Doxorubicin-ebeve

Leaflet accompanying the packaging: patient information

Doxorubicin-Ebewe, 2 mg/ml, concentrate for solution for infusion

Doxorubicin hydrochloride

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

• 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 symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, please tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet:

• 1. What Doxorubicin-Ebewe is and what it is used for
• 2. Important information before using Doxorubicin-Ebewe
• 3. How to use Doxorubicin-Ebewe
• 4. Possible side effects
• 5. How to store Doxorubicin-Ebewe
• 6. Contents of the packaging and other information

1. What Doxorubicin-Ebewe is and what it is used for

The medicine contains a substance called doxorubicin. Doxorubicin is used in the following indications: soft tissue sarcomas and bone sarcomas, malignant lymphoma, non-Hodgkin's lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, thyroid cancer, breast cancer, ovarian cancer, bladder cancer, small cell lung cancer, neuroblastoma.
In some studies, it has been found that doxorubicin can be administered into the bladder.
The use of the medicine provides significant benefits in the treatment of: multiple myeloma, endometrial cancer, cervical cancer, Wilms tumor (a type of malignant kidney tumor), head and neck tumors, stomach cancer, pancreatic cancer, prostate cancer, testicular cancer, and liver cancer.

2. Important information before using Doxorubicin-Ebewe

When not to use Doxorubicin-Ebewe

• in patients with known hypersensitivity to doxorubicin, drugs with a similar chemical structure, or any of the other components of this medicine (listed in section 6);
• in patients with severe bone marrow depression (including patients with an increased tendency to bleed);
• in patients with pre-existing or severe heart disease (such as unstable angina, progressive heart failure, severe arrhythmias, and conduction disorders, acute inflammatory cardiomyopathy, cardiomyopathy) or who have had a myocardial infarction in the last 6 months;
• in patients who have previously received a maximum cumulative dose of another anthracycline drug (e.g., doxorubicin or daunorubicin);
• with severe liver disease;
• in patients with acute infection;
• in patients with oral mucositis;
• in pregnant or breastfeeding women.

Administration into the bladder

• in patients with urethral stricture, in whom a catheter cannot be inserted;
• in patients with invasive tumors that infiltrate the bladder wall;
• in patients with urinary tract infections or bladder inflammation
• in patients with blood in the urine.

Warnings and precautions

Before using Doxorubicin-Ebewe, discuss it with your doctor.
Doxorubicin can only be used under the supervision of a doctor with experience in the use of anticancer chemotherapy. The patient should be in the hospital at least during the first phase of treatment, as close monitoring and laboratory tests are necessary. Before treatment with doxorubicin, and in some cases during administration of the medicine, the doctor will order blood tests to assess bone marrow function and perform tests to assess heart, liver, and urinary system function.
Doxorubicin has a toxic effect on the heart. The risk of such an effect is higher in patients who have previously undergone chest radiation, who have received other drugs similar to doxorubicin, and who are receiving drugs that inhibit the contractility of the heart muscle or have a toxic effect on the heart (e.g., trastuzumab), in patients with heart disease, in the elderly (> 70 years), and in children and adolescents.
In patients receiving anthracyclines after completing treatment with other substances with a toxic effect on the heart (e.g., trastuzumab), there may also be an increased risk of such an effect.
You should immediately consult a doctor if you:

• experience pain in the mouth, have inflammation or ulcers of the oral mucosa;
• experience shortness of breath, palpitations, accelerated or slowed heart rate, have swelling;
• urinate less;
• notice easy bruising or bleeding;
• experience pain, stinging, or burning at the injection site;
• experience pain or burning during urination.

Both men and women should use effective contraception during treatment and for a certain period after stopping the medicine (see "Pregnancy, breastfeeding, and fertility").
There is a possibility of red discoloration of the urine, especially the first portion after administration. No special action is required.

Doxorubicin-Ebewe and other medicines

Tell your doctor or nurse about all medicines you are taking or have recently taken, as well as any medicines you plan to take.
It is especially important to inform your doctor about radiation therapy and the use of the following medicines:

• other anticancer medicines;
• medicines used to treat high blood pressure and heart disease;
• methotrexate (a medicine used, among other things, to treat cancer, rheumatoid arthritis, and psoriasis);
• cimetidine and ranitidine (medicines that reduce stomach acid secretion);
• rifampicin (an antibiotic);
• barbiturates (medicines used, among other things, to treat insomnia);
• cyclosporine (a medicine used to prevent organ rejection);
• antiepileptic drugs (such as carbamazepine, phenytoin, valproate);
• medicines used to treat HIV infection (e.g., ritonavir);
• antibacterial medicines (e.g., chloramphenicol, sulfonamides);
• medicines used to treat mental illnesses (e.g., clozapine);
• digoxin (a medicine used to treat heart disease).

During treatment with doxorubicin, live vaccines should not be used due to the risk of developing a generalized, life-threatening disease. The risk is higher in patients with impaired immune system function. Patients treated with doxorubicin should avoid contact with people who have recently been vaccinated against polio during therapy.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, consult your doctor before using this medicine.
Contraception in women of childbearing age and men
Women
It cannot be excluded that doxorubicin has a negative effect on the fetus. In women of childbearing age, effective contraception should always be used during treatment and for at least 6.5 months after the last dose of Doxorubicin-Ebewe. You should discuss suitable contraception methods with your doctor.
Men
During doxorubicin therapy, genetic material damage (harm to sperm) may occur. Effective contraception should always be used during treatment and for at least 3.5 months after the last dose of Doxorubicin-Ebewe.
Pregnancy
Using Doxorubicin-Ebewe during pregnancy is contraindicated.
Breastfeeding
Using Doxorubicin-Ebewe during breastfeeding is contraindicated. Breastfeeding women should stop breastfeeding during doxorubicin treatment.
Fertility
In women, doxorubicin may cause infertility during treatment. It may also cause amenorrhea. Ovulation and menstruation return after treatment, but premature menopause may occur.
Doxorubicin may harm sperm. Reduced or absent sperm count may be permanent, but cases have been reported where sperm count returned to normal. This may occur after several years after treatment.
Due to the risk of irreversible infertility, advice should be sought on the possibility of preserving (freezing) sperm before starting treatment.

Driving and using machines

Patients who experience any side effects of the medicine that may have a negative impact on the ability to drive or operate machinery (drowsiness, nausea, or vomiting) should not drive or operate machinery.

Doxorubicin-Ebewe contains sodium

The medicine contains 3.54 mg of sodium (the main component of common salt) per 1 ml of concentrate.
The medicine contains 17.7 mg of sodium in a 5 ml vial. This corresponds to 0.88% of the maximum recommended daily intake of sodium in the diet for adults.
The medicine contains 88.5 mg in a 25 ml vial. This corresponds to 4.42% of the maximum recommended daily intake of sodium in the diet for adults.
The medicine contains 177 mg in a 50 ml vial. This corresponds to 8.85% of the maximum recommended daily intake of sodium in the diet for adults.
The medicine contains 354 mg in a 100 ml vial. This corresponds to 17.7% of the maximum recommended daily intake of sodium in the diet for adults.
The medicine can be diluted in a 0.9% sodium chloride solution. The sodium content from the diluent should be taken into account when calculating the total sodium content in the prepared dilution of the medicine.

3. How to use Doxorubicin-Ebewe

Doxorubicin-Ebewe can only be administered under the supervision of a doctor specializing in clinical oncology with experience in the use of anticancer chemotherapy.
The medicine is administered by intravenous injection lasting 2-5 minutes or by intravenous infusion with 0.9% sodium chloride solution, 5% glucose solution, or an intravenous infusion solution containing sodium chloride and glucose.
Doses of the medicine depend on the patient's condition, body weight, bone marrow and organ function (liver, heart), and the administration schedule (only Doxorubicin-Ebewe [monotherapy] or this medicine in combination with other cytotoxic drugs).
If the medicine is used as monotherapy, the most common recommendation is to administer a dose of 50-75 mg/m2 body surface area (BSA) in an intravenous infusion every three weeks. The medicine can be administered intravenously once every three weeks at a dose of 20 mg/m2 BSA for three consecutive days.
The cumulative dose in a patient's lifetime should not be exceeded, which is 550 mg/m2 BSA. This dose is 450 mg/m2 BSA in patients treated with chest radiation, patients with heart disease, or when the patient is taking other oncology drugs with cardiotoxic effects not belonging to the anthracycline group. Patients with a risk of heart function disorders should not be given cumulative doses greater than 450-550 mg/m2 BSA, and in the case of pre-existing heart disease or previous radiation therapy to the heart or chest, doses greater than 400 mg/m2 BSA should not be administered.
In the case of bladder cancer, a dose of 50 mg in 50 ml of physiological solution is recommended, administered into the bladder using a sterile catheter. Initially, the medicine is administered once a week, and then once a month. There is no restriction on the maximum cumulative dose.
The dose should be reduced in the following patients: those who are simultaneously taking other cytotoxic drugs with similar effects to doxorubicin, with liver function disorders, with an increased risk of heart function disorders, and in children.
If you feel that the effect of Doxorubicin-Ebewe is too strong or too weak, consult your doctor or pharmacist.

Using a higher dose of Doxorubicin-Ebewe than recommended

Probably, symptoms of overdose would be an intensified form of the pharmacological effect.
In case of using a higher dose of the medicine than recommended, consult your doctor or pharmacist immediately.
If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The side effects of doxorubicin are usually reversible. The toxic effects limiting the dose are bone marrow depression and cardiotoxicity.
Very common side effects(may occur in more than 1 in 10 people)
Infections, bone marrow depression (leukopenia, neutropenia, anemia, and thrombocytopenia), hypoxia or tissue necrosis, neutropenia with fever, thrombophlebitis, nausea, vomiting, oral mucositis, mucositis, local toxic effects, nail detachment, rash, redness, photosensitivity, alopecia, fever, weakness, chills, changes in the electrocardiogram (ECG), abnormal activity of some liver enzymes (transaminases), weight gain.
Common side effects(may occur in less than 1 in 10 people)
Generalized infection (sepsis), conjunctivitis, cardiotoxicity, e.g., cardiomyopathy, accelerated or slowed heart rate, arrhythmias, heart failure, thrombophlebitis, bleeding, esophagitis, abdominal pain or burning sensation, pruritus, hypersensitivity to radiation (recall reactions), excessive skin and nail pigmentation, urticaria, reaction at the injection site.
After administration into the bladder, bladder inflammation with painful urination, frequent urination, hematuria, polyuria, nocturia, urgency, necrosis, bladder and urethral spasms may occur.
Uncommon side effects(may occur in less than 1 in 100 people)
Septic shock (a severe, life-threatening reaction following sepsis), secondary myeloid leukemia, arrhythmias, accelerated or irregular heartbeat (palpitations), heart failure leading to shortness of breath and may cause swelling, cardiac arrest, thrombosis, gastrointestinal bleeding, colitis, ulcerative stomatitis, necrotizing colitis (sometimes with severe infection).
Rare side effects(may occur in less than 1 in 1000 people)
Angioedema of the eyelids and tongue with breathing difficulties, blue discoloration of the skin and mucous membranes due to low oxygen levels in the blood, respiratory disorders, nasal mucosal edema, accelerated breathing, shortness of breath, radiation pneumonitis.
Very rare side effects(may occur in less than 1 in 10,000 people)
Severe allergic reaction (anaphylaxis), severe heart function disorders (atrioventricular block, bundle branch block), shock, mucosal ulcers, oral mucosa discoloration, erythema multiforme, generalized muscle disease (myasthenia), amenorrhea, reduced or absent sperm count, malaise and (or) weakness, secondary oral cavity tumors.
Side effects with unknown frequency(frequency cannot be estimated from available data)
Anaphylactic reaction, keratitis, lacrimation, hot flashes, hepatotoxicity, transient increase in liver enzyme activity, redness and pain of the hands and feet, joint pain, red discoloration of the urine (1 to 2 days after administration), acute renal failure, venous sclerosis.
Reporting side effects
If you experience any side effects, including those not listed in this leaflet, please tell 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, tel.: +48 22 49 21 301 / fax: +48 22 49 21 309 / website: https://smz.ezdrowie.gov.pl
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Doxorubicin-Ebewe

Store the medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after EXP.
The expiry date refers to the last day of the month.
Store and transport in a cool place (2°C - 8°C).
Store in the outer packaging to protect from light.

6. Contents of the packaging and other information

What Doxorubicin-Ebewe contains

The active substance of the medicine is doxorubicin hydrochloride.
One ml of concentrate contains 2 mg of doxorubicin hydrochloride.
A 5 ml vial contains 10 mg of doxorubicin hydrochloride.
A 25 ml vial contains 50 mg of doxorubicin hydrochloride.
A 50 ml vial contains 100 mg of doxorubicin hydrochloride.
A 100 ml vial contains 200 mg of doxorubicin hydrochloride.
The other ingredients of the medicine are: hydrochloric acid 10% (to adjust pH), sodium chloride, water for injections.

What Doxorubicin-Ebewe looks like and what the packaging contains

Doxorubicin-Ebewe is a clear, red concentrate in a type I glass vial, closed with a gray rubber stopper coated with Teflon and an aluminum cap, in a cardboard box. The vials may be placed in protective packaging made of plastic (ONKO-Safe or Sleeving).
Packaging sizes:
1 vial of 5 ml;
1 vial of 25 ml;
1 vial of 50 ml;
1 vial of 100 ml.

Marketing authorization holder

EBEWE Pharma Ges.m.b.H. Nfg. KG
Mondseestraße 11
A-4866 Unterach, Austria

Manufacturer

Fareva Unterach GmbH
Mondseestraße 11
4866 Unterach, Austria
EBEWE Pharma Ges.m.b.H. Nfg. KG
Mondseestraße 11
A-4866 Unterach, Austria

For more information, please contact:

Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warszawa
tel. 22 209 70 00

Date of last revision of the leaflet:

Information intended only for healthcare professionals:

• Storage of the medicinal product after first opening and after dilution

After opening
The concentrate should be drawn from the vial immediately before use. From a microbiological point of view, the product should be used immediately. Otherwise, the user is responsible for the storage conditions and storage time of the remaining product in the vial. The product remaining in the vial after the first draw should not be stored for more than 24 hours at a temperature between 2°C and 8°C, unless the draw was performed under controlled, tested aseptic conditions. In this case, the solution stored in the refrigerator or at room temperature, with or without access to light, retains its physicochemical stability for 28 days.
After dilution
From a microbiological point of view, the product should be used immediately. Otherwise, the user is responsible for the storage conditions and storage time of the prepared solution. The prepared solutions should not be stored for more than 24 hours at a temperature between 2°C and 8°C, unless the dilution was performed under controlled, tested aseptic conditions. Physical and chemical stability has been demonstrated for 28 days for a solution at a concentration of 1 mg/ml, diluted with 0.9% NaCl or 5% glucose solution, stored in the refrigerator or at room temperature, with or without access to light, and for 28 days for a solution at a concentration of 0.1 mg/ml, diluted with 0.9% NaCl or 5% glucose solution, stored in the refrigerator, and up to 96 hours at room temperature, with or without access to light.

• Instructions for preparation, administration of the medicine, and disposal of its remnants

Doxorubicin can be administered by intravenous injection lasting 2-5 minutes or by intravenous infusion with a 0.9% sodium chloride solution, 5% glucose solution, or an intravenous infusion solution containing sodium chloride and glucose.
Due to different dosing schedules, it is recommended to use the medicine only under the supervision of a doctor with experience in cytotoxic therapy.
Intravenous bolus injection of the medicine causes a higher peak concentration of the medicine in the blood, which may have a more cardiotoxic effect.
Due to the toxic properties of the substance, the following safety rules should be observed:

• preparation, administration, and disposal of the product can only be performed by trained personnel, and as with all cytostatic drugs, caution should be exercised to avoid contact with the medicine by pregnant women;
• persons preparing doxorubicin should wear protective clothing: safety glasses, gowns, disposable gloves, and masks;
• all equipment and materials used to prepare the medicine or clean up the preparation area, including gloves, should be placed in hazardous waste bags and incinerated at high temperatures (700°C).

In case of accidental contact with the skin or eyes, rinse them with a large amount of water or soapy water or a sodium bicarbonate solution. Consult a doctor.
In case of spillage, the solution should be neutralized with a diluted sodium hypochlorite solution (1% hypochlorite solution), preferably left overnight, and then rinsed with water.
All materials used for cleaning should be disposed of in the manner described above.

• Procedure in case of extravasation

Extravasation causes severe and progressive tissue necrosis. The symptom of extravasation is pain and (or) a burning sensation at the site of intravenous administration of doxorubicin. In case of extravasation, the injection should be stopped immediately and the medicine should be administered into a different vein. Ice packs should be applied to the site of extravasation. In case of extravasation, within 6 hours, it is recommended to administer dexrazoxane intravenously (dosage and further information can be found in the Summary of Product Characteristics of dexrazoxane). If there are contraindications to its administration, 99% dimethyl sulfoxide (DMSO) solution should be applied locally to an area of skin twice as large as the affected area (4 drops per 10 cm of skin surface) and this procedure should be repeated 3 times a day for 14 days. Due to the opposite mechanism, the affected area should be alternately cooled (ice packs to reduce pain) and DMSO applied (vasoconstriction versus vasodilation). Other methods described in the literature are questionable and have no established value. The opinion of a specialist in plastic surgery should be sought and a wide excision of the affected area should be considered.

• Incompatibilities

Avoid contact of the medicinal product with alkaline solutions, as this would cause hydrolysis of the medicine. Do not mix doxorubicin with heparin and 5-fluorouracil, as a precipitate may form. It is not recommended to mix doxorubicin with other medicines.