ARACYTIN 100 mg /5 Ml Powder And Solvent For Injectable Solution

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1. ARACYTIN 100 mg/5 ml powder and solvent for injectable solution, 500 mg/10 ml powder and solvent for injectable solution
   1. What is Aracytin and what is it used for
   2. What you need to know before you are given Aracytin
   3. How to administer Aracytin
   4. Possible side effects
   5. How to store Aracytin
   6. Contents of the pack and other information

ARACYTIN 100 mg/5 ml powder and solvent for injectable solution, 500 mg/10 ml powder and solvent for injectable solution

Cytarabine

Read this leaflet carefully before you are given this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet:

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

1. What is Aracytin and what is it used for

Aracytin contains the active substance cytarabine, which belongs to a group of medicines called
pyrimidine analogues, used in the treatment of cancers. Pyrimidine is one of the molecules
that make up the DNA of cells.
Aracytin is used for the treatment of acute myeloid leukemia (a type of cancer of the white
blood cells) in adults and children. White blood cells are the cells responsible for
the body's defense.
Aracytin is also used in the treatment of other types of white blood cell cancers (leukemias)
when previous treatments have not worked or have not proven adequate.
Cytarabine works by interfering with the growth of cancer cells which are eventually
destroyed.

2. What you need to know before you are given Aracytin

Aracytin must not be given to you or your child if:

• you are allergic to cytarabine, or to any of the other ingredients of this medicine (listed in section 6);
• you are taking or have taken medicines that cause a severe reduction in the cells produced by the bone marrow, such as red blood cells, white blood cells, platelets (bone marrow suppression), unless your doctor decides that treatment with this medicine is the best thing for you or your child (see section Other medicines and Aracytin);
• you have a severe reduction in the cells produced by the bone marrow (red blood cells, white blood cells, platelets) for reasons other than your illness (leukaemia) and not due to taking medicines;
• you suffer from a brain disease that primarily causes progressive loss of memory, self-awareness and knowledge, inability to concentrate, continuous drowsiness. This disease may occur spontaneously or following the administration of medicines such as methotrexate or after undergoing radiation therapy (radiotherapy) (see section Other medicines andAracytin).

Warnings and precautions
Talk to your doctor or nurse, beforeyou are given Aracytin, if you think that any of the
following conditions apply to you or your child:

• you are pregnant or think you may be pregnant, because Aracytin should not be taken during pregnancy (see section Pregnancy, breastfeeding and fertility);
• you are taking or have taken medicines that cause a severe reduction in the cells produced by the bone marrow, such as red blood cells, white blood cells, platelets (bone marrow suppression). In this case, you or your child may be subject to close medical monitoring and your doctor may decide that treatment with Aracytin is not suitable for you or your child;
• your liver or kidneys are not working properly, because in these cases the administration of this medicine may more easily cause adverse effects on the central nervous system. Therefore, your doctor may decide to use a lower dose of Aracytin;
• you have been or are going to be vaccinated with vaccines called “live” or “attenuated”. Aracytin lowers the immune defenses and the simultaneous administration of these types of vaccines should be avoided, because serious or fatal infections may occur. You may, however, be vaccinated with vaccines called “killed” or “inactivated”, even if the effect of this type of vaccination may be reduced by the administration of Aracytin.

The doctor will check your health afterthe administration of Aracytin, as serious adverse effects may occur (see section 4 Possible side effects).

Regular medical checks during treatment with Aracytin
During treatment, the doctor will subject you or your child to regular checks:

• of the blood, to check especially the number of white blood cells and platelets;
• of the bone marrow, to check for the presence or disappearance of cancer cells;
• of the liver and kidneys (also in this case with blood tests) to rule out that Aracytin is affecting the function of these organs in any way;
• of the blood and/or other specific tests to check for the possible presence of infections, as Aracytin increases susceptibility to infections;
• of uric acid levels in the blood, because Aracytin may increase them.

The doctor will assess your health status, or that of your child, and will explain the risks and benefits of treatment with Aracytin to you in detail.

Children
The safety of Aracytin in children has not been established. The doctor will decide whether this medicine can
be given to children based on their condition.

Other medicines and Aracytin
Tell your doctor if you or your child are taking, have recently taken or might
take any other medicine.
It is particularly important that you tell your doctor if you or your child are taking the
following medicines, because the doses of these medicines or those of Aracytin may be
modified or it may be necessary to monitor them over time:

• digoxin (a medicine used to treat heart problems);
• gentamicin (an antibiotic used to treat bacterial infections);
• fluorocytosine (a medicine used to treat infections caused by fungi), because the simultaneous administration of fluorocytosine and Aracytin may determine a decrease in the effects of fluorocytosine;
• methotrexate (a medicine used to treat some chronic inflammatory diseases and some types of cancer), because the simultaneous administration of methotrexate and Aracytin can cause headache, paralysis, coma and stroke-like symptoms (see section 4 Possible side effects).

Caution is necessary if you or your child:

• are taking or have taken medicines that cause a severe reduction in the cells produced by the bone marrow (see section Warnings and precautions);
• have been or are going to be vaccinated (see section Warnings andprecautions).

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant, are planning a pregnancy, or are breastfeeding with
breast milk, ask your doctor for advice before you are given this medicine.

Pregnancy
Avoid becoming pregnant while being treated with Aracytin as it can harm the
unborn child (congenital abnormalities), especially if administered during the first 3 months of pregnancy.
If you are already pregnant, your doctor will decide whether it is preferable for you to start treatment with
Aracytin.
The possible harm to the unborn child is considerably reduced if therapy with Aracytin is started
during the second or third trimester of pregnancy. If you are given Aracytin during
pregnancy, your baby may be born with a severe reduction in the cells
produced by the bone marrow (white blood cells, red blood cells, platelets), an alteration in the levels of
mineral salts in the blood, an increase in a particular type of white blood cells called “eosinophils”
(specialized in protecting the body from germs and allergens), an increase in
some types of antibodies, very high fever, severe blood infection (sepsis) or may die.
If you are given Aracytin during pregnancy, your baby may be born
before term.
Contraception in women of childbearing potential
Women must always use an effective method of birth control (contraception)
to prevent pregnancy during treatment and for 6 months after the last dose. Talk to
your doctor about the most suitable contraceptive methods for you and your partner.
Contraception in men
Male patients with female partners of childbearing potential must always use
highly effective contraceptive methods to prevent pregnancy during treatment and for
3 months after the last dose.

Breastfeeding
Aracytin must not be given during breastfeeding as it is not known whether
this medicine passes into breast milk. The doctor will decide whether it is preferable for you to stop
breastfeeding for the duration of therapy with Aracytin and for at least one week
after the last dose or to stop therapy with Aracytin.

Fertility
This medicine can cause disappearance of the normal menstrual cycle in women and cessation
of sperm production in men, especially when Aracytin is administered
together with other medicines for the treatment of leukaemia. The probability that these
effects develop increases with increasing dose and duration of treatment with this medicine.
In addition, this medicine can cause damage to the chromosomes of sperm, with
consequent risk of malformations or damage to the foetus.

Driving and using machines
This medicine does not alter or negligibly alters the ability to drive vehicles or
use machinery. However, it is advisable not to engage in these activities during treatment
with Aracytin. If you have doubts, consult your doctor.
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially
‘sodium-free’.

3. How to administer Aracytin

This medicine must be administered to you or your child under the supervision of
doctors experienced in cancer therapy with antineoplastic drugs.
This medicine can only be used in suitable facilities (hospital, clinics and nursing homes), which
ensure the immediate and effective treatment of any complications, even serious ones,
caused by the disease or by therapy with Aracytin.
This medicine, if administered for a long time, can cause the development of other tumors,
different from your disease (leukemia). The doctor will decide if this medicine is suitable for you or
for your child and for how long it should be administered.
Administration can occur by injection into a vein quickly (intravenous) or
slowly (infusion) or by injection under the skin (subcutaneous). The doctor will establish the duration
of treatment and the dose of Aracytin that must be administered to you or your child each
day and will monitor the response to treatment and clinical conditions.
The recommended dose for the treatment of acute myeloid leukemia in association with other
antineoplastic drugs is 100 mg/m per day administered as a continuous intravenous infusion
(for 1-7 days) or 100 mg/m administered intravenously every 24 hours (for 1-7 days).

If you or your child have received more Aracytin than you should
High doses of Aracytin can cause a severe reduction in cells produced by the bone
marrow, such as red blood cells, white blood cells, platelets (bone marrow depression). In such cases
the administration of antibiotics or a blood transfusion may be necessary.
Very serious reactions affecting the nervous system, stomach, intestines,
lungs, heart and skin can occur, sometimes even fatal (see paragraph 4 Possible side
effects).
Total hair loss (alopecia) and eye reactions may also occur.
If you are concerned because you think you or your child may have received a dose of
Aracytin higher than you should, inform your doctor or another healthcare professional immediately.

If a dose of Aracytin is forgotten
Since this medicine will be administered to you or your child under close medical supervision,
it is unlikely that a dose will be forgotten. However, inform the doctor if you think
that a dose has been forgotten.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
The severity of side effects depends on the dose administered, the
frequency and the route of administration.
Immediatelyconsult your doctor if you or your child experience any of the following side
effects because they can be serious:

Very common(may affect more than 1 in 10 people):

• infections caused by viruses, bacteria, fungi or parasites in any part of the body, widespread infection throughout the body (sepsis), pneumonia;
• reactions affecting the brain and cerebellum, drowsiness;
• fluid accumulation in the lungs (pulmonary edema) or decreased ability of the lung to pass oxygen into the blood (respiratory distress);
• inability of the bone marrow to produce the normal amount of blood cells (bone marrow failure).

Common(may affect up to 1 in 10 people):

• acute inflammation of the part of the intestine called the colon (colitis), with death of the cells that make up the wall of the colon (necrotizing colitis). This condition can be

accompanied by pain and discomfort especially in the lower abdomen and passage of
stool that appears normal, but contains blood not visible to the naked eye (your doctor may
advise you to undergo a laboratory test to detect the possible presence
of blood not visible to the naked eye).

Not known(frequency cannot be estimated based on available data):

• allergic reaction, which may manifest mainly with difficulty breathing, swelling of the eyelids, face or lips, skin rashes, itching and possibly other symptoms;
• degeneration and death of tissues of the stomach and intestines (gastrointestinal necrosis);
• ulcer of the intestine and stomach;
• presence of air bubbles in the wall of the intestine. This condition can sometimes represent the beginning of necrotizing colitis (see above Common side effects);
• inflammation of the membrane lining the inside of the abdomen, which can cause abdominal pain, even very strong, which may force you to assume a fetal position (peritonitis);
• heart disease (cardiomyopathy);
• collection of pus inside the liver (hepatic abscess);
• personality change;
• coma, convulsions, abnormal functioning of the peripheral nerves causing impaired ability to move (peripheral motor neuropathy) or altered sensitivity (peripheral sensory neuropathy);
• inflammation of the membrane surrounding the heart (pericarditis);
• inflammation of the pancreas (pancreatitis), which can cause sudden and/or episodic, very severe and intense abdominal pain, particularly localized in the upper abdomen.

Other side effects that may occur:
Very common(may affect more than 1 in 10 people):

• low number of platelets in the blood (thrombocytopenia), low number of red blood cells (anemia), presence of immature red blood cells in the blood and bone marrow (megaloblastic anemia), low number of white blood cells (leukopenia), low number of reticulocytes (young red blood cells);
• low levels of hemoglobin (a substance contained in red blood cells);
• inflammation of the mouth (stomatitis), mouth ulcer, anal ulcer, anal inflammation, diarrhea, vomiting, nausea, abdominal pain;
• abnormal liver function;
• patchy hair loss (alopecia), skin rash;
• cytarabine syndrome. 6-12 hours after the administration of Aracytin, fever, muscle pain (myalgia), bone pain, chest pain, skin rash, conjunctivitis and malaise may occur. These symptoms are generally treatable or can be prevented by administering other medicines (corticosteroids);
• fever;
• disease of the transparent anterior membrane of the eye (cornea).

Common(may affect up to 1 in 10 people):

• skin ulcer;
• skin peeling.

Not known(frequency cannot be estimated based on available data):

• pain and inflammation of the deeper layers of the skin at the injection site;
• swelling of the skin due to allergy (allergic edema);
• decreased appetite;
• nerve inflammation, dizziness, headache;
• conjunctivitis, conjunctivitis with blood loss;
• inflammation of the veins with formation of blood clots (thrombophlebitis);
• feeling of difficulty breathing (dyspnea), pain inside the mouth and throat;
• esophageal ulcer, inflammation of the esophagus;
• jaundice (yellowing of the skin and eyes), liver damage, elevated levels of bilirubin in the blood (a substance produced by the liver);
• redness, swelling, swelling and peeling of the palm of the hands and soles of the feet (palmo-plantar erythrodysesthesia syndrome), hives, itching, freckles;
• kidney damage, inability of the bladder to empty (urinary retention);
• chest pain;
• slowed heartbeat (bradycardia).

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor or nurse. You can also report side effects directly
to https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . By reporting side
effects you can help provide more information on the safety of this
medicine.

5. How to store Aracytin

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack and vial
after “Expiry”. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
The reconstituted solution must be used immediately. For further information, see the
section intended exclusively for doctors and healthcare professionals.

6. Contents of the pack and other information

What Aracytin contains
The active ingredient is cytarabine.
Each 100 mg vial contains 100 mg of cytarabine.
Each 500 mg vial contains 500 mg of cytarabine.
The other ingredients are: hydrochloric acid for pH adjustment, sodium hydroxide for pH
adjustment, water for injections (contained in the solvent vial).

Description of Aracytin and contents of the pack
Aracytin 100 mg/5 ml: 1 glass vial with rubber stopper and aluminium crimp cap containing
the lyophilised powder + 1 glass vial of 5 ml containing the solvent.
Aracytin 500 mg/10 ml: 1 glass vial with rubber stopper and aluminium crimp cap containing
the lyophilised powder + 1 glass vial of 10 ml containing the solvent.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Pfizer Italia S.r.l.
Via Isonzo, 71
04100 Latina
Italy

Manufacturer
Corden Pharma Latina S.p.A
Via Murillo, 7
04013 Sermoneta,
Latina, Italy

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The following information is intended exclusively for doctors and healthcare professionals:
Instructions for opening the vial:Apply pressure with your thumb placed over the point
marked on the vial.

Information on dilution and storage of the reconstituted solution

• Do not administer the product if the reconstituted solution is not clear;
• After reconstitution of the solution, chemical and physical stability is 24 hours at no more than 30°C and 48 hours in a refrigerator (2°C-8°C). From a microbiological point of view, the product must be used immediately. If not used immediately, the times and conditions of use are the responsibility of the user and should normally not exceed 24 hours at a temperature between 2°C and 8°C, unless the reconstitution has taken place under controlled and validated aseptic conditions.

Compatibility
Cytarabine is compatible with the following medicines at the concentrations indicated:
5% Dextrose in water for eight hours
Cytarabine 0.8 mg/ml and sodium cephalothin 1.0 mg/ml
Cytarabine 0.4 mg/ml and sodium prednisolone phosphate 0.2 mg/ml
Cytarabine 16 mcg/ml and vincristine sulfate 4 mcg/ml
Cytarabine 0.4 mg/ml and methotrexate 0.2 mg/ml
Aracytin must not be mixed with medicines other than those listed above.

Incompatibility
The reconstituted solution is incompatible with the following medicines:
Heparin
Insulin
5-fluorouracil
Penicillins (such as nafcillin, oxacillin and penicillin G)
Methylprednisolone sodium succinate
Vitamin B complex