Baxter

PACKAGE LEAFLET: INFORMATION FOR THE PATIENT ONKOTRONE Injection 2 mg/ml concentrate for solution for infusion Mitoxantrone

Read all of this leaflet carefully before you are given this medicine.

•    Keep this leaflet. You may need to read it again.

•    If you have any further questions, ask your doctor 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 any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist straightaway.

Throughout this leaflet, ONKOTRONE Injection 2 mg/ml concentrate for solution for infusion will be called ONKOTRONE.

In this leaflet:

1.    What ONKOTRONE is and what it is used for

2.    Before you are given ONKOTRONE

3.    How you will be given ONKOTRONE

4.    Possible side effects

5.    How to store ONKOTRONE

6.    Further information

1 What ONKOTRONE is and what it is used for

ONKOTRONE contains a medicine called mitoxantrone. It is a cytotoxic drug or anti-cancer drug. It works by killing cancer cells, this is sometimes called ‘chemotherapy’.

It is used to treat lots of different cancers. ONKOTRONE is often used together with other anti-cancer drugs or radiotherapy.

2 Before you are given ONKOTRONE

Do not have ONKOTRONE if:

•    you have ever had an allergic reaction to the active ingredient or any of the other ingredients (listed in Section 6). An allergic reaction can include shortness of breath, wheezing, rash, itching or swelling of the face and lips.

•    you are a child under 16 years of age

•    you have severe liver problems

•    you are pregnant, trying to become pregnant or are breast feeding.

Tell your doctor if:

•    you have a very bad infection (septicaemia)

•    you have liver or kidney problems. Your doctor will check how well your liver and kidneys are working by doing a blood test

•    you have heart problems.

Using other medicines and treatments

Tell your doctor or nurse if you are taking or have recently

taken any other medicines, including medicines you have

obtained without a prescription.

In particular, tell them about the following medicines or

treatments as they may not work well with ONKOTRONE:

•    medicines called ‘cytotoxic’ because the side effects, especially on your bone marrow, are likely to be much worse

•    medicines called anti-cancer drugs or if you are having radiotherapy, because this can cause a type of blood cancer called ‘leukaemia’ or ‘acute myeloid leukaemia’ (AML)

•    vaccines which contain a ‘live virus’. You should not have these while having ONKOTRONE.

•    Men or women should not try to have a child during treatment or for at least 6 months after treatment. You should use an effective contraceptive. Ask your doctor for advice.

•    Some doctors recommend not trying to get pregnant for one year after the end of treatment with ONKOTRONE. This is because babies have a higher chance of being born prematurely or being of low birth weight.

•    Talk to your doctor about freezing sperm or eggs before your treatment starts.

Do not breast-feed while you are having ONKOTRONE.

Effects on your blood and immune system

•    Blood cells are made in your bone marrow. Three different types of blood cell are made:

-    red blood cells, which carry oxygen around your body

-    white blood cells, which fight infection, and

-    platelets, which help your blood to clot.

•    After an injection of ONKOTRONE your blood count of the three types of cell will drop. Your doctor will know that your blood count will reach its lowest level about 6 to 15 days after your injection. Most people recover to a normal blood count within 21 days. If you have had a lot of chemotherapy in the past, your blood count may take a little longer to return to normal.

•    You may be more likely to get infections when your blood count drops. Try to avoid close contact with people who have coughs, colds and other infections. If you do get an infection, speak to your doctor.

•    Your doctor will check that your bone marrow cells are high enough before and during treatment with ONKOTRONE.

Tests you may have with ONKOTRONE

•    ONKOTRONE may damage your heart, the more you are given the more likely this is. Your doctor will carry out tests, such as an ECG or ‘Muga’ scan before you start your treatment. You may notice that your heart beat changes, tell your doctor if this happens.

•    You will also have blood tests during your treatment with ONKOTRONE to check your blood cell levels or blood count.

What to do if you see a different doctor, or have to go to hospital

Do not take any other medicines unless your doctor knows you are taking ONKOTRONE. If you see a different doctor or have to go to hospital for any reason, tell them that you are taking ONKOTRONE and about any other medicines you are taking.

3 How you will be given ONKOTRONE

The usual dose

•    Your doctor will decide how much of the medicine you need and when you will need to be given it.

•    ONKOTRONE will be diluted and then injected slowly into a vein. This is called an infusion. It is often given with other anti-cancer drugs or steroids. Sometimes it is given at the same time as, or close to, radiotherapy treatment.

•    How it is given to you and how often will depend on:

-    the type of cancer you have

-    how big you are (a combination of your height and weight)

-    your general health

-    whether you are being given other anti-cancer drugs or having radiotherapy.

•    The injection will usually take at least 5 minutes or possibly up to half an hour depending on the dose.

•    If you are not sure about how you will be given your injection or have any other questions about your treatment, ask your doctor, nurse or pharmacist.

If you think a dose of ONKOTRONE has been missed

Contraception, pregnancy and breast-feeding

Do not become pregnant while taking ONKOTRONE. This is because it can damage your unborn baby, leading to stillbirths or a deformed child. Tell your doctor if you are pregnant, think you might be pregnant or are trying to become pregnant.

It is unlikely that you will miss a dose of ONKOTRONE, because it is always given to you by a trained and qualified person. If you do miss a dose, speak to your doctor as soon as possible.

Turn over leaflet for further information.

Technical Information

ONKOTRONE Injection

This technical leaflet does not include all the information about the product. Refer to the Summary of Product Characteristics before use.

Dosage and Administration Intravenous application:

1. Advanced Breast Cancer, Non-Hodgkin's Lymphoma, Hepatoma.

During monotherapy, a dose of 14 mg/m² ONKOTRONE is recommended as the initial dose for the first cycle. This dose can be repeated after 21 days.

In patients with diminished bone marrow reserves as a result of previous radiation and/or chemotherapy or those in a general poor state of health, the initial dose should be reduced to 12 mg/m² or as appropriate for the haematological status.

For each repeated application of ONKOTRONE, the dose should be adjusted in each case in accordance with the individual patient’s progress and the extent and duration of myelosuppression. If leucocyte and platelet counts have returned to normal after 21 days then the original dose can be repeated.

The following general recommendations can be given for dose adjustment in the treatment of advanced breast cancer, non-Hodgkin’s lymphoma and hepatoma:

If you are given too much ONKOTRONE

It is unlikely that you will be given too much ONKOTRONE, because it is always given by a trained and qualified person. If you think this has happened, you should speak to your doctor or the hospital where it was given.

4 Possible side effects

Like all medicines, ONKOTRONE can cause side effects, although not everybody gets them. The following side effects may happen with this medicine.

Tell your doctor immediately, if you notice any of the following serious side effects, you may need urgent medical treatment:

•    getting bruises without knocking yourself, or bleeding from your gums. This may be caused by the platelet levels in your blood getting too low

•    your heart starts to beat very rapidly. This could be a sign of heart damage within the first day after starting ONKOTRONE

•    very pale, lethargic and tired. This may be a sign of low red blood cells (anaemia). Usually, no treatment is required, your body will eventually replace the red blood cells. If you are very anaemic, you may need a blood transfusion

•    sudden serious signs of allergy such as rash, itchy skin, swelling of your face, lips or tongue, shortness of breath, wheezing (anaphylactic shock).

Other possible side effects include:

Very common (affecting more than 1 in 10 people)

•    feeling sick and being sick. This can last for about 24 hours after the injection. However, there are very effective anti-sickness medicines, which your doctor will prescribe for you. This means that most people are not troubled too much by sickness

•    hair loss. You may just notice this as a little extra loss of hair when you are combing or washing your hair, or you may lose most or all of your hair. The amount of hair which you lose will depend on the dose, the thickness of your hair and whether you are also having other anti-cancer drugs. If you are having ONKOTRONE in combination with other anti-cancer drugs, you are much more likely to lose your hair than if you are having it alone

•    tiredness and weakness

•    fever (high temperature)

•    women’s periods stop or sometimes heavier than normal

•    low sperm count

Common (affecting less than 1 in 10 people)

•    a lowering of the white blood cell count (very common in people with prostate cancer). You will probably not notice any signs when your white blood cell count drops, but you will be more likely to get infections.

•    shortness of breath, pain and swelling of your gut and mouth

•    loss of appetite, diarrhoea, tummy pain, constipation

•    blue coloured urine, feeling sleepy or confused

•    fits (seizures or convulsions), stabbing pain, loss of muscle strength (neuritis)

•    tingling, pins-and-needles or numbness

Uncommon (affecting less than 1 in 100 people)

•    heart failure and chest pain

•    bleeding in your stomach. Signs may include black stools that look like ‘tar’ or vomiting blood or bits that look like coffee grounds

•    serious infections (a high temperature, feeling cold and shivery, or hot and sweaty, or any signs of infection such as a cough, or stinging on passing water)

•    difficulty breathing, liver problems (may include yellowing of the skin and eyes and tenderness in the stomach)

Rare (affecting less than 1 in 1,000 people)

•    weakness, shortness of breath or yellowing of your skin or eyes (jaundice)

•    heart attack, blue coloured whites of your eyes, veins or nails and loose nails. This discoloration will fade and disappear after treatment stops.

•    certain cancers of the blood (such as acute myeloid leukaemia and myelodysplastic syndrome or MDS)

•    changes in the results of laboratory tests for liver and kidney function.

Very rare (affecting less than 1 in 10,000 people)

•    injection site skin reactions such as damage to the skin and phlebitis (tender blood vessel with area of hot red skin)

•    damage to your heart, finding that you pick up infections very easily.

Although these side effects can be serious, your doctor will have considered the risk of side effects with the risk to you of your cancer. If you have any questions about these side effects, or if you notice any other side effects or problems, you should tell your doctor or pharmacist.

5 How to store ONKOTRONE

•    Because ONKOTRONE is usually given in hospital it will be stored safely and correctly by the hospital staff.

If you do need the storage conditions they are given below.

•    Keep out of the reach and sight of children.

•    Do not use ONKOTRONE after the expiry date which is stated on the label after EXP. The expiry date refers to the last day of that month.

•    Do not store above 25°C.

•    Do not freeze.

•    Once opened, the vials can be used for 7 days if stored as above.

•    Diluted solutions can be stored as above for 4 days. Medicines should not be disposed of via wastewater or household waste. If you have any medicine left over, take it back to your pharmacist.

6 Further information

What ONKOTRONE contains

The active substance is mitoxantrone hydrochloride.

The strength of ONKOTRONE is 2 mg mitoxantrone/ml. Each vial contains 20 mg, 25 mg or 30 mg mitoxantrone depending on the size of the vial.

The other ingredients are sodium chloride, sodium acetate, acetic acid, sterile water (called ‘water for injections’).

What ONKOTRONE looks like and contents of the pack

ONKOTRONE is a dark blue solution in clear glass vials.

Marketing Authorisation Holder and Manufacturer

The Marketing Authorisation holder is:

Baxter Healthcare Ltd

Caxton Way, Thetford, Norfolk, IP24 3SE, UK

Send all enquiries to this address.

ONKOTRONE is manufactured by:

Baxter Oncology GmbH

Kantstrasse 2, 33790 Halle/Westfalen, Germany

This leaflet was last approved in 07/2008

For information about ONKOTRONE or to request this leaflet in formats such as audio or large print please contact the Marketing Authorisation Holder: Tel: 01635 206345.

Baxter and Onkotrone are trademarks of Baxter International Inc.

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ONKOTRONE combined with other cytotoxic agents has been successful in the treatment of acute non-lymphocytic leukaemia.

Most clinical experience has been with mitoxantrone combined with cytosine arabinoside. For induction, mitoxantrone has been given at a dose of 10-12 mg/m² for 3 days in combination with 100 mg/m² of cytosine arabinoside for 7 days (by continuous infusion). Combination therapy

The use of any cytotoxic agents, including cytosine arabinoside or etoposide, with mitoxantrone may cause greater myelosuppression than when mitoxantrone is used alone. If ONKOTRONE is combined with other myelotoxic agents, it is advisable to reduce the initial dose recommended for monotherapy by 2 to 4 mg/m² ONKOTRONE.

Dose modification or prolongation of the dosage interval should be adjusted according to the clinical condition of the patient and the haematological and non-haematological parameters. Reference to published literature should be made for information on dosage modification/administration.

Mode and duration of application

ONKOTRONE should not be given intrathecally

ONKOTRONE should only be administered by experienced oncologists.

Intravenous application:

ONKOTRONE can be administered as a slow intravenous injection over not less than 5 min. The most appropriate way is to inject ONKOTRONE diluted to at least 50 mls, slowly into a fast-running intravenous infusion. Isotonic saline or a 5% glucose solution are suitable carrier solutions and diluent. ONKOTRONE should not be mixed with other drugs in the same solution.

ONKOTRONE can be infused for short periods (15-30 min). The calculated dose should be diluted with 50 to 100 ml of one of the above mentioned infusion solutions.

If extravasation occurs, the administration should be stopped immediately and restarted using a different vein. To date, only isolated cases of severe local reactions (necroses) have been described due to extravasation.

Marketing Authorisation number: PL 00116/0398

Further information on ONKOTRONE is available from the Marketing Authorisation holder:

Baxter Healthcare Ltd

Caxton Way, Thetford, Norfolk, IP24 3SE, UK

Telephone: 01635 206345

This leaflet was last revised in January 2008

Baxter and Onkotrone are trademarks of Baxter International Inc.