CITARABINE PFIZER 20 mg/mL Injectable Solution and Perfusion Solution

Introduction

Package Leaflet: Information for the User

Cytarabine Pfizer 20 mg/ml Solution for Injection and Infusion

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• 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.

Contents of the Package Leaflet

1. What is Cytarabine Pfizer and what is it used for
2. What you need to know before you use Cytarabine Pfizer
3. How to use Cytarabine Pfizer
4. Possible side effects
5. Storage of Cytarabine Pfizer
6. Contents of the pack and further information

1. What is Cytarabine Pfizer and what is it used for

Cytarabine Pfizer is used in adults and children. The active substance is cytarabine.

Cytarabine belongs to a group of medicines called cytotoxics; these medicines are used to treat acute leukemias (blood cancer where you have too many white blood cells in your blood), which includes the prophylaxis and treatment of central nervous system (CNS) involvement (meningeal leukemia). Cytarabine interferes with the proliferation of cancer cells, which are eventually destroyed.

Cytarabine is also used to treat some types of chronic leukemia.

Induction of remission consists of intensive treatment to reduce the extent of leukemia. When it works, the balance of blood cells becomes normalized to some extent, and your health improves. This period of relative good health is called remission.

Maintenance treatment is a milder treatment to make the remission that occurs last as long as possible. Relatively low doses of cytarabine are used to keep leukemia under control and prevent it from worsening.

2. What you need to know before you use Cytarabine Pfizer

Do not use Cytarabine Pfizer:

• If you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6).
• If you are already taking medicines that reduce the ability of the bone marrow to produce blood cells.

Warnings and precautions

Consult your doctor or pharmacist before starting treatment with Cytarabine Pfizer.

• If your bone marrow is affected, treatment should be started under close medical supervision.
• Cytarabine markedly reduces the production of blood cells in the bone marrow. This can increase the predisposition to infections or bleeding. Blood cell counts may continue to decrease until one week after treatment is stopped. Your doctor will perform regular blood tests and examine your bone marrow if necessary.
• If you have or have had liver or kidney problems. During treatment with cytarabine, your liver and kidney function should be monitored. If your liver and/or kidney are not functioning properly before treatment, cytarabine can only be administered with extreme caution.
• If you have or have had gout, as cytarabine can cause an increase in uric acid.
• Severe and sometimes potentially life-threatening side effects can occur in the central nervous system, intestines, or lungs.
• If you are given cytarabine intravenously in combination with methotrexate intrathecally, you may experience severe side effects in your nervous system, especially in young patients and adolescents.
• If you need to be vaccinated while being treated with this medicine, as live or attenuated vaccines should not be administered, and the response to killed or inactivated vaccines may be diminished.

If you are in any of the above cases, consult your doctor before using this medicine.

Children and adolescents

The safety of this medicine for use in infants has not been established.

Other medicines and Cytarabine Pfizer

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

• If you receive medicines containing 5-fluorocytosine (a medicine used to treat fungal infections).
• If you take medicines containing beta-acetyldigoxin, which is used to treat certain heart conditions.
• If you take gentamicin (an antibiotic to treat bacterial infections).
• If you receive medicines containing cyclophosphamide, vincristine, and prednisone, which are used in cancer treatment programs.
• If you are given cytarabine intravenously in combination with methotrexate intrathecally.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before using this medicine.

Pregnancy

You should not become pregnant while you or your partner are being treated with cytarabine. If you are sexually active, you are advised to use effective contraceptive methods to avoid pregnancy during treatment, regardless of your sex. Cytarabine can cause birth defects, so it is important that if you think you are pregnant, you inform your doctor. Both men and women should use effective contraceptive methods during treatment and for 6 months after the last dose.

Contraception in women of childbearing age

Women should always use effective contraceptive methods (contraception) to avoid pregnancy during treatment and for 6 months after the last dose. Consult your doctor about the contraceptive methods that are suitable for you and your partner.

Contraception in men

Male patients with female partners of childbearing age should always use highly effective contraceptive methods to prevent pregnancy during treatment and for 3 months after the last dose.

Breastfeeding

Breastfeeding should be discontinued during treatment with Cytarabine Pfizer and for at least one week after the last dose or treatment should be discontinued, as this medicine may be harmful to breast-fed babies.

Fertility

Due to the potential risk of infertility after treatment, you should consider the possibility of preserving sperm before starting treatment with cytarabine.

Driving and using machines

Cytarabine has a mild or moderate influence on the ability to drive and use machines due to adverse reactions (such as alteration of normal brain function and dizziness).

Cytarabine Pfizer contains sodium

This medicine contains 2.67 mg of sodium (a major component of table salt/cooking salt) in each milliliter. This is equivalent to 0.13% of the maximum recommended daily intake of sodium for an adult.

This medicine contains 13.35 mg of sodium (a major component of table salt/cooking salt) in each 5 ml vial. This is equivalent to 0.67% of the maximum recommended daily intake of sodium for an adult.

This medicine contains 66.75 mg of sodium (a major component of table salt/cooking salt) in each 25 ml vial. This is equivalent to 3.34% of the maximum recommended daily intake of sodium for an adult.

3. How to use Cytarabine Pfizer

Method and route of administration

Cytarabine should be administered only under the supervision of a doctor with experience in the use of this type of treatment. Consult your doctor or pharmacist if you have any doubts.

This medicine can be administered intravenously as a rapid injection (bolus) or infusion, subcutaneously, and intrathecally.

In case of doubt, consult your doctor or nurse again.

Posology

Your doctor will determine the dose and duration of treatment, as well as the most suitable route of administration for you, according to your condition, either as induction treatment or maintenance treatment, and according to your weight or body surface area and response to treatment.

Your doctor will indicate the number of treatment cycles you need.

During treatment, you will require frequent examinations, including blood tests. Your doctor will tell you how often you need to do this and will perform regular checks on:

• Blood to check if you have low blood cell counts that require treatment.
• Liver (also through blood tests) to check that cytarabine does not negatively affect its function.
• Kidneys (also through blood tests) to check that cytarabine does not negatively affect their function.
• Uric acid levels in the blood: cytarabine may increase uric acid levels in the blood. If your uric acid levels are too high, you may be given another medicine.

If you receive more Cytarabine Pfizer than you should

This medicine will be administered to you in the hospital, so it is unlikely that you will receive more cytarabine than you should; however, some of the known serious side effects of the medicine may appear, such as mouth ulcers, or the number of white blood cells and platelets (which contribute to blood clotting) in the blood may decrease. In such cases, you may need antibiotics or blood transfusions. Mouth ulcers can be treated to reduce discomfort during the healing process.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The side effects of cytarabine depend on the dose. The digestive tract is usually the most affected organ, as well as the blood.

Very common side effects (may affect more than 1 in 10 patients) include:

• Infections, generalized infection, pneumonia.
• Reduction in the number of red blood cells, white blood cells, and/or platelets in the blood.
• Depression of the bone marrow, i.e., alteration of the immune system with loss of the ability to fight infections or diseases.
• Alteration of normal brain function and cerebellum*, feeling of sleepiness*.
• Disorder of the cornea of the eye*.
• Accumulation of fluid in the lungs*, difficulty breathing*.
• Nausea, vomiting, diarrhea, inflammation or ulcers in the mouth or anus, abdominal pain.
• Liver alteration.
• Rash, hair loss.
• Fever, cytarabine syndrome (consists of muscle pain, bone pain, and sometimes chest pain, fever, conjunctivitis, rash, and discomfort, which usually appears 6-12 hours after administration and is treated with corticosteroids).
• Changes in the appearance of bone marrow and blood cells.

Common side effects (may affect up to 1 in 10 patients) include:

• Inflammation of a portion of the intestine with death of intestinal cells (necrotizing colitis)*.
• Ulcers on the skin, peeling*.

Side effects of unknown frequency (cannot be estimated from the available data) include:

• Severe allergic reaction.
• Inflammation at the injection site.
• Localized appearance of pus in the liver*.
• Fluid retention of allergic origin.
• Lack of appetite.
• Change in personality*.
• Toxicity to the nervous system, inflammation of the nerves, headache, dizziness, coma*, alterations in motor and sensory function of the peripheral nervous system* (when administered intrathecally), in children, a rare inflammatory disorder that causes damage to the material that covers the nerves (leukoencephalopathy) may appear, paralysis of the legs and lower part of the body (paraplegia), progressive ascending paralysis, progressive toxicity, seizures.
• Conjunctivitis (infection in an area of the eye that can occur with rash), conjunctivitis with hemorrhage*, blindness (when administered intrathecally).
• Inflammation of the tissue that covers the heart (pericarditis), slower than normal heart rate (sinus bradycardia).
• Heart disease (cardiomyopathy)*, increase in heart size (cardiomegaly)*.
• Obstruction and inflammation of the blood vessel where the injection is performed (thrombophlebitis).
• Sore throat, shortness of breath, inflammation of a part of the lung tissue*.
• Ulcer in the esophagus, inflammation in the esophagus, gastrointestinal ulcer*, presence of cysts in the intestinal wall*, peritonitis*, death of intestinal cells*, pancreatitis (inflammation of the pancreas).
• Yellowish color of the skin, liver damage*, increase in bilirubin levels*.
• Hives, skin spots, itching.
• Urinary retention, alteration in the kidneys.
• Chest pain.
• Reaction at the injection site.
• Rash on the palms of the hands and soles of the feet.

• Due solely to high doses of cytarabine

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Medicines and Healthcare Products Agency (AEMPS) website: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Cytarabine Pfizer

Keep this medicine out of the sight and reach of children.

Store in the original packaging to protect from light between 15°C and 25°C until use.

Do not use this medicine after the expiry date which is stated on the carton and label after EXP. The expiry date is the last day of the month stated.

Do not use this medicine if you notice signs of deterioration.

Disposal of unused medicine and all materials derived from its use will be carried out in accordance with local regulations for cytotoxic agents.

6. Contents of the pack and further information

Composition of Cytarabine Pfizer

• The active substance is cytarabine. Each milliliter of solution contains 20 mg of cytarabine.

A 5 ml vial contains 100 mg of cytarabine.

A 25 ml vial contains 500 mg of cytarabine.

• The other ingredients are sodium chloride, hydrochloric acid, sodium hydroxide, and water for injections.

Appearance of Cytarabine Pfizer and contents of the pack

It is presented as a clear, colorless or slightly yellowish solution in 5 and 25 ml vials.

• 5 ml vial in a pack of 1 vial.
• 25 ml vial in a pack of 1 vial.

Not all pack sizes may be marketed.

Marketing authorization holder

Pfizer, S.L.

Avda. de Europa, 20 B

Parque Empresarial La Moraleja

28108 Alcobendas (Madrid)

Spain

Manufacturer

Pfizer Service Company BV

Hoge Wei, 10

B-1930 Zaventem

Belgium

Date of last revision of this leaflet:December 2022.

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency for Medicines and Healthcare Products (AEMPS) http://www.aemps.gob.es/

This information is intended only for healthcare professionals

Administration of cytarabine, like the rest of cytostatics, should be performed by personnel with experience in the use of chemotherapy.

Method of administration

The solution can be administered intravenously as a rapid injection (bolus) or infusion, subcutaneously, and intrathecally. Cytarabine is not active orally. High total doses are better tolerated when administered as a bolus than as a slow infusion, although no clear difference has been demonstrated between the two types of administration. When cytarabine is administered intravenously at high doses or intrathecally, solvents containing benzyl alcohol should not be used. A common practice is to dilute with sodium chloride 9 mg/ml solution free of preservatives and use immediately.

The chemical and physical stability in use of infusion solutions has been demonstrated, and cytarabine is stable at concentrations between 0.1 mg/ml to 1.0 mg/ml in water for injections; 5% dextrose injection solution; and 0.9% sodium chloride injection solution, in PVC infusion bags for up to a maximum of 4 days at 25°C/60% relative humidity, exposed to ambient light, and at 2-8°C, protected from light.

From a microbiological point of view, the medicine, once diluted, should be used immediately. In case it is not used immediately, the in-use storage times and conditions are the responsibility of the user and normally should not be greater than 24 hours stored at 2-8°C, unless the dilution is carried out under controlled and validated aseptic conditions.

Intravenous administration

For intravenous administration (infusion), the recommended solutions for preparing the dilution are:

• Water for injections.
• 5% dextrose injection solution.
• 0.9% sodium chloride injection solution.

The infusion time for each dose is between 1 and 3 hours.

As with all parenteral medicines, intravenous mixtures should be inspected visually for clarity, particles, precipitates, changes in color, and leaks before administration, whenever the solution and container allow it. Solutions that show turbidity, particles, precipitates, changes in color, or leaks should not be used.