Pharmacotherapeutic group: Oxytocin and analogues
ATC code: H01BB03
The pharmacological and clinical properties of carbetocin are those of a long acting oxytocin agonist.
Like oxytocin, carbetocin selectively binds to oxytocin receptors in the smooth muscle of the uterus, stimulates rhythmic contractions of the uterus, increases the frequency of existing contractions, and raises the tone of the uterus musculature.
On the postpartum uterus, carbetocin is capable of increasing the rate and force of spontaneous uterine contractions. The onset of uterine contraction following carbetocin is rapid after intravenous or intramuscular administration, with a firm contraction being obtained within 2 minutes.
A single 100 micrograms intravenous or intramuscular dose of carbetocin administered after the delivery of the infant is sufficient to maintain adequate uterine contraction that prevents uterine atony and excessive bleeding comparable with an oxytocin infusion lasting for several hours.
Clinical efficacy and safety
The efficacy of carbetocin in the prevention of postpartum haemorrhage due to uterine atony following Caesarean section was established in a randomised, active controlled, double-blind, double dummy, parallel-group trial designed to establish the efficacy and safety of carbetocin compared to oxytocin 25 IU. Six-hundred fifty-nine healthy pregnant women undergoing elective Caesarean section under epidural anaesthesia received either carbetocin 100 µ g/ml as an IV bolus dose or oxytocin 25 IU as an 8 h IV infusion.
The results of analysis of the primary endpoint, the need for additional oxytocic intervention, showed that additional oxytocic intervention was required in 15 (5%) of the subjects receiving carbetocin 100 µ g IV compared with 32 (10%) of the subjects in the oxytocin 25 IU group (p=0.031).
The efficacy of carbetocin in the prevention of postpartum haemorrhage following vaginal delivery was established in one randomised, active controlled, double-blind trial. In total 29645 subjects were randomised to receive a single intramuscular dose of either carbetocin 100 µ g or oxytocin 10 IU. For the primary endpoint of blood loss of ≥ 500 mL or use of additional uterotonics, similar rates were obtained in both treatment groups (carbetocin: 2135 subjects, 14.47%; oxytocin: 2122 subjects, 14.38%; relative risk [RR] 1.01; 95% CI: 0.95 to 1.06), demonstrating non-inferiority of carbetocin compared with oxytocin with regard to the primary endpoint.
Paediatric population
In the clinical development of carbetocin for prevention of postpartum haemorrhage following vaginal delivery 151 women between 12 and 18 years of age received carbetocin at the recommended dosage of 100 µ g and 162 received oxytocin 10 IU. Efficacy and safety was similar for the two treatment arms in these patients.