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DOXORUBICIN 2MG/ML CONCENTRATE FOR SOLUTION FOR INFUSION

Active substance(s): DOXORUBICIN HYDROCHLORIDE

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Package leaflet: Information for the user

Doxorubicin 2 mg/ml Concentrate for
Solution for Infusion
Doxorubicin hydrochloride

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 further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to
others. It may harm them, even if their symptoms signs of illness are the
same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This
includes any possible side effects not listed in this leaflet.
What is in this leaflet:
1. What Doxorubicin concentrate for solution for infusion is and what it is
used for
2. What you need to know before you are given Doxorubicin concentrate
for solution for infusion
3. How Doxorubicin concentrate for solution for infusion is given
4. Possible side effects
5. How to store Doxorubicin concentrate for solution for infusion
6. Contents of the pack and other information
1. What Doxorubicin concentrate for solution for infusion is
and what it is used for
The name of your medicine is “Doxorubicin 2 mg/ml Concentrate for
Solution for Infusion” but in the rest of the leaflet it will be called
‘Doxorubicin concentrate for solution for infusion’.
Doxorubicin is one of a group of medicines called the anthracyclines.
These drugs are also known as cancer drugs, chemotherapy, or "chemo".
They are used in the treatment of various cancers to slow or stop the
growth of cancer cells. A combination of different types of cancer drugs
will often be used to achieve better results and minimize side effects.
Doxorubicin concentrate for solution for infusion is used to treat the
following forms of cancer:
• breast cancer
• cancer of the connective tissue, ligaments, bone, muscle (sarcoma)
• cancer develops within the stomach or intestine
• lung cancer
• lymphomas, a cancer affecting the immune system
• leukaemia, a cancer that causes abnormal production of blood cell
• cancer of the thyroid gland
• advance ovarian and endometrial cancer (a cancer of the lining of the
uterus or of the uterus)
• bladder cancer
• advance neuroblastoma (a cancer of the nerve cells commonly found in
children)
• malignant renal tumour in children (Wilm´s tumour)
• myeloma (cancer of the bone marrow)
2. What you need to know before you are given Doxorubicin
concentrate for solution for infusion
You should not be given Doxorubicin concentrate for solution for
infusion
- if you are allergic to Doxorubicin hydrochloride or any of the other
ingredients of this medicine (listed in section 6) or to other anthracycline;.
- if you have been told your blood is thin (your bone marrow is not
working well).
- if you have previously been treated with doxorubicin or similar
chemotherapy drugs like, idarubicin, epirubicin or danuorubicin as
previous treatment with these similar medicines can increase the risk of
side effects with Doxorubicin concentrate for solution for infusion.
- if you tend to bleed easily.

The following information is intended for medical or healthcare
professionals only
Posology and method of administration
Doxorubicin Injection should be administered only under the supervision
of a qualified physician with extensive experience in cytotoxic treatment.
Also, patients must be carefully and frequently monitored during the
treatment.
Due to the risk of often lethal cardiomyopathy, the risks and benefits of
the individual patient should be weighted before each application.
Doxorubicin is administered intravenously and intravesically and must not
be administered orally, subcutaneously, intramuscularly or intrathecally.
Doxorubicin can be administered intravenously as bolus within minutes, as
short infusion for up to an hour or as continuous infusion for up to 96 hours.
The solution is given via the tubing of a freely running intravenous
infusion of sodium chloride 9 mg/ml (0.9%) solution for injection or
dextrose 50 mg/ml (5%) solution for injection within 2 to 15 minutes. This
technique minimises the risk of thrombophlebitis or perivenous
extravasation, which can lead to severe local cellulites, vesication and
tissue necrosis. A direct intravenous injection is not recommended due to
the risk of extravasation, which may occur even in the presence of
adequate blood return upon needle aspiration.

- if you suffer from any kind of infection.
- if you suffer from mouth ulcers.
- if your liver is not working well.
- if you suffer from an infection of the bladder (in case the medicine is
given to you by an administration in to your bladder).
- if there is blood in your urine
- had a heart attack
- impaired heart function
- serious abnormality of the heart beat (arrhythmia)
You should not receive the medicine through a catheter (a thin flexible
tube) into your bladder if you have:
- a tumour that has grown into the bladder wall
- an urinary tract infection
- bladder inflammation
- problems with the insertion of a catheter
Warnings and precautions
Talk to your doctor or pharmacist if you have or have had any of the
following medical conditions or illnesses:
- poor blood cell production in the bone marrow
- heart problems
- liver disorders
- kidney disorders
You should also tell your doctor:
- if you have ever received doxorubicin or any similar anti-cancer
medicine (anthracycline) for the treatment of cancer
- if you have received radiation treatment to the upper body
Before starting and during treatment with Doxorubicin concentrate for
solution for infusion your doctor will perform the following tests:
- blood counts
- function tests of your heart, liver and kidney
Doxorubicin strongly reduces blood cell production in the bone marrow.
This may make you more prone to infections or bleeding. It should be
made sure that severe infections and/or bleedings can be treated without
delay and efficaciously.
Tell your doctor immediately:
• if you feel a stinging or burning pain at the site of injection. Such a pain
can occur if the medicine leaks out of the vein.
Your doctor will monitor your heart function carefully during the treatment
because:
• doxorubicin may damage the heart muscle
• doxorubicin treatment may lead to heart failure after a certain cumulative
dose (adding up of single doses)
• the risk for a heart muscle damage is higher if you have previously
received medicines that may damage the heart or radiotherapy of the
upper body.
The levels of uric acid (showing that cancer cells are destroyed) in your
blood may be high during treatment. Your doctor will tell you if you need to
take any medicine to control this.
- Existing infections should be treated before Doxorubicin concentrate for
solution for infusion therapy is started.
- This medicinal product is generally not recommended in combination
with live, attenuated vaccines. Contact to persons recently vaccinated
against polio should be avoided.
- As Doxorubicin concentrate for solution for infusion is excreted mainly via the
liver and in the bile, its excretion can be reduced if liver function is impaired or
the bile ducts narrowed, and this can lead to severe secondary side effects.
Doxorubicin concentrate for solution for infusion can turn the urine red.
This is not a sign of damage to health.
Other medicines and Doxorubicin concentrate for solution for
infusion
Tell your doctor if you are taking, have recently taken or might take any
other medicines.

Intravenous administration:
The dosage of doxorubicin depends on dosage regimen, general status
and previous treatment of the patient. Dose schedule of doxorubicin
hydrochloride administration could vary according to indication (solid
tumours or acute leukaemia) and according to its use in the specific
treatment regimen (as single agent or in combination with other cytotoxic
agents or as a part of multidisciplinary procedures that include
combination of chemotherapy, surgical procedure and radiotherapy and
hormonal treatment).
Monotherapy
Dosage is usually calculated on the basis of body surface area (mg/m2). On
this basis, a dose of 60 - 75 mg/m2 body surface area is recommended
every three weeks when doxorubicin is used as a single agent.
Combination regimen
When doxorubicin hydrochloride is administered in combination with other
antitumour agents with overlapping toxicity, such as high-dose i.v.
cyclophosphamide or related anthracycline compounds such as
daunorubicin, idarubicin and/or epirubicin, the dosage of doxorubicin
should be reduced to 30-60 mg/m2 every 3 – 4 weeks.

The following medications can interact with Doxorubicin 2 mg/ml
concentrate for solution for infusion:
• Other cytostatics (medication against cancer) e.g. trastuzumab,
anthracyclines (daunorubicin, epirubicin, idarubicin), cisplatin,
cyclophosphamide, ciclosporin, cytarabine, dacarbazine, dactinomycin,
fluorouracil, mitomycin C, taxanes (e.g. paclitaxel), mercaptopurine,
methotrexate, streptozocin
• Cardioactive drugs (medication to treat heart diseases) e.g. calcium
channel blockers, verapamil, and digoxin
• Medicines that lower the uric acid level in your blood
• Inhibitors of cytochrome P-450 (drugs that stop the substance
cytochrome P-450, which is a important for detoxification of your body,
from working: e.g. cimetidine), drugs inducing cytochrome P–450 (e.g.
rifampicin, barbiturates including phenobarbital)
• Antiepileptic drugs (e.g. carbamazepine, phenytoin, valproate)
• Antipsychotics: Clozapine (drug used for schizophrenia)
• Heparin (prevents the clotting of blood)
• Antiretroviral drugs (medication against special forms of viruses).
• Chloramphenicol and sulphonamides (medication against bacteria)
• Progesterone (e.g. at threatening miscarriage)
• Amphotericin B (drugs used against fungal diseases)
• Live vaccines (e.g. polio (myelitis), malaria)
Please note that this can also apply to recently used medicines.
Pregnancy, breast-feeding and fertility
Pregnancy
It is known that doxorubicin passes through the placenta and harms the
foetus in animal experiments. If you are pregnant, your doctor will give
you doxorubicin only if the benefits of the treatment outweigh the potential
harm for the unborn child. Tell your doctor immediately if you are pregnant
or think you are pregnant.
Breast-feeding
Do not breast-feed while you are treated with Doxorubicin concentrate for
solution for infusion. The medicine can be passed on to the baby through
the breast milk.
Fertility
If you are a woman, you should not get pregnant during treatment with
doxorubicin or up to 6 months after treatment.
If you are a man, you should take adequate precautions to ensure that
your partner does not become pregnant during your treatment with
doxorubicin or up to 6 months after treatment and to seek advice on
cryo-conservation (or cryo-preservation) of sperm prior to treatment
because of the possibility of irreversible infertility due to therapy with
doxorubicin.
If you are considering becoming parents after the treatment please
discuss this with your doctor.
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
Due to the frequent occurrence of nausea and vomiting, driving cars and
operation of machinery should be discouraged.
Doxorubicin concentrate for solution for infusion contains Sodium
This medicinal product contains 0.15 mmol (3.5 mg) sodium per ml. To be
taken into consideration by patients on a controlled sodium diet.
3. How Doxorubicin concentrate for solution for infusion is given
Method and routes of administrations
Doxorubicin concentrate for solution for infusion can only be given under
supervision by a doctor with experience in cancer treatment.
Dosage: Your doctor will decide about the dose you will receive.
Do not administer the medicine your self. Your medicine will be given to you
as part of an intravenous infusion, into a blood vessel, under the direction of
specialists. You will be monitored regularly both during and after your
treatment. If you suffer from superficial bladder cancer it is possible that you
may receive your medicine into your bladder (intravesical use).
Dosage
The Dosage is usually calculated on the basis of your body surface area. 60-75 mg
per square metre of body surface area may be given every 3 weeks when used

In patients, who cannot receive the full dose (eg. in case of
immunosuppression, old age), an alternative dosage is 15-20 mg/m² body
surface per week.
Intravesical administration:
Doxorubicin may be used by intravesical instillation for the treatment of
superficial bladder carcinoma or in prophylaxis of tumour recurrence after
transurethral resection (T.U.R) in patients with high risk of recurrence. The
recommended doxorubicin hydrochloride dose for local intravesical
treatment of superficial bladder tumours is instillation of 30-50 mg in
25-50 ml of sodium chloride 9 mg/ml (0.9%) solution for injection. The
optimal concentration is about 1 mg/ml. Generally the solution should be
retained intravesically for 1 to 2 hours. During this period the patient
should be turned 90° every 15 minutes. The patient should not drink fluids
for 12 hours prior to the treatment to avoid undesired dilution with urine
(this should reduce the production of urine to about 50 ml/h). The
instillation may be repeated with an interval of 1 week to 1 month,
dependent on whether the treatment is therapeutic or prophylactic.
Patients with impaired hepatic function
Since doxorubicin hydrochloride is mainly excreted via liver and bile, the
elimination of the medicinal product may be decreased in patients with

alone. The dosage may need to be reduced to 30-60 mg per square metre of body
surface area and the treatment interval prolonged when given in combination with
other anti-tumour drugs. Your doctor will advise you of how much you will need. If
given weekly the recommended dose is 15 - 20 mg per square metre of body
surface area. Your doctor will advise you of how much you will need.
Patients with reduced liver and renal functions
If liver or kidney function is reduced, the dosage should be decreased.
Your doctor will advise you of how much you will need.
Children/elderly or patients after radiotherapy
The dosage may need to be reduced in children and the elderly or if you
have received any radiotherapy. Your doctor will advise you or how much
you need.
Patient with bone marrow suppression
The dosage may need to be reduced in patient with bone marrow
suppression. Your doctor will advise you of how much you need.
Obese patients
The starting dose may be reduced in obese patients or the dose interval
may be prolonged. Your doctor will advise you of how much you need and
how often.
If you are given more Doxorubicin concentrate for solution for
infusion than you should
During and after treatment your doctor or nurse will carefully monitor you.
The symptoms of an overdose are an extension of doxorubicin’s possible
side effects. Particularly the blood changes, gastro-intestinal and heart
problems. Heart disorders may even occur up to six month after you
received the over dose.
In case of an overdose your doctor will take appropriate measures. Such
as a blood transfusion and/or treatment with antibiotics.
Please tell your doctor if any of the symptoms occur.
If you missed a dose of Doxorubicin concentrate for solution for
infusion
Your doctor will decide on the duration of your treatment with Doxorubicin
concentrate for solution for infusion. If the treatment is stopped before the
advised courses of treatment is finished. The effects of the doxorubicin
therapy might be reduced. Ask your doctor for advice if you wish to stop
the treatment.
If you have any further questions on the use of this product, ask your
doctor or pharmacist.
4. Possible side effects
Like all medicines, this medicine can cause side effects, although not
everybody gets them.
Please contact your doctor or nurse immediately if you notice any of the
following side effects:
• Feeling dizzy, feverish, short of breath with a tight chest or throat or
have an itchy rash. This type of allergic reaction can be very serious.
• Anaemia (a low red blood cell count) that can leave you feeling tired and
lethargic.
• White blood cell counts (Which fight infection) can also drop, increasing
the chance of infections and raised temperature (fever)
• Platelets (these are cells that help the blood to clot) can be affected
which could make you bruise or bleed more easily. It is important to seek
medical advice if this happens. Your doctor should test your blood cell
count during treatment.
• Doxorubicin may cause decreased activity in your bone marrow. Your
doctor should test your blood cell count during treatment.
Frequency:
Very common (more than 1 in 10 patients)
Common (more than 1 in 100 patients, but less than 1 in 10 patients)
Uncommon (more than 1 in 1000 patients, but less than 1 in 100 patients)
Rare (more than 1 in 10,000 patients, but less than 1 in 1,000 patients)
Very rare (less than 1 in 10.000 patients)
Not known (can not be estimated from the available data)

hepatic function impairment or bile flow obstruction and this could result in
severe secondary effects.
General dose adjustment recommendations in patients with hepatic
function impairment are based on serum bilirubin concentration:
Serum Bilirubin Recommended Dose
20-50 micro mole/L
½ normal dose
> 50 micro mol/L
¼ normal dose
Doxorubicin is contraindicated in patients with severe liver function
disorder.
Patients with impaired renal function
In patients with renal insufficiency (GFR < 10 ml/min), only 75% of the
planned dose should be given.
In order to avoid cardiomyopathy, it is recommended that the cumulative
total lifetime dose of Doxorubicin (including related drugs such as
daunorubicin) should not exceed 450-550mg/m2 body surface area. If a
patient with concomitant heart disease receives mediastinal and/or heart
irradiation, prior treatment with alkylating agents, and high-risk
patients (with arterial hypertension since > 5 years, with prior
coronary, valvular or myocardial heart damage, age over 70 years)
with a maximum total dose of 400 mg/m2 body surface area should not be

Common
cardiomyopathy (heart muscle disease)
ECG (electrocardiogram) changes
bone-marrow suppression(deficiency in blood cells causing infection and
bleeding)
changes to the blood count (leukopenia, neutropenia)
nausea (feeling sick)
vomiting (being sick)
mucositis (inflammation of membranes in digestive tract)
stomatitis (inflammation of membranes in the mouth)
anorexia (eating disorder)
diarrhoea – may result in dehydration
chemical cystitis (bladder inflammation) sometimes haemorrhagic (with
blood in urine) following administration in to the bladder
alopecia (hair loss) normally reversible
sepsis (bacteria infection)
septicaemia (bacterial infection of blood)
Uncommon
Ulceration and necrosis (death of cell/tissue) of the colon (intestine) in
combination with cytarabine
phlebitis (inflammation of a vein)
gastrointestinal bleeding
abdominal pain
local hypersensitivity reaction of the field of radiation
dehydration
Rare
secondary acute myeloid leukaemia (blood cancer developed after
treatment for another cancer) when in combination with anti-neoplastic
drugs which damage the DNA
tumour lysis syndrome (complications of having chemotherapy)
conjunctivitis (inflammation of the outermost layer of the eye)
urticaria (hives)
exanthema (type of rash)
erythematous reactions (rash-like symptoms) along the vein used for the
injection
hyperpigmentation (darkened areas) of the skin and nails
onycholysis (loosening of the nails)
anaphylactic reaction (severe allergic reactions with or without shock
including skin rash, pruritis (itching), )
shivering
fever
dizziness
Not known
Acute lymphocytic leukaemia (disease in which too many immature white
blood cells called lymphoblasts are found in the blood and bone marrow)
acute myelogenous leukaemia (disease in which too many immature
blood-forming cells are found in the blood and bone marrow)
Thrombophlebitis (vein inflammation under the skin)
thromoembolism (clot formed in a blood vessel)
decreased amounts of a blood clotting factor (thrombocytes)
shock
chills
Inflammation of food pipe (oesophagitis)
inflammation of the large intestine (colitis)
arrhythmia (irregular heartbeat)
heart failure (loss of cardiac function)
hyperuricaemia (high uric acid level in blood)
bronchospasm (coughing or difficulty in breathing because of narrowing
sudden of airways)
pneumonitis (inflammation of lung tissue)
amenorrhoea (absence of menstruation)
oligospermia (low sperm volume)
acute renal (kidney) failure (low urine output/or no urine)keratitis
(inflammation of the cornea of the eye)
lacrimation (excessive secretion of tears)
acral erythema (swelling and numbness of the hands and feet)
plantar-palmar dysaesthesia (hand-to-foot syndrome is a distinctive and
relatively frequent skin toxic reaction)
excessive pigmentation of oral mucosa
feeling of intense heat (hot flushes)
azoospermia (lack of sperml
Anaemia (reduction of red blood cells)

exceeded and the cardiac function of these patients should be monitored.
Dose in children
Dosage in children may need to be reduced, please refer to treatment
protocols and the specialist literature.
Obese patients
A reduced starting dose or prolonged dose interval might need to be
considered in obese patients.
Incompatibilities
Doxorubicin should not be mixed with heparin, as a precipitate may form
and it should not be mixed with 5-fluorouracil as degradation may occur.
Prolonged contact with any solution of an alkaline pH should be avoided,
as it will result in hydrolysis of the drug.
Until detailed compatibility information about miscibility is available,
Doxorubicin should not be mixed with other medicinal products than 0.9%
sodium chloride injection and 5% dextrose injection.
Prepared infusion solutions
Chemical and physical in-use stability has been demonstrated in 0.9% sodium
chloride injection and 5% dextrose injection for up to 28 days at 2 – 8 °C and

A stinging or burning sensation at the administration site in relation to
extravasation. Extravasation can lead to local death of calls of the tissue
which may require surgical measures
liver toxicity
Transient increase of liver enzymes
asthenia (loss or lack of bodily strength; weakness; debility)
Other Side effects: Doxorubicin concentrate for solution for infusion may
cause a red colouration of the urine for one or two days after
administration. This is normal and nothing to worry about.
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 Doxorubicin concentrate for solution for infusion
Keep out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the vial
or outer carton. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C - 8°C). Keep the vial in the outer carton in
order to protect from light.
Do not use this medicine if you notice that the solution is not clear, red
and free of particles.
Single use only.
Any unused product or waste material should be disposed of in
accordance with local requirements.
Observe guidelines for handling cytotoxic drugs.
Unopened vials: 18 months
Opened vials: The product should be used immediately after opening the vial.
Chemical and physical in-use stability has been demonstrated in 0.9% sodium
chloride injection and 5% dextrose injection for up to 28 days at 2 – 8°C and for
up to 7 days at 25°C when prepared in glass containers protected from light.
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°C to
8°C, unless dilution has taken place in controlled and validated aseptic condition.
6. Contents of the pack and other information
What Doxorubicin concentrate for solution for infusion contains:
Doxorubicin concentrate for solution for infusion contains the active
ingredient Doxorubicin Hydrochloride.
1 ml contains 2 mg Doxorubicin hydrochloride
Each 5 ml vial contains 10 mg of Doxorubicin hydrochloride.
Each 10 ml vial contains 20 mg of Doxorubicin hydrochloride.
Each 25 ml vial contains 50 mg of Doxorubicin hydrochloride.
Each 50 ml vial contains 100 mg of Doxorubicin hydrochloride.
Each 100 ml vial contains 200 mg of Doxorubicin hydrochloride.
The other ingredients are sodium chloride, hydrochloric acid (for pH
adjustment) and water for injections.
What Doxorubicin concentrate for solution for infusion looks like
and contents of the pack:
Doxorubicin concentrate for solution for infusion is a clear, red solution,
which is practically free from particles.
Pack sizes: 1 X 5 ml vial, 1 X 10 ml vial, 1 X 25 ml vial, 1 X 50 ml vial,
1 X 100 ml vial
Not all pack sizes may be marketed.
Marketing Authorisation Holder and manufacturer:
Accord Healthcare Limited
Sage House, 319, Pinner Road, North Harrow, Middlesex, HA1 4HF,
United Kingdom
The leaflet was last revised in 01/2014

for up to 7 days at 25°C when prepared in glass containers protected from light.
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°C to 8°C, unless dilution has taken place in
controlled and validated aseptic condition.
Disposal
Remnants of the medicinal product as well as all materials that have been
used for dilution and administration must be destroyed according to
hospital standard procedures applicable to cytotoxic agents with due
regard to current laws related to the disposal of hazardous waste.
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.
Shelf life and storage
Unopened vials: 18 months
Opened vials: The product should be used immediately after opening the vial.
Store in a refrigerator (2°C - 8°C).
Keep the vial in the outer carton in order to protect from light.

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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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