IDARUBICIN SANDOZ 1 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Idarubicina Sandoz 1 mg/ml concentrate for solution for infusion

Idarubicina, hydrochloride

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the pack

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

1. What Idarubicina Sandoz is and what it is used for

Idarubicina Sandoz contains the active substance idarubicina, which belongs to a group of medicines called anthracyclines. Idarubicina interferes with the growth and proliferation of body cells and is used in the treatment of certain cancers (chemotherapy).

Idarubicina is used in the treatment of different types of leukemia (cancer of white blood cells).

Idarubicina, in combination with cytarabine, is used for induction of remission as first-line therapy in children with acute myeloid leukemia (AML) who have not received previous treatment.

2. What you need to know before you use Idarubicina Sandoz

Do not use Idarubicina Sandoz if:

• you have had an allergic reaction (hypersensitivity) to idarubicina or to any of the other components of this medicine (listed in section 6), or to other anthracyclines or anthracenediones,
• your liver or kidneys are not functioning properly,
• you have uncontrolled infections,
• you have severe heart muscle problems (cardiomyopathy),
• you have an acute inflammatory disease of the heart,
• you have a severe heart disease,
• you have severe abnormal heart rhythms,
• you have recently had a heart attack,
• your bone marrow is not producing enough blood cells (however, in this case, your doctor will decide whether to start treatment if the benefit to you outweighs the risk),
• you have previously received treatment with maximum doses of idarubicina and/or other similar anticancer medicines such as daunorubicina or doxorubicina,
• you have a tendency to bleed,
• you have inflammation of the mouth,
• you are breastfeeding (see "Pregnancy, breastfeeding, and fertility"),
• you have recently been vaccinated against yellow fever.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before using idarubicina if:

• you suffer from bone marrow depressioncaused by previous treatment. Idarubicina may affect your bone marrow and prevent it from producing enough blood cells. Your doctor may want to delay the next cycle of your treatment until your blood has recovered. You will need to have regular blood tests to check this.

• you have had heart problemsin the past or are currently receiving treatment for them; please make sure your doctor is aware of them. Idarubicina may cause heart damage. Your heart function will be checked through various tests before and during your treatment (ECG, MUGA scan [a special imaging technique that shows the veins] or ECHO [ultrasound of the heart]). Heart damage with idarubicina can occur, especially with high doses, and may not be detected for several weeks, so regular tests are required during this period.

• you have kidney or liver problems. The function of your kidneys and liver may be impaired with idarubicina. To monitor these changes, your blood will need to be tested before and regularly during treatment. It is essential that you do not miss these blood tests.

Before starting and during treatment with idarubicina, regular blood tests, liver, kidney, and heart checks will be carried out. Infants and children seem to be more sensitive to cardiotoxicity from anthracyclines; therefore, regular and long-term checks are necessary in these patients.

Your doctor will perform regular checks, including:

• blood tests to ensure there are enough blood cells for blood function,
• blood tests to check uric acid levels,
• blood tests to check if your kidneys and liver are working properly,
• heart tests since idarubicina may affect your heart.

Based on the results of these tests, your doctor will decide whether idarubicina is not suitable for your treatment or if a reduced dose is needed.

High doses of idarubicina may worsen side effects such as mouth sores or decrease the number of blood cells and platelets (which help blood to clot). If this happens, you may need antibiotics or blood transfusions. Mouth ulcers can be treated and cured, making them less uncomfortable.

You should not receive live vaccinations (e.g., yellow fever) since severe or life-threatening infections may occur. Please ask your doctor for advice if you want to be vaccinated.

If you have an infection, it should be controlled before starting treatment.

Idarubicina may harm the fetus. Both women and men should use effective contraceptive methods during treatment with idarubicina (see "Pregnancy, breastfeeding, and fertility").

Your urine may turn red for 1 or 2 days after treatment with idarubicina. Please consult your doctor if you have any doubts or concerns about the color of your urine.

Please also consult your doctor if you are receiving radiation therapy at the same time or have received it 2 or 3 weeks before starting treatment.

Other medicines and Idarubicina Sandoz

Tell your doctor or pharmacist if you are using or have recently used or might use other medicines, including those obtained without a prescription.

In particular, inform your doctor or pharmacist if you are using or have recently used any of the following medicines:

• cancer medicines that affect bone marrow function,
• medicines that affect kidney and/or liver function,
• medicines that can damage the heart (e.g., cyclophosphamide),
• medicines for pre-existing heart disease (calcium channel blockers),
• any vaccine received in the last few months,
• immunosuppressive medicines (such as cyclosporine or tacrolimus),
• medicines to prevent blood clotting (e.g., phenprocoumon or acenocoumarol).

Pregnancy, breastfeeding, and fertility

Do notbe treated with idarubicina unless clearly indicated by your doctor. Inform your doctor if you are pregnant, breastfeeding, think you may be pregnant, or plan to become pregnant. Your doctor will need to consider the potential risks to you or your child.

Avoid becoming pregnant while you or your partner are being treated with idarubicina. If you are sexually active, you should use effective contraceptive methods to prevent pregnancy. Idarubicina may harm the fetus, so it is essential to inform your doctor if you think you might be pregnant.

Contraception in women of childbearing age

You must always use an effective contraceptive method while receiving idarubicina and for at least 6.5 months after the last dose. Talk to your doctor about suitable contraceptive methods for you and your partner.

Contraception in men

Men should always use effective contraceptive methods while receiving idarubicina and for at least 3.5 months after the last dose.

If you wish to have children after completing treatment, please consult your doctor for advice on available genetic techniques.

Treatment with idarubicina may cause irreversible infertility in men. Talk to your doctor about the possibility of sperm preservation if you wish to father a child in the future.

You should not breastfeed during treatment with idarubicina, as some of the medicine may pass into breast milk and potentially harm your baby.

Consult your doctor or pharmacist before starting to use any medicine.

Driving and using machines

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

Please consult your doctor before driving or using machines.

3. How to use Idarubicina Sandoz

Idarubicina will be administered to you by intravenous infusion (drip):

• Your doctor will prescribe the required amount (dose). The dose is determined based on your overall health, weight, and height.
• Based on your weight and height, your doctor will calculate your body surface area. This is necessary because the dose is usually calculated as "milligrams per square meter" (mg/m2), administered over 3 consecutive days.
• However, your doctor may need to adjust the dose based on your overall health and any other treatment you are receiving.

AML

• If the child is receiving idarubicina hydrochloride, in addition to another anti-leukemic medicine (cytarabine), the recommended dose is in the range of 10-12 mg/m2, administered slowly into a vein once a day for 3 consecutive days. This is repeated every 3 weeks.

4. Possible side effects

Like all medicines, Idarubicina Sandoz can cause side effects, although not everybody gets them.

Talk to your doctor or nurse immediately:

• if you have a stinging or burning sensation at the injection site while idarubicina is being administered. This may mean that the rest of the dose should be administered in another vein,
• if you have chills (like flu) or skin rash, it may be an allergic reaction to one of your medicines,
• if you have a sore throat or fever after treatment or any bleeding or bruising, it may be due to the medicine reducing the number of cells in your blood.

Side effects that may occur with the following frequencies:

Very common side effects(may affect more than 1 in 10 patients)

• infections,
• reduction in the number of the following blood cells:
  • reduction of red blood cells(anemia) that can make you feel tired and drowsy,
  • reduction of white blood cells(leukopenia or neutropenia) increasing the risk of infections, increased temperature or fever, and chills (like flu).

Severe infections may occur after treatment with idarubicina alone or in combination and may be life-threatening,

• reduction of platelets(thrombocytopenia), which can make you bruise more easily or bleed more than usual if you injure yourself,

• reduced number of all types of blood cells (pancytopenia),
• loss of appetite (anorexia),
  • feeling sick (nausea), discomfort (vomiting), or diarrhea,

• pain or ulcers in the mouth (stomatitis), which may not appear until 3-10 days after treatment,
• inflammation of the mucous membranes (mucositis),
• abdominal pain,
• burning sensation,
• you may lose all or part of your hair, which usually grows back when treatment is finished,
• irritation or burning sensation at the injection site (local toxicity),
• red discoloration of the urine, which may appear for a few days after treatment. This is quite normal and should not concern you,
• fever and chills,
• headache.

Common side effects(may affect up to 1 in 10 patients)

• the heart does not have enough strength to pump blood properly (congestive heart failure),
• heart muscle damage (cardiomyopathy), characterized by shortness of breath, swelling of the lungs, swelling that changes with body position, heart and liver enlargement, decreased urine production, fluid retention in the abdomen, fluid accumulation around the lungs, abnormal heartbeat (galloping rhythm),
• heart injuries and irregularities (abnormally slow or fast heartbeat, changes in rhythm, ineffective heart work),
• local inflammation of the veins where the infusion is administered (phlebitis),
• inflammation of the veins due to a blood clot (thrombophlebitis) or bleeding in different areas (hemorrhage),
• bleeding in the stomach or intestine,
• itching,
• skin that has been damaged by radiation therapy may become very sensitive,
• increased liver enzymes and bilirubin (blood values),
• skin rash,
• abdominal pain.

Uncommon side effects(may affect up to 1 in 100 patients)

• blood poisoning (sepsis, septicemia),
• blood cancer after treatment (secondary leukemia),
• complications that may occur after cancer treatment, produced by breakdown products of the destruction of cancer cells (tumor lysis syndrome),
• high uric acid levels in the blood (may cause gout),
• water loss (dehydration),
• changes in the electrocardiogram (ECG),
• heart attack (myocardial infarction),
• shock,
• inflammation of the esophagus and intestine (may be severe and cause perforation),
• change in nail and skin color,
• itching,
• severe tissue injury (cellulitis and necrosis).

Rare side effects(may affect up to 1 in 1,000 patients)

• bleeding in the brain,

Very rare side effects(may affect up to 1 in 10,000 patients)

• severe allergic reactions (anaphylaxis), symptoms including fainting, skin rash or hives, itching, swelling of the lips and face, difficulty breathing, loss of consciousness,
• inflammation of the sac surrounding the heart (pericarditis),
• inflammation of the heart muscle (myocarditis),
• defects in the heart's electrical conduction system,
• blockage of blood vessels due to a clot in the circulatory system (thromboembolic events), including the possibility of blockage of the pulmonary veins (pulmonary embolism),
• redness of the skin (flushing),
• stomach ulcers,
• numbness, swelling, and painful redness of the palms of the hands and soles of the feet.

Side effects with frequency not known, the frequency cannot be estimated from the available data.

• local reaction at the injection site.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Idarubicina Sandoz

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

Do not use this medicine after the expiry date stated on the packaging after CAD/EXP. The expiry date is the last day of the month indicated.

Store in a refrigerator (between 2°C and 8°C).

Keep the vial in the original packaging to protect it from light.

The diluted solution is chemically stable when stored for up to 14 days at 2°C-8°C and at room temperature (20°C-25°C); however, it is recommended that, in line with good pharmaceutical practices, the solution should not be stored for more than 24 hours at 2°C-8°C.

The medicine does not contain any preservative. Therefore, if aseptic preparation cannot be guaranteed, the medicine should be prepared before use, and any remaining preparation should be discarded.

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

6. Container Content and Additional Information

Composition of Idarubicina Sandoz

• The active ingredient is idarubicina hydrochloride. Each ml of concentrate for solution for infusion contains 1 mg of idarubicina hydrochloride.

Each 5 ml vial contains 5 mg of idarubicina hydrochloride.

Each 10 ml vial contains 10 mg of idarubicina hydrochloride.

Each 20 ml vial contains 20 mg of idarubicina hydrochloride.

• The other components are glycerol, diluted hydrochloric acid (for pH adjustment), sodium hydroxide (for pH adjustment), and water for injectable preparations.

Product Appearance and Container Content

This medicinal product is presented as a concentrate for solution for infusion.

Transparent orange to red solution, free of particles

Colorless glass type I vial with a halobutyl rubber stopper coated with fluoropolymer with or without a protective plastic coating (Onco-safe or Sleeving). The vials are sealed with an aluminum cap. “Onco-Safe” and Sleevingdo not come into contact with the medicinal product and provide additional protection during transport, increasing the safety of medical and pharmaceutical personnel.

Package sizes: 1x5mg/5ml, 5x5mg/5ml, 10x5mg/5ml, 1x10mg/10ml, 5x10mg/10ml, 10x10mg/10ml, 1x20mg/20ml, 5x20mg/20ml, 10x20mg/ml.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Sandoz Farmacéutica, S.A.

Centro Empresarial Parque Norte

Edificio Roble

C/ Serrano Galvache, 56

28033 Madrid

Spain

Manufacturer

Ebewe Pharma Ges.m.b.H. Nfg. KG

Mondseestraße 11

4866 Unterach

Austria

or

Fareva Unterach GmbH

Mondseestraße 11

4866 Unterach

Austria

Date of the Last Revision of this Prospectus:02/2024.

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

-------------------------------------------------------------------------------------------------------------------------

This information is intended only for doctors or healthcare professionals:

Special Precautions for Disposal and Other Handling

Due to the toxic nature of the compound, the following protection recommendations should be followed:

• Personnel handling this medicinal product should be instructed in the safe handling techniques of these preparations.
• Pregnant women should be excluded from handling this medicinal product.
• Personnel handling idarubicina should wear protective clothing (e.g., protective glasses, gowns, and gloves, and disposable masks).
• All handling should be performed in a safety cabinet or isolated area.
• The work surface should be protected with absorbent, laminated, and disposable paper.
• All material used for reconstitution, administration, or cleaning, including gloves, should be disposed of in high-risk material bags for destruction by high-temperature incineration.
• Any spill or leak should be treated with diluted sodium hypochlorite solution (1% available chlorine), preferably by soaking, and then with water. Decolorization shows the loss of cytostatic potential.
• All cleaning materials should be disposed of as indicated above.
• In case of accidental contact with skin or eyes, it should be treated immediately by washing with plenty of water or soap and water or with a sodium bicarbonate solution.
• Discard unused solution.
• Idarubicina Sandoz is for single use only.
• Only transparent solutions should be used.
• Before administration, the solution should be brought to room temperature.
• Idarubicina should not be prepared more than 24 hours before administration.
• The risk of bacterial contamination due to handling should be taken into account.

i. Intravenous Administration

Idarubicina Sandoz should be administered only by the intravenous route.

The infusion can be prepared by diluting Idarubicina Sandoz with 0.9% sodium chloride or 5% glucose.

Alternatively, the required volume of undiluted product can be administered slowly through an intravenous infusion system over 5 to 10 minutes or by free intravenous infusion with 0.9% sodium chloride or 5% glucose.

Direct injection is not recommended due to the risk of extravasation, which can occur even with adequate blood return by aspiration of the needle.

ii. Disposal

Disposal of unused medicinal product and all materials used for its reconstitution, dilution, and administration should be carried out in accordance with hospital regulations regarding cytotoxic agents and current legislation on the disposal of hazardous waste.

Incompatibilities

This medicinal product should not be mixed with other medicinal products except with 0.9% sodium chloride or 5% glucose.

Posology and Method of Administration

Only by the intravenous route.

Should not be used by the intrathecal route.

The dose is normally calculated based on body surface area.

Posology

Acute Myeloid Leukemia (AML)

Adults

• 12 mg/m2 daily by intravenous route for 3 days in combination with cytarabine,

or

• 8 mg/m2 daily by intravenous route for 5 days with or without combination.

Pediatric Population

In children with AML, the recommended dose of idarubicina hydrochloride in combination with cytarabine is 10-12 mg/m2 of body surface area daily for 3 days by slow intravenous injection.

NOTE:These are general guidelines. Consult individual protocols for exact dosing.

The total maximum dose should not exceed 120 mg/m2 of body surface area.

Acute Lymphoblastic Leukemia (ALL)

Adults

The recommended dose in adults is 12 mg/m2 daily by intravenous route for 3 days in appropriate combination regimens.

Pediatric Population

10 mg/m2 daily by intravenous route for 3 days, in appropriate combination regimens.

However, these dosing schedules should take into account the patient's hematological situation and the doses of other cytotoxic medicinal products when used in combination.

Administration of a second dose should be delayed in patients who develop severe mucositis until recovery from this toxicity, and a 25% dose reduction is recommended.

The total maximum dose should not exceed 120 mg/m2 of body surface area.

Patients with Hepatic and/or Renal Impairment

A dose adjustment may be required in patients with renal or hepatic impairment.

Shelf Life

2 years.

Chemical and physical stability has been demonstrated during use for 14 days at 2°C-8°C and at 25°C.

From a microbiological point of view, the medicinal product should be used immediately.

If not used immediately, the time and conditions of storage before use are the responsibility of the user and normally should not exceed 24 hours at 2°C to 8°C, unless dilution takes place in controlled and validated aseptic conditions.

Special Precautions for Storage

Store in a refrigerator (between 2°C-8°C).

Keep in the original packaging to protect from light.