Leaflet: information for the user

Epirubicina Teva 2mg/ml injectable solution and for infusion EFG

Read this leaflet carefully before you start using this medicinebecause it contains important information for you.

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

1. What isEpirubicina Teva 2mg/mland what it is used for

2. What you need to know before you start usingEpirubicina Teva 2mg/ml

3. How to useEpirubicina Teva 2mg/ml

4. Possible side effects

5. Storage ofEpirubicina Teva 2mg/ml

6. Contents of the pack and additional information

Epirubicina belongs to the group of cytostatics (cancer medications).

Epirubicina prevents cancer cells from growing and ultimately eliminates them.

Epirubicina Teva is used in the treatment of

-breast cancer;

-stomach cancer;

-Epirubicina is also administered intravesically (directly into the bladder) to treat early (superficial) bladder cancer and helps to prevent bladder cancer recurrence after surgery.

Epirubicina is often used in combination with other cancer medications for cancer treatment (polychemotherapy regimens).

No use Epirubicina Teva 2mg/ml

• if you areallergicto epirubicin, to similar medicines (called anthracyclines or anthracenediones, see below) or to any of the other components of this medicine (listed in section 6);
• if you arebreastfeeding

Do not administer Epirubicina Teva 2 mg/ml in the following situations, depending on the administration route:

Parenteral (intravenous) route:

-if you have beenpreviously treated with high dosesof another cancer medicine, including doxorubicin and daunorubicin, which belong to the same group of medicines as Epirubicina Teva 2mg/ml (calledanthracyclines). These medicines have similar side effects (including effects on the heart);

-if you have or have hadheart problems;

-if you have alow white blood cell count;

-if you have asevere liver disorder;

-if you have anacute severe infection.

Intravesical (directly into the bladder) route::

-if the cancer has penetrated the bladder wall;

-if you have a urinary tract infection;

-if you have bladder pain or inflammation;

-if your doctor has difficulty inserting the catheter (tube) into your bladder;

-if there is a large volume of urine remaining in your bladder after attempting to empty it;

• if there is blood in your urine;
• if your bladder is contracted.

Precautions and warnings

Consult your doctor or pharmacist before starting to use Epirubicina Teva 2 mg/ml:

• if you areelderlyor achild, because there is a greater risk of severe heart side effects. Your cardiac function will be checked before and after treatment with epirubicin.
• if you have hadheart problemsin the past or if you are currently experiencing these problems. You must inform your doctor. The dose of epirubicin will be adjusted. Your doctor will regularly check if your heart is functioning correctly.
• if you have beenpreviously treatedwith cancer medicines (anthracyclines (such as doxorubicin or daunorubicin), anthracenediones or trastuzumab) or if you have received radiation in the chest area, due to the increased risk of severe heart side effects. Inform your doctor as this will affect the determination of the total dose of epirubicin to be administered.
• if you havekidney or liver problems. This may cause an increase in side effects. Your kidney and liver functions will be regularly checked, and if necessary, the dose will be adjusted.
• ifyou are planningto have children. Both men and women should use effective contraceptive methods during treatment and for at least 6.5 months (women) or 3.5 months (men) after treatment. Both should seek genetic counseling (see “Pregnancy, breastfeeding and fertility”).
• if you haveinfections or bleeding. Epirubicin may affect the bone marrow. The number of white blood cells in your blood may decrease, making you more susceptible to infections (leucopenia). Bleeding may occur more easily (thrombocytopenia). These side effects are temporary. The decrease in white blood cell count is greater after 10-14 days after administration and usually returns to normal 21 days after administration. Your doctor will regularly perform blood tests.
• if you have recently been given or plan to be given anyvaccine.

Be particularly careful during treatment with Epirubicina Teva 2 mg/ml:

• to check your blood uric acid level. Your doctor will check this.
• if blood clots form in your blood vessels (thromboembolism) that may lead to inflammation of the vein (thrombophlebitis) or obstruction of the pulmonary artery (pulmonary embolism).
• if you experience severe inflammation or ulcers in your mouth.
• if you notice aburning sensationat the injection site. This may indicate that epirubicin has leaked out of the vein. Inform your doctor about this.

Children and adolescents

The safety and efficacy of epirubicin have not been established in children.

Use of Epirubicina Teva 2 mg/ml with other medicines

Inform your doctor or pharmacist if you are taking/using, have taken/used or may need to take/use any other medicine.

An interaction means that the medicines you use together may affect the effect of the other and/or their side effects. It may occur with the concurrent use of this solution and:

• previous or concurrent administration of other epirubicin-related products (also called anthracyclines; (for example, cancer medicines such asmitomycin-C, dacarbazine, dactinomycin andcyclophosphamide)),other medicines thatcan affectthe heart(for example cancer medicinessuch as5-fluorouracil, cyclophosphamide, cisplatin, taxanes, trastuzumab)orcalcium channel blockers(used to treat high blood pressure or some heart diseases); the damage to the heart may increase. In these cases, a more intense control of heart function will be necessary.
• epirubicin may increase the effect of radiation and even some time after it (epirubicin) it may cause severe side effects in the irradiated area.
• paclitaxel and docetaxel(cancer medicines); when paclitaxel is administered before epirubicin or when docetaxel is administered immediately after epirubicin, the amount of epirubicin in the blood increases, which may cause an increase in side effects.
• dexverapamil(medicine for treating some heart problems); if used together with epirubicin, it may have negative effects on the bone marrow.
• interferon alfa-2b(medicine used against some types of cancer and lymphomas and in certain forms of hepatitis).
• quinine(medicine for treating malaria and leg cramps); it may increase the speed of epirubicin distribution in the body, which may negatively affect red blood cells.
• dexrazoxane(medicine sometimes used with doxorubicin to reduce the risk of heart problems); the time epirubicin stays in the body may decrease, which may reduce the effect of epirubicin.
• cimetidine(medicine for treating stomach ulcers); it increases the amount of epirubicin in the blood, which may cause an increase in side effects.
• previous or concomitant treatment with other medicines that may affect the bone marrow (for exampleother cancer medicines, sulfonamides and chloramphenicol(antibiotics), diphenylhydantoin(antiepileptic),amidopyrine derivatives(analgesics),medicines against certain viruses); the formation of blood cells may be affected.
• medicines that cause heart failure
• medicines that affect liver function; the hepatic degradation of epirubicin may be altered, which may reduce the effect of epirubicin or increase side effects.
• live vaccines or attenuated vaccines; there is a risk of developing a fatal disease, so this combination is not recommended.

Use of Epirubicina Teva 2mg/ml with food and drinks

Do not drink during the 12 hours before administration if epirubicin is administered into the bladder.

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medicine.

Pregnancy and fertility

Epirubicin may cause fetal damage if used during pregnancy.Animal studies have shown that epirubicin is harmful to the fetus and may cause malformations.

It is very important to inform your doctor if you are pregnant or become pregnant during treatment. Epirubicina hydrochloride 2 mg/ml should not be used during pregnancy, unless your doctor considers it absolutely necessary to start immediate treatment with epirubicin.

If you become pregnant during treatment with epirubicin, it is recommended that you receive genetic counseling. Some reports referring to pregnant women indicate that epirubicin was associated with heart problems in newborns and fetuses, including fetal death.

Women of childbearing age should use effective contraceptive methods during treatment and for at least 6.5 months after the last dose. Men in treatment with epirubicin should use effective contraceptive methods during treatment and for at least 3.5 months after the last dose.

Treatment with epirubicin may cause infertility. Both men and women should seek advice on preserving fertility before treatment.

Epirubicin may cause amenorrhea or premature menopause in premenopausal women.

Breastfeeding

The excretion of epirubicin in breast milk is unknown. You should stop breastfeeding during treatment with Epirubicina Teva 2 mg/mland for at least 7 days after the last dose.

Driving and operating machinery

Do not drive or operate machinery as many patients have experienced nausea or vomiting during treatment.

Epirubicina Teva 2mg/ml contains sodium

This medicine contains 18 mg of sodium (main component of table salt/for cooking) in each 5 ml vial. This is equivalent to 0.9% of the maximum daily sodium intake recommended for an adult.

This medicine contains 35 mg of sodium (main component of table salt/for cooking) in each 10 ml vial. This is equivalent to 1.8% of the maximum daily sodium intake recommended for an adult.

This medicine contains 89 mg of sodium (main component of table salt/for cooking) in each 25 ml vial. This is equivalent to 4.4% of the maximum daily sodium intake recommended for an adult.

This medicine contains 266 mg of sodium (main component of table salt/for cooking) in each 75 ml vial. This is equivalent to 13.3% of the maximum daily sodium intake recommended for an adult.

This medicine contains 354 mg of sodium (main component of table salt/for cooking) in each 100 ml vial. This is equivalent to 17.7% of the maximum daily sodium intake recommended for an adult.

Epirubicin Teva 2mg/ml should be administered only under the supervision of a doctor experienced in the use of this type of treatment. Consult with your doctor or pharmacist if you have any doubts.

Your doctor will perform blood tests while you are being treated with epirubicin. This is done to measure the effect of the medication. Your doctor will also perform tests to check the functioning of your heart. Blood tests and heart function checks will be done before and during treatment with epirubicin.

The administered dose will depend on the type of cancer you have, your health, your age, the functioning of your liver, and the other medications you are taking.

Administration via vein (intravenous administration)

The dose is determined based on your overall health status and any previous treatments, taking into account your height and weight. The dose is expressed in milligrams per square meter of body surface area.

This medication is administered as an intravenous injection over 3-5 minutes or as a venous perfusion for a maximum of 30 minutes.

When epirubicin hydrochloride is administered alone, i.e., without other cancer medications, the recommended dose is 60-90 mg/m2of body surface area. This dose is administered as a single dose or divided over 2-3 consecutive days. This is repeated every 21 days. In combination with other cancer medications, the doses are reduced.

Administration is performed through a catheter or by perfusion with a saline or glucose solution (sugar solution).

Higher doses are used for the treatment of breast cancer (100-120mg/m2) of body surface area).

Administration into the bladder (intravesical administration)

The medication can be administered directly into the bladder (for the treatment of bladder cancer) through a catheter. If this method is used, you should not drink any liquids 12 hours before treatment to avoid diluting the medication too much in the urine.

After administration, the medication solution should be left in the bladder for 1-2 hours. Occasionally, you may need to change your position to ensure the medication reaches the entire bladder.

When urinating after medication administration, be careful not to let the urine come into contact with your skin. If it does, wash the affected area well with water and soap, but do not rub.

If you use more Epirubicin Teva 2mg/ml than you should

This medication will be administered to you in the hospital, so the risk of overdose is unlikely. This can affect your heart, decrease your blood cell count, and cause gastrointestinal toxic effects (mainly mucositis). You may notice mouth sores. If you think you have been given too much Epirubicin Teva 2 mg/ml, contact your doctor immediately.

In case of overdose or accidental ingestion, contact the Toxicological Information Service (91) 562 04 20.

If you forget to use Epirubicin Teva 2mg/ml

This medication will be administered to you in the hospital, so the risk of missing a dose is unlikely.

Consult with your doctor if you have any doubts.

If you interrupt treatment with Epirubicin Teva 2mg/ml

Consult with your doctor.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

More than 10% of patients treated may develop side effects. The most common side effects are decreased blood cell production (myelosuppression), gastrointestinal side effects, loss of appetite (anorexia), hair loss (alopecia), and infection.

The following side effects may occur, among others:

Very common: may affect more than 1 in 10 people

• Infection
• Eye inflammation (conjunctivitis or keratitis)
• Decreased blood cell production (bone marrow depression; resulting in decreased white blood cells, red blood cells, and platelets), which implies increased susceptibility to infections and fever, anemia, bruises, and bleeding when injured
• Headaches, redness along the vein (phlebitis)
• Nausea and vomiting (often occurring within the first 24 hours in almost all patients), inflammation of the mucous membrane of the mouth (stomatitis), inflammation of the mucous membrane (mucositis; may occur 5 to 10 days after treatment initiation), diarrhea that may lead to dehydration.
• Hair loss (alopecia, in 60-90% of treated cases. This implies poor beard growth in men. Hair loss is dose-dependent and reversible in most cases)
• Skin lesions
• Red urine color for 1 or 2 days after administration
• Absence of menstruation (amenorrhea)
• General feeling of discomfort, fever
• Changes in levels of certain enzymes (transaminases)
• Bladder inflammation (cystitis), sometimes with bleeding, after direct administration into the bladder

Common: may affect up to 1 in 10 people

• Loss of appetite (anorexia), dehydration
• Reduced heart function with resulting congestion (congestive heart failure), heart failure (shortness of breath, fluid accumulation in the body (edema), liver enlargement, fluid accumulation in the abdominal cavity (ascites), fluid accumulation in the lungs (pulmonary edema), pleural effusions, abnormal heart rhythm (gallop rhythm)), increased heart rate originating from the lower heart chambers (ventricular tachycardia), slow heart rate (bradycardia), cessation of impulse transmission in the heart (AV block, branch block)
• Decreased fraction of blood pumped by a ventricle with each heartbeat (decreased ejection fraction)
• Bleeding (hemorrhage), skin redness (rubor)
• Inflammation of the esophageal mucous membrane (esophagitis), abdominal pain, erosion, and ulcers in the gastrointestinal tract
• Dermatological reactions, intense itching (pruritus), skin disorders
• Increased skin and nail pigmentation (hyperpigmentation)
• Redness at the infusion site, chills
• Local reactions such as burning sensation and frequent urge to urinate after administration into the bladder have been observed

Uncommon: may affect up to 1 in 100 people

• Blood poisoning (sepsis), lung infection (pneumonia)
• Certain types of blood cancer (acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML)).
• Vascular inflammation with the formation of a blood clot, often felt as pain with a hard core with red skin around it (thrombophlebitis)
• Formation of blood clots (embolism, arterial embolism), including formation of blood clots in the lungs (pulmonary embolism, in isolated cases with fatal outcome)
• Gastrointestinal bleeding
• Dermatological reactions with formation of small bumps (urticaria), skin redness (erythema)
• Feeling of weakness (asthenia)

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

• Severe immediate allergic reaction, including shock, with or without anaphylactic shock, including skin rash and itching, fever, and chills.
• Increased uric acid levels in the blood (hyperuricemia)
• Dizziness
• Cardiotoxicity (e.g., ECG abnormalities, arrhythmias, heart muscle disease (cardiomyopathy))
• Absence of sperm in the semen (azoospermia).
• Fever (extremely high)

Unknown: cannot be estimated from available data

• Blood poisoning and shock (septic shock) due to decreased blood cell production (myelosuppression)
• Bleeding, tissue hypoxia
• Certain nerve disorders (peripheral neuropathy), headache
• Shock
• Abdominal discomfort, oral mucosa erosion, mouth ulceration, mouth pain, burning sensation in the mucous membrane, bleeding from the mouth (hemorrhage), oral cavity discoloration (oral pigmentation)
• Sensitivity to light (photosensitivity) or allergic reaction to radiation (radiation recall reaction)
• Increased protein levels in the urine (proteinuria) in patients treated with a high dose
• Local pain, severe inflammation of the tissue (cellulitis), tissue death (tissue necrosis), venous wall thickening or hardening (fleboesclerosis) after accidental injection outside the vein

Intravesical (in the bladder):The severe reactions affecting the whole body, as well as allergic reactions, are rare when Epirubicina Teva 2 mg/ml is administered into the bladder.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect not listed in this leaflet. You can also report them directly through the Spanish Medicines for Human Use Pharmacovigilance System Website:www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep out of sight and reach of children.

Do not use this medication after the expiration date that appears on the label/box after CAD. The expiration date is the last day of the month indicated.

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

Refrigerated storage and transportation.

Do not freeze.

After the first opening, the medication must be used immediately.

Chemical and physical stability is as follows:

From a microbiological point of view, the medication must be used immediately. If not used immediately, storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at 2-8°C.

Storage of the injection solution in cold conditions may lead to the formation of a gelatinous product. This gelatinous product will pass from slightly viscous to a mobile solution after 2 hours and at most 4 hours at controlled temperature (15-25 ºC).

Medicines should not be disposed of through the drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of Epirubicin Teva 2mg/ml

-The active ingredient is epirubicin hydrochloride; 1 ml of solution contains 2 mg of epirubicin hydrochloride.

-The other components are sodium chloride, hydrochloric acid, and water for injection.

Aspect of the product and content of the package

Epirubicin Teva 2 mg/ml is a medicinal product in the form of a transparent, colorless, and slightly red solution for injection and infusion. It is marketed in glass vials for injection with 5 ml (10 mg), 10 ml (20 mg), 25 ml (50 mg), 75 ml (150 mg), or 100ml (200 mg) of injectable and infusion solution.

The product may only be marketed in some package sizes.

Holder of the marketing authorization and responsible for manufacturing

Holder

Teva Pharma S.L.U.

C/ Anabel Segura, 11. Edificio Albatros B, 1st floor

Alcobendas, 28108 Madrid (Spain)

Responsible for manufacturing

Pharmachemie B.V.

Swensweg 5

PO Box 552

2003 RN Haarlem, Netherlands

This medicinal product is authorized in the member states of the European Economic Area and in the United Kingdom (Northern Ireland) with the following names:

Belgium:EPIRUBICINE TEVA 2 mg/ml

Denmark:Epirubicin Teva solution for injection or infusion

France:EPIRUBICINE TEVA CLASSICS 2 mg/ml, solution injectable or for perfusion

Germany:Epi Teva 2 mg/ml Injektionslösung or Infusionslösung

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