Carbetocin
Also known as: 1-deamino-1-monocarba-(2-O-methyltyrosine)-oxytocin, Duratocin, Lonactene, oxytocin analog, heat-stable carbetocin, HSC
Synthetic oxytocin receptor agonist; uterotonic peptide hormone analog
What it is
Carbetocin is a long-acting synthetic oxytocin analog used by obstetricians and midwives worldwide to prevent life-threatening postpartum hemorrhage after childbirth. It is the first thermostable uterotonic approved by WHO for use in settings without reliable refrigeration, making it especially valuable in low- and middle-income countries where cold-chain infrastructure is limited.
The scientific side
carbetocin is a synthetic structural analog of the endogenous nonapeptide hormone oxytocin. It was designed by replacing the amino-terminal cysteine with a carbetocin residue (deamination at position 1), substituting a methylene bridge for the disulfide bond, and introducing a 2-O-methyltyrosine at position 2. These modifications render the cyclic structure resistant to enzymatic degradation by oxytocinase and aminopeptidases, dramatically prolonging its half-life and duration of uterotonic action compared to native oxytocin. Carbetocin exerts its primary therapeutic effects via selective, high-affinity agonism at the oxytocin receptor (OTR), a Gq/G11-coupled G protein-coupled receptor expressed abundantly on uterine myometrial smooth muscle cells. OTR activation triggers phospholipase C-beta signaling, generating inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 mobilizes calcium from sarcoplasmic reticulum stores, while DAG activates protein kinase C. The resulting rise in intracellular calcium activates myosin light chain kinase, driving actin-myosin cross-bridge cycling and sustained uterine smooth muscle contraction. Unlike the brief, rhythmic contractions induced by oxytocin infusion, a single IV or IM dose of carbetocin produces sustained uterine tone lasting 60 minutes or longer, substantially reducing the risk of uterine atony — the leading cause of postpartum hemorrhage. Multiple randomized controlled trials included in these abstracts confirm carbetocin achieves superior or equivalent uterine tone compared to oxytocin, with lower rates of additional uterotonic use and reduced intraoperative blood loss, particularly during cesarean delivery in high-risk populations including women with obesity (PMID 42102921). Carbetocin also demonstrates a more favorable hemodynamic profile than oxytocin. Where oxytocin bolus frequently causes transient hypotension, tachycardia, and flushing due to vascular V2-like receptor actions, carbetocin's structural modifications reduce these vasodilatory off-target effects, yielding more stable mean arterial pressure and heart rate intraoperatively (PMID 40951045, 42553864, 41156081). Preclinical data (PMID 40324652) further suggest carbetocin may act as a biased OTR ligand with distinct signal transduction from oxytocin, including sex-dependent antinociceptive properties in animal models, though this has not been studied clinically. The heat-stable formulation (Carbetocin-HS) maintains potency for up to three years at temperatures up to 30°C without refrigeration (PMID 40487679).
Class: Synthetic oxytocin receptor agonist; uterotonic peptide hormone analog
Administration & storage
- Administration
- Intravenous (IV) bolus: 100 µg administered as a slow IV injection over 30–60 seconds immediately after delivery of the infant (cesarean or vaginal delivery). Rapid IV bolus should be avoided due to hemodynamic effects.Intramuscular (IM) injection: 100 µg IM into the lateral thigh or deltoid immediately following delivery of the infant — used in the WHO CHAMPION trial and in resource-limited settings where IV access may not be available.No oralintranasalor subcutaneous administration routes have been studied for carbetocin.
- Storage
- Refrigerated formulation (Duratocin and equivalents): store at 2–8°C (36–46°F); do not freeze; protect from light. Once removed from refrigerator, use immediately. Heat-stable WHO-prequalified formulation: may be stored at ambient temperature up to 30°C (86°F) for up to 3 years per manufacturer specifications and WHO assessment (PMID 40487679). Do not use beyond the labeled expiry date. Do not expose any formulation to temperatures exceeding 30°C even transiently if the refrigerated formulation is used.
- Cautions
- Carbetocin is intended for SINGLE-DOSE USE ONLY. Repeat dosing is not supported by clinical evidence and may increase hemodynamic adverse effects. If uterotonic augmentation is needed after an initial carbetocin dose, add a different uterotonic agent rather than re-dosing carbetocin.,Hemodynamic monitoring is required following IV administration: transient drops in blood pressure, tachycardia, and flushing can occur, particularly with rapid IV bolus injection. Administer as a SLOW IV bolus over 30–60 seconds; have vasopressor support available in high-risk patients.,CONTRAINDICATED during active labor and before delivery of the infant — carbetocin must only be administered AFTER delivery. Pre-delivery administration can cause fetal distress or uterine hyperstimulation.,Contraindicated in patients with known hypersensitivity to carbetocin, oxytocin, or any formulation excipient.,Use with caution in patients with cardiovascular disease, epilepsy, migraine, or any condition that may be exacerbated by fluid retention.,Carbetocin is not approved for labor induction, labor augmentation, or any obstetric indication other than postpartum uterotonic prophylaxis.
Legal & regulatory status
Carbetocin is not approved by the US FDA for any indication as of 2026. It is not available by prescription in the United States. An investigational new drug (IND) pathway would be required for clinical use. This…
Carbetocin is not listed on the WADA Prohibited List and is not considered a performance-enhancing substance for athletes. Its primary pharmacological action — uterine smooth muscle contraction and oxytocin receptor…
Carbetocin (Duratocin) is approved by Health Canada for the prevention of uterine atony and excessive bleeding following elective cesarean section under epidural or spinal anesthesia. It is available by prescription in…
What it's studied for
- Prevention of postpartum hemorrhage after vaginal delivery — noninferiority to oxytocin Phase III RCT (WHO CHAMPION trial)
- Prevention of uterine atony and hemorrhage during cesarean section Human RCT and retrospective cohort
- Carbetocin versus oxytocin with tranexamic acid — hemorrhage prevention in cesarean delivery Phase III RCT
- Prevention of PPH in women with obesity undergoing cesarean delivery Systematic review and meta-analysis
- Thermostable uterotonic for PPH prevention in low- and middle-income countries without reliable cold chain Implementation research and systematic review
- Timing optimization — pre- versus post-placental delivery administration Phase III RCT
- Cost-effectiveness analysis — PPH prevention in vaginal delivery (France tertiary center) Human observational (before-after cohort)
- Exploratory preclinical use — antinociception via biased oxytocin receptor agonism Animal (preclinical only)
Safety signals
- Transient hypotension and tachycardia following IV administration
- Hemodynamic instability greater than reported for IM route — rapid IV bolus effect
- Marginally lower post-delivery hemoglobin compared to oxytocin (vaginal delivery)
- Headache, nausea, flushing, and chest tightness following injection
- Increased rate of manual placenta removal when administered before placental delivery
- Uterine hyperstimulation risk if administered before fetal delivery (off-label misuse scenario)
- Lack of efficacy in severe uterine pathology — refractory atony in anatomically abnormal uteri
Frequently asked
Is carbetocin approved in the United States?
No. As of 2026, carbetocin is not approved by the US FDA for any indication. It is not available by prescription in the United States. Oxytocin (Pitocin) remains the FDA-approved standard for PPH prevention in the US. Carbetocin is approved in Canada (Duratocin) and has WHO prequalification for its heat-stable formulation for use in low- and middle-income countries.
How is carbetocin different from oxytocin?
Carbetocin is a synthetic analog of oxytocin engineered for prolonged action and thermostability. Key differences: (1) Duration — a single dose of carbetocin produces sustained uterine tone for 60+ minutes, compared to oxytocin which requires continuous infusion to maintain effect; (2) Heat stability — the WHO-prequalified heat-stable formulation is active for up to 3 years at ≤30°C without refrigeration, while oxytocin degrades rapidly outside cold chain; (3) Hemodynamic profile — carbetocin causes less hypotension and tachycardia than equivalent oxytocin bolus doses in clinical trials.
What dose of carbetocin is used to prevent postpartum hemorrhage?
The clinically studied and approved dose is 100 micrograms (µg) as a single dose, administered either as a slow IV injection over 30–60 seconds (for cesarean delivery) or as an intramuscular injection (for vaginal delivery). This single dose is given immediately after delivery of the infant. Repeat dosing is not recommended — if the uterus remains atonic, additional different uterotonic agents should be added per institutional protocols.
Can carbetocin be used for labor induction?
No. Carbetocin is approved and studied exclusively as a postpartum uterotonic to prevent hemorrhage after delivery. It must not be used to induce or augment labor. Administration before delivery carries serious risks including uterine hyperstimulation and fetal distress. Oxytocin, dinoprostone, and misoprostol are the agents studied and approved for labor induction.
Does carbetocin need to be refrigerated?
It depends on the formulation. The standard refrigerated formulation (Duratocin, used in Canada and other countries) requires storage at 2–8°C and must not be frozen. A separate thermostable (heat-stable) formulation has been developed specifically for use in settings without reliable cold-chain infrastructure — this version is stable for up to 3 years at ambient temperatures up to 30°C. The heat-stable formulation received WHO prequalification and is being deployed in low- and middle-income countries through WHO and UNICEF supply chains.
Is carbetocin safe for women with obesity?
Available evidence suggests carbetocin may actually be more effective than oxytocin in women with obesity undergoing cesarean delivery. A 2026 meta-analysis of three RCTs found carbetocin significantly reduced blood loss (by approximately 230 mL), PPH incidence (RR 0.19), and transfusion rates compared to oxytocin in this population. The hemodynamic stability advantage of carbetocin over oxytocin bolus is clinically relevant in obese patients who may already have elevated cardiovascular risk. Standard dosing of 100 µg IV is used without weight-based adjustment in the published trials.