Adult Dosing

Acute nonlymphocytic leukemia

• For induction, 12 mg/m²/day by IV infusion on days 1 to 3 in combination with cytarabine
• Given cytarabine 100 mg/m² for 7 days as a 24 hr infusion on days 1-7

Pain related to advanced hormone-refractory prostate cancer

• 12-14 mg/m² IV infusion over 15 to 30 mins q21 days

Multiple sclerosis

• 12 mg/m² IV infusion over 5-15 mins q3 months

Pediatric Dosing

• Safety and effectiveness in pediatric patients have not been established

[Outline]

• Adult Dosing
• Pediatric Dosing

• Management of acute nonlymphocytic leukemia (ANLL) in adults in combination with other antineoplastic agents
• As initial chemotherapy for patients with pain associated with advanced hormone-refractory prostate cancer in combination with corticosteroids
• To prevent neurologic disability and/or the frequency of clinical relapses in Secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis

• Hypersensitivity to any of the ingredients of the product
• SC, IM, IT, or intra-arterial administration
• Pregnancy
• ANC <1500 (multiple sclerosis or prostate CA use)
• LVEF < lower limit of normal (multiple sclerosis use)
• Clinically significant LVEF decr. (multiple sclerosis use)
• Cumulative dose >140 mg/m^2 (multiple sclerosis use)
• Hepatic impairment (multiple sclerosis use)

• Administer only under supervision of a physician experienced in cancer chemotherapy. Give slowly into freely flowing IV infusion, never give SC, IM, or intra-arterially. Severe local tissue damage may occur if there is extravasation during administration
• It is not for intrathecal use as severe injury with permanent sequelae can result
• Except for treatment of acute nonlymphocytic leukemia, do not use if baseline neutrophil count <1500 cells/mm³. Monitor peripheral blood count frequently as neutropenia may be severe and result in infection
• Potentially fatal CHF may occur during therapy or months to years after discontinuation. Risk increases with cumulative dose and may occur w/ or w/o cardiac risk factors; risk also increases with history or presence of active cardiovascular dz, concomitant radiotherapy to mediastinal/pericardial area, prior anthracycline or anthracenedione therapy, or concomitant cardiotoxic drugs. Risk of symptomatic CHF was estimated to be 2.6% in cancer pts with cumulative dose up to 140 mg/m². Assess baseline cardiac status including LVEF
• Do not use in MS patients if LVEF <50%. Reevaluate cardiac status including LVEF in MS prior to each dose and discontinue if clinically significant reduction in LVEF. Max 140 mg/m² cumulative dose in MS patients. Evaluate LVEF in MS yearly after discontinuation to monitor for late occurring cardiotoxicity
• Secondary acute myelogenous leukemia has been reported in both MS and cancer patients. In 1774 patients with breast cancer who received mitoxantrone concomitantly with other cytotoxic agents and radiotherapy, the cumulative risk of developing treatment-related AML, was estimated as 1.1% and 1.6% at 5 and 10 years, respectively
• Refractory secondary leukemia is more common when anthracyclines are given in combination with DNA-damaging antineoplastic agents, when patients have been heavily pretreated with cytotoxic drugs, or when doses of anthracyclines have been escalated

Renal Dose Adjustment

• Renal impairment: No dose adjustments

Hepatic Dose Adjustment

• Hepatic impairment
• Multiple sclerosis: Avoid use
• All other indications: Consider dose adjustments; dosage adjustment not defined

• When mitoxantrone is administered in high doses, severe myelosuppression will occur. Laboratory and supportive measures must be available for hematologic monitoring.Antibiotics, blood and blood products must be available
• Ensure full hematologic recovery before undertaking consolidation
• Do not start mitoxantrone in patients with pre-existing myelosuppression
• Cardiac events including decreases in left ventricular ejection fraction (LVEF) and irreversible congestive heart failure can occur in both MS and cancer patients. Patients with prior treatment with anthracyclines, prior mediastinal radiotherapy, or with preexisting cardiovascular disease are at an increased risk of cardiac toxicity
• Functional cardiac changes such as decreases in LVEF and CHF may occur in patients with hormone-refractory prostate cancer treated with mitoxantrone
• Acute congestive heart failure may occasionally occur in patients treated for ANLL
• Start hypouricemic therapy before starting treatment for leukemia and monitor uric acid levels frequently during treatment
• It may cause fetal harm when administered to a pregnant woman. Advise women of childbearing potential to avoid becoming pregnant
• Secondary acute myelogenous leukemia (AML) has been reported in multiple sclerosis and cancer patients treated with mitoxantrone
• Perform baseline evaluation of LVEF by echocardiogram or multigated radionuclide angiography (MUGA)
• Monitor CBC, including platelets, LFTs prior to each course of therapy
• Perform frequent peripheral blood cell counts
• MS patients should undergo annual quantitative LVEF evaluation after stopping treatment to monitor for late-occurring cardiotoxicity
• Monitor serum uric acid levels and start hypouricemic therapy prior to the initiation of antileukemic therapy

Pregnancy Category:D

Breastfeeding: Most sources consider breastfeeding to be contraindicated during maternal antineoplastic drug therapy.Drug may be detected in milk for at least 28 days after a dose. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 13 April 2010)

• Mitoxantrone inhibits topoisomerase II, interferes with RNA, intercalates into deoxyribonucleic acid (DNA) through hydrogen bonding, causes crosslinks and strand breaks
• Metabolized by liver
• Excreted in feces and urine (primarily unchanged)
• Half-life: 75 hrs

US Trade Name(s)

• Novantrone (Discontinued)

US Availability

mitoxantrone (generic)

• INJ: 20 mg/10 mL
• INJ: 25 mg/12.5 mL
• INJ: 30 mg/15 mL

Novantrone

• INJ: 2 mg/mL (10 mL vials)

Canadian Trade Name(s)

• Only generic available

Canadian Availability

mitoxantrone (generic)

• INJ: 2 mg/mL (10, 12.5 mL vials)

UK Trade Name(s)

• Onkotrone

UK Availability

mitoxantrone (generic)

• INJ: 2 mg/mL (10 mL vial)

Onkotrone

• INJ: 2 mg/mL (10, 12.5, 15 mL vial)

Australian Trade Name(s)

• Novantrone
• Onkotrone

Australian Availability

mitoxantrone (generic)

• INJ: 10 mg/5 mL
• INJ: 20 mg/10 mL
• INJ: 25 mg/12.5 mL

Novantrone, Onkotrone

• INJ: 20 mg/10 mL
• INJ: 25 mg/12.5 mL

[Outline]

Hematology/Oncology

Antineoplastics

Antibiotics/Antineoplastics

Pricing data from www.DrugStore.com in U.S.A.

• Novantrone 2 MG/ML CONC [Vial] (SERONO)
  10 ml = $1340.7
  30 ml = $3980.72

Warning: This pricing information is subject to change at the sole discretion of DS Pharmacy. For the most current and up-to-date pricing information, please visit drugstore.com.