DEFINITY

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DEFINITY (DEFINITY).

How it works

Definity (perflutren) is an ultrasound contrast agent composed of lipid-coated microspheres filled with perfluoropropane gas. It enhances ultrasound signal by increasing backscatter from blood, improving visualization of cardiac chambers and blood flow.

What the body does with it

Metabolism	Perflutren gas is eliminated unchanged via exhalation through the lungs. The lipid microspheres are metabolized in the liver via phospholipid metabolism.
Excretion	Eliminated primarily via exhalation (perfluoropropane gas) and renal excretion (shell components). Approximately <1% of the administered dose is excreted unchanged in urine over 24 hours; the lipid shell components are metabolized via endogenous pathways with biliary/fecal elimination.
Half-life	The terminal half-life of the perfluoropropane gas is approximately 1.3 minutes (rapid clearance from the blood pool via exhalation). The lipid components have a half-life of approximately 6 hours.
Protein binding	Negligible; perfluoropropane gas does not bind to plasma proteins. Lipid shell components may bind to albumin and lipoproteins to a moderate extent (binding data not quantified).
Volume of Distribution	Mean apparent volume of distribution for perfluoropropane is approximately 0.1 L/kg (confined primarily to the vascular space due to size limitations).
Bioavailability	Not applicable (administered intravenously only); bioavailability is 100% via IV route.
Onset of Action	Intravenous bolus: Immediate echocardiographic contrast enhancement (visible within 30-60 seconds after injection).
Duration of Action	Echocardiographic contrast enhancement lasts approximately 5-10 minutes after bolus injection, with peak intensity at 3-5 minutes. Enhancement decreases progressively as gas bubbles dissipate.

Classification & Brands

Dosing & administration

0.5 mL as a bolus intravenous injection, followed by a 10 mL saline flush. A second dose of 0.5 mL may be administered if clinically necessary. Alternatively, a 1.3 mL infusion diluted in 50 mL saline administered at 4 mL/min intravenously.

Dosage form	INJECTABLE
Renal impairment	No dose adjustment required for renal impairment; no clinical studies have been conducted in patients with renal failure.
Liver impairment	No dose adjustment required for hepatic impairment; no clinical studies have been conducted in patients with hepatic impairment.
Pediatric use	Safety and efficacy in pediatric patients have not been established; no recommended dose.
Geriatric use	No specific dose adjustment recommended for elderly patients; clinical studies did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for DEFINITY (DEFINITY).

Breastfeeding	No data on excretion in human milk; M/P ratio unknown. Caution advised due to potential for gastrointestinal disturbance or allergic reaction in infant.
Teratogenic Risk	Definity (perflutren lipid microspheres) is pregnancy category B. No evidence of fetal harm in animal studies; no adequate human studies in pregnant women. Use only if clearly needed.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Serious cardiopulmonary reactions, including fatalities, have occurred during or within 30 minutes after administration. Risk is higher in patients with unstable cardiopulmonary conditions. Resuscitation equipment and trained personnel must be readily available.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Intra-arterial injection.","Known or suspected right-to-left, bidirectional, or transient right-to-left cardiac shunts.","Hypersensitivity to perflutren or any component of Definity."]

Clinical Precautions

Precautions

["Risk of serious cardiopulmonary reactions, including fatal cardiac arrest, in patients with unstable cardiopulmonary conditions (e.g., acute myocardial infarction, unstable angina, worsening heart failure, significant arrhythmias).","Monitor vital signs and ECG during and for at least 30 minutes after administration.","Do not administer intra-arterially because of risk of end-organ damage.","Use with caution in patients with pulmonary hypertension (pulmonary artery pressure >50 mmHg) or right-to-left, bidirectional, or transient right-to-left cardiac shunts."]

Clinical Tips & Counseling

Drug interactions

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DEFINITY

Clinical safety rating: caution

Comprehensive clinical and safety monograph for DEFINITY (DEFINITY).

How it works

What the body does with it

Metabolism	Perflutren gas is eliminated unchanged via exhalation through the lungs. The lipid microspheres are metabolized in the liver via phospholipid metabolism.
Excretion	Eliminated primarily via exhalation (perfluoropropane gas) and renal excretion (shell components). Approximately <1% of the administered dose is excreted unchanged in urine over 24 hours; the lipid shell components are metabolized via endogenous pathways with biliary/fecal elimination.
Half-life	The terminal half-life of the perfluoropropane gas is approximately 1.3 minutes (rapid clearance from the blood pool via exhalation). The lipid components have a half-life of approximately 6 hours.
Protein binding	Negligible; perfluoropropane gas does not bind to plasma proteins. Lipid shell components may bind to albumin and lipoproteins to a moderate extent (binding data not quantified).
Volume of Distribution	Mean apparent volume of distribution for perfluoropropane is approximately 0.1 L/kg (confined primarily to the vascular space due to size limitations).
Bioavailability	Not applicable (administered intravenously only); bioavailability is 100% via IV route.
Onset of Action	Intravenous bolus: Immediate echocardiographic contrast enhancement (visible within 30-60 seconds after injection).
Duration of Action	Echocardiographic contrast enhancement lasts approximately 5-10 minutes after bolus injection, with peak intensity at 3-5 minutes. Enhancement decreases progressively as gas bubbles dissipate.

Classification & Brands

Dosing & administration

Dosage form	INJECTABLE
Renal impairment	No dose adjustment required for renal impairment; no clinical studies have been conducted in patients with renal failure.
Liver impairment	No dose adjustment required for hepatic impairment; no clinical studies have been conducted in patients with hepatic impairment.
Pediatric use	Safety and efficacy in pediatric patients have not been established; no recommended dose.
Geriatric use	No specific dose adjustment recommended for elderly patients; clinical studies did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for DEFINITY (DEFINITY).

Breastfeeding	No data on excretion in human milk; M/P ratio unknown. Caution advised due to potential for gastrointestinal disturbance or allergic reaction in infant.
Teratogenic Risk	Definity (perflutren lipid microspheres) is pregnancy category B. No evidence of fetal harm in animal studies; no adequate human studies in pregnant women. Use only if clearly needed.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

["Intra-arterial injection.","Known or suspected right-to-left, bidirectional, or transient right-to-left cardiac shunts.","Hypersensitivity to perflutren or any component of Definity."]