Product Information for the User

Citarabina Pfizer 20 mg/ml Injectable Solution and for Infusion

Read this entire product information carefully before starting to use this medication, as it contains important information for you.

• Keep this product information, as you may need to refer to it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this product information. See section 4.

1. What is Citarabina Pfizer and how is it used

2. What you need to know before starting to use Citarabina Pfizer

3. How to use Citarabina Pfizer

4. Possible adverse effects

5. Storage of Citarabina Pfizer

6. Contents of the package and additional information

Citarabina Pfizer is used in adults and in children. The active ingredient is citarabina.

Citarabina belongs to a group of medications called cytotoxics; these medications are used to treat acute leukemias (blood cancer characterized by having too many leukocytes in the blood), which includes prophylaxis and treatment of central nervous system involvement or CNS (meningeal leukemia). Citarabina interferes with the proliferation of cancerous cells, which are eventually destroyed.

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

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

Maintenance treatment is a lighter treatment to make the remission that manifests last as long as possible. Low doses of citarabina are used to maintain leukemia under control and prevent it from relapsing.

Do not use Citarabina Pfizer:

• If you are allergic to the active ingredient or any of the other components of this medication (listed in section 6).
• If you are already taking medications that reduce the ability of the bone marrow to produce blood cells.

Warnings and precautions

Consult your doctor or pharmacist before starting to use Citarabina Pfizer.

• If your bone marrow is affected, treatment should be initiated under close medical supervision.
• Citarabina significantly reduces the production of blood cells in the bone marrow. This can increase the risk of infections or bleeding. Blood cell counts may continue to decrease up to a week after stopping treatment. Your doctor will perform periodic blood tests and examine your bone marrow if necessary.
• If you have or have had liver or kidney problems. During treatment with citarabina, your liver and kidney functions should be monitored. If your liver and/or kidneys do not function properly before treatment, citarabina can only be administered with maximum caution.
• If you have or have had gout, as citarabina can cause elevated uric acid levels.
• Severe and sometimes life-threatening adverse effects may occur in the central nervous system, intestines, or lungs.
• If you are administered citarabina intravenously in combination with metotrexato intrathecally, as you may experience severe adverse effects in your nervous system, especially in young patients and adolescents.
• If you need to be vaccinated while on treatment with this medication, as live or attenuated virus vaccines should not be administered and the response to inactivated or killed vaccines may be reduced.

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

Children and adolescents

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

Other medications and Citarabina Pfizer

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

• If you receive medications containing 5-fluorocitosina (a medication used to treat fungal infections).
• If you take medications containing beta-acetildigoxina, which is used to treat certain heart conditions.
• If you take gentamicina (an antibiotic to treat bacterial infections).
• If you receive medications containing ciclofosfamida, vincristina, and prednisona, which are used in cancer treatment programs.
• If you are administered citarabina intravenously in combination with metotrexato intrathecally.

Pregnancy, breastfeeding, and fertility
If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor before using this medication.

Pregnancy

You should not become pregnant while you or your partner are being treated with citarabina. If you are a sexually active person, you are recommended to use effective contraceptive methods to avoid pregnancy during treatment, regardless of your sex. Citarabina can cause congenital anomalies, so it is essential to inform your doctor if you think you are pregnant. Both men and women should use effective contraceptive methods during treatment and for 6 months after.

Contraception in fertile women

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 in fertile ageshould always use highly effective contraceptive methods to prevent pregnancy during treatment and for 3 months after the last dose.

Breastfeeding

You should stop breastfeeding during treatment with Citarabina Pfizer and for at least one week after the last doseor stop treatment, as this medication may be harmful to infants.

Fertility

Due to the potential risk of infertility after treatment, you should consider preserving semen before starting treatment with citarabina.

Driving and operating machinery
Citarabina has a mild or moderate influence on the ability to drive or operate machinery due to adverse reactions (such as altered normal brain function and dizziness).

Citarabina Pfizer contains sodium

This medication contains 2.67 mg of sodium (main component of table salt/for cooking) per milliliter. This is equivalent to 0.13% of the maximum daily sodium intake recommended for an adult.

This medication contains 13.35 mg of sodium (main component of table salt/for cooking) per 5 ml vial. This is equivalent to 0.67% of the maximum daily sodium intake recommended for an adult.

This medication contains 66.75 mg of sodium (main component of table salt/for cooking) per 25 ml vial. This is equivalent to 3.34% of the maximum daily sodium intake recommended for an adult.

Method and Route of Administration

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

This medicationcan be administered via intravenous injection as a rapid bolus or infusion, subcutaneously, and intrathecally.

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

Dosage

Your doctor will establish the dosage and duration of treatment as well as the most suitable route of administration for you, according to your condition, whether as an induction treatment or as a 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 be responsible for performing regular tests of:

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

If you receive more Citarabina Pfizer than you should

This medication will be administered in the hospital, so it is unlikely that you will receivemore citarabina than you should; howeversome of the known severe side effects of the medication, such as mouth ulcers, may appear, or your white blood cell and platelet counts (which contribute to blood clotting) may decrease in the blood. In this case, you may need antibiotics or blood transfusions. Mouth ulcers can be treated to reduce discomfort during the healing process.

Like all medicines, this medicinecan cause side effects, although not everyone will experience them.

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

Frequent 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 its immune system with loss of the ability to fight infections or diseases.
• Alteration of the normal function of the brain and cerebellum*, feeling of sleepiness*.
• Corneal disorder 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 dysfunction.
• Rash, hair loss.
• Fever, citarabine 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 cells and blood cells.

Frequent 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, desquamation*.

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

• Severe allergic reaction.
• Inflammation at the injection site.
• Localized pus formation in the liver*.
• Retention of allergenic fluid.
• Loss 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 may appear a rare inflammatory disorder that causes damage to the material covering the nerves (leukoencephalopathy necrosis), paralysis of the legs and lower body (paraplegia), ascending progressive paralysis, progressive toxicity, convulsions.
• Conjunctivitis (infection in a part of the eye that may be accompanied by rash),conjunctivitis with hemorrhage*, blindness (when administered intrathecally).
• Inflammation of the tissue covering the heart (pericarditis),slower or irregular heart rhythm(sinus bradycardia).
• Heart disease (cardiomyopathy)*, enlargement of the heart (cardiomegaly)*.
• Obstruction and inflammation of the blood vessel where the injection is made (thrombophlebitis).
• Throat pain, 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*, inflammation of the pancreas (pancreatitis).
• Yellowish discoloration of the skin, liver damage*, increase in bilirubin levels*.
• Urticaria, skin rash, itching.
• Urinary retention, kidney dysfunction.
• Chest pain.
• Reaction at the injection site.
• Skin rash on the palms of the hands and soles of the feet.

*Due solely to high doses of citarabine

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through theSistema Español de Farmacovigilancia de Medicamentos de Uso Humano: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

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

Do not use this medication after the expiration date appearing on the box and label after CAD. The expiration date is the last day of the month indicated.

Do not use this medication if you observe signs of deterioration.

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

Citarabina Pfizer Composition

• The active ingredient is citarabine. Each milliliter of solution contains 20 mg of citarabine.

A vial of 5 ml contains 100 mg of citarabine.

A vial of 25 ml contains 500 mg of citarabine.

• The other components are sodium chloride, hydrochloric acid, sodium hydroxide, and water for injection preparations.

Appearance of Citarabina Pfizer and packaging contents

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

• Vial of 5 ml in a 1 vial box.
• Vial of 25 ml in a 1 vial box.

Only some packaging sizes may be commercially available.

Marketing Authorization Holder

Pfizer, S.L.

Avda. de Europa, 20 B

Parque Empresarial La Moraleja

28108 Alcobendas (Madrid)

Spain

Responsible for manufacturing

Pfizer Service Company BV

Hoge Wei, 10

B-1930 Zaventem

Belgium

Last review date of this leaflet:December 2022.

The detailed and updated information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

This information is intended solely for healthcare professionals

Citarabine administration, like the rest of the chemotherapeutic agents, should be performed by personnel with experience in the use of chemotherapy.

Administration form

The solution can be administered intravenously as a rapid injection (in bolus) or by infusion, subcutaneously, and intrathecally. Citarabine is not active orally. High total doses are better tolerated when administered in bolus than in slow infusion, although no clear difference has been demonstrated between the two types of administration. When citarabine 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 preservative-free and use immediately.

The chemical and physical stability of the infusion solutions has shown that citarabine is stable at concentrations between 0.1 mg/ml to 1.0 mg/ml in water for injection preparations; 5% dextrose injection; and 0.9% sodium chloride injection, in PVC infusion bags 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 times and conditions of stability in use are the responsibility of the user and normally should not exceed 24 hours stored between 2 and 8°C, unless the dilution is carried out in controlled and validated aseptic conditions.

Intravenous administration

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

• Water for injection preparations.
• 5% dextrose injection.
• 0.9% sodium chloride injection.

The infusion time for each dose ranges from 1 to 3 hours.

Like all parenteral medications, intravenous mixtures should be visually inspected to see if there is 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.