One ml solution contains 7.5 mg atosiban free-base in the form of atosiban acetate.

Solution for injection Visual appearance: clear, colourless solution without particles

TRACTOCILE is indicated to delay imminent pre-term birth in pregnant 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%

− age 18 years

− a gestational age from 24 until 33 completed weeks

− a normal fetal heart rate

Treatment with TRACTOCILE should be initiated and maintained by a physician experienced in the treatment of pre-term labour.

TRACTOCILE is administered intravenously in three successive stages: an initial bolus dose (6.75 mg), performed with TRACTOCILE 7.5 mg/ml solution for injection, immediately followed by a continuous high dose infusion (loading infusion 300 micrograms/min) of TRACTOCILE 7.5 mg/ml concentrate for solution for infusion during three hours, followed by a lower dose of TRACTOCILE 7.5 mg/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 TRACTOCILE 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 (See Summary of Product Characteristics of TRACTOCILE 7.5 mg/ml, concentrate for solution for infusion). In the case of persistence of uterine contractions during treatment with TRACTOCILE, alternative therapy should be considered.

There is no data available regarding the need for dose adjustments in patients with renal or liver insufficiency.

The following table shows the full posology of the bolus injection followed by the infusion:

Re-treatment

In case a re-treatment with atosiban is needed, it should also commence with a bolus injection of TRACTOCILE 7.5 mg/ml, solution for injection followed by infusion with TRACTOCILE 7.5 mg/ml, concentrate for solution for infusion.

TRACTOCILE should 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

− Intrauterine growth retardation and abnormal fetal heart rate

− Antepartum uterine haemorrhage requiring immediate delivery

− Eclampsia and severe pre-eclampsia requiring delivery

− Intrauterine fetal death

− Suspected intrauterine infection

− Placenta praevia

− Abruptio placenta

− Any other conditions of the mother or fetus, in which continuation of pregnancy is hazardous

− Known hypersensitivity to the active substance or any of the excipients.

When atosiban is used in patients in whom premature rupture of membranes cannot be excluded, the benefits of delaying delivery should be balanced against the potential risk of chorioamnionitis.

There is no experience with atosiban treatment in patients with impaired function of the liver or kidneys

Atosiban has not been used in patients with an abnormal placental site.

There is only limited clinical experience in the use of atosiban in multiple pregnancies or the gestational age group between 24 and 27 weeks, because of the small number of patients treated. The benefit of atosiban in these subgroups is therefore uncertain.

Re-treatment with TRACTOCILE is possible, but there is only limited clinical experience available with multiple re-treatments, up to 3 re-treatments.

In case of intrauterine growth retardation, the decision to continue or reinitiate the administration of TRACTOCILE depends on the assessment of fetal maturity.

Monitoring of uterine contractions and fetal heart rate during administration of atosiban and in case of persistent uterine contractions should be considered.

As an antagonist of oxytocin, atosiban may theoretically facilitate uterine relaxation and postpartum bleeding therefore blood loss after delivery should be monitored. However, inadequate uterus contraction postpartum was not observed during the clinical trials.

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 were performed in healthy, female volunteers with betamethasone and labetalol. No clinically relevant interaction was observed between atosiban and betamethasone. When atosiban and labetalol were co-administrated, C_max of labetalol was decreased by 36% and T_max increased by 45 minutes. However, the extent of labetalol bioavailability in terms of AUC did not change. The interaction observed has no clinical relevance. Labetalol had no effect on atosiban pharmacokinetics.

No interaction study has been performed with antibiotics, ergot alkaloids, and anti-hypertensive agents other than labetalol.

Possible undesirable effects of atosiban were described for the mother during the use of atosiban in clinical trials. The observed undesirable effects were generally of a mild severity. In total 48% of the patients treated with atosiban experienced undesirable effects.

For the newborn, the clinical trials did not reveal any specific undesirable effects of atosiban. The infant adverse events were in the range of normal variation and were comparable with both placebo and beta-mimetic group incidences.

The undesirable effects in the women were the following:

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