For Single Use Only, Discard Unused Portion 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. stability at room temperature and -20 C. 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. Discard Unused Portion.CONTAINS NO BACTERIOSTATIC PRESERVATIVE, Boxed Warnings, %%EOF The overall incidence of adverse reactions was similar among all racial and ethnic groups. 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). The maximal duration of stability at room temperature (25C) of these antibiotics diluted in normal saline has been reported as follows by the manufacturer of the elastomeric pumps: flucloxacillin, 24 h at concentrations up to 70 g/L; cefazolin, 48 h at 16.7 g/L; cefepime, 24 h at 20 g/L; piperacillin, 24 h at 80 g/L; and tazobactam, 24 h at . In 1975, Wolfert and Cox 3 recognized that pharmacists were often asked about the stability of refrigerated medications that are accidentally stored at room-temperature. A sterile syringe or cap should be attached to the ViaLok until use. Smaller, incremental dose amounts of 0.2mL to 0.3mL are better suited for current ultrasound system technology. Always have cardiopulmonary resuscitation personnel and equipment readily available prior to DEFINITY RT administration and monitor all patients for hypersensitivity reactions. 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. The safety of activated Definity with the use of end-systolic triggering has not been evaluated. Of these, 144 (8.4%) had at least one adverse reaction (Table 6.1). 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)]. Definity may be injected by either an intravenous (IV) bolus or infusion. 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. 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. 2.4 DEFINITY Activation, Preparation and Handling Instructions 1. The recommended bolus dose for activated Definity is 10 microliters (microL)/kg of the activated product by intravenous bolus injection within 30-60 seconds, followed by a 10 mL saline flush. Serious cardiopulmonary reactions, including fatalities, have occurred uncommonly during or following perflutren-containing microsphere administration [see Warnings and Precautions (5.1)]. (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. Storage above this temperature for more than a short time could jeopardize their stability and activity. In the 2 baseline controlled studies, ejection fraction results were evaluated in comparison to MRI. hb```e``$W00 P9@e DEFINITY RT [package insert]. N. Billerica, MA: Lantheus Medical Imaging, Inc. VialMix RFID User's Guide. DEFINITY RT is supplied as a single patient use 2 mL RFID-tagged clear glass vial containing a colorless, uniformly clear to translucent (hazy) viscous solution in packages of twenty (20) single patient use vials. Sonne C, Xie F, Lof J, et al. The pH is 5.2 to 6.4. SECTION 10: STABILITY AND REACTIVITY . Becher H, Burns PN. 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. Biochemical Data Summary. No clinically important pulmonary hemodynamic, systemic hemodynamic, or ECG changes were observed. For ordering, tel. 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. 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). Patients with pulmonary artery systolic pressure greater than 75 mmHg were excluded from this study. Do not administer Definity by intra-arterial injection [see CONTRAINDICATIONS (4)]. Drug class: Ultrasound contrast media. No significant findings on the fetus were observed. 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. 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. The pharmacokinetics of activated DEFINITY RT in pediatric subjects has not been studied. WARNING: SERIOUS CARDIOPULMONARY REACTIONS. Kitzman DW, Goldman ME, Gillam LD, Cohen JL, Aurigemma GP, Gottdiener JS. Store a backup cassette for 24 hours at room temperature or for up to 8 days refrigerated then administer for 24 hours without ice packs. 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. FDA Safety Recalls, 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. shell properties, and stability of Definity Himanshu Shekhar,1 Nathaniel J. Smith,1 Jason L. Raymond,2 and Christy K. Holland1,3 . In a crossover trial of 64 patients randomized to both bolus and infusion, the duration of clinically useful contrast enhancement for fundamental imaging was approximately 3.4 minutes after a 10 microL/kg bolus and was approximately 7.1 minutes during the continuous infusion of 1.3 mL activated Definity in 50 mL saline at a rate of 4 mL/min. Rapidly swirl the upright vial for 10seconds, Withdraw 10 L/kg DEFINITY RT into the syringe. 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. DEFINITY RT is supplied as a single patient use 2 mL RFID-tagged clear glass vial containing colorless, uniformly clear to translucent (hazy) viscous solution in packages of twenty (20) single patient use vials. 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. 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 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)]. 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). Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. In contrast insulin levels decreased in serum gel tubes both centrifuged and whole blood (66% of baseline, p = 0.01 and 76% of baseline p = 0.01, by 24 hours respectively). The targeting moiety that targets DNA is typically an antibody, or variant, fragment, or fusion protein derived therefrom that binds . Nine of these patients were discontinued after the first injection. 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). Assay of antibacterial activity. DEFINITY RT contains PEG. Fatal cardiopulmonary and hypersensitivity reactions and other serious but non-fatal adverse reactions were uncommonly reported. There were 15 discontinuations reported with a mean age of 41.5 years. 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.) 2. It is not always possible to reliably establish a causal relationship to drug exposure due to the presence of underlying conditions. (For Massachusetts and International, call 978-667-9531), PRINCIPAL DISPLAY PANEL - 16x2 mL Single-Dose Containers Carton, 16x2 mL Single-Dose Containers 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. 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. To find out more about how we use cookies, read our PRIVACY POLICY. 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). Fatal cardiopulmonary and anaphylactoid events and other serious but non-fatal adverse reactions were uncommonly reported. Permalink. Mathay, Conny, et al. 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