Among 25 women who received dinoprostone, prostaglandin E2 20 mg suppository every 3 hours, 71% had nausea.[32756] In other trials with the vaginal suppository, approximately two-thirds experienced vomiting, approximately two-fifths had diarrhea, and approximately one-third had nausea.[41180] In contrast, < 1% of dinoprostone vaginal insert recipients had nausea, vomiting, diarrhea, or abdominal pain.[41178] The vomiting and/or diarrhea that is occasionally seen when dinoprostone is used for preinduction cervical ripening is likely due to the contractile effect of dinoprostone on smooth muscle; the reactions are usually transient and reversible once dinoprostone administration ceases. The pretreatment or concurrent administration of antiemetic and antidiarrheal drugs considerably decreases the incidence of gastrointestinal effects common with all prostaglandins used for abortion; consider such co-therapies as an integral part of patient care.[32757]

Approximately 10% of dinoprostone, prostaglandin E2 suppository recipients had transient diastolic blood pressure decreases of > 20 mmHg, and 2 cases of myocardial infarction after the use of dinoprostone have been reported in patients with a history of cardiovascular disease. Of note, large doses of another prostaglandin carboprost tromethamine can raise blood pressure, probably by contracting the vascular smooth muscle; the most frequent adverse reactions observed with the use of dinoprostone for abortion are related to its contractile effect on smooth muscle. Clinically significant effects on blood pressure have not been noted with dinoprostone doses used for terminating pregnancy, but cautious use of dinoprostone is advised for patients with a history of hypotension or hypertension. Other adverse events that may be related to dinoprostone-induced vasomotor and vasovagal effects include flushing, hot flashes, dizziness, syncope, lightheadedness, chest pain (unspecified), diaphoresis, and cardiac arrhythmias.[32757] [41180]

Use of dinoprostone, prostaglandin E2 is associated with transient fever that may be due to its effect on hypothalamic thermoregulation.[41180] Among 25 recipients of dinoprostone suppositories 20 mg every 3 hours until abortion, 79% had chills, and 92% had fever.[32756] Among other suppository recipients, 50% had temperature elevations in excess of 2 degrees F, and 10% had shivering and chills. In all cases, temperature returned to normal on dinoprostone discontinuation; temperature usually reverts to baseline 2—6 hours after dinoprostone discontinuation or suppository removal. In contrast to the suppository, fever was noted in < 1% of dinoprostone vaginal insert recipients and in 1.4% of dinoprostone gel recipients.[41178] [41179] In regard to dinoprostone use for pregnancy termination, differentiation of post-abortion endometritis from drug-induced temperature elevations is difficult. Determining the time of onset may help discern the fever cause; dinoprostone-induced fever usually occurs within 15—45 minutes of suppository administration while endometritis-induced temperature elevations typically present on day 3 after the abortion procedure. Uterine and other physical findings consistent with endometritis include incomplete evacuation of the uterus, histology consistent with endometrial inflammation, foul-smelling lochia and leukorrhea, and uterine tenderness. Force fluids in patients with drug-induced fever and no clinical or bacteriological evidence of an infectious process; no other simple empirical measures for temperature reduction are necessary, as fever is transient or self-limiting.[32757]

Use of dinoprostone, prostaglandin E2 suppositories for pregnancy termination may cause a cervical laceration. For example, posterior cervical perforation has been noted with another prostaglandin carboprost tromethamine. As cervical trauma can be asymptomatic, carefully examine the cervix immediately after the completion of dinoprostone-induced abortion. Take corrective measures as necessary.[32757]

Uterine contraction is a common and expected effect of dinoprostone, prostaglandin E2. Among 25 women who received a 20 mg suppository every 3 hours until delivery, 88% had uterine muscle cramps and 33% had headache.[32756] Headache was also noted in 10% of other suppository recipients, and arthralgia, mastalgia, back pain, leg cramps, musculoskeletal pain, paresthesias, vaginal pain, weakness, and cramping similar to dysmenorrhea have been observed.[41180] Back pain was also noted among 3.1% of 884 dinoprostone vaginal gel recipients.[41179]

According to the manufacturers of dinoprostone vaginal gel and insert, during postmarketing surveillance, an increased risk of postpartum disseminated intravascular coagulation (DIC) has been reported in patients whose labor was induced by dinoprostone. The frequency of this adverse event appears to be rare; reported in less than 1 per 1,000 labors (less than 0.1%) in patients receiving the vaginal gel (Prepidil). Risk factors for DIC include pregnant females 30 years or older, those with complications during pregnancy, and those with a gestational age over 40 weeks. Therefore, use dinoprostone with considerable caution in these groups, and monitor carefully for the possibility of fibrinolysis in the postpartum period.[41178] [41179]

The intravaginal placement of dinoprostone vaginal gel and vaginal insert (Prepidil and Cervidil, respectively) may result in inadvertent disruption and subsequent embolization of antigenic tissue causing in rare circumstances the development of anaphylactoid syndrome of pregnancy (amniotic fluid embolism). Carefully monitor for clinical signs of amniotic fluid embolism syndrome including hypotension, hypoxemia and respiratory failure, DIC, coma or seizures and provide supportive care as needed.[41178] [41179]

Uterine rupture or perforation is a potentially life-threatening adverse event that has been noted among women who received dinoprostone; prostaglandin E2 for pregnancy termination and for cervical ripening. Consider uterine rupture if high-tone myometrial contractions are sustained. Cautious use of the suppositories is advised for women with compromised (scarred) uteri.[41180] Of note, the vaginal insert and the vaginal gel are contraindicated for use by women with a previous cesarean section.[41179] [41178] Among women who had various induction methods for pregnancy termination, the incidence of uterine rupture was 3.8% among women with a prior cesarean as compared with 0.2% of women without such a history.[54356] Use of laminaria tents and/or conservative uterine stimulation in at risk patients may decrease the risk of rupture.[32763]

Respiratory effects associated with dinoprostone, prostaglandin, E2 use include dyspnea, chest tightness, cough, and wheezing. Dinoprostone vaginal suppositories are contraindicated for use by patients with active pulmonary disease; use all dinoprostone formulations with caution in patients with a history of asthma or other bronchospasm.[41178] [41179] [41180]

Serious hypersensitivity reactions, including anaphylactoid reactions, anaphylaxis, and angioedema have been noted postmarketing experience with dinoprostone.[41179] [41180] Onset of these reported reactions occurred within minutes to hours after initiation with dinoprostone. Rash (unspecified) has been observed with dinoprostone, prostaglandin E2 administration.[41180] Watch for signs and symptoms of local and systemic hypersensitivity. If a hypersensitivity reaction is suspected, if possible remove the dinoprostone from the patient, assess for potential causes of the event, and institute symptomatic and supportive therapy.[41179] [41180]

Blurred vision and ocular pain have been noted with dinoprostone, prostaglandin E2.[41180] Cautious use of dinoprostone is advised for patients with glaucoma or raised intraocular pressure.[41179]

The use of the dinoprostone vaginal insert may cause uterine tachysystole (excessively frequent uterine contractions) with or without fetal heart rate changes. In placebo-controlled trials, 2.8% to 2.9% of women who received the vaginal insert experienced uterine tachysystole with fetal distress compared to 0% to 0.3% of women who received placebo. During these trials, 2% to 4.7% of treated women experienced uterine tachysystole without fetal distress compared to 0% of women who received placebo. Also, 2.9% to 3.8% of women who received the vaginal insert experienced fetal distress without uterine tachysystole vs. 1% to 1.2% of the women who received placebo. In the cases of uterine tachysystole, uterine hyperstimulation reversed within 2 to 13 minutes of removal of the vaginal insert, using the retrieval system. Tocolytics were required in one of the 5 cases. When the vaginal insert was removed for fetal distress, there was a return to a normal rhythm and there were no neonatal sequelae. During use of the vaginal insert, carefully monitor uterine activity, fetal status, and the progression of cervical dilatation and effacement. Remove the vaginal insert with any evidence of persistent tachysystole with or without fetal heart rate changes, uterine hypersystole/hypertonicity, fetal distress, or if labor commences.[41178]

Dinoprostone is contraindicated when prolonged contraction of the uterus may be detrimental to fetal safety and uterine integrity. Cephalopelvic disproportion or signs of fetal distress where delivery is not imminent contraindicate use of dinoprostone. Certain maternal problems contraindicate use of dinoprostone such as a history of difficult labor (prolonged contraction of the uterus) or traumatic delivery, conditions of decreased uterine wall integrity ( e.g., history of grand multiparity, caesarean section, or major uterine surgery such as myomectomy), or any hyperactive or hypertonic uterine patterns (uterine atony). Such maternal problems may increase the risk of uterine rupture and associated fetal and maternal complications. Cautious use is warranted in patients with prelabor rupture of membranes (PROM), in cases of non-vertex or non-singleton presentation, and in patients with a history of uterine hypertony when administering dinoprostone vaginal products for cervical ripening.[41178] [41179] The use of the vaginal insert may also cause uterine tachysystole with or without fetal heart rate changes. While using the vaginal insert, carefully monitor uterine activity, fetal status and the progression of cervical dilatation and effacement. Remove the vaginal insert with any evidence of uterine tachysystole, uterine hypersystole/hypertonicity, fetal distress, or if labor commences. Prostaglandins, including the vaginal insert, may potentiate the effect of oxytocin. Remove the vaginal insert at least 30 minutes before administration of an oxytocic agent is initiated and continue to carefully monitor uterine activity. Remove the vaginal insert prior to amniotomy or following rupture of membranes because the higher vaginal pH that occurs with rupture of membranes may result in a higher release rate of dinoprostone from the insert.[41178]

Dinoprostone is contraindicated in individuals who have placenta previa or who have had abnormal uterine bleeding during the course of the current pregnancy, vasa previa, or genital herpes infection.[41178] [41179]

Prostaglandins, including dinoprostone, can cause increased intraocular pressure and constriction of pupils. Consider non-prostaglandin cervical ripening procedures in individuals with glaucoma. If dinoprostone must be used in individuals with glaucoma, administer with caution.[41178] [41179]

Use dinoprostone gel with caution in individuals with a history of asthma.[41179]

Use dinoprostone gel with caution in individuals with hepatic failure or dysfunction. In humans, prostaglandin E is extensively metabolized in the lungs, and the resulting metabolites are further metabolized in the liver and kidney.[41179]

Use dinoprostone gel with caution in individuals with renal impairment or renal failure, as the major route of elimination for dinoprostone after metabolism is the kidney.[41179]

Dinoprostone is approved for cervical ripening prior to delivery at term.[41178] [41179] Prostaglandin E2 produced an increase in skeletal anomalies in rats and rabbits. No effect would be expected clinically, when used as indicated, since dinoprostone is administered in late pregnancy after the period of organogenesis. Dinoprostone has been shown to be embryotoxic in rats and rabbits, and any dose that produces sustained increased uterine tone could put the embryo or fetus at risk.[41179] In a report of a 3-year pediatric follow-up study, there were no deleterious effects noted on physical examination or psychomotor evaluation of 51 infants born following maternal treatment with the vaginal insert.[41178] The patient's uterine activity should be carefully monitored for uterine hyperstimulation. Remove dinoprostone in cases of uterine hyperstimulation, if labor commences, and prior to amniotomy.[41178] [41179]

Dinoprostone is not recommended to be given concurrently with breast-feeding. Insufficient information is available on the effects of maternal dinoprostone administration on milk production and the effects on the breastfed child.[41178] [41179] However, use of dinoprostone during labor for cervical ripening is of short duration and is unlikely to have a significant clinical effect on breast milk production several hours or days after dinoprostone use was stopped.[70365] Oral dinoprostone has been used off-label for inhibition of postpartum lactation and reduction of engorgement.[70365]