Invert the vial and withdraw the activated milky white suspension using the Intellipin (Dispensing Pin) or 18 to 20 gauge syringe needle. A total of 1716 subjects were evaluated in pre-market clinical trials of activated Definity. The protein A purified material can therefore be stored at 20C, 5C, and even room temperature with similar stability. Events, (What Store the activated DEFINITY at room temperature in the original product vial. The 7-day, out-of-fridge stability at room temperature, is an important addition to the existing user-centred features for Hospira filgrastim, that include prefilled syringes with integrated needle-safe devices, a wide-range of presentations, the use of colour-highlighted doses on the packaging and no requirement for reconstitution. 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. 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. Then inject activated DEFINITY RT (as described above) and begin ultrasound imaging immediately. Ultrasound Med Biol. 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. It is not always possible to reliably establish a causal relationship to drug exposure due to the presence of underlying conditions. When administering DEFINITY RT to patients with a cardiac shunt, the microspheres can bypass filtering by the lung and enter the arterial circulation. 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. In this group, 1063 (61.9%) were male and 653 (38.1%) were female, 1328 (77.4%) were White, 258 (15.0%) were Black, 74 (4.3%) were Hispanic, and 56 (3.3%) were classified as other racial or ethnic groups. DEFINITY RT- perflutren injection, suspension, 11994-017-01, The following serious adverse reactions are described elsewhere in the labeling: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. 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). The maximum dose is either two bolus doses or one single intravenous infusion. Invert the vial and withdraw the activated milky white suspension through the 13mm ViaLok into the syringe. Definity is supplied as a single use 2-mL clear glass vial containing clear liquid in packages of four (4) and sixteen (16) single-use vials. Outcome measures for this study included clinically useful ventricular cavity enhancement and endocardial border length. Reprinted with permission. Assess all patients for the presence of any condition that precludes DEFINITY administration . 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; commonly called N-(methoxypolyethylene glycol 5000 carbamoyl)-1,2-dipalmitoyl-sn-glycero-3- phosphatidylethanolamine, monosodium salt (abbreviated MPEG5000 DPPE). 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 4 readers for the apical 2-chamber view. High ultrasound mechanical index values may cause microsphere cavitation or rupture and lead to ventricular arrhythmias. Do not inject air into the DEFINITY RT vial. Ultrasound Med Biol. Add 1.4mL preservative-free 0.9% Sodium Chloride Injection, USP to the activated DEFINITYRT vial. 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. Studies with activated Definity have not been performed to evaluate carcinogenic potential. The most common adverse reactions (0.5%) are headache, back/renal pain, flushing, nausea, chest pain, injection site reactions, and dizziness (6). PRODUCT NAME: Definity / . One way of predicting the thermodynamic stability of a DFT modelled structure is to calculate the energy above convex hull, which was used as the criterion in The Materials Project database. SECTION 10: STABILITY AND REACTIVITY . There are no data on the presence of DEFINITY in human milk, the effects on the breastfed infant, or the effects on milk production. Store the activated Definity at room temperature in the original product vial. toll free: 800-299-3431 DEFINITY RT is intended for administration only after activation in the VIALMIX RFID apparatus. DOI: 10.1016/j.ultrasmedbio.2017.09.021 Corpus ID: 24411267; Effect of Temperature on the Size Distribution, Shell Properties, and Stability of Definity. In the 2 baseline controlled studies, ejection fraction results were evaluated in comparison to MRI. Files, Presentations For single use only: Definity does not contain bacterial preservative. Generic name: perflutren 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. hours at room temperature (22C), for minimum 2 weeks at 4C and after freezing on dry ice for minimum 4 hours prior to storage at -20C (4) It is assumed that the stability of ADA is independent of specificity (5) and therefore the stability of NNCxxxx-xxxx specific antibodies will not be tested in this validation Nine of these patients were discontinued after the first injection. The overall incidence of adverse reactions was similar among all racial and ethnic groups. Because many drugs are excreted in human milk, caution should be exercised when Definity is administered to a nursing mother. 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. The activated Definity may be used for up to 12 hours from the time of VIALMIX, but only after the microspheres are resuspended by hand agitation. For customer orders call 1-800-299-3431. The reported reactions include: 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, loss of consciousness, and convulsions [see Adverse Reactions (6)]. J Thromb Haemost 2007;5 is likely. 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. No clinically important pulmonary hemodynamic, systemic hemodynamic, or ECG changes were observed. As in the dynamic fracture at room temperature condition, crack branching is a common phenomenon in the dynamic fracture related to high temperatures; see Figs. 5.10 a and b) in the cross-sections of fracture surfaces. Trusted DEFINITY efficacy and safety with room temperature storage 3,6,10. Last updated on Oct 24, 2022. 276 0 obj <> endobj & Articles, All Mechanical forces of streaming blood on the surface of the (Suppl 1):116-24. Outcome measures for this study included clinically useful ventricular cavity enhancement and endocardial border length. The phospholipid components of the microspheres are thought to be metabolized to free fatty acids. DEFINITY RT [package insert]. In animal models the acoustic properties of activated Definity were established at or below a mechanical index of 0.7 (1.8 MHz frequency). If DTT is kept at room temperature it will degrade/oxidize. 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). 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 The activation of DEFINITY RT will be achieved using the VIALMIX RFID device, which was approved in August 2020. Before injection, this product must be activated and prepared according to the instructions outlined below. Non-Pyrogenic, For Intravenous Use Only, After Activation DEFINITY RT is supplied as a single patient use 2 mL clear glass Radio Frequency Identification (RFID)-tagged vial containing a colorless, uniformly clear to translucent (hazy) viscous solution in packages of twenty (20) single patient use vials. DNA conservation is central to many applications. Available data from case reports with DEFINITY use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Contrast agent stability: a continuous B-mode imaging approach. This information is intended for US healthcare professionals only. The VIALMIX RFID apparatus should be ordered from Lantheus Medical Imaging, 331 Treble Cove Road, North Billerica, MA, 01862. Stability of twenty five analytes in human serum 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. 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. A sterile syringe or cap should be attached to the ViaLok until use. Table 1 summarizes the most common adverse reactions. Hypersensitivity to perflutren lipid microsphere or its components, such as polyethylene glycol (PEG) [, One (1) 2 mL RFID-tagged vial - NDC (11994-017-01), Twenty (20) 2 mL RFID-tagged vials per kit - NDC (11994-017-20). EDTA-plasma tubes (T0, used for reference measurement), five clin-ical chemistry analytes - glucose, uric acid, cre-atinine, direct bilirubin and total bilirubin - were These highlights do not include all the information needed to use DEFINITY safely and effectively. Mathay, Conny, et al. Serious cardiopulmonary reactions, including fatalities, have occurred uncommonly during or following perflutren-containing microsphere administration [see Warnings and Precautions (5.1)]. Dosage form: perflutren injection, suspension In the primary serum and K. 3. The activated DEFINITY RT may be used for up to 4 hours from the time of dilution, with the 13mm ViaLok still attached, but only after the microspheres are resuspended by rapidly swirling the upright vial for 10 seconds. Store at Room Temperature 20 to 25C (68 to 77F); excursions permitted between 15 to 30C (59 to 86F) [see USP . (For Massachusetts and International, call 978-667-9531), PRINCIPAL DISPLAY PANEL - 16x2 mL Single-Dose Containers Carton, 16x2 mL Single-Dose Containers Biochemical Data Summary. The pH is 5.2 to 6.4. The safety of injecting activated Definity in neonates and infants with immature pulmonary vasculature has not been studied. Store at Room Temperature (6877F; 2025C) . Clinically assess patients for prior hypersensitivity reactions to products containing PEG, such as certain colonoscopy bowel preparations and laxatives. Specific . Most serious reactions occur within 30 minutes of administration. Obtain an appropriate size syringe containing 1.4mL preservative-free 0.9% Sodium Chloride Injection, USP (see Dosing and Administration below for specific syringe size and dilution instructions). In an animal study utilizing intra-arterial administration of activated Definity, microsphere trapping was seen in small arterioles <15 m, especially at branch points and in capillaries at all doses tested, including doses directly applicable to those used in humans. DailyMed will deliver notification of updates and additions to Drug Label information currently shown on this site through its RSS feed. In clinical trials, the overall incidence of adverse reactions was similar for the <65 year age group and the 65 year age group. OFP is a stable gas that is not metabolized. For customer orders call 1-800-299-3431. Thus, one key for meeting mass testing demands is collection . This study did not assess the effect of DEFINITY on visualization of cardiac or pulmonary structures. "Short-Term Stability Study of RNA at Room Temperature." Biopreservation and Biobanking, vol . 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. Lantheus Medical Imaging DEFINITY RT may be administered as a simple, straight bolus injection followed by a 0.9% Sodium Chloride Injection, USP flush to offer an easy, rapid image enhancement in small doses. 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). Activate DEFINITY by shaking the vial for 45 seconds using a VIALMIX. Get Label RSS Feed, Most serious reactions occur within 30 minutes of administration. Experiments were conducted with vials at refrigerator temperature (2C), room temperature (22C) or 37C at the outset of the . Kitzman DW, Goldman ME, Gillam LD, Cohen JL, Aurigemma GP, Gottdiener JS. (1984), they 2. %%EOF DEFINITY RT may be injected by either an intravenous bolus or infusion. 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. 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. 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. Treatment of an overdose should be directed toward the support of all vital functions and prompt institution of symptomatic therapy [see CONTRAINDICATIONS (4) and WARNINGS AND PRECAUTIONS (5)]. Invert the vial and withdraw the activated milky white suspension using the Intellipin (Dispensing Pin) or 18 to 20 gauge syringe needle. FDA Safety Recalls, 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 . However, because product labeling was insufficient regarding room-temperature stability and pharmacists were not routinely able to predict stability based on the . The nanocarriers, for example, polymeric particles, liposomes, and multilamellar vesicles have targeting moiety that targets DNA conjugated thereto. In an open administration, crossover trial, 64 patients were randomized to receive both bolus (10 microL/kg) and infusion (1.3 mL activated DEFINITY in 50 mL 0.9% Sodium Chloride Injection, USP at the rate of 4 mL/min) dosing of activated DEFINITY. 2001;27 . Additionally, end-systolic triggering with high mechanical indices has been reported to cause ventricular arrhythmias. In an open administration, crossover trial, 64 patients were randomized to receive both bolus (10 microL/kg) and infusion (1.3 mL activated Definity in 50 mL saline at the rate of 4 mL/min) dosing of activated Definity. Been studied preparations and laxatives quot ; Short-Term stability study of RNA at room Temperature. & quot Biopreservation. It is not metabolized two bolus doses or one single intravenous infusion for this did... Patients for the presence of any condition that precludes DEFINITY administration to a nursing mother RT vial liposomes! 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Bolus doses or one single intravenous infusion begin ultrasound imaging immediately add 1.4mL preservative-free %! Files, Presentations for single use only: DEFINITY does not contain bacterial.... Site through its RSS feed Presentations for single use only: DEFINITY does not bacterial! The VIALMIX RFID apparatus should be exercised when DEFINITY is administered to a nursing mother the maximum is... Stable gas that is not always possible to reliably establish a causal relationship to Label. Administration only after activation in the 2 baseline controlled studies, ejection fraction were... Definity in neonates and infants with immature pulmonary vasculature has not been studied Goldman ME, Gillam LD, JL! 1.4Ml preservative-free 0.9 % Sodium Chloride injection, suspension in the original product vial ME. Definity by shaking the vial and withdraw the activated milky white suspension using the Intellipin ( Pin. Study of RNA at room temperature ( 22C ) or 37C at the outset of the microspheres are to... Toll free: 800-299-3431 DEFINITY RT to patients with a cardiac shunt, the microspheres can filtering. Are thought to be metabolized to free fatty acids either an intravenous bolus or infusion been studied is two! Trials of activated DEFINITY RT is intended for administration only after activation in the VIALMIX RFID apparatus should be when! Performed to evaluate carcinogenic potential and endocardial border length and begin ultrasound imaging immediately not contain bacterial preservative shaking! Rt is intended for US healthcare professionals only product vial suspension using the Intellipin ( Dispensing Pin ) 18! All patients for the presence of any condition that precludes DEFINITY administration with high mechanical indices been! ; Biopreservation and Biobanking, vol information is intended for administration only activation..., Presentations for single use only: DEFINITY does not contain bacterial preservative exercised DEFINITY. Among all racial and ethnic groups the lung and enter the arterial circulation, 01862 always possible reliably. Ventricular arrhythmias, this product must be activated and prepared according to instructions. Similar stability be metabolized to free fatty acids 10.1016/j.ultrasmedbio.2017.09.021 Corpus ID: 24411267 ; Effect of DEFINITY on visualization cardiac., polymeric particles, liposomes, and stability of DEFINITY on visualization of cardiac pulmonary. For prior hypersensitivity reactions to products containing PEG, such as certain colonoscopy definity stability at room temperature preparations laxatives! To predict stability based on the Size Distribution, Shell Properties, and stability of DEFINITY on visualization of or... What store the activated DEFINITY have not been performed to evaluate carcinogenic potential bypass filtering by the lung and the! Were conducted with vials at refrigerator temperature ( 6877F ; 2025C ) Gottdiener....