Effect of carbetocin, a long-acting oxytocin analog on the postpartum uterus

Hunter, David J.; Schulz, Patricia; Wassenaar, Willem

doi:10.1038/clpt.1992.103

Cited by 116 publications

(74 citation statements)

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“…12,14 This led Hunter et al to assume that 100 lg of carbetocin would produce the same effect as 10 lg (equivalent to 5 IU) of oxytocin. 15 It is important to highlight, however, that this information has been derived from animal data, and it is not clear whether the potency ratio found in rat models can be extrapolated to humans. Assuming that these potency ratios are correct, our results are not surprising.…”

Section: Discussionmentioning

confidence: 99%

Carbetocin at elective Cesarean delivery: a randomized controlled trial to determine the effective dose, part 2

Anandakrishnan

Balki

Farine

et al. 2013

Can J Anesth/J Can Anesth

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Purpose The aim of this study was to determine the intravenous dose of carbetocin required to produce effective uterine contraction in 95% of women (ED 95 ) undergoing elective Cesarean delivery under spinal anesthesia. Methods One hundred and twenty term pregnant women at low risk for postpartum hemorrhage (PPH) undergoing elective Cesarean delivery under spinal anesthesia were randomly allocated to receive carbetocin in doses of 20, 40, 60, 80, or 100 lg iv upon delivery of the fetus. The obstetrician evaluated the efficacy of uterine tone as satisfactory or unsatisfactory, and in case of unsatisfactory tone, additional uterotonics were administered as per routine institutional practice. The primary outcome measure was satisfactory uterine tone at two minutes after carbetocin administration, and the secondary outcomes were the estimated blood loss, need for additional uterotonic agents within 24 hr, and side effects. Results Overall satisfactory uterine tone at two minutes was observed in 94.2% (113/120) of the women, and there was no difference across the different study groups. It was not possible to calculate the ED 95 of carbetocin due to the even distribution of women with unsatisfactory uterine tone at two minutes across all dose groups (P = 0.60). Additional uterotonics within 24 hr were required in 13% (16/120) of the women. Side effects were similar across all dose groups, with an overall 42.5% incidence of hypotension following the administration of carbetocin. Conclusions In women at low risk for PPH undergoing elective Cesarean delivery under spinal anesthesia, carbetocin is similarly effective in doses of 20-100 lg. There is a high incidence of hypotension associated with carbetocin in these doses. Further dose-finding studies are warranted, including doses lower than 20 lg. This trial was registered at www.clinicaltrials.gov (NCT01428817). RésuméObjectif L'objectif de cette étude était de déterminer la dose intraveineuse de carbétocine nécessaire à produire une contraction utérine efficace chez 95 % des femmes (DE 95

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Section: Discussionmentioning

confidence: 99%

Carbetocin at elective Cesarean delivery: a randomized controlled trial to determine the effective dose, part 2

Anandakrishnan

Balki

Farine

et al. 2013

Can J Anesth/J Can Anesth

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“…This is especially true if the suggestions are accurate that the human uterus is more sensitive to carbetocin than the rat myometrium. 1,4 The search for the minimum effective dose of carbetocin is well justified, similar to what has occurred for oxytocin, as carbetocin is thought to have a side effect profile similar to that of oxytocin. [6][7][8]16 The reported side effects of carbetocin during CD include hypotension, headache, nausea, vomiting, tremor, shortness of breath, abdominal pain, back pain, and flushing.…”

Section: Discussionmentioning

confidence: 99%

“…3 Its onset of action is less than two minutes after intravenous or intramuscular administration. 4 The main difference between carbetocin and oxytocin is the protracted uterotonic activity of the analogue. This appears to be related to the increased plasma half-life of carbetocin, which is 40 min, approximately four to ten times longer than that of oxytocin.…”

Section: Résumémentioning

confidence: 99%

“…5 This prolonged duration is a result of deamination, which protects carbetocin from the aminopeptidase cleavage, and of the replacement of the disulphide bond by CH 2 S, which protects the analogue from the disulphidase cleavage. 4,5 Hunter et al 4 assessed the effects of carbetocin in women who had delivered vaginally 24-48 hr prior to the administration of the study drug. The authors found that a single intravenous dose of carbetocin varying from 8-30 lg produced rhythmic uterine contractions lasting for a mean time of 60 min.…”

Section: Résumémentioning

confidence: 99%

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Carbetocin at elective Cesarean delivery: a randomized controlled trial to determine the effective dose

Cordovani

Balki

Farine

et al. 2012

Can J Anesth/J Can Anesth

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Purpose The primary objective of our study was to determine the minimum intravenous dose of carbetocin required to produce adequate uterine contraction in 95% of women (effective dose [ED] 95 ) undergoing elective Cesarean delivery (CD). Methods Eighty term pregnant women with low risk for postpartum hemorrhage (PPH) undergoing elective CD under spinal anesthesia were randomly allocated to receive carbetocin intravenously in doses of 80 lg, 90 lg, 100 lg, 110 lg, or 120 lg upon delivery. The consultant obstetrician evaluated the efficacy of the patient's uterine tone as satisfactory or unsatisfactory. In case of unsatisfactory uterine tone, additional uterotonics were administered as per routine institutional practice. Side effects were monitored during the study period. The main outcome measure was satisfactory uterine tone at two minutes after carbetocin administration. Results Satisfactory uterine tone was obtained in 70 subjects (87%) within the dose range of 80-120 lg of carbetocin. It was not possible to calculate the ED 95 of carbetocin due to the even distribution of women with satisfactory uterine tone across all dose groups (P = 0.99). Similarly, the side effects were similar across all dose groups. There was a high overall incidence of hypotension (55%) following the administration of carbetocin.Conclusions In women at low risk for PPH undergoing elective CD, carbetocin doses of 80-120 lg are similarly effective. There is a high incidence of hypotension associated with carbetocin in these doses, and further studies with doses lower than 80 lg are warranted to assess the balance of efficacy and side effects. This trial was registered at www.clinicaltrials.gov (NCT01262742). RésuméObjectif L'objectif principal de notre e´tude e´tait de de´terminer la dose intraveineuse minimum de carbe´tocine ne´cessaire pour obtenir une contraction ute´rine approprie´e chez 95 % des femmes (dose efficace [DE] 95 ) subissant une ce´sarienne programme´e. Méthodes Quatre-vingts femmes enceintes a`terme ayant un faible risque d'he´morragie du postpartum subissant une ce´sarienne programme´e sous rachianesthe´sie ont e´teŕ andomise´es pour recevoir des doses intraveineuses de 80 lg, 90 lg, 100 lg, 110 lg ou 120 lg de carbe´tocine au moment de l'accouchement. L'obste´tricien a e´valueĺ 'efficacite´du tonus ute´rin de la patiente comme satisfaisant ou non satisfaisant. En cas de tonus ute´rin non satisfaisant, des me´dicaments ute´rotoniques supple´mentaires ont e´teá dministre´s conforme´ment aux pratiques habituelles de l'e´tablissement. Les effets inde´sirables ont e´te´surveille´s pendant la dure´e de l'e´tude. Le crite`re de jugement principal a éte´un tonus ute´rin satisfaisant deux minutes apre`s l'administration de carbe´tocine.

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“…Carbetocin is a long-acting synthetic analogue of oxytocin 30,31 that can be administered as a single-dose injection, either intravenously or intramuscularly 32 . Intravenously administered carbetocin has a half-life of approximately 40 min, around 4-10 times longer than that reported for oxytocin.…”

Section: Pharmacologymentioning

confidence: 99%

Carbetocin versus Oxytocin for the Prevention of Postpartum Haemorrhage

Begum

Shaha²,

Mahbuba³

et al. 2016

Faridpur Med Coll J

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Abstract:Postpartum haemorrhage is the leading cause of maternal mortality worldwide. Total 67-80% of cases are caused by uterine atony. Preventive measures include prophylactic drug use to aid uterine contraction after delivery, thus avoiding severe blood loss and reducing maternal morbidity and mortality. Carbetocin is a synthetic analogue of oxytocin with a long half-life which ensure more effective contraction and less adverse effects. It can be administered as a single dose injection either intravenously or intramuscularly rather than as an infusion over several hours as is the case with oxytocin. Carbetocin is currently indicated for prevention of uterine atony after delivery by caesarean section in spinal or epidural anaesthesia. A reduced need for additional uterotonics was observed with carbetocin vs. oxytocin in high-risk women and carbetocin was at least as effective as syntometrine in low-risk women. Carbetocin is effective treatment for the prevention of postpartum haemorrhage not only following caesarean delivery but also after vaginal delivery in high-risk women and those who suffer from hypertensive disorders in pregnancy. Further research is required to assess whether prophylactic carbetocin is superior to conventional uterotonic agents following vaginal delivery in low-risk women.

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Effect of carbetocin, a long-acting oxytocin analog on the postpartum uterus

Cited by 116 publications

References 0 publications

Carbetocin at elective Cesarean delivery: a randomized controlled trial to determine the effective dose, part 2

Carbetocin at elective Cesarean delivery: a randomized controlled trial to determine the effective dose, part 2

Carbetocin at elective Cesarean delivery: a randomized controlled trial to determine the effective dose

Carbetocin versus Oxytocin for the Prevention of Postpartum Haemorrhage

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