How is carboprost tromethamine used to treat postpartum hemorrhage due to uterine atony, what is the recommended dosing regimen and maximum cumulative dose, what are its contraindications and common adverse effects, and what alternative uterotonics should be considered for a patient with asthma or prostaglandin hypersensitivity?

Carboprost Tromethamine for Postpartum Hemorrhage

Clinical Use and Indication

Carboprost tromethamine is a second-line uterotonic agent used to treat postpartum hemorrhage due to uterine atony when first-line therapy with oxytocin and uterine massage has failed. 1, 2

• Carboprost is a prostaglandin F2α analogue that induces strong myometrial contractions to control bleeding from uterine atony 1, 2
• It should be administered after oxytocin has proven inadequate, as oxytocin remains the first-line uterotonic for both prophylaxis and treatment of uterine atony 1, 3
• Carboprost demonstrates rapid and successful response in approximately 90% of cases of severe postpartum hemorrhage unresponsive to conventional therapy 2

Dosing Regimen

The standard dose is 0.25 mg (250 mcg) administered by deep intramuscular injection. 2

• Doses may be repeated at 15 to 90-minute intervals as needed 2
• Maximum cumulative dose is 2 mg (8 doses total) 2
• Slow administration is strongly recommended to minimize cardiovascular side effects 3

Common Adverse Effects

The most frequent side effects include:

• Gastrointestinal symptoms: nausea, vomiting, and diarrhea 2
• Transient mild temperature elevation 2
• Transient moderate blood pressure elevation 2
• Bronchospasm (particularly concerning in asthmatic patients) 1

Important caveat: Patients with preeclampsia did not demonstrate serious blood pressure elevations in clinical studies, though caution is still warranted 2

Contraindications

Carboprost is absolutely contraindicated in patients with:

• Active asthma or reactive airway disease (due to risk of severe bronchospasm) 1
• Hypersensitivity to prostaglandins 1
• Active cardiovascular disease where prostaglandin-induced increases in pulmonary artery pressure would be undesirable 4

Alternative Uterotonics for Contraindicated Patients

For patients with asthma or prostaglandin hypersensitivity, methylergonovine is the preferred second-line uterotonic agent. 1, 5

• Methylergonovine showed superior efficacy compared to carboprost in a propensity score-matched analysis, with reduced risk of hemorrhage-related morbidity (relative risk 1.7 for carboprost vs methylergonovine) 5
• However, methylergonovine is contraindicated in patients with hypertension due to vasoconstriction risk 4

Alternative Treatment Algorithm:

• If asthma present but no hypertension: Use methylergonovine as second-line agent 1, 5
• If both asthma and hypertension present: Consider misoprostol (prostaglandin E1 analogue with less bronchospasm risk than carboprost) or proceed directly to mechanical interventions 1, 6
• Adjunctive therapy: Tranexamic acid 1 gram IV over 10 minutes should be administered within 3 hours of bleeding onset in all cases of postpartum hemorrhage, regardless of cause 4

Clinical Effectiveness Considerations

Treatment failure with carboprost was associated with chorioamnionitis in clinical studies 2

• Combined therapy with multiple uterotonics demonstrates additive or synergistic effects superior to oxytocin monotherapy 6
• If carboprost fails, proceed rapidly to mechanical interventions (intrauterine balloon tamponade with 90% success rate) or surgical interventions rather than repeating maximum doses 4