Atosiban Sun

Atosiban EVER 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

Atosiban is administered intravenously in three successive stages: an initial bolus dose (6.75 mg), performed with Atosiban 6.75 mg/0.9 ml solution for injection, immediately followed by a continuous high dose infusion (loading infusion 300 micrograms/min) of Atosiban 37.5 mg/5 ml concentrate for solution for infusion during three hours, followed by a lower dose of Atosiban 37.5 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 Atosiban therapy should preferably not exceed 330.75 mg of atosiban.

Very common (affects more than 1 in 10 people): feeling sick (nausea).
Common (affects less than 1 in 10 people): headache, feeling dizzy, hot flushes, being sick (vomiting), fast heartbeat, Low blood pressure. Signs may include feeling dizzy or light-headed, A reaction at the site where the injection was given, high blood sugar.
Uncommon (affects less than 1 in 100 people): high temperature (fever), difficulty sleeping (insomnia), itching, rash.

When Atosiban EVER 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 EVER 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 EVER is excreted in the urine. In patients with impaired hepatic function, Atosiban EVER should be used with caution
There is only limited clinical experience in the use of Atosiban EVER 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 EVER in these subgroups is therefore uncertain.
Re-treatment with Atosiban EVER 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 Atosiban EVER depends on the assessment of fetal maturity.
Monitoring of uterine contractions and fetal heart rate during administration of Atosiban EVER and in case of persistent uterine contractions should be considered.
As an antagonist of oxytocin, Atosiban EVER 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 beta- mimetics are known to be associated with increased risk of pulmonary oedema. Therefore, Atosiban EVER should be used with caution in case of multiple pregnancy and/or concomitant administration of other medicinal products with tocolytic activity

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.