Dosing and uses of Mitoxantrone (Novantrone)
Adult dosage forms and strengths
injectable solution
- 2mg/mL
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
Pediatric dosage forms and strengths
<12 years old: Safety and efficacy not established
Geriatric dosage forms and strengths
Secondary progressive multiple sclerosis
12 mg/m² short IV (5-15 minutes) infusion q3Months
Acute nonlymphocytic leukemia
Induction12 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
Mitoxantrone (Novantrone) adverse (side) effects
>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
Warnings
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
Contraindications
Hypersensitivity
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 and lactation
Pregnancy category: d
Lactation: excreted in breast milk, do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Mitoxantrone (Novantrone)
Mechanism of action
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
Pharmacokinetics
Half-life elimination: 5.8 d
Protein Bound: 95%
Metabolism: Liver
Absorption: Poor (PO)
Vdss: >1000 L/m²; 14 L/kg
Excretion: Feces (25%); urine (11%)
Administration
IV Incompatibilities
Additive: heparin
Y-site: amphotericin B cholesteryl sulfate, aztreonam, cefepime, doxorubicin liposomal, paclitaxel, piperacillin/tazobactam, propofoL
IV Compatibilities
Additive: cyclophosphamide, cytarabine, hydrocortisone Na-phosphate(?), hydrocortisone Na-succinate, KCL
Y-site: allopurinol, amifostine, cladribine, etoposide, filgrastim, fludaraine, gatifloxacin, gemcitabine, granisetron, linezolid, melphalan, ondansetron, sargramostim, teniposide, thiotepa, vinorelbine
IV Preparation
Dilute in at least 50 mL of NS or D5W
Standard dilution (IVPB): dose/100 mL D5W or Ns
IV Administration
Administered through tubing of freely running solution typically over 15-30 min (5-15 min for MS) or cont infusion over 24 hr
Do not give in less than 3 min
Storage
Store intact vials at room temp or refrigeration
Partially used concentrate vials may be stored for 7 d at 15-25°C or 14 d under refrigeration, but not frozen
