DOXORUBICIN AUROVITAS 2 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

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

Doxorubicin hydrochloride

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you experience any side effects, talk to your doctor or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Doxorubicin Aurovitas and what is it 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 or uterine mucosa cancer.
• 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 you use Doxorubicin Aurovitas

Do not use Doxorubicin Aurovitas

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

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

Doxorubicin Aurovitas must not be administered intravenously

• if after previous treatment with anticancer medicines you were told that you had a persistent decrease in blood cell production (your bone marrow is not working properly).
• if after previous treatment with anticancer medicines you had 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 working properly.
• if you have previously been treated with doxorubicin or other anthracyclines and have received the maximum cumulative dose of them.

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

Doxorubicin Aurovitas must not be administered 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 bladder inflammation.
• 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

Consult your doctor or nurse before starting treatment with this medicine:

• if you are or may be pregnant, see the section on pregnancy and breastfeeding.
• if you have been treated with radiotherapy before.
• if you are trying to become pregnant, may want to become pregnant in the future, or if you want to father a child.
• if you have kidney problems.
• if you have or have had any heart problems.

Doxorubicin greatly reduces the production of blood cells in the bone marrow. This can make you more prone to infections or bleeding. Inform your doctor if you experience fever or other signs of infection or bleeding.

Vaccination is not recommended. You should avoid contact with people who have been recently vaccinated against polio.

Doxorubicin should only be administered under the supervision of a qualified doctor with experience in anticancer treatments. Additionally, patients should be carefully and frequently monitored, e.g. blood tests and heart, liver, and kidney function tests.

If you experience a burning sensation or pain at the injection site, inform your doctor or another healthcare professional. This pain can occur if the medicine leaks out of the vein, and you will need appropriate treatment.

There have been reports of interstitial lung disease in patients receiving liposomal pegylated doxorubicin, including fatal cases. Symptoms of interstitial lung disease are cough and difficulty breathing, sometimes with fever, which are not caused by physical activity. Seek medical attention immediately if you experience symptoms indicative of interstitial lung disease.

Other medicines and Doxorubicin Aurovitas

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines. This is especially important for:

• other anticancer medicines, e.g. anthracyclines (daunorubicin, epirubicin, idarubicin, trastuzumab), cyclophosphamide, cytarabine, cisplatin, fluorouracil, taxanes (e.g. paclitaxel), mercaptopurine, methotrexate, streptozocin.
• cyclosporin (used in organ and tissue transplants).
• medicines for heart diseases (cardioactive drugs), e.g. calcium channel blockers and digoxin.
• medicines that reduce uric acid levels in the blood.
• rifampicin (antibiotic).
• cimetidine (used in the treatment of heartburn and stomach ulcers).
• live vaccines (e.g. poliomyelitis).
• 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 may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

In animal experiments, it has been observed that doxorubicin crosses the placenta and causes damage to the fetus. Therefore, doxorubicin should not be administered if you are pregnant or think you may be pregnant.

If you are a woman, you should not become pregnant during treatment or for 6 months after treatment with doxorubicin. If you are a man, you should take adequate precautions to ensure that your partner does not become pregnant during treatment or for 6 months after treatment with doxorubicin. Therefore, sexually active men and women should use effective contraceptive methods during treatment and for 6 months after the end of treatment.

Male patients should also seek advice on the cryopreservation (or cryoconservation) of sperm before treatment, due to the possibility of irreversible infertility as a result of treatment with doxorubicin. 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 (less than 1 mmol) of sodium per ml of concentrate, which should be taken into account in the treatment of patients with low-sodium diets.

3. How to use Doxorubicin Aurovitas

Doxorubicin should only be administered under the supervision of a doctor with experience in anticancer treatments.

Form and administration routes

The medicine will be administered to you by intravenous infusion, into a blood vessel, under the supervision of a specialist. Do not administer the medicine yourself. You will undergo regular checks during and after treatment. If you suffer from 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 can be administered, e.g. once a week every 3 weeks or even with longer intervals between doses. The dose and frequency also depend on other anticancer medicines used, as well as the type of disease and your overall health. Your doctor will decide what dose to administer to 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 period, you will need to turn 90 degrees every 15 minutes.

Do not drink anything in the 12 hours beforebladder administration to avoid unwanted dilution of the medicine with urine. Bladder administration can be repeated at an interval of 1 week to 1 month. Your doctor will decide how often you need it.

Use in children

The dose should be reduced in children. Your doctor will indicate the necessary amount.

If you use more Doxorubicin Aurovitas than you should

Since this medicine is administered by a doctor, it is unlikely that you will be given an overdose.

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

An acute overdose worsens side effects such as mouth sores, decrease in white blood cell and platelet count, and can cause heart problems. In case of overdose, your doctor will decide what treatment you should receive. Heart disorders can appear up to six months after an overdose.

If you are administered more doxorubicin than you should, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medicine and the amount administered.

If you miss a dose of Doxorubicin Aurovitas

Your doctor will decide the duration of your treatment with this medicine. If treatment is interrupted before completing the recommended treatment cycles, the effects of treatment with doxorubicin may be reduced. Consult your doctor if you want to interrupt treatment.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Contact your doctor or nurse immediately:

• if you feel dizzy, have a fever, shortness of breath with chest or throat tightness, or have a skin rash with itching. This can be a type of allergic reaction that can be very serious;
• if you feel tired and apathetic. This can be a sign of anemia (low red blood cell count);
• if you have a fever or other signs of infection. This can be a sign of a low white blood cell count;
• if you bruise or bleed more easily. This can be a sign of a low platelet count.

Very common (may affect more than 1 in 10 people)

• nausea, vomiting, abdominal pain, digestive system problems, diarrhea.
• mucosal inflammation, e.g. of the mouth or esophagus.
• hair loss (usually reversible), skin redness, skin sensitivity to natural or artificial light (photosensitivity).
• red coloration of the urine for 1 or 2 days after administration. This is normal and does not need to be a concern.
• bone marrow suppression (deficiency of blood cells) including reduction in white blood cell count (causing infections), platelet count (causing bleeding and bruising), and red blood cell count (anemia; which can cause paleness of the skin and weakness or difficulty breathing).
• serious heart complications (cardiotoxicity), such as heart muscle damage or rapid, slow, or irregular heartbeat. The effects can appear soon after starting treatment or be observed several years later.
• fever.
• weight gain.

Common (may affect up to 1 in 10 people)

• bacterial infection.
• bacterial infection of the blood.
• heart rhythm disorders (irregular heartbeat, increased heart rate, decreased heart rate), reduction in the amount of blood pumped by the heart, deterioration of heart muscle function (cardiomyopathy) which can be life-threatening.
• bleeding (hemorrhage).
• eating disorder (anorexia).
• local allergic reaction at the radiation treatment site.
• itching.
• difficulty or pain when urinating, bladder inflammation after bladder administration, sometimes with bladder irritation, blood in the urine, pain when urinating, increased frequency of urination, or decreased amount of urine.

Uncommon (may affect up to 1 in 100 people)

• acute blood cancer (certain types of leukemia).
• vein inflammation.
• stomach or intestinal bleeding.
• ulcers in the mucous membranes of the mouth, pharynx, esophagus, stomach, and intestines.
• ulcers and possible tissue death in the colon when doxorubicin is used 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 skin and nail areas; nail loss (onycholysis).
• severe allergic reactions with or without shock, including skin rash, itching, fever, and feeling of cold (anaphylactic reactions).
• chills.
• dizziness.
• secondary leukemia (blood cancer that develops after treatment of another cancer), when the medicine is combined with other anticancer medicines that damage DNA.
• tumor lysis syndrome (complications of chemotherapy caused by the breakdown products of dead cancer cells, which can affect, for example, the blood and kidneys).
• reactions at the injection site, including redness, rash, and pain, vein inflammation (phlebitis), thickening or hardening of the vein walls (phlebosclerosis).
• burning sensation or pain at the injection site that occurs if the medicine leaks out of the vein. This can cause local tissue death and requires appropriate treatment, sometimes surgical.

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

• redness of the face.
• changes in heart function (non-specific changes in the ECG), isolated cases of life-threatening irregular heartbeat (arrhythmias), heart failure, inflammation of the pericardium and myocardium, loss of nerve impulses in the heart.
• blood clots in blood vessels.
• coloration of the mouth lining (pigmentation).
• swelling and numbness of the hands and feet (palmar-plantar erythrodysesthesia), blistering, tissue damage, especially to hands and feet, which causes redness, swelling, blisters, tingling or burning sensation caused by the leakage of the medicine into the tissues.
• acute kidney failure.
• abnormally high uric acid levels in the blood.
• absence of menstruation.
• fertility problems in men (reduced or absent active sperm).

Frequency not known (cannot be estimated from the available data)

• increased tear production.
• cough or difficulty breathing due to sudden narrowing of the airways, possibly accompanied by fever, which is not caused by physical activity (interstitial lung disease).
• lung inflammation.
• liver toxicity, which can sometimes evolve into permanent liver tissue damage (cirrhosis).
• transient increase in liver enzymes.
• thick, scaly, or rough skin plaques (actinic keratosis).
• severe joint pain and swelling.
• weakness.
• healed radiation injury (in the skin, lungs, throat, stomach and intestinal mucosa, heart) may recur with doxorubicin treatment.
• corneal inflammation (keratitis).

Reporting of side effects

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

5. Storage of Doxorubicina 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 carton after EXP. The expiry date refers to the last day of the month stated.

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 transparent, red, and particle-free.

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

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

6. Package Contents and Additional Information

Composition ofDoxorubicina Aurovitas

• The active ingredient is doxorubicin hydrochloride. Each vial contains 2 mg/ml of doxorubicin hydrochloride.
• The other ingredients are sodium chloride, hydrochloric acid, and water for injectable preparations.

Appearance of the Productand Package Contents

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

Doxorubicina Aurovitas is packaged in colorless glass vials with a bromobutyl rubber stopper and sealed with an aluminum cap with a polypropylene disc. The vial may be packaged with or without a protective plastic wrapper.

Package 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

Not all package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization 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

O

Generis Farmacêutica, S.A.

Rua João de Deus, nº 19, Venda Nova

2700-487 Amadora

Portugal

For further information on this medicine, please contact the local representative of the marketing authorization holder:

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

Date of Last Revision of this Leaflet: November 2023

Detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/).

This information is intended only for healthcare professionals:

Doxorubicina Aurovitas 2mg/ml Concentrate for Solution for Infusion EFG

Doxorubicin is a potent cytotoxic agent that should only be prescribed, prepared, and administered by professionals who have received training in the safe handling of the preparation. For dosage and administration recommendations, see section 4.2 of the Summary of Product Characteristics. For handling, preparation, and disposal of doxorubicin, the following guidelines should be observed:

This medicine is for single use.

Preparation

1. Cytotoxic drugs should be prepared by personnel who have received training in the safe handling of the preparation. Consult local recommendations on cytotoxics before starting.
2. Pregnant women should not be involved in the preparation of this medicine.
3. Personnel handling doxorubicin should wear protective clothing: glasses, gowns, gloves, and disposable masks.
4. All items used for administration or cleaning, including gloves, should be discarded in high-risk waste disposal bags for incineration at high temperature (700°C).
5. All cleaning materials should be disposed of as indicated above.
6. Always wash hands after removing gloves.

Do not use this medicine if the solution is not transparent, red, and particle-free.

Contamination

1. In case of skin or mucous membrane contact, wash the affected area thoroughly with water and soap or a sodium bicarbonate solution. However, do not rub the skin with a brush. A mild cream can be used to treat transient skin irritation.
2. In case of eye contact, remove the eyelid and wash the affected eye with plenty of water for at least 15 minutes or with a 9 mg/ml (0.9%) sodium chloride solution. Then, seek evaluation by a doctor or ophthalmologist.
3. In case of spill or leak, treat with a 1% sodium hypochlorite solution or simply with a phosphate buffer (pH >8) until the solution is cleaned. Use a cloth/sponge and keep it in the affected area. Rinse twice with water. Put all cloths in a plastic bag and seal it for incineration.

Stability in Use

Open Vials:chemical and physical stability in use has been demonstrated for 28 days at 2-8°C. From a microbiological point of view, the medicine should be used immediately unless the opening method prevents the risk of microbiological contamination. If not used immediately, the in-use storage conditions and times are the responsibility of the user.

Prepared Infusion Solutions:chemical and physical stability has been demonstrated after dilution, protected from light, for:

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

From a microbiological point of view, the medicine should be used immediately. If not used immediately, the storage conditions and times before use are the responsibility of the user and should not normally exceed 24 hours at 2°C to 8°C, unless the dilution has taken place under controlled and validated aseptic conditions.

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

Disposal

For single use. Disposal of unused medicine and all materials that have come into contact with it should be carried out in accordance with local regulations. Recommendations for the handling of cytotoxic drugs should be followed.

Note:

The dosage of liposomal doxorubicin and that of conventional doxorubicin, as in Doxorubicina Aurovitas, are different. The two formulations should not be interchanged.

Incompatibilities

Doxorubicin should not be mixed with heparin, as a precipitate forms, or with 5-fluorouracil, as it may degrade. Prolonged contact with any alkaline pH solution should be avoided, as it will cause hydrolysis of the drug.

In the absence of compatibility studies, this medicine should not be mixed with other medicines.