Important Administration Instructions

• DEFINITY RT is intended for administration only after activation in the VIALMIX RFID apparatus. Before injection, this product must be activated, diluted, and prepared according to the instructions outlined below. The VIALMIX RFID apparatus should be ordered from Lantheus Medical Imaging, 331 Treble Cove Road, North Billerica, MA, 01862. For customer orders call 1-800-299-3431.
• 13mm ViaLok (packaged separately) must be used in the dilution process of Definity RT.
• DEFINITY RT may be injected by either an intravenous bolus or infusion. Do not administer DEFINITY RT by intra-arterial injection [see Warnings and Precautions (5.3)].
• The maximum dose is either two bolus doses or one single intravenous infusion. The safety of bolus and infusion dosing in combination or in sequence, has not been studied.

Dosage

Imaging Guidelines

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

In a crossover trial of 64 patients randomized to both bolus and infusion using DEFINITY, 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 0.9% Sodium Chloride Injection, USP at a rate of 4 mL/min.

DEFINITY RT Activation, Preparation and Handling Instructions

There are two formulations of perflutren lipid microspheres that have differences concerning storage and preparation. Follow the preparation and storage procedures, as well as directions for activation of DEFINITY RT carefully and adhere to strict aseptic procedures during preparation.

1. Activate DEFINITY RT by shaking the vial for 45 seconds using a VIALMIX RFID device.
   Note: illustrations of this procedure are contained in the VIALMIX RFID User's Guide.
   Do not use this drug unless it has completed a full 45 second activation cycle in the VIALMIX RFID. DEFINITY RT will not be properly activated unless the full 45 second activation cycle is completed. Error messages will display if the vial is not properly activated. Do not reactivate the vial if VIALMIX RFID did not properly activate the vial. Never reactivate a successfully activated DEFINITY RT vial (see step 2). A VIALMIX RFID that is not functioning properly must never be used. Only use a vial activated from a properly functioning VIALMIX RFID. Refer to the VIALMIX RFID User's Guide to ensure that a properly functioning VIALMIX RFID is used.

2. Immediately after VIALMIX RFID activation, but no more than 15 minutes, place the activated 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.

3. Obtain a syringe containing 1.4 mL preservative-free 0.9% Sodium Chloride Injection, USP.
4. Attach the 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.
5. 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 milky white homogenous suspension with a presence of foam/bubbles.
6. The product must be used within 5 minutes of dilution. 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.
7. 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.
8. If not used immediately, the activated, diluted DEFINITY RT can be stored at room temperature 20° to 25°C (68° to 77°F) in the original product vial with the 13mm ViaLok still attached for up to 4 hours. A sterile syringe or cap should be attached to the Luer fitting on the ViaLok until use.
9. Invert the vial and withdraw the activated milky white suspension through the 13mm ViaLok into the syringe. Do not inject air into the DEFINITY RT vial.
10. Use the product immediately after its withdrawal from the vial; do not allow the product to stand in the syringe.
11. For bolus dosing, withdraw appropriate volume based on patient weight (kg) for administration. For infusion dosing, dilute 1.3 mL Definity RT in 50 mL of preservative-free 0.9% Sodium Chloride Injection, USP. [see Dosage and Administration ( 2.2)].