Atosiban Acetate
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.
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.
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 must not be used in the following conditions:Gestational age below 24 or over 33 completed weeksPremature rupture of the membranes >30 weeks of gestationAbnormal foetal heart rateAntepartum uterine haemorrhage requiring immediate deliveryEclampsia and severe pre-eclampsia requiring deliveryIntrauterine foetal deathSuspected intrauterine infectionPlacenta praeviaAbruptio placentaAny other conditions of the mother or foetus, in which continuation of pregnancy is hazardous
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.
If you are pregnant and breast-feeding an earlier child, you should stop breast-feeding while you are givenAtosiban.
When Atosiban Sun 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 Sun 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 Sun is excreted in the urine. In patients with impaired hepatic function, Atosiban Sun should be used with cautionThere is only limited clinical experience in the use of Atosiban Sun 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 Sun in these subgroups is therefore uncertain.Re-treatment with Atosiban Sun 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 Sun depends on the assessment of fetal maturity.Monitoring of uterine contractions and fetal heart rate during administration of Atosiban Sun and in case of persistent uterine contractions should be considered.As an antagonist of oxytocin, Atosiban Sun 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 Sun should be used with caution in case of multiple pregnancy and/or concomitant administration of other medicinal products with tocolytic activity
Other preparations
Store in a refrigerator (2°C-8°C). Keep away from light & moisture. Keep out of the reach of children.
{'Indications': 'Atosiban Sun 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 minutesa cervical dilation of 1 to 3 cm (0-3 for nulliparas) and effacement of ≥50%a gestational age from 24 until 33 completed weeksa normal fetal heart rate'}