Mitoxantron Sandoz

Leaflet accompanying the packaging: patient information

Mitoxantron Sandoz, 2 mg/ml, concentrate for solution for infusion

Mitoxantronum

Please read carefully the contents of the leaflet before using the medicine, as it contains important information for the patient.

• Please keep this leaflet, as you may need to read it again.
• In case of any doubts, please consult a doctor, pharmacist, or nurse.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should inform their doctor or nurse. See section 4.

Table of contents of the leaflet:

• 1. What is Mitoxantron Sandoz and what is it used for
• 2. Important information before using Mitoxantron Sandoz
• 3. How to use Mitoxantron Sandoz
• 4. Possible side effects
• 5. How to store Mitoxantron Sandoz
• 6. Contents of the packaging and other information

1. What is Mitoxantron Sandoz and what is it used for

Mitoxantron Sandoz contains the active substance mitoxantrone. Mitoxantron Sandoz belongs to a group of medicines called anticancer medicines. Additionally, it belongs to a class of anticancer medicines called anthracenediones. Mitoxantron Sandoz prevents the growth of cancer cells, which eventually leads to their death. This medicine also suppresses the activity of the immune system and is therefore used to treat a certain form of multiple sclerosis, if there are no other treatment options.

Mitoxantron Sandoz is used to treat:

• advanced breast cancer (with metastases);
• a certain type of lymph node cancer (non-Hodgkin's lymphoma);
• a blood cancer in which the bone marrow (the spongy tissue inside the large bones) produces too many white blood cells (acute myeloid leukemia);
• a white blood cell cancer (chronic myeloid leukemia) in a stage where it is difficult to control the number of white blood cells (blast crisis); in this indication, Mitoxantron Sandoz is used in combination with other medicines;
• pain caused by prostate cancer in advanced stages (in combination with corticosteroids);
• highly active relapsing form of multiple sclerosis and rapidly progressing disability, in a situation where there are no other treatment options (see sections 2 and 3).

2. Important information before using Mitoxantron Sandoz

When not to use Mitoxantron Sandoz

• if the patient is allergic to mitoxantrone or any of the other ingredients of this medicine (listed in section 6);
• if the patient is allergic to sulfites;
• if the patient has a certain type of asthma (bronchial asthma) with allergy to sulfites;
• if the patient is breastfeeding (see section "Pregnancy, breastfeeding, and fertility").

In the case of use in the treatment of multiple sclerosis:

• if the patient is pregnant.

Warnings and precautions

Mitoxantron Sandoz should be administered under the supervision of a doctor with experience in the use of cytotoxic anticancer medicines. Mitoxantron Sandoz should be administered in a slow, freely flowing infusion (drip) into a vein.

The medicine must not be administered subcutaneously, intramuscularly, or intra-arterially. In case of extravasation of Mitoxantron Sandoz during administration, severe local tissue damage may occur.

Mitoxantron Sandoz must not be injected into the space around the brain or spinal cord (intrathecal injection), as this may cause severe damage with permanent disability.

Before starting treatment with Mitoxantron Sandoz, the patient should discuss the following with their doctor, pharmacist, or nurse:

• if the patient has liver problems;
• if the patient has kidney problems;
• if the patient has previously received Mitoxantron Sandoz;
• if the patient has heart problems;
• if the patient has previously undergone chest radiation therapy;
• if the patient is taking medicines that affect the heart;
• if the patient has been previously treated with anthracyclines or anthraquinones, such as daunorubicin or doxorubicin;
• if the patient's bone marrow is not working properly (its function is impaired) or the patient is in poor general condition;
• if the patient has an infection; such an infection should be cured before starting treatment with Mitoxantron Sandoz.
• if the patient plans to be vaccinated or immunized during treatment. Vaccination and immunization may not work if administered during treatment with Mitoxantron Sandoz and for 3 months after the end of treatment;
• if the patient is pregnant or trying to become pregnant/if the patient is trying to father a child;
• if the patient is breastfeeding. Breastfeeding should be discontinued before starting treatment with Mitoxantron Sandoz.

If any of the following symptoms occur during treatment with Mitoxantron Sandoz, the patient should immediately inform their doctor, pharmacist, or nurse:

• fever, infection, unexplained bleeding or bruising, weakness, and fatigue;
• shortness of breath (also at night), cough, fluid retention (swelling of the ankles or feet), heart palpitations (irregular heartbeat). These symptoms may occur during treatment or months, or even years after the end of treatment with Mitoxantron Sandoz.

The doctor may need to adjust the dose or interrupt or permanently discontinue treatment with Mitoxantron Sandoz.

Blood tests before and during treatment with Mitoxantron Sandoz

Mitoxantron Sandoz may change the results of blood morphology. Before starting treatment and during treatment with Mitoxantron Sandoz, the doctor will perform blood tests to determine blood morphology. The doctor will perform blood tests more frequently, paying particular attention to the number of white blood cells (neutrophils) in the blood:

• if the patient has a low number of a certain type of white blood cell (neutrophils) (less than 1500 cells/mm^3);
• if the patient is receiving Mitoxantron Sandoz in high doses (>14 mg/m^2 body surface area for 3 days).

Heart function tests before and during treatment with Mitoxantron Sandoz

Mitoxantron Sandoz may damage the heart and cause heart function disorders or, in more severe cases, heart failure. The risk of such side effects is higher if the patient receives higher doses of Mitoxantron Sandoz or:

• has heart function disorders;
• has previously undergone chest radiation therapy;
• is taking medicines that affect the heart;
• has been previously treated with anthracyclines or anthraquinones, such as daunorubicin or doxorubicin;

The doctor will perform heart function tests before starting treatment with Mitoxantron Sandoz and will regularly repeat them during treatment. In the case of using Mitoxantron Sandoz in the treatment of multiple sclerosis, the doctor will examine heart function before starting treatment, before each subsequent dose, and once a year for 5 years after the end of treatment.

Acute myeloid leukemia (AML) and myelodysplastic syndrome

A certain class of anticancer medicines (topoisomerase II inhibitors), including Mitoxantron Sandoz, may cause the following diseases when used alone, especially in combination with chemotherapy and/or radiation therapy:

• white blood cell cancer (acute myeloid leukemia)
• bone marrow disorder leading to the production of abnormal blood cells and leading to leukemia (myelodysplastic syndrome).

Discoloration of urine and tissues

Mitoxantrone may cause blue-green discoloration of urine lasting for 24 hours after administration. It may also cause blue discoloration of the whites of the eyes, skin, and nails.

Contraception in men and women

Men must not father a child and must use contraceptive measures throughout the treatment period and for at least 6 months after its completion. Women of childbearing potential must have a negative pregnancy test result before each dose administration and must use effective contraception throughout the treatment period and for at least 4 months after the completion of treatment with Mitoxantron Sandoz.

If this medicine is used during pregnancy or the patient becomes pregnant during treatment, the doctor should be informed due to the risk to the fetus.

Fertility

This medicine is associated with the risk of transient or permanent cessation of menstrual bleeding in women of childbearing potential.

Children and adolescents

There is only very limited experience with the use of Mitoxantron Sandoz in children and adolescents. This medicine should not be used in children and adolescents from birth to 18 years of age, as its safety and efficacy in children and adolescents have not been established.

Mitoxantron Sandoz and other medicines

The patient should inform their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take. This is especially important in the case of any of the following medicines.

Medicines that increase the risk of side effects of Mitoxantron Sandoz:

• medicines that may cause heart damage (e.g., anthracyclines);
• medicines that suppress the production of blood cells by the bone marrow (myelosuppressive medicines);
• medicines that suppress the immune system (immunosuppressive medicines);
• vitamin K antagonists, especially if the patient is receiving Mitoxantron Sandoz due to cancer;
• topoisomerase II inhibitors (a class of anticancer medicines that includes mitoxantrone) used in combination with other medicines in chemotherapy and/or radiation therapy. They may cause: acute myeloid leukemia; myelodysplastic syndrome.

In case of doubt about whether the patient is taking any of the above medicines, they should consult their doctor or pharmacist.

Such medicines should be used with caution or discontinued during treatment with Mitoxantron Sandoz. If the patient is taking any of these medicines, the doctor may prescribe an alternative medicine.

The patient should also inform their doctor if they are already taking Mitoxantron Sandoz and the doctor prescribes a new medicine that the patient has not taken at the same time as Mitoxantron Sandoz.

Vaccination and immunization (vaccines) may not work during treatment with Mitoxantron Sandoz and for 3 months after the end of treatment.

Pregnancy, breastfeeding, and fertility

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist before using this medicine.

Pregnancy

Mitoxantron Sandoz may cause harm to the unborn child.

Therefore, pregnancy should be avoided. Mitoxantron Sandoz should not be used in the treatment of multiple sclerosis if the patient is pregnant (especially during the first three months of pregnancy). If the patient becomes pregnant during treatment with Mitoxantron Sandoz, they should immediately inform their doctor and discontinue treatment with Mitoxantron Sandoz.

The patient must avoid becoming pregnant. Men must use effective contraception during treatment and for at least 6 months after its completion. Women of childbearing potential must have a negative pregnancy test result before each dose administration and must use effective contraception during treatment and for at least 4 months after the completion of treatment with Mitoxantron Sandoz.

Breastfeeding

Mitoxantron Sandoz passes into breast milk and may cause serious side effects in the breastfed child. Breastfeeding should be discontinued during treatment with mitoxantrone and for 1 month after the end of treatment.

Fertility

Mitoxantron Sandoz is associated with the risk of transient or permanent cessation of menstrual bleeding in women of childbearing potential. Therefore, the patient should discuss this with their doctor if they plan to become pregnant in the future; it may be possible to freeze eggs.

There is no available data on men. However, in male animals, testicular damage and decreased sperm count in semen have been observed.

Driving and using machines

Mitoxantron Sandoz has a minor influence on the ability to drive and use machines. This is due to possible side effects such as confusion and fatigue (see section 4).

If the patient experiences such side effects, they should not drive or operate machines.

Mitoxantron Sandoz contains sodium

Vial of 10 mg/5 ml:

This medicine contains less than 1 mmol (23 mg) of sodium per vial, which means the medicine is considered "sodium-free".

Vial of 20 mg/10 ml:

This medicine contains 34.14 mg of sodium (the main component of common salt) per vial, which corresponds to 1.7% of the maximum recommended daily intake of sodium in the diet for adults.

3. How to use Mitoxantron Sandoz

Mitoxantron Sandoz will be administered to the patient under the supervision of a doctor with experience in the use of cytotoxic chemotherapy. This medicine must always be administered in an infusion (drip) into a vein and must always be diluted before administration. The infusion solution may leak out of the vein into the surrounding tissues (extravasation). In such a case, the infusion must be discontinued and administered into a different vein. Contact between Mitoxantron Sandoz and the body, especially the skin, mucous membranes (the moist lining of body cavities, e.g., the mouth), and eyes, should be avoided.

The dose of Mitoxantron Sandoz will be calculated by the doctor individually for each patient. The recommended dose is calculated based on the body surface area and is determined in square meters (m^2) based on height and weight. Additionally, blood tests will be performed regularly during treatment. The dosing of the medicine will be adjusted based on the results of these tests.

Typically, the dose used is:

Breast cancer with metastases, non-Hodgkin's lymphoma

If Mitoxantron Sandoz is used alone:

The recommended initial dose of Mitoxantron Sandoz is 14 mg/m^2 body surface area, administered as a single intravenous dose; this dose can be repeated every 21 days if the blood morphology parameters return to acceptable values.

A lower initial dose (12 mg/m^2 body surface area or lower) is recommended for patients with a low bone marrow reserve, e.g., due to previous chemotherapy or poor general condition.

Subsequent doses will be determined precisely by the doctor.

During subsequent treatment cycles, the previous dose can usually be repeated if the white blood cell and platelet counts return to normal within 21 days.

Combination therapy (if the medicine is used in combination with another)

Mitoxantron Sandoz is used in combination therapy. The efficacy of combining Mitoxantron Sandoz with other cytotoxic medicines, including cyclophosphamide and 5-fluorouracil or methotrexate and mitomycin C, has been demonstrated in the treatment of breast cancer with metastases.

Mitoxantron Sandoz is also used in various combinations in the treatment of non-Hodgkin's lymphoma, but currently available data are limited and no specific treatment regimen can be recommended.

Generally, when Mitoxantron Sandoz is used in combination chemotherapy, its initial dose should be reduced by 2-4 mg/m^2 body surface area compared to the dose recommended for single use.

Acute myeloid leukemia

If the medicine is used alone for the treatment of relapse (recurrence of cancer):

The recommended dose for induction of remission is 12 mg/m^2 body surface area, administered intravenously once a day for five consecutive days (the total dose is 60 mg/m^2 body surface area over 5 days).

In combination with other medicines for the treatment of cancer:

The required dose will be determined precisely by the doctor. It may be necessary to modify it if:

• the combination of medicines limits the production of white and red blood cells and platelets by the bone marrow more than Mitoxantron Sandoz used alone.
• the patient has severe kidney or liver problems.

Treatment of blast crisis (chronic) myeloid leukemia

Mitoxantron Sandoz used alone for the treatment of relapse:

The recommended dose in case of relapse is 10-12 mg/m^2 body surface area, administered intravenously once a day for five consecutive days (the total dose is 50-60 mg/m^2 body surface area).

Advanced prostate cancer resistant to castration

The recommended dosing of Mitoxantron Sandoz is 12-14 mg/m^2 body surface area, administered in a short intravenous infusion every 21 days in combination with small oral doses of corticosteroids (hormonal medicines that suppress the immune system).

Multiple sclerosis

Mitoxantron Sandoz will be administered under the supervision of a doctor with experience in the use of chemotherapy in the treatment of multiple sclerosis.

The recommended dosing of mitoxantrone is 12 mg/m^2 body surface area in a short intravenous infusion (about 5-15 minutes); such infusions can be repeated every 1-3 months. The maximum cumulative lifetime dose should not exceed 72 mg/m^2 body surface area.

In case of repeated administration of mitoxantrone, doses should be adjusted based on the extent and duration of the decrease in the number of white and red blood cells and platelets in the blood.

Elderly patients

Elderly patients should receive doses from the lower end of the dosing range due to possible impairment of liver, kidney, or heart function, as well as possible other diseases and concomitant medicines.

In case of any further doubts about the use of this medicine, the patient should consult their doctor, pharmacist, or nurse.

4. Possible side effects

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

The most serious side effects are heart damage (toxic effect on the heart muscle) and myelosuppression (suppression of bone marrow activity).

Some side effects can be serious.

If the patient experiences any of the following symptoms, they should immediately inform their doctor:

• the skin becomes pale, and the patient feels weak or experiences sudden shortness of breath (these may be symptoms of a decreased number of red blood cells);
• unusual tendency to bruise or bleed, such as coughing up blood, blood in vomit or urine, or black stools (possible symptoms of a decreased number of platelets);
• difficulty breathing;
• chest pain, shortness of breath, irregular heartbeat, or fluid retention (swelling of the ankles or feet) (possible symptoms of heart disease);
• severe itching rash (hives), swelling of the hands, feet, ankles, face, lips, mouth, or throat (which may cause difficulty breathing or swallowing) or a feeling of impending fainting (these may be symptoms of a severe allergic reaction);
• fever or infection.

In patients treated for cancer:

Very common (may occur in more than 1 in 10 patients)

• Infections
• Low number of red blood cells, which may cause fatigue and shortness of breath (anemia). Blood transfusion may be necessary.
• Low number of a certain type of white blood cell (neutrophils).
• Nausea (feeling sick)
• Vomiting
• Hair loss

Common (may occur in up to 1 in 10 patients)

• Low number of platelets, which may cause bruising or bleeding.
• Low number of a certain type of white blood cell (granulocytes)
• Fatigue, weakness, and lack of energy
• Loss of appetite
• Heart attack
• Shortness of breath
• Constipation
• Diarrhea
• Mouth and lip inflammation
• Fever
• Severe heart failure (a condition in which the heart is unable to pump enough blood)

Uncommon (may occur in up to 1 in 100 patients)

• Suppression of bone marrow activity - may be greater or longer-lasting if the patient has previously been treated with chemotherapy or radiation therapy
• Insufficient production of blood cells by the bone marrow (bone marrow failure)
• Abnormal number of white blood cells
• Severe allergic reactions (anaphylactic reaction, including anaphylactic shock) - sudden itching rash (hives), swelling of the hands, feet, ankles, face, lips, mouth, or throat (which may cause difficulty breathing or swallowing) or a feeling of impending fainting
• Upper respiratory tract infections
• Urinary tract infections
• Blood poisoning (sepsis)
• Infections caused by microorganisms that do not normally cause disease in people with a healthy immune system (opportunistic infections)
• White blood cell cancer (acute myeloid leukemia, AML)
• Bone marrow disorder leading to the production of abnormal blood cells and leading to leukemia (myelodysplastic syndrome, MDS)
• Changes in body weight
• Metabolic disorders (tumor lysis syndrome)
• Anxiety
• Confusion
• Headache
• Numbness
• Irregular or slow heart rhythm
• Abnormal ECG (electrocardiogram) reading
• Decreased volume of blood pumped by the left ventricle of the heart, without symptoms
• Bruising
• Severe bleeding
• Low blood pressure
• Abdominal pain
• Bleeding in the stomach or intestines, which may cause blood in vomit, bleeding during bowel movements, or black tarry stools
• Mucous membrane inflammation
• Pancreatitis
• Liver function disorders
• Skin inflammation (rash)
• Nail disorders (e.g., nail separation from the nail bed, changes in nail appearance and structure)
• Rash
• Change in the color of the whites of the eyes
• Skin discoloration
• Leakage of the solution into the surrounding tissues (extravasation):
• redness (erythema)
• swelling
• pain
• burning sensation and/or skin discoloration
• necrosis of tissue fragments, requiring their removal and skin grafting
• Abnormal results of blood tests evaluating liver and kidney function (increased aspartate aminotransferase activity, increased creatinine and urea levels in the blood)
• Kidney damage, causing swelling and weakness (nephropathy)
• Change in urine color
• Swelling (edema)
• Taste disorders
• Pathological absence of menstrual bleeding

Rare (may occur in up to 1 in 1000 patients)

• Heart muscle damage that prevents it from pumping blood properly (cardiomyopathy)
• Lung inflammation

In patients treated for multiple sclerosis:

Very common (may occur in more than 1 in 10 patients)

• Infections, including upper respiratory tract and urinary tract infections
• Nausea (feeling sick)
• Hair loss
• Pathological absence of menstrual bleeding

Common (may occur in up to 1 in 10 patients)

• Low number of red blood cells, which may cause fatigue and shortness of breath (anemia). The patient may require blood transfusion.
• Low number of a certain type of white blood cell (granulocytes)
• Constipation
• Vomiting
• Diarrhea
• Mouth and lip inflammation
• Abnormal number of white blood cells
• Headache
• Irregular heart rhythm
• Abnormal ECG (electrocardiogram) reading
• Decreased volume of blood pumped by the left ventricle of the heart, without symptoms
• Abnormal results of blood tests evaluating liver function (increased aspartate aminotransferase activity)

Uncommon (may occur in up to 1 in 100 patients)

• Lung inflammation
• Blood poisoning (sepsis)
• Infections caused by microorganisms that do not normally cause disease in people with a healthy immune system (opportunistic infections)
• White blood cell cancer (acute myeloid leukemia, AML)
• Bone marrow disorder leading to the production of abnormal blood cells and leading to leukemia (myelodysplastic syndrome, MDS)
• Insufficient production of blood cells by the bone marrow (bone marrow failure)
• Suppression of bone marrow activity - may be greater or longer-lasting if the patient has previously been treated with chemotherapy or radiation therapy
• Low number of platelets, which may cause bruising or bleeding
• Low number of a certain type of white blood cell (neutrophils)
• Severe allergic reaction (anaphylactic reaction, including anaphylactic shock) - sudden itching rash (hives), swelling of the hands, feet, ankles, face, lips, mouth, or throat (which may cause difficulty breathing or swallowing) or a feeling of impending fainting
• Loss of appetite
• Changes in body weight
• Anxiety
• Confusion
• Numbness
• Fatigue, weakness, and lack of energy
• Severe heart failure (a condition in which the heart is unable to pump enough blood)
• Heart muscle damage that prevents it from pumping blood properly (cardiomyopathy)
• Slow heart rhythm
• Heart attack
• Unusual tendency to bruise
• Severe bleeding
• Low blood pressure
• Shortness of breath
• Abdominal pain
• Bleeding in the stomach or intestines, which may cause blood in vomit, bleeding during bowel movements, or black tarry stools
• Mucous membrane inflammation
• Pancreatitis
• Liver function disorders
• Nail disorders (e.g., nail separation from the nail bed, changes in nail appearance and structure)
• Rash
• Change in the color of the whites of the eyes
• Skin discoloration
• Leakage of the solution into the surrounding tissues (extravasation):
• redness (erythema)
• swelling
• pain
• burning sensation and/or skin discoloration
• necrosis of tissue fragments, requiring their removal and skin grafting
• Abnormal results of blood tests evaluating kidney function (increased creatinine and urea levels in the blood)
• Kidney damage, causing swelling and weakness (nephropathy)
• Change in urine color
• Swelling (edema)
• Fever
• Sudden death

Rare (may occur in up to 1 in 1000 patients)

No data available

Reporting of side effects

If side effects occur, including any side effects not listed in the leaflet, the patient should inform their doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl

Side effects can also be reported to the marketing authorization holder.

Reporting side effects will help to gather more information on the safety of the medicine.

5. How to store Mitoxantron Sandoz

The medicine should be stored out of sight and reach of children.

Do not use this medicine after the expiry date stated on the carton and label after EXP.

The expiry date refers to the last day of the month.

There are no special storage instructions for the medicine.

After the first opening of the vial, the concentrate should be diluted immediately.

The resulting solution after dilution remains stable for 24 hours at room temperature and for a maximum of 3 days at 2°C-8°C.

Due to microbiological purity, the diluted medicine should be used immediately.

Otherwise, the responsibility for the storage conditions and storage time before administration to the patient lies with the user. The solution should not be stored for more than 24 hours at 2°C-8°C, unless the dilution has been performed under controlled and validated aseptic conditions.

Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Mitoxantron Sandoz contains

• The active substance of the medicine is mitoxantrone (in the form of mitoxantrone hydrochloride). Each milliliter of the concentrate contains 2 mg of mitoxantrone (in the form of mitoxantrone hydrochloride).
• The other ingredients of the medicine are: sodium chloride, sodium acetate, glacial acetic acid, anhydrous sodium sulfate, diluted hydrochloric acid (for pH adjustment), water for injections.

What Mitoxantron Sandoz looks like and contents of the pack

Mitoxantron Sandoz is a clear, blue solution, without visible particles.

The medicine is available in vials made of colorless glass. Cardboard boxes contain 1 vial containing 10 mg of mitoxantrone in 5 ml or 20 mg of mitoxantrone in 10 ml.

Package sizes: 1 x 5 ml and 1 x 10 ml.

Not all package sizes may be marketed.

Marketing authorization holder

Sandoz GmbH

Biochemiestrasse 10

6250 Kundl, Austria

Manufacturer

EBEWE Pharma Ges.m.b.H. Nfg.KG

Mondseestrasse 11

4866 Unterach, Austria

Fareva Unterach GmbH

Mondseestraße 11

4866 Unterach, Austria

For further information on the medicine and its names in the Member States of the European Economic Area, please contact:

ul. Domaniewska 50 C

02-672 Warszawa

tel. 22 209 70 00

Date of last revision of the leaflet: 06/2021