Carbetocin

A long-acting synthetic oxytocin analog approved outside the United States as Duratocin and Pabal to prevent postpartum hemorrhage, with a heat-stable form on the WHO Essential Medicines List; intranasal carbetocin failed in Prader-Willi syndrome.

Also referenced as: Duratocin, Pabal, Lonactene, ACP-101, LV-101, FE 992097, carbetocin acetate, Carbetocin Ferring

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What is Carbetocin?

Carbetocin is a synthetic nonapeptide analog of oxytocin, chemically 1-deamino-1-monocarba-2-(O-methyl)-tyrosine-oxytocin: the N-terminal amino group is removed, the disulfide bridge is replaced by a thioether (carba) link, and the tyrosine at position 2 is O-methylated. Those three changes protect the molecule from the aminopeptidases and disulfide reductases that clear oxytocin within minutes, giving carbetocin a terminal half-life measured in tens of minutes rather than a few minutes and a single-injection duration of uterine activity that lasts an hour or more. First approved in Canada on June 20, 1997 as Duratocin and in the United Kingdom on October 6, 1997 as Pabal (Lonactene in Mexico), carbetocin is approved in more than 80 countries as a uterotonic for preventing postpartum hemorrhage, and a heat-stable formulation has been on the WHO Model List of Essential Medicines since 2019. It has never been approved in the United States or Japan; the only US-directed program, an intranasal formulation for hyperphagia in Prader-Willi syndrome, ended in 2025 after a failed confirmatory trial. Carbetocin acetate is available as a research-market peptide, usually listed alongside oxytocin.

How it works

• Full-affinity but partial oxytocin-receptor agonist. In rat myometrium, carbetocin binds the oxytocin receptor with an affinity comparable to oxytocin and contracts the tissue through the same inositol-phosphate (Gq) pathway, but its maximal contractile effect is about half of oxytocin’s (2.70 versus 5.22 g) and its EC50 roughly ten times higher (48.0 versus 5.62 nM), so it behaves as a partial agonist that can also antagonize oxytocin in vitro (pA2 8.21); its affinity for the vasopressin V1 receptor is much lower and for the renal V2 receptor very low (Engstrøm et al., European Journal of Pharmacology, 1998, 355(2–3):203–210).
• Metabolic resistance and a prolonged uterine action. The deamino, carba, and O-methyl modifications slow enzymatic degradation; in 40 women 24 to 48 hours postpartum, a single intravenous dose of 8 to 30 µg produced a tetanic uterine contraction within 2 minutes lasting about 6 minutes followed by rhythmic contractions for about 60 minutes, and intramuscular doses of 10 to 70 µg produced a tetanic contraction lasting about 11 minutes followed by rhythmic activity for about 2 hours (Hunter et al., Clinical Pharmacology and Therapeutics, 1992, 52(1):60–67). The Canadian product monograph gives a geometric mean terminal half-life of 33 minutes intravenously and 55 minutes intramuscularly, 77% intramuscular bioavailability, and less than 1% renal excretion of unchanged drug.
• Biased, non-recycling receptor signaling. At the human oxytocin receptor, carbetocin is a partial agonist that activates only the Gq pathway, does not recruit β-arrestin, drives receptor internalization through a β-arrestin-independent route, and does not allow the receptor to recycle to the plasma membrane; it does not activate vasopressin V1a or V1b receptors and may antagonize them (Passoni et al., Journal of Neuroendocrinology, 2016, 28(4), doi:10.1111/jne.12363).
• Heat stability by formulation. The heat-stable product is 0.1 mg/mL carbetocin in a sodium succinate buffer with mannitol and methionine at pH 5.45; it kept at least 95% peptide purity for 3 years at 30 °C and 75% relative humidity, 6 months at 40 °C, 3 months at 50 °C, and 1 month at 60 °C, which is what allows distribution without a cold chain (Malm et al., Journal of Peptide Science, 2018, 24(6):e3082).

Research status

Carbetocin’s obstetric evidence base is large and mature; its neuropsychiatric program is finished.

• Early cesarean trials. Boucher et al. (1998), Journal of Perinatology 18(3):202–207, compared a single 100 µg intravenous dose with a 16-hour oxytocin infusion in 57 women and found better uterine tone and a nonsignificant 29 mL reduction in blood loss. Dansereau et al. (1999), American Journal of Obstetrics and Gynecology 180(3 Pt 1):670–676: in the 694-patient double-blind Canadian multicenter trial, a single 100 µg intravenous dose was compared with an 8-hour oxytocin infusion after elective cesarean section; additional uterotonic intervention was needed in 4.7% of carbetocin patients versus 10.1% of oxytocin patients. Attilakos et al. (2010), BJOG 117(8):929–936, found the same pattern in a double-blind UK trial against 5 IU oxytocin (33.5% versus 45.5% needing additional oxytocics; relative risk 0.74, 95% CI 0.57–0.95).
• Cochrane review of carbetocin. Su et al. (2012), Cochrane Database of Systematic Reviews CD005457: 11 trials and 2,635 women. Carbetocin reduced the need for therapeutic uterotonics after cesarean delivery (RR 0.62, 95% CI 0.44–0.88) and the need for uterine massage, with no significant difference from oxytocin in postpartum hemorrhage or severe postpartum hemorrhage; against syntometrine after vaginal birth it produced slightly lower blood loss (mean difference −48.84 mL) and much less nausea (RR 0.24) and vomiting (RR 0.21).
• Network meta-analysis of all uterotonics. Gallos et al. (2018), Cochrane Database of Systematic Reviews CD011689: 140 trials and 88,947 women. Carbetocin ranked among the three most effective strategies for preventing blood loss of 500 mL or more (RR 0.72 versus oxytocin, 95% CI 0.52–1.00) and had the most favorable side-effect profile of the three, but the carbetocin evidence was graded very low quality for that outcome and low quality for blood loss of 1,000 mL or more because the trials were small and at high risk of bias. The companion health-technology assessment (Gallos et al., 2019, Health Technology Assessment 23(9):1–356) reported that when the analysis was restricted to high-quality studies carbetocin lost its ranking and was comparable to oxytocin. The April 16, 2025 update of the review (122 trials, 121,931 women) rated carbetocin’s effect on blood loss of 500 mL or more as similar to oxytocin with high-certainty evidence, found it probably reduces the use of additional uterotonics (RR 0.74), and identified it as the only agent not associated with more side effects than oxytocin.
• CHAMPION trial of heat-stable carbetocin. Widmer et al. (2018), New England Journal of Medicine 379(8):743–752: a WHO-coordinated, double-blind noninferiority trial in 29,645 women at 23 sites in 10 countries, randomized to 100 µg intramuscular heat-stable carbetocin or 10 IU intramuscular oxytocin immediately after vaginal birth. Blood loss of at least 500 mL or use of additional uterotonics occurred in 14.5% versus 14.4% (relative risk 1.01, 95% CI 0.95–1.06), meeting the noninferiority margin of 1.16; for blood loss of at least 1,000 mL (1.51% versus 1.45%; relative risk 1.04, 95% CI 0.87–1.25) the confidence interval crossed the margin of 1.23, so noninferiority was not established for severe hemorrhage. Both drugs were refrigerated to preserve blinding, so the trial did not measure carbetocin’s advantage where oxytocin degrades. On the strength of CHAMPION, WHO recommended heat-stable carbetocin for postpartum hemorrhage prevention in 2018 in settings where oxytocin cannot be kept refrigerated, the heat-stable formulation entered the WHO Model List of Essential Medicines in 2019 (TRS 1021), Swissmedic approved Carbetocin Ferring on May 13, 2020 as the first product under its procedure for global health products, and WHO prequalified heat-stable carbetocin in 2022.
• Dose-finding at cesarean. Khan et al. (2014), Canadian Journal of Anaesthesia 61(3):242–248: a sequential-allocation study in 40 women under spinal anesthesia estimated the intravenous ED90 at 14.8 µg (95% CI 13.7–15.8), less than one-fifth of the labeled 100 µg dose, with hypotension in 37.5% of participants. As of November 2026, ClinicalTrials.gov lists 15 recruiting or not-yet-recruiting carbetocin trials, all investigator-led obstetric or gynecologic studies in Canada, France, Turkey, Israel, Saudi Arabia, Egypt, and Nigeria, several of them Toronto studies of dose-response, hemodynamics, and calcium co-administration at cesarean delivery.
• Phase 2 in Prader-Willi syndrome. Dykens et al. (2018), JCI Insight 3(12):e98333 (NCT01968187): a Ferring-sponsored, 14-day, double-blind trial in which 38 participants aged 10 to 18 were randomized to intranasal carbetocin (FE 992097) 9.6 mg or placebo three times daily and 37 were treated. The caregiver-rated Hyperphagia in PWS Questionnaire-Responsiveness total score fell 15.6 points with carbetocin versus 8.9 with placebo (P = 0.029). Levo Therapeutics subsequently licensed the intranasal program from Ferring as LV-101.
• CARE-PWS phase 3. Roof et al. (2023), Journal of Clinical Endocrinology and Metabolism 108(7):1696–1708 (NCT03649477): participants aged 7 to 18 were randomized to 9.6 mg, 3.2 mg, or placebo three times daily for 8 weeks, with a 56-week extension. Enrollment was closed on March 12, 2020 because of the COVID-19 pandemic, with 138 randomized and 130 dosed against a target of 175. The prespecified primary endpoints for 9.6 mg versus placebo were not met (HQ-CT difference −1.2, P = 0.349; CY-BOCS difference −0.6, P = 0.600); the lower 3.2 mg dose showed nominally significant improvements in HQ-CT (difference −3.1, P = 0.016), anxiousness and distress (PADQ, P = 0.027), and clinical global impression of change (P = 0.027). Levo filed a new drug application on this basis; the FDA’s Psychopharmacologic Drugs Advisory Committee reviewed LV-101 on November 4, 2021 and voted that substantial evidence of effectiveness had not been provided, and the FDA issued a complete response letter in January 2022 asking for an additional study of the 3.2 mg dose.
• COMPASS PWS phase 3. Roof et al. (2026), Clinical Therapeutics, published online July 22, 2026 (NCT06173531): after Acadia Pharmaceuticals acquired Levo in June 2022 and renamed the drug ACP-101 (which held orphan drug, fast track, and rare pediatric disease designations), it ran the confirmatory 12-week trial of 3.2 mg three times daily versus placebo in 175 participants aged 5 to 30 (85 carbetocin, 90 placebo) from November 27, 2023 to August 19, 2025, and the trial did not meet its primary endpoint. The HQ-CT change at week 12 was −4.8 with carbetocin versus −5.1 with placebo (difference 0.3, 95% CI −1.8 to 2.4; P = 0.79), with no separation on any secondary endpoint; the most common adverse events were headache (7.2%) and pyrexia (6.0%). Acadia announced the result on September 24, 2025 and stated that it does not intend to investigate ACP-101 any further; the open-label extension (NCT06420297, 168 participants) was terminated because the parent study’s primary endpoint was not met and closed on December 19, 2025. Separately, a Ferring-supported thorough QT study in 49 healthy adults (Clinical and Translational Science, 2026) found no clinically relevant QTc prolongation at a supratherapeutic 650 µg intravenous exposure. As of November 2026, no carbetocin application is pending at the FDA and no sponsor has an active US development program.

Common dosage forms

• Solution for injection, 100 µg/mL (Duratocin, Pabal). The approved presentation in Canada, Europe, Australia, China, Latin America, and elsewhere: 1 mL single-use vials or ampoules of carbetocin acetate for intravenous or intramuscular injection.
• Heat-stable carbetocin (Carbetocin Ferring), 100 µg/mL. The Swissmedic-approved, WHO-prequalified formulation in sodium succinate, mannitol, and methionine, supplied as 1 mL ampoules for intramuscular or intravenous use; it is the presentation listed on the WHO Essential Medicines List.
• Intranasal spray (FE 992097/LV-101/ACP-101). A multidose nasal spray used only in the Prader-Willi syndrome trials; it was never approved or marketed anywhere, and development ended in 2025.

Key considerations

• Regulatory status. The Research Market status reflects the absence of any FDA-approved carbetocin product. Carbetocin is approved in more than 80 countries for postpartum hemorrhage prevention, and the only US-directed program, intranasal ACP-101 for Prader-Willi syndrome, ended after COMPASS PWS in 2025.
• An approved obstetric drug with a narrow label. Everywhere it is licensed, carbetocin is indicated for a single injection after delivery to prevent postpartum hemorrhage due to uterine atony, not for labor induction or augmentation or for treating established hemorrhage. Because its uterine action cannot be stopped by withdrawing the drug, labels contraindicate use before delivery of the infant.
• Noninferior to oxytocin, not clearly superior. CHAMPION showed noninferiority to oxytocin for blood loss of 500 mL or more but did not establish it for severe hemorrhage, and the 2019 health-technology assessment and the 2025 Cochrane update both rate its effect as similar to oxytocin. Its practical case rests on heat stability, single-dose convenience, and a cleaner side-effect profile than the combination regimens, not on a larger effect size.
• Hemodynamic and oxytocin-like adverse effects. Flushing, warmth, headache, nausea, abdominal pain, tremor, hypotension, and tachycardia are the labeled reactions, and hypotension occurred in 37.5% of women in the cesarean dose-finding study. Labels restrict use in serious cardiovascular disease, and the oxytocin-like antidiuretic effect means water retention and hyponatremia cannot be excluded with repeated exposure.
• Not interchangeable with oxytocin, and not a nasal oxytocin substitute. Carbetocin is a partial, Gq-biased agonist that internalizes the oxytocin receptor without recycling it and does not activate vasopressin V1a or V1b receptors, so central effects seen with oxytocin cannot be assumed, and two phase 3 trials of the intranasal form did not demonstrate efficacy for hyperphagia. Duratocin, Pabal, Lonactene, Carbetocin Ferring, FE 992097, LV-101, and ACP-101 all denote the same molecule, carbetocin acetate.