if you are pregnant or breast feeding women
 if you have serious impaired liver function
 if you are homozygotic for dihydropyrimidine dehydrogenase (DPD) enzyme

Warnings and precautions
Talk to your doctor or pharmacist or nurse before using Agicil. Take special care with Agicil:









if the number of cells in your blood become too low (you will have blood tests to check this)
if you have oral ulceration, fever or hemorrhage at any site or weakness (these symptoms
may be the consequence of the very low number of cells in your blood),
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 problem with your heart. Tell your doctor if you experience any chest pain
during treatment.
ifyou have reduced activity/deficiency of the enzyme DPD (dihydropyrimidine
dehydrogenase).
if you have had high-dose pelvic radiation.
if you have gastrointestinal side effects (stomatitis, diarrhoea, bleeding from the G.I. tract)
or hemorrhage at any site.

Other medicines and Agicil
Tell your doctor or nurse if you are using, have recently used or might use any other medicines.
In particular tell your doctor if you are taking any of the following medicines because they affect
how Agicil works:















Methotrexate (an anti-cancer medicine)
Metronidazole (an antibiotic)
Calcium leucovorin (also called calcium folinate - used to reduce the harmful effects of anticancer medicines)
Allopurinol (used to treat gout)
Cimetidine (used to treat stomach ulcers)
Warfarin (used to treat blood clots)
Interferon alpha 2a,brivudin, sorivudine and analogues (an antiviral)
Cisplatin (an anti-cancer medicine)
Phenytoin (used to control epilepsy/fits and irregular heart rhythm)
Vaccines
Vinorelbine (an anti-cancer medicine)
Cyclophosphamide (an anti-cancer medicine)
Levamisol (medicine used to treat worm infection)
Tamoxifen (an anti-cancer medicine)

The above medicines affect the effect of Fluorouracil.
Pregnancy, breast-feeding and fertility
You must not take this medicine if you are pregnant or planning to become pregnant.

If you are a woman of childbearing potential you must use an effective method of contraception
while taking this medicine andat least for 6 months afterwards. If pregnancy occurs during your
treatment you must inform your doctor and should use genetic counselling.
Since it is not known whether fluorouracil passes into breast milk, breast-feeding must be
discontinued if the mother is treated with Agicil.
If you are a man you should avoid fathering a child during and for up to 6 months following
cessation of treatment with Agicil. You are advised to sought conservation of sperm prior to
treatment because of the possibility of irreversible infertility due to therapy with flurouracil.
Ask your doctor for advice before taking any medicine.
Driving and using machines
Do not drive or use machines because fluorouracil may produce side effects like nausea and
vomiting. It can also produce adverse events on your nervous system and visual changes. If you
experience any of these effects, do not drive or use any tools or machines, because they may
impair your ability to drive or use machines
Agicil contains sodium
This product contains sodium approximately from 0.34 to 0.39mmol/ml (or 7.9–9.0 mg/ml) of
solution in the form of Sodium Hydroxide. This information should be taken into consideration
in patients with controlled intake ofsodium.
3. How to use Agicil
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.
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 into a vein either as a normal injection or a
slow injection via a drip (infusion).
If you are given more Agicil than you should
As this medicine will be given to you whilst you are in hospital is unlikely that you will be given
too little or too much, however, tell your doctor or nurse if you have any concerns.
You will need to have blood tests during and after treatment with Agicil 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.
Nausea, vomiting, diarrhoea, severe mucositis and gastrointestinal ulceration and bleeding may
occur if you have too much fluorouracil.

If you have any further question on the use of this medicine ask your doctor.
4.

Possible side effects

Like all medicines, this medicine can have 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
your bowel motions are bloodstained or black
your mouth becomes sore or develops ulcers
numbness, tingling or tremor in the hands or feet
quickening of your heart rate and breathlessness
feeling confused or feeling unsteady on your feet, coordination problems in arms and legs,
thinking/speech difficulties, vision/memory problems

These are serious side effects. You may need urgent medical attention.
Very common (may affect more than 1 in 10 patients)
 Ischemic ECG
 Neutropenia (an
abnormalities (an
abnormally low level of
insufficient supply of
neutrophils in the blood)
blood to an organ, usually
due to a blocked artery)
 Anemia (decrease in
 Pancytopenia (a disorder
number of red blood cells
in which the bone marrow
that can cause tiredness
greatly decreases or stops
and lack of energy )
production of blood cells)

 High fever and a sharp
drop in circulating
granular white blood cells
 Inflammation of the
rectum or anus
 Nausea

 Leucopoenia (an abnormally
low number of white blood
cells in the circulating blood)
 Decrease in the production of
blood cells

 The inflammation of the
lining of the mouth and
digestive tract
 Loss of appetite

 Pharyngitis (inflammation of
the mucous membranes
lining the throat)
 Watery diarrhoea

 Vomiting

 Hair loss

 Delayed wound healing

 Bleeding from the nose

 Hand-foot syndrome (a toxic
skin reaction That may cause
redness, tenderness, and
possibly peeling of the palms
and soles)

 General weakness
 Inflammation of the
mucous lining of the
mouth

 Tiredness
 Inflammation of the
esophagus (the tube that
connects your mouth to
your stomach)

 Fatigue
 Lack of energy

 Increase in uric acid in the
blood
Common (may affect up to1 in 10 patients)
 Angina pectoris (severe chest pain )
Uncommon (may affect up to 1 in 100 patients)
 Abnormal heart rhythm
 Heart attack
 Myocarditis
(inflammatory disease of
the heart muscle)

 Heart failure

 Cardiac shock
 Dehydration

 Low blood pressure
 Bacterial infection in the
bloodstream or body
tissues
 Headache

 Myocardial ischemia (lack of
oxygen to the heart muscle)
 Dilative cardiomyopathy (a
type of heart disease in which
the heart muscle is
abnormally enlarged,
thickened and/or stiffened)
 Sleepiness
 Gastrointestinal ulceration
and bleeding, casting off the
skin
 Sensations of imbalance and
unsteadiness
 Feeling sick

 Rhythmic motions of the
eyes
 Symptoms of Parkinson's  Pyramidal signs
disease (a progressive
movement disorder
marked by tremors,
rigidity, slow movements)
 Inflammation of the skin
 Skin alterations such as dry  A skin eruption accompanying
skin, cracks (fissure), loss
certain infectious diseases
of skin (erosion), redness ,
pruritic maculopapular
rash (rash that originates
on the arms and then
moves to the arms, and
then chest)
 Appearance of itchy, red
 Sensitivity to sun
 Darkening of parts of the skin
marks on the skin
(photosensitivity)
(hyperpigmentation)
 Streaky darkening
 Changes in the nails (e.g.
 Paronychia (Inflammation of
(hyperpigmentation) or
blue coloring near the
the tissue surrounding a

lightenng
(depigmentation) near the
veins.
 An inflammation of the
matrix of the nail with
formation of pus and
shedding of the nail
 Secretion of tears

 Eye movement
disturbance
 decrease in visual
sharpness
 lower eyelid turns
outwards

surface, darkening
(hyperpigmentation);
misshapen nails, pain and
thickening of the nail bed.
 Sperm or egg (ovum)
production disorder
 Blurred vision,

 Optic neuritis (a vision
disorder characterized by
inflammation of the optic
nerve)
 excessive sensitivity to
light and the aversion to
sunlight or well-lit places
 Blocked tear ducts

Rare (may affect up to 1 in 1,000 patients)
 Insufficient blood flow in  discoloration of the
brain, intestine and
fingers, toes, and
peripheral organs
occasionally other areas
 swelling (inflammation) of  severe, whole-body
a vein caused by a blood
allergic reaction
clot
(anaphylaxis)
 systemic vasodilation
 confusion
(widening of blood
vessels) which results in
low blood pressure
Very rare (may affect up to 1 in 10,000 patients)
 Cardiac arrest (sudden
 Sudden cardiac death
cessation of heartbeat and
(unexpected death due to
cardiac function)
heart problems)




Acute cerebellar
syndrome
Mental confusion or
impaired awareness
especially regarding to




Difficulty pronouncing
words clearly
Partial or total loss of
the ability to
communicate verbally or

fingernail)

 liver cell damage

 Inflammation or redness of the
lining of the white part of the
eye and the underside of the
eyelid.
 double vision

 oculardisease characterized by
chronic inflammation of the
eyelid margins
 A layer or mass of dead tissue
separated from surrounding
living tissue, as in a wound, a
sore, or an inflammation.
 Generalized allergic reaction
 Development of a clot within
blood vessels, can occur in
arteries or veins
 Increase in thyroid hormonesT4 (thyroxine), T3
(trijodthyronin)

 Symptoms of
leucoencephalopathy (diseases
affecting the white substance of
the brain) including ataxie (loss
of the ability to coordinate
muscular movement)
 Confusion


Abnormal muscular
weakness or fatigue





time, place or identity
Convulsion or coma in
patients receiving high
doses of fluorouracil and
in patients with
dihydropyrimidine
dehydrogenase
deficiency
inflammation of the gall
bladder





using written words.
kidney failure



Damage of liver cells (cases
with fatal outcome)

slow progressive
destruction of the small
bile ducts

Not known (frequency can not be estimated from the available data):
 fever
 numbness or weakness of the arms and legs
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist or nurse. This includes any possible
side effects not listed in this leaflet.
You can also report side effects directly via the Yellow Card Scheme at:
www.mhra.gov.uk/yellowcard.By reporting side effects you can help provide more information
on the safety of this medicine.
5.

How to store Agicil

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date, which is stated on the label and carton after EXP.
Single use only. Discard any unused portion.
Storage of the unopened vial: Do not store above 25°C. Do not refrigerate or freeze.
Shelf life after dilution:Chemical and physical in-use stability has been demonstrated for 5 days
at 20-21°C and for 24 hours at 2°C to 8°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 dilution has taken place in
controlled and validated aseptic conditions.
Do not use this medicine if it appears brown or dark yellow in solution.
Do not use if you notice that the container is damaged or particles/crystals are visible.

Since this product will be administered by a healthcare professional, the medical staff are
responsible for the correct storage of the product both before and during its use, as well as for the
correct disposal
6.

Contents of the pack and other information

What Agicil contains
-

The active substance is fluorouracil.One (1) ml of solution contains 50 mg of fluorouracil.
The other ingredients are water for injections and sodium hydroxide.

What Agicil looks like and content of the pack
Agicil is clear colourless to yellow solution available in Type I flint moulded vials with a grey
rubber closure and grey flip-off aluminium seal.
Each 10 ml vial contains 500 mg of fluorouracil.
Each 20 ml vial contains 1 g of fluorouracil.
Each 50 ml vial contains 2.5g of fluorouracil.
Each 100 ml vial contains 5 g of fluorouracil.
Agicil is available in packs of 1, 5 or 10 vials.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Mylan
Potters Bar
Hertfordshire
EN6 1TL
United Kingdom
Manufacturer:
Pharmadox Healthcare Ltd.
KW20A Kordin Industrial park, Paola
PLA 3000, Malta
The leaflet was last revised in 10/2014
--------------------------------------------------------------------------------------------------------------------The following information is intended for medical or healthcare professionals only:

INSTRUCTIONS FOR USE/HANDLING, PREPARATION AND DISPOSAL GUIDE
FOR USE WITH FLUOROURACIL INJECTION
Cytotoxic Handling Guidelines
Fluorouracil should be administered only by or under the supervision of a qualified physician
who is experienced in the use of cancer chemotherapeutic drugs.
Preparation guidelines:
Contamination
In the event of contact with the skin or eyes, the affected area should be washed with copious
amounts of water or normal saline. Hydrocortisone cream 1% 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.
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.
First Aid
Eye contact: Irrigate immediately with water and seek medical advice.
Skin contact: Wash thoroughly with soap and water and remove-contaminated clothing.
Inhalation, Ingestion: Seek medical advice.
Disposal
Syringes, containers, absorbent materials, solution and any other contaminated material should
be placed in a thick plastic bag or other impervious container, marked as cytotoxic waste and
incinerated at a minimum of 700°C.
Chemical inactivation can be achieved by 5% sodium Hypochlorite over 24 hours.
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
onlyin the designated area.
c) The personnel carrying out these procedures should be adequately protected with special
clothing, two pairs of gloves one latex, one PVC, (the latex being worn beneath the PVC), this
covers differences in permeabilities to the various antineoplastics, and eye shields. Luerlock
syringes and fittings should always be used both in the preparation of cytotoxic products and for
their administration.
d) Pregnant personnel are advised not to handle chemotherapeutic agents.
(e) Refer to local guidelines before commencing.
Instructions for use
Fluorouracil injection can be given by intravenous injection or infusion.
Incompatibilities

Fluorouracil is incompatible with calcium folinate, carboplatin, cisplatin, cytarabine, diazepam,
doxorubicin, droperidol, filgrastim, gallium nitrate, methotrexate, metoclopramide, morphine,
ondansetrone, parenteral nutrition, vinorelbin, otheranthracyclines.
Formulated solutions are alkaline and it is recommended that admixture with acidic drugs or
preparations should be avoided.
In the absence of compatibility studies, this medicinal product must not be mixed with other
medicinal products.
Preparation Instructions
Fluorouracil injection may be diluted with glucose 5% injection or sodium chloride
0.9%injection or water for injections immediately before parenteral use.
Dosage and Administration
Selection of an appropriate dose and treatment regime 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 1gram. 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 is used as the basis for 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.
ADULT DOSE
The following regimen have been recommended for use as a single agent.
Initial Treatment:
This may be in the form of an infusion or an injection, the former usually being preferred
because of lesser toxicity.
Intravenous Infusion:
15 mg/kg bodyweight or 600 mg/m2 but not more than 1 g per infusion, diluted in 500 ml of 5%
glucose or 0.9% NaCl injection and given by intravenous infusion at a rate of 40 drops per
minute 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 (stomatitis, diarrhea, leucopenia or thrombocytopenia) or a total dose of 1215 g has been reached.
Intravenous Injection:

12 mg/kg bodyweight or 480 mg/m2 may be given daily for 3 days and then, if there is no
evidence of toxicity (stomatitis, diarrhea, leucopenia or thrombocytopenia), 6 mg/kg or 240
mg/m2 on alternate days for 3 further doses (day 5-7-9). An alternative regime is 15 mg/kg as a
single intravenous injection once a week throughout the course.
Maintenance Therapy:
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.
Treatment can be continued with intravenous injections of 5 – 10 mg/kg bodyweight or 200-400
mg /m2 at weekly intervals.
In combination with Irradiation:
Irradiation combined with 5-FU 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 5-FU should be used.
Combination with other cytostatic agents:
Fluorouracil can be used with other cytostatic agents. In this case the standard dose is reduced.
Special populations
Renal or hepatic impairment.
Caution is advised and the dose might need to be reduced in patients with renal or hepatic
impairment.
CHILDREN
Fluorouracil is not recommended for use in children due to insufficient data on safety and
efficacy.
ELDERLY
No dosage adjustment necessary.
Shelf Life and storage
Shelf-life of unopened vial
10 months. Single use only. Discard any unused portion.
Do not store above 25°C. Do not refrigerate or freeze,
If a precipitate has formed as a result of exposure to low temperature, 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.
Shelf Life after dilution
Chemical and physical in-use stability with the selected physiological solutions (0.9 % sodium
chloride, 5 % dextrose and water for injections) at concentration 2.0 mg/ml has been
demonstrated for 120 hours at 20-21°C and for 24 hours at 2°C to 8°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 dilution has taken place in
controlled and validated aseptic conditions

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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