Mitoxantrone – Uses, Dosage, Side Effects, Interaction

Use in Cancer

Mitoxantrone hydrochloride is approved to be used with other drugs to treat:

• Acute non-lymphocytic leukemia in adults.
• Prostate cancer. It is used as palliative treatment in patients with advanced disease that is hormone-refractory (does not respond to hormone treatment).

Mitoxantrone hydrochloride is also being studied in the treatment of other types of cancer.

Contraindications

• a bacterial infection?.
• an infection? due to a fungus.
• a bad infection.
• decreased function of bone marrow?.
• anemia?.
• decreased blood platelets.
• low levels of white blood cells.
• low levels of a type of white blood cell called neutrophils.

Dosage?

 Strengths: 2 mg/mL

Acute Nonlymphocytic Leukemia

• INDUCTION THERAPY: 12 mg/m2 IV daily on days 1 to 3 (in combination with cytarabine at 100 mg/m2 given as a continuous 24-hour IV infusion on days 1 to 7)
• SECOND INDUCTION THERAPY (if needed in the event of an incomplete antileukemic response to the first induction): 12 mg/m2 IV daily on days 1 and 2 (in combination with cytarabine given as a continuous 24-hour IV infusion on days 1 to 5)
• CONSOLIDATION THERAPY: 12 mg/m2 given IV daily on days 1 and 2 (in combination with cytarabine given as a continuous 24-hour IV infusion on days 1 to 5). The first course is given approximately 6 weeks after the final induction course and the second is generally administered 4 weeks after the first.
• The IV infusion should be given over 5 to 15 minutes.
• Most complete remissions from ANLL occur during initial induction therapy. In the event of an incomplete antileukemic response, a second induction course may be administered.
• Second inductions should be withheld until severe or life-threatening nonhematologic toxicity associated with the first induction dose is cleared.
• For the initial therapy of acute nonlymphocytic leukemia (ANLL) in adults (includes myelogenous, promyelocytic, monocytic, and erythroid acute leukemias) in combination with other approved drug(s)

Multiple Sclerosis

• 12 mg/m2 given as a short (approximately 5 to 15 minute) IV infusion every 3 months
• The IV infusion should be given over 5 to 15 minutes.
• Evaluation of left ventricular ejection fraction (LVEF) by echocardiogram? or multiple gated acquisition (MUGA) scan is recommended prior to all doses.
• LVEF evaluations are recommended if signs of congestive heart failure? develop.
• This drug should not be administered to MS patients who have received a cumulative lifetime dose of 140 mg/m2 or more, or those with either an LVEF less than 50% or a clinically significant reduction in LVEF.
• Complete blood counts, including platelets, should be monitored prior to each dose and if signs of infection develop.
• This drug should not be administered to MS patients with neutrophil? counts less than 1500 cells/mm3.
• Liver function tests should also be monitored prior to each dose. Use of this drug in MS abnormal liver function tests is not recommended.
• Women who are capable of becoming pregnant (even if they are using birth control) should have a pregnancy test before each dose.

Prostate Cancer

• 12 to 14 mg/m2 given as a short IV infusion every 21 days (in combination with corticosteroids)
• The IV infusion should be given over 5 to 15 minutes.

US BOXED WARNINGS:

• This drug should be administered under the supervision of a physician experienced in the use of cytotoxic chemotherapy agents.
• This drug should be given slowly into a freely flowing IV infusion. It should never be given subcutaneously, IM, or intra-arterially. Severe local tissue damage may occur if 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, this drug 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 this drug.
• Cardiotoxicity: Congestive heart failure (CHF), potentially fatal, may occur either during therapy or months to years after termination of therapy. The risk increases with cumulative 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 anthracene diones, 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, 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 starting therapy. All patients should have baseline quantitative evaluation of left ventricular ejection fraction (LVEF) using appropriate methodology (e.g., echocardiogram, multi-gated radionuclide angiography (MUGA), MRI).
• MULTIPLE SCLEROSIS PATIENTS: MS patients with a baseline LVEF below the lower limit of normal should not be treated with this drug. 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 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 therapy to monitor for late-occurring cardiotoxicity.
• SECONDARY LEUKEMIA: Therapy in patients with MS and in patients with cancer increases the risk of developing secondary acute myeloid leukemia.

Patient advice:

• Patients should be informed of the availability of a Medication Guide and instructed to read it prior to initiating treatment and prior to each infusion.
• Patients should be advised that this drug can cause myelosuppression and be informed of signs of myelosuppression.
• Patients should be advised that this drug can cause congestive heart failure that may lead to death, even in people who have never had heart problems before.
• Patients with MS should be advised that they should receive cardiac monitoring prior to each dose and yearly after stopping therapy.
• Patients should be advised that this drug may impart a blue-green color to the urine and/or sclera for 24 hours after administration.

Side Effects

The Most Common

• nausea
• vomiting
• diarrhea
• constipation
• heartburn
• loss of appetite
• sores on the mouth and tongue
• runny or stuffed nose
• thinning or loss of hair
• changes in the area around or under fingernails and toenails
• missed or irregular menstrual periods
• extreme tiredness
• weakness
• headache
• back pain
• unusual bleeding or bruising
• small red or purple dots on the skin
• hives
• itching
• rash
• difficulty swallowing
• shortness of breath
• fainting
• dizziness
• pale skin
• yellowing of the skin or eyes
• seizures
• redness, pain, swelling, burning, or blue discoloration at the site where the injection was given

More common

• Black, tarry stools
• bladder pain
• bloody or cloudy urine
• cough or shortness of breath
• difficult, burning, or painful urination
• dizziness
• fainting
• fast, slow, or irregular heartbeat
• frequent urge to urinate
• lower back or side pain
• pale skin
• stomach pain
• swelling or inflammation of the mouth
• troubled breathing with exertion
• ulcers, sores, or white spots in the mouth
• unusual bleeding or bruising
• unusual tiredness or weakness
• Absent, missed, or irregular menstrual periods
• back pain
• body aches or pains
• congestion
• constipation
• diarrhea
• dryness or soreness of the throat
• hair loss
• headache
• longer or heavier menstrual periods
• nausea or vomiting
• oral bleeding
• pain or tenderness around the eyes and cheekbones
• runny nose
• sneezing
• stopping of menstrual bleeding
• stuffy nose
• tender, swollen glands in the neck
• thinning of the hair

Rare

• Blood in the urine or stools
• decrease in urination
• fever or chills
• pinpoint red spots on the skin
• seizures
• sore, red eyes
• swelling of the feet and lower legs
• yellow eyes or skin
• Blue skin at the place of injection
• pain or redness at the place of injection
• skin rash

Drug Interactions

Pregnancy and Lactation

AU TGA pregnancy category: D
US FDA pregnancy category: D

Pregnancy

This drug can cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women with who are capable of becoming pregnant, even if they are using birth control, should have a pregnancy test, before receiving each dose of this drug. Women of childbearing potential should be advised to avoid becoming pregnant. During therapy and for at least 6 months after termination of therapy, effective contraception should be practiced by patients of reproductive age, of either sex

Lactation

Most sources consider breastfeeding to be contraindicated during maternal antineoplastic drug therapy, such as mitoxantrone. It might be possible to breastfeed safely during intermittent therapy with an appropriate period of breastfeeding abstinence, but the duration of abstinence is not clear. In one patient, mitoxantrone was still detectable in milk 28 days after a dose of 6 mg per square meter. Chemotherapy may adversely affect the normal microbiome and chemical makeup of breast milk. Women who receive chemotherapy during pregnancy are more likely to have difficulty nursing their infant.

One mother received 3 daily doses of 6 mg/sq. m. of mitoxantrone intravenously along with 5 daily doses of etoposide 80 mg/sq. m. and cytarabine 170 mg/sq. m. intravenously. She resumed breastfeeding her infant 3 weeks after the third dose of mitoxantrone at a time when mitoxantrone was still detectable in milk. The infant had no apparent abnormalities at 16 months of age.

One mother received 3 daily doses of 6 mg/sq. m. of mitoxantrone intravenously along with 5 daily doses of etoposide 80 mg/sq. m. and cytarabine 170 mg/sq. m. intravenously. She resumed breastfeeding her infant 3 weeks after the third dose of mitoxantrone at a time when mitoxantrone was still detectable in milk. The infant had no apparent abnormalities at 16 months of age.