Last updated on November 18th, 2025 at 06:25 pm
Summary
Mitoxantrone is licensed to treat MS in a few countries (though not in the UK). It is typically used to treat active secondary progressive, progressive relapsing, or worsening relapsing remitting MS. It is a repurposed chemotherapy agent and is given as an intravenous infusion. Mitoxantrone is associated with quite severe toxicity (infections, cardiotoxicity, premature ovarian failure and secondary leukaemia) so it is not used often. In some countries, it is used as a true induction therapy followed by a maintenance DMT, typically interferon-beta or glatiramer acetate. Because mitoxantrone is toxic to the heart, a limited cumulative dose can be given safely over a lifetime. I have kept mitoxantrone on the list of essential DMTs because it is generic and hence is available for treating MS in resource-poor settings.
Trade name
Novantrone.
Mode of action
Mitoxantrone is an immune constitution therapy. It works by inhibiting the enzyme topoisomerase II which unwinds DNA. As a result, it disrupts DNA synthesis and DNA repair in cells and causes them to die. White blood cells are particularly sensitive to its actions.
Efficacy
High to very high.
Immunosuppression
Yes.
Infusion protocols
It is either given as a monthly infusion for 6 months, or every 3 months for up to 2 years, or as a combination of these two protocols. The total lifetime dose of mitoxantrone should not exceed 140 mg/m² and cardiac monitoring (ECG and ejection fraction) needs to be performed to detect any signs of cardiomyopathy.
Adverse events and special precautions
Infection: mitoxantrone causes a low white cell count that may result in increased susceptibility to infection. Chest infections and urinary tract infections are common. Broken skin or ingrown toenails may become areas harbouring infection. Neutropenia may develop and hence susceptibility to neutropenic sepsis, including infection with Listeria monocytogenes. Patients who are negative for varicella zoster virus should receive the VZV vaccine.
Nausea and vomiting (mild) may occur during treatment and the next day.
Hair thinning may occur temporarily. Hair loss is uncommon (occurring in fewer than 3% of people with MS who receive mitoxantrone).
Cardiotoxicity: a heart scan (MUGA or ECG) must be completed at baseline (before the first dose) and then 3-monthly before administration of the next dose. Mitoxantrone treatment may have to be stopped if the tests show a significant decrease in cardiac function.
Extravasation: pain and inflammation may occur along the path of a vein through which mitoxantrone is administered if the drug accidentally infiltrates the tissue outside the vein.
Leukaemia related to the drug is a risk in ~1 in 200–400 subjects with MS treated with mitoxantrone.
Infertility: transient lack of periods may occur in ~12% of patients and premature menopause in ~10% of patients.
Pregnancy and breastfeeding are contraindicated when using mitoxantrone.