dinoprostone (Rx)

1-10%

Gel

• Fever/temperature elevations (1%)
• GI upset (6%)
• Abnormal uterine contractions (7%)
• Warm feeling in vagina (2%)
• Back pain (3%)

Insert

• Hypertonic uterine dysfunction with fetal distress (3%)
• Hypertonic uterine dysfunction without fetal distress (2-5%)

<1%

Gel

• Amnionitis
• Premature rupture of membranes
• Uterine rupture
• Postpartum disseminated intravascular coagulation

Insert

• Hypotention
• Uterine rupture
• Postpartum disseminated intravascular coagulation

Frequency Not Defined

Suppository

• Chest pain
• Arrhythmia
• Syncope
• Chest tightness
• Skin discoloration
• Endometritis
• Dehydration
• Hot flashes
• Vaginitis
• Vulvitis
• Paresthesia
• Hearing impairment
• Eye pain
• Blurred vision
• Diaphoresis

Postmarketing Reports

Hypersensitivity reactions (e.g., Anaphylactic reaction, anaphylactic shock)

Cardiovascular disorders: Myocardial Infarction in women with a history of myocardial infarction

Nervous system disorders: Headache

Contraindications

Gel

• Hypersensitivity to the drug or components
• Patients for whom oxytocic drugs are contraindicated
• History of cesarean section or major uterine surgery
• Cephalopelvic disproportion present
• Cases of fetal distress where delivery not imminent
• History of difficult labor or traumatic delivery
• 6 or more previous term pregnancies (grand multiparae)
• Cases with hyperactive or hypertonic uterine patterns
• Unexplained vaginal bleeding during pregnancy
• Cases where vaginal delivery not indicated
• Cases with nonvertex presentation

Insert

• Hypersensitivity to prostaglandins
• Cases of fetal distress where delivery not imminent
• Unexplained vaginal bleeding during pregnancy
• Cephalopelvic disproportion present
• Patients currently receiving IV oxytocic drugs
• 6 or more previous term pregnancies (grand multiparae)
• Conditions for which induction of labor contraindicated
• Patients for whom oxytocic drugs are contraindicated
• Previous cesarean section or other uterine surgery expected to affect uterine integrity (eg, myomectomy)
• When prolonged contraction of the uterus may negatively affect fetal safety or uterine integrity
• Uterine rupture or other associated obstetrical complications

Suppository

• Hypersensitivity to dinoprostone, acute pelvic inflammatory disease
• Active pulmonary, cardiac, hepatic, renal disease or acute pelvic inflammatory disease

Cautions

Administer in hospital setting with obstetric care facility

Use caution in patients with epilepsy, glaucoma, hepatic/renal impairment, pulmonary disease

Wait 30 min following removal of insert, or 6-12 hr following gel application, before administering other oxytocic drugs

Do not administer gel above level of internal os

Remove insert before amniotomy

Patients with cervical laceration with resultant retention of placenta and severe hemorrhage may require blood transfusions

Closely monitor with acute vaginitis, anemia, cardiovascular disease, cervical stenosis, cervicitis, diabetes mellitus, endocervical lesions, glaucoma, hypertension, hypotension, jaundice, mild pre-eclampsia, multiparity, severe pre-eclampsia, seizures with epilepsy, surgery of uterus or cervix, uterine fibroids

Increased risk of postpartum disseminated intravascular coagulation in women aged 30 years or older, those with complications during pregnancy, and those with gestational age >40 weeks; assess for evolving fibrinolysis in the immediate postpartum period; promptly institute therapy consisting of prompt removal of the source of procoagulant material, replacement of depleted clotting factors and, in some cases, anticoagulation with heparin

Inadvertent disruption and subsequent embolization of antigenic tissue causing in rare circumstances the development of anaphylactoid syndrome of pregnancy

Life-threatening hypersensitivity reactions including anaphylaxis and angioedema reported; onset occurred within minutes to hours after initiation with therapy; If a hypersensitivity reaction is suspected, remove (dinoprostone gel application, if possible; assess for other potential causes of event, and institute symptomatic and supportive therapy, as needed

Disseminated intravascular coagulation

• Use with caution in women at high risk of postpartum disseminated intravascular coagulation (DIC); physiologic or pharmacologic induction of labor, is associated with an increased risk of DIC during the postpartum period
• Promptly institute therapy consisting of prompt removal of source of procoagulant material, replacement of depleted clotting factors and, in some cases, anti-coagulation with heparin

Amniotic fluid embolism syndrome

• Use of dinoprostone-containing products may result in inadvertent disruption and subsequent embolization of antigenic tissue causing the development of a rare syndrome known as the amniotic fluid embolism syndrome, which can be fatal
• Monitor patients for clinical signs of amniotic fluid embolism syndrome including hypotension, hypoxemia and respiratory failure, DIC, coma or seizures and provide supportive care as needed

Uterine tachysystole and uterine hypersystole/ hypertonicity

• Therapy may cause uterine tachysystole with or without fetal heart rate changes
• While receiving therapy, carefully monitor uterine activity, fetal status and progression of cervical dilatation and effacement
• Discontinue therapy with any evidence of uterine tachysystole, uterine hypersystole/hypertonicity, fetal distress, or if labor commences
• Therapy is contraindicated when prolonged contraction of the uterus is detrimental to fetal safety or uterine integrity, such as previous cesarean section or major uterine surgery, because of risk of uterine rupture and obstetrical complications (e.g., need for hysterectomy and occurrence of fetal or neonatal death)
• Prostaglandins may potentiate effect of oxytocin; stop administration at least 30 minutes before administration of an oxytocic agent is initiated and continue to carefully monitor uterine activity
• Stop drug prior to amniotomy or following rupture of membranes because the higher vaginal pH that occurs with rupture of membranes may result in higher release rate of dinoprostone
• Prostaglandins can lead to raised intraocular pressure and constriction of pupils; consider non-prostaglandin cervical ripening procedures in patients with glaucoma

Pregnancy

Indicated for initiation and/or continuation of cervical ripening in pregnant women at or near term in whom there is a medical or obstetrical indication for induction of labor

Limited available data with use in pregnant women do not show a clear association with adverse developmental outcomes; relevant animal reproduction data with dinoprostone is not available

When therapy was removed for fetal distress, there was a return to normal rhythm and there were no neonatal sequelae; remove therapy in the event of persistent tachysystole with or without fetal heart rate changes, and follow established institutional protocols in management of patients

Lactation

Concomitant administration of is not indicated in breastfeeding women; there is no information on effects of maternal administration on breastfed child

Insufficient information is available on effects of maternal administration on milk production

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Relaxes cervical smooth muscle; stimulates uterine contractions similar to those observed during labor

Pharmacokinetics

Peak plasma time: 0.5-0.75 hr

Onset: In most first and second trimester pregnancies, slight uterine contractions begin within 10 min

Duration: Contractions continue for 2-3 hr following vaginal insertion of a dinoprostone suppository

Metabolism: Rapidly in the maternal lungs, kidneys, spleen, and other tissues, primarily by oxidation of side chains to at least 9 inactive metabolites

Half-life: 2.5-5 min

Excretion: Urine (principally); feces (small amount)