EPIRUBICINA 2 мг/мл Инъекционный или инфузионный раствор

Содержание инструкции

1. Epirubicina Teva 2 mg/ml injectable solution or infusion solution
   1. What is Epirubicina Teva and what is it used for
   2. What you need to know before you use Epirubicina Teva
   3. How to use Epirubicina Teva
   4. Possible side effects
   5. How to store Epirubicina Teva
   6. Contents of the pack and other information
   7. FORMULATION
   8. SPECIAL PRECAUTIONS FOR STORAGE
   9. NATURE AND CONTENTS OF CONTAINER
   10. INCOMPATIBILITIES
   11. RECOMMENDATIONS FOR SAFE HANDLING
   12. PREPARATION OF THE SOLUTION
   13. 1 Preparation for intravenous administration
   14. 2 Preparation for intravesical administration
   15. DISPOSAL

Epirubicina Teva 2 mg/ml injectable solution or infusion solution

Epirubicin hydrochloride

Generic medicine

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

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

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

Epirubicin belongs to the group of cytotoxic drugs (products used to fight cancer).
Epirubicin prevents cancer cells from growing further, eventually causing their
death.
Epirubicin is used for the treatment of:

• breast cancer;
• stomach cancer;
• epirubicin hydrochloride is also used via intravesical route (directly into the bladder) in the treatment of early (superficial) bladder cancer and to prevent recurrence of bladder cancer after surgery. Epirubicin is often used simultaneously with other anticancer drugs (in so-called polychemotherapy regimens).

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

Do not use Epirubicina Teva

• if you are allergicto epirubicin, to similar medicines (called anthracyclines or anthracenediones, see below) or to any of the other ingredients of this medicine (listed in section 6);
• if you are breast-feeding.

Depending on the route of administration, you must not use Epirubicina Teva if you are in the following
situations:
Intravenous administration (into a vein):

• if you have previously been treated with high dosesof other anticancer medicines, including doxorubicin and daunorubicin, which belong to the same group of medicines

as epirubicin hydrochloride 2 mg/ml (called anthracyclines). These agents cause similar side
effects (including those on the heart);

• if you suffer from or have suffered from heart problems;
• if you have a low number of blood cells;
• if you suffer from a severe liver dysfunction;
• if you suffer from a severe acute infection.

Intravesical administration (directly into the bladder):

• if the cancer has penetrated the bladder wall;
• if there is an infection of the urinary tract;
• if there is pain or inflammation of the bladder;
• if the doctor has difficulty inserting a catheter (small tube) into the bladder;
• if a significant amount of urine remains in the bladder after attempting to empty it;
• if your urine contains blood;
• if you have a contracted bladder.

Warnings and precautions
Talk to your doctor or pharmacist before using Epirubicina Teva:

• if you are elderlyor a child, due to the increased risk of serious heart side effects. Your heart function will be checked before and after treatment with epirubicin.
• if you have had heart problemsin the past or are currently having them. You must tell your doctor. The dose of epirubicin will need to be adjusted. The doctor will check at regular intervals that your heart is functioning properly.
• if you have been treated previouslywith anticancer products (anthracyclines (such as doxorubicin or daunorubicin), anthracenediones or trastuzumab) or if you have undergone radiation therapy to the chest area, as the risk of serious heart side effects is higher. Tell your doctor, as this data is considered to determine the total dose of epirubicin that will be administered to you.
• if you suffer from a disorder of the liver or kidneys. This could cause an increase in side effects. Your kidney and liver function will be checked periodically and, if necessary, the dose will be adjusted.
• if you want to have children. Both men and women must use effective contraceptive measures during therapy and for 6.5 months (women) or 3.5 months (men) after therapy. Both men and women are advised to seek genetic counseling (See section “Pregnancy, breastfeeding and fertility”).
• if you suffer from infections or bleeding. Epirubicin can affect the bone marrow. The number of white blood cells in the blood will be reduced, which will make you more prone to infections (leukopenia). Bleeding may occur more easily (thrombocytopenia). These side effects are transient in nature. The reduction in the number of white blood cells is greatest 10-14 days after administration and levels usually return to normal 21 days after administration. Your doctor will check your blood regularly.
• if you have recently had or are planning to have any type of vaccination.

Take special care during treatment with Epirubicina Teva:

• check the level of uric acid in the blood. The doctor will need to monitor this.
• if blood clots form in your blood vessels (thromboembolism) which can lead to inflammation of the veins (thrombophlebitis) or pulmonary artery obstruction (pulmonary embolism)
• if you have severe inflammation or ulcers in your mouth.
• if you experience a burning sensationat the site of administration. This may indicate that the epirubicin is leaking from the blood vessel. Tell your doctor if this occurs.

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

Other medicines and Epirubicina Teva
Tell your doctor or pharmacist if you are taking, have recently taken or
may take any other medicines.
The term “interaction” means that the products (medicines) used at the same time can
influence each other's effects and/or side effects. An interaction can occur in case
of concomitant use of this solution with:

• previous or concomitant use of other products related to epirubicin (so-called anthracyclines; for example, anticancer agents mitomycin-C,dacarbazine,dactinomycin andcyclophosphamide), other drugsthat can affect the heart(for example, anticancer agents 5-fluorouracil, cyclophosphamide, cisplatin, taxanes, trastuzumab) or calcium channel blockers(used to treat high blood pressure or certain heart conditions); the risk to the heart may increase. Therefore, particularly careful monitoring of the heart is necessary.
• epirubicin can potentiate the effect of radiation and even after a certain period of time from exposure to radiation can cause serious side effects in the irradiated area.
• paclitaxeland docetaxel(used for some types of cancer); when paclitaxel is administered before epirubicin or docetaxel is administered immediately after epirubicin, the amount of epirubicin in the blood increases, which may cause an increase in side effects.
• dexverapamil(used to treat some heart disorders); when used together with epirubicin, it can have a negative effect on the bone marrow.
• interferonα-2b(a product used for some tumors and lymphomas, and for some forms of hepatitis).
• quinine(a product used in the treatment of malaria and for leg cramps); quinine can accelerate the distribution of epirubicin in the body, which can have a negative effect on red blood cells.
• dexrazoxane(sometimes used together with doxorubicin to reduce the risk of heart problems); the time of permanence of epirubicin in the body can be reduced, which may cause a reduction in the effect of epirubicin.
• cimetidine(used to reduce acidity in the stomach); the amount of epirubicin in the blood increases, which may cause an increase in side effects.
• previous or concomitant therapy with other products capable of affecting the bone marrow (for example other anticancer drugs, sulfonamides and chloramphenicol(antibiotics),diphenylhydantoin(anticonvulsant), amidopyrine derivatives(analgesics),products against certain viruses); the formation of blood cells may be disturbed.
• products that cause heart failure.
• products that affect liver function; the degradation of epirubicin through the liver may be affected, which may cause a reduction in the effect of epirubicin or an increase in side effects.
• live or live attenuated vaccines; there is a risk of a life-threatening illness, so this combination is not recommended.

Epirubicina Teva with food and drink
When epirubicin is administered into the bladder, do not drink for 12 hours before
administration.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant, are planning to become pregnant, or are breastfeeding
ask your doctor or pharmacist for advice before you are given this
medicine.

Pregnancy and fertility
The use of epirubicin during pregnancy can cause harm to the fetus. In studies conducted on animals,
epirubicin has been shown to be harmful to the fetus and can cause deformities.
It is very important to inform your doctor if you are pregnant or become pregnant during treatment. Epirubicina Teva should not be used during pregnancy, unless your doctor considers that immediate treatment with epirubicin is absolutely
necessary.
If pregnancy occurs during therapy with epirubicin, genetic counseling is recommended.
Some reports referring to pregnant women indicate that epirubicin has been associated with
heart problems in newborns and infants, including fetal death.
Women of childbearing potential must use effective contraceptive methods during treatment and for at least
6.5 months after the last dose. Men undergoing therapy with epirubicin must use effective contraceptive
methods during treatment and for at least 3.5 months after the last dose.
Treatment with epirubicin can cause infertility. Before treatment, both men and
women should seek advice on fertility preservation. Epirubicin can cause absence
of the menstrual cycle or early menopause in premenopausal women.

Breast-feeding
It is not known whether epirubicin is excreted in breast milk. It is recommended to discontinue
breast-feeding during therapy with Epirubicina Teva and for at least 7 days after the last dose.

Driving and using machines
Since many people report severe nausea or vomiting during therapy, it is
not recommended to drive vehicles and operate machinery.

Epirubicina Teva contains sodium
This medicine contains 18 mg of sodium (the main component of table salt) per 5 ml vial
This is equivalent to 0.9% of the recommended daily intake of salt for an
adult.
This medicine contains 35 mg of sodium (the main component of table salt) per 10 ml vial
This is equivalent to 1.8% of the recommended daily intake of salt for an
adult.
This medicine contains 89 mg of sodium (the main component of table salt) per 25 ml vial
This is equivalent to 4.4% of the recommended daily intake of salt for an
adult.
This medicine contains 266 mg of sodium (the main component of table salt) per 75 ml vial
This is equivalent to 13.3% of the recommended daily intake of salt for an
adult.
This medicine contains 354 mg of sodium (the main component of table salt) per 100 ml vial
This is equivalent to 17.7% of the recommended daily intake of salt for an
adult.

3. How to use Epirubicina Teva

Epirubicina Teva will only be administered to you under the supervision of a doctor specializing in
this type of therapy. If you have any doubts, consult your doctor or pharmacist.
During the administration of epirubicin, your doctor will perform blood tests. These are needed to
evaluate the effect of the medicine. The doctor will also perform tests to check cardiac function. Both the blood test and the cardiac function tests are performed before and during
treatment with epirubicin.
The dose you receive depends on the type of cancer, your health conditions, your
age, liver function, and any other medicines you are taking.

Administration by vein (intravenous administration)
Based on your overall health conditions and any previous treatments, the
dosage schedule is determined, also taking into account your height and weight. The quantities
indicated in the dosage schedule are expressed as a number of milligrams per square meter of
body surface area.
This medicine will be administered by intravenous injection over 3-5 minutes or by
intravenous infusion lasting a maximum of 30 minutes.
If only epirubicin hydrochloride is administered, without other anticancer medicines, the recommended dose is 60-90 mg/m² of body surface area. This dose is administered in a single
dose or distributed over 2-3 consecutive days. Administration should be repeated every 21 days. In
case of combination with other anticancer agents, the dose must be reduced.
Administration is via a catheter or a second continuous infusion line of
physiological solution or glucose (solution containing sugar).
Higher doses may be administered for the treatment of breast cancer (100-120
mg/m² of body surface area).

Administration through the bladder (intravesical administration)
The product can be administered directly into the bladder (for the treatment of bladder cancer) via a catheter. If this method is adopted, avoid consuming any
liquids for 12 hours before therapy, so as to prevent urine from diluting the
medicine too much. The dissolved medicine should be retained in the bladder for at least 1-2 hours after
administration. You may occasionally need to change position to ensure that the medicine
reaches all parts of the bladder.
When emptying the bladder after administering the medicine, make sure that urine does not come
into contact with the skin. If contact occurs, wash the area carefully with water and soap, without
rubbing.

If you use more Epirubicina Teva than you should
Since this medicine is administered by medical personnel, the risk of overdose is
unlikely. It may affect the heart, reduce the number of blood cells, and cause toxic
gastrointestinal effects (mainly mucositis). You may notice ulcers in your mouth. If you suspect that
you have been given too much Epirubicina Teva, contact your doctor immediately.

If you forget to use Epirubicina Teva
Since this medicine is administered by medical personnel, it is unlikely that you will forget a dose.
If you have any doubts, consult your doctor.

If you stop using Epirubicina Teva
Consult your doctor.
If you have any doubts about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
It is expected that more than 10% of patients treated will experience side effects. The most common side
effects are a decrease in blood cells (myelosuppression), gastrointestinal side effects, loss of appetite
(anorexia), hair loss (alopecia) and infection.
In addition, the following side effects may occur:

Very common:may affect more than 1 in 10 people

• infection
• inflammation of the eye (conjunctivitis or keratitis)
• decreased production of blood cells (bone marrow suppression; which causes a deficiency of white blood cells, red blood cells, platelets), which determines increased susceptibility to infections and fever, anemia, bruising and bleeding when injured
• hot flashes, redness of the veins (phlebitis)
• nausea and vomiting (often appear within the first 24 hours (in almost all patients)), inflammation of the mucous membranes of the mouth (stomatitis), inflammation of the mucous membranes (mucositis; may appear 5 to 10 days after the start of treatment), diarrhea with resulting dehydration
• hair loss (alopecia, in 60-90% of treated cases. In men it involves poor beard growth. Alopecia is dose-dependent and in most cases reversible)
• skin lesions
• reddish coloration of urine for 1-2 days after administration.
• absence of menstrual cycle (amenorrhea)
• feeling of general malaise, fever
• changes in the levels of some enzymes (transaminases).
• inflammation of the bladder (cystitis), sometimes with bleeding, after intravesical administration.

Common: may affect up to 1 in 10 people

• loss of appetite (anorexia), dehydration
• reduced heart function resulting in blood congestion (congestive heart failure), heart failure (dyspnea, fluid accumulation throughout the body (edema), enlargement of the liver, fluid accumulation in the abdominal cavity (ascites), fluid accumulation in the lungs (pulmonary edema), pleural effusion, abnormal heart rhythm (gallop rhythm)), increased heart rate originating in the lower chambers of the heart (ventricular tachycardia), decreased heart rate (bradycardia), interruption of cardiac impulse transmission (atrioventricular block, bundle branch block)
• decrease in the fraction of blood pumped by a ventricle with each heartbeat (decreased ejection fraction)
• bleeding (hemorrhage), redness of the skin (flushing)
• inflammation of the esophagus mucosa (esophagitis, abdominal pain, erosion and ulcers in the gastrointestinal tract
• skin rash, severe itching, skin changes
• darkening of the skin and nails (hyperpigmentation)
• redness at the infusion site, chills
• local reactions such as burning sensation and frequent urge to urinate have been observed after administration into the bladder.

Uncommon:may affect up to 1 in 100 people

• blood infection (sepsis), lung infection (pneumonia)
• some forms of blood cancer (acute lymphocytic leukemia [ALL], secondary acute myeloid leukemia [AML])
• vascular inflammation with the formation of a blood clot, often felt as a painful and rather hard cord with the overlying skin reddened (thrombophlebitis).
• formation of blood clots (embolism, arterial embolism), including blood clots in the lungs (pulmonary embolism, in isolated cases with fatal outcome)
• bleeding in the gastrointestinal tract
• skin rash with the formation of small bumps (urticaria), redness of the skin (erythema)
• feeling of weakness (asthenia)

Rare:may affect up to 1 in 1,000

• severe and immediate allergic reaction (anaphylactic/anaphylactoid reaction) with or without shock, including rash and itching; fever and chills
• increased levels of uric acid in the blood (hyperuricemia)
• dizziness
• cardiotoxicity (e.g. changes in ECG, arrhythmias, heart muscle disease (cardiomyopathy))
• lack of sperm in semen (azospermia)
• fever (very high) Not known:frequency cannot be estimated based on available data
• blood infection and shock (septic shock) as a consequence of decreased production of blood cells (myelosuppression)
• bleeding, oxygen deficiency in tissues
• a certain nerve disorder (peripheral neuropathy), headache
• shock
• abdominal discomfort, erosion of the oral mucosa, ulceration of the mouth, oral cavity pain, burning sensation of the mucosa, bleeding from the mouth (oral hemorrhage), discoloration of the oral cavity (oral pigmentation)
• sensitivity to light (photosensitivity) or allergic reactions in case of radiation (radiation recall reactions)
• increased amount of protein in the urine (proteinuria) in patients who have been treated with high doses
• local pain, severe inflammation of the tissue (cellulitis), tissue death (tissue necrosis), thickening or hardening of the vein walls (phlebosclerosis) after accidental injection outside the vein

Intravesical administration (into the bladder):Serious side effects affecting the
whole body and allergic reactions are rare in case of intravesical administration of
Epirubicina Teva 2 mg/ml.

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed
in this leaflet. You can also report side effects directly through the
national reporting system at www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects you can help provide more information on the safety
of this medicine.

5. How to store Epirubicina Teva

Keep out of the sight and reach of children.
Do not use Epirubicina Teva after the expiry date which is stated on the packaging after EXP. The
expiry date refers to the last day of that month.
Store in a refrigerator (2-8°C).
Store and transport in a refrigerator.
Do not freeze.
After first opening, the product must be used immediately.
The chemical and physical stability during use is as follows:

From a microbiological point of view, the product must be used immediately. If not used
immediately, the storage times in use and the conditions before use are the responsibility of the
user and, as a rule, should not exceed 24 hours at 2-8°C.
Storage of the injectable solution in a refrigerator may cause the product to gel. This gelled
product returns to a slightly viscous state and then to a normal state after 2-4 hours of
equilibration at controlled room temperature (15-25°C).
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Epirubicina Teva contains

• The active ingredient is epirubicin hydrochloride; 1 ml contains 2 mg of epirubicin hydrochloride.
• The other ingredients are sodium chloride, hydrochloric acid and water for injections.

Description of the appearance of Epirubicina Teva and contents of the pack
Epirubicina Teva 2 mg/ml is a medicine in the form of a clear, red solution,
for injection or infusion. It is available in glass vials for injection containing 5 ml (10 mg),
10 ml (20 mg), 25 ml (50 mg), 75 ml (150 mg) or 100 ml (200 mg) of injectable or for
infusion solution.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder
Teva Italia S.r.l. - Piazzale Luigi Cadorna, 4 - 20123 Milan

Manufacturer
Pharmachemie B.V. - Swensweg 5 - PO Box 552 -2003 RN Haarlem, Netherlands

This medicinal product is authorised in the Member States of the European Economic Area and in the
United Kingdom (Northern Ireland) under the following denominations:
Belgium EPIRUBICINE TEVA 2 mg/ml
Denmark Epirubicin Teva solution for injection or infusion
France EPIRUBICINE TEVA CLASSICS 2 mg/ml,
solution injectable ou pour perfusion
Germany Epi Teva 2 mg/ml Injektionslösung oder Infusionslösung
Greece Epirubicin HCl / PCH, ενέσιμο διάλυμα ή διάλυμα για έγχυση 2 mg/ml
Hungary Epirubicin-Teva 2mg/ml oldatos injekció vagy infúzió
Italy Epirubicina Teva 2 mg/ml soluzione iniettabile o per infusione
Luxembourg EPIRUBICINE TEVA 2 mg/ml
Netherlands Epirubicine HCl Pharmachemie 2 mg/ml
oplossing voor injectie of intraveneuze infusie.
Norway Epirubicin Teva 2 mg/ml injeksjons/infusjonsvæske, oppløsning
Portugal Epirrubicina Teva Solução injectável ou para perfusão
Slovenia Epirubicin Teva 2 mg/ml, raztopina za injiciranje ali infundiranje
Spain Epirubicina Teva 2mg/ml solución para inyección ó perfusión EFG
Sweden Epirubicin Teva 2 mg/ml injektions/infusionsvätska, lösning
United Kingdom
(Northern Ireland) Epirubicin 2mg/ml solution for injection or infusion
The following information is intended exclusively for healthcare professionals:

GUIDE TO PREPARATION FOR USE OF EPIRUBICINA TEVA 2 MG/ML
SOLUTION FOR INJECTION OR INFUSION
__________________________________________________________________________
It is important to read the entire content of this procedure before preparing Epirubicina
Teva 2 mg/ml solution for injection or infusion.

1. FORMULATION

Epirubicin hydrochloride 2 mg per ml of solution for injection or infusion.
Excipients:
sodium chloride
hydrochloric acid for pH adjustment
water for injections

2. SPECIAL PRECAUTIONS FOR STORAGE

Store in refrigerator (2°C-8°C).
Store and transport in refrigerator.
Do not freeze.
The chemical and physical stability during use is as follows:

From a microbiological point of view, the product must be used immediately. If not used
immediately, the storage times in use and pre-use conditions are the responsibility of
the user and, as a rule, should not exceed 24 hours at 2-8°C.
Storage of the injectable solution in the refrigerator may cause gelification of the
product. This gelified product passes to a slightly viscous state and then to a normal state after 2-4 hours of equilibration at controlled room temperature (15-25°C).

3. NATURE AND CONTENTS OF CONTAINER

Epirubicina Teva 2 mg/ml is available in colorless type 1 glass vials with a bromobutyl rubber stopper, aluminum seal and snap closure, containing respectively 5 ml, 10 ml, 25 ml, 75 ml and 100 ml of solution for injection or infusion.
Each pack contains only 1 vial.
Not all pack sizes may be marketed.

4. INCOMPATIBILITIES

Prolonged contact with alkaline solutions should be avoided, as it may cause hydrolysis. Epirubicina Teva 2 mg/ml should not be mixed with heparin, due to possible precipitation.
This medicine should not be mixed with other medicines except with NaCl 0.9% solution, glucose 5% solution or sterile water.

5. RECOMMENDATIONS FOR SAFE HANDLING

If it is necessary to prepare an infusion solution, this task must be carried out by trained personnel
under controlled aseptic conditions.
The preparation of an infusion solution must be carried out in a dedicated aseptic area.
Personnel working with Epirubicina Teva must wear protective gloves, safety glasses and
mask.
Epirubicina Teva does not contain preservatives and therefore should be considered a single-use product.
After use, unused medicine and waste derived from this medicine must be disposed of in
compliance with the regulations provided for cytotoxic agents. See also the “Disposal” section.
The spilled or leaked medicinal product can be inactivated with 1% sodium hypochlorite solution or
simply with a phosphate buffer (pH >8) until the solution becomes discolored. All
materials used for cleaning must be disposed of as described in the
“Disposal” section.
Pregnant women should avoid contact with cytotoxic agents.
Excreta and vomit must be cleaned with caution.
A damaged vial must be treated with the same precautions and must be considered a
contaminated waste. Contaminated waste must be stored in appropriate containers properly
labeled. See the “Disposal” section.

6. PREPARATION OF THE SOLUTION

Epirubicina is intended exclusively for intravenous or intravesical use.

6.1 Preparation for intravenous administration

Epirubicina Teva 2 mg/ml can be diluted with 0.9% NaCl solution or 5% glucose solution and
administered intravenously. The solution must be prepared immediately before
use.
It is advisable that the red solution, which must be clear and transparent, is injected through
the catheter of a continuous intravenous infusion of physiological saline or 5% glucose within
a maximum of 30 minutes (depending on the dose and volume of the infusion). The needle must be
adequately inserted into the vein. This method reduces the risk of thrombosis and extravasation, which
could cause severe cellulitis and necrosis. In case of extravasation, administration must be stopped
immediately. Injection into small veins and repeated injections
into the same vein can cause venous sclerosis.
For treatment with a high dose, epirubicina can be administered as an intravenous bolus
over 3-5 minutes or as an infusion with a maximum duration of 30 minutes.

6.2 Preparation for intravesical administration

For intravesical administration, Epirubicina Teva 2 mg/ml must be diluted with 0.9% NaCl solution or with sterile water. The concentration of the dilution must be 0.6-1.6 mg/ml.

Dilution table for solutions to be instilled into the bladder

7. DISPOSAL

Unused medicine, all materials used in the preparation and administration, or that have come into contact with epirubicin hydrochloride in any way, must be disposed of in accordance with current local regulations.