Carboprost Tromethamine

The adverse effects of HEMABATE Sterile Solution are generally transient and reversible when therapy ends. The most frequent adverse reactions observed are related to its contractile effect on smooth muscle.

In patients studied, approximately two-thirds experienced vomiting and diarrhea, approximately onethird had nausea, one-eighth had a temperature increase greater than 2° F, and one-fourteenth experienced flushing.

The pretreatment or concurrent administration of antiemetic and antidiarrheal drugs decreases considerably the very high incidence of gastrointestinal effects common with all prostaglandins used for abortion. Their use should be considered an integral part of the management of patients undergoing abortion with HEMABATE.

Of those patients experiencing a temperature elevation, approximately one-sixteenth had a clinical diagnosis of endometritis. The remaining temperature elevations returned to normal within several hours after the last injection.

Adverse effects observed during the use of HEMABATE for abortion and for hemorrhage, not all of which are clearly drug related, in decreasing order of frequency include:

The most common complications when HEMABATE was utilized for abortion requiring additional treatment after discharge from the hospital were endometritis, retained placental fragments, and excessive uterine bleeding, occurring in about one in every 50 patients.

Post-Marketing Experience

Hypersensitivity reactions (e.g. Anaphylactic reaction, Anaphylactic shock, Anaphylactoid reaction, Angioedema).

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Dosage Forms & Strengths

injectable solution

• 250mcg/mL

Abortion

Initial: 250 mcg IM; THEN repeat PRN q1.5-3.5hr OR

An initial, optional test dose of 100 mcg IM; THEN increase dose to 500 mcg if response is inadequate with 250 mcg doses

No more than 1200 mcg total dose or 2 days of continuous administration

Refractory Postpartum Uterine Bleeding

Initial 250 mcg IM, repeat PRN q15-90min

No more than 2000 mcg or 8 doses

Not applicable

Black Box Warning

Potent oxytocic agent; use strict aderence to recommended dosing

Only medically-trained personnel should administer the product in a hospital setting that can provide immediate care and acute surgical facilities

Contraindications

Hypersensitivity

Acute pelvic inflammatory disease

Active cardiac, pulmonary, renal or hepatic disease

Cautions

History of glaucoma or raised IOP

Asthma, hypertension/hypotension, cardiovascular disease

Transient fever observed with treatment possibly as a result of carboprost's effect on hypothalamic thermoregulation

Caution in patients with anemia, jaundice, renal impairment, hepatic impairment diabetes or epilepsy

To decrease GI side effects pretreatment or concomitant use with antiemetic and antidiarrheal agents recommended

Not for IV

Rare cases of cardiovascular collapse reported with prostaglandins

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).1 14 15 16

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.1

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]).1 8 9 10 12 13 20

Contraindications

• Known hypersensitivity to carboprost.1

• Acute pelvic inflammatory disease.1

• Active cardiac, pulmonary, renal, or hepatic disease.1

Warnings/Precautions

Warnings

Administer by qualified professional personnel in a hospital where intensive care and surgical facilities are immediately available.1

Carboprost does not affect the fetoplacental unit.1 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.1

If the pregnancy is not terminated with carboprost, complete abortion using another method.1

Risk of cervical trauma; examine each patient for cervical injuries after abortion is complete.1 14 Caution in patients with a compromised (scarred) uterus.1

Carboprost tromethamine injection contains as a preservative benzyl alcohol, which has been associated with toxicity (fatalities) in neonates.1 (See Pediatric Use under Cautions.)

General Precautions

Proliferation of long bones reported in neonates receiving long-term therapy with alprostadil (prostaglandin E1).1 22 No evidence that short-term administration of carboprost has similar effects on bone.1

Caution in patients with history of asthma, seizure disorders, diabetes, or anemia.1 24

Transient fever (i.e., temperature elevations >1.1°C) reported in approximately 12.5% of patients.1 When used for termination of pregnancy, may be difficult to distinguish drug-induced temperature elevations from post-abortion endometritis.1

Increased BP reported.1 13 20 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.1 13

Caution in patients with hypertension, hypotension, or cardiovascular disease.1

Chorioamnionitis may contribute to postpartum uterine atony and hemorrhage; individuals with chorioamnionitis experiencing postpartum hemorrhage have failed to respond to carboprost.1 8 9 10 12 13

Specific Populations

Category C.1

Not indicated in pediatric patients.1

Large amounts of benzyl alcohol (i.e., 100–400 mg/kg daily) have been associated with toxicity (fatal “gasping syndrome”) in neonates;1 2 3 4 5 6 7 each mL of carboprost tromethamine injection contains 9.45 mg of benzyl alcohol.1

Caution in patients with hepatic disease, including jaundice.1 Contraindicated in patients with active hepatic disease.1

Caution in patients with renal disease.1 Contraindicated in patients with active renal disease.1

Common Adverse Effects

Vomiting,1 10 14 15 18 20 diarrhea,1 10 13 14 15 18 nausea,1 13 20 fever,1 20 flushing.1 14 15

Storage

Parenteral

2–8°C.1

• Elicits pharmacologic responses usually produced by endogenous prostaglandin F2α; more potent and has longer duration of activity on the uterus than prostaglandin F2α.15 17 18

• Increases the amplitude and frequency of uterine contractions throughout pregnancy; uterine response to the drug increases with the duration of pregnancy.23

• After delivery, uterine contractions impede uterine blood flow.1

• Produces cervical dilation.15

• Produces contraction of vascular smooth muscle; may result in increased BP.1 10 20

• Causes stimulation of the smooth muscle of the GI tract, increasing GI motility.1 18

• Stimulates transient bronchoconstriction in some patients.1 12

Use carboprost tromethamine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into a muscle.
• You may be given another drug to lower certain side effects of this medicine.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Upset stomach or throwing up.
• Loose stools (diarrhea).
• Fever.
• Flushing.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.