Mitozantrone

DAE Class; Rx

Common Brand Names; NOVANTRONE

• Antineoplastics, Anthracenediones; 
• Multiple Sclerosis Treatments

Anthracenedione; DNA-reactive agent with cell cycle nonspecific cytocidal activity that intercalates into DNA resulting in cross-links and strand breaks; inhibits DNA and RNA synthesis

Indicated for 

• Secondary Progressive Multiple Sclerosis
• Acute Nonlymphocytic Leukemia
• Prostate Cancer
• Peripheral T-cell Lmphoma (Orphan)

Hypersensitivity

>10%

Nausea (55%)

Upper respiratory infection (51%)

Alopecia (38%

Urinary tract infection (29%)

Amenorrhea (28%)

Diarrhea (25%)

Stomatitis (15%)

Constipation (14%)

1-10%

Headache (6%)

Back pain (6%)

Frequency Not Defined

Decreased left ventricular ejection fraction

Cardiotoxicity

Myelosuppression

Hepatotoxicity

Abnormal LFT’s

Black Box Warnings

The drug should be administered under the supervision of an experienced cancer chemotherapy physician in a facility equipped to manage complications

Administer slowly into a freely flowing intravenous infusion and never administer IM, SC, or intra-arterially or intrathecally

Severe injury with permanent sequelae can result from intrathecal administration. Severe local tissue damage can occur if extravasation occurs during administration

Do not administer therapy to patients with baseline neutrophil counts <1,500 cells/mm³. Perform peripheral blood cell counts to monitor the occurrence of bone marrow suppression, primarily neutropenia, that may be severe and result in infection

Cardiotoxicity

• Potentially fatal CHF may occur either during therapy or months to years after termination of therapy. The risk increases with cumulative doses and may occur whether or not cardiac risk factors are present. History of cardiovascular disease, radiotherapy to the mediastinal/pericardial area, previous therapy with other anthracyclines or anthracenediones, or the use of other cardiotoxic drugs may increase the risk
• To mitigate the cardiotoxicity risk with this agent, prescribers should consider the following
• All patients should be assessed for cardiac signs and symptoms by history, physical examination, ECG prior to the start of therapy, and have a baseline evaluation of left ventricular ejection fraction (LVEF) using appropriate methodology (eg, echocardiogram, multi-gated radionuclide angiography [MUGA])
• Patients with multiple sclerosis (MS) should be assessed for cardiac signs and symptoms by history, physical examination, and ECG prior to each dose. Patients with a baseline LVEF below the lower limit of normal should not be treated with mitoxantrone. Patients with MS 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 patients with MS 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. These patients should not receive a cumulative dose >140 mg/sq.meter and should undergo yearly quantitative LVEF evaluation after stopping mitoxantrone to monitor for late occurring cardiotoxicity

Secondary acute myelogenous leukemia

• Secondary AML has been reported in patients with MS and cancer who treated with mitoxantrone. Also seen when patients are treated concurrently with anthracyclines. Mitoxantrone is an anthracenedione, a related drug
• The occurrence of 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

Cautions

Not indicated for primary progressive MS

Risk of cardiotoxicity & secondary AML

Avoid pregnancy

If extravasation occurs, stop immediately & restart in another vein

Hepatic impairment

Pregnancy Category: D

Lactation: excreted in breast milk, do not nurse

Secondary Progressive Multiple Sclerosis

12 mg/m² short IV (5-15 minutes) infusion q3Months  

Not to exceed lifetime cumulative dose of 140 mg/m²

Acute Nonlymphocytic Leukemia

Induction

• 12 mg/m²/day IV on days 1-3 with cytarabine 100 mg/m²/day IV contunuous infusion on days 1-7  
• Second induction with same doses of mitoxantrone for 2 days & cytarabine for 5 days may be given if incomplete antileukemic response & no severe nonhematologic toxicity in first induction
• Consolidation: 12mg/m²/day for 2 days, repeat in 4 weeks

Prostate Cancer

12-14 mg/m² q21Days every 3 weeks in combination with corticosteroids  

Peripheral T-cell Lmphoma (Orphan)

Orphan designation of liposomal mitoxantrone for peripheral T-cell lymphoma

Mitozantrone