Doxorubicin Accord Healthcare Italia

Patient Information Leaflet: Information for the User

DOXORUBICIN ACCORD HEALTHCARE ITALIA

2 mg/ml concentrate for solution for infusion
Generic medicine
Please 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.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those listed in this leaflet, inform your doctor or pharmacist. See section 4. Contents of this leaflet:
  1. What Doxorubicin concentrate for solution for infusion is and what it is used for
  2. What you need to know before taking Doxorubicin concentrate for solution for infusion
  3. How to take Doxorubicin concentrate for solution for infusion
  4. Possible side effects
  5. How to store Doxorubicin concentrate for solution for infusion
  6. Contents of the pack and other information

1. What Doxorubicin concentrate for solution for infusion is and what it is used for

The name of your medicine is DOXORUBICINA ACCORD HEALTHCARE ITALIA, but in the following sections of this
leaflet it will be referred to as 'Doxorubicin concentrate for solution for infusion'.
Doxorubicin belongs to a group of medicines known as anthracyclines. These medicines are also known as
anticancer or chemotherapeutic agents. They are used to treat various types of cancer by slowing down or
stopping the growth of cancer cells. Often, a combination of different types of anticancer medicines is used
to achieve better results and reduce unwanted side effects.
Doxorubicin concentrate for solution for infusion is used to treat the following types of cancer:

• breast cancer;
• cancer of connective tissue, ligaments, bones, and muscles (sarcoma);
• cancer developing within the stomach or intestine;
• lung cancer;
• lymphoma, a cancer affecting the immune system;
• leukemia, a cancer causing abnormalities in blood cell production;
• thyroid gland cancer;
• advanced-stage ovarian and endometrial cancer (a cancer affecting the lining of the uterus or the uterus itself);
• bladder cancer;
• advanced neuroblastoma (a nerve cell cancer commonly found in children);
• malignant kidney cancer in children (Wilms' tumour);
• myeloma (cancer of the bone marrow).

2. What you should know before using Doxorubicin concentrate for solution for infusion

Do not take Doxorubicin concentrate for solution for infusion:
if you are allergic to doxorubicin hydrochloride or to any of the other ingredients of this medicine
(listed in section 6), to anthracenediones, or to other anthracyclines.
if you suffer from persistent suppression of your bone marrow’s ability to produce blood cells (myelosuppression).
if you have previously been treated with doxorubicin or similar chemotherapeutic agents such as idarubicin,
epirubicin, or daunorubicin, since prior treatment with these similar drugs may increase the risk of side effects with Doxorubicin concentrate for solution for infusion.
if you have any type of infection.
if you have mouth ulcers.
if your liver is not functioning properly.
if you have had a heart attack.
if your cardiac function is impaired.
if you have a severe heart rhythm disorder (arrhythmia).
if you are breastfeeding (see section “Pregnancy, breastfeeding and fertility”).

The medicine must not be administered through a catheter (a thin, flexible tube) directly into the bladder
if you are allergic to doxorubicin hydrochloride or to any of the other ingredients of this medicine
(listed in section 6), to anthracenediones, or to anthracyclines;
if you have a tumour that has invaded the bladder wall;
if you have a urinary tract infection;
if you have inflammation of the bladder;
if you have blood in your urine (haematuria);
if you have difficulties with catheter insertion;
if you are breastfeeding (see section “Pregn游戏副本

3. How to take Doxorubicin concentrate for solution for infusion

Method and route of administration
Doxorubicin concentrate for solution for infusion must be administered only under the supervision of a physician experienced in anticancer therapies.
Your doctor will determine the appropriate dose to administer.
Do not self-administer this medicine. The medicine will be administered to you as an intravenous infusion into a blood vessel under the supervision of specialists. During and after treatment, you will undergo regular monitoring. If you have superficial bladder cancer, the medicine may be administered directly into the bladder (intravesical administration).

Dosage
Generally, the dosage is calculated based on body surface area. When used alone, the usual dose is 60–75 mg per square meter of body surface area every 3 weeks. When administered in combination with other anticancer medicines, the dose may be reduced to 30–60 mg per square meter of body surface area, and the interval between treatments may be prolonged. Your doctor will advise you on the appropriate dose. If the medicine is administered weekly, the recommended dose is 15–20 mg per square meter of body surface area. Your doctor will advise you on the appropriate dose.

Patients with impaired hepatic and renal function
If liver or kidney function is impaired, the dose must be reduced. Your doctor will advise you on the appropriate dose.

Children/Elderly patients or patients who have undergone radiotherapy
Dose reduction may be necessary in children, elderly patients, or if you have previously undergone 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, the initial dose may be reduced or the interval between doses may be extended. Your doctor will advise you on the appropriate dose and treatment frequency.

If you take more Doxorubicin concentrate for solution for infusion than you should
During and after treatment, your doctor or nurse will closely monitor you. Symptoms of overdose reflect an exaggeration of the possible side effects of doxorubicin, particularly blood abnormalities, and gastrointestinal and cardiac problems. Cardiac disorders may appear even up to six months after overdose.
In case of overdose, your doctor will take appropriate measures, for example, blood transfusion and/or treatment with antibiotics.
Inform your doctor if you experience any of these symptoms.

If you forget to take a dose of Doxorubicin concentrate for solution for infusion
The duration of treatment with Doxorubicin concentrate for solution for infusion is determined by your doctor. If treatment is interrupted before completion of the recommended cycles, the effectiveness of doxorubicin therapy may be reduced. If you wish to discontinue treatment, consult your doctor.

If you stop treatment with Doxorubicin concentrate for solution for infusion
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
In some individuals, this medicine may cause a severe, potentially life-threatening allergic reaction (anaphylaxis). Contact your doctor immediately if you suddenly develop breathing difficulties, swelling of the face and throat, or feel generally unwell (shock).
Doxorubicin greatly reduces the immune system's ability to respond, thus greatly increasing the risk of infection or infestation, which may lead to a generalized infection due to microbes entering the bloodstream (blood poisoning). Contact your doctor immediately if you develop a high fever, as blood poisoning can be fatal.
Other possible side effects include:
Very common: may affect more than 1 in 10 people

• Infection
• Loss of appetite (anorexia)
• Inflammation in the mouth (stomatitis) / inflammation of mucous membranes (mucositis)
• Diarrhea
• Feeling unwell (nausea) or being sick (vomiting)
• Decrease in blood cell counts: red blood cells (anaemia), all or certain white blood cells (leucopenia, 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 head and body (alopecia and interruption of beard growth)
• Fever, feeling of weakness (asthenia), chills
• Abnormal ECG (electrical trace of your heart)
• Asymptomatic reductions in left ventricular ejection fraction
• Changes in liver enzyme levels (transaminases)
• Weight gain in patients with early breast cancer
• Damage to the heart muscle (cardiotoxicity).

Common: may affect up to 1 in 10 people

• Inflammation of the conjunctiva, the membrane covering the front of the eye and the inside of the eyelids (conjunctivitis)
• Changes in heart function, particularly heart rhythm (sinus tachycardia), reduced amount of blood pumped by the heart into the body (congestive heart failure)
• Inflammation of the oesophagus (oesophagitis)
• Stomach ache
• Itchy rash, skin rash, skin and nail discoloration (hyperpigmentation)
• Blood poisoning
• Redness and swelling may develop at the injection site
• Local side effects when administered into the bladder, such as inflammation of the bladder (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 developing after treatment for another cancer), when doxorubicin is used in combination with other anticancer drugs that damage DNA
• Tumour lysis syndrome (chemotherapy complications due to breakdown products from dying cancer cells, which may, for example, affect the blood and kidneys).

Not known: (frequency cannot be determined from the available data)

• Dehydration
• Increased urea in the blood (hyperuricaemia)
• Blood cancer (acute lymphocytic leukaemia, acute myeloid leukaemia)
• Shock
• Inflammation of the corneal surface (keratitis), increased tear production
• Increased heart rate (tachyarrhythmias), loss of nerve impulses from the heart (atrioventricular block and bundle branch block)
• Inflammation of a vein (phlebitis), complete blockage of a vein (thrombophlebitis), redness, bleeding problems (haemorrhage)
• Irritation or bleeding in the intestine, pain or ulcers in the mouth that may not appear until 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
• Itchy skin and other skin disorders
• Hypersensitivity of irradiated skin (radiation recall reactions)
• Red discoloration of the urine
• Women may also find that their menstrual cycles stop (amenorrhoea), but these should return to normal after stopping the drug. In some cases, early menopause may occur.
• In men, doxorubicin may cause a decrease or absence of sperm (oligospermia, azoospermia), but this may return to normal after stopping the drug.
• Feeling unwell or malaise
• Liver toxicity
• Temporary increase in liver enzymes
• Condition in which the kidney stops functioning (acute renal failure)
• Shortness of breath due to spasm of the respiratory muscles (bronchospasm).

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please inform your doctor or pharmacist. You can also report side effects directly via the website: https://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 Doxorubicin concentrate for infusion solution

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial or outer packaging.
The expiry date refers to the last day of the month.
Store in a refrigerator (2°C-8°C). Keep the vial in the outer packaging to protect the medicine from light.
Do not use this medicine if you notice that the solution is not clear, red and free from particles.
Single-use medicinal product.
Any unused medicine or waste material derived from this medicine must be disposed of in accordance with
local regulations.
Observe the guidelines for handling cytotoxic medicinal products.
Sealed vials: 18 months.
Opened vials: the product must be used immediately after opening the vial.
Chemical and physical in-use stability has been demonstrated in 0.9% sodium chloride injection and 5% dextrose injection for up to 28 days at 2°C-8°C and up to 7 days at 25°C, when the preparation was stored in glass containers protected from light.
From a microbiological standpoint, the product should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at 2°C-8°C, unless the dilution was carried out under controlled and validated aseptic conditions.

6. Package contents and other information

What Doxorubicin concentrate for solution for infusion contains:
Doxorubicin concentrate for solution for infusion contains the active substance doxorubicin hydrochloride.
1 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 excipients are: sodium chloride, hydrochloric acid (for pH adjustment) and water for injections.

Description of the appearance of Doxorubicin concentrate for solution for infusion and contents of the pack:
Doxorubicin concentrate for solution for infusion is a clear, red solution, practically free from particles.
Pack sizes:
1 × 5 ml vial
1 × 10 ml vial
1 × 25 ml vial
1 × 50 ml vial
1 × 100 ml vial
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer:
Marketing Authorisation Holder
Accord Healthcare S.L.U.
World Trade Center,
Moll de Barcelona,
s/n, Edifici Est 6ª planta,
08039 Barcelona,
Spain

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

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

The following information is intended exclusively for physicians and healthcare professionals.
Dosage and method of administration
Injectable doxorubicin must be administered only under the supervision of a qualified physician experienced in cytotoxic therapy. In addition, patients must be closely and regularly monitored during treatment.
Due to the risk of potentially fatal cardiomyopathy, the risks and benefits must be evaluated for each individual patient prior to each administration.
Doxorubicin is administered intravenously and intravesically and must not be administered orally, subcutaneously, intramuscularly, or intrathecally. Doxorubicin may be administered intravenously either as a bolus over a few minutes, as a short infusion lasting up to one hour, or as a continuous infusion for up to 96 hours.
The solution should be administered through an intravenous infusion line into an injectable solution of 9 mg/ml sodium chloride (0.9%) or an injectable solution of 50 mg/ml dextrose (5%) over 3–50 minutes. This technique reduces the risk of thrombophlebitis or perivenous extravasation, which may lead to severe local cellulitis, blistering, and tissue necrosis. Direct intravenous injection is not recommended due to the risk of extravasation, which may occur even when adequate blood return is confirmed by aspiration with a needle.
Intravenous administration:
The dosage of doxorubicin depends on the dosing regimen, the patient's general condition, and prior treatments administered. The dosage of doxorubicin hydrochloride may vary according to the indication (solid tumors or acute leukemia) and according to its use within a specific therapeutic regimen (as monotherapy or in combination with other cytotoxic agents, or as part of multidisciplinary procedures including combination chemotherapy, surgery, radiotherapy, and hormonal therapy).
Monotherapy
Generally, the dosage is calculated based on body surface area (mg/m²). Based on this, when doxorubicin is used as monotherapy, a recommended dose is 60–75 mg/m² of body surface area every three weeks.
Combination therapies
When doxorubicin hydrochloride is administered in combination with other antitumor agents having overlapping toxicities, such as high-dose intravenous cyclophosphamide or related anthracycline compounds such as daunorubicin, idarubicin, and/or epirubicin, the dose of doxorubicin should be reduced to 30–60 mg/m² every 3–4 weeks.
In patients who cannot tolerate the full dose (e.g., due to immunosuppression or advanced age), an alternative dose is 15–20 mg/m² of body surface area weekly.
Intravesical administration:
Doxorubicin may be administered via intravesical instillation for the treatment of superficial bladder carcinoma or as prophylaxis to prevent tumor recurrence after transurethral resection (TUR) in patients at high risk of recurrence. The recommended dose of doxorubicin hydrochloride for local intravesical treatment of superficial bladder tumors is 30–50 mg in 25–50 ml of an injectable solution of 9 mg/ml sodium chloride (0.9%) for instillation. The optimal concentration is approximately 1 mg/ml. The solution should generally remain in the bladder for 1–2 hours. During this period, the patient should be rotated 90° every 15 minutes. To avoid unwanted dilution with urine, the patient should not drink fluids during the 12 hours preceding treatment (this reduces urine production to approximately 50 ml/h).
Instillations may be repeated at intervals ranging from 1 week to 1 month, depending on whether the treatment is therapeutic or prophylactic.
Patients with impaired hepatic function
Since doxorubicin hydrochloride is primarily excreted via the liver and bile, drug elimination may be reduced in patients with impaired hepatic function or biliary obstruction, potentially leading to serious adverse effects.
General recommendations for dose adjustment in patients with impaired hepatic function are based on serum bilirubin levels:

Doxorubicin is contraindicated in patients with severe impairment of hepatic function.
Patients with impaired renal function
In patients with renal failure (GFR <10 ml/min), only 75% of the intended dose should be administered.
To avoid the development of cardiomyopathy, it is recommended not to exceed a cumulative lifetime dose of doxorubicin of 450–550 mg/m² of body surface area (including related drugs such as daunorubicin). Patients with concomitant heart disease undergoing mediastinal irradiation and/or previously treated with alkylating agents, and high-risk patients (with arterial hypertension for >5 years, previous coronary, valvular or myocardial cardiac damage, age over 70 years), should not exceed a maximum cumulative dose of 400 mg/m² of body surface area, and cardiac function in these patients must be monitored.
Dosage in children
A dose reduction may be necessary in children. Refer to treatment protocols and specialist literature.
Obese patients and patients with neoplastic infiltration of the bone marrow
In obese patients and in patients with neoplastic infiltration of the bone marrow, a reduction in the initial dose or longer dosing intervals may need to be considered.
Incompatibilities
Doxorubicin must not be mixed with heparin, as precipitation may occur, and must not be mixed with 5-fluorouracil due to the possibility of degradation. Prolonged contact with any alkaline pH solution should be avoided, as it may cause hydrolysis of the medicinal product. Until detailed compatibility data are available, doxorubicin must not be mixed with other medicinal products except with 0.9% sodium chloride injection and 5% dextrose injection.
Reconstituted infusion solutions
Chemical and physical in-use stability has been demonstrated in 0.9% sodium chloride injection and 5% dextrose injection for up to 28 days at 2°C–8°C and up to 7 days at 25°C, when the preparation was stored in glass containers protected from light.
From a microbiological standpoint, the product should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at 2°C–8°C, unless dilution has been carried out under controlled and validated aseptic conditions.
Disposal
Residues of the medicinal product and all materials used for dilution and administration must be destroyed according to standard hospital procedures applicable to cytotoxic agents, in compliance with current regulations on disposal of hazardous waste.
Any unused medicine and waste materials derived from this medicine must be disposed of in accordance with local regulations.
Shelf life and storage
Sealed vials: 18 months.
Opened vials: the product must be used immediately after opening the vial.
Store in a refrigerator (2°C–8°C).
Keep the vial in the outer packaging to protect the medicine from light.