Mitoxantrone, an anthracenedione agent, reduces relapse rate as well as numbers of T2 and gadolinium-enhancing lesions on MRI in patients with relapsing-remitting MS or early secondary progressive MS (with active inflammatory disease and evidence of substantial disease worsening over short periods of time) [23, 47]. There is no proven benefit for patients with relapse independent progression. The drug is generally used in patients with aggressive relapsing-remitting or secondary progressive disease. For patients with progressive disease, The NNT for 2 years to prevent one patient from worsening by 1 EDSS point was 11.
7.3.1 Mode of Action
Mitoxantrone reduces T- and B-cell immunity by inhibition of both DNA and RNA synthesis.
Patients may notice a temporary blue discoloration of the urine and sclerae. Leukopenia and neutropenia occur commonly. CBC should be monitored closely, and if the white blood cell count drops to less than 3,000/|l or if neutrophils are less than 1,500/l, mitoxantrone should be held. Liver function tests (LFTs) should also be monitored, and therapy held if LFTs increase by more than 2.5 beyond the upper limits .
Cardiomyopathy is dose-dependent and may be as great as 6% in patients receiving 140mg/m2 or less . Prior to each infusion, patients should have an echocardiogram to evaluate their ejection fraction. Delayed effects of mitoxantrone on cardiac function have been reported. Antiemetic premedication (with ondansetron) may alleviate nausea during and for several days after infusion. Alopecia, amenorrhea, and infertility may also occur. Mitoxantrone is teratogenic. Leukemia occurs in approximately 1% of patients and generally responds to treatment.
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