No information provided.
Do not administer Optison to patients with known or suspected hypersensitivity to perflutren, blood, blood products or albumin.
The following serious adverse reactions are described elsewhere in the labeling:
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 :Â SELECTED 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 ExperienceIn 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.
Optison is indicated for use in patients with suboptimal echocardiograms to opacify the left ventricle and to improve the delineation of the left ventricular endocardial borders.
The median duration of Optison contrast enhancement for each of the four doses of Optison, 0.2 (40% of recommended dose), 0.5, 3.0, and 5 mL , were approximately one, two, four, and five minutes, respectively.
After injection of Optison, diffusion of the perflutren gas out of the microspheres is limited by the low partition coefficient of the gas in blood that contributes to the persistence of the microspheres.
The pharmacokinetics of the intact microspheres of Optison in humans are unknown.
DistributionThe binding of perflutren to plasma proteins and its partitioning into blood cells are unknown. However, perflutren protein binding is expected to be minimal due to the low partition coefficient of the gas in blood.
EliminationFollowing intravenous injection, perflutren is cleared with a pulmonary elimination half-life of 1.3 ± 0.69 minutes (mean ± SD).
Metabolism
Perflutren is a stable gas that is not metabolized. The human albumin component of the microsphere is expected to be handled by the normal metabolic routes.
Excretion
Perflutren is eliminated through the lungs within 10 minutes. The mean ± SD recovery was 96% ± 23%. The perflutren concentration in expired air peaked approximately 30-40 seconds after administration.
Injectable suspension: 3 mL single-patient use vial containing a clear liquid lower layer and a white liquid upper layer, and a headspace filled with perflutren gas. Each mL of Optison contains 5-8x108 protein-type A microspheres, 10 mg albumin human, and 0.22 ± 0.11 mg perflutren. The sterile suspension is homogeneous, opaque, and milky-white after resuspension.
Optison is supplied as 3 mL single-patient use vials containing a clear liquid lower layer, a white liquid upper layer, and a headspace filled with perflutren gas and is homogeneous, opaque, and milky-white after resupsension. Each mL contains 5-8 x108 protein-type A microspheres, 10 mg albumin human, and 0.22 ± 0.11 mg perflutren:
Five (5) - 3 mL vials per carton NDC 0407-2707-03
Eighteen (18) - 3mL vials per carton NDC 0407-2707-18
Store OPTISON refrigerated between 2°-8°C (36°-46°F).
Caution: Do not freeze.
Distributed by GE Healthcare Inc., Marlborough, MA 01752 U.S.A. Manufactured by GE Healthcare AS, Oslo, Norway. Revised: Sep 2016
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 ReactionsIn 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 ShuntsIn 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 IndexHigh 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.
PRECAUTIONS GeneralThis product contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral disease. A theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) also is considered extremely remote. No cases of transmission of viral disease or CJD have ever been identified for albumin.
Laboratory TestsImmunologic tests of serum immunoglobulins, cytokines, and complement were monitored in a 3 week study of 20 healthy volunteers and 30 patients who received OPTISON or a 1% albumin control. Clinically relevant changes in the measured parameters were not noted. In another study 5 subjects received a skin test with OPTISON one year after receiving OPTISON. One subject had a positive skin test and was not given a repeat dose of OPTISON.
Carcinogenesis, Mutagenesis, and Impairment of FertilityAnimal studies were not carried out to determine the carcinogenic potential of OPTISON.
The result of the following genotoxicity studies with OPTISON were negative: 1) Salmonella/Escherichia coli reverse mutation assay, 2) in vitro mammalian chromosome aberration assay using Chinese hamster ovary cells (CHO) with and without metabolic activation, 3) CHO/HGPRT forward mutation assay, and 4) in vivo mammalian micronucleus assay.
Pregnancy Category COPTISON administered intravenously to rats during organogenesis at doses of 0.25, 5.0 and 10.0 mL/kg/day was fetotoxic at 0.25 and 5.0 mL/kg (approximately 0.2 and 5 times the recommended maximum human dose, respectively, based on body surface area). Fetotoxicity was characterized by an increased incidence of reversible delayed pelvic ossification, the incidence of which was not related to dose. Signs of maternal toxicity at 5 mL/kg included respiratory and motor signs. Maternal death occurred at 10 mL/kg. A no observable adverse effect level (NOAEL) for fetotoxicity was not determined. Teratogenic effects were not observed at doses up to 10 mL/kg/day. The NOAEL for maternal toxicity was 0.25 mL/kg.
OPTISON administered intravenously to rabbits during organogenesis at doses of 0.25, 2.5 and 5.0 mL/kg/day was embryofetal toxic at 2.5 and 5.0 mL/kg (approximately 5 and 10 times the recommended maximum human dose, respectively, based on body surface area). Embryofetal toxicity was characterized by a decrease in fetal body weight and an increase in embryofetal death. Teratogenic effects (cleft palates and dilation of the lateral ventricles of the brain associated with skull abnormalities and compression deformities) were observed at 2.5 mL/kg but not 5 mL/kg. Neither the incidence nor the severity of embryofetal toxicity and teratogenicity exhibited a dose-dependent relationship. Maternal toxicity (significant suppression of body weight gain, abnormal stool) was observed at 2.5 and 5.0 mL/kg with the greatest effect observed at 2.5 mL/kg. The NOAEL for embryofetal and maternal toxicity was 0.25 mL/kg (approximately 0.5 times the recommended maximum human dose).
Adequate or well-controlled studies were not conducted in pregnant women. OPTISON should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing MothersIt is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk caution should be exercised when OPTISON is administered to a nursing woman.
Pediatric UseSafety and efficacy have not been established in pediatric patients, or in patients with congenital heart disease (see WARNINGS).
The following serious adverse reactions are described elsewhere in the labeling:
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 :Â SELECTED 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 ExperienceIn 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.
DRUG INTERACTIONSNo information provided.
