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Perflutren Lipid Microspheres

Generic name: perflutren systemic

Brand names: Definity, Optison, Definity RT

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.

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]


Mechanism of Action

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

Use: Off Label

Focal liver lesion evaluationbyes

Data from several observational studies support the use of perflutren lipid microspheres in the evaluation of focal liver lesions Brannigan 2004, Jang 2009, Wilson 2007, Won 2014. Additional trials may be necessary to further define the role of perflutren lipid microspheres in this setting.

The World Federation for Ultrasound in Medicine and Biology guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) in the liver provides general advice on the use of ultrasound contrast agents (eg, perflutren lipid microspheres) when evaluating focal liver lesions.


Hypersensitivity to perflutren or to any component of the formulation.

Dosage and Administration

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)

Focal liver lesion evaluation (off-label use): IV bolus: 0.1 to 0.6 mL per injection followed by a 5 mL saline flush; may be repeated at a minimum of every 5 minutes (ie, when most microbubbles have vanished) up to a maximum total dose of 10 microliters (mcL)/kg (Brannigan 2004; Jang 2009; WFUMB-EFSUMB [Claudon 2013]; Wilson 2007; Won 2014)

Dosing: Geriatric

Refer to adult dosing.


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):

Cardiovascular imaging: Administer only after activation in the Vialmix apparatus. Administer within 30 to 60 seconds of activation; follow each injection with a 10 mL saline flush.

Focal liver lesion evaluation (off-label use): Administer only after activation in the Vialmix apparatus. Follow each injection with a 5 mL saline flush (Brannigan 2004; Jang 2009).

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

There are no known significant interactions.

Adverse Reactions

1% to 10%:

Cardiovascular: Flushing (1%)

Central nervous system: Headache (2%)

Gastrointestinal: Nausea (1%)

Neuromuscular & skeletal: Back pain (1%)

Renal: Renal pain (1%)

<1%, postmarketing, and/or case reports: 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


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 of administration. Assess all patients for the presence of any condition that precludes administration. 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). However, multiple retrospective and prospective studies involving the use of perflutren-based ultrasound contrast agents have suggested they may be safely used in patients with significant cardiopulmonary disease (ie, acute coronary syndromes, heart failure, COPD, pulmonary hypertension) or critical illness (Dolan 2009; Kurt 2009; Kusnetzky 2008; Main 2008; Main 2014; Nucifora 2008; Wei 2008; Wei 2012; Weiss 2012; Wever-Pinzon 2012).
  • 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. Patients with small degrees of right-to-left shunting through patent foramen ovales (those that result in transient appearance of saline contrast in the left atrium or ventricle and do not fill the left atrial or LV cavity) are not considered at an increased risk for microvascular occlusion with perflutren-based ultrasound contrast agents (ASE [Porter 2014]); Kalra 2014; Muskula 2017; Parker 2013).

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 (rare); signs and symptoms of anaphylactoid reactions (rare). Monitor patient as appropriate based upon patient clinical disposition; specific monitoring parameters based upon perflutren lipid microspheres administration are not necessary (Muskula 2017).


Pregnancy Considerations

Due to the very short half-life, administration during pregnancy is not expected to result in clinically relevant fetal exposure.

Patient Education

What is this drug used for?

  • It is used before a heart imaging test.

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

  • Chest pain
  • Abnormal heartbeat
  • Shortness of breath
  • Fast heartbeat
  • Slow heartbeat
  • Severe dizziness
  • Severe headache
  • Seizures
  • Burning or numbness feeling
  • Flushing
  • Vision changes
  • Passing out
  • Signs of a significant reaction like 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. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Source: Wolters Kluwer Health. Last updated January 29, 2020.