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Dinoprostone (Cervical/Vaginal)


Note: This monograph contains information on both the dinoprostone vaginal suppositories and the vaginal system (a suppository within a retrieval device). Each may be inappropriately referred to as dinoprostone vaginal insert in other types of information. It is important to avoid confusing the two dosage forms, since each has a different use and strength.


VA CLASSIFICATION
Primary: HS200
Secondary: GU600; GU900

Commonly used brand name(s): Cervidil; Prepidil; Prostin E.

Some other commonly used names are
prostaglandin E 2 or PGE 2 {11}.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Prostaglandin—

oxytocic—

abortifacient—

antihemorrhagic (postabortion uterine bleeding; postpartum uterine bleeding)—

Indications

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

Accepted

Abortion, elective—Dinoprostone vaginal suppositories are used for aborting midtrimester pregnancy (from the twelfth through the twentieth week of gestation as calculated from the first day of the last normal menstrual period) {02} {04} {05} {07} {12} {13} {25} {26} {50} {52} {67} {68} {75}.

Abortion, missed (treatment) or
Abortion, therapeutic—Dinoprostone vaginal suppositories are indicated for evacuation of the uterine contents in management of missed abortion or for therapeutic abortion in cases of intrauterine fetal death up to 28 weeks of gestational age as calculated from the first day of the last normal menstrual period {02} {04} {05} {07} {12} {13} {28} {50} {64} {67} {75}. Dinoprostone vaginal gel or suppository is not approved for use as an abortifacient in cases of intrauterine fetal death at more than 28 weeks' gestation because it is associated with an increased risk of uterine rupture {01} {64}. Confirmation of intrauterine fetal death should be made prior to use of dinoprostone for missed abortion or intrauterine fetal death {04} {05} {50}.

Cervical ripening—Prior to induction of labor when medically indicated, dinoprostone cervical gel or dinoprostone vaginal system {11} is used to initiate or continue ripening an unfavorable cervix in pregnant patients at or near term {07} {19} {28} {31} {32} {33} {34} {37}. The vaginal system is removed when active labor begins {11}. [Extemporaneously prepared dinoprostone gels have also been used in cervical ripening prior to induction of labor and prior to abortion procedures, such as vacuum curettage] {07} {08} {12} {19} {26} {28} {31} {32} {33} {37} {52} {54} {56} {57} {58} {59} {60} {64} {67} {71} {74}.

[Hemorrhage, postpartum (treatment)] or
[Hemorrhage, postabortion (treatment)]—Dinoprostone vaginal suppositories are used to reduce blood loss and correct uterine atony postpartum and postabortion in patients unresponsive to conventional treatment such as oxytocin, ergonovine, or methylergonovine {12} {14} {66}.

Hydatidiform mole, benign (treatment)—Although vacuum curettage is preferred, dinoprostone vaginal suppositories are indicated for evacuation of the uterine contents in the treatment of nonmetastatic benign hydatidiform mole {04} {05} {12} {28} {50} {65} {75}.

Labor, induction of—Dinoprostone vaginal gel is used for induction of labor at or near term {12} {16} {18} {29} {34} {43} {44} {46} {52} {54} {55} {59} {62} {70} {76} {77}.

Unaccepted
Dinoprostone vaginal suppository is not indicated for use to terminate a pregnancy of greater than 28 weeks gestation or when a fetus in utero has reached a stage of viability {02}. Also, the vaginal suppository or vaginal gel should not be used for cervical ripening {02} {46}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:


Description
    Dinoprostone vaginal system: The system includes a flat suppository contained within a retrieval device (polyester pouch with string) {11}. The suppository in the vaginal system (polyethylene oxide and urethane copolymer) measures 29 mm by 9.5 mm with a thickness of 0.8 mm {11}.

Chemical group—
    Dinoprostone is the naturally occurring prostaglandin E 2 {04} {05} {12} {50} {52} {77}.
Molecular weight—
    352.47 {51} {53}

Mechanism of action/Effect:


For uterine stimulation:

Dinoprostone appears to act directly on the myometrium, but this has not been completely established {05} {17} {22} {38} {50} {69} {72}. It stimulates myometrial contractions in the gravid uterus that are similar to the contractions that occur in the term uterus during natural labor {07} {09} {22} {23} {31} {38} {42} {51} {68} {69} {77}. These contractions are usually sufficient to cause abortion {07} {38} {54} {68}. Uterine response to prostaglandins increases gradually throughout pregnancy {23} {24} {54} {55}. Dinoprostone does not act directly on the fetoplacental unit and is not considered a fetocidal agent {02}.



For cervical ripening:

Dinoprostone softens the cervix and facilitates cervical dilation and effacement {11} {33} {37} {77}. Dinoprostone stimulates collagenase secretion, and thus reduces the collagen network within the cervix. By favorably changing the cervical score, dinoprostone reduces the number of failed inductions or instrumental deliveries, shortens the induction-to-delivery interval, and reduces the amount of oxytocin that may be needed {83}. The dose of dinoprostone used locally to ripen the cervix is lower than that used to stimulate the uterus {11} {72}. Although not prominent with low local doses, uterine stimulation may occur with the dinoprostone vaginal system or cervical gel {01}.



Other actions/effects:

Dinoprostone stimulates the smooth muscle of the gastrointestinal tract {14} {38} {77}. It may also cause bronchodilation or bronchoconstriction and vasodilation {15} {18} {67} {77}. Dinoprostone can elevate body temperature due to its effect on hypothalamic thermoregulation {38}.

Absorption:

Dinoprostone vaginal system for cervical ripening—Absorbed at a rate of 0.3 mg per hour over 12 hours while the vaginal system is in place. Systemic effects are seen rarely, although the systemic contributions of dinoprostone and its metabolites are difficult to assess due to the prostaglandins endogenously produced during labor {11}.

Protein binding:

73%, to albumin {51} {77}.

Biotransformation:

Rapid metabolism of dinoprostone occurs primarily in the local tissues; any systemic absorption of the medication is cleared mainly in the maternal lungs {11} and, secondarily, at sites such as the liver and kidneys {53}.

Half-life:

Less than 5 minutes {11} {51} {77}.

Onset of action:

Uterine stimulation—Contractions begin within 10 minutes following insertion of a dinoprostone vaginal suppository.

Time to peak effect:

Uterine stimulation—The mean abortion time with dinoprostone is about 17 hours (range, 12 to 24 hours) {07} {28} {29} {40} {41} {52}.

Duration of action:

Uterine stimulation—Contractions persist for 2 to 6 hours following insertion of a 20-mg dinoprostone vaginal suppository {67}.

Cervical ripening—Continues, while in place, for up to 12 hours per dinoprostone vaginal system {11}. On removal, action lasts 2 to 13 minutes {11}.

Elimination:
    Primarily renal as metabolites {38} {51}, with a small amount excreted in the feces.


Precautions to Consider

Cross-sensitivity and/or related problems

Patients hypersensitive to oxytocin or other oxytocics may be hypersensitive to dinoprostone, even when it is used only for cervical ripening. Also, patients allergic to other prostaglandins, such as misoprostol, may be allergic to dinoprostone.

Carcinogenicity

Studies have not been done in animals or humans on the carcinogenicity of dinoprostone {02} {04} {05} {38} {50} {51} {77}.

Mutagenicity

The micronucleus test, Ames assay, and unscheduled DNA synthesis assay revealed no evidence of mutagenicity with dinoprostone {11}.

Pregnancy/Reproduction

Pregnancy—
Any pregnancy termination that fails with dinoprostone should be completed by another method.

Proliferation of bone has been reported with clinical use of prostaglandin E 1 during prolonged therapy {12} {38} {53} {77}. There is no evidence to date that the short-term use of dinoprostone (prostaglandin E 2) causes proliferation of bone in the fetus {38} {51} {53} {77} and is unlikely since it is administered after the period of organogenesis {11} {53}.

Although animal studies with dinoprostone did not reveal teratogenic properties, dinoprostone has been shown to be embryotoxic in rats and rabbits {04} {05} {09} {38} {50} {77}. In animal studies, prostaglandins of the E and F series have caused proliferation of bone with high doses {16} {77}.

FDA Pregnancy Category C {02} {38}.


Labor and delivery—

Use of high doses may result in excessive uterine tone, causing decreased uterine blood flow and fetal distress {02} {33} {38} {43} {51} {54}.

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 {02} {04} {05} {06} {14} {25} {17} {38} {50} {51} {55} {74} {75} {77} {78}    (concurrent or sequential use with dinoprostone potentiates the effects of endogenous and exogenous oxytocin and can produce uterine hypertonus, uterine rupture, cervical laceration, or fetal distress, especially in the absence of adequate cervical dilation. Although oxytocin is used sequentially with dinoprostone for therapeutic advantage, a delay between administering oxytocin and dinoprostone is recommended: oxytocin may be administered 30 minutes after removal of the dinoprostone vaginal system, 6 to 12 hours after insertion of cervical gel or vaginal suppository, or 12 to 24 hours after insertion of vaginal gel. The patient should be continuously monitored {11} {51})

    (dinoprostone should not be used for cervical ripening or uterine stimulation if the patient is already receiving oxytocin or any other oxytocic agent {11})



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 {12} {14} {16} {22} {25} {27} {36} {51} {55} {66} {67}
Heart rate, maternal or fetal {07} {13} {14} {17} {22} {25} {27} {33} {36} {51} {58} {67}    (may be decreased or increased, especially with large doses {16} {12} {13} {14} {17} {22} {25} {27} {51}; a decrease in diastolic blood pressure of greater than 20 mm of Hg has been reported in approximately 10% of patients receiving dinoprostone {25})


Body temperature {14} {18} {28} {52} {66} {67}    (a temperature increase of greater than 1.1 °C [2 °F] usually occurs within 15 to 45 minutes following insertion of suppository {04} {05} {50}; this effect has not been seen with the doses of the cervical gel used for cervical ripening {38}. Body temperature returns to normal within 2 to 6 hours after discontinuation of medication or removal of suppository from vagina {04} {05} {50})


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 to dinoprostone or other prostaglandin E2 analogs, such as misoprostol {07} {48} {51} {55} {64} {77}
» Conditions that contraindicate vaginal delivery or induction of labor, including {06} {41} {51} {77}
Actively contracting or hypertonic uterus {53}
Cephalopelvic disproportion, significant {06} {41} {48} {51} {54} {77} or
Fetal distress without imminent delivery {11}
Fetal malpresentation {06} {41} {51} {54} {77}
Multiparity greater than six, history of {53}
Pelvic inflammatory disease, acute {04} {05} {14} {48} {50} {55}
Uterine or vaginal bleeding, unexplained {53}    (induction of labor, vaginal delivery, or prolonged contractions are not generally recommended {41} {51} {77})


Risk-benefit should be considered when the following medical problems exist
Anemia, or history of {04} {05} {50}    (increased incidence of excessive uterine bleeding postabortion or postpartum with use of dinoprostone in doses that induce cervical ripening or stimulate the uterus {27} {29} {41} {52})


Asthma, or history of {04} {05} {06} {07} {25} {48} {50} {51} {52} {55} {57} {64} {75} {77}    (increased risk of bronchoconstriction when dinoprostone is used in doses that induce uterine stimulation, including use in patients with a history of childhood asthma without adult asthma {18} {25})


» Cardiac disease, active, including Eisenmenger complex {04} {05} {50} {54} {55} {60} {66}    (when dinoprostone is used in doses that stimulate the uterus, a decrease in blood pressure and bradycardia may result in cardiovascular collapse and angina pectoris {48})


Cardiovascular disease, history of or {04} {05} {50} {66} {77}
Hypertension, or history of or {04} {05} {07} {50} {55} {60} {64} {66} {75}
Hypotension, history of {04} {05} {50} or
Preeclampsia {07} {14} {66} {67}    (condition may be aggravated by possible vasoconstriction or decreased blood pressure; two cases of myocardial infarction have occurred in patients with a history of cardiovascular disease with use of dinoprostone in doses that stimulate the uterus {04} {05} {50})


Cervical stenosis or {27} {29} {54}
Uterine surgery, history of {07} {14} {25} {51} {54} {57} {64} {77}    (increased risk of uterine rupture with use of dinoprostone in doses that stimulate the uterus {04} {05} {50} {51})


Cervicitis {74} {78} or
Endocervical lesions, infected or {04} {05} {50} {78}
Vaginitis, acute {04} {05} {50} {78}    (in some cases, medically induced cervical ripening may increase risk of cervical injury or chronic cervicitis {74} {78})


Epilepsy, or history of {04} {05} {06} {14} {25} {50} {51} {75} {77}    (rarely, when used in doses that stimulate the uterus, dinoprostone has been reported to cause seizures in patients with epilepsy whose seizures were poorly controlled prior to its use {14} {16} {24} {25} {27} {77})


Glaucoma {06} {14} {51} {57} {77}    (increases in intraocular pressure and miosis have been reported rarely during the use of prostaglandins; dinoprostone may have similar effects when used in doses that stimulate the uterus {30})


Hepatic disease, active {04} {05} {14} {50} {51} {55} {66} {77} {78} or
Renal disease, active {04} {05} {14} {50} {51} {55} {66} {77} {78}    (metabolism and elimination of dinoprostone may be impaired, resulting in prolonged half-life {47} {78})


» Hypersensitivity to dinoprostone or other oxytocics, history of {53}
Hypertonus, uterine, history of {53}    (excessive dosage, use of dinoprostone in doses that stimulate the uterus, or, to a lesser extent, sequential use of dinoprostone with oxytocin at doses that induce cervical ripening may cause uterine hypertonicity with spasm and tetanic contraction that can lead to posterior cervical perforations, cervical lacerations, uterine rupture, and hemorrhage {01} {12} {54} {59} {77})


Pulmonary disease, active {14} {48} {55} {66} {75}    (use of dinoprostone in doses that stimulate the uterus may decrease pulmonary blood flow and increase pulmonary arterial pressure {14} {22} {27})



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):

Blood pressure, maternal and {04} {05} {06} {15} {38} {50} {51}
Contractions, frequency, duration, and force of and {07} {15} {33} {38} {51} {77}
Heart rate, fetal and maternal and {04} {05} {06} {07} {15} {33} {38} {50} {51} {77}
Temperature, maternal and
Uterine tone {07} {15} {33} {51} {77}    (monitoring of these parameters is recommended at frequent intervals during abortion procedure or labor and delivery; well-hydrating patient with an electrolyte solution counteracts the decreased peripheral-resistance and induced vasodilatation {07} {15} {38} {51} {77} {81})

    (continuous monitoring of uterine activity and fetal state is especially recommended for patients with known history of hypertonic contractility or tetanic uterine contractions {38} {53})

    (maternal temperature increases of greater than 2° F (1.1° C) occurs in 50% of patients 15 to 45 minutes after vaginal suppository administration and normalizes within 2 to 6 hours after therapy is discontinued; differentiation between endometritis pyrexia and dinoprostone-induced pyrexia should be considered {02})


Vaginal examination {25} {51} {54} {77}    (recommended prior to each dose and after delivery or abortion to monitor cervical response and to check for signs of cervical trauma {25} {28} {38} {51} {54} {77})




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}{66}(swelling of face, inside the nose, and eyelids; hives; shortness of breath; trouble in breathing; tightness in chest; wheezing)
    
bradycardia (slow heartbeat){14}{15}{22}{25}{27}{59}
    
bronchoconstriction (wheezing; troubled breathing; tightness in chest)—especially in asthmatics{14}{16}{18}{22}{25}{27}{36}{55}{67}{71}
    
increased uterine pain accompanying abortion —correlates with efficacy{12}{14}{17}{22}{25}{27}{58}{68}
    
peripheral vasoconstriction (pale, cool, or blotchy skin on arms or legs; weak or absent pulse in arms or legs)—possibly severe{12}{14}{22}{27}
    
substernal pressure or pain {13}{22}(pressing or painful feeling in chest)
    
tachycardia (fast heartbeat){13}{22}{67}
    
uterine hypertonus (severe cramping of the uterus){07}{33}{51}{55}{57}{59}{60}{61}{63}{66}{69}{74}{77}


Note: If uterine hypertonus occurs with dinoprostone at any dose, fetal distress or uterine rupture can result. Uterine rupture has occurred with use of the cervical gel to cause cervical ripening {53}.
Systemic effects of bradycardia, bronchoconstriction, substernal pressure or pain, and tachycardia are seen rarely when dinoprostone is used for cervical ripening {11}.



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Abdominal or stomach cramps{77}
    
diarrhea —about 40% with use of 20-mg suppositories{04}{05}{07}{12}{13}{14}{17}{25}{26}{27}{28}{31}{36}{41}{44}{50}{51}{52}{55}{57}{59}{64}{66}{67}{68}{74}{75}{77} ; 1% with use of cervical gel or vaginal system
    
fever, transient —about 50% with use of 20-mg suppositories{04}{05}{07}{14}{18}{25}{28}{50}{52}{55}{59}{64}{66}{71}{74}{75}{77} ; 1% with use of cervical gel or vaginal system
    
nausea —about 33% with use of 20-mg suppositories{04}{05}{13}{14}{15}{16}{17}{27}{31}{33}{50}{52}{55}{57}{64}{66}{68}{74}{77} ; 1% with use of cervical gel or vaginal system
    
vomiting —about 67% with use of vaginal suppository or vaginal gel{04}{05}{07}{12}{13}{14}{25}{26}{27}{28}{31}{33}{34}{41}{44}{50}{52}{55}{57}{58}{59}{64}{66}{67}{68}{74}{75}{77} ; 1% with use of cervical gel or vaginal system

Incidence less frequent
—for vaginal suppositories or vaginal gel, about 10% with use of 20-mg suppositories    
Chills or shivering{04}{05}{14}{25}{28}{36}{50}{55}{74}
    
headache{04}{05}{14}{22}{25}{50}

Incidence rare
—for vaginal suppositories or vaginal gel    
Flushing{18}
    
ileus, adynamic{13}{31} (constipation, tender or mildly bloated abdomen)
    
vulvar edema{55}{74}



Those indicating possible postabortion complications and the need for medical attention if they occur after medication is discontinued
    
Endometritis (continuing chills; shivering; continuing fever—usually on third day post-abortion; foul-smelling vaginal discharge; pain in lower abdomen){04}{05}{13}{27}{50}{52}{64}{71}
    
unusual increase in uterine bleeding{06}{14}{25}{27}{28}{35}{52}{65}




Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Dinoprostone (Cervical/Vaginal).

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

Before using this medication
»   Conditions affecting use, especially:
Allergies to dinoprostone or other prostaglandins or hypersensitivity to dinoprostone, oxytocin, or other oxytocics

Pregnancy—Any pregnancy termination that fails with dinoprostone should be completed by another method
Other medical problems, especially cardiac disease or conditions that contraindicate vaginal delivery or induction of labor

Proper use of this medication
» Remaining in supine position for 10 minutes following insertion of suppository, 10 to 30 minutes following application of cervical gel, 30 minutes following application of vaginal gel, and 2 hours following insertion of vaginal system

» Proper dosing

» Proper storage


Side/adverse effects
Signs of potential side effects, especially anaphylaxis, bradycardia, bronchoconstriction, increased uterine pain accompanying abortion, peripheral vasoconstriction, substernal pressure or pain, tachycardia, uterine hypertonus

Fetal distress can result if maternal uterine hypertonus occurs at any dose of dinoprostone

Signs of postabortion complications, such as endometritis or unusual increase in uterine bleeding, after medication has been discontinued


General Dosing Information
Patients receiving dinoprostone should be hospitalized and under the supervision of a physician experienced in its use {02} {11}.

Procedures for applying dinoprostone should be carefully followed. Amnionitis and intrauterine fetal sepsis have been associated with extra-amniotic intrauterine administration of dinoprostone {53}.

When it is used in doses that stimulate the uterus, experts recommend that antiemetic and antidiarrheal medications be administered prior to or concurrently with dinoprostone to decrease the possibility of gastrointestinal side effects {14} {28} {52} {58} {64} {67}. Narcotic analgesics may be given for uterine pain {28} {52} {58} {67}.

In those patients with profuse vaginal bleeding or ruptured membranes, blood or fluid present in the cervix and vagina may cause expulsion of dinoprostone, thereby interfering with the absorption and efficacy of dinoprostone {75}.

For cervical ripening
When using a water-miscible lubricant to aid the insertion of dinoprostone vaginal system, avoid applying excessive amounts; otherwise, premature release of dinoprostone can occur {11}.

Avoid applying the dinoprostone cervical gel above the cervical os because of the greater possibility of causing uterine hyperstimulation. Select the proper catheter for cervical application of the cervical gel, depending on whether the cervix is effaced: use the 10-mm catheter with no effacement, and the 20-mm catheter with 50% effacement {53}.

For uterine stimulation
Confirmation of intrauterine fetal death should be made prior to use of dinoprostone for missed abortion or intrauterine fetal death {04} {05} {50}.

Dinoprostone is not feticidal and may result in delivery of a live fetus {04} {05} {50} {52}.

Safety considerations for handling this medication
Dinoprostone should be handled cautiously {53}. Suggested precautions for handling, preparing, and disposing of dinoprostone include the following:    • Avoid skin contact with dinoprostone, washing hands immediately with soap and water after administration {53}.
   • Use proper technique to prevent contamination of the medication, work area, and operator during transfer to patient.
   • Cautiously and properly dispose of catheters, vaginal retrieval system, and unused medication {11} {53}.


For treatment of adverse effects
Treatment is primarily symptomatic, conservative, and supportive and may include the following {78}:    • Repositioning the patient and giving oxygen {53} may be adequate to ease transient abnormal uterine contractions, especially if dinoprostone was used for cervical ripening {53}. Removing the vaginal system reverses uterine hyperstimulation within 2 to 13 minutes without need for tocolytic therapy in most cases {11}.
   • Sponging or irrigation with sterile saline of upper vagina to remove residual dinoprostone or removing vaginal suppository or system to prevent further absorption {11} {60} {74} {78}.
   • Using tocolytic therapy, such as ritodrine, terbutaline, or magnesium sulfate, to treat uterine hyperstimulation {07} {33} {55} {59} {60} {61} {74} {78}. Data on treating dinoprostone-induced adverse effects with prostaglandin antagonists are presently insufficient {11}.



Cervical Dosage Forms

DINOPROSTONE CERVICAL GEL

Usual adult and adolescent dose
Cervical ripening
Intracervical, 0.5 mg placed into the cervical canal, just below the internal cervical os, using the syringe and catheter provided. Patient should remain in supine position for at least fifteen to thirty minutes following administration. A need for an additional dose is determined by the physician and ensuing clinical events {07} {38} {51} {55} {57} {62} {64} {78}.


Usual adult prescribing limits
Cervical ripening
Maximum cumulative dose is 1.5 mg (7.5 mL) in 24 hours {38}.


Strength(s) usually available
U.S.—


0.5 mg per 2.5 mL (3 grams) prefilled single-use syringe (Rx) [Prepidil{38}]

Canada—


0.5 mg per 2.5 mL (3 grams) prefilled single-use syringe (Rx) [Prepidil{51}{53}]

Note: Packaging contains two catheter tips (10 and 20 mm). {38} {53}


Packaging and storage:
Store between 2 and 8° C (36 and 46° F). {38} {51} {53}

Preparation of dosage form:
Bring medication to room temperature just prior to administration. Do not force warming by use of external heat source, such as water bath or microwave oven. {38}

Each application is for single use and unused contents should be discarded, including the small amount of gel remaining in the catheter {38}.



Vaginal Dosage Forms

DINOPROSTONE VAGINAL GEL

Usual adult and adolescent dose
Induction of labor
Intravaginal, 1 mg placed into the posterior fornix of the vaginal canal {77}. The patient should remain in supine position for at least fifteen to thirty minutes after administration. A dose of 1 or 2 mg may be repeated once, six hours later, if needed {38} {77}.


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

Canada—


1 mg per 2.5 mL (3 grams) applicatorful (Rx) [Prostin E2{77}]


2 mg per 2.5 mL (3 grams) applicatorful (Rx) [Prostin E2{77}]

Packaging and storage:
Store below 2 and 8 °C (36 and 46 °F) {04} {05} {50} {77}.

Preparation of dosage form:
Bring medication to room temperature just prior to administration. Do not force warming by use of external heat source, such as water bath or microwave oven. {38}


DINOPROSTONE VAGINAL SUPPOSITORIES

Usual adult and adolescent dose
Abortifacient
Intravaginal, 20 mg, repeated every three to five hours, adjusted according to patient response until abortion occurs {02} {04} {05} {09} {12} {50} {64} {67} {75}. Patient should remain in supine position for at least ten minutes following insertion {02}.


Usual adult prescribing limits
Abortifacient
Maximum cumulative dose is 240 mg {09}; continuous administration of dinoprostone for more than 2 days is not recommended {02} {03} {04} {05} {12} {50}.


Strength(s) usually available
U.S.—


20 mg (Rx) [Prostin E2{02}{04}{05}{50}]

Canada—
Not commercially available.

Packaging and storage:
Store below –20 °C (–4 °F), unless otherwise specified by manufacturer {02}.

Preparation of dosage form:
Bring medication to room temperature just prior to administration. Do not force warming by use of external heat source, such as water bath or microwave oven. {02}


DINOPROSTONE VAGINAL SYSTEM

Note: This monograph contains information on both the dinoprostone vaginal suppositories and the vaginal system (a suppository within a retrieval device). Each may be inappropriately referred to as dinoprostone vaginal insert in other types of information. It is important to avoid confusing the two dosage forms, since each has a different use and strength.


Usual adult and adolescent dose
Cervical ripening
Intravaginal, 10 mg (one system delivering 0.3 mg per hour) placed transversely into the posterior fornix of the vaginal canal and removed upon onset of active labor or twelve hours after insertion, whichever occurs first {11}. The patient should remain in supine position for at least two hours after administration {11}.

Note: A minimal amount of lubricant should be used to aid system insertion {11}.



Strength(s) usually available
U.S.—


10 mg (Rx) [Cervidil{11}]

Canada—
Not commercially available.

Packaging and storage:
Store below 2 and 8 °C (36 and 46 °F) {11}, unless otherwise specified by manufacturer.

Preparation of dosage form:
Warming is not necessary {11}.



Revised: 08/20/1997



References
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  1. Prostin E2 package insert (Upjohn—US), Rev 5/86.
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  1. Prostin E2 package insert (Upjohn—US), Rev 11/88, Rec 3/89.
  1. Prostin E2 (Upjohn). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 24th ed. Ottawa: Canadian Pharmaceutical Association; 1989. p. 759-60.
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