Carbetocin
[CAS# 37025-55-1]

Identification

• Classification: Biochemical >> Peptide
• Name: Carbetocin
• Synonyms: (2S)-N-[(2S)-1-[(2-amino-2-oxoethyl)amino]-4-methyl-1-oxopentan-2-yl]-1-[(3R,6S,9S,12S,15S)-6-(2-amino-2-oxoethyl)-9-(3-amino-3-oxopropyl)-12-[(2S)-butan-2-yl]-15-[(4-methoxyphenyl)methyl]-5,8,11,14,17-pentaoxo-1-thia-4,7,10,13,16-pentazacycloicosane-3-carbonyl]pyrrolidine-2-carboxamide
• Molecular Formula: C₄₅H₆₉N₁₁O₁₂S
• Molecular Weight: 988.16
• CAS Registry Number: 37025-55-1
• EC Number: 253-312-6
• SMILES: CC[C@H](C)[C@H]1C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CSCCCC(=O)N[C@H](C(=O)N1)CC2=CC=C(C=C2)OC)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N)CC(=O)N)CCC(=O)N

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Boiling point: 1477.9±65.0 ºC 760 mmHg (Calc.)^*
• Flash point: 847.6±34.3 ºC (Calc.)^*
• Solubility: DMSO 61 mg/mL, Water <1 mg/mL, Ethanol 61 mg/mL (Expl.)
• Index of refraction: 1.533 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS08 Danger
• Hazard Statements: H312+H332-H317-H361
• Precautionary Statements: P203-P261-P271-P272-P280-P302+P352-P304+P340-P317-P318-P321-P333+P317-P362+P364-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Reproductive toxicity	Repr.	2	H361
Skin sensitization	Skin Sens.	1	H317

Discovory and Applicatios

Carbetocin is a synthetic long‑acting analogue of the natural hormone oxytocin that has been developed to prevent excessive bleeding after childbirth by promoting sustained contraction of the uterine smooth muscle. It belongs to the class of uterotonic agents, drugs that enhance uterine tone and reduce the risk of postpartum haemorrhage (PPH), which remains a leading cause of maternal morbidity and mortality worldwide. Carbetocin’s design modifies the peptide structure of oxytocin to confer a prolonged duration of action and improved stability relative to oxytocin, permitting effective uterine contraction with a single dose administration rather than the continuous infusion typically required for oxytocin. This structural and functional distinction underlies its clinical utility and differentiates it from the endogenous hormone.

Carbetocin was first described in the scientific literature in the late 20th century, with early clinical evaluations conducted in the 1990s, and it has since been approved for medical use in multiple countries for the prevention of PPH following caesarean section under regional anaesthesia. Its development was driven by the need for an effective uterotonic with a longer half‑life and greater stability than oxytocin, addressing limitations such as oxytocin’s short plasma half‑life and requirement for cold storage. In many regions, especially low‑resource settings where maintaining a cold chain is challenging, a more stable peptide agent like carbetocin offers practical advantages in obstetric care.

Pharmacologically, carbetocin acts as an agonist at peripheral oxytocin receptors located on the myometrium, the smooth muscle layer of the uterus. Activation of these receptors triggers a cascade of intracellular events that increase intracellular calcium and lead to rhythmic myometrial contractions and improved uterine tone after delivery. The peptide’s molecular modifications prolong its half‑life compared to oxytocin, with typical elimination half‑life estimates ranging from approximately 40 to 100 minutes, allowing effective uterine contraction from a single injection. Carbetocin’s mechanism of action is similar in principle to oxytocin but its extended duration and single‑dose administration make it especially suited for clinical use in preventing PPH.

Clinical research has examined the efficacy of carbetocin compared with oxytocin, and the evidence indicates that carbetocin reduces the need for additional uterotonic agents after caesarean section and maintains adequate uterine tone. Randomized trials have demonstrated that a single dose of carbetocin results in fewer requirements for further oxytocic interventions than standard oxytocin infusions, though the overall incidence of PPH may not differ significantly. Carbetocin’s side effect profile is generally similar to that of oxytocin, with common adverse events including nausea, vomiting, headache, and transient haemodynamic changes, although some studies suggest a lower incidence of certain adverse effects compared with other uterotonics.

In addition to its established use following caesarean delivery, carbetocin has been investigated for prevention of PPH after vaginal birth, though evidence for routine use in this context remains less definitive and practice guidelines vary. Research into heat‑stable formulations of carbetocin has gained prominence as these newer formulations retain potency without refrigeration, offering a significant clinical advantage in low‑ and middle‑income countries where maintaining cold chain logistics poses a barrier to effective obstetric care.

Overall, carbetocin’s development represents a significant advance in obstetric pharmacotherapy for PPH prevention. By combining the uterotonic efficacy of oxytocin with improved pharmacokinetic properties, carbetocin has become an important tool in maternal health, particularly in settings where simplicity of dosing and thermal stability are essential. Ongoing research seeks to further define its role across diverse clinical settings and populations.

References

Su LL, Chong YS, Samuel M (2022) Carbetocin for preventing postpartum haemorrhage. Cochrane Database of Systematic Reviews Issue 3 Art. No.: CD005457.pub4 DOI: 10.1002/14651858.CD005457.pub4

Pierson RA, McDermott WG, Katz M, et al. (1999) Double‑blind comparison of carbetocin versus oxytocin in prevention of uterine atony after caesarean section. American Journal of Obstetrics and Gynecology 180(3) 670–676 DOI: 10.1016/S0002-9378(99)70271-1

Su LL, Chong YS, Samuel M (2012) Carbetocin for preventing postpartum haemorrhage. Cochrane Database of Systematic Reviews Issue 4 Art. No.: CD005457.pub4 DOI: 10.1002/14651858.CD005457.pub4