TOCOBAN -6.75

It is indicated to delay imminent pre-term birth in pregnant adult women with:  regular uterine contractions of at least 30 seconds duration at a rate of 4 per 30 minutes

 a cervical dilation of 1 to 3 cm (0-3 for nulliparas) and effacement of 50% 

 a gestational age from 24 until 33 completed weeks  a normal fetal heart rate.

Delay imminent pre-term birth in pregnant adult women

It binds to membrane bound oxytocin receptors on the myometrium and prevents oxytocin-stimulated increases in inositol triphosphate production. This ultimately prevents release of stored calcium from the sarcoplasmic reticulum and subsequent opening of voltage gated calcium channels. This shutdown of cytosolic calcium increase prevents contractions of the uterine muscle, reducing the frequency of contractions and inducing uterine quiescence. Atosiban has more recently been found to act as a biased ligand at oxytocin receptors. It acts as an antagonist of Gq coupling, explaining the inhibition of the inositol triphosphate pathway thought to be responsible for the effect on uterine contraction, but acts as an agonist of Gi coupling. This agonism produces a pro-inflammatory effect in the human amnion, activating pro-inflammatory signal tranducer NF-κB. It is thought that this reduces atosiban's effectiveness compared to agents which do not produce inflammation as inflammatory mediators are known to play a role in the induction of labour.

Treatment with it should be initiated and maintained by a physician experienced in the treatment of
pre-term labour.
itis administered intravenously in three successive stages: an initial bolus dose (6.75 mg),
performed with it6.75 mg/0.9 ml solution for injection, immediately followed by a continuous high
dose infusion (loading infusion 300 micrograms/min) of it37.5 mg/5 ml concentrate for solution for
infusion during three hours, followed by a lower dose of it37.5 mg/5 ml concentrate for solution for
infusion (subsequent infusion 100 micrograms/min) up to 45 hours. The duration of the treatment should not
exceed 48 hours. The total dose given during a full course of ittherapy should preferably not exceed
330.75 mg of atosiban.
Intravenous therapy using the initial bolus injection should be started as soon as possible after diagnosis of
pre-term labour. Once the bolus has been injected, proceed with the infusion (See Summary of Product
Characteristics of it37.5 mg/5 ml, concentrate for solution for infusion). In the case of persistence
of uterine contractions during treatment with Tractocile, alternative therapy should be considered.

It is unlikely that atosiban is involved in cytochrome P450 mediated drug-drug interactions as in vitro investigations have shown that atosiban is not a substrate for the cytochrome P450 system, and does not inhibit the drug metabolising cytochrome P450 enzymes. Interaction studies have been performed with labetalol and betamethasone in healthy, female volunteers. No clinically relevant interaction was found between atosiban and bethamethasone or labetalol.

It must not be used in the following conditions: -Gestational age below 24 or over 33 completed weeks 

- Premature rupture of the membranes >30 weeks of gestation 

- Abnormal foetal heart rate

- Antepartum uterine haemorrhage requiring immediate delivery 

- Eclampsia and severe pre-eclampsia requiring delivery

- Intrauterine foetal death 

- Suspected intrauterine infection 

- Placenta praevia 

- Abruptio placenta 

- Any other conditions of the mother or foetus, in which continuation of pregnancy is hazardous 

- Hypersensitivity to the active substance(s) or to any of the excipients

The most commonly reported
side effect in the mother is nausea 

Atosiban should only be used when pre-term labour has been diagnosed between 24 and 33 completed weeks of gestation. If during pregnancy the woman is already breast-feeding an earlier child, then breast-feeding should be discontinued during treatment with it, since the release of oxytocin during breast-feeding may augment uterine contractility, and may counteract the effect of tocolytic therapy. In atosiban clinical trials no effects were observed on breast-feeding. Small amounts of atosiban have been shown to pass from plasma into the breast milk of breast-feeding women. Embryo-fetal toxicity studies have not shown toxic effects of atosiban. No studies were performed that covered fertility and early embryonic development

Few cases of atosiban overdosing were reported, they occurred without any specific signs or symptoms. There is no known specific treatment in case of an overdose.

Store in a refrigerator (2°C-8°C). Keep away from light & moisture. Keep out of the reach of children.

-