Bolus

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. If necessary, a second 10 microliters (microL)/kg dose followed by a second 10 mL saline flush may be administered 30 minutes after the first injection to prolong contrast enhancement.

Infusion

The recommended infusion dose for activated DEFINITY® is via an IV infusion of 1.3 mL added to 50 mL of preservative-free saline. The rate of infusion should be initiated at 4.0 mL/minute, but titrated as necessary to achieve optimal image enhancement, not to exceed 10 mL/minute.

Imaging

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® (as described above) and begin ultrasound imaging immediately. Evaluate the activated DEFINITY® echocardiogram images in combination with the non-contrast echocardiogram images.

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.

DEFINITY® Activation, Preparation and Handling Instructions

1. Allow the vial to warm to room temperature before starting the activation procedure.
2. Activate DEFINITY® by shaking the vial for 45 seconds using a VIALMIX®.
   
   Note: illustrations of this procedure are contained in the VIALMIX® Users Guide.
   
   Do not use this drug unless it has completed a full 45 second activation cycle in the VIALMIX®. DEFINITY® will not be properly activated unless the full 45 second activation cycle is completed. Do not reactivate the vial if VIALMIX® did not complete a full 45 second cycle. Do not reactivate a successfully activated DEFINITY® vial (see step 3). Do not use a VIALMIX® that is not functioning properly. Refer to the "VIALMIX® User's Guide" for the "VIALMIX® calibration and replacement procedures" to ensure that a properly functioning VIALMIX® is used.
3. Immediately after activation in the VIALMIX®, activated DEFINITY® appears as a milky white suspension and may be used immediately after activation. If the product is not used within 5 minutes of VIALMIX® activation, the microspheres should be resuspended by 10 seconds of hand agitation by inverting the vial before the product is withdrawn in a syringe. 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. Store the activated DEFINITY® at room temperature in the original product vial.
4. Invert the vial and withdraw the activated milky white suspension using the Intellipin™ (Dispensing Pin) or 18 to 20 gauge syringe needle. Withdraw the material from the middle of the liquid in the inverted vial. Do not inject air into the DEFINITY® VIAL.
5. Use the product immediately after its withdrawal from the vial; do not allow the product to stand in the syringe.

For single use only: DEFINITY® does not contain bacterial preservative. Bacterial contamination with the risk of post-administration septicemia can occur following the puncture of the elastomeric septum. It is essential to follow directions for activation of DEFINITY® carefully and to adhere to strict aseptic procedures during preparation.