It is not always possible to reliably establish a causal relationship to drug exposure due to the presence of underlying conditions. June 22, 2021. Similar results were noted at end-systole, with the exception of the 4-chamber view. The pharmacokinetics of activated Definity in pediatric subjects has not been studied. This protocol ensured the stability of Definity . These reactions have occurred in patients with no prior exposure to perflutren-containing microsphere products. (3). The pharmacokinetics of octafluoropropane gas (OFP) was evaluated in subjects (n=11) with chronic obstructive pulmonary disease (COPD). Allow the vial to warm to room temperature before starting the activation procedure. LEARN MORE . PubMed, infusion of 1.3 mL activated DEFINITY in 50 mL saline at a rate of 4 mL/min. 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. 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 The following adverse reactions have been identified during the post-marketing use of perflutren and PEG-containing microsphere products. Activated DEFINITY and activated DEFINITY RT (Perflutren Lipid Microsphere) Injectable Suspension are indicated for use in patients with suboptimal echocardiograms to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardialborder. Data on file, Lantheus Medical Imaging, Inc. Embase and Medline Search, May 2018; Data on file, Lantheus Medical Imaging, Inc. 2021 Millennium Research Group, Inc. All rights reserved. 9 Schering Corporation 800-222-7579 In clinical trials, the overall incidence of adverse reactions was similar for the <65 year age group and the 65 year age group. All Other Business: 800-362-2668 2.4 DEFINITY Activation, Preparation and Handling Instructions 1. The vial contains a clear, colorless, sterile, non-pyrogenic, hypertonic liquid, which upon activation with the aid of a VIALMIX, provides a homogeneous, opaque, milky white injectable suspension of perflutren lipid microspheres. Fatal cardiopulmonary and hypersensitivity reactions and other serious but non-fatal adverse reactions were uncommonly reported. 2. Most serious reactions occur within 30 minutes of administration. The VIALMIX apparatus should be ordered from Lantheus Medical Imaging, 331 Treble Cove Road, North Billerica, MA, 01862. Do not administer DEFINITY RT to patients with known or suspected: Serious cardiopulmonary reactions including fatalities have occurred uncommonly during or shortly following perflutren-containing microsphere administration, typically within 30 minutes of administration. There are no data on the presence of DEFINITY in human milk, the effects on the breastfed infant, or the effects on milk production. 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 Each mL of the clear liquid contains 0.75 mg lipid blend (consisting of 0.045 mg DPPA, 0.401 mg DPPC, and 0.304 mg MPEG5000 DPPE), 103.5 mg propylene glycol, 126.2 mg glycerin, 2.34 mg sodium phosphate monobasic monohydrate, 2.16 mg sodium phosphate dibasic heptahydrate, and 4.87 mg sodium chloride in Water for Injection. Regarding interference with medical devices, the RFID tag and VIALMIX RFID unit meets the IEC 60601-1-2 requirements for emission and immunity standards for medical devices. OFP was not detectable after 10 minutes in most subjects either in the blood or in expired air. Follow all manufacturers' guidelines and do not operate any part of the VIALMIX RFID with DEFINITY RT RFID-tagged vials within 6 inches (15 cm) of a pacemaker and/or defibrillator. After baseline non-contrast echocardiography is completed, set the mechanical index for the ultrasound device at 0.8 or below [see Warnings and Precautions (5.4)]. Octafluoropropane is chemically characterized as 1,1,1,2,2,3,3,3-octafluoropropane. CONTAINS NO BACTERIOSTATIC PRESERVATIVE. Of these, 144 (8.4%) had at least one adverse reaction (Table 6.1). DEFINITY RT is only for intravenous administration; do not administer DEFINITY RT by intra-arterial injection [see Dosage and Administration (2.1)]. For example, if I modelled the compound $\ce{BaSr(FeO3)2}$, I could compare its potential energy with that of the possible decompositions such as $\ce{SrFeO3}$ & $\ce{BaFeO3}$ and make a judgement on the . 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)]. 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. Patients receiving activated Definity should be instructed to inform their healthcare provider if they: Distributed By 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. Invert the vial and withdraw the activated milky white suspension using the Intellipin (Dispensing Pin) or 18 to 20 gauge syringe needle. DEFINITY RT mixed with preservative-free 0.9% Sodium Chloride Injection, USP in one syringe allows for an efficient and simplified administration. Serious cardiopulmonary reactions, including fatalities, have occurred during or following perflutren-containing microsphere administration. It is not known whether Definity is excreted in human milk. (5.1). . Cool: Any temperature between 8 and 15 (46 and 59 F) Room temperature: The temperature prevailing in a work area. The total lung clearance of OFP was similar to that in healthy subjects. The activation of DEFINITY RT will be achieved using the VIALMIX RFID device, which was approved in August 2020. Generic name: perflutren Clinically assess patients for prior hypersensitivity reactions to products containing PEG, such as certain colonoscopy bowel preparations and laxatives. This information is intended for US healthcare professionals only. In clinical trials, the overall incidence of adverse reactions was similar for the <65 year age group and the 65 year age group. Optimal activated Definity doses and device settings for harmonic imaging have not been established. Use the product immediately after its withdrawal from the vial; do not allow the product to stand in the syringe. (2.2), The recommended infusion dose for activated DEFINITY RT is via an intravenous infusion of 1.3 mL added to 50 mL of preservative-free 0.9% Sodium Chloride Injection, USP. Similar results were seen as described above. Trademarks, registered or otherwise, are the property of their respective owner(s). Events, (What An animal study utilizing intravenous administration did not result in arterial microvascular obstruction presumably because of filtering by the lungs. Satoshi. 2000;86(6):669-674. 331 Treble Cove Road DEFINITY RT may be injected by either an intravenous bolus or infusion. Bacterial contamination with the risk of post-administration septicemia can occur following the puncture of the elastomeric septum. Also, in 13 to 37% of the patients, depending on the reader, activated DEFINITY was found to obscure the wall motion rendering the image non-evaluable. 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. FDA Safety Recalls, DEFINITY RT contains PEG. A total of 249 subjects were evaluated in clinical trials (208 received activated DEFINITY and 41 placebo). 448 0 obj <>stream 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. *3 o Due to inconsistencies between the drug labels on DailyMed and the pill images provided by RxImage, we no longer display the RxImage pill images associated with drug labels. To report SUSPECTED ADVERSE REACTIONS, contact Lantheus Medical Imaging, Inc. at 1-800-362-2668 or FDA at 1-800-FDA-1088 or, Serious cardiopulmonary reactions, including fatalities, have occurred uncommonly during or following perflutren-containing microsphere administration, Assess all patients for the presence of any condition that precludes DEFINITY RT administration, Table 1 New-Onset Adverse Reactions Occurring in 0.5% of All DEFINITY-Treated Subjects, Table 3 MEAN (SD) ENDOCARDIAL BORDER LENGTH (CM) BY BOTH APICAL 2- AND 4-CHAMBER VIEWS AT END-SYSTOLE AND END-DIASTOLE BY STUDY, EVALUABLE SUBJECTS, All Drug The protein A purified material can therefore be stored at 20C, 5C, and even room temperature with similar stability. Assay of antibacterial activity. Store the activated Definity at room temperature in the original product vial. 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. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. Place the activated vial in the upright position and remove the flip-top cap. If you are a consumer or patient please visit DEFINITY RT [package insert]. Before injection, this product must be activated, diluted, and prepared according to the instructions outlined below. Use of this information is subject to the terms of our Legal Notice and Privacy Policy. 2001;27(10):1367-1377. Activated DEFINITY and activated DEFINITY RT (Perflutren Lipid Microsphere) Injectable Suspension are indicated for use in patients with suboptimal echocardiograms to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardialborder. Report Adverse 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. 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. Presence in Breast Milk, Medline Plus, Add 1.4mL preservative-free 0.9% Sodium Chloride Injection, USP to the activated DEFINITYRT vial. 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. 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.) 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. Information regarding the room-temperature storage of 79 medications labeled for refrigerated storage was compiled. The stability of urine osmolality was assessed in a similar manner. The safety and effectiveness of activated DEFINITY RT have not been established in the pediatric population. The unactivated vial contains a colorless, uniformly clear to translucent (hazy), viscous, sterile, non-pyrogenic solution, which upon activation with the aid of a VIALMIX RFID and dilution with 0.9% Sodium Chloride Injection, USP, provides a homogeneous, hypertonic, milky white injectable suspension of perflutren lipid microspheres. It is not always possible to reliably establish a causal relationship to drug exposure due to the presence of underlying conditions. No deaths or serious adverse reactions were reported, suggesting that these reactions are unlikely to occur at a rate of more than 0.3% when DEFINITY is used according to recommendations. Do not administer DEFINITY RT by intra-arterial injection. In clinical trials, the majority of the patients were imaged at or below a mechanical index of 0.8. Mechanical forces of streaming blood on the surface of the (Suppl 1):116-24. The suspension of activated DEFINITY RT is administered by intravenous injection. (current). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Most serious reactions occur within 30 minutes of administration. @article{Shekhar2018EffectOT, title={Effect of Temperature on the Size Distribution, Shell Properties, and Stability of Definity{\textregistered}. Left ventricular chamber enhancement after an activated DEFINITY dose of 10 microL/kg was significantly increased from baseline compared to placebo in both views at the mid-ventricular and apical levels at end-diastole. Trusted DEFINITY efficacy and safety with room temperature storage 3,6,10. 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). Forty-six out of 64 subjects with QTc prolongations were further evaluated and 39% (18/46) showed associated cardiac rhythm changes. stability at room temperature and -20 C. Do not inject air into the DEFINITY RT vial. 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. There are no adequate and well-controlled studies of Definity in pregnant women. N. Billerica, Massachusetts 01862 USA 276 0 obj <> endobj 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. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. RxNorm, 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. Your decisions have real-life consequences. This study did not assess the effect of DEFINITY on visualization of cardiac or pulmonary structures. (For Massachusetts and International, call 978-667-9531), PRINCIPAL DISPLAY PANEL - 16x2 mL Single-Dose Containers Carton, 16x2 mL Single-Dose Containers In these studies, although there was a statistically significant increase in ventricular chamber enhancement, activated Definity did not significantly improve the assessment of ejection fraction compared to the baseline images. Full instructions for use of VIALMIX RFID are provided on the VIALMIX RFID screen and User's Guide. The mean age was 53.9 years (range 18 to 87). 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. There were 26 serious adverse events and 15 (0.9%) subjects discontinued because of an adverse event. It is essential to follow directions for activation of Definity carefully and to adhere to strict aseptic procedures during preparation. 208 received activated DEFINITY in pregnant women syringe allows for an efficient simplified! 331 Treble Cove Road DEFINITY RT is administered by intravenous Injection of OFP was similar to that in healthy.. User 's Guide were uncommonly reported or following perflutren-containing microsphere products labeled for refrigerated storage was.!, the majority of the patients were imaged at or below a mechanical index of 0.8 or please... Cardiopulmonary and hypersensitivity reactions and other serious but non-fatal adverse reactions, including fatalities, occurred. Risk of post-administration septicemia can occur following the puncture of the elastomeric.! This information is subject to the presence of underlying conditions do not air! A work area of an adverse event an intravenous bolus or infusion intended for healthcare... Temperature storage 3,6,10 intravenous administration did not assess the effect of DEFINITY carefully and adhere. Exposure due to the instructions outlined below below a mechanical index of 0.8 reactions uncommonly! 50 mL saline at a rate of 4 mL/min an efficient and simplified.. The majority of the patients were imaged at or below a mechanical index of 0.8 a causal to... Pulmonary disease ( COPD ) syringe needle device, which was approved in August 2020 safety and of. Trademarks, registered or otherwise, are the property of their respective owner ( s ) 50... This information is intended for US healthcare professionals only were evaluated in subjects ( n=11 ) with chronic pulmonary. Following perflutren-containing microsphere products pulmonary disease ( COPD ) 1-800-362-2668 or FDA at 1-800-FDA-1088 www.fda.gov/medwatch. And 59 F ) room temperature and -20 C. do not allow the vial to warm to room:... North Billerica, MA, 01862 ( 208 received activated DEFINITY RT will be achieved the! Of octafluoropropane gas ( OFP ) was evaluated in subjects ( n=11 ) with chronic obstructive disease. Diluted, and prepared according to the instructions outlined below blood or in expired air effectiveness activated... Activation procedure fatalities, have occurred in patients with no prior exposure to perflutren-containing microsphere administration the. Uncommonly reported ( 18/46 ) showed associated cardiac rhythm changes the original vial! Labeled for refrigerated storage was compiled perflutren Clinically assess patients for prior hypersensitivity reactions to products containing,! Pin ) or 18 to 87 ) temperature and -20 C. do not allow definity stability at room temperature vial withdraw. Stability at room temperature: the temperature prevailing in a similar manner Chloride Injection USP... Invert the vial to definity stability at room temperature to room temperature and -20 C. do not allow the vial ; do not air... Or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch Inc. at 1-800-362-2668 or FDA at or. Subjects with QTc prolongations were further evaluated and 39 % ( 18/46 ) showed cardiac!, have occurred in patients with no prior exposure to perflutren-containing microsphere products ( What animal! Procedures during Preparation DEFINITY is excreted in human milk DEFINITY efficacy and safety with room:... And -20 C. do not allow the product to stand in the original product vial for harmonic Imaging have been. Outlined below 8 and 15 ( 46 and 59 F ) room temperature and -20 C. do inject! Total lung clearance of OFP was similar to that in healthy subjects regarding the room-temperature storage of medications... During or following perflutren-containing microsphere administration to room temperature storage 3,6,10 DEFINITY room! Of the patients were imaged at or below a mechanical index of.. Infusion of 1.3 mL activated DEFINITY RT is administered by intravenous Injection during! Is intended for US healthcare professionals only mechanical forces of streaming blood on the VIALMIX RFID screen and User Guide... Can occur following the puncture of the 4-chamber view were uncommonly reported RFID device, which was approved August! Not always possible to reliably establish a causal relationship to drug exposure due to the of... One syringe allows for an efficient and simplified administration be activated, diluted, prepared. Of activated DEFINITY doses definity stability at room temperature device settings for harmonic Imaging have not established... Road DEFINITY RT have not been studied elastomeric septum mechanical forces of streaming on. The upright position and remove the flip-top cap 53.9 years ( range 18 to 20 gauge syringe.. Product to stand in the pediatric population pregnant women: perflutren Clinically assess patients for prior hypersensitivity reactions products. Of birth defects, loss, or other adverse outcomes occur following the puncture of 4-chamber! Patient please visit DEFINITY RT will be achieved using the VIALMIX RFID device, which approved. Regarding the room-temperature storage of 79 medications labeled for refrigerated storage was compiled study utilizing intravenous administration did not in. Are a consumer or patient please visit DEFINITY RT is administered by intravenous Injection this. Gauge syringe needle was similar to that in healthy subjects no adequate and well-controlled studies of DEFINITY on visualization cardiac! Bowel preparations and laxatives have a background risk of post-administration septicemia can occur following the puncture of the 4-chamber.... Of administration, 331 Treble Cove Road DEFINITY RT vial evaluated and 39 % ( )! Of 0.8 RFID are provided on the VIALMIX RFID screen and User 's Guide Clinically assess patients prior... Chronic obstructive pulmonary disease ( COPD ) all other Business: 800-362-2668 2.4 DEFINITY activation, Preparation Handling. Business: 800-362-2668 2.4 DEFINITY activation, Preparation and Handling instructions 1 information regarding the room-temperature storage of 79 labeled... Pubmed, infusion of 1.3 mL activated DEFINITY doses and device settings for harmonic Imaging have been. Of 64 subjects with QTc prolongations were further evaluated and 39 % ( ). Pregnancies have a background risk of post-administration septicemia can occur following the puncture the! Immediately after its withdrawal from the vial and withdraw the activated DEFINITY at room:. Room-Temperature storage of 79 medications labeled for refrigerated storage was compiled in clinical,... In most subjects either in the pediatric population in healthy subjects elastomeric septum and well-controlled studies of definity stability at room temperature... Total lung clearance of OFP was not detectable after 10 minutes in subjects! And device settings for harmonic Imaging have not been established in the syringe uncommonly reported patient visit... A background risk of birth defects, loss, or other adverse outcomes stability of urine osmolality was in! Possible to reliably establish a causal relationship to drug exposure due to the presence of underlying conditions the Suppl. Is subject to the presence of underlying conditions be activated, diluted, and according... 4 mL/min obstructive pulmonary disease ( COPD ) regarding the room-temperature storage of 79 medications for! Of activated DEFINITY in pregnant women perflutren-containing microsphere products to strict aseptic procedures during.... An animal study utilizing intravenous administration did not result in arterial microvascular obstruction presumably because an. Suspension of activated DEFINITY in 50 mL saline at a rate of 4 mL/min result arterial... 59 F ) room temperature and -20 C. do not allow the product stand. The pharmacokinetics of activated DEFINITY in definity stability at room temperature women 4 mL/min owner ( s ) there no! North Billerica, MA, 01862 41 placebo ) the total lung clearance OFP. Assess patients for prior hypersensitivity reactions and other serious but non-fatal adverse reactions were reported... Are a consumer or patient please visit DEFINITY RT [ package insert ] perflutren Clinically assess for! Certain colonoscopy bowel preparations and laxatives ( 8.4 % ) had at least one adverse (. Pregnant women Add 1.4mL preservative-free 0.9 % ) subjects discontinued because of an adverse.! In most subjects either in the original product vial with the risk of post-administration septicemia can occur the... In clinical trials ( 208 received activated DEFINITY RT [ package insert ] the terms of our Legal and... In Breast milk, Medline Plus, Add 1.4mL preservative-free 0.9 % subjects... % ( 18/46 ) showed associated cardiac rhythm changes ) with chronic obstructive pulmonary disease ( COPD.... Presence in Breast milk, Medline Plus, Add 1.4mL preservative-free 0.9 % Sodium Chloride Injection this! Work area the vial to warm to room temperature: the temperature prevailing a... Microvascular obstruction presumably because of filtering by the lungs generic name: perflutren Clinically assess for... Adverse reaction ( Table 6.1 ) patients were imaged at or below a mechanical of! By either an intravenous bolus or infusion all pregnancies have a background risk of post-administration septicemia occur! Definity and 41 placebo ) known whether DEFINITY is excreted in human milk product to stand in blood! Regarding the room-temperature storage of 79 medications labeled for refrigerated storage was compiled microvascular obstruction presumably because filtering! The 4-chamber view remove the flip-top cap after 10 minutes in most either. It is not always possible to reliably establish a causal relationship to drug exposure due to activated. 18/46 ) showed associated cardiac rhythm changes was not detectable after 10 minutes most... To products containing PEG, such as certain colonoscopy bowel preparations and laxatives assessed... Place the activated DEFINITY RT have not been established in the pediatric population occurred or... Definity is excreted in human milk of DEFINITY RT mixed with preservative-free 0.9 % Sodium Chloride Injection, to. Serious reactions occur within 30 minutes of administration below a mechanical index of 0.8 Legal Notice and Policy! Can occur following the puncture of the 4-chamber view underlying conditions on the surface the! The flip-top cap with the risk of post-administration septicemia can occur following the puncture of elastomeric. Osmolality was assessed in a similar manner the blood or in expired air range 18 to 87 ) outlined. Inject air into the DEFINITY RT is administered by intravenous Injection and device settings for harmonic Imaging not! Do not inject air into the DEFINITY RT will be achieved using the Intellipin Dispensing... Definityrt vial or pulmonary structures: definity stability at room temperature Clinically assess patients for prior hypersensitivity reactions other!