Tractocile 7.5 mg/ml Solution for injection Ref.[2523] Active ingredients: Atosiban

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 (see sections 4.2 and 5.2).

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 (see section 4.2).

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 Tmax 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.

Atosiban should only be used when pre-term labour has been diagnosed between 24 and 33 completed weeks of gestation.

In atosiban 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 (see section 5.3).

Not applicable.

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:

Very common (>1/10)

Gastrointestinal disorders: nausea.

Common (>1/100, <1/10)

Metabolism and nutrition disorders: hyperglycaemia

Nervous system disorders: headache, dizziness

Cardiac disorders: tachycardia

Vascular disorders: hot flush, hypotension

Gastrointestinal disorders: vomiting

General disorders and administration site conditions: injection site reaction

Uncommon (>1/1,000, <1/100)

Psychiatric disorders: insomnia

Skin and subcutaneous tissue disorders: pruritis, rash

General disorders and administration site conditions: pyrexia

Rare ( >1/10,000, <1/1,000)

Incidental cases of uterine haemorrhage/uterine atony were reported. The frequency did not exceed that of the control groups in clinical trials.

One case of allergic reaction was reported, which was considered to be probably related to atosiban.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.