Mitozantrone Injection

Generic Name: Mitozantrone
Product Name: Mitozantrone Injection

Indication

Mitozantrone (also known as Mitoxantrone) is an anti-cancer (chemotherapy) medication used to treat a number of conditions as follows:

• Metastatic breast cancer meaning the cancer has spread to other areas of the body via the bloodstream.
• Non-Hodgkin’s lymphoma.
• Certain types of leukaemia.
• Advanced prostate cancer that can’t be treated with hormones. In these cases it is used as the initial chemotherapy agent in combination with steroid medications.

There is also speculation that it may be used in the treatment of progressive forms of multiple sclerosis in the future. To date however, there is limited evidence proving its benefit for this indication. Mitozantrone may have been administered to you for a reason other than those listed above or may not be suitable for you even if you do have one of these conditions. You should discuss with your doctor whether Mitozantrone is a suitable medication for you.

Action

Mitozantrone belongs to a family of chemotherapy (anti-cancer) drugs called anthracyclines. These medications act by directly binding DNA in cells to break some of the strands and block DNA production. Mitozantrone also inhibits an enzyme involved in DNA repair which further damages DNA. These effects help to stop cancer cells proliferating. Cells do not have to be actively dividing to be affected by Mitozantrone, as is the case with some chemotherapy drugs. Furthermore, Mitozantrone causes slightly less damage to the heart than other anthracyclines.

Dose advice

Before receiving Mitozantrone you should tell your doctor:

1. If you are pregnant or intend on becoming pregnant- There is limited experience using Mitozantrone in pregnant women so it is generally not recommended during pregnancy. Your doctor will be able to discuss the risks and benefits of using this drug whilst you are pregnant.
2. If you are breastfeeding or intend to breastfeed- Mitozantrone is excreted in the breast milk and may cause adverse effects on your child. Therefore it is recommended that you don’t breastfeed during your therapy.
3. If you have any other medical conditions- In particular tell your doctor if you have conditions affecting your bone marrow or any heart, kidney or liver disease. These conditions may increase your risk of side effects.
4. If you are allergic to any medications, foods or dyes. Mitozantrone should not be used if you have an allergy or sensitivity to this medication.
5. Any other medications you are taking (including those bought from supermarkets or the chemist). Most importantly it is important to know any anti-cancer drugs you are using or have used in the past.

Dosing

Mitozantrone comes as a clear solution at a strength of 2mg/mL of solution. It comes in glass vials of 5, 10 and 12.5mL which equal doses of 10, 20 and 25mg respectively.

Mitozantrone is a dangerous drug as it works by killing cells, therefore it can only be given by trained personnel. Prior to giving the drug, they will carefully dilute it and then carefully add it into your body via a slow running drip in the arm. The person administering the medication will wear protective gear to avoid the drug coming in contact with their skin or eyes as this could have dangerous consequences. The infusion will normally run for several minutes and the medical staff will monitor you to make sure it does not escape out of the blood vessels.

Chemotherapy agents are usually given in cycles. Therefore you may be given this medication for 1-5 days and then have a repeat dose every after a specified number of days.

The usual doses of Mitozantrone need to be matched to specific protocol for your cancer being treatment. Your doctor will determine a suitable dose based on a calculation of your body surface area. If this is the only chemotherapy agent you are receiving around 14mg per meter squared will be used. If you have been using, or are currently using other chemotherapy drugs a lower dose of around 12mg/m² is needed. The total amount of the drug you receive should not be more than 140mg/m² as high doses may damage your bone marrow and lead to serious infections.

During your treatment with Mitozantrone you will need regular blood count checks to determine whether it is safe to continue treatment with this drug. This includes checking your full blood count, liver function tests (LFT) and kidney function before every cycle of medication. As drugs of the anthracycline class can also cause damage to your heart, your doctor will perform an ECG and other tests every three or so cycles.

Mitozantrone can increase your risk of infections so you should try to avoid contact with people with infections and watch out for signs of infection such as fever or cough. If you think you may have an infection see your doctor immediately. Following your dose of Mitozantrone you may notice your urine and the whites of your eyes and fingernails may be stained slightly blue-green for a day or two. This is a normal side effect that will resolve on its own so should not cause alarm.

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Common side effects

Like all medications, Mitozantrone can cause side effects in some patients which you should be aware of. As it is an anti-cancer medication that helps to kill cancer cells, it is understandable that it will have some effects on the normal cells of the body. Fortunately most patients tolerate Mitozantrone well and any side effects that do occur are mild and transient for the few days following the dose. Furthermore, the benefits of this medication in treating cancer usually far outweigh the risks of side effects. However, you should look out for any side effects as some of them can be serious and require medical attention (as discussed below).

If you notice any of the following symptoms or anything else that you think may be associated with this drug, make sure you discuss them with your doctor. The following lists the main side effects of Mitozantrone which occur in more than 5% of patients. If you are receiving Mitozantrone for leukaemia you may experience more frequent and serious side effects.

• Nausea and vomiting: This is by far the most common side effect but in most patients it is only mild. Your doctor can prescribe medications called antiemetics to stop you feeling nauseous and control these symptoms.
• Diarrhoea.
• Hair loss (called alopecia): This is reversible following cessation of therapy.
• Mouth ulcers.
• Esophagitis: Inflammation of the oesophagus.
• Bone marrow suppression: In particular, Mitozantrone can cause a fall in your white blood cell count which impairs your ability to fight infections. The fall is worst about ten days following your dose. Thrombocytopaenia (reduced platelets which stop bleeding) and anaemia (reduced red blood cells) are rarer complications of this treatment.
• Blue-green discolouration of the urine for approximately one day following administration. Rarely the skin, nails and eyes may become slightly discoloured also.
• Altered taste.
• Conjunctivitis.

Uncommon side effects

As fore mentioned, a small number of patients will have more serious side effects that need to be identified and treated early. The most serious side effects to look out for include:

• Cardiovascular changes: Mitozantrone can be toxic to the heart and in severe cases cause congestive heart failure. You should tell your doctor if you notice your heart beating irregularly (arrhythmias), shortness of breath or swelling of the extremities.
• Severe allergic reaction: Very rarely patients may be allergic to Mitozantrone and develop rashes, urticaria, difficulty breathing or hypotension. Very few patients however get a full blown anaphylactic reaction.
• Severe bone marrow suppression: Very rarely will your white blood count fall to extremely low levels. This is more likely if you have had other chemotherapy or radiotherapy in the past. Neutropenia may lead to serious infections such as urinary tract infection (UTI), pneumonia, sepsis or fungal infections. You should tell your doctor immediately if you think you may have an infection. Bleeding due to thrombocytopaenia and anaemia are rare.
• Inflammation of the vein used for injection: If some of the drug leaks out of the vessel being used for injection you may get severe skin changes and tissue necrosis. The person administering the drug will carefully watch for this and cease the infusion promptly if it occurs.
• Overdose: Very high doses of Mitozantrone can be toxic to the liver, gastrointestinal tract, kidneys and bone marrow causing life threatening effects. There is not antidote available.

Do not be alarmed by these long lists of side effects. Most patients tolerate Mitozantrone well and you may not experience any. It is however important that you are aware of the common and serious side effects so they can be treated promptly. In addition, the above lists are not necessary exhaustive and you may experience symptoms other than those listed. If you have any queries or concerns about the side effects of Mitozantrone make sure you discuss them with your doctor.

References

1. Australian Medicines Handbook- 14.3.2 Mitozantrone, AMH Pty Ltd. 2006.
2. Kasper, Braunwald, Fauci, Hauser, Longo, Jameson, Isselbacher. Harrison’s Principles of Internal Medicine. 16th Edition. McGraw-Hill. 2005.
3. MIMS online- Prescribing Information. Mitozantrone Injection, MIMS Australia Pty Ltd 2003.
4. MitoXANTRONE Injection, USP (concentrate)- Product Information, Mayne Pharma (USA) Inc. 2006. Available from: [PDF File]

For further information talk to your doctor.