Active substance(s): DAUNORUBICIN HYDROCHLORIDE
DAUNORUBICIN 20MG POWDER FOR I.V. INJECTION
Read all of this leaflet carefully before you start taking 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 or nurse
• If you get any side effects talk to your doctor or nurse. This includes any possible side effects
not listed in this leaflet (see section 4).
What is in this leaflet:
1. What daunorubicin is and what it is used for
2. What you need to know before you take daunorubicin
3. How you will be given daunorubicin
4. Possible side effects
5. How to store daunorubicin
6. Contents of the pack and other information
1. WHAT DAUNORUBICIN IS AND WHAT IT IS USED FOR
The name of your medicine is Daunorubicin 20mg Powder for I.V. Injection (called daunorubicin in
this leaflet). It belongs to a group of medicines used to treat acute leukaemia.
Daunorubicin works by attacking and destroying the abnormal white blood cells which are present
in a person with leukaemia.
Information about Leukaemia
Leukaemia is the name for a number of diseases of the white blood cells, which form part of your
blood. These cells are produced in your bone marrow. In leukaemia, the white blood cells multiply
in an uncontrolled and abnormal way.
The most common signs of leukaemia are:
• Increased number of white cells in the blood. This causes easy bruising and nose bleeds
• Feeling tired, faint, dizzy, having pale skin. These could be symptoms of anaemia
• Extreme tiredness (exhaustion), and headaches
• Bone and joint pain
• Severe infection and fever
2. WHAT YOU NEED TO KNOW BEFORE YOU TAKE DAUNORUBICIN
Before treatment, you should discuss the risks and benefits of this medicine with your doctor.
Do not have daunorubicin if:
• You are sensitive to, or allergic to, daunorubicin or other anthracyclines or any of the other
ingredients of this medicine (listed in section 6)
Signs of an allergic reaction include: a rash, swallowing or breathing problems, swelling of
your lips, face, throat or tongue
• You have chicken pox or shingles, or you have been in recent contact with anyone who has
chicken pox or shingles
• You have an infection, fever or high temperature
• You have any heart problems
• You are pregnant or breastfeeding
• You have a lot of mouth ulcers
Do not have daunorubicin if any of the above applies to you. If you are not sure, talk to your doctor or nurse.
Warnings and precautions
Talk to your doctor or nurse before you are given daunorubicin if:
• You have had radiation treatment to the chest
• You have had any other medicines to treat leukaemia (or cancer)
• You have or have ever had gout
• You have or have ever had kidney stones or any other kidney problems
• You have any liver problems
• You are sexually active, you are advised to use effective birth control to prevent pregnancy
during treatment, whether you are male or female.
Talk to your doctor or nurse during use of daunorubicin:
• If you notice any pain in your side, blood in your urine or reduced amount of urine. When your
disease is very severe, your body may not be able to clear all the waste products from the
dying cancer cells. This is called tumour lysis syndrome and can cause kidney failure and
heart problems soon after the first dose of daunorubicin. Your doctor will be aware of this and
may give you other medicines to help prevent it.
• If you have abdominal pain as a result of inflammation of the bowels (colitis).
If you are not sure if any of the above apply to you, talk to your doctor or nurse before being
Other medicines and daunorubicin
Tell your doctor or pharmacist if you are taking, have recently taken or might take any:
• other medicines that may affect your heart for example, medicines to treat cancer such as
5-fluorouracil, cyclophosphamide, cisplatin, taxanes, calcium channel blockers used to control high
blood pressure, chest pain, and irregular heartbeats and if you are receiving chest radiotherapy.
• other medicines that may affect the bone marrow for example, other cancer treatments,
sulphonamide, chloramphenicol (used to treat infection), diphenylhydantoin (used to treat
epilepsy), amidopyrine-derivative (used to relieve pain), antiretroviral agents (used to treat HIV
infection) may alter the formation of blood cells
• other medicines that may affect your liver e.g barbiturates (drugs used in epilepsy or sleep
disorders) and rifampicin (a drug used to treat TB - Tuberculosis)
• live attenuated vaccines
Pregnancy, breast-feeding and fertility
Do not have daunorubicin if you are pregnant, might become pregnant or think you might be
pregnant as daunorubicin can be very damaging to your unborn baby (embryo). If pregnancy
occurs during treatment this should be discussed with your doctor.
Both female and male patients must take special precautions in their sexual activity if there is
any possibility for pregnancy to occur:
• For a girl or woman of childbearing age:
You must have a negative pregnancy test before treatment and each month during treatment.
This should be discussed with your doctor.
• For men:
Do not have sex with a pregnant woman unless you use a condom. This will lessen the
possibility for daunorubicin to be left in the woman's body.
You and your female partner must each use an effective contraceptive during the time you are taking
daunorubicin and for 6 months after stopping treatment. This should be discussed with your doctor.
Men who wish to father children in the future should seek advice about freezing sperm before
treatment with daunorubicin is started.
If you are a woman who is breast-feeding, you must not take daunorubicin. Discontinue
breast-feeding before starting to take daunorubicin.
Driving and using machines
You may feel and/or be sick after being given this medicine, therefore special care should be
taken when driving or using machines.
There is no information available about how daunorubicin might affect your ability to drive or use machines.
Powder for I.V. Injection
For the Medical and Pharmaceutical Professions only
STORE BELOW 25ºc PROTECT FROM LIGHT.
Solutions of Daunorubicin should be freshly prepared;
store at 2-8ºC in the dark and use within 24 hours
Daunorubicin is a microcrystalline orange-red hygroscopic
sterile powder supplied in vials containing the equivalent of
20mg daunorubicin (as hydrochloride) and mannitol as a
Daunorubicin is an anthracycline glycoside antibiotic and a
potent antileukaemic agent. It also has immuno suppressant
effects. The exact mechanism of antineoplastic action of
daunorubicin is uncertain but may involve binding to DNA by
intercalation between base pairs and inhibition of DNA and
RNA synthesis by template disordering and steric obstruction.
Daunorubicin is most active in the S-phase of cell division but
is not cycle phase-specific. Tumour cell cross resistance has
been observed between daunorubicin and doxorubicin.
No controlled paediatric studies have been conducted.
The literature mentions the use of daunorubicin in
treatment regimens for ALL and AML, including paediatric
age groups. However, due to the ongoing search for a
balance in gain or maintenance of efficacy and a decrease
in toxicity, the use of daunorubicin in the treatment of
paediatric ALL and AML is fluctuating in clinical practice,
mainly depending on risk stratification and specific
subgroups. Published studies suggest no differences in
safety profile between paediatric patients and adults.
Daunorubicin is rapidly taken up by the tissues, especially by
the kidneys, spleen, liver and heart. It does not cross the
blood-brain barrier, subsequent release of drug and its
metabolites from the tissue is slow (t1/2 = 55 hours).
Daunorubicin is rapidly metabolised in the liver. The major
metabolite daunorubicinol is also active. Daunorubucin is
excreted slowly in the urine, mainly as metabolites with 25%
excreted in the first 5 days. Biliary excretion also makes a
significant (40%) contribution to elimination.
DOSAGE AND ADMINISTRATION
Daunorubicin is extremely irritating to tissues and may only
be administered intravenously.
Do not administer by the intramuscular or subcutaneous
The contents of a vial should be reconstituted with 4ml water
for injections giving a concentration of 5mg per ml. The
calculated dose of Daunorubicin should be further diluted
with normal saline to give a final concentration of 1mg per ml.
This solution should be injected over a 20 minute period into
the tubing, or side-arm, of a well placed, rapidly flowing i.v.
infusion of normal saline (to minimise extravasation and
possible tissue necrosis). Alternatively, the Daunorubicin may
be added to a minibag of sodium chloride injection 0.9%w/v
and this solution infused into the side-arm of a rapidly flowing
infusion of normal saline.
Adults: 40-60mg/m2 on alternate days for a course of up
to three injections for the induction of remissions.
Acute myelogenous leukaemia:
The recommended dose is 45mg/m2.
Acute lymphocytic leukaemia:
The recommended dose is 45mg/m2
Paediatric patients: Daunorubicin dosage for children (over
2 years) is usually calculated based
on the body surface area and adjusted
to meet the individual requirements
of each patient, on the basis of
clinical response and the patients’
haematological status. Courses may be
repeated after 3 to 6 weeks.
Current specialised protocols and
guidelines should be consulted for
appropriate treatment regimen.
For children over 2 years the maximal
cumulative dose is 300 mg/m2.
For children under 2 years of age
(or below 0.5m2 body surface area),
the maximum cumulative dose is
Elderly: Daunorubicin should be used with care in
patients with inadequate bone marrow reserves
due to old age. A reduction of up to 50% in dosage
The number of injections required varies widely from
patient to patient and must be determined in each case
according to response and tolerance.
Daunorubicin should be administered through a large vein and
the infusion should be kept free flowing. When second or
subsequent injections are given, the doses and the time intervals
depend on the effect of the previous doses and must be the
subject of careful deliberation, examination of the peripheral
blood and, under some circumstances, of the bone marrow.
The effect of Daunorubicin on the disease process and on the
normal blood precursors cannot be exactly predicted for any
particular case. The difference between incomplete treatment,
a satisfactory remission, and overdosage with possible
irreversible aplasia of the bone marrow depends on the correct
choice of dosage, time intervals and total number of doses. The
dosage should be reduced in patients with impaired hepatic or
renal function. A 25% reduction is recommended in patients
with serum bilirubin concentrations of 20-50 μmol/l or
creatinine or above 105-265 μmol/l. A 50% reduction is
recommended in cases with serum bilirubin concentrations of
above 50 μmol/l or creatinine or above 265 μmol/l.
Do not use in patients recently exposed to, or with existing
chicken pox or herpes zoster.
PRECAUTIONS AND WARNINGS
Daunorubicin should be used under direction of a clinician
conversant with the management of acute leukaemia and
cytotoxic chemotherapy. The haematological status of
patients should be monitored regularly.
Daunorubicin which might depress the bone marrow to the
point where anti-infective agents would no longer be effective.
If during Daunorubicin treatment, the patient becomes febrile
treatment with broad spectrum antibiotics should be initiated.
If facilities are available, patients should be treated in a
germ-free environment or, where this is not possible, reverse
barrier nursing and aseptic precautions should be employed.
Anti-infective therapy should be employed in the presence of
suspected or confirmed infection and during a phase of
aplasia. It should be continued for some time after the
marrow has regenerated. Care should also be used in
patients at risk of infection.
Rapid destruction of a large number of leukaemia cells may
cause a rise in the blood uric acid or urea (tumour lysis
syndrome) and so it is a wise precaution to check these
concentrations three or four times a week during the first
week of treatment. Fluids should be administered and
allopurinol used in severe cases to prevent the development
Patients with heart disease should not be treated with this
potentially cardiotoxic drug. Cardiotoxicity, if it occurs, is likely to
be heralded by either a persistent tachycardia, shortness of
breath and swelling of feet and lower limbs, or by minor changes
in the electrocardiogram and for this reason an
electrocardiographic examination should be made at regular
intervals during treatment. Cardiotoxicity usually appears within
1 to 6 months after initiation of therapy. It may develop suddenly
and not be detected by routine ECG. It may be irreversible and
fatal but responds to treatment if detected early.
The risk of congestive heart failure increases significantly when
the total cumulative dosage exceeds 600mg/m2 in adults,
300mg/m2 in children over 2 years or 10mg/kg in children
under 2 years. Cardiotoxicity may be more frequent in children
and the elderly. The dosage should be modified if previous or
concomitant cardiotoxic drug therapy is used. Daunorubicin
should be used with care in patients at risk of hyperuricaemia
(e.g. in the presence of gout, urate and renal calculi), tumour
cell infiltration of the bone marrow and in patients with
inadequate bone marrow reserves due to previous cytotoxic
drug or radiation therapy. The cumulative dose of
Daunorubucin should be limited to 400mg/m2 when radiation
therapy to the mediastinum has been previously administered.
The dose of Daunorubicin should not be repeated in the
presence of bone marrow depression or buccal ulceration.
Care should be taken to avoid extravasation during intravenous
administration. All steps should be taken to avoid tissuing and
bandages should not be used. Facial flushing or erythematous
streaking along the vein indicates too rapid injection. If tissue
necrosis is suspected, the infusion should be stopped
immediately and resumed in another vein. Where extravasation
has occurred, an attempt should be made to aspirate the fluid
back through the needle. The effected area may be injected
with hydrocortisone. Sodium bicarbonate (5ml of 8.4% w.v
solution) may also be injected in the hope that through pH
changes the drug will hydrolyse. The opinion of a plastic
surgeon should be sought as skin grafting may be required.
Application of ice packs may help to decrease local
discomfort and also prevent extension. Liberal application of
corticosteroid cream and dressing the area with sterile gauze
should then be carried out.
USE IN PREGNANCY
Daunorubicin crosses the placenta and experiments in animals
have shown it to be mutagenic, carcinogenic and teratogenic.
There is also the possibility that treatment during pregnancy
may produce delayed effects in the offspring.
If appropriate, the mother should be offered the opportunity
of a therapeutic abortion.
Owing to potential toxic risks to infants, breastfeeding should
be discontinued during treatment.
Bone marrow depression: in every patient bone marrow
function will be depressed by treatment with Daunorubicin
and in a variable proportion of cases, severe aplasia with
develop. The consequence may include severe infection and
opportunistic infection. Leucopenia is usually more
significant than thrombocytopenia. The nadir for leucopenia
usually occurs between 10-14 days and recover occurs
gradually over the next 1-2 weeks. Bone marrow depression
must be anticipated in every case by eliminating infection
before the treatment, by isolating the patient from infection
during the treatment and by means of supportive therapy.
This includes the continuous administration of anti-infective
agents, the administration of platelet-rich plasma or fresh
whole blood transfusion and, under some circumstances, the
transfusion of white cell concentrates.
Cases of colitis, enterocolitis and neutropenic enterocolitis
(typhlitis) have been observed in patients treated with
daunorubicin. Treatment discontinuation and prompt
appropriate medical treatment are recommended.
Other less serious adverse reactions that have been reported
(in order of reducing frequency) are: stomatitis, alopecia,
phlebitis, fever, anaemia, nausea, vomiting, mucositis,
diarrhoea and rash. The urine may be temporarily coloured
red after treatment.
Although no cases have been reported to our knowledge,
overdosage may result in drastic myelosuppression and severe
cardiotoxicity with or without transient reversible ECG changes
leading to congestive heart failure.
Treatment should be supportive and symptomatic.
Vials containing Daunorubicin should be stored below 25°C
and protected from light. Solutions of Daunorubicin should
be used immediately after preparation or stored at 2-8°C and
used within 24 hours. The solutions should be protected
from light. The reconstituted solution does not contain an
antimicrobial preservative. Daunorubicin solutions are
unstable above pH8, decomposition being indicated by a
change from red to blue-purple colour.
Daunorubicin injection is compatible with sodium chloride
injection 0.9%. However a precipitate may form immediately
if the solution is mixed with heparin sodium injection or
dexamethasone sodium phosphate injection.
LEGAL CATEGORY: POM
Box of 1 x 20mg and 10 x 20mg vials.
Spill or Leak Procedures: Daunorubicin injection may be
neutralised with sodium hypochlorite prior to disposal of
unused drug or if a vial is accidentally broken.
The neutralised drug can be disposed of in the sink.
SPECIAL PROTECTION INFORMATION
Daunorubicin should only be handled by staff experienced
with cytotoxic drugs. Further information on handling is
available from the Marketing Authorisation holder.
Text issued August 2016
3. HOW YOU WILL BE GIVEN DAUNORUBICIN
How daunorubicin is given
• Daunorubicin is a medicine used in hospitals
• It will be given to you by a doctor or nurse as an injection into one of your veins
• It will be given over about 20 minutes (this is called an intravenous infusion)
• It should never be given as a single injection under the skin or into a muscle
• The site of injection should not be covered or bandaged
Tell your doctor or nurse straight away if:
• You have any pain, swelling or warmth around the vein where daunorubicin is being injected
• You notice that your face is red while the injection is being given to you. This may be a sign
that the injection is being given too quickly
How much daunorubicin will be given
• The exact dose will be determined by your doctor. It will depend on your age, height, weight
and your general medical condition. The usual dose for a person weighing 70kg (12 stone)
would be about 80mg
• Your course of treatment may be altered, depending on how your body reacts to the medicine
• Daunorubicin may be given alone or in combination with other medicines to treat or prevent
Tests while having daunorubicin
Your condition will be closely monitored during treatment. This may involve blood, urine tests or
heart monitoring (called ECG).
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.
4. POSSIBLE SIDE EFFECTS
Like all medicines, this medicine can cause side effects, although not everybody who is given
this medicine will be affected in the same way. If you are worried about side effects you should
discuss them with your doctor, who will explain the risks and benefits of your treatment.
Some of the side effects can be lessened or treated by other medicines or therapy.
Tell your doctor or nurse straight away if:
• You have pain, swelling or warmth in or around the vein where daunorubicin is being injected
• You have a red face while daunorubicin is being injected. This may be a sign that the injection
is being given too quickly
• You get fevers, chills or other signs of infection
• You have any severe infections, such as those of the blood (sepsis), which may also cause low blood
pressure (septic shock, a life-threatening form of sepsis) or inflammation of the lungs (pneumonia)
• You have difficulty in breathing
• You have swelling of the feet or legs
• You have an uneven or fast heart beat
• You have black or tarry bowel motions
• You are being sick (vomiting) and bring up blood or dark brown coffee-coloured granules
• You notice any unusual bleeding or bruising
Tell your doctor or nurse if you notice any of the following side effects:
• You feel sick (nausea) or are sick (vomit)
• You have diarrhoea
• You have inflammation of the bowel
• You have a skin rash
• You have sores in the mouth or on the lips
Other side effects include:
• decreased numbers of different types of blood cells (granulocytopenia, leukopenia and
neutropenia, anaemia) which may cause tiredness, fever or increased risk of bleeding
• changes in metabolism caused by dying cancer cells releasing their contents into the
bloodstream (tumour lysis syndrome)
• feeling very dry and thirsty (dehydration)
• inflammation of mucous membranes (mucositis), of the mouth with areas of painful erosions,
ulceration and bleeding (stomatitis) and of the oesophagus (oesophagitis)
• loss of appetite
• increased pigmentation (hyperpigmentation) of skin and nails
• Daunorubicin can make your urine turn red for a couple of days after each dose
• Medicines like daunorubicin often cause temporary loss of hair. After your treatment finishes
your hair should grow back
• Disease of the bone marrow
There have been reports of secondary tumours (secondary leukaemia) following use of
daunorubicin in combination with other anti-cancer drugs.
After stopping treatment
After you have finished your course of treatment, you may still get side effects. Tell your doctor
or nurse straightaway if:
• You have difficulty in breathing
• You have swelling of the feet or legs
• You get an uneven or fast heart beat
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. 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 DAUNORUBICIN
• Keep this medicine out of the sight and reach of children.
• Daunorubicin should not be used after the expiry date which is stated on the carton. The
expiry date refers to the last day of the month.
• The vials of powder should be kept at room temperature and protected from light.
• The daunorubicin solutions made up from the powder should be stored at between 2 - 8°C,
protected from light and used within 24 hours.
• Following the injection, daunorubicin will be disposed of carefully by the doctor or nurse.
6. CONTENTS OF THE PACK AND OTHER INFORMATION
What Daunorubicin 20mg Powder for I.V. Injection contains
The active ingredient is daunorubicin hydrochloride. Each vial contains 20mg of daunorubicin.
Each vial also contains mannitol.
What Daunorubicin 20mg Powder for I.V. Injection looks like and contents of the pack
Daunorubicin 20mg Powder for I.V. Injection comes as a vial containing a red powder. The
solution prepared with this powder is also red.
The vials are available in packs of 1 and 10 vials.
Marketing Authorisation Holder and Manufacturer
Marketing authorisation holder
One Onslow Street,
GU1 4YS, UK.
Cenexi - Laboratoires Thissen S.A.
This leaflet was last revised in August 2016
Zentiva is a registered trademark.
DAUNORUBICIN PDR FOR INJ LEAFLET
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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.