Version May 2024
Note: Prostin E2 has been discontinued in the United States for >1 year. In the United States, dinoprostone is available as an endocervical gel (Prepidil), insert (Cervidil), and suppository (Prostin E2). Additional dosage forms and products with similar names but different indications are also available in Canada. The pharmacokinetic properties vary by dosage form and are not interchangeable. Medication errors have occurred when the incorrect dosage form was used (Ref).
Cervical ripening:
Cervidil insert: Vaginal: Insert 10 mg transversely into the posterior fornix of the vagina; Cervidil is a timed-release formulation that releases 0.3 mg/hour and can be used for up to 12 hours. Remove after 12 hours, prior to amniotomy or following rupture of membranes, or with the onset of active labor. Remove in cases of uterine tachysystole, uterine hypersystole/hypertonicity, or fetal distress. Remove prior to administration of oxytocin; the manufacturer recommends waiting ≥30 minutes after removing the dinoprostone vaginal insert before initiating oxytocin.
Prepidil gel: Endocervical: Using catheter supplied with gel, insert 0.5 mg into the cervical canal. May repeat every 6 hours if needed. Maximum cumulative dose: 1.5 mg/24 hours. Note: The manufacturer recommends waiting 6 to 12 hours after dinoprostone gel administration before initiating oxytocin.
Prostin E2 tablet [Canadian product]: Oral:
Induction: Initial: 0.5 mg and then repeat 0.5 mg dose 1 hour later; may give additional 0.5 mg dose on an hourly basis as needed for satisfactory uterine response. Maintain patient at the lowest effective dose. Note: Failure to induce regular contractions after 8 hours indicates failed induction and alternative management of patient should be considered. If patient vomits an intact tablet during therapy repeat dose. If patient vomits intact tablets following 2 successive doses, withhold therapy until next scheduled dose. If patient vomits a partial tablet or if no tablet is visible, continue at next regularly scheduled dose. Note: Avoid use of oxytocin until ≥1 hour after administration of the last dinoprostone oral tablet.
Parity ≥2 times or Bishop Score of ≥6: Administer 0.5 mg hourly throughout induction (discontinue hourly dose for excessive uterine activity)
Nulliparous or multiparous and resistant to induction (Bishop Score <6): If inadequate response after 2 hours of therapy may increase dose in 0.5 mg increments at hourly intervals up to a maximum single dose of 1.5 mg.
Maintenance of labor: 0.5 mg dose; may occasionally withhold hourly dose to assess need for further dosing
Prostin E2 gel [Canadian product]: Vaginal: Initial: Using prefilled syringe, insert 1 mg into the posterior fornix of the vaginal canal; may give 1 additional dose of 1 to 2 mg 6 hours later if needed. Note: Avoid use of oxytocin for 12 to 24 hours after administration of dinoprostone vaginal gel.
Termination of intrauterine pregnancy: Prostin E2 suppository: Vaginal: Insert 20 mg (1 suppository) high in vagina, repeat at 3- to 5-hour intervals until abortion occurs; continued administration for longer than 2 days is not recommended.
Females of reproductive age: Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Gastrointestinal: Diarrhea, nausea, vomiting
Miscellaneous: Fever
1% to 10%:
Cardiovascular: Decreased diastolic blood pressure
Genitourinary: Hypertonic uterine contractions (2% to 5%), hypertonic uterine contractions with fetal distress (3%), uterine contractions (abnormal: 7%), vaginal discomfort (warm feeling: 2%)
Nervous system: Chills, headache, shivering
Neuromuscular & skeletal: Back pain (3%)
<1%: Gastrointestinal: Abdominal pain
Frequency not defined:
Cardiovascular: Cardiac arrhythmia, chest pain, chest tightness, flushing, syncope
Dermatologic: Diaphoresis, skin rash
Endocrine & metabolic: Hot flash
Genitourinary: Breast tenderness, endometritis, urinary retention, vaginal pain, vaginismus, vaginitis, vulvitis
Nervous system: Dizziness, paresthesia
Neuromuscular & skeletal: Arthralgia, asthenia, lower limb cramp (nocturnal), muscle cramps, myalgia, neck stiffness, tremor
Ophthalmic: Blurred vision, eye pain
Otic: Auditory impairment
Respiratory: Cough, dyspnea, laryngitis, pharyngitis, wheezing
Postmarketing:
Cardiovascular: Acute myocardial infarction (with history of prior MI or history of cardiovascular disease), amniotic fluid embolism (anaphylactoid syndrome of pregnancy), hypotension
Genitourinary: Premature rupture of membranes, uterine rupture
Hematologic & oncologic: Disseminated intravascular coagulation (postpartum)
Hypersensitivity: Anaphylactic shock, anaphylaxis, angioedema, hypersensitivity reaction, nonimmune anaphylaxis
Generally, labor induction is contraindicated whenever spontaneous labor or vaginal delivery is contraindicated (ACOG 2009); manufacturer specific contraindications are listed by dosage form.
All dosage forms: Hypersensitivity to prostaglandins or any component of the formulation
Endocervical gel (Prepidil): Patients in whom oxytocic drugs are contraindicated including: History of cesarean section or major uterine surgery; presence of cephalopelvic disproportion; fetal distress when delivery is not imminent; unexplained vaginal bleeding during this pregnancy; history of difficult labor and/or traumatic delivery; ≥6 previous term pregnancies with nonvertex presentation; hyperactive or hypertonic uterine patterns; obstetric emergencies when surgical intervention would be favorable. Use is also contraindicated with placenta previa or when vaginal delivery is not indicated (eg, vasa previa, active herpes genitalia)
Canadian labeling (Prepidil): Additional contraindications (not in US labeling): History of epilepsy; fetal malpresentation; overdistention of the uterus (multiple pregnancies, polyhydramnios); ruptured amniotic membranes or suspected chorioamnionitis; concurrent use with other oxytocics
Suppository (Prostin E2): Acute pelvic inflammatory disease; active cardiac, pulmonary, renal, or hepatic disease
Tablet (oral) (Prostin E2 [Canadian product]): Patients in whom oxytocic drugs are generally contraindicated or where prolonged contractions of the uterus are considered inappropriate. Active cardiac, pulmonary, renal, or hepatic disease; simultaneous use with other oxytocics; history of cesarean section or major uterine surgery; presence of cephalopelvic disproportion; history of difficult labor and/or traumatic delivery; ≥6 pregnancies; suspected or clinically evident preexisting fetal distress; overdistention of the uterus (multiple pregnancy, polyhydramnios); preexisting uterine hypertonus; situations where a responsible physician is unavailable; engagement of head not taken place; unexplained vaginal bleeding during this pregnancy; fetal malpresentation; gynecological, obstetrical, or medical conditions that preclude vaginal delivery; pregnancy complicated by abnormal position of the placenta or umbilical cord; history of or existing pelvic inflammatory disease unless adequately treated
Vaginal gel (Prostin E2 [Canadian product]): Simultaneous use with other oxytocics; history of cesarean section or major uterine surgery; presence of cephalopelvic disproportion; history of difficult labor and/or traumatic delivery; ≥6 term pregnancies; suspected or clinically evident preexisting fetal distress; overdistention of the uterus (multiple pregnancy, polyhydramnios); preexisting uterine hypertonus; situations where a responsible physician is unavailable; engagement of head not taken place; unexplained vaginal bleeding during this pregnancy; fetal malpresentation; gynecological, obstetrical, or medical conditions that preclude vaginal delivery; pregnancy complicated by abnormal position of the placenta or umbilical cord; ruptured amniotic membranes or suspected chorioamnionitis; history of or existing pelvic inflammatory disease unless adequately treated; active cardiac, pulmonary, renal, or hepatic disease.
Vaginal insert (Cervidil): Patients in whom induction of labor is contraindicated; patients in whom oxytocic drugs are contraindicated; history of cesarean section or major uterine surgery (eg, myomectomy) expected to affect uterine integrity; patients in whom prolonged contraction of the uterus may be detrimental to fetal safety; presence of cephalopelvic disproportion; fetal distress when delivery is not imminent; unexplained vaginal bleeding during this pregnancy; patients already receiving IV oxytocic drugs; ≥6 previous term pregnancies
Canadian labeling (Cervidil): Additional contraindications (not in US labeling): Placenta previa; history of difficult labor and/or traumatic delivery; overdistention of the uterus (multiple pregnancies, polyhydramnios); history of uterine cervix rupture; fetal malpresentation; history of uncontrolled epilepsy; history of or existing pelvic inflammatory disease unless adequately treated
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• Amniotic fluid embolism syndrome: Intracervical placement of endocervical gel, vaginal gel, or vaginal insert may cause inadvertent disruption and embolization of antigenic tissue leading to amniotic fluid embolism syndrome (also known as anaphylactoid syndrome of pregnancy); rare but often fatal.
• Disseminated intravascular coagulation: Postpartum disseminated intravascular coagulation has been reported following dinoprostone for labor induction. Patients at high risk include patients ≥30 years of age, GA >40 weeks, or patients with pregnancy complications.
• Hypersensitivity reactions: Serious life-threatening hypersensitivity reactions, including anaphylaxis and angioedema, have been noted. Onset of reactions may occur within minutes to hours following initiation of therapy.
Disease related concerns:
• Cardiovascular disease: Use caution in patients with cardiovascular disease; manufacturer labeling for some dosage forms contraindicate use in active cardiovascular disease (refer to contraindications field).
• Epilepsy: Use with caution in patients with epilepsy.
• Glaucoma: Use caution in patients with glaucoma; may increase intraocular pressure and constrict pupils.
• Hepatic impairment: Use caution in patients with hepatic impairment; manufacturer labeling for some dosage forms (eg, suppository, tablet, vaginal gel) contraindicate use in active hepatic disease.
• Pulmonary disease: Use caution in patients with a history of asthma; manufacturer labeling for some dosage forms (eg, suppository, tablet, vaginal gel) contraindicate use with active pulmonary disease.
• Renal impairment: Use caution in patients with renal impairment; manufacturer labeling for some dosage forms (eg, suppository, tablet, vaginal gel) contraindicate use in active renal disease.
Concurrent drug therapy issues:
• Oxytocin: Dinoprostone may potentiate the effects of oxytocin; observe product-specific dosing intervals.
Dosage form specific issues:
• Endocervical gel: Prepidil: Use caution with ruptured membranes.
• Suppository: Prostin E2: When used for termination of pregnancy, dinoprostone is not considered feticidal, but is used to terminate pregnancy due to its ability to stimulate uterine contractions; do not use if fetus has reached the stage of viability. Transient pyrexia and decreased BP may be observed with treatment. Use caution with history of hypotension or hypertension; cardiovascular disease; anemia; jaundice; diabetes; compromised uteri; cervicitis, endocervical infections, or acute vaginitis. Measures should be taken to ensure complete abortion. Commercially available suppositories should not be used for extemporaneous preparation of any other dosage form of drug. Do not use for cervical ripening or other indications in patients with term pregnancy.
• Vaginal gel (Prostin E2 [Canadian product]): For intravaginal use only; not for intracervical use. Uterine hyperstimulation may occur if placed in the extra-amniotic space.
Other warnings/precautions:
• Experienced personnel: Dinoprostone should be used only by medically trained personnel in a hospital with strict adherence to recommended doses.
Prostin E2 has been discontinued in the United States for >1 year.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Gel, Vaginal:
Prepidil: 0.5 mg/3 g (3 g)
Insert, Vaginal:
Cervidil: 10 mg (1 ea)
Suppository, Vaginal:
Prostin E2: 20 mg (5 ea [DSC])
No
Gel (Prepidil Vaginal)
0.5 mg/3 g (per gram): $303.20
INST (Cervidil Vaginal)
10 mg (per each): $628.78
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gel, Vaginal:
Prepidil: 0.5 mg/3 g (2.5 mL)
Prostin E2: 1 mg/3 g (2.5 mL); 2 mg/3 g (2.5 mL)
Insert, Vaginal:
Cervidil: 10 mg (10 ea)
Tablet, Oral:
Prostin E2: 0.5 mg
Note: In the United States, dinoprostone is available as an endocervical gel (Prepidil), insert (Cervidil), and suppository (Prostin E2). Additional dosage forms and products with similar names but different indications are also available in Canada. The pharmacokinetic properties vary by dosage form and are not interchangeable. Medication errors have occurred when the incorrect dosage form was used (Ref).
Endocervical gel: Prepidil: Bring to room temperature just prior to use. Do not force the warming process (eg, water bath, microwave). Avoid contact with skin while handling; wash hands thoroughly with soap and water after administration. For cervical ripening, patient should be supine in the dorsal position. The appropriate catheter length should be based on degree of effacement; 20 mm for no effacement; 10 mm if 50% effaced. Patient should remain supine for 15 to 30 minutes following administration.
Tablet (oral): Prostin E2 [ Canadian product]: Administer with small amount of water.
Vaginal gel: Prostin E2 [Canadian product]: For intravaginal use only (not for intracervical use). Using prefilled syringe, dose is placed in the posterior fornix of the vagina. Patient should remain in lateral or supine position for 30 minutes to prevent leakage. Syringe contains overfill and is designed to deliver a dose of 1 or 2 mg dinoprostone. Syringe is for single use only.
Vaginal insert: Cervidil: Keep frozen until use; product does not need warmed prior to use. Only open package along the tear mark; do not open with sharp objects which may compromise or cut the knitted polyester pouch which is the retrieval system for the polymeric slab. To use, remove from the foil package and immediately place 1 vaginal insert transversely in the posterior fornix of the vagina. A water miscible lubricant may be used to facilitate insertion (avoid excessive use of lubricant which could prevent optimal swelling and release of dinoprostone from the vaginal insert). To avoid movement away from the proper position, tuck some of the excess retrieval system into the vagina, leaving a small amount outside the vagina for easy retrieval. Patients should remain in the recumbent position for 2 hours after insertion, but thereafter may be ambulatory (ensure the vaginal insert remains in place). Do not use without retrieval system. Ensure complete removal of system at completion of therapy.
Vaginal suppository: Prostin E2: Insert high into vagina after removal from its foil package. Bring to room temperature just prior to use. Patient should remain supine for 10 minutes following insertion.
Oral: Tablet (oral) [Canadian product]: Administer with small amount of water. Use of oxytocin should be avoided until ≥1 hour after administration of the last oral tablet.
Intravaginal: Note: In the United States, dinoprostone is available as an endocervical gel (Prepidil), insert (Cervidil), and suppository (Prostin E2). Additional dosage forms and products with similar names but different indications are also available in Canada. The pharmacokinetic properties vary by dosage form and are, therefore, not interchangeable. Medication errors have occurred when the incorrect dosage form was used (Ref).
Vaginal gel: (Prostin E2 [Canadian product]): For intravaginal use only (not for intracervical use). Using prefilled syringe, dose is placed in the posterior fornix of the vagina. Patient should remain in lateral or supine position for 30 minutes to prevent leakage. Syringe contains overfill and is designed to deliver a dose of 1 or 2 mg dinoprostone. Syringe is for single use only. Use of oxytocin should be avoided for 12 to 24 hours after administration of vaginal gel.
Vaginal insert (Cervidil): Keep frozen until use; product does not need warmed prior to use. Only open package along the tear mark; do not open with sharp objects which may compromise or cut the knitted polyester pouch which is the retrieval system for the polymeric slab. To use, remove from the foil package and immediately place one vaginal insert transversely in the posterior fornix of the vagina. A water miscible lubricant may be used to facilitate insertion (avoid excessive use of lubricant which could prevent optimal swelling and release of dinoprostone from the vaginal insert). Patients should remain in the recumbent position for 2 hours after insertion, but thereafter may be ambulatory (ensure the vaginal insert remains in place). Do not use without retrieval system. Ensure complete removal of system at completion of therapy. The manufacturer recommends waiting ≥30 minutes after removing the dinoprostone vaginal insert before initiating oxytocin.
Vaginal suppository (Prostin E2): Insert high into vagina after removal from its foil package. Bring to room temperature just prior to use. Patient should remain supine for 10 minutes following insertion.
Intracervical: Endocervical gel (Prepidil): Bring to room temperature just prior to use. Do not force the warming process (eg, water bath, microwave). Avoid contact with skin while handling; wash hands thoroughly with soap and water after administration. For cervical ripening, patient should be supine in the dorsal position. The appropriate catheter length should be based on degree of effacement; 20 mm for no effacement; 10 mm if 50% effaced. Patient should remain supine for 15 to 30 minutes following administration. The manufacturer recommends waiting 6 to 12 hours after dinoprostone gel administration before initiating oxytocin.
Hazardous agent (NIOSH 2016 [group 3]).
Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage. NIOSH recommends double gloving, a protective gown, and (if liquid that could splash) eye/face protection for administration (NIOSH 2016). Assess risk to determine appropriate containment strategy (USP-NF 2017).
Cervical ripening for labor induction:
Endocervical gel (Prepidil): Promote cervical ripening in patients at or near term in whom there is a medical or obstetrical indication for the induction of labor.
Tablet (oral) (Prostin E2 [Canadian product]): Elective induction of labor; when indications for induction of labor exist (eg, premature rupture of amniotic membranes, toxemia of pregnancy, Rh incompatibility, diabetes mellitus, hypertension, postmaturity, intrauterine death or fetal growth retardation).
Vaginal gel (Prostin E2 [Canadian product]): Induction of labor in patients at or near term with singleton pregnancy, vertex presentation, and favorable induction features.
Vaginal insert (Cervidil): Initiation and/or continuation of cervical ripening in patients at or near term in whom there is a medical or obstetrical indication for the induction of labor.
Termination of intrauterine pregnancy: Suppositories (Prostin E2): Termination of pregnancy from 12th through 20th week of gestation as calculated from the first day of the last normal menstrual period; evacuation of uterine contents in cases of missed abortion or intrauterine fetal death up to 28 weeks of gestation as calculated from the first day of the last normal menstrual period; management of benign hydatidiform mole (nonmetastatic gestational trophoblastic disease).
Prostin E2 may be confused with Prostin VR (alprostadil)
Cervidil brand name for dinoprostone [US, Canada, Australia, New Zealand], but also the brand name for gemeprost [Italy]
Different formulations: Dinoprostone is available as an endocervical gel (Prepidil), insert (Cervidil), and suppository (Prostin E2). Prepidil and Cervidil are used to promote cervical ripening while Prostin E2 is used to evacuate the uterine contents in cases of missed abortion or intrauterine fetal death. Medication errors have occurred when Prostin E2 suppository was cut in half and administered to induce labor (Institute for Safe Medication Practices [ISMP] 2013).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Carbetocin: Dinoprostone may enhance the adverse/toxic effect of Carbetocin. Specifically, Carbetocin oxytocic effects may be enhanced. Risk X: Avoid combination
Carboprost Tromethamine: May enhance the adverse/toxic effect of Oxytocic Agents. Specifically, oxytocic effects may be enhanced. Risk X: Avoid combination
Oxytocin: Dinoprostone may enhance the adverse/toxic effect of Oxytocin. Specifically, oxytocic effects may be enhanced. Management: Concomitant use of dinoprostone and oxytocin is not recommended. If used sequentially, monitor uterine activity closely. Administer oxytocin 30 minutes after removing dinoprostone vaginal insert and 6 to 12 hours after the application of dinoprostone gel. Risk D: Consider therapy modification
Adverse events have been observed in animal reproduction studies. Although these effects would not be expected in humans when administered after the period of organogenesis, a sustained increase in uterine tone may have increased risks of adverse events to the fetus.
Fetal distress without corresponding maternal uterine hyperstimulation was observed in 3% to 4% of infants exposed to Cervidil in utero. Normal rhythm returns following removal. No adverse effects on physical or psychomotor function were observed in a 3-year follow-up study of 51 exposed infants. Abnormal fetal heart rates were observed in 17% of infants exposed to Prepidil gel in utero. Deceleration, intrauterine fetal sepsis, fetal depression, and fetal acidosis have also been reported with administration of the endocervical gel.
When used for termination of pregnancy, dinoprostone is not considered feticidal, but is used to terminate pregnancy due to its ability to stimulate uterine contractions; do not use if fetus has reached the stage of viability. A previable fetus may show transient life signs if aborted by dinoprostone. Failed pregnancy termination with dinoprostone should be completed by another method.
Endogenous PGE2 is present in breast milk (Shimizu 1992).
Dinoprostone was found to inhibit lactation following oral administration (England 1988).
Gel, insert: Fetal heart rate, uterine activity, progression of cervical dilation and effacement; signs of amniotic fluid embolism (eg, coma, disseminated intravascular coagulation [evolving fibrinolysis], hypotension, hypoxemia, respiratory failure, seizures).
Tablet: Uterine activity; excessive uterine activity is contractions >5 per 10 minutes and/or the internal tonus consistently >15 mm Hg.
Suppository: Confirmation of fetal death.
Dinoprostone (prostaglandin E2) is an endogenous hormone found in low concentrations in most tissues of the body. When administered as an abortifacient, it stimulates uterine contractions similar to those seen during natural labor. When administered for labor induction, it relaxes the smooth muscle of the cervix allowing dilation and passage of the fetus through the birth canal.
Onset of action (uterine contractions): Vaginal suppository: Within 10 minutes.
Duration: Vaginal insert: 0.3 mg/hour over 12 hours; Vaginal suppository: Up to 2 to 3 hours.
Absorption: Vaginal suppository: Slow.
Metabolism: Metabolized in the lungs; forms metabolites, which are further metabolized in the liver and kidney.
Half-life elimination: 2.5 to 5 minutes.
Time to peak, plasma: Endocervical gel: 30 to 45 minutes.
Excretion: Primarily urine; feces (small amounts).
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