Prospecto: information for the patient

ZAVEDOS 1 mg/ml concentrate for solution for infusion

(Hydrochloride of idarubicin)

Read the entire prospect carefully before starting to use this medication, because it contains important information for you.

• Keep this prospect, as you may have to read it again.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only to you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor, pharmacist, or nurse, even if they are adverse effects that do not appear in this prospect. See section 4.

1.What is Zavedos and for what it is used

2.What you need to know before starting to use Zavedos

3.How to use Zavedos

4.Possible adverse effects

5Storage of Zavedos

6.Contents of the package and additional information

Zavedos is an anticancer antibiotic that belongs to the anthracyclines group and is used for the treatment of different types of cancers. This medication is administered via intravenous route. Zavedos acts by inhibiting the cell cycle, preventing the proliferation of cancerous cells.

Adults:

Zavedos may be used alone or in combination with other anticancer medications for the treatment of acute myeloid leukemia and acute lymphocytic leukemia as second-line treatment.

Children:

Zavedos may be used alone or in combination with other anticancer medications such as citarabina, for the treatment of acute myeloid leukemia as first-line treatment and acute lymphocytic leukemia as second-line treatment

No use Zavedos

- if you are allergic to idarubicin or any of the other components of this medication (listed in section 6) or to other cancer medications in the same group (anthracyclines or anthracenediones)

- if you have or have had severe liver and/or kidney problems

- if you have or have had uncontrolled infections

- if you have or have had severe heart problems or if you have recently had a myocardial infarction

- if your bone marrow function is decreased, that is, if your immune system is altered and you have lost the ability to fight infections or diseases

- if you have received previous treatment with maximum doses of this medication and/or other cancer medications in the same group (anthracyclines or anthracenediones)

- if you are breastfeeding your child, you must stop breastfeeding

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use Zavedos

• If you have recently had mouth ulcers (stomatitis), decreased neutrophil count (neutropenia), decreased platelet count (thrombocytopenia), or generalized infections. In these cases, your doctor must ensure that you have recovered before starting treatment with Zavedos.
• If you are or have been taking medications that can suppress heart contractions, if you have or have had any heart disease, if you have or have had heart problems, or if you have received radiation therapy in areas close to the heart.
• If during treatment you experience a decrease in red blood cells, white blood cells, and/or platelets.
• If you have received or are receiving treatment with other medications in the same group as Zavedos (anthracyclines).
• If you start to experience swelling, weight gain, pain without known cause, increased temperature, difficulty moving, and/or tingling, sensation of "choking" or difficulty breathing, faster heart rate, or chest pain, symptoms associated with thrombophlebitis or thromboembolic phenomena, seek immediate medical attention.
• If you have been previously treated with other therapies (medications, radiation therapy) that may have decreased bone marrow function.
• If you develop mouth ulcers and difficulty swallowing.
• If you have or have had liver or kidney problems.
• If you experience elevated uric acid levels, it will be necessary to monitor them and ensure adequate fluid intake.
• If you plan to be vaccinated, as a result of the administration of Zavedos, your ability to fight infections or diseases may be affected.
• If you are male, you must use effective contraceptive methods during treatment, as this medication may affect fertility. It is recommended that men who wish to become fathers in the future seek advice on sperm preservation before treatment.

Zavedos should only be administered under the supervision of experienced doctors in the use of medications for leukemia.

Inform your doctor or pharmacist if you are taking or have recently taken trastuzumab (a medication used to treat certain types of cancer). Trastuzumab may remain in the body for up to 7 months. As trastuzumab may affect the heart, do not use Zavedos until 7 months after stopping trastuzumab. If Zavedos is used before this time, your cardiac function must be closely monitored.

Your doctor will regularly check your condition to ensure that Zavedos is having the expected effect.

Before starting treatment with Zavedos and while you are receiving this medication, blood tests, liver function tests, kidney function tests, and heart function tests will be performed periodically. Since infants and children are more sensitive to the cardiotoxicity of anthracyclines, they should also undergo long-term follow-up to evaluate heart function.

This medication may cause a reddish discoloration of the urine for 1-2 days after administration.

Zavedos may affect male fertility. Discuss sperm preservation with your doctor before starting treatment. Both men and women should use effective contraceptive methods (see "Pregnancy, breastfeeding, and fertility").

If you wish to have children after treatment with Zavedos, discuss your options with your doctor.

Use of Zavedos with other medications

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

Zavedos may increase the adverse effects or modify the action of other medications, such as those used to treat heart problems, cancer, anticoagulants, or immunosuppressants (ciclosporin).

Concomitant use with live attenuated vaccines (e.g., yellow fever) is not recommended. A killed vaccine should be used if available.

Pregnancy, breastfeeding, and fertility

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

Pregnancy

Avoid becoming pregnant if you or your partner are receiving Zavedos treatment.

Zavedos may harm the fetus, so it is essential to inform your doctor if you think you are pregnant.

Contraception in fertile women

You must always use an effective birth control method (contraception) while receiving Zavedos and for at least 6.5 months after the last dose. Discuss suitable contraceptive methods with your doctor.

Contraception in men

Males must always use effective contraceptive methods while receiving Zavedos and for at least 3.5 months after the last dose.

Breastfeeding

Do not breastfeed while receiving Zavedos and for at least 14 days after the last dose, as part of the medication may pass into the milk and potentially harm your child.

Fertility

Both men and women should seek advice on preserving fertility before treatment.

Driving and operating machinery

The effect of Zavedos on the ability to drive and operate machinery is unknown.

Zavedos will be administered by a healthcare professional.

Zavedos is administered slowly through an intravenous infusion over a period of 5 to 10 minutes using a sodium chloride 0.9% or 5% dextrose solution.

Your doctor will determine the most suitable dose and treatment duration based on your condition and response to treatment. If you have any doubts, consult your doctor or nurse again.

Adults:

• In acute myeloid leukemia:

In adults, it is recommended to administer 12 mg/m 2 per day, intravenously, for 3 days in combination with citarabine (another cancer treatment medication). Zavedos can also be administered as a single medication or with other medications at a dose of 8 mg/m 2 , intravenously, for 5 days.

• In acute lymphocytic leukemia:

As a single medication, the recommended dose is 12 mg/m 2 per day, intravenously, for 3 days.

Children:

As a single medication, the recommended dose is 10 mg/m 2 per day, intravenously, for 3 days.

If the child is to be treated with idarubicin and another leukemia medication, such as citarabine, the recommended dose is between 10-12 mg/m 2 per day, intravenously, for 3 days.

Patients with altered liver and/or kidney function:

Your doctor will consider reducing the dose if your bilirubin and/or creatinine levels (substances used to assess liver and kidney function) are above 2 mg/dl. Zavedos should not be administered to patients with severe liver or kidney dysfunction.

If you receive more Zavedos than you should:

Although unlikely, if you receive more Zavedos than you should, you may experience some of the known side effects of the medication (mainly affecting the heart and bone marrow). If this occurs, appropriate supportive measures will be applied.

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

The very common side effects (may affect more than 1 in 10 patients) are:

• Infection.
• Decrease in platelets in the blood (thrombocytopenia), severe decrease in white blood cells (leucopenia, neutropenia), decrease in the number of red blood cells (anemia).
• Loss of appetite.
• Nausea, vomiting, inflammation of the mucous membrane of the mouth and/or gums (mucositis/stomatitis), diarrhea, abdominal pain or burning sensation.
• Hair loss.
• Red discoloration of urine for 1-2 days after administration.
• Fever, headache, chills.

The common side effects (may affect up to 1 in 10 patients) are:

• Decrease in heart rate (bradycardia),loss of the heart's ability to pump blood (congestive heart failure),increase in heart rate (tachycardia), alterations in heart rhythm (arrhythmias),decrease in the force with which the heart pumps blood (decrease in left ventricular ejection fraction), heart muscle disease (myocarditis).
• Bleeding (bleeding), local inflammation of a vein (phlebitis), inflammation and obstruction of a vein (thrombophlebitis).
• Gastrointestinal bleeding, stomach pain.
• Increased liver enzymes and bilirubin (substances used for liver function evaluation).
• Rash, itching (pruritus), increased sensitivity of the skin area exposed to radiation (“radiation recall reaction”).

The rare side effects (may affect up to 1 in 100 patients) are:

• Sepsis, septicemia.
• Secondary leukemia (acute myeloid leukemia and myelodysplastic syndrome).
• Dehydration.
• Hyperuricemia (increase in uric acid in the blood).
• Myocardial infarction and electrocardiogram alterations.
• Shock.
• Esophageal inflammation, inflammation of a part of the intestine (colitis, including severe enterocolitis and neutropenic enterocolitis with perforation).
• Red spots accompanied by itching (urticaria), skin and nail spots (hyperpigmentation), severe cellulitis, tissue necrosis.

The rare side effects (may affect up to 1 in 1000 patients) are:

• Cerebral hemorrhages.

The very rare side effects (may affect up to 1 in 10,000 patients) are:

• Severe generalized allergic reaction (anaphylaxis).
• Pericarditis and myocarditis inflammation of the tissue covering the heart, and deterioration of cardiac conduction from the atria to the ventricles (atrioventricular and branch block).
• Obstruction of a blood vessel with material transported by the blood (thromboembolism), hot flashes.
• Mucosal alterations of the stomach (erosion and ulceration in the stomach).
• Redness, sensitivity, and/or peeling of the palms of the hands and soles of the feet (acral erythema).

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

• Decrease in blood cells (pancytopenia).
• Tumor lysis syndrome.
• Local reaction.

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 prospectus. You can also report them directly through theSpanish System for Pharmacovigilance of Medicines for Human Use: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.

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Do not use this medication if you observe that the packaging is damaged or open.

Store the vial in the outer packaging to protect it from light. Store and transport refrigerated (between 2 °C and 8 °C).

This medication must be usedimmediately after opening the vial. If it is not used immediately, the storage times and conditions are the responsibility of the user.

Any unused product or residue will be disposed of in accordance with local regulations.

Composition of Zavedos

• The active ingredient is idarubicin hydrochloride
• The other components are: glycerol (E-422), hydrochloric acid (for pH adjustment), water for injectable preparations.

Appearance of the product and contents of the package

Zavedos 1 mg/mlconcentrated solution for infusionis presented in glass vials with a silicone halobutyl stopper sealed with an aluminum capsule with a plastic flip-off closure.

The vials are coated with a protective plastic called “ONCO-TAIN®”, to reduce the risk of spillage in case of breakage.

The product has a reddish orange color.

Zavedos 1 mg/ml concentrated solution for infusion is presented in vials of 5 ml, 10 ml and 20 ml packaged in cardboard boxes.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization:

Pfizer, S.L

Avda Europa 20B

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: June 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/

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This information is intended solely for healthcare professionals:

Zavedos should be administered by specialized personnel in chemotherapy for leukemias.

Protection measures:Due to the toxic nature of the compound, the following protection recommendations should be followed:

• Personnel should be instructed in handling techniques.
• Pregnant women should avoid handling this medication.
• Personnel handling idarubicin should wear protective clothing: protective glasses, gowns, gloves, and disposable masks.
• Handling should be performed in a designated area (preferably under laminar flow). The work surface should be protected with absorbent, plasticized, and disposable paper.
• All materials used for administration or cleaning, including gloves, should be disposed of in high-risk waste bags for destruction by high-temperature incineration.
• Any spill or leak should be treated with diluted sodium hypochlorite solution (1% available chlorine), preferably by soaking, and then with water.
• In case of accidental contact with the skin or eyes, it should be treated immediately with abundant water or soap and water or with a sodium bicarbonate solution.
• In case of eye contact, remove the eyelid(s) and wash the affected eye(s) with abundant water for at least 15 minutes. Then, seek medical attention.
• Wash hands thoroughly after removing gloves.
• Dispose of unused solution.

Disposal:

The disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations for cytotoxic agents.