Monitoring for Cardiotoxicity in Patients with MS Post-Mitoxantrone Therapy An Update

Mitchell Wallin MD, MPH, Washington, DC VA Medical Center, MS Center of Excellence-East
Ruth Whitham MD, Portland VA Medical Center, MS Center of Excellence-West
Kathy Tortorice, Pharm D, Pharmacy Benefits Management, Hines VA Medical Center

FDA Recommendations 
VA Pharmacy Benefit Management Service Response 
MSCoE Cardiac Monitoring Guidelines 
For VA Providers 
References

FDA Recommendations

The Food and Drug Agency (FDA) posted an alert in July 2008 recommending that all patients with multiple sclerosis (MS) treated with mitoxantrone receive annual left ventricular ejection fraction (LVEF) monitoring to evaluate for cardiotoxicity. Monitoring for cardiac toxicity is best done through an echocardiogram or MUGA (Multiple Gated Acquisition) scan. This recommendation was based on recent surveillance data that showed 4 patients had significant drops (> 10 %) in cardiac ejection fraction up to 17 months post therapy.
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VA Pharmacy Benefit Management Service Response

There were no recommendations given by the FDA on how long to monitor LVEF or when to refer to a specialist. An earlier FDA alert in 2005 recommended that LVEF be evaluated prior to initiating mitoxantrone therapy and prior to the administration of each dose. In August 2008, the VA Pharmacy Benefit Management Service sent a response memo to all VA providers summarizing this information along with the 2005 FDA alert and provided some background from the medical literature.

Based on the new August 2008 alert, patients with MS that have received mitoxantrone in the past should be identified at local VA facilities. This can be done with the help of clinical records or pharmacy databases at a local facility. The national pharmacy benefits administration and the MSCoEs may also be able to assist sites in identifying patients treated with mitoxantrone within VA facilities. Mitoxantrone therapy received outside the VA healthcare system will have to be determined by evaluation of past records or interview and also should be taken into account. The maximum recommended lifetime dose of mitoxantrone is 140mg/m2. The most recent echocardiogram or MUGA scan should be identified for comparison purposes.
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MSCoE Cardiac Monitoring Guidelines

In consultation with PBM pharmacists and cardiology experts, the MSCoEs feel the following cardiac monitoring guidelines are reasonable for MS patients that have received mitoxantrone in the past.

A single follow-up echocardiogram or MUGA scan should be ordered in all MS patients that have received mitoxantrone in the past. Based on the results of this study, two courses of action may be taken:

• If the ejection fraction is normal (>50%), no further monitoring is required unless cardiac symptoms develop.
• If the ejection fraction has decreased from prior studies, is < 46%, or if the patient has cardiac symptoms (e.g. dyspnea or peripheral edema), a referral to a cardiology specialist should be made for evaluation. Studies suggest that early treatment in patients with congestive heart failure can improve long-term outcomes.

Further monitoring of LVEF in patients with MS that have received mitoxantrone in the past should take place on an individual basis.
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For VA Providers

If you would like more information on patients receiving mitoxantrone at your facility please contact William “Joel” Culpepper II, PhD, MA, Associate Director for Epidemiology & Outcomes MSCoE, East at 410.605.7000, x4341 or by email at william.culpepper@va.gov.
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References

• Food and Drug Administration (FDA) Alert. 07/29/2008. Accessed 10/09/2008.
• National PBM Response to FDA Memorandum: Information for Healthcare Professionals, August 18, 2008.
• McCullough PA, Philbin EF, Spertus JA, et al. Opportunities for improvement in the diagnosis and treatment of heart failure. Clin Cardiol 2003;26:231-7.

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Last Updated: October 2009