Peptide Schedule
Atosiban (Tractocile)9 residues (approx.)CYITNCPRGEach bubble = one amino acid. Size = residue mass. Color = chemical class.Uses closest standard amino acids for non-standard residues.Atosiban (Tractocile)
Benefits
About Atosiban (Tractocile)
Atosiban is a synthetic nonapeptide analogue of oxytocin that acts as a competitive antagonist at both oxytocin (OT) and vasopressin V1a receptors. Marketed in Europe under the brand name Tractocile, it was approved by the EMA in January 2000 and remains the only oxytocin receptor antagonist licensed for tocolysis — the pharmacological delay of preterm labor. Unlike beta-agonist tocolytics (e.g., ritodrine, terbutaline) which carry significant cardiovascular side effects, atosiban's receptor-selective mechanism gives it a substantially better maternal safety profile. In six pivotal clinical trials, atosiban significantly increased the proportion of women undelivered at 48 hours compared to placebo, providing a critical window for corticosteroid administration to accelerate fetal lung maturity. Atosiban's onset of action is rapid — uterine contractions are significantly reduced within 10 minutes of bolus injection, achieving stable uterine quiescence. The drug has minimal placental transfer (fetal-to-maternal ratio of 0.12), and plasma protein binding is 46-48%. It is metabolized to one major metabolite (M1) that retains roughly 10% of the parent compound's activity at the oxytocin receptor.
Who Should Consider Atosiban (Tractocile)
- Pregnant women at 24-33 weeks gestation with preterm uterine contractions
- Patients requiring tocolysis to allow corticosteroid administration for fetal lung maturity
- Women who cannot tolerate beta-agonist tocolytics due to cardiovascular side effects
- Patients needing time for maternal transfer to a facility with neonatal intensive care
How Atosiban (Tractocile) Works
Atosiban competitively antagonizes oxytocin at oxytocin receptors (OTRs) and vasopressin at V1a receptors on uterine myometrial cells. By blocking OTR-coupled Gq/11 signaling, it prevents the intracellular calcium mobilization and phospholipase C activation that drives myometrial contraction. Atosiban also suppresses oxytocin-mediated release of prostaglandins PGE2 and PGF2α from decidual tissue, further reducing uterine contractile drive. The dual OTR/V1a antagonism is pharmacologically significant because vasopressin V1a receptors are upregulated in the myometrium during late pregnancy and contribute to contractile tone independently of oxytocin signaling. At recommended doses, atosiban achieves steady-state plasma concentrations of approximately 442 ng/mL within one hour of initiating infusion, providing rapid and sustained tocolytic effect.
What to Expect
Rapid onset of tocolytic effect after IV bolus; significant reduction in uterine contractions.
Steady-state plasma concentration achieved (~442 ng/mL); stable uterine quiescence.
Transition from high-dose loading infusion (300 mcg/min) to maintenance infusion (100 mcg/min).
Critical treatment window: corticosteroids administered to mature fetal lungs; majority of patients remain undelivered.
Rapid decline in plasma levels after stopping infusion (terminal half-life ~1.7 hours). Uterine activity may return.
Dosing Protocol
| Level | Dose / Injection | Frequency |
|---|---|---|
| Beginner | 6.75mg | Single dose |
| Moderate | 6.75mg | Single dose |
| Aggressive | 6.75mg | Single dose |
Note: Atosiban is administered IV only in a hospital setting: 6.75 mg bolus over 1 minute, then 300 mcg/min infusion for 3 hours, then 100 mcg/min for up to 45 hours. Maximum total dose per course is 330.75 mg. EU-approved (Tractocile) since January 2000; NOT FDA-approved. Treatment should not exceed 48 hours. Not for use before 24 weeks or after 33 weeks gestation.
How to Inject Atosiban (Tractocile)
Atosiban is administered exclusively by IV in a hospital/clinical setting under obstetric supervision. Step 1: Bolus injection of 6.75 mg (one 0.9 mL vial) given slowly over 1 minute. Step 2: Immediately start a continuous high-dose infusion at 300 mcg/min for 3 hours (54 mg). Step 3: Reduce to a maintenance infusion at 100 mcg/min for up to 45 hours (up to 270 mg). The total treatment duration should not exceed 48 hours, with a maximum cumulative dose of 330.75 mg. For infusion preparation, dilute 5 mL concentrate vials (37.5 mg/5 mL) in 0.9% sodium chloride, Ringer's lactate, or 5% glucose solution. Monitor uterine activity and fetal heart rate throughout.
Cycling Protocol
Atosiban is not cycled. It is given as a single acute course of up to 48 hours in a hospital setting for preterm labor management. Re-treatment may be initiated if contractions recur, using the same bolus + infusion protocol.
Pharmacokinetics
Source: Terminal half-life (tβ) from EMA SmPC; initial half-life (tα) 0.21 hours. Clearance 41.8 L/h, Vd 18.3 L.
Loading the interactive decay curve.
Side Effects
Atosiban is generally well-tolerated with a favorable safety profile compared to other tocolytic agents. The most common side effect is nausea, occurring in more than 10% of patients. Common reactions (1-10%) include headache, dizziness, tachycardia, and vomiting. Uncommon effects (0.1-1%) include hypotension, hot flushes, pruritus, rash, uterine hemorrhage, injection site reactions, and pyrexia. Rare effects include allergic reactions, hyperglycemia, insomnia, and uterine atony. Post-marketing surveillance has identified respiratory events including dyspnea and pulmonary edema, particularly when used with concomitant tocolytics or in multiple pregnancies.
Contraindications
- Gestational age below 24 weeks or over 33 completed weeks
- Premature rupture of membranes after 30 weeks gestation
- Abnormal fetal heart rate indicating fetal distress
- Antepartum uterine hemorrhage requiring immediate delivery
- Eclampsia or severe preeclampsia requiring delivery
- Intrauterine fetal death
- Suspected intrauterine infection (chorioamnionitis)
- Placenta previa or abruptio placentae
- Known hypersensitivity to atosiban or any excipients
- Hepatic impairment — use with caution, monitor liver function
Drug Interactions
- Oxytocin and prostaglandins — pharmacological antagonism; concurrent use would negate the tocolytic effect of atosiban
- Other tocolytic agents — concomitant use may increase risk of pulmonary edema, especially in multiple pregnancies
- Betamethasone — no clinically relevant interaction identified in studies
- Labetalol — no clinically relevant interaction identified in studies
- CYP450-metabolized drugs — atosiban is not a CYP450 substrate and does not inhibit CYP450 enzymes; minimal interaction potential
Storage & Stability
Molecular Profile
Related Peptides
References
- The pharmacokinetics of the oxytocin antagonist atosiban in pregnant women with preterm uterine contractionsPubMed 7573268
- An oxytocin receptor antagonist (atosiban) in the treatment of preterm labor: a randomized, double-blind, placebo-controlled trial with tocolytic rescueClinical Trial
- Treatment of preterm labor with the oxytocin antagonist atosibanPubMed 8688103
- Treatment of preterm labor with the oxytocin and vasopressin antagonist atosibanPubMed 10224602
- Tractocile (atosiban) EMA Product InformationFDA Label
- Atosiban SmPC — UK Electronic Medicines CompendiumReview