Carbetocin 100micrograms/1ml solution for injection ampoules

BackgroundPostpartum haemorrhage is a leading cause of maternal mortality, particularly in low-income and middle-income countries. Several pharmacological agents, such as oxytocin, ergot alkaloids, prostaglandins, and tranexamic acid, have been used prophylactically to prevent postpartum haemorrhage. However, the optimal prophylactic regimen and the comparative efficacy of these agents and their combinations have not been fully elucidated for individuals undergoing caesarean delivery. We aimed to conduct a network meta-analysis to assess different agents for postpartum haemorrhage prophylaxis in caesarean deliveries.MethodsIn this systematic review and meta-analysis, we conducted a Bayesian network meta-analysis of randomised controlled trials (RCTs) evaluating the relative effectiveness of different prophylactic agents and their combinations for postpartum haemorrhage in caesarean deliveries. We searched MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, and Web of Science from database inception to Nov 7, 2023, for RCTs that enrolled adult pregnant women (ie, older than 18 years) undergoing a caesarean delivery; compared prophylactic strategies (monotherapy or combination drug therapy) with placebo or another active prophylactic regimen; administered prophylactic strategies of any parenteral dosage or regimen systemically before surgical incision or immediately after birth for preventing postpartum haemorrhage; and reported our prespecified endpoints of interest. Quasi-randomised trials, trials evaluating prophylactic strategies exclusively comparing different dosages, routes, or regimens of the same prophylactic agent, trials that included vaginal delivery, single-arm studies, conference abstracts, studies not published in English, and studies with overlapping populations were excluded. Ten authors reviewed study reports and supplementary materials and extracted the data. Two authors performed these tasks independently for each study. For data reported in graphical format, extraction was performed with graph digitising web software. The primary outcome was postpartum haemorrhage (ie, blood loss of ≥1000 mL following caesarean delivery). We fitted a Bayesian random-effects network meta-analysis model to compare multiple regimens simultaneously, with results presented as risk ratios (RRs) and their respective 95% credible intervals (CrIs). Only strategies reported by two or more studies were included in the network. If a prophylactic strategy was reported by only one study, it was included if at least 1000 patients were allocated in each study group. We also synthesised head-to-head RCTs separately to assess differences between regimens with league tables. To assess the hierarchy of treatments based on efficacy, we estimated surface under the cumulative ranking curve (SUCRA) probabilities. This review is registered at PROSPERO, CRD42023488236.FindingsThe search strategy yielded 3339 studies. After removing duplicates, 2241 studies remained, of which a total of 2022 were excluded on the basis of title or abstract screening. After full-text review, 167 RCTs (with 44 817 patients) evaluating monotherapy with or various combinations of oxytocin, carbetocin, carboprost, ergot alkaloids, misoprostol, and tranexamic acid were included in the final analysis. Across all 167 studies, 12 868 patients received oxytocin monotherapy, 5849 patients received tranexamic acid monotherapy, 2964 patients received carbetocin monotherapy, 1773 patients received misoprostol monotherapy, and 100 patients received carboprost monotherapy. The most common combination therapy was tranexamic acid plus oxytocin (n=5331) followed by misoprostol plus oxytocin (n=2983). Oxytocin plus tranexamic acid (RR 0·44 [95% CrI 0·33-0·58]) and carbetocin (0·54 [0·37-0·74]) were the only interventions that were more effective than oxytocin alone in reducing postpartum haemorrhage. Oxytocin plus tranexamic acid ranked as the most effective intervention for postpartum haemorrhage prophylaxis with a SUCRA probability value of 0·85. Most prophylactic combinations reduced intraoperative blood transfusions and the need for additional uterotonics. Two maternal deaths were reported among 29 412 patients. No significant heterogeneity was detected for postpartum haemorrhage (I2=6%), blood transfusion (I2=0%), and additional uterotonics (I2=7%).InterpretationCarbetocin alone and oxytocin plus tranexamic acid were superior to oxytocin monotherapy for preventing postpartum haemorrhage in caesarean deliveries. Oxytocin plus tranexamic acid ranked as the most effective intervention for postpartum haemorrhage prevention. These results are crucial in highlighting the comparative efficacy and hierarchy of prophylactic agents for postpartum haemorrhage prevention, especially given the widespread availability and low cost associated with oxytocin and tranexamic acid.FundingNone.

Abstract licence: CC BY

Abstract Objective: To evaluate the safety and efficacy of carbetocin for reducing blood loss following vaginal delivery (VD). Methods: Databases, including MEDLINE, Scopus, Web of Science, EMBASE, Cochrane Library, Scopus, and clinical trial registries, were screened from inception to November 2024 using keywords related to carbetocin, postpartum hemorrhage (PPH), postpartum blood loss, and VD. Only randomized controlled trials included participants who underwent VD, totaling 19 studies including 69,884 women. Seventeen studies were published in English, one in Spanish, and one in Chinese. The extracted data included study location, number of participants and characteristics, intervention (including dose, route, and timing of administration), primary and secondary outcome parameters, and trial registration details. Results: Thirteen studies with 64,731 participants compared carbetocin to oxytocin. Blood loss in the first 24 h was assessed in ten trials (7403 participants), which reported a mean difference ( MD ) of −28.13 mL (95% confidence interval ( CI ): −51.76, −4.50; P = 0.020). The difference between antepartum and postpartum hemoglobin levels was measured in seven trials (2737 participants), which reported an MD of −0.39 g/dl (95% CI : −0.48, −0.29; P 500 mL and severe PPH > 1000 mL were reported in ten and seven studies (64,416 and 63,789 participants, respectively), with odds ratios ( OR s) of 0.99 (95% CI : 0.89, 1.10; P = 0.800) and 0.98 (95% CI : 0.89, 1.09; P = 0.720), respectively. The need for additional uterotonics was assessed in ten trials (34,852 participants), with an OR of 0.67 (95% CI : 0.49, 0.90; P = 0.008). Six studies (10,145 participants) compared carbetocin to syntometrine. Blood loss in the first 24 h was assessed in five trials (4853 participants), which reported an MD of −35.29 mL (95% CI : −75.68, 5.09; P = 0.090). The difference between the antepartum and postpartum hemoglobin levels was measured in four trials (860 participants), which reported an MD of −0.29 g/dl (95% CI : −0.48, −0.09; P = 0.004). PPH > 500 mL and severe PPH > 1000 mL were reported in five and four studies (4835 and 4733 participants, respectively), with OR s of 1.09 (95% CI : 0.96, 1.24; P = 0.170) and 0.93 (95% CI : 0.78, 1.09; P = 0.360), respectively. The need for additional uterotonics was calculated in five trials (4933 participants), with an OR of 0.93 (95% CI : 0.60, 1.46; P = 0.770). Conclusion: Carbetocin administration was associated with reduced blood loss during the first 24 h after VD, a less severe decrease in postpartum hemoglobin levels, and a reduced need for additional uterotonics compared with oxytocin administration. Registration: Registration number CRD42023492407

Abstract licence: CC BY-NC-ND 4.0

Postpartum haemorrhage (PPH) is a leading cause of maternal death. Preventing PPH can spare women from experiencing the trauma and risks of PPH, reduce the strain on overstretched health systems, and probably produce better outcomes than a strategy solely focused on PPH treatment. Prevention of PPH is often interpreted as provision of uterotonic drugs to contract the uterus at the time of childbirth. Although uterotonics are a central strategy for PPH prevention, several other approaches can prevent PPH or ameliorate its severity. These approaches include addressing the unmet need for contraception, remedying anaemia and other modifiable risk factors for PPH, optimising medical conditions that predispose to PPH, and tackling the rise in caesarean births in many countries. Effective delivery of preventive care requires early and regular antenatal care and planned birth at appropriately resourced health facilities. Social and behavioural change interventions for improving contraceptive provision and uptake, targeting adolescents, postpartum women, geographically remote communities, and families on low income, are a priority. Effective interventions to tackle anaemia include the management of heavy menstrual bleeding, pre-pregnancy or antenatal haemoglobin testing and oral or intravenous iron treatment, dietary improvements, and-on rare occasions-blood transfusion. Risk factors for PPH that need attention include high BMI, multiple pregnancy, gestational diabetes, pre-eclampsia, macrosomia, and several medical conditions. Caesarean births are associated with a substantial increase in PPH risk and should therefore only be done when medically indicated. A Cochrane network meta-analysis of 122 trials, with 121 931 women, found that the combinations of oxytocin plus misoprostol, or oxytocin plus ergometrine, were the most effective prophylaxis for PPH when given at the time of childbirth; however, these combinations had a higher risk of side-effects compared with single-drug prophylaxis. Oxytocin and carbetocin were the most effective single drugs for PPH prophylaxis, with minimal side-effects. Single uterotonic prophylaxis with either oxytocin or carbetocin is, therefore, recommended for routine prophylaxis. However, if oxytocin or carbetocin is not accessible, misoprostol is an alternative. Combination prophylaxis with oxytocin plus misoprostol can be considered for women at high risk of PPH. Ergometrine alone and oxytocin plus ergometrine combination are no longer recommended due to hypertension-related safety concerns. A robust implementation approach that engages various stakeholders to promote change, ensures the supply of quality-assured medicines and devices, provides training and support, and secures ongoing political and financial commitment is necessary to translate evidence into global impact.

Abstract licence: CC BY-NC-ND