FDA Updates Definity Optison WarningJul 17, 2008 | Parker Waichman LLP
Healthcare providers were notified today about labeling changes for Definity and Optison, micro-bubble contrast agents used in sonograms of the heart. The revised Boxed Warning and Warnings continue to highlight the risk of serious cardiopulmonary reactions during or within 30 minutes following the administration of Definity and Optison.
Definity, marketed by Lantheus Medical Imaging, and Optison, distributed by GE Healthcare, are used during echocardiograms, ultrasound imaging procedures that take a detailed, moving picture of the heart. In October 2007 the Food & Drug Administration (FDA) said that it knew of at least 7 deaths associated with the administration of either Definity or Optison. Four of those fatalities occurred either during infusion or within 30 minutes following the administration of the contrast agent. The FDA said that most 200-plus serious but non-fatal reactions reported to the agency also occurred in the same time frame.
As a result of these reports, the FDA requested that the labeling on Definity and Optison be modified to include a black box warning about the cardiac problems associated with these agents. The agency also said that Definity and Optison should not be used in patients who were acutely ill, such as those with congestive heart failure.
Since October 2007, the FDA has received post-market reports of five deaths following the administration of Definity; no deaths were reported for Optison. All patients who died following the administration of Definity had severe underlying medical conditions. Three of the deaths were associated with cardiac arrest that occurred within 30 minutes following Definity administration. Most patients had multiple co-morbidities. Following the October 2007, the FDA has also received approximately 60 reports of serious non-fatal reactions following Definity administration.
Despite the continuing reports of deaths related to the contrast agents, many cardiologists complained that that restriction robbed them of an important diagnostic tool. In today's notice to healthcare providers, the FDA said several of the warnings that were added to the labeling in October 2007 were removed because the agency determined that, in some patients, the benefits from the diagnostic information that could be obtained through the use of Definity and Optison may outweigh the risk for serious cardiopulmonary reactions, even among some patients at particularly high risk for these reactions.
As part of the revision, the FDA removed warnings that Definity and Optison should not be administered to patients with worsening or clinically unstable congestive heart failure, acute myocardial infarction or acute coronary syndromes, serious ventricular arrhythmias or high risk of arrhythmias due to prolongation of the QT interval, respiratory failure, severe emphysema, and pulmonary emboli or other conditions that cause pulmonary hypertension.
The label revisions recommend that high-risk patients with pulmonary hypertension or unstable cardiopulmonary conditions be closely monitored during and for at least 30 minutes after administration of these contrast agents.
Along with the label changes, the FDA says it is now requiring that manufacturers of micro-bubble contrast agents conduct clinical studies to more thoroughly assess the risks for serious cardiopulmonary reactions.