DOXORUBICINA 2 mg /Ml Concentrate For Infusion Solution

Зміст інструкції

1. What Doxorubicina Aurobindo is and what it is used for
2. What you need to know before you receive Doxorubicina Aurobindo
3. How to administer Doxorubicina Aurobindo
4. Possible side effects
5. How to store Doxorubicina Aurobindo
6. Contents of the pack and other information

Doxorubicina Aurobindo 2 mg/ml concentrate for solution for infusion
Generic medicine

Read this leaflet carefully before 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 or pharmacist.
• If any side effects occur, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Doxorubicina Aurobindo is and what it is used for

Doxorubicina Aurobindo belongs to a group of anticancer medicines called anthracyclines.
Doxorubicina Aurobindo is used in the treatment of the following types of cancer:

• small cell lung carcinoma,
• bladder cancer,
• bone cancer,
• breast cancer,
• blood cancer,
• cancer of the lymphatic system (Hodgkin's and Non-Hodgkin's lymphoma),
• bone marrow cancer,
• thyroid gland cancer,
• soft tissue cancer (in adults),
• recurrent ovarian cancer or in the mucous membrane lining the uterus,
• some types of kidney cancer that affect children (Wilms' tumor),
• certain types of advanced-stage cancer of the nerve cells that affect children (neuroblastoma).

Doxorubicina Aurobindo is also used in combination with other anticancer drugs.

2. What you need to know before you receive Doxorubicina Aurobindo

Do not take Doxorubicina Aurobindo:

• if you are allergic to doxorubicin or any of the excipients of this medicine (listed in section 6);
• if you are allergic to drugs of the anthracycline or anthracenedione class;
• if you are breastfeeding.

Consult your doctor if any of the above conditions apply to you.

Doxorubicina Aurobindo must not be administered intravenously:

• if a persistent reduction in red blood cell production has been found after previous chemotherapy (your bone marrow is not functioning properly);
• if severe inflammation or ulcers of the mouth have been found after previous chemotherapy;
• if you suffer from heart problems;
• if you tend to bleed easily;
• if you suffer from any type of general infection;
• if your liver is not functioning properly;
• if you have received previous therapy with doxorubicin or other anthracyclines up to the maximum cumulative dose.

Contact your doctor if any of the above conditions apply to you.

Doxorubicina Aurobindo must not be administered intravesically:

• if you have a tumor that has grown into the wall of the bladder;
• if you have a urinary tract infection;
• if you have inflammation of the bladder;
• if there is blood in your urine;
• if you have problems with instillation (e.g. urethral obstruction). Contact your doctor if any of the above conditions apply to you.

Warnings and precautions
Talk to your doctor or pharmacist before receiving Doxorubicina Aurobindo

• if you believe you are (or may become) pregnant. See also sections "Pregnancy" and "Breastfeeding";
• if you have had radiotherapy in the past;
• if you are trying to become pregnant or are planning a pregnancy or if it is likely that you will try to conceive a child in the future;
• if you have kidney problems;
• if you have or have had heart problems.

Doxorubicin strongly reduces the production of blood cells in the bone marrow. This may
make you more susceptible to infections or bleeding. Tell your doctor if you have a fever or other
signs of infection or if you have any bleeding.
Vaccination is not recommended. Avoid contact with people recently vaccinated
against poliomyelitis.
Doxorubicina Aurobindo must only be administered under the supervision of a qualified doctor,
experienced in cancer therapies. Patients must also be monitored carefully and frequently for
example, blood parameter control and tests of heart, liver and kidney function.
Immediately inform your doctor or medical staff if you feel pain or burning
at the site of administration. This pain may occur in case of extravasation (leakage of the
medicine from the venous bed into the surrounding tissues) and may require appropriate treatment.

Other medicines and Doxorubicina Aurobindo
Tell your doctor if you are taking, have recently taken or might take any other medicines.
This is particularly important for:

• other cancer medicines e.g. anthracyclines (daunorubicin, epirubicin, idarubicin, trastuzumab), cyclophosphamide, cytarabine, cisplatin, fluorouracil, taxanes (e.g. paclitaxel), mercaptopurine, methotrexate, streptozocin;
• cyclosporine (used in organ and tissue transplants);
• cardioactive drugs (medicines for heart diseases), for example calcium channel blockers, digoxin;
• medicines that lower uric acid levels in the blood;
• rifampicin (an antibiotic);
• cimetidine (used in the treatment of heartburn and stomach ulcers);
• live vaccines (e.g. for poliomyelitis);
• phenytoin, carbamazepine, valproate, phenobarbital and other barbiturates (used in the treatment of epilepsy);
• chloramphenicol and sulfonamides (medicines for infections);
• amphotericin B (medicine for fungal infections);
• medicines against viral infections, such as ritonavir (used to treat HIV);
• clozapine (an antipsychotic);
• amidopyrine derivatives (for pain and inflammation).

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant or are planning a pregnancy, ask your doctor or
pharmacist for advice before using this medicine.
It is known that doxorubicin crosses the placenta and causes fetal damage in animal experiments.
Therefore, doxorubicin should not be administered during pregnancy. Immediately inform your doctor if
you are pregnant or believe you may be pregnant.
Women must not become pregnant during treatment with Doxorubicina Aurobindo or within
six months after treatment. Men must take adequate precautions to ensure that their
partner does not become pregnant during and up to 6 months after treatment with doxorubicin. Men and
women of childbearing potential should therefore use effective contraceptive methods during and up to 6 months
after treatment.
Due to the possibility that doxorubicin therapy may cause irreversible infertility, men are advised to
ask about the possibility of cryopreservation (cryopreservation) of sperm before
starting treatment. Talk to your doctor if you want to have children after treatment.
The drug is excreted in breast milk. Do not breastfeed during treatment with Doxorubicina
Aurobindo.

Driving and using machines
Due to the frequent occurrence of nausea and vomiting, it is advisable not to drive vehicles and use
machinery.

Doxorubicina Aurobindo contains sodium
This medicinal product contains 3.54 mg (<1 mmol) of sodium per ml of concentrate. This must be
taken into consideration for patients who are on a low-sodium diet.

3. How to administer Doxorubicina Aurobindo

Doxorubicina Aurobindo must only be administered under the supervision of a doctor experienced in
cancer therapy.

Method and route of administration
The medicine will be administered to you by intravenous infusion, into a blood vessel, under the supervision of
specialists. Do not self-administer the medicine. You will be monitored regularly both during and after the
treatment. If you suffer from superficial bladder cancer, the medicine may be administered to you
via the intravesical route. The medicine must be diluted before use.

Intravenous administration
The dosage is generally calculated based on the body surface area. Doxorubicina Aurobindo
can be administered, for example, once a week, every three weeks, or with more spaced intervals of
administration over time. The dose and frequency also depend on other anticancer drugs used, the type of
disease and the general state of health. Your doctor will determine the dose you will receive.

Instillation into the bladder
The dosage is 30-50 mg of doxorubicin in 25-50 ml of saline solution. The solution must
remain in the bladder for 1-2 hours. During this period, it should be rotated approximately 90° every 15 minutes.
You must refrain from drinking any liquids for a period of 12 hours beforebladder instillation to
avoid unwanted dilution of the medicine with urine. The instillation may be repeated at intervals of
1 week to 1 month. Your doctor will tell you the necessary frequency.

Use in children
The dosage must be reduced in children. Your doctor will advise you on how much to take.

If you take more Doxorubicina Aurobindothan you should
Since the doctor will administer the medicine to you, it is unlikely that you will receive too much.
However, if in doubt, contact your doctor or nurse immediately.
Acute overdose worsens side effects such as mouth ulcers, reduces the number of
white blood cells and platelets in the blood and can cause heart problems. In case of overdose, you must
receive appropriate treatment, which will be established by the doctor. Heart problems may manifest
up to six months after the overdose.

If you miss a dose of Doxorubicina Aurobindo
The doctor will decide the duration of your treatment with Doxorubicina Aurobindo. If the treatment is
interrupted before the end of the recommended treatment cycles, the effects of doxorubicin therapy may be reduced.
Ask your doctor for advice if you want to stop treatment.
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.

Seek immediate medical attention or contact a nurse if you experience:

• dizziness, fever, shortness of breath with tightness in the chest or throat, or a itchy rash. This could be a type of allergic reaction that can be very serious;
• feeling tired and lethargic. This may be a sign of anemia (low number of red blood cells in the blood);
• if you develop a fever or symptoms of infection. This may be a sign of a low number of white blood cells;
• increased ease of bruising and bleeding. This may be a sign of a low number of platelets in the blood. Very common (may affect more than 1 in 10 people):
• nausea, vomiting, abdominal pain, digestive disorders, diarrhea;
• inflammation of the mucous membranes, for example, in the mouth or esophagus;
• hair loss (usually reversible), skin redness, skin sensitivity to artificial or natural light (photosensitivity);
• reddish urine for one or two days after administration. This is normal and should not cause concern;
• bone marrow suppression (deficiency of blood cells) including a reduction in the number of white blood cells (causing infection), platelets (causing bleeding and bruising) and red blood cells (anemia; therefore, the skin may appear pale and weakness or difficulty breathing may occur);
• serious heart complications (cardiotoxicity), such as damage to the heart muscle or a fast, slow or irregular heartbeat. Effects may occur shortly after starting treatment or after several years;
• fever. Common (may affect up to 1 in 10 people)
• bacterial infection;
• bacterial blood infection;
• heart rhythm disturbances (irregular heartbeat, fast heartbeat, decreased heartbeat);
• reduction in the amount of blood pumped by the heart, deterioration of heart function (cardiomyopathy) which can be life-threatening;
• bleeding (hemorrhage);
• eating disorder (anorexia);
• local allergic reaction of the irradiation field;
• itching;
• difficulty or pain during urination, bladder inflammation following intravesical instillation, sometimes with bladder irritation, blood in the urine, pain during urination, needing to urinate more frequently, reduced urine production.

Uncommon (may affect up to 1 in 100)

• acute leukemia (certain types of leukemia);
• inflammation of a vein;
• bleeding in the stomach or intestines;
• ulceration of the mucous membranes of the mouth, pharynx, esophagus and gastrointestinal tract;
• ulcers and potential death of cells/tissues of the colon when Doxorubicina Aurobindo is administered in combination with cytarabine;
• dehydration.

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

• inflammation of the outermost layer of the eye (conjunctivitis);
• urticaria, skin rashes and redness;
• dark areas of the skin and nails, nail loss (onycholysis);
• severe allergic reactions with or without shock including rash, itching, fever and chills (anaphylactic reactions);
• chills;
• dizziness;
• secondary leukemia (blood cancer, developed after treatment for another cancer) when Doxorubicina Aurobindo is used in combination with other anticancer drugs that damage DNA;
• tumor lysis syndrome (complications of chemotherapy due to products originating from the lysis of dead tumor cells which for example can have effects on the blood and kidneys);
• reaction around the injection site including redness, rash and pain and inflammation of the vein (phlebitis), thickening or hardening of the vein wall (phlebosclerosis);
• sensation of pain or burning at the administration site related to extravasation. This can cause death of the local tissue cells, requiring appropriate intervention, in some cases surgical measures.

Very rare (may affect up to 1 in 10,000)

• facial flushing;
• changes in heart function (non-specific changes in the ECG trace), isolated cases of life-threatening irregular heartbeat (arrhythmias), heart failure, inflammation of the pericardium/myocardium, loss of nerve impulses in the heart;
• formation of a blood clot in a blood vessel;
• discoloration (pigmentation) of the oral mucosa;
• swelling and numbness of the hands and feet (acral erythema), blister formation, tissue damage especially in the hands and feet causing redness, swelling, blisters, tingling or burning sensation where extravasation of the drug occurs in the tissue (palmo-plantar erythrodysesthesia syndrome);
• acute kidney failure;
• abnormally elevated uric acid levels in the blood;
• absence of menstrual cycle;
• fertility problems in men (reduction or absence of sperm).

Not known (frequency cannot be estimated from available data)

• increased tear production;
• cough or difficulty breathing caused by a sudden narrowing of the airways;
• inflammation of the lungs;
• liver toxicity, which can sometimes cause permanent damage to the liver tissue (cirrhosis);
• transient increase in liver enzymes;
• fat, hair loss or scaly skin patches (actinic keratosis);
• severe pain and swelling of the joints;
• weakness;
• radiation damage (to the skin, lungs, throat, esophagus, stomach and intestinal mucosa, heart) already healing, may reappear after administration of doxorubicin.

Reporting of side effects
If you get 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 national reporting system at www.agenziafarmaco.gov.it/it/responsabili . By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Doxorubicina Aurobindo

Keep out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the vial and the outer packaging
after EXP. The expiry date refers to the last day of the month.
Store in a refrigerator (2-8°C). Keep the vial in the outer packaging to protect it from light.
Do not use this medicine if you notice that the solution is not clear, red and free from particles.
Unused product and waste derived from this medicine must be disposed of in accordance with
current local regulations. Follow the guidelines for handling cytotoxic drugs.
Medicines should not be disposed of via drains 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 Doxorubicina Aurobindo contains

• The active substance is doxorubicin hydrochloride. Each vial contains 2 mg/ml of doxorubicin hydrochloride.

The excipients are: sodium chloride, hydrochloric acid and water for injections.

Description of the appearance of Doxorubicina Aurobindo and contents of the pack
Doxorubicina Aurobindo concentrate for solution for infusion is a clear, red solution.
Doxorubicina Aurobindo is contained in a colorless glass vial fitted with a rubber stopper and sealed
with an aluminum crimp cap with a polypropylene disc. The vial will be packaged with or without
a protective plastic coating.
Pack sizes:
1 vial of 5 ml
1 vial of 25 ml
1 vial of 50 ml
1 vial of 100 ml

Marketing Authorisation Holder
Eugia Pharma (Malta) Limited
Vault 14, Level 2, Valletta Waterfront,
Floriana FRN 1914, Malta

Manufacturer responsible for batch release
Generis Farmacêutica, S.A. – Rua João de Deus, no 19, Venda Nova – 2700-487 Amadora (Portugal)
APL Swift Services (Malta) Ltd – HF26, Hal Far Industrial Estate, Hal Far, Birzebbugia - BBG 3000 (Malta)

This medicinal product is authorised in the Member States of the European Economic Area with the following
denominations:
Belgium Doxorubicin AB 2 mg/ml concentrate for solution for infusion
Germany Doxorubicin Aurobindo 2 mg/ml Konzentrat zur Herstellung einer Infusionslösung
Italy Doxorubicina Aurobindo
Netherlands Doxorubicine HCl Aurobindo 2 mg/ml concentrate for solution for infusion
Portugal Doxorrubicina Aurovitas
Spain Doxorubicina Aurovitas 2 mg/ml concentrated for solution for perfusion EFG
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The following information is intended exclusively for doctors or healthcare professionals:
Doxorubicina Aurobindo 2 mg/ml concentrate for solution for infusion
Doxorubicin is a potent cytotoxic agent and must only be prescribed, prepared and administered by
professionals trained in the safe use of the preparation. For recommendations on dosage and
method of administration see section 4.2 of the SmPC of this medicinal product. During
handling, preparation and disposal of doxorubicin, follow the following guidelines.
For single use only.
Preparation

• 1. Cytotoxic agents must only be prepared for administration by personnel trained in the safe handling of such preparations. Before starting, refer to local guidelines on cytotoxic substances.
• 2. Pregnant personnel should be excluded from handling the drug.
• 3. Personnel handling doxorubicin must wear protective clothing: safety glasses, gown, gloves and disposable mask.
• 4. All items used for administration or cleaning, including gloves, must be placed in high-risk waste disposal bags for incineration at high temperature (700°C).
• 5. All materials used for cleaning must be disposed of as previously indicated.
• 6. Always wash your hands after removing gloves. Do not use Doxorubicina Aurobindo if you notice that the solution is not clear, red and free of particles.

Contamination

• 1. In case of contact with skin or mucous membranes, thoroughly clean the affected area with soap and water or a sodium bicarbonate solution. However, do not scrub the skin using a brush. A mild cream can be used to treat transient skin pain.
• 2. In case of contact with the eye(s), lift the eyelid(s) and wash the affected eye(s) with plenty of water for at least 15 minutes or with normal sodium chloride 9 mg/ml (0.9%) injectable solution. Consult a doctor or ophthalmologist for advice.

• 3. Spills or leaks should be treated with a 1% sodium hypochlorite solution or phosphate buffer (pH>8) until the solution discolors. Use a cloth or sponge stored in the designated area.

Rinse twice with water. Place all contaminated clothing in a plastic bag and
seal for incineration.
In-use stability

Opened vials:Chemical and physical stability has been demonstrated during use for 28 days at a temperature
of 2-8°C. From a microbiological point of view, the product must be used immediately, unless the
method of opening precludes the risk of microbial contamination. Otherwise, the storage times and conditions
in use are the responsibility of the user.

Prepared solution for infusion: Chemical and physical stability of the drug after dilution, when
protected from light, has been demonstrated for up to:

• 7 days at 2-8°C and 2 days at 25 °C in a 0.9% sodium chloride solution (PE bottle) at a concentration of 1.25 mg/ml
• 24 hours at 2-8°C and 25°C in a 5% glucose solution (PP bags) at concentrations of 1.25 mg/ml
• 2 days at 2-8°C and 7 days at 25°C in a 0.9% sodium chloride solution (PE bottle) at a concentration of 0.5 mg/ml
• 24 hours at 2-8°C and 7 days at 25°C in a glucose solution (PE bags) at a concentration of 0.5 mg/ml.
• From a microbiological point of view, the product must be used immediately. If immediate use is not possible, the user is responsible for the storage times and conditions: generally no more than 24 hours at a temperature of 2 to 8°C, unless the dilution has taken place under controlled and validated aseptic conditions.

The storage times of the opened vial and the diluted infusion solution are not additive.
Disposal
Unused product and waste derived from this medicinal product must be disposed of in accordance with
current local regulations. Follow the guidelines for handling cytotoxic drugs
Note:
The dosage for the administration of liposomal doxorubicin and doxorubicin (conventional)
as in Doxorubicina Aurobindo is different.
The two formulations are not interchangeable.
Incompatibilities
Doxorubicin should not be mixed with heparin as a precipitate may form and should not
be mixed with 5-fluorouracil as degradation may occur. Prolonged contact with alkaline pH solutions should be avoided as it causes hydrolysis of the drug.
In the absence of compatibility studies, this medicine should not be mixed with other medicines.