Perflutren

FDA Drug Information • Also known as: Definity, Definity Rt

Brand Names: Definity, Definity Rt
Drug Class: Contrast Agent for Ultrasound Imaging [EPC]
Route: INTRAVENOUS
Dosage Form: INJECTION, SUSPENSION
Product Type: HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: SERIOUS CARDIOPULMONARY REACTIONS Serious cardiopulmonary reactions, including fatalities, have occurred uncommonly during or following perflutren-containing microsphere administration. Most serious reactions occur within 30 minutes of administration. Assess all patients for the presence of any condition that precludes DEFINITY RT administration [see Contraindications (4) ] . Always have resuscitation equipment and trained personnel readily available [see Warnings and Precautions (5.1) ] . WARNING: SERIOUS CARDIOPULMONARY REACTIONS Serious cardiopulmonary reactions, including fatalities, have occurred uncommonly during or following perflutren-containing microsphere administration. Most serious reactions occur within 30 minutes of administration. Assess all patients for the presence of any condition that precludes DEFINITY RT administration ( 4 ). Always have resuscitation equipment and trained personnel readily available ( 5.1 ).

Description

11 DESCRIPTION DEFINITY RT (perflutren lipid microsphere) injectable suspension is, after activation, an ultrasound contrast agent for intravenous use. The perflutren lipid microspheres are composed of perflutren 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]- ω-methoxypoly(ox-1,2-ethanediyl), monosodium salt; commonly called N-( m ethoxy p oly e thylene g lycol 5000 carbamoyl)-1,2- d i p almitoyl-sn-glycero-3- p hosphatidyl e thanolamine, monosodium salt (abbreviated MPEG5000 DPPE). Perflutren is chemically characterized as 1,1,1,2,2,3,3,3-octafluoropropane. It has a molecular weight of 188, empirical formula of C 3 F 8 and has the following structural formula: DPPA has a molecular weight of 670, empirical formula of C 35 H 68 O 8 PNa, and following structural formula: DPPC has a molecular weight of 734, empirical formula of C 40 H 80 NO 8 P, and following structural formula: MPEG5000 DPPE has an approximate molecular weight of 5750 represented by empirical formula C 265 H 527 NO 123 PNa, contains <100ppm Ca 2+ and Mg 2+ and the following structural formula: Prior to activation, perflutren is in the headspace of the vial with a concentration of 6.52 mg/mL which is confirmed by positive IR spectroscopic testing in every vial. The lipid blend is in the clear, colorless to translucent (hazy), viscous sterile solution. Each mL of the solution contains 3.75 mg lipid blend (consisting of 0.225 mg DPPA, 2.005 mg DPPC, and 1.520 mg MPEG5000 DPPE) and the following inactive ingredients: 517.5 mg propylene glycol, 631 mg glycerin, 0.370 mg anhydrous sodium acetate, and 0.030 mg glacial acetic acid. The pH is 5.2 to 6.4....

What Is Perflutren Used For?

1 INDICATIONS AND USAGE DEFINITY RT is indicated, after activation, for use in adult and pediatric patients with suboptimal echocardiograms to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border. DEFINITY RT is an ultrasound contrast agent indicated, after activation, for use in adult and pediatric patients with suboptimal echocardiograms to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Adult Patients Bolus: 10 microL/kg intravenously over 30 seconds to 60 seconds followed by a 10 mL flush of 0.9% Sodium Chloride Injection. Infusion: 1.3 mL added to 50 mL of 0.9% Sodium Chloride Injection intravenously starting at 4 mL/minute, titrating as necessary, not to exceed 10 mL/minutes. The maximum dose is two bolus doses 30 minute apart or one single infusion. ( 2.2 ) Pediatric Patients Bolus: 3 microL/kg over 30 seconds to 60 seconds by intravenous bolus injection followed by a 5 mL flush of 0.9% Sodium Chloride Injection. The maximum dose is two bolus doses 30 minute apart. ( 2.3 ) See Full Prescribing Information for imaging instructions and preparation ( 2.4 , 2.5 ). 2.1 Important Preparation and Administration Instructions There are two formulations, DEFINITY and DEFINITY RT, that have differences in preparation and storage. Ensure of the correct product when following the directions for preparation and storage. DEFINITY RT must be activated using the VIALMIX RFID device and diluted before administration according to the instructions outlined below [see Dosage and Administration (2.5) ] . DEFINITY RT is for intravenous use only and must not be administered by intra-arterial injection [see Warnings and Precautions (5.3) ] . For adult patients, DEFINITY RT can be administered by either an intravenous bolus or infusion. The maximum dose is either two bolus doses or one single infusion. Do not administer the bolus and infusion dosing in combination or in sequence [see Dosage and Administration (2.2) ] . For pediatric patients, DEFINITY RT is administered by an intravenous bolus injection only. The maximum dose is two bolus doses [see Dosage and Administration (2.3) ]. 2.2 Recommended Dosage in Adult Patients Bolus Dosing The recommended bolus dose in adult patients is 10 microL/kg of activated DEFINITY RT administered intravenously over 30 seconds to 60 seconds followed by a 10 mL flush of 0.9% Sodium Chloride Injection, USP. If necessary, administer a second 10 microL/kg dose followed by a second 10 mL flush of 0.9% Sodium Chloride Injection, USP 30 minutes after the first injection to prolong contrast enhancement. Infusion Dosing The recommended infusion dose in adult patients is 1.3 mL of activated DEFINITY RT added to 50 mL of preservative-free 0.9% Sodium Chloride Injection, USP administered intravenously. Initiate infusion at 4 mL/minute, titrating the infusion rate as necessary to achieve optimal image enhancement, not to exceed 10 mL/minute. 2.3 Recommended Dosage in Pediatric Patients Bolus Dosing The recommended bolus dose in pediatric patients is 3 microL/kg of activated DEFINITY RT administered intravenously over 30 seconds to 60 seconds followed by a 5 mL flush of 0.9% Sodium Chloride Injection, USP. If necessary, administer a second bolus at a dose of 3 microL/kg to 5 microL/kg, followed by a second 5 mL flush of 0.9% Sodium Chloride Injection, USP 30 minutes after the first injection to...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Serious Cardiopulmonary Reactions [see Warnings and Precautions (5.1) ] Hypersensitivity Reactions [see Warnings and Precautions (5.2) ] Pain Episodes in Patients with Sickle Cell Disease [see Warnings and Precautions (5.5) ] The most common adverse reactions (≥0.5%) are headache, back/renal pain, flushing, nausea, chest pain, injection site reactions, and dizziness. ( 6 ) 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. 6.1 Clinical Trials Experience 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. Adverse Reactions in Adults Safety of DEFINITY RT was evaluated in a total of 1,716 adult subjects who received DEFINITY, another formulation of perflutren lipid microspheres, in pre-market clinical trials. In this group, 1,063 (62%) were male and 653 (38%) were female, 1,328 (77%) were White, 258 (15%) were Black or African American, 74 (4%) were Hispanic, and 56 (3%) were classified as other racial or ethnic groups. The mean age was 56 years (range 18 to 93). Among the 1,716 subjects, 19 (1.1%) suffered serious cardiopulmonary adverse reactions. Adverse reactions that led to discontinuation in a total of 15 (0.9%) subjects receiving DEFINITY in the clinical trials included urticaria, pruritus, dizziness, chest pain, dyspnea, and back pain. Table 1 summarizes the most common adverse reactions occurring at ≥0.5%. Table 1 Adverse Reactions Occurring in ≥0.5% of All DEFINITY-Treated Subjects DEFINITY (N=1716) Total Number of Adverse Reactions 269 Total Number of Subjects with an Adverse Reaction 144 (8.4%) Body system Preferred term n (%) N=Sample size 1716 subjects who received activated DEFINITY n=Number of subjects reporting at least one Adverse Reaction Application Site Disorders 11 (0.6) Injection Site Reactions 11 (0.6) Body as a Whole 41 (2.4) Back/renal pain 20 (1.2) Chest pain 13 (0.8) Central and peripheral nervous system disorder 54 (3.1) Headache 40 (2.3) Dizziness 11 (0.6) Gastrointestinal system 31 (1.8) Nausea 17 (1.0) Vascular (extracardiac) disorders 19 (1.1) Flushing 19 (1.1) 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 Musculoskeletal: Arthralgia 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 Urinary: Albuminuria Adverse Reactions in Pediatric Patients In a study of DEFINITY in 40 pediatric patients 1 month of age and older, no new safety signals were observed [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.2) ] . In published studies of DEFINITY in 149 patients 5 years to 24 years of age (mean age 16.8 years; 56% male) clinically indicated for echocardiography, no additional safety signals were observed. 6.2 Postmarketing Experience Adverse Reactions from Observational Studies In a prospective, multicenter, open-label registry of 1,053 patients receiving DEFINITY in routine clinical practice, heart rate, respiratory rate, and pulse oximetry were monitored for 30 minutes after DEFINITY administration. No deaths...

Contraindications

4 CONTRAINDICATIONS DEFINTY RT is contraindicated in patients with known or suspected hypersensitivity to Perflutren lipid microsphere or its components, such as polyethylene glycol (PEG) [see Warnings and Precautions (5.2) and Description (11) ]. Known or suspected hypersensitivity to perflutren lipid microsphere or its Components, such as polyethylene glycol (PEG) ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Available data from case reports with DEFINITY RT use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. DEFINITY RT has a very short half-life; therefore, administration of DEFINITY RT to a pregnant woman is not expected to result in clinically relevant fetal exposure. No adverse developmental outcomes were observed in animal reproduction studies with administration of activated DEFINITY, another formulation of perflutren lipid microspheres, 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 ) . All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data DEFINITY was administered intravenously to rats at doses of 0.1mL/kg, 0.3 mL/kg, and 1 mL/kg (approximately 0.8, 2.4, and 8 times the recommended maximum human dose based on body surface area); DEFINITY doses were administered daily from day 6 to day 17 of gestation. DEFINITY was administered intravenously to rabbits at doses of 0.1mL/kg, 0.3 mL/kg, and 1 mL/kg (approximately, 1.6, 4.8, and 16 times the recommended maximum human dose based on body surface area); DEFINITY doses were administered daily from day 7 to day 19 of gestation. No significant findings on the fetus were observed.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied DEFINITY RT (perflutren lipid microsphere) injectable suspension is supplied in a single-patient use clear glass Radio Frequency Identification (RFID)-tagged vial containing 6.52 mg/mL perflutren in the headspace of the vial and 3.75 mg/mL of a lipid blend in a colorless, uniformly clear to translucent (hazy) viscous solution phase with 0.35 mL volume. DEFINITY RT is available in the following packages: One (1) RFID-tagged vial per carton - NDC (11994-017-01) Twenty (20) RFID-tagged vials per carton - NDC (11994-017-20) Order VIALMIX RFID from Lantheus Medical Imaging Storage and Handling Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. 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.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.