carboprost
Regulatory sources consulted
Approved indications
- Termination of pregnancy between 13 and 20 weeks in specified circumstances and postpartum hemorrhage due to uterine atony unresponsive to conventional measures.
Contraindications
Absolute
- Hypersensitivity to carboprost, including prior anaphylaxis or angioedema.
- Acute pelvic inflammatory disease.
- Active cardiac, pulmonary, renal, or hepatic disease.
Clinical warnings
- Major warning · Potent uterotonic for hospital use with intensive care and surgery available. It may cause bronchospasm, hypertension, uterine rupture, pulmonary edema, septic shock, or anaphylaxis. — DailyMed, SPL set_id 84efd1c0-6323-4469-9535-237f96fcb383
- Major warning · Use cautiously with a history of asthma, hypotension or hypertension, cardiovascular, renal, or hepatic disease, anemia, jaundice, diabetes, or epilepsy, and in a compromised or scarred uterus. — DailyMed, SPL set_id 84efd1c0-6323-4469-9535-237f96fcb383
- Major warning · Carboprost is not a feticidal agent. If a pregnancy termination with carboprost is not completed, it must be completed by another method. — DailyMed, SPL set_id 84efd1c0-6323-4469-9535-237f96fcb383
Drug interactions
- HighOther oxytocic agents
Mechanism: Carboprost may augment their uterotonic activity.
Recommendation: Do not use concomitantly.
DailyMed, SPL set_id 84efd1c0-6323-4469-9535-237f96fcb383https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=84efd1c0-6323-4469-9535-237f96fcb383
Adverse events
Common (≥1%)
Vomiting · Diarrhea · Nausea · Temperature increase · Flushing or hot flashes
Pregnancy and lactation
It is used for its uterotonic effect in specific obstetric indications; any sustained increase in uterine tone may endanger the embryo or fetus.
Recent literature (PubMed)
Postpartum hemorrhage is the leading cause of maternal morbidity and mortality worldwide, with uterine atony estimated to account for 70% to 80% of cases, thereby remaining the single most common cause. Pharmacotherapy remains the first-line preventative therapy for postpartum hemorrhage. These therapies may be single (oxytocin, carbetocin, methylergonovine, ergometrine, misoprostol, prostaglandin analogs, or tranexamic acid) or combination therapies, acting in an additive, infra-additive, or synergistic fashion to prevent postpartum hemorrhage. Evidence is strong for the use of oxytocin, the first-line uterotonic agent in the United States for prevention of postpartum hemorrhage. Although carbetocin, a long-acting analog of oxytocin, is not yet available for use in the United States, it is likely the most effective single pharmacologic therapy for prevention of postpartum hemorrhage and need for additional uterotonics. Use of second-line uterotonics such as methylergonovine, misoprostol, and carboprost in combination with oxytocin has an additive or synergistic effect and a greater risk reduction for postpartum hemorrhage prevention compared with oxytocin alone. Therefore, combined therapy rather than oxytocin alone should be advised for preventing postpartum hemorrhage. Tranexamic acid has been found to be both effective and safe for decreasing maternal mortality in women with postpartum hemorrhage, and prophylactic use of tranexamic acid may decrease the need for packed red blood cell transfusions and/or uterotonics. The WOMAN-2 Trial, designed to assess if tranexamic acid prevents postpartum hemorrhage in women with moderate to severe anemia undergoing vaginal delivery, is currently recruiting participants. The additive, infra-additive, or synergistic action of oxytocin in combination with other second-line therapies deserves further study.
Uterotonics are the mainstay of management for postpartum haemorrhage and an understanding of their use is essential for the obstetric anaesthetist. First-line uterotonics comprise oxytocin and carbetocin, which act on the oxytocin receptor, and recent research has shown that lower doses of first-line uterotonics can be used to adequate effect. The oxytocin receptor is known to undergo desensitisation with exposure to the agonist over time and with increasing concentrations. Therefore, second-line uterotonics, such as ergometrine, carboprost, sulprostone or misoprostol, need to be considered earlier than they have been in past clinical practice. Choice of second-line uterotonic will vary depending on the comorbidities of the patient. This article will outline each of the available first- and second-line uterotonics, their mechanisms of action, pharmacokinetics, side effects and contraindications. Comparisons between them will also be discussed, as well as differences in superiority and guidance on dosing, based on recent evidence.
Postpartum 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. In 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 graph
To evaluate the comparative efficacy of two of the most commonly used second-line uterotonics-methylergonovine maleate and carboprost tromethamine. We conducted a double-blind randomized trial at two large academic perinatal centers in patients undergoing nonemergency cesarean delivery with uterine atony refractory to oxytocin, as diagnosed by the operating obstetrician. The intervention included administration of a single dose of intramuscular methylergonovine or carboprost intraoperatively at diagnosis. The primary outcome, uterine tone on a 0-10 numeric rating scale 10 minutes after study drug administration, was rated by operating obstetricians blinded to the drug administered. Secondary outcomes included uterine tone score at 5 minutes, administration of additional uterotonic agents, other interventions for uterine atony or hemorrhage, quantitative blood loss, urine output, postpartum change in serum hematocrit, transfusion, length of hospital stay, adverse drug or transfusion reactions, and postpartum hemorrhage complications. A sample size of 50 participants per group was planned to detect a 1-point difference (with estimated within-group SD of 1.5) in the mean primary outcome with 80% power at a two-sided α level of 0.05 while accounting for potential protocol violations. A total of 1,040 participants were enrolled, with 100 randomized to receive one of the study interventions. Mean±SD 10-minute uterine tone scores were 7.3±1.7 after methylergonovine and 7.6±2.1 after carboprost, with an adjusted difference in means of -0.1 (95% CI, -0.8 to 0.6, P =.76). Additional second-line uterotonics were required in 30.0% of the methylergonovine arm and 34.0% in the carboprost arm (adjusted odds ratio 0.72, 95% CI, 0.27-1.89, P =.505), and geometric mean quantitative blood loss was 756 mL (95% CI, 636-898) and 708 mL (95% CI, 619-810) (adjusted ratio of geometric means 1.06, 95% CI, 0.86-1.31, P =.588), respectively. No differences were detected in the occurrence of ot
The most frequent and harmful side effect of childbirth is obstetric haemorrhage. Postpartum haemorrhage (PPH) remains the primary cause of maternal mortality worldwide. Most PPH-related deaths take place in the first 24 hours of life. It is commonly believed that prompt diagnosis and treatment could avert the majority of PPH-related deaths. The rapid transition of haemorrhage from the remunerated to the decompensated stage is frequently overlooked. For this reason, anticipation, early detection, and management are crucial to reducing the risk of severe PPH (SPPH) or improving its clinical outcomes. Third-stage labour is a high-risk period for PPH. Active management of PPH is an effective intervention to lessen the incidence of PPH and has been promoted as a means of lowering fatality rates. Currently, prostaglandins (PGs) are advised as a second-line uterotonic medication. Strong uterotonic drugs such as carboprost tromethamine play a physiological role in human parturition, helping to birth the fetus and controlling PPH. Prostaglandins have a major effect on uterine tone, which minimizes blood loss. Their discovery, together with the use of their counterparts as uterotonics, has improved PPH management. In order to assist healthcare professionals in managing PPH promptly and minimizing adverse effects on both the mother and the newborn, this review will describe the causes of the disorder, the strategies that have been tried to treat it, and the role that carboprost plays in preventing it.