Atosiban Accord
Oxytocin receptor antagonist for delaying preterm birth
Quick facts about Atosiban Accord
Key takeaways about Atosiban Accord
- Hospital-only medication: Atosiban Accord must be administered intravenously under specialist obstetric supervision in a hospital setting
- Delays preterm birth by up to 48 hours: The primary goal is to provide enough time for corticosteroid administration to improve foetal lung maturity
- Better tolerated than beta-agonists: Atosiban has significantly fewer cardiovascular and metabolic side effects compared to older tocolytic agents
- Gestational window 24-33 weeks: Not recommended before 24 weeks or after 33 completed weeks of gestation
- Maximum treatment duration 48 hours: Total treatment should not exceed 48 hours per course, and retreatment may be considered if contractions recur
What Is Atosiban Accord and What Is It Used For?
Atosiban Accord is a tocolytic medication containing atosiban, a synthetic peptide that blocks oxytocin receptors in the uterus. It is used to delay imminent preterm birth in pregnant women between 24 and 33 completed weeks of gestation who have regular uterine contractions, cervical dilation of 1-3 cm, and an intact amniotic membrane or minimal rupture.
Preterm birth, defined as delivery before 37 completed weeks of gestation, affects approximately 10% of all pregnancies worldwide and is the leading cause of neonatal morbidity and mortality. The primary objective of tocolytic therapy with atosiban is not to prevent preterm delivery altogether, but rather to delay it by 48 hours to 7 days. This critical window allows for two essential interventions: the administration of antenatal corticosteroids (such as betamethasone or dexamethasone) to accelerate foetal lung maturation, and the transfer of the mother to a tertiary care centre with neonatal intensive care capabilities if needed.
Atosiban works through a highly specific mechanism. It is a competitive antagonist at oxytocin receptors located on uterine smooth muscle cells (myometrial cells). Oxytocin is a naturally occurring hormone that plays a central role in initiating and sustaining uterine contractions during labour. By binding to these receptors without activating them, atosiban prevents oxytocin from triggering the intracellular calcium release cascade that causes muscle contraction. This results in a dose-dependent reduction in both the frequency and intensity of uterine contractions.
In addition to its action on oxytocin receptors, atosiban also has some affinity for vasopressin V1a receptors, which contributes to its overall pharmacological profile. However, its selectivity for the oxytocin receptor is considerably greater, which is a key advantage from a safety perspective. Unlike beta-adrenergic agonists (such as ritodrine or salbutamol) that were historically used as tocolytics, atosiban does not affect cardiac beta-receptors, resulting in a significantly lower risk of maternal cardiovascular side effects such as tachycardia, palpitations and pulmonary oedema.
Atosiban was first approved by the European Medicines Agency (EMA) in 2000 under the brand name Tractocile. Atosiban Accord is a generic formulation manufactured by Accord Healthcare, containing the same active substance and demonstrating bioequivalence with the reference product. It is available in two presentations: a 6.75 mg/0.9 mL solution for injection in a pre-filled syringe (for the initial bolus dose) and a 37.5 mg/5 mL concentrate for solution for infusion (for the subsequent continuous infusion).
Atosiban Accord is not available in all countries. It is approved in the European Union, the United Kingdom, and several other markets, but it is not approved by the US Food and Drug Administration (FDA). In the United States, other tocolytic agents such as nifedipine and indomethacin are more commonly used.
What Should You Know Before Taking Atosiban Accord?
Before receiving Atosiban Accord, your doctor will assess whether you meet the criteria for treatment, including gestational age between 24 and 33 weeks, regular uterine contractions, and adequate cervical dilation. Several conditions make atosiban unsuitable, including eclampsia, placenta praevia, placental abruption, foetal distress, and intrauterine infection.
Because atosiban is administered exclusively in hospital settings by healthcare professionals, the decision to use it is made by the treating obstetrician after a thorough clinical assessment. However, understanding the contraindications and precautions is important for patients and their families to be informed about the treatment being received.
Contraindications
Atosiban Accord must not be used in the following situations, as the risks of delaying delivery outweigh the potential benefits of tocolysis:
- Gestational age less than 24 weeks or more than 33 completed weeks – insufficient evidence of benefit outside this range
- Premature rupture of membranes after 30 weeks of gestation – increased risk of infection with prolonged tocolysis
- Intrauterine foetal death – no clinical benefit to delaying delivery
- Suspected intrauterine infection (chorioamnionitis) – delivery is the definitive treatment for intrauterine infection
- Placenta praevia or placental abruption – conditions requiring urgent delivery
- Eclampsia or severe pre-eclampsia – delivery is the definitive treatment
- Abnormal foetal heart rate pattern (foetal distress) – immediate delivery may be required
- Intrauterine growth restriction with abnormal Doppler findings – requires careful monitoring and potentially urgent delivery
- Hypersensitivity to atosiban or any excipient – risk of allergic reaction
Warnings and Precautions
Several clinical situations require special caution when using atosiban. Your treating team will carefully evaluate these factors before and during treatment:
- Multiple pregnancies: While atosiban can be used in twin or higher-order pregnancies, clinical experience is more limited. The risk-benefit balance must be carefully assessed, as multiple pregnancies carry inherently higher risks of complications.
- Hepatic or renal impairment: Atosiban is metabolised in the liver and eliminated partly through the kidneys. Patients with significant hepatic or renal dysfunction may have altered drug clearance, though no specific dose adjustments are currently recommended in mild to moderate impairment.
- Retreatment: If contractions recur after an initial course of atosiban, retreatment may be considered. However, clinical data on repeated courses are limited. The total number of retreatment cycles should generally not exceed three.
- Cervical dilation greater than 4 cm: When cervical dilation exceeds 4 cm, the likelihood of successfully delaying delivery is substantially reduced. Tocolysis may still be attempted to gain time for steroid administration, but the expected benefit diminishes.
Pregnancy and Breastfeeding
Atosiban is, by its very nature, a medication used during pregnancy. It has been studied in clinical trials involving thousands of pregnant women between 24 and 33 weeks of gestation. Animal reproductive studies and clinical data have not shown evidence of teratogenicity or adverse effects on foetal development attributable to atosiban at recommended doses.
Regarding breastfeeding, it is not known whether atosiban is excreted in human breast milk. However, given that atosiban is a peptide that would likely be degraded in the infant's gastrointestinal tract, and considering that it is used only acutely (for a maximum of 48 hours) in a clinical setting well before the onset of lactation in most cases, the risk to a breastfed infant is considered negligible. The EMA Summary of Product Characteristics states that caution should be exercised, but breastfeeding is generally not contraindicated after treatment with atosiban.
How Does Atosiban Accord Interact with Other Drugs?
Atosiban has a relatively low potential for drug interactions because it is metabolised by enzymatic degradation rather than through cytochrome P450 pathways. However, it should not be combined with other tocolytic agents, and caution is needed when used alongside medications that affect uterine contractility or cardiovascular function.
One of the clinical advantages of atosiban over older tocolytic agents is its low propensity for pharmacokinetic drug interactions. Because atosiban is a peptide, it is metabolised through enzymatic hydrolysis rather than through hepatic cytochrome P450 (CYP) enzyme pathways. This means it is unlikely to interact with the many drugs that are metabolised by or that inhibit CYP enzymes. Nevertheless, several pharmacodynamic interactions and clinical considerations are relevant.
During tocolytic therapy with atosiban, patients in preterm labour commonly receive concurrent medications including antenatal corticosteroids (betamethasone or dexamethasone) for foetal lung maturation, antibiotics for Group B streptococcus prophylaxis or suspected infection, and magnesium sulphate for foetal neuroprotection. Clinical experience has shown that atosiban can be safely administered alongside these medications without significant interactions.
| Interacting Drug | Type | Effect | Recommendation |
|---|---|---|---|
| Other tocolytics (nifedipine, ritodrine, salbutamol) | Pharmacodynamic | Additive uterine relaxation, increased risk of adverse effects | Avoid concurrent use; switch between agents if needed |
| Oxytocin (Syntocinon) | Pharmacodynamic | Mutual antagonism at oxytocin receptors | Allow adequate washout before initiating oxytocin for induction |
| Betamethasone / Dexamethasone | None significant | No clinically relevant interaction | Safe to co-administer; this is standard practice |
| Magnesium sulphate | Pharmacodynamic | Both have uterine relaxant properties; possible additive effect | Can be used together under close monitoring |
| Antibiotics (Group B strep prophylaxis) | None significant | No known interaction | Safe to co-administer |
| Carbetocin | Pharmacodynamic | Antagonism of carbetocin effects at oxytocin receptors | Not clinically relevant as used at different stages |
Major Interactions
The most clinically significant interaction is with other tocolytic agents. Combining atosiban with another tocolytic such as nifedipine (a calcium channel blocker) or a beta-agonist like ritodrine could lead to excessive uterine relaxation and increase the risk of side effects associated with each agent. Current guidelines recommend using only one tocolytic agent at a time. If a switch between agents is necessary due to lack of efficacy or side effects, adequate washout time should be allowed.
Minor Interactions
When oxytocin is administered after atosiban treatment (for example, to induce or augment labour), the competitive antagonism at the oxytocin receptor may initially reduce the effectiveness of oxytocin. However, due to the relatively short elimination half-life of atosiban (approximately 1.7 hours), this effect diminishes rapidly. It is generally recommended to wait at least a few hours after discontinuing atosiban before starting oxytocin, though clinical judgement should guide the exact timing based on the clinical situation.
What Is the Correct Dosage of Atosiban Accord?
Atosiban Accord is administered in three stages: an initial bolus injection of 6.75 mg over 1 minute, followed by a high-dose infusion of 18 mg/hour for 3 hours, then a lower-dose infusion of 6 mg/hour for up to 45 hours. The maximum total treatment duration is 48 hours.
The dosing regimen for atosiban has been established through extensive clinical trials and is standardised across all approved formulations. Treatment is administered exclusively by healthcare professionals in a hospital setting with appropriate monitoring equipment. The three-step dosing protocol ensures rapid achievement of therapeutic plasma levels followed by sustained tocolytic activity.
| Stage | Route | Dose | Duration | Formulation Used |
|---|---|---|---|---|
| Step 1: Initial bolus | IV injection | 6.75 mg (0.9 mL) | Over 1 minute | Pre-filled syringe (6.75 mg/0.9 mL) |
| Step 2: High-dose infusion | IV infusion | 18 mg/hour (24 mL/hour) | 3 hours | Concentrate for infusion (37.5 mg/5 mL) |
| Step 3: Low-dose infusion | IV infusion | 6 mg/hour (8 mL/hour) | Up to 45 hours | Concentrate for infusion (37.5 mg/5 mL) |
The total dose of atosiban administered over a full 48-hour treatment course is approximately 330 mg. The infusion solution is prepared by diluting the concentrate (37.5 mg/5 mL vials) in a compatible intravenous solution such as 0.9% sodium chloride, Ringer's lactate solution, or 5% glucose solution.
Adults
The standard three-step regimen described above applies to all adult women meeting the treatment criteria (24-33 completed weeks of gestation with regular uterine contractions). No dose adjustments are required based on body weight within the normal range. The treatment should be initiated as soon as the diagnosis of threatened preterm labour is confirmed and the decision to use tocolysis has been made.
Preparation of the Infusion Solution
For step 2 (high-dose infusion): Withdraw 10 mL from a 100 mL bag of 0.9% NaCl. Add two vials of Atosiban Accord concentrate (2 x 5 mL = 75 mg) to produce a concentration of 0.75 mg/mL. Infuse at 24 mL/hour to deliver 18 mg/hour.
For step 3 (low-dose infusion): Use the same concentration preparation. Reduce the infusion rate to 8 mL/hour to deliver 6 mg/hour.
Children and Adolescents
Atosiban Accord is not indicated for use in children or non-pregnant adolescents. The medication is specifically designed for the management of preterm labour in pregnant women. There are no paediatric dosing data, as the condition treated by atosiban does not occur in the paediatric population outside of the context of teenage pregnancy, where the standard adult dosing protocol applies.
Elderly
There is no relevant use of atosiban in elderly patients. The therapeutic indication (preterm labour) occurs exclusively during reproductive years. No dosing recommendations for elderly patients exist as the clinical scenario does not arise.
Missed Dose
As atosiban is administered as a continuous intravenous infusion in a hospital setting, the concept of a missed dose in the traditional sense does not apply. If the infusion is accidentally interrupted, it should be restarted as soon as possible. The clinical team will assess whether the interruption has been long enough to warrant restarting the full dosing protocol from the bolus injection stage. Brief interruptions (a few minutes) generally require only resumption of the infusion at the appropriate rate for the treatment stage.
Overdose
There have been few reported cases of atosiban overdose. In clinical trials, doses up to 800 mg were administered without specific adverse events beyond those seen at therapeutic doses. No specific antidote for atosiban exists. In the event of an overdose, treatment is supportive and symptomatic. The infusion should be discontinued, and the patient monitored for any signs of excessive uterine relaxation or other adverse effects. Due to the relatively short elimination half-life of atosiban (approximately 1.7 hours), effects of an overdose would be expected to resolve relatively quickly.
What Are the Side Effects of Atosiban Accord?
The most common side effects of atosiban include nausea (affecting approximately 12% of patients), headache, dizziness, hot flushes, vomiting, and injection site reactions. Atosiban has a significantly better side effect profile compared to beta-agonist tocolytics, with far fewer cardiovascular and metabolic effects.
Like all medicines, Atosiban Accord can cause side effects, although not everybody gets them. The side effect profile of atosiban is generally considered favourable compared to other tocolytic agents, particularly beta-agonists. This is because atosiban acts selectively on oxytocin and vasopressin receptors and does not significantly affect adrenergic, dopaminergic, or other receptor systems. The Worldwide Atosiban versus Beta-agonists Study (WAABS) and subsequent clinical experience have consistently confirmed that atosiban has fewer maternal side effects than beta-agonists.
The following side effects have been reported in clinical trials and post-marketing surveillance. They are categorised according to their frequency of occurrence:
Very Common
- Nausea (approximately 12% of patients)
Common
- Headache
- Dizziness
- Hot flushes / flushing
- Vomiting
- Tachycardia (fast heart rate)
- Hypotension (low blood pressure)
- Injection site reactions (redness, pain, swelling)
- Hyperglycaemia (elevated blood sugar)
Uncommon
- Insomnia
- Pruritus (itching)
- Rash
- Pyrexia (fever)
Rare
- Allergic reactions / hypersensitivity
- Uterine haemorrhage (post-partum)
- Uterine atony
The neonatal safety profile of atosiban has been carefully evaluated. In the original regulatory trials, there was a numerical (but not statistically significant) increase in foetal and neonatal deaths in the atosiban group compared to placebo, which was attributed to imbalances in baseline prognostic factors rather than a drug effect. Subsequent large-scale post-marketing surveillance and meta-analyses have not confirmed this signal, and regulatory agencies have concluded that atosiban does not increase neonatal mortality when used according to the approved indications.
Since atosiban is administered in hospital under medical supervision, any adverse reactions will be promptly identified and managed by the clinical team. However, patients should immediately report symptoms such as difficulty breathing, severe chest pain, heavy vaginal bleeding, signs of allergic reaction (rash, facial swelling, or breathing difficulty), or any sudden change in the baby's movement pattern.
How Should You Store Atosiban Accord?
Atosiban Accord should be stored below 25°C, protected from light, and kept in the original packaging. Once diluted for infusion, the solution should be used within 24 hours. Do not freeze. As a hospital-use medicine, storage is managed by hospital pharmacy staff.
Proper storage of Atosiban Accord is essential to maintain its stability, potency, and sterility. As this is a hospital-use medication, storage is the responsibility of the hospital pharmacy and clinical staff. However, understanding the storage requirements provides insight into how the medication is handled.
Unopened Product
- Temperature: Store below 25°C. Do not freeze.
- Light protection: Keep the vials and pre-filled syringes in the original outer carton to protect from light.
- Shelf life: The shelf life of the unopened product is typically 3 years from the date of manufacture when stored under recommended conditions.
After Preparation
- Once the concentrate has been diluted for infusion, the prepared solution should be used immediately. If not used immediately, in-use stability has been demonstrated for up to 24 hours at 2-8°C (refrigerator temperature).
- From a microbiological standpoint, the diluted product should be used immediately after preparation. If not used immediately, the user is responsible for the conditions and duration of in-use storage.
- The pre-filled syringe (bolus dose) is for single use only. Any unused solution should be discarded.
Disposal
Any unused medicinal product or waste material should be disposed of in accordance with local hospital guidelines and pharmaceutical waste regulations. Do not dispose of medicines via household waste or wastewater. These measures help to protect the environment.
What Does Atosiban Accord Contain?
The active substance is atosiban (as atosiban acetate). Each pre-filled syringe contains 6.75 mg of atosiban in 0.9 mL. Each vial of concentrate contains 37.5 mg of atosiban in 5 mL. Excipients include mannitol, hydrochloric acid, and water for injections.
Active Substance
Atosiban is the active pharmaceutical ingredient in Atosiban Accord. Chemically, atosiban is a synthetic nonapeptide analogue of oxytocin, with modifications at positions 1, 2, and 4 of the peptide chain that convert it from an agonist to an antagonist at the oxytocin receptor. Its full chemical name is 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin, and it has a molecular weight of approximately 994.2 daltons. It is present in the formulation as atosiban acetate.
Excipients
The excipients (inactive ingredients) in Atosiban Accord serve important roles in maintaining the stability, pH, and isotonicity of the solution:
- Mannitol: Used as a tonicity-adjusting agent to make the solution isotonic with blood, ensuring it can be safely administered intravenously.
- Hydrochloric acid (dilute): Used for pH adjustment to maintain the solution within an optimal pH range (approximately 4.5) for stability and compatibility.
- Water for injections: The solvent used to dissolve the active substance and excipients, meeting pharmacopoeial standards for injectable preparations.
Physical Appearance
Atosiban Accord solution for injection (pre-filled syringe) and concentrate for solution for infusion (vial) are both clear, colourless solutions, free from visible particles. Before use, the solution should be visually inspected, and any containers showing discolouration, turbidity, or particulate matter should not be used.
Frequently Asked Questions About Atosiban Accord
Atosiban Accord is used to delay imminent preterm birth in pregnant women between 24 and 33 completed weeks of gestation. It works by blocking oxytocin receptors in the uterus, reducing uterine contractions. The primary goal is to buy time (ideally 48 hours) for the administration of corticosteroids to promote foetal lung maturity and, when needed, for maternal transfer to a hospital with neonatal intensive care facilities. It is administered intravenously and is strictly a hospital-use medication given under specialist obstetric supervision.
Atosiban Accord is given in three sequential steps, all intravenously: first, a bolus injection of 6.75 mg over 1 minute using the pre-filled syringe; second, a high-dose infusion of 18 mg/hour for 3 hours; and third, a low-dose infusion of 6 mg/hour for up to 45 hours. The maximum total treatment duration is 48 hours per course. If preterm contractions recur, the treatment course may be repeated.
The most common side effect is nausea, affecting approximately 12% of patients. Other common side effects include headache, dizziness, hot flushes, vomiting, fast heart rate (tachycardia), low blood pressure (hypotension), elevated blood sugar (hyperglycaemia), and injection site reactions. Importantly, atosiban has significantly fewer cardiovascular side effects compared to beta-agonist tocolytics such as ritodrine, which is one of its key clinical advantages.
No. Atosiban Accord is not recommended for use before 24 weeks of gestation. The approved indication is for pregnancies between 24 and 33 completed weeks. Before 24 weeks, the evidence for the safety and efficacy of tocolysis is insufficient, and the viability of the foetus at these very early gestational ages means the risk-benefit balance of delaying delivery is different. Treatment decisions in very early preterm labour require careful individual assessment by the clinical team.
Atosiban has a more favourable side effect profile compared to beta-agonists (such as ritodrine and salbutamol), with significantly fewer cardiovascular side effects like rapid heart rate, palpitations, and fluid overload. In terms of efficacy at delaying delivery by 48 hours (the primary therapeutic goal), clinical trials show similar effectiveness across different tocolytic classes. Nifedipine (a calcium channel blocker) is often considered an alternative, and some guidelines recommend it as first-line therapy, particularly in settings where atosiban is not available or is more expensive. The choice between agents depends on local guidelines, clinical circumstances, and the patient's medical history.
Yes, if uterine contractions recur after an initial treatment course, atosiban can be re-administered. The full three-step dosing protocol (bolus followed by high-dose and low-dose infusions) is used for retreatment, exactly as for the initial course. However, clinical data on repeated courses is more limited, and the general recommendation is that no more than three treatment courses should be given in total. The clinical team will carefully assess the benefit of retreatment against the potential risks at each stage.
References
- European Medicines Agency (EMA). Tractocile (atosiban) – Summary of Product Characteristics. Last updated 2024. Available at: EMA Tractocile EPAR
- Worldwide Atosiban versus Beta-agonists Study Group. Effectiveness and safety of the oxytocin antagonist atosiban versus beta-adrenergic agonists in the treatment of preterm labour. BJOG: An International Journal of Obstetrics & Gynaecology. 2001;108(2):133-142.
- Flenady V, Reinebrant HE, Liley HG, et al. Oxytocin receptor antagonists for inhibiting preterm labour. Cochrane Database of Systematic Reviews. 2014;(6):CD004452. doi:10.1002/14651858.CD004452.pub3
- Royal College of Obstetricians and Gynaecologists (RCOG). Tocolysis for Women in Preterm Labour. Green-top Guideline No. 1b. 2022.
- National Institute for Health and Care Excellence (NICE). Preterm labour and birth. NICE guideline [NG25]. Updated 2022. Available at: NICE NG25
- World Health Organization (WHO). WHO recommendations on interventions to improve preterm birth outcomes. Geneva: WHO; 2015.
- van Vliet EOG, Nijman TAJ, Schuit E, et al. Nifedipine versus atosiban for threatened preterm birth (APOSTEL III): a multicentre, randomised controlled trial. The Lancet. 2016;387(10033):2117-2124.
- Papatsonis D, Flenady V, Cole S, Liley H. Oxytocin receptor antagonists for inhibiting preterm labour. Cochrane Database of Systematic Reviews. 2005;(3):CD004452.
- British National Formulary (BNF). Atosiban. Available at: BNF online
About the Editorial Team
This article has been written and medically reviewed by the iMedic Medical Editorial Team, comprising licensed physicians and pharmacologists with expertise in obstetrics, maternal-foetal medicine, and clinical pharmacology.
iMedic Editorial Team – specialists in pharmacology and obstetrics with clinical experience in perinatal medicine.
iMedic Medical Review Board – independent panel of specialist physicians reviewing all content according to international guidelines (EMA, RCOG, NICE, WHO).
Evidence standard: All medical claims in this article are supported by Level 1A evidence from systematic reviews, randomised controlled trials, and international clinical guidelines. The GRADE framework is used to assess the quality of evidence.
Conflict of interest: The iMedic editorial team has no financial relationships with pharmaceutical companies. This content is independently produced with no commercial funding.