Mitoxantrone


Generic Medicine Info
Indications and Dosage
Intravenous
Blast crisis in chronic myeloid leukaemia
Adult: 10-12 mg/m2 daily as a single dose for 5 days. Dose may be slowly injected into a free-flowing IV infusion of 0.9% NaCl or 5% glucose solution over at least 3-5 minutes or as short IV infusion over 15-30 minutes. Dosing reduction, interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).

Intravenous
Metastatic breast cancer, Non-Hodgkin's lymphoma
Adult: As monotherapy: Initially, 14 mg/m2 as a single dose then repeat every 3 weeks. In patients with inadequate bone marrow reserves: May decrease initial dose to 12 mg/m2. In combination therapy: May initiate dose at 7-8 mg/m2 or 10-12 mg/m2. All doses may be slowly injected into a free-flowing IV infusion of 0.9% NaCl or 5% glucose solution over at least 3-5 minutes or as short IV infusion over 15-30 minutes. Dosing reduction, interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).

Intravenous
Acute myeloid leukaemia
Adult: For induction: As monotherapy: 12 mg/m2 daily for 5 days. In combination with a 7-day course of cytarabine: 12 mg/m2 daily for 3 days; for incomplete response, may repeat at 12 mg/m2 daily for 2 days in combination with a 5-day course of cytarabine. For consolidation therapy: In combination with a 5-day course of cytarabine: Start approx 6 weeks after initiation of the final induction course: 12 mg/m2 daily for 2 days then repeat in 4 weeks. All doses may be slowly injected into a free-flowing IV infusion of 0.9% NaCl or 5% glucose solution over at least 3-5 minutes or as short IV infusion over 15-30 minutes. Dosing reduction, interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).

Intravenous
Progressive relapsing multiple sclerosis, Relapsing remitting multiple sclerosis, Secondary progressive multiple sclerosis
Adult: In patients with neutrophil counts of above 1,500 cells/mm3 and LVEF of >50%: 12 mg/m2 once every 3 months via infusion over 5-15 minutes. Max lifetime cumulative dose: 140 mg/m2. Dosing reduction, interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).

Intravenous
Advanced hormone-refractory prostate cancer
Adult: In combination with corticosteroids: 12-14 mg/m2 once every 3 weeks, continued until disease progression or unacceptable toxicity occurs. Dose may be slowly injected into a free-flowing IV infusion of 0.9% NaCl or 5% glucose solution over at least 3-5 minutes or as short IV infusion over 15-30 minutes. Dosing reduction, interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Hepatic Impairment
Metastatic breast cancer; Non-Hodgkin's lymphoma; Acute myeloid leukaemia; Blast crisis in chronic myeloid leukaemia; Advanced hormone-refractory prostate cancer:
Dose adjustment may be required.

Secondary progressive multiple sclerosis; Progressive relapsing multiple sclerosis; Relapsing remitting multiple sclerosis:
Not recommended.
Reconstitution
Dilute further in 50-100 mL of 0.9% NaCl or 5% glucose solution.
Incompatibility
May precipitate with heparin.
Contraindications
Neutrophil counts of <1,500 cells/mm3 (except if used in acute myeloid leukaemia [AML]). Hepatic impairment (when used for multiple sclerosis [MS]). Pregnancy and lactation. Concurrent administration with live virus vaccines.
Special Precautions
Patient with predisposing factors for therapy-induced cardiotoxicity (e.g. history or current CV disease, prior or concomitant radiotherapy to the mediastinal/pericardial area, prior anthracycline or anthracenedione therapy), diabetes. Not indicated for the treatment of primary progressive MS. Not recommended in patients with pre-existing myelosuppression as a result of previous chemotherapy. Not recommended when baseline LVEF below the lower limit of normal or if clinically significant reduction in LVEF is observed during therapy (when used for MS). Hepatic impairment.
Adverse Reactions
Significant: Acute CHF (when used for AML or MS), functional cardiac changes, severe myelosuppression, secondary AML, myelodysplastic syndrome (MDS), increased risk of transitory or persistent amenorrhoea, hyperuricaemia, tumour lysis syndrome; blue-green colouration of urine, saliva, sweat, tears (for 24 hours after infusion); blue-green tinged sclera; extravasation resulting in erythema, burning, swelling, pain and skin discolouration (blue).
Blood and lymphatic system disorders: Anaemia, leucopenia, neutropenia, thrombocytopenia, granulocytopenia.
Cardiac disorders: Arrhythmia.
Gastrointestinal disorders: Nausea, vomiting, diarrhoea, constipation, stomatitis.
General disorders and administration site conditions: Lethargy, asthenia, fatigue, pyrexia, oedema.
Investigations: Abnormal ECG, elevated AST.
Metabolism and nutrition disorders: Anorexia, hyperglycaemia.
Nervous system disorders: Headache.
Respiratory, thoracic and mediastinal disorders: Dyspnoea, upper respiratory tract infection.
Skin and subcutaneous tissue disorders: Alopecia.
Potentially Fatal: Myocardial toxicity, CHF, infection; AML (when used for MS).
IV/Parenteral: D
Patient Counseling Information
This drug may cause confusion and fatigue, if affected, do not drive or operate machinery. Use effective contraceptive method during therapy and for at least 4 months (for women) or 6 months (for men) following cessation of therapy.
Monitoring Parameters
Perform pregnancy test before therapy in females of reproductive potential or before each dose (when used for MS). Evaluate cardiac-related signs and symptoms (e.g. history, ECG, physical exam) before starting therapy or before each dose (when used for MS); LVEF with echocardiogram, multiple-gated acquisition (MUGA) or MRI before initial dose and periodically during therapy, or before each dose (when used for MS); perform annual evaluation of LVEF after discontinuing therapy (when used for MS). When used for MS: Screen for latent infections (e.g. TB, hepatitis) before starting therapy (in high-risk population or countries with high TB burden). Monitor CBC with differentials, uric acid (when used for leukaemia), electrolytes, urea, LFTs; injection site for extravasation; hypersensitivity reactions, myelosuppression.
Overdosage
Symptoms: Bone marrow depression (e.g. extreme agranulocytosis), necrotising angina, critical thrombocytopenia, myelosuppression; gastrointestinal tract and mouth ulceration, haemorrhagic enterocolitis (with massive bleeding), diarrhoea; persistent renal and hepatic toxicity. Management: Symptomatic and supportive treatment. May give granulocyte colony-stimulating factor and thrombocyte concentrates for agranulocytosis and thrombocyte. Provide haematological support during prolonged bone marrow depression and administer antibiotics for infection prophylaxis. Maintain electrolyte and fluid balance; monitor renal, hepatic and cardiac function.
Drug Interactions
May increase risk of cardiac toxicity with other cardiotoxic drugs (e.g. anthracyclines). May increase risk of developing secondary AML or MDS with other antineoplastic and/or radiotherapy. May increase risk of myelosuppression with other myelosuppressive agents (e.g. drugs used for treatment of breast cancer). May increase risk of excessive immunodepression and lymphoproliferative syndrome with other immunosuppressive agents. May increase risk of bleeding with vitamin K antagonists. May result in increased bioavailability with BCRP transporter inhibitors (e.g. eltrombopag, gefitinib). May result in decreased exposure with BCRP transporter inducers.
Potentially Fatal: Increased risk of infection and other adverse effects (e.g. vaccinia gangrenosa, generalised vaccinia) with live virus vaccine (e.g. yellow fever vaccination).
Action
Description: Mitoxantrone, a synthetic anthracenedione derivative, is a potent inhibitor of topoisomerase II, an enzyme responsible for uncoiling and repairing damaged deoxyribonucleic acid (DNA). It intercalates into DNA through hydrogen bonding, thereby causing cross-links and breaking of strands. Additionally, it binds to nucleic acid and suppresses the synthesis of DNA and ribonucleic acid (RNA) by template disordering and steric obstruction. It also decreases replication by binding to DNA topoisomerase II.
Pharmacokinetics:
Distribution: Enters breast milk. Rapidly and extensively distributed into kidney, liver, heart, bone marrow, lungs. Plasma protein binding: 78%.
Metabolism: Metabolised in the liver.
Excretion: Via faeces (25%); urine (11%; 65% as unchanged drug). Terminal elimination half-life: 23-215 hours.
Chemical Structure

Chemical Structure Image
Mitoxantrone

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 4212, Mitoxantrone. https://pubchem.ncbi.nlm.nih.gov/compound/Mitoxantrone. Accessed Aug. 26, 2021.

Storage
Store between 15-25°C. Opened vials: Store between 15-25°C for up to 7 days or 2-8°C for up to 14 days. This is a cytotoxic drug, follow applicable procedures for receiving, handling, administration, and disposal.
ATC Classification
L01DB07 - mitoxantrone ; Belongs to the class of cytotoxic antibiotics, anthracyclines and related substances. Used in the treatment of cancer.
References
Anon. Mitoxantrone. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 01/06/2021.

Baxter Healthcare Ltd. Onkotrone 2 mg/mL Concentrate for Injection data sheet 22 October 2020. Medsafe. http://www.medsafe.govt.nz. Accessed 01/06/2021.

Buckingham R (ed). Mitoxantrone Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/06/2021.

Joint Formulary Committee. Mitoxantrone. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/06/2021.

Mitoxantrone 2 mg/mL Concentrate for Solution for Infusion (Accord Healthcare Limited). MHRA. https://products.mhra.gov.uk. Accessed 01/06/2021.

Mitoxantrone 2 mg/mL Sterile Concentrate (EBEWE Pharma Ges.m.b.H Nfg. KG). MHRA. https://products.mhra.gov.uk. Accessed 01/06/2021.

Mitoxantrone Baxter (Baxter Oncology GMBH). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 01/06/2021.

Mitoxantrone Injection, Solution, Concentrate (Hospira, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 01/06/2021.

Disclaimer: This information is independently developed by MIMS based on Mitoxantrone from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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