Perfluoropropane-Albumin Microsphere Injection

Clinical Value

The ultrasound contrast agent (UCA) plays an important role in clinical diagnosis, treatment and clinical research. The internationally approved echocardiographic contrast agents are used for same clinical indications: patients with poor left ventricular opacification (LVO) and left ventricular endocardial border delineation (EBD) in routine echocardiography in the resting state.

American Society of Echocardiography (ASE) guidelines recommend: if imaging quality of the heart is poor in at least two out of the six stages, ultrasonic contrast should be applied to enhance the image quality.

Application of contrast agent in LVO enhances the possibility, accuracy and repeatability of qualitative and quantitative echocardiographic assessments of left ventricular structure and function in the resting state, or during exercise or pharmacological stress, making it easier for the diagnosis or assessment of intracardiac space occupying lesion, such as tumors and thrombus. Meanwhile, it improves the visibility of right ventricle and large vessels and reinforces the Doppler signal which is used to assess valve function. The UCA can also be used for echocardiographic study in emergency rooms, intensive care units, cardiac catheterization rooms and operation rooms. The effective application of contrast agent in echocardiography will optimize and improve the cost-effectiveness of examination and may help improve clinical outcomes.

In recent years, great progress has been made in the application of Perfluoropropane-Albumin Microsphere Injection for myocardial blush grades and ultrasonography of parenchymatous organs, such as liver, kidneys, mammary glands and pancreatic gland. Clinicians have established a complete set of methods to qualitatively identify various masses in parenchymatous organs with Perfluoropropane-Albumin Microsphere Injection.

Accurate assessment of ventricular wall motion and wall thickness ratio;
Correct measurement of left ventricular ejection fraction;
Clear diagnosis of apical hypertrophic cardiomyopathy;
Clear diagnosis of intracardiac mural thrombus;

Potential real-time evaluation of the value of myocardial perfusion;

Clinical Outcomes

Clinical experiments in seven hospitals, including Zhongshan Hospital under Fudan University, Rui Jin Hospital under Shanghai Jiao Tong University School of Medicine, Changhai Hospital of Shanghai, Chinese PLA General Hospital, West China Hospital of Sichuan University, Qilu Hospital of Shandong University and Beijing Chao-Yang Hospital, prove that 98.6% of intima imaging quality has been enhanced and the identification of left ventricular endocardial border has been significantly improved. In the meanwhile, the application of Perfluoropropane-Albumin Microsphere Injection does not affect the function of liver or kidneys, or the results of blood and urine routine examinations and electrocardiogram (ECG) results. Therefore, it is a safe and effective cardiac ultrasound contrast agent, suitable for patients with poor imaging quality in routine echocardiography, and can be promoted for extensive clinical use.

[Name]

Generic name: Perfluoropropane-Albumin Microsphere Injection

[Composition] Main Ingredient: 1% of perfluoropropane-albumin microsphere. Excipient: 0.9% of sodium chloride injection.

[Description] The bottom layer is transparent liquid without any foreign matter , turbidity or sedimentation. The top layer is white microspheres. It becomes even, opaque, white suspension after it's mixed.

[Indications] Patients with poor imaging quality in routine echocardiography; improvement of left ventricular endocardial border identification; improvement of imaging effect, lesion detection rate and accuracy of lesion characterization in parenchymatous organs, such as liver, kidneys and mammary glands.

[Specification] 3ml/bottle.

[Usage and dosage] Peripheral intravenous injection; recommended dose: 0.01ml/kg each injection.

1. Preparation: check the package to make sure it's up to the standard, mix the drug evenly without shaking it hard to avoid microsphere rupture or foam. To keep the pressure constant to avoid rupture, insert another needle into the rubber plug to connect to the outside air while extracting solution, and then extract the suspension into the syringe.
2. Injection: The patient should be in the left recumbent position (for the convenience of echocardiography). Inject the tee joint scalp needle into the hand vein or median cubital vein of the right upper limb. Extract 10ml 0.9% sodium chloride injection with10ml syringe and connect to one end of the needle. Extract the shaken Perfluoropropane-Albumin Microsphere Injection with 1ml or 2ml syringe and connect to the other end of the needle. Start with the dose of 1ml/sec and gradually increase the dose to 0.02ml/kg, with two injections at maximum in total.

[Adverse reactions] According to domestic and foreign clinical studies, the adverse reactions with the occurrence rate higher than 0.5% include: headache (5.4%), nausea and vomiting (4.3%), hot flashes or flushing sensation (3.6%) and dizziness (2.5%). Other adverse reactions include: chills, flu-like symptoms, discomfort, weakness, fatigue, chest pain, dyspnea, diarrhea, discomfort at the injection site, erythema, taste alteration and slight changes in the heart rate and blood pressure. The adverse reactions with the occurrence rate lower than 0.5% include: joint pain, back pain, physical or muscle pain or sclerosis, rubella, dry mouth, heart palpitations, paresthesia, photophobia, ventricular premature beats, pruritus, rash, irritability, allergy, tinnitus tremor, blurred vision, asthma, cough, color changes at the injection site and the sense of burning in the eyes.

[Contraindications]

1. The product should not be used in patients with a history of allergy to food, drug, albumin and other blood products.
2. The product should be used with caution in patients with mitral stenosis and congenital heart disease with intracardiac shunt. This product can enter the arterial circulation directly without lung filtration, so it should be used with extreme caution in patients with congenital heart disease.
3. The product must not be used in patients with heart functional class IV and severe arrhythmia.
4. The product must not be used in patients with severe pulmonary hypertension, pulmonary emphysema, pulmonary vasculitis, pulmonary embolism, asthma, adult respiratory distress syndrome and respiratory failure.
5. The product should be used with caution in patients with liver and kidney dysfunction.
6. The product should be used with caution in patients with psychosis and epilepsy.

[Precautions]

1. The product must be used in strict accordance with the package insert and physician must fully master the operating procedures and safety.
2. Whenever a protein-containing product is applied to human body, it might cause allergic reaction. Therefore, drugs for emergency treatment of allergy, such as epinephrine, antihistamine drugs and glucocorticoids, should be prepared.

[Administration for pregnant and lactating women]Animal reproductive toxicity test did not show that the product would impair fertility or cause harm to fetus. However, there is no data of strictly controlled clinical research conducted on pregnant women at present. Therefore, the product should not be used in pregnant women unless it is necessary and should be used with caution in lactating women.

[Administration for children] For there is no safe and effective information, the product should be used with caution in children.

[Administration for elderly patients] For there is no safe and effective information, the product should be used with caution in elderly patients.

[Drug Interaction] Data unavailable yet.

[Overdose] In case of drug overdose, start symptomatic treatment immediately and monitor vital signs periodically.

[Clinical trial] A multicenter self controlled blind evaluation phase III clinical study was conducted to evaluate the efficacy and safety of clinical use of Perfluoropropane-Albumin Microsphere Injection. Three hundred and two patients (64.2% male, 35.8% female) with unclear border visualization of left ventricle in two (or more) out of the six stages were selected. Patients were intravenously injected with the contrast agent (0.01ml/kg) and then real-time contrast echocardiography was conducted. Evaluation indexes of the contrast effect are the identification effect of left ventricular and right ventricular endocardial border. The results showed that, Perfluoropropane-Albumin Microsphere Injection can improve the quality of 98.6% of unclear border imaging, with the occurrence rate of adverse reaction being 0.3%, including mild nausea and diarrhea (see Adverse Reactions for more details).

[Pharmacology and toxicology] Perfluoropropane-Albumin Microsphere Injection is gas-filled microsphere preparation and can significantly strengthen the acoustic reflection signal in ultrasound diagnostic instrument. After peripheral intravenous injection, it can enhance the left cardiac ultrasound contrast effect without causing adverse effect on hemodynamics or electrocardiogram.

[Pharmacokinetics] Pharmacokinetics study on this product has not been conducted. The following kinetic data are obtained from using the same type of Perfluoropropane-Albumin Microsphere Injection in Chinese patients. After intravenous administration, perfluoropropane will be immediately released and exhaled out of the human body. When the dosages of administration reaches 0.02ml/kg, 0.03ml/kg and 0.04ml/kg, respectively, Tmzx of perfluoropropane in breath is 0.42±0.14 (min), 0.39±0.13 (min) and 0.44±0.17 (min), respectively; T1/2 is 1.84±0.2 (min), 1.95±0.73 (min) and 2.22±0.53 (min). The call-out volume of perfluoropropane in one minute after the administration (AUCO-1min) accounts for 0.49 (49%)±0.02 (2%) of the total call-out volume (AUCO-∞) on average. The call-out volume of perfluoropropane in 15 minute after administration accounts for 0.96 (96%)±0.02 (2%) of the total (AUCO-∞).

[Storage Conditions] Store at 2-8℃. Protect from freezing and light. Do not invert or shake vigorously.

[Package] Penicillin bottle, 3ml/bottle.

[Shelf Life] 24 months.

[Standard] YBSO1672006 Perfluoropropane-Albumin Microsphere Injection Manufacturing and Verification Procedures (Trial).

[Registered number of approval] S20083098