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Carbetocin

A long-acting oxytocin analogue given as a single injection to prevent postpartum haemorrhage. Its heat-stable formulation is on the WHO Essential Medicines List because it survives without refrigeration — but Cochrane finds it no better than oxytocin at preventing bleeding, and its separate career as an intranasal drug for Prader-Willi syndrome ended in a failed Phase 3 in 2025.

BStrongWell-Studied
Last updated 17 citations
TL;DR

Carbetocin is a modified version of oxytocin that lasts much longer in the body — about 33 to 55 minutes instead of a few minutes. That means one injection does the job of an oxytocin drip, which is why it is used right after birth to stop the uterus bleeding. It works about as well as oxytocin rather than better, and its real advantage is that a heat-stable version does not need a fridge. A nasal-spray version was tested for the hunger symptoms of Prader-Willi syndrome and failed.

What is Carbetocin?

Carbetocin is a synthetic, long-acting analogue of oxytocin, used in hospitals to prevent postpartum haemorrhage caused by uterine atony — a uterus that fails to clamp down after delivery. It is given once, as a single 100-microgram dose, and is not repeated. Three chemical changes separate it from oxytocin. The free amino group at position 1 is removed (deamination). The disulfide bridge that closes oxytocin's ring is replaced by a more stable thioether, giving the carba-1 structure. And the tyrosine at position 2 carries a methyl group on its phenol oxygen, making it O-methyl-tyrosine. The molecule is C45H69N11O12S with a molecular weight of about 988, and the full chemical name is 1-deamino-1-carba-2-tyrosine(O-methyl)-oxytocin. Those changes exist for one reason: to resist the enzymes that destroy oxytocin. Oxytocin's plasma half-life is roughly one to six minutes, which is why it has to be given as a continuous infusion to maintain uterine tone. Carbetocin's terminal half-life is a median of 33 minutes after intravenous dosing and 55 minutes after intramuscular dosing, with intramuscular bioavailability around 77 percent. A firm uterine contraction appears within about two minutes, and uterotonic activity persists for several hours from a single injection. Carbetocin has never been approved by the FDA for any indication. It is approved and widely used across Europe, Canada, Asia, Africa and Latin America, and the heat-stable formulation sits on the WHO Model List of Essential Medicines.

What Carbetocin Is Investigated For

Carbetocin has had two entirely separate careers, and they ended very differently. The obstetric career is a success, with an important qualification. Carbetocin is a genuinely established uterotonic with one of the largest randomised evidence bases in obstetrics. The WHO CHAMPION trial (Widmer et al., NEJM 2018) randomised 29,645 women across 23 sites in 10 countries and found heat-stable carbetocin 100 micrograms intramuscularly noninferior to oxytocin 10 IU for the composite of blood loss of at least 500 mL or use of additional uterotonics — 14.5 percent versus 14.4 percent. The qualification is that noninferior is the ceiling, not the floor. The 2025 Cochrane network meta-analysis (Gallos et al., 122 trials, 121,931 women) places carbetocin as having similar effects to oxytocin for blood loss of at least 500 mL at high certainty, and little or no difference for blood loss of at least 1000 mL or blood transfusion. The two highest-ranked agents in that network were not carbetocin: they were ergometrine plus oxytocin and misoprostol plus oxytocin. What Cochrane did find distinctive is the side-effect profile. In its words, all uterotonic agents except for carbetocin were associated with increased risks of side effects compared with oxytocin. Carbetocin also reduces the use of additional uterotonics (RR 0.74, 95 percent CI 0.59 to 0.94, low certainty), a finding echoed in a 2025 meta-analysis of 17 trials in low-risk caesarean delivery, where rescue uterotonic use fell (OR 0.53) while the incidence of postpartum haemorrhage itself did not differ at all (OR 1.08, 95 percent CI 0.81 to 1.44). The honest summary is that carbetocin buys convenience, tolerability and supply-chain resilience rather than superior haemostasis. The neuropsychiatric career is a failure, and an instructive one. Because carbetocin is a selective oxytocin-receptor agonist with a longer half-life than oxytocin, it was developed as an intranasal treatment for hyperphagia in Prader-Willi syndrome. A small Ferring-funded trial (Dykens et al., JCI Insight 2018, n=37 over 14 days) was positive. The Phase 3 CARE-PWS trial (n=130) missed both primary endpoints, with only nominal significance at the lower 3.2-mg dose. The FDA issued a Complete Response Letter in January 2022 after an advisory committee voted 12 to 1 that substantial evidence of effectiveness had not been provided, and asked for a confirmatory study. That study — COMPASS PWS, n=175, properly powered — reported a treatment difference of 0.3 points on the hyperphagia scale (95 percent CI -1.8 to 2.4, P=0.79), with the placebo group numerically ahead and no separation on any secondary or exploratory endpoint. Acadia discontinued the programme in September 2025.

Prevention of postpartum haemorrhage at caesarean delivery
Strong90%
Prevention of postpartum haemorrhage after vaginal birth
Strong90%
Reducing the need for additional (rescue) uterotonics
Moderate70%
Uterotonic coverage where cold-chain storage is unreliable
Strong90%
Hyperphagia in Prader-Willi syndrome (intranasal, discontinued)
Limited15%

History & Discovery

Carbetocin belongs to a wave of oxytocin analogues designed in the 1960s and 1970s, when peptide chemists set out to work out which parts of the oxytocin molecule could be altered without losing receptor binding. Three modifications proved compatible with full agonist activity while slowing enzymatic clearance: deamination at position 1, replacement of the disulfide bridge with a thioether to give a carba analogue, and O-methylation of the position-2 tyrosine. Combining all three produced 1-deamino-1-carba-2-tyrosine(O-methyl)-oxytocin — carbetocin. Ferring Pharmaceuticals developed it commercially, and it reached approval first in Canada as Duratocin and then across Europe as Pabal through national and decentralised procedures rather than a single centralised EMA authorisation. The original indication was narrow — prevention of uterine atony after elective caesarean under epidural or spinal anaesthesia — and was later widened in several jurisdictions to include emergency caesarean and vaginal birth. The decisive chapter opened in the 2010s with a supply-chain problem rather than a pharmacological one. Oxytocin requires refrigeration, and postpartum haemorrhage kills disproportionately in places where cold chains are unreliable, meaning the standard of care was often degraded before it reached the woman who needed it. Ferring and MSD developed a room-temperature-stable carbetocin formulation and, with WHO, ran CHAMPION — 29,645 women across 10 countries — which reported noninferiority to oxytocin in 2018. The WHO Expert Committee added heat-stable carbetocin to the Model List of Essential Medicines in 2019. The parallel neuropsychiatric chapter began from a different premise: that carbetocin's receptor selectivity and longer half-life made it a better tool than oxytocin for engaging central oxytocin circuits. Levo Therapeutics took intranasal carbetocin (LV-101) into Prader-Willi syndrome on the strength of a 37-participant trial, and filed after the Phase 3 CARE-PWS trial missed its primary endpoints but produced a nominal signal at the lower dose. An FDA advisory committee voted 12 to 1 against on 4 November 2021 and a Complete Response Letter followed in January 2022. Acadia Pharmaceuticals acquired Levo and ran the confirmatory COMPASS PWS trial the FDA had asked for; it failed unambiguously, and on 24 September 2025 Acadia said it did not intend to investigate intranasal carbetocin any further.

How It Works

Carbetocin binds the oxytocin receptor on uterine smooth muscle and makes the uterus contract, clamping shut the blood vessels at the placental site. It is chemically armoured against the enzymes that destroy oxytocin, so a single injection holds the uterus contracted for hours where oxytocin needs a continuous drip.

Carbetocin is a selective agonist at the oxytocin receptor (OXTR), a class A G-protein-coupled receptor that couples principally to Gq/11. Receptor occupancy activates phospholipase C-beta, generating inositol trisphosphate and diacylglycerol, releasing calcium from the sarcoplasmic reticulum and opening voltage-gated calcium channels. The rise in intracellular calcium drives calcium-calmodulin activation of myosin light-chain kinase and produces phasic, rhythmic contraction of myometrial smooth muscle superimposed on a raised resting tone. Mechanical compression of the spiral arteries at the placental bed — rather than any effect on the coagulation cascade — is what arrests bleeding. Oxytocin receptor density in the myometrium rises steeply through pregnancy and peaks at term, which is why uterotonics work at delivery and have little effect on a non-pregnant uterus. The pharmacodynamic difference from oxytocin is entirely one of duration. Deamination at position 1, substitution of the disulfide bridge with a thioether, and O-methylation of the position-2 tyrosine together make the molecule resistant to aminopeptidase and disulfide-reductase attack, and to the placental oxytocinase that clears circulating oxytocin in pregnancy. Plasma half-life rises from roughly one to six minutes to a median of 33 minutes intravenously and 55 minutes intramuscularly, with elimination biphasic, volume of distribution at pseudo-equilibrium around 22 litres, and less than 1 percent of the dose excreted unchanged in urine — clearance is almost entirely non-renal. Clinically this converts an infusion into a bolus: a firm contraction within about two minutes, uterotonic activity sustained for several hours, and no opportunity to adjust or withdraw the drug once given. Two secondary pharmacological properties matter. Carbetocin retains the weak vasopressin V2-like antidiuretic activity shared across the oxytocin family, which is the basis for the theoretical water-intoxication risk. And it is more selective for OXTR over vasopressin receptors than oxytocin itself, which was the stated rationale for developing it as a central nervous system drug — selective oxytocin-receptor agonism in a molecule that survives long enough to act. Animal work supports central activity, with systemic carbetocin dose-dependently preventing anxiety-like behaviour after chronic social defeat stress in rats through an antagonist-reversible, receptor-mediated mechanism. The human programme built on that rationale nonetheless failed, which is a caution about how far receptor selectivity and half-life carry a central hypothesis on their own.

Evidence Snapshot

Overall Confidence85%

Human Clinical Evidence

Strong for the obstetric indication and negative for the neuropsychiatric one. The obstetric base includes CHAMPION (29,645 women, 10 countries) and a 2025 Cochrane network meta-analysis spanning 122 trials and 121,931 women, which rates carbetocin at high certainty as having effects similar to oxytocin for blood loss of at least 500 mL and at moderate certainty as making little or no difference for blood loss of at least 1000 mL or blood transfusion. Rescue uterotonic use is reduced (RR 0.74, low certainty), and Cochrane identifies carbetocin as the only agent in the network not associated with increased side effects versus oxytocin. In Prader-Willi syndrome the intranasal formulation failed two of three trials, including the properly powered 175-participant COMPASS PWS confirmatory study (treatment difference 0.3 points, P=0.79, no separation on any secondary endpoint).

Animal / Preclinical

Moderate and mostly supportive of mechanism rather than of any indication. Comparative pharmacokinetics in cows and gilts confirm rapid absorption, intramuscular bioavailability above 80 percent and short elimination, consistent with the human profile. Central-nervous-system work is more interesting than extensive: chronic systemic carbetocin dose-dependently prevented anxiety-like behaviour in rats subjected to social defeat stress, an effect abolished by the oxytocin-receptor antagonists atosiban and L-368,899, confirming it is receptor-mediated. These models supported the human central-nervous-system hypothesis that subsequently failed.

Mechanistic Rationale

Strong and unusually clean. The target is a well-characterised GPCR whose myometrial density peaks at term; the three structural modifications have an explicit, testable purpose — resisting the specific enzymes that clear oxytocin — and the measured pharmacokinetics confirm they achieved it. The rationale for the obstetric use is essentially settled. The rationale for the central-nervous-system use was coherent in principle (selective oxytocin-receptor agonism with a workable half-life) but has now been tested and found not to translate.

Research Gaps & Open Questions

What the current literature has not yet settled about Carbetocin:

  • 01The right dose is genuinely unresolved. The labelled 100 micrograms was fixed early, and dose-finding studies have repeatedly found that substantially smaller doses produce adequate uterine tone at elective caesarean, yet no regulator has revised the label and the entire efficacy base — CHAMPION included — tests only 100 micrograms. Whether a lower dose would retain efficacy while reducing tachycardia, flushing and nausea has not been settled in an adequately powered trial.
  • 02Whether carbetocin's advantage in rescue-uterotonic use translates into any outcome that matters to a woman. The pattern across meta-analyses is consistent: fewer additional uterotonics, no difference in the incidence of postpartum haemorrhage, no difference in transfusion. Whether that represents a real clinical benefit, better uterine tone that happens to be visible only in a process measure, or clinicians responding to a drug they know lasts longer, has not been disentangled.
  • 03Effectiveness in women at genuinely high risk. Most trials recruited low-risk populations, and the one signal of superiority — in women with obesity undergoing caesarean — rests on three trials and 269 participants. Twin pregnancy, placenta praevia, prolonged labour and previous postpartum haemorrhage are where a better uterotonic would matter most, and are where the evidence is thinnest; dedicated trials in twin pregnancy are still enrolling.
  • 04Whether the heat-stable formulation delivers in practice the advantage it promises in principle. CHAMPION kept both drugs refrigerated to preserve blinding, so it demonstrated pharmacological noninferiority but could not test the cold-chain hypothesis that justifies the formulation. The question of how much maternal morbidity is actually averted by removing the refrigeration requirement in real health systems remains an implementation question rather than an answered one.
  • 05Why the central oxytocin hypothesis failed. The Prader-Willi programme was built on a coherent rationale — selective oxytocin-receptor agonism in a molecule with a usable half-life — supported by animal models in which systemic carbetocin produces receptor-mediated behavioural effects. Whether the failure reflects inadequate central nervous system penetration after intranasal dosing, the wrong endpoint, the wrong population, or a mistaken premise about oxytocin signalling in Prader-Willi syndrome is not known, and the programme's discontinuation means it is unlikely to be answered.
  • 06Long-term maternal or neonatal follow-up. Carbetocin is given once, at a moment of maximal physiological flux, and the trials measure outcomes over hours to days. Systematic longer-term follow-up of mothers or infants exposed to it is essentially absent from the literature.

Forms & Administration

Carbetocin is supplied as a 1 mL ampoule or vial containing 100 micrograms, as a solution for injection. There is no oral, sublingual, topical or consumer form, and the investigational intranasal spray has been discontinued. Route depends on the mode of birth. At caesarean section under epidural or spinal anaesthesia it is given intravenously only, slowly over one minute. After vaginal birth it may be given either intravenously or intramuscularly. In both cases it is administered only after delivery of the infant, as soon as possible afterwards and preferably before delivery of the placenta. It is intended for single use. No further dose of carbetocin is given, and the label warns of cumulative exposure if oxytocin or methylergometrine follows. This is the practical difference from oxytocin at the bedside: one injection replaces an infusion that would otherwise need to be hung, titrated and monitored for several hours. Two formulations exist. The original requires refrigerated storage. The heat-stable formulation, developed for use where cold chains are unreliable, does not — and it is that version that appears on the WHO Model List of Essential Medicines and that was tested in CHAMPION.

Dosing & Protocols

The ranges below reflect protocols commonly discussed in the literature and by clinicians — not a prescription. Actual dosing for any individual should be determined by a qualified healthcare provider who knows the patient.

Typical Range

A single 100-microgram dose (one 1 mL ampoule). No second dose is given.

Frequency

Once only, immediately after delivery of the infant and preferably before delivery of the placenta.

Timing Considerations

Time of day

Not applicable — administration is tied to the moment of delivery, not to the clock.

Relative to meals

Not applicable.

Relative to exercise

Not tied to exercise timing.

The only timing that matters is the relationship to delivery: after the infant is born, as soon as possible, and preferably before the placenta is delivered. Administration at any point before delivery of the infant is contraindicated.

Protocol Notes

Carbetocin is a hospital-administered medicine given by a clinician in the minutes after birth; there is no outpatient, self-administered or take-home form, and nothing here constitutes guidance for use outside that setting. Route follows mode of delivery. At caesarean section under epidural or spinal anaesthesia the label specifies intravenous administration only, injected slowly over about one minute — rapid injection increases the risk of hypotension and flushing. After vaginal birth either intravenous or intramuscular administration is acceptable; the intramuscular route has around 77 percent bioavailability, reaches peak concentration at roughly 30 minutes and was the route used in CHAMPION, which matters because intramuscular injection needs neither intravenous access nor an infusion pump and is therefore the practical route in low-resource and community settings. The single-dose rule is the part most often misunderstood. Carbetocin is not titrated and not repeated. If bleeding continues, management escalates to other agents — but the label notes a risk of cumulative exposure where oxytocin or methylergometrine is given after carbetocin, and advises against combining it with prostaglandins. Clinically, a firm contraction should be evident within about two minutes, and uterotonic activity persists for several hours from that one injection. Dose-finding research has repeatedly suggested that doses well below 100 micrograms produce adequate uterine tone at elective caesarean, and the appropriate dose is an area of continuing trial activity. No regulator has revised the labelled dose, and the 100-microgram figure is what the evidence base — including CHAMPION — actually tests.

Carbetocin is not FDA-approved in the United States for any indication. Where it is approved, it is a prescription-only, hospital-administered medicine for use immediately after birth. It must never be used before delivery of the infant or to induce labour.

Timeline of Effects

Onset

Fast and essentially identical by either route. A firm uterine contraction is obtained within about two minutes of intravenous or intramuscular administration. After intramuscular injection, plasma concentrations peak at roughly 30 minutes, but the uterine response does not wait for the peak — receptor occupancy at the myometrium is sufficient well before then. In practice the clinician assesses uterine tone within the first few minutes and decides on escalation from there.

Peak Effect

Uterotonic activity persists for several hours from the single dose, which is the entire point of the molecule: one injection achieves what would otherwise require an oxytocin infusion running for hours. Plasma elimination is biphasic with a median terminal half-life of 33 minutes intravenously and 55 minutes intramuscularly, so the duration of uterine effect substantially outlasts measurable drug concentrations — a reminder that half-life and duration of pharmacological action are not the same quantity.

After Discontinuation

The concept does not really apply, because carbetocin is given once in a single clinical event rather than taken over time. There is no withdrawal, tolerance, rebound or taper. The clinically relevant corollary is the opposite one: because the effect cannot be stopped or reversed once the injection is given, the decision to administer has to be right at the moment it is made. That irreversibility is the reason the drug is contraindicated at every stage before the infant is delivered.

Common Questions

Is carbetocin approved in the United States?

No. Carbetocin has never been approved by the FDA for any indication, and there is no carbetocin product in the Drugs@FDA database or the FDA label repository. The only American regulatory file was the intranasal formulation for Prader-Willi syndrome, which received a Complete Response Letter in January 2022 and was abandoned in 2025 after its confirmatory trial failed. US obstetric practice uses oxytocin, with methylergonovine, misoprostol and carboprost as second-line agents. This is a genuine US-versus-rest-of-world divergence rather than a safety signal: carbetocin is approved and routinely used in Canada, the UK, the EU, Australia and much of Asia, Africa and Latin America.

Is carbetocin better than oxytocin at preventing postpartum bleeding?

Mostly no, and the best evidence says so clearly. The 2025 Cochrane network meta-analysis of 122 trials and 121,931 women rates carbetocin as having similar effects to oxytocin for blood loss of at least 500 mL (high-certainty evidence), and as making little or no difference for blood loss of at least 1000 mL or for blood transfusion (moderate-certainty evidence). The CHAMPION trial was designed as a noninferiority study and met that bar for its composite endpoint, but noninferiority was not demonstrated for the 1000 mL outcome because events were too rare to power it. Where carbetocin does separate is in reducing the need for rescue uterotonics and in tolerability — Cochrane singles it out as the only agent in the network not associated with increased side effects compared with oxytocin. Some signal exists in specific higher-risk groups: a 2026 meta-analysis in women with obesity undergoing caesarean found a reduced incidence of postpartum haemorrhage (RR 0.19), but it pooled only three trials and 269 participants.

Why does heat-stable carbetocin matter so much?

Because oxytocin degrades without refrigeration, and most postpartum haemorrhage deaths happen where refrigeration is unreliable. Oxytocin requires a cold chain from manufacture to the point of delivery; where that chain breaks, women receive a drug that may have lost potency, with no way to tell. The heat-stable carbetocin formulation developed with Ferring and MSD does not require cold storage, which is why the WHO Expert Committee added it to the Model List of Essential Medicines in 2019 under uterotonics, as a 100 micrograms per mL heat-stable parenteral injection. CHAMPION deliberately kept both drugs refrigerated so the comparison tested pharmacology rather than storage — the trial proves carbetocin works as well as properly stored oxytocin, and the cold-chain advantage is an argument about the real world the trial could not itself measure.

What happened to carbetocin nasal spray for Prader-Willi syndrome?

It failed its confirmatory trial and the programme was stopped. The sequence is worth following closely because it is a textbook example of an early signal not replicating. A 37-participant, 14-day trial (Dykens et al., 2018) found a significant reduction in hyperphagia. The Phase 3 CARE-PWS trial in 130 participants then missed both of its primary endpoints, with improvements that reached only nominal significance at the lower 3.2-mg dose — and that trial had stopped enrolling early because of COVID-19. An FDA advisory committee voted 12 to 1 against substantial evidence of effectiveness on 4 November 2021, and the agency issued a Complete Response Letter in January 2022 calling the drug generally safe and well tolerated but the efficacy data insufficient. Acadia acquired the programme and ran COMPASS PWS, a 12-week trial in 175 people aged 5 to 30 designed around FDA feedback and testing exactly the 3.2-mg dose that had looked promising. The treatment difference on the Hyperphagia Questionnaire for Clinical Trials was 0.3 points (P=0.79) in favour of placebo, with no separation on any secondary or exploratory endpoint. On 24 September 2025 Acadia stated it does not intend to investigate intranasal carbetocin any further.

Can carbetocin be used to induce or augment labour?

No — this is an absolute contraindication, and it is the single most important safety point on the page. The label states that use of carbetocin at any stage before delivery of the infant is not appropriate, and lists pregnancy, labour before delivery of the infant, and use to induce labour among its contraindications. The reason is pharmacological rather than regulatory caution: carbetocin produces a sustained contraction lasting hours and cannot be titrated or switched off. Oxytocin's very short half-life is what makes induction manageable — an infusion can be slowed or stopped and uterine activity subsides. A long-acting uterotonic given before birth risks sustained hypertonic contraction with the fetus still in utero. Carbetocin is given once, after the infant is delivered, preferably before delivery of the placenta.

Does carbetocin have the social and bonding effects attributed to oxytocin?

There is no human evidence that it does, and the one well-powered attempt to show a central behavioural effect failed. Carbetocin binds the same oxytocin receptor and is more selective for it than oxytocin is, and animal work supports central activity — a 2025 rat study found that systemic carbetocin dose-dependently prevented the anxiety-like effect of chronic social defeat stress, an effect blocked by oxytocin-receptor antagonists. But the human translation did not follow: the intranasal Prader-Willi programme measured anxiousness and distress alongside hyperphagia and found no separation from placebo on any of those measures in COMPASS PWS. Treat claims about carbetocin as a longer-lasting social or bonding agent as unsupported in humans.

Does carbetocin affect the heart?

Less than its reputation suggests, on current evidence. Oxytocin can cause dose-dependent myocardial effects, and the concern carried over to its long-acting analogue. A double-blind randomised trial in Oslo (BJOG 2025) gave 215 women undergoing planned caesarean either oxytocin 2.5 IU or carbetocin 100 micrograms intravenously and measured cardiac troponin I at 6 to 10 hours postpartum: there was no difference in troponin change between the groups. A 2026 thorough QT study in 42 healthy adults used a supratherapeutic 650-microgram intravenous infusion and found no predicted QTc prolongation of clinical or regulatory concern, with a placebo-corrected change of 4.5 msec at high clinical exposure — well under the 10 msec threshold. Carbetocin does raise heart rate (a mean maximum increase of 16.7 bpm in that study). Significant cardiovascular disorders remain a labelled contraindication.

How is carbetocin different from oxytocin chemically?

Three modifications, all aimed at slowing its breakdown. Position 1 is deaminated, removing the free amino group that peptidases attack. The disulfide bond that closes oxytocin's six-residue ring is replaced by a thioether, producing the carba-1 structure that resists reduction. And the position-2 tyrosine carries a methyl group on its phenolic oxygen. The result is a molecule of about 988 daltons against oxytocin's 1007, with a terminal half-life of 33 minutes intravenously and 55 minutes intramuscularly instead of oxytocin's one to six minutes. That is the whole design brief: one injection instead of an infusion.

Who Carbetocin Is NOT For

Contraindications
  • •Pregnancy and labour before delivery of the infant — carbetocin must never be given at any stage before the baby is born.
  • •Use for the induction of labour, which is explicitly contraindicated; its sustained, non-titratable action is incompatible with managing uterine activity before birth.
  • •Known hypersensitivity to carbetocin, to oxytocin, or to any excipient of the formulation.
  • •Liver disease.
  • •Kidney disease.
  • •Significant cardiovascular disorders, including serious cardiac disease.
  • •Epilepsy.
  • •Children under 12 years — there is no relevant use in this group, and safety and efficacy in adolescents have not been established for the injectable product.

Drug & Supplement Interactions

No dedicated interaction studies have been conducted. Trials found no interaction with analgesics, spasmolytics or epidural and spinal anaesthetic agents, but the label is explicit that because carbetocin is structurally close to oxytocin, interactions reported with oxytocin cannot be excluded — including severe hypertension when a vasoconstrictor is given alongside caudal block anaesthesia, and arrhythmias. The interactions that matter most in practice are with the other uterotonics. Ergot alkaloids such as methylergometrine may have their blood-pressure effect increased by carbetocin, and giving oxytocin or methylergometrine after carbetocin carries a risk of cumulative exposure — relevant precisely because carbetocin is the agent most likely to be followed by rescue medication when bleeding continues. Concurrent use of prostaglandins and carbetocin is not recommended; where they are given together, close monitoring is advised. Halothane and cyclopropane, the volatile anaesthetics, may both enhance the hypotensive effect and weaken the uterine response to carbetocin. A theoretical interaction worth naming is with large-volume electrolyte-free intravenous fluids. Carbetocin shares oxytocin's weak antidiuretic activity, so the combination creates a potential route to dilutional hyponatraemia and water intoxication, even though the single-dose regimen makes this far less likely than with a prolonged oxytocin infusion.

Safety Profile

Safety Information

Common Side Effects

Nausea and vomitingAbdominal painPruritus (itching)Flushing and feeling of warmthHeadacheTremorTransient increase in heart rate (a mean maximum of about 17 bpm at supratherapeutic intravenous dosing)Hypotension, more likely with rapid intravenous administrationMetallic taste

Cautions

  • • Hospital-only medicine administered by a clinician immediately after delivery — it is not self-administered, not available for outpatient use, and not obtainable legally outside a clinical setting.
  • • Absolutely contraindicated before delivery of the infant and for labour induction. Its long duration of action cannot be reversed or titrated.
  • • Single use only. No further carbetocin should be given, and giving oxytocin or methylergometrine afterwards carries a risk of cumulative exposure.
  • • Contraindicated in liver or kidney disease, significant cardiovascular disorders, and epilepsy.
  • • Cross-reactive hypersensitivity: anyone with a hypersensitivity to oxytocin should not receive carbetocin.
  • • Like oxytocin, it has antidiuretic activity. Water intoxication with hyponatraemia is a theoretical risk, particularly where large volumes of electrolyte-free fluid are given.
  • • Not FDA-approved in the United States, so American clinicians have no approved route to use it.

What We Don't Know

The evidence base is unusually deep for the single obstetric indication and unusually thin for everything else. Dose-optimisation is one open question: the labelled 100-microgram dose was set early, and dose-finding work has suggested considerably smaller doses may be sufficient at elective caesarean, but no regulator has revised the label. Comparative effectiveness in women at high risk of haemorrhage — multiple pregnancy, placenta praevia, prolonged labour — is less well characterised than in the low-risk populations most trials recruited, and dedicated trials in twin pregnancies are still enrolling. Long-term or repeated-exposure safety has not been studied because the drug is given once in a lifetime event. Finally, the collapse of the intranasal programme leaves central oxytocin-receptor pharmacology in humans largely unresolved: carbetocin crosses into a behavioural space in animal models that it has never been shown to reach in people.

Myths & Misconceptions

Myth

Carbetocin is a stronger or more effective version of oxytocin.

Reality

It is a longer-acting version, which is not the same thing. The 2025 Cochrane network meta-analysis of 122 trials and 121,931 women rates carbetocin as having effects similar to oxytocin for blood loss of at least 500 mL at high certainty, and as making little or no difference for blood loss of at least 1000 mL or for blood transfusion. CHAMPION was explicitly designed as a noninferiority trial — the question it asked was whether carbetocin is not meaningfully worse, not whether it is better. The genuine advantages are duration (one injection instead of an infusion), tolerability (Cochrane identifies it as the only agent in the network not associated with increased side effects versus oxytocin) and heat stability. Potency is not among them.

Myth

Carbetocin is EMA-approved.

Reality

There is no centralised European Medicines Agency authorisation for carbetocin. It is authorised through national and decentralised procedures (reference DK/H/2872/001), with separate national marketing authorisations held in individual member states, mostly by Ferring. The distinction matters because it means there is no single EMA product page, no EMA assessment report of the kind a centralised approval generates, and labelling that can vary between countries. Sources that describe carbetocin as EMA-approved are compressing a decentralised regulatory history into a convenient shorthand.

Myth

The nasal spray for Prader-Willi syndrome worked but the FDA rejected it.

Reality

The FDA asked for confirmation, got it, and the answer was no. The Complete Response Letter in January 2022 did not dispute safety — the agency described the drug as generally safe and well tolerated — but found the efficacy data for the 3.2-mg dose insufficient and requested a confirmatory study. Acadia ran exactly that study. COMPASS PWS enrolled 175 participants, tested the same 3.2-mg dose, and produced a treatment difference of 0.3 points on the primary hyperphagia measure (P=0.79) with the placebo arm numerically ahead and no separation on any secondary or exploratory endpoint. Acadia discontinued the programme in September 2025. The regulatory caution was vindicated rather than overruled.

Myth

Carbetocin can be used to start or speed up labour because it is a stronger uterotonic.

Reality

This is the most dangerous misreading of the drug, and the label contradicts it twice over: pregnancy and labour before delivery of the infant are contraindications, and so is use for labour induction. The property that makes carbetocin convenient after birth — a single dose producing hours of sustained uterine activity — makes it unusable before birth, because there is no way to slow it, stop it or reverse it if contractions become hypertonic while the fetus is still in utero. Oxytocin's very short half-life is a safety feature in that context, not a limitation.

Myth

Because it is an oxytocin analogue, carbetocin produces the bonding and trust effects attributed to intranasal oxytocin.

Reality

No human study supports this. Carbetocin is more selective for the oxytocin receptor than oxytocin itself and animal models do show centrally mediated, antagonist-reversible behavioural effects — in rats, chronic systemic carbetocin prevented the anxiety-like consequences of social defeat stress. But the only well-powered human test of carbetocin on behavioural endpoints was the Prader-Willi programme, which measured anxiousness and distress alongside hyperphagia and found no separation from placebo on any of them. Receptor selectivity and a longer half-life did not produce a demonstrable central effect in people.

Myth

Heat-stable carbetocin is a different drug from regular carbetocin.

Reality

It is the same molecule in a different formulation. The pharmacology, dose and route are unchanged; what differs is that the heat-stable presentation does not require refrigerated storage. That single property is why the WHO Expert Committee listed it as an essential medicine in 2019 — oxytocin degrades without a cold chain, and postpartum haemorrhage kills disproportionately where cold chains fail. CHAMPION deliberately kept both study drugs refrigerated so that blinding held, which means the trial proved the pharmacology and left the storage advantage as a logistical argument rather than a trial result.

Published Research

17 studies

The Effect of Carbetocin on Cardiac Repolarization: A Randomized, Placebo- and Positive-Controlled QT/QTc Study in Healthy Adults.

Clinical TrialPMID: 42802704

Carbetocin Nasal Spray for the Treatment of Hyperphagia in Prader-Willi Syndrome: Results From the Randomized, Placebo-Controlled, Phase 3 Compass PWS Study.

The confirmatory trial that ended the programme. 175 participants aged 5 to 30 randomised 1:1 to intranasal carbetocin 3.2 mg three times daily or placebo for 12 weeks (NCT06173531). Least-squares mean change in the Hyperphagia Questionnaire for Clinical Trials was -4.8 with carbetocin and -5.1 with placebo — a treatment difference of 0.3 (95 percent CI -1.8 to 2.4, P=0.79) favouring placebo, with no separation on any secondary or exploratory endpoint. The dose tested was precisely the one that had shown nominal benefit in CARE-PWS.

Randomized Controlled TrialPMID: 42486751

Diagnosis and treatment of postpartum haemorrhage: a race against time.

Systematic ReviewPMID: 42285120

Prevention of postpartum haemorrhage: from evidence to implementation at scale.

ReviewPMID: 42285117

Carbetocin vs oxytocin for prevention of postpartum hemorrhage in women with obesity undergoing cesarean delivery: A systematic review and meta-analysis.

Meta-AnalysisPMID: 42102921

Comparing oxytocin alternatives for postpartum hemorrhage prevention in vaginal and caesarean births: a systematic review and meta-analysis.

Meta-AnalysisPMID: 42050041

Effects of oxytocin receptor ligands on anxiogenic-like effect, social avoidance and changes on medial prefrontal cortex oxytocin receptor expression evoked by chronic social defeat stress in rats.

Animal StudyPMID: 41238073

Effects of Prophylactic Oxytocin or Carbetocin on Troponin Release and Postpartum Haemorrhage at Planned Caesarean Delivery: A Double-Blind Randomised Controlled Trial.

Randomized Controlled TrialPMID: 40772429

Prophylactic strategies for prevention of postpartum haemorrhage in caesarean delivery: a systematic review and Bayesian network meta-analysis of randomised controlled trials.

Network Meta-AnalysisPMID: 40712613

Uterotonic agents for preventing postpartum haemorrhage: a network meta-analysis.

The 2025 Cochrane update, with trustworthiness screening: 122 trials, 121,931 women, seven uterotonics across 48 countries. Carbetocin has effects similar to oxytocin for blood loss of at least 500 mL (high certainty) and makes little or no difference for blood loss of at least 1000 mL or blood transfusion (moderate certainty). It reduces use of additional uterotonics (RR 0.74, 95 percent CI 0.59 to 0.94, low certainty). The two highest-ranked agents were ergometrine plus oxytocin and misoprostol plus oxytocin — not carbetocin. Notably, all agents except carbetocin were associated with increased side-effect risks versus oxytocin.

Network Meta-AnalysisPMID: 40237648

A systematic review and meta-analysis of randomized trials comparing carbetocin to oxytocin in prevention of postpartum hemorrhage after cesarean delivery in low-risk women.

17 trials and 3,667 participants undergoing low-risk caesarean. Carbetocin reduced the need for additional uterotonics (OR 0.53, 95 percent CI 0.39 to 0.72) but made no difference to the incidence of postpartum haemorrhage itself (OR 1.08, 95 percent CI 0.81 to 1.44, P=0.61, I-squared 0 percent). The clean separation between those two outcomes is the most useful single result for understanding what carbetocin does and does not buy.

Meta-AnalysisPMID: 39722234

The future of child and adolescent clinical psychopharmacology: A systematic review of phase 2, 3, or 4 randomized controlled trials of pharmacologic agents without regulatory approval or for unapproved indications.

Systematic ReviewPMID: 37001575

Intranasal Carbetocin Reduces Hyperphagia, Anxiousness, and Distress in Prader-Willi Syndrome: CARE-PWS Phase 3 Trial.

The trial whose title overstates its result. 130 participants aged 7 to 18 randomised to carbetocin 9.6 mg, 3.2 mg or placebo three times daily for eight weeks. Both primary endpoints — hyperphagia and obsessive-compulsive symptoms at the 9.6-mg dose — showed numeric improvement that was not statistically significant. Only the 3.2-mg arm reached nominal significance on hyperphagia, anxiousness-and-distress and clinical global impression. Enrolment stopped early because of COVID-19. This is the dataset the FDA declined in January 2022.

Randomized Controlled TrialPMID: 36633570

The Prader-Willi Syndrome Anxiousness and Distress Behaviors Questionnaire: Development and Psychometric Validation.

Observational StudyPMID: 36202701

Pharmacokinetics and bioavailability of carbetocin after intravenous and intramuscular administration in cows and gilts.

Animal StudyPMID: 31856330

Heat-Stable Carbetocin versus Oxytocin to Prevent Hemorrhage after Vaginal Birth.

The WHO CHAMPION trial — 29,645 women across 23 sites in 10 countries, the largest trial in the field. Heat-stable carbetocin 100 micrograms intramuscularly was noninferior to oxytocin 10 IU for blood loss of at least 500 mL or use of additional uterotonics (14.5 percent versus 14.4 percent; RR 1.01, 95 percent CI 0.95 to 1.06). Noninferiority was not shown for blood loss of at least 1000 mL (1.51 versus 1.45 percent) because event rates were too low to power that comparison. Both drugs were kept refrigerated to preserve blinding, so the trial tested pharmacology rather than the cold-chain advantage.

Randomized Controlled TrialPMID: 29949473

Intranasal carbetocin reduces hyperphagia in individuals with Prader-Willi syndrome.

The Ferring-funded signal that started the programme: 37 adolescents aged 10 to 18 (17 carbetocin, 20 placebo) treated for 14 days. Hyperphagia scores fell by 15.6 points versus 8.9 on placebo (P=0.029), with several secondary endpoints also significant. Read alongside CARE-PWS and COMPASS PWS, it is a case study in how a small, short, industry-funded positive trial can fail to survive adequate powering.

Randomized Controlled TrialPMID: 29925684

Quick Facts

Class
Oxytocin Receptor Agonist (Long-Acting Analogue)
Tier
B
Evidence
Strong
Safety
Well-Studied
Updated
Oct 2026
Citations
17PubMed

Also known as

PabalDuratocinDuratobalLonacteneHeat-stable carbetocinLV-101ACP-1011-deamino-1-carba-2-tyrosine(O-methyl)-oxytocin

Tags

HormonalReproductivePrescriptionObstetric

Evidence Score

Overall Confidence85%

Clinical Trials

View Clinical Trials

Links to ClinicalTrials.gov for reference. Listing does not imply endorsement.