Mitoxantrone is a synthetic antracenedione developed as an antineoplastic agent but which has been found effective in secondary progressive and progressive-relapsing multiple sclerosis (MS). Therapy is limited by dose-related cardiotoxicity as well as toxicity in other organs.


Recommended dose: 12 mg per square meter body surface area (BSA) every 3 months, administered as a 5-15 minute intravenous infusion.


Cardiotoxicity may develop with a cumulative dose of 100 mg per square meter BSA (8 or 9 doses). Patients should not receive cumulative doses > 120 mg per square meter BSA (10 doses) according to MKSAP (>= 140 mg per square meter BSA is stated as the maximum dose in the PDR).


Additional concerns:

(1) bone marrow toxicity with neutropenia and/or thrombocytopenia

(2) teratogenic effect in pregnant women

(3) prolonged half-life in patients with liver disease


Recommended testing prior to dosing:

(1) The patient should have the left ventricular ejection fraction performed by echocardiogram or MUGA:

(1a) before the first dose

(1b) if there is evidence of congestive heart failure

(1c) if the patient has had a cumulative dose >= 100 mg per meter square BSA.

(2) The absolute neutrophil count should be monitored before each dose.

(3) Liver function tests should be monitored before each dose.

(4) Women of child-bearing age should have a pregnancy test before dosing even if on birth control.


A dose should be deferred if:

(1) LVEF < 50%

(2) evidence of congestive heart failure

(2) absolute neutrophil count is < 1,500 per µL

(3) abnormal liver function tests

(4) positive pregnancy test


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