Leaflet: information for the user

Doxorubicina Aurovitas 2mg/ml concentrated solution for EFG infusion

Hidrocloruro de doxorubicina

Read this 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 side effects, consult your doctor or nurse, even if they are not listed in this leaflet. See section 4.

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

2.What you need to know before starting to useDoxorubicina Aurovitas

3.How to administerDoxorubicina Aurovitas

4.Possible side effects

5.Storage ofDoxorubicina Aurovitas

6.Contents of the pack and additional information

DoxorubicinaAurovitasis part of a group of cancer medications called anthracyclines. Doxorubicinais used to treat the following types of cancer:

-Small cell lung cancer.

-Bladder cancer.

-Bone cancer.

-Breast cancer.

-Blood cancer.

-Lymphoma (Hodgkin and non-Hodgkin).

-Myeloma.

-Thyroid cancer.

-Soft tissue cancer (in adults).

-Recurrent ovarian or uterine cancer.

-A type of kidney cancer in children (Wilms tumor).

-A type of nervous system cancer in children (neuroblastoma).

Doxorubicina is also used in combination with other cancer medications.

No use Doxorubicina Aurovitas

-if is allergic to doxorubicin or any of the other components of this medication (listed in section 6).

-if is allergic to medications in the anthracycline or anthracenedione group.

-if is breastfeeding.

If any of these situations affect you, consult your doctor.

Do not administer Doxorubicina Aurovitas intravenously

-if after a previous treatment with cancer medications, they told you that you had a persistent decrease in blood cell production (your bone marrow does not work well).

-if after a previous treatment with cancer medications, 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 does not work well.

-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 affect you, consult your doctor.

Do not administer Doxorubicina Aurovitas in the bladder

-if you have a tumor that has grown in 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 affect you, consult your doctor.

Warnings and precautions

Consult your doctor or nurse before starting to use this medication:

-if you are or may be pregnant, see the section on pregnancy and breastfeeding.

-if you have been treated with radiation therapy previously.

-if you are trying to get pregnant, may want to get pregnant in the future, or want to father a child.

-if you have kidney problems.

-if you have or have had any heart problems.

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

Do not recommend vaccination. Avoid contact with people recently vaccinated against polio.

Doxorubicina should only be administered under the supervision of a qualified doctor with experience in cancer treatments. Additionally, patients should be carefully and frequently monitored, for example, blood counts and tests of heart, liver, and kidney function.

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

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

Other medications and Doxorubicina Aurovitas

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication. This is especially important in the case of:

-other cancer medications, for example, anthracyclines (daunorubicin, epirubicin, idarubicin, trastuzumab), cyclophosphamide, cytarabine, cisplatin, fluorouracil, taxanes (e.g., paclitaxel), mercaptopurine, methotrexate, streptozocin.

-ciclosporin (used in organ and tissue transplants).

-heart medications (cardioactive drugs), for example, calcium channel blockers and digoxin.

-medications that reduce blood uric acid levels.

-rifampicin (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 (infection medications).

-amphotericin B (a medication for fungal infections).

-medications 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, or think you may be pregnant, consult your doctor or pharmacist before using this medication.

In animal experiments, doxorubicin has been observed to cross the placenta and cause damage to the fetus. Therefore, do not administer doxorubicin if you are pregnant or think you may be.

If you are a woman, do not become pregnant during treatment or for 6 months after treatment with doxorubicin. If you are a man, take the necessary 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 treatment.

Male patients should also seek advice on sperm cryopreservation (or cryopreservation) before treatment, due to the possibility of irreversible infertility as a result of treatment with doxorubicin. If you are considering becoming parents after treatment, consult your doctor.

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

Driving and operating machinery

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

Doxorubicina Aurovitas contains sodium

This medication contains 3.54 mg (<1 mmol) of sodium per ml of concentrate, which should be taken into account in the treatment of patients with low-sodium diets.

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

Form and routes of administration

The medication will be administered by intravenous infusion, in a vein, under the supervision of a specialist. Do not administer the medication yourself. You will undergo regular monitoring during treatment and after it. If you have superficial bladder cancer, it is possible that you may receive the medication directly into the bladder. This medication must be diluted before use.

Intravenous administration

The dose is usually calculated based on body surface area.Doxorubicin can be administered, for example, once a week every 3 weeks or with longer intervals between doses. The dose and frequency also depend on other cancer medications used, as well as the type of disease and your overall health status. Your doctor will decide what dose to administer.

Instillation in the bladder

The dose is 30‑50mg of doxorubicin in 25‑50ml of physiological serum. The solution must remain in the bladder for 1‑2hours. During this period, you will need to turn 90º every 15minutes.

You should not drink anything in the 12 hours prior to administration in the bladder, to avoid an unwanted dilution of the medication with urine. Bladder administration may be repeated with an interval of 1 week to 1 month.Your doctor will decide how often you need it.

Use in children

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

If you use more Doxorubicin Aurovitas than you should

Since this medication will be 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 can worsen adverse effects such as mouth sores, decreased white blood cell and platelet count in the blood, and may cause heart problems. In case of overdose, your doctor will decide what treatment you should receive. Heart problems may appear up to six months after an overdose.

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

If you forgot to use a dose of Doxorubicin Aurovitas

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

If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Seek immediate medical attention from your doctor or nurse:

-if you havedizziness,fever,shortness of breathwithchest or throat tightnessor have askin rash with itching. This can be a severe allergic reaction;

-if you feelfatiguedandapathetic. This can be a sign of anemia (low red blood cell count in the blood);

-if you havefeveror otherinfection symptoms. This can be a sign of low white blood cell count in the blood;

-if you noticebruisingorbleedingmore easily. This can be a sign of low platelet count in the blood.

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

-nausea, vomiting, abdominal pain, digestive system problems, diarrhea.

-inflammation of mucous membranes, e.g., of the mouth or esophagus.

-hair loss (usually reversible), skin redness, skin sensitivity to natural or artificial light (photosensitivity).

-red urine color for 1 or 2 days after administration. This is normal and there is no need to worry.

-bone marrow suppression (blood cell deficiency) including reduction in white blood cell count (causing infections), platelet count (causing bleeding and bruising) and red blood cell count (anemia; causing pale skin and weakness or difficulty breathing).

-severe cardiac complications (cardiotoxicity), such as heart muscle damage or irregular heartbeat, which can appear shortly after starting treatment or several years later.

-fever.

-weight gain.

Common (may affect up to 1 in 10 people)

-bacterial infection.

-bloodstream infection.

-cardiac arrhythmias (irregular heartbeat, increased heart rate, decreased heart rate), reduced blood volume pumped by the heart, heart muscle deterioration (myocarditis) that can be life-threatening.

-bleeding (hemorrhage).

-eating disorder (anorexia).

-local allergic reaction in the area treated with radiation.

-itching.

-difficulty or pain urinating, inflammation of the bladder after administration in the bladder, sometimes with irritation of the bladder, blood in the urine, pain urinating, increased frequency of urination or decreased urine volume.

Uncommon (may affect up to 1 in 100 people)

-acute leukemia in the blood (certain types of leukemia).

-inflammation of a vein.

-gastrointestinal hemorrhage.

-ulcers in the mucous membrane of the mouth, pharynx, esophagus, stomach, and intestines.

-ulcers and possible cell/tissue death in the colon when doxorubicin is used with the medication citarabina.

-dehydration.

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

-inflammation of the outer layer of the eye (conjunctivitis).

-urticaria; skin rash and redness.

-skin darkening in areas and nails; nail loss (onycholysis).

-severe allergic reactions with or without shock,including skin rash, itching, fever, and feeling cold (anaphylactic reactions).

-chills.

-dizziness.

-leukemia secondary (blood cancer that develops after treatment for another cancer), when the medication is combined with other cancer medications 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 that include redness, rash, and pain, inflammation of the vein (phlebitis), thickening or hardening of the walls of the vein (phlebosclerosis).

-burning or stinging sensation at the injection site that occurs if the medication leaks out of the vein. Thiscan cause local cell death in tissuesand requires proper treatment, sometimes surgical.

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

-face redness.

-changes in heart function (non-specific changes in ECG), isolated cases of life-threatening irregular heartbeat (arrhythmias), heart failure, pericarditis and myocarditis, loss of nerve impulses in the heart.

-blood clots in blood vessels.

-coloration of the oral mucosa (pigmentation).

-swelling and numbness of the hands and feet (erythema acral), vesicle formation, tissue damage, especially in hands and feet, causing redness, swelling, blisters, tingling, or burning sensation produced by the leakage of the medication to the tissues (erythrodysthesia palmoplantar syndrome).

-acute kidney failure.

-high levels of uric acid in the blood.

-amenorrhea.

-male fertility problems (reduced or absent active sperm).

Frequency not known (cannot be estimated from available data)

-increased tear production.

-shortness of breath or difficulty breathing due to sudden narrowing of the airways, possibly accompanied by fever, not caused by physical activity (interstitial lung disease).

-inflammation of the lungs.

-liver toxicity, which can sometimes progress to permanent liver tissue damage (cirrhosis).

-transient increase in liver enzymes.

-thick, scaly, or rough skin patches (actinic keratosis).

-intense pain and swelling in the joints.

-weakness.

-radiation-induced lesions (in the skin, lungs, throat, stomach, and intestine mucosa, heart) that have been cured can reappear with doxorubicin treatment.

-keratitis (inflammation of the cornea of the eye).

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use:www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

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

Do not use this medicationafter the expiration date that appears on the vial and on the box after CAD. The expiration date is the last day of the month indicated.

Store in refrigerator (between 2°C and 8°C). Store the vial in the outer packaging to protect it from light.

Do not use this medicationif you observe that the solution is not transparent, red, and particle-free.

The disposal of unused medication and all materials that have been in contact with it will be carried out in accordance with local regulations. Recommendations related to the handling of cytotoxic drugs should be followed.

Medications should not be disposed of through drains or in the trash. Ask your doctor how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition ofDoxorubicina Aurovitas

-The active principle is hydrochloride of doxorubicina. Each vial contains 2mg/ml of hydrochloride of doxorubicina.

-The other components are sodium chloride, hydrochloric acid and water for injectable preparations.

Appearance of the productand contents of the package

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

Doxorubicina Aurovitasis packaged in colorless glass vials with 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.

Packaging sizes:

1 vial of 5ml

10 vials of 5ml

1 vial of 10ml

10 vials of 10ml

1 vial of 25ml

1 vial of 50ml

1 vial of 75ml

1 vial of 100ml

Only some packaging sizes may be commercially available.

Marketing authorization holder and responsible manufacturer

Marketing authorization holder

Eugia Pharma (Malta) Limited

Vault 14, Level 2, Valletta Waterfront

Floriana, FRN 1914

Malta

Responsible 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

Further information about this medicine can be obtained by contacting the local representative of the marketing authorization holder:

Aurovitas Spain, S.A.U.

Avda. de Burgos, 16-D

28036 Madrid

Spain

Last review date of this leaflet: November 2023

The detailed information about this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/).

This information is intended solely for healthcare professionals:

Doxorubicina Aurovitas 2mg/ml concentrated for perfusion solution EFG

Doxorubicina is a potent cytotoxic agent that should only be prescribed, prepared and administered by professionals who have received training in the safe use of the preparation. For consultation of dosage recommendations and administration, see section4.2 of the Technical Dossier. For manipulation, preparation and disposal of doxorubicina, 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.Women who are pregnant should not be involved in the preparation of this medicine.

3.Personnel responsible for handling doxorubicina should wear protective clothing: glasses, gowns, gloves and disposable masks.

4.All elements used for administration or cleaning, including gloves, should be disposed of in high-risk waste bags for incineration at high temperature (700°C).

5.All cleaning materials should be disposed of as indicated above.

6.Wash your 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 bicarbonate solution. However, do not scrub the skin with a brush. A mild cream may be used to treat transient skin irritation.

2.In case of eye contact, remove the eyelid and wash the affected eyes with plenty of water for at least 15 minutes or with a 9 mg/ml sodium chloride solution (0.9%). Then, seek medical 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

Opened vials:chemical and physical stability 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 storage and use conditions are the responsibility of the user.

Perfusion solutions prepared:chemical and physical stability has been demonstrated after dilution, protected from light until:

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

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

The storage times of the opened vial and the diluted perfusion solution are not additive.

Disposal

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

Nota:

The dosage of doxorubicina S-liposomal and the dosage of doxorubicina (conventional), as in Doxorubicina Aurovitas, are different. The two formulations cannot be interchanged.

Incompatibilities

Doxorubicina should not be mixed with heparin, as a precipitate forms, nor with 5‑fluorouracil, as it may degrade. Prolonged contact with any alkaline solution should be avoided, as the drug will undergo hydrolysis.

Without studies of compatibility, this medicine should not be mixed with other medicines.