Mitoxantrone

Mitoxantrone is a prescription medication used to decrease the number of symptoms and slow the development of disability in those with certain forms of multiple sclerosis (MS). Mitoxantrone injection is also used to relieve pain in people with advanced prostate cancer. Mitoxantrone is also used to treat certain types of leukemia.

Mitoxantrone belongs to a group of drugs called anthracenediones. Mitoxantrone treats MS by stopping certain cells of the immune system from reaching the brain and spinal cord and causing damage. Mitoxantrone treats cancer by stopping the growth and spread of cancer cells.

This medication is available in an injectable form to be given directly into a vein (IV) by a healthcare professional.

Common side effects include nausea, stomach pain, diarrhea, and constipation.

Mitoxantrone is a prescription medication used to decrease the number of symptoms and slow the development of disability in those with certain forms of multiple sclerosis (MS). Mitoxantrone injection is also used together with steroid medications to relieve pain in people with advanced prostate cancer who did not respond to other medications. Mitoxantrone injection is also used together with other medications to treat certain types of leukemia.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Mitoxantrone may be found in some form under the following brand names:

• Novantrone

The most common side effects of mitoxantrone include:

• blue-green colored urine for about 24 hours after receiving mitoxantrone. This color change is harmless.
• bluish coloring of the whites of your eyes for about 24 hours after receiving mitoxantrone. This color change is harmless.
• nausea
• constipation
• diarrhea
• stomach pain
• hair loss
• fever and chills due to infections
• cough and sore throat due to upper respiratory tract infection
• mouth sores due to mouth infection
• loss of your menstrual period

This is not a complete list of this medication’s side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements.

Using mitoxantrone certain other medicines may cause serious side effects.

Especially tell your doctor if you take or have taken:

• medicines for cancer treatment
• medicines that may affect your heart

Ask your doctor or pharmacist for a list of these medicines if you are not sure if you take or have taken any of these medicines.

This is not a complete list of mitoxantrone drug interactions. Ask your doctor or pharmacist for more information.

Mitoxantrone can cause serious side effects, including:

• a decrease in the ability of your bone marrow to make blood cells (myelosuppression). Your doctor may do blood tests during treatment with mitoxantrone to check your blood cell counts. The symptoms of myelosuppression can include:
  • feeling tired
  • increased infections
  • bruising and bleeding easily

• heart problems (congestive heart failure) that may lead to death even in people who have never had heart problems before. Heart failure can happen while you receive mitoxantrone, or months to years after you stop receiving mitoxantrone. Your risk of heart failure increases the more mitoxantrone you receive.
• acute myeloid leukemia (AML). Receiving mitoxantrone increases your risk of AML. AML is a cancer of the blood-forming cells of your bone marrow. Symptoms of AML can include:
  • feeling unusually tired and weak
  • increased infections
  • bruising and bleeding easily
  • fever
  • pain in your bones
  • trouble breathing
  • unexplained weight loss
  • night sweats

• skin problems at your injection site. If mitoxantrone leaks out of your vein, skin problems can happen that may lead to serious skin damage (necrosis). Necrosis may need to be repaired surgically. Tell your doctor right away if you have any of the following problems at your injection site:
  • redness
  • swelling
  • pain
  • burning
  • skin turns a bluish color

Call your doctor or get medical help right away if you have any of these problems during or after treatment with mitoxantrone:

• shortness of breath
• swelling of your ankles or feet
• sudden weight gain
• fast heartbeat or pounding in your chest

Before receiving mitoxantrone for the first time, you should have the following tests done:

• physical examination
• a test to check your heart’s electrical activity (electrocardiogram)
• a test to check your heart’s ability to pump blood

If you receive mitoxantrone to treat Multiple Sclerosis (MS), your doctor should also do the tests above:

• before you receive each mitoxantrone dose
• yearly after you stop receiving mitoxantrone treatment

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of mitoxantrone, there are no specific foods that you must exclude from your diet.

Before you receive mitoxantrone, tell your doctor if you have:

• received mitoxantrone in the past
• heart problems
• liver problems
• kidney problems
• low blood cell counts
• an infection
• had radiation treatment in your chest area
• any other medical conditions
• are pregnant or plan to become pregnant. Mitoxantrone may harm your unborn baby. Women who are able to become pregnant should use effective birth control (contraception) while using mitoxantrone and should have a pregnancy test, with known results, before receiving each dose of mitoxantrone. Talk to your doctor about using effective birth control while you receive mitoxantrone.
• are breastfeeding or plan to breastfeed. Mitoxantrone can pass into your breast milk and may harm your baby. Talk to your doctor about the best way to feed your baby if you receive mitoxantrone. Do not breastfeed while receiving mitoxantrone.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

This medication falls into category D. Mitoxantrone may harm the unborn baby. If you are using mitoxantrone, even if you are using birth control, your doctor should give you a pregnancy test before treatment.

Tell your doctor if you are breastfeeding or plan to breastfeed.

Mitoxantrone has been detected in human breast milk. Because of the possibility for adverse reactions in nursing infants from mitoxantrone, a choice should be made whether to stop nursing or to the stop use of this medication. The importance of the drug to the mother should be considered.

• Mitoxantrone is given by slow infusion through a needle placed in a vein (intravenous infusion) in your arm.
• Your doctor will tell you how often you will receive mitoxantrone.
• If you receive mitoxantrone to treat MS, your doctor should check how well your heart is working before each mitoxantrone dose. Talk to your doctor if you have not had your heart tests done before your mitoxantrone dose.
• Your doctor will do blood tests during your treatment with mitoxantrone to check your blood cell counts.
• If you are a woman of childbearing age taking mitoxantrone to treat MS, your doctor should do a pregnancy test before each mitoxantrone dose, even if you are using birth control.
• If you receive mitoxantrone to treat MS, there is a limit to the total amount of mitoxantrone you can receive during your lifetime. There is a higher risk of heart failure with increasing total lifetime doses of mitoxantrone.

Multiple Sclerosis

• The recommended dosage of mitoxantrone is 12 mg/m² every 3 months.

Hormone-Refractory Prostate Cancer

• The recommended dosage of mitoxantrone is 12 to 14 mg/m² every 21 days.

Combination Initial Therapy for ANLL in Adults

• For induction, the recommended dosage is 12 mg/m² on Days 1 to 3
• In the event of an incomplete response, a second induction course may be given.
• For consolidation, 12 mg/m² on Days 1 and 2.

If this medication is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if an overdose is suspected, seek emergency medical attention.

Mitoxantrone Injection, USP should be administered under the supervision of a physician experienced in the use of cytotoxic chemotherapy agents.

Mitoxantrone should be given slowly into a freely flowing intravenous infusion. It must never be given subcutaneously, intramuscularly, or intra-arterially. Severe local tissue damage may occur it there is extravasation during administration.

NOT FOR INTRATHECAL USE. Severe injury with permanent sequelae can result from intrathecal administration.

Except for the treatment of acute nonlymphocytic leukemia, mitoxantrone therapy generally should not be given to patients with baseline neutrophil counts of less than 1,500 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving mitoxantrone.

Cardiotoxicity: Congestive heart failure (CHF), potentially fatal, may occur either during therapy with mitoxantrone or months to years after termination of therapy. Cardiotoxicity risk increases with cumulative mitoxantrone dose and may occur whether or not cardiac risk factors are present. Presence or history of cardiovascular disease, radiotherapy to the mediastinal/pericardial area, previous therapy with other anthracyclines or anthracenediones, or use of other cardiotoxic drugs may increase this risk. In cancer patients, the risk of symptomatic CHF was estimated to be 2.6% for patients receiving up to a cumulative dose of 140 mg/m2. To mitigate the cardiotoxicity risk with mitoxantrone, prescribers should consider the following:

All Patients:

• All patients should be assessed for cardiac signs and symptoms by history, physical examination, and ECG prior to start of mitoxantrone therapy.
• All patients should have baseline quantitative evaluation of left ventricular ejection fraction (LVEF) using appropriate methodology (ex. Echocardiogram, multi-gated radionuclide angiography (MUGA), MRI, etc.).

Multiple Sclerosis Patients:

• MS patients with a baseline LVEF below the lower limit of normal should not be treated with mitoxantrone.
• MS patients should be assessed for cardiac signs and symptoms by history, physical examination and ECG prior to each dose.
• MS patients should undergo quantitative reevaluation of LVEF prior to each dose using the same methodology that was used to assess baseline LVEF. Additional doses of mitoxantrone should not be administered to multiple sclerosis patients who have experienced either a drop in LVEF to below the lower limit of normal or a clinically significant reduction in LVEF during mitoxantrone therapy.
• MS patients should not receive a cumulative mitoxantrone dose greater than 140 mg/m2.
• MS patients should undergo yearly quantitative LVEF evaluation after stopping mitoxantrone to monitor for late occurring cardiotoxicity.

Secondary Leukemia:

• Mitoxantrone therapy in patients with MS and in patients with cancer increases the risk of developing secondary acute myeloid leukemia.