FARMORUBICINA 50 mg POWDER FOR INJECTABLE SOLUTION AND FOR INFUSION

Introduction

Package Leaflet: Information for the Patient

Farmorubicina 50 mg Powder for Solution for Injection and Infusion

Epirubicin 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.

• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Package Leaflet

1. What is Farmorubicina 50 mg Powder and what is it used for
2. What you need to know before you start using Farmorubicina 50 mg Powder
3. How to use Farmorubicina 50 mg Powder
4. Possible side effects
   1. Storage of Farmorubicina 50 mg Powder

1. Contents of the pack and further information

1. What is Farmorubicina 50 mg Powder and what is it used for

Farmorubicina is an anticancer antibiotic medicine belonging to the anthracycline group, used to treat different types of cancer, administered intravenously (in a vein) or intravesically (direct injection into the urinary bladder). Farmorubicina acts in a cytotoxic manner: inhibiting the cell cycle and preventing the proliferation of cancer cells.

Farmorubicina can be used alone or in combination with other medicines, in the treatment of the following types of cancer:

• Breast cancer.
• Soft tissue sarcoma: malignant tumors that can affect cartilage, muscles, fat, blood vessels, or other tissues.
• Stomach cancer.
• Lung cancer of small cells (a special type of lung cancer).
• Advanced ovarian cancer.
• Early (superficial) tumors of the bladder and as a prevention of possible recurrences after surgery.

2. What you need to know before you start using Farmorubicina 50 mg Powder

Do not use Farmorubicina 50 mg Powder:

• If you are allergic to the active substance (epirubicin hydrochloride), to other anticancer agents of the same group (anthracyclines), or to any of the other components of this medicine (listed in section 6).

Do not use Farmorubicina if administration is by intravenous route:

• If you have fewer blood cells than normal, decreased bone marrow activity, altering the ability to fight infections or diseases.
• If you have severe liver problems.
• If you have severe heart problems (severe heart failure, recent myocardial infarction, severe arrhythmias, unstable angina, and cardiomyopathy).
• If you have previously been treated with high doses of epirubicin hydrochloride or other anticancer agents of the same group (anthracyclines). These medicines have similar side effects.
• If you have a severe generalized acute infection.

Do not use Farmorubicina if administration is by intravesical route:

• If you have urinary tract infections, bladder inflammation, or blood in the urine.
• If you have a tumor that has penetrated the bladder wall.
• If you have problems with catheterization (tube in the bladder).

Warnings and precautions

Consult your doctor or pharmacist before starting to use Farmorubicina 50 mg Powder.

• If you have or have had heart problems or if you are receiving or have received radiotherapy in areas close to the heart.
• If you have received treatment with other anthracyclines.
• If you are being treated with other medicines for cancer treatment.
• If you are being treated with other medicines that can suppress heart contraction.
• If your immune system is altered, i.e., you have lost the ability to fight infections or diseases.
• If you have or have had liver problems.
• If you have or have had kidney problems.
• If you have or have had gout, as epirubicin may cause an increase in uric acid.
• If you need to be vaccinated while being treated with this medicine, as live or attenuated vaccines should not be administered, and the response to inactivated or killed vaccines may be diminished.
• If you notice a feeling of discomfort at the injection site or its surroundings during infusion (possible leakage of fluid into the surrounding tissue).
• If you have stomatitis or mucositis (painful lips or ulcers in the mouth).
• If you are pregnant or think you may be pregnant (see section Pregnancy, breastfeeding, and fertility).
• If you are breastfeeding (see section Pregnancy, breastfeeding, and fertility).
• If you are male or female, you should use effective contraceptive methods during treatment with epirubicin, given the toxic potential of the medicine (see section Pregnancy, breastfeeding, and fertility).
• If you are taking or have recently taken trastuzumab (a medicine used to treat certain types of cancer). Trastuzumab can remain in the body for up to 7 months. As trastuzumab can affect the heart, you should not use Farmorubicina until 7 months after stopping trastuzumab. If Farmorubicina is used before this time, then your heart function should be carefully monitored.
• In pregnant women, some reports have linked epirubicin to heart problems in newborns and fetuses, including fetal death.

Using Farmorubicina 50 mg Powder with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

They may increase the side effects or alter the action of other medicines, such as those used to treat heart disorders, cancer, ulcers, and medicines that alter the immune system.

Certain types of vaccines (live and attenuated) should not be administered during treatment with epirubicin.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

You should not use Farmorubicina during pregnancy unless your doctor considers that immediate treatment is of vital importance. Your doctor will inform you of the potential risks of receiving this medicine during pregnancy.

Both men and women should seek advice on fertility preservation before treatment. Women of childbearing age should use effective contraceptive methods during treatment with epirubicin and for at least 6.5 months after the last dose. Men should use effective contraceptive methods during treatment and for at least 3.5 months after the last dose.

Do not breastfeed while being treated with Farmorubicina and for at least 7 days after the last dose.

Farmorubicina may cause loss of menstruation and infertility during treatment.

Driving and using machines

No studies on the effects of Farmorubicina on the ability to drive and use machines have been performed.

It is unknown whether Farmorubicina has any effect on the ability to drive vehicles or operate machinery. However, you should not drive if you experience any adverse event (nausea or vomiting) that may alter your ability to drive vehicles or operate machinery.

Farmorubicina 50 mg Powder contains methyl parahydroxybenzoate

Farmorubicina 50 mg Powder may cause allergic reactions (possibly delayed) and, exceptionally, bronchospasm (sudden feeling of suffocation) because it contains methyl parahydroxybenzoate.

This medicine does not contain sodium. However, it may be prepared with a solution containing sodium. Inform your doctor if you are on a low-salt (sodium) diet.

3. How to use Farmorubicina 50 mg Powder

Farmorubicina 50 mg Powder should only be administered under the supervision of a doctor with experience in the use of this type of treatment. Consult your doctor or pharmacist if you have any doubts.

Your doctor will determine the dose and duration of treatment, as well as the most suitable administration route for you, according to your condition and response to treatment.

Your doctor will indicate the number of treatment cycles you need.

If you use more Farmorubicina than you should

This medicine will be administered in the hospital, so it is unlikely that you will receive more Farmorubicina than you should; however, some of the known serious side effects of the medicine may appear.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount ingested.

4. Possible side effects

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

If you experience side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet.

Very common side effects (may affect more than 1 in 10 people) include:

• Infections,
• Conjunctival inflammation (conjunctivitis).
• Decreased number of red blood cells (anemia) that can make you feel tired or sleepy (lethargy), decreased number of different types of white blood cells (leukopenia, neutropenia, granulocytopenia), febrile neutropenia, decreased number of platelets (thrombocytopenia), which can make you bruise or bleed more easily when injured.
• Corneal inflammation (keratitis).
• Hot flashes
• Venous inflammation (phlebitis).
• Nausea, vomiting, inflammation of the mouth mucosa (stomatitis), inflammation of the mucous membranes of the gastrointestinal tract, diarrhea.
• Hair loss (alopecia), skin toxicity near the area of medicine administration.
• Absence of menstruation (amenorrhea).
• Discomfort, fever.
• Changes in liver enzyme levels (transaminases) indicating possible liver problems.
• Red color in the urine for 1 or 2 days after administration of the medicine, this is normal and should not cause concern.
• Cystitis after administration of the medicine directly into the bladder, in some cases, blood may appear in the urine.

Common side effects (may affect up to 1 in 10 people) include:

• Lack of appetite, dehydration.
• Increased heart rate (ventricular tachycardia), disorders in the conduction of heart impulses (atrioventricular block and bilateral branch block), decreased heart rate (bradycardia), cardiac disorders (congestive heart failure) that can cause difficulty breathing (dyspnea).
• Bleeding, appearance of red color on the skin and mucous membranes (flushing).
• Esophageal inflammation (esophagitis), gastrointestinal pain, gastrointestinal erosion, gastrointestinal ulcer. - Skin rash, itching, abnormal skin and nail pigmentation, skin lesions.
• Frequent need to urinate (pollakiuria).
• Redness of the skin (erythema) at the injection site, chills.
• Pain or burning at the injection site.
• Alteration in heart function tests (decreased ejection fraction).

Uncommon side effects (may affect up to 1 in 100 people) include:

• Generalized infection (sepsis), pneumonia.
• Malignant tumor of blood-forming tissue (different types of leukemia: acute myeloid leukemia and acute lymphocytic leukemia).
• Venous inflammation due to the presence of a blood clot (thrombophlebitis), obstruction of a blood vessel (embolism).
• Obstruction of a pulmonary artery (pulmonary embolism).
• Gastrointestinal tract bleeding.
• Reddish rash and itching on the skin (urticaria), skin redness (erythema).
• Feeling of tiredness (asthenia).

Rare side effects (may affect up to 1 in 1,000 people) include:

• Severe allergic reaction (anaphylactic reaction), local reactions such as a burning sensation in the bladder and may increase the number of times you urinate after intravesical administration.
• Increased uric acid in the blood (hyperuricemia).
• Cardiac toxicity that can cause anomalies in the electrocardiogram.
• Decreased number of sperm in the semen (azoospermia).
• Dizziness.

Side effects of unknown frequency (cannot be estimated from the available data) include:

• Shock caused by a generalized infection (septic shock), pain at the injection site, severe inflammation of the soft tissues under the skin (cellulitis).
• Shock, hardening of the vein in which the injection was performed (phlebosclerosis).
• Lack of oxygen in the tissues as a consequence of decreased bone marrow function (hypoxia).
• Abdominal discomfort, appearance of pigmentation (brown spots) on the oral mucosa.
• Sensitivity to light (photosensitivity).
• Death of the affected tissue (soft tissue necrosis) after an accidental injection outside the vein, pain.
• Increased sensitivity of the irradiated skin (radiation recall reaction).

When the medicine is administered directly into the bladder for the treatment of superficial tumors of the bladder, severe allergic reactions are rare, but local reactions such as a burning sensation in the bladder and increased frequency of urination may occur. Cystitis may also occur. These adverse reactions are usually reversible.

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 them directly through the Spanish Medicines Monitoring System for Human Use: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Farmorubicina 50 mg Powder

No special storage conditions are required.

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

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of the month shown.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Content and Additional Information

Composition of Farmorubicina 50 mg Powder

• The active ingredient is epirubicin hydrochloride.
• The other components (excipients) are: anhydrous lactose and methyl parahydroxybenzoate (E-218).

Appearance of the Product and Container Content

Transparent glass vials with a rubber stopper containing lyophilized powder of a reddish color.

It is presented in a format of 1 vial.

Marketing Authorization Holder

Pfizer, S.L.

Avda. de Europa 20B

Parque Empresarial La Moraleja

28108 Alcobendas (Madrid)

Manufacturer

Latina Pharma S.p.A

Via Murillo, 7

04013 Sermoneta (LT)

Italy

Date of the Last Revision of this Prospectus: March 2023

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

IMPORTANT INFORMATION FOR HEALTHCARE PROFESSIONALS

Reconstitution of the Lyophilized Powder before Administration

Dissolve the Farmorubicina 50 mg powder for injectable and perfusion solution in 25 ml of sterile saline solution or water for injectable preparations, to obtain a final concentration of 2 mg/ml.

To reduce the microbiological risk, it is recommended that reconstitution be performed immediately before use.

The content of the vial is under negative pressure. To minimize the formation of aerosol during reconstitution, particular attention should be paid when inserting the needle. Inhaling the aerosol produced during reconstitution should be avoided.

After reconstitution of the powder, the obtained solution should be used immediately. The unused portion should be discarded.

Intravenous Administration

It is recommended to administer the medication through an intravenous perfusion system (using 0.9% saline solution), after verifying that the needle is well inserted into the vein. To minimize the risk of thrombosis or extravasation of the medication, the usual perfusion times range from 3 to 20 minutes, depending on the dose and volume of the solution to be perfused. Bolus injection is not recommended due to the risk of extravasation, which can occur due to aspiration of the needle (see section 4.4), even in the presence of adequate blood return.

Intravesical Administration

For intravesical administration, the planned dose (in the form of reconstituted solution) should be diluted in sterile saline solution or water for injectable preparations to reach a volume of 50 ml.

The epirubicin solution should be instilled through a catheter, left to act for one hour, after which the patient is asked to empty the bladder. During instillation, the patient should be rotated to ensure greater contact of the solution with the bladder mucosa of the pelvis. To avoid unwanted dilution with urine, the patient should not ingest any liquid in the 12 hours prior to instillation.

Protection Measures

Due to the toxic nature of the compound, the following protection recommendations should be followed:

• Personnel should be instructed in the techniques of reconstitution and handling.
• Pregnant women should avoid handling this medication.
• Personnel handling epirubicin should wear protective clothing: protective glasses, gowns, gloves, and disposable masks.
• Reconstitution should be performed in a designated area (preferably under a laminar flow system). The work surface should be protected with absorbent, plasticized, and disposable paper.
• All material used for reconstitution, administration, or cleaning, including gloves, should be disposed of in high-risk residual material bags for destruction by high-temperature incineration.
• Any spill or leak should be treated with diluted sodium hypochlorite solution (1% available chlorine), preferably by soaking, and then with water.
• All cleaning materials should be discarded as indicated above.
• In case of skin contact, wash the affected area well with water and soap or with sodium bicarbonate solution. In any case, do not rub the skin with a brush.
• In case of eye contact, remove the eyelid(s) and wash the affected eye(s) with a large amount of water for at least 15 minutes. Then, seek medical attention.
• Always wash hands after removing gloves.

The elimination of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.