Zavedos

Package Leaflet: Information for the Patient

Zavedos, 1 mg/ml, Solution for Injection

Idarubicin Hydrochloride

Read the package 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. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

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

2. Important information before using Zavedos

When not to use Zavedos

Warnings and precautions

Zavedos should be used under the supervision of a doctor experienced in the administration of chemotherapy. The doctor should start treatment with Zavedos after the acute symptoms of previous chemotherapy toxicity have subsided, such as oral mucositis, decreased neutrophil count, decreased platelet count, and generalized infections.
Before starting treatment with Zavedos, you should discuss the following with your doctor:

• If you have heart problems. Before starting treatment with Zavedos, your doctor should assess your heart function and then monitor it during therapy to minimize the risk of severe heart failure. You should tell your doctor if you are taking or have recently taken trastuzumab (a medicine used to treat certain types of cancer). Trastuzumab can remain in the body for up to 7 months. Since trastuzumab can affect the heart, Zavedos should not be used for up to 7 months after stopping trastuzumab. If Zavedos is used before this time, heart function should be closely monitored.
• If you have a low blood cell or platelet count. Before starting treatment with Zavedos and during therapy, your doctor should order a blood test.
• If you have an increased number of abnormal white blood cells (you may have developed leukemia).
• If you have gastrointestinal problems. Zavedos may cause vomiting, inflammation, or ulceration of the gastrointestinal mucosa.
• If you have liver or kidney disease. Your doctor should assess liver or kidney function before starting and during treatment with Zavedos.
• You may experience reactions at the injection site.
• Leakage of the medicine outside the vein during administration can cause local pain and severe tissue damage. If the medicine leaks outside the vein, administration should be stopped immediately.
• If you have an increased level of uric acid in the blood (you may have developed tumor lysis syndrome).
• If you are scheduled for vaccination. Patients taking Zavedos should avoid live, attenuated vaccines.
• As with other cytostatic agents, thrombophlebitis may occur.
• In men, Zavedos may affect fertility and cause irreversible infertility. You should discuss fertility preservation with your doctor before starting treatment. Both women and men should use effective contraception methods (see "Pregnancy, breastfeeding, and fertility").
• Patients who plan to have children after treatment should be advised to consult a specialist.

Zavedos may cause urine to turn red for 1-2 days after administration.

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 affect the action of Zavedos:

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

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 taking this medicine.
Pregnancy
You should avoid becoming pregnant if you or your partner are taking Zavedos.
Zavedos has been shown to be harmful to the fetus, so it is essential to tell your doctor if you suspect you are pregnant. Zavedos should not be used during pregnancy unless the potential benefits outweigh the risks to the fetus.
Contraception in women of childbearing age
You should always use effective contraception methods while taking Zavedos and for at least 6.5 months after the last dose. You should discuss contraception methods suitable for you and your partner with your doctor.
Contraception in men
You should always use effective contraception methods while taking Zavedos and for at least 3.5 months after the last dose.
Breastfeeding
You should not breastfeed while taking this medicine and for at least 14 days after the last dose, as the medicine may pass into human milk and harm the baby.
Fertility
Both women and men should seek advice on fertility preservation before starting treatment.

Driving and using machines

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

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.
Your doctor will calculate the correct dose for you based on your body surface area.
The medicine is given as a slow intravenous infusion.
Acute non-lymphoblastic leukemia
In adult patients, the recommended dose is 12 mg/m2 per day, given intravenously for 3 days in combination with cytarabine. Another dosing schedule used in both single-agent therapy and combination therapy is 8 mg/m2 given intravenously for 5 days.
In children, the recommended dose is 10-12 mg/m2 per day, given intravenously for 3 days in combination with cytarabine.
Acute lymphoblastic leukemia
In adult patients, the recommended dose is 12 mg/m2 per day, given intravenously for 3 days.
In children, the recommended dose is 10 mg/m2 per day, given intravenously for 3 days.
Your doctor may change the recommended dose, taking into account your condition and the use of other cytotoxic agents.
Your doctor may consider reducing the dose in patients with liver or kidney failure.

Using a higher dose of Zavedos than recommended

Very high doses of idarubicin hydrochloride can be cardiotoxic within 24 hours and cause severe bone marrow suppression within 1-2 weeks. Cases of delayed onset of heart failure have been reported even after several months of overdose of anthracycline drugs.

Missing a dose of Zavedos

You should not take a double dose to make up for a forgotten dose.

Stopping treatment with Zavedos

Only your doctor can decide to stop treatment.
If you have any further questions on 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;
• decreased platelet count, decreased white blood cell count, decreased neutrophil count, decreased red blood cell count,
• decreased or lost appetite,
• nausea, vomiting, oral mucositis and/or gastritis, diarrhea, abdominal pain or burning sensation,
• hair loss,
• urine turning red for 1-2 days after administration,
• fever, headache, chills.

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

• heart failure, slow or fast heart rate, heart rhythm disorders, heart muscle disease,
• bleeding, phlebitis, thrombophlebitis,
• gastrointestinal bleeding, abdominal pain,
• increased liver enzyme activity and increased bilirubin levels,
• rash, itching, hypersensitivity of irritated skin.

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

• blood infection (sepsis),
• secondary leukemia,
• dehydration,
• increased uric acid levels in the blood,
• heart attack, ECG abnormalities,
• shock,
• esophagitis, colitis,
• hives, skin and nail hyperpigmentation,
• connective tissue inflammation, tissue necrosis.

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

• cerebral hemorrhage.

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

• severe, generalized allergic reaction,
• pericarditis, myocarditis, atrioventricular block, bundle branch block,
• thromboembolic complications, heat strokes,
• gastric ulcers or perforation,
• redness of the skin of the limbs.

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

• abnormal decrease in all blood cell counts,
• tumor lysis syndrome (a condition resulting from the rapid breakdown of cancer cells),
• local skin reactions.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist, or nurse. You can also report side effects directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
You can also report side effects to the marketing authorization holder or its representative.
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 which is stated on the carton after EXP. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C - 8°C).
Keep the vial in the outer packaging to protect 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 storage time.
Medicines should 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), water for injections.

What Zavedos looks like and contents of the pack

A clear, orange-red, particle-free solution for injection in a 5 ml or 10 ml glass vial of type I, with a transparent plastic sleeve (Oncotain sleeve), 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 authorization holder

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

Importer

Pfizer Service Company BV
Hoge Wei 10
1930 Zaventem
Belgium
To obtain more detailed information on this medicine, please contact the local representative of the marketing authorization holder:
Pfizer Polska Sp. z o.o., phone 22 335 61 00

Date of last revision of the leaflet:

Information intended for healthcare professionals only:

Zavedos is intended for single use and any unused medicine should be disposed of. The solution should be diluted immediately before use and the infusion started promptly. The infusion should be completed within 24 hours of preparation, and any remaining solution should be discarded.
Idarubicin hydrochloride should be administered intravenously only. The infusion should be given over 5-10 minutes through previously inserted intravenous infusion lines, through which 0.9% sodium chloride or 5% glucose solution flows. Direct rapid injection of the medicine is not recommended due to the risk of extravasation, which may occur even if the needle is properly positioned in the vein, confirmed by the presence of blood during aspiration. This technique limits the risk of thrombophlebitis and extravasation of the medicine around the vein, which could lead to severe complications such as subcutaneous tissue inflammation or necrosis.
After administration of idarubicin hydrochloride into small blood vessels or after repeated infusions into the same vein, vein hardening may occur.
Incompatibilities
Idarubicin hydrochloride should not be mixed with other medicines. Contact with a solution of alkaline pH should be avoided, as it may cause degradation of Zavedos. Idarubicin hydrochloride should not be mixed with heparin due to the possibility of precipitate formation.
The following precautions should be taken due to the toxicity of the substance:

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