FDA Issues Reminder Novantrone Warning

The FDA issued a health alert yesterday to neurological and oncological healthcare providers who use Novantrone and generic mitoxantrone. The statement was sent as a reminder about previous recommendations which have been issued about the safe use of the drug.

Doctors who use Novantrone have been urged to evaluate left ventricular ejection fraction (LVEF) before each treatment, to monitor for possible cardiac toxicity and to provide information to patients with multiple sclerosis who receive the drug.

Novantrone (mitoxantrone hydrochloride for injection concentrate) is an immunosuppressant used for treatment of secondary progressive forms of multiple sclerosis (SPMS), leukemia and other types of cancer. The medication, which is injected intravenously, was approved for treatment of SPMS in October 2000 and is currently manufactured by EMD Serono, Inc. and OSI Pharmaceuticals, Inc.

The medication is effective against multiple sclerosis in the short term, reducing relapses and disability. However, it is not intended for long-term therapy because it can cause severe dose-dependent cardiotoxicity, liver damage and congestive heart failure (CHF). Other Novanntrone side effects include nausea, chest pain, temporary hair loss, diarrhea, skin rash and mouth sores.

According to the FDA, case reports in medical literature and post marketing adverse event reports indicate that Novantrone and generic mitoxantrone can result in decreases in LVEF, a sign of impaired heart function, and congestive heart failure in MS patients who received cumulative doses of Novantrone that were less than 100mg/m2 of body surface area.

In March 2005, the warning label of Novantrone was amended to indicate that LVEF needs to be evaluated in multiple sclerosis patients before initiating mitoxantrone treatment and before each dose of the drug is given. Recommendations were also added that cardiac monitoring should be carried out to detect cardiac toxicity that may have developed during or after termination of treatment.

The FDA alert was issued as a reminder to doctors, since the agency indicates that they continue to see poor adherence to the recommendations in clinical practice. The FDA is currently working with the manufacturers of Novantrone and generic mitoxantrone hydrochloride to educate healthcare providers about the importance of cardiac monitoring in multiple sclerosis patients using the drug.

Healthcare providers are also asked to ensure that MS patients who have completed mitoxantrone treatment receive annual quantitative LVEF evaluation to detect cardiac toxicity that may develop later. All MS patients are also to be informed about the risks and problems that may develop when using the drug.