Mitoxantrone
Antitumour antibiotics
Antitumour antibioticsHigh alert
An error with this medicine can cause serious harm: double checks and protocols are used.
Dark-blue anthracenedione that blocks topoisomerase II. For leukaemia, prostate cancer and worsening multiple sclerosis; it can damage the heart late.
Quick facts
- Group
- Antitumour antibiotics
- Target
- DNA topoisomerase II (and DNA, by intercalation)
- Used for
- Initial treatment · Secondary progressive
- Key effects
- Nausea · Thinning or loss of hair · Tiredness
- Monitor
- Ejection fraction at baseline · Liver tests
- ATC
- L01DB07
No doses: the clinician sets them by the current guideline.
Mechanism of action
The crystal shows mitoxantrone wedged in DNA at the cleavage site of human topoisomerase IIβ, the sister isoform of IIα.
Mitoxantrone is a synthetic anthracenedione related to the anthracyclines. It slips between DNA base pairs and is a potent inhibitor of topoisomerase II: the enzyme cuts both DNA strands but cannot rejoin them, so double-strand breaks build up and the cell dies. It also causes cross-links and interferes with RNA. It forms fewer quinone free radicals than doxorubicin, so it is somewhat less cardiotoxic, but heart damage still occurs. In multiple sclerosis it keeps immune cells from reaching the brain and spinal cord and damaging them.
- Mitoxantrone intercalates into DNA
- Topoisomerase II cuts DNA but cannot reseal it
- Double-strand breaks accumulate and the cell dies
Indications
- Initial treatment of acute non-lymphocytic (myeloid) leukaemia in adults, with other drugs such as cytarabine. Acute leukaemia (AML and ALL) →
- Pain from advanced hormone-refractory prostate cancer, with a corticosteroid. Prostate cancer →
- Secondary progressive, progressive relapsing or worsening relapsing-remitting multiple sclerosis, to reduce disability and relapses. Multiple sclerosis →
Adverse effects
Common
- Nausea, vomiting, mouth sores
- Thinning or loss of hair (less than with doxorubicin)
- Blue-green urine for about a day and a bluish tint of the whites of the eyes
- Missed or irregular periods
- Tiredness, headache, back pain
Contraindications
- Previous allergy to mitoxantrone
- Multiple sclerosis with a low baseline ejection fraction, or a cumulative dose already at the limit
- Any route other than intravenous (never intrathecal, subcutaneous, intramuscular or intra-arterial)
Key interactions
- Previous anthracyclines or mediastinal radiotherapy
- Add to the risk of heart damage.
- Other topoisomerase II inhibitors and cytotoxics
- Add myelosuppression and raise the risk of secondary leukaemia.
What is monitored
- Ejection fraction at baseline; in multiple sclerosis before every dose and yearly after stopping
- Blood count before each dose
- Liver tests
- Pregnancy test before each dose in women with multiple sclerosis who could become pregnant
Administration and safety
- Intravenous only: given slowly into a freely running infusion; never intrathecal, subcutaneous, intramuscular or intra-arterial.
- Concentrate: it must be diluted before use.
- Vesicant: if burning, swelling or blue colour appears at the site, the infusion is stopped and restarted in another vein.
- Hazardous drug: prepared and disposed of under cytotoxic-drug procedures.
Pregnancy and breastfeeding
Can harm the fetus; pregnancy and breastfeeding are avoided, and women with multiple sclerosis have a pregnancy test before each dose.
Nursing care
- Confirm a recent ejection fraction and keep track of the cumulative dose.
- Check the infusion site often for pain, swelling or blue discoloration.
- Tell the patient that urine may turn blue-green and the eyes slightly blue for a short time.
- Teach to report fever, infection signs, breathlessness, swelling or palpitations, even years later.
Pharmacokinetics
- Absorption
- Intravenous infusion only.
- Distribution
- Very wide: it binds tissues strongly, and tissue levels exceed blood levels late after a dose.
- Elimination
- Through the bile and urine; a small part of a dose is recovered in a few days. Clearance falls in liver impairment.
- Half-life
- Long terminal half-life, about 75 hours (median), very variable.
Test yourself
Think of the answer, then tap the question to see it.
What harmless colour changes should a patient expect after mitoxantrone?
Blue-green urine for about a day and a bluish tint of the whites of the eyes.
Why is the ejection fraction checked before each dose in multiple sclerosis?
Mitoxantrone causes cumulative, dose-related heart failure that may appear months to years later.
Which late cancer is linked to mitoxantrone and other topoisomerase II inhibitors?
Secondary acute myeloid leukaemia.
What are the three approved uses of mitoxantrone?
Acute myeloid leukaemia, painful hormone-refractory prostate cancer, and worsening multiple sclerosis.
Connections
← Back to the class: Antitumour antibiotics
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - MITOXANTRONE injection, solution, concentrate (DailyMed (U.S. National Library of Medicine), 2021); Mitoxantrone Injection: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2019); Human topoisomerase iibeta in complex with DNA and mitoxantrone (RCSB Protein Data Bank, 2013).
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Representative model, for educational purposes only.