Mitoxantrone treatment of multiple sclerosis: safety considerations.
Treatment of patients with mitoxantrone for worsening multiple sclerosis (MS) requires careful monitoring for possible adverse events. Common side effects that are minor and easily managed include transient leukopenia and elevated liver enzymes, nausea, alopecia, bluish discoloration of urine, and urinary tract infections. Amenorrhea, severe infection, cardiac toxicity, and toxic leukemias are more serious adverse events associated with mitoxantrone treatment but occur infrequently. The potential for clinically significant heart failure is low and is dose-related. Subclinical reductions in left ventricular ejection fraction may occur with serial doses, underscoring the importance of careful monitoring before initiating and during treatment. The risk for chronic cardiomyopathy limits the approved cumulative dose of mitoxantrone for treatment of MS to 140 mg/m2. Dexrazoxane has a cardioprotective effect when used with anthracycline in the treatment of patients with neoplasms. Studies under way address whether concomitant administration of dexrazoxane with mitoxantrone might decrease the risk for cardiac toxicity in MS patients and perhaps increase the allowable cumulative dose of mitoxantrone. A phase IV clinical study of mitoxantrone (RENEW) is in progress to assess the long-term safety and tolerability of treatment. Careful laboratory and cardiac monitoring can reduce the possibility of adverse events and enhance patient safety.
Cohen
Bruce A
BA
Davee Department of Neurology, Northwestern University, 710 North Lake Shore Drive, Abbott Hall 1121, Chicago, Illinois 60611, USA. bac106@northwestern.edu
Mikol
Daniel D
DD
D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced / Q000517:prevention & control; D016903:Drug Monitoring; D006333:Heart Failure / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use / Q000633:toxicity; D007938:Leukemia / Q000139:chemically induced; D008942:Mitoxantrone / Q000009:adverse effects* / Q000627:therapeutic use / Q000633:toxicity; D009103:Multiple Sclerosis / Q000188:drug therapy*
D007166:Immunosuppressive Agents; D008942:Mitoxantrone