Farmorubicin

Patient Information Leaflet: Information for the User

FARMORUBICIN 10 mg/5 ml infusion solution, 50 mg/25 ml infusion solution, 200 mg/100 ml infusion solution for intravenous use

Epirubicin hydrochloride
Please read this leaflet carefully before this medicine is administered to you because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4. Contents of this leaflet:
  1. What Farmorubicin is and what it is used for
  2. What you need to know before Farmorubicin is administered
  3. How Farmorubicin is administered
  4. Possible side effects
  5. How to store Farmorubicin
  6. Contents of the pack and other information

1. What Farmorubicin is and what it is used for

Farmorubicin contains the active substance epirubicin hydrochloride, which belongs to a group of
medicines called cytotoxic antibiotics, which act against tumours. Epirubicin works by interfering with
the growth of tumour cells, which are eventually destroyed.
Farmorubicin is used in adults to treat various types of cancer:

• breast cancer;
• malignant lymph node tumours (lymphomas);
• soft tissue tumours (sarcomas);
• stomach and bowel cancer (colorectal);
• liver cancer;
• pancreatic cancer;
• head or neck cancer (cervicofacial region);
• lung cancer;
• ovarian cancer;
• blood cancer (leukaemias).

Farmorubicin 10 mg/5 ml and 50 mg/25 ml is also used directly into the bladder ( intravesical
route ) for the treatment of early-stage (superficial) bladder cancer and to prevent recurrence of bladder
cancer after surgical intervention (transurethral resection).

2. What you should know before Farmorubicin is administered

Farmorubicin must not be administered:

• if you are allergic to epirubicin hydrochloride, to other medicines in the same group (anthracyclines or anthracenediones), or to any of the other components of this medicine (listed in section 6);
• if you are breastfeeding.

Farmorubicin must not be administered intravenously ( intravenous administration ):

• if you have a low number of blood cells (myelosuppression) before starting treatment with this medicine;
• if you have severe liver problems (severe hepatic insufficiency);
• if you have severe heart problems such as heart failure, severe arrhythmia, unstable angina pectoris, or have recently had a heart attack;
• if you have previously been treated for cancer with maximum cumulative doses of this medicine or of other medicines belonging to the anthracycline or anthracenedione group (see section “Other medicines and Farmorubicin”);
• if you currently have a severe infection.

Farmorubicin must not be administered directly into the bladder ( intravesical administration ):

• if you have a urinary tract infection;
• if you have bladder inflammation;
• if you have noticed blood in your urine (hematuria);
• if the cancer has invaded the bladder wall;
• if the doctor has difficulty inserting a catheter into the bladder.

Warnings and precautions
Talk to your doctor or nurse BEFORE Farmorubicin is administered if you think any of the following conditions apply to you:

• you have previously undergone cancer therapy ( cytotoxic therapy ) that may have caused toxicity-related problems such as mouth inflammation and ulcers (stomatitis), reduced numbers of white blood cells, red blood cells, and platelets in the blood, and generalized infections throughout the body. Before starting treatment with Farmorubicin, these toxic effects must have disappeared or significantly diminished;
• you have or have previously had a heart problem. Farmorubicin can cause disturbances in heart function (cardiotoxicity), especially if you have previously had heart problems. Furthermore, the risk of such disturbances increases if you are currently or recently undergoing radiotherapy to the chest area, if you have previously been treated with other anticancer medicines similar to Farmorubicin (called anthracyclines or anthracenediones), or if you are taking other medicines that affect heart function (e.g., trastuzumab), particularly if you are elderly. Trastuzumab (a medicine used to treat certain cancers) may take up to 7 months to be eliminated from the body. Because trastuzumab can affect the heart, Farmorubicin must not be administered until at least 7 months after stopping trastuzumab. If Farmorubicin is administered within this time period, cardiac function must be closely monitored (see section “Other medicines and Farmorubicin”). In pregnant women, there have been reports linking epirubicin to heart problems in newborns and fetuses, including fetal death;
• you have liver and/or kidney problems. In such cases, the toxic effects of Farmorubicin may be greater than expected, and your doctor will prescribe a lower dose of this medicine.

Inform your doctor or nurse if any of the following conditions occur or worsen DURING treatment with Farmorubicin (see also section 4 “Possible side effects”):

• heart problems which may be:

  • acute (occurring immediately after starting treatment): increased or decreased heart rate and disturbances in heart rhythm (arrhythmias). These disturbances are easily detectable by electrocardiogram (ECG) and are usually not severe enough to require discontinuation of treatment;
  • delayed (occurring long after starting treatment, sometimes 2–3 months after initiation, or even months or years after treatment ends). The most common manifestations of delayed toxicity are: inability of the heart to pump sufficient blood to meet the body’s needs (heart failure or congestive heart failure). The most common symptoms include: difficulty breathing (dyspnea), fluid accumulation in the lungs (pulmonary edema), swelling in other parts of the body, especially in the legs and ankles (dependent edema), enlargement of the heart (cardiomegaly) and liver (hepatomegaly), reduced urine output (oliguria), fluid accumulation in the abdomen (ascites) and in the space between the lungs and chest wall (pleural effusion), and abnormal heart rhythm (gallop rhythm). Sometimes, heart failure can be severe and lead to death;

• decrease in the blood of the total number of white blood cells (leukopenia) or of a specific type of white blood cells called neutrophils (neutropenia), or of platelets (thrombocytopenia), or of red blood cells (anemia). Typically, the lowest white blood cell count occurs 10–14 days after starting treatment and returns to normal by day 21. Sometimes, the consequences of reduced blood cells can be serious, including fever, infections in various organs and in the bloodstream, shock, hemorrhage, reduced oxygen supply to the brain, and death;

• development of leukemia (blood cancer) not present before starting treatment with Farmorubicin (secondary leukemia). Leukemia may appear 1–3 years after completing treatment with Farmorubicin and is more likely if this medicine is given at high doses or in combination with other anticancer medicines or radiotherapy;

• vomiting and inflammation of the mouth mucosa (stomatitis). In severe cases, mucosal ulcers may also occur. Typically, these lesions resolve within three weeks of treatment;

• liver problems, as this increases the risk of systemic toxic effects from this medicine. Your doctor will adjust the dose of Farmorubicin based on your condition;

• inflammation of the vein (phlebitis) where repeated injections of Farmorubicin have been given, inflammation and blockage of the vein (thrombophlebitis), or leakage of the medicine from the vein ( extravasation ). If extravasation occurs, local pain, blisters, and skin redness may develop; in more severe cases, necrosis may occur, and administration of Farmorubicin must be immediately stopped. Necrosis may appear several weeks after extravasation. These risks can be avoided by strictly following the instructions for intravenous administration of Farmorubicin (see section 3 “How to administer Farmorubicin”);

• excessive increase in uric acid levels in the blood;

• inflammation and blood clot formation in veins, mainly in the legs and pelvis ( thrombophlebitis ) and in the lungs ( pulmonary embolism ). In some cases, pulmonary embolism may be fatal.

Inform your doctor or nurse if any of the following conditions occur or worsen DURING intravesical administration of Farmorubicin ( intravesical administration ) (see also section 4 “Possible side effects”):

• difficulty urinating (dysuria), frequent passage of small amounts of urine without increased fluid intake (pollakiuria), frequent need to urinate at night (nocturia), painful, slow, and intermittent urination often drop by drop (stranguria), presence of blood in the urine (hematuria), bladder discomfort, necrosis of the inner bladder wall, bladder compression.

During treatment with Farmorubicin, you must not receive vaccinations with live or attenuated vaccines, as serious or even fatal infections may occur due to weakened immune defenses. However, you may receive vaccinations with killed or inactivated vaccines, although the effectiveness of such vaccinations may be reduced.
This medicine may cause irreversible damage that could also affect future children.
Therefore, women of childbearing potential must be informed about the need to use an effective contraceptive method during treatment with epirubicin. If you wish to have children after stopping treatment, consult a specialist doctor; before treatment, both men and women should seek advice on methods to preserve fertility (see section “Pregnancy, Breastfeeding and Fertility”).
Before and during treatment with Farmorubicin, your doctor will perform frequent and regular laboratory tests to assess your condition and the effectiveness of this medicine.

Other medicines and Farmorubicin
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicine.
The following medicines may increase the effectiveness and/or toxic effects of Farmorubicin:

• other anticancer medicines. When Farmorubicin is administered concomitantly with other anticancer drugs, toxic effects on the bone marrow, blood, stomach, intestines, and heart may increase;
• medicines toxic to the heart or medicines to lower blood pressure (called “calcium antagonists”). When Farmorubicin is administered together with these medicines, the risk of heart function disturbances (cardiotoxicity) may increase;
• trastuzumab, a medicine used to treat certain cancers. Trastuzumab may take up to 7 months to be eliminated from the body. Since trastuzumab can affect the heart, Farmorubicin must not be administered until at least 7 months after stopping trastuzumab. If Farmorubicin is administered within this time period, cardiac function must be closely monitored;
• cimetidine (a medicine used to reduce stomach acidity);
• paclitaxel and docetaxel (medicines used for certain types of cancer). If you are to receive treatment with these medicines, they should be administered at least 24 hours after Farmorubicin to reduce adverse effects;
• dexverapamil (a medicine used to treat certain heart conditions);
• quinine (a medicine used to treat malaria);
• interferon α b (a product used for certain cancers, lymphomas, and forms of hepatitis);
• dexrazoxane (a medicine used to treat extravasation of drugs);
• other medicines that affect the bone marrow: sulfonamides and chloramphenicol (antibiotics), phenytoin (a medicine for epilepsy), amidopyrine derivatives (substances used in tests for a bacterium causing gastritis), antiretroviral agents (medicines for HIV infection). During treatment with Farmorubicin, you must not receive live vaccines. However, vaccination with killed or inactivated vaccines is possible (see section “Warnings and precautions”).

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or nurse before receiving this medicine.

Pregnancy
Avoid becoming pregnant while undergoing treatment with Farmorubicin, as this medicine may harm the unborn child (congenital abnormalities). This medicine should not be used during pregnancy unless your doctor considers immediate treatment to be essential.

Breastfeeding
Do not breastfeed during treatment with Farmorubicin and for at least 7 days after the last dose.

Fertility
Farmorubicin may have negative effects on fertility in both men and women. In women, problems such as temporary absence of menstruation (amenorrhea) or permanent cessation (early menopause) may occur. In men, damage to sperm may occur. Moreover, this medicine may cause irreversible infertility in men. Before treatment, both men and women should seek advice on methods to preserve fertility.

Contraception
Women of childbearing potential must use an effective contraceptive method during treatment with epirubicin and for at least 6.5 months after the last dose. Men must use an effective contraceptive method during treatment and for at least 3.5 months after the last dose.

Driving and use of machines
Farmorubicin does not impair the ability to drive or operate machinery.

Farmorubicin contains sodium
Farmorubicin 10 mg/5 ml (2 mg/ml) infusion solution contains 17.7 mg of sodium (the main component of table salt) in each 5 ml vial. This corresponds to 0.9% of the maximum daily dietary intake recommended for an adult.
Farmorubicin 50 mg/25 ml (2 mg/ml) infusion solution contains 88.5 mg of sodium in each 25 ml vial. This corresponds to 4.4% of the maximum daily dietary intake recommended for an adult.
Farmorubicin 200 mg/100 ml (2 mg/ml) infusion solution contains 354 mg of sodium in each 100 ml vial. This corresponds to 17.7% of the maximum daily dietary intake recommended for an adult.
This medicine may be prepared with a solution containing sodium. Inform your doctor if you are on a low-salt (low-sodium) diet.

3. How to administer Farmorubicin

This medicine must be administered to you or your child under the supervision of physicians
experienced in cancer therapy with antineoplastic drugs.
This medicine may only be used in suitable facilities (hospitals, clinics, and healthcare centers)
that ensure immediate and effective treatment of any complications, even severe ones, caused by
the disease or by therapy with Farmorubicin.
If your doctor considers it necessary, they may decide to administer Farmorubicin in combination with
other anticancer medicines. In this case, the recommended doses must be reduced.

Intravenous administration (endovenous):
Farmorubicin as single anticancer medicine
The recommended dose is 60–90 mg/m² of body surface area, administered every 21 days, depending
on your health status.

Treatment of lung cancer
When Farmorubicin is used alone in patients who have not previously received any treatment
for lung cancer, the recommended dose is, depending on the type of tumor:

• 120 mg/m² of body surface area administered on 1 day. Treatment should be repeated every 3 weeks;
• 135 mg/m² of body surface area administered on day 1, or 45 mg/m² administered on days 1, 2, and 3. Treatment should be repeated every 3 weeks.

Treatment of breast cancer
Recommended doses are up to 135 mg/m² of body surface area when Farmorubicin is used alone, and up to 120 mg/m² when treatment includes combination with other medicines, administered every 3–4 weeks.
In adjuvant therapy following surgical removal of early-stage breast cancer with lymph node involvement, recommended doses range from 100 mg/m² to 120 mg/m², administered every 3–4 weeks.
The dose and frequency of administration depend on the type of cancer, your health status, your age, liver function, and other medicines you are taking.

Farmorubicin 10 mg/5 ml and 50 mg/25 ml
Intravesical administration (inside the bladder):
In the treatment of bladder cancer, the recommended dose ranges from 50 to 80 mg per week of Farmorubicin 10 mg/5 ml or 50 mg/25 ml, administered for 8 weeks, depending on the type of tumor and patient tolerance.

For prevention of bladder tumor recurrence, the recommended dose is 50 mg per week, repeated for 4 weeks, followed by monthly administrations of the same dose up to one year.

If too much Farmorubicin has been administered
If you think you have been given more Farmorubicin than you should have, inform your doctor or nurse immediately, as the following may occur:

• reduction in the number of blood cells, particularly a decrease in white blood cells (leukopenia) and in the number of platelets (thrombocytopenia);
• toxic effects on the stomach and intestines;
• serious heart problems (acute cardiac alterations).

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Immediately contact your doctor if you experience any of the following side effects because they are serious:

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

• marked reduction in the production of blood cells in the bone marrow (myelosuppression), which may cause:
  • reduction in the number of red blood cells (anaemia), which may make you feel tired and lethargic
  • reduction in the number of white blood cells (cells that fight infections), which may increase the risk of infections and fever (leucopenia)
  • reduction in the number of certain types of white blood cells - neutrophils and granulocytes (neutropenia and granulocytopenia)
  • reduction in platelets (blood platelets that help blood clotting), which may increase the risk of bruising or bleeding more easily when injured (thrombocytopenia)
  • reduction in certain types of white blood cells - neutrophils - accompanied by fever (febrile neutropenia)
• inflammation of the veins (phlebitis)

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

• reduced heart function (heart failure) (see section 2 “Warnings and precautions”). Heart problems may manifest as difficulty in breathing (dyspnoea), swelling in various parts of the body due to fluid accumulation, especially in the feet, ankles, legs and arms, liver enlargement, fluid accumulation and swelling in the abdomen (ascites), fluid accumulation between the lung and chest wall (pleural effusion)
• severe disturbance of heart rhythm (ventricular arrhythmia)
• certain types of heart rhythm disturbances (atrioventricular block, bundle branch block)
• slow heart rate (bradycardia)
• bleeding from blood vessels (haemorrhage)
• pain or burning in the gastrointestinal tract
• gastrointestinal tract ulcers
• inflammation of the mucosa of the gastrointestinal tract

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

• high fever, chills, general malaise, possible sensation of cold arms and legs due to blood infections
• certain types of blood cell cancers (acute lymphocytic leukaemia, acute myeloid leukaemia) (see section 2 “Warnings and precautions”)
• blockage of a vein by a blood clot (embolism), which may break loose and travel via the bloodstream to the lungs, causing pain and shortness of breath (pulmonary embolism)
• blockage of an artery (arterial embolism)
• swelling and pain in the arms or legs due to inflammation of a blood vessel where repeated injections of the medicine have been administered (see section 2 “Warnings and precautions”), or vessel occlusion caused by a blood clot
• bleeding from the gastrointestinal tract (gastrointestinal haemorrhage)

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

• absence of spermatozoa in semen
• allergic reactions following administration of Farmorubicin directly into the bladder
• severe allergic reaction (anaphylaxis, anaphylactic shock, anaphylactoid reaction)

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

• life-threatening condition in which blood pressure is too low (shock)
• abdominal disorder
• septic shock
• lack of oxygen to tissues
• tissue death (tissue necrosis) following leakage of the medicine from the vein where the needle was inserted. In this case, administration of Farmorubicin will be immediately stopped (see section 2 “Warnings and precautions”)

The following side effects may also occur:
Very common (may affect more than 1 in 10 people):

• eye inflammation, red eyes and watery eyes (conjunctivitis)
• infections
• inflammation of the transparent part of the eye called the cornea (keratitis)
• hot flushes
• nausea
• vomiting
• diarrhoea
• inflammation of the mucosa of the mouth (stomatitis)
• painful inflammation and ulceration of the mucous membranes lining the digestive tract
• hair loss (alopecia)
• skin lesions
• absence of menstruation (amenorrhoea)
• malaise
• fever
• changes in levels of certain liver enzymes (transaminases)
• inflammation of the bladder (chemical cystitis) following intravesical administration. Symptoms may include: difficulty urinating (dysuria), frequent passage of small amounts of urine without concurrent fluid intake (pollakiuria), frequent need to urinate during the night (nocturia), painful, slow and intermittent urination, often drop by drop (stranguria), presence of blood in the urine (haematuria), bladder discomfort, necrosis of the inner bladder wall (see section 2 “Warnings and precautions”)
• reddish discoloration of the urine (for 1 or 2 days after administration of Farmorubicin)

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

• reduced appetite
• loss of water or fluids from the body (dehydration)
• inflammation of the mucosa of the oesophagus (oesophagitis)
• skin redness (flushing)
• skin rash, itching, skin disorders, darkening of the skin and nails (hyperpigmentation)
• irritation at the injection site
• chills
• reduction in the amount of blood pumped by the heart into the body (left ventricular ejection fraction)
• burning sensation following administration of Farmorubicin directly into the bladder
• increased need to urinate more frequently than normal following administration of Farmorubicin directly into the bladder

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

• lung infection (pneumonia)
• urticaria
• erythema
• muscle weakness (asthenia)

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

• dizziness
• abnormalities in the electrocardiogram (ECG) due to disturbances in heart function
• increased levels of uric acid in the blood (hyperuricaemia)

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

• lesions of the mucous membranes of the mouth, pain and burning sensation in the mucous membranes, bleeding from the mouth and appearance of dark spots inside the mouth
• skin redness or other skin reactions similar to sunburn when exposed to sunlight or ultraviolet rays (e.g., in a tanning bed)
• increased sensitivity of skin previously treated with radiotherapy
• pain at the injection site
• cellulitis
• thickening of the walls of blood vessels (phlebosclerosis)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system at 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 Farmorubicina

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial after "Exp.". The expiry date refers to the last day of that month.
Store in a refrigerator (2°C-8°C).
Do not dispose of any medicine via wastewater or household waste. Healthcare professionals know how to safely dispose of unused medicines. This will help protect the environment.

6. Package contents and other information

What Farmorubicin 10 mg/5 ml infusion solution contains

• The active substance is epirubicin hydrochloride. Each vial contains 10 mg of epirubicin hydrochloride.
• The other components are: sodium chloride, water for injections, hydrochloric acid (for pH adjustment).

What Farmorubicin 50 mg/25 ml infusion solution contains

• The active substance is epirubicin hydrochloride. Each vial contains 50 mg of epirubicin hydrochloride.
• The other components are: sodium chloride, water for injections, hydrochloric acid (for pH adjustment).

What Farmorubicin 200 mg/100 ml solution for intravenous infusion contains

• The active substance is epirubicin hydrochloride. Each vial contains 200 mg of epirubicin hydrochloride.
• The other components are: sodium chloride, water for injections, hydrochloric acid (for pH adjustment).

Description of the appearance of Farmorubicin and contents of the pack

Farmorubicin 10 mg/5 ml and 50 mg/25 ml infusion solution is available in a pack containing 1
vial in glass with a rubber stopper and an aluminum and plastic seal. Each vial is packaged in a transparent plastic pouch (Onco-tain).
Farmorubicin 200 mg/100 ml solution for intravenous infusion is available in a pack containing 1
vial in glass with a rubber stopper and an aluminum and plastic seal. Each vial is packaged in a transparent plastic pouch (Onco-tain).

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder
Pfizer Italia S.r.l.
Via Isonzo, 71
04100 Latina
Italy

Manufacturer
Pfizer Service Company BV
Hermeslaan 11
1932 Zaventem
Belgium

The following information is intended exclusively for physicians or healthcare professionals

Incompatibility
Farmorubicin must not be mixed with heparin due to chemical incompatibility, which, in certain proportions, may lead to the formation of a precipitate.

Dosage
For intravenous administration
Conventional dosage regimen
When Farmorubicin is used as a single antineoplastic agent, the recommended dose in adults is 60–90 mg/m² body surface area, administered by intravenous injection over 5–10 minutes at 21-day intervals, depending on hematopoietic status.

High-dose dosage regimen
Lung carcinoma
Farmorubicin, as a single agent in high-dose treatment of lung carcinoma, should be administered according to the following regimens:

• small cell lung carcinoma in previously untreated patients: 120 mg/m² on day 1, every 3 weeks;
• non-small cell lung carcinoma (epidermoid, squamous, and adenocarcinoma) in previously untreated patients: 135 mg/m² on day 1 or 45 mg/m² on days 1, 2, 3, every three weeks.

Breast carcinoma
Doses up to 135 mg/m², when used as a single agent, and up to 120 mg/m² when used in combination, administered every 3–4 weeks, have proven effective and well tolerated in patients with breast carcinoma. In the adjuvant treatment of early-stage breast cancer with positive lymph nodes, recommended doses range from 100 mg/m² to 120 mg/m², administered every 3–4 weeks. The drug should be administered either as an intravenous bolus over 5–10 minutes or as an intravenous infusion over a maximum of 30 minutes.

Lower doses (60–75 mg/m² or 105–120 mg/m² in high-dose regimens) are recommended for patients with reduced bone marrow reserve due to prior chemotherapy and/or radiotherapy, advanced age, or bone marrow infiltration by tumor.
The total dose per cycle may be divided over 2–3 consecutive days.
When used in combination with other antineoplastic agents, doses should be appropriately reduced.
Since the main route of elimination of the drug is the hepatobiliary system, dose reduction of Farmorubicin is recommended in patients with impaired liver function to avoid increased overall toxicity.
In general, when serum bilirubin levels range between 1.4–3 mg/100 ml and bromsulfalein (BSP) retention is 9–15%, it is recommended to administer half the normal dose.
If bilirubin levels and BSP retention are even higher, one-quarter of the normal dose is recommended.
Mild impairment of renal function does not appear to be a reason for modifying the recommended doses, given the low renal excretion of Farmorubicin.

FARMORUBICIN 10 mg/5 ml and 50 mg/25 ml
Intravesical administration
For the treatment of transitional cell papillary carcinomas, weekly instillations of 50 mg (in 25–50 ml of physiological saline solution) are recommended, repeated for 8 weeks; in case of local toxicity (chemical cystitis), the single dose should be reduced to 30 mg. For the treatment of carcinoma in situ, the dose may be increased to 80 mg, depending on individual tolerance.
For the prevention of recurrences following transurethral resection of superficial tumors, weekly instillations of 50 mg are recommended for 4 weeks, followed by monthly instillations of the same dose for up to one year.

Method of administration
Farmorubicin is not active orally and must not be administered by intramuscular or intrathecal routes.

Intravenous administration
Intravenous administration should be performed over 5–10 minutes through the tubing of an ongoing physiological saline infusion, after confirming that the needle is properly positioned within the vein. This technique reduces the risk of drug extravasation and ensures adequate flushing of the vein at the end of administration.
If Farmorubicin leaks out of the vein during administration, tissue damage up to necrosis may occur.
Phlebosclerosis may occur when the injection is administered into small veins or repeatedly into the same vein.

FARMORUBICIN 10 mg/5 ml and 50 mg/25 ml
Intravesical administration
The Farmorubicin solution, administered via catheter, should be retained in the bladder for one hour, after which the patient should be instructed to empty the bladder. During instillation, it may be appropriate to rotate the patient’s pelvis to ensure broader contact of the solution with the bladder mucosa.

Special precautions for disposal and handling
The following safety measures, applicable to all antineoplastic agents, are recommended:

• personnel should be trained in proper handling techniques;
• pregnant personnel must be excluded from such tasks;
• personnel handling the drug should wear protective clothing: goggles, gowns, masks, and disposable gloves;
• all items used for administration and cleaning, including gloves, should be placed in disposable high-risk waste bags for high-temperature incineration;
• in case of accidental contact of the drug with skin or eyes, immediately wash the skin thoroughly with soap and water and the eyes with a sodium bicarbonate solution. Monitor the patient closely with specialist follow-up;
• in case of accidental contamination of objects with the drug, immerse them in a 1% hypochlorite solution, then rinse thoroughly with water;
• cleaning materials must be disposed of as described above. Unused medicine and waste materials derived from this medicine must be disposed of in accordance with applicable local regulations.
  For further information, refer to the Summary of Product Characteristics.

Patient Information Leaflet: Information for the User

FARMORUBICIN 10 mg/5 ml powder and solvent for solution for infusion, 50 mg powder for solution for infusion

Epirubicin hydrochloride
Please read this leaflet carefully before this medicine is administered to you because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4. Contents of this leaflet:
  1. What Farmorubicin is and what it is used for
  2. What you need to know before being given Farmorubicin
  3. How Farmorubicin is administered
  4. Possible side effects
  5. How to store Farmorubicin
  6. Contents of the pack and other information

1. What Farmorubicin is and what it is used for

Farmorubicin contains the active substance epirubicin hydrochloride, which belongs to a group of
medicines called cytotoxic antibiotics, which act against tumours. Epirubicin works by interfering
with the growth of tumour cells, which are eventually destroyed.
Farmorubicin is used in adults to treat various types of cancer:

• breast cancer;
• malignant tumours of the lymph nodes (lymphomas);
• tumours of soft tissues (sarcomas);
  • stomach and intestinal cancer (colorectal);
• liver cancer;
• pancreatic cancer;
• head or neck cancer (cervicofacial region);
• lung cancer;
• ovarian cancer;
• blood cancer (leukaemias).

Farmorubicin is also used directly into the bladder ( intravesical route ) for the treatment of
early-stage (superficial) bladder cancer and to prevent recurrences of bladder cancer
after surgery (transurethral resection).

2. What you should know before Farmorubicin is administered

Farmorubicin must not be administered:

• if you are allergic to epirubicin hydrochloride, to other medicines in the same group (anthracyclines or anthracenediones), or to any of the other ingredients of this medicine (listed in section 6);
• if you are breastfeeding.

Farmorubicin must not be administered intravenously ( intravenous administration ):

• if you have a low number of blood cells (myelosuppression) prior to starting treatment with this medicine;
• if you suffer from severe liver problems (severe hepatic insufficiency);
• if you suffer from serious heart problems such as heart failure, severe arrhythmia, unstable angina pectoris, or have recently had a heart attack;
• if you have previously been treated with maximum cumulative doses of this medicine or of other medicines belonging to the anthracycline or anthracenedione group (see section “Other medicines and Farmorubicin”);
• if you currently have a severe infection.

Farmorubicin must not be administered directly into the bladder ( intravesical administration ):

• if you have a urinary tract infection;
• if you have bladder inflammation;
• if you have noticed blood in your urine (haematuria);
• if the cancer has penetrated the bladder wall;
• if the doctor has difficulty inserting a catheter into the bladder.

Warnings and precautions
Talk to your doctor or nurse BEFORE Farmorubicin is administered if you think any of the following conditions apply to you:

• you have undergone cancer therapy ( cytotoxic therapy ) that may have caused toxic effects such as mouth inflammation and ulcers (stomatitis), reduced numbers of white blood cells, red blood cells and platelets in the blood, and generalized infections in various parts of the body. Before starting treatment with Farmorubicin, these toxic effects must have disappeared or significantly diminished;
• you suffer or have previously suffered from a heart problem . Farmorubicin may cause disturbances in heart function (cardiotoxicity), especially if you have previously had heart disorders. Moreover, the risk of such disturbances increases if you are currently undergoing or have recently undergone radiotherapy to the chest area, if you have been treated with other anticancer medicines similar to Farmorubicin (called anthracyclines or anthracenediones), or if you are taking other medicines that affect heart function (e.g. trastuzumab), particularly if you are elderly. Trastuzumab (a medicine used in the treatment of certain cancers) may take up to 7 months to be eliminated from the body. Since trastuzumab may affect the heart, Farmorubicin must not be administered until 7 months after stopping trastuzumab. If Farmorubicin is administered within this time interval, heart function must be closely monitored (see section “Other medicines and Farmorubicin”). There have been reports in pregnant women indicating that epirubicin has been associated with heart problems in newborns and fetuses, including fetal death;
• you have liver and/or kidney problems. In this case, the toxic effects of Farmorubicin may be greater than expected, and your doctor will prescribe a lower dose of this medicine.

Inform your doctor or nurse if any of the following conditions appear or worsen DURING treatment with Farmorubicin (see also section 4 “Possible side effects”):

• heart problems which may be:

  • acute (occurring immediately after the start of treatment): increased or decreased heart rate and disturbances in heartbeat rhythm (arrhythmias). These disorders are easily detectable by electrocardiogram (ECG) and are usually not serious enough to require discontinuation of treatment with this medicine;
  • delayed (occurring long after the start of treatment, sometimes 2-3 months after initiation, or even months or years after treatment ends). The most common manifestations of delayed toxicity are:
    • inability of the heart to supply adequate blood flow to meet the body's demands (heart failure or cardiac insufficiency). The most common symptoms are: difficulty breathing (dyspnoea), fluid accumulation in the lungs (pulmonary oedema), swelling in other parts of the body, especially in the legs and ankles (dependent oedema), enlargement of the heart (cardiomegaly) and liver (hepatomegaly), reduced urine production (oliguria), fluid accumulation in the abdomen (ascites) and in the space between the lungs and chest wall (pleural effusion), and irregular heartbeat (gallop rhythm). Sometimes, heart failure can be severe and lead to death;

• decrease in the blood of the total number of white blood cells (leucopenia) or of a type of white blood cells called neutrophils (neutropenia), or of platelets (thrombocytopenia), or of red blood cells (anaemia). Typically, the decrease in white blood cells is maximal 10-14 days after starting treatment and returns to normal by day 21. Sometimes, the consequences of this decrease in blood cells can be serious, including fever, infections in various organs and in the blood, shock, bleeding, reduced oxygen supply to the brain, and death;

• development of blood cancer ( leukaemia ) not present before starting treatment with Farmorubicin (secondary leukaemia). Leukaemia may appear 1-3 years after completing treatment with Farmorubicin and is more likely to occur if this medicine is administered at high doses or in combination with other anticancer medicines or radiotherapy;

• vomiting and inflammation of the mouth mucosa (stomatitis). In severe cases, mucosal ulcers may also occur. Typically, these lesions resolve within the third week of treatment;

• liver problems , as this increases the risk of systemic toxic manifestations from this medicine. Your doctor will adjust the dosage of Farmorubicin according to your condition;

• inflammation of the vein (phlebitis) where repeated injections of Farmorubicin have been administered, inflammation and blockage of the vein (thrombophlebitis), leakage of the medicine from the vein where the needle was inserted ( extravasation ). In case of extravasation, local pain, blisters, redness of the skin may occur, and in more severe cases, necrosis; therefore, administration of Farmorubicin must be immediately stopped . Necrosis may appear several weeks after extravasation. These risks can be avoided by strictly following the instructions for intravenous administration of Farmorubicin (see section 3 “How to administer Farmorubicin”);

• excessive increase in the amount of uric acid in the blood;

• inflammation and formation of blood clots in veins, mainly in the legs and pelvis ( thrombophlebitis ) and in the lungs ( pulmonary embolism ). In some cases, pulmonary embolism may lead to death.

Inform your doctor or nurse if any of the following conditions appear or worsen DURING administration of Farmorubicin directly into the bladder ( intravesical administration ) (see also section 4 “Possible side effects”):

• difficulty urinating (dysuria), frequent production of small amounts of urine without concurrent fluid intake (pollakiuria), frequent need to urinate at night (nocturia), painful, slow and intermittent urination, often drop by drop (stranguria), presence of blood in the urine (haematuria), bladder discomfort, necrosis of the inner bladder wall, bladder compression.

During treatment with Farmorubicin, you must not receive vaccination with vaccines called “live” or “attenuated” , because, due to low immune defences, severe or fatal infections may occur. However, you may receive vaccination with vaccines called “killed” or “inactivated”, although the effectiveness of such vaccination may be reduced.
This medicine may cause irreversible damage that could also affect future children.
Therefore, women of childbearing potential must be informed about the need to use an effective contraceptive method during treatment with epirubicin. If you wish to have children after stopping treatment, consult a specialist doctor; before treatment, both men and women should seek advice on methods to preserve fertility (see section “Pregnancy, Breastfeeding and Fertility”).
Before and during treatment with Farmorubicin, your doctor will perform frequent and regular laboratory tests to assess your condition and the effectiveness of this medicine.

Other medicines and Farmorubicin
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicines.
The following medicines may increase the effectiveness and/or toxic effects of Farmorubicin:

• other anticancer medicines . When Farmorubicin is administered concomitantly with other anticancer medicines, toxic effects on the bone marrow, blood, stomach and intestine, and heart may increase;
• medicines toxic to the heart or medicines used to lower blood pressure (called “calcium antagonists”). When Farmorubicin is administered concomitantly with these medicines, the risk of disturbances in heart function (cardiotoxicity) may increase;
• trastuzumab , a medicine used to treat certain cancers. Trastuzumab may take up to 7 months to be eliminated from the body. Since trastuzumab may affect the heart, Farmorubicin must not be administered until 7 months after stopping trastuzumab. If Farmorubicin is administered within this time interval, heart function must be closely monitored;
• cimetidine (a medicine to reduce stomach acidity);
• paclitaxel and docetaxel (medicines used for certain types of cancer). If you are to receive treatment with these medicines, they should be administered at least 24 hours after Farmorubicin to reduce undesirable effects;
• dexverapamil (a medicine used to treat certain heart disorders);
• quinine (a medicine used against malaria);
• interferon α b (a medicine used for certain cancers and lymphomas and for certain forms of hepatitis);
• dexrazoxane (used to treat extravasation of medicines);
• other medicines acting on the bone marrow: sulfonamides and chloramphenicol (antibiotics), phenytoin (a medicine for epilepsy), amidopyrine derivatives (substances used in tests for detecting a bacterium causing gastritis), antiretroviral agents (medicines against HIV infection). During treatment with Farmorubicin, you must not receive vaccination with live vaccines. Vaccination with killed or inactivated vaccines is possible (see section “Warnings and precautions”).

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or nurse before this medicine is administered.
Pregnancy
Avoid becoming pregnant while being treated with Farmorubicin, as this medicine may harm the unborn child (congenital abnormalities). This medicine must not be used during pregnancy unless your doctor considers immediate treatment to be essential.
Breastfeeding
Do not breastfeed during treatment with Farmorubicin and for at least 7 days after the last dose.
Fertility
Farmorubicin may have negative effects on fertility in both men and women. In women, problems such as temporary absence of menstruation (amenorrhoea) or permanent absence (premature menopause) may occur. In men, damage to spermatozoa may occur. Furthermore, this medicine may cause irreversible infertility in men. Before treatment, both men and women should seek advice on methods to preserve fertility.

Contraception
Women of childbearing potential must use an effective contraceptive method during treatment with epirubicin and for at least 6 and a half months after the last dose. Men must use an effective contraceptive method during treatment and for at least 3 and a half months after the last dose.

Driving and using machines
Farmorubicin does not affect the ability to drive vehicles or operate machinery.

Farmorubicin contains methyl para-hydroxybenzoate
Farmorubicin contains methyl para-hydroxybenzoate. It may cause allergic reactions (including delayed reactions) and, exceptionally, bronchospasm.

Farmorubicin 10 mg/5 ml powder and solvent for solution for infusion contains 17.7 mg of sodium (main component of table salt) in each vial. This corresponds to 0.9% of the maximum daily recommended dietary intake for an adult.

This medicine may be prepared with a solution containing sodium. Inform your doctor if you are on a low-salt (sodium) diet.

3. How to Administer Farmorubicin

This medicine must be administered to you or your child under the supervision of physicians
experienced in cancer therapy with antineoplastic drugs.
This medicine may only be used in suitable facilities (hospitals, clinics, and medical centers)
that ensure immediate and effective treatment of any complications, even severe ones, caused
by the disease or by therapy with Farmorubicin.
If your doctor considers it necessary, they may decide to administer Farmorubicin in combination with
other anticancer medicines. In this case, the recommended doses must be reduced.

Intravenous administration (endovenous):
Farmorubicin as a single anticancer medicine
The recommended dose is 60–90 mg/m² of body surface area, administered every 21 days, depending
on your health status.

Lung cancer treatment
When Farmorubicin is used alone in patients who have not previously received any treatment for lung cancer, the recommended dose, depending on the type of tumor, is:

• 120 mg/m² of body surface area administered on 1 day. Treatment should be repeated every 3 weeks;
• 135 mg/m² of body surface area administered on day 1, or 45 mg/m² of body surface area administered on days 1, 2, and 3. Treatment should be repeated every 3 weeks.

Breast cancer treatment
The recommended doses are up to 135 mg/m² of body surface area when Farmorubicin is used alone, and up to 120 mg/m² of body surface area when treatment includes combination with other medicines, administered every 3–4 weeks. In adjuvant therapy following surgical removal of early-stage breast cancer with lymph node involvement, the recommended doses range from 100 mg/m² to 120 mg/m², administered every 3–4 weeks. The dose and frequency of administration depend on the type of cancer, your health status, your age, liver function, and other medicines you are taking.

Intravesical administration (into the bladder):
For the treatment of bladder cancer, the recommended dose ranges from 50 to 80 mg weekly for 8 weeks, depending on the type of tumor and patient tolerance. For prevention of recurrence of bladder tumors, the recommended dose is 50 mg weekly for 4 weeks, followed by monthly administrations of the same dose for up to 1 year.

If too much Farmorubicin has been administered
If you think you have been given more Farmorubicin than you should have, inform your doctor or nurse immediately, as the following may occur:

• reduction in blood cells, particularly a decrease in white blood cells (leukopenia) and in platelets (thrombocytopenia);
• toxic effects on the stomach and intestines;
• severe heart problems (acute cardiac alterations).

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
Contact your doctor immediately if you experience any of the following side effects because they are serious:

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

• marked reduction in the production of blood cells in the bone marrow (myelosuppression which may cause):
  • reduction in the number of red blood cells (anaemia), which may make you feel tired and lethargic
  • reduction in the number of white blood cells (cells that fight infections), which may increase the risk of infections and fever (leucopenia)
  • reduction in certain types of white blood cells – neutrophils and granulocytes (neutropenia and granulocytopenia)
  • reduction in platelets (blood platelets that help blood clotting), which may lead to bruising or bleeding more easily when injured (thrombocytopenia)
  • reduction in certain types of white blood cells – neutrophils – accompanied by fever (febrile neutropenia)
• inflammation of the veins (phlebitis)

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

• reduced heart function (heart failure) (see section 2 “Warnings and precautions”). Heart problems may present as difficulty in breathing (dyspnoea), swelling in various parts of the body due to fluid accumulation, especially in the feet, ankles, legs and arms, liver enlargement, fluid accumulation and swelling in the abdomen (ascites), fluid accumulation in the space between the lung and chest wall (pleural effusion)
• severe disturbance in heart rhythm (ventricular arrhythmia)
• certain types of heart rhythm disturbances (atrioventricular block, bundle branch block)
• slow heart rate (bradycardia)
• bleeding from blood vessels (haemorrhage)
• pain or burning in the gastrointestinal tract
• ulcers in the gastrointestinal tract
• inflammation of the mucosa of the gastrointestinal tract

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

• high fever, chills, general malaise, possible sensation of cold arms and legs due to blood infections
• certain types of blood cell cancers (acute lymphocytic leukaemia, acute myeloid leukaemia) (see section 2 “Warnings and precautions”)
• blockage of a vein by a blood clot (embolism) that may break loose and travel through the bloodstream to the lungs, causing chest pain and shortness of breath (pulmonary embolism)
• blockage of an artery (arterial embolism)
• swelling and pain in the arms or legs due to inflammation of a blood vessel where repeated injections of the medicine have been administered (see section 2 “Warnings and precautions”), or vessel occlusion caused by a blood clot
• bleeding from the gastrointestinal tract (gastrointestinal haemorrhage)

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

• absence of sperm in semen
• allergic reactions following administration of Farmorubicin into the bladder
• severe allergic reaction (anaphylaxis, anaphylactic shock, anaphylactoid reaction)

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

• life-threatening condition in which blood pressure is too low (shock)
• abdominal disorder
• septic shock
• lack of oxygen to tissues
• tissue death (tissue necrosis) following leakage of the medicine from the vein where the needle was inserted. In this case, administration of Farmorubicin will be immediately stopped (see section 2 “Warnings and precautions”)

The following side effects may also occur:

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

• eye inflammation, red eyes and watery eyes (conjunctivitis)
• infections
• inflammation of the transparent part of the eye called the cornea (keratitis)
• hot flushes
• nausea
• vomiting
• diarrhoea
• inflammation of the mucous membrane of the mouth (stomatitis)
• painful inflammation and ulceration of the mucous membranes lining the digestive tract
• hair loss (alopecia)
• skin lesions
• absence of menstruation (amenorrhoea)
• malaise
• fever
• changes in levels of certain liver enzymes (transaminases)
• inflammation of the bladder (chemical cystitis) following intravesical administration. Symptoms may include: difficulty urinating (dysuria), frequent passage of small amounts of urine without concurrent fluid intake (pollakiuria), frequent need to urinate during the night (nocturia), painful, slow and interrupted urination, often drop by drop (stranguria), presence of blood in the urine (haematuria), bladder discomfort, necrosis of the inner bladder wall (see section 2 “Warnings and precautions”)
• reddish discoloration of the urine (for 1 or 2 days after administration of Farmorubicin)

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

• reduced appetite
• loss of water or fluids from the body (dehydration)
• inflammation of the oesophageal mucosa (oesophagitis)
• skin redness (flushing)
• skin rash, itching, skin disorders, darkening of the skin and nails (hyperpigmentation)
• irritation at the injection site
• chills
• decrease in the amount of blood pumped by the heart into the body (left ventricular ejection fraction)
• burning sensation following administration of Farmorubicin directly into the bladder
• increased need to urinate more frequently than normal following administration of Farmorubicin directly into the bladder

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

• lung infection (pneumonia)
• urticaria
• erythema
• muscle weakness (asthenia)

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

• dizziness
• abnormalities in the electrocardiogram (ECG) due to disturbances in heart function
• increased levels of uric acid in the blood (hyperuricaemia)

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

• damage to the mouth mucosa, pain and burning sensation in the mucosa, bleeding from the mouth and appearance of dark spots inside the mouth
• redness or other skin reactions resembling sunburn when exposed to sunlight or ultraviolet rays (e.g., in a solarium)
• increased sensitivity of skin previously treated with radiotherapy
• pain at the injection site
• cellulitis
• thickening of blood vessel walls (phlebosclerosis)

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse.
You can also report side effects directly via the national reporting system at 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 Farmorubicina

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton, vial, and bottle after "Exp.". The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
The reconstituted solution must be used immediately.
Do not dispose of medicines via wastewater or household waste. Healthcare professionals know how to dispose of unused medicines properly. This will help protect the environment.

6. Package contents and other information

What Farmorubicina 10 mg/5 ml powder and solvent for solution for infusion contains

• The active substance is epirubicin hydrochloride. Each vial contains 10 mg of epirubicin hydrochloride.
• The other components are: methyl parahydroxybenzoate and lactose. The solvent vial contains saline solution.

What Farmorubicina 50 mg powder for solution for infusion contains

• The active substance is epirubicin hydrochloride. Each vial contains 50 mg of epirubicin hydrochloride.
• The other components are: methyl parahydroxybenzoate and lactose.

Description of the appearance of Farmorubicina and contents of the pack
Farmorubicina 10 mg/5 ml powder and solvent for solution for infusion is available in a pack containing 1 glass vial of 10 mg with rubber stopper and aluminium seal + 1 solvent ampoule of 5 ml.
Farmorubicina 50 mg powder for solution for infusion is available in a pack containing 1 glass vial of 50 mg with rubber stopper and aluminium seal.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Pfizer Italia S.r.l.
Via Isonzo, 71
04100 Latina
Manufacturer
Latina Pharma S.p.A.
Via Murillo, 7
04013 Sermoneta (LT)
Italy

The following information is intended exclusively for physicians or healthcare professionals

Reconstitution information:
From a chemical and physical standpoint, the reconstituted solution is chemically stable for 24 hours if stored at room temperature and for 48 hours if stored at 2°C/8°C.
From a microbiological standpoint, the reconstituted solution should be used immediately. If not used immediately, the times and conditions of use are under the responsibility of the user and should normally not exceed 24 hours at a temperature between 2°C and 8°C, unless reconstitution has taken place under controlled, validated aseptic conditions.

Incompatibilities
Farmorubicin must not be mixed with heparin due to chemical incompatibility, which in certain proportions may lead to the formation of a precipitate.

Dosage
Intravenous administration
Conventional dosing regimen
When Farmorubicin is used as a single antineoplastic agent, the recommended dose in adults is 60–90 mg/m² of body surface area, administered by intravenous injection over 5–10 minutes every 21 days, according to hematological conditions.

High-dose regimen
Lung carcinoma
Farmorubicin as a single agent in high-dose treatment of lung carcinoma should be administered according to the following regimens:

• small cell lung carcinoma in untreated patients: 120 mg/m² on day 1, every 3 weeks;
• non-small cell lung carcinoma (epidermoid, squamous, and adenocarcinoma) in untreated patients: 135 mg/m² on day 1 or 45 mg/m² on days 1, 2, and 3, every three weeks.

Breast carcinoma
Doses up to 135 mg/m², when used as a single agent, and up to 120 mg/m² when used in combination, administered every 3–4 weeks, have proven effective and well tolerated in patients with breast carcinoma. In the adjuvant treatment of early-stage breast cancer with positive lymph nodes, recommended doses range from 100 mg/m² to 120 mg/m² administered every 3–4 weeks. The drug should be administered as an intravenous bolus over 5–10 minutes or as an intravenous infusion over a maximum of 30 minutes. Lower doses (60–75 mg/m² or 105–120 mg/m² in high-dose regimens) are recommended for patients with reduced bone marrow reserve due to prior chemotherapy and/or radiotherapy, advanced age, or bone marrow neoplastic infiltration. The total dose per cycle may be divided over 2–3 consecutive days. When used in combination with other antineoplastic agents, doses should be appropriately reduced.

Since the main route of elimination of the drug is hepatobiliary, it is advisable to reduce the dose of Farmorubicin in patients with impaired liver function to avoid increased overall toxicity.
In general, when serum bilirubin levels range between 1.4–3 mg/100 ml and bromosulfophthalein (BSP) retention is 9–15%, it is recommended to administer half the normal dose.
If bilirubin levels and BSP retention are even higher, one-quarter of the normal dose is recommended.
Mild to moderate impairment of renal function does not appear to require dose adjustment, given the low renal excretion of Farmorubicin.

Intravesical administration
For the treatment of transitional cell papillary carcinomas, weekly instillations of 50 mg repeated for 8 weeks are recommended; in case of local toxicity (chemical cystitis), the single dose should be reduced to 30 mg. In the treatment of carcinoma in situ, the dose may be increased to 80 mg according to individual tolerance.
For prophylaxis of recurrences following transurethral resection of superficial tumors, weekly instillations of 50 mg for 4 weeks, followed by monthly instillations of the same dose for up to one year, are recommended.

Method of administration
Farmorubicin is not active orally and must not be administered by intramuscular or intrathecal routes.

Intravenous administration
Intravenous administration should be performed over 5–10 minutes through the tubing of an ongoing physiological saline infusion, after ensuring that the needle is properly positioned within the vein. This technique reduces the risk of drug extravasation and ensures adequate vein flushing at the end of administration.
If Farmorubicin leaks out of the vein during administration, tissue damage up to necrosis may occur.
Phlebitis or venous sclerosis may occur when the injection is performed into small vessels or repeatedly into the same vein.

Intravesical administration
The Farmorubicin solution, to be instilled via catheter, should be retained in the bladder for one hour, after which the patient should be instructed to empty the bladder. During instillation, it may be appropriate to rotate the patient’s pelvis to ensure broader contact of the solution with the bladder mucosa.

Preparation of the solution
Intravenous use: Farmorubicin dissolves completely in both water and physiological saline solution. The latter is preferred, as it yields an isotonic solution, which is generally better tolerated.

Intravesical use: The selected dose of Farmorubicin must always be dissolved in 50 ml of physiological
solution or sterile distilled water. After adding the diluent, the vial should be shaken to ensure complete
dissolution of the drug.

Special precautions for disposal and handling
The following safety measures, applicable to all antineoplastic agents, are recommended:

• personnel should be trained in proper handling techniques;
• pregnant personnel must be excluded from such tasks;
• personnel handling the drug should wear protective clothing: goggles, gowns, masks, and disposable gloves;
• a specific area should be designated for reconstitution of the drug (preferably equipped with a vertical laminar flow system); the work surface should be protected with absorbent paper with a plastic backing;
• all items used for administration and cleaning, including gloves, should be placed in disposable high-risk waste bags for high-temperature incineration;
• in case of accidental contact of the drug with skin or eyes, immediately wash the skin thoroughly with soap and water, and rinse eyes with a sodium bicarbonate solution. Monitor the patient closely with regular specialist examinations;
• in case of accidental contamination of objects with the drug, immerse them in a 1% hypochlorite solution, then rinse thoroughly with water;
• cleaning materials must be disposed of as previously indicated. Unused medicine and waste materials derived from this medicine must be disposed of in accordance with current local regulations. For further information, consult the Summary of Product Characteristics.