Last reviewed 2026-04-20 · How we verify

Novantrone (MITOXANTRONE)

Novantrone works by interfering with the enzyme topoisomerase, which is necessary for DNA replication and cell division.

Mitoxantrone (Novantrone) is a marketed drug primarily indicated for secondary progressive multiple sclerosis, with a key composition patent expiring in 2028. Its mechanism of action, which interferes with topoisomerase, provides a distinct therapeutic approach in managing disease progression. The primary risk is the presence of multiple off-patent competitors in the same class, including doxorubicin, daunorubicin, epirubicin, idarubicin, and valrubicin, which may limit market share and revenue potential.

At a glance

Mechanism of action

Mechanism of Action. Mitoxantrone, DNA-reactive agent that intercalates into deoxyribonucleic acid (DNA) through hydrogen bonding, causes crosslinks and strand breaks. Mitoxantrone also interferes with ribonucleic acid (RNA) and is potent inhibitor of topoisomerase II, an enzyme responsible for uncoiling and repairing damaged DNA. It has cytocidal effect on both proliferating and nonproliferating cultured human cells, suggesting lack of cell cycle phase specificity.Mitoxantrone has been shown in vitro to inhibit cell, cell, and macrophage proliferation and impair antigen presentation, as well as the secretion of interferon gamma, TNF, and IL-2.

Approved indications

• Multiple Sclerosis - Secondary Progressive
• Multiple Sclerosis - Progressive Relapsing
• Multiple Sclerosis - Worsening Relapsing-Remitting
• Advanced Hormone-Refractory Prostate Cancer
• Acute Nonlymphocytic Leukemia

Boxed warnings

• WARNING Mitoxantrone injection (concentrate) should be administered under the supervision of a physician experienced in the use of cytotoxic chemotherapy agents. Mitoxantrone injection (concentrate) should be given slowly into a freely flowing intravenous infusion. It must never be given subcutaneously, intramuscularly, or intra-arterially. Severe local tissue damage may occur if there is extravasation during administration (see ADVERSE REACTIONS, General, Cutaneous and DOSAGE AND ADMINISTRATION, Preparation and Administration Precautions ). NOT FOR INTRATHECAL USE. Severe injury with permanent sequelae can result from intrathecal administration (see WARNINGS, General ). Except for the treatment of acute nonlymphocytic leukemia, mitoxantrone injection (concentrate) therapy generally should not be given to patients with baseline neutrophil counts of less than 1,500 cells/mm 3 . 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 mitoxantrone injection (concentrate). Cardiotoxicity Congestive heart failure (CHF), potentially fatal, may occur either during therapy with mitoxantrone injection (concentrate) or months to years after termination of therapy. Cardiotoxicity risk increases with cumulative mitoxantrone injection (concentrate) 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 anthracenediones, 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/m 2 . To mitigate the cardiotoxicity risk with mitoxantrone injection (concentrate), 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 start of mitoxantrone injection (concentrate) therapy. - All patients should have baseline quantitative evaluation of left ventricular ejection fraction (LVEF) using appropriate methodology (ex. Echocardiogram, multi-gated radionuclide angiography (MUGA), MRI, etc.). Multiple Sclerosis Patients - MS patients with a baseline LVEF below the lower limit of normal should not be treated with mitoxantrone injection (concentrate). - 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 injection (concentrate) 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 mitoxantrone injection (concentrate) therapy. - MS patients should not receive a cumulative mitoxantrone injection (concentrate) dose greater than 140 mg/m 2 . - MS patients should undergo yearly quantitative LVEF evaluation after stopping mitoxantrone injection (concentrate) to monitor for late occurring cardiotoxicity. Secondary Leukemia Mitoxantrone injection (concentrate) therapy in patients with MS and in patients with cancer increases the risk of developing secondary acute myeloid leukemia. For additional information, see WARNINGS and DOSAGE AND ADMINISTRATION .

Common side effects

• nausea
• alopecia
• menstrual disorder
• amenorrhea
• upper respiratory tract infection
• urinary tract infection
• stomatitis
• arrhythmia
• diarrhea
• urine abnormal
• ECG abnormal
• constipation

Drug interactions

• corticosteroids

Key clinical trials

• Testing the Addition of an Anti-cancer Drug, M3814, to the Usual Treatment (Mitoxantrone, Etoposide, and Cytarabine) for Relapsed or Refractory Acute Myeloid Leukemia (PHASE1)
• Venetoclax, Azacitidine and Liposomal Mitoxantrone for Newly Diagnosed AML (NA)
• Venetoclax, Azacitidine, and Mitoxantrone Hydrochloride Liposome Versus Idarubicin and Cytarabine in Newly Diagnosed AML (PHASE3)
• A Study to Learn More About the Study Medicine Called Inotuzumab Ozogamicin (InO) in Children (1 to <18 Years) With First Relapse ALL (PHASE2)
• A Real-world Study of Characteristics, Treatment Patterns, and Clinical Outcomes Among Lutetium-177 Vipivotide Tetraxetan Treated Patients
• A Global Study of Midostaurin in Combination With Chemotherapy to Evaluate Safety, Efficacy and Pharmacokinetics in Newly Diagnosed Pediatric Patients With FLT3 Mutated AML (PHASE2)
• IMPACT-AML: A Randomized Pragmatic Clinical Trial for Relapsed or Refractory Acute Myeloid Leukemia. (PHASE3)
• CLAG-M or FLAG-Ida Chemotherapy and Reduced-Intensity Conditioning Donor Stem Cell Transplant for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Chronic Myelomonocytic Leukemia (PHASE1)

Primary sources

Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.

Competitive intelligence

For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:

• Novantrone CI brief — competitive landscape report
• Novantrone updates RSS · CI watch RSS