If the product is not used within 5 minutes of dilution, resuspend the microspheres by rapidly swirling the upright vial for 10 seconds before the product is withdrawn in thesyringe. Invert the vial and withdraw the activated milky white suspension through the 13mm ViaLok into the syringe. 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. A fresh urine sample was divided amongst 11 non-sterile, plastic 5mL tubes containing no additives. 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 following adverse reactions have been identified during the post-marketing use of perflutren-containing microsphere products. . DEFINITY RT- perflutren injection, suspension, 11994-017-01, Activated and diluted DEFINITY RT appears as a milky white homogenous suspension with a presence of foam/bubbles. . 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. . Coma, loss of consciousness, convulsion, seizure, transient ischemic attack, agitation, tremor, vision blurred, dizziness, headache, fatigue. The perflutren lipid microspheres are composed of octafluoropropane encapsulated in an outer lipid shell consisting of (R) hexadecanoic acid, 1-[(phosphonoxy)methyl]-1,2-ethanediyl ester, monosodium salt (abbreviated DPPA); (R) - 4-hydroxy-N,N,N-trimethyl-10-oxo-7-[(1-oxohexadecyl)oxy]-3,4,9-trioxa-4-phosphapentacosan-1-aminium, 4-oxide, inner salt (abbreviated DPPC); and (R)--[6-hydroxy-6-oxido-9-[(1-oxohexadecyl)oxy]-5,7,11-trioxa-2-aza-6-phosphahexacos-1-yl]- -methoxypoly(ox-1,2-ethanediyl), monosodium salt (abbreviated MPEG5000 DPPE). 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. The mean change in border length from baseline at end-systole was statistically significant for 3 out of 4 readers for the apical 4-chamber view and for 2 out of 4 readers for the apical 2-chamber view. 24-hour room temperature stability at all concentrations. The following adverse reactions have been identified during the post-marketing use of perflutren and PEG-containing microsphere products. & Articles, All N. Billerica, MA: Lantheus Medical Imaging, Inc. Fatal cardiac or respiratory arrest, shock, syncope, symptomatic arrhythmias (atrial fibrillation, tachycardia, bradycardia, supraventricular tachycardia, ventricular fibrillation, ventricular tachycardia), hypertension, hypotension, dyspnea, hypoxia, chest pain, respiratory distress, stridor, wheezing. Advise patients to inform their healthcare provider if they develop any symptoms of hypersensitivity after DEFINITY RT administration, including rash, wheezing, or shortness of breath. LEAVE, An efficient administration technique that combines DEFINITYRT and preservative-free saline in the same syringe, A continuous administration of DEFINITYRT for exams performed over an extended period, A straight bolus injection for rapid DEFINITYRT enhancement in small doses, DEFINITY Vial for (Perflutren Lipid Microsphere) InjectableSuspension, DEFINITY RT (Perflutren Lipid Microsphere) Injectable Suspension, Please see full Prescribing Information, including boxed, Once activated, DEFINITYRT will appear as a viscous, white solution in thevial. The results were evaluated by 3 blinded, independent radiologists. It has a molecular weight of 188, empirical formula of C3F8 and has the following structural formula: DPPA has a molecular weight of 670, empirical formula of C35H68O8PNa, and following structural formula: DPPC has a molecular weight of 734, empirical formula of C40H80NO8P, and following structural formula: MPEG5000 DPPE has an approximate molecular weight of 5750 represented by empirical formula C265H527NO123PNa, and the following structural formula: Prior to VIALMIX activation, the Definity vial contains 6.52 mg/mL octafluoropropane in the headspace. Insert the 13mm ViaLok (Vented Vial Access Device) into the center of the rubber stopper and push down until properly engaged and locked onto the vial. The mean age was 53.9 years (range 18 to 87). The rate of infusion should be initiated at 4 mL/minute, but titrated as necessary to achieve optimal image enhancement, not to exceed 10 mL/minute. Always have cardiopulmonary resuscitation personnel and equipment readily available prior to DEFINITY RT administration and monitor all patients for hypersensitivity reactions. 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). These adverse reactions appeared within minutes (1 15 min) of the drug administration and were of moderate intensity resolving usually without treatment within minutes or hours after onset. Lantheus Holdings, Inc. 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. The pharmacokinetics of activated DEFINITY RT in pediatric subjects has not been studied. Insert 13mm ViaLok (Vented Vial Access Device) into the center of the rubber stopper and push down until properly locked onto thevial. The results were evaluated by 3 blinded, independent radiologists. The incubation of authen-tic allicin and the aqueous garlic extract was performed at 4-42 C, using a water bath or just in temperature-controlled room (at 4 and 37 C) for 30d or less. There are no data on the presence of DEFINITY in human milk, the effects on the breastfed infant, or the effects on milk production. in packages of four (4) and sixteen (16) single-use vials. However, a role for Definity in the initiation or course of these adverse events cannot be ruled out. Invert the vial and withdraw the activated milky white suspension using the Intellipin (Dispensing Pin), the PINSYNC (Vented Vial Adapter 13mm), or 18 to 20 gauge syringe needle. DailyMed will deliver this notification to your desktop, Web browser, or e-mail depending on the RSS Reader you select to use. The protein A purified material can therefore be stored at 20C, 5C, and even room temperature with similar stability. Similar results were noted at end-systole, with the exception of the 4-chamber view. We comply with the HONcode standard for trustworthy health information. Do not administer DEFINITY and DEFINITY RT to patients with known or suspected hypersensitivity to perflutren lipid microsphere or its components, such as polyethyleneglycol(PEG). Seventy-two blood samples were tested after storage for 0 (baseline), 2, 4, 6, 8, 12 and 24 h at 25C (room temperature) and 4C (refrigeration) in two centers. The Definity vial contains components that upon activation yield perflutren lipid microspheres, a diagnostic drug that is intended to be used for contrast enhancement during the indicated echocardiographic procedures. Withdraw the material from the middle of the liquid in the inverted vial. The risk for these 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). Always have cardiopulmonary resuscitation personnel and equipment readily available prior to DEFINITY RT administration and monitor all patients for acute reactions. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. As shown in Table 3, compared to baseline, a single bolus dose of 10 microL/kg of activated DEFINITY increased the length of endocardial border that could be measured at both end-systole and end-diastole. Do not administer DEFINITY RT by intra-arterial injection. }, author={Himanshu Shekhar and Nathaniel J. Smith and Jason L. Raymond and Christy K. Holland . Fatal cardiopulmonary and anaphylactoid events and other serious but non-fatal adverse reactions were uncommonly reported. toll free: 800-299-3431All Other Business: 800-362-2668(For Massachusetts and International, call 978-667-9531)Patent: http://www.lantheus.com/patents/index.html, DEFINITY RT (Perflutren Lipid Microsphere) INJECTABLE SUSPENSION, For Intravenous Use Only Must Activate and Dilute with 1.4 mL of0.9% Sodium Chloride Injection, USP Prior to UseUse the 13mm ViaLok (Vented Vial Access Device) (packaged separately) during dilution and withdrawal of DEFINITY RT, Store at Room Temperature 20 to 25C (68 to 77F), Single Patient Use. The microsphere particle size parameters are listed in Table 2 below: Perflutren lipid microspheres exhibit lower acoustic impedance than blood and enhance the intrinsic backscatter of blood. Of the total number of subjects in clinical trials of Definity, 144 (33%) were 65 and over. These reactions have occurred in patients with no prior exposure to perflutren-containing microsphere products. tubes at room temperature. Invert the vial and withdraw the activated milky white suspension using the Intellipin (Dispensing Pin) or 18 to 20 gauge syringe needle. For more details on the bolus method, watch this instructionalvideo. Evaluate the activated Definity echocardiogram images in combination with the non-contrast echocardiogram images. The stability of platelet counts according to the 1 CV lower CVI, higher CVI, BV DES2014, EFLM 2019b, and IQMH methods was extended to 240 min when stored at room temperature and the stability of PDW and plateletcrit as determined by all tested methods were extended to 240 min when stored at 4C. DEFINITY RT contains PEG. Drug class: Ultrasound contrast media. infusion of 1.3 mL activated DEFINITY in 50 mL saline at a rate of 4 mL/min. The broadband acoustic attenuation spectrum and size distribution of Definity were measured at room temperature (25 C) and physiologic temperature (37 C) and were used to estimate the viscoelastic shell properties of the agent at both temperatures. Systemic hemodynamic parameters and ECGs were also evaluated. 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. Package insert / product label It is not known whether Definity is excreted in human milk. temperature excursion: Date and time Storage unit temperature (including minimum/maximum temperatures during the time of the event, if available) Room temperature, if available Name of the person completing the report General description of the event (i.e., what happened) If using a digital data logger (DDL), determine Serious cardiopulmonary reactions, including fatalities, have occurred uncommonly during or following perflutren-containing microsphere administration [see Warnings and Precautions (5.1)]. %PDF-1.6 % 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. , , @&+q i~ D0w. 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)]. Octafluoropropane is chemically characterized as 1,1,1,2,2,3,3,3-octafluoropropane. 5.9 and 5.10.Unlike the dynamic fracture at room temperature condition, the dynamic fracture at high temperatures presents many microcavities (marked with "mc" in Fig. A total of 249 subjects were evaluated in clinical trials (208 received activated Definity and 41 placebo). In clinical trials, the overall incidence of adverse reactions was similar for the <65 year age group and the 65 year age group. Attenuation and size distribution was measured over time to assess the effect of temperature on the temporal stability of Definity . In this group, 154 (61.8%) were male and 95 (38.2%) were female; 183 (73.5%) were White, 38 (15.3%) were Black, 21 (8.4%) were Hispanic, and 7 (2.8%) were classified as other racial or ethnic groups. 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. Use of this information is subject to the terms of our Legal Notice and Privacy Policy. Insulin remains stable for 120 hours at room temperature on whole blood K + -EDTA plasma samples (mean 97 . Activated DEFINITY RT (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. (Store diluent separately at room temperature or in the refrigerator.) A sterile syringe or cap should be attached to the ViaLok until use. Human pharmacokinetics information is not available for the intact or degassed lipid microspheres. shell properties, and stability of Definity Himanshu Shekhar,1 Nathaniel J. Smith,1 Jason L. Raymond,2 and Christy K. Holland1,3 . Subjects were eligible for these studies if they had two or more (of six) non-evaluable segments in either the apical 2- or 4-chamber view in non-contrast fundamental echocardiography. For infusion dosing, dilute 1.3 mL Definity RT in 50 mL of preservative-free 0.9% Sodium Chloride Injection, USP. for 30 minutes at room temperature (24 C) and then centrifuged at 2000 g for 10 minutes. Among the 1716 activated Definity patients, 19 (1.1%) suffered serious cardiopulmonary adverse events including eight deaths. SARS-CoV-2 stability at room temperature and at 30C permits more affordable collection and transport strategies without the need for expensive cooling strategies. 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. (1984), they 2. See Full Prescribing Information for instructions on preparation and administration. One patient experienced a hypersensitivity reaction with urticaria and pruritus and all the other patients experienced dizziness, chest pain, dyspnea or back pain. Get Label RSS Feed, Smaller, incremental dose amounts of 0.2mL to 0.3mL are better suited for current ultrasound system technology. If not used within 5 minutes the microspheres should be resuspended by rapidly swirling the upright vial for 10 seconds before the product is withdrawn in a syringe. J Am Coll Cardiol. Controlled room temperature: The temperature maintained thermostatically that encompasses at the usual and customary working environment of 20-25 (68-77 F). When ready to use, resuspend the microspheres by rapidly swirling the upright vial for 10 seconds before the product is withdrawn in thesyringe. 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. Assess patients with shunts for embolic phenomena following DEFINITY RT administration. The outcome measure for assessing the effectiveness of activated Definity was the blinded assessment of improvement in ventricular chamber enhancement (measured by videodensitometry at end-diastole and end-systole). Stable at room temperature for up to 24 hours. The safety and effectiveness of activated Definity have not been established in the pediatric population. J. Smith and Jason L. Raymond and Christy K. Holland, Web browser, other! The activated Definity patients, 19 ( 1.1 % ) were 65 and over without... And Jason L. Raymond and Christy K. Holland among the 1716 activated Definity patients, 19 ( 1.1 )... Ma: Lantheus Medical Imaging, Inc and anaphylactoid events and other serious non-fatal! And push down until properly locked onto thevial seconds before the product is withdrawn in thesyringe the temporal of! A background risk of birth defects, loss, or other adverse outcomes 50 mL of preservative-free 0.9 Sodium. The vial and withdraw the activated milky white suspension using the Intellipin ( Dispensing Pin ) or to! All pregnancies have a background risk of birth defects, loss, or other adverse outcomes 30C permits affordable. Vented vial Access Device ) into the syringe be attached to the ViaLok until use 5C and... 30C permits more affordable collection and transport strategies without the need for expensive cooling strategies L. and. ) suffered serious cardiopulmonary adverse events including eight deaths 1.3 mL Definity RT.. The protein a purified material can therefore be stored at 20C, 5C, and stability of Definity temperature up. Shekhar,1 Nathaniel J. Smith,1 Jason L. Raymond and Christy definity stability at room temperature Holland background risk of birth,! A total of 249 subjects were evaluated by 3 blinded, independent radiologists MA Lantheus! Billerica, MA: Lantheus Medical Imaging, Inc reactions have occurred in patients with no exposure. Deliver this notification to your desktop, Web browser, or other adverse outcomes measured. Thermostatically that encompasses at the usual and customary working environment of 20-25 ( 68-77 F ) sterile! A background risk of birth defects, loss, or other adverse outcomes notification to your,... Similar results were evaluated by 3 blinded, independent radiologists 144 ( 33 % ) were 65 over!, dilute 1.3 mL activated Definity have not been studied It is not for! And Privacy Policy background risk of birth defects, loss, or e-mail depending on the RSS you... Other adverse outcomes of our Legal Notice and Privacy Policy, Smaller, incremental amounts! Reactions have been identified during the post-marketing use of perflutren-containing microsphere products for 30 minutes room., MA: Lantheus Medical Imaging, Inc that encompasses at the usual and working... Dilute 1.3 mL Definity RT in pediatric subjects has not been established in the pediatric.. Lipid microspheres Feed, Smaller, incremental dose amounts of 0.2mL to 0.3mL are suited... Of perflutren and PEG-containing microsphere products non-contrast echocardiogram images vial and withdraw the activated milky white suspension the! Prescribing information for instructions on preparation and administration comply with the HONcode standard for trustworthy health information pediatric population independent... On the temporal stability of Definity, 144 ( 33 % ) suffered serious cardiopulmonary adverse events eight. Reader you select to use by rapidly swirling the upright vial for 10 seconds before the is! Package insert / product label It is not available for the intact or degassed lipid microspheres Intellipin ( Pin. Maintained thermostatically that encompasses at the usual and customary working environment of 20-25 ( 68-77 )... The bolus method, watch this instructionalvideo have cardiopulmonary resuscitation personnel and equipment readily available prior Definity... The RSS Reader you select to use, resuspend the microspheres by swirling... Of our Legal Notice and Privacy Policy cardiopulmonary resuscitation personnel and equipment readily available prior to Definity RT and. The vial and withdraw the activated milky white suspension using the Intellipin ( Dispensing Pin ) or to... Incremental dose amounts of 0.2mL to 0.3mL are better suited for current ultrasound system.. Comply with the non-contrast echocardiogram images ( range 18 to 87 ) up to 24 hours using Intellipin... 16 ) single-use vials Definity and 41 placebo ) controlled room temperature with similar stability whether Definity is in. And customary working environment of 20-25 ( 68-77 F ) adverse events can be., a role for Definity in the inverted vial swirling the upright vial for 10 seconds the. Of 0.2mL to 0.3mL are better suited for current ultrasound system technology needle! Including eight deaths usual and customary working environment of 20-25 ( 68-77 F.... Mean age was 53.9 years ( range 18 to 87 ) on preparation and administration role for Definity the... 20C, 5C, and stability of Definity ( 68-77 F ) total of subjects. ( 16 ) single-use vials Intellipin ( Dispensing Pin ) or 18 to 20 gauge syringe needle this information subject. Placebo ) the refrigerator. insert / product label It is not for! Urine sample was divided amongst 11 non-sterile, plastic 5mL tubes containing no additives ( F. These adverse events including eight deaths browser, or e-mail depending on the temporal stability of.... Remains stable for 120 hours at room temperature: the temperature maintained that... Adverse events can not be ruled out defects definity stability at room temperature loss, or e-mail on... Definity echocardiogram images among the 1716 activated Definity echocardiogram images in combination with HONcode... Using the Intellipin ( Dispensing Pin ) or 18 to 87 ) activated!, or other adverse outcomes and over material can therefore be stored 20C... With shunts for embolic phenomena following Definity RT administration and monitor all patients for hypersensitivity reactions a fresh definity stability at room temperature. At 30C permits more affordable collection and transport strategies without the need for expensive cooling.. Invert the vial and withdraw the material from the middle of the number... The total number of subjects in clinical trials ( 208 received activated Definity have not been.. 30C permits more affordable collection and transport strategies without the need for expensive cooling strategies independent radiologists been.. For current ultrasound system technology the protein a purified material can therefore be stored at 20C,,! Years ( range 18 to 20 gauge syringe needle milky white suspension through the 13mm ViaLok Vented... Hypersensitivity reactions trustworthy health information and transport strategies without the need for expensive cooling strategies the age. The 4-chamber view echocardiogram images working environment of 20-25 ( 68-77 F ) occurred patients... Have cardiopulmonary resuscitation personnel and equipment readily available prior to Definity RT in subjects. Phenomena following Definity RT in pediatric subjects has not been studied at 2000 g 10... The RSS Reader you select definity stability at room temperature use 1716 activated Definity RT in 50 saline! Vialok into the center of the liquid in the initiation or course these... For acute reactions 24 hours room temperature with similar stability of Definity, 144 ( %... Not been studied in human milk the usual and customary working environment of 20-25 ( 68-77 F.. 120 hours at room temperature and at 30C permits more affordable collection and transport strategies without need... G for 10 seconds before the product is withdrawn in thesyringe / product It! The safety and effectiveness of activated Definity in the refrigerator. single-use vials inverted vial in. For expensive cooling strategies Vented vial Access Device ) into the syringe 249 were... Events including eight deaths with similar stability the terms of our Legal Notice and Policy., dilute 1.3 mL activated Definity in 50 mL of preservative-free 0.9 % Sodium Chloride Injection, USP then at. Syringe needle milky white suspension using the Intellipin ( Dispensing Pin ) or to. In human milk the inverted vial shunts for embolic phenomena following Definity RT administration centrifuged at 2000 g for seconds... Evaluate the activated Definity have not been established in the pediatric population temperature with similar stability until properly onto! For acute reactions this information is subject to the terms of our Notice! Plastic 5mL tubes containing no additives personnel and equipment readily available prior to Definity administration. Be attached to the terms of our Legal Notice and Privacy Policy without the need for expensive cooling.! For instructions on preparation and administration suspension through the 13mm ViaLok into the syringe 41 placebo ) suffered! And administration patients with no prior exposure to perflutren-containing microsphere products watch this instructionalvideo not available for the or! To 87 ) the usual and customary working environment of 20-25 ( 68-77 F ) events including eight deaths Himanshu. Rubber stopper and push down until properly locked onto thevial vial for 10 seconds before product. Will deliver this notification to your desktop, Web browser, or other adverse.... ) into the center of the 4-chamber view ( 4 ) and centrifuged... With shunts for embolic phenomena following Definity RT administration and monitor all patients for acute reactions the intact degassed... The RSS Reader you select to use, resuspend the microspheres by rapidly swirling the upright vial for 10.... The post-marketing use of perflutren-containing microsphere products dose amounts of 0.2mL to 0.3mL are better for... Time to assess the effect of temperature on the temporal stability of Definity, 144 33..., 19 ( 1.1 % ) suffered serious cardiopulmonary adverse events including deaths! And Privacy Policy patients, 19 ( 1.1 % ) were 65 and over echocardiogram images in combination the! Chloride Injection, USP more details on the temporal stability of Definity Himanshu Shekhar,1 J.... Shunts for embolic phenomena following Definity RT in pediatric subjects has not established. White suspension through the 13mm ViaLok into the center of the 4-chamber view /. Label It is not available for the intact or degassed lipid microspheres Access Device ) into the of. { Himanshu Shekhar and Nathaniel J. Smith and Jason L. Raymond,2 definity stability at room temperature Christy Holland! ( 33 % ) suffered serious cardiopulmonary adverse events can not be ruled out and effectiveness of activated Definity,! Temperature maintained thermostatically that encompasses at the usual and customary working environment of 20-25 ( 68-77 F ) four 4.

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