Mitoxantrone 2 Mg/Ml Concentrate For Solution For Infusion
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PACKAGE LEAFLET: INFORMATION FOR THE USER
Mitoxantrone 2 mg/ml concentrate for solution for infusion
Mitoxantrone
Read all of this leaflet carefully before you start using this medicine because it contains important information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor, pharmacist or nurse.
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.
What is in this leaflet
1. What Mitoxantrone 2 mg/ml solution is and what it is used for
2. What you need to know before you take Mitoxantrone 2 mg/ml solution
3. How to take Mitoxantrone 2 mg/ml solution
4. Possible side effects
5. How to store Mitoxantrone 2 mg/ml solution
6. Contents of the pack and other information
1. What Mitoxantrone 2 mg/ml solution is and what it is used for
Mitoxantrone 2 mg/ml solution belongs to the group of medicines known as antineoplastic or anti-cancer drugs. It also belongs to the subgroup of anti-cancer medicines called anthracyclines. Mitoxantrone 2 mg/ml solution prevents cancer cells from growing, as a result of which they eventually die.
Use in the treatment of:
• Advanced stage (metastatic form) of breast cancer.
• A certain form of lymph node cancer (non-Hodgkin's lymphoma).
• Acute non-lymphocytic leukaemia in adults. Leukaemia is a type of cancer of the blood in which the bone marrow makes too many white blood cells.
For the treatment of the aforementioned cancers, Mitoxantrone 2mg/ml solution can be used alone or in combination with other anti-cancer medicines.
• Pain caused by prostate cancer at an advanced stage when:
• The prostate cancer does not respond well to the hormone treatment (i.e. is not sensitive)
• The existing pain-relieving treatments do not work adequately for you or if you cannot take adequate pain-relieving medicines.
Mitoxantrone 2 mg/ml solution is combined in this case with a low dose of corticosteroids e.g. prednisone).
2. What you need to know before you take Mitoxantrone 2 mg/ml solution
Do not use Mitoxantrone 2 mg/ml solution
• If you are hypersensitive (allergic) to Mitoxantrone or any of the other ingredients of this medicine (listed in section 6).
• If your bone marrow function is severely depressed (if too few red blood cells are being made).
• If you are breast-feeding (for further information about breast-feeding read the section “Pregnancy and breast-feeding”).
Mitoxantrone 2 mg/ml solution is not indicated for subcutaneous (administered under the skin), intramuscular (administered in a muscle), intrathecal (injected into the space under the brain or spinal cord) or intra-arterial injection (injected into the artery).”
Warnings and precautions
• If your bone marrow is not working well (is depressed) or if you are in generally poor health
- your doctor will carry out blood tests more often, in which he will in particular monitor the number of white blood cells (neutrophilic leukocytes) in the blood.
• If you have ever
- undergone radiotherapy of the chest.
- had a heart abnormality.
In these cases it is to be expected that you will develop severe heart problems such as:
- heart failure or deterioration in heart function.
• If you have these heart problems:
- you must nevertheless receive the full dose of Mitoxantrone 2 mg/ml solution
- regular monitoring must be carried out to see whether your heart is working properly.
• If you have an infection. This should be treated before the treatment with Mitoxantrone 2 mg/ml solution is started.
• You should also be aware that Mitoxantrone 2 mg/ml solution can cause discolouration of:
- your urine (your urine can be stained blue-green for up to a day after treatment)
- your skin and nails (these can be stained blue).
- the whites of your eyes (these can be stained blue).
All these discolourations are transient and can last a few days.
Careful supervision by your doctor is recommended when you have severe liver failure (damage of liver), oedema (accumulation of fluid in the connective tissue), ascites (accumulation of fluid in the abdominal cavity) or pleural effusion (abnormal amount of fluid around the lung).
Using other medicines
Inform your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
You should be extra careful if you are using one of the following types of medicines:
- Other bone marrow suppressant medicines which reduce the activity of the bone marrow (myelosuppressive, e.g. anti-cancer medicines). These can do more damage to your bone marrow if they are used together with Mitoxantrone. These can also increase the damage Mitoxantrone does to your bone marrow.
- Other products which can damage the heart (called anthracyclines), since the damage these medicines cause to your heart can be increased.
- Topoisomerase II inhibitors (a group of anti-cancer medicines, including Mitoxantrone) in combination with other anti-cancer medicines and/or radiotherapy against cancer. This can lead to:
- A cancer of the white blood cells (acute myeloid leukaemia).
- A bone marrow abnormality which causes abnormally formed blood cells which can develop into leukaemia (myelodysplastic syndrome MDS).
- Vaccinations. Immunisation (protection against the vaccination substances) may not work during treatment with Mitoxantrone.
Pregnancy, breast-feeding and fertility
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Mitoxantrone damage your unborn child. Therefore you should not receive Mitoxantrone if:
- you are pregnant (specifically the first three months of the pregnancy).
- you might be pregnant, or wish to become pregnant.
If you become pregnant during the treatment with Mitoxantrone 2 mg/ml solution , you must tell your doctor immediately and stop the treatment with Mitoxantrone 2 mg/ml solution . You should avoid becoming pregnant. If you or your partner are being treated with Mitoxantrone, you must use an effective method of contraception during the treatment and for at least 6 months after discontinuing the treatment.
You must not be treated with Mitoxantrone 2 mg/ml solution during the breast-feeding period. Breast-feeding must be stopped before the treatment is started. Mitoxantrone can reach the baby via breast milk.
Driving and using machines
The use of Mitoxantrone 2 mg/ml solution can have a minor or moderate effect on your ability to drive and use machines. This is caused by the possible side effects (see under 4. “Possible side effects”).
If you suffer from these side effects, do not drive any vehicles and/or use any machines.
Important information about some of the ingredients of Mitoxantrone 2 mg/ml solution
This medicinal product contains 0.148 mmol sodium/ ml. The sodium content per injection for:
- 1 x 5 ml vial is 0.739 mmol sodium.
- 1 x 10 ml vial is 1.478 mmol sodium.
Caution is advised in patients on a controlled sodium diet.
3. How to use Mitoxantrone 2 mg/ml solution
Always take/use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.
Posology and method of administration
Mitoxantrone 2 mg/ml solution will be given to you only by a doctor or nurse. It must always be administered as an intravenous infusion (in a vein) and must always be diluted before use. The infusion liquid can leak out of the vein into the tissue (extravasation). If this happens, the infusion must be stopped and restarted in another vein. You should avoid contact with Mitoxantrone 2 mg/ml solution, especially with the skin, mucous membranes and eyes. The individual dose of Mitoxantrone 2 mg/ml solution is calculated by your doctor. The recommended dose is based on your body surface area, which is calculated in square metres. In addition your blood will be tested regularly during the treatment. The dosage of the medicine will be adjusted in accordance with the results of these tests.
Use in children and adolescents aged up to 18 years:
There is little experience in children and adolescents.
The usual dose is
Metastatic breast cancer, Non-Hodgkin's lymphoma
If Mitoxantrone 2 mg/ml solution is used alone:
- the initial dose is 14 mg per square metre body surface area, administered in 1 single intravenous dose. This can be repeated after 21 days if your blood values have returned to acceptable levels.
If your bone marrow reserve is low, you should initially receive a lower dose of 12 mg per square metre.
Your doctor will decide precisely which subsequent dosage you need. This depends on how much and for how long your bone marrow activity has been reduced (depressed).
If used in combination therapy (e.g. with other cytostatics such as cyclophosphamide and 5-fluorouracil, or methotrexate and mitomycin C):
- As a guide, you should receive 2 to 4 mg less per square metre than when Mitoxantrone 2 mg/ml solution is used alone.
Acute non- lymphocytic leukaemia
If used alone for a recurrence (return of the cancer):
- the recommended dose is 12 mg per square metre, administered as a once daily intravenous dose for 5 days (total of 60 mg per square metre per 5 days).
If used with other agents against cancer (e.g. cytarabine, etoposide):
- Your doctor will decide exactly what dose you must be administered. This dose must be adjusted if:
•The combination of medicines depresses the bone marrow more than Mitoxantrone alone.
•If you suffer from liver or renal failure.
To relieve pain in hormone-refractory prostate cancer
L
The recommended dose is 12 mg per square metre and is administered:
- as an intravenouis infusion over a short period.
- at an interval of 21 days.
- in combination with orally administered 10 mg prednisone (a hormonal medicine that suppresses the immune system).
Your doctor will decide about any adjustment of the dosage. This is dependent on the extent and the duration of the reduction (suppression) of bone marrow activity.
If you use more Mitoxantrone 2 mg/ml solution than you should
Your liver, kidneys, gastrointestinal tract and your ability to make red blood cells can be affected. Rarely, severe leukopenia (abnormally low white blood cell count) with an infection can result in death. The doctor will monitor your condition closely and treat you for these symptoms.
If you have any further questions on 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 everybody gets them.
If any of the following happen, tell the doctor
immediately:
• reduction in red blood cells, which can make the skin pale and cause weakness or breathlessness
• bruising, unusual bleeding, such as coughing up blood, blood in your vomit or urine, or black stools (platelet reduction)
• breathing difficulties
• chest pain
• abnormal heart beats
• severe allergic reaction - you may experience a sudden itchy rash (hives), swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty in swallowing or breathing), and you may feel you are going to faint.
Very common (may affect more than 1 in 10
people):
- Myelosuppression (reduced activity of the bone marrow). This limits the quantity of Mitoxantrone that can be administered. Your bone marrow can be more depressed or depressed for a longer period if
•you have had chemotherapy.
•you have had radiotherapy.
- Bone marrow hypoplasia (abnormal reduction in the number of blood cells in an organ or in tissue.
- Transient leukopenia: a low number of leukocytes (white blood cells) with a minimum at 10-13 days after the treatment. Leukopenia is severe in 6% of cases.
- Anaemia (if the body has a shortage of red blood cells).
- Low number of a special type of white blood cells (granulocytopenia and neutropenia).
- Abnormal white blood cell count (leukocytes).
- Nausea (feeling sick) and vomiting (mild form) occurs in approximately half of all patients. Severe nausea and vomiting occur in 1% of patients.
- Stomatitis (inflammation of the inside of the mouth).
- Diarrhoea.
- Abdominal pain
- Constipation.
- Mucositis (inflamed mucous membranes).
- Changed sense of taste.
- Alopecia (hair loss). Some hair loss occurs in half of all patients. Severe hair loss occurs rarely.
- Transient change in the ECG after long-term treatment.
- Arrhythmia (heart rhythm disturbances).
- Increased urea concentration in the blood.
- Infections.
- Infections of the upper airways.
- Infections of the urinary tract.
- Bleeding.
- Fever.
- Absence of menstruation.
Common (may affect up to 1 in 10 people):
- Dizziness
- Drowsiness.
- Neuritis (infection of the nerves).
- Convulsion (seizures).
- Mild form of paraesthesia (tingling).
- Headache.
- The volume of blood that the left ventricle can pump is reduced, but there are no symptoms.
- Inflammation of the nasal mucous membranes (runny and itchy nose).
- Discolouration of the urine. This occurs 24 hours after the administration of Mitoxantrone.
- Renal disturbances (nephrotoxicity).
- Elevated liver enzyme concentrations (in blood tests).
- Changes in chemical values in the blood (elevated creatinine and nitrogen concentration in the blood).
- Thrombocytopenia (a low number of platelets -a blood cell involved in the coagulation of the blood).
- Heart failure after long-term treatment, sinus bradycardia (slowed heart beat).
- Heart problems which can cause shortness of breath or swelling of the ankles.
- Chest pain.
- Gastrointestinal bleeding.
- Red rash.
- Erythema (skin inflammations).
- Anorexia (loss of appetite).
- Pneumonia (lung inflammation).
- Sepsis (blood poisoning).
- Hypotension (low blood pressure).
- Fatigue.
- Oedema (swelling).
- Hepatotoxicity (liver abnormalities).
Uncommon (may affect up to 1 in 100 people)
- Dyspnoea (shortness of breath).
- Blue staining of the skin and nails.
- Transient blue staining of the whites of the eyes.
- Allergic reactions including eczema (skin rash or itching), dyspnoea (shortness of breath), hypotension (low blood pressure).
- Anxiety.
- Confusion.
element in combination therapy with other medicines. It also occurred when Mitoxantrone was used alone.
Very rare (may affect up to 1 in 10,000 people)
- Changes in weight.
Unknown (frequency cannot be estimated from the available data)
- Acute leukaemia (cancer of the white blood cells).
- Acute myeloid leukaemia (AML, cancer of the white blood cells).
- Myelodysplastic syndrome (MDS), a bone marrow abnormality which causes the formation of abnormal blood cells which leads to leukaemia. AML and MDS can be caused by topoisomerase II inhibitors if these are used with other anti-cancer medicines and/or radiotherapy. Topoisomerase II inhibitors are a group of anti-cancer medicines to which Mitoxantrone belongs.
- Conjunctivitis (inflammation of the mucous membranes in the eye and the eyelids).
- Cardiomyopathy (weakening or change in the structure of the heart muscle).
- Myocardial infarction (heart attack).
- Pancreatitis (inflammation of the pancreas).
- Opportunistic infections (infections which are caused by microorganisms which do not normally cause diseases with a healthy immune system).
- Hyperuricaemia (elevated concentration of uric acid in the blood).
- Extravasation (leakage of medicines form the vein into the surrounding tissue which can lead to •Erythema (reddening)
•Swelling
•Pain
•Burning feeling and/or discolouration of the skin •Tissue necrosis (death of tissue cells) which can lead to the need for excision (the process of removing dead cells) and skin transplantation
- Phlebitis (local vein infection).
- Bruises.
- Weakness.
- Anaphylactic reaction including anaphylactic shock (allergic reaction which causes breathing problems, swelling of skin, lips and tongue).
- Nail abnormalities (e.g. detachment of the nail from the nail bed, changes in nail texture and structure).
If you have leukaemia, you will have more frequent and severe side effects. In particular inflammation of the oral mucosa (inflammation of the inside of the mouth) and mucositis (inflammation of the mucous membranes) can occur.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the the national reporting system (see contact details below). By reporting side effects you can help provide more information on the safety of this medicine.
United Kingdom
Yellow Card Scheme
Website: www.mhra.gov.uk/vellowcard
Malta
ADR Reporting
Website:www.medicinesauthority.gov.mt/adrportal
5. How to store Mitoxantrone 2 mg/ml solution
Keep out of the sight and reach of children.
Do not use Mitoxantrone 2 mg/ml solution after the expiry date which is stated on the package after EXP The expiry date is the last day of the month. Unopened vial and diluted product: Store below 25°C. Do not refrigerate or freeze.
Chemical and physical stability of the diluted product has been demonstrated for a period of 7 days or 14 days at 15-25°C and 2-8 °C respectively in partially used vials.
From a microbiological point of view, unless the method of opening/reconstitution/dilution precludes the risk of microbial contamination, the product should be used immediately.
If not used immediately, in-use storage times and conditions are the responsibility of the user.
Do not throw away medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
6. Contents of the pack and other information
The active substance is Mitoxantrone hydrochloride, equivalent to 2 mg/ml Mitoxantrone.
The other ingredients are: sodium chloride, anhydrous sodium acetate, glacial acetic acid, water for injections.
What Mitoxantrone 2 mg/ml solution looks like and contents of the pack
Concentrate for solution for infusion in a glass vial with a rubber stopper.
1 vial containing 5 ml concentrate for solution for infusion contains 10 mg Mitoxantrone (as hydrochloride).
1 vial containing 10 ml concentrate for solution for infusion contains 20 mg Mitoxantrone (as hydrochloride).
1 vial containing 15 ml concentrate for solution for infusion contains 30 mg Mitoxantrone (as hydrochloride).
Appearance: Dark blue solution
Marketing Authorisation Holder and Manufacturer
Accord Healthcare Limited
Sage House, 319, Pinner Road, North Harrow,
Middlesex, HA1 4HF, United Kingdom
Rare (may affect up to 1 in 1,000 people) This leaflet was last revised in 01/2015.
- Tumour lysis syndrome. This causes hyperuricaemia, hyperkalaemia and hyperphosphataemia (elevated concentrations of uric acid, potassium, phosphate and reduced concentration of calcium in the blood). This occurred when Mitoxantrone was used as an