Strimax 2 Mg/Ml Concentrate For Solution For Infusion
Package leaflet: Information for the use Strimax 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, nurse or pharmacist.
- This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
- 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 Strimax is and what it is used for
2. What do you need to know before you use Strimax
3. How to use Strimax
4. Possible side effects
5. How to store Strimax
6. Contents of the pack and other information.
1. What Strimax is and what it is used for
Strimax 2 mg/ml concentrate for solution for infusion (referred to as Strimax throughout this leaflet) contains Mitoxantrone (as hydrochloride). It is an anti-cancer medicine belonging to the group of medicines called anthracyclines and related substances.
Chemotherapy (treatment with an anti-cancer medicine) with mitoxantrone is used in the treatment of breast cancer, adult leukaemia and non-Hodgkin’s lymphoma.
2. What you need to know before you use Strimax Do not use Strimax:
• By injection into the layer of fat between the skin and the muscle (subcutaneous), an injection given into a muscle (intramuscular), injection into the sheath surrounding the spinal cord (intrathecal) or injection within an artery (intra-arterial).
• if you are suffering from severe bone marrow suppression.
• if you are breast feeding (for further information see Pregnancy and breast-feeding).
• if you are allergic to mitoxantrone or any of the other ingredients of this medicine (listed in section 6).
Warnings and precautions
Talk to your doctor before receiving Strimax:
• if you have problems with bone marrow or if you have a poor general health
- Your doctor will test your blood more frequently, particularly with regard to the number of white blood cells (Neutrophils).
• if you are being treated with other types of cancer chemotherapy and/or radiotherapy
• if you have heart disease, prior treatment with anthracyclines (which belong to the same group of medicines than mitoxantrone) or prior thoracic radiotherapy, You are more likely to develop more serious heart problems such as heart failure or reduced cardiac function. You may receive the full dose of Strimax however, as a precaution you will have regular examinations of cardiac function.
• if you have problems with your liver
• if you have an infection. Any infections should be treated either before or after treatment with Strimax.
• You must be aware that Strimax can cause discoloration of
- Urine (may be blue-green for upto one day after treatment)
- Skin and nails (can be coloured blue)
- Eyes (can be coloured blue)
- Any discoloration is temporary and could last upto a few days.
Vaccinations are not recommended whilst you are undergoing treatment with mitoxantrone. Some vaccines may not be effective if they are given while you are taking mitoxantrone at the same time.
Other medicines and Strimax
Tell your doctor if you are taking, have recently taken or might take other medicines.
Strimax when given with other medicines used in the treatment of cancers and/or radiotherapy may cause a certain type of blood cancer (leukaemia) or bone marrow disorder called myelodysplasia.
Special care is needed if you are to receive the following medicines whilst being treated with mitoxantrone.
• medicines that may damage your heart (e.g Anthracyclines) because the adverse effects these medicines have on the heart can be strengthened
• Topoisomerase II inhibitors (a groups of anticancer medicines including mitoxantrone) in combination with other chemotherapy and/or radiotherapy. These can cause
- Cancer of white blood cells (acute myeloid leukemia, AML)
- A bone marrow disorder that causes abnormally shaped blood cells and leads to leukemia (myelodysplastic syndrome)
• Other medicinal products that may cause bone marrow suppression.
You may have regular blood tests and tests to check your heart.
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
Pregnancy and breast-feeding
If you are pregnant, planning to become pregnant or breast-feeding you should not be given Strimax unless your doctor has specifically recommended it. Breast-feeding should be stopped before starting treatment and your doctor will tell you when you can restart after the treatment has finished.
Men and women undergoing treatment with this medicine should use effective contraception during treatment and for at least 6 months after treatment has stopped.
Driving and using machines
Mitoxantrone has been reported to cause drowsiness and confusion. Do not drive or operate machinery or take part in activities where these symptoms could put you or others at risk.
Strimax contains sodium metabisulfite
This medicine contains sodium metabisulphite, which may rarely cause severe hypersensitivity reactions and bronchospasm.
Strimax contains sodium
This medicine contains 3.2 mg of sodium per 1 ml of solution. This should be taken into consideration by patients on a controlled sodium diet.
3. How to use Strimax
Strimax is a powerful medicine and your doctor will want to do a number of tests on you before you start your treatment. These tests will continue during the course of your treatment and will include both blood tests to monitor your liver and kidney function, and also heart tests such as ECG.
Your medicine will be given to you in a hospital. It will be diluted with a saline or dextrose solution and given as a drip into a vein. The dose will depend on your medical condition, whether other medicines are to be given at the same time and on a measure of your body size.
The duration of your treatment will depend on your condition and how you respond to the treatment.
For Breast cancer and non-Hodgkins lymphoma:
You will usually receive a starting dose of 14mg/m2 of your body surface area. This dose may be adjusted depending on your condition or whether you have previously received anticancer treatment. The time between treatments is not normally less than 21 days and will depend on your response to the medicine, which will be monitored by your doctor. If Strimax is used with other medicine the starting dose may be reduced to between 10 and 12 mg/m2 of your body surface area.
For combination therapy (eg with other chemotherapeutic agents such as cyclophosphamide and 5-fluorouracil, methothrexate and mitomycin C), as a guide, you should receive 2 to 4 mg/sq.m2 less than when Strimax is used alone.
For Acute non-lymphocytic Leukaemia:
For exclusive use in relapse (when your cancer has come back), the recommended dose is 12mg/m2 given as a single intravenous dose daily for five consecutive days.
When used in combination with other chemotherapeutic agents (eg cytosine arabinoside), your doctor will determine the exact dose of each medicine you should receive.
Your dosage may need adjustment if
• The combination of medicines causes more severe suppression of bone marrow than if Strimax were used alone.
• You have liver or kidney disease.
Use in children and adolescents
Experience treating children and adolescents with Strimax is limited.
If you are given more Strimax than you should
As a doctor or nurse will be giving you your medicine, it is unlikely that you will receive more medicine than you should. However, if you have any concerns you should let your doctor or nurse know immediately.
In the event of an overdose your liver, kidney, digestive system and your body’s ability to produce blood cells may be affected. In rare cases, severe leukopenia (sharp decrease in the number of white blood cells) with infection resulting in death may occur.
Your doctor will carefully monitor your condition and treat these symptoms.
If you have any further questions on use of this medicine, ask your doctor or nurse.
4. Possible side effects
Like all medicines, this medicine can cause side effects although not everybody gets them.
A few people given mitoxantrone may develop a severe allergic reaction.
If any of the following happen, tell your doctor immediately:
• breathing difficulties
• chest pain or palpitations
• 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.
• if the medicine leaks outside the vein whilst it is being injected (the surrounding tissue may be severely damaged and may need to be operated on or require a skin graft)
The above serious side effects need urgent medical attention.
If you experience any of the following tell your doctor as soon as possible:
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
- you have had infections
• 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.
• Low number of a special type of white blood cells (granulocytopenia and neutropenia).
• Anaemia (if the body has a shortage of red blood cells).
• Thrombocytopenia (a low number of platelets - a blood cell involved in the coagulation of the blood)
• Abnormal white blood cell count (leukocytes).
• Fever
• Transient change in the ECG after long-term treatment.
• Haemorrhagia
• Nausea (feeling sick) and vomiting (mild form) occurs in approximately half of the patients. Severe nausea and vomiting occur in 1% of patients.
• Mucositis (inflamed mucous membranes).
• Stomatitis (inflammation of the inside of the mouth).
• Diarrhoea.
• Abdominal pain
• Constipation.
• Anorexia (loss of appetite).
• Alopecia (hair loss). Some hair loss occurs in half of the patients. Severe hair loss occurs rarely.
• Infections
Common (may affect up to 1 in 10 people)
• Infections of the upper airways.
• Pneumonia (lung inflammation).
• Sepsis (blood poisoning).
• Fatigue
• Oedema (swelling)
• Anorexia (loss of appetite).
• The volume of blood that the left chamber can pump is reduced, but there are no symptoms.
• Cardiac insufficiency.
• Heart failure after long-term treatment.
• Sinus bradycardia (slowed heart beat).
• Chest pain.
• Hypotension (low blood pressure).
• Gastrointestinal bleeding.
• Hepatotoxicity (liver abnormalities).
• Rash.
• Erythema (skin inflammations).
• Renal disturbances (nephrotoxicity).
Uncommon (may affect up to 1 in 100 people)
• Immunosuppression
• Anaphylactic reaction including anaphylactic shock (allergic reaction which causes breathing problems, swelling of skin, lips and tongue).
• Allergic reactions including eczema (skin rash or itching), dyspnoea (shortness of breath), hypotension (low blood pressure).
• Anxiety.
• Confusion.
• Dizziness
• Somnolence (Drowsiness)
• Neuritis (infection of the nerves).
• Convulsion (seizures).
• Mild form of paraesthesia (tingling).
• Headache.
• Transient blue staining of the whites of the eyes.
• Conjunctivitis (inflammation of the mucous membranes in the eye and the eyelids).
• Arrhythmia (heart rhythm disturbances).
• Elevated liver enzyme concentrations & bilirubin (in the blood tests).
• Severe impairment of hepatic function.
• Blue staining of the skin and nails.
• Changes in chemical values in the blood (elevated creatinine and nitrogen concentration in the blood).
• Staining of the urine. This occurs 24 hours after the administration of mitoxantrone.
• Amenorrhoea (Absence of menstruation)
Rare (may affect up to 1 in 1000 people)
Cardiomyopathy (weakening or change in the structure of the heart muscle). Hyperuricaemia (high level of uric acid in the blood)
Very rare (may affect up to 1 in 10000 people)
• Changes in weight.
Frequency not known
• Infections of the urinary tract
• 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 anticancer medicines to which mitoxantrone belong.
• Myocardial infarction (heart attack).
• Dyspnoea (shortness of breath).
• Nail abnormalities (e.g. detachment of the nail from the nail bed, changes in nail texture and structure).
- 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).
• Weakness
If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet.
5. How to store Strimax
Keep this medicine out of the sight and reach of children.
Store below 25°C. Do not refrigerate or freeze.
Do not use this medicine after the expiry date which is stated on the package after EXP. The expiry date refers to the last day of that month.
Chemical and physical in use stability of the diluted product has been demonstrated for 24 hours at 25°C and for 72 hours at 2-8°C in:
• Sodium chloride 9 mg/ml (0.9 %),
• Glucose 50 mg/ml (5 %), or
• Sodium chloride 9 mg/ml (0.9 %) and Glucose 50 mg/ml (5 %) solution.
From a microbiological point of view, the diluted product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C.
This medicine will be prepared and administered to you by healthcare staff. Any unused medicine must be disposed of by the healthcare staff.
Do not use this medicine if you notice any visible particles or deterioration.
Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
6. Content of the pack and other information What Strimax contains
The active substance is mitoxantrone (as hydrochloride). Each ml contains 2 mg mitoxantrone (as hydrochloride).
Each 10 ml vial contains 20 mg of mitoxantrone (as hydrochloride).
The other ingredients are glacial acetic acid, sodium acetate anhydrous, sodium chloride, sodium metabisulfite and water for injection.
What Strimax looks like and contents of the pack
The name of your medicine is Strimax 2 mg/ml concentrate for solution for infusion and is a dark blue solution packaged in Type 1flint vials with a rubber stopper and aluminum seal.
The product is available in packs of 1 vial. Each vial contains 10 ml of solution equivalent to 20 mg mitoxantrone.
Marketing Authorisation Holder
Mylan
Potters Bar, Hertfordshire EN6 1TL United Kingdom
Manufacturer
Agila Specialties Polska Sp. z o.o 10, Daniszewska Str, 03-230 Warsaw Poland
This leaflet was last revised in 10/2014.
The following information is intended for medical or healthcare professionals only:
Instructions for use
Strimax should be given by intravenous infusion.
For single use only.
Syringes containing this product should be labelled ‘FOR INTRAVENOUS USE ONLY’.
Care should be taken to avoid contact of mitoxantrone with skin, mucous membranes or eyes. Vials should be dispensed in upright position in order to prevent drops of mitoxantrone collecting in the stopper during preparation and leading to potential aerosolisation of the solution.
Dilute the required volume of Mitoxantrone Injection to at least 50 ml using a solution of
• Sodium chloride 9 mg/ml (0.9 %),
• Glucose 50 mg/ml (5 %), or
• Sodium chloride 9 mg/ml (0.9 %) and Glucose 50 mg/ml (5 %) solution.
Use Leur-lock fittings on all syringes and sets. Large bore needles are recommended to minimise pressure and the possible formation of aerosols. The latter may also be reduced by the use of a venting needle. Administer the resulting solution over not less than 3 minutes via the tubing of a freely running intravenous infusion of the above fluids. Mitoxantrone should not be mixed with other drugs in the same infusion.
If extravasation occurs the administration should be stopped immediately and restarted in another vein.
a) Handling Cytotoxic drugs
Mitoxantrone, in common with other potentially hazardous cytotoxic drugs, should only be handled by adequately trained personnel. Pregnant staff should not be involved in the reconstitution or administration of Mitoxantrone.
Care should be taken to avoid contact of Mitoxantrone with the skin, mucous membranes, or eyes. The use of goggles, gloves and protective gowns is recommended during preparation, administration and disposal and the work surface should be covered with disposable plastic-backed absorbent paper.
Aerosol generation should be minimised. Mitoxantrone can cause staining. Skin accidentally exposed to Mitoxantrone should be rinsed copiously with warm water and if the eyes are involved standard irrigation techniques should be used.
b) Spillage disposal
The following clean-up procedure is recommended if Mitoxantrone is spilled on equipment or environmental surfaces. Prepare a 50% solution of fresh concentrated bleach (any recognised proprietary brand containing either sodium or calcium hypochlorite) in water. Wet absorbent tissues in the bleach solution and apply the wetted tissues to the spillage. The spillage is deactivated when the blue colour has been fully discharged. Collect up the tissues with dry tissues. Appropriate protective equipment should be worn during the clean-up procedure.
For single use only. Any unused product or waste material should be disposed of in accordance with local requirements.
All Mitoxantrone contaminated items (e.g. syringes, needles, tissues etc.) should be treated as toxic waste and disposed of accordingly. Incineration is recommended.
Posology and method of administration
FOR INTRAVENOUS USE ONLY.
Mitoxantrone should be given by intravenous infusion.
Mitoxantrone concentrate must be diluted prior to use.
Care should be taken to avoid contact of mitoxantrone with skin, mucous membranes or eyes. See section 6.6 of the SPC, Instructions for use and handling for further directions.
For single use only. Any unused solution should be discarded.
Syringes containing this product should be labeled ‘MITOXANTRONE, FOR INTRAVENOUS USE ONLY’.
Metastatic breast cancer, Non-Hodgkin’s lymphoma: a) Single Agent Dosage:
The recommended initial dosage of Mitoxantrone as a single agent is 14 mg/m2 of body surface area, given as a single intravenous dose which may be repeated at 21-day intervals. A lower initial dosage (12 mg/m2 or less) is recommended in patients with inadequate bone marrow reserves e.g. due to prior chemotherapy or poor general condition.
Dosage modification and the timing of subsequent dosing should be determined by clinical judgment depending on the degree and duration of myelosuppression. For subsequent courses the prior dose can usually be repeated if white blood cell and platelet counts have returned to normal levels after 21 days. The following table is suggested as a guide to dosage adjustment in the treatment of metastatic breast cancer and non-Hodgkin's lymphoma according to haematological nadir (which usually occurs about 10 days after dosing).
Nadir after prior dose:
|
WBC (per mm3) |
Platelets (per mm3) |
Time to recovery |
Subsequent dose after adequate haematological recovery |
|
>1,500 AND |
>50,000 |
21 days |
Repeat prior dose after recovery |
|
>1,500 AND |
>50,000 |
>21 days |
Withhold until recovery then repeat prior dose |
|
<1,500 OR |
<50,000 |
Any duration |
Decrease by 2 mg/m2 from prior dose after recovery |
|
<1,000 OR |
<25,000 |
Any duration |
Decrease by 4 mg/m2 from prior dose after recovery |
b) Combination Therapy:
Mitoxantrone has been administered as a component of a combination therapy. In cases of metastatic breast cancer, combinations of Mitoxantrone with other cytotoxic agents including cyclophosphamide and 5-fluorouracil, or methotrexate and mitomycin C, appeared to be effective. For information on dose adjustments and method of administration, please refer to the published literature.
As a guide, when Mitoxantrone is used in combination chemotherapy with another myelosuppressive agent, the initial dose of Mitoxantrone should be reduced by 2-4 mg/m2 below the doses recommended for single agent use. Subsequent doses, as outlined in the table above, depend on the degree and duration of myelosuppression.
Adult acute non-lymphocytic leukaemia:
a) Single Agent Dosage in Relapse:
The recommended dosage for remission induction is 12 mg/m2 of body surface area, given as a single intravenous dose daily for five consecutive days (total of 60 mg/m2). In clinical studies with a dosage of 12 mg/m2 daily for 5 days, patients who achieved a complete remission did so as a result of the first induction course.
b) Combination Therapy:
Mitoxantrone has been used in combination regimens for the treatment of acute non-lymphocytic leukaemia (ANLL). Most clinical experience has been with Mitoxantrone combined with cytosine arabinoside. This combination has been used successfully for primary treatment of ANLL as well as in the treatment of relapse.
Use cytarabine between parentheses following the “cytosine arabinoside.
An effective regimen for induction in previously untreated patients has been Mitoxantrone 10-12 mg/m2 IV for 3 days combined with cytosine arabinoside 100 mg/m2 IV for 7 days (by continuous infusion). This is followed by second induction and consolidation courses as thought appropriate by the treating clinician. In clinical studies, duration of therapy in induction and consolidation courses with Mitoxantrone have been reduced to 2 days, and that of cytosine arabinoside to 5 days. However, modification to the above regimen should be carried out by the treating clinician depending on individual patient factors.
Efficacy has also been demonstrated with Mitoxantrone in combination with etoposide in patients who had relapsed or who were refractory to primary conventional chemotherapy. The use of Mitoxantrone in combination with etoposide, as with other cytotoxics, may result in greater myelosuppression than with Mitoxantrone alone.
Reference should be made to the published literature for information on specific dosage regimens. Mitoxantrone should be used by clinicians experienced in the use of chemotherapy regimens. Dosage adjustments should be made by the treating clinician as appropriate, taking into account toxicity, response and individual patient characteristics.
Children and adolescents:
As experience with Mitoxantrone in paediatric leukaemia is limited, dosage recommendations in this patient population cannot at present be given.
Hepatic impairment
Mitoxantrone is not recommended in patients with abnormal liver function tests because its clearance is reduced by hepatic impairment and laboratory measurements cannot predict the degree of this. Therefore, appropriate dose adjustments cannot be recommended. Liver function tests should be performed prior to each course of therapy. Careful supervision is recommended when treating patients with severe hepatic insufficiency. The safety of Mitoxantrone in such patients has not been established.
Method of administration:
For intravenous use only.
Dilute the required volume of Mitoxantrone Sterile Concentrate to at least 50 ml in either of the following infusion solutions: sodium chloride 9 mg/ml (0.9%), glucose 50 mg/ml (5%), or sodium chloride 9 mg/ml (0.9 %) and glucose 50 mg/ml (5 %). Use Leur-lock fittings on all syringes and sets. Large bore needles are recommended to minimise pressure and the possible formation of aerosols.
The latter may also be reduced by the use of a venting needle.
Administer the resulting solution over not less than 3 minutes via the tubing of a freely running intravenous infusion of the above fluids. Mitoxantrone should not be mixed with other drugs in the same infusion.
If extravasation occurs, the administration should be stopped immediately and restarted in another vein. Storage
As packaged for sale
Store below 25°C. Do not refrigerate or freeze.
In use
Chemical and physical in use stability of the diluted product has been demonstrated for 24 hours at 25°C and for 72 hours at 2-8°C in
• Sodium chloride 9 mg/ml (0.9 %),
• Glucose 50 mg/ml (5 %), or
• Sodium chloride 9 mg/ml (0.9 %) and Glucose 50 mg/ml (5 %) solution.
From a microbiological point of view, the diluted product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C.