ONKOTRONE 10 mg Koncentrat Do Sporządzania Roztworu Infuzyjnego

Treść ulotki

1. ONKOTRONE 10 mg concentrate for solution for infusion, 20 mg concentrate for solution for infusion, 25 mg concentrate for solution for infusion, 30 mg concentrate for solution for infusion
   1. What is Onkotrone and what it is used for
   2. What you need to know before using Onkotrone
   3. How to use Onkotrone
   4. Possible side effects
   5. How to store Onkotrone
   6. Contents of the pack and other information

ONKOTRONE 10 mg concentrate for solution for infusion, 20 mg concentrate for solution for infusion, 25 mg concentrate for solution for infusion, 30 mg concentrate for solution for infusion

Mitoxantrone dihydrochloride

Read this leaflet carefully before you use this medicine as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, or pharmacist or nurse.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, or pharmacist or nurse. See section 4.

Contents of this leaflet:

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

1. What is Onkotrone and what it is used for

Onkotrone contains the active substance mitoxantrone. Onkotrone belongs to the group of medicines known
as antineoplastic or anticancer medicines. It also belongs to the subgroup of anticancer medicines
called anthracyclines. Onkotrone prevents cancer cells from growing, consequently the cells
die.
Onkotrone is used in the treatment of:

• advanced breast cancer (metastatic form);
• a form of cancer of the lymph nodes (non-Hodgkin's lymphoma);
• a cancer of the blood in which the bone marrow (the spongy tissue found inside the large bones) produces too many white blood cells (acute myeloid leukemia);
• a cancer of the white blood cells (chronic myeloid leukemia) in the stages where it is difficult to control the number of white blood cells (blastic crisis). Onkotrone is used in association with other medicines in this indication;
• pain caused by advanced prostate cancer in association with corticosteroids;

2. What you need to know before using Onkotrone

Do not use Onkotrone
If you are allergic to mitoxantrone or any of the other ingredients of this medicine (listed in
section 6).

• if you are allergic to sulfites;
• if you have a form of asthma (bronchial asthma) with allergy to sulfites;
• if you are breastfeeding (see section “Pregnancy and breastfeeding”)

Warnings and precautions
Onkotrone must be administered under the supervision of a doctor experienced in the use of medicines
that are toxic to cells (cytotoxic chemotherapeutic agents).
Onkotrone must be administered with a slow and free-flowing intravenous infusion.
Onkotrone must not be administered under the skin (subcutaneously), into a muscle (intramuscularly)
or into an artery (intraarterially). Serious tissue damage may occur if Onkotrone leaks
into the surrounding tissues (extravasation) during administration.
Onkotrone must not be injected into the space under the brain or spinal cord (intrathecal injection) because this may cause serious injury with permanent damage.

Tell your doctor, pharmacist or nurse before using Onkotrone:

• if you have liver problems.
• if you have kidney problems.
• if you have previously used Onkotrone
• if your heart is not functioning properly
• if you have previously had radiation therapy to the chest
• if you have previously used other medicines that have an effect on the heart
• if you have previously had therapies with anthracyclines or anthracenediones, for example daunorubicin or doxorubicin
• if your bone marrow is not functioning properly (is depressed) or if your health condition is serious
• if you have an infection. This infection must be treated before taking Onkotrone.
• if you need to have a vaccine or immunization during the treatment period. Vaccinations and immunizations may not be effective during treatment with Onkotrone and for 3 months after the end of treatment.
• if you are pregnant or if you and your partner are trying to become pregnant.
• if you are breastfeeding. You must stop breastfeeding before taking Onkotrone.

Immediately inform your doctor, pharmacist or nurse if any of these signs
or symptoms occur during treatment with Onkotrone:

• fever, infections, unusual bleeding or bruising, weakness and fatigue;
• shortness of breath (including shortness of breath at night), cough, fluid retention (swelling) in the ankles or legs, heart palpitations (irregular heartbeat). This may occur during therapy with Onkotrone, or months or years after therapy. The doctor may modify the treatment or stop the therapy with Onkotrone, temporarily or permanently.

Blood tests before and during treatment with Onkotrone
Onkotrone can change the count of your blood cells. Before starting Onkotrone and during the
treatment, your doctor will perform a blood test to count the number of your blood
cells. The doctor will perform blood tests more frequently, to monitor in particular the number of
white blood cells (neutrophils) in the blood:

• if you have a low count of a certain type of white blood cells (neutrophils) (less than 1,500 cells/mm );
• if you are using Onkotrone in high doses (>14 mg/m per day x 3 days).

Heart function tests before and during treatment with Onkotrone
Onkotrone can damage the heart and worsen heart function or, in more severe cases, cause
heart failure. You are more likely to experience these side effects if you take high
doses of Onkotrone, or:

• if your heart is not functioning properly
• if you have been treated previously with radiation therapy to the chest
• if you have previously used other medicines that have an effect on the heart
• if you have previously had therapies with anthracyclines or anthracenediones, for example daunorubicin or doxorubicin Your doctor will perform heart function tests before starting therapy with Onkotrone and at regular intervals during therapy.

Acute myeloid leukemia (AML) and myelodysplastic syndrome
A group of anticancer medicines (Topoisomerase II inhibitors), including Onkotrone, can cause the
following conditions when used alone but especially in combination with other chemotherapy and/or
radiotherapy:

• cancer of the white blood cells (acute myeloid leukemia, AML)
• a disorder of the bone marrow that causes abnormally shaped blood cells and leads to leukemia (myelodysplastic syndrome)

Change in the color of urine and other tissues
Mitoxantrone can cause a blue-green discoloration of the urine for 24 hours after administration.
A bluish discoloration of the whites of the eyes, skin and nails may also occur.

Contraception in men and women
Men must not father a child and must use contraception during and for at least 6 months
after therapy. Women of childbearing potential must have a negative pregnancy test before each
dose, and must use effective contraceptive methods during therapy and for at least 4 months after
stopping therapy. If this medicine is used during pregnancy, or if a
pregnancy begins while taking this medicine, inform the doctor because there may be risks to the
fetus.

Fertility
This medicine may increase the risk of persistent absence of menstruation (amenorrhea) in
women of childbearing potential. Therefore, you must inform the doctor if you are planning a future pregnancy;
it may be necessary to freeze your eggs. There is no data available for men.
However, damage to the testicles and a reduction in the number of
spermatozoa have been observed in male animals.

Driving and operating machinery
Onkotrone has a marginal effect on the ability to drive and operate machinery. This is due
to possible side effects, such as confusion or fatigue (see section 4).
If you experience these side effects, do not drive or operate any machinery.

3. How to use Onkotrone

Dosage and method of administration
Onkotrone will be administered under the supervision of a doctor experienced in the use of cytotoxic
chemotherapeutic agents. It must always be administered as an intravenous infusion (into a vein)
and must always be diluted first. The infusion liquid may leak from the vein and spread into the
tissues (extravasation). In this case, the infusion must be stopped and resumed in a different vein. Contact with Onkotrone should be avoided, especially with the skin, mucous membranes (the moist surfaces of the body, such as the inside of the mouth) and eyes. The individual dose of Onkotrone is calculated
by your doctor. The recommended dose is based on your body surface area, calculated in square meters
(m²) using height and weight. In addition, regular blood tests will be performed during the
treatment. The dosage of the medicine will be adjusted based on the results of these tests.
The usual dose is:

Metastatic breast cancer, non-Hodgkin's lymphoma
If Onkotrone is used alone:
of body surface area, administered
as a single intravenous dose, repeatable at intervals of 21 days if your blood values have returned
to acceptable levels.
The initial recommended dosage for Onkotrone is 14 mg/m²
or less) in patients with low bone marrow reserves,
e.g. due to previous chemotherapy or compromised general conditions.
The doctor will decide the exact subsequent dose you need.
A lower initial dosage (12 mg/m²) is recommended
For subsequent cycles, the previous dose can usually be repeated if the platelet count and
blood cell count have returned to normal levels after 21 days.
Combination therapy (if used with other agents)
Onkotrone has been administered as part of a combination therapy. In metastatic breast cancer
combinations of Onkotrone with other cytotoxic agents, including cyclophosphamide and 5-
fluorouracil or methotrexate and mitomycin C have proven effective.
Onkotrone has also been used in various combinations for non-Hodgkin's lymphoma; however, the data at
the moment are limited and it is not possible to recommend specific dosage regimens.
As a guide, when Onkotrone is used in combination chemotherapy, the initial dose of
Onkotrone should be reduced by 2-4 mg/m² compared to the doses recommended for use as a single agent.

Acute myeloid leukemia:
If used alone for relapses (return of cancer)
of body surface area,
administered daily as a single intravenous dose for five consecutive days (60 mg/m²
The recommended dosage for inducing remission is 12 mg/m²
in
total for 5 days).
If used with other anticancer agents:
The doctor will decide the exact dose you need. The dose may be adjusted if:

• The combination of medicines reduces the production of red blood cells, white blood cells and platelets in the bone marrow more than Onkotrone alone.
• If you have serious liver or kidney problems.

Treatment of blast crisis in chronic myeloid leukemia
Used alone for relapses
The recommended dosage for relapse is 10 to 12 mg/m² of body surface area, administered
daily as a single intravenous dose for five consecutive days (50 to 60 mg/m² in total).

Advanced castration-resistant prostate cancer
The recommended dosage of Onkotrone is 12 or 14 mg/m² in short intravenous infusion every 21 days,
in association with low oral doses of corticosteroids (hormonal therapy used to suppress the
immune system).

Elderly patients
Elderly patients should receive a dose at the lower limit of the dosage range, because
they may have reduced hepatic, renal or cardiac function, or they may have other pathologies or
treatments with other medicines.
If you have any questions about the use of this medicine, ask your doctor, pharmacist or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
The most serious side effects are heart damage (myocardial toxicity) and
myelosuppression (reduced bone marrow activity).

Some side effects may be serious

Tell your doctor immediately if any of the following occur:

• If your skin becomes pale and you feel weak or suddenly short of breath, this may be a sign of a reduction in red blood cells.
• Unusual bruising or bleeding, such as coughing up blood, or blood in your vomit or urine, or black stools (possible sign of reduced platelets).
• Differences or worsening of breathing.
• Chest pain, shortness of breath, changes in heartbeat (faster or slower), fluid retention (swelling) in the ankles or legs (possible signs or symptoms of heart problems).
• Severe skin rash with itching (hives), swelling of the hands, feet, ankles, face, lips, mouth or throat (which can cause difficulty swallowing or breathing), feeling like you are about to faint: these may be signs of a serious allergic reaction
• Fever or infections

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

• Infections
• Decreased number of red blood cells, which can cause fatigue and shortness of breath (anemia). You may need a blood transfusion
• Decreased number of some white blood cells (neutrophils and leukocytes)
• Nausea
• Vomiting
• Hair loss

Common (may affect up to 1 in 10 people)

• Decreased number of platelets, which can cause bleeding or bruising.
• Decreased number of some white blood cells (granulocytes).
• Loss of appetite.
• Fatigue, weakness and lack of energy.
• Congestive heart failure (a serious condition in which the heart is no longer able to pump enough blood).
• Heart attack.
• Shortness of breath.
• Constipation.
• Diarrhea.
• Inflammation of the mouth and lips.
• Fever.

Uncommon (may affect up to 1 in 100 people)

• Reduced bone marrow activity. If you have undergone chemotherapy or radiotherapy, your bone marrow may be more depressed, or depressed for a longer period.
• Insufficient production of blood cells in the bone marrow (bone marrow failure).
• Abnormal number of white blood cells.
• Severe allergic reaction (anaphylactic reaction, including anaphylactic shock) - you may experience a sudden itchy rash (hives), swelling of the hands, feet, ankles, face, lips, mouth or throat, which can cause difficulty swallowing or breathing, and you may feel like you are about to faint).
• Upper airway infections.
• Urinary tract infections.
• Blood poisoning (sepsis).
• Infections caused by microorganisms that normally do not cause disease in a healthy immune system (opportunistic infections).
• Cancer of the white blood cells (acute myeloid leukemia, AML).
• Bone marrow abnormality that causes the formation of abnormal blood cells and leads to leukemia (myelodysplastic syndrome, MDS).
• Weight changes.
• Metabolic disorders (tumor lysis syndrome).
• Anxiety.
• Confusion.
• Headache.
• Tingling sensation.
• Irregular or slowed heartbeat.
• Abnormalities in the electrocardiogram.
• Decreased volume of blood that can be pumped from the left ventricle, without symptoms.
• Bruising.
• Severe bleeding.
• Low blood pressure.
• Abdominal pain.
• Bleeding in the stomach or intestines, which can cause blood in the vomit, bleeding when defecating or black tarry stools.
• Inflammation of the mucous membranes.
• Inflammation of the pancreas.
• Liver abnormalities.
• Skin inflammation (erythema).
• Nail abnormalities (e.g., detachment of the nail from the nail bed, changes in the consistency and structure of the nail).
• Skin rash.
• Changes in the color of the white part of the eyes.
• Changes in skin color.
• Leakage of fluid into the surrounding tissue (extravasation): o Redness (erythema). o Swelling. o Pain. o Burning sensation and/or changes in skin color. o Death of tissue cells, which may lead to the need to remove dead cells and perform a skin transplant.
• Abnormal blood test results to check liver and kidney function (elevated aspartate aminotransferase levels, high creatinine and blood urea nitrogen concentrations).
• Kidney damage, resulting in swelling and weakness (nephropathy).
• Changes in urine color.
• Abnormal absence of menstruation (amenorrhea).
• Swelling (edema).
• Taste disturbances.

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

• Lung inflammation (pneumonia).
• Damage to the heart muscle that prevents it from pumping normally (cardiomyopathy).

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor, pharmacist or nurse. You can also report side effects directly
through the website http://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 Onkotrone

Keep this medicine out of the sight and reach of children.
Do not store at a temperature above 25°C. Do not freeze.
Do not use this medicine after the expiry date stated on the label. The expiry date refers to the last day of that month.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Onkotrone contains

• The active ingredient is 10 mg 20 mg 25 mg 30 mg In 5 ml 10 ml 12,5 ml 15 ml

Mitoxantrone bicloridrato mg 11,640 23,280 29,100 34,920
equivalent to Mitoxantrone mg 10 20 25 30

• The other ingredients are sodium chloride, sodium acetate trihydrate (see section 2. Onkotrone contains sodium), acetic acid, water for injections.

Description of the appearance of Onkotrone and contents of the pack
Onkotrone is presented as a dark blue liquid, packaged in glass vials with a
rubber stopper and metal crimp seal.
Onkotrone is available in the following packs:
1 vial with 10 mg of Mitoxantrone in 5 ml of infusion solution.
1 vial with 20 mg of Mitoxantrone in 10 ml of infusion solution.
1 vial with 25 mg of Mitoxantrone in 12,5 ml of infusion solution.
1 vial with 30 mg of Mitoxantrone in 15 ml of infusion solution.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Baxter S.p.A.
Piazzale dell’Industria, 20
00144 ROMA

Manufacturer
Baxter Oncology GmbH
Kantstrasse 2
D-33790 Halle/Westfalen (Germany)

Other sources of information
More detailed information on this medicine is available on the website of the Italian Medicines Agency.