2 mg / ml concentrate for solution for infusion
mitoxantrone (as hydrochloride)
What Mitoxantron Ebewe is and what it is used for
Mitoxantrone Ebewe contains the active substance mitoxantrone. Mitoxantrone Ebewe belongs to a group of medicines called chemotherapy drugs or cancer medicines. It is also part of a subgroup of cancer drugs called anthracyclines. Mitoxantrone Ebewe prevents cancer cells from growing, causing them to eventually die. The drug also inhibits the immune system and is used for this reason to treat a specific form of multiple sclerosis in cases where there are no other treatment options.
Mitoxantrone Ebewe is used to treat:
- advanced (metastatic) breast cancer
- a form of lymph node cancer ( non-Hodgkin’s lymphoma )
- a form of blood cancer in which a bone marrow (the fungal tissue inside the large skeletal bones) produces too many white blood cells ( acute myeloid leukemia )
- a type of cancer of the white blood cells ( chronic myeloid leukemia ) at a stage where it is difficult to keep the number of white blood cells under control ( blast crisis ). Mitoxantron Ebewe is used in combination with other medicines for this use
- pain caused by prostate cancer in an advanced stage and then in combination with corticosteroids ( cortisone )
- multiple sclerosis (MS) with very active relapses associated with rapid development of disability in cases where there are no other treatment options (see sections 2 and 3).
Mitoxantrone contained in Mitoxantron Ebewe may also be approved for the treatment of other conditions not mentioned in this product information. Ask your doctor, pharmacist, or other healthcare professionals if you have any further questions, and always follow their instructions.
What you need to know before you use Mitoxantron Ebewe
Do not use Mitoxantron Ebewe
- if you are allergic to mitoxantrone or any of the other ingredients of this medicine (listed in section 6)
- if you are allergic to sulphite
- if you have a form of asthma ( bronchial asthma ) with a sulphite allergy
- if you are breast-feeding (see section “Pregnancy and breast-feeding”).
For use in the treatment of multiple sclerosis (MS):
- if you are pregnant.
Warnings and cautions
Mitoxantrone Ebewe should be given under the supervision of a specialist physician experienced in the use of chemotherapy or cancer drugs ( cytotoxic chemotherapy ).
Mitoxantrone Ebewe should be given as a slow, free-flowing infusion (drip) into a vein.
Mitoxantrone Ebewe must not be given under the skin ( subcutaneously ), in a muscle ( intramuscularly ), or an artery (intraarterial). Severe local tissue damage can occur if Mitoxantron Ebewe leaks into the surrounding tissue (so-called extravasation) when given.
Mitoxantrone Ebewe must also not be injected into the spinal fluid ( intrathecal injection ), as this can lead to severe injuries with a permanent disability.
Talk to your doctor, pharmacist, or nurse before taking Mitoxantrone Ebewe if you:
- have liver problems
- have kidney problems
- have used Mitoxantron Ebewe before
- have heart problems
- previously received radiation treatment of the chest
- use drugs that affect the heart
- have been previously treated with anthracyclines or anthracenediones, such as daunorubicin or doxorubicin
- have problems with bone marrow one or if you have poor general condition
- have an infection . Any infection should be treated before using Mitoxantron Ebewe
- should be vaccinated or immunized during treatment. Vaccinations and immunizations may not have the intended effect during treatment with Mitoxantron Ebewe and for 3 months after stopping treatment
- is pregnant or if you and your partner are trying to conceive
- ammar. You should stop breast-feeding before taking Mitoxantron Ebewe
If you get any of the following signs or symptoms during treatment with Mitoxantrone Ebewe, tell your doctor, pharmacist, or nurse immediately:
- fever, infection , unexplained bleeding or bruising, feeling weak or if you get tired easily
- shortness of breath (even at night), cough, fluid retention (swelling) in the ankles or legs, palpitations (irregular heartbeat). This can occur either during treatment or months to years after stopping treatment with Mitoxantron Ebewe.
Your doctor may need to adjust or stop the treatment, either temporarily or for good.
Blood tests before and during treatment with Mitoxantrone Ebewe
Mitoxantrone Ebewe can affect the number of blood cells. Before starting and during treatment with Mitoxantrone Ebewe, you will be given blood samples to check your blood cells. In the following conditions, the doctor will prescribe more frequent blood test checks to count in particular the number of white blood cells (neutrophilic leukocytes ) in the blood:
- if you have a low number of a particular type of white blood cell ( neutrophils ) (less than 1,500 cells / mm 3 )
- if you are taking high doses of Mitoxantron Ebewe (more than 14 mg / m 2 per day for 3 days).
Cardiac function is monitored before and during treatment with Mitoxantrone Ebewe
Mitoxantrone Ebewe can damage the heart and cause impaired heart function or, in more severe cases, heart failure. You are more likely to suffer from these side effects if you take higher doses of Mitoxantrone Ebewe or:
- if you have heart problems
- if you have previously received radiation therapy to your chest
- if they are already taking other medicines that affect the heart
- if you have been previously treated with anthracyclines or anthracenediones, such as daunorubicin or doxorubicin.
Your doctor will check your heart function before you start Mitoxantron Ebewe and regularly during treatment. If you are receiving Mitoxantron Ebewe to treat multiple sclerosis, your doctor will check your heart function before starting treatment, before each subsequent dose, and annually for up to 5 years after stopping treatment.
Acute myeloid leukemia (AML) and myelodysplastic syndrome
A group of cancer drugs ( topoisomerase II inhibitors), including Mitoxantron Ebewe, can cause the following diseases when used separately but in particular in combination with other chemotherapy drugs, cancer drugs, and/or radiation therapy:
- cancer of the white blood cells ( acute myeloid leukemia , AML)
- bone marrow disorders that cause abnormally shaped blood cells and lead to leukemia ( myelodysplastic syndrome )
Discoloration of urine and tissue er
Mitoxantrone may cause a blue-green discoloration of the urine for 24 hours after infusion. Bluish discoloration of the whites of the eyes, skin, and nails can also occur.
Pregnancy protection in men and women
Men must not make their female partners pregnant and must use contraception during treatment and for at least 6 months after the end of treatment. Women who can have children should show a negative pregnancy test before each dose and use an effective contraceptive during treatment and for at least 4 months after stopping treatment. If you are taking this medicine during pregnancy or if you become pregnant while taking this medicine, tell your doctor, as it may pose a risk to the fetus.
Fertility
This medicine may increase the risk of the temporary or permanent absence of menstruation ( amenorrhea ) in women who may have children.
Children and young people
There is little experience of use in children and adolescents.
Do not give this medicine to children and adolescents from birth to 18 years of age, as the safety and efficacy in children and adolescents have not been established.
Other medicines and Mitoxantron Ebewe
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. It is especially important that you indicate if you are taking any of the following medicines:
Medicines that may increase the risk of side effects with Mitoxantrone Ebewe:
- Medicines that can harm the heart (eg anthracyclines )
- Drugs that inhibit the bone marrow production of blood cells and platelets (myelosuppressive substances)
- Drugs that inhibit the immune system (immunosuppressive substances)
- Antivitamin K, especially if you are taking Mitoxantron Ebewe as a treatment for cancer
- Topoisomerase II inhibitors (a group of cancer drugs, including mitoxantrone) in combination with other chemotherapy drugs , cancer drugs and / or radiation therapy. These can cause:
- cancer of the white blood cells ( acute myeloid leukemia , AML)
- bone marrow disorders that cause abnormally shaped blood cells and lead to leukemia ( myelodysplastic syndrome ).
Ask your doctor or pharmacist if you are not sure if any of your medicines are listed in the list above.
These medicines should be used with caution or may need to be avoided during treatment with Mitoxantrone Ebewe. If you are taking any of these, your doctor may need to prescribe an alternative medicine for you.
You should also tell your doctor if you are already taking Mitoxantrone Ebewe and you are receiving a new medicine that you have not already used with Mitoxantrone Ebewe.
Vaccinations and immunizations (protection against vaccines) may not work during treatment with Mitoxantrone Ebewe and for three months after stopping treatment.
Pregnancy, breastfeeding and fertility
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
Mitoxantrone Ebewe can harm your unborn baby. Therefore, you should avoid getting pregnant during treatment. Mitoxantrone Ebewe must not be used as a treatment for multiple sclerosis if you are pregnant (especially not during the first three months of pregnancy).
If you become pregnant while taking Mitoxantrone Ebewe, tell your doctor immediately and stop taking Mitoxantrone.
Ebewe.
You should avoid getting pregnant. Men must use an effective contraceptive during treatment and for at least 6 months after stopping treatment. Women who can have children should show a negative pregnancy test before each dose and use an effective contraceptive during treatment and for at least 4 months after stopping treatment.
Breast-feeding
Mitoxantrone Ebewe is excreted in breast milk and may cause serious side effects in your baby. You must not breastfeed while using mitoxantrone and for up to one month after the last infusion.
Fertility
Mitoxantrone Ebewe may increase the risk of the temporary or permanent absence of menstruation ( amenorrhea ) in women who may have children. You should therefore talk to your doctor if you plan to have children in the future. You may then need to freeze eggs. For men, there is no data. In male animals, however, damage to the testicles and a reduced number of sperm have been observed.
Driving and using machines
Mitoxantrone Ebewe has a minor effect on the ability to drive and use machines. This is due to possible side effects, such as confusion and fatigue (see section 4).
Do not drive or use any machines if you experience any of these side effects.
You are responsible for assessing whether you are fit to drive a motor vehicle or perform work that requires sharpened attention. One of the factors that can affect your ability in these respects is the use of drugs due to their effects and/or side effects. Descriptions of these effects and side effects can be found in other sections. Read all the information in this leaflet for guidance. If you are not sure, talk to your doctor or pharmacist.
Mitoxantrone Ebewe contains sodium
For 5 ml vial:
This medicine contains less than 1 mmol (23 mg) sodium per vial, ie essentially ‘sodium-free’.
For 10 ml vial:
This medicine contains 34.14 mg sodium (the main ingredient in table salt/table salt) per vial. This corresponds to 1.7% of the maximum recommended daily intake of sodium for adults.
How to use Mitoxantron Ebewe
You will receive Mitoxantron Ebewe under the supervision of a specialist doctor with experience in chemotherapy or cancer drugs. It should always be given as an intravenous infusion (into a vein) and should always be diluted before use. The infusion fluid may leak from the vein into the surrounding tissue (extravasation). If this happens, one infusion must be stopped and started in another vein.
Avoid direct contact with Mitoxantrone Ebewe, especially through the skin, mucous membranes, and eyes.
Dose one of Mitoxantrone Ebewe is adjusted individually by your doctor.
Dose one is based on your body surface area measured in square meters (m 2 ) and which is calculated using length and weight. Blood samples will also be taken regularly during treatment. Dosage one of the drug will be adjusted depending on the result of these blood tests.
The usual dose is:
Metastatic breast cancer, non-Hodgkin’s lymphoma
When only Mitoxantron Ebewe is used:
The recommended starting dose is 14 mg / m 2 body surface area, given as a single intravenous dose. This can be repeated at 21-day intervals if your blood levels have returned to acceptable levels.
If you have bone marrow problems, for example, due to previous chemotherapy drugs, cancer drugs, or a bad general condition, you should receive a lower dose the first time, 12 mg / m 2 or less.
Your doctor will decide on the next dose.
For subsequent treatments, the previous dose can usually be repeated if the number of white blood cells and platelets has returned to normal levels after 21 days.
In combination therapy (if used with other drugs):
Mitoxantrone Ebewe has been given as part of combination therapies. In metastatic breast cancer, combinations with other chemotherapy drugs such as cyclophosphamide and 5-fluorouracil, or methotrexate and mitomycin C are effective.
Mitoxantrone Ebewe has also been used in various combinations for non-Hodgkin’s lymphoma, but knowledge of this is currently limited and there is no specific recommendation for treatment.
As a guide, the starting dose of Mitoxantrone Ebewe, when used in combination therapy with other chemotherapy drugs, should be 2 to 4 mg / m 2 lower than when Mitoxantron Ebewe alone is used.
Acute myeloid leukemia
For single use in case of relapse (when your cancer has returned):
The recommended dose for initial treatment is 12 mg / m 2 body surface area, given as a single intravenous dose for five consecutive days (total 60 mg / m 2 body surface area over five days).
When used in combination with other chemotherapy drugs:
Your doctor will decide exactly what dose you should receive. Your dosage may need to be adjusted if:
- the combination of the drugs reduces the bone marrow’s production of both white and red blood cells and platelets to a greater degree than just Mitoxantron Ebewe.
- you have severe liver or kidney problems.
Treatment of blast crisis in ( chronic ) myeloid leukemia
For single use in case of relapse
The recommended dose for relapse is 10 to 12 mg / m 2 body surface area, given as a single intravenous dose for five consecutive days (total 50 to 60 mg / m 2 ).
Advanced castration-resistant prostate cancer
The recommended dose is 12 to 14 mg / m 2, given as a short-term intravenous infusion at 21-day intervals, in combination with low oral doses of corticosteroids ( cortisone that inhibits the immune system).
Multiple sclerosis
You will receive Mitoxantron Ebewe under the supervision of a specialist doctor with experience in chemotherapy for the treatment of multiple sclerosis.
The recommended dose of mitoxantrone is normally 12 mg / m 2 body surface area, given as a short-term intravenous infusion (approximately 5 to 15 minutes) that can be repeated every three months. The total dose over a lifetime must not exceed 72 mg / m 2.
If mitoxantrone is given repeatedly, dose adjustments should be made depending on the size of the white and red blood cells and platelets and how long they last.
Elderly patients
Elderly patients should receive the lowest recommended starting doses due to the risk of hepatic, renal, or cardiac impairment and any other diseases or treatment with other drugs.
If you have any further questions on the use of this product, ask your doctor, pharmacist, or nurse.
Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
The most serious side effects are damage to the heart (cardiac toxicity) and myelosuppression (decreased formation of blood cells and platelets in the bone marrow ).
Some side effects can be serious
If any of the following happens, tell your doctor immediately:
- If you become pale and feel weak or suffer from sudden shortness of breath, this may be a sign of decreased red blood cell count .
- Abnormal bruising or bleeding, such as bloody cough, vomiting or urine, or black stools (which may indicate a decrease in the number of platelets ).
- New or worsening breathing difficulties.
- Chest pain, shortness of breath, altered heart rate (fast or slow), fluid retention (swelling) in the ankles or legs (which may indicate heart problems).
- Severe, itchy hives or swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty swallowing or breathing), or if you feel you are about to faint, these may be signs of a severe allergic reaction reaction .
- Fever or infection is.
For patients being treated for cancer:
Very common (may affect more than 1 user in 10):
- Infection is
- Low number of red blood cells , which can cause feelings of fatigue and shortness of breath ( anemia ). You may need a blood transfusion .
- Low number of certain types of white blood cells ( neutrophils and leukocytes )
- Nausea
- Vomiting
- Hair loss
Common (may affect up to 1 in 10 people):
- Low platelet count , which may cause bleeding and bruising
- Low number of a certain type of white blood cell ( granulocytes )
- Fatigue, feeling of weakness and lack of energy
- Loss of appetite
- Myocardial infarction
- Shortness of breath
- Constipation
- Diarrhea
- Inflammation of the mouth and lips
- Fever
- Congestive heart failure (a serious condition in which the heart cannot pump enough blood)
Uncommon (may affect up to 1 in 100 people):
- Decreased formation of blood cells and platelets in the bone marrow . The inhibition of bone marrow can be stronger or more prolonged if you have previously been treated with chemotherapy , cancer drugs or undergone radiation therapy.
- Insufficient formation of blood cells in bone marrow (bone marrow failure)
- Abnormal white blood cell count
- Severe allergic reaction ( anaphylactic reaction , including anaphylactic shock ). You may experience sudden itchy hives , swollen hands, feet, ankles, face, lips, mouth or throat, which may cause difficulty swallowing or breathing and you may feel dizzy.
- Upper respiratory tract infection
- Urinary tract infection
- Blood poisoning ( sepsis )
- Infections caused by microorganisms that do not normally cause diseases when the immune system is good (opportunistic infections )
- Cancer of the white blood cells ( acute myeloid leukemia [AML])
- Abnormal bone marrow , which causes the formation of abnormal blood cells and leads to leukemia ( myelodysplastic syndrome [MDS])
- Weight changes
- Metabolic disorders (effects on heart rhythm and kidney problems caused by substances from the breakdown of cancer cells, so-called tumor lysis syndrome)
- Anxiety
- Confusion
- Headache
- Knitting
- Irregular heartbeat or slow heartbeat
- Abnormal ECG
- Reduction in the amount of blood that the left ventricle of the heart can pump, without causing any symptoms
- Bruises
- Heavy bleeding
- Low blood pressure
- Abdominal pain
- Bleeding in the stomach or intestines, this may manifest as blood in vomit and stool, or black, tar-like stool
- Mucositis
- Pancreatitis
- Abnormal liver values
- Skin inflammations ( erythema )
- Nail disorders (eg detachment of the nail from the nail bed , altered nail surface and structure)
- Rash
- Discolored whites of the eyes
- Skin discolorations
- Leakage of fluid to surrounding tissue (extravasation):
- Redness ( erythema )
- Swelling
- Pain
- Abnormal liver and kidney values in blood samples (elevated levels of aspartate aminotransferase , creatinine and urea-bound nitrogen in the blood)
- Kidney damage, which causes swelling and feeling of weakness ( nephropathy )
- Discolored urine
- Swelling ( edema )
- Taste disorders.
- Abnormal missed periods ( amenorrhea )
Rare (may affect up to 1 in 1,000 people):
- Damage to the heart muscle, which prevents it from functioning properly ( cardiomyopathy ).
- Pneumonia
For patients treated for multiple sclerosis:
Very common (may affect more than 1 user in 10)
- Infection er, including upper respiratory tract infections and urinary tract infections
- Nausea
- Hair loss
- Abnormal missed periods ( amenorrhea )
Common (may affect up to 1 in 10 people):
- Low number of red blood cells , which can cause feelings of fatigue and shortness of breath ( anemia ). You may need a blood transfusion .
- Low number of certain types of white blood cells ( granulocytes and leukocytes )
- Constipation
- Vomiting
- Diarrhea
- Inflammation of the mouth and lips
- Low white blood cell count
- Headache
- Irregular heartbeat
- Abnormal ECG
- Reduction in the amount of blood that the left ventricle of the heart can pump, without causing any symptoms
- Abnormal liver values in blood tests (elevated levels of aspartate aminotransferase )
Uncommon (may affect up to 1 in 100 people)
- Pneumonia
- Blood poisoning ( sepsis )
- Infections caused by microorganisms that do not normally cause diseases when the immune system is normal (opportunistic infections ).
- Cancer of the white blood cells ( acute myeloid leukemia [AML])
- Abnormal bone marrow , which causes the formation of abnormal blood cells and leads to leukemia ( myelodysplastic syndrome [MDS])
- Insufficient formation of blood cells in bone marrow (bone marrow failure)
- Decreased formation of blood cells and platelets in the bone marrow . The inhibition of bone marrow can be stronger or more prolonged if you have previously been treated with chemotherapy or undergone radiation therapy.
- Low platelet count , which may cause bleeding and bruising
- Low number of a certain type of white blood cell ( neutrophils )
- Severe allergic reaction ( anaphylactic reaction , including anaphylactic shock ). You may experience sudden itchy hives , swollen hands, feet, ankles, face, lips, mouth or throat, which may cause difficulty swallowing or breathing and you may feel dizzy.
- Loss of appetite
- Weight changes
- Anxiety
- Confusion
- Knitting
- Fatigue, feeling of weakness and lack of energy
- Congestive heart failure (a serious condition in which the heart cannot pump enough blood)
- Damage to the heart muscle, which prevents it from functioning properly ( cardiomyopathy ).
- Slow heartbeat
- Myocardial infarction
- Unusual bruises
- Heavy bleeding
- Low blood pressure
- Shortness of breath
- Abdominal pain
- Bleeding in the stomach or intestines, this may manifest as blood in vomit and stool, or black, tar-like stool
- Mucositis
- Pancreatitis
- Abnormal liver values
- Nail disorders (eg detachment of the nail from the nail bed , altered nail surface and structure)
- Rash
- Discolored whites of the eyes
- Skin discolorations
- Leakage of fluid to surrounding tissue (extravasation):
- Redness ( erythema )
- Swelling
- Pain
- Burning and / or discoloration of the skin
- Cell death, which can lead to the removal of dead tissue and the transplantation of new skin
- Abnormal liver and kidney values in blood samples (elevated levels of creatinine and urea-bound nitrogen in the blood)
- Kidney damage, which causes swelling and feeling of weakness ( nephropathy )
- Discolored urine
- Swelling ( edema )
- Fever
- Sudden death
Rare (may affect up to 1 in 1,000 people):
No.
How to store Mitoxantron Ebewe
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label after EXP. The expiration date is the last day of the specified month.
No special storage instructions.
The concentrate should be diluted immediately after the first opening.
Diluted solution is stable for 24 hours at room temperature and a maximum of 3 days at 2–8 ° C.
From a microbiological point of view, the diluted product should be used immediately. If the product is not used immediately, the storage time and storage conditions before use are the user’s responsibility. The storage time should not normally exceed 24 hours at 2 to 8 ° C unless dilution has taken place under controlled, validated aseptic conditions.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.
Contents of the pack and other information
Content declaration
- The active substance is mitoxantrone (as hydrochloride). Each ml contains 2 mg mitoxantrone (as hydrochloride).
- The other ingredients are sodium chloride, sodium acetate, concentrated acetic acid, sodium sulphate, hydrochloric acid (for pH adjustment) and water for injections.
What the medicine looks like and contents of the pack
The clear, blue solution, is free from particles. Packed in colorless glass vials, in outer carton. 1, 5, or 10 identical vials containing 10 mg mitoxantrone per 5 ml or 20 mg mitoxantrone per 10 ml are packaged in a carton.
Pack sizes: 1 x 5 ml, 5 x 5 ml, 10 x 5 ml, 1 x 10 ml, 5 x 10 ml and 10 x 10 ml.
Not all pack sizes may be marketed.
Marketing Authorization Holder and Manufacturer
Marketing Authorisation Holder
EBEWE Pharma Ges. Mb H Nfg. KG, Mondseestrasse 11, 4866 Unterach, Austria
Manufacturer
EBEWE Pharma Ges. Mb H Nfg. KG, Mondseestrasse 11, 4866 Unterach, Austria
or
Fareva Unterach GmbH, Mondseestrasse 11, 4866 Unterach, Austria
Contact the representative of the marketing authorization holder if you would like to know more about this medicine.
Local representative
Sandoz A / S, Edvard Thomsens Vej 14, 2300 Copenhagen S, Denmark