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Carbetocin
A long-acting synthetic oxytocin analog used to prevent postpartum hemorrhage following cesarean delivery, with a duration of action approximately 4-10 times longer than oxytocin.
Overview
Carbetocin is a synthetic long-acting analog of oxytocin designed for the prevention of postpartum hemorrhage (PPH), the leading cause of maternal death worldwide. The peptide was created by modifying the oxytocin molecule at three positions: deamination of the N-terminal cysteine, replacement of the disulfide bridge with a thioether linkage (which prevents enzymatic cleavage), and methylation of the tyrosine residue at position 2. These modifications increase resistance to enzymatic degradation by aminopeptidases and disulfidases, resulting in a half-life of approximately 40 minutes compared to 3-4 minutes for oxytocin.
Carbetocin exerts its uterotonic effect by binding to oxytocin receptors on uterine smooth muscle cells, stimulating rhythmic contractions of the upper uterine segment and sustained contraction (tetanus) that compresses the uterine blood vessels at the placental site. This mechanical compression of blood vessels is the primary mechanism by which the uterus achieves hemostasis after delivery (a process termed "physiological ligation"). The prolonged duration of action of carbetocin means a single dose provides sustained uterotonic activity, potentially eliminating the need for continuous oxytocin infusion after cesarean delivery.
The landmark CHAMPION trial (Carbetocin HAeMorrhage prevention), conducted by the WHO and published in the New England Journal of Medicine in 2018, compared heat-stable carbetocin to oxytocin in over 29,000 women delivering vaginally in 10 countries. The trial demonstrated that heat-stable carbetocin was non-inferior to oxytocin for the prevention of PPH. Critically, the heat-stable formulation of carbetocin does not require cold-chain storage, making it particularly valuable for low-resource settings where refrigeration is unreliable — precisely the settings where PPH causes the most maternal deaths.
Carbetocin is approved in many countries for the prevention of uterine atony and PPH following cesarean delivery. Following the CHAMPION trial, the WHO included heat-stable carbetocin in its recommendations for PPH prevention, and it was added to the WHO Model List of Essential Medicines in 2019.