1 Ultrasound From Bracco Diagnostics Inc.— A GLOBAL LEADER IN ENHANCED ULTRASOUND LUMASON FOR FOCAL LIVER LESIONS PRODUCT MONOGRAPH Our commitment to you… The ultrasound contrast agent LUMASON® (sulfur hexafluoride lipid-type A microspheres) for injectable suspension, known internationally as SonoVue®, was approved by the U.S. Food and Drug Administration (FDA) in 2014 for echocardiography, to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border, in adult patients with suboptimal echocardiograms. Bracco Diagnostics Inc. is proud to introduce a second indication for LUMASON. As of March 2016, LUMASON was approved for use in ultrasonography of the liver for characterization of focal liver lesions in adult and pediatric patients.1 LUMASON consists of microspheres that encapsulate an inert gas [sulfur hexafluoride (SF6)] in a phospholipid shell. LUMASON is provided in a single-use, 3-part kit that includes all components necessary for reconstitution, and requires no refrigeration for storage or mechanical agitation for reconstitution.1 Bracco Diagnostics Inc. is dedicated to providing imaging agents and solutions that improve diagnostic efficacy, patient safety, and cost effectiveness. LUMASON has been developed to meet the needs of modern ultrasound imaging practices. Please see full Prescribing Information including boxed WARNING by clicking here. 1 INDICATIONS AND USAGE LUMASON is an ultrasound contrast agent indicated for use: • in echocardiography to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border in adult patients with suboptimal echocardiograms • in ultrasonography of the liver for characterization of focal liver lesions in adult and pediatric patients CONTRAINDICATIONS LUMASON is contraindicated in patients with: • Known or suspected right-to-left, bi-directional, or transient right-to-left cardiac shunts • History of hypersensitivity reactions to sulfur hexafluoride lipid microsphere components or to any of the inactive ingredients in LUMASON IMPORTANT SAFETY INFORMATION: WARNING: SERIOUS CARDIOPULMONARY REACTIONS Serious cardiopulmonary reactions, including fatalities, have occurred uncommonly during or following the injection of ultrasound contrast agents, including sulfur hexafluoride lipid microspheres [see Warnings and Precautions (5.1)]. Most serious reactions occur within 30 minutes of administration [see Warnings and Precautions (5.1)]. • Assess all patients for the presence of any condition that precludes administration [see Contraindications (4)]. • Always have resuscitation equipment and trained personnel readily available [see Warnings and Precautions (5.1)]. The risk for serious cardiopulmonary reactions may be increased among patients with unstable cardiopulmonary conditions (acute myocardial infarction, acute coronary artery syndromes, worsening or unstable congestive heart failure, or serious ventricular arrhythmias [see Warnings and Precautions (5.1)]). Please see full Prescribing Information including boxed WARNING by clicking here. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. Manufactured for Bracco Diagnostics Inc., Monroe Township, NJ 08831 by Bracco Suisse S.A., Plan-les-Ouates Geneve, Switzerland (LUMASON lyophilized powder vial-25 mg lipid-type A/60.7 sulfur hexafluoride gas); Vetter Pharma-Fertigung GmbH & Co. KG, 88212 Ravensburg, Germany (Sodium Chloride 0.9% Injection, USP); B. Braun Melsungen AG, 34212 Melsungen, Germany (Mini-Spike). LUMASON is a registered trademark of Bracco Diagnostics Inc. SonoVue is a registered trademark of Bracco Suisse S.A. 2 3 TABLE OF CONTENTS LUMASON Description .........................................................................9 Mechanism of Action...........................................................................9 Pharmacodynamic Properties ....................................................................9 Pharmacokinetic Properties .....................................................................10 Pharmacokinetics in Special Populations...........................................................11 Indication...................................................................................12 Clinical Studies ..............................................................................12 Boxed Warning ..............................................................................13 Contraindications.............................................................................14 Warnings and Precautions......................................................................14 Adverse Reactions............................................................................15 Use in Specific Populations .....................................................................17 Patient Counseling Information ..................................................................17 Recommended Dose for Ultrasound of the Liver .....................................................19 Dosage Forms and Strengths ...................................................................19 Storage and Handling .........................................................................19 LUMASON Preparation ........................................................................20 LUMASON Administration ......................................................................24 Please see full Prescribing Information including boxed WARNING by clicking here. 3 INDICATIONS AND USAGE LUMASON is an ultrasound contrast agent indicated for use: • in echocardiography to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border in adult patients with suboptimal echocardiograms • in ultrasonography of the liver for characterization of focal liver lesions in adult and pediatric patients CONTRAINDICATIONS LUMASON is contraindicated in patients with: • Known or suspected right-to-left, bi-directional, or transient right-to-left cardiac shunts • History of hypersensitivity reactions to sulfur hexafluoride lipid microsphere components or to any of the inactive ingredients in LUMASON IMPORTANT SAFETY INFORMATION: WARNING: SERIOUS CARDIOPULMONARY REACTIONS Serious cardiopulmonary reactions, including fatalities, have occurred uncommonly during or following the injection of ultrasound contrast agents, including sulfur hexafluoride lipid microspheres [see Warnings and Precautions (5.1)]. Most serious reactions occur within 30 minutes of administration [see Warnings and Precautions (5.1)]. • Assess all patients for the presence of any condition that precludes administration [see Contraindications (4)]. • Always have resuscitation equipment and trained personnel readily available [see Warnings and Precautions (5.1)]. The risk for serious cardiopulmonary reactions may be increased among patients with unstable cardiopulmonary conditions (acute myocardial infarction, acute coronary artery syndromes, worsening or unstable congestive heart failure, or serious ventricular arrhythmias [see Warnings and Precautions (5.1)]). Please see full Prescribing Information including boxed WARNING by clicking here. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. Manufactured for Bracco Diagnostics Inc., Monroe Township, NJ 08831 by Bracco Suisse S.A., Plan-les-Ouates Geneve, Switzerland (LUMASON lyophilized powder vial-25 mg lipid-type A/60.7 sulfur hexafluoride gas); Vetter Pharma-Fertigung GmbH & Co. KG, 88212 Ravensburg, Germany (Sodium Chloride 0.9% Injection, USP); B. Braun Melsungen AG, 34212 Melsungen, Germany (Mini-Spike). LUMASON is a registered trademark of Bracco Diagnostics Inc. SonoVue is a registered trademark of Bracco Suisse S.A. 4 5 LUMASON FOR LIVER ULTRASOUND AT A GLANCE • LUMASON® (sulfur hexafluoride lipid-type A microspheres) for injectable suspension is a second-generation ultrasound contrast agent that has been developed to provide an optimal backscattered signal over a broad frequency range, with good pressure stability and persistence in the blood stream.2 • LUMASON is characterized by a microsphere structure consisting of a low solubility gas (sulfur hexafluoride, SF6) stabilized by a phospholipid shell.1 • LUMASON is indicated: (1) in echocardiography for use in adult patients with suboptimal echocardiograms to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border, and (2) in ultrasonography of the liver for use in adult and pediatric patients to characterize focal liver lesions1 • LUMASON is contraindicated in patients with: • Known or suspected right-to-left, bi-directional, or transient right-to left cardiac shunts • History of hypersensitivity reactions to sulfur hexafluoride lipid microsphere components or to any of the inactive ingredients in LUMASON1 • For ultrasonography of the liver, LUMASON provides dynamic patterns of differential signal intensity enhancement between focal liver lesions and liver parenchyma during the arterial, portal-venous, and late phases of signal intensity enhancement of the microvasculature.1 • LUMASON is provided in a 3-part kit, allowing for easy reconstitution, and requires no refrigeration. Each kit contains a LUMASON vial containing 25 mg lipid-type A lyophilized powder with headspace filled with 60.7 mg of SF6; a prefilled syringe containing