perflutren (Rx)

>10%

QTc prolongation

1-10%

Headache (2.3-5.4%)

Nausea/vomiting (1-4.3%)

Flushing/warn sensation (1.1-3.6%)

Dizziness (0.62.5%)

Altered taste (1.8%)

Chills/fever (1.4%)

Back/renal pain (1.2%)

Chest pain (0.8-1.1%)

Dyspnea (1.1%)

Flu-like symptoms (1.1%)

Malaise/weakness/fatigue (1.1%)

Injection site discomfort (0.6-1.1%)

<1%

Erythema (0.7%)

Postmarketing Reports

Fatal cardiac arrests and other serious but nonfatal adverse reactions were uncommonly reported

Most of these uncommon reactions included serious cardiopulmonary reactions and signs (eg, cardiac or respiratory arrest, hypotension, supraventricular and ventricular arrhythmias, respiratory distress or decreased oxygenation)

Neurologic reactions: loss of consciousness or convulsions

Hypersensitivity reactions

Acute pain episodes including vaso-occlusive crisis in patients with sickle cell disease

Contraindications

Hypersensitivity to perflutren to lipid microsphere or components; Optison brand also warns for hypersensitivity to blood, blood products, or albumin

Cautions

For IV use only; do not administer by intra-arterial injection

Chronic pulmonary vascular disorder

Serious cardiopulmonary reactions, including fatalities, have occurred uncommonly during or shortly following administration (see Black Box Warnings)

In patients with cardiac shunts, perflutren-containing microspheres can bypass the pulmonary particle-filtering mechanisms and directly enter the arterial circulation resulting in microvascular embolization that may cause occlusion and ischemia; assess patients with shunts for embolic phenomena following administration

QT prolongation reported

Therapy not recommended for use at mechanical indices > 0.8

Assess patients for presence of conditions that preclude therapy administration; always have cardiopulmonary resuscitation personnel and equipment readily available prior to administration and monitor all patients for acute reactions

Pain episodes in sickle cell disease

• Acute pain episodes shortly following therapy administration reported in patients with sickle cell disease (SCD); pain episodes included moderate to severe back pain and vaso-occlusive crisis; if patient with sickle cell disease experiences new or worsening pain, discontinue therapy

Hypersensitivity reactions

• Anaphylaxis, with manifestations that may include death, shock, bronchospasm, throat tightness, angioedema, edema (pharyngeal, palatal, mouth, peripheral, localized), swelling (face, eye, lip, tongue, upper airway), facial hypoesthesia, rash, urticaria, pruritus, flushing, and erythema; these reactions have occurred in patients with no prior exposure to perflutren-containing microsphere products
• Product contains PEG; there may be increased risk of serious reactions including death in patients with prior hypersensitivity reaction(s) to PEG
• Clinically assess patients for prior hypersensitivity reactions to products containing PEG, such as certain colonoscopy bowel preparations and laxatives
• Always have cardiopulmonary resuscitation personnel and equipment readily available prior to product administration and monitor all patients for hypersensitivity reactions

Pregnancy

Available data from case reports with use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

This drug has a very short half-life; therefore, administration to a pregnant woman is not expected to result in clinically relevant fetal exposure

Animal data

• No adverse developmental outcomes observed in animal reproduction studies with administration in pregnant rats and rabbits during organogenesis at doses up to 8 and 16 times, respectively, maximum human dose based on body surface area

Lactation

There are no data on presence in human milk, effects on breastfed infant, or effects on milk production; developmental and health benefits of breastfeeding should be considered along with mother's clinical need for therapy and any potential adverse effects on breastfed infant from treatment or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Definity: Suspension of microspheres of human serum albumin with perflutren for contrast enhancement of the endocardial borders during echocardiography

Optison: A stable gas that creates an echogenic contrast effect in the blood and allows improved delineation of the left ventricular endocardial border

IV Preparation

Definity RT, Definity

• Definitiy RT: Warm vial to room temperature before activation process
• Activate by shaking vial 45 sec using a Vialmix
• May use immediately after activation; if not used within 5 min, resuspend by 10 sec hand agitation (inversion)
• May use for up to 12 hr after Vialmix activation, but only after resuspension
• Invert the vial and withdraw the activated milky white suspension using the Intellipin (Dispensing Pin) or 18- or 20-gauge syringe needle
• Withdraw the material from the middle of the liquid in the inverted vial
• Do not inject air into the vial
• Use immediately after withdrawal into syringe; do not let stand in syringe

Optison

• The vial contains a clear liquid lower layer and a white upper layer that, after resuspension by gentle mixing, provides a homogeneous, opaque, milky-white suspension for IV injection
• Do not use the product if the upper white layer is absent; this indicates that the microspheres may have been damaged and may result in poor or no echo contrast
• Invert the vial and gently rotate to resuspend the microspheres; this process will allow the product to come to room temperature before use
• Inspect the vial for complete resuspension; failure to adequately resuspend product may cause an under delivery of the microspheres, and may result in inadequate contrast
• Do not use product if after resuspension the solution appears to be clear rather than opaque milky-white
• Vent the vial with a sterile vent spike or with a sterile 18-gauge needle before withdrawing the suspension into the injection syringe
• Do not inject air into the vial
• Invert syringe to resuspend
• Inject within 1 min; if 1 min is exceeded invert syringe to remix

Storage

Definity RT

• Unopened vials: Store at room temperature of 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)

Definity, Optison

• Unopened vials: Store refrigerated at 2-8ºC (36-46ºF)
• Do not freeze