Active substance: CYTARABINE

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20mg/ml and 100mg/ml
Solution for infusion or injection

children should receive the higher dose and the adults
the lower.
Elderly Patients: There is no information to suggest
that a change in dosage is warranted in the elderly.
Nevertheless, the elderly patient does not tolerate
drug toxicity as well as the younger patient, and
particular attention should thus be given to drug
induced leucopenia, thrombocytopenia, and anaemia,
with appropriate initiation of supportive therapy when

Cytarabine 20mg/ml
Cytarabine 100mg/ml


1 ml of solution contains 20mg of cytarabine.
1 ml of solution contains 100mg of cytarabine.
For a full list of excipients see Section 6.1

Solution for infusion or injection.

4.1 Therapeutic indications

Cytotoxic. For induction of remission in acute myeloid
leukaemia in adults and for other acute leukaemias of
adults and children.

4.2 Posology and method of administration

By intravenous infusion or injection, or subcutaneous
Dosage recommendations may be converted from those
in terms of bodyweight to those related to surface area by
means of nomograms, as presented in Documenta Geigy.
1) Remission induction:
a) Continuous treatment:
i) Rapid injection - 2 mg/kg/day is a judicious starting
dose. Administer for 10 days. Obtain daily blood
counts. If no antileukaemic effect is noted and there
is no apparent toxicity, increase to 4 mg/kg/day and
maintain until therapeutic response or toxicity is
evident. Almost all patients can be carried to toxicity
with these doses.
ii) 0.5 - 1.0 mg/kg/day may be given in an infusion
of up to 24 hours duration. Results from one hour
infusions have been satisfactory in the majority of
patients. After 10 days this initial daily dose may be
increased to 2 mg/kg/day subject to toxicity. Continue
to toxicity or until remission occurs.
b) Intermittent treatment:
3 - 5 mg/kg/day are administered intravenously on
each of five consecutive days. After a two to nine day
rest period, a further course is given. Continue until
response or toxicity occurs.
The first evidence of marrow improvement has been
reported to occur 7 - 64 days (mean 28 days) after the
beginning of therapy.
In general, if a patient shows neither toxicity nor
remission after a fair trial, the cautious administration
of higher doses is warranted. As a rule, patients
have been seen to tolerate higher doses when given
by rapid intravenous injection as compared with
slow infusion. This difference is due to the rapid
metabolism of Cytarabine and the consequent short
duration of action of the high dose.
2) Maintenance therapy: Remissions which have been
induced by Cytarabine, or by other drugs, may be
maintained by intravenous or subcutaneous injection
of 1 mg/kg once or twice weekly.
Children: Children appear to tolerate higher doses
than adults and, where dose ranges are quoted, the

4.3 Contra-indications

Therapy with Cytarabine should not be considered
in patients with pre-existing drug-induced bone
marrow suppression, unless the clinician feels that
such management offers the most hopeful alternative
for the patient. Cytarabine should not be used in the
management of non-malignant disease, except for

4.4 Special warnings and special
precautions for use

Warnings: Cytarabine is a potent bone marrow
suppressant. Therapy should be started cautiously in
patients with pre-existing drug-induced bone marrow
suppression. Patients receiving this drug must be under
close medical supervision and, during induction therapy,
should have leucocyte and platelet counts performed
daily. Bone marrow examinations should be performed
frequently after blasts have disappeared from the
peripheral blood.
Facilities should be available for management of
complications, possibly fatal, of bone marrow suppression
(infection resulting from granulocytopenia and other
impaired body defences, and haemorrhage secondary to
thrombocytopenia). Anaphylactic reactions have occurred
with cytarabine treatment. Anaphylaxis that resulted in
acute cardiopulmonary arrest and required resuscitation
has been reported. This occurred immediately after the
intravenous administration of Cytarabine.
Severe and at times fatal CNS, GI and pulmonary toxicity
(different from that seen with conventional therapy
regimens of Cytarabine) has been reported following
some experimental Cytarabine dose schedules. These
reactions include reversible corneal toxicity; cerebral and
cerebellar dysfunction, usually reversible; somnolence;
convulsion; severe gastro-intestinal ulceration, including
pneumatosis cystoides intestinalis, leading to peritonitis;
sepsis and liver abscess; and pulmonary oedema.
Cytarabine has been shown to be carcinogenic in
animals. The possibility of a similar effect should
be borne in mind when designing the long-term
management of the patient.
Precautions: Patients receiving Cytarabine must be
monitored closely. Frequent platelet and leucocyte counts
are mandatory. Suspend or modify therapy when drug
induced marrow depression has resulted in a platelet
count under 50,000 or a polymorphonuclear count under
1,000 per cubic mm. Counts of formed elements in the
peripheral blood may continue to fall after the drug is
stopped, and reach lowest values after drug-free intervals
of five to seven days. If indicated, restart therapy when
definite signs of marrow recovery appear (on successive
bone marrow studies). Patients whose drug is withheld
until ‘normal’ peripheral blood values are attained may
escape from control.
Peripheral motor and sensory neuropathies after

consolidation with high doses of cytarabine, daunorubicin,
and asparaginase have occurred in adult patients with
acute non lymphocytic leukemia. Patients treated with high
doses of cytarabine should be observed for neuropathy
since dose schedule alterations may be needed to avoid
irreversible neurologic disorders.
Severe and sometimes fatal pulmonary toxicity, adult
respiratory distress syndrome and pulmonary oedema have
occurred following high dose schedules with cytarabine
When intravenous doses are given quickly, patients are
frequently nauseated and may vomit for several hours
afterwards. This problem tends to be less severe when the
drug is infused.
The human liver apparently detoxifies a substantial fraction
of an administered dose of cytarabine. Use the drug
with caution and at reduced dose in patients whose liver
function is poor.
Periodic checks of bone marrow, liver and kidney functions
should be performed in patients receiving Cytarabine.
The safety of this drug for use in infants is not established.
Like other cytotoxic drugs, Cytarabine may induce
hyperuricaemia secondary to rapid lysis of neoplastic
cells. The clinician should monitor the patient’s blood uric
acid level and be prepared to use such supportive and
pharmacological measures as may be necessary to control
this problem.
Immunosuppressant Effects/Increased Susceptibility
to Infections. Administration of live or live-attenuated
vaccines in patients immunocompromised by
chemotherapeutic agents including cytarabine, may result
in serious or fatal infections. Vaccination with a live vaccine
should be avoided in patients receiving cytarabine. Killed
or inactivated vaccines may be administered; however, the
response to such vaccines may be diminished.

4.5 Interaction with Other Medicaments
and Other Forms of Interaction

5-Fluorocytosine should not be administered with
Cytarabine as the therapeutic efficacy of 5-Fluorocytosine
has been shown to be abolished during such therapy.
Reversible decreases in steady-state plasma digoxin
concentrations and renal glycoside excretion were
observed in patients receiving beta-acetyldigoxin and
chemotherapy regimens containing cyclophosphamide,
vincristine and prednisone with or without Cytarabine or
procarbazine. Steady-state plasma digitoxin concentrations
did not appear to change. Therefore, monitoring of plasma
digoxin levels may be indicated in patients receiving similar
combination chemotherapy regimens. The utilisation
of digitoxin for such patients may be considered as an
An in-vitro interaction study between gentamicin and
Cytarabine showed a Cytarabine related antagonism for
the susceptibility of K.pneumoniae strains. In patients
on Cytarabine being treated with gentamicin for a
K.pneumoniae infection, a lack of a prompt therapeutic
response may indicate the need for re-evaluation of
antibacterial therapy.

4.6 Pregnancy and Lactation

Cytarabine is known to be teratogenic in some animal
species. The use of Cytarabine in women who are, or who
may become, pregnant should be undertaken only after
due consideration of the potential benefits and hazards.
This product should not normally be administered to
patients who are pregnant or to mothers who are

Continued overleaf...




20mg/ml and 100mg/ml
Solution for infusion or injection

Avoid becoming pregnant while you or your
partner is being treated with Cytarabine.
If you are sexually active, you are advised
to use effective birth control to prevent
pregnancy during treatment, whether you are
male or female. Cytarabine may cause birth
defects, so it is important to tell your doctor if
you think you are pregnant.

Read all of this leaflet carefully
before you start taking this

• Keep this leaflet. You may need to read
it again.
• If you have any further questions, ask
your doctor or pharmacist.
• This medicine has been prescribed for
you. Do not pass it on to others. It may
harm them, even if their symptoms are
the same as yours.
• 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

In this leaflet:

1. What Cytarabine is and what it is
used for
2. Before you are given Cytarabine
3. How Cytarabine is given to you
4. Possible side effects
5. How to store Cytarabine
6. Further information

1. What Cytarabine is and
what it is used for

• Cytarabine is used in adults and children.
The active ingredient is cytarabine.
• Cytarabine is one of a group of the
medicines known as cytotoxics, these
medicines are used in the treatment of
acute leukaemias (cancer of blood where
you have too many white blood cells).
Cytarabine interferes with the growth
of cancer cells, which are eventually
• Cytarabine is also used for the induction
and maintenance of remission of leukaemia.
• Remission induction is an intensive
treatment to force leukaemia into retreat.
When it works, the balance of cells in your
blood becomes more normal and your
health improves. This relatively healthy spell
is called a remission.

• Maintenance therapy is a milder treatment
to make your remission last as long as
possible. Quite low doses of Cytarabine are
used to keep the leukaemia under control
and stop it flaring up again.
You should consult your doctor if you are
unsure why you have been given Cytarabine.

2. Before you are given
Do not use Cytarabine if you:

• are allergic (hypersensitive) to cytarabine,
or any of the other ingredients of
Cytarabine 20mg/ml and 100mg/ml
Solution for Injection.
• are already taking medicines that have
caused you to have a low blood count
caused by suppression of your bone

You should stop breast-feeding before
starting treatment with Cytarabine because
this medicine may be harmful to infants being
Ask your doctor or pharmacist for advice
before taking any medicine.

Driving and using machinery

If feeling unwell following treatment with
Cytarabine you should avoid driving or using
Ask your doctor or pharmacist for advice
before taking any medicine.

3. How Cytarabine is given
to you

Take special care with Cytarabine:
• Tell your doctor if your liver is not working
properly. This will help your doctor decide
if Cytarabine is suitable for you.
• If you have had or are due to have any
vaccination including a live or liveattenuated vaccination.

Cytarabine will be given to you by infusion
into a vein (through a ‘drip’) or by injection
under the direction of specialists in hospital.
Your doctor will decide what dose to give
and the number of days’ treatment you will
receive depending on your condition.
The dose of Cytarabine will be decided by
your doctor based on your condition being
treated for, whether you are in induction or
maintenance therapy and your body surface
area. Your body weight and height will be
used to calculate your body surface area.

Taking other medicines

Regular Check-ups

Tell your doctor or pharmacist if you are:
• given medicines containing
5-Fluorocytosine (a medicine used to treat
fungal infections).
• taking medicines containing digitoxin or
beta-acetyldigoxin which are used to treat
certain heart conditions.
• taking Gentamicin (an antibiotic used to
treat bacterial infections).
• given medicines containing
cyclophosphamide, vincristine and
prednisone which are used in cancer
treatment programmes.
• taking or have recently taken any other
medicines, even those not prescribed.

During treatment you will need regular checks
including blood tests. Your doctor will tell you
how often this should be done. He/she will be
making regular checks of:
• Your blood - to check for low blood cell
counts that may need treatment.
• Your liver - again using blood tests - to
check that Cytarabine is not affecting the
way it functions in a harmful way.
• Your kidneys - again using blood tests - to
check that Cytarabine is not affecting the
way it functions in a harmful way.
• Blood uric acid levels - Cytarabine may
increase uric acid levels in the blood.
Another medicine may be given if your uric
acid levels are too high.
Continued overleaf...

If you receive high doses of

High doses can worsen side effects like sores
in the mouth or may decrease the number
of white blood cells and platelets (these help
the blood to clot) in the blood. Should this
happen, you may need antibiotics or blood
transfusions. Mouth ulcers can be treated to
make them less uncomfortable as they heal.

4. Possible side effects

Like all cytotoxic medicines, Cytarabine
causes side effects, although these can vary
from patient to patient.
Tell your doctor or nursing staff who
will be monitoring you during this time
immediately, if you suffer from the following
symptoms after taking this medicine:
• An allergic reaction such as sudden
wheeziness, difficulty in breathing, swelling
of eyelids, face or lips, rash or itching
(especially affecting the whole body).
• You are feeling tired and lethargic.
• You have flu like symptoms e.g. raised
temperature or fever and chills.
• You bruise more easily or bleed more than
usual if you hurt yourself. These are the
symptoms of low numbers of blood
cells. Tell your doctor or nursing staff
immediately if you experience these

Other side effects that may occur

If any of these side effects gets serious
please tell your doctor or nursing staff
• Reactions at Injection site:
inflammation to your veins (caused by a
blood clot).
• Effects on your nervous system:
Headaches or feeling dizzy, feeling of pins
and needles, shaking and fits, drowsiness,
experience problems in walking, speech
problems, involuntary muscular movement,
changes in your personality, tiredness,
weakness, fainting.
• Effects on your skin and hair:
Hair loss is common and may be quite
severe. Hair normally re-grows when
your treatment course ends. A rash or
ulceration on your skin, peeling of the
skin, itching or increased freckles. You
may get an infection, including infection or
inflammation at the site of your injection.
• Effects on your stomach, intestines:
Feeling sick, being sick, diarrhoea, loss of
appetite, abdominal pain.

• Effects on your mouth, gullet and
anus: Inflammation of the gullet, causing
heartburn may make you feel sick, and the
appearance of sores in the mouth, lips, or
on the anus (back passage).
• Effects on your pancreas: Pancreatitis
(pain in the upper abdomen) often
accompanied by feeling sick or vomiting.
Tell your doctor if this happens to you.
• Effects on your liver: Liver damage
(seen as yellowing of the skin and whites
of the eye).
• Effects on your kidneys, bladder and
urine: Difficulty or pain when passing
urine. Blood in your urine and impaired
kidney function.
• Effects on your hands, face and body:
Feeling hot and feverish, conjunctivitis, and
pain and numbness in joints, fingers, toes
or face, swelling of the abdomen, legs,
ankles and feet.
• Effects on respiratory system and
chest: Shortness of breath, pneumonia,
short or stabbing chest pain, build up of
fluid in the lungs, sore throat.
• Effects on your muscles and bone:
muscle pain, bone pain.
• Effects on your heart and circulation:
fast heart beat.
• Effects on your eyes and vision: eye
infection, irritation, pain and blurred vision,
visual loss.
“Cytarabine Syndrome”
Sometimes the following side effects can
happen together 6 to 12 hours after receiving
Cytarabine. Feeling generally unwell with a
high temperature, pain in bone, muscle and
sometimes the chest, blistery rash, sore eyes.
This is called “Cytarabine Syndrome” and can
be treated.
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
nursing staff immediately.

5. How to store Cytarabine

Keep out of the reach and sight of
Hospital staff will store your medicine safely.
The unopened vials should be stored in the
original container between 15ºC and 25ºC
until ready for use.
Cytarabine should not be used after the
expiry date which is stamped on the pack.
The expiry date refers to the last day of that

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.

4.7 Effects on ability to drive and use

Cytarabine has no effect on intellectual function or
psychomotor performance. Nevertheless, patients receiving
chemotherapy may have an impaired ability to drive or
operate machinery and should be warned of the possibility
and advised to avoid such tasks if so affected.

4.8 Undesirable effects

6. Further Information
What Cytarabine contains

The active ingredient is cytarabine.
The other ingredients in Cytarabine 20mg/ml
are hydrochloric acid, sodium hydroxide,
nitrogen, water for injections and sodium
The other ingredients in Cytarabine 100mg/ml
are hydrochloric acid, sodium hydroxide,
nitrogen and water for injections.

What Cytarabine looks like and
contents of the pack

Cytarabine is a solution available in two
strengths: 20mg/ml and 100mg/ml.
Cytarabine containing 20mg/ml is supplied in
plastic vials containing 100mg (5ml) or
500mg (25ml).
Cytarabine containing 100mg/ml is supplied in
plastic vials containing 1000mg (10ml) or
2000mg (20ml).

Marketing Authorisation Holder:
Pharmacia Limited
Ramsgate Road
CT13 9NJ
United Kingdom


Pfizer Service Company BVBA
10 Hoge Wei
1930 Zaventem

Company Contact address:

If you have any comments on the way this
leaflet is written, please contact Medical
Information at Pfizer Limited in Walton Oaks,
Tadworth, Surrey, Tel: 01304 616161.
Date leaflet was last revised; 05/2012
Ref: CC 9_7


Because Cytarabine is a bone marrow suppressant,
anaemia, leucopenia, thrombocytopenia, megaloblastosis
and reduced reticulocytes can be expected as a result of
its administration. The severity of these reactions are dose
and schedule dependent.
Cellular changes in the morphology of bone marrow and
peripheral smears can be expected.
Most frequent adverse reactions include nausea, vomiting,
diarrhoea, fever, rash, anorexia, oral and anal inflammation
or ulceration, and hepatic dysfunction.
- Infections and infestations: Pneumonia, sepsis, cellulitis
at injection site, liver abscess
- Immune system disorders: Anaphylaxis, allergic
- Metabolism and nutrition disorders: Anorexia
- Nervous system disorders: Neural toxicity, neuritis,
dizziness, headache
- Eye disorders: Conjunctivitis (may occur with rash)
- Cardiac disorders: Pericarditis
- Vascular disorders: Thrombophlebitis
- Respiratory, thoracic and mediastinal disorders:
Shortness of breath, sore throat
- Gastrointestinal disorders: Pancreatitis, esophageal
ulceration, abdominal pain, diarrhoea, esophagitis,
nausea/vomiting, oral and anal inflammation or
- Hepatobiliary disorders: Hepatic dysfunction, jaundice
- Skin and subcutaneous tissue disorders: Skin
ulceration, alopecia, freckling, rash, pruritus, urticaria
- Renal and urinary disorders: Renal dysfunction, urinary
- General disorders and administration site conditions:
Chest pain, fever
High Dose Therapy (see section 4.4)
- Infections and infestations: Sepsis, liver abscess
- Nervous system disorders: cerebral and cerebellar
dysfunction including personality changes, somnolence,
and convulsion; peripheral motor and sensory
- Eye disorders: Corneal toxicity
- Cardiac disorders: Cardiomyopathy with subsequent
- Respiratory, thoracic and mediastinal disorders: Adult
respiratory distress syndrome, pulmonary oedema
- Skin and subcutaneous tissue disorders: Skin rash
leading to desquamation, alopecia
Viral, bacterial, fungal, parasitic, or saprophytic infections,
in any location in the body, may be associated with the
use of Cytarabine alone or in combination with other
immunosuppressive agents following immunosuppressant
doses that affect cellular or humoral immunity. These
infections may be mild, but can be severe.
A Cytarabine syndrome has been described. It is
characterised by fever, myalgia, bone pain, occasionally
chest pain, maculopapular rash, conjunctivitis and
malaise. It usually occurs 6 - 12 hours following drug
administration. Corticosteroids have been shown to be
beneficial in treating or preventing this syndrome. If the
symptoms of the syndrome are serious enough to warrant
treatment, corticosteroids should be contemplated as well
as continuation of therapy with Cytarabine.
Cases of pancreatitis have been observed with the
induction of Cytarabine.

Cytarabine is not recommended for intrathecal use;
however, the following side-effects have been reported
with such use. Expected systemic reactions: bone marrow
depression, nausea, vomiting. Occasionally, severe spinal
cord toxicity even leading to quadriplegia and paralysis,
necrotising encephalopathy, with or without convulsion,
blindness and other isolated neurotoxicities have been

4.9 Overdose

Cessation of therapy, followed by management of ensuing
bone marrow depression including whole blood or platelet
transfusion and antibiotics as required.

5.1 Pharmacodynamic properties

ATC Code: L01BC01
Cytarabine, a pyrimidine nucleoside analogue, is an
antineoplastic agent which inhibits the synthesis
of deoxyribonucleic acid. It also has antiviral and
immunosuppressant properties. Detailed studies on
the mechanism of cytotoxicity in vitro suggests that the
primary action of Cytarabine is inhibition of deoxycytidine
synthesis, although inhibition of cytidylic kinases and
incorporation of the compound into nucleic acids may
also play a role in its cytostatic and cytocidal actions.

5.2 Pharmacokinetic properties

Cytarabine is deaminated to arabinofuranosyl uracil in
the liver and kidneys. After intravenous administration to
humans, only 5.8% of the administered doses is excreted
unaltered in urine within 12 - 24 hours, 90% of the
dose is excreted as the deaminated product. Cytarabine
appears to be metabolised rapidly, primarily by the liver
and perhaps by the kidney. After single high intravenous
doses, blood levels fall to unmeasurable levels within
15 minutes in most patients. Some patients have in
demonstrable circulating drug as early as 5 minutes after

5.3 Preclinical Safety Data

Cytarabine is embryotoxic and teratogenic when
administered to rodents during the period of
organogenesis at clinically relevant doses. It is reported
that cytarabine causes developmental toxicity, including
damage to the developing brain, when administered
during the peri- and postnatal period. No formal fertility
studies have been reported however sperm head
abnormalities were observed following cytarabine
treatment in mice.
Cytarabine is mutagenic and clastogenic and produced
malignant transformation of rodent cells in vitro.

6.1 List of excipients
Cytarabine 20mg/ml
Hydrochloric Acid
Sodium Hydroxide
Water for injections
Sodium Chloride

Cytarabine 100mg/ml
Hydrochloric Acid
Sodium Hydroxide
Water for injections

6.3 Shelf-life

Cytarabine 20mg/ml
Cytarabine 100mg/ml

12 months
18 months

6.4 Special precautions for storage

Store at 15°C - 25°C. Keep container in outer carton.
Cytarabine should not be stored at refrigerated
temperatures (2-8ºC).

6.5 Nature and contents of container

Polypropylene vials, closed with either a West S63/1704
Grey EPDM rubber stopper or a West 4110/40 Grey
FluroTec® Plus-faced rubber stopper, and sealed with an
aluminium crimp with a plastic flip-off top.
Cytarabine 20mg/ml
Cytarabine is supplied as vials containing
20mg/ml cytarabine in 5ml (100mg) in packs of 5, or
25ml (500mg) as single vials.
Cytarabine 100mg/ml
Cytarabine is supplied as single vials containing
100mg/ml cytarabine in 10ml (1g) or 20ml (2g).

6.6 Instructions for use, handling and

Cytarabine 100mg/ml only:
Prior to use, vials of Cytarabine 100mg/ml must be
warmed to 55°C, for 30 minutes, with adequate shaking,
and allowed to cool to room temperature.
Cytarabine 20mg/ml & 100mg/ml:
Once opened, the contents of each vial must be used
immediately and not stored. Discard any unused portion.
Water for injections, 0.9% saline or 5% dextrose
are commonly used infusion fluids for Cytarabine.
Compatibility must be assured before mixing with any
other substance.
Infusion fluids containing Cytarabine should be used
Disposal and Spills: To destroy, place in a high risk
(for cytotoxics) waste disposal bag and incinerate at
1100ºC. If spills occur, restrict access to the affected
area and adequate protection including gloves and safety
spectacles should be worn. Limit the spread and clean
the area with absorbent paper/material. Spills may also
be treated with 5% sodium hypochlorite. The spill area
should be cleaned with copious amounts of water. Place
the contaminated material in a leak proof disposal bag for
cytotoxics and incinerate at 1100ºC.

Pharmacia Limited
Ramsgate Road
Kent CT13 9NJ

Cytarabine 20mg/ml
Cytarabine 100mg/ml

PL 0032/0197
PL 0032/0198

03 June 1999


Ref: CC 9_7

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal
product must not be mixed with other medicinal products
except those mentioned in section 6.6.


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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.