Traktotsil

General characteristics. Structure:

Concentrate for preparation of solution for infusions of 7,5 mg/ml - 1 фл.
Active agent: an atozibana acetate (in terms of атозибан) - 7,5 mg
excipients: Mannitolum — 50 mg; Acidum hydrochloricum — to рН 4,5; water for injections — to 1 ml

Pharmacological properties:

Blocking oksitotsinovy retseptolra.

Pharmacodynamics. Traktotsil is active component of drug атозибан, synthetic peptide, being the competitive antagonist of human oxytocin at the level of receptors.

Atoziban, contacting oxytocin receptors, reduces the frequency of uterine reductions and a tone of a myometrium, leading to suppression of contractility of a uterus. Also атозибан contacts vasopressin receptors, oppressing effect of vasopressin, but at the same time does not exert impact on CCC.

In case of development of premature births in the woman атозибан in the recommended doses suppresses reductions of a uterus and provides to a uterus functional rest. Relaxation of a uterus begins right after introduction of an atoziban, within 10 min. sokratitelny activity of a myometrium considerably decreases, maintaining stable functional rest of a uterus (<4 reductions/h) during 12 h.

Pharmacokinetics. Pharmacokinetic indicators (Vd, Cl, T1/2).

Distribution. Later in/in infusion (300 mkg/min. during 6–12 h) Cmax of an atoziban in plasma is reached during 1 h after the beginning of infusion (on average (442±73) ng/ml, in the range from 298 to 533 ng/ml). Linkng with proteins of plasma makes 46–48%. Atoziban gets through a placental barrier. After administration of drug Traktotsil with a speed of 300 mkg/min. the ratio of concentration of an atoziban in an organism of mother is equal in an organism of a fruit and concentration of an atoziban to 0,12. Average Vd value — (18,3 ± 6,8) l.

Metabolism. In a blood plasma and urine 2 metabolites are identified. The ratio of concentration of the main metabolite of M1 and concentration of an atoziban in a blood plasma made 1,4 and 2,8 on the second hour of infusion and after its termination respectively. The metabolite of M1 has pharmacological activity on an equal basis with atozibany and gets into breast milk.

The inhibition atozibany isoforms of P450 cytochrome is improbable.

Removal. After the infusion termination concentration of drug in plasma quickly decreases with values initial (Ta) and final (Tp) T1/2 (0,21±0,01) and (1,7±0,3) h, respectively. Average value of clearance of drug — (41,8±8,2) l/h.

Atoziban is defined in urine in very small quantities, its concentration in urine is 50 times lower than concentration of M1. The quantity of the atoziban removed with a stake was not defined.

Indications to use:

Traktotsil is applied at threat of premature births at pregnant women in the following cases:
- regular reductions of a uterus lasting not less than 30 with and with a frequency more than 4 within 30 min.;
- disclosure of a neck of uterus from 1 to 3 cm (0–3 cm for not giving birth women);
- the age is more senior than 18 years;
- duration of gestation from 24 to 33 full weeks;
- normal ChSS at a fruit.

Route of administration and doses:

Traktotsil is entered in/in at once after diagnosis premature births into 3 stages:

1) at the beginning, within 1 min. I is entered фл. on 0,9 ml of drug without cultivation (an initial dose — 6,75 mg);

2) right after it during 3 h infusion of drug in a dose of 300 mkg/min. is carried out (rate of administering — 24 ml/h, a dose of an atoziban — 18 mg/h);

3) after that drug infusion Traktotsil in a dose of 100 mkg/min. is carried out long (to 45 h) (rate of administering — 8 ml/h, a dose of an atoziban — 6 mg/h).

The general duration of treatment should not exceed 48 h. The maximum dose of drug Traktotsil on all course should not exceed 330 mg.

If there is a need for repeated use of drug Traktotsil, it is also necessary to begin with the 1st stage which infusional administration of drug (stages of the 2nd and 3rd) will follow.

Repeated use can be begun after the first use of drug at any time, it is possible to repeat it to 3 cycles.

If after 3 cycles of therapy by drug Traktotsil the sokratitelny uterine activity does not decrease, it is necessary to consider a question of use of other drug.

The instruction for preparation of solution for infusion (stage 2nd and 3rd)

The concentrate is parted in one of the following solutions:

- 0,9% of solution of sodium of chloride;

- Ringer's solution of acetate;

- 5% glucose solution.

From the bottle containing 100 ml of one of above-mentioned solutions for cultivation merge 10 ml. Then enter 10 ml into a bottle (2 фл.) drug Traktotsil for obtaining concentration of 75 mg / 100 ml.

Period of validity of the prepared solution for infusions of 24 h. Not to apply if in solution not dissolved particles are visible or solution changed color.

Features of use:

In case of lack of decrease in a sokratitelny uterine activity during administration of drug Traktotsil it is necessary to carry out monitoring of reductions of a uterus, and also to watch fruit ChSS. Also it is necessary to consider the possibility of use of other drugs.

Experience of use of an atoziban for patients with an abnormal liver function and kidneys is absent.

Atoziban is not applied in cases of an abnormal implantation of placenta. As the antagonist of oxytocin, атозибан can theoretically promote a relaxation of a uterus and provoke puerperal uterine bleeding therefore it is necessary to carry out constantly blood loss degree assessment after the delivery.

Influence on ability to drive the car and mechanisms requiring special attention. It is inapplicable, considering indications to use.

Side effects:

From a GIT: very often (> 1/10) — nausea, is more rare — vomiting.
From a metabolism: often (> 1/100, <1/10) — a hyperglycemia.
From TsNS: often (> 1/100, <1/10) — a headache, dizziness; seldom (> 1/1000, <1/100) — sleeplessness.
From CCC: often (> 1/100, <1/10) — tachycardia, arterial hypotension, inflows.
From skin: seldom (> 1/1000, <1/100) — an itch, skin rash.
Local reactions: seldom (> 1/1000, <1/100) — a hyperthermia in an injection site.
From reproductive organs: very seldom (> 1/10000, <1/1000) — uterine bleeding / atony of a uterus.

If any of the side effects specified in the instruction are aggravated, or any other side effects which are not specified in the instruction developed, it is necessary to report about it to the doctor.

Interaction with other medicines:

Traktotsil does not influence pharmacokinetics of the drugs which are metabolized with P450 cytochrome participation.

At combined use of drug Traktotsil and betamethasone clinically significant interactions were not noted.

Labetalol does not influence drug pharmacokinetics Traktotsil.

Drug interaction Traktotsil with antibiotics is improbable.

Combined use of drug Traktotsil with alkaloids of an ergot is inexpedient in connection with opposite pharmacological action and indications to use.

Contraindications:

- duration of gestation less than 24 or more 33 full weeks;
- a premature rupture of covers at pregnancy more than 30 weeks;
- pre-natal arrest of development of a fruit;
- abnormal ChSS at a fruit;
- the uterine bleeding demanding immediate childbirth;
- the eclampsia and a heavy preeclampsia demanding immediate childbirth;
- pre-natal death of a fruit;
- suspicion of inside uterine infection;
- placental presentation;
- placental detachment;
- any conditions of mother and a fruit at which preservation of pregnancy constitutes danger;
- breastfeeding;
- hypersensitivity to an atoziban or to one of drug components.

With care: in case of suspicion on a premature rupture of covers drug use Traktotsil for prolongation of childbirth should be compared with potential risk of development of a horioamnionit. About care to apply Traktotsil at polycarpous pregnancy, and also at duration of gestation of 24-27 weeks (due to the lack of sufficient clinical experience).

Use at pregnancy and feeding by a breast
Traktotsil it is necessary to apply only in case of the diagnosed premature births from 24 to 33 full weeks of pregnancy.
Traktotsil is contraindicated when breastfeeding.

Overdose:

Several cases of overdose are known. Specific symptoms and signs are absent. The specific antidote is unknown.

Treatment consists in a symptomatic and maintenance therapy.

Storage conditions:

In the place protected from light, at a temperature not above 25 °C.
To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Concentrate for preparation of solution for infusions, 7,5 mg/ml. On 0,9 ml of drug in the colourless bottle with a capacity of 2 ml from glass like I corked by a bromobutilovy stopper of gray color and hermetically closed by a cover like "flip-off".

On 5 ml of drug in the colourless bottle with a capacity of 5 ml from glass like I corked by a bromobutilovy stopper of gray color and hermetically closed by a cover like "flip-off". On 1 фл. place in plastic packaging and in a cardboard pack.