Section 04 · Monograph
Mitoxantrone
Reviewed Nov 2026FDA label
NovantroneAnthracenedione (chemo)
- Forms
- IV: 2mg/mL
- Dose
- 12mg/m² every 3 months (lifetime dose cap)
- MOA
- Intercalates DNA, immunosuppressive
Black Box Warning
- Cardiotoxicity (can be irreversible, cumulative, and dose-related) — reduced left ventricular ejection fraction and heart failure reported
- Should not be given with baseline LVEF <50% or clinically significant reduction in LVEF
- Secondary acute myeloid leukemia risk
- Requires LVEF assessment before each dose
Indications
- Reduction of neurologic disability and/or frequency of clinical relapses in secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting MSFDA-labeled
Mechanism of Action
- Synthetic anthracenedione, DNA-reactive agent
- Intercalates into DNA causing crosslinks and strand breaks, inhibits topoisomerase II
- Suppresses proliferation of T cells, B cells, and macrophages, reducing immune-mediated CNS damage
Full Dosing
Adult / usual
- 12 mg/m2 IV infusion every 3 months
- Maximum lifetime cumulative dose of 140 mg/m2 due to cardiotoxicity risk
Contraindications
- Baseline LVEF less than lower limit of normal
- Preexisting cardiomyopathy
Drug Interactions
- Additive cardiotoxicity with other cardiotoxic agents (e.g., anthracyclines)
- Additive myelosuppression with other bone marrow suppressants
Adverse Effects
- Nausea
- Alopecia (usually mild)
- Blue-green urine discoloration (harmless)
- Menstrual disorders/amenorrhea
- Myelosuppression (leukopenia)
- Cardiotoxicity
- Secondary leukemia
- Hepatotoxicity
Monitoring Parameters
- LVEF (echocardiogram or MUGA scan) before every dose and periodically after discontinuation
- CBC with differential before each dose
- Liver function tests
- Signs/symptoms of heart failure
Pregnancy & Lactation
- May cause fetal harm; effective contraception advised
- Contraindicated during breastfeeding — discontinue nursing