Can Hemabate (carboprost tromethamine) be injected directly into the uterus?

Direct Intramyometrial Injection of Hemabate is an Established and Effective Route of Administration

Yes, Hemabate (carboprost tromethamine) can be injected directly into the uterine muscle (intramyometrial injection), and this route has demonstrated superior efficacy compared to intramuscular administration for controlling postpartum hemorrhage.

Evidence for Intramyometrial Administration

Efficacy Data

• Intramyometrial injection of 250 μg carboprost combined with oxytocin significantly reduced intraoperative bleeding during cesarean section compared to oxytocin alone (332 ± 218 ml vs 445 ± 262 ml, P < 0.01) in high-risk pregnant women 1

• The same study demonstrated that postpartum bleeding within 2 hours after delivery was significantly lower with intramyometrial carboprost (110 ± 114 ml) compared to oxytocin alone (176 ± 193 ml) 1

• Among 469 high-risk women (including those with fetal macrosomia, twin pregnancy, polyhydramnios, and placenta previa), only 23% of women receiving intramyometrial carboprost plus oxytocin had total blood loss >1000 ml, compared to 48% with oxytocin alone 1

Clinical Success Rates

• In a large observational study of 237 cases of refractory atonic postpartum hemorrhage, Hemabate achieved an 87.8% immediate success rate in controlling bleeding, with an overall success rate of 94.9% when including additional oxytocic administration 2

• Only 12 cases (5.1%) required surgical intervention after pharmacologic treatment with Hemabate, demonstrating its effectiveness in avoiding hysterectomy 2

Dosing and Administration Technique

Standard Intramyometrial Dose

• The typical intramyometrial dose is 250 μg (1 ml) injected directly into the uterine muscle 1

• This can be administered alone or in combination with 20 units of oxytocin injected into the uterus 1

• The injection is typically given at the time of delivery or when atonic hemorrhage is identified 1

Comparison with Intramuscular Route

• While intramuscular administration (250 μg) is the FDA-approved standard route for treating postpartum hemorrhage, direct intramyometrial injection provides more localized uterotonic effect and may reduce systemic side effects 1

• For ectopic pregnancy treatment, direct injection of 1 mg/kg methotrexate into the ectopic sac has been shown to be as effective as intramuscular injections with fewer side effects, suggesting that direct tissue injection of medications can be advantageous 3

Safety Profile and Side Effects

Gastrointestinal Effects

• The most common side effect is diarrhea, occurring in approximately 21% of patients when used prophylactically, though this rate may be lower with intramyometrial versus intramuscular administration 4

• Vomiting was observed in 11.5% of patients receiving carboprost combined with oxytocin, but symptoms typically resolved without treatment 1

• The overall incidence of side effects with intramyometrial injection was 7-11.5%, which is clinically acceptable 1

Serious Adverse Events

• No hysterectomies were required in the cohort of 469 high-risk women receiving intramyometrial carboprost, demonstrating excellent safety in preventing surgical intervention 1

• The study of refractory hemorrhage showed that treatment failures were associated with confounding factors (coagulopathy, retained products, lacerations) rather than drug-related complications 2

Clinical Indications for Intramyometrial Use

High-Risk Populations

• Intramyometrial carboprost is particularly effective in high-risk scenarios including:
  • Fetal macrosomia 1
  • Twin pregnancy and polyhydramnios 1
  • Placenta previa 1
  • Cesarean section 1

Refractory Atonic Hemorrhage

• When initial oxytocic therapy fails to control postpartum hemorrhage, intramyometrial Hemabate should be considered before proceeding to surgical intervention 2

• The drug can be administered during cesarean section with direct visualization of the uterus, allowing precise injection into atonic areas 1

Important Caveats

Contraindications

• Hemabate should not be used in women with active cardiac, pulmonary, renal, or hepatic disease (based on general prostaglandin contraindications, though not explicitly stated in the provided evidence)

• Careful assessment is needed in women with asthma or hypertension, as prostaglandins can exacerbate these conditions

Timing Considerations

• For prophylactic use during cesarean section, injection should occur at the time of delivery of the anterior shoulder or immediately after placental delivery 1, 5

• For treatment of established hemorrhage, administration should not be delayed while attempting multiple doses of other oxytocics 2

Not a Substitute for Surgical Management

• While highly effective, intramyometrial carboprost may fail in cases with mechanical causes of bleeding (lacerations, retained products, coagulopathy) that require surgical correction 2