Atosiban Acetate

Primary Indication:

• Treatment of preterm labor (between 24 and 33 completed weeks of gestation):
• Indicated to delay imminent preterm birth in pregnant women with:
• Regular uterine contractions lasting ≥30 seconds at a frequency of ≥4 per 30 minutes.
• Cervical dilation between 1 and 3 cm (0–3 cm for nulliparous women).
• Effacement of ≥50%.
• Intact amniotic membranes and a singleton pregnancy.

Important Off-Label/Clinically Accepted Uses:

• Currently, no major off-label uses are widely established in clinical guidelines. Use is typically restricted to hospital settings under obstetric supervision.

Route: Intravenous (IV) administration only.

Recommended Adult Dosing:

• Initial Bolus: 6.75 mg (0.9 mL of 7.5 mg/mL solution) administered slowly over 1 minute.
• First Continuous Infusion: 18 mg/hour over 3 hours (i.e., 24 mL/hour).
• Subsequent Maintenance Infusion: 6 mg/hour up to 45 hours (i.e., 8 mL/hour).

Maximum duration of treatment: 48 hours
Total maximum dose per treatment course: 330.75 mg

Elderly: Not applicable (not used in postmenopausal populations).

Pediatric: Not applicable.

Renal/Hepatic Impairment: No specific adjustments required; however, use with caution due to lack of extensive data.

Atosiban Acetate is a competitive antagonist of the oxytocin receptor. It inhibits oxytocin-induced uterine contractions by blocking oxytocin binding on the uterine smooth muscle. At higher concentrations, it also antagonizes vasopressin (V1a) receptors. By reducing intracellular calcium levels in uterine muscle cells, Atosiban decreases myometrial contractility and suppresses preterm labor without significant cardiovascular effects, making it a well-tolerated tocolytic agent.

• Absorption: Administered intravenously; complete bioavailability.
• Distribution: Volume of distribution ≈ 0.3 L/kg; protein binding ≈ 46–48%.
• Metabolism: Metabolized by peptidases in the liver and kidneys into inactive metabolites.
• Elimination:
• Half-life: Approx. 18 minutes (initial), terminal half-life up to 1.7 hours.
• Excretion primarily via the urine (∼50% as metabolites).
• Steady-state levels achieved rapidly due to IV administration.

• Pregnancy: Classified as Category B (US FDA - historical); human studies suggest low risk. Used during pregnancy specifically for obstetric intervention (i.e., delaying labor).
• Lactation:
• Excretion into human milk is minimal.
• No harmful effects observed in neonates breastfed post-therapy.
• Caution is still advised during breastfeeding immediately after use due to limited long-term data.

• Primary Class: Tocolytic Agent (Labor Suppressant)
• Sub-class: Oxytocin Receptor Antagonist

• Hypersensitivity to Atosiban or any excipients.
• Gestational age <24 or >33 completed weeks.
• Premature rupture of membranes at gestational age >30 weeks.
• Intrauterine fetal death or lethal fetal anomaly.
• Antepartum uterine hemorrhage requiring immediate delivery.
• Eclampsia or severe preeclampsia requiring delivery.
• Intrauterine infection.
• Placenta previa or abruptio placentae.

• Should only be used in a hospital setting with access to facilities for continuous maternal and fetal monitoring.
• Discontinue if labor progresses despite therapy.
• Monitor for:
• Uterine contractions
• Fetal heart rate
• Maternal vital signs
• Use caution in women with impaired liver or kidney function.
• Not recommended in multiple pregnancies or pregnancies >33 weeks due to limited safety data.
• Avoid repeated treatment cycles unless absolutely necessary.

Common Adverse Effects:

• Gastrointestinal: Nausea, vomiting
• Reproductive system: Uterine contractions, injection site reactions
• General: Headache, dizziness, tachycardia

Serious/Rare Effects:

• Hypotension
• Hyperglycemia
• Rash or allergic reactions
• Fetal or neonatal complications (rare and usually associated with underlying obstetric conditions rather than Atosiban itself)

• No significant CYP450 enzyme interactions.
• Can be co-administered with corticosteroids (e.g., betamethasone) used for fetal lung maturation.
• Avoid concomitant use with other tocolytics such as beta-agonists (e.g., ritodrine) due to increased risk of additive cardiovascular effects.

• Recent EMA guidelines confirm Atosiban as a first-line tocolytic option due to a favorable safety profile compared to beta-agonists.
• Preferred for women at risk of preterm delivery who cannot tolerate nifedipine or other agents.
• No changes in dosing or contraindications as of current regulatory updates (FDA/EMA/NICE 2023–2025).

• Storage Temperature: Store below 25°C.
• Light Protection: Keep in original packaging to protect from light.
• Handling: Do not freeze. Do not shake.
• Reconstitution: Not applicable (comes ready to use).
• Shelf-life after opening: Use immediately after opening the vial; discard unused portion.