Final Program
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FINAL PROGRAM MINNEAPOLIS CONVENTION CENTER, MINNEAPOLIS, MN WWW.ASESCIENTIFICSESSIONS.ORG DISEASE BASED FOCUS ON THE ROLE OF ECHO IN DIAGNOSIS AND GUIDING THERAPY Please Visit Booth 715 To place an order, call 1-800-299-3431 or visit www.definityimaging.com Please Visit Booth 715 To place an order, call 1-800-299-3431 or visit www.definityimaging.com 515835-1211 to-left cardiac shunts phospholipid-encapsulated microspheres (Table 6.1 Cont’d) All activated can bypass the pulmonary particle-filtering mechanisms and DEFINITY® directly enter the arterial circulation resulting in microvascular (N=1716) occlusion and ischemia. In an animal study utilizing intra- ® Central and peripheral nervous arterial administration of activated DEFINITY , microsphere system disorder 54 (3.1) trapping was seen in small arterioles <15 µm, especially at branch points and in capillaries at all doses tested, including Headache 40 (2.3) doses directly applicable to those used in humans. An animal Dizziness 11 (0.6) FOR INTRAVENOUS USE study utilizing intravenous administration did not result in arterial microvascular obstruction presumably because of Gastrointestinal system 31 (1.8) BRIEF SUMMARY filtering by the lungs. Do not administer DEFINITY® by intra- Nausea 17 (1.0) arterial injection [see CONTRAINDICATIONS]. Please See Full Prescribing Information available at Vascular (extracardiac) disorders 19 (1.1) www.definityimaging.com for additional information. High Ultrasound Mechanical Index: Flushing 19 (1.1) High ultrasound mechanical index values may cause WARNING: SERIOUS CARDIOPULMONARY REACTIONS microsphere cavitation or rupture and lead to ventricular N=Sample size 1716 subjects who received activated ® Serious cardiopulmonary reactions, including fatalities, arrhythmias. Additionally, end-systolic triggering with high DEFINITY have occurred uncommonly during or following perflutren- mechanical indices has been reported to cause ventricular n=Number of subjects reporting at least one Adverse containing microsphere administration [See WARNINGS arrhythmias. The safety of activated DEFINITY® at mechanical Reaction AND PRECAUTIONS]. Most serious reactions occur within indices greater than 0.8 has not been evaluated [see DOSAGE 30 minutes of administration. AND ADMINISTRATION]. The safety of activated DEFINITY® Other adverse reactions that occurred in ≤0.5% of the activated DEFINITY®-dosed subjects were: • Assess all patients for the presence of any condition with the use of end-systolic triggering has not been evaluated. that precludes DEFINITY® administration [See QTc Prolongation: Body as a Whole: Fatigue, fever, hot flushes, pain, rigors, and syncope CONTRAINDICATIONS]. ECG parameters for doses up to 10 microL/kg were • Always have resuscitation equipment and trained personnel monitored in 221 subjects at multiple time points from 1 hour Cardiovascular: Abnormal ECGs, bradycardia, tachycardia, readily available. to 72 hours after the first bolus injection. In the 221 subjects, palpitation, hypertension and hypotension QTc prolongations of >30 msec were noted in 64 (29%) Digestive: Dyspepsia, dry mouth, tongue disorder, DESCRIPTION subjects. Forty-six out of 64 subjects with QTc prolongations toothache, abdominal pain, diarrhea and vomiting DEFINITY® (Perflutren Lipid Microsphere) Injectable were further evaluated and 39% (18/46) showed associated Hematology: Granulocytosis, leukocytosis, leukopenia, Suspension is an ultrasound contrast agent. The DEFINITY® cardiac rhythm changes. The effects of concomitant drugs and eosinophilia vial contains components that upon activation yield perflutren were not studied. Musculoskeletal: Arthralgia lipid microspheres, a diagnostic drug that is intended to Nervous System: Leg cramps, hypertonia, vertigo and be used for contrast enhancement during the indicated ADVERSE REACTIONS paresthesia echocardiographic procedures. The vial contains a clear, Clinical Trials Experience Platelet, Bleeding, and Clotting: Hematoma colorless, sterile, non-pyrogenic, hypertonic liquid, which A total of 1716 subjects were evaluated in pre-market clinical ® Respiratory: Coughing, hypoxia, pharyngitis, rhinitis and upon activation with the aid of a VIALMIX , provides a ®. In this group, 1063 (61.9%) trials of activated DEFINITY dyspnea homogeneous, opaque, milky white injectable suspension of were male and 653 (38.1%) were female, 1328 (77.4%) were perflutren lipid microspheres. The suspension of activated White, 258 (15.0%) were Black, 74 (4.3%) were Hispanic, Special Senses: Decreased hearing, conjunctivitis, ® DEFINITY is administered by intravenous injection. and 56 (3.3%) were classified as other racial or ethnic abnormal vision and taste perversion groups. The mean age was 56.1 years (range 18 to 93). Of Skin: Pruritus, rash, erythematous rash, urticaria, increased INDICATIONS AND USAGE these, 144 (8.4%) had at least one adverse reaction (Table sweating, and dry skin ® Activated DEFINITY (Perflutren Lipid Microsphere) Injectable 6.1). There were 26 serious adverse events and 15 (0.9%) Urinary: Albuminuria Suspension is indicated for use in patients with suboptimal subjects discontinued because of an adverse event. echocardiograms to opacify the left ventricular chamber and Deaths and Serious Adverse Events Postmarketing Experience to improve the delineation of the left ventricular endocardial Among the 1716 activated DEFINITY® patients, 19 (1.1%) In a prospective, multicenter, open-label registry of 1053 border. ® suffered serious cardiopulmonary adverse events including patients receiving DEFINITY in routine clinical practice, eight deaths. The deaths occurred several days after activated heart rate, respiratory rate, and pulse oximetry were CONTRAINDICATIONS ® ® monitored for 30 minutes after DEFINITY administration. ® DEFINITY administration and appeared to be related to Do not administer DEFINITY to patients with known or No deaths or serious adverse reactions were reported, suspected: the course of underlying disease. Of the 11 other serious adverse events, which appeared within days of the drug suggesting that these reactions are unlikely to occur at a rate ® • Right-to-left, bi-directional, or transient right-to-left administration (2-15 days), all appeared to be a progression of more than 0.3% when DEFINITY is used according to cardiac shunts, underlying cardiac and non-cardiac disease. However, a role recommendations. • Hypersensitivity to perflutren [see WARNINGS for DEFINITY® in the initiation or course of these adverse The following adverse reactions have been identified during AND PRECAUTIONS]. events cannot be ruled out. the post-marketing use of perflutren-containing microsphere ® Do not administer DEFINITY by intra-arterial injection. Discontinuations products. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible There were 15 discontinuations reported with a mean age of WARNINGS AND PRECAUTIONS to reliably estimate their frequency or establish a causal 41.5 years. Nine of these patients were discontinued after relationship to drug exposure. Serious Cardiopulmonary Reactions: the first injection. One patient experienced a hypersensitivity Serious cardiopulmonary reactions including fatalities have reaction with urticaria and pruritus and all the other patients Fatal cardiopulmonary and anaphylactoid events and other occurred uncommonly during or shortly following perflutren- experienced dizziness, chest pain, dyspnea or back pain. serious but non-fatal adverse reactions were uncommonly containing microsphere administration, typically within 30 These adverse reactions appeared within minutes (1 – reported. These events typically occurred within 30 minutes ® minutes of administration. The risk for these reactions may 15 min) of the drug administration and were of moderate of DEFINITY administration. These serious events may be be increased among patients with unstable cardiopulmonary intensity resolving usually without treatment within minutes increased among patients with unstable cardiopulmonary conditions (acute myocardial infarction, acute coronary or hours after onset. conditions (acute myocardial infarction, acute coronary artery syndromes, worsening or unstable congestive heart failure, artery syndromes, worsening or unstable congestive heart For all adverse reactions, the overall incidence of adverse or serious ventricular arrhythmias [see WARNINGS AND failure, or serious ventricular arrhythmias). Always have experiences was similar for the <65 year age group and the cardiopulmonary resuscitation personnel and equipment PRECAUTIONS]. ® > 65 year age group, similar in males and in females, similar readily available prior to DEFINITY administration and among all racial or ethnic groups, and similar for bolus and Reported reactions included: monitor all patients for acute reactions. infusion dosing. Table 6.1 summarizes the most common Cardiopulmonary The reported reactions include: fatal cardiac or respiratory adverse reactions. Fatal cardiac or respiratory arrest, shock, syncope, arrest, shock, syncope, symptomatic arrhythmias (atrial Table 6.1. New-Onset Adverse Reactions Occurring in symptomatic arrhythmias (atrial fibrillation, tachycardia, fibrillation, tachycardia, bradycardia, supraventricular ≥0.5% of All Activated DEFINITY®-Treated Subjects bradycardia, supraventricular tachycardia, ventricular tachycardia, ventricular fibrillation, ventricular tachycardia), fibrillation, ventricular tachycardia), hypertension, hypertension, hypotension,