Zavedos

Package leaflet: Information for the patient

Zavedos, 1 mg/ml, solution for injection
Idarubicini hydrochloridum
Please read carefully the entire leaflet before use, as it contains
important information for the patient.

• Keep this leaflet for future reference.
• If you have any doubts, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents

1. What Zavedos is and what it is 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 Zavedos is and what it is used for

Zavedos contains the active substance idarubicin hydrochloride, which belongs to a group of medicines
called cytotoxic and antimitotic agents.
Zavedos is used in adult patients for the treatment of acute non-lymphoblastic leukemia
(both as first-line treatment and in patients with relapsed disease or refractory to therapy),
and acute lymphoblastic leukemia (as second-line treatment).
Zavedos is used in children for the treatment of acute myeloid leukemia in combination with cytarabine
(as first-line treatment), and acute lymphoblastic leukemia (as second-line treatment).

2. Important information before using Zavedos

When not to use Zavedos

• if the patient is allergic to idarubicin or to any of the other ingredients of this medicine (listed in section 6), other anthracyclines or anthracenediones,
• if the patient has severe liver impairment,
• if the patient has severe kidney impairment,
• if the patient has severe cardiomyopathy (heart muscle disease),
• if the patient has severe heart failure,
• if the patient has recently suffered a myocardial infarction (heart attack),
• if the patient has severe cardiac arrhythmias,
• if the patient has persistent bone marrow suppression (inhibition of bone marrow function),
• if the patient has previously been treated with the maximum cumulative doses of idarubicin hydrochloride and/or other drugs from the anthracycline or anthracenedione group,
• if the patient is breastfeeding.

Warnings and precautions
Zavedos should be administered under the supervision of a physician experienced in chemotherapy. Treatment with Zavedos should be initiated only after resolution of acute toxicities from prior chemotherapy, such as oral mucositis, neutropenia, thrombocytopenia, and systemic infections.
Before starting Zavedos, discuss the following with your doctor:

• If the patient has heart function disorders. Prior to initiating treatment with Zavedos, the doctor should assess cardiac function and monitor it throughout therapy to minimize the risk of severe heart failure. Inform the doctor if the patient is taking or has recently taken trastuzumab (a medicine used in the treatment of certain cancers). Trastuzumab may remain in the body for up to 7 months. Since trastuzumab can affect the heart, Zavedos should not be used within 7 months after the last dose of trastuzumab. If Zavedos is administered before this period has elapsed, cardiac function must be closely monitored.
• If the patient has low blood cell or platelet counts. The doctor should order blood tests before starting and during treatment with Zavedos.
• If the patient has elevated levels of abnormal white blood cells (the patient may have developed leukemia).
• If the patient has gastrointestinal problems. Zavedos may cause vomiting, inflammation, or ulceration of the gastrointestinal mucosa.
• If the patient has liver or kidney disease. The doctor should evaluate liver or kidney function before and during treatment with Zavedos.
• The patient may experience reactions at the injection site.
• Extravasation (leakage of the drug outside the vein) during administration may cause local pain and severe tissue damage. If extravasation occurs, administration of the drug must be stopped immediately.
• If the patient develops elevated uric acid levels in the blood (tumor lysis syndrome may have developed).
• If the patient has planned vaccinations. Patients receiving Zavedos should avoid vaccines containing live, attenuated microorganisms.
• As with other cytotoxic drugs, thrombophlebitis (vein inflammation with clot formation) may occur.
• In men, Zavedos may affect fertility and cause irreversible infertility. Discuss fertility preservation with the doctor before starting treatment. Both women and men should use effective contraception (see "Pregnancy, breastfeeding and fertility").
• Patients who plan to have children after completing treatment should be advised to consult an appropriate specialist.

Zavedos may cause red discoloration of urine for 1–2 days after administration.
Zavedos and other medicines
Inform the doctor about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
The following medicines may affect the action of Zavedos:

• other cytotoxic drugs with cardiotoxic effects,
• medicines used to treat cardiovascular diseases, e.g. calcium channel blockers such as verapamil,
• oral anticoagulants,
• vaccines containing live, attenuated microorganisms (e.g. yellow fever vaccine),
• cyclosporine A, a medicine used, among others, to prevent transplant rejection,
• and radiotherapy.

Pregnancy, breastfeeding and fertility

If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to have a child, she should consult a doctor or pharmacist before using this medicine.
Pregnancy
Avoid becoming pregnant if the woman or her partner is using Zavedos.
Zavedos has been shown to have harmful effects on the fetus. It is important to inform the doctor if pregnancy is suspected. Zavedos should not be used during pregnancy unless the potential benefits outweigh the risks to the fetus.
Contraception in women of childbearing potential
Effective contraception must always be used during treatment with Zavedos and for at least 6.5 months after the last dose. Discuss appropriate contraceptive methods with the doctor for both the woman and her partner.
Contraception in men
Effective contraception must always be used during treatment with Zavedos and for at least 3.5 months after the last dose.
Breastfeeding
Breastfeeding must be avoided during treatment with this medicine and for at least 14 days after the last dose, as the drug may pass into human milk and harm the infant.
Fertility
Both women and men should seek advice regarding fertility preservation before starting treatment.
Driving and operating machinery
No studies have been conducted on the effects of Zavedos on the ability to drive vehicles or operate machinery.

3. How to use Zavedos

This medicine should always be used as directed by the physician. In case of doubts, consult a
physician or pharmacist.
The physician will calculate the appropriate dose for the patient based on the patient's total body surface area (m²).
The medicine is administered as a slow intravenous infusion.

Acute non-lymphoblastic leukemia
In adult patients, the recommended dose is 12 mg/m² per day administered intravenously for
3 days in combination with cytarabine. Another dosing regimen used both as monotherapy and in combination with other agents is 8 mg/m² administered intravenously for 5 days.
In pediatric patients, the recommended dose is 10–12 mg/m² per day administered intravenously for 3 days in combination with cytarabine.

Acute lymphoblastic leukemia
In adult patients, the recommended dose is 12 mg/m² per day administered intravenously for 3 days.
In pediatric patients, the recommended dose is 10 mg/m² per day administered intravenously for 3 days.

The physician may adjust the recommended dosage based on the patient's condition and concomitant use of other cytotoxic drugs.
The physician may consider dose reduction in patients with hepatic or renal impairment.

Use of a higher than recommended dose of Zavedos
Very high doses of idarubicin hydrochloride may have toxic effects on the heart within 24 hours and cause severe bone marrow suppression within 1 to 2 weeks. Cases of delayed onset heart failure have been reported even several months after overdosage with anthracycline drugs.

Missed dose of Zavedos
Do not administer a double dose to make up for a missed dose.

Discontinuation of Zavedos treatment
The decision to discontinue treatment is made by the physician.

If you have any further questions about the use of this medicine, consult your physician or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although they do not occur in everyone.
Very common (may occur in more than 1 in 10 people):

• infections;
• decreased platelet count, decreased white blood cell count, decreased neutrophil count, decreased red blood cell count;
• decreased appetite or loss of appetite;
• nausea, vomiting, inflammation of the mucous membrane of the mouth and/or stomach, diarrhoea, abdominal pain or burning sensation;
• hair loss;
• red discoloration of urine for 1–2 days after administration of the medicine;
• fever, headache, chills.

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

• heart failure, slow or fast heart rate, heart rhythm disorders, cardiomyopathy;
• bleeding, phlebitis, thrombophlebitis;
• gastrointestinal bleeding, abdominal pain;
• increased liver enzyme activity and increased bilirubin concentration;
• rash, itching, skin hypersensitivity with irritation.

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

• blood infection (sepsis);
• secondary leukaemia;
• dehydration;
• increased blood uric acid concentration;
• myocardial infarction, abnormalities in ECG recording;
• shock;
• oesophagitis, colitis;
• urticaria, excessive pigmentation of skin and nails;
• connective tissue inflammation, tissue necrosis.

Rare (may occur in up to 1 in 1,000 people):

• intracranial haemorrhage.

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

• severe generalized allergic reaction;
• pericarditis, myocarditis, atrioventricular block, bundle branch block;
• thromboembolic complications, hot flushes;
• gastric erosions or ulceration;
• erythema of the limbs.

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

• abnormal decrease in all blood cells;
• tumour lysis syndrome (a metabolic disorder syndrome resulting from rapid breakdown of tumour cells);
• local skin reactions.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the 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
Adverse reactions can also be reported to the marketing authorisation holder or its representative.
Reporting adverse reactions helps provide more information on the safety of the 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: Expiry date (EXP). The expiry date refers to the last day of the stated month.
Store in a refrigerator (2°C – 8°C).
Keep the vial in its outer packaging to protect it from light.
Each vial is for single use only, and its contents should be used immediately after opening. If the medicine is not used immediately, the user is responsible for the storage conditions and duration.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Zavedos contains

• The active substance is idarubicin hydrochloride. One vial contains 5 mg or 10 mg of idarubicin hydrochloride.
• The other ingredients are glycerol, hydrochloric acid (for pH adjustment), and water for injections.

What Zavedos looks like and contents of the pack
A clear, orange-red solution for injection, free from visible solid particles,
in a 5 ml or 10 ml Type I glass vial with a transparent plastic sleeve (protective cap "Oncotain"),
packaged in a cardboard box.
Zavedos is available in packs containing one 5 ml vial or one 10 ml vial.
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Brussels
Belgium
Importer
Pfizer Service Company BV
Hermeslaan 11
1932 Zaventem
Belgium
For further information on this medicinal product, contact the local representative of the Marketing Authorisation Holder:
Pfizer Polska Sp. z o.o., tel. 22 335 61 00

Information intended exclusively for healthcare professionals:

Zavedos is intended for single use only, and any unused portions must be discarded.
Dilution should be performed immediately before use, and the infusion should be started promptly.
The infusion must be completed within 24 hours of preparation, after which any remaining solution must be discarded.
Idarubicin hydrochloride must be administered intravenously only. The infusion should be given over 5 to 10 minutes through an intravenous line previously flushed with 0.9% sodium chloride solution or 5% glucose solution. Rapid direct injection is not recommended due to the risk of extravasation, which may occur even with correct needle placement in the vein confirmed by blood return upon aspiration. This technique minimizes the risk of thrombosis and perivenous leakage of the drug, which could lead to severe complications such as subcutaneous tissue inflammation or necrosis.
Repeated administration into small blood vessels or repeated infusions into the same vein may result in phlebosclerosis.

Pharmaceutical incompatibilities
Idarubicin hydrochloride must not be mixed with other medicinal products. Contact with alkaline pH solutions should be avoided, as this may lead to degradation of Zavedos. Idarubicin hydrochloride must not be mixed with heparin due to the possibility of precipitate formation.

The following precautions must be observed due to the toxicity of the substance:

• Personnel must be trained in the correct techniques for preparing and administering the drug;
• Pregnant women must not be involved in handling or administering this drug;
• Staff handling the drug must wear protective clothing: goggles, gowns, masks, and disposable gloves;
• A designated area should be set aside for drug solution preparation (preferably equipped with a vertical laminar airflow system); the work surface should be protected with absorbent pads backed with plastic material;
• Equipment used for reconstituting, administering, and disposing of the drug, including gloves, must be placed in single-use bags designated for high-risk waste and incinerated at high temperature;
• Accidental spills of the drug should be neutralized with a diluted sodium hypochlorite solution (1% available chlorine), preferably by soaking, followed by rinsing with water;
• All materials used for cleaning up drug contamination must be disposed of as described above;
• In case of accidental contact with skin or eyes, immediately rinse thoroughly with large amounts of water, or water with soap or sodium bicarbonate solution, and seek medical advice;
• In case of eye contact, lift the eyelid(s) and rinse the eye(s) continuously with copious amounts of water for at least 15 minutes, then seek immediate medical attention;
• Hands must always be washed after removing gloves;
• Any unused drug residues or waste must be disposed of in accordance with local regulations.