New Recommendations from the FDA Concerning the Monitoring of Cardiac Function in People Taking Mitoxantrone
In July 2008, the FDA issued new recommendations for cardiac monitoring of people taking mitoxantrone (marketed as Novantrone® by EMD Serono and also available in generic form). In addition to the earlier recommendation that left ventricular ejection fraction (LVEF) be evaluated before initiating treatment and prior to the administration of each dose, the FDA further recommends that all patients with MS who have completed treatment with mitoxantrone receive yearly quantitative LVEF evaluations to detect late-occurring cardiac toxicity.
In March 2005, the FDA added a black box warning to the prescribing information for mitoxantrone, recommending that left ventricular ejection fraction (LVEF) be evaluated before initiating treatment and prior to the administration of each dose. These recommendations were made in response to post-marketing reports and case reports in the medical literature that described LVEF decreases or congestive heart failure in patients with multiple sclerosis (MS). Congestive heart failure (CHF), which is potentially fatal, may occur during therapy with mitoxantrone and for months to years after stopping therapy. The risk of cardiotoxicity (occurrence of heart muscle damage) rises with increasing cumulative doses and may occur whether or not risk factors for cardiac disease are present.
In July 2008—in response to information from a post-marketing safety study that demonstrated that many physicians are not following these recommendations in clinical practice—the FDA issued additional recommendations for cardiac monitoring of people taking mitoxantrone. The FDA is reaffirming the importance of the recommendations listed in the black box warning about cardiotoxicity and further recommending that all patients with MS who have completed treatment with mitoxantrone receive yearly quantitative LVEF evaluations to detect late-occurring cardiac toxicity.
Summary of recommendations regarding cardiotoxicity
- Before beginning therapy with mitoxantrone:
- Patients must be assessed for signs and symptoms of cardiac disease by history, physical examination and electrocardiogram (ECG).
- A baseline quantitative evaluation of LVEF using an appropriate methodology [echocardiogram, multi-gated radionuclide angiography (MUGA), or magnetic resonance imaging (MRI)] must be performed.
- Patients with MS who have a baseline LVEF below the lower limit of normal should not be treated with mitoxantrone.
- Before each subsequent dose:
- Patients should be assessed for cardiac signs and symptoms by history, examination and ECG and undergo a quantitative reevaluation of LVEF using the same methodology for each assessment.
- Additional doses of mitoxantrone should not be given to people who have experienced a drop in LVEF to below the lower limit of normal or have a clinically significant reduction in LVEF during treatment.
- After completing treatment with mitoxantrone (with a maximum cumulative dose no greater than 140mg/m2), patients should undergo yearly LVEF evaluation to monitor for late-occurring cardiotoxicity, using the same methodology that was used for assessments that were done during treatment.
Novantrone® is a registered trademark of Immunex Corp.
The National MS Society is proud to be a source of information about MS. Our comments are based on professional advice, published experience and expert opinion, but do not represent individual therapeutic recommendation or prescription. For specific information and advice, consult your personal physician.