Epimedac 2 mg/ml roztvur do vstzhikivani

Leaflet accompanying the packaging: patient information

Epimedac, 2 mg/ml, solution for injection

Epirubicin hydrochloride

Read the leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, so you can read it again if you need to.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• If the patient experiences any side effects, including those not listed in this leaflet, they should inform their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Epimedac and what is it used for
• 2. Important information before taking Epimedac
• 3. How to take Epimedac
• 4. Possible side effects
• 5. How to store Epimedac
• 6. Contents of the packaging and other information

1. What is Epimedac and what is it used for

Epirubicin hydrochloride, the active substance of Epimedac, belongs to a group of active substances called anthracyclines. These cytotoxic active substances are used to treat cancer.
Epimedac is used to treat:

• breast cancer;
• advanced ovarian cancer;
• stomach cancer;
• small cell lung cancer (a special type of lung cancer);
• superficial or very limited bladder cancer.

2. Important information before taking Epimedac

Epimedac should not be administered if

• the patient is allergic to epirubicin hydrochloride or any of the other ingredients of this medicine (listed in section 6) or to anthracyclines (e.g., doxorubicin and daunorubicin).
• the patient is allergic to anthracenediones (a group of cancer medicines).
• the patient has permanent bone marrow depression caused by previous treatment with other cytotoxic medicines or radiotherapy.
• the patient is being treated with maximum doses of epirubicin or other anthracyclines (e.g., doxorubicin or daunorubicin) and anthracenediones (cancer medicines).
• the patient has or has had heart problems (e.g., arrhythmias, reduced heart function, heart attack, heart muscle disorders, acute myocarditis, unstable angina).
• the patient has severe liver function disorders.
• the patient has a systemic infection (an infection that affects the whole body).
• the patient is breastfeeding.
• the patient has severe inflammation of the mucous membranes and (or) stomach.

In the case of administration to the bladder, Epimedac should not be administered if

• the patient has a urinary tract infection.
• the tumor has penetrated the bladder wall.
• there are problems with the insertion of a catheter into the bladder.
• the patient has cystitis.
• the patient has blood in the urine.
• the patient has bladder spasm.
• after urination, a large amount of urine remains in the bladder.

Warnings and precautions

Special caution should be exercised (to be discussed with the doctor) if

• the patient has liver or kidney function disorders.
• the patient experiences discomfort at the injection site or nearby (the solution for injection may have leaked into the surrounding tissues).
• the patient has a reduced number of white and red blood cells and platelets.
• the patient has oral mucositis or mucositis (painful lips or aphthae in the mouth).
• the patient has previously undergone radiotherapy to the chest or taken medicines that may have adverse effects on the heart.
• the patient has been recently vaccinated or plans to be vaccinated in the near future.
• the patient has previously taken trastuzumab (a medicine used to treat certain types of cancer).

Children

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

Epimedac and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take, including those obtained without a prescription, and especially:

• medicines that may affect the heart, such as other anticancer medicines (e.g., 5-fluorouracil, cyclophosphamide, cisplatin, taxanes) or calcium channel blockers (e.g., verapamil, dexverapamil) and radiotherapy used simultaneously or previously.
• medicines that may affect liver function.
• cimetidine (a medicine usually used to treat stomach ulcers and heartburn); cimetidine may enhance the effect of epirubicin.
• paclitaxel (a medicine used to treat cancer): treatment with epirubicin and paclitaxel should be administered with at least a 24-hour interval between the administration of these two medicines.
• docetaxel (a medicine used to treat cancer).
• quinine (a medicine used to treat malaria and leg cramps).
• interferon alfa-2b (a medicine used to treat certain types of cancer and lymphomas, as well as some forms of hepatitis).
• medicines that may affect blood morphology (e.g., other cytotoxic medicines, antibiotics such as sulfonamides and chloramphenicol, antiepileptic medicines such as phenytoin, antiretroviral medicines used to treat HIV infection, and painkillers such as aminopyrine derivatives).
• dexrazoxane (used in the prevention of cardiotoxicity caused by prolonged accumulation of epirubicin).
• trastuzumab. The elimination of trastuzumab (a medicine used to treat certain types of cancer) from the body may take up to 7 months. Trastuzumab may affect the heart; therefore, patients should not take epirubicin for up to 7 months after stopping trastuzumab treatment. If epirubicin is administered before the end of this period, the patient's heart function should be closely monitored.
• antibiotics such as sulfonamides and certain diuretics; may cause increased uric acid levels in the blood.
• heparin (a medicine that prevents blood clotting); may lead to a loss of effectiveness of both epirubicin and heparin.

In case of vaccination, the doctor should be informed that the patient is taking epirubicin before administering the vaccine.

Pregnancy, breastfeeding, and fertility

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor before taking this medicine.
Epirubicin hydrochloride, the active substance of Epimedac, may cause birth defects; therefore, it is essential to inform the doctor if the patient suspects they are pregnant. In pregnant women, epirubicin has been associated with heart disorders in newborns and unborn children, including fetal death. Epimedac should not be administered during pregnancy unless the doctor explicitly recommends it. Women should avoid becoming pregnant if they or their partner are taking Epimedac.
Women of childbearing age should use effective contraception during epirubicin treatment and for at least 7 months after the last dose. Men should use effective contraception during treatment and for at least 4 months after the last dose. If the patient or their partner becomes pregnant during Epimedac treatment, genetic counseling is recommended.
Men planning to have children should seek advice on sperm freezing before starting Epimedac treatment.
The patient must stop breastfeeding before, during, and for at least 7 days after the last dose of Epimedac, as the medicine may harm the breastfed child.

Driving and using machines

Epimedac may cause nausea and vomiting, which can temporarily impair the ability to drive and operate machines.

Epimedac contains sodium

The medicine contains 0.154 mmol (or 3.54 mg) of sodium per ml of solution for injection. Different packaging sizes of Epimedac contain the following amounts of sodium:
5 ml vial:
This packaging contains less than 1 mmol (23 mg) of sodium, which means the medicine is considered "sodium-free".
10 ml vial:
This packaging contains 35.42 mg of sodium (the main component of table salt).
This corresponds to 1.77% of the maximum recommended daily intake of sodium in the diet for adults.
25 ml vial:
This packaging contains 88.55 mg of sodium (the main component of table salt).
This corresponds to 4.43% of the maximum recommended daily intake of sodium in the diet for adults.
50 ml vial:
This packaging contains 177.1 mg of sodium (the main component of table salt).
This corresponds to 8.86% of the maximum recommended daily intake of sodium in the diet for adults.
100 ml vial: This packaging contains 354.21 mg of sodium (the main component of table salt).
This corresponds to 17.71% of the maximum recommended daily intake of sodium in the diet for adults.

3. How to take Epimedac

Epimedac is administered to patients under the supervision of a doctor specializing in this type of treatment. Before and during Epimedac treatment, the doctor monitors various laboratory parameters (e.g., red blood cell count, uric acid levels in the blood, liver function) and closely monitors heart function. Heart function monitoring will also be performed for several weeks after the end of Epimedac treatment.
The dosage of Epimedac depends on the type of disease being treated, the patient's response to treatment, and other medicines being taken by the patient.
The dose of Epimedac is based on the patient's body surface area. The dose is calculated based on the patient's height and weight.
The recommended dose of Epimedac is 60-90 mg per square meter of body surface area. The medicine is administered as an intravenous injection, i.e., into a blood vessel (vein), over three to five minutes.
The patient receives an injection every three weeks.
In the treatment of small cell lung cancer, a higher dose of 120 mg per square meter of body surface area is administered as an intravenous injection over three to five minutes or as an infusion (drip) lasting up to 30 minutes, also every three weeks.
In the treatment of breast cancer, the doctor decides on the dosage and procedure.
Doses are reduced in case of low white and red blood cell counts, liver or kidney function disorders, or when the medicine is used in combination with other cytotoxic medicines.
Epimedac can also be administered directly into the bladder to treat superficial bladder cancer or to prevent cancer recurrence after tumor removal. The dosage depends on the type of bladder cancer.
To prevent unwanted dilution of Epimedac by urine, the patient should not drink fluids for 12 hours before the procedure.
The patient remains under close observation before, during, and after Epimedac treatment.

Administration of a higher dose of Epimedac than recommended

If the patient is administered a higher dose of Epimedac than recommended, they may experience symptoms such as severe heart disorders, significant reduction in blood cell count, severe inflammation of the mucous membranes and stomach, and severe circulatory disorders. The adverse reactions may be more severe.
If these symptoms occur, Epimedac administration will be stopped immediately, and treatment of the symptoms will be initiated. In case of severe heart disorders, it may be necessary to consult a cardiologist. In case of a significant reduction in blood cell count, the patient may receive blood transfusions.

4. Possible side effects

Like all medicines, Epimedac can cause side effects, although not everybody gets them.
Inform your doctor immediatelyto discuss further action if you notice any side effects.
For one or two days after Epimedac administration, the urine may have a red color. This is normal and should not cause concern.

Very common: may occur in more than 1 in 10 people

• Infection
• Suppression of white blood cell production in the bone marrow (myelosuppression), reduced white blood cell count (leukopenia), reduced count of specific types of white blood cells (granulocytopenia and neutropenia), reduced red blood cell count (anemia)

and a low count of certain white blood cells accompanied by fever (febrile neutropenia), reduced platelet count (thrombocytopenia)

• Mucositis, oral mucositis, vomiting, watery stools or frequent bowel movements (diarrhea), nausea, which can cause loss of appetite and abdominal pain
• Hair loss, usually reversible
• Red urine color for 1-2 days after treatment
• Amenorrhea
• Conjunctivitis, keratitis
• Hot flashes
• Skin changes
• Phlebitis
• Discomfort (malaise), fever
• Changes in the activity of certain liver enzymes (aminotransferases)
• Cystitis (chemical cystitis), sometimes with blood in the urine, observed after intravesical administration

Common: may occur in up to 1 in 10 people

• Dehydration
• Heart function disorder (congestive heart failure). Symptoms may include: shortness of breath (dyspnea) fluid accumulation in the legs (edema) liver enlargement fluid accumulation in the abdominal cavity (ascites) fluid accumulation in the lungs (pulmonary edema) fluid accumulation between the chest wall and lungs (pleural effusion) third heart sound (gallop rhythm)
• Local toxic effect on skin tissue, rash, itching, excessive skin pigmentation and nail discoloration, skin changes
• Redness along the vein (injection site reaction)
• Bleeding
• Redness of the skin
• Chills
• Loss of appetite
• Asymptomatic changes in heart function (asymptomatic reduction in left ventricular ejection fraction)
• Life-threatening irregular heartbeats (ventricular tachycardia), slow heart rate, heart conduction disorders (atrioventricular block, bundle branch block)
• Cystitis (chemical cystitis), pain and burning during urination, blood in the urine, frequent urination, observed after intravesical administration
• Gastrointestinal ulcers, erosions, and changes in the stomach, gastrointestinal bleeding, chest pain, dysphagia, and esophagitis caused by mucositis

Uncommon: may occur in up to 1 in 100 people

• Certain types of blood cancer (acute lymphoblastic leukemia, acute myeloblastic leukemia)
• Blood infection (sepsis), lung infection (pneumonia)
• Weakness (asthenia)
• Redness of the skin (flushing), urticaria
• Vascular occlusion
• Swelling and pain in the legs or arms due to vascular inflammation, with possible blood clot formation
• Blood clots in the lungs causing chest pain and shortness of breath

Rare: may occur in up to 1 in 1000 people

• Sudden life-threatening allergic reaction. Symptoms of such a reaction include sudden allergic symptoms, such as rash, itching, or urticaria on the skin, swelling of the face, lips, tongue, or other parts of the body, shortness of breath, wheezing, or difficulty breathing; allergic reactions after intravesical administration of the medicine
• Increased uric acid levels in the blood
• Dizziness
• Cardiotoxic effects causing abnormalities in the ECG (electrocardiogram), various types of irregular heartbeats (arrhythmias), or heart muscle disease (cardiomyopathy)
• Azoospermia

Frequency not known: frequency cannot be estimated from the available data

• A life-threatening condition that occurs when blood pressure is too low due to a blood infection (septic shock)
• A life-threatening condition that occurs when blood pressure is too low (shock)
• A sudden drop in blood pressure that occurs sometimes with skin reactions or rash (anaphylactic shock)
• Due to bone marrow suppression (myelosuppression), tissue hypoxia may occur
• Vascular occlusion due to blood clot displacement (thromboembolic disease)
• Thickening of vein walls, local pain, severe inflammation of the subcutaneous tissue
• Excessive discoloration of the oral mucosa
• Sensitivity to light, sensitivity of the skin previously exposed to radiation (radiation recall)
• Severe tissue damage after leakage of the injected solution into the surrounding tissues
• Headache
• Pain

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, inform your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw,
phone: +48 22 49-21-301, fax: + 48 22 49-21-309,
website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help gather more information on the safety of the medicine.

5. How to store Epimedac

Store in a refrigerator (2°C – 8°C).
Keep the vial in the outer packaging to protect it from light.
Store the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and carton after:
"Expiry date (EXP)". The expiry date refers to the last day of the month.
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. Contents of the packaging and other information

What Epimedac contains

• The active substance is epirubicin hydrochloride.
• The other ingredients are sodium chloride, hydrochloric acid, and water for injections.

1 ml of solution contains 2 mg of epirubicin hydrochloride.
One 5 ml vial contains 10 mg of epirubicin hydrochloride.
One 10 ml vial contains 20 mg of epirubicin hydrochloride.
One 25 ml vial contains 50 mg of epirubicin hydrochloride.
One 50 ml vial contains 100 mg of epirubicin hydrochloride.
One 100 ml vial contains 200 mg of epirubicin hydrochloride.

What Epimedac looks like and contents of the packaging

Epimedac is a clear, red solution.
The medicine is supplied in single vials.

Marketing authorization holder and manufacturer

medac
Gesellschaft für klinische
Spezialpräparate mbH
Theaterstr. 6
22880 Wedel
Germany
Phone: +49 4103 8006-0
Fax: +49 4103 8006-100

This medicine is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Denmark
Epirubicin "medac" 2 mg/ml injection solution

Finland
Epirubicin medac 2 mg/ml injectable solution

Germany
Epimedac 2 mg/ml solution for injection

Norway
Epirubicin medac 2 mg/ml injection solution

Poland
Epimedac 2 mg/ml solution for injection

Portugal
Epirrubicina medac 2 mg/ml solution for injection

Slovakia
Epimedac 2 mg/ml solution for injection

United Kingdom
(Northern Ireland)
Epirubicin hydrochloride 2 mg/ml solution for injection

Date of last revision of the leaflet: 22.06.2023

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Information intended for healthcare professionals only:
Epimedac can be diluted in glucose 50 mg/ml (5%) or sodium chloride 9 mg/ml (0.9%) solution and administered as an intravenous infusion. The infusion solution should be prepared immediately before use.
The solution for injection does not contain preservatives. Any unused product or waste materials should be disposed of in accordance with local regulations.

Pharmaceutical incompatibilities

Avoid prolonged contact of the medicinal product with alkaline pH solutions (including sodium bicarbonate solutions), as this may lead to hydrolysis (degradation) of the active substance. Only the diluents described below should be used.
A physical incompatibility of the medicinal product with heparin has been reported.
Do not mix the medicinal product with other medicinal products, except those listed below.

Stability after preparation

Epimedac can be diluted in aseptic conditions, in glucose 50 mg/ml (5%) or sodium chloride 9 mg/ml (0.9%) solution, and administered as an intravenous infusion. Chemical and physical stability has been demonstrated for 48 hours at 25 ºC, protected from light.
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. The storage time should not exceed 24 hours at 2-8 ºC, provided that the dilution has been made in controlled and validated aseptic conditions.

Instructions for the safe handling and disposal of anticancer medicines:

• 1. Preparation of the infusion solution should be performed by trained personnel in aseptic conditions.
• 2. Preparation of the infusion solution should be performed in an area designated as aseptic.
• 3. Wear appropriate, protective, single-use gloves, safety glasses, a gown, and a face mask.
• 4. Use safety measures to prevent accidental contact of the medicinal product with the eyes. In case of eye contact, flush the eye with plenty of water and (or) sodium chloride 9 mg/ml (0.9%) solution.
• 5. In case of skin contact, wash the skin thoroughly with soap and water or sodium bicarbonate solution. Do not scrub the skin with a hard brush. Wash hands after removing gloves.
• 6. Spilled medicinal product should first be flooded with a diluted sodium hypochlorite solution (containing 1% chlorine), preferably by soaking, and then rinsed with water. All materials used for cleaning should be disposed of as described below.
• 7. Pregnant women should not come into contact with cytotoxic preparations.
• 8. When disposing of items (syringes, needles, etc.) used to reconstitute and (or) dilute cytotoxic medicinal products, caution should be exercised and appropriate safety measures taken. Any unused product or waste materials should be disposed of in accordance with local regulations.