Human Albumin Microspheres And Perflutren
FDA Drug Information • Also known as: Optison Perflutren Protein-Type A Microspheres
- Brand Names
- Optison Perflutren Protein-Type A Microspheres
- Drug Class
- Contrast Agent for Ultrasound Imaging [EPC]
- Route
- INTRAVENOUS
- Dosage Form
- INJECTION, SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
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 [see Warnings and Precautions (5.1) ]. Assess all patients for the presence of any condition that precludes OPTISON administration [see Contraindications (4) ]. Always have resuscitation equipment and trained personnel readily available [see Warnings and Precautions (5.1) ] . WARNING: SERIOUS CARDIOPULMONARY REACTIONS See full prescribing information for complete boxed warning. Serious cardiopulmonary reactions, including fatalities, have occurred uncommonly during or following perflutren-containing microsphere administration. Most serious reactions occur within 30 minutes of administration ( 5.1 ). Assess all patients for the presence of any condition that precludes OPTISON administration ( 4 ). Always have resuscitation equipment and trained personnel readily available ( 5.1 ).
Description
11 DESCRIPTION OPTISON (perflutren protein-type A microspheres) injectable suspension is an ultrasound contrast agent for intravenous use. Perflutren is chemically characterized as 1,1,1,2,2,3,3,3-perflutren with a molecular weight of 188, an empirical formula of C 3 F 8 , and the following structural formula: Each mL contains 5-8×10 8 protein-type A microspheres, 10 mg albumin human, 0.22 ± 0.11 mg perflutren, and the following inactive ingredients: 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 to 7.4. The protein in the microsphere shell makes up approximately 5% to 7% (w/w) of the total protein in the suspension. The microsphere particle size parameters are listed in Table 3. OPTISON is supplied as a clear liquid lower layer, a white liquid upper layer, and a headspace filled with perflutren gas, and after resuspension, OPTISION is a sterile, homogeneous, opaque, and milky-white suspension. Table 3. Microsphere Size Distribution Parameter Mean diameter (range) 3 to 4.5 µm Percent less than 10 µm 95% Maximum diameter 32 µm Chemical Structure
What Is Human Albumin Microspheres And Perflutren Used For?
1 INDICATIONS AND USAGE OPTISON is indicated for use in adult and pediatric patients with suboptimal echocardiograms to opacify the left ventricle and to improve the delineation of the left ventricular endocardial borders. OPTISON is an ultrasound contrast agent indicated for use in adult and pediatric patients with suboptimal echocardiograms to opacify the left ventricle and to improve the delineation of the left ventricular endocardial borders ( 1 ).
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Adults 0.5 mL intravenously at a rate not exceeding 1 mL/s. If contrast enhancement is inadequate after the dose of 0.5 mL, additional doses of 0.5 mL may be repeated up to a total of 5 mL in a 10-minute period with a maximum total dose of 8.7 mL in any one patient study ( 2.1 ). Pediatric Patients 28 kg or less: 0.2 mL diluted with 0.2 mL of 0.9% Sodium Chloride Injection. 29 kg to 40 kg: 0.3 mL diluted with 0.3 mL of 0.9% Sodium Chloride Injection. 41 kg or more: 0.4 mL diluted with 0.4 mL of 0.9% Sodium Chloride Injection. Administer intravenously at a rate not exceeding 0.05 mL/s. If contrast enhancement is inadequate after the initial dose, up to four additional doses of the same diluted volume may be repeated for further contrast enhancement as needed ( 2.1 ). Follow the OPTISON injection with a flush of 0.9% Sodium Chloride Injection or 5% Dextrose Injection ( 2.3 ). See full prescribing information for preparation instructions ( 2.2 ). 2.1 Recommended Dosage Adults The recommended dose in adults is 0.5 mL administered intravenously at a rate not exceeding 1 mL/s [see Dosage and Administration (2.3) ] . If the contrast enhancement is inadequate after the dose of 0.5 mL, additional doses of 0.5 mL may be repeated for further contrast enhancement as needed. The maximum total dose is 5 mL in any 10-minute period. The maximum total dose is 8.7 mL in any one patient study. Pediatric Patients The recommended dose by body weight in pediatric patients is shown in Table 1. Administer by intravenous injection at a rate not exceeding 0.05 mL/s [see Dosage and Administration (2.3) ] . If the contrast enhancement is inadequate after the initial dose, up to four additional doses of the same diluted volume may be repeated for further contrast enhancement as needed. OPTISON must be diluted with 0.9% Sodium Chloride Injection to form a 1:1 dilution for pediatric administration [see Dosage and Administration (2.2) ]. Table 1. Recommended Dose of OPTISON by Body Weight in Pediatric Patients Body Weight Dose 28 kg or less 0.2 mL of OPTISON diluted with 0.2 mL of 0.9% Sodium Chloride Injection 29 kg to 40 kg 0.3 mL of OPTISON diluted with 0.3 mL of 0.9% Sodium Chloride Injection 41 kg or more 0.4 mL of OPTISON diluted with 0.4 mL of 0.9% Sodium Chloride Injection 2.2 Preparation Instructions General Visually inspect the OPTISON vial. Do not use if the container has been damaged, the protective seal and/or rubber cap have been entered, or the upper white layer is absent (may indicate the microspheres have been damaged and may result in poor or no echo contrast). Invert the vial and gently rotate to resuspend the microspheres. This process will allow the product to come to room temperature (20°C to 25°C or 68°F to 77°F) before use. Inspect the vial for complete resuspension. Do not use if the suspension appears to be clear rather than opaque and milky-white. Vent the OPTISON vial with a sterile vent spike or with a sterile 18-gauge...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Serious Cardiopulmonary Reactions [see Warnings and Precautions (5.1) ] Hypersensitivity Reactions [see Warnings and Precautions (5.2) ] Common adverse reactions (incidence ≥ 0.5%) were: headache, nausea and/or vomiting, warm sensation or flushing, dizziness, dysgeusia, chills or fever, flu-like symptoms, malaise/weakness/fatigue, chest pain, dyspnea, injection site discomfort, and erythema ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact GE HealthCare at 1-800-654-0118 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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. Adverse Reactions in Adults The safety of OPTISON was evaluated in 279 adult patients in clinical studies. These patients were 69% male, 31% female, 71% White, 19% Black or African American, 9% Hispanic or Latino, and 1% other racial or ethnic groups. Adverse reactions reported in ≥ 0.5% of patients who received OPTISON by intravenous injection are given in Table 2. Table 2. Adverse Reactions Reported in ≥ 0.5% of the Adult Patients who Received OPTISON in Controlled Clinical Studies Adverse Reaction OPTISON n=279 % Body as a Whole Headache 5.4 Warm Sensation/Flushing 3.6 Chills/fever 1.4 Flu-like Symptoms 1.1 Malaise/Weakness/Fatigue 1.1 Cardiovascular System Dizziness 2.5 Chest Pain 1.1 Digestive System Nausea and/or Vomiting 4.3 Respiratory System Dyspnea 1.1 Skin & Appendages Injection Site Discomfort 1.1 Erythema 0.7 Special Senses Dysgeusia 1.8 Adverse reactions reported in < 0.5% of patients who received OPTISON included: Body as a Whole: induration, discoloration at the injection site Cardiovascular system : premature ventricular contractions, palpitations Digestive system : dry mouth Immune system disorders : hypersensitivity Musculoskeletal and connective tissue disorders : back pain, arthralgia, body or muscle aches Nervous system : tremor, paresthesia, irritableness Respiratory system : oxygen saturation decline due to coughing, wheezing Skin and appendages : urticaria, rash, pruritus Special Senses : tinnitus, visual blurring, photophobia, burning sensation in the eyes Adverse Reactions in Pediatric Patients Overall, the safety profile observed in pediatric patients from the clinical study was consistent with the safety profile in adult patients [see Clinical Studies (14.2) ]. 6.2 Postmarketing Experience Adverse Reactions from Observational Studies In a prospective, post-marketing safety surveillance study of OPTISON used in routine clinical practice, a total of 1,039 patients received OPTISON. These patients had an average age of 59.9 years (min, max: 20, 97) and were 62% male, 38% female, 83% White, 14% Black or African American, 2% Asian, and 1.5% other racial or ethnic groups. Overall, 17% of patients reported at least one adverse event. No deaths or serious adverse reactions were reported in this study. Adverse Reactions from Postmarking Spontaneous Reports The following adverse reactions have been identified during the postmarketing use of OPTISON or other perflutren-containing microspheres. 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. Cardiopulmonary 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 or decreased oxygenation, stridor, wheezing. Immune System Anaphylaxis with manifestations that may include...
Contraindications
4 CONTRAINDICATIONS OPTISON is contraindicated in patients with known or suspected hypersensitivity to perflutren or albumin [see Warnings and Precautions (5.2) ] . Known or suspected hypersensitivity to perflutren or albumin ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary There are no data with OPTISON use in pregnant women to inform any drug-associated risks. No adverse developmental outcomes were observed in animal reproduction studies with intravenous administration of OPTISON to pregnant rats and rabbits during organogenesis at doses up to at least 5 and 10 times the recommended human dose based on body surface area ( see Data ). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data OPTISON was administered intravenously to rats at doses of 0.25, 5 and 10 mL/kg/day (approximately 0.2, 5, and 10 times the recommended maximum human dose of 8.7 mL, respectively, based on body surface area) and to rabbits at 0.25, 2.5, and 5 mL/kg/day (approximately 0.5, 5, and 10 times the recommended maximum human dose, respectively, based on body surface area) during organogenesis. No significant findings attributable solely to a direct effect on the fetus were detected in the studies.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied OPTISON (perflutren protein-type A microspheres) injectable suspension is supplied at concentrations of 5-8×10 8 /mL protein-type A microspheres, 10 mg/mL albumin human, and 0.22 ± 0.11 mg/mL perflutren as a clear liquid lower layer, a white liquid upper layer, and a headspace filled with perflutren gas in 3 mL single-patient use vials. After resuspension, OPTISON is a sterile, homogeneous, opaque, and milky-white injectable suspension. Five (5) – 3 mL vials per carton Eighteen (18) – 3 mL vials per carton NDC 0407-2707-03 NDC 0407-2707-18 Storage and Handling Upon receipt, store OPTISON refrigerated between 2°C to 8°C (36°F to 46°F). Storage at room temperature (up to 25°C or 77°F) for up to 24 hours is permitted. Do not freeze.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.