Doxorubicin accord

Package leaflet: Information for the user

Doxorubicinum Accord, 2 mg/mL, concentrate for solution for infusion
Doxorubicini hydrochloridum
Please read all of this leaflet carefully before using this medicine, because it contains
important information for the patient.

• Keep this leaflet so that you can read it again if necessary.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm other people, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of the leaflet:

1. What Doxorubicinum Accord is and what it is used for
2. Important information before using Doxorubicinum Accord
3. How to use Doxorubicinum Accord
4. Possible side effects
5. How to store Doxorubicinum Accord
6. Contents of the pack and other information

1. What Doxorubicinum Accord is and what it is used for

Doxorubicin belongs to a group of medicines called anthracyclines. These medicines are also known as antineoplastic or chemotherapeutic agents, or “chemotherapy”. These medicines are used in the treatment of various types of cancer, to slow down or stop the growth of cancer cells. To achieve better results and reduce side effects, a combination of different antineoplastic medicines is often used.
Doxorubicinum Accord is used in the treatment of the following types of cancer:

• Breast cancer
• Cancer of connective tissue, ligaments, bones, and muscles (sarcoma)
• Stomach or intestinal cancer
• Lung cancer
• Lymphomas – cancers of the immune system
• Leukaemia, a cancer which causes disorders in blood cell production
• Thyroid gland cancer
• Advanced ovarian cancer and cancer of the uterus (endometrial or uterine cancer)
• Bladder cancer
• Advanced neuroblastoma (a cancer of nerve cells, usually occurring in children)
• Malignant kidney tumour in children (Wilms' tumour)
• Multiple myeloma (a cancer of the bone marrow)

2. Important information before using Doxorubicinum Accord

When not to use Doxorubicinum Accord

• if the patient is allergic to doxorubicin hydrochloride or any of the other ingredients of this medicine (listed in section 6) or to another anthracycline,
• if the patient has persistent suppression of the bone marrow's ability to produce blood cells (myelosuppression),
• if the patient has previously been treated with doxorubicin or similar chemotherapeutic agents such as idarubicin, epirubicin or daunorubicin, because prior treatment with these drugs may increase the risk of adverse effects associated with the use of Doxorubicinum Accord,
• if the patient has any infection,
• if the patient has impaired liver function,
• if the patient has had a heart attack,
• if the patient has heart function disorders,
• if the patient has severe heart rhythm disturbances (arrhythmia),
• if the patient is breastfeeding (see also section "Pregnancy, breastfeeding and fertility").

The medicine should not be administered through a urinary catheter (a thin, flexible tube) in the following cases:

• if the patient is allergic to doxorubicin hydrochloride or any of the other ingredients of this medicine (listed in section 6), anthracenediones or other anthracyclines,
• if the patient has a tumour invading the bladder wall,
• if the patient has a urinary tract infection,
• if the patient has cystitis (inflammation of the bladder),
• if the patient has blood in the urine (haematuria),
• if the patient has difficulty inserting the catheter,
• if the patient is breastfeeding (see also section "Pregnancy, breastfeeding and fertility").

Warnings and precautions
If the patient currently has or has previously had any of the following conditions or diseases, inform the doctor:

• reduced production of blood cells in the bone marrow,
• heart diseases,
• liver disorders,
• kidney disorders.

Also inform the doctor if:

• the patient has previously been treated with doxorubicin or any other similar anticancer medicine (anthracycline) used in cancer treatment,
• the patient has previously undergone radiotherapy to the upper part of the body,
• the patient is currently taking or has recently taken trastuzumab (a medicine used in the treatment of certain cancers). Trastuzumab may remain in the body for up to 7 months. Since trastuzumab may affect the heart, doxorubicin should not be administered within 7 months after stopping trastuzumab. If doxorubicin is administered earlier, cardiac function must be carefully monitored.

Before starting treatment with Doxorubicinum Accord and during treatment, the doctor will perform the following tests:

• blood count,
• assessment of heart, liver and kidney function.

During treatment with doxorubicin, the bone marrow may not produce enough red and white blood cells and platelets, and their numbers may change; for this reason, blood tests should be performed before and during each treatment cycle. Due to low levels of blood cells and/or platelets, the following symptoms may occur: fever, infections, sepsis, bleeding and tissue damage. If fever occurs, contact the doctor immediately.
Skin rash along the vein used for drug administration is common and may lead to phlebitis (vein inflammation). Hardening or thickening of the vein wall may also occur, especially with repeated administration into a small vein. If the drug leaks from the blood vessel into surrounding tissues (extravasation), local pain, severe inflammation of subcutaneous tissue (connective tissue inflammation) and tissue damage may occur. If a burning sensation occurs during injection, inform the nurse immediately. The infusion must be stopped immediately and the needle reinserted into another vein.
The doctor will closely monitor heart function during treatment because:

• doxorubicin may damage the heart muscle,
• treatment with doxorubicin may lead to heart failure after a certain cumulative dose has been administered (gradual administration of single doses),
• patients who have previously received medicines that may damage the heart muscle or who have undergone radiotherapy to the upper part of the body are at higher risk of heart muscle damage.

Generally, this medicine should not be used in combination with live attenuated vaccines. Avoid contact with individuals recently vaccinated against polio.
During treatment with doxorubicin, mucositis (inflammation of mucous membranes, mainly in the mouth, less frequently in the oesophagus) may occur, with symptoms such as pain or burning, rash, superficial ulceration of the mucous membrane (often affecting the entire surface of the tongue or under the tongue), bleeding and infection. Inflammatory conditions in the mouth usually appear shortly after drug administration, and in severe cases may progress to mucosal ulceration within a few days. In most cases, adverse symptoms resolve within 3 weeks of treatment.
Nausea, vomiting and sometimes diarrhoea may occur. These can be prevented or alleviated with appropriate treatment recommended by the doctor.
Red discoloration of urine (which is normal and related to the colour of the drug). Inform the doctor if this discoloration persists for more than a few days or if the patient suspects blood in the urine. Inform the doctor if such symptoms occur.
Doxorubicin may impair fertility and may damage reproductive cells. Both men and women must use effective contraception during treatment and for a period after treatment with doxorubicin has ended (see section "Pregnancy, breastfeeding and fertility"). If a female patient plans to become pregnant after treatment with doxorubicin, she should discuss genetic counselling and fertility preservation options with her doctor before starting treatment.

Skin reactions and hypersensitivity reactions:

• hair loss and inhibition of beard growth may occur. This adverse effect is usually temporary, and complete hair regrowth typically occurs within two to three months after completion of treatment.
• sudden redness, particularly of the face, skin and nail discoloration, and increased sensitivity to sunlight may occur.
• in rare cases, allergic reactions (hypersensitivity) may occur; symptoms and signs may include rash and itching (pruritus, urticaria), as well as fever, chills and anaphylactic shock.

Doxorubicinum Accord and other medicines
Inform the doctor about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
Doxorubicinum Accord may interact with the following medicines:

• other cytotoxic (anticancer) medicines, e.g. trastuzumab, anthracyclines (daunorubicin, epirubicin, idarubicin), cisplatin, cyclophosphamide, cyclosporine, cytarabine, dacarbazine, dactinomycin, fluorouracil, mitomycin C, taxanes (e.g. paclitaxel), mercaptopurine, methotrexate and streptozocin,
• cyclosporine may enhance the effect of doxorubicin and may cause prolonged suppression of bone marrow function and reduced blood cell counts (cases of coma and seizures have also been reported during concomitant administration of cyclosporine and doxorubicin),
• cardioactive medicines (medicines used to treat heart diseases), e.g. calcium channel blockers, verapamil and digoxin,
• cytochrome P-450 inhibitors (medicines that inhibit the activity of cytochrome P-450, an important substance for the body's detoxification process, e.g. cimetidine), cytochrome P-450 inducers (e.g. rifampicin, barbiturates including phenobarbital),
• antiepileptic medicines (e.g. carbamazepine, phenytoin, valproate),
• antipsychotic medicines: clozapine (a medicine used to treat schizophrenia),
• warfarin (an anticoagulant medicine),
• antiretroviral medicines (medicines used to treat infections caused by specific types of viruses),
• chloramphenicol and sulfonamides (medicines used to treat bacterial infections),
• amphotericin B (a medicine used to treat fungal diseases),
• vaccines containing live microorganisms (e.g. polio [poliomyelitis], malaria),
• some medicines affect the concentration and clinical effect of doxorubicin (e.g. St. John's wort),
• paclitaxel: may enhance the effect of doxorubicin.

Please note that this may also apply to medicines recently taken.

Pregnancy, breastfeeding and fertility
Pregnancy
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult a doctor or pharmacist before using this medicine.
Animal studies have shown that doxorubicin crosses the placenta and harms the foetus.
If the patient is pregnant, the doctor will prescribe doxorubicin only if the benefits of treatment outweigh the potential risks to the unborn child. Inform the doctor immediately if the patient is pregnant or suspects she may be pregnant.
Women should not become pregnant during treatment with doxorubicin or for 7 months after the end of treatment. Men should take appropriate precautions to ensure their partner does not become pregnant during treatment with doxorubicin and for 4 months after the end of treatment.

Breastfeeding
Breastfeeding must be avoided during treatment with Doxorubicinum Accord and for at least 14 days after the last dose. The medicine may pass into breast milk and may harm the infant.

Effect on fertility
Before starting treatment, men should seek advice regarding sperm cryopreservation due to the possibility of irreversible infertility caused by doxorubicin treatment. If patients are considering having children after treatment, they should discuss this with their doctor.
Before taking any medicine, consult a doctor or pharmacist.

Driving and operating machinery
Due to frequent occurrence of nausea and vomiting after administration of the medicine, driving and operating machinery are not recommended.

Doxorubicinum Accord contains sodium
This medicine contains 0.15 mmol (3.5 mg) of sodium per millilitre. This should be taken into account in patients who are monitoring their sodium intake. Different package sizes of this medicinal product contain the following amounts of sodium:
This medicine contains less than 1 mmol of sodium (23 mg) in each 5 mL vial, meaning the medicine is considered "sodium-free".
This medicine contains 35.42 mg of sodium (main component of table salt) in each 10 mL vial. This corresponds to 1.77% of the WHO recommended maximum daily sodium intake for an adult.
This medicine contains 88.55 mg of sodium (main component of table salt) in each 25 mL vial. This corresponds to 4.43% of the WHO recommended maximum daily sodium intake for an adult.
This medicine contains 177.10 mg of sodium (main component of table salt) in each 50 mL vial. This corresponds to 8.85% of the WHO recommended maximum daily sodium intake for an adult.
This medicine contains 354.20 mg of sodium (main component of table salt) in each 100 mL vial. This corresponds to 17.71% of the WHO recommended maximum daily sodium intake for an adult.

3. How to use Doxorubicinum Accord

Method and route of administration
Doxorubicinum Accord must be administered only under the supervision of a physician experienced
in the use of anticancer therapy.
The dose will be determined by the physician.
Do not take the medicine without discussing it with your doctor. The medicine will be administered as an intravenous infusion into a blood vessel under the supervision of specialist physicians. The patient will undergo regular monitoring during treatment and after its completion. In patients with superficial bladder cancer, administration of the drug into the bladder may be necessary.

Dosage
The dose is usually calculated based on the patient's body surface area. A dose of 60–75 mg per
square metre of body surface area may be repeated every 3 weeks when doxorubicin is used as monotherapy. When doxorubicin is used in combination with other anticancer drugs, the dose may need to be reduced to 30–60 mg per square metre of body surface area, and the interval between treatments may need to be increased. Your doctor will advise you on the appropriate dose. When the drug is administered once weekly, a dose of 15–20 mg per square metre of body surface area is recommended. Your doctor will advise you on the appropriate dose.

Patients with impaired liver or kidney function
The dose should be reduced in patients with impaired kidney or liver function. Your doctor will advise you on the appropriate dose.

Children, elderly patients, and/or patients previously treated with radiotherapy
Dose reduction may also be necessary in children, elderly patients, or patients previously treated with radiotherapy. Your doctor will advise you on the appropriate dose.

Patients with bone marrow suppression
Dose reduction may be necessary in patients with bone marrow suppression. Your doctor will advise you on the appropriate dose.

Obese patients
In obese patients, it may be necessary to reduce the initial dose or extend the intervals between doses. Your doctor will advise you on the appropriate dose and frequency.

Administration of a higher than recommended dose of Doxorubicinum Accord
Your doctor or nurse will closely monitor you during and after treatment. Symptoms of overdose are typically an extension of the possible adverse effects of doxorubicin. This particularly includes changes in blood parameters, gastrointestinal effects, and heart disease. Myocardial disorders may occur even up to 6 months after overdose.
In case of overdose, the doctor will take appropriate measures. Blood transfusion and/or antibiotic treatment may be necessary.
Inform your doctor if any adverse effects occur.

Missed dose of Doxorubicinum Accord
Your doctor will decide on the duration of treatment with Doxorubicinum Accord. If treatment is interrupted before the recommended end time, the effectiveness of doxorubicin may be reduced.
Consult your doctor before discontinuing the medicine.

Discontinuation of Doxorubicinum Accord
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
In some people, this medicine may cause a potentially life-threatening severe allergic reaction (anaphylaxis). If the patient experiences sudden onset of breathing difficulties, immediately contact a doctor, swelling of the face and throat, and general malaise (shock).
Doxorubicin significantly reduces the immune system's ability to respond, therefore there is a high risk of infections, which may lead to systemic infection due to microorganisms entering the bloodstream (sepsis).
In case of high fever, contact a doctor immediately, as sepsis can lead to death.

Other adverse reactions that may occur include:

Very common: may affect more than 1 in 10 people

• Infection
• Loss of appetite (anorexia)
• Inflammation of the mucous membranes of the mouth (mucositis)
• Diarrhoea
• Nausea or vomiting
• Decreased number of blood cells: red blood cells (anaemia), all or certain types of white blood cells (leukopenia, neutropenia), and platelets (thrombocytopenia)
• Redness, swelling, numbness, pain, and tingling in the palms of the hands and soles of the feet (palmar-plantar erythrodysesthesia or acral erythema)
• Hair loss from the head and body (alopecia and inhibition of beard growth)
• Fever, feeling of weakness (asthenia), chills
• Abnormal ECG findings (test of the heart's electrical activity)
• Asymptomatic decrease in left ventricular ejection fraction
• Changes in liver enzyme activity (transaminases)
• Increased body weight in patients with early-stage breast cancer
• Damage to the heart muscle (cardiotoxicity)

Common: may affect up to 1 in 10 people

• Conjunctivitis, i.e. inflammation of the membrane covering the front of the eye and inner eyelids
• Heart function disorders, especially heart rhythm (sinus tachycardia), reduced amount of blood pumped by the heart to the body (congestive heart failure)
• Oesophagitis
• Abdominal pain
• Itchy rash, rash, skin and nail discoloration (excessive pigmentation)
• Sepsis
• At the injection site, redness and swelling may occur
• Local adverse reactions after intravesical administration, such as bladder inflammation (chemical cystitis)

Uncommon: may affect up to 1 in 100 people

• Embolism (blood clot in a blood vessel)

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

• Secondary leukaemia (blood cancer arising as a result of treatment for another cancer), when doxorubicin is used in combination with other antineoplastic medicines that damage DNA
• Tumour lysis syndrome (a complication of chemotherapy caused by products released from dying tumour cells, which may affect, for example, blood and kidneys)

Frequency unknown: frequency cannot be estimated from the available data

• Dehydration
• Increased blood urea levels (hyperuricaemia)
• Blood cancer (acute lymphoblastic leukaemia, acute myeloid leukaemia)
• Shock
• Inflammation of the corneal surface, increased tear production
• Increased heart rate (tachyarrhythmia), disturbances in the heart's electrical conduction (atrioventricular block, bundle branch block)
• Phlebitis, complete blockage of veins (thrombophlebitis), hot flushes, bleeding (haemorrhage)
• Irritation or bleeding in the intestines, pain or ulceration of the mouth, which may appear 3–10 days after treatment, discoloration inside the mouth
• Increased sensitivity of the skin to sunlight
• Inflammation of the large intestine (colitis) and inflammation of the stomach lining (gastritis)
• Itching and other skin disorders
• Hypersensitivity of irradiated skin (recurrence of radiation-induced symptoms)
• Red discoloration of urine
• In women, menstrual periods may stop, but periods should return to normal after stopping treatment. In some cases, early menopause may occur.
• In men, doxorubicin may cause absence or reduced number of sperm (oligospermia, azoospermia), but this condition may return to normal after stopping treatment.
• Nausea or malaise
• Toxic effect on the liver
• Transient increase in liver enzyme activity
• Condition in which the kidneys stop functioning (acute kidney failure)
• Shortness of breath caused by constriction of the airway muscles (bronchospasm)

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform a doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration 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
Adverse reactions can also be reported to the marketing authorisation holder.
By reporting adverse reactions, additional information on the safety of the medicine can be collected.

5. How to store Doxorubicinum Accord

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial or the outer cardboard
package under 'Expiry date (EXP)'. The expiry date refers to the last day of the specified month.
Store in a refrigerator (2°C - 8°C). Keep the vial in the outer packaging to protect it from
light.
Do not use this medicine if the solution is not clear, red, and free from particulate matter. For single use only.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.
Follow the instructions for the preparation and handling of cytotoxic medicines.
Unopened vials: 18 months
Opened vials: The medicine should be used immediately after opening the vial.
Chemical and physical in-use stability has been demonstrated for the medicine prepared in light-protected glass containers, diluted with 0.9% sodium chloride solution for injection or glucose solution for injection, for up to 28 days at 2°C to 8°C and for up to 7 days at 25°C.
From a microbiological point of view, the medicine should be used immediately. If it is not used immediately, the responsibility for storage conditions and duration lies with the user. In such cases, the solution should not be stored for longer than 24 hours at 2°C to 8°C, unless the dilution was carried out under controlled and validated aseptic conditions.

6. Contents of the pack and other information

What Doxorubicinum Accord contains
The active substance is doxorubicin hydrochloride.
Each mL contains 2 mg of doxorubicin hydrochloride.
Each 5 mL vial contains 10 mg of doxorubicin hydrochloride.
Each 10 mL vial contains 20 mg of doxorubicin hydrochloride.
Each 25 mL vial contains 50 mg of doxorubicin hydrochloride.
Each 50 mL vial contains 100 mg of doxorubicin hydrochloride.
Each 100 mL vial contains 200 mg of doxorubicin hydrochloride.
The other ingredients are: sodium chloride, hydrochloric acid (for pH adjustment) and water for injections.

What Doxorubicinum Accord looks like and contents of the pack
Doxorubicinum Accord is a clear red solution, essentially free from solid particles.
Pack sizes:
1 vial of 5 mL
1 vial of 10 mL
1 vial of 25 mL
1 vial of 50 mL
1 vial of 100 mL
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Accord Healthcare Polska Sp. z o.o.
Taśmowa Street 7
02-677 Warsaw
Tel: +48 22 577 28 00

Manufacturer/Importer
Accord Healthcare Polska Sp. z o.o.
Lutomierska Street 50
95-200 Pabianice
Accord Healthcare single member S.A.
64th Km National Road Athens Lamia
32009 Schimatari
Greece

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

| Country | Brand Name | |-------------|----------------| | United Kingdom (Northern Ireland) | Doxorubicin 2 mg/ml Concentrate for Solution for Infusion | | Austria | Doxorubicin Accord 2 mg/ml Konzentrat zur Herstellung einer Infusionslösung | | Belgium | Doxorubicin Accord 2 mg/ml concentrat oplossing voor infusie / concentrat pour solution pour perfusion / Konzentrat zur Herstellung einer Infusionslösung | | Bulgaria | Доксорубицин Акорд 2 mg/ml концентрат за инфузионен разтвор (Doksorubitsin Akord 2 mg/ml kontsentrat za infuzionen raztvor) | | Germany | Doxorubicin Accord 2 mg/ml Konzentrat zur Herstellung einer Infusionslösung | | Denmark | Doxorubicin Accord | | Estonia | Doxorubicin Accord 2 mg/ml | | Spain | Doxorubicin Accord 2 mg/ml concentrado para solución para perfusión | | Finland | Doxorubicin Accord 2 mg/ml infuusiokonsentraatti, liuosta varten / koncentrat till infusionsvätska, lösning | | Hungary | Doxorubicin Accord 2 mg/ml koncentrátum oldatos infúzióhoz | | Ireland | Doxorubicin 2 mg/ml Concentrate for Solution for Infusion | | Italy | Doxorubicina AHCL | | Lithuania | Doxorubicin Accord 2 mg/ml koncentratas infuziniam tirpalui | | Latvia | Doxorubicin Accord 2 mg/ml koncentrāts infūziju šķīduma pagatavošanai | | Netherlands | Doxorubicin Accord 2 mg/ml Concentraat voor oplossing voor infusie |

Information intended exclusively for healthcare professionals

Dosage and administration
Doxorubicin solution for infusion must be administered only under the supervision of a physician
experienced in the use of cytotoxic agents. Patients must also be closely and regularly monitored during
treatment.
Due to the risk of potentially fatal cardiomyopathy, the risks and benefits should be evaluated for each
individual patient prior to every administration.
Doxorubicin is administered intravenously or intravesically. It must not be given orally, subcutaneously,
intramuscularly, or intra-arterially. Doxorubicin may be administered as an intravenous bolus over several
minutes, as a short infusion lasting up to one hour, or as a continuous infusion not exceeding 96 hours.
The solution should be given through a freely flowing intravenous line using either 0.9% sodium chloride
solution (9 mg/mL) for injection or 5% glucose solution (50 mg/mL) for injection, administered over 3 to
10 minutes. This technique minimizes the risk of thrombophlebitis or extravasation, which may lead to
localized, severe connective tissue inflammation, blistering, and tissue necrosis. Direct intravenous
injection is not recommended due to the risk of extravasation, which may occur even when correct
venous placement of the needle has been confirmed by blood aspiration.

Intravenous administration
The dose of doxorubicin depends on the dosing regimen, the patient's general condition, and prior
treatment history. The dose of doxorubicin hydrochloride may vary depending on the indication (solid
tumors or acute leukemia) and the specific treatment regimen used (the drug may be administered as
monotherapy, in combination with other cytotoxic agents, or as part of a multidisciplinary approach
involving chemotherapy, surgery, radiotherapy, and hormonal therapy).

Monotherapy
The dose is usually calculated based on body surface area (mg/m²). When doxorubicin is used as
monotherapy, the recommended dose is 60–75 mg/m² of body surface area (BSA), administered every
three weeks.

Combination therapy regimen
When doxorubicin hydrochloride is administered concurrently with other antineoplastic agents that
have overlapping toxicities, such as high-dose intravenous cyclophosphamide or other anthracycline
derivatives (e.g., daunorubicin, idarubicin, and/or epirubicin), the doxorubicin dose should be reduced
to 30–60 mg/m² BSA every 3–4 weeks.
For patients who cannot receive a full dose of the medicinal product (e.g., due to immunosuppression or
advanced age), an alternative dosing schedule is 15–20 mg/m² body surface area per week.

Intravesical administration
Doxorubicin may be used as an intravesical instillation for the treatment of superficial bladder cancer or
for prophylaxis of tumor recurrence after transurethral resection in patients at high risk of recurrence.
For local treatment of superficial bladder cancer, an intravesical instillation of doxorubicin hydrochloride
30–50 mg in 25–50 mL of 0.9% sodium chloride solution (normal saline) for injection (9 mg/mL) is
recommended. The optimal concentration is 1 mg/mL. The solution should typically remain in the
bladder for 1 to 2 hours. During this time, the patient should be rotated 90° every 15 minutes. To avoid
dilution by urine, patients should refrain from fluid intake for 12 hours before treatment (which should
reduce urine production to approximately 50 mL/h). Instillations may be repeated at intervals ranging from
weekly to monthly, depending on whether the treatment is therapeutic or prophylactic.

Patients with hepatic impairment
Since doxorubicin is primarily metabolized in the liver and excreted via bile, elimination of the drug may
be delayed in patients with impaired liver function or obstructed biliary flow, potentially leading to severe
adverse effects.
General dose modification recommendations for patients with hepatic impairment are based on serum
bilirubin levels:

Doxorubicin is contraindicated in patients with severe hepatic dysfunction.
Patients with renal impairment
In patients with renal failure (GFR < 10 mL/min), only 75% of the intended dose should be administered.
To avoid cardiomyopathy, it is recommended that the cumulative lifetime dose of doxorubicin (including related agents such as daunorubicin) should not exceed 450–550 mg/m² body surface area. In patients with pre-existing heart disease, those who have received mediastinal irradiation and/or cardiac irradiation prior to treatment with alkylating agents, and in high-risk patients (with arterial hypertension for >5 years, history of coronary, valvular or myocardial disease, or aged over 70 years), the maximum total dose should not exceed 400 mg/m² body surface area, and cardiac function should be closely monitored.
Dosing in children
Dose reduction may be necessary in children. Treatment protocols and specialist literature should be consulted.
Obese patients and patients with bone marrow infiltration by tumour
In obese patients and in patients with tumour infiltration of the bone marrow, consideration should be given to reducing the initial dose or extending the interval between doses.
Pharmaceutical incompatibilities
Doxorubicin should not be mixed with heparin, as precipitation may occur, nor should it be mixed with 5-fluorouracil, as degradation may result. Prolonged contact with any alkaline solution should be avoided, as this may lead to hydrolysis of the drug.
Until detailed compatibility data on co-administration are available, doxorubicin should not be mixed with any medicinal products other than 0.9% sodium chloride injection and 5% glucose injection.
Prepared infusion solutions
Chemical and physical stability of the medicinal product has been demonstrated when prepared in light-protected glass containers, for up to 28 days at 2°C to 8°C and up to 7 days at 25°C, after dilution in 0.9% sodium chloride injection and 5% glucose injection.
From a microbiological standpoint, the medicinal product should be used immediately. If not used immediately, the responsibility for storage conditions and duration prior to use lies with the user. The solution should not be stored for longer than 24 hours at 2°C to 8°C, unless dilution has been carried out under controlled and validated aseptic conditions.
Disposal of medicinal product waste
Residual medicinal product, as well as all materials used for dilution and administration, must be disposed of in accordance with standard hospital procedures for cytotoxic agents, taking into account current regulations on hazardous waste disposal.
Any unused medicinal product or waste material should be disposed of in accordance with local regulations.
Shelf life and storage conditions
Unopened vials: 18 months.
Opened vials: The medicinal product should be used immediately after opening the vial.
Store in a refrigerator (2°C – 8°C).
Keep the vial in the outer packaging to protect from light.