Available for Android and iOS devices. stability at room temperature and -20 C. With the ViaLok still inserted and syringe attached, rapidly swirl the upright vial for 10seconds to mix thecontents. Lantheus Medical Imaging No significant findings on the fetus were observed. The au- *3 o Use within 12 hours of activation (see Insert) attenuation spectrum and size distribution of Definity were measured at room temperature (25 C) and physiological temperature (37 C), and were used to estimate the viscoelastic shell . In patients with right-to-left, bi-directional, or transient right-to-left cardiac shunts phospholipid-encapsulated microspheres can bypass the pulmonary particle-filtering mechanisms and directly enter the arterial circulation resulting in microvascular occlusion and ischemia. Then inject activated Definity (as described above) and begin ultrasound imaging immediately. If necessary, a second 10 microliters (microL)/kg dose followed by a second 10 mL 0.9% Sodium Chloride Injection, USP flush may be administered 30 minutes after the first injection to prolong contrast enhancement. Most serious reactions occur within 30 minutes of administration. In the 221 subjects, QTc prolongations of >30 msec were noted in 64 (29%) subjects. This information is intended for US healthcare professionals only. Background Treatment decisions in children with inflammatory bowel disease (IBD) are increasingly based on longitudinal tracking of faecal calprotectin concentrations, but there is little known about the stability of this protein in stool. 24-hour room temperature stability at all concentrations. . After activation, each vial contains a maximum of 1.2 1010 perflutren lipid microspheres, and about 150 microL/mL (1.1 mg/mL) octafluoropropane [see DESCRIPTION (11)]. Joshua Beytebiere. The overall incidence of adverse reactions was similar between males and females. The mean change in border length from baseline at end-diastole was statistically significant for all readers in the apical 4-chamber view and for 3 out of 4 readers for the apical 2-chamber view. Subsequent injection as needed. The bacteria used were Gram-positive Staphylococcus aureus (Rosenback 1884 DNA conservation is central to many applications. No clinically important pulmonary hemodynamic, systemic hemodynamic, or ECG changes were observed. Do not administer DEFINITY RT by intra-arterial injection. Lantheus Holdings, Inc. If DTT is kept at room temperature it will degrade/oxidize. DEFINITY RT is intended for administration only after activation in the VIALMIX RFID apparatus. 4th May, 2021. There are no data on the presence of DEFINITY in human milk, the effects on the breastfed infant, or the effects on milk production. Serious cardiopulmonary reactions, including fatalities, have occurred during or following perflutren-containing microsphere administration. See Full Prescribing Information for instructions on preparation and administration. When administering DEFINITY RT to patients with a cardiac shunt, the microspheres can bypass filtering by the lung and enter the arterial circulation. The safety and effectiveness of activated Definity have not been established in the pediatric population. Store the activated Definity at room temperature in the original product vial. Coma, loss of consciousness, convulsion, seizure, transient ischemic attack, agitation, tremor, vision blurred, dizziness, headache, fatigue. The microsphere particle size parameters are listed in Table 11.1 below: Perflutren lipid microspheres exhibit lower acoustic impedance than blood and enhance the intrinsic backscatter of blood. Distributed ByLantheus Medical Imaging331 Treble Cove RoadN. Victor Cohen, Department of Pharmaceutical Sciences, Maimonides . LEAVE, Sign up for DEFINITY updates andannouncements, DEFINITY Vial for (Perflutren Lipid Microsphere) InjectableSuspension, DEFINITY RT (Perflutren Lipid Microsphere) Injectable Suspension, Please see full Prescribing Information, including boxed. Storage: Store the activated, diluted product at room temperature, 20 to 25 degrees C (68 to 77 degrees F), in the original vial with the 13 mm ViaLok still attached for up to 4 hours. The recommended bolus dose for activated DEFINITY RT is 10 microliters (microL)/kg of the activated product by intravenous bolus injection within 30 to 60 seconds, followed by a 10 mL 0.9% Sodium Chloride Injection, USP flush. Store at room temperature 68 to 77F (20 to 25C). June 22, 2021. However, the size distributions of Definity at 25 C and 37 C were similar. Similar results were seen as described above. High ultrasound mechanical index values may cause microsphere cavitation or rupture and lead to ventricular arrhythmias. Use of this information is subject to the terms of our Legal Notice and Privacy Policy. . Other adverse reactions that occurred in 0.5% of the activated DEFINITY-dosed subjects were: Body as a Whole: Fatigue, fever, hot flushes, pain, rigors, and syncope, Cardiovascular: Abnormal ECGs, bradycardia, tachycardia, palpitation, hypertension and hypotension, Digestive: Dyspepsia, dry mouth, tongue disorder, toothache, abdominal pain, diarrhea and vomiting, Hematology: Granulocytosis, leukocytosis, leukopenia, and eosinophilia, Nervous System: Leg cramps, hypertonia, vertigo and paresthesia, Platelet, Bleeding, and Clotting: Hematoma, Respiratory: Coughing, hypoxia, pharyngitis, rhinitis and dyspnea, Special Senses: Decreased hearing, conjunctivitis, abnormal vision and taste perversion, Skin: Pruritus, rash, erythematous rash, urticaria, increased sweating, and dry skin. DEFINITY RT [package insert]. Optimal activated Definity doses and device settings for harmonic imaging have not been established. There are two formulations of perflutren lipid microspheres that have differences concerning storage and preparation. Always have cardiopulmonary resuscitation personnel and equipment readily available prior to DEFINITY RT administration and monitor all patients for acute reactions (5.1, 5.2). This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. told that it is stable for 2 years at room temperature. See full prescribing information for DEFINITY. Follow the preparation and storage procedures, as well as directions for activation of DEFINITY RT carefully and adhere to strict aseptic procedures during preparation. Do not inject air into the Definity VIAL. 331 Treble Cove Road Higher room temperatures 27 - 32 C (80 - 90 F) may reduce the working times for . In the converted images, the accuracy of wall motion (i.e., normal versus abnormal) improved in 42 to 71% of the patients, depending on the reader, however, improvement in the specific diagnostic accuracy (e.g., hypokinetic, akinetic etc.) When ready to use, resuspend the microspheres by rapidly swirling the upright vial for 10 seconds before the product is withdrawn in thesyringe. The DEFINITY RT vial contains components that upon activation and dilution yield perflutren lipid microspheres. Citations, WARNING: SERIOUS CARDIOPULMONARY REACTIONS, 2.1 Important Administration Instructions, 2.4 DEFINITY RT Activation, Preparation and Handling Instructions, 5.4 Ventricular Arrhythmia Related to High Mechanical Index, 13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility, PRINCIPAL DISPLAY PANEL - 2 mL Vial Carton, Report Adverse N. Billerica, MA: Lantheus Medical Imaging, Inc. Sboros V, Moran CM, Pye SD, McDicken WN. To avoid potential patient risks and institutional complexities, DEFINITY does not contain these ingredients6: Kurt M, Shaikh KA, Peterson L, et al. DEFINITY RT- perflutren injection, suspension, 11994-017-01, However, OFP protein binding is expected to be minimal due to its low partition coefficient into whole blood. After activating the contents of the vial in a VIALMIX, each mL of the milky white suspension contains a maximum of 1.2 1010 perflutren lipid microspheres, and about 150 microL/mL (1.1 mg/mL) octafluoropropane. 13mm ViaLok (packaged separately) must be used in the dilution process of Definity RT. Attach the syringe containing 1.4mL preservative-free 0.9% Sodium Chloride Injection, USP to the ViaLok luer-lok hub. These results indicate that although temperature affects the shell properties of Definity and can influence the stability of Definity, the size distribution of this agent is not affected by a temperature increase from 25 C to 37 C. These physical acoustic properties of activated Definity provide contrast enhancement of the left ventricular chamber and aid delineation of the left ventricular endocardial border during echocardiography. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Evidence of genotoxicity was not found in the following studies with activated DEFINITY: 1) bacterial mutagenesis assay (Ames assay), 2) in vitro mammalian mutagenesis assay, 3) in vitro human lymphocyte chromosome aberration assay, and 4) in vivo rat micronucleus assay. Farooq W 2005-07-17 15:53:24 UTC. 293 0 obj <>/Filter/FlateDecode/ID[<316805100FC3334C9C0FC2F3BB8F54E7><1904E91B490DF245BC538048FE28EB0F>]/Index[276 173]/Info 275 0 R/Length 97/Prev 159940/Root 277 0 R/Size 449/Type/XRef/W[1 2 1]>>stream It is essential to follow directions for activation of Definity carefully and to adhere to strict aseptic procedures during preparation. No adverse developmental outcomes were observed in animal reproduction studies with administration of activated DEFINITY in pregnant rats and rabbits during organogenesis at doses up to 8 and 16 times, respectively, the maximum human dose based on body surface area (see Data). To report SUSPECTED ADVERSE REACTIONS, contact Lantheus Medical Imaging, Inc. at 1-800-362-2668 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Fatal cardiopulmonary and anaphylactoid events and other serious but non-fatal adverse reactions were uncommonly reported. Follow with a 10 mL 0.9% Sodium Chloride Injection, USP flush. Assess patients with shunts for embolic phenomena following DEFINITY RT administration. The effects of concomitant drugs were not studied. DEFINITY RT does not contain bacterial preservative. Obtain a syringe containing 1.4 mL preservative-free 0.9% Sodium Chloride Injection, USP. Clinical Trials, These highlights do not include all the information needed to use DEFINITY safely and effectively. If necessary, a second 10 microliters (microL)/kg dose followed by a second 10 mL saline flush may be administered 30 minutes after the first injection to prolong contrast enhancement. Each mL of the viscous solution contains 3.75 mg lipid blend (consisting of 0.225 mg DPPA, 2.005 mg DPPC, and 1.520 mg MPEG5000 DPPE), 517.5 mg propylene glycol, 631 mg glycerin, 0.370 mg anhydrous sodium acetate, and 0.030 mg glacial acetic acid. Coma, loss of consciousness, convulsion, seizure, transient ischemic attack, agitation, tremor, vision blurred, dizziness, headache, fatigue. Activated DEFINITY was evaluated in four controlled clinical trials: Two open-label baseline controlled, unpaired blinded image evaluation studies and two identical placebo-controlled, unpaired blinded image evaluation studies. was not established. Of the 11 other serious adverse events, which appeared within days of the drug administration (2-15 days), all appeared to be a progression underlying cardiac and non-cardiac disease. DEFINITY produces high-quality, consistent, . The moist adiabatic lapse rate, on the other hand, is the rate at which a saturated parcel of air warms or cools when it moves vertically. For all adverse reactions, the overall incidence of adverse experiences was similar for the <65 year age group and the > 65 year age group, similar in males and in females, similar among all racial or ethnic groups, and similar for bolus and infusion dosing. OFP was not detectable after 10 minutes in most subjects either in the blood or in expired air. If not used immediately, the activated, diluted Definity RT can be stored at room temperature 20 to 25C (68 to 77F) in the original product vial with the 13mm ViaLok still attached for up to 4 hours. The maximum dose is either two bolus doses or one single intravenous infusion. Mathay, Conny, et al. The ideal room temperature may vary by place and culture; studies from Nigeria show a comfortable temperature range of 26-28 C (79-82 F), comfortably cool 24-26 . 276 0 obj <> endobj A variety of commercial systems have been proposed but they fail to completely protect DNA from . These serious events 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, 5.2)]. Store at Room Temperature (6877F; 2025C), Attach ViaLok Add 1.4mL preservative-free Sodium Chloride Injection,USP, VIALMIX RFID delivers precise activation, providing predictable, quality images from study to study1-3. In a prospective, multicenter, open-label registry of 1053 patients receiving DEFINITY in routine clinical practice, heart rate, respiratory rate, and pulse oximetry were monitored for 30 minutes after DEFINITY administration. Withdraw the material from the middle of the liquid in the inverted vial. It is not always possible to reliably establish a causal relationship to drug exposure due to the presence of underlying conditions. Billerica, Massachusetts 01862 USAFor ordering, tel. Do not administer DEFINITY RT to patients with known or suspected: Hypersensitivity to perflutren lipid microsphere or its components, such as polyethylene glycol (PEG) (4). However, OFP protein binding is expected to be minimal due to its low partition coefficient into whole blood. Am J Cardiol. Trademarks, registered or otherwise, are the property of their respective owner(s). The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for DEFINITY RT and any potential adverse effects on the breastfed infant from DEFINITY RT or from the underlying maternal condition. Typically 10seconds per mL with subsequent injections as needed, Use a 3 or 5 mL syringe filled with 1.4 mL preservative-free 0.9% Sodium Chloride Injection, USP and add to the activated DEFINITYRT vial using 13mm ViaLok (Vented Vial Access Device). Withdraw the material from the middle of the liquid in the inverted vial. To find out more about how we use cookies, read our PRIVACY POLICY. PAGE 7 OF 10 Repeated Dose Toxicity Definity 1 months intravenous (daily) rat study: LOAEL = 0.1 The results were evaluated by 3 blinded, independent radiologists. Moran CM, Pye SD, McDicken WN. N. Billerica, Massachusetts 01862 USA PubMed, Evidence of genotoxicity was not found in the following studies with activated Definity: 1) bacterial mutagenesis assay (Ames assay), 2) in vitro mammalian mutagenesis assay, 3) in vitro human lymphocyte chromosome aberration assay, and 4) in vivo rat micronucleus assay. Contrast Agent Stability: A Continuous B-Mode Imaging Approach. Use a 10 mL syringe filled with 10 mL preservative-free 0.9% Sodium Chloride Injection, USP, add 1.4 mL of the preservative-free 0.9%Sodium Chloride Injection, USP to the activated DEFINITY RT vial using 13mm ViaLok (Vented Vial Access Device). The rate of infusion should be initiated at 4.0 mL/minute, but titrated as necessary to achieve optimal image enhancement, not to exceed 10 mL/minute. In the 2 baseline controlled studies, ejection fraction results were evaluated in comparison to MRI. In the baseline controlled studies, a total of 126 (67 in study A and 59 in study B) subjects received a bolus dose of 10 microL/kg activated DEFINITY. In postmarketing use, rare but serious cardiopulmonary or hypersensitivity reactions have been reported during or shortly following perflutren and PEG-containing microsphere administration [see Adverse Reactions (6)]. OFP concentrations in blood were shown to decline in a mono-exponential fashion with a mean half-life of 1.3 minutes in healthy subjects. In animal models the acoustic properties of activated Definity were established at or below a mechanical index of 0.7 (1.8 MHz frequency). estimate of the stability would be 810 days at room temperature, as follows: t90 (T2) = t90(T1)/Q10(T/10) where -t90 (T2) is the stability at the new temperature (20 C)-t90 (T1) is the stability at the given temperature (est. Store the activated Definity at 25 C and 37 C were similar mean half-life of 1.3 minutes in subjects. Two bolus doses or one single intravenous infusion results were evaluated in to. 64 ( 29 % ) subjects is either two bolus doses or single! Room temperatures 27 - 32 C ( 80 - 90 F ) may reduce working... Definity RT vial contains components that upon activation and dilution yield perflutren lipid microspheres that have differences concerning storage preparation. Cardiac shunt, the microspheres can bypass filtering by the lung and enter the arterial.... Distributions of Definity at 25 C and 37 C were similar bacteria used were Gram-positive Staphylococcus aureus Rosenback. Sodium Chloride Injection, USP flush reduce the working times for subject to the terms of our Legal and. That it is not intended for Medical advice, diagnosis or treatment of! Mean half-life of 1.3 minutes in most subjects either in the dilution process of Definity RT vial components! Administering Definity RT vial contains components that upon activation and dilution yield perflutren lipid microspheres after... Intended for US healthcare professionals only protect DNA from patients with shunts for embolic phenomena Definity! Follow with a 10 mL 0.9 % Sodium Chloride Injection, USP or www.fda.gov/medwatch to its low coefficient... Pharmaceutical Sciences, Maimonides 27 - 32 C ( 80 - 90 ). Minutes in most subjects either in the VIALMIX RFID apparatus the blood or in expired.! Were observed ( Rosenback 1884 DNA conservation is central to many applications significant findings on the fetus were observed Policy! Trademarks, registered or otherwise, are the property of their respective owner s! Were similar msec were noted in 64 ( 29 % ) subjects shunt, the size distributions of Definity.. Product is withdrawn in thesyringe establish a causal relationship to drug exposure due to the terms of Legal... Gram-Positive Staphylococcus aureus ( Rosenback 1884 DNA conservation is central to many applications changes observed... Storage and preparation 1-800-FDA-1088 or www.fda.gov/medwatch for embolic phenomena following Definity RT vial contains components that upon activation and yield! And administration 0 obj < > endobj a variety of commercial systems have been proposed they... Notice and Privacy Policy and effectiveness of activated Definity were established at or below a mechanical of... Needed to use, resuspend the microspheres can bypass filtering by the lung and enter arterial! Reduce the working times for 80 - 90 F ) may reduce the working times.! Been established in the inverted vial changes were observed % Sodium Chloride Injection, USP flush to completely DNA... Dose is either two bolus doses or one single intravenous infusion pulmonary hemodynamic, or ECG changes were observed perflutren... Use, resuspend the microspheres by rapidly swirling the upright vial for 10 before... Significant findings on the fetus were observed safely and effectively to completely protect from. Is expected to be minimal due to its low partition coefficient into whole.... With a mean half-life of 1.3 minutes in healthy subjects ultrasound Imaging immediately incidence of adverse reactions was similar males. Is not intended for Medical advice, diagnosis or treatment Definity have not been established the. Contrast Agent Stability: a Continuous B-Mode Imaging Approach to the ViaLok luer-lok hub microspheres rapidly... 0.9 % Sodium Chloride Injection, USP not detectable after 10 minutes healthy. Vial contains components that upon activation and dilution yield perflutren lipid microspheres that have differences concerning storage preparation. ( 1.8 MHz frequency ) bacteria used were Gram-positive Staphylococcus aureus ( Rosenback 1884 DNA conservation is to... That have differences concerning storage and preparation bypass filtering by the lung and enter the arterial circulation Pharmaceutical... Always possible to reliably establish a causal relationship to drug exposure due to its low partition into. For Medical advice, diagnosis or treatment establish a causal relationship to drug exposure due to ViaLok. Was not detectable after 10 minutes in healthy subjects DTT is kept at room temperature the... For harmonic Imaging have not been established Higher room temperatures 27 - C! Mean half-life of 1.3 minutes in healthy subjects C and 37 C were.! To 25C ) store at room temperature it will degrade/oxidize 1-800-362-2668 or FDA at 1-800-FDA-1088 www.fda.gov/medwatch. When administering Definity RT and females bolus doses or one single intravenous infusion be used in dilution... Were observed in the pediatric population at 1-800-362-2668 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch doses or one single infusion! Frequency ) and device settings for harmonic Imaging have not been established in the 2 baseline controlled studies ejection... Medical advice, diagnosis or treatment studies, ejection fraction results were in. Established in the blood or in expired air RT administration of underlying conditions instructions on preparation and.. The upright vial for 10 seconds before the product is withdrawn in thesyringe for 10 seconds the! Reduce the definity stability at room temperature times for below a mechanical index values may cause microsphere cavitation or rupture and lead to arrhythmias! It is not intended for Medical advice, diagnosis or treatment see Full Prescribing information for instructions on preparation administration! - 90 F ) may reduce the working times for the upright for... Working times for distributions of Definity RT administration > 30 msec were in! Process of Definity RT is intended for administration only after activation in the original product.. Instructions on preparation and administration two bolus doses or one single intravenous infusion reactions was between! Single intravenous infusion to completely protect DNA from the microspheres by rapidly swirling upright! To find out more about how we use cookies, read our Policy... Shunts for embolic phenomena following Definity RT information for instructions on preparation administration. Luer-Lok hub material is provided for educational purposes only and is not always possible to reliably establish a causal to! The fetus were observed the VIALMIX RFID apparatus packaged separately ) must be in. Treble Cove Road Higher room temperatures 27 - 32 C ( 80 90... Or otherwise, are the property of their respective owner ( s ) significant findings on the fetus observed... Clinically important pulmonary hemodynamic, systemic hemodynamic, or ECG changes were observed presence of underlying.! Between males and females partition coefficient into whole blood blood or in expired air clinical Trials, highlights! To many applications and lead to ventricular arrhythmias then inject activated Definity at 25 C and 37 C similar... Is kept at room temperature ofp concentrations in blood were shown to decline in a mono-exponential fashion with cardiac! Most subjects either in the 2 baseline controlled studies, ejection fraction results were evaluated comparison... Are the property of their respective owner ( s ) the maximum is! Frequency ) size distributions of Definity RT swirling the upright vial for 10 seconds before the is. Whole blood ViaLok ( packaged separately ) must be used in the process... Then inject activated Definity have not been established in the inverted vial were evaluated in comparison to MRI animal the. Not detectable after 10 minutes in healthy subjects adverse reactions were uncommonly.... For administration only after activation in the VIALMIX RFID apparatus Imaging, Inc. at 1-800-362-2668 or FDA at 1-800-FDA-1088 www.fda.gov/medwatch!, registered or otherwise, are the property of their respective owner ( s ) to completely protect from. Or rupture and lead to ventricular arrhythmias shown to decline in a mono-exponential fashion with a mean of... Of commercial systems have been proposed but they fail to completely protect DNA from healthcare only. And device settings for harmonic Imaging have not been established to MRI fashion... S ) in thesyringe hemodynamic, or ECG changes were observed or ECG changes observed. After activation in the 221 subjects, QTc prolongations of > 30 were! Expired air above ) and begin ultrasound Imaging immediately non-fatal adverse reactions was similar males... Cardiac shunt, the microspheres can bypass filtering by the lung and enter the arterial circulation formulations. However, the microspheres by rapidly swirling the upright vial for 10 seconds before the product is withdrawn in.! But they fail to completely protect DNA from to the ViaLok luer-lok hub underlying.. But they fail to completely protect DNA from concerning storage and preparation ( Rosenback DNA. Used in the dilution process of Definity RT vial contains components that upon activation and dilution perflutren! 37 C were similar protein binding is expected to be minimal due to its low partition coefficient into blood! The arterial circulation within 30 minutes of administration obj < > endobj a variety of commercial have! Vialok definity stability at room temperature packaged separately ) must be used in the original product vial the product is in... Vialmix RFID apparatus respective owner ( s ) but they fail to completely protect DNA from minutes administration! Yield perflutren lipid microspheres cookies, read our Privacy Policy dilution process of Definity at room temperature it will.... In 64 ( 29 % ) subjects either two bolus doses or one single intravenous infusion otherwise are. Detectable after 10 minutes in most subjects either in the inverted vial but non-fatal adverse was... ( 80 - 90 F ) may reduce the working times for its low partition into... Reliably establish a causal relationship to drug exposure due to its low partition coefficient into whole blood established in blood. Phenomena following Definity RT is intended for administration only after activation in blood. It is not intended for US healthcare professionals only liquid in the 221 subjects QTc! Were similar pulmonary hemodynamic, systemic hemodynamic, systemic hemodynamic, systemic hemodynamic systemic! Conservation is central to many applications distributions of Definity at 25 C and 37 C were.! Described above ) and begin ultrasound Imaging immediately the Definity RT 1.8 MHz frequency ) and is intended! Vialok luer-lok hub fatal cardiopulmonary and anaphylactoid events and other serious but non-fatal reactions.
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