Optison

Name: Optison

Pharmacology

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

Side effects

The following serious adverse reactions are described elsewhere in the labeling:

  • Serious Cardiopulmonary Reactions [see WARNINGS AND PRECAUTIONS]
  • Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Optison was administered in clinical studies in 279 patients. Of these patients there were 192 (68.8%) men and 87 (31.2%) women. The racial demographics were 199 (71.3%) Caucasian, 52 (18.6%) Black, 24 (8.6%) Hispanic, and 4 (1.4%) other racial or ethnic groups.

In these patients, 47 (16.8%) reported at least one adverse reaction. Of these one reaction was serious and required treatment with antihistamines for hypersensitivity manifestations of dizziness, nausea, flushing and temperature elevation. Deaths were not reported during the clinical studies.

Of the reported adverse reactions following the use of Optison the most frequently reported were headache (5.4%), nausea and/or vomiting (4.3%), warm sensation or flushing (3.6%), and dizziness (2.5%). The most common adverse reactions observed in clinical studies of Optison are given in Table 1.

Table 1 :├é┬áSELECTED ADVERSE REACTIONS REPORTED IN ≥ 0.5% OF THE SUBJECTS WHO RECEIVED OPTISON™ IN CONTROLLED CLINICAL STUDIES)

No. of Patients Exposed to Optison 279
No. of Patients Reporting on Adverse Reactions 47 (16.8%)
Body as a Whole 38 (13.6%)
Headache 15 (5.4%)
Warm Sensation/Flushing 10 (3.6%)
Chills/fever 4 (1.4%)
Flu-like Symptoms 3 (1.1%)
Malaise/Weakness/Fatigue 3 (1.1%)
Cardiovascular System 12 (4.3%)
Dizziness 7 (2.5%)
Chest Pain 3 (1.1%)
Digestive System 12 (4.3%)
Nausea and/or Vomiting 12 (4.3%)
Nervous System 3 (1.1%)
Respiratory System 5 (1.8%)
Dyspnea 3 (1.1%)
Skin & Appendages 11 (3.9%)
Injection Site Discomfort 3 (1.1%)
Erythema 2 (0.7%)
Special Senses 9 (3.2%)
Altered Taste 5 (1.8%)
(1) Patients are counted separately within each body system.
(2) The body system is reported if the aggregate is ≥ 0.5%. Details are not shown if the subsystem is not ≥ 0.5%.

Adverse reactions reported in < 0.5% of subjects who received Optison included: arthralgia, back pain, body or muscle aches, induration, urticaria, dry mouth, palpitations, paresthesia, photophobia, premature ventricular contraction, pruritus, rash, irritableness, hypersensitivity, tinnitus, tremor, visual blurring, wheezing, oxygen saturation decline due to coughing, discoloration at the injection site, and burning sensation in the eyes.

Postmarketing Experience

In a prospective, post-marketing safety surveillance study of Optison used in routine clinical practice, a total of 1039 subjects received Optison. Of these patients, 648 (62.4%) were male and 391 (37.6%) were female with average age of 59.9 years (min, max: 20, 97). The racial distributions were 864 (83.2%) White, 141 (13.6%) Black, 18 (1.7%) Asian, and 16 (1.5%) other racial or ethnic groups. Overall, 175 patients (16.8%) reported at least one adverse event. No serious adverse reactions, including deaths, were reported in this study.

The following adverse reactions have been identified during the postmarketing use of Optison. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiac arrests and other serious but non-fatal adverse reactions were uncommonly reported. Most of these reactions included cardiopulmonary symptoms and signs such as cardiac arrest, hypotension, supraventricular and ventricular arrhythmias, respiratory distress or decreased oxygenation. Reports also identified neurologic reactions (loss of consciousness or convulsions) as well as hypersensitivity reactions [see WARNINGS AND PRECAUTIONS].

How is Optison (perflutren)given?

Perflutren 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 perflutren. This is to make sure you do not have an allergic reaction to the medicine.

Precautions While Using Optison

It is very important that your doctor check your 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 have a chest pain, fast, slow, pounding, or irregular heartbeat, lightheadedness, dizziness, or fainting, or troubled breathing.

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

This medicine contains albumin, which is made from human blood. All donated blood is tested for certain viruses. Although your risk for getting a virus from the medicine is very low, talk with your doctor if you have concerns.

Optison Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

Less common
  • Chest pain
  • feeling of warmth
  • fever or chills
  • redness of the face, neck, arms, and occasionally, upper chest
  • trouble breathing
Rare
  • Hives or welts, itching, or skin rash
  • fast, irregular, pounding, or racing heartbeat or pulse
  • redness of the skin
Incidence not known
  • Blurred vision
  • chest discomfort
  • cold, clammy skin
  • confusion
  • convulsions
  • dizziness
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • fainting
  • fast, pounding, or irregular heartbeat or pulse
  • fast, weak pulse
  • feeling of warmth
  • headache
  • hoarseness
  • irritation
  • joint pain, stiffness, or swelling
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • lightheadedness, dizziness, or fainting
  • nervousness
  • no blood pressure or pulse
  • noisy breathing
  • pounding in the ears
  • redness of the face, neck, arms, and occasionally, upper chest
  • stopping of heart
  • sweating
  • tightness in the chest
  • troubled swallowing
  • unconsciousness
  • unusual tiredness or weakness

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common
  • Bad, unusual, or unpleasant (after) taste
  • change in taste
  • cough
  • discomfort at the injection site
  • nausea or vomiting
  • sore throat
  • stuffy or runny nose
Rare
  • Back pain
  • body or muscle aches
  • burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
  • change in color vision
  • continuing ringing or buzzing or other unexplained noise in the ears
  • difficulty with moving
  • difficulty seeing at night
  • discoloration of the skin at the injection site
  • dry mouth
  • hearing loss
  • increased sensitivity of the eyes to sunlight
  • muscle pain or stiffness

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

How do I store and/or throw out Optison?

  • If you need to store this medicine at home, talk with your doctor, nurse, or pharmacist about how to store it.

Optison Description

Optison™ (Perflutren Protein-Type A Microspheres Injectable Suspension, USP) is a sterile non-pyrogenic suspension of microspheres of human serum albumin with perflutren for contrast enhancement during the indicated ultrasound imaging procedures. 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 intravenous injection.

Perflutren is chemically characterized as 1,1,1,2,2,3,3,3-perflutren with a molecular weight of 188, an empirical formula of C3F8 and it has the following structural formula:

Each mL of Optison contains 5.0-8.0×108 protein-type A microspheres, 10 mg Albumin Human, USP, 0.22 ± 0.11 mg/mL perflutren, 0.2 mg N-acetyltryptophan, and 0.12 mg caprylic acid in 0.9% aqueous sodium chloride. The headspace of the vial is filled with perflutren gas. The pH is adjusted to 6.4-7.4. The protein in the microsphere shell makes up approximately 5-7% (w/w) of the total protein in the liquid. The microsphere particle size parameters are listed in Table 1.

Table 1 Microsphere Particle Size Parameters
Mean diameter (range) 3.0-4.5µm (max. 32.0µm)
Percent less than 10µm 95%

Warnings

Serious Cardiopulmonary Reactions

Serious cardiopulmonary reactions including fatalities have occurred uncommonly during or shortly following perflutren-containing microsphere administration, typically within 30 minutes of administration. The risk for these reactions may be increased among patients with unstable cardiopulmonary conditions (acute myocardial infarction, acute coronary artery syndromes, worsening or unstable congestive heart failure, or serious ventricular arrhythmias).

The reported reactions to perflutren-containing microspheres include: fatal cardiac or respiratory arrest, shock, syncope, symptomatic arrhythmias (atrial fibrillation, tachycardia, bradycardia, supraventricular tachycardia, ventricular fibrillation, ventricular tachycardia), hypertension, hypotension, dyspnea, hypoxia, chest pain, respiratory distress, stridor, wheezing, loss of consciousness, and convulsions (see ADVERSE REACTIONS).

Always have cardiopulmonary resuscitation personnel and equipment readily available prior to Optison administration and monitor all patients for acute reactions.

Anaphylactoid Reactions

In postmarketing use, uncommon but serious anaphylactoid reactions were observed during or shortly following perflutren-containing microsphere administration including:

Shock, hypersensitivity, 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 have occurred in patients with no prior exposure to perflutren-containing microsphere products (see ADVERSE REACTIONS).

Systemic Embolization of Optison in Patients with Cardiac Shunts

In patients with right-to-left, bi-directional, or transient right-to-left cardiac shunts perflutren-containing microspheres can bypass the pulmonary particle-filtering mechanisms and directly enter the arterial circulation resulting in microvascular occlusion and ischemia. Do not administer Optison by intra-arterial injection (see CONTRAINDICATIONS).

High Ultrasound Mechanical Index

High ultrasound mechanical index values may cause microsphere cavitation or rupture and lead to ventricular arrhythmias. Additionally, end-systolic triggering with high mechanical indices has been reported to cause ventricular arrhythmias. The safety of Optison at mechanical indices greater than 0.8 has not been evaluated. The safety of Optison with the use of end-systolic triggering has not been evaluated.

How is Optison Supplied

Optison (Perflutren Protein-Type A Microspheres Injectable Suspension, USP) is available in a carton of five 3 mL fills in single use 3 mL vials.

NDC 0407-2707-03

STORAGE

Store Optison refrigerated between 2°-8°C (36°-46°F).

Caution: Do not freeze.

Distributed by GE Healthcare Inc., Princeton, NJ 08540

Manufactured by Mallinckrodt Inc., St. Louis, MO 63042

Optison™ is a trademark of GE Healthcare.

GE and the GE Monogram are trademarks of General Electric Company.

ALBUNEX® is a trademark of Mallinckrodt Inc.

© 2012 General Electric Company - All rights reserved.

OPT-1F
Revised August 2012

Printed in USA

For Healthcare Professionals

Applies to perflutren: intravenous suspension

General

The most frequently reported adverse reactions were headache, nausea and/or vomiting, warm sensation or flushing, dizziness, and back pain.[Ref]

Cardiovascular

Common (1% to 10%): Chest pain
Uncommon (0.1% to 1%): Abnormal ECGs, bradycardia, tachycardia, palpitation, hypertension, hypotension
Postmarketing reports: Fatal cardiac arrest, shock, syncope, symptomatic arrhythmias (atrial fibrillation, tachycardia, bradycardia, supraventricular tachycardia, ventricular fibrillation/tachycardia), hypertension, hypotension[Ref]

Serious but uncommon cardiopulmonary reactions, including fatalities, have been reported during or following administration of this medication. Most serious reactions occurred within 30 minutes of administration.

QTc prolongation of greater than 30 milliseconds occurred in 29% (64/221) of patients evaluated. Of these patients 72% (46/64) were further evaluated and 39% (18/46) were found to have cardiac rhythm changes. (Definity(R))[Ref]

Dermatologic

Common (1% to 10%): Flushing
Uncommon (0.1% to 1%): Pruritus, rash, erythematous rash, urticaria, increased sweating, dry skin[Ref]

Gastrointestinal

Common (1% to 10%): Nausea
Uncommon (0.1% to 1%): Dyspepsia, dry mouth, tongue disorder, abdominal pain, diarrhea, vomiting[Ref]

Musculoskeletal

Common (1% to 10%): Back pain
Uncommon (0.1% to 1%): Arthralgia[Ref]

Nervous system

Common (1% to 10%): Headache
Uncommon (0.1% to 1%): Leg cramps, hypertonia, vertigo, paresthesia, dizziness, taste perversion
Postmarketing Reports: Coma, loss of consciousness, convulsion, seizure, transient ischemic attack, agitation, tremor, vision blurred, dizziness, headache, fatigue[Ref]

Renal

Common (1% to 10%): Renal pain[Ref]

Genitourinary

Uncommon (0.1% to 1%): Albuminuria[Ref]

Hematologic

Uncommon (0.1% to 1%): Granulocytosis, leukocytosis, leukopenia, eosinophilia, hematoma[Ref]

Local

Uncommon (0.1% to 1%): Injection site reaction[Ref]

Ocular

Uncommon (0.1% to 1%): Conjunctivitis, abnormal vision[Ref]

Other

Uncommon (0.1% to 1%): Decreased hearing[Ref]

Respiratory

Uncommon (0.1% to 1%): Coughing, hypoxia, pharyngitis, rhinitis, dyspnea
Postmarketing reports: Fatal respiratory arrest, dyspnea, hypoxia, respiratory distress, stridor, wheezing[Ref]

Hypersensitivity

Postmarketing reports of anaphylactic/anaphylactoid reactions have included: anaphylactic shock, hypersensitivity, 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.[Ref]

Postmarketing reports: Anaphylactic/anaphylactoid reactions[Ref]

Some side effects of Optison may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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