The new “black box” labeling for Definity® has been released by the FDA as of 10 Oct 2007.

Please download the document in its entirety from the FDA site here:

http://www.fda.gov/cder/foi/label/2007/021064s007lbl.pdf

We have summarized the salient points.

Contraindications:

Do not administer DEFINITY® to patients with known or suspected:

-Right-to-Ieft, bi-directional, or transient right-to-left cardiac shunts

-Worsening or clinically unstable congestive heart failure

-Acute myocardial infarction or acute coronary syndromes

-Serious ventricular arrhythmias or high risk for arrhythmias due to prolongation of the QTinterval

-Respiratory failure, as manifest by signs or symptoms of carbon dioxide retention or hypoxemia,

-Severe emphysema, pulmonary emboli or other conditions that cause pulmonary hypertension due to compromised pulmonary arterial vasculature,

-Hypersensitivity to perflutren

Warnings:

High ultrasound mechanical index values may cause microsphere cavitation or rupture and lead to ventricular arrhythmias. Additionally, end-systolic triggering with high mechanical indices has been reported to cause ventricular arrhythmias. The safety of activated DEFINITY® at mechanical indices greater than 0.8 has not been evaluated. The safety of activated DEFINITY® with the use of end-systolic triggering has not been evaluated.

Post-marketing reports of four patients experienced fatal cardiac arrests either during or within30 minutes of DEFINITY® administration.

-one patient received DEFINITY® and underwent a cardiac stress test

-two patients had severe congestive heart failure

the fourth was undergoing mechanical ventilation for respiratory failure.

Other uncommon but serious reactions observed during or shortly following DEFINITYCI administration included cardiac or respiratory arrest,loss of consciousness, convulsions, symptomatic arrhythmias (atrial fibrilation, supraventricular

tachycardia, ventricular tachycardia or fibrilation), hypotension, respiratory distress or cardiacischemia.

Post-marketing reports of acute anaphylactoid reactions including shock, bronchospasm, upper airway swelling, loss of consciousness, urticaria and pruritus, have occurred in patients with no prior exposure to DEFINITYII. Monitor all patients for signs and symptoms of anaphylactoid reactions

Serious cardiopulmonary reactions, including fatalities, have occurred during or within 30 minutes following DEFINITY® administration.

-Assess all patients for the presence of any condition that precludes DEFINITY®

administration

-Monitor patients during and for 30 minutes following DEFINITY® administration,

including vital sign measurements and electrocardiography in all patients and cutaneous oxygen saturation in patients at risk for hypoxemia.

-Always have resuscitation equipment and trained personnel readily available.