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Perflutren Lipid Microspheres


(per FLOO tren LIPid MI kro SFIRS)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, solution [preservative free]: OFP 6.52 mg/mL and lipid blend 0.75 mg/mL (2 mL) [following activation, forms a suspension containing perflutren lipid microspheres 1.2 x 1010/mL and OFP 1.1 mg/mL]

Brand Names: U.S.

  • Definity

Pharmacologic Category

  • Diagnostic Agent


Activated perflutren lipid microspheres provide contrast enhancement of the endocardial borders during echocardiography.


Octafluoropropane gas (OFP): Not metabolized; Phospholipid component: Metabolized to free fatty acids

Onset of Action


Duration of Action

IV bolus: 3.4 minutes; IV infusion: 7.1 minutes

Half-Life Elimination

OFP: 1.3 minutes (healthy patients); 1.9 minutes (patients with COPD)

Use: Labeled Indications

Cardiovascular imaging: Opacification of the left ventricular chamber and improvement of delineation of the left ventricular endocardial border in patients with suboptimal echocardiograms


Hypersensitivity to perflutren or to any component of the formulation.

Dosing: Adult

Cardiovascular imaging: Dose should be given following baseline noncontrast echocardiography. Imaging should begin immediately following dose and compared to noncontrast image. Mechanical index for the ultrasound device should be set at ≤0.8.

IV bolus: 10 microliters (mcL)/kg of activated product, followed by 10 mL saline flush; may repeat in 30 minutes (followed by 10 mL saline flush) if needed (maximum dose per imaging study: 2 bolus doses)

IV infusion: Initial: 4 mL/minute (or 240 mL/hour) of prepared infusion; titrate to achieve optimal image (maximum dose per imaging study: 1 IV infusion)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).


Prior to administration, product must be activated. To activate, first bring vial to room temperature. Vial should then be shaken for 45 seconds using the Vialmix apparatus (which should be obtained from the manufacturer). Do not use if the 45 second activation cycle has not been completed. Following activation, the product will appear as a milky white suspension and may be used immediately. Activated product must be used within 12 hours. If not used within 5 minutes of activation, resuspend by inverting the vial and using hand agitation for 10 seconds. To withdraw product, invert vial and aseptically position needle (18 or 20 gauge) or dispensing pin (Intellipin) in center of liquid; do not inject air. Once withdrawn from vial into a syringe, use immediately by administering as an undiluted bolus, a diluted bolus, or as an IV infusion. Do not allow product to stand in syringe. Product does not contain bacterial preservative. Vial is for single use only.

Bolus (undiluted): Withdraw activated product into a 3 or 5 mL syringe.

Bolus (diluted): Withdraw 8.7 mL of preservative free saline into a 10 mL syringe; then, using the same syringe, slowly withdraw 1.3 mL of activated product into the syringe. Gently hand agitate syringe to evenly distribute microspheres prior to injection. Some have also prepared diluted bolus using 1.5 mL of activated product and 8.5 mL of preservative free saline (Kusnetzky 2008).

IV infusion: Withdraw 1.3 mL activated product into a 3 or 5 mL syringe; then add to 50 mL preservative free saline. Gently squeeze IV bag to evenly distribute microspheres prior to administration.


IV bolus (undiluted): Administer only after activation in the Vialmix apparatus. Administer within 30 to 60 seconds, follow with 10 mL saline flush; a second dose may be administered 30 minutes after the first dose (followed by 10 mL saline flush) to prolong contrast enhancement.

IV bolus (diluted): Administer only after activation in the Vialmix apparatus. Administer slowly up to 3 mL of solution; subsequent boluses of 1 to 2 mL may be used as needed.

IV infusion rate: Initially, 4 mL/minute (or 240 mL/hour) up to 10 mL/minute (or 600 mL/hour); adjust flow rate for optimal image enhancement.


Prior to activation, store under refrigeration, 2°C to 8°C (36°F to 46°F). Following activation, store at room temperature in original vial.

Drug Interactions

Highest Risk QTc-Prolonging Agents: Moderate Risk QTc-Prolonging Agents may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination

Hydroxychloroquine: May enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Avoid combination

Ivabradine: May enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Avoid combination

MiFEPRIStone: May enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Avoid combination

Moderate Risk QTc-Prolonging Agents: May enhance the QTc-prolonging effect of other Moderate Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

Probucol: May enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Avoid combination

Promazine: May enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Avoid combination

QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying): May enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy

Vinflunine: May enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Avoid combination

Adverse Reactions

>10%: Cardiovascular: Prolonged Q-T interval on ECG (29%; >30 msec)

1% to 10%:

Cardiovascular: Flushing (1%)

Central nervous system: Headache (2%)

Gastrointestinal: Nausea (1%)

Neuromuscular & skeletal: Back pain (1%)

Renal: Renal pain (1%)

<1% (Limited to important or life-threatening): Abdominal pain, agitation, albuminuria, anaphylactoid reaction, anaphylactic shock, angioedema, arthralgia, atrial fibrillation, auditory impairment, bradycardia, bronchospasm, chest pain, coma, conjunctivitis, cough, diarrhea, dizziness, diaphoresis, dysgeusia, dyspnea, dyspepsia, ECG abnormality, edema (localized edema, mouth edema, palatal edema, peripheral edema, pharyngeal edema), eosinophilia, erythema, fatigue, fever, granulocytosis, hematoma, hot flash, hypertension, hypersensitivity reaction, hypertonia, hypotension, hypoxemia, hypoxia, injection site reaction, leg cramps, leukocytosis, leukopenia, loss of consciousness, pain, palpitations, paresthesia, pharyngitis, pruritus, respiratory distress, rhinitis, rigors, seizure, shock, skin rash (including erythematous rash), stridor, supraventricular tachycardia, swelling (facial swelling, swelling of eye, swelling of lips, swollen tongue, upper airway swelling), syncope, tachycardia, transient ischemic attacks, tremor, urticaria, ventricular fibrillation, ventricular tachycardia, vertigo, visual disturbance, vomiting, xerostomia

ALERT: U.S. Boxed Warning

Serious cardiopulmonary reactions:

Serious cardiopulmonary reactions, including fatalities, have occurred uncommonly during or following perflutren-containing microsphere administration. Most serious reactions occur within 30 minutes of administration. Assess all patients for the presence of any condition that precludes perflutren administration. Always have resuscitation equipment and trained personnel readily available.


Concerns related to adverse effects:

• Anaphylactoid reactions: Postmarketing reports of anaphylactoid reactions (eg, shock, hypersensitivity, bronchospasm, throat tightness, angioedema, edema [oropharyngeal, palatal, peripheral, and localized], swelling [face, eye, lip, tongue, upper airway], facial hypoesthesia, rash, urticaria, pruritus, flushing, and erythema) have been reported in patients with no prior exposure. Monitor for signs and symptoms of anaphylactoid reactions.

• Serious cardiopulmonary reactions: [US Boxed Warning]: Serious cardiopulmonary reactions (including fatalities) have occurred during or following administration; most serious reactions occur within 30 minutes. Ensure patient does not have any contraindications for use. Equipment for resuscitation and trained personnel experienced in handling medical emergencies should always be immediately available. Risk may be increased in patients with unstable cardiopulmonary conditions (eg, acute MI, acute coronary artery syndromes, worsening or unstable HF, serious ventricular arrhythmias).

• Ventricular arrhythmias: High ultrasound mechanical indices with or without end-systolic triggering may cause microsphere cavitation or rupture and lead to ventricular arrhythmias. Safety of activated perflutren lipid microspheres with mechanical indices >0.8 or use of end-systolic triggering has not been established.

Disease-related concerns:

• Cardiac shunts: Assess patients with cardiac shunts for embolic phenomena following administration; perflutren lipid microspheres can bypass filtering by the lung and enter the arterial circulation.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Appropriate use: Product must be activated prior to use. For IV administration only; do not administer by intra-arterial injection.

Monitoring Parameters

Cardiopulmonary reactions; cardiac rhythm monitoring; signs and symptoms of anaphylactoid reactions; heart rate, respiratory rate, and pulse oximetry (during and for 30 minutes following infusion)

Pregnancy Risk Factor


Pregnancy Considerations

Adverse events were not observed in animal reproduction studies.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Have patient report immediately to prescriber angina, arrhythmia, shortness of breath, tachycardia, bradycardia, severe dizziness, severe headache, wheezing, seizures, burning or numbness feeling, flushing, or passing out (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating, and advising patients.