Zavedos

Package leaflet: Information for the user

ZAVEDOS 5 mg/5 ml powder and solvent for injectable solution for intravenous use, 10 mg powder for injectable solution for intravenous use

Idarubicin hydrochloride
Please read this leaflet carefully before you are given this medicine because it contains important information for you.

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

Contents of this leaflet:

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

1. What Zavedos is and what it is used for

Zavedos contains the active substance called idarubicin hydrochloride, which belongs to a group of medicines known as cytotoxic antibiotics used to treat tumours. Zavedos works by interfering with the growth of tumour cells.
Zavedos is used:

• in adults and children for the treatment of acute myeloid leukaemia, a blood cancer;
• in adults and children for the treatment of acute lymphocytic leukaemia, a blood cancer, when previous treatments have not worked or were not suitable.

2. What you must know before you are given Zavedos

Zavedos must not be administered to you if:

• you are allergic to idarubicin, to other medicines in the same group (anthracyclines or anthracenediones), or to any of the other ingredients of this medicine (listed in section 6);
• you have severe liver problems (severe hepatic insufficiency);
• you have severe kidney problems (severe renal insufficiency);
• you have severe heart problems (severe cardiomyopathy), severe arrhythmia, or have recently had a heart attack;
• you have a low number of blood cells (myelosuppression);
• you have previously received the maximum cumulative dose of idarubicin hydrochloride and/or other medicines belonging to the anthracycline and anthracenedione group (see section “Other medicines and Zavedos”);
• you are breastfeeding (see section “Pregnancy, breastfeeding and fertility”).

Warnings and precautions
Talk to your doctor or nurse before you are given Zavedos if:

• you have undergone cancer treatment (cytotoxic therapy) that may have caused toxic effects such as inflammation and ulcers in the mouth (stomatitis), reduced numbers of white blood cells, red blood cells, and platelets in the blood, and generalized infections in various parts of the body. Before starting treatment with Zavedos, these toxic effects should have disappeared or significantly diminished;

• you have or have previously had a heart problem. Zavedos can cause disturbances in heart function (cardiac toxicity), especially if you have previously had heart problems. Additionally, the risk of such disturbances increases if you are currently undergoing or have recently undergone radiotherapy to the chest area, if you have been treated with other anticancer medicines similar to Zavedos (called anthracyclines or anthracenediones), or if you are taking other medicines that affect heart function (e.g. trastuzumab). Trastuzumab (a medicine used in the treatment of certain cancers) may take up to 7 months to be eliminated from the body. Because trastuzumab can affect the heart, Zavedos must not be administered until 7 months after discontinuation of trastuzumab. If Zavedos is administered within this time interval, cardiac function must be closely monitored (see section “Other medicines and Zavedos”);

• you have a liver problem or kidney problem. In such cases, the toxic effects of Zavedos may be greater than expected, and your doctor will prescribe a lower dose of this medicine. Inform your doctor or nurse if any of the following conditions appear or worsen during treatment with Zavedos (also see section 4 “Possible side effects”):

• heart problems, which may include:

  • acute (occurring shortly after the start of treatment): increased or decreased heart rate and irregular heartbeat (arrhythmias). These disturbances are easily detected by electrocardiogram (ECG) and are usually not serious enough to require discontinuation of treatment;
  • delayed (occurring long after the start of treatment, sometimes 2-3 months later, or even months or years after treatment ends). The most common manifestations of delayed toxicity are:
    • inability of the heart to pump sufficient blood to meet the body's needs (heart failure or congestive heart failure). Common symptoms include: difficulty breathing (dyspnea), fluid accumulation in the lungs (pulmonary edema), swelling in other parts of the body, especially in the legs and ankles (dependent edema), enlargement of the heart (cardiomegaly) and liver (hepatomegaly), reduced urine output (oliguria), fluid accumulation in the abdomen (ascites) and in the space between the lungs and chest wall (pleural effusion), and abnormal heart rhythm (gallop rhythm). Sometimes, heart failure can be severe and lead to death;
    • inflammation of the membrane surrounding the heart (pericarditis);
    • inflammation of the heart muscle (myocarditis). Children are more likely to develop heart problems (see section “Children”).

• decrease in the total number of white blood cells (leukopenia) or of a specific type of white blood cells called neutrophils (neutropenia), or of platelets (thrombocytopenia), or of red blood cells (anemia). Typically, the decrease in white blood cells and platelets is most pronounced 10-14 days after starting treatment and returns to normal by day 21. Sometimes, the consequences of reduced blood cell counts can be serious, including fever, infections in various organs and in the bloodstream, shock, hemorrhage, reduced oxygen supply to the brain, and death;

• development of blood cancer (leukemia) that was not present before starting treatment with Zavedos (secondary leukemia). Leukemia may appear 1-3 years after completing treatment with Zavedos and is more likely if this medicine is given at high doses or in combination with other anticancer medicines;

• vomiting and inflammation of the mucous membranes of the mouth (stomatitis) and esophagus. In severe cases, ulcers of the mucosa, stomach, and intestines may occur, potentially leading to perforation and bleeding. Typically, these lesions resolve within three weeks of treatment;

• liver problems and kidney problems, as this increases the risk of systemic toxic effects from this medicine. Your doctor will adjust the dosage of Zavedos based on your condition;

• inflammation of the vein (phlebitis) where repeated injections of Zavedos have been administered, inflammation and blockage of the vein (thrombophlebitis), or leakage of the medicine from the vein where the needle was inserted (extravasation). In case of extravasation, local pain, blistering, and redness of the skin may occur, and in more severe cases, necrosis may develop. Therefore, administration of Zavedos must be immediately discontinued. These risks can be avoided by strictly following the instructions for intravenous administration of Zavedos;

• excessive increase in the level of uric acid in the blood;

• inflammation and formation of blood clots in veins, primarily in the legs and pelvis (thrombophlebitis) and in the lungs (pulmonary embolism).

You may notice red-colored urine, which may last up to 1-2 days after administration of Zavedos.

During treatment with Zavedos, you must not receive a vaccination with live or attenuated vaccines (e.g. yellow fever vaccine), as serious or even fatal infections may occur due to your weakened immune defenses. However, you may receive killed or inactivated vaccines, although the effectiveness of such vaccination may be reduced. Therefore, consult your doctor before receiving any vaccination.

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”). Ask your doctor for advice if you wish to have children after treatment with Zavedos.

Before and during treatment with Zavedos, your doctor will perform frequent and regular laboratory tests to monitor your condition and assess the effectiveness of this medicine.

Children
Newborns and children are more susceptible to the cardiac toxic effects of Zavedos. Therefore, periodic and long-term monitoring of heart function is necessary.

Other medicines and Zavedos
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicines.

The following medicines may increase the effectiveness and/or toxic effects of Zavedos:

• cyclosporine (a medicine used to prevent organ transplant rejection);
• other anticancer medicines. When Zavedos is administered concomitantly with other anticancer drugs, toxic effects on the bone marrow may increase;
• medicines potentially toxic to the heart or medicines to lower blood pressure (calcium channel blockers). When Zavedos is administered together with these medicines, the risk of heart function disturbances (cardiac toxicity) may increase;
• oral anticoagulants (medicines used to reduce blood clot formation in veins);
• Medicines that affect kidney and/or liver function.

During treatment with Zavedos, you must not be vaccinated with live vaccines (e.g. yellow fever vaccine), as this may lead to a potentially fatal condition (fatal systemic vaccine disease). If deemed necessary by your doctor, an inactivated vaccine may be administered (see section “Warnings and precautions”).

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, are planning pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
Avoid becoming pregnant while you or your partner are undergoing treatment with Zavedos.
Zavedos may harm the unborn child; therefore, it is important to discuss with your doctor if pregnancy is suspected. If you are pregnant, your doctor will prescribe this medicine only if strictly necessary.

Contraception in women of childbearing potential
You must always use an effective contraceptive method during treatment with Zavedos and for at least 6.5 months after the last dose. Discuss suitable contraceptive methods with your doctor.

Contraception in men
Men must always use an effective contraceptive method during treatment with Zavedos and for at least 3.5 months after the last dose.

Breastfeeding
Do not breastfeed during treatment with Zavedos and for at least 14 days after the last dose, as part of the medicine may pass into breast milk and could harm the baby.

Fertility
Both men and women should seek information about fertility preservation before starting treatment.

Driving and use of machines
There are no data available to determine the effect of this medicine on the ability to drive vehicles or operate machinery.

3. How Zavedos is administered

Zavedos must be administered under the supervision of physicians experienced in cancer therapy with
anticancer drugs.
This medicinal product may only be used in suitable facilities (hospitals, clinics, and healthcare centers)
that ensure immediate and effective treatment of any complications, even severe ones, caused by the
disease or by therapy with Zavedos.
If considered necessary by the physician, Zavedos may be administered in combination with other
medicinal products for tumor treatment.

• Treatment of acute myeloid leukemia, a blood cancer
  In adults, the recommended dose is 8 mg/m² of body surface area per day for 5 days. When used in combination with cytarabine, the recommended dose is 12 mg/m² of body surface area per day for 3 days. In children, the recommended dose is 10–12 mg/m² of body surface area per day for 3 days in combination with cytarabine.
• Treatment of acute lymphocytic leukemia
  In adults, the recommended dose is 12 mg/m² of body surface area per day for 3 days. In children, the recommended dose is 10 mg/m² of body surface area per day for 3 days.

Your doctor will determine the most appropriate dose and frequency of administration of Zavedos (idarubicin hydrochloride) for you, based on your health status and concomitant use of other anticancer medicinal products.
Method of administration
Zavedos is administered to you intravenously.
If you have been given more Zavedos than you should have
If you think you have been given more Zavedos than required, inform your doctor or nurse immediately, as the following may occur:

• severe reduction in the number of all blood cells, such as white blood cells, red blood cells, and platelets (myelosuppression), usually within 1–2 weeks;
• serious heart problems within the first 24 hours. Heart damage may also appear several months after overdose with this medicinal product;
• intestinal bleeding and severe mucosal damage.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Immediately contact your doctor if you or your child experience any of the following side effects, as they may be serious:

• significant reduction in the production of blood cells (white blood cells, red blood cells, platelets) in the bone marrow
• heart problems (heart failure, cardiomyopathy) (see section 2 “Warnings and precautions”)
• inflammation of the vein (phlebitis) or inflammation and blockage of the vein (thrombophlebitis)
• bleeding inside the stomach and/or intestines
• blood infections (sepsis, septicaemia)
• blood cell tumours (acute myeloid leukaemia, myelodysplastic syndrome) (see section 2 “Warnings and precautions”)
• heart attack
• shock
• tissue death
• bleeding in the brain
• severe allergic reaction
• blockage of a vein by a blood clot (thromboembolism)

The following side effects may also occur:
Very common (may affect more than 1 in 10 people):

• infection
• loss of appetite (anorexia)
• inflammation and/or ulceration of the mucous lining of the mouth (mucositis, stomatitis)
• diarrhoea
• vomiting
• nausea
• abdominal pain
• burning sensation in the stomach
• hair loss (alopecia)
• reddish discoloration of the urine for 1 or 2 days after administration (see section 2 “Warnings and precautions”)
• fever
• headache
• chills

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

• bleeding
• decreased heart rate
• increased heart rate (tachycardia)
• abnormalities in the echocardiogram due to disturbances in heart function
• stomach ache
• increased liver enzymes and bilirubin, a substance produced by the liver
• skin rash
• itching
• increased sensitivity of skin exposed to radiation

Uncommon (may affect up to 1 in 100 people):

• dehydration
• increased levels of uric acid in the blood (hyperuricaemia)
• abnormalities in the electrocardiogram (ECG) due to disturbances in heart function
• inflammation of the oesophagus (oesophagitis)
• inflammation of part of the intestine (colitis)
• darker pigmentation of the skin and nails (hyperpigmentation)
• hives
• cellulitis

Very rare (may affect up to 1 in 10,000 people):

• inflammation of the outer surface or muscle of the heart (pericarditis/myocarditis)
• changes in heart rate
• hot flushes
• stomach lesions
• tingling, burning, inflammation and swelling of the palms of the hands and soles of the feet (acral erythema)

Not known (frequency cannot be estimated from the available data):

• reduction in the number of all blood cells (pancytopenia)
• breakdown of tumour cells (tumour lysis syndrome)
• local reaction

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor or pharmacist. You can also report side effects directly via the national reporting system at 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 Zavedos

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton, vial, and bottle after "Exp.". 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. Any unused portion of the solution should be discarded.
Do not dispose of medicines via wastewater or household waste. Healthcare professionals know how to dispose of unused medicines properly. This will help protect the environment.

6. Package contents and other information

What Zavedos contains
The active substance is idarubicin hydrochloride.
Zavedos 5 mg/5 ml powder and solvent for injectable solution
Each vial of powder contains 5 mg of idarubicin hydrochloride.
The other component is lactose.
The solvent vial contains water for injections.
Zavedos 10 mg powder for injectable solution
Each vial of powder contains 10 mg of idarubicin hydrochloride.
The other component is lactose.

Description of the appearance of Zavedos and contents of the pack
Zavedos 5 mg/5 ml powder and solvent for injectable solution is available in a pack containing 1 glass vial with rubber stopper and aluminium seal + 1 glass solvent vial of 5 ml.
Zavedos 10 mg powder for injectable solution is available in a pack containing 1 glass vial with rubber stopper and aluminium seal.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Pfizer Italia S.r.l.
Via Isonzo, 71
04100 Latina
Manufacturer
Corden Pharma Latina S.p.A, Via Murillo, 7 - 04013 Sermoneta, Latina (Italy)

The following information is intended exclusively for physicians or healthcare professionals

Reconstitution information:
From a chemical and physical standpoint, the reconstituted solution is chemically stable for 48 hours if
stored at 2°C/8°C and for 24 hours at room temperature.
Discard any unused portion of the solution.
From a microbiological standpoint, the reconstituted solution should be used immediately. If not used
immediately, the duration and conditions of storage are under the responsibility of the user and should
normally not exceed 24 hours between 2°C and 8°C, unless reconstitution has taken place under controlled
and validated aseptic conditions.

Incompatibilities
Zavedos (idarubicin hydrochloride) must not be mixed with heparin, as this may lead to precipitate formation.
It is also not advisable to mix Zavedos (idarubicin hydrochloride) with other medicinal products.
Prolonged contact with any alkaline pH solution should be avoided, as this would result in drug degradation.

Dosage
Acute Myeloid Leukemia (AML)
Adults: the recommended dose of Zavedos (idarubicin hydrochloride) is 12 mg/m² intravenously daily for 3 days in combination with cytarabine.
An alternative dosage regimen used in AML, either as monotherapy or in combination, is 8 mg/m² intravenously daily for 5 days.
Children: the recommended intravenous dose of Zavedos (idarubicin hydrochloride) is 10–12 mg/m² daily for 3 days in combination with cytarabine.
NOTE: These are general guidelines. For precise dosing, refer to individual protocols.

Acute Lymphoblastic Leukemia (ALL)
Adults: in monotherapy, the recommended dose is 12 mg/m² intravenously daily for 3 days.
Children: in monotherapy, the recommended dose is 10 mg/m² intravenously daily for 3 days.
NOTE: These are general guidelines. For precise dosing, refer to individual protocols.
The suggested dosage regimens should always be adjusted according to the patient's hematological status and, in combination regimens, according to the doses of other cytotoxic agents.
Dosage is usually calculated based on body surface area.

Method of administration
Zavedos must be administered only by intravenous route.
The reconstituted solution should be administered intravenously over 5–10 minutes through the side port of an ongoing physiological saline infusion, after ensuring that the needle is properly positioned within the vein. This technique reduces the risk of thrombosis or perivenous extravasation, which may lead to severe cellulitis and necrosis.
Phlebitis may occur if the injection is administered into small vessels or repeatedly into the same vein.

Special precautions for disposal and handling
The vial containing the powder for reconstitution is under negative pressure to prevent aerosol formation during reconstitution; particular caution should be exercised when inserting the needle into the vial.
Avoid inhaling any aerosol that may be generated during reconstitution.
To prepare the injectable solution, the contents of the Zavedos Powder for Injectable Solution vial should be dissolved in Water for Injections. The volumes of diluent to be used are: 5 mL for the 5 mg vial and 10 mL for the 10 mg vial.
The following safety measures, applicable to all antineoplastic agents, are recommended:

• personnel should be trained in proper reconstitution and handling techniques;
• pregnant personnel should be excluded from these tasks;
• personnel handling the drug should wear protective clothing: goggles, gowns, masks, and disposable gloves;
• a designated area should be established for drug reconstitution (preferably equipped with a vertical laminar flow system); the work surface should be protected with absorbent paper with a plastic backing;
• all materials used for reconstitution, administration, and cleaning, including gloves, should be placed in high-risk waste disposal bags for high-temperature incineration;
• in case of accidental contact of the drug with skin or eyes, immediately wash thoroughly with abundant water, water and soap, or a sodium bicarbonate solution, and seek medical attention;
• accidental spills or leaks of the drug should be decontaminated with a 1% sodium hypochlorite solution, followed by rinsing with water;
• cleaning materials should be disposed of as described above.

For further information, consult the Summary of Product Characteristics.

Package leaflet: information for the user

ZAVEDOS 5 mg/5 ml injectable solution for intravenous use, 10 mg/10 ml injectable solution for intravenous use

Idarubicin hydrochloride
Please read this leaflet carefully before this medicine is administered to you as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult the doctor or nurse treating you or your child.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet:

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

1. What Zavedos is and what it is used for

Zavedos contains the active substance called idarubicin hydrochloride, which belongs to a group of
medicines known as cytotoxic antibiotics that act against tumours. Zavedos works by interfering with the
growth of tumour cells.
Zavedos is used:

• in adults and children for the treatment of acute myeloid leukaemia, a blood cancer;
• in adults and children for the treatment of acute lymphocytic leukaemia, a blood cancer, when previous treatments have not worked or were not suitable.

2. What you must know before you are given Zavedos

Zavedos must not be administered to you if:

• you are allergic to idarubicin, to other medicines in the same group (anthracyclines or anthracenediones), or to any of the other ingredients of this medicine (listed in section 6);
• you have severe liver problems (severe hepatic insufficiency);
• you have severe kidney problems (severe renal insufficiency);
• you have severe heart problems (severe cardiomyopathy), severe arrhythmia, or have recently had a heart attack;
• you have a low number of blood cells (myelosuppression);
• you have previously received the maximum cumulative dose of hydrochloride idarubicin and/or of other medicines belonging to the anthracycline and anthracenedione group (see section “Other medicines and Zavedos”);
• you are breastfeeding (see section “Pregnancy, breastfeeding and fertility”).

Warnings and precautions
Please speak with your doctor or nurse before Zavedos is administered to you, if:

• you have previously undergone cancer treatment (cytotoxic therapy) that may have caused toxic effects such as inflammation and ulcers in the mouth (stomatitis), reduced numbers of white blood cells, red blood cells, and platelets in the blood, and generalized infections throughout the body. Before starting treatment with Zavedos, these toxic effects must have disappeared or significantly diminished;
• you currently suffer or have previously suffered from a heart condition. Zavedos may cause disturbances in heart function (cardiac toxicity), especially if you have previously had heart problems. Moreover, the risk of such disturbances increases if you are currently undergoing or have recently undergone radiotherapy to the chest area, if you have been treated with other anticancer medicines similar to Zavedos (called anthracyclines or anthracenediones), or if you are taking other medicines that affect heart function (e.g. trastuzumab). Trastuzumab (a medicine used in the treatment of certain cancers) may take up to 7 months to be eliminated from the body. Since trastuzumab can affect the heart, Zavedos must not be administered until 7 months after stopping trastuzumab. If Zavedos is administered within this time period, heart function must be closely monitored (see section “Other medicines and Zavedos”);
• you have a liver condition or kidney problems. In such cases, the toxic effects of Zavedos may be greater than expected, and your doctor will prescribe a lower dose of this medicine. Inform your doctor or nurse if any of the following conditions appear or worsen during treatment with Zavedos (also see section 4 “Possible side effects”):
• heart problems, which may include:
  • acute (occurring shortly after starting treatment): increased or decreased heart rate and irregular heartbeat (arrhythmias). These disturbances are easily detectable by electrocardiogram (ECG) and are usually not serious enough to require discontinuation of treatment;
  • delayed (appearing long after the start of treatment, sometimes 2-3 months later, or even months or years after treatment ends). The most common manifestations of delayed toxicity are:
    • inability of the heart to pump sufficient blood to meet the body’s needs (heart failure or congestive heart failure). Common symptoms include: difficulty breathing (dyspnea), fluid accumulation in the lungs (pulmonary edema), swelling in other parts of the body, especially in the legs and ankles (dependent edema), enlargement of the heart (cardiomegaly) and liver (hepatomegaly), reduced urine output (oliguria), fluid accumulation in the abdomen (ascites) and in the space between the lungs and chest wall (pleural effusion), and abnormal heart rhythm (gallop rhythm). Sometimes, heart failure can be severe and lead to death;
    • inflammation of the membrane surrounding the heart (pericarditis);
    • inflammation of the heart muscle (myocarditis). Children are more likely to experience heart problems (see section “Children”).
• decreased total number of white blood cells (leukopenia) or of a specific type of white blood cells called neutrophils (neutropenia), or decreased platelets (thrombocytopenia), or decreased red blood cells (anemia). Typically, the reduction in white blood cells and platelets is most pronounced 10-14 days after starting treatment and returns to normal by day 21. Sometimes, the consequences of reduced blood cells can be severe, including fever, infections in various organs and in the bloodstream, shock, bleeding, reduced oxygen supply to the brain, and death;
• development of blood cancer (leukemia) not present before starting treatment with Zavedos (secondary leukemia). Leukemia may appear 1-3 years after completing treatment with Zavedos and is more likely to occur if this medicine is given at high doses or in combination with other anticancer medicines;
• nausea and vomiting, and inflammation of the mucous membranes of the mouth (stomatitis) and esophagus. In severe cases, ulcers of the mucosa, stomach, and intestine may develop, potentially leading to perforation and bleeding. Typically, these lesions resolve within three weeks of treatment;
• liver and kidney problems, as the risk of systemic toxic effects from this medicine increases. Your doctor will adjust the dosage of Zavedos based on your condition;
• inflammation of the vein (phlebitis) where repeated injections of Zavedos have been administered, inflammation and blockage of the vein (thrombophlebitis), or leakage of the medicine from the vein where the needle was inserted (extravasation). In case of extravasation, local pain, blistering, and redness of the skin may occur, and in more severe cases, necrosis may develop. Therefore, administration of Zavedos must be immediately stopped. These risks can be avoided by strictly following the instructions for intravenous administration of Zavedos;
• excessive increase in the level of uric acid in the blood;
• inflammation and formation of blood clots in veins, primarily in the legs and pelvis (thrombophlebitis) and in the lungs (pulmonary embolism). You may notice red-colored urine lasting up to 1-2 days after administration of Zavedos.

During treatment with Zavedos, you must not receive vaccinations with live or attenuated vaccines (e.g. yellow fever vaccine), as severe or even fatal infections may occur due to your weakened immune defenses. However, you may receive inactivated or killed vaccines, although their effectiveness may be reduced. Therefore, consult your doctor before receiving any vaccination.
Zavedos may affect male fertility. Discuss fertility preservation with your doctor before starting treatment. Both men and women must use effective contraception methods (see section “Pregnancy, breastfeeding and fertility”). Consult your doctor if you wish to have children after treatment with Zavedos.
Before and during treatment with Zavedos, your doctor will perform frequent and regular laboratory tests to monitor your condition and the effectiveness of this medicine.

Children
Newborns and children are more susceptible to the cardiac toxic effects of Zavedos. Therefore, heart function must be periodically monitored over a prolonged period.

Other medicines and Zavedos
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicines.
The following medicines may increase the efficacy and/or toxic effects of Zavedos:

• cyclosporine (a medicine used to prevent organ transplant rejection);
• other anticancer medicines. When Zavedos is administered concomitantly with other anticancer drugs, toxic effects on the bone marrow may increase;
• medicines potentially toxic to the heart or medicines to lower blood pressure (calcium channel blockers). When Zavedos is administered together with these medicines, the risk of heart function disturbances (cardiac toxicity) may increase;
• oral anticoagulants (medicines used to reduce blood clot formation in veins);
• Medicines that affect kidney and/or liver function.

During treatment with Zavedos, you must not be vaccinated with live vaccines (e.g. yellow fever vaccine), as this may lead to a potentially fatal condition (fatal systemic vaccine-related disease). If deemed necessary by your doctor, an inactivated vaccine may be administered (see section “Warnings and precautions”).

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
Avoid becoming pregnant while you or your partner are undergoing treatment with Zavedos.
Zavedos may harm the unborn child; therefore, it is important to speak with your doctor if you think you may be pregnant. If you are pregnant, your doctor will prescribe this medicine only if strictly necessary.

Contraception in women of childbearing potential
You must always use an effective contraceptive method during treatment with Zavedos and for at least 6.5 months after the last dose. Discuss suitable contraceptive methods with your doctor.

Contraception in men
Men must always use an effective contraceptive method during treatment with Zavedos and for at least 3.5 months after the last dose.

Breastfeeding
Do not breastfeed during treatment with Zavedos and for at least 14 days after the last dose, as part of the medicine may pass into breast milk and could harm the baby.

Fertility
Both men and women should discuss fertility preservation options with their doctor before starting treatment.

Driving and using machines
There are no available data on the effect of this medicine on the ability to drive vehicles or operate machinery.

3. How Zavedos is administered

Zavedos must be administered under the supervision of physicians experienced in cancer therapy with
anticancer drugs.
This medicinal product may only be used in suitable facilities (hospitals, clinics, and healthcare centers)
that ensure immediate and effective treatment of any complications, even severe ones, caused by the
disease or by therapy with Zavedos.
If considered necessary by the physician, Zavedos may be administered in combination with other
medicinal products for the treatment of cancer.

• Treatment of acute myeloid leukaemia, a blood tumour
  In adults, the recommended dose is 8 mg/m² of body surface area per day for 5 days. When used in combination with cytarabine, the recommended dose is 12 mg/m² of body surface area per day for 3 days. In children, the recommended dose is 10–12 mg/m² of body surface area per day for 3 days in combination with cytarabine.
• Treatment of acute lymphocytic leukaemia
  In adults, the recommended dose is 12 mg/m² of body surface area per day for 3 days. In children, the recommended dose is 10 mg/m² of body surface area per day for 3 days.

Your doctor will determine the most appropriate dose and frequency of administration of Zavedos (idarubicin hydrochloride) for you, based on your health status and concomitant use of other anticancer medicinal products.
Method of administration
Zavedos is administered to you intravenously.
If you have been given more Zavedos than you should have
If you think you have been given more Zavedos than required, inform your doctor or nurse immediately, as the following may occur:

• severe reduction in the number of all blood cells, such as white blood cells, red blood cells, and platelets (myelosuppression), usually within 1–2 weeks;
• serious heart problems within the first 24 hours. Heart damage may also occur several months after overdose with this medicinal product;
• intestinal bleeding and severe mucosal damage.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Immediately contact your doctor if you or your child experience any of the following side effects, as they may be serious:

• marked reduction in the production of blood cells (white blood cells, red blood cells, platelets) in the bone marrow
• heart problems (heart failure, cardiomyopathy) (see section 2 "Warnings and precautions")
• inflammation of a vein (phlebitis), or inflammation and blockage of a vein (thrombophlebitis)
• bleeding inside the stomach and/or intestines
• blood infections (sepsis, septicemia)
• blood cell cancers (acute myeloid leukemia, myelodysplastic syndrome) (see section 2 "Warnings and precautions")
• heart attack
• shock
• tissue death
• bleeding in the brain
• severe allergic reaction
• blockage of a vein by a blood clot (thromboembolism)

The following side effects may also occur:
Very common (may affect more than 1 in 10 people):

• infection
• loss of appetite (anorexia)
• inflammation and/or ulceration of the mouth lining (mucositis, stomatitis)
• diarrhoea
• vomiting
• nausea
• abdominal pain
• burning sensation in the stomach
• hair loss (alopecia)
• reddish discoloration of urine for 1 or 2 days after administration (see section 2 "Warnings and precautions")
• fever
• headache
• chills

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

• bleeding
• decreased heart rate
• increased heart rate (tachycardia)
• abnormalities in the echocardiogram due to heart function disorders
• stomach ache
• increased liver enzymes and bilirubin, a substance produced by the liver
• skin rash
• itching
• increased sensitivity of skin exposed to radiation

Uncommon (may affect up to 1 in 100 people):

• dehydration
• increased levels of uric acid in the blood (hyperuricaemia)
• abnormalities in the electrocardiogram (ECG) due to heart function disorders
• inflammation of the oesophagus (oesophagitis)
• inflammation of part of the intestine (colitis)
• darker pigmentation of the skin and nails (hyperpigmentation)
• urticaria
• cellulitis

Very rare (may affect up to 1 in 10,000 people):

• inflammation of the outer surface or muscle of the heart (pericarditis/myocarditis)
• changes in heart rhythm
• hot flushes
• stomach lesions
• tingling, burning, inflammation and swelling of the palms of the hands and soles of the feet (acral erythema)

Not known (frequency cannot be estimated from the available data):

• reduction in the number of all blood cells (pancytopenia)
• breakdown of tumour cells (tumour lysis syndrome)
• local reaction

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, inform your doctor or pharmacist. You can also report side effects directly via the national reporting system at 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 Zavedos

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial after "Exp.". The expiry date refers to the last day of that month.
Store in a refrigerator (2°C – 8°C). Keep in the original packaging to protect the medicine from light.
Do not dispose of any medicine via wastewater or household waste. Healthcare professionals know how to safely dispose of unused medicines. This will help protect the environment.

6. Package contents and other information

What Zavedos contains
The active substance is idarubicin hydrochloride.
Zavedos 5 mg/5 ml injectable solution
Each vial contains 5 mg of idarubicin hydrochloride.
The other components are: glycerol, hydrochloric acid and water for injections.
Zavedos 10 mg/10 ml injectable solution
Each vial contains 10 mg of idarubicin hydrochloride.
The other components are: glycerol, hydrochloric acid and water for injections.

Description of the appearance of Zavedos and contents of the pack
Zavedos 5 mg/5 ml injectable solution is available in a pack containing 1 vial made of polypropylene with a rubber stopper and an aluminium and plastic seal cap.
Zavedos 10 mg/10 ml injectable solution is available in a pack containing 1 vial made of polypropylene with a rubber stopper and an aluminium and plastic seal cap.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Pfizer Italia S.r.l.
Via Isonzo, 71
04100 Latina
Manufacturer
Pfizer Service Company bvba - Hoge Wei 10, 1930 Zaventem (Belgium)

The following information is intended exclusively for physicians or healthcare professionals

Incompatibilities
Zavedos (idarubicin hydrochloride) must not be mixed with heparin, as this may lead to the formation
of a precipitate.
It is also not advisable to mix Zavedos (idarubicin hydrochloride) with other drugs.
Prolonged contact with any alkaline pH solution should be avoided, as this would result in
drug degradation.

Dosage
Acute myeloid leukemia (AML)
Adults: the recommended dose of Zavedos (idarubicin hydrochloride) is 12 mg/m² intravenously daily for 3 days in combination with cytarabine.
Another dosage regimen used in AML, either as monotherapy or in combination, is 8 mg/m² intravenously daily for 5 days.
Children: the recommended intravenous dose of Zavedos (idarubicin hydrochloride) is 10–12 mg/m² daily for 3 days in combination with cytarabine.
NOTE: These are general guidelines. For precise dosing, refer to individual protocols.

Acute lymphoblastic leukemia (ALL)
Adults: in monotherapy, the recommended dose is 12 mg/m² intravenously daily for 3 days.
Children: in monotherapy, the recommended dose is 10 mg/m² intravenously daily for 3 days.
NOTE: These are general guidelines. For precise dosing, refer to individual protocols.
The suggested dosage regimens should always be adjusted according to the patient's hematological status and, in combination therapy, according to the doses of other cytotoxic drugs.
Dosage is usually calculated based on body surface area.

Method of administration
Zavedos must be administered only by intravenous route.
The ready-to-use solution should be administered intravenously over 5–10 minutes through the administration set of an ongoing physiological saline infusion, after ensuring that the needle is properly positioned within the vein. This technique reduces the risk of thrombosis or perivenous extravasation, which may lead to severe cellulitis and necrosis.
Phlebitis may occur when the injection is administered into small vessels or repeated in the same vein.

Special precautions for disposal and handling
The following safety measures, applicable to all antineoplastic agents, are recommended:

• personnel should be trained in proper reconstitution and handling techniques;
• pregnant personnel must be excluded from these tasks;
• personnel handling the drug should wear protective clothing: goggles, gowns, masks, and disposable gloves;
• a specific area should be designated for drug reconstitution (preferably equipped with a vertical laminar flow system); the work surface should be protected with absorbent paper with a plastic backing;
• all items used for reconstitution, administration, and cleaning, including gloves, should be placed in leak-proof, high-risk waste bags for high-temperature incineration;
• in case of accidental contact of the drug with skin or eyes, immediately flush thoroughly with abundant water, water and soap, or a sodium bicarbonate solution, and seek medical assistance;
• accidental spills or leaks of the drug should be cleaned up with a 1% sodium hypochlorite solution, followed by rinsing with water;
• cleaning materials should be disposed of as described above.

For further information, consult the Summary of Product Characteristics.

Package leaflet: information for the user

ZAVEDOS 5 mg hard capsules, 10 mg hard capsules, 25 mg hard capsules

Idarubicin hydrochloride
Please read this leaflet carefully before taking this medicine because 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 pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Zavedos is and what it is used for
2. What you need to know before taking Zavedos
3. How to take Zavedos
4. Possible side effects
5. How to store Zavedos
6. Contents of the pack and other information

1. What Zavedos is and what it is used for

Zavedos contains the active substance called idarubicin hydrochloride, which belongs to a group of
medicines known as cytotoxic antibiotics that act against tumours. Zavedos works by interfering
with the growth of tumour cells.
Zavedos is used in adults for the treatment of a blood cancer known as acute non-lymphoblastic leukaemia, or for advanced breast cancer when previous treatments have not worked or were not suitable.
It may also be used in combination with other anti-cancer medicines.

2. What you should know before taking Zavedos

Do not take Zavedos:

• if you are allergic to idarubicin, to other medicines in the same group (anthracyclines or anthracenediones), or to any of the other ingredients of this medicine (listed in section 6);
• if you have severe liver problems (severe hepatic insufficiency);
• if you have severe kidney problems (severe renal insufficiency);
• if you have severe heart problems (severe cardiomyopathy), serious arrhythmia, or have recently had a heart attack;
• if you have a low number of blood cells (myelosuppression);
• if you have previously received the maximum cumulative dose of hydrochloride idarubicin and/or other medicines belonging to the anthracycline and anthracenedione group (see section “Other medicines and Zavedos”);
• if you are breastfeeding (see “Pregnancy, breastfeeding and fertility”).

Warnings and precautions
Talk to your doctor or pharmacist BEFORE taking Zavedos if:

• you have undergone cancer therapy (cytotoxic therapy) that may have caused toxic effects such as mouth inflammation and ulcers (stomatitis), reduced numbers of white blood cells, red blood cells and platelets in the blood, and generalized infections. Before starting treatment with Zavedos, these toxic effects must have disappeared or significantly diminished;
• you have or have previously had a heart problem. Zavedos can cause disturbances in heart function (cardiac toxicity), especially if you have previously had heart disorders. Moreover, the risk of such disturbances increases if you are currently undergoing or have recently undergone radiotherapy to the chest area, if you have been treated with other anticancer medicines similar to Zavedos (called anthracyclines or anthracenediones), or if you are taking other medicines that cause heart function disturbances (e.g. trastuzumab). Trastuzumab (a medicine used in the treatment of certain cancers) may take up to 7 months to be eliminated from the body. Since trastuzumab can affect the heart, Zavedos must not be administered until 7 months after discontinuation of trastuzumab. If Zavedos is administered within this time interval, cardiac function must be closely monitored (see section “Other medicines and Zavedos”);
• you have a liver problem or kidney problem. In such cases, the toxic effects of Zavedos may be greater than expected, and your doctor will prescribe a lower dose of this medicine.

Inform your doctor or pharmacist if any of the following conditions occur or worsen
during treatment with Zavedos (see also section 4 “Possible side effects”):

• heart problems, which may include:
  • acute (occurring immediately after the start of treatment): increased or decreased heart rate and disturbances in heartbeat rhythm (arrhythmias). These disturbances are easily detectable by electrocardiogram (ECG) and are usually not serious enough to require discontinuation of treatment with this medicine;
  • delayed (occurring long after the start of treatment, sometimes 2–3 months later, or even months or years after the end of treatment). The most common manifestations of delayed toxicity are:
    • inability of the heart to supply adequate blood flow to meet the body's needs (heart failure or cardiac insufficiency). The most common symptoms are: difficulty breathing (dyspnea), fluid accumulation in the lungs (pulmonary edema), swelling in other parts of the body, especially in the legs and ankles (dependent edema), enlargement of the heart (cardiomegaly) and liver (hepatomegaly), reduced urine production (oliguria), fluid accumulation in the abdomen (ascites) and in the space between the lungs and chest wall (pleural effusion), and abnormal heart rhythm (gallop rhythm). Sometimes, heart failure can be severe and lead to death;
    • inflammation of the membrane surrounding the heart (pericarditis);
    • inflammation of the heart muscle (myocarditis).
• decreased levels in the blood of total white blood cells (leukopenia) or of a specific type of white blood cells called neutrophils (neutropenia), or of platelets (thrombocytopenia), or of red blood cells (anemia). Typically, the decrease in white blood cells and platelets is maximal 10–14 days after the start of treatment and returns to normal levels by day 21. Sometimes, the consequences of reduced blood cell counts may be severe, including fever, infections in various organs and in the bloodstream, shock, hemorrhage, reduced oxygen supply to the brain, and death;
• development of blood cancer (leukemia) not present before starting treatment with Zavedos (secondary leukemia). Leukemia may appear 1–3 years after the end of treatment with Zavedos and is more likely to occur if this medicine is administered at high doses or in combination with other anticancer medicines;
• vomiting and inflammation of the mucous membranes of the mouth (stomatitis) and esophagus. In severe cases, ulcers of the mucosa, stomach, and intestines may also occur, potentially leading to perforation and bleeding. Typically, these lesions resolve within the third week of treatment;
• liver problems and kidney problems, as this increases the risk of systemic toxic effects from this medicine. Your doctor will adjust the dosage of Zavedos (idarubicin hydrochloride) according to your condition;
• excessive increase in the amount of uric acid in the blood;
• inflammation and formation of blood clots in veins, primarily in the legs and pelvis (thrombophlebitis) and in the lungs (pulmonary embolism).

During treatment with Zavedos, you may notice a red discoloration of the urine, which may last
up to 1–2 days after administration of this medicine.
During treatment with Zavedos, you must not receive a vaccination with vaccines known as
“live” or “attenuated” (e.g. yellow fever vaccine), because, due to weakened immune defenses,
severe or fatal infections may occur. However, you may receive vaccination with vaccines known as “killed” or “inactivated,” although the effectiveness of such vaccination may be reduced. Therefore, consult your doctor before receiving any vaccination.
Zavedos may affect male fertility. Discuss fertility preservation with your doctor before starting treatment. Both men and women must use effective contraceptive methods (see section “Pregnancy, breastfeeding and fertility”). Ask your doctor for advice if you wish to have children after treatment with Zavedos.
Before and during treatment with Zavedos, your doctor will perform frequent and regular laboratory tests to monitor your condition and the effectiveness of this medicine.

Other medicines and Zavedos
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
The following medicines may increase the efficacy and/or toxic effects of Zavedos:

• cyclosporine (a medicine used to prevent organ transplant rejection);
• other anticancer medicines. When Zavedos is administered concomitantly with other anticancer medicines, toxic effects on the bone marrow may increase;
• medicines potentially toxic to the heart or medicines to lower blood pressure (called “calcium channel blockers”). When Zavedos is administered concomitantly with these medicines, the risk of heart function disturbances (cardiac toxicity) may increase;
• oral anticoagulants (medicines used to reduce blood clot formation in veins);
• medicines that affect renal and/or hepatic function.

During treatment with Zavedos, you must not be vaccinated with live vaccines (e.g. yellow fever vaccine), as this may result in a potentially fatal condition (fatal systemic vaccine disease). If deemed necessary by your doctor, an inactivated vaccine may be administered (see section “Warnings and precautions”).

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
Avoid becoming pregnant while you or your partner are undergoing treatment with Zavedos.
Zavedos may harm the unborn child; therefore, it is important to discuss with your doctor if pregnancy is suspected. If pregnancy occurs, your doctor will prescribe this medicine only if strictly necessary.

Contraception in women of childbearing potential
You must always use an effective contraceptive method during treatment with Zavedos and for at least 6.5 months after the last dose. Discuss suitable contraceptive methods with your doctor.

Contraception in men
Men must always use an effective contraceptive method during treatment with Zavedos and for at least 3.5 months after the last dose.

Breastfeeding
Do not breastfeed during treatment with Zavedos and for at least 14 days after the last dose, as part of the medicine may pass into breast milk and could harm the baby.

Fertility
Both men and women should seek information on fertility preservation before starting treatment.

Driving and using machines
There are no data available to assess the effect of this medicine on the ability to drive vehicles or operate machinery.

3. How to take Zavedos

Take this medicine exactly as instructed by your doctor or pharmacist.
If you have any doubts, consult your doctor or pharmacist.
This medicine must be prescribed under the supervision of physicians experienced in cancer therapy with antineoplastic drugs.
If the doctor considers it necessary, they may decide to administer Zavedos in combination with other
medicines for cancer treatment.

• Treatment of blood cancer (acute non-lymphoblastic leukaemia) The recommended dose is 30 mg/m² of body surface area per day for 3 days. When used in combination with other antineoplastic medicines, the recommended dose is 15 to 30 mg/m² of body surface area per day for 3 days.
• Treatment of advanced breast cancer The recommended dose is 45 mg/m² of body surface area, taken either as a single dose or divided over 3 consecutive days (15 mg/m² per day). The treatment cycle should be repeated every 3–4 weeks, depending on your condition. When used in combination with other antineoplastic medicines, the recommended dose is 35 mg/m² of body surface area taken in a single

day.
Patients with liver problems
If your liver is not functioning properly, your doctor may decide to prescribe you a reduced dose.
Method of administration
Zavedos capsules must be taken orally and swallowed directly from the bottle to avoid direct skin contact.
Swallow the capsules whole with some water. The capsules must not be sucked, chewed, opened, or broken.
If the powder inside the capsules comes into accidental contact with eyes, skin, or mucous membranes, wash thoroughly with water and contact your doctor immediately.
It is recommended to take this medicine during a light meal.
If you take more Zavedos than you should
If you take an excessive dose of this medicine, inform your doctor immediately, as you may experience:

• severe reduction in the number of all blood cells, such as white blood cells, red blood cells, and platelets (myelosuppression), usually within 1–2 weeks;
• serious heart problems within the first 24 hours. Heart damage may also occur several months after overdose;
• intestinal bleeding and severe damage to mucous membranes.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Immediately contact your doctor if you experience any of the following side effects, as they may be serious:

• significant reduction in the production of blood cells (white blood cells, red blood cells, platelets) in the bone marrow
• heart problems (heart failure, cardiomyopathy) (see section 2 “Warnings and precautions”)
• inflammation of a vein (phlebitis) or inflammation and blockage of a vein (thrombophlebitis)
• bleeding into the stomach and/or intestine
• blood infections (sepsis, septicaemia)
• blood cell cancers (acute myeloid leukaemia, myelodysplastic syndrome) (see section 2 “Warnings and precautions”)
• heart attack
• shock
• tissue death
• bleeding in the brain
• severe allergic reaction
• blockage of a vein by a blood clot (thromboembolism)

The following side effects may also occur:
Very common (may affect more than 1 in 10 people):

• infection
• loss of appetite (anorexia)
• inflammation and/or ulceration of the mouth lining (mucositis, stomatitis)
• diarrhoea
• vomiting
• nausea
• abdominal pain
• burning sensation in the stomach
• hair loss (alopecia)
• reddish discoloration of the urine for 1 or 2 days after administration (see section 2 “Warnings and precautions”)
• fever
• headache
• chills

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

• bleeding
• decreased heart rate
• increased heart rate (tachycardia)
• abnormalities in the echocardiogram due to heart function disorders
• stomach ache
• increased liver enzymes and bilirubin, a substance produced by the liver
• skin rash
• itching
• increased sensitivity of skin exposed to radiation

Uncommon (may affect up to 1 in 100 people):

• dehydration
• increased levels of uric acid in the blood (hyperuricaemia)
• abnormalities in the electrocardiogram (ECG) due to heart function disorders
• inflammation of the oesophagus (oesophagitis)
• inflammation of part of the intestine (colitis)
• darker pigmentation of the skin and nails (hyperpigmentation)
• urticaria
• cellulitis

Very rare (may affect up to 1 in 10,000 people):

• inflammation of the outer surface or muscle of the heart (pericarditis/myocarditis)
• changes in heart rate
• hot flushes
• lesions in the stomach
• tingling, burning, inflammation, and swelling of the palms of the hands and soles of the feet (acral erythema)

Not known (frequency cannot be estimated from the available data):

• reduction in the number of all blood cells (pancytopenia)
• breakdown of tumour cells (tumour lysis syndrome)
• local reaction

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at the following address:
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 Zavedos

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial after "Exp.". The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Zavedos contains
The active substance is idarubicin hydrochloride.
Each 5 mg capsule contains 5 mg of idarubicin hydrochloride.
The other components are: microcrystalline cellulose, glyceryl palmitostearate.
The capsule shell contains gelatin, titanium dioxide (E171), and red iron oxide (E172).
Each 10 mg capsule contains 10 mg of idarubicin hydrochloride.
The other components are: microcrystalline cellulose, glyceryl palmitostearate.
The capsule shell contains gelatin, titanium dioxide (E171), and red iron oxide (E172).
Each 25 mg capsule contains 25 mg of idarubicin hydrochloride.
The other components are: microcrystalline cellulose, glyceryl palmitostearate.
The capsule shell contains gelatin and titanium dioxide (E171).

Description of the appearance of Zavedos and contents of the pack
The capsules are packaged in glass bottles.
Each bottle contains 1 hard capsule of 5 mg, or 10 mg, or 25 mg.

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

Manufacturer
5 mg and 10 mg capsules:
Corden Pharma Latina S.p.A.
Via Murillo, 7
04013 Sermoneta
Latina
Italy

25 mg capsules:
Actavis Italy S.p.A.
Viale Pasteur 10
20014 Nerviano (MI)
Italy