ZAVEDOS 1mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Patient Information Leaflet

ZAVEDOS 1 mg/ml concentrate for solution for infusion

(Idarubicina hydrochloride)

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.
• 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.

Contents of the pack

1. What is Zavedos and what is it used for
2. What you need to know before you use Zavedos
3. How to use Zavedos
4. Possible side effects

5 Storage of Zavedos

1. Contents of the pack and further information

1. What is Zavedos and what is it used for

Zavedos is an anticancer antibiotic belonging to the anthracycline group and is used to treat different types of cancer. This medicine is administered intravenously. Zavedos works by inhibiting the cell cycle, preventing the proliferation of cancer cells.

Adults:

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

Children:

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

2. What you need to know before you use Zavedos

Do not use Zavedos

• if you are allergic to idarubicina or any of the other ingredients of this medicine (listed in section 6) or to other anticancer medicines of the same group (anthracyclines or anthracenediones)
• if you have or have had severe liver and/or kidney problems
• if you have uncontrolled infections
• if you have or have had severe heart problems or if you have recently had a heart attack
• if your bone marrow function is decreased, i.e., your immune system is altered and you have lost the ability to fight infections or diseases
• if you have previously received treatment with maximum doses of this medicine and/or other anticancer medicines of the same group (anthracyclines or anthracenediones)
• if you are breastfeeding, you must stop breastfeeding

Warnings and precautions

Consult your doctor or pharmacist or nurse before starting treatment with 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 should ensure that you have recovered before starting treatment with Zavedos.
• If you are or have been treated with medicines that can suppress heart contraction, if you have or have had heart disease, if you have or have had cardiac 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 medicines of the same group as Zavedos (anthracyclines).
• If you start to experience swelling, feeling of weight, pain without known cause, increased temperature, difficulty moving, and/or tingling, feeling of "shortness of breath" or difficulty breathing, increased heart rate, or chest discomfort, symptoms associated with thrombophlebitis or thromboembolic phenomena, go immediately to your doctor.
• If you have been previously treated with other therapies (medicines, 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 have high levels of uric acid, it will be necessary to control them and ensure sufficient fluid intake.
• If you intend to get vaccinated, as a consequence of the administration of Zavedos, your ability to fight infections or diseases may be affected.
• If you are male, you should use effective contraceptive methods during treatment, as this medicine may alter fertility. It is recommended that men who wish to be fathers in the future seek advice on sperm preservation before treatment.

Zavedos should only be administered under the supervision of doctors with experience in the use of medicines for leukemia.

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

Your doctor will regularly check your condition to see if Zavedos is having the expected effect.

Before starting treatment with Zavedos and while you are being treated with this medicine, you will have regular blood tests, liver function tests, kidney function tests, and heart tests. Since infants and children are more sensitive to the toxicity of anthracyclines on the heart, they should also have long-term follow-up to evaluate heart function.

This medicine may cause a red coloration of the urine during 1-2 days after administration.

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

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

Using Zavedos with other medicines

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

It is possible that Zavedos may increase the side effects or alter the action of other medicines, such as those used for heart disorders, cancer treatment, anticoagulants, or immunosuppressants (ciclosporin).

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

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Pregnancy

Avoid becoming pregnant if you or your partner are being treated with Zavedos.

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

Contraception in women of childbearing age

You must always use an effective method of birth control (contraception) while receiving Zavedos and for at least 6.5 months after the last dose. Talk to your doctor about suitable contraceptive methods for you and your partner.

Contraception in men

Men should 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 some of the medicine may pass into breast milk and potentially harm your child.

Fertility

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

Driving and using machines

It is not known if Zavedos has any effect on the ability to drive and use machines.

3. How to use Zavedos

Zavedos will be administered by a healthcare professional.

Zavedos is administered slowly intravenously, through an intravenous infusion system, over 5 to 10 minutes with 0.9% sodium chloride or 5% dextrose.

Your doctor will determine the most suitable dose and duration of treatment according to your condition and response to treatment. If in doubt, consult your doctor or nurse again.

Adults:

• In acute myeloid leukemia:

In adults, it is recommended to administer 12 mg/m2 daily, intravenously, for 3 days in combination with cytarabine (another medicine used to treat cancer). Zavedos may also be administered as a single medicine or with other medicines at a dose of 8 mg/m2, intravenously, for 5 days.

• In acute lymphocytic leukemia:

As a single medicine, the recommended dose is 12 mg/m2 daily, intravenously, for 3 days.

Children:

As a single medicine, the recommended dose is 10 mg/m2 daily, intravenously, for 3 days.

If the child is to be treated with idarubicina and another medicine for leukemia, such as cytarabine, the recommended dose is 10-12 mg/m2 daily, intravenously, for 3 days.

Patients with altered liver and/or kidney function:

Your doctor will consider a dose reduction if you have bilirubin and/or creatinine levels (substances used to evaluate liver and kidney function) above 2 mg/dl. Zavedos should not be administered in patients with severe liver or kidney function alterations.

If you receive more Zavedos than you should

Although unlikely, if you receive more Zavedos than you should, some of the known side effects of the medicine may appear (mainly on the heart and bone marrow). If this happens, supportive measures will be applied.

4. Possible side effects

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

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

• Infection.
• Decrease in platelets in the blood (thrombocytopenia), severe decrease in white blood cells (leukopenia, neutropenia), decrease in red blood cells (anemia).
• Lack 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 coloration of the urine during 1-2 days after administration.
• Fever, headache, chills.

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

• Decreased heart rate (bradycardia), loss of heart's ability to pump blood (congestive heart failure), increased heart rate (tachycardia), alterations in heart rhythm (tachyarrhythmias), decreased heart's ability to pump blood (decreased left ventricular ejection fraction), heart muscle disease (myocardial disease).
• Bleeding (hemorrhage), local vein inflammation (phlebitis), vein inflammation and obstruction (thrombophlebitis).
• Gastrointestinal bleeding, stomach pain.
• Increased liver enzymes and bilirubin (substances used to evaluate liver function).
• Rash, itching (pruritus), increased sensitivity of the skin area exposed to radiation ("radiation recall reaction").

The uncommon side effects (may affect up to 1 in 100 people) are:

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

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

• Cerebral hemorrhage.

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

• Severe generalized allergic reaction (anaphylaxis).
• Inflammation of the tissue covering the heart (pericarditis) and the heart muscle tissue (myocarditis), deterioration of the conduction of cardiac impulses from the atria to the ventricles (atrioventricular and bundle branch block).
• Obstruction of a blood vessel with material transported by the blood (thromboembolism), hot flashes.
• Alterations of the stomach mucosa (erosion and ulceration in the stomach).
• Redness, sensitivity, and/or peeling of the palms of the hands and soles of the feet (palmar-plantar erythrodysesthesia).

The side effects with frequency not known (cannot be estimated from the available data) include:

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

Reporting of side effects

If you experience 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 through the Spanish Medicines Agency's website: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Zavedos

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

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

Do not use this medicine if you notice that the packaging is damaged or opened.

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

This medicine should be used immediately after opening the vial. If not used immediately, the in-use storage times and conditions are the responsibility of the user.

Any unused product or waste material should be disposed of in accordance with local regulations.

6. Contents of the pack and further information

Composition of Zavedos

• The active substance is idarubicina hydrochloride
• The other ingredients are: glycerol (E-422), hydrochloric acid (for pH adjustment), water for injections.

Appearance and packaging

Zavedos 1 mg/ml concentrate for solution for infusionis presented in transparent glass vials with a rubber stopper sealed with an aluminum cap with a plastic flip-off closure.

The vials are covered with a protective plastic called "ONCO-TAIN", to reduce the risk of spillage in case of breakage.

The product has an orange-red color.

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

Marketing authorization holder and manufacturer

Marketing authorization holder:

Pfizer, S.L.

Avda Europa 20B

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: June 2022

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

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This information is intended only for healthcare professionals:

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

Protective 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 medicine.
• Personnel handling idarubicina should wear protective clothing: protective glasses, gowns, gloves, and masks.
• Handling should be performed in a designated area (preferably under a laminar flow system). The work surface should be protected with absorbent, plasticized, and disposable paper.
• All material 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 skin or eyes, it should be treated immediately by washing with plenty of water or soap and water or with a sodium bicarbonate solution.
• In case of eye contact, remove the eyelid and wash the affected eye with plenty of water for at least 15 minutes. Then, seek medical attention.
• Always wash your hands after removing gloves.
• Discard unused solution.

Elimination:

Elimination of unused medicine and all materials that have come into contact with it should be carried out in accordance with local regulations for cytotoxic agents.