Carboprost (Monograph)

Brand name: Hemabate
Drug class: Oxytocics
VA class: HS875
Chemical name: (5Z,9α,11α,13E,15S)-9,11,15-Trihydroxy-15-methyl-prosta-5,13-dien-1-oic acid
Molecular formula: C₂₁H₃₆O₅•C₄H₁₁NO₃
CAS number: 58551-69-2

Introduction

Stimulates uterine smooth muscle; synthetic derivative of prostaglandin F_2α.

Uses for Carboprost

Termination of Pregnancy

Termination of intrauterine pregnancy during the second trimester (weeks 13–20 of gestation, dated from the first day of the last menstrual period).

Used after failure of another method (e.g., in the event of premature rupture of membranes with loss of hypertonic abortifacients accompanied by inadequate uterine activity, when repeated intra-amniotic drug administration needed to expel fetus); used to induce abortion after membrane rupture.

Postpartum Hemorrhage

Treatment of postpartum hemorrhage in the presence of uterine atony that has not responded to usual therapy (i.e., IV oxytocin, uterine massage, IM ergot alkaloids [unless contraindicated]).

Carboprost Dosage and Administration

General

To minimize adverse GI effects, consider pretreatment use or concurrent administration of antiemetic and antidiarrheal agents.

Administration

IM Administration

Administer by deep IM injection.

For postpartum hemorrhage, has been administered directly into the uterine corpus^{† [off-label]}.

Dosage

Available as carboprost tromethamine; dosage is expressed in terms of carboprost.

Closely adhere to recommended dosage. Dosage determined by uterine response.

Adults

Termination of Pregnancy

IM

Initially, 250 mcg. Alternatively, initiate with test dose of 100 mcg.

Subsequently, 250 mcg at 1.5- to 3.5-hour intervals depending on uterine response. After several 250-mcg doses, may increase dose to 500 mcg if uterine contractility is inadequate. Maximum total dose is 12 mg.

Postpartum Hemorrhage

IM

Initially, 250 mcg; repeat every 15–90 minutes up to a maximum total dose of 2 mg. Single dose usually adequate. Clinician should determine the need for additional doses and dosing interval based on clinical events.

Prescribing Limits

Adults

Termination of Pregnancy

IM

Maximum total dose is 12 mg; continuous administration for >2 days not recommended.

Postpartum Hemorrhage

IM

Maximum total dose is 2 mg.

Cautions for Carboprost

Contraindications

• Known hypersensitivity to carboprost.

• Acute pelvic inflammatory disease.

• Active cardiac, pulmonary, renal, or hepatic disease.

Warnings/Precautions

Warnings

Administer by qualified professional personnel in a hospital where intensive care and surgical facilities are immediately available.

Considerations in Patients Undergoing Termination of Pregnancy

Carboprost does not affect the fetoplacental unit. Possibility exists that a previable fetus could exhibit transient signs of life following carboprost-induced abortion; carboprost is not indicated if the fetus has reached the stage of viability.

If the pregnancy is not terminated with carboprost, complete abortion using another method.

Risk of cervical trauma; examine each patient for cervical injuries after abortion is complete. Caution in patients with a compromised (scarred) uterus.

Benzyl Alcohol in Neonates

Carboprost tromethamine injection contains as a preservative benzyl alcohol, which has been associated with toxicity (fatalities) in neonates. (See Pediatric Use under Cautions.)

General Precautions

Musculoskeletal Effects

Proliferation of long bones reported in neonates receiving long-term therapy with alprostadil (prostaglandin E₁). No evidence that short-term administration of carboprost has similar effects on bone.

Concomitant Diseases

Caution in patients with history of asthma, seizure disorders, diabetes, or anemia.

Fever

Transient fever (i.e., temperature elevations >1.1°C) reported in approximately 12.5% of patients. When used for termination of pregnancy, may be difficult to distinguish drug-induced temperature elevations from post-abortion endometritis.

Cardiovascular Effects

Increased BP reported. Increase in BP was observed in 4% of women receiving the drug for postpartum hemorrhage in 1 study; specific treatment for hypertension was not needed.

Caution in patients with hypertension, hypotension, or cardiovascular disease.

Chorioamnionitis

Chorioamnionitis may contribute to postpartum uterine atony and hemorrhage; individuals with chorioamnionitis experiencing postpartum hemorrhage have failed to respond to carboprost.

Specific Populations

Pregnancy

Category C.

Pediatric Use

Not indicated in pediatric patients.

Large amounts of benzyl alcohol (i.e., 100–400 mg/kg daily) have been associated with toxicity (fatal “gasping syndrome”) in neonates; each mL of carboprost tromethamine injection contains 9.45 mg of benzyl alcohol.

Hepatic Impairment

Caution in patients with hepatic disease, including jaundice. Contraindicated in patients with active hepatic disease.

Renal Impairment

Caution in patients with renal disease. Contraindicated in patients with active renal disease.

Common Adverse Effects

Vomiting, diarrhea, nausea, fever, flushing.

Drug Interactions

May increase activity of other oxytocic agents; concomitant use not recommended.

Carboprost Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following IM administration; peak plasma concentrations attained in 20–30 minutes.

Onset

When used for postpartum hemorrhage, increase in uterine tone and decreased bleeding noted after about 45 minutes.

Elimination

Metabolism

Metabolized principally via ω-oxidation and to limited extent via ω-oxidation to a number of metabolites. Metabolized more slowly than naturally occurring prostaglandin F_2α.

Elimination Route

Excreted in urine (83%), mainly as metabolites.

Stability

Storage

Parenteral

Injection

2–8°C.

Actions

• Elicits pharmacologic responses usually produced by endogenous prostaglandin F_2α; more potent and has longer duration of activity on the uterus than prostaglandin F_2α.

• Increases the amplitude and frequency of uterine contractions throughout pregnancy; uterine response to the drug increases with the duration of pregnancy.

• After delivery, uterine contractions impede uterine blood flow.

• Produces cervical dilation.

• Produces contraction of vascular smooth muscle; may result in increased BP.

• Causes stimulation of the smooth muscle of the GI tract, increasing GI motility.

• Stimulates transient bronchoconstriction in some patients.

Advice to Patients

• Importance of women informing clinicians if they plan to breast-feed.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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