TRACTOCILE Solution for injection Ref.[6331] 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. Renal impairment is not likely to warrant a dose adjustment, since only a small extent of atosiban is excreted in the urine. In patients with impaired hepatic function, atosiban should be used with caution (see sections 4.2 and 5.2).

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.

Multiple pregnancy and medicinal products with tocolytic activity like calcium channel blockers and betamimetics are known to be associated with increased risk of pulmonary oedema. Therefore, atosiban should be used with caution in case of multiple pregnancy and/or concomitant administration of other medicinal products with tocolytic activity (see section 4.8).

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.

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 Tractocile, 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 (see section 5.3).

Not relevant.

Possible adverse reactions of atosiban were described for the mother during the use of atosiban in clinical trials. In total 48% of the patients treated with atosiban experienced adverse reactions during the clinical trials. The observed adverse reactions were generally of a mild severity. The most commonly reported adverse reaction in the mother is nausea (14%).

For the newborn, the clinical trials did not reveal any specific adverse reactions of atosiban. The infant adverse reactions were in the range of normal variation and were comparable with both placebo and betamimetic group incidences.

The frequency of adverse reactions listed below is defined using the following convention: Very common (≥1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Immune system disorders

Rare: Allergic reaction

Metabolism and nutrition disorders

Common: Hyperglycaemia

Psychiatric disorder

Uncommon: Insomnia

Nervous system disorders

Common: Headache, Dizziness

Cardiac disorders

Common: Tachycardia

Vascular disorders

Common: Hypotension, Hot flush

Gastrointestinal disorders

Very common: Nausea

Common: Vomiting

Skin and subcutaneous tissue disorders

Uncommon: Pruritis, Rash

Reproductive system and breast disorder

Rare: Uterine haemorrhage, uterine atony

General disorders and administration site conditions

Common: Injection site reaction

Uncommon: Pyrexia

Post-marketing experience

Respiratory events like dyspnoea and pulmonary oedema, particularly in association with concomitant administration of other medicinal products with tocolytic activity, like calcium antagonists and betamimetics, and/or in women with multiple pregnancy, have been reported post-marketing.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

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