What are the dosing instructions, pharmacology, and contraindications of Hemabate (carboprost tromethamine) in a postpartum female with severe hemorrhage?

Hemabate (Carboprost Tromethamine) for Postpartum Hemorrhage

Direct Answer

Hemabate is indicated for postpartum hemorrhage due to uterine atony that has failed conventional management with oxytocin and other first-line uterotonics, administered as 250 mcg intramuscularly with repeat doses every 15-90 minutes as needed, up to a maximum of 2 mg (8 doses). 1

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Indications

Hemabate is specifically indicated for treatment of postpartum hemorrhage due to uterine atony that has not responded to conventional methods including intravenous oxytocin and uterine massage. 1

• Prior treatment must include IV oxytocin and manipulative techniques such as uterine massage before Hemabate administration 1
• Unless contraindicated, intramuscular ergot preparations should also be attempted before Hemabate 1
• Hemabate is a second-line agent, not for routine prophylaxis or first-line treatment 1, 2

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Dosing Instructions

Initial Dose

• 250 mcg (1 mL) administered deep intramuscularly 1
• Use a tuberculin syringe for accurate dosing 1

Repeat Dosing

• Additional 250 mcg doses can be given at intervals of 15-90 minutes based on clinical response 1
• The interval between doses should be determined by the attending physician based on uterine contractility and ongoing bleeding 1
• In clinical trials, 73% of successful cases responded to a single injection 1

Maximum Dose

• Total cumulative dose must not exceed 2 mg (8 doses of 250 mcg) 1
• This maximum dose limit is critical for safety 1

Clinical Response Timeline

• Rapid response typically occurs after intramuscular injection 3
• Most successful cases respond within the first one to two doses 1, 3

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Pharmacology

Mechanism of Action

Carboprost tromethamine is a synthetic 15-methyl analogue of prostaglandin F2-alpha that induces strong myometrial contractions. 3

• Acts directly on uterine smooth muscle to produce sustained uterine contractions 3
• More potent and longer-acting than natural prostaglandin F2-alpha due to the 15-methyl modification 3

Route and Absorption

• Administered intramuscularly only for postpartum hemorrhage 1
• Produces rapid uterine response after IM injection 3

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Contraindications

Absolute Contraindications (from FDA labeling)

The FDA label does not explicitly list absolute contraindications for the postpartum hemorrhage indication, but the following warrant extreme caution:

• Active cardiac, pulmonary, renal, or hepatic disease (relative contraindication requiring careful risk-benefit assessment) 1
• Acute pelvic inflammatory disease 1

Important Precautions

Hypertension and Preeclampsia:

• Use with caution in patients with hypertension 3
• However, clinical data show that patients with preeclampsia did not demonstrate serious blood pressure elevations with Hemabate use 3
• Transient moderate blood pressure elevation can occur but is generally well-tolerated 3

Chorioamnionitis:

• Treatment failure was observed in patients with chorioamnionitis 3
• Consider alternative interventions if infection is present 3

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Side Effects

Common Side Effects

• Gastrointestinal symptoms: Nausea, vomiting, and diarrhea are the most frequent side effects 3, 4
• Diarrhea occurred in approximately 7-11.5% of patients in clinical studies 4
• These symptoms typically resolve spontaneously without treatment 4

Other Side Effects

• Transient mild temperature elevation 3
• Transient moderate blood pressure elevation 3
• Overall incidence of side effects ranges from 2.6% to 11.5% depending on dosing regimen 4

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Clinical Efficacy Data

Success Rate

• Successful control of hemorrhage in approximately 90% of cases (18 of 20 patients in key studies) 3
• Treatment failures were primarily associated with chorioamnionitis 3

Comparative Effectiveness

• When used prophylactically with oxytocin during cesarean section in high-risk patients, the combination significantly reduced intraoperative bleeding compared to oxytocin alone (332 mL vs 445 mL, P < 0.01) 4
• Postpartum bleeding within 2 hours was also significantly reduced (110 mL vs 176 mL) 4

Prevention of Surgical Intervention

• Hemabate has resulted in cessation of life-threatening bleeding and avoidance of emergency surgical intervention in a high proportion of cases 1

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Clinical Context and Treatment Algorithm

When to Use Hemabate

Step 1: Initial PPH management with oxytocin (5-10 IU IV/IM), uterine massage, manual uterine examination 2

Step 2: If bleeding persists after oxytocin, consider sulprostone (where available) or proceed to Hemabate 2

Step 3: Administer Hemabate 250 mcg IM if first-line uterotonics fail 1

Step 4: If bleeding continues, repeat Hemabate every 15-90 minutes up to 8 doses maximum 1

Step 5: If Hemabate fails, proceed to intrauterine balloon tamponade, interventional radiology, or surgery 2

Important Timing Consideration

• Hemabate should be administered within 30 minutes of PPH diagnosis if first-line agents fail (based on sulprostone timing recommendations, which is the European equivalent second-line agent) 2

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Critical Pitfalls to Avoid

Dosing Errors

• Never exceed 2 mg total dose (8 doses) - higher doses are associated with increased side effects without additional benefit 1
• Do not confuse the abortion dosing regimen (up to 12 mg over 2 days) with the postpartum hemorrhage regimen (maximum 2 mg) 1

Route of Administration

• Must be given intramuscularly, not intravenously - IV administration is not indicated for postpartum hemorrhage 1

Premature Use

• Do not use Hemabate as first-line therapy - oxytocin must be tried first 1, 2
• Ensure uterine massage and manual examination have been performed 2

Infection Consideration

• Be aware that chorioamnionitis may predict treatment failure 3
• Have a low threshold to proceed to surgical intervention if infection is present 3

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Adjunctive Therapy Considerations

While managing PPH with Hemabate, concurrent interventions should include:

• Tranexamic acid 1 g IV within 3 hours of birth if bleeding persists (can reduce mortality from hemorrhage) 5
• Fluid resuscitation and blood product replacement as needed 2
• Maintain fibrinogen >2 g/L during active hemorrhage 2
• Consider intrauterine balloon tamponade if Hemabate fails before proceeding to surgery 2