Among 26 recipients of carboprost 250 mcg IM every 3 hours until delivery, 85% had nausea.[32756] In other patients, approximately two-thirds experienced vomiting and diarrhea, and approximately one-third had nausea without vomiting. Other reported gastrointestinal events that may or may not be drug-related include hematemesis, epistaxis, epigastric or abdominal pain, gagging, retching, excessive thirst, taste alterations, xerostomia, dry throat, and fullness of throat. The most frequent adverse reactions observed are related to the contractile effect of carboprost tromethamine on smooth muscle, and the reactions are usually transient and reversible once carboprost administration ceases. The pretreatment or concurrent administration of antiemetic and antidiarrheal drugs considerably decreases the incidence of gastrointestinal effects common with all prostaglandins used for abortion; consider such co-therapies as an integral part of patient care.[32757]

Use of carboprost tromethamine is associated with transient fever that may be due to its effect on hypothalamic thermoregulation.[32757] Chills and shivering were reported in 2% of 815 patients who received carboprost tromethamine IM injections to induce abortion, and temperature increases greater than 1.1 degrees C occurred in 11% of the 815 patients.[32760] In another group of 26 women who received carboprost 250 mcg IM every 3 hours until delivery, 23% had fever, and 39% had chills.[32756] Temperature elevations exceeding 2 degrees F (1.1 degrees C) were observed in approximately one-eighth of the patients who received the recommended dosage regimen. In all cases, temperature returned to normal within several hours after the last injection. Differentiation of post-abortion endometritis from drug-induced temperature elevations is difficult. Of those patients experiencing a temperature elevation, approximately one-sixteenth had a clinical diagnosis of endometritis. Determining the time of onset may help discern the fever cause; carboprost tromethamine-induced fever usually occurs within 1—16 hours of administration while endometritis-induced temperature elevations typically present on day 3 after the abortion procedure. Uterine and other physical findings consistent with endometritis include incomplete evacuation of the uterus, histology consistent with endometrial inflammation, foul-smelling lochia and leukorrhea, and uterine tenderness. Force fluids in patients with drug-induced fever and no clinical or bacteriological evidence of an infectious process; no other simple empirical measures for temperature reduction are necessary, as fever is transient or self-limiting.[32757]

Hypertension was reported in 4% of 115 patients treated with carboprost tromethamine for postpartum hemorrhage; this increase in blood pressure was described as moderate and did not require medical intervention. The elevated blood pressure may have been due to a direct effect of carboprost or may have been a return to a status of pregnancy associated hypertension manifest by the correction of hypovolemic shock. Of note, large carboprost tromethamine doses can raise blood pressure, probably by contracting the vascular smooth muscle. Clinically significant elevated blood pressure has not been noted with the doses used for terminating pregnancy, but cautious use of the drug is advised for patients with a history of hypotension or hypertension. One-fourteenth of patients treated with carboprost tromethamine experienced flushing including hot flashes.[32757] Among 815 women who received carboprost for abortion induction, 8% had flushing or hot flashes.[32760] In another group of 50 women, 24 had a transient flushing sensation that usually occurred within 20 minutes of the first dose and lasted several minutes.[54395] Other adverse events that may be related to carboprost tromethamine-induced vasomotor and vasovagal effects include dizziness, tinnitus, syncope, lightheadedness, vertigo, chest pain (unspecified), palpitations, sinus tachycardia, diaphoresis, and vaso-vagal syndrome. The adverse effects of carboprost are generally transient and reversible with drug cessation.[32757]

Uterine rupture is a potentially life-threatening adverse event associated with carboprost tromethamine; cautious use is advised for women with compromised (scarred) uteri.[32757] Among women who had various induction methods for pregnancy termination, the incidence of uterine rupture was 3.8% among women with a prior cesarean as compared with 0.2% of women without such a history.[54356] Use of laminaria tents and/or conservative uterine stimulation in at risk patients may decrease the risk of rupture.[32763]

Posterior cervical perforation has been noted with carboprost tromethamine, but the incidence of cervical trauma such as cervical laceration is extremely small. Among 815 women who received carboprost for abortion induction, 1 had a minor cervical tear, and 1 had a cervical perforation.[32760] As cervical trauma can be asymptomatic, carefully examine the cervix immediately after the completion of carboprost tromethamine-induced abortion. Take corrective measures as necessary.[32757]

Among 815 women who received carboprost IM for abortion, 14 had a cough, 3 had dyspnea, 3 had chest tightness, and 2 had wheezing.[32760] Other respiratory effects associated with carboprost tromethamine use include bronchospasm, shortness of breath, hyperventilation, pulmonary edema, and respiratory distress. Carboprost is contraindicated for use by patients with active pulmonary disease; use with caution in patients with a history of asthma or other bronchospasm.[32757]

An injection site reaction specifically pain has been noted with carboprost, which is administered intramuscularly. Rash (unspecified) has also been observed.[32757] During post-marketing surveillance, hypersensitivity reactions, including anaphylactic shock, anaphylactoid reactions, and angioedema, have been reported.[32757] Watch for signs and symptoms of local and systemic hypersensitivity.

Uterine muscle cramps is a common and expected effect of carboprost tromethamine. Among 26 women who received 250 mcg IM every 3 hours until delivery, 96% had uterine cramps.[32756] Mastalgia, back pain, leg cramps, musculoskeletal pain, paresthesias, weakness, and cramping similar to dysmenorrhea have been observed among patients receiving carboprost tromethamine therapy.[32757] In a clinical trial, headache was reported in 9 of 815 patients receiving carboprost tromethamine IM injections to induce abortion.[32760]

Patients undergoing carboprost tromethamine therapy for abortion or for postpartum hemorrhage have experienced anxiety, blurred vision, dystonic reaction, drowsiness, insomnia, lethargy, nervousness, ocular pain, thyrotoxicosis, torticollis, and twitching eyelids; however, not all of these events are clearly drug related.[32757] Sleep disorders were reported in 6 of 815 patients who received carboprost tromethamine IM injections to induce abortion.[32760]

Use carboprost tromethamine with strict adherence to recommended dosages. Further, use of carboprost tromethamine is restricted to administration by qualified personnel in a hospital setting where emergency measures may be taken, if necessary. Carboprost tromethamine-induced termination may be expected to result in an incomplete abortion in approximately 20 percent of cases, necessitating further care and completion by another mechanism. Cervical laceration or other drug related adverse events may require acute care. Because cervical trauma can be asymptomatic, the cervix should be carefully examined following completion of the carboprost tromethamine-induced abortion.

Carboprost tromethamine is contraindicated in patients with known carboprost tromethamine hypersensitivity or hypersensitivity any excipients. The Hemabate brand of carboprost tromethamine contains benzyl alcohol as a preservative and should be avoided in patients with benzyl alcohol hypersensitivity.

Carboprost tromethamine is contraindicated in patients with acute pelvic inflammatory disease; treat patients with this type of infection as medically indicated to allow full recovery prior to the initiation of abortion procedures.

As compromised (scarred) uteri may increase the risk of uterine rupture and associated complications, use carboprost tromethamine with caution in patients with a history of caesarean section or major uterine surgery. Use of laminaria tents and/or conservative uterine stimulation in at risk patients may decrease the risk of rupture.[32763]

During the clinical trials with carboprost tromethamine, chorioamnionitis was identified as a complication contributing to postpartum uterine atony and hemorrhage in 8/115 (7%) of cases, 3 of which failed to respond to carboprost tromethamine therapy. Chorioamnionitis during labor may have an inhibitory effect on the uterine response to carboprost tromethamine similar to what has been reported for other oxytocic agents.

Use of carboprost tromethamine is contraindicated in patients with active cardiac disease. Carboprost tromethamine may stimulate vascular smooth muscle and may cause hypertension. Cautious use of carboprost in patients with hypertension may be advisable. Patients with cardiac disease were excluded from most trials, so data from the patient population are limited.

As carboprost tromethamine may elicit vaso-vagal syndrome, use with caution in patients with a history of hypotension.

Use of carboprost tromethamine is contraindicated in patients with active pulmonary disease. Carboprost tromethamine may stimulate bronchial smooth muscle and may cause bronchospasm. Cautious use of carboprost in patients with asthma may be advisable. Patients with pulmonary disease were excluded from most trials, so data from the patient population are limited.

Carboprost tromethamine is contraindicated for use in patients with active renal disease or hepatic disease. Further, cautious use of carboprost tromethamine is recommended in patients with a history of anemia, diabetes mellitus, jaundice, or epilepsy or other seizure disorder. Patients with these conditions were excluded from most trials, so data from the patient populations are limited.

The safety and effectiveness of carboprost tromethamine in children, infants, and neonates have not been established. Early study did include patients as young as 12 years of age, but data are limited.[32760] An accidental exposure of carboprost tromethamine 250 mcg IM in a newborn resulted in hypertension and elevations of both respiration and pulse rate within 15 minutes. Bronchospasm was treated with albuterol and oxygen; 10% dextrose IV was administered. Subsequently, fever, diarrhea, and dystonic movements or seizures were reported. The neonate's symptomatology resolved within 18 hours with patient discharge 24 hours after carboprost tromethamine injection. All neurological and developmental tests were normal at 3 months.[32764]

Carboprost tromethamine is embryotoxic in rats and rabbits; any dose that produces increased uterine tone could put the embryo or fetus at risk. Although not specifically proven of carboprost tromethamine, animal studies suggest that some prostaglandins have teratogenic potential. As such, any cases of incomplete abortion should be completed by another mechanism. Carboprost tromethamine is not indicated for pregnancy termination once the fetus in utero has reached the stage of viability. Carboprost tromethamine does not appear to directly affect the fetoplacental unit and should not be considered a feticidal agent. The previable fetus may exhibit transient life signs post-abortion.[32757]

It is not known if carboprost tromethamine is excreted into human breast milk. Because many drugs are excreted in human milk, breast-feeding mothers should receive carboprost tromethamine therapy with caution.[32757]