[drug name] general name: atosiban acetate injection English Name: atosiban acetate injection Chinese Pinyin: cusuan atoxican Zhusheye

[ingredients] main ingredients: atoxicam acetate chemical name: molecular formula: molecular weight: auxiliary materials: mannitol, hydrochloric acid, water for injection [properties] this product is a colorless clear liquid.

[indications] atoxicam is suitable for pregnant women with the following conditions to postpone the coming premature birth: - regular uterine contraction for at least 30 seconds at a time, ≥ 4 times every 30 minutes - cervical dilatation of 1-3cm (0-3cm in virgin women) and uterine softening / thinning ≥ 50% - age ≥ 18 years - 24-33 weeks of pregnancy - normal fetal heart rate

Related information
Usage and dosage: atoxicam must be used by a doctor with experience in the treatment of preterm birth. There are three consecutive steps in the intravenous administration of atosiban: the first single dose of 6.75mg was given with 7.5mg/ml of atosiban acetate injection (0.9ml / bottle), followed by a high dose of diluted atosiban acetate injection (300 μ g / min) for 3 hours, followed by a low dose of diluted atosiban acetate injection (100 μ g / min) for 45 hours.

The treatment time should not exceed 48 hours. In a complete course of treatment, the total dose of atoxicam should not exceed 330mg. Once diagnosed as premature, the first single dose intravenous infusion should be started as early as possible. After the completion of single dose intravenous infusion, intravenous drip therapy should be carried out.

Other treatments should be considered if there is sustained uterine contractions during the course of the atoxicam treatment. For patients with renal and liver dysfunction, there is no data on dose adjustment.

The following table lists the full dose of atrociban:

Step formula injection / infusion rate dose of atoxicam

1 0.9ml single dose intravenous infusion more than 1 minute 6.75mg

24 ml / h, 18 mg / h

  1. Follow up intravenous drip of 8ml / h and 6mg / h

Repeat treatment: if you need to repeat the treatment with atoxicam, you should also start to use a single dose of 7.5mg/ml of atoxicam injection, and then use a 7.5mg/ml solution of atoxicam for intravenous drip. Use and operation procedures before administration, it is necessary to check whether there are particles and discoloration in the vial.

Preparation for the first intravenous injection: take 0.9ml liquid from the 7.5mg/ml artosiban vial marked with 0.9ml for injection, and slowly inject one dose (more than 1 minute) through the vein under the strict supervision of the doctor in the obstetric ward. 7.5mg/ml of atrociban for injection should be used immediately.

Preparation and infusion: after intravenous injection with 0.9ml atrociban acetate injection, use atrociban acetate injection to prepare the infusion. The diluent can be one of the following: - 0.9% (w / V) sodium chloride injection, - sodium lactate ringer injection, - 5% (w / V) glucose injection.

Preparation method: take 10ml of solvent from the infusion bag (or infusion bottle) (100ml / bag or 100ml / bottle) containing the diluent and discard it. Take 10ml of atoxicam acetate injection and add it into the infusion bag (or infusion bottle) to prepare 75mg / 100ml of atoxicam for infusion. During intravenous infusion, the infusion speed of 24ml / h (18mg / h) shall be used first, and the loaded dose of drug shall be given for 3 hours (Administration) It should be carried out in the obstetrics department of the hospital and closely monitored by the medical staff).

After 3 hours of administration, the infusion rate decreased to 8 ml / h (6 mg / h). If one bag (or bottle) of infusion is not enough, the above preparation method can be repeated to prepare another bag (or bottle) of 100ml infusion for further use. If the volume of infusion bag (or infusion bottle) is not 100ml, the volume of atrociban acetate injection should be accurately converted before the same concentration of infusion is prepared.

In order to achieve the accuracy of dosage, it is recommended to use the infusion set with adjustable, and the adjustment unit is calculated as "drop / minute". Using intravenous micropump can set a suitable range of infusion speed within the recommended dose. Due to the lack of incompatibility data, this drug should not be mixed with other drugs.

If other drugs need to be given through the vein when using this product, they must be given in other parts of the body, so as to ensure the delivery speed of this product. - once the bottle is opened, the product should be diluted quickly. The diluted solution shall be used within 24 hours after preparation.

[adverse reactions] the adverse reactions of the mother are generally mild. In clinical trials, 48% of patients had adverse reactions. Maternal adverse reactions are as follows: very common (> 10%): nausea common (1-10%): Central and peripheral nervous system: headache, dizziness, gastrointestinal system: vomiting systemic: Hot tide cardiovascular: tachycardia, hypotension local: reaction metabolism and nutrition at injection site: high blood sugar is not common (0.1-1%): systemic: fever mental: insomnia skin and its accessories: Pruritus and rash are rare (< 0.1%): an unexpected case of uterine bleeding and lack of uterine tension has been reported. The incidence of clinical trials was not higher than that of the control group. There is a report of an allergic reaction that may be related to atoxicam.

For newborns, the clinical trial did not show any special adverse reactions. Adverse events in infancy were within the normal range of variation, and the incidence of adverse events was similar to that of placebo and β - receptor agonists.

[contraindications] the following conditions are not allowed to use atrociban: - prom with gestational age less than 24 weeks or more than 33 full weeks - prom with gestational age more than 30 weeks - intrauterine growth retardation and abnormal fetal heart rate - immediate delivery of prenatal uterine bleeding - eclampsia and severe preeclampsia need immediate separation of delivery - intrauterine fetal death - suspected intrauterine infection - placenta previa - early separation of placenta - any continued pregnancy Pregnancy harmful to mother and fetus - known to be allergic to active substances or any other excipients

[note] in women with PROM who cannot be excluded, the potential risk of postpartum delivery and choriositis should be weighed when using atoxicam. There is no experience of using atoxicam in patients with liver and kidney dysfunction (see [dosage] and [pharmacology and toxicology]).

The experience of using atoxicam in patients with placental position abnormality is still lacking. The clinical experience of using atoxicam in multiple pregnancies or at gestational age of 24-27 weeks is limited, and the benefits of atoxicam for such patients are uncertain. It can be used repeatedly, but the clinical experience of repeated application (up to 3 times) is limited (see [usage and dosage]).

In cases of intrauterine growth retardation, continued and renewed treatment with atoxicam depends on the assessment of fetal maturity. Uterine contraction and fetal heart rate should be monitored during the treatment with atoxicam. As an antagonist of oxytocin, atoxicam can theoretically promote the relaxation of uterus, so it may cause postpartum uterine contraction and postpartum hemorrhage, so postpartum blood loss should be monitored. However, during the clinical trial, no postpartum uterine contraction was observed.

[medication for pregnant women and lactating women] atoxicam can only be used when it is diagnosed as premature delivery when the pregnancy is 24 to 33 weeks. In the clinical trial of atoxicam, no effect on lactation was observed. A small amount of atoxicam can be secreted into milk through plasma. The preclinical study did not show that atoxicam has toxic effects on the fetus. There is no relevant research data on fertility and early embryo development.

[medication for children] this product is not suitable for children.

[medication for the elderly] this product is not suitable for the elderly.

[drug interaction] in vitro studies show that atoxicam is not the substrate of cytochrome P450 system, nor the cytochrome P450 enzyme that inhibits drug metabolism. Therefore, atoxicam does not participate in the drug interaction mediated by cytochrome P450. Clinical studies have shown that there is no drug interaction between atoxicam and betamethasone in healthy women.

At the same time, the peak concentration of rabeprolol in blood decreased by 36%, and the peak time was prolonged by 45 minutes. However, the bioavailability of rabeprolol did not change, and rabeprolol did not affect the pharmacokinetics of rabeprolol. There is no study on the interaction of atoxicam with antibiotics, ergot alkaloids and antihypertensive drugs except labetalol.

[overdose] there are few reports of atoxicam overdose. There were no special signs or symptoms of atoxican overdose. There is no specific treatment for atoxicam overdose.

[pharmacology and toxicology] atoxicam is a synthetic peptide, which can competitively inhibit oxytocin at receptor level. The results of animal experiments in rats and guinea pigs showed that the combination of oxytocin receptor with this product could reduce the contractile frequency and tension of uterus and inhibit the contraction of uterus. It also binds with vasopressin receptor to inhibit the action of vasopressin. No effect on cardiovascular system was found in animal test. At the time of preterm delivery, the use of the recommended dose of atoxicam can inhibit uterine contraction and make the uterus quiet. After the administration of this product, the uterus relaxed rapidly, the contraction of uterus decreased significantly within 10 minutes, and the uterus remained in a quiet state (< 4 contractions / hour, up to 12 hours).

Rats and dogs were given this product intravenously for two weeks, the dose was close to 10 times of the human treatment dose, or the toxicity test results of rats and dogs intravenously for three months showed that this product had no systemic toxic effect. There was no adverse reaction when the dose of subcutaneous injection was twice of that of human body. Reproductive toxicity test showed that there was no side effect on the mother and offspring of pregnant rats. The exposure of the rat fetus is 4 times of the dose of the patient's intravenous administration. The inhibition of lactation in animals may be due to the inhibition of oxytocin. In vivo and in vitro test results showed that the product had no mutagenic and carcinogenic effects.

[pharmacokinetic] pharmacokinetic data are from clinical research abroad. The steady-state plasma concentration in healthy non pregnant women increased proportionally with the dose. The steady-state plasma concentration (average 442 ± 73ng / ml, range 298-533ng / ml) was achieved within one hour after the intravenous infusion of atroxaban (300 μ g / min, 6-12 / h).

The plasma protein binding rate of the pregnant women was 46% - 48%. Atoxicam can pass through the placenta. After 300 μ g / min intravenous drip, the concentration ratio of atoxicam in the fetus and the mother was 0.12. It is not clear whether there is a fundamental difference between free atoxicam in the mother and fetus. Atoxicam cannot enter red blood cells. The mean value of the volume was 18.3 ± 6.8L. At the end of intravenous drip, the plasma concentration of atoxicam decreased rapidly, and the average clearance rate was 41.8 ± 8.2l/h.

The first half-life (t α) of atroban was 0.21 ± 0.01 hours, and the last half-life (t β) was 1.7 ± 0.3 hours. The clearance rate and half-life of atoxicam were not related to dose. Two metabolites can be identified in human plasma and urine. In vitro, the main metabolite M1 is as effective as the original compound in inhibiting oxytocin induced uterine contraction. The metabolite ml can be secreted from milk. At the end of the second hour, the ratio of plasma concentration of the main metabolite M1 (DES - (orn8, gly-nh29) - [Mpr1, d-tyr (ET) 2, thr4] - oxytocin to that of atrociban was 1.4 and 2.8, respectively.

It is not clear whether ml accumulates in the tissue. The content of atoxicam in urine is very small, and its concentration is 50 times lower than that of M1. The content of atoxicam in feces is not known. Patients with liver or kidney dysfunction have no experience in the use of atoxicam.

[storage] keep away from light, airtight and at 2-8 ℃.

[packaging] Xilin bottle. 1 bottle per box.

[validity period] 24 months.

[approval No.] gyzz h20184094

[manufacturer] company name: Chengdu shengnuo bio Pharmaceutical Co., Ltd





Chengdu Shengnuo Biotechnology Co.

Tel: 86-28-88203630

Fax: 86-28-88203630

Email: [email protected]


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Chengdu Shengnuo Biotechnology Co., Ltd. has "Chengdu polypeptide drug engineering technology research center" in Chengdu, mainly engaged in polypeptide, polypeptide drug and beauty peptide research. Our zero defect has passed the FDA certification, and now it has become the first-class professional peptide drug and product development, technology transfer, technical service and peptide drug industry in the scale production and export of China's parks.