Definity Rt

• Assess all patients for the presence of any condition that precludes DEFINITY RT administration

  [see

  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)

  ]

  .
• Always have resuscitation equipment and trained personnel readily available

  [see

  5.1 Serious Cardiopulmonary Reactions

  Serious cardiopulmonary reactions including fatalities have occurred uncommonly during or shortly following perflutren-containing microsphere administration, typically within 30 minutes of administration. 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). Always have cardiopulmonary resuscitation personnel and equipment readily available prior to DEFINITY RT administration and monitor all patients for acute reactions.

  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 (6.2)]

  .

  ]

  .

• 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 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.
    )
• 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 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 prolong contrast enhancement.
    )
• See Full Prescribing Information for imaging instructions and preparation (
  2.4 Imaging Instructions

  Adult Patients

  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)]

  . Then inject activated DEFINITY RT (as described above) and begin ultrasound imaging immediately

  [see Clinical Pharmacology(12.2)

  . Evaluate the DEFINITY RT echocardiogram images in combination with the non-contrast echocardiogram images.

  Pediatric Patients

  After baseline non-contrast echocardiography is completed, set the mechanical index for the ultrasound transducer at 0.3 or below

  [see Warnings and Precautions (5.4)]

  . Then inject activated DEFINITY RT (as described above) and begin ultrasound imaging immediately

  [see Clinical Pharmacology(12.2)

  . Evaluate the DEFINITY RT echocardiogram images in combination with the non-contrast echocardiogram images.
  ,
  2.5 Instructions for Activation, Preparation, and Handling of Definity RT

  • Adhere to strict aseptic procedures during preparation.
  • Activate DEFINITY RT by shaking the vial for 45 seconds using a VIALMIX RFID device.
    
    Note: Use only the drug activated in a properly functioning VIALMIX RFID for a full 45 second activation cycle. Do not reactivate the vial if VIALMIX RFID did not properly activate the vial. Never reactivate a successfully activated DEFINITY RT vial (see step 3).
    
    Refer to the VIALMIX RFID User's Guide for illustrations of the activation procedure and a properly functioning VIALMIX RFID

  • Immediately after activation, but no more than 15 minutes, place the activated DEFINITY RT vial in the upright position and remove the flip top cap. Insert the 13mm ViaLok (Vented Vial Access Device) into the center of the rubber stopper and push down until properly engaged and locked onto the vial.

  • Attach a syringe containing 1.4 mL preservative-free 0.9% Sodium Chloride Injection, USP to the 13mm ViaLok luer-lok hub. Add 1.4 mL of preservative-free 0.9% Sodium Chloride Injection, USP to the activated DEFINITY RT vial. Do not inject air into the DEFINITY RT vial.
  • With the 13mm ViaLok still inserted and syringe attached, rapidly swirl the upright vial for 10 seconds to mix the contents.
  • Activated and diluted DEFINITY RT appears as a homogenous milky white suspension with a presence of foam/bubbles. Use the product within 5 minutes of dilution. If not used within 5 minutes resuspend the microspheres by rapidly swirling the upright vial for 10 seconds before the product is withdrawn in a syringe.
  • 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 the activated, diluted DEFINITY RT at room temperature 20° to 25°C (68° to 77°F) in the original product vial with the 13mm ViaLok still attached. A sterile syringe or cap should be attached to the Luer fitting on the ViaLok until use.
  • Invert the vial and withdraw the activated homogeneous milky white suspension through the 13mm ViaLok into the syringe. Do not inject air into the DEFINITY RT vial.
  • Use the product immediately after its withdrawal from the vial: do not allow the product to stand in the syringe.
  • For infusion dosing in adult patients, dilute 1.3 mL of activated, diluted Definity RT further in 50 mL of preservative-free 0.9% Sodium Chloride Injection, USP.
  • Parenteral drug products should be inspected visually for foreign particulate matter and discoloration prior to administration, whenever solution and container permit
    .
  ).

DEFINITY RT is supplied in a single-patient use vial containing 6.52 mg/mL perflutren in the headspace and 3.75 mg/mL of a lipid blend as a clear colorless to translucent viscous solution with 0.35 mL volume. After activation and dilution each mL contains a maximum of 1.2 × 10¹⁰ perflutren lipid microspheres as a homogeneous milky white injectable suspension, and about 80 microL/mL (0.65 mg/mL) perflutren.

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

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.