Medication Guide App

Dinoprost (Parenteral-Local)


VA CLASSIFICATION
Primary: HS200
Secondary: DX900; GU600

Commonly used brand name(s): Prostin FAlpha.

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

*Not commercially available in the U.S.



Category:


Abortifacient—

uterine stimulant—

diagnostic aid (angiography)—

Indications

Accepted

Abortion, elective—Dinoprost is used for aborting second-trimester pregnancy (between the twelfth to eighteenth week of gestation {01} {11} {12} {13} {15} {24} {25} {27} {29}). Dinoprost can be used for first-trimester and midtrimester abortion, but the procedure is difficult because of the small amount of amniotic fluid present and it is associated with an increased incidence of side effects and failures. Dinoprost is sometimes used in combination with hypertonic saline, urea, or oxytocin. {12} {13} {25} {22}

Abortion, incomplete (treatment)1 or{11}{12}{27}
Abortion, therapeutic1{11}{12}{22}{24}{25}{26}{27}{28}—Dinoprost is used in incomplete abortion or for therapeutic abortion in cases of intrauterine fetal death and congenital abnormalities incompatible with life. {11} {12} {14} {27}

Labor, induction of1—Low-dose intravenous dinoprost has been used for medically indicated induction of labor at term. {11} {12} {15}

Angiography adjunct1—Dinoprost has been injected intra-arterially for use as a vasodilator to assist in angiography.

Unaccepted
Dinoprost is generally not useful in the treatment of benign hydatidiform mole because of the lack of fetal membranes and amniotic fluid. {12} {28}

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:

Chemical group—
    Dinoprost tromethamine is the tromethamine salt of naturally occurring prostaglandin F 2 alpha.
Molecular weight—
    475.62 {03}

Mechanism of action/Effect:

Dinoprost appears to act directly on the myometrium, but this has not been completely established. {01} {12} {11} {22} {23} Dinoprost stimulates myometrial contractions in the gravid uterus that are similar to the contractions that occur in the term uterus during labor. {01} {11} {22} These contractions are usually sufficient to cause abortion. {01} {11} Uterine response to prostaglandins increases gradually throughout pregnancy. {23} {24} Dinoprost also facilitates cervical dilatation and softening. {11} {12} {19} {26}


Other actions/effects:

Dinoprost stimulates the smooth muscle of the gastrointestinal tract, arterioles, and bronchioles. {01} {14} {22}

Absorption:

Dinoprost is slowly absorbed from the amniotic fluid into systemic circulation. {01} {11} Radiolabeled drug studies indicate that dinoprost and its metabolites freely cross the placenta. {01} Because higher drug concentrations were observed in the fetal liver, dinoprost likely selectively enters the liver via the umbilical vein and ductus venosus. {01}

Biotransformation:

Enzymatic dehydrogenation primarily in the maternal lungs and also in the liver. {22} {27}

Half-life:

The half-life of dinoprost in amniotic fluid is 3 to 6 hours {22}. The plasma half-life of dinoprost after intravenous administration is reported to be less than 1 minute. {22}

Time to peak concentration:

6 to 10 hours after single 40 mg intra-amniotic dose. {01}

Peak blood concentration

3 to 7 nanograms prostaglandin F 2alpha equivalents per mL after single 40 mg intra-amniotic dose. {01}

Time to peak effect:

The mean abortion time with dinoprost is about 20 to 24 hours {11} {25} {28}. Intra-amniotic administration of 5 to 10 mg of dinoprost (base) immediately after instillation of hypertonic urea results in a mean abortion time of 16 to 17 hours.

Elimination:
    Primarily renal as metabolites, with about 5% excreted in feces.


Precautions to Consider

Pregnancy/Reproduction

Pregnancy—
Any pregnancy termination with dinoprost that fails should be completed by another method {01}.

Proliferation of bone has been reported with clinical use of prostaglandin E 1 during prolonged therapy. {01} There is no evidence to date that the short-term use of dinoprost causes proliferation of bone in the fetus. {01}

In animal studies, prostaglandins of the E and F series have caused proliferation of bone with high doses. {01}


Labor and delivery—

Use of high doses may result in excessive uterine tone, causing decreased uterine blood flow and fetal distress {05}.

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}{11}{12}{14}    (concurrent use with dinoprost may result in uterine hypertonus, possibly causing uterine rupture or cervical laceration, especially in the absence of adequate cervical dilatation {01} {11} {12} {14}; although combinations are sometimes used for therapeutic advantage, when used concurrently, patient should be closely monitored {01} {11} {12} {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{04}{11}{12}{14}{16}{22}{26}{27}
Heart rate, maternal{04}{13}{14}{22}{25}{27}    (may be decreased or increased, especially with large doses {11} {12} {13} {14} {16} {22} {25} {27})


White blood cell count{01}{12}    (may be elevated {01} {12})


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 problem exists:
» Allergy or intolerance to dinoprost or other oxytocics{01}{06}{12}
» Asthma, or history of{01}{06}{12}{14}{22}{25}    (increased risk of bronchoconstriction {06} {12} {22})


Cephalopelvic disproportion, significant or{12}
Fetal malpresentation{12}    (induction of labor is not generally recommended {12})


» Pelvic inflammatory disease, active{01}{14}    (induction of uterine contractions is not recommended {12})


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


» Ruptured membranes—intra-amniotic or extra-amniotic route{22}    (increased risk of intravascular absorption of dinoprost {12} {22})


Risk-benefit should be considered when the following medical problems exist
Anemia, history of    (increased incidence of excessive uterine bleeding may occur with the use of prostaglandins in performance of abortion {11} {12} {27} {28})


» Cardiac disease, active    (decrease in blood pressure and bradycardia may result in cardiovascular collapse and angina pectoris {12} {14} {22} {27})


Cardiovascular disease, history of or{01}{12}{14}
Hypertension, history of or{01}{11}{14}{22}
Hypotension, history of{11}{14}{22} or
Preeclampsia{14}    (may be aggravated by possible vasoconstriction or decreased blood pressure {04} {11} {14} {22})


Cervical stenosis or{11}{27}
Uterine fibroids or{11}
Uterine surgery, history of{11}{12}{14}    (increased risk of uterine rupture {12})


Diabetes mellitus, history of{14}
Epilepsy, or history of{11}{12}{14}{16}{24}{25}{27}    (rarely, seizures have occurred during the use of prostaglandins in epileptics {01} {11} {12} {14} {16} {24} {25} {27})


Glaucoma{12}{14}    (increases in intraocular pressure and miosis have been reported rarely during the use of prostaglandins {01} {12} {14} {15})


» Hepatic disease, active or{14}
Hepatic disease, history of    (metabolism of dinoprost may be impaired, resulting in prolonged half-life {05})


Hypersensitivity to dinoprost or{01}{12}
Multiparity{01}{12}    (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} {12})


Jaundice, history of
» Renal disease, active{14}
Renal disease, history of

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 determinations{12} and
Uterine tone, resting    (monitoring of these parameters is recommended at frequent intervals during abortion procedure or labor and delivery {12})


Vaginal examination{13}    (recommended prior to each intra-amniotic dose to confirm correct positioning of catheter, and after delivery or abortion to check for signs of cervical trauma {01} {13})




Side/Adverse Effects

Note: Inadvertent intravascular administration or absorption may result in nausea, vomiting, bronchoconstriction, peripheral vasoconstriction, faintness, hypertension, and feelings of panic {11} {12}. Because dinoprost is rapidly metabolized, these effects are transient (lasting 15 to 30 minutes) and most are not usually a cause for concern. {01} {11}

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
    
Abdominal or stomach pain, severe or continuing{01}{25}
    
anaphylaxis, generalized {01}{11}{14}{27}(redness and itching of skin; hives; swelling of face, inside the nose, and eyelids; shortness of breath; trouble in breathing; wheezing; tightness in chest)
    
bradycardia {14}{15}{22}{25}{27}(slow heartbeat)
    
bronchoconstriction (wheezing; tightness in chest; shortness of breath; sudden coughing)—especially in asthmatics{01}{11}{12}{14}{15}{18}{22}{25}{27}
    
burning eyes{01}
    
chest pain{01}{11}{14}
    
double vision{01}
    
dysuria {01}{11}(difficult or painful urination)
    
hematuria {01}(blood in urine)
    
ileus, adynamic{13} (constipation, tender or mildly bloated abdomen)
    
increased uterine pain accompanying abortion —correlates with efficacy{12}{14}{17}{22}{25}{27}
    
pain in legs, back, or shoulder{01}{11}
    
paresthesias (numbness in legs or other body parts{01})
    
peripheral vasoconstriction {12}{14}{22}{27}(pale, cool, or blotchy skin on arms or legs; weak or absent pulse in arms or legs)
    
second-degree heart block {01}{14}{22}(decreased or irregular heartbeat)
    
substernal pressure or pain {13}{22}(pressing or painful feeling in chest)
    
tachycardia {13}{22}(fast heartbeat)
    
urinary retention {01}{11}(decreased frequency of urination)
    
uterine tetany {12}{22}(continuous and severe cramping of the uterus)



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Diarrhea —about 16%{01}{12}{13}{14}{25}{28}
    
nausea —about 25%{01}{11}{12}{13}{14}{15}
    
stomach cramps or pain —about 25%{01}
    
vomiting —about 57%{01}{11}{12}{13}{14}{15}{25}{28}

Incidence less frequent
—<1%{01}    
Anxiety{01}
    
breast engorgement {01}{11}{12}(fullness or tenderness of breasts)
    
burning feeling in breasts{01}{12}{22}
    
chills or shivering{01}{12}{14}{25}{28}
    
cough, continuing{01}
    
dizziness{01}{11}{12}{25}
    
drowsiness{01}{14}
    
fever, transient {11}{12}{14}{18}{25}{28}
    
flushing or redness of face{01}{12}{18}{22}
    
headache{01}{11}{12}{14}{22}{25}
    
hiccups{01}
    
increased sweating{01}
    
inflammation and pain at injection site{11}{12}{14}
    
unusual thirst{01}



Those indicating possible postabortion complications and the need for medical attention if they occur after medication is discontinued
    
Endometritis {12}{13}(continuing chills or shivering; continuing fever; foul-smelling vaginal discharge; pain in lower abdomen)
    
unusual increase in uterine bleeding{01}{11}{12}{13}{14}




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

Clinical effects of overdose
Although overdose by intra-amniotic administration of dinoprost has not been reported, exaggeration of the nausea, vomiting, and diarrhea that occur with normal doses would be expected. {01}

Treatment of overdose
Specific treatment—Surgical rupture of the amniotic sac (drug reservoir), if necessary {01} {22}.

Supportive therapy—Emphasis on intravenous fluid replacement {01}.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Dinoprost (Intra-amniotic).

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

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

Pregnancy—Because some prostaglandins are teratogenic in animals, any pregnancy termination with dinoprost that fails should be completed by another method
Other medical problems, especially pelvic inflammatory disease, ruptured membranes, cardiac disease, hepatic disease, pulmonary disease, or renal disease

Proper use of this medication

» Proper dosing


Side/adverse effects
Signs of potential side effects, especially anaphylaxis; bronchoconstriction; burning eyes; severe and continuing abdominal or stomach pain; double vision; dysuria; hematuria; paresthesias; leg, back, chest, or shoulder pain; second-degree heart block; urinary retention; endometritis; bradycardia; adynamic ileus; peripheral vasoconstriction; tachycardia; and increased uterine bleeding or pain


General Dosing Information
Dinoprost is not feticidal and may result in delivery of a live fetus {01} {12}; administration with hypertonic saline or urea results in fetal death. {12}

If dinoprost is ineffective, it is recommended that alternative methods such as hypertonic saline not be used until the uterus has stopped contracting. {01}

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

Dinoprost has also been administered extra-amniotically (between the fetal membranes and uterine wall), but this method of administration has some disadvantages {11}. Because more frequent dosing and prolonged administration is necessary, the risk of side effects due to systemic absorption of dinoprost and infection is increased {11} {12}. However, some clinicians prefer this route of administration between the thirteenth and fifteenth weeks of gestation when intra-amniotic administration is not feasible, or in cases of intrauterine fetal death {11}.

Dinoprost has been used to terminate pregnancies of more than 20 weeks' gestation in cases of anencephaly. Because of increased uterine sensitivity, lower doses and careful titration are necessary. One group of investigators began with a 5-mg intra-amniotic dose, which was doubled every hour until the appropriate contraction pattern was established.

Confirmation of intrauterine fetal death should be made prior to use of dinoprost for missed abortion or intrauterine fetal death.

Caution should be taken to prevent exposure of skin to dinoprost tromethamine. {01} {12} If dinoprost injection is spilled on the skin, it should be washed off immediately with soap and water. {01}


Parenteral Dosage Forms

DINOPROST TROMETHAMINE INJECTION USP

Note: The dosing and strength of the dosage form available are expressed in terms of dinoprost base.


Usual adult dose
Abortifacient
Intra-amniotic, 40 mg (base). {01} {11} The first 5 mg should be administered at a rate not exceeding 1 mg per minute to determine sensitivity and to confirm that the medication is not being administered intravascularly, with the remaining 35 mg being administered over the next five minutes if there are no adverse reactions. {01} {11}

An additional dose of 10 to 40 mg (base) may be administered twenty-four hours after the initial dose if the abortion process is not established or completed, provided the membranes are still intact. {01} {11}

Note: A transabdominal tap of the amniotic sac must be performed before intra-amniotic injection of dinoprost {11}; dinoprost should not be administered if a bloody amniotic fluid sample is obtained. {01} {11}


Induction of labor1
Intravenous infusion, 2.5 mcg per minute of a 50 mcg-per-mL solution, with the dose being doubled every hour if necessary to a maximum of 20 mcg per minute (total dose is generally 1 to 4 mg). {12}


Strength(s) usually available
U.S.—
Not commercially available.

Canada—


5 mg (base) per mL (Rx) [Prostin F2Alpha (benzyl alcohol 9 mg)]{01}

Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F), unless otherwise specified by manufacturer. Protect from freezing.

Preparation of dosage form:
To prepare a 50 mcg-per-mL solution—Using standard aseptic technique, dilute each 20 mg with 5% dextrose injection to a total volume of 400 mL.



Revised: 05/16/1994



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. Product Monograph. Prostin F 2Alpha. (UpJohn, Canada). Prepared 7/23/82. Received 7/88.
  1. USP/NF 1985 and supps 1-8, 1988.
  1. USAN and USP DDN 1989.
  1. Mayhew JF. Hypertensive response to dinoprost under anesthesia. Anesth Analg 1986; 65: 1248.
  1. Reviewer comment, Carboprost panel survey date 3-2-90.
  1. Panel comments, Carboprost panel survey date 3-2-90.
    1. Reynolds JEF (editor). Martindale, the extra pharmacopeia, 29th ed. London: The Pharmaceutical Press, 1989: 1367.
    1. Pernoll ML, 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.
    1. Dukes MNG, Beeley L (editors). Side effects of drugs annual 12. New York: Elsevier Science Publishers B.V., 1988: 373.
    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, 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, 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, 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, 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, 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, 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.
    Hide
    (web2)