What is 15-methyl prostaglandin F2α (PGF2α), also known as carboprost tromethamine?

What is 15-methyl PGF2α?

15-methyl PGF2α (carboprost tromethamine) is a synthetic prostaglandin analogue used as an oxytocic agent, primarily for treating postpartum hemorrhage due to uterine atony when conventional methods fail. 1

Chemical Structure and Formulation

• 15-methyl PGF2α is the (15S)-15 methyl analogue of naturally occurring prostaglandin F2α, formulated as the tromethamine salt for clinical use 1
• The commercial preparation contains carboprost tromethamine equivalent to 250 mcg of carboprost per mL, with a molecular formula of C21H36O5.C4H11NO3 and molecular weight of 489.64 1
• It is administered as a sterile intramuscular injection containing 83 mcg tromethamine, 9 mg sodium chloride, and 9.45 mg benzyl alcohol as preservative per mL 1

Primary Clinical Indication

• The drug is specifically indicated for controlling intractable atonic postpartum hemorrhage when uterine packing or surgical intervention would otherwise be the only alternatives 2
• In a clinical series of 16 patients with severe postpartum hemorrhage, 15 patients (93.75%) responded satisfactorily to intramuscular 15-methyl PGF2α with a mean of 1.75 injections (437.5 mcg total dose), avoiding hysterectomy 2
• The single treatment failure occurred in a patient with severe intrauterine infection, suggesting that alternative pathology may predict non-response 2

Mechanism of Action

• As a prostaglandin F2α analogue, carboprost induces strong myometrial contractions, directly addressing uterine atony that leads to postpartum hemorrhage 1
• The 15-methyl modification increases metabolic stability compared to natural prostaglandins, allowing for effective intramuscular administration 1

Dosing and Administration Routes

• The standard dose is 250 mcg administered intramuscularly, which can be repeated as needed 1, 2
• Alternative routes include intracervical or intramyometrial injection, with intracervical administration showing particularly efficient results even with a single 250 mcg dose 3
• The drug should be administered after conventional uterotonic methods (oxytocin, methylergonovine) have failed 2, 3

Clinical Efficacy Data

• Risk factors most commonly associated with postpartum hemorrhage requiring 15-methyl PGF2α include pregnancy-induced hypertension, prolonged labor, general anesthesia, and high multiparity 3
• Treatment failure rate is approximately 5.88%, typically indicating alternative pathology (such as retained placental tissue, coagulopathy, or uterine rupture) requiring laparotomy 3
• Every obstetric unit should maintain at least 3 ampules of carboprost tromethamine available for emergency use 3

Important Distinction from Related Compounds

• 15-methyl PGF2α (carboprost) must be distinguished from 11β-PGF2α, which is a metabolite of PGD2 used as a diagnostic marker for mast cell activation syndrome, not a therapeutic agent 4
• The nomenclature can be confusing: 9α,11α-PGF2 (also called PGF2α) is a metabolite of PGE2 or PGH2, while 9α,11β-PGF2 (also called 11β-PGF2α) is a metabolite of PGD2, both distinct from the therapeutic 15-methyl PGF2α 4

Safety Profile

• The incidence of side effects with intramuscular administration is very low in the acute postpartum hemorrhage setting 2
• Common side effects when used for abortion induction include vomiting and diarrhea, though these are less relevant in the emergency postpartum setting 5
• Preclinical studies demonstrated high embryolethality, making this drug contraindicated in ongoing pregnancy 6

Historical Context

• The drug has also been used for therapeutic termination of pregnancy and management of intrauterine fetal death during the second and third trimesters, with successful abortion achieved in 90 of 92 patients in one series 7
• Mean abortion induction time was 7.3 hours for intrauterine fetal death and 12.6 hours for therapeutic termination 7