Atosiban (Atosiban)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceAtosibanAtosiban
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  • Atosiban
    concentrate d / infusion 
    OBNINSKAYA CHEMICAL - PHARMACEUTICAL COMPANY, CJSC     Russia
  • Tractocyl
    concentrate d / infusion 
    Ferring AB     Sweden
    • Dosage form: & nbsptooncentrate for solution for infusion
    Composition:Hand 1 ml:

    active substance: atosibane acetate in terms of atosiban 7.5 mg;

    Excipients: mannitol 50.0 mg, 1M hydrochloric acid solution to pH 4.5, water for injection up to 1 ml.

    Description:Pa clear, colorless solution.

    Pharmacotherapeutic group:Generic activity suppressant - blocker of oxytocin receptors
    ATX: & nbsp

    G.02.C.X   Other drugs for use in gynecology

    G.02.C.X.01   Atosiban

    Pharmacodynamics:

    Atosiban is a synthetic peptide that is a competitive antagonist of human oxytocin at the receptor level. Atosiban, binding to the receptors of oxytocin, reduces the frequency of uterine contractions and the tone of the myometrium, leading to the suppression of uterine contractility. Atosiban also binds to vasopressin receptors, suppressing the effect of vasopressin, but does not affect the cardiovascular system.

    In the case of premature birth in women atosiban in recommended doses suppresses uterine contractions and provides the uterus with functional rest.Relaxation of the uterus begins immediately after the administration of atosiban. Within 10 min, the contractile activity of the myometrium is significantly reduced, maintaining a stable functional uterine rest (≤4 cuts per hour) for 12 hours.

    Pharmacokinetics:

    Pharmacokinetic parameters of atosiban (volume of distribution, clearance and half-life) are not dose-related.

    Distribution

    After intravenous (IV) infusion (300 μg / min for 6-12 hours), the maximum concentration of atosiban in the blood plasma is reached within 1 hour after the start of infusion (on average 442 ± 73 ng / ml, in the range from 298 to 533 ng / ml). Atosiban penetrates the placental barrier. The ratio of the concentration of atosiban in the fetal body and in the mother is equal to 0.12. The relationship of atosiban to plasma proteins in pregnant women is 46-48%. The average volume of distribution is 18.3 ± 6.8 liters.

    Metabolism

    In blood plasma and human urine, 2 metabolites were identified. The ratio of the concentration of the main metabolite M1 and the concentration of atosiban in blood plasma was 1.4 and 2.8 at the 2 nd hour of infusion and after its termination, respectively. Metabolite Ml has pharmacological activity on par with atosiban and penetrates into breast milk. Inhibition of cytochrome P450 isoforms by atosiban is unlikely.

    Excretion

    After stopping the infusion, the concentration of atosiban in the blood plasma rapidly decreases with the values ​​of the initial (tα) and the final (tβ) elimination half-life of 0.21 ± 0.01 and 1.7 ± 0.3 hours, respectively. The average clearance of the atosiban is 41.8 ± 8.2 l / h. Atosiban is detected in urine in very small amounts, its concentration in urine is 50 times lower than the concentration of metabolite Ml. The amount of atosiban withdrawn through the intestine was not determined.

    Indications:

    Atosiban is used to threaten premature births in pregnant women over 18 years of age in pregnancy from 24 to 33 full weeks with a normal heart rate in the fetus in the following cases:

    - regular uterine contractions lasting at least 30 seconds and a frequency of more than 4 within 30 minutes;

    - the opening of the cervix from 1 to 3 cm (0-3 cm for nulliparous women).
    Contraindications:

    - Hypersensitivity to atosiban or any of the auxiliaries of the drug in history;

    - the gestation period is less than 24 or more than 33 full weeks;

    - premature rupture of membranes during pregnancy for more than 30 weeks;

    - intrauterine growth retardation;

    - abnormal heart rate (HR) in the fetus;

    - uterine bleeding, requiring immediate delivery;

    - eclampsia and severe preeclampsia requiring immediate delivery;

    - intrauterine fetal death;

    - suspicion of chorioamnionitis;

    - placenta previa;

    - premature placental abruption;

    - any conditions of the mother and fetus, in which the retention of pregnancy is a danger;

    - the period of breastfeeding.

    Carefully:

    In case of suspicion of premature rupture of membranes, the use of atosiban for prolonging pregnancy should be compared with the potential risk of developing chorioamnionitis.

    Caution should be applied atosiban if there is a violation of the liver and kidney function, in case of multiple pregnancy, at the pregnancy period of 24-27 weeks (because of lack of sufficient clinical experience), and also when combined with other drugs with tocolytic effect.

    Pregnancy and lactation:

    Atosiban should be used only in the case of diagnosed preterm birth for a period of 24 to 33 full weeks of pregnancy.

    Atosiban is contraindicated in breastfeeding.

    Dosing and Administration:
    Atosiban is administered IV immediately after the diagnosis of "premature birth" in 3 stages:

    1) First, for 1 minute, I inject 0.9 ml of the drug without dilution (the initial dose is 6.75 mg);

    2) Immediately thereafter, infusion of atosibane at a dose of 300 μg / min (injection rate 24 ml / h, dose of atosiban 18 mg / h) is performed for 3 hours;

    3) After this, a prolonged (up to 45 h) infusion of atosiban at a dose of 100 mcg / min (rate of administration - 8 ml / h, dose of atosiban - 6 mg / h).

    The total duration of treatment should not exceed 48 hours. The maximum dose of atosiban for the entire course should not exceed 330.75 mg.

    If there is a need for re-application of atosiban, also should begin with the 1 st stage, followed by infusion of atosiban (stages 2 nd and 3 rd).

    Repeated use can begin at any time after the first use of the drug, repeat it can be up to 3 cycles.

    If after 3 cycles of therapy with atosiban the contractile activity of the uterus does not decrease, consideration should be given to the use of another tocolytic drug. Instructions for preparing a solution for infusion (stage 2 and 3)

    Concentrate is diluted in one of the following solutions:

    - 0.9% solution of sodium chloride;

    - Ringer's acetate solution;

    - 5% glucose solution.

    From a vial containing 100 ml of one of the above dilution solutions, 10 ml are drained. Then, 10 ml (2 bottles) of the drug are injected into the vial to give a concentration of 75 mg / 100 ml.

    Shelf life of the prepared solution for infusions is 24 hours. Do not use if dissolving particles are visible in solution or the solution has changed color.

    Special categories of patients

    Age under 18 years old

    Atosiban should not be used in pregnant women under 18 due to lack of data on efficacy and safety in patients of this age group.

    Impaired renal function

    Data on the use of the drug Atosiban patients with impaired renal function are absent.

    Impaired liver function

    Data on the use of the drug Atosiban patients with impaired liver function are absent.
    Side effects:

    Undesirable reactions are listed below for organs and systems, indicating the frequency of their occurrence. Frequency criteria: very often (≥1 / 10), often (≥1 / 100, <1/10), not often (≥1 / 1000, <1/100), rarely (≥1 / 10000, <1 / 1,000 ), very rarely (<1/10000), including individual messages.

    Immune system disorders: rarely allergic reactions.

    Disorders from the gastrointestinal tract: very often - nausea, often - vomiting.

    Disorders from the metabolism and nutrition: often hyperglycemia.

    Impaired nervous system: often - headache, dizziness; not often - insomnia.

    Heart Disease: often - tachycardia.

    Vascular disorders: often - arterial hypotension, hot flashes.

    Disturbances from the skin and subcutaneous tissues: not often - itching, skin rash.

    Violations of the genitals and breast: very rarely - uterine bleeding / atony of the uterus.

    General disorders and disorders at the site of administration: often - hyperthermia at the injection site, not often - fever.

    Overdose:

    There are several cases of overdose. Specific symptoms and signs are absent.

    Treatment is symptomatic and maintenance therapy. The specific antidote is unknown.

    Interaction:
    Atosiban does not affect the pharmacokinetics of drugs metabolized with cytochrome P450.

    With the combined use of atosiban and betamethasone, no clinically significantinteractions.

    Labetalol does not affect the pharmacokinetics of atosiban.

    The interaction of atosiban with antibiotics is unlikely.

    The joint application of atosiban with ergot alkaloids is impractical in connection with the opposite pharmacological action and indications for use.

    Special instructions:

    In the absence of a decrease in contractile activity of the uterus during the introduction of atosiban should monitor the contraction of the uterus, as well as monitor the heart rate in the fetus. Also consider the possibility of using other drugs.

    The decision to continue or resume infusion of atosiban during intrauterine fetal retardation depends on the evaluation of the degree of maturity of the fetus.

    The experience of using atosiban in pregnant women with a violation of the liver and kidneys is absent. Caution should be exercised when prescribing atosiban for this category of patients.

    Atosiban is not used in cases of abnormal attachment of the placenta.

    As an oxytocin antagonist atosiban can theoretically contribute to the relaxation of the uterus and provoke postpartum uterine bleeding, therefore, a continuous assessment of the degree of blood loss after labor is necessary.

    Effect on the ability to drive transp. cf. and fur:

    Not applicable, given indications for use.

    Form release / dosage:

    Concentrate for the preparation of a solution for infusions, 7.5 mg / ml.

    Packaging:

    For 0.9 ml of the preparation in a clear, colorless vial with a capacity of 2 ml of Type I glass, sealed with a gray bromobutyl plug and hermetically sealed with a "flip-off" cap.

    For 5 ml of the drug in a clear, colorless vial with a capacity of 6 ml of Type I glass, sealed with a gray bromobutyl plug and hermetically sealed with a "flip-off" cap.

    1 bottle per cardboard pack together with instructions for use.

    For hospitals: 9 or 21 or 121 bottles of 0.9 ml, 4 or 10 or 64 bottles of 5 ml, along with instructions for use in a box of cardboard.

    Storage conditions:In the dark place at a temperature of 2 to 8 ° C.
    Keep out of the reach of children.
    Shelf life:

    3 years.

    Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-003585
    Date of registration:25.04.2016 / 17.04.2017
    Expiration Date:25.04.2021
    The owner of the registration certificate:OBNINSKAYA CHEMICAL - PHARMACEUTICAL COMPANY, CJSC OBNINSKAYA CHEMICAL - PHARMACEUTICAL COMPANY, CJSC Russia
    Manufacturer: & nbsp
    Information update date: & nbsp08.10.2017
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