What Is the Diagnostic Use of B-Type Natriuretic Peptide?
Each bottle of lyophilized preparation contains: active ingredient: recombinant human brain natriuretic peptide 0.5mg
Recombinant human brain natriuretic peptide
- Neovivin (lyophilized recombinant human brain natriuretic peptide), this product is suitable for intravenous treatment of patients with acute decompensated heart failure who have difficulty breathing during rest or light movement. According to NYHA classification, it is greater than .
- Drug Name
- Lyophilized recombinant human brain natriuretic peptide
- Hanyu Pinyin
- Dong Gan Chong Zu Ren Nao Li Na Tai
New Bioactive Ingredients
- Each bottle of lyophilized preparation contains: active ingredient: recombinant human brain natriuretic peptide 0.5mg
Molecular formula: C 143 H 244 N 50 O 42 S 4
Molecular weight: 3464Da
Inactive ingredients: 8mg mannitol, 1.73mg disodium hydrogen phosphate, 0.93mg sodium dihydrogen phosphate, 9mg sodium chloride.
New biotin traits
- White powder or lumps.
Neo-biotin indications
- This product is suitable for intravenous treatment of patients with acute decompensated heart failure who have difficulty breathing during rest or light activity. According to NYHA classification, it is greater than .
New Biotin Specifications
- 0.5mg / piece.
Dosage and dosage of neoactivin
- Instructions
This product is administered as an intravenous bolus at a loading dose, followed by an intravenous infusion at a maintenance dose.
Recommended common dose
This product is first continuously infused intravenously at a rate of 0.0075 g / kg / min after a 1.5 g / kg intravenous impact.
Dosage range
Loading dose: 1.5-2ug / kg, maintenance dose rate: 0.0075-0.01ug / kg / min (recommended maintenance dose rate for starting intravenous drip is 0.0075ug / kg / min). Care should be taken to adjust the rate of increased instillation.
Medication
The domestic clinical trial of this product uses a continuous intravenous drip for 24 hours.
Best method for dose adjustment
Blood pressure changes should be closely monitored during administration. If hypotension occurs during the administration, the dose should be reduced or the administration should be stopped and other measures to restore blood pressure (such as infusion, change of body position, etc.) should be started. Since the duration of the hypotensive effect caused by recombinant human brain natriuretic peptide may be longer (average 2.2 hours), an observation period must be set before re-administration.
Preparation of intravenous liquid
Do not mix with similar products from other manufacturers. Whenever possible, use products of the same lot number.
Dilute the diluent 3 times from the infusion bag containing 250ml of diluent (recommended diluent: 5% glucose injection, 0.9% physiological saline, 5% glucose and 0.45% NaCl injection, 5% glucose and 0.2% NaCl injection), withdraw 1.5ml each time, and add them to 3 recombinant human brain natriuretic peptide preparation bottles (if the patient's weight is light, it is not necessary to dilute three drugs at the same time, you can use: from 100 Extract 16.7ml of the diluted solution from the infusion bag of ml diluted solution, discard it, and withdraw 1.5ml from the infusion bag, add it to one of the preparations of recombinant human brain natriuretic peptide, if a second medicine is needed , And then diluted in accordance with the above method).
Do not shake the medicine bottle. Gently shake the medicine bottle, so that all parts of the bottle, including the stopper, can come into contact with the diluent to ensure that the medicine is fully dissolved. Use only clear and colorless solutions.
The dissolved human brain natriuretic peptide drug solution was extracted from three medicine bottles, and all were injected into a 250 ml intravenous infusion bag. At this time, the drug concentration in the infusion bag was about 6 g / mL. Repeatedly invert the infusion bag to fully mix the drug (for light-weight patients using a 100ml infusion bag, withdraw the dissolved recombinant human brain natriuretic peptide drug solution from a preliminarily diluted vial, and inject all the above-mentioned discarded Use 16.7ml of diluted solution and 100ml intravenous infusion bag. At this time, the drug concentration of this product in the infusion bag is about 6g / mL. Repeatedly turning the infusion bag to fully mix the drug).
A 25-mL infusion syringe was prepared before the patient established a venous access for intravenous bolus and drip.
After preparing the infusion bag according to the above method, extract the recombinant human brain natriuretic peptide liquid (see the table below) that gives a venous impact, and inject the liquid in the infusion syringe into the blood vessel through the vein in about 60 seconds, and then Intravenous infusion of this product at a rate of 0.0075mL / kg / hr, that is, the infusion dose is 0.0075g / kg / min.
For accurate conversion of the volume of the venous fluid to be administered and the rate of intravenous infusion of 0.0075 g / kg / min, please refer to the following formula (or refer to the following dosage table):
Intravenous impact dose (mL) = subject's weight (kg) ÷ 4
Intravenous drip rate (mL / hr) = 0.075 × Subject's weight (kg)
Adjust the venous impact dose and intravenous drip rate of rhBNP according to body weight (loading dose is 1.5 g / kg, intravenous drip dose is 0.0075 g / kg / min)
Patient weight (kg) Impact dose volume (ml) Intravenous drip rate (ml / hr)
50 12.5 3.75
60 15.0 4.5
70 17.5 5.25
80 20.0 6.0
90 22.5 6.75
100 25 7.5
110 27.5 8.25
Stability after drug formulation
Since the medicine does not contain a preservative, the dissolved solution must be used within 24 hours. In any case, before using the drug by parenteral route, you should visually observe the presence of particles, discoloration, etc. in the liquid. After dissolving, the maximum storage time of this product at room temperature (20-25 ° C) or under refrigeration (2-8 ° C) should not exceed 24 hours.
Incompatibility
Recombinant human brain natriuretic peptides are physically and chemically resistant to injections such as heparin, insulin, bumetanide, enalapril, ethacrynate sodium, hydrazine, and furosemide, The simultaneous infusion of recombinant human brain natriuretic peptide with these drugs in the same intravenous catheter cannot be allowed. Preservative sodium metabisulfite is repelled by recombinant human brain natriuretic peptide. Therefore, injectable drugs containing sodium metabisulfite cannot be used simultaneously with recombinant human brain natriuretic peptide in the same infusion tube. Catheters must be flushed between the use of recombinant human brain natriuretic peptides and these repulsive drugs. Recombinant human brain natriuretic peptide can bind to heparin, and can bind to the inner layer of the heparin-coated catheter, thereby sometimes reducing the amount of recombinant human brain natriuretic peptide entering the patient. Therefore, the use of heparin-coated catheters for the infusion of natriuretic peptides in human brain is prohibited. However, simultaneous infusion of heparin using separate catheters is allowed.
Neoactivin adverse reactions
- The most common adverse effects of recombinant human brain natriuretic peptide administration are hypotension, and other adverse reactions are mostly headache, nausea, ventricular tachycardia, and elevated serum creatinine. Table 1 details the adverse reactions that may be associated with recombinant human brain natriuretic peptide therapy in completed clinical trials.
Table 1. Adverse reactions considered to be drug-related during the study
Taboo
- It is contraindicated in patients who are allergic to any one of the components of recombinant human brain natriuretic peptide and patients with cardiogenic shock or systolic blood pressure <90mmHg. The use of recombinant human brain natriuretic peptide should be avoided in patients suspected of or known to have low cardiac filling pressure.
New biotin precautions
- General considerations:
Allergic reactions should be properly prevented when this product is administered by injection. There have been no reports of severe allergic reactions when treated with recombinant human brain natriuretic peptide. Patients who are not suitable for use of vasodilators such as those with severe valvular stenosis, restrictive or obstructive cardiomyopathy, restrictive pericarditis, pericardial tamponade or other cardiac output that rely on venous return or are suspected of having a low filling pressure Patient (see Contraindications).
Renal function:
In some sensitive populations, recombinant human brain natriuretic peptide may have an effect on kidney function. In patients with severe heart failure where kidney function may depend on the renin-angiotensin-aldosterone system, treatment with recombinant human brain natriuretic peptide may cause hyperazotemia. For acute renal failure and renal dialysis, monitor blood biochemical indicators, especially elevated serum creatinine.
Cardiovascular:
Hypotension has occurred in VMAC trials conducted abroad and clinical trials conducted in China using recombinant human brain natriuretic peptide therapy. When hypotension occurred, the duration of symptomatic hypotension in the recombinant human brain natriuretic peptide group (average 2.2 hours) was longer than that in the nitroglycerin group (average 0.7 hours). Therefore, when using recombinant human brain natriuretic peptide therapy, blood pressure should be closely monitored. When hypotension occurs, the dose should be reduced or stopped. Patients with a baseline blood pressure of <100 mmHg have a higher incidence of hypotension, so the use of recombinant human brain natriuretic peptide therapy should be more cautious in such patients. When recombinant human brain natriuretic peptide is used in combination with other drugs that may cause hypotension, the incidence of hypotension may increase.
Allergy test:
At present, there have been no reports of allergic reactions to this product in clinical trials at home and abroad, and no allergic test has been performed on patients in practical applications after marketing.
Laboratory inspection:
In clinical trials, only one patient had a transient increase in serum creatinine.
Impact on mortality:
Compared with the most important control nitroglycerin, this product also shows roughly the same trend as foreign products. The effect on mortality remains to be further studied in the clinic.
Drug abuse and dependence:
At present, there is no research in this area at home and abroad.
Medication for pregnant women and lactating women
- At present, there is no research on animal development and reproductive toxicity of recombinant human brain natriuretic peptide at home and abroad, and it is not known whether the use of recombinant human brain natriuretic peptide will cause fetal toxicity or affect reproductive function when treating pregnant women. Therefore, it should only be used when doctors judge that the benefits of treatment with recombinant human brain natriuretic peptides outweigh the risks to the fetus. It is also unknown whether the drug is secreted from human milk. Therefore, it should be used with caution when using recombinant human brain natriuretic peptide in the treatment of lactating women.
Neo-vitamin children medication
- The safety and effectiveness of recombinant human brain natriuretic peptide in children have not been determined at home and abroad.
Neo-biotin medication for the elderly
- No difference was found between elderly patients and young patients when using recombinant human brain natriuretic peptide.
Neoactivin drug interactions
- Although there are many drugs used in combination with recombinant human brain natriuretic peptide in clinical trials at home and abroad, no special tests have been conducted to confirm the interaction of human brain natriuretic peptide for injection with other drugs. Except for the increased incidence of symptomatic hypotension when co-administration of an oral angiotensin-converting enzyme inhibitor with recombinant human brain natriuretic peptide (see note: cardiovascular), no other drug interactions have been observed phenomenon. This product does not exclude the use of diuretics. Recombinant human brain natriuretic peptide and other drugs include: diuretics, digoxin, oral angiotensin-converting enzyme inhibitors, anticoagulants, oral nitrates, statins, and third antiarrhythmic drugs , -receptor antagonists, dobutamine, calcium channel antagonists, angiotensin II receptor antagonists, and dopamine, although no specific evaluation of the effect on hemodynamic parameters has been performed, there is no evidence It suggests that there is any interaction between clinically significant hemodynamic parameters. No combination of intravenous vasodilators such as nitroglycerin, sodium nitroprusside, milrinone, or intravenous angiotensin-converting enzyme inhibitors has been evaluated.
Neobiotic overdose
- The expected response to an overdose is an excessive reduction in blood pressure. When this occurs, discontinuation of dosing, dose reduction and appropriate monitoring measures can be taken. In severe cases, expansion therapy can be taken.
Pharmacotoxicology
- Drug category
Human brain natriuretic peptide is a type B natriuretic peptide, an endogenous polypeptide secreted by the human body. It is a supplementary compensation mechanism produced by the human body after stress induced by heart failure. This product is a sterile lyophilized preparation produced by E. coli through recombinant DNA technology. It has the same amino acid sequence as the endogenous brain natriuretic peptide produced by ventricular muscle.
Mechanism
Human brain natriuretic peptides bind to specific natriuretic peptide receptors (which are linked to guanylate cyclase) and cause increased intracellular cyclic monophosphate guanosine (cGMP) concentrations and smooth muscle Cell relaxation. As a second messenger, cGMP can dilate arteries and veins, rapidly reduce systemic arterial pressure, right atrial pressure, and pulmonary capillary wedge pressure, thereby reducing the anteroposterior load of the heart, and rapidly reduce the degree of dyspnea and systemic symptoms in patients with heart failure.
Brain natriuretic peptide is a natural antagonist of the renin-angiotensin-aldosterone system (RAAS). It can antagonize endothelin, norepinephrine and aldosterone in cardiac muscle cells, cardiac fibroblasts and vascular smooth muscle cells. It can improve the glomerular filtration rate, enhance the excretion of sodium, reduce the secretion of renin and aldosterone, and also resist the effects of vasopressin and sympathetic nerves on sodium and water retention and hypertension. Brain natriuretic peptides participate in the regulation of blood pressure, blood volume, and water-salt balance, increase vascular permeability, reduce systemic vascular resistance, and plasma volume, thereby reducing the pre- and post-load of the heart and increasing cardiac output. This product has no positive muscle strength and does not increase myocardial oxygen consumption.
Clinical pharmacology
The entire trial was conducted in 12 cardiovascular clinical research bases nationwide. A total of 209 subjects were randomly enrolled and received drug treatment (105 cases in the product group and 104 in the control group), of which 103 cases were in the catheter group (51 in the product group). Cases, 52 cases in the control group) and 106 cases in the non-catheter group (54 cases in the product group and 52 cases in the control group).
In terms of efficacy analysis, evaluation of hemodynamic indicators, comparison of pulmonary capillary wedge pressure (PCWP) before and after administration, and (ITT) population analysis, both the product group and the control group showed a downward trend after administration. Pulmonary capillary wedge pressure (PCWP) decreased by an average of 9.13mmHg at the end of 24 hours of medication in this product group, and pulmonary capillary wedge pressure (PCWP) decreased by an average of 4.56mmHg at the end of 24 hours of administration in the control group. There was a significant difference (P = 0.0368). Consistent with the analysis of the program population (PP population), there was a significant difference in the change between the two groups (P = 0.0368).
The adjusted average of the pulmonary arterial pressure (PAP) detection values in this group was significantly different from the control group at 30 minutes, 1 hour, 2 hours, and 24 hours (P <0.05). At 24 hours after treatment, the test group The mean values of PAP test and control group decreased by 10.82mmHg and 4.09mmHg, respectively. There was no significant difference in PAP detection values at other time points between the two groups (P> 0.05).
The change in the mean value of CI detection values, the recombinant human brain natriuretic peptide group increased by 0.05 L / min / m2 at 1 hour and 24 hours after administration, and the control group increased by 0.11 L / min / m2 and 0.10 L / min / m2, but There was no significant difference between the test group and the control group in the change of the CI detection mean value after 1 hour and 24 hours.
The average value of RAP detection values changed, the product group decreased by 2.55mmHg and 4.83mmHg during 1 hour and 24 hours, respectively, and the control group increased by 2.57mmHg during 1 hour and decreased by 1.19mmHg during 24 hours. However, there was no significant difference in the statistical comparison between the RAP-adjusted averages of this product group and the control group at 1 hour and 24 hours.
Hemodynamic results showed that the improvement of hemodynamic function was significantly better than that of nitroglycerin during the 24-hour medication period.
Comparison of dyspnea and systemic clinical condition improvement rate at the end of 24 hours of medication between the two groups. Analysis of ITT and PP populations showed that the rate of dyspnea and systemic clinical condition improvement of this product group was significantly higher than that of the control group (P <0.05). Comparing the improvement rate of dyspnea between the two groups at 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, and 12 hours, the recombinant human brain natriuretic peptide group was also significantly higher than the control group (P <0.05)
Nonclinical toxicology research
Monkey acute toxicity test:
In this test, the acute toxicity of the intravenous administration of this product to monkeys was observed. The dose was 0.720 mg / kg-3.645 mg / kg. After 14 days of observation, no other acute toxicity was observed.
Monkey long-term toxicity test:
Observe the long-term toxicity to Rhesus monkeys by continuous intravenous infusion for 30 days. Methods: Twenty-four male and female rhesus monkeys were randomly divided into 4 groups according to body weight: blank control group, low-dose group, medium-dose group, and high-dose group, with 6 animals in each group. The doses in the low, middle and high dose groups were 0.03, 0.09 and 0.3 mg / kg, respectively. Each morning, the drug was injected intravenously into a vehicle provided by a 50 ml development unit for 30 consecutive days before feeding, and a blank control group was intravenously injected with the same amount of vehicle provided by the development unit. One day after the last administration, half of the animals were sacrificed for pathological dissection, and the other half were stopped for 15 days. Observe the symptoms and various indicators.
The results showed that:
The main effects of this product on cardiovascular and urinary system of monkeys are blood pressure and diuresis. The target organs for pharmacological toxicity of monkeys are: liver and kidney, and their effects are reversible. In clinical use, the effects of this product on blood pressure, liver, and kidney function should be closely monitored.
Carcinogenicity and genotoxicity tests:
At present, no specific research has been conducted on the carcinogenicity and genetic toxicity of recombinant human brain natriuretic peptide.
Pharmacokinetics
- There is no systematic domestic research data on the human pharmacokinetics of this product.
Clear:
Human natriuretic peptides in the human body are cleared from the circulatory system by three independent mechanisms (sorted in order of importance): 1) by binding to scavenger receptors on the cell surface and then entering the cell and being lysosome Proteolytic hydrolysis; 2) peptides are hydrolyzed and cleaved by endopeptidases such as neutral endopeptidases on vascular endothelium; 3) cleared by renal filtration (<2%).
Special population:
Although recombinant human brain natriuretic peptide is partially cleared through the kidneys, data from clinical trials suggest that patients with renal insufficiency do not need to be dose-adjusted. Between patients with chronic renal insufficiency (serum creatinine range: 2 mg / dL to 4.3 mg / dL) and patients with normal renal function, recombinant human brain natriuretic peptides affect pulmonary capillary wedge pressure (PCWP), heart There was no significant difference in the effects of the index (CI) and vasoconstrictive pressure (SBP). The clearance of the drug is not significantly affected by factors such as age, gender, basal concentration of endogenous brain natriuretic peptides, and severity of congestive heart failure (graded with PCWP, CI, and NYHA classification standards) Impact.
Neo-biotin storage
- Store at room temperature (not more than 30 ° C) in the dark, and best store at 2-8 ° C.
New Biotin Packaging
- Glass control injection bottle.
New Life
- 18 months.
New biotin implementation standards
- State Food and Drug Administration Standard YBS00502005
New biotin approval number
- National Medicine Standard S20050033
New biotin production enterprise
- Chengdu Nuodikang Biological Pharmaceutical Co., Ltd.
New biotin approval date
- November 10, 2009
New Biotin Revision Date
- June 26, 2009