What is the appropriate dose, route, timing, contraindications, side effects, storage requirements, and alternative uterotonics for using carbetocin to prevent or treat postpartum hemorrhage?

Carbetocin for Prevention of Postpartum Hemorrhage

Dosing and Administration

Carbetocin is administered as a single 100 µg dose, given either intravenously or intramuscularly, immediately after delivery of the baby. 1, 2

• Intravenous route: 100 µg IV bolus after delivery of the baby 3, 2
• Intramuscular route: 100 µg IM at the end of second stage of labor 4, 2
• The IV route is typically used during cesarean section, while IM administration is common for vaginal deliveries 2
• Unlike oxytocin, carbetocin requires only a single injection rather than continuous infusion over several hours 1

Clinical Efficacy

For cesarean deliveries, carbetocin significantly reduces the need for additional uterotonic agents compared to oxytocin, though it does not reduce the overall incidence of postpartum hemorrhage. 2

• Carbetocin reduces the need for therapeutic uterotonics by 38% compared to oxytocin in cesarean section (RR 0.62; 95% CI 0.44 to 0.88) 2
• Carbetocin reduces the need for uterine massage by 46% after cesarean delivery (RR 0.54; 95% CI 0.37 to 0.79) and by 30% after vaginal delivery (RR 0.70; 95% CI 0.51 to 0.94) 2
• When compared to syntometrine for vaginal deliveries, carbetocin results in approximately 49 ml less blood loss (MD -48.84 ml; 95% CI -94.82 to -2.85) 2
• Carbetocin is as effective as syntometrine in low-risk women and may be superior in high-risk women 1, 4

Mechanism and Pharmacology

• Carbetocin is a synthetic oxytocin analogue with a half-life 4-10 times longer than oxytocin 1
• It combines the safety profile of oxytocin with the sustained uterotonic activity of ergot alkaloids 1
• The prolonged duration of action eliminates the need for continuous infusion 1

Side Effects and Safety Profile

Carbetocin has a significantly better tolerability profile than syntometrine, with markedly lower rates of nausea, vomiting, and hypertension. 4, 2

Compared to Syntometrine:

• Nausea: 76% reduction (RR 0.24; 95% CI 0.15 to 0.40) 2
• Vomiting: 79% reduction (RR 0.21; 95% CI 0.11 to 0.39) 2
• Hypertension: Significantly lower incidence at both 30 minutes (0 vs 8 cases) and 60 minutes (0 vs 6 cases) post-delivery 4, 2
• No coronary artery spasm risk (unlike syntometrine) 4

Compared to Oxytocin:

• Similar overall safety profile 1, 5
• Comparable rates of headache, tremor, hypotension, flushing, abdominal pain, pruritus, and feeling of warmth 1
• Slightly higher incidence of maternal tachycardia (RR 1.68; 95% CI 1.03-3.57) 4
• Both drugs have hypotensive effects, though oxytocin may cause greater blood pressure reduction 3

Contraindications

Preeclampsia remains a contraindication to carbetocin administration in the European Union. 1

• Further studies are required to assess cardiovascular effects in preeclamptic patients before routine use can be advocated 1
• Carbetocin may become the drug of choice for high-risk women and those with hypertensive disorders once additional safety data are available 1

Current Indications

• Currently indicated for prevention of uterine atony after cesarean section delivery under spinal or epidural anesthesia 1
• Emerging evidence supports use after vaginal deliveries, particularly in high-risk women 1, 4
• May be considered as an alternative to syntometrine in low-risk women undergoing vaginal delivery 4

Storage Requirements

No specific storage requirements were provided in the available evidence.

Alternative Uterotonics

When carbetocin is unavailable or contraindicated, alternative agents include:

• Oxytocin: 5-10 IU IV or IM immediately postpartum; 20 IU in 1000 ml infusion over 8 hours 6, 7, 3
• Syntometrine: 1 ml IM (5 IU oxytocin + 0.5 mg ergometrine); contraindicated in hypertension and asthma 8, 7, 4
• Methylergonovine: 0.2 mg IM; contraindicated in hypertension (>10% risk of severe hypertension) and asthma (bronchospasm risk) 7
• Tranexamic acid: 1 g IV over 10 minutes within 3 hours of birth for all cases of PPH 6, 7

Clinical Context

Important caveat: While carbetocin shows promise, it is not mentioned in the most recent comprehensive PPH management guidelines 6, 7, which prioritize oxytocin as first-line and tranexamic acid as essential adjunctive therapy. Carbetocin should be viewed as an alternative uterotonic when available, particularly for cesarean deliveries where its single-dose convenience and reduced need for additional uterotonics offer practical advantages 2.