Lumason

IV Preparation

Using aseptic techniques, reconstitute vial using mini-spike with prefilled syringe contents (ie, 5 mL NaCl 0.9%)

Do not remove syringe and mini-spike from vial

Shake vigorously for 20 seconds, mixing all contents in the vial

Resulting suspension should appear as a homogenous, white, milky liquid; this indicates formation of sulfur hexafluoride lipid microspheres

Following reconstitution, resulting suspension contains 1.5-5.6 x10^8 lipid microspheres/mL with 45 mcg/mL of sulfur hexafluoride

Invert vial and syringe and slowly withdraw 2 mL of the reconstituted suspension into the syringe

Unscrew syringe from mini-spike and immediately connect the syringe to the dosage administration line (20 G)

Kit contains

• 2-compartment vial containing 25 mg of lipid-type A lyophilized powder and headspace fill of 60.7 mg sulfur hexafluoride
• Prefilled syringe containing 5 mL NaCl 0.9%
• Mini-spike

IV Administration

Administer suspension as IV bolus injection immediately after reconstitution

Provides useful echocardiographic signal intensity for 2 minutes following the injection

If not used immediately after reconstitution, the microspheres should be resuspended by a few seconds of hand agitation before the suspension is withdrawn into the syringe

Intravesical (Urinary Instillation) Preparation

Doses ≥1 mL: Invert the system and slowly withdraw the intended volume of suspension into the syringe

Doses <1 mL: Withdraw 2 mL of the reconstituted suspension into the 5 mL syringe and measure the volume of sulfur hexafluoride to inject by using the 0.2 mL graduations between the 1-2 mL marks

Intravesical (Urinary Instillation) Administration

Insert a sterile 6-8 french urinary catheter into the bladder under sterile conditions

Empty the bladder of urine, and then fill the bladder with 0.9% NaCl to ~33-50% of its predicted total volume

The total bladder volume in children is calculated as: [(age in years + 2) x 30] mL

Administer as an intravesical bolus injection through the urinary catheter

Continue filling the bladder with saline until the patient has the urge to micturate or at the first sign of back pressure to the infusion

Immediately following the first voiding, the bladder may be refilled with normal saline for a second cycle of voiding and imaging, without the need of a second administration

Storage

Unreconstituted kit: Store at room temperature 25°C (77°F); excursions permitted to 15-30°C (59-86°F)

Reconstituted suspension: May store at room temperature for up to 3 hr; does not contain antimicrobial preservative

Sulfur hexafluoride is injected into a vein through an IV. A healthcare provider will give you this injection just before the start of your echocardiogram.

Your heart rate, breathing, blood pressure, oxygen levels, and other vital signs will be watched closely for at least 30 minutes after you receive sulfur hexafluoride. This is to make sure you do not have an allergic reaction to the medicine.

Since this medicine is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

Since sulfur hexafluoride is given with an echocardiogram, you will not be on a regular dosing schedule.

Sulfur hexafluoride is an ultrasound contrast agent that is used to improve the quality of an echocardiogram (ultrasound of the heart). Sulfur hexafluoride works by changing the way ultrasound waves travel within your heart. This helps the ultrasound portray a sharper image of your heart.

Sulfur hexafluoride is used to allow certain segments of the heart to be seen more clearly on an echocardiogram.

Sulfur hexafluoride may also be used for purposes not listed in this medication guide.

Since sulfur hexafluoride is given with an echocardiogram, you will not be on a regular dosing schedule.

Get emergency medical help if you have any of these signs of an allergic reaction: hives, skin redness, rash; warmth, numbness, or tingly feeling; trouble breathing, tight feeling in your throat; swelling of your face, lips, tongue, or throat.

In rare cases, serious or fatal reactions may occur during the injection or shortly afterward. Tell your caregivers right away if you have:

• a light-headed feeling, like you might pass out;

• severe dizziness, or a cold sweat;

• chest pain, wheezing, trouble breathing;

• fast or slow heartbeats;

• severe headache, blurred vision, pounding in your neck or ears, anxiety, confusion; or

• slow heart rate, weak pulse, fainting, weak or shallow breathing.

You may be more likely to have a serious reaction if you have severe or uncontrolled heart problems (congestive heart failure, a recent heart attack, serious heart rhythm disorder).

Common side effects may include:

• nausea;

• headache;

• altered sense of taste;

• feeling hot; or

• pain or warmth where the medicine was injected.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

It is very important that your doctor check your or your child's progress very closely while you are receiving this medicine. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to receive it.

Serious heart or lung problems may occur while you are receiving this medicine. Tell your doctor right away if you or your child have a chest pain, fast, slow, pounding, or irregular heartbeat, lightheadedness, dizziness, or fainting, or troubled breathing.

This medicine may cause serious allergic reactions, including anaphylactic shock. This can be life-threatening and requires immediate medical attention. Tell your doctor right away if you or your child have a rash, itching, hoarseness, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth after receiving this medicine.

  Important Administration Instructions

Do not administer Lumason by intra-arterial injection [see Warnings and Precautions (5.3)].

  Recommended Dosage

Echocardiography

The recommended dose of Lumason after reconstitution is 2 mL administered as an intravenous bolus injection during echocardiography. During a single examination, a second injection of 2 mL may be administered to prolong contrast enhancement. Follow each Lumason injection with an intravenous flush using 5 mL of 0.9% Sodium Chloride Injection.

Ultrasonography of the Liver

Adults

The recommended dose of Lumason after reconstitution in adult patients is 2.4 mL administered as an intravenous injection during ultrasonography of the liver. During a single examination, a second injection of 2.4 mL may be administered, if needed. Follow Lumason injection with an intravenous flush using 5 mL of 0.9% Sodium Chloride Injection.

Pediatric Patients

The recommended dose of Lumason after reconstitution in pediatric patients is 0.03 mL per kg administered as an intravenous injection during ultrasonography of the liver. During a single examination, a second injection of 0.03 mL per kg may be administered, if needed. Do not exceed 2.4 mL per injection. Follow Lumason injection with an intravenous flush of 0.9% Sodium Chloride Injection.

Ultrasonography of the Urinary Tract

Pediatric Patients

The recommended dose of Lumason after reconstitution is 1 mL. The bladder may be refilled with normal saline for a second cycle of voiding and imaging, without the need of a second Lumason administration.

  Reconstitution Instructions

Contents of Lumason Kit

Lumason Reconstitution Steps:

• Inspect the Lumason kit and its components for signs of damage. Do not use the kit if the protective caps on the Lumason vial and prefilled syringe with 5 mL Sodium Chloride 0.9% Injection are not intact or if the kit shows other signs of damage.
• Under aseptic conditions, reconstitute Lumason by injecting the prefilled syringe with 5 mL Sodium Chloride 0.9% Injection into the Lumason vial using the following illustrated steps:

1. Connect the plunger rod to the prefilled syringe barrel by screwing it clockwise into the syringe (see Figure 1).

2. Open the Mini-Spike blister and remove the syringe tip cap (see Figure 2).

3. Open the Mini-Spike green cap and connect the syringe to the Mini-Spike by screwing it in clockwise (see Figure 3).

4. Remove the flip cap plastic protective cap from the vial, remove the Mini-Spike spike protection and position the spike in the center of the rubber stopper of the vial. Press firmly inward until the spike is fully inserted in the stopper (see Figure 4).

5. Empty the content of the syringe into the vial by pushing on the plunger rod (see Figure 5).

6. Shake vigorously for 20 seconds, mixing all the contents in the vial (see Figure 6). A homogeneous white milky liquid indicates formation of sulfur hexafluoride lipid microspheres.

7. For preparation of doses greater than or equal to 1 mL, invert the system and slowly withdraw the intended volume of suspension into the syringe (see Figure 7). For preparation of doses less than 1 mL, withdraw 2 mL of the reconstituted suspension into the 5 mL syringe and measure the volume of Lumason to inject by using the 0.2 mL graduations between the 1 mL and 2 mL marks.

8. Unscrew the syringe from the Mini-Spike (see Figure 8). Peel and remove the diluent label to display the reconstituted product label. For intravenous administration, immediately connect the syringe to a dose administration line (20 G) and administer as directed under the Administration Instructions below. For intravesical administration, immediately connect the syringe to a sterile urinary catheter (6 french to 8 french) and administer as directed under the Administration Instructions below.

• Following reconstitution, Lumason suspension contains 1.5 to 5.6 x108 microspheres/mL with 45 mcg/mL of sulfur hexafluoride.
• Use immediately after reconstitution. If the suspension is not used immediately after reconstitution, resuspend the microspheres for a few seconds by hand agitation before the suspension is drawn into the syringe. Reconstituted suspension within a vial may be used for up to 3 hours from the time of its reconstitution. Maintain the vial containing the reconstituted suspension at room temperature.

  Administration Instructions

Inspect visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The reconstituted suspension is milky-white, and does not contain visible particulate matter. Do not use the single-patient use vial for more than one patient.

Intravenous Administration

Administer Lumason as an intravenous bolus injection.

Intravesical Administration in Pediatric Patients

1. Insert a sterile 6 french to 8 french urinary catheter into the bladder under sterile conditions;
2. Empty the bladder of urine, and then fill the bladder with saline (sterile 0.9% sodium chloride solution) to approximately one third or half of its predicted total volume. The total bladder volume in children is calculated as [(age in years + 2) x 30] mL;
3. Administer Lumason as an intravesical bolus injection through the urinary catheter;
4. Continue filling the bladder with saline until the patient has the urge to micturate or at the first sign of back pressure to the infusion.
5. Immediately following the first voiding, the bladder may be refilled with normal saline for a second cycle of voiding and imaging, without the need of a second Lumason administration

Imaging Guidelines

Echocardiography

After baseline non-contrast echocardiography is complete, adjust the mechanical index for the ultrasound device to 0.8 or lower. Continue ultrasound imaging following Lumason injection.

Ultrasonography of the Liver

After identification of the target focal lesion on non-contrast ultrasound examination, hold transducer still while switching scanner to low mechanical index (≤ 0.4) contrast-specific imaging. Continue ultrasound imaging following Lumason injection.

Ultrasonography of the Urinary Tract

After baseline non-contrast ultrasound examination of the kidney and bladder, switch the scanner to low mechanical index (≤0.4) contrast specific imaging. Perform continuous alternate ultrasound imaging of the bladder, ureters, and kidneys during filling and voiding of the bladder.

For injectable suspension: Lumason is supplied as a 3-part single-patient use kit comprised of:

• one Lumason clear vial containing 25 mg of lipid-type A sterile white lyophilized powder with headspace filled with 60.7 mg of sulfur hexafluoride gas
• one prefilled syringe containing 5 mL Sodium Chloride 0.9% Injection, USP (Diluent)
• one Mini-Spike

Following reconstitution, Lumason is a homogeneous, milky white suspension containing1.5 to 5.6 x108 microspheres/mL with 45 mcg/mL of sulfur hexafluoride.

Lumason is contraindicated in patients with:

• history of hypersensitivity reactions to sulfur hexafluoride lipid microsphere components or to any of the inactive ingredients in Lumason

This drug should be used only if clearly needed. US FDA pregnancy category: B

Animal studies have failed to reveal evidence of fetal harm at doses up to 17 times the human dose based on body surface area. There are no controlled data in human pregnancy. US FDA pregnancy category B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.