Zavedos

Leaflet accompanying the packaging: patient information

Zavedos, 5 mg, powder for solution for injection

Zavedos, 10 mg, powder for solution for injection

Idarubicin hydrochloride

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. See section 4.

Table of contents of the leaflet

• 1. What is Zavedos and what is it used for
• 2. Important information before using Zavedos
• 3. How to use Zavedos
• 4. Possible side effects
• 5. How to store Zavedos
• 6. Contents of the pack and other information

1. What is Zavedos and what is it used for

Zavedos is a cytostatic medicine belonging to the group of anthracycline antibiotics used to treat the following blood cancers:

• Acute non-lymphoblastic leukemia (also known as acute myeloid leukemia). Zavedos induces remission in both first-line therapy and in patients with relapsed or refractory disease.
• Acute lymphoblastic leukemia - as a second-line drug.

Children:

• Acute myeloid leukemia - in combination with cytarabine as a first-line drug to induce remission.
• Acute lymphoblastic leukemia - as a second-line drug.

2. Important information before using Zavedos

When not to use Zavedos

• if the patient is hypersensitive to idarubicin or any of the other ingredients of this medicine (listed in section 6), other anthracyclines or anthracenediones,
• in patients with severe liver failure,
• in patients with severe kidney failure,
• with severe cardiomyopathy,
• in patients with severe heart failure,
• in patients with recent myocardial infarction,
• in patients with severe heart rhythm disorders,
• in patients with persistent bone marrow suppression,
• in patients previously treated with the maximum cumulative dose of idarubicin hydrochloride and/or other anthracyclines or anthracenediones,
• during breastfeeding.

Warnings and precautions

Zavedos should be used under the supervision of a doctor experienced in the administration of cytostatics (chemotherapy).
Treatment with Zavedos can be started after the acute symptoms of toxicity of previously used cytotoxic drugs have subsided, such as oral mucositis, neutropenia (reduced number of neutrophils), thrombocytopenia, and generalized infections.
Before starting treatment with Zavedos, the patient should discuss it with their doctor.

• In order to minimize the risk of severe heart damage, before starting treatment with Zavedos, the doctor should assess heart function and then monitor it during therapy. When the first symptoms of heart damage appear, the doctor should decide to discontinue the drug. The initial assessment of heart function should be performed using ECG (echocardiography) and ventriculography or echocardiography, especially in patients with increased risk of cardiotoxicity. The assessment of the left ventricular ejection fraction should be repeated, especially when the cumulative dose of anthracyclines taken by the patient is increased. During the entire observation period, the doctor should perform the assessment using the same method. Risk factors for cardiotoxicity are: active or latent cardiovascular disease, previous or concurrent irradiation of the mediastinum and/or pericardial area, previous treatment with other anthracyclines or anthracenediones, and concurrent use of drugs that may impair cardiac contractility or have cardiotoxic effects (e.g., trastuzumab). Patients should tell their doctor if they are taking or have recently taken trastuzumab (a drug used to treat certain cancers). Trastuzumab may remain in the body for up to 7 months. As trastuzumab may affect the heart, Zavedos should not be used for 7 months after the end of trastuzumab treatment. If Zavedos is used before this time, the patient's heart function should be closely monitored. The doctor should particularly closely monitor heart function in patients who have received high cumulative doses of the drug and in patients with risk factors. In infants and children, the susceptibility to cardiotoxicity of anthracyclines appears to be greater, so the doctor should perform long-term, periodic monitoring of heart function in these patients.
• Zavedos has a pronounced myelosuppressive effect (bone marrow suppression). In all patients who received a therapeutic dose of the drug, severe myelosuppression occurs. Before each treatment cycle with Zavedos and during its administration, the doctor should assess hematological parameters, including white blood cell count with smear. The main symptom of hematologic toxicity of the drug and the most common acute complication requiring dose reduction is dose-dependent, reversible leukopenia (reduced white blood cell count) and/or neutropenia (reduced number of neutrophils). Leukopenia and neutropenia usually have a severe course. Thrombocytopenia and anemia may also occur.
• There have been reports of secondary leukemias in patients treated with anthracyclines.
• Zavedos may cause vomiting. After administration of the drug, mucositis (mainly oral mucositis, less frequently esophageal mucositis) usually occurs quickly, which in severe cases can cause ulcers of the mucous membrane within a few days. In most patients, it resolves by the third week of treatment. Very rarely, severe gastrointestinal events (such as perforation or bleeding) have been observed.
• The doctor should assess liver and/or kidney function before starting and during therapy using standard laboratory tests (using bilirubin and creatinine serum levels as parameters).
• Administration of the drug into a small vessel or repeated administration into the same vein may cause venous wall fibrosis. Administration of the drug in accordance with the recommendations can minimize the risk of phlebitis and thrombophlebitis at the injection site.
• Extravasation of the drug during intravenous administration may cause local pain, severe tissue damage (blisters, severe connective tissue inflammation), and necrosis. If signs of extravasation occur during intravenous administration of the drug, the infusion should be stopped immediately.
• Zavedos may cause hyperuricemia (elevated uric acid levels in the blood), which is a result of increased purine catabolism accompanying the rapid breakdown of cancer cells under the influence of the drug ("tumor lysis syndrome"). After starting treatment, the doctor should assess uric acid, potassium, phosphate, and creatinine levels.
• Patients taking Zavedos should avoid live vaccinations. Inactivated vaccines (so-called "killed") can be administered, but the response to such vaccines may be weakened.
• The drug may cause urine to turn red for 1-2 days after administration.
• In men, Zavedos may affect fertility and cause irreversible infertility. Before starting treatment, patients should discuss fertility preservation with their doctor. Both women and men should use effective contraception methods (see "Pregnancy, breastfeeding, and fertility").
• Patients who plan to have children after completing treatment should be advised to consult a specialist.

Zavedos and other medicines

Tell your doctor about all medicines you are taking or have recently taken, as well as any medicines you plan to take.
The following medicines may interact with Zavedos:

• calcium channel blockers (e.g., verapamil) used to treat cardiovascular diseases,
• anticoagulants,
• live attenuated vaccines (e.g., yellow fever vaccine),
• cyclosporin A used to prevent transplant rejection.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, ask your doctor or pharmacist for advice before using this medicine.
Pregnancy
Pregnancy should be avoided if the woman or her partner is using Zavedos.
Zavedos has been shown to be harmful to the fetus, so it is essential to tell your doctor if you suspect pregnancy. Zavedos should not be used during pregnancy unless the potential benefits outweigh the risks to the fetus.
Contraception in women of childbearing age
Effective contraception methods should always be used during treatment with Zavedos and for at least 6.5 months after the last dose. Discuss contraception methods suitable for the woman and her partner with your doctor.
Contraception in men
Effective contraception methods should always be used during treatment with Zavedos and for at least 3.5 months after the last dose.
Breastfeeding
Do not breastfeed while using Zavedos and for at least 14 days after the last dose, as the drug may pass into human milk and harm the baby.
Fertility
Both women and men should consult their doctor about fertility preservation before starting treatment.

Driving and using machines

No studies have been conducted on the effect of Zavedos on the ability to drive and use machines.

Zavedos contains lactose

If you have been diagnosed with intolerance to some sugars, consult your doctor before taking the medicine.

3. How to use Zavedos

This medicine should always be used exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist.
Usually, the dose is calculated based on the patient's total body surface area.
Acute non-lymphoblastic leukemia/ acute myeloid leukemia
Adults: the recommended dose is 12 mg/m2 per day, intravenously, for 3 days, according to the combined treatment scheme with cytarabine.
Another dosing scheme used in monotherapy and combined treatment is 8 mg/m2 per day, intravenously, for 5 days.
Children: the recommended dose is 10-12 mg/m2 per day, intravenously, for 3 days, according to the combined treatment scheme with cytarabine.
Acute lymphoblastic leukemia
Adults: the recommended dose is 12 mg/m2 per day, intravenously, for 3 days in monotherapy.
Children: the recommended dose is 10 mg/m2 per day, intravenously, for 3 days in monotherapy.
However, the recommended dosing should be adjusted according to the patient's hematological disorders, and in the case of combined treatment, according to the doses of other cytotoxic drugs.
Liver and kidney failure
The doctor should consider reducing the dose in patients with bilirubin and/or creatinine levels above 2 mg%.

Using a higher dose of Zavedos than recommended

Very high doses of idarubicin hydrochloride may be toxic to the heart within 24 hours and cause severe bone marrow suppression within one to two weeks. Cases of delayed onset of heart failure have been reported even after several months of overdosing on anthracyclines.

Missing a dose of Zavedos

Do not take a double dose to make up for a forgotten dose.

Stopping treatment with Zavedos

The decision to stop treatment is made by the doctor.
If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Zavedos can cause side effects, although not everybody gets them.
Very common(may affect more than 1 in 10 people)

• infections
• thrombocytopenia (reduced platelet count)
• severe leukopenia (reduced white blood cell count)
• severe neutropenia (reduced number of neutrophils)
• anemia
• loss of appetite
• nausea
• vomiting
• mucositis (inflammation of the mucous membrane) of the mouth and/or stomach
• diarrhea
• abdominal pain or burning sensation
• hair loss
• red urine color for 1-2 days after administration
• fever
• headache
• chills

Common(may affect up to 1 in 10 people)

• congestive heart failure
• bradycardia (slow heart rate)
• sinus tachycardia (fast heart rate)
• tachyarrhythmia (heart rhythm disorder)
• asymptomatic reduction of left ventricular ejection fraction
• cardiomyopathy (heart muscle disease)
• bleeding
• local phlebitis
• thrombophlebitis
• gastrointestinal bleeding
• abdominal pain
• increased liver enzyme and bilirubin levels
• rash
• itching
• hypersensitivity of irritated skin

Uncommon(may affect up to 1 in 100 people)

• sepsis
• secondary leukemia (acute myeloid leukemia and myelodysplastic syndrome)
• dehydration
• hyperuricemia (elevated uric acid levels in the blood)
• myocardial infarction
• ECG abnormalities, such as non-specific ST-T changes
• shock
• esophagitis
• colitis
• urticaria
• excessive skin and nail pigmentation
• connective tissue inflammation
• necrosis

Rare(may affect up to 1 in 1,000 people)

• cerebral hemorrhage

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

• anaphylactic reaction
• pericarditis
• myocarditis
• atrioventricular block
• bundle branch block
• thromboembolic complications
• heat stroke
• ulcers or necrosis
• distal extremity erythema

Frequency not known(cannot be estimated from the available data)

• pancytopenia (reduced number of red blood cells, white blood cells, and platelets)
• tumor lysis syndrome
• local reactions

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder or its representative.

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 which is stated on the carton after EXP. The expiry date refers to the last day of that month.
Store in a temperature below 25°C.
The reconstituted solution can be stored at a temperature between 2°C and 8°C for 24 hours.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Zavedos contains

• The active substance of Zavedos is idarubicin hydrochloride. One vial contains 5 mg or 10 mg of idarubicin hydrochloride.
• The other ingredient is lactose.

What Zavedos looks like and contents of the pack

Red-orange powder.
A 5 ml or 10 ml glass vial with a rubber stopper and an aluminum cap, in a cardboard box.

Marketing authorization holder

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

Manufacturer

Actavis Italy S.p.A.
Viale Pasteur 10
20014 Nerviano (Milan)
Italy
To obtain more detailed information on this medicine, please contact the local representative of the marketing authorization holder:
Pfizer Polska Sp. z o.o.
tel. 22 335 61 00

Date of last revision of the leaflet: 11/2021

Information intended for healthcare professionals only:

Zavedos in the form of a reconstituted solution can only be administered intravenously. The infusion should be performed over 5 to 10 minutes through previously inserted cannulas for intravenous infusion, through which a 0.9% sodium chloride solution or 5% dextrose solution flows. Direct rapid injection of the drug is not recommended due to the risk of extravasation, which may occur even with proper placement of the needle in the vein, confirmed by the presence of blood during aspiration.
This technique limits the risk of thrombosis and extravasation of the drug around the vein, which could lead to severe complications in the form of connective tissue inflammation or necrosis.
After the injection, if the drug has been administered into small blood vessels or if repeated injections have been administered into the same vein, venous fibrosis may occur.
Incompatibilities
Zavedos should not be mixed with heparin due to the possibility of precipitation.
Mixing Zavedos with other medicines is also not recommended. Prolonged contact with a solution with a basic pH should be avoided, as it may cause the drug to degrade.
Zavedos in the form of a powder in a vial is under negative pressure, which is intended to prevent the formation of an aerosol during the preparation of the solution. Particular care should be taken when inserting the needle into the vial. Avoid inhaling any aerosol that may form during the dissolution of the drug.
Preparation of the solution
The contents of the 5 mg vial of idarubicin hydrochloride or 10 mg vial of idarubicin hydrochloride, powder for solution for injection, should be dissolved in 5 ml or 10 ml of water for injection, respectively.
The prepared solution is hypotonic, and therefore, during administration of the drug, the following precautions should be taken.

• personnel should be trained in the proper technique for preparing and administering the drug;
• women who are pregnant should be excluded from activities related to the administration of these drugs;
• workers handling the drug must wear protective clothing: goggles, gowns, masks, and single-use gloves;
• a dedicated area should be designated for preparing the solution (preferably with a vertical laminar airflow system); the work surface should be protected with an absorbent pad with a plastic backing;
• equipment used to dissolve and administer the drug, as well as to dispose of its residues, including gloves, should be placed in single-use bags for high-risk waste and incinerated at high temperature;
• accidental spills of the product should be neutralized with a diluted sodium hypochlorite solution (available chlorine content 1%), preferably by soaking, and then with water;
• in the event of eye contact, the eyelid(s) should be pulled back and the eye should be flushed with a large amount of water for at least 15 minutes. Then, medical help should be sought;
• any materials used to clean up spills of the drug should be disposed of as described above;
• after removing gloves, hands should always be washed;
• any unused product or waste should be disposed of in accordance with local regulations.