EPIRUBICIN HIKMA 2 mg/ml INTRAVESICAL SOLUTION AND INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Epirubicin Hikma 2 mg/mlintravesical and injectable solution EFG

epirubicin 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.

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 experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack:

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

1. What Epirubicin Hikma is and what it is used for

• This medicine is an injection that contains epirubicin hydrochloride. It belongs to a group of medicines called cytotoxics used for chemotherapy. This medicine works by slowing down or stopping the growth of cells that are growing rapidly, such as cancer cells, and increasing the likelihood that they will die. This medicine helps to kill cancerous tissue rather than normal healthy tissue.

• This medicine is used to treat various types of cancer, either alone or in combination with other medicines. The way it is used depends on the type of cancer being treated.

• It has been found to be particularly useful in the treatment of breast, ovarian, stomach, intestinal, and lung cancers.

• This medicine can also be placed directly into the bladder through a tube. This is sometimes used to treat abnormal cells or cancer of the bladder wall. It can be used after other treatments to prevent these cells from growing back.

Talk to your doctor if you do not feel better or if you feel worse.

2. What you need to know before you use Epirubicin Hikma

Do not use Epirubicin Hikma

• if you are allergic to epirubicin, to any of the other ingredients of this medicine (listed in section 6), or to other similar medicines used in chemotherapy (anthracyclines or anthracenediones); if you have infections that affect multiple organs
• if you have a urinary tract infection
• if you have bladder inflammation
• if you have invasive tumors penetrating the bladder
• if you have catheterization problems (your doctor has problems inserting a catheter (tube) into the bladder)
• if there is blood in the urine
• if you have a reduced ability to produce blood cells, which can lead to a low blood cell count, as it may reduce them further
• if you have previously received treatment with epirubicin or similar chemotherapy medicines, as previous treatment with these medicines may increase the risk of side effects if you have recently had a heart attack, have poor heart muscle activity, irregular and severe heart rhythm patterns, sudden chest pain, non-inflammatory heart muscle disease, or if you have experienced any other serious heart problems in the past, or are being treated for this
• if you have severe liver disease.
• if you are pregnant or breastfeeding;

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before using this medicine:

• • if your liver or kidneys are not working properly
  • if you have had or need to be vaccinated
  • if you currently have acute toxicity such as
• acute mouth inflammation
• low white blood cell count
• low platelet count or
• general infections

This will help your doctor decide if this medicine is suitable for you.

Other medicines and Epirubicin Hikma

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

• Cimetidine (a medicine used to treat stomach ulcers and heartburn). Cimetidine may increase the effect of this medicine.
• Calcium channel blockers (heart medicines)
• Quinine (a medicine for malaria)
• Antibiotics such as sulfonamide and chloramphenicol
• Antiretrovirals (medicines used to treat HIV infection)
• Diphenylhydantoin (a medicine used to treat epilepsy)
• Pain relievers such as amidopyrine derivatives
• Trastuzumab used in the treatment of cancer. If possible, your doctor should avoid treatment with epirubicin for up to 27 weeks after completing treatment with trastuzumab. If this medicine is used before this period, it is recommended to carefully monitor heart function.
• Vaccination with a live vaccine should be avoided in patients receiving epirubicin
• Paclitaxel or docetaxel (medicines used to treat cancer). When paclitaxel is administered before epirubicin, it may increase the concentration of epirubicin in the blood. However, when paclitaxel and docetaxel are administered simultaneously and after epirubicin, they do not have any effect on the concentration of epirubicin
• Dexverapamil (a medicine used to treat certain heart conditions)
• Dexrazoxane (a medicine used to prevent chronic cumulative cardiotoxicity caused by epirubicin)
• Interferon α2b (used to treat cancers)

Pregnancy, breastfeeding, and fertility

Pregnancy

If you are pregnant, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before using this medicine. You must not become pregnant while you or your partner are being treated with this medicine. If you are sexually active, you are advised to use effective contraception to prevent pregnancy during treatment, whether you are male or female. It may cause birth defects, so it is important that you inform your doctor if you think you are pregnant.

Breastfeeding

You must stop breastfeeding before starting treatment with this medicine, as some of the medicine may pass into breast milk and could harm your child.

Fertility

Men: There is a risk of infertility due to treatment with epirubicin, so male patients should consider the possibility of sperm preservation before undergoing treatment.

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

Driving and using machines

No special precautions are necessary, as long as you feel fully recovered after hospital treatment and you have discussed this with your doctor.

Epirubicin Hikma contains sodium

Epirubicin Hikma 10 mg/5 ml

This medicine contains less than 1 mmol of sodium (23 mg) per vial, i.e., it is essentially "sodium-free".

Epirubicin 20 mg/10 ml

This medicine contains 34.48 mg of sodium (a major component of table/cooking salt) in each vial. This is equivalent to 1.72% of the maximum recommended daily intake of sodium for an adult.

Epirubicin 50 mg/25 ml

This medicine contains 86.19 mg of sodium (a major component of table/cooking salt) in each vial. This is equivalent to 4.31% of the maximum recommended daily intake of sodium for an adult.

Epirubicin 200 mg/100 ml

This medicine contains 344.73 mg of sodium (a major component of table/cooking salt) in each vial. This is equivalent to 17.24% of the maximum recommended daily intake of sodium for an adult.

3. How to use Epirubicin Hikma

This medicine should only be administered under the supervision of a doctor or nurse with experience in chemotherapy. Normally, this medicine will be administered to you by a doctor or nurse through a drip (infusion) into a vein. Your doctor will decide the correct dose and the number of days you will receive treatment.

The dose will depend on the type of cancer you have, your overall health, height, and weight. Based on your height and weight, your doctor will calculate your body surface area, and the dose will be determined from this. This medicine can also be administered directly into the bladder to treat bladder cancer or to help prevent its recurrence. The dose depends on the type of bladder cancer you have. If the injection is administered directly into the bladder, you should not drink any fluids in the 12 hours before treatment, so that the urine does not dilute the medicine too much.

While one treatment cycle may be sufficient, it is usual for your doctor to recommend that you undergo more cycles after three or four weeks. You may need to undergo several cycles before your disease is under control and you feel better.

Regular checks performed by your doctor during treatment with Epirubicin Hikma

During treatment, your doctor will perform regular checks on:

• Blood - to check for low blood cell counts that may require treatment
• Heart function - heart damage can occur when high doses of this medicine are administered. This may not be detected for several weeks, so regular tests may be required during this period
• Liver - blood tests will be performed to check that this medicine is not affecting its function in a harmful way

• Uric acid levels in the blood - this medicine can increase uric acid levels in the blood, which could cause gout. You may be given another medicine if uric acid levels are too high.

If you receive more Epirubicin Hikma than you should

High doses can worsen side effects such as mouth ulcers or reduce the number of white blood cells (which fight infection) and platelets (which help blood clot) in the blood. If this happens, you may need antibiotics or blood transfusions. Mouth ulcers can be treated to cause less discomfort while they heal.

If you have any questions about using this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

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

Very common: (may affect more than 1 in 10 people)

• Infections
• Eye inflammation with red eyes and watery eyes
• Low red blood cell count (anemia), which can make you feel tired and lethargic
• Low white blood cell count (which fights infection), making you more likely to get infections and fever; (leukopenia)
• Low platelet count (which helps blood clot), which could cause bruising or bleeding more easily when injured
• Reduction in the number of certain types of white blood cells - granulocytes and neutrophils (granulocytopenia and neutropenia)
• Reduction in certain types of white blood cells accompanied by fever (febrile neutropenia)
• Inflammation of the clear part of the eye called the cornea
• Hot flashes
• Vein inflammation
• Nausea
• Vomiting
• Inflammation of the mucous membrane lining the mouth
• Diarrhea
• Hair loss
• Skin injury
• Red discoloration for 1 or 2 days after administration of epirubicin
• Absence of menstruation
• Painful and ulcerative inflammation of the mucous membranes lining the digestive tract
• General malaise
• High fever
• Changes in the levels of some liver enzymes
• After direct administration of epirubicin into the bladder, inflammation (cystitis) may occur

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

• Loss of appetite
• Dehydration or loss of body fluids
• Serious disruption of heart rhythm (ventricular arrhythmia)
• Conduction disorders due to cardiac impulse
• Certain types of heart rhythm disorders (AV block, bundle branch block)
• Slow heart rate (bradycardia)
• Insufficient pumping of blood by the heart, which can cause difficulty breathing, fluid accumulation, and an abnormal heart rate.
• Bleeding
• Redness of the skin
• Pain behind the breastbone, indigestion, and difficulty swallowing due to inflammation in the esophagus
• Pain or burning in the gastrointestinal tract
• Inflammation of the mucous membrane lining the gastrointestinal tract
• Ulcers in the gastrointestinal tract
• Rash, itching
• Abnormal nail discoloration
• Changes in skin
• Abnormal skin discoloration
• Frequent urination
• Redness at the infusion site
• Chills
• Local reactions such as a burning sensation
• Decreased heart function

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

•High fever, chills, general malaise, possible cold arms and legs due to blood poisoning

• Lung infection (pneumonia)
• Certain types of blood cancer (acute lymphatic leukemia, acute myeloid leukemia)
• Blockage in a blood vessel
• Inflammation and pain in the legs or arms due to inflammation of a blood vessel, possibly due to the presence of a blood clot
• Blood clots in the lungs that cause chest pain and shortness of breath
• Bleeding in the gastrointestinal tract
• Hives
• Redness of the skin
• Feeling of weakness

Contact your doctor or nurse immediately if you notice any of the following side effects. Although they are rare, these symptoms can be serious:

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

• Sudden, potentially life-threatening allergic reaction. Symptoms include, among others, sudden signs of allergy such as skin rash, itching, or hives, swelling of the face, lips, tongue, or other parts of the body, difficulty breathing, wheezing, or difficulty breathing
• Increased uric acid in the blood.
• Heart damage (cardiotoxicity)
• Absence of sperm in the semen
• Dizziness

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
• Insufficient oxygen supply to the tissue due to the inhibited production of blood cells in the bone marrow
• Appearance of dark spots inside the mouth
• Abdominal discomfort
• Redness of the skin or other reactions similar to sunburn when exposed to sunlight or ultraviolet rays
• Changes in the skin previously exposed to radiation

Reporting of side effects:

If you experience any side effects, talk to your doctor, pharmacist, or nurse. 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: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Epirubicin Hikma

Store and transport refrigerated (between 2°C and 8°C).

Keep in the outer packaging to protect from light.

Keep out of the reach and sight of children.

Do not use this medicine after the expiry date which is stated on the carton after EXP: MM/YYYY. The expiry date is the last day of the month shown.

Chemical and physical stability has been demonstrated after dilution in sodium chloride 0.9% or glucose 5% solution, for 72 hours when stored refrigerated.

From a microbiological point of view, the product should be used immediately. If not used immediately, the in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless the dilution has taken place in controlled and validated aseptic conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Container Content and Additional Information

Composition of Epirubicina Hikma

• The active ingredient is epirubicin hydrochloride.
• The other components are sodium lactate (50% solution), hydrochloric acid (1N) for pH adjustment, sodium chloride, and water for injectable preparations.

Epirubicina Hikma is an intravesical/injectable solution.

Product Appearance and Container Content

Red solution for injection packaged in transparent vials (type I glass) with a chlorobutyl rubber stopper and aluminum cap.

10 mg/5 ml

Container with 1 vial of 5 ml of solution.

20 mg/10 ml

Container with 1 vial of 10 ml of solution.

50 mg/25 ml

Container with 1 vial of 25 ml of solution.

200 mg/100 ml

Container with 1 vial of 100 ml of solution.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Hikma Farmacêutica (Portugal), S.A.

Estrada do Rio da Mó, 8, 8A e 8B

Fervença

2075-906 Terrugem SNT

Portugal

Tel.: +351 219608410

e-mail: portugalgeral@hikma.com

Manufacturer

Thymoorgan Pharmazie GmbH

Schiffgraben 23

D-38690 Goslar

Germany

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

Hikma España, S.L.U.

Calle Anabel Segura nº11, Edificio A, planta 1ª, oficina 2

28108 - Alcobendas, Madrid

Spain

This medication is authorized in the member states of the European Economic Area under the following names

Date of the last revision of this prospectus:05/2022

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

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This information is intended only for healthcare professionals

Epirubicina Hikma 2 mg/ml intravesical and injectable solution EFG

epirubicin hydrochloride

FOR INTRAVENOUS INJECTION OR INTRAVESICAL ADMINISTRATION

Incompatibilities

Prolonged contact between the medication and any alkaline pH solution (including sodium bicarbonate solutions) should be avoided, as this may cause hydrolysis of the active substance. Only the diluents detailed in the "Instructions for use" section should be used.

Neither the injectable solution nor any diluted solution should be mixed with any other medication. Physical incompatibility has been reported with heparin (precipitation).

Dilution Instructions

The injection can be administered through the tube of an intravenous saline perfusion in a uniform flow. When the injection is administered after dilution, the following instruction should be followed.

This medication can be further diluted under aseptic conditions with 5% glucose or 0.9% sodium chloride and administered as an intravenous perfusion.

The perfusion solution should be prepared immediately before use.

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

Safe Handling

This is a cytotoxic product; please follow the guidelines for the safe handling and disposal of antineoplastic medications.

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Storage

Store and transport refrigerated (between 2°C and 8°C).

Store in the outer packaging to protect it from light.

The chemical and physical stability has been demonstrated, after dilution with 0.9% sodium chloride or 5% glucose, for 72 hours when stored refrigerated. From a microbiological point of view, the product should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and should not normally exceed 24 hours at 2-8°C, unless the dilution has been performed under controlled and validated aseptic conditions.

Marketing Authorization Holder

Hikma Farmacêutica (Portugal), S.A.

Estrada do Rio da Mó, 8, 8A e 8B

Fervença

2075-906 Terrugem SNT

Portugal

portugalgeral@hikma.com

Date of the last revision of this prospectus:05/2022

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