Atosiban

/ Ferring Pharmaceuticals

Treatment with Atosiban-Ferring should be initiated and maintained by a physician experienced in the treatment of pre-term labour.
Atosiban-Ferring is administered intravenously in three successive stages: an initial bolus dose (6.75 mg), performed with Atosiban-Ferring 6.75 ml/0.9ml solution for injection, immediately followed by a continuous high dose infusion (loading infusion 300 µg/min) of Atosiban-Ferring 37.5 mg/5 ml concentrate for solution for infusion during three hours, followed by a lower dose of Atosiban-Ferring 37.5 mg/5 ml concentrate for solution for infusion (subsequent infusion 100 µg/min) up to 45 hours. The duration of the treatment should not exceed 48 hours. The total dose given during a full course of Atosiban-Ferring therapy should preferably not exceed 330 mg of the active substance.
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.
In the case of persistence of uterine contractions during treatment with Atosiban-Ferring, alternative therapy should be considered.
The following table shows the full posology of the bolus injection followed by the infusion:
Step 1:
Regimen: 0.9 ml intravenous bolus
Injection/infusion rate: Over 1 minute
Atosiban-Ferring dose: 6.75 mg
Step 2:
Regimen:: 3 hours intravenous loading infusion
Injection/infusion rate: 24 ml/hour
Atosiban-Ferring dose: 54 mg
Step 3:
Regimen:Subsequent intravenous infusion
Injection/infusion rate: 8 ml/hour
Atosiban-Ferring dose: Up to 270 mg

To delay imminent pre-term birth in pregnant women with: Regular uterine contractions of at least 30 seconds duration at a rate of 4 or more per 30 minutes; a cervical dilation of 1 to 3 cm (0-3 for nulliparas) and effacement of 50% or more; age: 18 years and above; a gestational age from 24 until 33 completed weeks; a normal fetal heart rate.

Gestational age below 24 or over 33 completed weeks, premature rupture of the membranes less than 30 weeks of gestation, intrauterine growth retardation and abnormal foetal heart rate, antepartum uterine hemorrh. requring immediate delivery, eclampsia and severe pre-eclampsia requiring delivery, intrauterine foetal death, suspected intrauterine infection, placenta previa, abruptio placenta, any other condition of mother or foetus which is hazardous, known hypersensitivity.

In patients whom premature rupture of membranes cannot be excluded, the benefits of delaying delivery should be balanced against the potential risk of chorioamnionitis.
See prescribing information for full details.

The most commonly reported adverse reaction in the mother is nausea (14%).
See prescribing information for full details.

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 metabolizing 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.

Atosiban-Ferring 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 Atosiban-Ferring, since the release of oxytocin during breast-feeding may augment uterine contractility, and may counteract the effect of tocolytic therapy.
In Atosiban-Ferring clinical trials, no effects were observed on lactation. Small amounts of atosiban have been shown to pass from plasma into the breast milk of lactating 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-Ferring overdosing were reported, they occurred without any specific signs or symptoms. There is no known specific treatment in case of an overdose.