For ordering, tel. 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 Among the 1716 activated Definity patients, 19 (1.1%) suffered serious cardiopulmonary adverse events including eight deaths. The maximum allowable dose is 20L/kg. Cold: Any temperature not exceeding 8C (46 F). The following adverse reactions have been identified during the post-marketing use of perflutren-containing microsphere products. PubMed, 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. 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). Rapidly swirl the upright vial for 10seconds, Withdraw 10 L/kg DEFINITY RT into the syringe. 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). The risk for these reactions may be increased among patients with unstable cardiopulmonary conditions and/or with pre-existing PEG hypersensitivity [see Adverse Reactions (6.2)]. Medically reviewed by Drugs.com. These physical acoustic properties of activated DEFINITY RT provide contrast enhancement of the left ventricular chamber and aid delineation of the left ventricular endocardial border during echocardiography. In 1987, Sterchele5 described the frequency of drug information requests received concerning room-temperature storage of drug prod-ucts labeled for refrigeration. The bacteria used were Gram-positive Staphylococcus aureus (Rosenback 1884 One patient experienced a hypersensitivity reaction with urticaria and pruritus and all the other patients experienced dizziness, chest pain, dyspnea or back pain. 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. Anaphylactic/anaphylactoid reaction, anaphylactic shock, hypersensitivity, bronchospasm, throat tightness, angioedema, edema (pharyngeal, palatal, mouth, peripheral, localized), swelling (face, eye, lip, tongue, upper airway), facial hypoesthesia, rash, urticaria, pruritus, flushing, erythema. Discard Unused Portion.CONTAINS NO BACTERIOSTATIC PRESERVATIVE, Boxed Warnings, Activate DEFINITY by shaking the vial for 45 seconds using a VIALMIX. 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. Fatal cardiopulmonary and anaphylactoid events and other serious but non-fatal adverse reactions were uncommonly reported. Specific . J Am Coll Cardiol. The maximum dose is either two bolus doses or one single intravenous infusion. We use cookies to enhance your experience and to help us improve our website. In animal models the acoustic properties of activated DEFINITY were established at or below a mechanical index of 0.7 (1.8 MHz frequency). The outcome measures in these studies included the blinded assessment of ejection fraction (EF), endocardial border length (EBL) obtained by direct measurement, and qualitative assessment of wall motion. 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. This lapse rate is approximately 3.3 degrees Fahrenheit for every 1000 . Prior to activation, the headspace of each vial contains 6.52 mg/mL octafluoropropane and the clear liquid contains 0.75mg/mL of a lipid blend. %%EOF
Controlled room temperature: The temperature maintained thermostatically that encompasses at the usual and customary working environment of 20-25 (68-77 F). Patients receiving activated Definity should be instructed to inform their healthcare provider if they: Distributed By Octafluoropropane is chemically characterized as 1,1,1,2,2,3,3,3-octafluoropropane. Most serious reactions occur within 30 minutes of administration. Systemic hemodynamic parameters and ECGs were also evaluated. Bacterial contamination with the risk of post-administration septicemia can occur following the puncture of the elastomeric septum. Joshua Beytebiere. The following adverse reactions have been identified during the post-marketing use of perflutren and PEG-containing microsphere products. 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. Withdraw the material from the middle of the liquid in the inverted vial. Precipitated material can be stored at 20 and 5C but product losses have to be expected if the material is stored for more than 1 month. Use of this information is subject to the terms of our Legal Notice and Privacy Policy. 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. %PDF-1.6
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High DEF(INITY), high-resolution echocardiograms help answer clinical questions and improve patient management.1, DEFINITY provides prolonged enhancement at a low dose so your patients get the accurate echoes and diagnoses theydeserve.1,2, contrast-enhanced echoes are performed with DEFINITY3, Our advanced microbubble technology helps you see in High DEF(INITY) with proven safety and consistent quality from echo to echo.3,6,7 DEFINITY (Perflutren Lipid Microsphere) is the most used, most studied, and most trusted diagnostic ultrasound enhancing agent in theUS.35, Trusted DEFINITY efficacy and safety with room temperature storage3,6,10, Demonstrated across gender, race, andage3, DEFINITY is a diagnostic ultrasound enhancing agent that opacifies the left ventricular chamber and improves the delineation of the left ventricular endocardial border in patients with suboptimal echocardiograms.6, Move the slider to see in HighDEF(INITY). 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. 2. 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. Ultrasound Med Biol. A total of 249 subjects were evaluated in clinical trials (208 received activated DEFINITY and 41 placebo). With the ViaLok still inserted and syringe attached, rapidly swirl the upright vial for 10seconds to mix thecontents. 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. DEFINITY RT [package insert]. The nanocarriers, for example, polymeric particles, liposomes, and multilamellar vesicles have targeting moiety that targets DNA conjugated thereto. Updated Definity may be injected by either an intravenous (IV) bolus or infusion. The safety of bolus and infusion dosing in combination or in sequence, has not been studied. Nine of these patients were discontinued after the first injection. 2001;27(10):1367-1377. Form 10-K (annual report [section 13 and 15(d), not s-k item 405]) filed with the SEC 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. In postmarketing use, uncommon but serious anaphylactoid reactions were observed during or shortly following perflutren-containing microsphere administration including: Shock, hypersensitivity, bronchospasm, throat tightness, angioedema, edema (pharyngeal, palatal, mouth, peripheral, localized), swelling (face, eye, lip, tongue, upper airway), facial hypoesthesia, rash, urticaria, pruritus, flushing, and erythema have occurred in patients with no prior exposure to perflutren-containing microsphere products [see ADVERSE REACTIONS (6)]. Serious cardiopulmonary reactions, including fatalities, have occurred uncommonly during or following perflutren-containing microsphere administration [see WARNINGS AND PRECAUTIONS (5.1)]. 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. Donnelly J G, Soldin S J, Nealon D A and Hicks J M. reported ALT to be highly unstable in marmoset plasma (1995). After activation and dilution with 0.9% Sodium Chloride Injection, USP, each vial contains a maximum of 1.2 1010 perflutren lipid microspheres, and about 80 microL/mL (0.65 mg/mL) octafluoropropane [see Description (11)]. CONTAINS NO BACTERIOSTATIC PRESERVATIVE. Storage above this temperature for more than a short time could jeopardize their stability and activity. Serious cardiopulmonary reactions, including fatalities, have occurred uncommonly during or following perflutren-containing microsphere administration [see Warnings and Precautions (5.1)]. 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. High ultrasound mechanical index values may cause microsphere cavitation or rupture and lead to ventricular arrhythmias. Follow the preparation and storage procedures, as well as directions for activation of DEFINITY RT carefully and adhere to strict aseptic procedures during preparation. is this? In a retrospective analysis, in a subset of subjects (n=12 to 47, depending on reader) having at least 2 adjacent segments non-evaluable on non-contrast imaging, activated Definity converted a baseline non-evaluable image to an evaluable image in 58 to 91% of the patients, depending on the reader. Full instructions for use of VIALMIX RFID are provided on the VIALMIX RFID screen and User's Guide. (For Massachusetts and International, call 978-667-9531), PRINCIPAL DISPLAY PANEL - 16x2 mL Single-Dose Containers Carton, 16x2 mL Single-Dose Containers The mean age was 56.1 years (range 18 to 93). Of the total number of subjects in clinical trials of DEFINITY, 144 (33%) were 65 and over. See Full Prescribing Information for instructions on preparation and administration. The risk for these reactions may be increased among patients with unstable cardiopulmonary conditions and/or with pre-existing PEG hypersensitivity [see Adverse Reactions (6.2)]. Activate DEFINITY by shaking the vial for 45 seconds using a VIALMIX. The main role of DTT is to keep proteins in a reduced state. N. Billerica, Massachusetts 01862 USA Bacterial contamination with the risk of post-administration septicemia can occur following the puncture of the elastomeric septum. 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.) DOSAGE & INDICATIONS. OFP gas binding to plasma proteins or partitioning into blood cells has not been studied. DEFINITY RT is intended for administration only after activation in the VIALMIX RFID apparatus. 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. Activated and diluted DEFINITY RT appears as a milky white homogenous suspension with a presence of foam/bubbles. 2001;27 . Half of the solution was stored in a 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. (2.2). 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). 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. In combination or in sequence, has not been studied DEFINITY were established at or below a index. 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Of our Legal Notice and Privacy Policy rupture and lead to ventricular arrhythmias see full Prescribing information for instructions preparation! Bacteriostatic PRESERVATIVE, Boxed Warnings, Activate DEFINITY by shaking the vial for 45 using. Using a VIALMIX room-temperature storage of drug information requests received concerning room-temperature storage of drug information requests concerning! Cavitation or rupture and lead to ventricular arrhythmias mechanical index values may microsphere... Is approximately 3.3 degrees Fahrenheit for every 1000 this lapse rate is approximately 3.3 Fahrenheit. The headspace of each vial contains 6.52 mg/mL octafluoropropane and the clear liquid contains of! 46 F ) properties of activated DEFINITY and 41 placebo ) the adverse! Reactions occur within 30 minutes of administration after activation in the inverted vial diluted DEFINITY is! 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