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standards of non-Merck sources.
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(dye noe PROST one)
Generic Available (U.S.)
No
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Endocervical gel: Promote cervical ripening in patients at or near term in whom there is a medical or obstetrical indication for the induction of labor
Suppositories: Terminate pregnancy from 12th through 20th week of gestation; evacuate uterus in cases of missed abortion or intrauterine fetal death up to 28 weeks of gestation; manage benign hydatidiform mole (nonmetastatic gestational trophoblastic disease)
Vaginal insert: 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
Pregnancy Risk Factor
C
Pregnancy Considerations
Skeletal anomalies and embryotoxicity have been observed in animal 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. No adverse effects on physical or psychomotor function were observed in a 3 year follow-up study of 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 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.
Lactation
Excretion in breast milk unknown
Breast-Feeding Considerations
Endogenous PGE2 can be detected in breast milk. High levels have been associated with diarrhea in nursing infants.
Contraindications
Hypersensitivity to prostaglandins or any component of the formulation
Endocervical gel and vaginal insert: Patients in whom oxytocic drugs are contraindicated; 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. In addition:
Endocervical gel: 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, placenta previa, when vaginal delivery is not indicated (eg, vasa previa, active herpes genitalia)
Vaginal insert: Patients already receiving I.V. oxytocic drugs, ≥6 previous term pregnancies
Suppository: Acute pelvic inflammatory disease; active cardiac, pulmonary, renal, or hepatic disease
Warnings/Precautions
Boxed warnings:
• Experienced personnel: See “Other warnings/precautions” below.
Concerns related to adverse effects:
• Disseminated intravascular coagulation (DIC): Postpartum DIC has been reported following dinoprostone for labor induction. Risk may be increased in women ≥30 years of age, gestation age >40 weeks, or women with pregnancy complications.
Disease related concerns:
• Hepatic impairment: Use caution in patients with hepatic impairment.
• Renal impairment: Use caution in patients with renal impairment.
Dosage form specific issues:
• Endocervical gel: Use caution with ruptured membranes, glaucoma, or a history of asthma. Intracervical placement of gel may lead to anaphylactoid syndrome of pregnancy (rare).
• Suppository: 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 blood pressure may be observed with treatment. Use caution with history of asthma; hypotension or hypertension; cardiovascular disease; anemia; jaundice; diabetes; epilepsy; 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 insert: Use caution with ruptured membranes; nonvertex or nonsingleton pregnancy; previous uterine hypertony; history of asthma or glaucoma. Must be removed prior to administration of oxytocin, in case of hyperstimulation or if labor begins, fetal or maternal distress, and prior to amniotomy. Intravaginal placement of insert may lead to anaphylactoid syndrome of pregnancy (rare).
Other warnings/precautions:
• Experienced personnel: [U.S. Boxed Warning]: Dinoprostone should be used only by medically-trained personnel in a hospital.
Adverse Reactions
Endocervical gel:
1% to 10%:
Central nervous system: Fever (1%)
Gastrointestinal: GI upset (6%)
Genitourinary: Abnormal uterine contractions (7%), warm feeling in vagina (2%)
Neuromuscular & skeletal: Back pain (3%)
Postmarketing and/or case reports: Amnionitis, anaphylactoid syndrome of pregnancy (amniotic fluid embolism), postpartum DIC, premature rupture of membranes, uterine rupture (with intracervical administration)
Suppository:
Frequency not defined:
Cardiovascular: Arrhythmia, chest pain, chest tightness, hypotension, syncope
Central nervous system: Chills, dizziness, fever, headache, shivering, tension
Dermatologic: Rash, skin discoloration
Endocrine & metabolic: Breast tenderness, endometritis, hot flashes
Gastrointestinal: Dehydration, diarrhea, nausea, vomiting
Genitourinary: uterine rupture, urinary retention, vaginal pain, vaginismus, vaginitis, vulvitis
Neuromuscular & skeletal: Arthralgia, backache, joint inflammation/pain (new or exacerbated), leg cramps (nocturnal), muscle cramp/pain, myalgia, paresthesia, stiff neck, tremor, weakness
Ocular: Blurred vision, eye pain
Otic: Hearing impairment
Respiratory: Cough, dyspnea, laryngitis, pharyngitis, wheezing
Miscellaneous: Diaphoresis
Postmarketing and/or case reports: MI
Vaginal insert:
1% to 10%: Genitourinary: Uterine hyperstimulation without fetal distress (2% to 5%), uterine hyperstimulation with fetal distress (3%)
<1%: Abdominal pain, diarrhea, fever, nausea, vomiting
Postmarketing and/or case reports: Anaphylactoid syndrome of pregnancy (amniotic fluid embolism), postpartum DIC, hypersensitivity reactions, hypotension, uterine rupture
Metabolism/Transport Effects
None known.
Drug Interactions
Carbetocin: Dinoprostone may enhance the therapeutic effect of Carbetocin. Risk X: Avoid combination
Oxytocin: Dinoprostone may enhance the therapeutic effect of Oxytocin. Risk D: Consider therapy modification
Storage
Endocervical gel should be stored under refrigeration at 2°C to 8°C (36°F to 46°F).
Suppositories must be kept frozen; store in freezer not above -20°C (-4°F).
Vaginal insert should be stored in freezer between -20°C and -10°C (-4°F and 14°F).
Mechanism of Action
A synthetic prostaglandin E2 abortifacient that stimulates uterine contractions similar to those seen during natural labor. Prostaglandin E2 plays a role in cervical ripening, which allows the fetus to pass through the birth canal.
Pharmacodynamics/Kinetics
Onset of action (uterine contractions): Vaginal suppository: Within 10 minutes
Duration: Vaginal insert: 0.3 mg/hour over 12 hours; Vaginal suppository: Up to 2-3 hours
Absorption: Vaginal suppository: Slow
Metabolism: Metabolized in the lungs; forms metabolites which are further metabolized in the liver and kidney
Half-life elimination: 2.5-5 minutes
Time to peak, plasma: Endocervical gel: 30-45 minutes
Excretion: Primarily urine; feces (small amounts)
Dosage
Females of reproductive age:
Abortifacient: Vaginal suppository: 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 advisable
Cervical ripening:
Endocervical gel: 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
Vaginal insert: Insert 10 mg transversely into the posterior fornix of the vagina (to be removed at the onset of active labor or after 12 hours)
Administration: Other
Endocervical gel: 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 15-30 minutes following administration. The manufacturer recommends waiting 6-12 hours after dinoprostone gel administration before initiating oxytocin.
Vaginal insert: One vaginal insert is placed transversely in the posterior fornix of the vagina immediately after removal from its foil package. Patients should remain in the recumbent position for 2 hours after insertion, but thereafter may be ambulatory. Do not use without retrieval system. Product does not need warmed prior to use. A water miscible lubricant may be used to facilitate insertion (avoid excessive use of lubricant). 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: 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.
Monitoring Parameters
Gel, insert: Fetal heart rate, uterine activity, progression of cervical dilation and effacement
Suppository: Confirmation of fetal death
Patient Education
Nausea and vomiting, cramping or uterine pain, or fever may occur. Report acute pain, respiratory difficulty, or skin rash. Closely monitor for vaginal discharge for several days. Report heavy vaginal bleeding, itching, malodorous or bloody discharge, or severe cramping.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Monitor temperature, uterine tone, and vaginal discharge closely throughout procedure and postprocedure. Monitor abortion for completeness (other measures may be necessary if incomplete).
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gel, endocervical:
Prepidil®: 0.5 mg/3 g (3 g)
Insert, vaginal:
Cervidil®: 10 mg (1s) [releases 0.3 mg/hour]
Suppository, vaginal:
Prostin E2®: 20 mg (5s)
References
Cusick W, Leuci D, Viscarello RR, et al, “Anaphylactoid Syndrome of Pregnancy After Intracervical Dinoprostone for Cervical Ripening: A Report of 3 Cases,” J Reprod Med, 2005, 50(3):225-8.
Novakov A, Segedi D, Milasinovic L, et al, “Induction of Labor by Endocervical Application of Prostaglandins and Intravenous Infusion of Oxytocin in Post-term Pregnancy,” Med Pregl, 1998, 51(9-10):419-26.
International Brand Names
Lexi-Comp.com
Last full review/revision October 2011
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