Atoziban 7.5mg/ml 5 ml

Pharmacotherapeutic group:

Rod activity suppressant – oxytocin receptor blocker

ATC:

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

G.02.C.X.01 Atoziban

Pharmacodynamics:

Atoziban is a synthetic peptide that is a competitive antagonist of human oxytocin at the receptor level. Atoziban binds to oxytocin receptors, reducing the frequency of uterine contractions and myometrial tone, leading to suppression of uterine contractility. Atoziban also binds to vasopressin receptors, inhibiting the effect of vasopressin, but has no effect on the cardiovascular system.

In the case of premature labor in a woman atoziban in the recommended doses suppresses uterine contractions and provides the uterus with functional peace.

The uterus relaxation begins immediately after injection of atoziban. Within 10 minutes myometrium contractile activity is significantly reduced, maintaining stable uterine functional rest (≤4 contractions per hour) for 12 h.

Pharmacokinetics:
Pharmacokinetic parameters of atoziban (volume of distribution, clearance and half-life) are independent of dose.

Distribution

After intravenous (IV) infusion (300 mcg/min for 6-12 h), the maximum plasma concentration of atoziban is reached within 1 h after infusion initiation (average 442±73 ng/mL, range 298 to 533 ng/mL). Atoziban penetrates through the placental barrier. The ratio of atoziban concentration in the fetus and in the maternal body is 0.12.

Atoziban binding to blood plasma proteins in pregnant women is 46-48%. Mean volume of distribution is 18.3±6.8 liters.

Metabolism

Two metabolites have been identified in human plasma and urine. The ratio of the concentration of the main metabolite M1 to the concentration of atoziban in blood plasma was 1.4 and 2.8 at the 2nd hour of infusion and after discontinuation, respectively. Metabolite Ml has pharmacological activity on a par with atoziban and penetrates into breast milk. Inhibition of cytochrome P450 isoforms by atoziban is unlikely.

Excretion

After discontinuation of infusion, plasma atoziban concentrations rapidly decrease with initial (tα) and final (tβ) elimination half times of 0.21±0.01 and 1.7±0.3 h, respectively. The average clearance of atoziban is 41.8±8.2 L/h.

Atoziban is detected in the urine in very small amounts, its concentration in the urine is 50 times lower than the concentration of the metabolite Ml. The amount of atoziban excreted through the intestine was not determined.

Indications

Atosiban is used when there is a threat of premature birth in pregnant women over 18 years of age during pregnancy from 24 to 33 completed weeks with a normal fetal heart rate in the following cases:

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

– cervical dilatation from 1 to 3 cm (0-3 cm for nulliparous women).

Pharmacological effect

Pharmacotherapeutic group:

Labor suppressant – oxytocin receptor blocker

ATX:

G.02.C.X Other preparations for gynecological use

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, by binding to oxytocin receptors, reduces the frequency of uterine contractions and myometrial tone, leading to suppression of uterine contractility. Atosiban also binds to vasopressin receptors, inhibiting the effect of vasopressin, but has no effect on the cardiovascular system.

If a woman develops premature labor, atosiban in recommended doses suppresses uterine contractions and provides functional rest to the uterus.

Relaxation of the uterus begins immediately after the administration of atosiban. Within 10 minutes, the contractile activity of the myometrium is significantly reduced, maintaining stable functional rest of the uterus (≤4 contractions per hour) for 12 hours.

Pharmacokinetics:
The pharmacokinetic parameters of atosiban (volume of distribution, clearance and half-life) are independent of dose.

Distribution

After intravenous (IV) infusion (300 mcg/min for 6-12 hours), the maximum plasma concentration of atosiban is achieved within 1 hour after the start of the infusion (average 442 ± 73 ng/ml, range from 298 to 533 ng/ml). Atosiban penetrates the placental barrier. The ratio of the concentration of atosiban in the fetus and in the mother is 0.12.

The binding of atosiban to plasma proteins in pregnant women is 46-48%. Average volume of distribution – 18.3±6.8 l.

Metabolism

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

Removal

After stopping the infusion, the concentration of atosiban in the blood plasma decreases rapidly with the initial (tα) and final (tβ) half-life values ​​of 0.21 ± 0.01 and 1.7 ± 0.3 hours, respectively. The average clearance of atosiban is 41.8±8.2 l/h.

Atosiban is detected in urine in very small quantities; its concentration in urine is 50 times lower than the concentration of the metabolite Ml. The amount of atosiban excreted through the intestine was not determined.

Special instructions

If there is no decrease in uterine contractility during the administration of atosiban, uterine contractions should be monitored and the fetal heart rate should be monitored. Other medications should also be considered.

The decision to continue or restart atosiban infusion during intrauterine retention depends on an assessment of fetal maturity.

There is no experience with the use of atosiban in pregnant women with impaired liver and kidney function. Caution should be exercised when prescribing atosiban to this category of patients.

Atosiban is not used in cases of abnormal placenta attachment.

As an oxytocin antagonist, atosiban may theoretically promote uterine relaxation and provoke postpartum uterine bleeding, so the degree of blood loss should be constantly assessed after childbirth.

Impact on the ability to drive vehicles. Wed and fur.:
Not applicable, given the indications for use.

Active ingredient

Atosiban

Composition

For 1 ml:

active ingredient: atosiban 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.

Pregnancy

Atosiban should only be used in cases of diagnosed preterm labor between 24 and 33 completed weeks of pregnancy.

Atosiban is contraindicated during breastfeeding.

Contraindications

– History of hypersensitivity to atosiban or any of the excipients of the drug;

– pregnancy period is less than 24 or more than 33 completed 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 continuation of pregnancy is dangerous;

– period of breastfeeding.

With caution:

If premature rupture of membranes is suspected, the use of atosiban to prolong pregnancy should be weighed against the potential risk of developing chorioamnionitis.

Atosiban should be used with caution in cases of impaired liver and kidney function, in multiple pregnancies, in 24-27 weeks of pregnancy (due to the lack of sufficient clinical experience), as well as when used together with other drugs that have a tocolytic effect.

Side Effects

Adverse reactions are listed below by organ and system, 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 reports.Immune system disorders: rarely – allergic reactions.Gastrointestinal disorders: very often – nausea, often – vomiting.Metabolic and nutritional disorders: often – hyperglycemia.Nervous system disorders: often – headache, dizziness; not often – insomnia.Cardiac disorders: often – tachycardia.Vascular disorders: often – arterial hypotension, hot flashes.Skin and subcutaneous tissue disorders: uncommon – itching, skin rash.Disorders of the genital organs and breast: very rarely – uterine bleeding/uterine atony.General disorders and disorders at the injection site: often – hyperthermia at the injection site, not often – fever.

Interaction

Atosiban does not affect the pharmacokinetics of drugs metabolized by cytochrome P450.

When atosiban and betamethasone were used together, no clinically significant interactions were observed.

Labetalol does not affect the pharmacokinetics of atosiban.

Interaction of atosiban with antibiotics is unlikely.

The combined use of atosiban with ergot alkaloids is inappropriate due to the opposite pharmacological action and indications for use.

Overdose

There are several known cases of overdose. There are no specific symptoms or signs.

Treatment consists of symptomatic and supportive therapy. A specific antidote is unknown.

Storage conditions

In a place protected from light, at a temperature of 2 to 8 ° C.
Keep out of the reach of children.

Shelf life

3 years.

Manufacturer

Farmidea Ltd., Latvia