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Anthracenedione cytotoxic Pregnancy: US label: '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... 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.' Animal data: fetal growth retardation in rats and increased premature delivery in rabbits at doses >= 0.1 mg/kg/day; no teratogenic effects were observed, but the maximum doses tested were well below the recommended human dose. No breast-feeding statement is present in the fetched text.

Mitoxantrone (Specialist drug)

Brand names: Onkotrone

Mitoxantrone is an anthracenedione cytotoxic used, under specialist supervision, in certain leukaemias, lymphomas, breast and prostate cancer, and occasionally in highly active multiple sclerosis.

Adult dose

Dose: Specialist use only; every figure below is US labelling. Acute non-lymphocytic leukaemia (ANLL) in adults, combination initial therapy — induction: '12 mg/m2 of mitoxantrone injection (concentrate) daily on Days 1 to 3 given as an intravenous infusion, and 100 mg/m2 of cytarabine for 7 days given as a continuous 24 hour infusion on Days 1 to 7'; consolidation: 'mitoxantrone injection (concentrate), 12 mg/m2 given by intravenous infusion daily on Days 1 and 2 and cytarabine, 100 mg/m2 for 5 days given as a continuous 24 hour infusion on Days 1 to 5'. Hormone-refractory prostate cancer: '12 to 14 mg/m2 given as a short intravenous infusion every 21 days'. Multiple sclerosis: '12 mg/m2 given as a short (approximately 5 to 15 minutes) intravenous infusion every 3 months'.
Route: IV infusion only. 'MITOXANTRONE INJECTION CONCENTRATE MUST BE DILUTED PRIOR TO USE' — dilute to at least 50 mL with 0.9% Sodium Chloride Injection or 5% Dextrose Injection and introduce slowly into the tubing of a freely running intravenous infusion 'over a period of not less than 3 minutes', preferably into a large vein. 'MITOXANTRONE INJECTION (CONCENTRATE) SHOULD NOT BE ADMINISTERED SUBCUTANEOUSLY.' Do not mix in the same infusion as heparin (a precipitate may form) or with other drugs.
Frequency: ANLL induction: daily on Days 1 to 3 of the course (a second induction course, if given, is mitoxantrone for 2 days and cytarabine for 5 days at the same daily dosage levels). ANLL consolidation: Days 1 and 2, the first course approximately 6 weeks after the final induction course and the second generally 4 weeks after the first. Prostate cancer: every 21 days. Multiple sclerosis: every 3 months.
MAXDOSE DELIBERATELY EMPTY — SAFETY-CRITICAL. This drug's dose-limiting hazard is CUMULATIVE cardiotoxicity, and the US label does state a cumulative lifetime ceiling together with a left-ventricular-ejection-fraction threshold, but that sentence is CORRUPTED in the fetched extraction (the comparison operators and the linking clause were lost, collapsing two separate restrictions into one unreadable fragment). The figures are therefore NOT reproduced anywhere in this draft: a cumulative lifetime cap printed next to a 12 mg/m2 per-dose figure, stripped of the words that make it cumulative, is a misread waiting to happen. Read the cumulative dose limit and the LVEF threshold directly from the full label before treating. SECOND INDUCTION COURSE (verbatim): 'In the event of an incomplete antileukemic response, a second induction course may be given... If severe or life-threatening nonhematologic toxicity is observed during the first induction course, the second induction course should be withheld until toxicity resolves.' 'Severe myelosuppression occurred' with the consolidation regimen. ADDITIONAL MS RESTRICTIONS (stated in DOSAGE AND ADMINISTRATION, not in CONTRAINDICATIONS): 'Mitoxantrone injection (concentrate) generally should not be administered to multiple sclerosis patients with neutrophil counts less than 1500 cells/mm3'; '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.' EXTRAVASATION: 'Care in the administration... will reduce the chance of extravasation'; avoid veins over joints or in extremities with compromised venous or lymphatic drainage; avoid contact with skin, mucous membranes or eyes; 'If any signs or symptoms of extravasation have occurred, including burning, pain, pruritis, erythema, swelling, blue discoloration, or ulceration, the injection or infusion should be immediately terminated and restarted in another vein.' STORAGE: in multidose use, after penetration of the stopper the remaining undiluted concentrate should be stored not longer than 7 days between 15 and 25 degrees C, or 14 days refrigerated; do not freeze; contains no preservative; discard unused infusion solutions immediately. INTERACTIONS (US label; this contract has no interactions field): 'postmarketing experience has not revealed any significant drug interactions in patients who have received mitoxantrone injection for treatment of cancer. Information on drug interactions in patients with multiple sclerosis is limited'; no evidence of interaction with concurrent corticosteroids. SOURCE LIMITS: the DOSAGE AND ADMINISTRATION and ADVERSE REACTIONS extracts are both marked '[…SECTION TRUNCATED AT SOURCE-FETCH LIMIT]', the WARNINGS section (cardiotoxicity, secondary leukaemia, myelosuppression) was not fetched at all, and no UK SPC is present — so this is not the complete posology or safety profile.

Dose adjustments

Renal

Not stated in the fetched sources. The label notes only that 'Mitoxantrone and its metabolites are excreted in bile and urine, but it is not known whether the metabolic or excretory pathways are saturable, may be inhibited or induced, or if mitoxantrone and its metabolites undergo enterohepatic circulation.' Renal failure was one of the adverse events leading to discontinuation in the 12 mg/m2 arm of MS Study 1.

Hepatic

US label, Hepatic Impairment: 'For patients with hepatic impairment, there is at present no laboratory measurement that allows for dose adjustment recommendations.' In multiple sclerosis specifically: '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.' No numeric adjustment is given.

Dose independently re-sourced from US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • Prior hypersensitivity to mitoxantrone — US label CONTRAINDICATIONS section lists this alone: 'Mitoxantrone injection (concentrate) is contraindicated in patients who have demonstrated prior hypersensitivity to it.'
  • RESTRICTION, not in the CONTRAINDICATIONS section: 'Mitoxantrone injection (concentrate) generally should not be administered to multiple sclerosis patients with neutrophil counts less than 1500 cells/mm3'
  • RESTRICTION, not in the CONTRAINDICATIONS section: mitoxantrone therapy in multiple sclerosis patients with abnormal liver function tests 'is not recommended'
  • RESTRICTION, not in the CONTRAINDICATIONS section: the label bars further mitoxantrone in multiple sclerosis above a cumulative lifetime dose and below a stated left-ventricular ejection fraction — the sentence carrying both figures is corrupted in the fetched text, so the thresholds must be read from the full label (see adultDose.notes)
  • Must not be given subcutaneously (US label, administration precautions)

Side effects

  • Multiple sclerosis trials (US label): 'The following clinical adverse experiences were significantly more frequent in the mitoxantrone injection groups: nausea, alopecia, urinary tract infection, and menstrual disorders, including amenorrhea'; alopecia 'consisted of mild hair thinning', and nausea was the only adverse event of severe intensity in more than one patient (three patients, 5%, in the 12 mg/m2 group)
  • Adverse events causing discontinuation in the 12 mg/m2 MS arm of Study 1 (9.7%, n=6): leukopenia, depression, decreased left ventricular function, bone pain and emesis, renal failure
  • Severe myelosuppression occurred with the ANLL consolidation regimen (US label, DOSAGE AND ADMINISTRATION)
  • Extravasation reactions: burning, pain, pruritus, erythema, swelling, blue discoloration or ulceration at the infusion site
  • INCOMPLETE LIST: the ADVERSE REACTIONS extract is marked '[…SECTION TRUNCATED AT SOURCE-FETCH LIMIT]' and the WARNINGS section — which carries the cardiotoxicity, secondary leukaemia and myelosuppression warnings — was not fetched at all

Monitoring

  • LVEF by echocardiogram or MUGA before the initial dose and before all subsequent doses — US label: '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'
  • LVEF again 'if signs or symptoms of congestive heart failure develop at any time during treatment'
  • Cumulative lifetime dose received — the ceiling exists in the label but its figure is corrupted in this bundle and must be read from the full label
  • Complete blood counts, including platelets, 'prior to each course of mitoxantrone injection (concentrate) and in the event that signs or symptoms of infection develop'
  • Liver function tests prior to each course
  • Pregnancy test with the result known before each dose in women with multiple sclerosis who are biologically capable of becoming pregnant, 'even if they are using birth control'
  • Infusion site during administration — terminate immediately and restart in another vein at any sign of extravasation

Clinical monograph

How it works

It intercalates DNA and inhibits topoisomerase II, causing DNA strand breaks and blocking DNA and RNA synthesis.

Prescribing in practice

  • It is cardiotoxic with a cumulative dose-related risk of heart failure, so left ventricular function is assessed before and during treatment and a lifetime cumulative limit is observed.
  • It causes myelosuppression and carries a risk of secondary leukaemia, and is a vesicant requiring careful intravenous administration.
  • It characteristically turns urine and sometimes the sclerae blue-green, and patients should be forewarned.

Monitoring

Monitor full blood count before each course and cardiac (left ventricular ejection fraction) function before and during treatment against the cumulative dose.

Counselling the patient

  • Expect a temporary blue-green discolouration of urine, and sometimes a bluish tinge to the whites of the eyes.
  • Report breathlessness, ankle swelling or palpitations, which may indicate heart strain.
  • Report fever, bruising or bleeding promptly.

Evidence & guidelines

Long-established cytotoxic used per the SPC; cumulative cardiac dose limits are standard oncology and MS-treatment practice.

Reference: SmPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

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