Mitoxantrone

Mitoxantrone, a 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 a potent inhibitor of topoisomerase II, an enzyme responsible for uncoiling and repairing damaged DNA.

• Mitoxantrone injection, USP (concentrate) is indicated for reducing neurologic disability and/or the frequency of clinical relapses in patients with secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis (i.e., patients whose neurologic status is significantly abnormal between relapses). Mitoxantrone injection, USP (concentrate) is not indicated in the treatment of patients with primary progressive multiple sclerosis.ICD-10: G35

• Mitoxantrone injection (concentrate) is contraindicated in patients who have demonstrated prior hypersensitivity to it.contraindicated

(See also WARNINGS .) Multiple Sclerosis The recommended dosage of mitoxantrone injection (concentrate) is 12 mg/m 2 given as a short (approximately 5 to 15 minutes) intravenous infusion every 3 months. Left ventricular ejection fraction (LVEF) should be evaluated by echocardiogram or MUGA prior to administration of the initial dose of mitoxantrone injection (concentrate) and all subsequent doses. In addition, LVEF evaluations are recommended if signs or symptoms of congestive heart failure develop at any time during treatment with mitoxantrone injection (concentrate). Mitoxantrone injection (concentrate) should not be administered to multiple sclerosis patients with an LVEF < 50%, with a clinically significant reduction in LVEF, or to those who have received a cumulative lifetime dose of > 140 mg/m 2 . Complete blood counts, including platelets, should be monitored prior to each course of mitoxantrone injection (concentrate) and in the event that signs or symptoms of infection develop. Mitoxantrone injection (concentrate) generally should not be administered to multiple sclerosis patients with neutrophil counts less than 1500 cells/mm 3 . Liver function tests should also be monitored prior to each course. Mitoxantrone injection (concentrate) therapy in multiple sclerosis patients with abnormal liver function tests is not recommended because mitoxantrone injection (concentrate) clearance is reduced by hepatic impairment and no laboratory measurement can predict drug clearance and dose adjustments.

WHEN MITOXANTRONE INJECTION IS USED IN HIGH DOSES (> 14 mg/m 2 /d × 3 days) SUCH AS INDICATED FOR THE TREATMENT OF LEUKEMIA, SEVERE MYELOSUPPRESSION WILL OCCUR. THEREFORE, IT IS RECOMMENDED THAT MITOXANTRONE INJECTION BE ADMINISTERED ONLY BY PHYSICIANS EXPERIENCED IN THE CHEMOTHERAPY OF THIS DISEASE. LABORATORY AND SUPPORTIVE SERVICES MUST BE AVAILABLE FOR HEMATOLOGIC AND CHEMISTRY MONITORING AND ADJUNCTIVE THERAPIES, INCLUDING ANTIBIOTICS. BLOOD AND BLOOD PRODUCTS MUST BE AVAILABLE TO SUPPORT PATIENTS DURING THE EXPECTED PERIOD OF MEDULLARY HYPOPLASIA AND SEVERE MYELOSUPPRESSION. PARTICULAR CARE SHOULD BE GIVEN TO ASSURING FULL HEMATOLOGIC RECOVERY BEFORE UNDERTAKING CONSOLIDATION THERAPY (IF THIS TREATMENT IS USED) AND PATIENTS SHOULD BE MONITORED CLOSELY DURING THIS PHASE. MITOXANTRONE INJECTION ADMINISTERED AT ANY DOSE CAN CAUSE MYELOSUPPRESSION. General Patients with preexisting myelosuppression as the result of prior drug therapy should not receive mitoxantrone injection unless it is felt that the possible benefit from such treatment warrants the risk of further medullary suppression. The safety of mitoxantrone injection (concentrate) in patients with hepatic insufficiency is not established (see CLINICAL PHARMACOLOGY ). Safety for use by routes other than intravenous administration has not been established. Mitoxantrone injection is not indicated for subcutaneous, intramuscular, or intra-arterial injection. There have been reports of local/regional neuropathy, some irreversible, following intra-arterial injection.

Multiple Sclerosis Mitoxantrone injection has been administered to 149 patients with multiple sclerosis in two randomized clinical trials, including 21 patients who received mitoxantrone injection in combination with corticosteroids. In Study 1, the proportion of patients who discontinued treatment due to an adverse event was 9.7% (n = 6) in the 12 mg/m 2 mitoxantrone injection arm (leukopenia, depression, decreased LV function, bone pain and emesis, renal failure, and one discontinuation to prevent future complications from repeated urinary tract infections) compared to 3.1% (n = 2) in the placebo arm (hepatitis and myocardial infarction). The following clinical adverse experiences were significantly more frequent in the mitoxantrone injection groups: nausea, alopecia, urinary tract infection, and menstrual disorders, including amenorrhea. Table 4a summarizes clinical adverse events of all intensities occurring in ≥ 5% of patients in either dose group of mitoxantrone injection and that were numerically greater on drug than on placebo in Study 1. The majority of these events were of mild to moderate intensity, and nausea was the only adverse event that occurred with severe intensity in more than one patient (three patients [5%] in the 12 mg/m 2 group). Of note, alopecia consisted of mild hair thinning. Two of the 127 patients treated with mitoxantrone injection in Study 1 had decreased LVEF to below 50% at some point during the 2 years of treatment.

Pregnancy Mitoxantrone injection may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant. Mitoxantrone is considered a potential human teratogen because of its mechanism of action and the developmental effects demonstrated by related agents. Treatment of pregnant rats during the organogenesis period of gestation was associated with fetal growth retardation at doses ≥ 0.1 mg/kg/day (0.01 times the recommended human dose on a mg/m 2 basis). When pregnant rabbits were treated during organogenesis, an increased incidence of premature delivery was observed at doses ≥ 0.1 mg/kg/day (0.01 times the recommended human dose on a mg/m 2 basis). No teratogenic effects were observed in these studies, but the maximum doses tested were well below the recommended human dose (0.02 and 0.05 times in rats and rabbits, respectively, on a mg/m 2 basis). There are no adequate and well-controlled studies in pregnant women. Women with multiple sclerosis who are biologically capable of becoming pregnant should have a pregnancy test prior to each dose, and the results should be known prior to administration of the drug. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to the fetus.

Metabolism

Pharmacokinetics of mitoxantrone in patients following a single intravenous administration of mitoxantrone injection can be characterized by a three-compartment model. The mean alpha half-life of mitoxantrone is 6 to 12 minutes, the mean beta half-life is 1.1 to 3.1 hours and the mean gamma (terminal or elimination) half-life is 23 to 215 hours (median approximately 75 hours).

There is no known specific antidote for mitoxantrone injection. Accidental overdoses have been reported. Four patients receiving 140 to 180 mg/m 2 as a single bolus injection died as a result of severe leukopenia with infection. Hematologic support and antimicrobial therapy may be required during prolonged periods of severe myelosuppression. Although patients with severe renal failure have not been studied, mitoxantrone injection is extensively tissue bound and it is unlikely that the therapeutic effect or toxicity would be mitigated by peritoneal or hemodialysis.

• Apr 11, 2006ANDAANDA077356Meitheal
• Apr 11, 2006ANDAANDA076871Hospira
• Apr 11, 2006ANDAANDA077496Fresenius Kabi Usa

1. 1Febrile Neutropenia75812%
2. 2Off Label Use4827.8%
3. 3Neutropenia4647.5%
4. 4Drug Ineffective4557.4%
5. 5Pyrexia3655.9%
6. 6Thrombocytopenia3445.6%
7. 7Sepsis3255.3%
8. 8Acute Myeloid Leukaemia2964.8%
9. 9Pneumonia2514.1%
10. 10Myelodysplastic Syndrome2373.8%
11. 11Pancytopenia2363.8%
12. 12Disease Progression2163.5%
13. 13Product Use In Unapproved Indication1993.2%
14. 14Infection1973.2%
15. 15Septic Shock1933.1%

Recent PubMed references pinned to Mitoxantrone as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• The role of mitoxantrone hydrochloride in lymph node harvesting and parathyroid gland identification in conventional and endoscopic thyroidectomy.
  International journal of medical sciences · 2026 · Liu Y, Zhou D, Cong R, et al.
  PMID 42080072DOI 10.7150/ijms.126168
• A molecular anchor for mitoxantrone: improving binding affinity to albumin for enhanced antitumor efficacy and safety.
  Journal of colloid and interface science · 2026 · Dai Y, Li L, Sun N, et al.
  PMID 42025033DOI 10.1016/j.jcis.2026.140537
• Mitoxantrone hydrochloride as a novel tracer for lymphatic mapping and complication reduction in thyroid cancer surgery: A single-center, randomized clinical study.
  Surgical oncology · 2026 · Cheng Y, Zhang S, Liu Z, et al.
  PMID 41990519DOI 10.1016/j.suronc.2026.102420
• RNA functional modulation by Mitoxantrone via RNA structural ensemble repartitioning.
  Nature communications · 2026 · Zhang C, Borovská I, Iobashvili T, et al.
  PMID 41872169DOI 10.1038/s41467-026-70801-9
• Combination of mitoxantrone hydrochloride liposome with cyclophosphamide, vincristine, and prednisone for patients with treatment-naive peripheral T-cell lymphoma: A multicenter, open-label, single-arm, phase 1b trial.
  Cancer · 2026 · Gao Y, Jiang M, Zhang X, et al.
  PMID 41863781DOI 10.1002/cncr.70360
• Venetoclax plus high-dose cytarabine and mitoxantrone as salvage treatment for relapsed or refractory acute myeloid leukaemia (RELAX): a multicentre, single-arm, phase 1/2 trial.
  The Lancet. Haematology · 2026 · Ruhnke L, Schliemann C, Mikesch JH, et al.
  PMID 41791831DOI 10.1016/S2352-3026(25)00358-8
• A Macrophage-Driven Multimodal Nanoplatform Conquers Ovarian Cancer Peritoneal Metastasis.
  ACS applied materials & interfaces · 2026 · Ji M, Liu H, Liang X, et al.
  PMID 41766459DOI 10.1021/acsami.5c24348
• Development of a near-infrared fluorescence sensing platform based on TCPP-His@ZIF-8 for highly sensitive mitoxantrone detection.
  Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy · 2026 · Wu P, Jiao Y, Cheng L, et al.
  PMID 41762800DOI 10.1016/j.saa.2026.127619

The 10 most recently updated of 418 ClinicalTrials.gov registrations naming Mitoxantrone as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Testing the Addition of an Anti-cancer Drug, M3814, to the Usual Treatment (Mitoxantrone, Etoposide, and Cytarabine) for Relapsed or Refractory Acute Myeloid Leukemia
  Active not recruiting · Phase 1 · Interventional · 48 enrolled · National Cancer Institute (NCI)
  NCT03983824updated 2026-06-11
• A Study to Learn More About the Study Medicine Called Inotuzumab Ozogamicin (InO) in Children (1 to <18 Years) With First Relapse ALL
  Recruiting · Phase 2 · Interventional · 100 enrolled · Pfizer
  NCT05748171updated 2026-06-11
• IMPACT-AML: A Randomized Pragmatic Clinical Trial for Relapsed or Refractory Acute Myeloid Leukemia.
  Recruiting · Phase 3 · Interventional · 339 enrolled · Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
  NCT06713837updated 2026-06-10
• R-CMOP in Patients With Newly Diagnosed Diffuse Large B-cell Lymphoma
  Recruiting · Phase 1 · Phase 2 · Interventional · 108 enrolled · Institute of Hematology & Blood Diseases Hospital, China
  NCT06594640updated 2026-06-10
• TR115 VS Investigator's Choice in Relapsed/Refractory Peripheral T/NK Cell Lymphoma
  Not yet recruiting · Phase 3 · Interventional · 180 enrolled · Tarapeutics Science Inc.
  NCT07639879updated 2026-06-10
• Venetoclax, Azacitidine and Liposomal Mitoxantrone for Newly Diagnosed AML
  Recruiting · Interventional · 27 enrolled · Institute of Hematology & Blood Diseases Hospital, China
  NCT07490288updated 2026-06-09
• TINI 2: Total Therapy for Infants With Acute Lymphoblastic Leukemia II
  Recruiting · Phase 1 · Phase 2 · Interventional · 90 enrolled · Tanja Andrea Gruber
  NCT05848687updated 2026-06-03
• Blinatumomab in Treating Younger Patients With Relapsed B-cell Acute Lymphoblastic Leukemia
  Active not recruiting · Phase 3 · Interventional · 669 enrolled · National Cancer Institute (NCI)
  NCT02101853updated 2026-06-03
• Bortezomib and Sorafenib Tosylate in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
  Completed · Phase 3 · Interventional · 1,645 enrolled · National Cancer Institute (NCI)
  NCT01371981updated 2026-06-02
• Biomarkers in Predicting Treatment Response to Sirolimus and Chemotherapy in Patients With High-Risk Acute Myeloid Leukemia
  Completed · Phase 2 · Interventional · 39 enrolled · Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
  NCT02583893updated 2026-05-29

Frequently asked questions

How does Mitoxantrone work?

Mitoxantrone, a 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 a potent inhibitor of topoisomerase II, an enzyme responsible for uncoiling and repairing damaged DNA.

What is Mitoxantrone used for?

According to FDA labeling, Mitoxantrone carries indications including: Mitoxantrone injection, USP (concentrate) is indicated for reducing neurologic disability and/or the frequency of clinical relapses in patients with secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis (i.e., patients whose neurologic status is significantly abnormal between relapses). Mitoxantrone injection, USP (concentrate) is not indicated in the treatment of patients with primary progressive multiple sclerosis.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Mitoxantrone?

Mitoxantrone is classified as Anthracyclines and related substances, Topoisomerase Inhibitor, Topoisomerase Inhibitors, Decreased DNA Integrity, Decreased RNA Integrity.

What are the contraindications for Mitoxantrone?

Mitoxantrone labeling lists contraindications including: Mitoxantrone injection (concentrate) is contraindicated in patients who have demonstrated prior hypersensitivity to it.. Always consult the full prescribing information and a clinician.