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CYTARABINE 100MG/ML

Active substance(s): CYTARABINE

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Cytarabine

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

4.3 Contraindications

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 immunosuppression.
Hypersensitivity to the active substance or to any of the
excipients listed in section 6.1.

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The following information is intended for medical or
healthcare professionals

1. NAME OF THE MEDICINAL PRODUCT

Cytarabine 20mg/ml solution for infusion or injection
Cytarabine 100mg/ml solution for infusion or injection

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2. QUALITATIVE AND QUANTITATIVE
COMPOSITION

1 ml of solution contains 20mg of cytarabine.
1 ml of solution contains 100mg of cytarabine.
For the full list of excipients, see section 6.1

3. PHARMACEUTICAL FORM
Solution for infusion or injection.

4. CLINICAL PARTICULARS
4.1 Therapeutic indications
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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

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By intravenous infusion or injection, or subcutaneous
injection.
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.
Paediatric population: Children appear to tolerate
higher doses than adults and, where dose ranges are
quoted, the 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 leukopenia, thrombocytopenia, and anaemia,
with appropriate initiation of supportive therapy when
indicated.

4.4 Special warnings and precautions
for use

General: Only physicians experienced in cancer
chemotherapy should use cytarabine.
Warnings:
Haematologic Effects: Cytarabine is a potent bone
marrow suppressant; the severity depends on the dose
of the drug and the schedule of administration. 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.
The main toxic effect of cytarabine is bone marrow
suppression with leukopenia, thrombocytopenia, anaemia,
megaloblastosis and reduced reticulocytes. Less serious
toxicity includes nausea, vomiting, diarrhoea and
abdominal pain, oral ulceration, and hepatic dysfunction
(see section 4.8).
Following 5-day constant infusions or acute injections of
50 mg/m² to 600 mg/m², white cell depression follows a
biphasic course. Regardless of initial count, dosage level,
or schedule, there is an initial fall starting the first 24 hours
with a nadir at days 7-9. This is followed by a brief rise
which peaks around the twelfth day. A second and deeper
fall reaches nadir at days 15-24. Then there is rapid rise
to above baseline in the next 10 days. Platelet depression
is noticeable at 5 days with a peak depression occurring
between days 12-15. Thereupon, a rapid rise to above
baseline occurs in the next 10 days.
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 (see section 4.8).
High Dose Schedules: 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 high dose
(2-3 g/m²) schedules with cytarabine. 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 (see section 4.8).
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 granulocyte
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 drugfree intervals of 12 to 24 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, sudden
respiratory distress syndrome and pulmonary oedema have
occurred following experimental high dose schedules with
cytarabine therapy.
Cases of cardiomyopathy with subsequent death have been
reported following experimental high dose cytarabine and
cyclophosphamide therapy when used for bone marrow
transplant preparation. This may be schedule dependent.
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.
Conventional Dose Schedules: Abdominal tenderness
(peritonitis) and guaiac positive colitis, with concurrent
neutropenia and thrombocytopenia, have been reported in
patients treated with conventional doses of cytarabine in
combination with other drugs. Patients have responded to
nonoperative medical management. Delayed progressive
ascending paralysis resulting in death has been reported
in children with AML following intrathecal and intravenous
cytarabine at conventional doses in combination with other
drugs.
Hepatic and/or Renal Function: The human liver apparently
detoxifies a substantial fraction of an administered dose
of cytarabine. In particular, patients with renal or hepatic
function impairment may have a higher likelihood of CNS
toxicity after high-dose treatment with 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.
Neurological: Cases of severe neurological adverse reactions
that ranged from headache to paralysis, coma and strokelike episodes have been reported mostly in juveniles and
adolescents given intravenous cytarabine in combination
with intrathecal methotrexate.
The safety of this drug for use in infants is not established.
Tumour Lysis Syndrome: 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.
Pancreatitis: Cases of pancreatitis have been observed with
the induction of cytarabine.
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 medicinal
products 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 alternative.
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.

Methotrexate: Intravenous cytarabine given concomitantly
with intrathecal methotrexate may increase the risk of
severe neurological adverse reactions such as headache,
paralysis, coma and stroke like episodes (see section
4.4).

4.6 Fertility, pregnancy and lactation

Pregnancy
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.
Because of the potential for abnormalities with cytotoxic
therapy, particularly during the first trimester, a patient
who is or who may become pregnant while on cytarabine
should be apprised of the potential risk to the foetus
and the advisability of pregnancy continuation. There
is a definite, but considerably reduced risk if therapy is
initiated during the second or third trimester. Although
normal infants have been delivered to patients treated
in all three trimesters of pregnancy, follow-up of such
infants would be advisable.
Breast-feeding
It is not known whether this drug is excreted in human
milk. Because many drugs are excreted in human milk
and because of the potential for serious adverse reactions
in nursing infants from cytarabine, a decision should be
made whether to discontinue nursing or to discontinue
the drug, taking into account the importance of the drug
to the mother.
This product should not normally be administered
to patients who are pregnant or to mothers who are
breast-feeding.

4.7 Effects on ability to drive and use
machines

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

Summary of the safety profile (see also section 4.4)
Most frequent adverse reactions include nausea,
vomiting, diarrhoea, fever, rash, anorexia, oral and anal
inflammation or ulceration, and hepatic dysfunction.
Blood and lymphatic system disorders:
Because cytarabine is a bone marrow suppressant,
anaemia, leukopenia, 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.
Infections and infestations:
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 and at times fatal.
Musculoskeletal and connective tissue disorders:
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.
The reported adverse reactions are listed below by
MedDRA System Organ Class and by frequency.
Frequencies are defined as: Very common (>10%),
Common (>1%, ≤10%), Uncommon (>0.1%, ≤1%),
Rare (>0.01%, ≤0.1%), and Frequency not known
(cannot be estimated from available data).

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PATIENT LEAFLET : Information for the user

Cytarabine

20mg/ml and 100mg/ml
Solution for infusion or injection
(Cytarabine)

Pregnancy

If you are pregnant, think you may be
pregnant or are planning to have a baby,
ask your doctor or pharmacist for advice
before you are given this medicine because
Cytarabine may cause birth defects. 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.

Breast-feeding
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, 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, pharmacist or nurse. This
includes any possible side effects not
listed in this leaflet. See section 4.

What is in this leaflet

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

1. What Cytarabine is and
what it is used for

• Cytarabine is used in adults and children.
• This medicine contains cytarabine, which
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 destroyed.
• 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, if
you do not feel better or if you feel worse.

2. What you need to know
before you are given
Cytarabine
Do not use Cytarabine:

• If you are allergic (hypersensitive) to
cytarabine, or any of the other ingredients of
this medicine (listed in section 6).
• If you are already taking medicines that
have caused you to have a low blood
count caused by suppression of your bone
marrow. Your doctor might not give this
medicine if you have a non-malignant
disease, except for immunosuppression.

Warnings and precautions

Tell your doctor if:
• your liver is not working properly. This will
help your doctor decide if Cytarabine is
suitable for you.
• you have had or are due to have
any vaccination including a live or
live-attenuated vaccination.
• you are given Cytarabine in combination
with methotrexate administered through
your spine, because cases of headache,
paralysis, coma and stroke-like symptoms
have been reported in children and young
adults given intravenous Cytarabine in
combination with intrathecal methotrexate.

Other medicines and Cytarabine

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, have recently taken or might
take any other medicines, even those not
prescribed.

You should stop breast-feeding before
starting treatment with Cytarabine because
this medicine may be harmful to infants being
breast-fed.

Driving and using machines

If you feel unwell following treatment with
Cytarabine you should avoid driving or using
machinery.

3. How Cytarabine is given
to you

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.

Regular Check-ups

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 - using blood tests - to check
that Cytarabine is not affecting the way it
functions in a harmful way.
• your kidneys - 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.

If you receive high doses of
Cytarabine:

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.
If you have any further questions on the use
of this medicine, ask your doctor, pharmacist
or nurse.

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4. Possible side effects

Like all cytotoxic medicines, this medicine
causes side effects, although not everybody
gets them.
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
symptoms.

Other side effects that may occur
are:
If any of these side effects gets serious
please tell your doctor or nursing staff
immediately.

Very common: may affect more
than 1 in 10 people

• Pneumonia, infection (which can become
serious and lead to organ failure),
• Insufficient production or decrease in
numbers of red blood cells, white blood
cells or platelets.
• Inflammation or appearance of sores in
the mouth, lips, or on the anus (back
passage), feeling sick, being sick,
diarrhoea, abdominal pain
• Liver damage
• Hair loss is common and may be quite
severe. Hair normally re-grows when your
treatment course ends. Skin rash
• Cytarabine syndrome, sometimes the
following side effects can happen together
6 to12 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.
• Feeling hot and feverish
• Abnormal bone marrow results from a
biopsy, or blood results from a smear test

Common: may affect up to 1 in 10
people
• Ulceration on your skin

Not known: frequency cannot be
estimated from the available data

• You may get an infection, including
infection or inflammation at the site of your
injection
• Loss of appetite
• Headaches or feeling dizzy, feeling of pins
and needles, shaking and fits, drowsiness
• Conjunctivitis
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• Pericarditis (inflammation of the covering
of the heart)
• Inflammation to your veins (caused by a
blood clot)
• Shortness of breath, sore throat, pain or
difficulty swallowing
• Pancreatitis (pain in the upper abdomen)
often accompanied by feeling sick or
vomiting, inflammation or ulcers in the
gullet, causing heartburn may make you
feel sick,
• Jaundice (seen as yellowing of the skin
and whites of the eye)
• Skin redness (similar to sunburn), pain and
numbness in joints, fingers, toes or face,
swelling of the abdomen, legs, ankles and
feet, a sensation of tingling or burning,
tenderness and tightness of the skin, thick
calluses on the palms and hands, itchy
skin rash, itching or increased freckles
• Difficulty or pain when passing urine.
Blood in your urine and impaired kidney
function
The following side effects have been reported
with high dose therapy:

Very common: may affect more
than 1 in 10 people

• Paralysis caused by cerebral disorder,
experience problems in walking, speech
problems, involuntary muscle movement
caused by cerebellar disorder, tiredness,
weakness, fainting
• Eye infection, irritation, pain and blurred
vision, visual loss
• Short or stabbing chest pain, build up of
fluid in the lungs

Common: may affect up to 1 in 10
people
• Peeling of the skin
• Infection and inflammation of the
intestines, most common in babies

Not known: Frequency cannot be
estimated from the available data

• A pus-filled mass inside the liver
• Changes in your personality
• Coma, convulsions, poor balance caused
by damage to nerves
• Fast heart beat, reduced function of the
heart, shortness of breath, dizziness,
swelling of legs, ankles, feet and veins in
the neck (cardiomyopathy), which can be
fatal
• Blood in vomiting or in stools
(gastrointestinal necrosis or ulcer),
stomach pain or tenderness (peritonitis)

Reporting of side effects

If you get any side effects, talk to your doctor,
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 Cytarabine

Keep out of the sight and reach of
children.
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 stated on the vial label and
carton after EXP. The expiry date refers to the
last day of that month.
Do not throw away any medicines via
wastewater or household waste. Ask your
pharmacist how to throw away medicines
you no longer use. These measures will help
protect the environment.

6. Contents of the pack and
other 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
chloride.
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 1000mg (10ml) or
2000mg (20ml).
Not all pack sizes may be marketed.

Marketing Authorisation Holder:
Pfizer Limited
Ramsgate Road
Sandwich
Kent
CT13 9NJ
United Kingdom

Manufacturer:

Pfizer Service Company BVBA
10 Hoge Wei
1930 Zaventem
Belgium

Company Contact Address:

For further information on your medicine
contact Medical Information at Pfizer Limited,
Walton Oaks, Tadworth, Surrey,
Tel: 01304 616161.
This leaflet was last revised in 12/2015.
Ref: CC 13_0

ZZZ000ZZ

Adverse Reactions Table
Infections and Infestations:
Very common
Sepsis, pneumonia, infection a
Frequency not known
Injection site cellulitis, liver abscess
Blood and Lymphatic System Disorders:
Very common
Bone marrow failure, thrombocytopenia, anaemia, anaemia megaloblastic,
leukopenia, reticulocyte count decreased
Immune System Disorders:
Anaphylactic reaction, allergic oedema
Frequency not known
Metabolism and Nutrition Disorders:
Frequency not known
Decreased appetite
Nervous System Disorders:
Frequency not known
Neurotoxicity, neuritis, dizziness, headache
Eye Disorders:
Conjunctivitis b
Frequency not known
Cardiac Disorders:
Frequency not known
Pericarditis
Vascular Disorders:
Frequency not known
Thrombophlebitis
Respiratory, Thoracic and Mediastinal Disorders:
Dyspnoea, oropharyngeal pain
Frequency not known
Gastrointestinal Disorders:
Very common
Stomatitis, mouth ulceration, anal ulcer, anal inflammation, diarrhoea, vomiting,
nausea, abdominal pain
Pancreatitis, oesophageal ulcer, oesophagitis
Frequency not known
Hepatobiliary Disorders:
Very common
Hepatic function abnormal
Frequency not known
Jaundice
Skin and Subcutaneous Tissue Disorders:
Alopecia, rash
Very common
Common
Skin ulcer
Frequency not known
Palmar-plantar erythrodysaesthesia syndrome, urticaria, pruritus, ephelides
Musculoskeletal, Connective Tissue and Bone Disorders:
Very common
Cytarabine syndrome
Renal and Urinary Disorders:
Frequency not known
Renal impairment, urinary retention
General Disorders and Administration Site Conditions:
Pyrexia
Very common
Frequency not known
Chest pain, injection site reaction c
Investigations:
Very common
Biopsy bone marrow abnormal, blood smear test abnormal
a
may be mild, but can be severe and at times fatal
b
may occur with rash and may be hemorrhagic with high dose therapy
c
pain and inflammation at subcutaneous injection site
Adverse reactions reported in association with high dose therapy (see section 4.4) are included in the following table:
Adverse Reactions Table (High Dose Therapy)
Infections and Infestations:
Frequency not known
Liver abscess, sepsis
Psychiatric Disorders:
Frequency not known
Personality change a
Nervous System Disorders:
Very common
Cerebral disorder, cerebellar disorder, somnolence
Frequency not known
Coma, convulsion, peripheral motor neuropathy, peripheral sensory neuropathy
Eye Disorders:
Very common
Corneal disorder
Cardiac Disorders:
Frequency not known
Cardiomyopathy b
Respiratory, Thoracic and Mediastinal Disorders:
Very common
Acute respiratory distress syndrome, pulmonary oedema
Gastrointestinal Disorders:
Common
Necrotising colitis
Frequency not known
Gastrointestinal necrosis, gastrointestinal ulcer, pneumatosis intestinalis,
peritonitis
Hepatobiliary Disorders:
Frequency not known
Liver injury, hyperbilirubinaemia
Skin and Subcutaneous Tissue Disorders:
Common
Skin exfoliation
a
Personality change was reported in association with cerebral and cerebellar dysfunction.
b
With subsequent death

Other adverse reactions
A diffuse interstitial pneumonitis without clear cause
that may have been related to cytarabine was reported
in patients treated with experimental intermediate
doses of cytarabine (1g/m²) with and without other
chemotherapeutic agents (meta-AMSA, daunorubicin,
VP-16).
A syndrome of sudden respiratory distress, rapidly
progressing to pulmonary oedema and a radiographically
pronounced cardiomegaly has been reported following
experimental high dose therapy with cytarabine used for
the treatment of relapsed leukemia; fatal outcome has
been reported.
Intrathecal use
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
reported.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation
of the medicinal product is important. It allows continued
monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any
suspected adverse reactions via the Yellow Card Scheme
at www.mhra.gov.uk/yellowcard.

4.9 Overdose

Cessation of therapy, followed by management of ensuing
bone marrow depression including whole blood or platelet
transfusion and antibiotics as required.
There is no antidote for overdosage of cytarabine. Doses of
4.5g/m² by intravenous infusion over 1 hour every 12 hours
for 12 doses has caused an unacceptable increase in
irreversible CNS toxicity and death.

5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Pyrimidine analogues,
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 indemonstrable
circulating drug as early as 5 minutes after injection.

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 periand 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.

6.2 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.

6.3 Shelf-life

Cytarabine 20mg/ml
Cytarabine 100mg/ml

18 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 (2-8°C).

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).
Not all pack sizes may be marketed.

6.6 Special precautions for disposal and
other handling

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
immediately.
Disposal and Spills: To destroy, place in a high risk (for
cytotoxics) waste disposal bag and incinerate at 1100°C.
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 1100°C.

7. MARKETING AUTHORISATION HOLDER

Pfizer Limited
Ramsgate Road
Sandwich
Kent CT13 9NJ
UK

8. MARKETING AUTHORISATION NUMBER

Cytarabine 20mg/ml
Cytarabine 100mg/ml

PL 00057/0954
PL 00057/0955

9. DATE OF FIRST AUTHORISATION/
RENEWAL OF AUTHORISATION
03 June 1999

10. DATE OF REVISION OF THE TEXT
12/2015

LEGAL CATEGORY
POM

Ref: CC 13_0

6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients

Cytarabine 20mg/ml
Hydrochloric Acid
Sodium Hydroxide
Nitrogen
Water for injections
Sodium Chloride

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

ZZZ000ZZ

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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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