TRACTOCILE SOLUTION FOR INJECTION (Each ml contains Atosiban 7.5mg)

Indications

• Management of preterm labor between 24 and 33 weeks of gestation
• Prevention of premature birth

Dosage

Adults: Initially by intravenous injection: 6.75 mg over 1 minute, then an intravenous infusion of 18 mg/hour for 3 hours, followed by a reduction to 6 mg/hour for up to 45 hours. Maximum duration of treatment is 48 hours.

Mechanism of action

Atosiban binds to membrane-bound oxytocin receptors on the myometrium, preventing oxytocin-stimulated increases in inositol triphosphate production. This inhibition blocks the release of stored calcium from the sarcoplasmic reticulum and the opening of voltage-gated calcium channels, leading to a decrease in cytosolic calcium levels and preventing uterine contractions. Additionally, atosiban acts as a biased ligand at oxytocin receptors, antagonizing Gq coupling and agonizing Gi coupling, which may contribute to its pro-inflammatory effects in the human amnion.

Pharmacodynamics

Atosiban effectively reduces the frequency of uterine contractions, promoting uterine quiescence and thereby delaying preterm birth in adult females. Its action is essential in managing cases of premature labor to enhance fetal outcomes.

Pharmacokinetics

Atosiban is administered via intravenous injection, where it exhibits rapid distribution. Its pharmacokinetic profile includes a half-life that supports its use in continuous infusion for maintaining therapeutic levels. The drug is primarily metabolized via enzymatic processes and excreted through renal pathways, necessitating caution in patients with renal impairment.

Contra-indications

• Eclampsia
• Epilepsy
• Pre-eclampsia

Adverse effects

• Dizziness
• Headache
• Hot flush
• Hyperglycaemia
• Hypotension
• Nausea
• Tachycardia

Precautions

• Asthma
• Cardiovascular disease (avoid if severe)
• Hyponatraemia
• Migraine
• Intra-uterine growth restriction

Pregnancy

Atosiban is used for the treatment of uncomplicated premature labour between 24 and 33 weeks of gestation.

Breast-feeding

Information not available.

Storage

Store at 2 to 8 degrees Celsius. Protect from light.

Formulations

• Solution for injection

Mechanism of action

Atosiban is a synthetic peptide oxytocin antagonist. It resembles oxytocin with has modifications at the 1, 2, 4, and 8 positions. The N-terminus of the cysteine residue is deaminated to form 3-mercaptopropanic acid at position 1, at position 2 L-tyrosine is modified to D-tyrosine with an ethoxy group replacing the phenol , threonine replaces glutamine at postion 4, and ornithine replaces leucine at position 8. 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.

Pharmacodynamics

Atosiban reduces the frequency of uterine contractions to delay pre-term birth in adult females and induces uterine quiescence.