EPIRUBICIN AUROVITAS 2 mg/ml INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Epirubicina Aurovitas 2 mg/ml Solution for Injection EFG

Epirubicina 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 or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Package Leaflet

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

1. What is Epirubicina Aurovitas and what is it used for

Epirubicin is a cancer medicine. Sometimes, treatment with a cancer medicine is called chemotherapy. Epirubicin belongs to a group of medicines called anthracyclines. These medicines work by slowing down or stopping the growth of cells that are growing too quickly, and by increasing the chances of cell death.

Epirubicin is used to treat various types of cancer. The way it is used depends on the type of cancer being treated.

When injected into the bloodstream, epirubicin is used to treat breast, stomach, and lung cancers, as well as advanced ovarian cancer.

When injected into the bladder through a tube, epirubicin is used to treat bladder cancer. It can also be used after other treatments to prevent the growth of these types of cells again.

2. What you need to know before you use Epirubicina Aurovitas

Do not use Epirubicina Aurovitas

• If you are allergic to epirubicin hydrochloride or any of the other ingredients of this medicine (listed in section 6).
• If you are allergic to other medicines similar to epirubicin (which belong to a group of medicines called anthracyclines, such as doxorubicin or daunorubicin).
• If you are allergic to medicines that belong to the group of anthracenediones (including medicines used to treat cancer).
• If you are breastfeeding.

Epirubicin must not be injected into a vein (intravenously) if:

• You know that your blood cell count is low, caused by previous treatment with other anti-tumor medicines or radiation therapy.
• You are being treated with other chemotherapeutic agents at maximum doses, such as epirubicin and/or other anthracyclines (like doxorubicin or daunorubicin) and anthracenediones, which can increase the risk of side effects.
• You have or have had heart problems.
• You have any severe acute infection.
• You have severe liver problems.

Epirubicin must not be injected into the bladder if:

• You have a urinary tract infection (including the kidneys, bladder, and urethra).
• There are tumors that penetrate the bladder.
• There are problems placing the tube in the bladder.
• You have inflammation of the bladder.
• You have blood in your urine (hematuria).

Warnings and precautions

Consult your doctor before starting treatment with Epirubicina Aurovitas:

• If you have liver or kidney problems.
• If you have been given or are going to be given any vaccine.

You must inform your doctor before starting treatment, as you will need to take greater precautions.

Your doctor will also perform regular blood tests:

• To ensure that your blood cell count is not too low.
• To monitor uric acid levels and other factors in your blood.
• To check that your heart and liver are functioning normally.
• If you have received or are going to receive radiation therapy in the area near the heart.

You must inform your doctor if you experience swelling and pain in the mouth or mucous membranes.

It is possible that your urine may appear red in color for one or two days after administration.

Children

There is no data on the safety and efficacy of epirubicin in children.

Other medicines and Epirubicina Aurovitas

Tell your doctor if you are taking, have recently taken, or might take any other medicines. In particular:

• Cimetidine (used to reduce stomach acid).
• Trastuzumab (used in the treatment of cancer) may take up to 7 months to be eliminated from the body. As trastuzumab can affect the heart, you must not use epirubicin until 7 months after finishing treatment with trastuzumab. If epirubicin is used before this time, cardiac function must be closely monitored.
• Paclitaxel and docetaxel (used in some types of cancer).
• Interferon alfa-2b (used in some types of cancer and lymphoma, and in certain types of yellow fever).
• Quinine (used to treat malaria and leg cramps).
• Dexverapamil (used to treat certain heart conditions).
• Medicines that can affect your heart, such as 5-fluorouracil, cyclophosphamide, cisplatin, taxanes (used to treat cancer), or calcium channel blockers (used to treat high blood pressure or certain heart diseases).
• Medicines that can affect the liver.
• Live vaccines.
• Other medicines that can affect the bone marrow (such as other cancer medicines), sulfonamides, and chloramphenicol (antibacterial medicines), diphenylhydantoin (antiepileptic), amidopyrine derivatives (some medicines used to treat, for example, pain and fever), and some antiviral medicines.
• Dexrazoxane (a medicine used to prevent the chronic toxic effects of epirubicin on the heart).

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.

Pregnancy

Epirubicin may cause birth defects if used during pregnancy, so it is essential that you inform your doctor if you are pregnant or become pregnant during treatment. You must not use epirubicin during pregnancy unless your doctor explicitly tells you to.

If you or your partner are being treated with epirubicin, it is recommended that you use an effective contraceptive method to prevent pregnancy. If you become pregnant during treatment or wish to have children after treatment, it is recommended that you have genetic counseling.

Breastfeeding

Epirubicin may be harmful to breastfed babies, so women must stop breastfeeding before starting treatment with epirubicin and for at least 7 days after the last dose.

Fertility

There is a risk of infertility due to treatment with epirubicin. Male patients should consider the possibility of preserving sperm before treatment.

Epirubicin may cause the absence of menstruation or premature menopause in premenopausal women.

Both men and women should seek advice on preserving fertility before treatment. Women of childbearing age must use effective contraceptive methods during treatment with epirubicin and for at least 6.5 months after the last dose. Men must use effective contraceptive methods during treatment and for at least 3.5 months after the last dose.

Driving and using machines

Epirubicin may cause episodes of nausea and vomiting, which can temporarily reduce your ability to drive or use machines.

Epirubicina Aurovitas contains sodium

This medicine contains 0.154 mmol of sodium (3.54 mg) per ml of solution for injection. The different pack sizes of Epirubicina Aurovitas contain the following amounts of sodium:

25 ml vial: this medicine contains 88.55 mg of sodium (a major component of table/cooking salt) per vial. This is equivalent to 4.43% of the maximum recommended daily intake of sodium for an adult.

50 ml vial: this medicine contains 177.1 mg of sodium (a major component of table/cooking salt) per vial. This is equivalent to 8.86% of the maximum recommended daily intake of sodium for an adult.

100 ml vial: this medicine contains 354.21 mg of sodium (a major component of table/cooking salt) per vial. This is equivalent to 17.71% of the maximum recommended daily intake of sodium for an adult.

This medicine can be prepared for administration with solutions that contain sodium. Inform your doctor if you are on a low-salt diet.

3. How to use Epirubicina Aurovitas

Epirubicin will be administered to you by a doctor or nurse, either into a vein or directly into the bladder. Your doctor will decide the correct dose and the number of days you will receive the treatment, which will depend on the type of cancer you have, your state of health, height, weight, liver function, and any other treatment you may be receiving.

By injection or infusion into a vein

Epirubicin can be administered by injection into a vein over 3-5 minutes. It can also be diluted before being slowly infused, usually drop by drop, into a vein over 30 minutes.

Administration into the bladder

If the injection is made into the bladder, you must not drink any fluids in the 12 hours before treatment, so that the urine does not dilute the medicine too much. After administration, the solution must be kept in the bladder for 1-2 hours. Sometimes you will need to change your position to ensure that the medicine reaches all parts of the bladder.

You must be careful not to let the contents of the bladder come into contact with the skin when you urinate. In case of contact with the skin, wash the affected area well with water and soap, but do not rub.

Your doctor will perform regular blood tests to detect any unwanted effects. To detect possible heart damage, your doctor will also monitor your heart for several weeks after treatment has finished.

If you receive more Epirubicina Aurovitas than you should

This may affect the heart, reduce the number of blood cells, and cause gastrointestinal problems (mainly mucositis). You may notice the appearance of sores in the mouth. However, since this medicine will be administered to you while you are in the hospital, it is unlikely that you will be given too little or too much.

If you are given more epirubicin than you should, consult your doctor or pharmacist immediately or call the Toxicology Information Service, telephone 91 562 04 20, indicating the medicine and the amount administered.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If any of the following side effects occur when epirubicin is administered by infusion into a vein, tell your doctor immediately, as they are very serious side effects. You may need urgent medical attention:

• If redness, pain, or inflammation appear at the injection site; tissue damage can occur if the solution is accidentally injected outside a vein.
• If you have symptoms of heart problems or blood clots in the lungs, such as chest pain, shortness of breath, swelling of the ankles (these effects can appear up to several weeks after finishing treatment with epirubicin).
• If you have a severe allergic reaction, with symptoms including fainting, skin rash, swelling of the face, and difficulty breathing or wheezing. In some cases, you may experience a collapse.
• Fever, with a body temperature above 41°C (hyperpyrexia).

If you experience any of the following side effects, tell your doctor as soon as possible:

Very common: may affect more than 1 in 10 people

• Infection.
• Suppression of blood cell production in the bone marrow (myelosuppression), decrease in the number of white blood cells (leukopenia), decrease in the number of a special type of white blood cells (granulocytopenia and neutropenia), decrease in the number of red blood cells (anemia), and low levels of certain white blood cells accompanied by fever (febrile neutropenia), decrease in the number of platelets (thrombocytopenia).
• Inflammation of a mucous membrane (mucositis), inflammation inside the mouth (stomatitis), discomfort (vomiting), watery or frequent stools (diarrhea), feeling of discomfort (nausea), which can cause loss of appetite and abdominal pain.
• Hair loss, usually reversible, decrease in beard growth.
• Red coloration of the urine during 1 or 2 days after administration.
• Absence of menstruation.
• Redness of the eyes (conjunctivitis), inflammation of the cornea of the eye (keratitis).
• Hot flashes.
• Skin lesions.
• Inflammation of a vein (phlebitis).
• Feeling of discomfort, fever.
• Changes in the levels of some liver enzymes (called transaminases).
• Chemical cystitis, sometimes with blood in the urine, has been observed after administration into the bladder.

Common: may affect up to 1 in 10 people

• Loss of water (dehydration).
• Worsening of heart function (congestive heart failure). Symptoms may include:
  • Difficulty breathing (dyspnea).
  • Fluid accumulation in the legs (edema).
  • Enlargement of the liver.
  • Fluid accumulation in the abdominal cavity (ascites).
  • Fluid accumulation in the lungs (pulmonary edema).
  • Fluid accumulation between the chest and lungs (pleural effusion).
  • Third heart sound (gallop rhythm).
• Local cutaneous toxicity, skin rash, itching, increased skin pigmentation and nails, skin changes.
• Redness along the vein (erythema at the infusion site).
• Bleeding.
• Redness of the skin.
• Chills.
• Decreased or lost appetite.
• Asymptomatic changes in heart function (asymptomatic drops in left ventricular ejection fraction).
• Potentially life-threatening irregular heartbeats (ventricular tachycardia), decreased heart rate, alteration in the conduction of heart impulses (atrioventricular block, bundle branch block).
• After administration into the bladder, bacterial cystitis, pain or burning when urinating, frequent need to urinate have been observed.
• Ulcers in the gastrointestinal tract, erosions, and gastric lesions, gastrointestinal bleeding, pain behind the sternum, indigestion, and difficulty swallowing due to inflammation of the esophagus, pain or burning in the gastrointestinal tract, inflammation of the mucous membrane of the gastrointestinal tract and inside the mouth with a burning sensation and pain.

Uncommon: may affect up to 1 in 100 people

• Certain types of blood cancer (lymphocytic leukemia, myeloid leukemia).
• Blood poisoning (sepsis), lung infection (pneumonia).
• Feeling of weakness (asthenia).
• Redness of the skin (erythema), hives.
• Blockage in a blood vessel.
• Inflammation and pain in the legs or arms due to inflammation of a blood vessel possibly caused by a blood clot.
• Formation of blood clots in the lungs that cause chest pain and difficulty breathing.

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

• Sudden, potentially life-threatening allergic reaction. Symptoms include sudden signs of allergy, such as skin rash, itching, or hives on the skin, swelling of the face, lips, tongue, or other parts of the body, difficulty breathing or wheezing, allergic reactions after administration of the medicine into the bladder.
• Increased levels of uric acid in the blood.
• Dizziness.
• Toxic effects on the heart, such as anomalies in the ECG (electrocardiogram), different types of irregular heartbeats (arrhythmias), or heart muscle disease (cardiomyopathy).
• Absence of sperm in the semen.

Frequency not known: cannot be estimated from the available data

• Potentially life-threatening condition that occurs when blood pressure is too low as a result of blood poisoning (septic shock).
• Potentially life-threatening condition in which blood pressure is too low (shock).
• Rapid decrease in blood pressure, sometimes with skin reactions or rash.
• Inadequate oxygenation of tissues may occur as a result of suppression of blood cell production in the bone marrow (myelosuppression).
• Blockage of a blood vessel by a blood clot (thromboembolism).
• Thickening of the walls of the veins, local pain, severe cellulitis.
• Increased coloration of the mucous membrane of the mouth.
• Increased sensitivity to light (photosensitivity), hypersensitivity of irradiated skin (radiation recall reaction).
• Severe tissue damage after leakage of the injectable solution into the surrounding tissue.
• Headache.
• Pain.

If epirubicin hydrochloride is injected directly into the bladder, you may experience pain or difficulty urinating. You may also notice blood in your urine.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Epirubicina Aurovitas

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

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

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

Do not use this medicine after the expiry date stated on the carton and label, after EXP. The expiry date is the last day of the month indicated.

Do not use this medicine if you notice any visible signs of deterioration.

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. Package Contents and Additional Information

Composition of Epirubicina Aurovitas

• The active ingredient is epirubicin hydrochloride. Each milliliter of injectable solution contains 2 mg of epirubicin hydrochloride.
• The other ingredients are sodium chloride, hydrochloric acid (for pH adjustment), and water for injectable preparations.

Appearance of the Product and Package Contents

Epirubicina Aurovitas 2 mg/ml injectable solution EFG is a clear red solution.

Package sizes:

1 vial of 25 ml (50 mg/25 ml)

1 vial of 50 ml (100 mg/50 ml)

1 vial of 100 ml (200 mg/100 ml)

A 25 ml vial of Epirubicina Aurovitas 2 mg/ml injectable solution EFG contains 50 mg of epirubicin hydrochloride, equivalent to 46.75 mg of epirubicin.

A 50 ml vial of Epirubicina Aurovitas 2 mg/ml injectable solution EFG contains 100 mg of epirubicin hydrochloride, equivalent to 93.5 mg of epirubicin.

A 100 ml vial of Epirubicina Aurovitas 2 mg/ml injectable solution EFG contains 200 mg of epirubicin hydrochloride, equivalent to 187 mg of epirubicin.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Eugia Pharma (Malta) Limited

Vault 14, Level 2, Valletta Waterfront

Floriana, FRN 1914

Malta

Manufacturer

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate, Hal Far

Birzebbugia, BBG 3000

Malta

O

Generis Farmacêutica, S.A.

Rua João de Deus, nº 19, Venda Nova

2700-487 Amadora

Portugal

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

This medicine is authorized in the Member States of the European Economic Area under the following names:

Date of the last revision of this leaflet: August 2025

Detailed information on this medicine 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 healthcare professionals:

Epirubicina Aurovitas 2 mg/ml injectable solution EFG

Instructions for use

ANTINEOPLASTIC MEDICINE

Incompatibilities

Prolonged contact with alkaline pH solutions (including solutions containing bicarbonates) should be avoided, as they produce hydrolysis of the medicine. Only the diluents indicated in the "Instructions for use" section should be used.

The injectable solution or any diluted solution should not be mixed with any other medicine. Physical incompatibility with heparin has been reported.

Epirubicin should not be mixed with other medicines.

Instructions for use

Intravenous administration:it is recommended to administer the medicine through the tube of an intravenous saline perfusion in a uniform flow (0.9% sodium chloride). To minimize the risk of thrombosis or perivenous extravasation, the usual perfusion times range from 3 to 20 minutes, depending on the dose and volume of the perfusion solution. Direct injection is not recommended due to the risk of extravasation, which can occur even in the presence of adequate blood return in the aspiration needle.

Intravesical administration:before administration, Epirubicina Aurovitas should be diluted in sterile water for injectable preparations or in a sterile 0.9% saline solution. Epirubicin should be instilled using a catheter and should be retained in the bladder for 1-2 hours. During instillation, the patient should change position to ensure that the bladder mucosa is completely in contact with the solution. To avoid excessive dilution of the urine, the patient should be informed not to drink any liquid in the 12 hours prior to instillation. The patient should be instructed to urinate once the instillation is complete.

The injectable solution does not contain preservatives, and any unused amount from the vial should be discarded immediately.

Guidelines for the safe handling and disposal of antineoplastic medicines:

1. The preparation of a perfusion solution should be carried out by qualified personnel under aseptic conditions.

1. The preparation of a perfusion solution should be made in an aseptic area designated for this purpose.

1. Disposable protective gloves, protective glasses, gown, and mask should be used.

1. Precautions should be taken to avoid accidental contact of the medicine with the eyes. In case of contact with the eyes, wash abundantly with water and/or 0.9% sodium chloride solution. Then, consult a doctor for clinical evaluation.

1. In case of skin contact, wash the affected area well with water and soap or with a sodium bicarbonate solution. However, do not scrub the skin using a brush. Always wash your hands after removing gloves.

1. Spills or leaks should be treated with a diluted sodium hypochlorite solution (1% available chlorine), preferably by first soaking and then washing with water. All cleaning materials should be disposed of as described below.

1. Pregnant women should not handle cytotoxic preparations.

1. Caution should be exercised and adequate precautions taken when disposing of materials (syringes, needles, etc.) used to reconstitute and/or dilute cytotoxic medicines. The disposal of unused medicine or waste material will be carried out in accordance with local requirements.

Storage Conditions

Medicine in the commercial package:

Store in a refrigerator (between 2°C and 8°C). Keep the vial in the outer packaging to protect it from light.

After the first opening of the package:

From a microbiological point of view, the product should be used immediately after the first puncture of the rubber stopper. If not used immediately, the times and conditions of storage before use are the responsibility of the user.

After dilution of the injectable solution:

The product should be used immediately after the first puncture of the rubber stopper. If not used immediately, the times and conditions of storage before use are the responsibility of the user.

For more information, consult the Summary of Product Characteristics of Epirubicina Aurovitas 2 mg/ml injectable solution EFG.