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Nov.17.2022

Carboprost Tromethamine

Indications/Dosage

Labeled

  • postpartum bleeding
  • pregnancy termination

NOTE: Like other potent oxytocic agents, carboprost tromethamine should be used only with strict adherence to recommended dosages and administered by medically trained personnel in a hospital that can provide immediate intensive and surgical care.

Off-Label

  • hemorrhagic cystitis
† Off-label indication

For pregnancy termination

for pregnancy termination between weeks 13—20 gestation dated from the first day of the last menstrual period

Intramuscular dosage

Adults

100 mcg (0.4 mL) optional test dose may be administered initially; 250 mcg (1 mL) by deep IM injection repeated every 1.5—3.5 hours, depending on uterine response, is recommended. May increase the dose to 500 mcg (2 mL) IM if inadequate uterine contraction persists after several doses. Do not exceed the 12 mg (48 mL) Maximum Dosage Limit; administration for more than 48 hours is not recommended.

for second trimester pregnancy termination in women with intact intrauterine membranes

Intra-amniotic dosage†

Adults

1.5 mg intra-amniotic injection, repeated once at 24 hours, if necessary, resulted in abortion in 43 of 61 study patients within 24 hours and in all 61 study patients within 48 hours; all women were between 12 and 24 weeks gestation.[32762] Alternately, a 2.5 mg single intra-amniotic injection resulted in abortion within 24 hours in 23 of 26 patients of 17—24 weeks gestation.[32761]

for second trimester pregnancy termination when there is failure of expulsion of the fetus during the course of treatment by another method

Intramuscular dosage

Adults

100 mcg (0.4 mL) optional test dose may be administered initially; 250 mcg (1 mL) by deep IM injection repeated every 1.5—3.5 hours, depending on uterine response, is recommended. May increase the dose to 500 mcg (2 mL) IM if inadequate uterine contraction persists after several doses. Do not exceed the 12 mg (48 mL) Maximum Dosage Limit; administration for more than 48 hours is not recommended.

for second trimester pregnancy termination with the premature rupture of membranes in intrauterine methods with loss of drug and insufficient or absent uterine activity

Intramuscular dosage

Adults

100 mcg (0.4 mL) optional test dose may be administered initially; 250 mcg (1 mL) by deep IM injection repeated every 1.5—3.5 hours, depending on uterine response, is recommended. May increase the dose to 500 mcg (2 mL) IM if inadequate uterine contraction persists after several doses. Do not exceed the 12 mg (48 mL) Maximum Dosage Limit; administration for more than 48 hours is not recommended.

for second trimester pregnancy termination when there is a requirement of a repeat intrauterine instillation of drug for expulsion of the fetus

Intramuscular dosage

Adults

100 mcg (0.4 mL) optional test dose may be administered initially; 250 mcg (1 mL) by deep IM injection repeated every 1.5—3.5 hours, depending on uterine response, is recommended. May increase the dose to 500 mcg (2 mL) IM if inadequate uterine contraction persists after several doses. Do not exceed the 12 mg (48 mL) Maximum Dosage Limit; administration for more than 48 hours is not recommended.

for second trimester pregnancy termination when there is an inadvertent or spontaneous rupture of membranes in the presence of a previable fetus and absence of adequate activity for expulsion

Intramuscular dosage

Adults

100 mcg (0.4 mL) optional test dose may be administered initially; 250 mcg (1 mL) by deep IM injection repeated every 1.5—3.5 hours, depending on uterine response, is recommended. May increase the dose to 500 mcg (2 mL) IM if inadequate uterine contraction persists after several doses. Do not exceed the 12 mg (48 mL) Maximum Dosage Limit; administration for more than 48 hours is not recommended.

For the treatment of postpartum bleeding due to uterine atony that is unresponsive to conventional management

NOTE: Prior treatment should include the use of intravenously administered oxytocin, manipulative techniques such as uterine massage and, unless contraindicated, intramuscular ergot preparations.[32757]

Intramuscular dosage

Adults

250 mcg IM every 15 to 90 minutes as needed. However, it is unlikely that additional doses will be of benefit if no response after 3 doses. Max: 2 mg.[27827] [32757] [68179]

Intramyometrial dosage†

Adults

250 mcg by intramyometrial injection every 15 to 90 minutes as needed. However, it is unlikely that additional doses will be of benefit if no response after 3 doses. Max: 2 mg.[27827] [68179]

For the treatment of refractory hemorrhagic cystitis†

NOTE: Consider premedication to minimize bladder spasms (oxybutynin 5—10 mg PO with or without belladonna; opium suppositories).

Intravesicular dosage†

Adults

0.8 mg/dL in 50 mL of saline instilled into the bladder for 60 minutes every 6 hours for 4 doses led to hematuria resolution in 4 of 13 patients with refractory, grade 3 or 4 hemorrhagic cystitis after bone marrow transplantation; a bladder irrigation of 0.02% hydrocortisone in saline was used between carboprost instillations. Elevation of the carboprost dose to 1 mg/dL in 50 mL of saline using the same protocol resulted in resolution of hematuria in an additional 5 patients.

Investigators recommend treatment for 48 hours after resolution of hematuria or for a total of 7 days with an additional 7 day treatment duration at the previously effective dose if hematuria recurs after therapy discontinuation.[29345]

Therapeutic Drug Monitoring

Maximum Dosage Limits

  • Adults

    Maximum dosage limits are indication specific. 12 mg IM total dose, up to a maximum recommended duration of 48 hours for pregnancy termination; 2 mg IM for postpartum bleeding.

  • Elderly

    Safety and efficacy have not been established.

  • Adolescents

    Safety and efficacy have not been established.

  • Children

    Safety and efficacy have not been established.

Patients with Hepatic Impairment Dosing

Carboprost tromethamine is contraindicated for use in patients with hepatic impairment.

Patients with Renal Impairment Dosing

Carboprost tromethamine is contraindicated for use in patients with renal impairment.

† Off-label indication
Revision Date: 11/17/2022, 08:11:33 AM

References

27827 - American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 183: Postpartum Hemorrhage. Obstet Gynecol 2017;130:e168-e186. Reaffirmed 2019.29345 - Ippoliti C, Przepiorka D, Mehra R, et al. Intravesicular carboprost for the treatment of hemorrhagic cystitis after marrow transplantation. Urology 1995;46:811-5.32757 - Hemabate (carboprost tromethamine injection, USP) package insert. New York, NY: Pfizer, Inc.; 2013 Dec.32761 - Perry KG, Rinehart BK, Terrone DA, et al. Second-trimester uterine evacuation: a comparison of intra-amniotic (15s)-15-methyl-prostaglandin F2alpha and intravaginal misoprostol. Am J Obstet Gynecol 1999;181:1057-61.32762 - Su LL, Biswas A, Choolani M, et al. A prospective, randomized comparison of vaginal misoprostol versus intra-amniotic prostaglandins for midtrimester termination of pregnancy. Am J Obstet Gynecol 2005;193:1410-4.68179 - California Maternal Quality Care Collaborative. Improving Health Care Response to Obstetric Hemorrhage V3.0. Errata 7.18.22. Accessed November 17, 2022. Available on the World Wide Web at https://www.cmqcc.org/resources-tool-kits/toolkits/ob-hemorrhage-toolkit.

How Supplied

Carboprost Tromethamine Solution for injection

Carboprost Tromethamine 250mcg/mL Solution for Injection (70121-1680) (Amneal Biosciences) null

Carboprost Tromethamine Solution for injection

Carboprost Tromethamine 250mcg/mL Solution for Injection (43598-0698) (Dr. Reddy's Laboratories, Inc.) null

Carboprost Tromethamine Solution for injection

Carboprost Tromethamine 250mcg/mL Solution for Injection (81298-5010) (Long Grove Pharmaceuticals, LLC) nullCarboprost Tromethamine 250mcg/mL Solution for Injection package photo

Carboprost Tromethamine Solution for injection

Carboprost Tromethamine 250mcg/mL Solution for Injection (69784-0240) (Woodward Pharma Services LLC ) null

Carboprost Tromethamine Solution for injection

Carboprost Tromethamine 250mcg/mL Solution for Injection (NOVAPLUS) (43598-0917) (Dr. Reddy's Laboratories, Inc.) null

Carboprost Tromethamine Solution for injection

Carboprost Tromethamine 250mcg/mL Solution for Injection (PREMIER ProRx) (43598-0919) (Dr. Reddy's Laboratories, Inc.) null

Carboprost Tromethamine Solution for injection

Hemabate 250mcg/ml Solution for Injection (00009-0856) (Pfizer Inc.) null

Description/Classification

Description

Carboprost tromethamine is the tromethamine salt of the (15S)-15 methyl analogue of naturally occurring prostaglandin F2-alpha. Clinically, carboprost tromethamine, an oxytocic, is used as a treatment for refractory postpartum uterine bleeding and as an abortifacient in gestation weeks 13 to 20 or in the second trimester under specific conditions. Comparative data for abortion are available for another FDA-approved prostaglandin analogue, dinoprostone. Among pregnant women of 14—24 weeks gestation, the cumulative abortion rate after 24 hours of drug receipt was 96% with dinoprostone 20 mg intravaginal suppositories and was 69% with carboprost 250 mcg IM; 8 patients who got carboprost as compared with 1 patient who got dinoprostone delivered after 24 hours of drug receipt. The mean times to delivery of the fetus and of the placenta were significantly shorter with dinoprostone, but carboprost is recommended to be given every 1.5—3 hours whereas dinoprostone is given every 3—5 hours; in the study, both drugs were given every 3 hours until delivery.[32756] Treatment selection is highly physician specific; consider medical history of patient, gestational age of fetus, and the availability of emergency medical and follow-up care. The high incidence of transient gastrointestinal adverse events, the possibility of incomplete expulsion of uterine contents, and patient disfavor of IM administration may limit carboprost tromethamine use. Sales of carboprost are restricted to hospitals only. Carboprost was approved by the FDA in 1979.

Classifications

  • Genito-urinary System and Sex Hormones
    • Other Gynecologicals
      • Labor Inducers
Revision Date: 07/06/2015, 04:27:00 PM

References

32756 - Borgida AF, Rodis JF, Hanlon W, et al. Second-trimester abortion by intramuscular 15-methyl-prostaglandin F2alpha or intravaginal prostaglandin E2 suppositories: a randomized trial. Obstet Gynecol 1995;85:697-700.

Administration Information

General Administration Information

For storage information, see the specific product information in the How Supplied section.

Route-Specific Administration

Injectable Administration

  • Administer only by medically trained personnel in a hospital that can provide immediate and intensive medical and surgical care.

  • Use with strict adherence to recommended dosages. Each ml of Hemabate contains carboprost tromethamine equivalent to 250 mcg of carboprost.

  • Inspect visually prior to administration. Discard the solution if particulate matter or discoloration is seen.

Intramuscular Administration

  • Inject deeply into a large muscle such as the deltoid muscle.[32760]

  • Aspirate prior to injection to avoid injecting into a blood vessel.

Other Injectable Administration

Intramyometrial Injection:

NOTE: Carboprost tromethamine is not approved by the FDA for intramyometrial administration.

  • May be administered directly into the uterus following cesarean section.[32765]

  • Aspirate prior to injection to avoid injecting into a blood vessel.

 

Intra-amniotic Injection:

NOTE: Carboprost tromethamine is not approved by the FDA for intra-amniotic administration.

  • Use ultrasound or equivalent to allow visualization of the amniotic cavity for administration.[32762][32761]

 

Intravesicular Administration:[29345]

NOTE: Carboprost tromethamine is not approved by the FDA for intravesicular administration.

  • Dilute appropriate dose in 50 mL of saline.

  • Evacuate blood clots by hand irrigation immediately prior to dose administration.

  • Instill dose then clamp bladder irrigation line for 60 minutes.

  • Instruct patient to change positions every 15 minutes during therapy.

  • Resume bladder irrigation after draining carboprost.

  • Use intravesicular dilution within 1 hour of preparation.[29345]

Clinical Pharmaceutics Information

From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database
Revision Date: 07/06/2015, 08:03:59 AMCopyright 2004-2023 by Lawrence A. Trissel. All Rights Reserved.

References

29345 - Ippoliti C, Przepiorka D, Mehra R, et al. Intravesicular carboprost for the treatment of hemorrhagic cystitis after marrow transplantation. Urology 1995;46:811-5.32760 - Schwallie PC, Lamborn KR. Induction of abortion by intramuscular administration of (15S)-15-methyl PGF2-alpha An overview of 815 cases. J Reprod Med 1979;23:289-93.32761 - Perry KG, Rinehart BK, Terrone DA, et al. Second-trimester uterine evacuation: a comparison of intra-amniotic (15s)-15-methyl-prostaglandin F2alpha and intravaginal misoprostol. Am J Obstet Gynecol 1999;181:1057-61.32762 - Su LL, Biswas A, Choolani M, et al. A prospective, randomized comparison of vaginal misoprostol versus intra-amniotic prostaglandins for midtrimester termination of pregnancy. Am J Obstet Gynecol 2005;193:1410-4.32765 - Bruce SL, Paul RH, Van Dorsten JP. Control of postpartum uterine atony by intramyometrial prostaglandin. Obstet Gynecol 1982;59:47S-50S.

Adverse Reactions

Mild

  • abdominal pain
  • anxiety
  • back pain
  • chills
  • cough
  • diaphoresis
  • diarrhea
  • dizziness
  • drowsiness
  • dysmenorrhea
  • epistaxis
  • fever
  • flushing
  • headache
  • hyperventilation
  • injection site reaction
  • insomnia
  • lethargy
  • mastalgia
  • muscle cramps
  • musculoskeletal pain
  • nausea
  • ocular pain
  • paresthesias
  • rash
  • shivering
  • syncope
  • tinnitus
  • vertigo
  • vomiting
  • weakness
  • xerostomia

Moderate

  • blurred vision
  • chest pain (unspecified)
  • dyspnea
  • dystonic reaction
  • hot flashes
  • hypertension
  • palpitations
  • sinus tachycardia
  • thyrotoxicosis
  • wheezing

Severe

  • anaphylactic shock
  • anaphylactoid reactions
  • angioedema
  • bronchospasm
  • cervical laceration
  • hematemesis
  • pulmonary edema
  • torticollis
  • uterine rupture

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]

Revision Date: 12/17/2013, 03:29:44 PM

References

32756 - Borgida AF, Rodis JF, Hanlon W, et al. Second-trimester abortion by intramuscular 15-methyl-prostaglandin F2alpha or intravaginal prostaglandin E2 suppositories: a randomized trial. Obstet Gynecol 1995;85:697-700.32757 - Hemabate (carboprost tromethamine injection, USP) package insert. New York, NY: Pfizer, Inc.; 2013 Dec.32760 - Schwallie PC, Lamborn KR. Induction of abortion by intramuscular administration of (15S)-15-methyl PGF2-alpha An overview of 815 cases. J Reprod Med 1979;23:289-93.32763 - Baxi L. Midtrimester pregnancy termination. Am J Obstet Gynecol 1997;176:952. Letter.54356 - Chapman SJ, Crispens M, Owen J, et al. Complications of midtrimester pregnancy termination The effect of prior cesarean delivery termination. Am J Obstet Gynecol 1996;175:889-92.54395 - Robins J, Mann LI. Midtrimester pregnancy termination by intramuscular injection of a 15-methyl analogue of prostaglandin F2 alpha. American journal of obstetrics and gynecology 1975;123:625-31.

Contraindications/Precautions

Absolute contraindications are italicized.

  • benzyl alcohol hypersensitivity
  • cardiac disease
  • hepatic disease
  • pulmonary disease
  • renal disease
  • anemia
  • asthma
  • breast-feeding
  • caesarean section
  • children
  • chorioamnionitis
  • diabetes mellitus
  • hypertension
  • hypotension
  • incomplete abortion
  • infants
  • infection
  • jaundice
  • neonates
  • pregnancy
  • seizure disorder
  • surgery
  • trauma

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]

Revision Date: 07/03/2019, 10:47:49 AM

References

32757 - Hemabate (carboprost tromethamine injection, USP) package insert. New York, NY: Pfizer, Inc.; 2013 Dec.32760 - Schwallie PC, Lamborn KR. Induction of abortion by intramuscular administration of (15S)-15-methyl PGF2-alpha An overview of 815 cases. J Reprod Med 1979;23:289-93.32763 - Baxi L. Midtrimester pregnancy termination. Am J Obstet Gynecol 1997;176:952. Letter.32764 - Mrvos R, Kerr FJ, Krenzelok EP. Carboprost exposure in a newborn with recovery. Clin Toxicol 1999;37:865-7.

Mechanism of Action

Carboprost tromethamine has stimulatory effects on uterine, gastrointestinal, and possibly other smooth muscle. Administration results in myometrial contractions in the gravid uterus similar to labor contractions at the end of a full term pregnancy. Carboprost tromethamine-induced uterine contractions will usually cause complete evacuation of the uterus; however, abortion may be incomplete in as many as 20 percent of patients receiving the drug. Postpartum, the resultant myometrial contractions provide hemostasis at the site of placentation. Common adverse reactions associated with carboprost tromethamine use (i.e., vomiting and/or diarrhea) are the result of smooth muscle stimulation of the human gastrointestinal tract. In laboratory animals and in humans, large doses of carboprost tromethamine can raise blood pressure, probably by contracting the vascular smooth muscle; this effect has not been clinically significant with the doses of carboprost tromethamine used for terminating pregnancy. In susceptible patients, carboprost tromethamine may cause transient bronchoconstriction.

Revision Date: 07/06/2015, 05:39:10 PM

References

Pharmacokinetics

Carboprost tromethamine is administered by intramuscular injection; off-label administration methods studied include intra-amniotic injection, intramyometrial injection, and intravesicular administration. The estimated plasma half-life of endogenous prostaglandin F2-alpha is 15 seconds due to rapid inactivation at the site of carbon 15. The structure of carboprost tromethamine contains an additional methyl group at carbon 15, which blocks similar metabolism. Carboprost, thus, has a longer half-life of 8 minutes. The longer half-life of carboprost makes the analogue more suitable for IM administration as compared with the endogenous prostaglandin.[32758] Carboprost tromethamine is inactivated by beta-oxidation with subsequent urinary elimination of the major metabolite.[32759]

 

In a clinical trial of 25 patients at 14—24 weeks gestation who received a regimen of carboprost tromethamine 250 mcg IM injections every 3 hours, the mean time to delivery of the fetus was 21.2 +/-11.2 hours.[32756] In a clinical trial of 815 cases of carboprost tromethamine-induced abortion conducted between 6 and 27 weeks of gestation, the investigators noted that the amount of medication required for fetal expulsion increased with gestational age and that time to abortion increased with gravidity, parity, and gestational age.[32760]

Route-Specific Pharmacokinetics

Intramuscular Route

Following IM injection of carboprost tromethamine, time to peak plasma concentration was measured to be between 15 and 60 minutes. In a pharmacokinetic study of 5 patients undergoing abortion, the average peak concentrations of drug were slightly higher following each successive IM injection of the prostaglandin, but the concentrations always decreased to concentrations less than the preceding peak values by two hours after each injection.

Revision Date: 11/16/2009, 04:36:58 PM

References

32756 - Borgida AF, Rodis JF, Hanlon W, et al. Second-trimester abortion by intramuscular 15-methyl-prostaglandin F2alpha or intravaginal prostaglandin E2 suppositories: a randomized trial. Obstet Gynecol 1995;85:697-700.32758 - Green K, Christensen N, Bygdeman M. The chemistry and pharmacology of prostaglandins, with reference to human reproduction. J Reprod Fertil 1981;62:269-81.32759 - Bygdeman M. Pharmacokinetics of prostaglandins. Best Pract Res Clin Obstet Gynaecol 2003;17:707-16.32760 - Schwallie PC, Lamborn KR. Induction of abortion by intramuscular administration of (15S)-15-methyl PGF2-alpha An overview of 815 cases. J Reprod Med 1979;23:289-93.

Pregnancy/Breast-feeding

pregnancy

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]

breast-feeding

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]

Revision Date: 07/03/2019, 10:47:49 AM

References

32757 - Hemabate (carboprost tromethamine injection, USP) package insert. New York, NY: Pfizer, Inc.; 2013 Dec.

Interactions

Level 2 (Major)

  • Dinoprostone, Prostaglandin E2
  • Ergonovine
  • Methylergonovine
  • Oxytocin
Dinoprostone, Prostaglandin E2: (Major) Carboprost tromethamine may augment the activity of other oxytocics. Augmentation can result in uterine hypertonus with subsequent uterine rupture, particularly in the absence of adequate cervical dilation. The concurrent use of carboprost tromethamine and other oxytocic drugs is not recommended. [9600] Ergonovine: (Major) Carboprost tromethamine may augment the activity of other oxytocics. Augmentation can result in uterine hypertonus with subsequent uterine rupture, particularly in the absence of adequate cervical dilation. The concurrent use of carboprost tromethamine and other oxytocic drugs is not recommended. [9600] Methylergonovine: (Major) Carboprost tromethamine may augment the activity of other oxytocics. Augmentation can result in uterine hypertonus with subsequent uterine rupture, particularly in the absence of adequate cervical dilation. The concurrent use of carboprost tromethamine and other oxytocic drugs is not recommended. [9600] Oxytocin: (Major) Carboprost tromethamine may augment the activity of other oxytocics. Augmentation can result in uterine hypertonus with subsequent uterine rupture, particularly in the absence of adequate cervical dilation. The concurrent use of carboprost tromethamine and other oxytocic drugs is not recommended. [9600]
Revision Date: 08/01/2017, 09:53:00 AM

References

9600 - Hemabate (carboprost tromethamine injection, USP) package insert. New York, NY: Pfizer, Inc.; 2013 Dec.

Monitoring Parameters

  • pelvic exam
  • pregnancy testing

US Drug Names

  • Hemabate
;