Usage
Carboprost tromethamine is prescribed for the treatment of postpartum hemorrhage (PPH) due to uterine atony unresponsive to conventional methods (e.g., uterine massage, oxytocin, ergot alkaloids). It is also used for second-trimester abortion. It is classified as an oxytocic prostaglandin analog belonging to the prostaglandin F2α class. Carboprost acts by binding to prostaglandin F2α receptors in the myometrium, stimulating powerful uterine contractions. This leads to compression of myometrial blood vessels, controlling PPH. In the case of abortion, the contractions cause expulsion of uterine contents.
Alternate Names
Carboprost trometamol, Carboprost tromethamine
Brand Names: Hemabate
How It Works
Pharmacodynamics: Carboprost mimics the action of naturally occurring prostaglandin F2α. Binding to myometrial prostaglandin F2α receptors causes potent and prolonged uterine contractions leading to vasoconstriction and hemostasis.
Pharmacokinetics:
- Absorption: Rapidly absorbed after intramuscular (IM) administration.
- Metabolism: Primarily metabolized in the lungs, with further hepatic metabolism via omega-oxidation.
- Elimination: Excreted mainly in urine (approximately 83%), with a small amount excreted in feces. The plasma half-life is approximately 20-30 minutes.
Mode of Action: Carboprost binds to and activates prostaglandin F2α receptors in the uterine smooth muscle. This receptor activation triggers intracellular signaling cascades that result in increased myometrial calcium levels, initiating potent and sustained uterine contractions.
Elimination Pathways: Primarily renal excretion, with some fecal elimination.
Dosage
Standard Dosage
Adults:
- Postpartum Hemorrhage: 250 mcg IM initially, repeated every 15-90 minutes as needed, up to a maximum total dose of 2 mg (8 doses).
- Second-Trimester Abortion: 250 mcg IM initially, followed by 250-500 mcg every 1.5-3.5 hours, up to a maximum total dose of 12 mg. An optional test dose of 100 mcg may be considered.
Children: Carboprost is not indicated for use in children.
Special Cases:
- Elderly Patients: No specific dosage adjustments are required for elderly patients.
- Patients with Renal Impairment: Contraindicated in patients with active renal disease.
- Patients with Hepatic Dysfunction: Contraindicated in patients with active hepatic disease.
- Patients with Comorbid Conditions: Use with caution in patients with asthma, cardiovascular disease, diabetes, epilepsy, glaucoma, or raised intraocular pressure.
Clinical Use Cases
The dosages described above are generally suitable for both intubation/surgical procedures and for postpartum hemorrhage management in the intensive care unit (ICU) or emergency department. There are no specific dosage recommendations for mechanical ventilation.
Dosage Adjustments
Dose adjustments are not recommended due to the contraindications in patients with renal or hepatic dysfunction. Adjustments based on clinical response are necessary. Close monitoring of uterine tone and bleeding is crucial.
Side Effects
Common Side Effects
Nausea, vomiting, diarrhea, fever, flushing, chills, headache, pelvic pain or cramping.
Rare but Serious Side Effects
Hypersensitivity reactions (anaphylaxis, angioedema), severe pelvic pain, uterine rupture, perforated uterus, excessive bleeding, bronchospasm, hypertension, cardiovascular collapse.
Long-Term Effects
No specific long-term effects have been reported with the short-term use typical for this medication.
Adverse Drug Reactions (ADR)
Anaphylaxis, angioedema, uterine rupture, perforated uterus, cardiovascular collapse.
Contraindications
Active cardiac, pulmonary, renal, or hepatic disease; acute pelvic inflammatory disease; hypersensitivity to carboprost or any component of the formulation. Pregnancy (except for indicated use in second-trimester abortion and postpartum hemorrhage).
Drug Interactions
Oxytocin (synergistic effect on uterine contractions); dinoprostone, ergonovine, methylergonovine, mifepristone, and misoprostol (concurrent use is not recommended); eluxadoline (may increase carboprost levels).
Pregnancy and Breastfeeding
Pregnancy: Contraindicated except for termination of second-trimester pregnancy or treatment of postpartum hemorrhage. Carboprost crosses the placenta and can cause fetal damage or death.
Breastfeeding: Although there are no adequate studies, carboprost may be excreted in breast milk. It is recommended to avoid breastfeeding for at least 6 hours after administration.
Drug Profile Summary
- Mechanism of Action: Binds to prostaglandin F2α receptors, causing myometrial contractions.
- Side Effects: Nausea, vomiting, diarrhea, fever, flushing, chills, severe pelvic pain, hypertension, bronchospasm.
- Contraindications: Active cardiac, pulmonary, renal, or hepatic disease; acute pelvic inflammatory disease.
- Drug Interactions: Oxytocin, other uterotonics, eluxadoline.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy except for termination and PPH; Caution during breastfeeding.
- Dosage: PPH: 250 mcg IM every 15-90 min (max 2 mg); Abortion: 250 mcg IM initially, then 250-500 mcg every 1.5-3.5 hrs (max 12 mg).
- Monitoring Parameters: Uterine tone, bleeding, vital signs, respiratory function.
Popular Combinations
Carboprost is generally not used in combination with other uterotonics due to the risk of additive effects and increased side effects. Its use following other interventions like oxytocin or ergot alkaloids is common.
Precautions
Standard precautions apply for allergies and baseline assessment of organ function. Caution in patients with history of asthma, seizures, cardiovascular disease, or glaucoma. Avoid intravenous administration.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Carboprost?
A: For PPH: 250 mcg IM initially, repeated every 15-90 minutes as needed (max 2 mg). For second-trimester abortion: 250 mcg IM initially, then 250-500 mcg every 1.5-3.5 hours (max 12 mg).
Q2: What is the primary mechanism of action of Carboprost?
A: Carboprost stimulates uterine contractions by binding to prostaglandin F2α receptors in the myometrium.
Q3: What are the most common side effects of Carboprost?
A: Nausea, vomiting, diarrhea, fever, and flushing.
Q4: Is Carboprost safe to use in patients with asthma?
A: Carboprost should be used with caution in asthmatic patients due to the risk of bronchospasm.
Q5: Can Carboprost be administered intravenously?
A: No, Carboprost should never be administered intravenously. It must be given by deep intramuscular injection.
Q6: Can Carboprost be used to induce labor?
A: No, Carboprost is not indicated for labor induction.
Q7: What are the contraindications to using Carboprost?
A: Active cardiac, pulmonary, renal, or hepatic disease; acute pelvic inflammatory disease; hypersensitivity.
Q8: What is the maximum cumulative dose of Carboprost for PPH?
A: 2 mg (8 doses).
A: Carboprost is primarily metabolized in the lungs, with some hepatic metabolism via omega-oxidation.
