Medication Guide App

Carboprost (Systemic)


VA CLASSIFICATION
Primary: HS200
Secondary: GU600

Commonly used brand name(s): Hemabate; Prostin/15M.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Oxytocic—

abortifacient—

antihemorrhagic (postpartum and postabortal uterine bleeding)—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Abortion or
[Abortion, incomplete (treatment)]1—Carboprost is used for aborting midtrimester pregnancy (between the thirteenth and twentieth weeks of gestation as calculated from the first day of the last normal menstrual period). {01} {04} {09} {10} {11} {12} {13} {14} {15} {17} {22} {25} {26} {27} {28} {29} {32} Carboprost is also indicated for second trimester abortion when other methods lead to failure of expulsion of the fetus, premature rupture of membranes with insufficient or absent uterine activity, and requirement of a repeat intrauterine instillation of drug for expulsion of the fetus, or when rupture of membranes in the presence of a previable fetus occurs without adequate activity for expulsion. {01} {04} {09} {20} {25} Carboprost can be used for abortion in the early weeks of pregnancy, but its use is associated with an increased incidence of side effects and failures. {10} {33} Carboprost is sometimes used in combination with hypertonic saline, urea, or oxytocin. {13} {22} {25}
—Carboprost is used for induction of labor in cases of intrauterine fetal death. {28}

Postpartum hemorrhage (treatment)1—Carboprost is indicated to reduce blood loss and correct uterine atony during the postpartum period in patients unresponsive to conventional treatment such as oxytocin, ergonovine, or methylergonovine. {01} {04} {09} {10} {11} {12} {14}

[Hydatidiform mole, benign (treatment)]1or{28}
[Induction of labor]1or{14}{15}{28}{29}
[Cervical ripening]1{11}{12}{14}{19}{20}{21}{26}—Carboprost has been used in the treatment of benign hydatidiform mole, for medically indicated induction of labor at term, and to ripen the cervix prior to abortion procedures such as vacuum curettage. However, experience with the use of carboprost for these indications is limited. {28} {29}

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:


Chemical name
    Prosta-5,13-dien-1-oic acid, 9,11,15-trihydroxy-15-methyl, (5 Z,9 alpha,11 alpha,13 E,15 S)-, compound with 2-amino-2-(hydroxymethyl)-1,3-propanediol (1:1) {03} {07} {36}.

Chemical group—
    Carboprost tromethamine is the tromethamine salt of the (15 S)-15 methyl analog of naturally occurring prostaglandin F 2-alpha {01} {04} {09} {11}.
Molecular weight—
    489.65

Mechanism of action/Effect:

Carboprost appears to act directly on the myometrium, but this has not been completely established {01} {04} {09} {16} {22}. Carboprost stimulates myometrial contractions in the gravid uterus similar to the contractions occurring in the term uterus during natural labor {01} {04} {09} {10} {22} {23}. These contractions are usually sufficient to cause abortion {01} {04} {09} {10}. Uterine response to prostaglandins increases gradually throughout pregnancy {23} {24}. Carboprost also facilitates cervical dilatation and softening.


Other actions/effects:

Carboprost stimulates the smooth muscle of the gastrointestinal tract, arterioles, and bronchioles {10} {14} {22}.

Biotransformation:

Primarily hepatic oxidation and some enzymatic dehydrogenation in maternal lung tissues; occur more slowly than with prostaglandin F 2alpha, due to the presence of a 15-methyl group {10} {12} {27} {37} {39}.

Time to peak concentration:

15 to 60 minutes {01} {04} {09} {37} {39}.

Peak serum concentration:

2060 picograms of 15-methyl-prostaglandin F 2alpha per mL at 30 minutes after a single intramuscular dose of 250 mcg, declining to 770 picograms per mL after 2 hours; slightly increased to 2663 picograms per mL at 30 minutes post-dosing with a second dose 2 hours later, declining to 1047 picograms per mL after 2 hours {01} {04} {09} {37} {39}.

Time to peak effect:

The mean abortion time with carboprost is about 16 hours {11} {25} {27} {28}.

Elimination:
    Primarily renal as metabolites {10} {37} {39}; rapid and nearly complete at 24 hours after intravenous, subcutaneous, or intramuscular dosing {37} {39}.


Precautions to Consider

Carcinogenicity

Studies have not been done in either animals or humans. {01} {04} {09} {14}

Mutagenicity

No evidence of mutagenicity was found in the micronucleus test or Ames assay {01} {04} {09} {14}.

Pregnancy/Reproduction

Pregnancy—
Although studies have not been done in humans, any pregnancy termination with carboprost that fails should be completed by another method {01} {04} {09} {10}.

Proliferation of bone has been reported with clinical use of prostaglandin E 1 during prolonged therapy {10}. However, there is no evidence to date that the short-term use of carboprost causes proliferation of bone in the fetus {10}.

Studies in rats and rabbits found that carboprost causes embryotoxicity {01} {04} {09}. Carboprost did not cause teratogenicity in animal studies {01} {04} {09} {10} {11} {16}. Prostaglandins of the E and F series have caused proliferation of bone with high doses in other animal studies {10}.

FDA Pregnancy Category C {01} {04} {09} {10} {11}.


Labor and delivery—

Use of high doses may result in excessive uterine tone, causing decreased uterine blood flow and fetal distress {37} {39}. Carboprost is not feticidal and may result in delivery of a live fetus {01} {04} {09} {10} {11}.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

Oxytocin or other oxytocics{01}{04}{09}{10}{14}{25}{27}    (concurrent use with carboprost may result in uterine hypertonus, possibly causing uterine rupture or cervical laceration, especially in the absence of adequate cervical dilatation {10} {14} {25}; although combinations are sometimes used for therapeutic advantage, patient should be monitored closely when this combination is used {10} {14} {25})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Blood pressure, maternal or{10}{11}{12}{14}{16}{22}{25}{27}
Heart rate, maternal{13}{14}{22}{25}{27}    (may be decreased or increased, especially with large doses {10} {11} {12} {13} {14} {16} {22} {25} {27})


Body temperature{01}{04}{09}{10}{11}{14}{18}    (a temperature increase of greater than 1.1 °C [2 °F] usually occurs within 1 to 16 hours after the first injection, and the temperature returns to normal within several hours after the last injection {01} {04} {09} {10} {18})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Allergy or intolerance to carboprost or other oxytocics{11}{34}
» Asthma, or history of{01}{04}{09}{10}{11}{14}{22}{25}{35}{36}    (increased risk of bronchospasm {14})


» Pulmonary disease, active{10}{11}{14}    (use of carboprost may decrease pulmonary blood flow and increase pulmonary arterial pressure {10} {14} {22} {27} {36})


Risk-benefit should be considered when the following medical problems exist {32}
Adrenal disease, history of{01}{04}{09}    (carboprost stimulates steroid production)


Anemia{01}{04}{09}{10}{11}    (increased incidence of excessive uterine bleeding may occur with the use of prostaglandins in performance of abortion {11} {12} {27} {28})


» Cardiac disease, active{10}{11}{14}    (decrease in blood pressure and bradycardia may result in cardiovascular collapse and angina pectoris {14} {22} {27})


Cardiovascular disease, history of or{01}{04}{09}{11}{14}
Hypertension, or history of or{01}{04}{09}{10}{11}{14}{22}
Hypotension, or history of{01}{04}{09}{14} or
Preeclampsia{14}    (may be aggravated by possible vasoconstriction or decreased blood pressure {30})


Cervical stenosis or{10}{27}{29}
Uterine fibroids or
Uterine surgery, history of{01}{04}{09}{10}{11}{14}{25}    (increased risk of uterine rupture)


Diabetes mellitus, history of{10}{11}{14}
Epilepsy, or history of{01}{04}{09}{10}{11}{14}{25}    (rarely, seizures have occurred during the use of prostaglandins {10} {14} {16} {24} {25} {27} {30})


Glaucoma{14}    (increase in intraocular pressure and miosis have occurred rarely during the use of prostaglandins {14} {15} {30})


» Hepatic disease, active,{10}{11}{14} or
Hepatic disease, history of{01}{04}{09}{10}{11}    (metabolism of carboprost may be impaired, resulting in prolonged half-life {37} {39})


Hypersensitivity to carboprost or{01}{04}{09}{10}{14} {17}
Multiparity{01}{04}{09}{14}{17}    (excessive dosage or use with oxytocin may cause uterine hypertonicity with spasm and tetanic contraction, which can lead to posterior cervical perforations, cervical lacerations, uterine rupture, and hemorrhage {01} {04} {09} {14} {17} {25})


Jaundice, history of{01}{04}{09}{10}{11}
» Pelvic inflammatory disease, acute{10}{11}{14}    (induction of uterine contractions is not generally recommended)


» Renal disease, active{10}{11}{14}
Renal disease, history of{10}{11}

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Contractions—frequency, duration and force of and
Temperature, pulse, and blood pressure, maternal and
Uterine tone, resting    (monitoring of these parameters is recommended at frequent intervals during abortion procedure or labor and delivery)


Vaginal examination    (recommended prior to each dose and postabortion or postdelivery to check for signs of cervical trauma {01} {04} {09} {10} {11} {28} {37})




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent or rare
    
Anaphylaxis, generalized {14}{27}(swelling of face, inside the nose, and eyelids; hives; shortness of breath; trouble in breathing; tightness in chest; wheezing)
    
bradycardia {14}{22}{27}(slow heartbeat)
    
bronchoconstriction (wheezing; trouble in breathing; tightness in chest)—most likely in asthmatic patients{01}{04}{09}{10}{14}{16}{18}{22}{25}{27}
    
hypertension (severe and continuing headache)—with very large doses
    
ileus, adynamic{13}{31} (constipation; tender or mildly bloated abdomen)
    
increased uterine pain accompanying abortion —correlates with efficacy{10}{17}{22}{27}
    
inflammation and pain at injection site{10}{14}{25}
    
peripheral vasoconstriction, possibly severe {22}{27}(pale, cool, or blotchy skin on arms or legs; weak or absent pulse in arms or legs)
    
substernal pressure or pain {10}{13}{22}(pressing or painful feeling in chest)
    
tachycardia {10}{13}{22}(fast heartbeat)



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Diarrhea —about 67%{01}{04}{09}{10}{11}{12}{13}{14}{17}{25}{26}{27}{28}
    
nausea —about 33%{01}{04}{09}{10}{13}{14}{16}{17}{27}
    
vomiting —about 67%{01}{04}{09}{10}{11}{12}{13}{14}{25}{26}{27}{28}

Incidence less frequent
    
Chills or shivering{01}{04}{09}{10}{14}{25}{28}
    
dizziness{10}{25}
    
fever, transient —about 12%{01}{04}{09}{10}{11}{14}{18}{25}{28}
    
flushing or redness of face —about 7%{01}{04}{09}{10}{17}{18}{22}
    
headache{01}{04}{09}{10}{14}{22}{25}
    
stomach cramps or pain{01}{04}{09}{14}{25}



Those indicating possible postabortion complications and the need for medical attention if they occur after medication is discontinued
    
Endometritis {01}{04}{09}{10}{13}{27}(continuing chills; shivering; continuing fever—usually on third day after abortion; foul-smelling vaginal discharge; pain in lower abdomen)
    
unusual increase in uterine bleeding{01}{04}{09}{10}{14}{25}{27}{28}




Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Treatment of overdose
Supportive therapy—Emphasis on intravenous fluid replacement {30}.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Carboprost (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Allergies or intolerance to carboprost or other oxytocics

Pregnancy—Because some prostaglandins are teratogenic in animals, any pregnancy termination with carboprost that fails should be completed by another method {30}
Other medical problems, especially lung disease, cardiac disease, liver disease, pelvic inflammatory disease, or renal disease

Proper use of this medication

» Proper dosing


Side/adverse effects
Signs of potential side effects, especially adynamic ileus, anaphylaxis, bradycardia, bronchoconstriction, chest pain or pressure, endometritis, fever, hypertension, inflammation and pain at injection site, peripheral vasoconstriction, tachycardia, and uterine bleeding or pain


General Dosing Information
Carboprost is sometimes used in combination with hypertonic saline or urea in the performance of abortion {13} {22} {25}.

It is recommended that antiemetic and antidiarrheal medications be administered prior to or concurrently with carboprost to decrease the incidence and severity of gastrointestinal side effects. {01} {04} {09} {10} {11} {14} {28} Narcotic analgesics may be given for uterine pain. {28} {34}

If carboprost is ineffective, it is recommended that alternative methods such as hypertonic saline not be used until the uterus has stopped contracting {30}. Continuous administration of carboprost for more than two days is not recommended {01} {04} {09} {11}.

Caution should be taken to prevent exposure of skin to carboprost tromethamine {10} {12}. If carboprost injection is spilled on the skin, it should be washed off immediately with soap and water {10}.


Parenteral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to indications and/or categories of use that are not included in U.S. product labeling.

CARBOPROST TROMETHAMINE INJECTION USP

Usual adult and adolescent dose
Abortifacient
[Intra-amniotic, 2.5 mg (base) administered over five minutes{10} . An additional dose of 2.5 mg may be administered twenty-four hours after the initial dose if abortion has not occurred, provided the membranes are intact{10}]or

Deep intramuscular, initially 250 mcg (0.25 mg) (base), the dosage being repeated every one and one-half to three and one-half hours, depending on uterine response {01} {04} {09} {10} {11} {12}. Dose may be increased to 500 mcg (0.5 mg) if uterine contractility is inadequate after several doses of 250 mcg (0.25 mg) {01} {10} {11} {12}.

Note: An optional test dose of 100 mcg (0.1 mg) of carboprost (base) may be administered initially {01} {04} {09} {10} {12}.
Continuous administration for more than two days is not recommended. {01} {04} {09} {11}


Antihemorrhagic, postpartum and postabortal uterine bleeding1
Deep intramuscular, 250 mcg (0.25 mg) (base) {01} {04} {09}. If necessary, the dosage may be repeated at fifteen- to ninety-minute intervals on the basis of response {01} {04} {09} {12}.


Usual adult prescribing limits
Abortifacient
Intra-amniotic: 5 mg (base) {10}.

Intramuscular: 6 to 12 mg (base), cumulative {04} {09} {10} {11} {12}. Continuous administration for more than two days is not recommended {01} {04} {09} {11}.

Antihemorrhagic, postpartum and postabortal uterine bleeding1
2 mg (base), cumulative. {01} {04} {09}


Strength(s) usually available
U.S.—


250 mcg (0.25 mg) (base) per mL (Rx) [Hemabate{04}{09}]

Canada—


250 mcg (0.25 mg) (base) per mL (Rx) [Prostin/15M{10}]

Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F). {01} {04} {09}



Revised: 06/08/1994



References

Note: All references used in the development and earlier revisions of this monograph have not yet been incorporated into the computer database and, therefore, are not listed below. Citations for information not yet referenced in the monograph will be provided upon request.

  1. Prostin/15m package insert, Upjohn, 10/86. Rec. 7/7/88.
  1. USP/NF XXI and supps. 1-8. 1985.
  1. USAN/DDN 1988.
  1. Hemabate package insert (Upjohn, US) Rev 10/88. Rec 3/89.
  1. Facts and Comparisons,(loose-leaf) ``Abortifacients'': 118j-n. Revised 9/85.
  1. CPS 1988.
  1. USAN/DDN 1989.
  1. Phone call to mfr.
  1. Hemabate package insert (Upjohn, US) Rev 4/89. Rec 10/23/89.
  1. Prostin/15M product monograph (Upjohn, Canada) Preparation date 7/26/82. Rec 8/2/89.
  1. American Medical Association. Drug Evaluations, 6th ed. Chicago: Author, 1986: 817-8.
  1. Reynolds JEF (editor). Martindale, the extra pharmacopeia, 29th ed. London: The Pharmaceutical Press, 1989: 1367.
  1. Pernoll ML and Benson RC (editors). Current obstetric and gynecologic diagnosis and management, 6th ed. Norwalk, CT: Appleton & Lange, 1987: 608-9.
  1. Dukes MNG (editor). Meyler's side effects of drugs, 10th ed. New York: Elsevier Science Publishers B.V., 1984: 812-5.
  1. Dukes MNG (editor). Side effects of drugs annual 8. New York: Elsevier Science Publishers B.V., 1984: 388.
  1. Dukes MNG (editor). Side effects of drugs annual 9. New York: Elsevier Science Publishers B.V., 1985: 360-1.
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  1. Davies DM (editor). Textbook of adverse drug reactions, 3rd ed. New York: Oxford University Press, 1985: 185, 683-4, 482-3.
  1. Elder MG. Prostaglandins as cervical ripeners [letter]. Lancet 1983 October 8: 847.
  1. Laurensen NH, Seidman S, and Wilson KH. Cervical priming prior to first-trimester suction abortion with a single 15-methyl-prostaglandin F 2 vaginal suppository. Am J Obstet Gynecol 1979; 135: 1116-8.
  1. Christiansen NJ, Bygdeman M, and Green K. Comparison of different prostaglandin analogues and laminaria for pre-operative dilatation of the cervix in the late first trimester abortion. Contraception 1983; 27: 56-61.
  1. Partridge BL, Key T, and Reisner LS. Life-threatening effects of intravascular absorption of PGF 2 during therapeutic termination of pregnancy. Anesth Analg 1988; 67: 111-3.
  1. Wigvist N et al. Prostaglandins and uterine contractility. Acta Obstet Gynecol Scand Supp 1983; 113: 23-9.
  1. Sederberg-Olsen J and Olsen CE. Prostaglandin-oxytocin induction of mid-trimester abortion complicated by grand-mal seizures. Acta Obstet Gynecol Scand 1983; 62: 79-81.
  1. Kajanoja P. Induction of abortion by prostaglandins in the second trimester of pregnancy: a review. Acta Obstet Gynecol Scand Supp 1983; 113: 145-51.
  1. Fylling P and Jerve F. Experience with prostaglandins for therapeutic abortion in Norway: their need and their benefits. Acta Obstet Gynecol Scand Supp 1983; 113: 113-6.
  1. Lange AP. Prostaglandins as abortifacients in Denmark. Acta Obstet Gynecol Scand Supp 1983; 113: 117-24.
  1. Christensen NJ and Bygdeman M. The use of prostaglandins for termination of abnormal pregnancy. Acta Obstet Gynecol Scand Supp 1983; 113: 153-7.
  1. Lange AP et al. Labor induction with prostaglandins. Acta Obstet Gynecol Scand Supp 1983; 113: 177-85.
    1. AMA. Current Medical Information and Terminology, 5th ed. Chicago: Author, 1981.
    1. Panel comments, Panel survey date 3/2/90.
    1. Panel comment. Panel survey date 3/2/90.
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    1. Panel comment. Panel survey date 3/2/90.
    1. Panel comment. Panel survey date 3/2/90.
    1. Mfr comment. Panel survey date 3/2/90.
    1. Panel comment.Panel survey date 3/2/90.
    1. Carboprost tromethamine—human pharmacokinetic review—March 1986 (Received 3/14/90).
    1. Hemabate package insert (Upjohn, US) Received 3/14/90. Revised 11/89.
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