Activated DEFINITY® (Perflutren Lipid Microsphere) Injectable Suspension is indicated for use in patients with suboptimal echocardiograms to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border.The safety and efficacy of DEFINITY® with exercise stress or pharmacologic stress testing have not been established.

Do not administer DEFINITY® to patients with known or suspected:Right-to-left, 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 QT interval,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 (see WARNINGS).Do not administer DEFINITY® by intra-arterial injection.

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Cardiac shunt --

Congestive heart failure -- complication of heart diseases; defective cardiac filling and/or impaired contraction and emptying, resulting in the heart's inability to pump a sufficient amount of blood to meet the needs of the body tissues or to be able to do so only with an elevated filling pressure.

Acute myocardial infarction --

Acute Coronary Syndrome -- An episode of MYOCARDIAL ISCHEMIA that generally lasts longer than a transient anginal episode but that does not usually result in MYOCARDIAL INFARCTION.

Ventricular arrhythmia -- Irregular heart beat resulting from a pathologic process in the cardiac ventricles.--2004

cardiac arrhythmia -- any variation from the normal rhythm or rate of the heart beat.

Respiratory Failure -- respiratory function fails to maintain adequate oxygen supply and carbon dioxide removal.

Physical findings -- Objective evidence of disease perceptible to the examining physician.

Symptoms -- An indication that a person has a condition or disease. Some examples of symptoms are headache, fever, fatigue, nausea, vomiting, and pain.

Hypercapnia -- A clinical manifestation of abnormal increase in the amount of carbon dioxide in arterial blood.

Pathological accumulation of air in tissues -- A pathological accumulation of air in tissues or organs.

Pulmonary Emphysema -- Enlargement of air spaces distal to the TERMINAL BRONCHIOLES where gas-exchange normally takes place. This is usually due to destruction of the alveolar wall. Pulmonary emphysema can be classified by the location and distribution of the lesions.

Pulmonary Embolism -- Blocking of the PULMONARY ARTERY or one of its branches by an EMBOLUS.

Pulmonary Hypertension -- Increased VASCULAR RESISTANCE in the PULMONARY CIRCULATION, usually secondary to HEART DISEASES or LUNG DISEASES.

Hypersensitivity -- Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen.

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 (see CONTRAINDICATIONS).

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.In postmarketing use, four patients experienced fatal cardiac arrests either during or within 30 minutes of DEFINITY® administration; one patient received DEFINITY® and underwent a cardiac stress test, two patients had severe congestive heart failure and the fourth was undergoing mechanical ventilation for respiratory failure.

Other uncommon but serious reactions observed during or shortly following DEFINITY® administration included cardiac or respiratory arrest, loss of consciousness, convulsions, symptomatic arrhythmias (atrial fibrillation, supraventricular tachycardia, ventricular tachycardia or fibrillation), hypotension, respiratory distress or cardiac ischemia (see ADVERSE REACTIONS).Activated DEFINITY® given at a dose of 1 mL/kg (13.5x the maximum human dose based on body surface area) increased the respiratory rate and pulmonary arterial pressure (300% and 188%, respectively) in dogs.

One dog died displaying clinical signs consistent with cardiopulmonary collapse.

Signs consistent with cardiopulmonary collapse were also noted in rats dosed with activated DEFINITY® (multiple-dose study) and included deaths at doses >0.3 mL/kg (2.5x the maximum human dose based on body surface area).

Additionally, histopathological pulmonary lesions were detected in rats at doses above 0.1 mL/kg (20% lower than the maximum human dose based on body surface area).