Description
Pharmacological action
Anti-labor agent, an oxytocin receptor blocker. Atosiban is a synthetic peptide that is a competitive antagonist of human oxytocin at the receptor level. Atosiban binding to oxytocin receptors, 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, inhibiting the effect of vasopressin, but does not affect the cardiovascular system.
In the event of a premature birth in a woman, atosiban in the recommended doses suppresses uterine contractions and provides the uterus with a functional rest. Uterine relaxation begins immediately after administration of atosiban, within 10 minutes the contractile activity of the myometrium decreases significantly, maintaining stable functional rest of the uterus ( 4 contractions per hour) for 12 hours.
Pharmacokinetics
Pharmacokinetic parameters (Vd, clearance and T1 / 2) are not dose dependent. After iv infusion (300 Ојg / mi for 6-12 h), Cmax of atosiban in plasma is achieved within 1 h after the start of the infusion (average 442 В± 73 ng / ml, in the range from 298 to 533 ng / ml). Binding to plasma proteins is 46-48%. Atosiban crosses the placental barrier. After the administration of atosiban at a rate of 300 Ојg / min, the ratio of the concentration of atosiban in the fetus to the concentration of atosiban in the mother is 0.12. The average value of Vd is 18.3 В± 6.8 l.
2 metabolites have been identified in blood plasma and urine. 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 second hour of the infusion and after its termination, respectively. The metabolite M1 has pharmacological activity along with atosiban and is excreted in breast milk.
Atosiban inhibition of isoenzymes of the cytochrome P450 system is unlikely.
After the cessation of infusion, the plasma concentration of the drug rapidly decreases with the values ​​of T1 / 2 -phase and T1 / 2 -phase 0.21 ± 0.01 and 1.7 ± 0.3 h, respectively. The average clearance is 41.8 ± 8.2 l / h.
Atosiban is detected in urine in very small quantities, its concentration in the urine is 50 times lower than the concentration of M1. The amount of atosiban excreted in the feces was not determined
Indications
If there is a threat of premature birth in pregnant women: regular uterine contractions lasting at least 30 seconds and a frequency of more than 4 for 30 minutes, the cervix opens from 1 to 3 cm (0-3 cm for nulliparous women) over 18 years of age from 24 to 33 full weeks normal fetal heart rate.
Contraindications
Pregnancy 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 in the fetus uterine bleeding requiring immediate delivery eclampsia and severe pre-eclampsia, requiring intrauterine delivery requiring early delivery infection, placenta previa, placental abruption, any condition of the mother and fetus in which pregnancy is present The risk of breastfeeding is hypersensitivity to atosiban.
Special instructions
If you suspect premature rupture of the membranes, the benefits of using atosiban to prolong labor should be weighed against the potential risk of chorioamnionitis.
Use caution with atosiban for multiple pregnancies, as well as for a gestational age of 24-27 weeks (due to lack of sufficient clinical experience).
In the case of persistent uterine contractions during administration of atosiban, uterine contractions should be monitored and fetal heart rate should be monitored. You should also consider using other drugs.
There is no experience with atosiban in patients with impaired liver and kidney function. Atrosiban
is not used in cases of abnormal attachment of the placenta.
In case of fetal retardation of the fetus, the decision to continue administration or re-administration of atosiban depends on the assessment of fetal maturity.
As an oxytocin antagonist, atosiban can theoretically promote uterine relaxation and provoke postpartum uterine bleeding, so you should constantly evaluate the degree of blood loss after childbirth.
Influence on the ability to drive vehicles and drive machinery
Atoshiban does not affect the ability to drive a car and machinery.
Composition
1 ml contains:
Active substances: atosiban – 7.5 mg,
Excipients: mannitol – 50 mg, hydrochloric acid solution 1M – up to pH 4.5, water d / and – up to 1 ml.
Dosage and administration
I / O is administered immediately after the diagnosis of premature birth is made in three stages: 1) 6.75 mg is initially administered in an initial dose within 1 min 2) immediately after that, an infusion of 300 μg / min is carried out for 3 hours (24 ml / h administration rate, 18 mg / h atosiban dose) 3) after this continuous (up to 45 hours) infusion of atosiban at a dose of 100 μg / min (injection rate of 8 ml / h, atosiban dose of 6 mg / h).
The total duration of treatment should not exceed 48 hours. The maximum dose of atosiban for the entire course is 330 mg.
If there is a need for repeated use of atosiban, you should also start from stage 1, followed by infusion (stages 2 and 3). Repeated use can be started at any time after the first use of the drug, it can be repeated up to 3 cycles. If after 3 cycles of atosiban therapy, the contractile activity of the uterus persists, the use of another drug should be considered.
Side effects
From the digestive system: very often (> 1/10) – nausea, less often – vomiting.
From the side of metabolism: often (> 1/100, <1/100) - hyperglycemia. From the nervous system: often (> 1/100, <1/100) - headache, rarely dizziness (> 1/1000, <1/100) - insomnia. From the cardiovascular system: often (> 1/100, <1/100) - tachycardia, arterial hypotension, hot flashes. From the skin: rarely (> 1/1000, <1/100) - itching, skin rash. From the reproductive system: very rarely (> 1/10 000, <1/1000) - uterine bleeding, uterine atony. Other: very rare (> 1/10 000, < 1/1000) - allergic reactions. Active ingredient Atosiban Terms of delivery from pharmacies Prescription dosage form infusion solution Appointment by Pregnant II and III trimester by doctor’s appointment, Children by doctor’s appointment, Adults33 doctor’s appointment