Doxorubicin Aurovitas 2 mg/ml concentrate for solution for infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Doxorubicin Aurovitas 2mg/ml concentrate for solution for infusion EFG

Doxorubicin hydrochloride

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• If you experience any adverse reactions, consult your doctor or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Doxorubicin Aurovitas is and what it is used for

Doxorubicin Aurovitas belongs to a group of anticancer medicines called anthracyclines. Doxorubicin is used to treat the following types of cancer:

• Small cell lung cancer
• Bladder cancer
• Bone cancer
• Breast cancer
• Blood cancer
• Lymphatic system cancer (Hodgkin's and non-Hodgkin's lymphoma)
• Bone marrow cancer
• Thyroid gland cancer
• Soft tissue cancer (in adults)
• Recurrent ovarian cancer or cancer of the lining of the uterus (endometrium)
• A type of kidney cancer in children (Wilms' tumor)
• A type of nerve cell cancer in children (neuroblastoma)

Doxorubicin is also used in combination with other anticancer medicines.

2. What you need to know before starting to use Doxorubicin Aurovitas

Do not use Doxorubicin Aurovitas

• if you are allergic to doxorubicin or to any of the other ingredients of this medicine (listed in section 6).
• if you are allergic to medicines belonging to the anthracycline or anthracenedione group.
• if you are breastfeeding.

If any of these situations apply to you, consult your doctor.

Do not be given Doxorubicin Aurovitas intravenously

• if, after previous treatment with anticancer medicines, you were told that you had a persistent reduction in blood cell production (your bone marrow is not functioning properly).
• if, due to prior treatment with anticancer medicines, you experienced severe inflammation or ulcers in the mouth.
• if you have any heart problems.
• if you tend to bleed easily.
• if you have any type of infection.
• if your liver is not functioning properly.
• if you have previously been treated with doxorubicin or other anthracyclines and have received the maximum cumulative dose of these drugs.

If any of these situations apply to you, consult your doctor.

Do not be given Doxorubicin Aurovitas into the bladder

• if you have a tumor that has grown into the bladder wall.
• if you have a urinary tract infection.
• if you have inflammation of the bladder.
• if you have blood in your urine.
• if you have problems with instillation (e.g., urethral obstruction).

If any of these situations apply to you, consult your doctor.

Warnings and precautions

Talk to your doctor or nurse before starting to use this medicine:

• if you are or might be pregnant; see the section on pregnancy and breastfeeding.
• if you have previously undergone radiotherapy.
• if you are trying to become pregnant, plan to become pregnant in the future, or wish to father a child.
• if you have kidney problems.
• if you have or have previously had any heart problems.

Doxorubicin greatly reduces the production of blood cells in the bone marrow. This may make you more susceptible to infections or bleeding. Inform your doctor if you develop fever or any other sign of infection or bleeding.

Vaccination is not recommended. You should avoid contact with individuals recently vaccinated against polio.

Doxorubicin should only be administered under the supervision of a qualified physician experienced in cancer treatments. Additionally, patients must be carefully and frequently monitored, for example, blood status and tests of heart, liver, and kidney function.

If you experience stinging or burning at the injection site, inform your doctor or other healthcare professional. This pain may occur if the medication leaks out of the vein and requires appropriate treatment.

Cases of interstitial lung disease, including fatal cases, have been reported in patients receiving pegylated liposomal doxorubicin. Symptoms of interstitial lung disease include cough and shortness of breath, sometimes with fever, not caused by physical activity. Seek immediate medical attention if you experience symptoms suggestive of interstitial lung disease.

Other medicines and Doxorubicin Aurovitas

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines. This is especially important in the case of:

• other anticancer 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).
• medicines for heart conditions (cardioactive drugs), e.g., calcium channel blockers and digoxin.
• medicines that reduce uric acid levels in the blood.
• rifampicin (an antibiotic).
• cimetidine (used in the treatment of heartburn and stomach ulcers).
• live vaccines (e.g., polio).
• phenytoin, carbamazepine, valproate, phenobarbital, and other barbiturates (used in the treatment of epilepsy).
• chloramphenicol and sulfonamides (medicines for infections).
• amphotericin B (a medicine for fungal infections).
• medicines for viral infections, such as ritonavir (used to treat HIV infection).
• clozapine (an antipsychotic).
• amidopyrine derivatives (for pain and inflammation).

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you might be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Animal studies have shown that doxorubicin crosses the placenta and causes fetal harm. Therefore, doxorubicin must not be administered if you are pregnant or suspect you may be pregnant.

If you are a woman, you must not become pregnant during treatment and for up to 6 months after treatment with doxorubicin. If you are a man, you must take appropriate precautions to ensure your partner does not become pregnant during treatment and for up to 6 months after treatment with doxorubicin. Therefore, sexually active men and women must use effective contraception during treatment and for 6 months after completion of treatment.

Male patients should also seek advice regarding sperm cryopreservation (or cryopreservation) before treatment due to the risk of irreversible infertility caused by doxorubicin treatment. If you are considering becoming a parent after treatment, consult your doctor.

The drug passes into breast milk. Do not breastfeed while being treated with doxorubicin.

Driving and using machines

Due to the frequent occurrence of nausea and vomiting, do not drive or operate machinery.

Doxorubicin Aurovitas contains sodium

This medicine contains 3.54 mg (<1 mmol) of sodium per ml of concentrate, which should be taken into account when treating patients on low-sodium diets.

3. How Doxorubicina Aurovitas is administered

Doxorubicin must only be administered under the supervision of a physician experienced in cancer treatments.

Form and routes of administration

The medicine will be given to you by intravenous infusion into a blood vessel, under the supervision of a specialist. Do not administer the medicine yourself. You will undergo periodic check-ups during and after treatment. If you have superficial bladder cancer, you may receive the medicine directly into the bladder. This medicine must be diluted before use.

Intravenous administration

The dose is usually calculated based on body surface area. Doxorubicin may be administered, for example, once weekly every 3 weeks, or even at longer intervals between doses. The dose and frequency also depend on other anticancer medications used, as well as the type of disease and your general health status. Your doctor will decide the appropriate dose for you.

Bladder instillation

The dose is 30–50 mg of doxorubicin in 25–50 ml of physiological saline. The solution should remain in the bladder for 1–2 hours. During this time, you will need to rotate your body 90º every 15 minutes.

You must not drink anything during the 12 hours prior to bladder administration, to avoid unwanted dilution of the medicine by urine. Bladder instillation may be repeated at intervals ranging from 1 week to 1 month. Your doctor will decide how frequently it is needed.

Use in children

The dose should be reduced in children. Your doctor will advise you on the required amount.

If you use more Doxorubicina Aurovitas than you should

As this medicine is administered by a doctor, it is unlikely that you will receive an overdose.

However, inform your doctor or nurse immediately if you have any doubts.

An acute overdose worsens adverse effects such as mouth sores, decreased numbers of white blood cells and platelets in the blood, and may cause heart problems. In case of overdose, your doctor will decide what treatment you should receive. Heart disorders may occur up to six months after an overdose.

If you have been given more doxorubicin than you should, contact your doctor or pharmacist immediately or call the Toxicology Information Service at telephone number 91 562 04 20, indicating the medicine and the amount administered.

If you forget to use a dose of Doxorubicina Aurovitas

Your doctor will decide on the duration of your treatment with this medicine. If treatment is interrupted before completing the recommended treatment cycles, the effectiveness of doxorubicin therapy may be reduced. Consult your doctor if you wish to discontinue treatment.

If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Contact your doctor or nurse immediately if:

• you feel dizzy, have a fever, shortness of breath with tightness in the chest or throat, or develop a rash with itching. These may be signs of an allergic reaction, which can be very serious;
• you feel tired and listless. This may be a sign of anemia (low number of red blood cells in the blood);
• you have a fever or other signs of infection. This may be a sign of a low number of white blood cells in the blood;
• you develop bruises or bleed more easily. 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, gastrointestinal disturbances, diarrhea.
• inflammation of mucous membranes, e.g., in the mouth or esophagus.
• hair loss (usually reversible), skin redness, skin sensitivity to natural or artificial light (photosensitivity).
• red discoloration of the urine for 1 or 2 days after administration. This is normal and not a cause for concern.
• bone marrow suppression (reduced blood cells), including reduced numbers of white blood cells (leading to infections), platelets (leading to bleeding and bruising), and red blood cells (anemia; which may cause pale skin, weakness, or difficulty breathing).
• severe cardiac complications (cardiotoxicity), such as damage to the heart muscle or rapid, slow, or irregular pulse. These effects may occur shortly after starting treatment or may appear several years later.
• fever.
• weight gain.

Common (may affect up to 1 in 10 people)

• bacterial infection.
• bacterial infection of the blood.
• cardiac arrhythmias (irregular heartbeat, increased heart rate, decreased heart rate), reduced blood output from the heart, worsening of heart muscle function (cardiomyopathy), which may be life-threatening.
• bleeding (hemorrhage).
• eating disorder (anorexia).
• local allergic reaction in areas treated with radiation.
• itching.
• difficulty or pain when urinating, bladder inflammation after administration into the bladder, sometimes with bladder irritation, blood in the urine, painful urination, increased frequency of urination, or decreased urine volume.

Uncommon (may affect up to 1 in 100 people)

• acute cancer of the blood (certain types of leukemia).
• inflammation of a vein.
• bleeding from the stomach or intestines.
• ulcers in the mucous membranes of the mouth, pharynx, esophagus, stomach, and intestines.
• ulcers and possible death of cells/tissues in the colon when doxorubicin is used together with the medicine cytarabine.
• dehydration.

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

• inflammation of the outer layer of the eye (conjunctivitis).
• hives; skin rash and redness.
• darkening of areas of the skin and nails; nail loss (onycholysis).
• severe allergic reactions with or without shock, including skin rash, itching, fever, and chills (anaphylactic reactions).
• chills.
• dizziness.
• secondary leukemia (blood cancer that develops after treatment for another cancer), when the medicine is combined with other cancer medicines that damage DNA.
• tumor lysis syndrome (chemotherapy complications caused by breakdown products of dead cancer cells, which may affect, for example, the blood and kidneys).
• reactions at the injection site, including redness, rash, and pain; inflammation of the vein (phlebitis); thickening or hardening of the vein walls (phlebosclerosis).
• burning or stinging sensation at the injection site if the medicine leaks outside the vein. This may cause local tissue cell death and may require appropriate treatment, sometimes surgical.

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

• facial flushing.
• changes in heart function (non-specific changes in ECG), isolated cases of life-threatening irregular heartbeat (arrhythmias), heart failure, inflammation of the pericardium and myocardium, loss of nerve impulses in the heart.
• formation of blood clots in blood vessels.
• discoloration of the lining of the mouth (pigmentation).
• 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 due to leakage of the medicine into surrounding tissues (palmar-plantar erythrodysesthesia syndrome).
• acute kidney failure.
• abnormally high levels of uric acid in the blood.
• absence of menstruation.
• fertility problems in men (reduced or absent active sperm).

Frequency not known (cannot be estimated from available data)

• increased tear production.
• cough or difficulty breathing due to sudden narrowing of the airways, possibly accompanied by fever, not triggered by physical activity (interstitial lung disease).
• lung inflammation.
• liver toxicity, which in some cases may progress to permanent liver tissue damage (cirrhosis).
• transient increase in liver enzymes.
• thick, scaly, or rough skin patches (actinic keratosis).
• severe joint pain and swelling.
• weakness.
• previously healed radiation injury (in the skin, lungs, throat, stomach and intestinal mucosa, heart) may reappear during treatment with doxorubicin.
• keratitis (inflammation of the cornea of the eye).

Reporting of adverse effects

If you experience any adverse effects, talk to your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Doxorubicin Aurovitas

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the vial and outer carton after EXP. The expiry date refers to the last day of the month indicated.

Store in a refrigerator (between 2°C and 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.

Disposal of unused medicine and of all materials that have been in contact with it must be carried out in accordance with local regulations. Recommendations for handling cytotoxic drugs should be followed.

Medicines should not be disposed of via wastewater or household waste. Ask your doctor how to dispose of containers and medicines you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Doxorubicina Aurovitas

• The active substance is doxorubicin hydrochloride. Each vial contains 2 mg/mL of doxorubicin hydrochloride.
• The other components are sodium chloride, hydrochloric acid and water for injections.

Nature of the medicinal product and contents of the container

Doxorubicina Aurovitas concentrate for solution for infusion is a transparent red solution.

Doxorubicina Aurovitas is packed in colourless glass vials with bromobutyl rubber stoppers and sealed with aluminium caps with polypropylene discs. The vial may be packed with or without a protective plastic overwrap.

Pack sizes:

1 vial of 5 mL

10 vials of 5 mL

1 vial of 10 mL

10 vials of 10 mL

1 vial of 25 mL

1 vial of 50 mL

1 vial of 75 mL

1 vial of 100 mL

Only certain pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

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

Manufacturer

APL Swift Services (Malta) Limited
HF26, Hal Far Industrial Estate, Hal Far
Birzebbugia, BBG 3000
Malta

Or

Generis Farmacêutica, S.A.
Rua João de Deus, nº 19, Venda Nova
2700-487 Amadora
Portugal

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

Aurovitas Spain, S.A.U.
Avda. de Burgos, 16-D
28036 Madrid
Spain

Date of the most recent revision of this package leaflet: November 2023

Detailed information about this medicinal product is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/).

This information is intended for healthcare professionals only:

Doxorubicina Aurovitas 2 mg/mL concentrate for solution for infusion EFG

Doxorubicin is a potent cytotoxic agent and should only be prescribed, prepared and administered by healthcare professionals trained in the safe use of such preparations. For dosage and administration recommendations, refer to section 4.2 of the Summary of Product Characteristics. The following guidelines must be observed for handling, preparation and disposal of doxorubicin:

This medicinal product is for single use only.

Preparation

1. Cytotoxic medicinal products must be prepared by personnel trained in the safe handling of such preparations. Consult local recommendations regarding cytotoxic agents before starting.
2. Pregnant women must not be involved in the preparation of this medicinal product.
3. Personnel handling doxorubicin must wear protective clothing: goggles, gowns, disposable gloves and masks.
4. All materials used for administration or cleaning, including gloves, must be disposed of in high-risk waste disposal bags for incineration at high temperature (700°C).
5. All cleaning materials must be disposed of as indicated above.
6. Always wash hands after removing gloves.

Do not use this medicinal product if the solution is not clear, red and free from particles.

Contamination

1. In case of contact with skin or mucous membranes, thoroughly wash the affected area with water and soap or sodium bicarbonate solution. However, do not rub the skin with a brush. A mild cream may be used to treat transient skin irritation.
2. In case of eye contact, hold the eyelid open and flush the affected eyes with copious amounts of water for at least 15 minutes or with a 9 mg/mL (0.9%) sodium chloride solution. Subsequently, seek medical or ophthalmological evaluation.
3. In case of spillage or leakage, treat with a 1% sodium hypochlorite solution or simply with phosphate buffer (pH >8) until the solution is cleaned. Use a cloth/sponge and keep it in place over the affected area. Rinse twice with water. Place all cloths into a plastic bag, seal it, and incinerate.

Use during storage

Opened vials: Chemical and physical in-use stability has been demonstrated for 28 days at 2–8°C. From a microbiological standpoint, the medicinal product should be used immediately unless the method of opening prevents the risk of microbiological contamination. If not used immediately, the conditions and duration of storage prior to use are the responsibility of the user.

Prepared infusion solutions: Chemical and physical stability after dilution, protected from light, has been demonstrated up to:

• 7 days at 2–8°C and 2 days at 25°C after dilution in 0.9% sodium chloride solution (PE bottle) at a concentration of 1.25 mg/mL.
• 24 hours at 2–8°C and at 25°C after dilution in 5% glucose solution (PP bag) at a concentration of 1.25 mg/mL.
• 2 days at 2–8°C and 7 days at 25°C after dilution in 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 after dilution in 5% glucose solution (PP bag) at a concentration of 0.5 mg/mL.

From a microbiological standpoint, the medicinal product should be used immediately. If not used immediately, the conditions and duration of storage prior to use are the responsibility of the user and normally should not exceed 24 hours at 2°C to 8°C, unless dilution has taken place under controlled, aseptic and validated conditions.

The storage times for the opened vial and the diluted infusion solution are not additive.

Disposal

For single use only. Any unused medicinal product and all materials that have come into contact with it must be disposed of in accordance with local regulations. Recommendations for handling cytotoxic drugs must be followed.

Note:

The dosing regimens for S-liposomal doxorubicin and conventional doxorubicin, such as in Doxorubicina Aurovitas, are different. The two formulations are not interchangeable.

Incompatibilities

Doxorubicin must not be mixed with heparin, as a precipitate forms, or with 5-fluorouracil, due to possible degradation. Prolonged contact with any alkaline pH solution should be avoided, as drug hydrolysis will occur.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.