Deaths Prompt New Warnings for Micro-Bubble Contrast Agents

ROCKVILLE, Md., Oct. 12 -- Eleven deaths and nearly 200 reports of serious cardiopulmonary events have been linked to microbubble contrast agents (Definity and Optison) used in echocardiography, the FDA reported today.

DuPont Pharmaceuticals, maker of Definity, and GE Healthcare, maker of Optison, agreed to labeling changes emphasizing the risk for serious cardiopulmonary reactions and contraindication for use in patients with unstable cardiopulmonary status, said the agency.

Most of the deaths occurred within 12 hours of administration among patients with severe underlying conditions. In four cases, patients died after cardiac arrest within 30 minutes of receiving Definity.

Many of the 190 serious non-fatal reactions reported with Definity and nine reports with Optison also occurred within minutes of administration and were suggestive of anaphylactic or cardiopulmonary reactions, the FDA said.

The labeling changes included:

• A boxed warning for cardiopulmonary reactions.
• Warnings for cardiopulmonary and hypersensitivity reactions with recommendations to monitor vital signs, cardiac rhythm, oxygen saturation and to have equipment and trained personnel readily available for resuscitation.
• Contraindications for high-risk patients, specifically those with known cardiac shunts, clinically unstable or recent worsening of congestive heart failure, symptomatic arrhythmias or at elevated risk for arrhythmias.
• A cautionary statement that the safety and efficacy of Definity in exercise or pharmacological stress testing have not been established.

The manufacturers will conduct a postmarketing safety study to monitor risk of serious cardiovascular reactions, the FDA said.

Meanwhile, the FDA suggested that physicians should monitor all patients receiving these contrast agents for serious cardiopulmonary reactions during infusion and for 30 minutes after administration.

The FDA also recommended that all patients should be assessed for the following conditions before use:

• Right-to-left, bi-directional, or transient right-to-left cardiac shunts
• Clinically unstable or recent worsening congestive heart failure.
• Acute myocardial infarction.
• Serious ventricular arrhythmias or at high risk for arrhythmias due to QT prolongation.
• Respiratory failure.
• Severe emphysema, pulmonary emboli or other conditions that compromise pulmonary arterial vasculature.