Carboprost Tromethamine

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intramuscular [strength expressed as base]:

Hemabate: 250 mcg/mL (1 mL) [contains benzyl alcohol]

Generic: 250 mcg/mL (1 mL)

Pharmacology

Mechanism of Action

Carboprost is an analog of naturally occurring prostaglandin F₂ alpha (dinoprost); carboprost stimulates uterine contractility which usually results in expulsion of the products of conception and is used to induce abortion between 13-20 weeks of pregnancy. When used postpartum, hemostasis at the placentation site is achieved through the myometrial contractions produced by carboprost.

Pharmacokinetics/Pharmacodynamics

Time to Peak

Serum: IM: 30 minutes

Use: Labeled Indications

Termination of pregnancy: For aborting pregnancy between week 13 and 20 of gestation as calculated from the first day of the last normal menstrual period and in the following conditions related to second trimester abortion: Failure of expulsion of the fetus during the course of treatment by another method; premature rupture of membranes in intrauterine methods with loss of drug and insufficient or absent uterine activity; requirement of a repeat intrauterine instillation of drug for expulsion of the fetus; inadvertent or spontaneous rupture of membranes in the presence of a previable fetus and absence of adequate activity for expulsion.

Refractory postpartum uterine hemorrhage: Treatment of postpartum hemorrhage due to uterine atony that has not responded to conventional methods of management. Prior treatment should include the use of intravenously (IV) administered oxytocin, manipulative techniques such as uterine massage and, unless contraindicated, intramuscular ergot preparations.

Contraindications

Hypersensitivity to carboprost tromethamine or any component of the formulation; acute pelvic inflammatory disease; active cardiac, pulmonary, renal, or hepatic disease.

Documentation of allergenic cross-reactivity for drugs in this class is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosage and Administration

Dosing: Adult

Refractory postpartum uterine bleeding: IM: Initial: 250 mcg; if needed, may repeat at 15- to 90-minute intervals; maximum total dose: 2 mg (8 doses)

Termination of pregnancy: IM: 250 mcg, then 250 mcg at 1.5- to 3.5-hour intervals, depending on uterine response; a 500 mcg dose may be given if uterine response is not adequate after several 250 mcg doses; do not exceed 12 mg total dose or continuous administration for >2 days. Note: A 100 mcg test dose may be considered.

Dosing: Geriatric

Refer to adult dosing.

Administration

IM: Administer deep IM (use a tuberculin syringe for termination of pregnancy); rotate site if repeat injections are required. Do not inject IV

Storage

Store under refrigeration at 2°C to 8°C (36°F to 46°F).

Drug Interactions

Oxytocic Agents: Carboprost Tromethamine may enhance the adverse/toxic effect of Oxytocic Agents. Specifically, oxytocic effects may be enhanced. Avoid combination

Adverse Reactions

Frequency not always defined. Effects due to increased smooth muscle contractility are most common and are generally transient and reversible upon discontinuation of therapy.

Cardiovascular: Chest pain, chest tightness, flushing, hypertension, palpitations, septic shock syncope, tachycardia, vasodepressor syncope

Central nervous system: Anxiety, chills, choking sensation, disturbed sleep, dizziness, drowsiness, dystonia, headache, increased body temperature (may be drug-induced or due to postabortion endometritis), lethargy, nervousness, paresthesia, shivering, vertigo

Dermatologic: Diaphoresis, skin rash

Endocrine & metabolic: Hot flash, increased thirst, thyroid storm

Gastrointestinal: Diarrhea (approximately 67%), vomiting (approximately 67%), nausea (approximately 33%), dysgeusia, epigastric pain, gag reflex, hematemesis, hiccups, retching, xerostomia

Genitourinary: Breast tenderness, cervical perforation (posterior), endometritis (from intrauterine device [IUD]), gynecological pain (dysmenorrhea-like pain), retained placenta (fragment), urinary tract infection, uterine perforation, uterine rupture, sacculation of uterus, uterine hemorrhage

Local: Pain at injection site

Neuromuscular & skeletal: Back pain, leg cramps, myalgia, torticollis, weakness

Ophthalmic: Blepharospasm, blurred vision, eye pain

Otic: Tinnitus

Respiratory: Asthma, bronchospasm, cough, dry throat, dyspnea, epistaxis, hyperventilation, pulmonary edema, respiratory distress, throat irritation (fullness of throat), upper respiratory tract infection, wheezing

<1%, postmarketing, and/or case reports: Hypersensitivity reaction (includes anaphylactic shock, anaphylactoid reaction, anaphylaxis, angioedema)

Warnings/Precautions

Concerns related to adverse effects:

• Fever: Transient fever may be observed with treatment and is believed to be due to carboprost’s effect on hypothalamic thermoregulation; use caution to distinguish between fever induced by the drug and fever associated with postabortion endometritis.
• Gastrointestinal effects: Pretreatment or concomitant use of antiemetic and antidiarrheal agents is recommended to decrease the incidence of gastrointestinal effects.
• Hypertension: Increased blood pressure may be observed with treatment; degree of hypertension observed is generally moderate and does not require treatment.

Disease-related concerns:

• Anemia: Use with caution in patients with anemia.
• Asthma: Use with caution in patients with a history of asthma; therapy may cause transient bronchoconstriction.
• Cardiovascular disease: Use with caution in patients with cardiovascular disease, including hypotension or hypertension.
• Compromised uteri: Use oxytocic agents with caution in patients with compromised (scarred) uterus.
• Diabetes: Use with caution in patients with diabetes mellitus.
• Hepatic impairment: Use with caution in patients with hepatic disease, including jaundice.
• Renal impairment: Use with caution in patients with renal disease.
• Seizures: Use with caution in patients with a history of seizure disorder.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.

Other warnings/precautions:

• Potent oxytocic agent: [US Boxed Warning] Potent oxytocic agent; use only with strict adherence to recommended dosing. Carboprost should be used only by medically-trained personnel in a hospital which can provide immediate intensive care and acute surgical facilities.

Monitoring Parameters

Termination of pregnancy: Confirmation of fetal death; cervical exam after termination of pregnancy

Pregnancy

Pregnancy Considerations

Teratogenic effects were not observed in animal reproduction studies. When used for termination of pregnancy, carboprost is not considered feticidal, but is used to terminate pregnancy due to its ability to stimulate uterine contractions; use is not indicated if the fetus has reached a stage of viability in utero. Complete termination of pregnancy may not be induced in ~20% of cases and should therefore be completed in another way.

Patient Education

What is this drug used for?

• It is used to end a pregnancy.
• It is used to stop or treat bleeding that happens after a birth or an abortion.
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Nausea
• Vomiting
• Diarrhea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.