Leaflet: information for the user

Epirubicin Aurovitas 2 mg/ml injectable solution EFG

Hydrochloride of epirubicin

Read this leaflet carefully before you start using this medicine, because 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 or pharmacist.
• This medicine has been prescribed only for you, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Epirubicina is a cancer medication. Sometimes, treatment with a cancer medication is called chemotherapy. Epirubicina is part of a group of medications called anthracyclines. These medications act on actively growing cells, slowing or stopping their growth, and increasing the likelihood of cell death.

Epirubicina 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, epirubicina is used to treat breast, stomach, and lung cancers, as well as advanced ovarian cancer.

When injected into the bladder through a tube, epirubicina is used to treat bladder wall cancer. It can also be used after other treatments to prevent those types of cells from growing back.

No use Epirubicina Aurovitas

•If you are allergic to hydrochloride epirubicin or any of the other components of this medication (listed in section 6).

•If you are allergic to other similar medications (which belong to a group of drugs called anthracyclines, such as doxorubicin or daunorubicin).

•If you are allergic to medications that belong to the anthracenodione group (including medications used to treat cancer).

•If you are breastfeeding.

Do not inject epirubicin into a vein (intravenous) if:

•You know that yourblood cell count is low, caused by previous treatment with other antitumor drugs or radiation therapy.

•You are being treated with otherchemotherapeutic agentsat maximum doses like epirubicin and/or other anthracyclines (such as doxorubicin or daunorubicin) and anthracenodiones, which may increase the risk of adverse effects.

•You have or have hadheart problems.

•You have a severe acute infection.

•You have severe liver problems.

Do not inject epirubicin 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 catheter in the bladder.

•You have inflammation in the bladder.

•You have blood in your urine (hematuria).

Warnings and precautions

Consult your doctor before starting to use Epirubicina Aurovitas:

•If you have liver or kidney problems.

•If you have been administered or will be administered any vaccine.

You must inform your doctor before starting treatment, as you must have greater caution.

Your doctor will also perform regular analyses

•To ensure that your blood cell count is not too low.

•To control the levels of uric acid and other factors in the blood.

•To check that your heart and liver are functioning normally.

•If you have received or will receive radiation therapy in the area near the heart.

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

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

Children

No data are available on safety and efficacy in children.

Other medications and Epirubicina Aurovitas

Inform your doctor if you are taking, have taken recently, or may take any other medication. Especially:

•Cimetidine (used to reduce stomach acidity).

•Trastuzumab (used in cancer treatment) may take up to 7 months to be eliminated from the body. As trastuzumab can affect the heart, do not use epirubicin until 7 months after completing trastuzumab treatment. 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 some heart conditions).

•Medications that can affect the heart, such as 5-fluorouracil, cyclophosphamide, cisplatin, taxanes (used to treat cancer) or calcium channel blockers (used to treat high blood pressure or some heart conditions).

•Medications that may affect the liver.

•Live vaccines.

•Other medications that may affect the bone marrow (such as other cancer medications), sulfonamides, and chloramphenicol (antibiotics), diphenylhydantoin (antiepileptic), amidopyrine derivatives (some medications to treat, for example, pain and fever) and some antiviral medications.

•Dexrazoxane (medication used to prevent chronic toxic effects on the heart produced by epirubicin).

Pregnancy, breastfeeding, and fertility

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

Pregnancy

Epirubicin may cause birth defects when used during pregnancy, so you must inform your doctor if you are pregnant or become pregnant during treatment. Do not use epirubicin during pregnancy unless your doctor clearly indicates it.

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 treatmentor if you wish to have children after completing treatment, it is recommended that you undergo a genetic consultation.

Breastfeeding

Epirubicin may be harmful to infants, so women must interrupt breastfeeding before starting epirubicin treatment.

Fertility

There is a risk of sterility due to epirubicin treatment. Male patients should consider preserving sperm before treatment.

Epirubicin may cause amenorrhea or premature menopause in premenopausal women.

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

Driving and operating machinery

Epirubicin may cause episodes of nausea and vomiting, which may temporarily impair your ability to drive or operate machinery.

Epirubicina Aurovitas contains sodium

This medication contains 0.154 mmol of sodium (3.54 mg) per 1 ml of injectable solution. The different sizes of Epirubicina Aurovitas containers contain the following amounts of sodium:

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

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

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

This medication can be prepared for administration with solutions that contain sodium. Inform your doctor if you follow a low-sodium diet.

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

Through injection or infusion into a vein

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

Administering it into the bladder

If the injection is given into the bladder, you should not drink any liquids in the 12 hours leading up to the treatment, so that the urine does not dilute the medication too much. After administration, the solution should be left in the bladder for 1-2 hours. You may need to change your position to ensure that the medication reaches all parts of the bladder.

You should take care to avoid contact between the bladder contents and your skin when urinating. If skin contact occurs, wash the affected area thoroughly 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 is completed.

If you receive more Epirubicina Aurovitas than you should

It may affect the heart, decrease the number of blood cells, and cause gastrointestinal problems (mainly mucositis). You may notice the appearance of sores in your mouth. However, since this medication will be administered while you are in the hospital, it is unlikely that you will receive either too little or too much of the medication.

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

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

If any of the following side effects appear when epirubicin is administered through a vein, inform your doctor immediately, as they are very serious side effects that may require urgent medical attention:

•Redness, pain, or inflammation at the injection site; tissue damage may occur if accidentally injected outside a vein.

•Heart problems or blood clots in the lungs, such as chest pain, shortness of breath, swelling of the ankles (these effects may appear several weeks after completing epirubicin treatment).

•Severe allergic reaction, with symptoms including dizziness, skin rash, facial swelling, 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, inform 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), decreased white blood cell count (leucopenia), decreased count of a specific type of white blood cell (granulocytopenia and neutropenia), decreased red blood cell count (anemia), and low levels of certain white blood cells accompanied by fever (neutropenic fever), decreased platelet count (thrombocytopenia).

•Mucosal membrane inflammation (mucositis), inflammation inside the mouth (stomatitis), discomfort (vomiting), watery or frequent stools (diarrhea), nausea, which may cause loss of appetite and abdominal pain.

•Hair loss, usually reversible, decreased beard growth.

•Red urine color for 1 or 2 days after administration.

•Amenorrhea.

•Conjunctivitis, corneal inflammation.

•Hot flashes.

•Skin lesions.

•Phlebitis.

•Discomfort, fever.

•Changes in liver enzyme levels (transaminases).

•Chemical cystitis, sometimes with blood in the urine, after administration in the bladder.

Common: may affect up to 1 in 10 people

•Dehydration.

•Heart function deterioration (congestive heart failure). Symptoms may include:

-Difficulty breathing (dyspnea).

-Swelling of the legs (edema).

-Enlarged liver.

-Fluid accumulation in the abdominal cavity (ascites).

-Fluid accumulation in the lungs (pulmonary edema).

-Fluid accumulation between the thorax and lungs (pleural effusion).

-Third heart sound (gallop rhythm).

•Local skin toxicity, skin rash, itching, increased skin and nail pigmentation, skin changes.

•Redness along the vein (erythema at the perfusion site).

•Bleeding.

•Redness of the skin.

•Chills.

•Loss of appetite.

•Asymptomatic changes in heart function (asymptomatic falls in left ventricular ejection fraction).

•Potentially fatal irregular heartbeats (ventricular tachycardia), decreased heart rate, alteration in heart impulse conduction (atrioventricular block, branch block).

•After administration in the bladder, chemical cystitis, urinary pain or burning, frequent urination.

•Gastrointestinal ulcers, erosions, and lesions, gastrointestinal bleeding, pain or burning behind the sternum, indigestion, and difficulty swallowing due to esophageal inflammation, pain or burning in the gastrointestinal tract, inflammation of the mucous membrane of the gastrointestinal tract and inside the mouth with a sensation of burning and pain.

Uncommon: may affect up to 1 in 100 people

•Some types of blood cancer (acute lymphocytic leukemia, acute myeloid leukemia).

•Blood poisoning (sepsis), lung infection (pneumonia).

•Weakness (asthenia).

•Redness of the skin (erythema), urticaria.

•Vascular blockage.

•Inflammation and pain in the legs or arms due to possible presence of a blood clot in a vein.

•Blood clots in the lungs causing chest pain and difficulty breathing.

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

•Severe, potentially fatal allergic reaction. Symptoms include sudden signs of allergy, such as skin rash, itching, or urticaria, facial swelling, difficulty breathing, wheezing, or shortness of breath, allergic reactions after administration of the medication in the bladder.

•Increased levels of uric acid in the blood.

•Dizziness.

•Toxic effects on the heart, such as ECG abnormalities, different types of irregular heartbeats (arrhythmias), or heart muscle disease (cardiomyopathy).

•Absence of sperm in the semen.

Frequency not known: cannot be estimated from available data

•Potentially fatal condition that occurs when blood pressure is too low due to blood poisoning (septic shock).

•Potentially fatal condition where blood pressure is too low (shock).

•Decrease in blood pressure, sometimes with skin reactions or rash.

•Inadequate oxygenation of tissues due to suppression of blood cell production in the bone marrow (myelosuppression).

•Obstruction of a blood vessel by a blood clot (thromboembolism).

•Vein wall thickening, local pain, severe cellulitis.

•Increased mucosa coloration in the mouth.

•Increased sensitivity to light (photosensitivity), skin hypersensitivity to radiation (radiation recall reaction).

•Severe tissue damage after leakage of the injected solution into surrounding tissue.

•Headache.

•Pain.

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

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 prospectus. You can also report them directly through the Spanish System of Pharmacovigilance of Medicines for Human Use:www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

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

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

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

Do not use this medicationif you observe any visible sign of deterioration.

Medicines should not be disposed of through 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 Aurovitas

-The active ingredient is epirubicin hydrochloride. Each milliliter of injectable solution contains 2 mg of epirubicin hydrochloride.

-The other components are sodium chloride, hydrochloric acid (for pH adjustment) and water for injection preparations.

Aspect of the product and contents of the package

EpirubicinAurovitas2 mg/ml injectable solution EFG is a transparent solution of red color.

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)

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

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

One vial of 100 ml of Epirubicin 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 commercially available.

Marketing authorization holder and manufacturer responsible

Marketing authorization holder

Eugia Pharma (Malta) Limited

Vault 14, Level 2, Valletta Waterfront

Floriana, FRN 1914

Malta

Manufacturer responsible

APL Swift Services (Malta) Ltd.

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

For more information about this medicine, please contact 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 with the following names:

Last review date of this leaflet: December 2023

For detailed information about this medicine, please visit the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/).

This information is intended solely for healthcare professionals:

Epirubicina Aurovitas 2 mg/ml injectable solution EFG

Instructions for use

ANTINEOPLASTIC MEDICINE

Incompatibilities

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

The injectable solution and any diluted solution should not be mixed with any other medication. Incompatibility with heparin has been reported.

Epirubicin should not be mixed with other medications.

Instructions for use

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

Intravesical administration:before administration,Epirubicina Aurovitas should bediluted in sterile water for injection 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 vesical mucosa of the pelvis is in contact with the solution. To avoid excessive dilution of urine, the patient should be instructed not to drink any liquids 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 should be discarded immediately after any unused amount from the vial.

Guidelines for safe handling and disposal of antineoplastic drugs:

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

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

3.Disposable protective gloves, protective glasses, a suitable gown, and mask should be used.

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

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

6.Leaks or spills should be treated with a 1% available chlorine solution, preferably by soaking it first and then washing it with water. All cleaning materials should be disposed of as described below.

7.Female personnel who are pregnant should not handle cytotoxic preparations.

8.Care should be taken and appropriate precautions should be taken when disposing of the used material (syringes, needles, etc.) used to reconstitute and/or dilute cytotoxic drugs. The disposal of unused medication or waste material will be carried out in accordance with local requirements.

Storage conditions

Medicine in the package for commercialization:

Store in refrigerator (between 2°C and 8°C). Store 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 storage times and conditions 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 storage times and conditions before use are the responsibility of the user.

For more information, please consult the Technical Data Sheet of Epirubicin Aurovitas 2 mg/ml injectable solution EFG.