Traktocil, 7.5 mg/ml 5 ml

The active ingredient of Tractocil is atoziban, a synthetic peptide that is a competitive antagonist of human oxytocin at the receptor level.

Atoziban, binding to oxytocin receptors, reduces 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 cardiovascular system.

In cases of premature labor in women atoziban inhibits uterine contractions and provides uterine functional rest in recommended doses. Uterine relaxation begins immediately after administering atoziban and myometrium contractile activity is significantly reduced within 10 minutes, maintaining stable functional peace of the uterus (<4 contractions/h) for 12 hours.

Pharmacokinetics

Pharmacokinetic parameters (Vd, Cl, T1/2).

Distribution.

After intravenous infusion (300 mcg/min for 6-12 h), the Cmax of atoziban in plasma is reached within 1 h after the start of infusion (average (442±73) ng/mL, range 298 to 533 ng/mL). Binding to plasma proteins is 46-48%. Atoziban penetrates through the placental barrier. After administration of Tractocil at a rate of 300 µg/min, the ratio of atoziban concentration in the fetus to that of atoziban in the mother is 0.12. The mean Vd value is (18.3 ± 6.8) l.

Metabolism.

Two metabolites have been identified in plasma and urine. The ratio of the concentration of the main metabolite M1 to the plasma concentration of atoziban was 1.4 and 2.8 at the second hour of infusion and after discontinuation of the infusion, respectively. M1 metabolite 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 drug concentration decreases rapidly with initial (Ta) and final (Tp) T1/2 values of (0.21±0.01) and (1.7±0.3) h, respectively. The mean drug clearance is (41.8±8.2) l/h.
Atoziban is determined in the urine in very small amounts, its concentration in the urine being 50 times lower than that of M1. The amount of atoziban excreted with feces was not determined.

Indications

Tractocil is used in the threat of preterm labor in pregnant women in the following cases:

• regular uterine contractions of at least 30 s and a frequency of more than 4 for 30 minutes;
• opening of the cervix from 1 to 3 cm (0-3 cm for non-pregnant women);
• over 18 years of age;
• gestational age from 24 to 33 full weeks;
• normal fetal heart rate.

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Active ingredient

Atoziban

Composition

Ingredients per 1 ml:

active ingredient:

atosiban acetate in terms of atosiban 7.5 mg;

excipients:

mannitol 50 mg,

hydrochloric acid to pH 4.5,

water for injection to 1 ml.

How to take, the dosage

Tractocil is administered by IV infusion immediately after the diagnosis of preterm labor in 3 stages:
1) at the beginning, within 1 minute I fl. 0.9 ml of the drug without dilution (initial dose – 6.75 mg);
2) immediately thereafter, an infusion of the drug at a dose of 300 mcg/min for 3 hours (infusion rate – 24 ml/h, atosiban dose – 18 mg/h);
3) followed by a prolonged (up to 45 h) infusion of the drug Tractocil at a dose of 100 mcg/min (infusion rate – 8 ml/h, atosiban dose – 6 mg/h).

The total duration of treatment should not exceed 48 hours. The maximum dose of Tractocil for the whole course should not exceed 330 mg.

If there is a need for repeated administration of Tractocil it is also necessary to start from the 1st stage followed by infusion of the drug (stages 2 and 3).
The repeated administration can be started at any time after the first drug administration, it can be repeated up to 3 cycles.
If after 3 cycles of therapy with Tractocil uterine contractility does not decrease, you should consider using another drug.

Instructions for preparation of the infusion solution (steps 2 and 3)

The concentrate is diluted in one of the following solutions:
– 0.9% sodium chloride solution;
– Ringer’s acetate solution;
– 5% glucose solution.

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Interaction

Interaction with other drugs

Tractocil has no effect on the pharmacokinetics of drugs that are metabolized with cytochrome P450.
No clinically significant interactions were observed when using Tractocil and betamethasone together.

Labetalol does not affect the pharmacokinetics of the drug Tractocil.

Interaction of the drug Tractocil with antibiotics is unlikely.

It is not advisable to use Tractocil together with ergot alkaloids due to the opposite pharmacological effects and indications for use.

Special Instructions

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

There is no experience of using atoziban in patients with impaired hepatic and renal function.

Atoziban is not used in cases of abnormal placental attachment. As an oxytocin antagonist, atoziban may theoretically promote uterine relaxation and provoke postpartum uterine bleeding, so the degree of blood loss after delivery should be continuously assessed.

Effect on driving and attention-demanding machinery. Not applicable, given the indications for use.

Contraindications

• Pregnancy less than 24 or more than 33 full weeks;
• preterm rupture of membranes in pregnancies of more than 30 weeks;
• intrauterine fetal retardation;
• Anomalous fetal heart rate;
• Uterine bleeding requiring an immediate delivery;
• eclampsia and severe pre-eclampsia requiring an immediate delivery
intrauterine fetal death;
• consideration of intrauterine infection;
• presentation of the placenta;
• placenta detachment;
• Breastfeeding;
• High sensitivity to atoziban or to one of the components of the drug.

With caution: if premature rupture of membranes is suspected, the use of Tractocil for prolongation of labor should be compared to the potential risk of chorioamnionitis. Caution should be exercised when using Tractocil in multiple gestation, as well as in 24-27 weeks’ gestation (due to lack of sufficient clinical experience).

Side effects

Gastrointestinal tract: very often (>1/10) – nausea, rarely – vomiting.

Metabolism: often (>1/100, <1/10) – hyperglycemia.

CNS: frequently (>1/100, <1/10) – headache, dizziness; rarely (>1/1000, <1/100) – insomnia.

Cardiovascular system: frequently (>1/100, <1/10) – tachycardia, arterial hypotension, hot flashes.

Skin: rarely (>1/1000, <1/100) – itching, skin rash.

Local reactions: rare (>1/1000, <1/100) – hyperthermia in the injection site.

Reproductive organs: very rare (>1/10000, <1/1000) – uterine bleeding/uterine atony.

If any of the side effects specified in the instructions worsen, or any other side effects not specified in the instructions develop, you should inform the doctor.

Overdose

Several cases of overdose are known. There are no specific symptoms and signs. The specific antidote is unknown.

Treatment consists of symptomatic and supportive therapy.

Pregnancy use

Tractocil should be used only in cases of diagnosed preterm labor from 24 to 33 full weeks of pregnancy.
Tractocil is contraindicated in breastfeeding.