CERVIDIL Vaginal insert Ref.[10770] Active ingredients: Dinoprostone

5.1 For Hospital Use Only

CERVIDIL should be administered in a hospital setting with an obstetrical care facility.

5.2 Disseminated Intravascular Coagulation

CERVIDIL should be used with caution in women at high risk of postpartum disseminated intravascular coagulation (DIC). Physiologic or pharmacologic induction of labor, including the use of CERVIDIL, is associated with an increased risk of DIC during the postpartum period. Women aged 30 years or older, those with complications during pregnancy and those with a gestational age over 40 weeks have an increased risk of DIC during the postpartum period. As soon as possible, assess for an evolving fibrinolysis in the immediate post-partum period. Therapy consisting of prompt removal of the source of procoagulant material, replacement of depleted clotting factors and, in some cases, anti-coagulation with heparin should be instituted promptly.

5.3 Amniotic Fluid Embolism Syndrome

The use of dinoprostone-containing products, including CERVIDIL, can result in inadvertent disruption and subsequent embolization of antigenic tissue causing the development of Amniotic Fluid Embolism Syndrome, a rare and often fatal obstetric condition.

Carefully 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.

5.4 Uterine Tachysystole and Uterine Hypersystole/Hypertonicity

The use of CERVIDIL may cause uterine tachysystole with or without fetal heart rate changes (see Table 1). While using CERVIDIL, carefully monitor uterine activity, fetal status and the progression of cervical dilatation and effacement. Remove CERVIDIL with any evidence of uterine tachysystole, uterine hypersystole/hypertonicity, fetal distress, or if labor commences. CERVIDIL 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 the risk of uterine rupture and obstetrical complications (e.g., need for hysterectomy and the occurrence of fetal or neonatal death). Prostaglandins, including CERVIDIL, may potentiate the effect of oxytocin [see Drug Interactions (7)]. Remove CERVIDIL at least 30 minutes before administration of an oxytocic agent is initiated and continue to carefully monitor uterine activity. Remove CERVIDIL 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.

5.5 Glaucoma

Prostaglandins, including CERVIDIL, can lead to raised intraocular pressure and constriction of pupils. Consider non-prostaglandin cervical ripening procedures in patients with Glaucoma.

The following adverse reactions are described, or described in greater detail, in other sections:

• Disseminated Intravascular Coagulation [see Warnings and Precautions (5.2)]
• Amniotic Fluid Embolism [see Warnings and Precautions (5.3)]
• Uterine Tachysytole and Uterine Hypersystole/Hypertonicity [see Warnings and Precautions (5.4)]

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In placebo-controlled trials of 658 pregnant women (320 CERVIDIL-treated women and 338 placebo-treated women), the following treatment related adverse reactions (see Table 1) occurred at an incidence greater than 2% (and greater than that reported in the placebo group) in the CERVIDIL group [see Clinical Studies (14)].

Table 1. Common Adverse Reactions (≥2%) in Pregnant Patients Near Term Gestation in Trial 1*, Trial 2*, and Trial 3^†:

^* Trial 1 (101-103) and Trial 2 (101-003) evaluated the dinoprostone insert only, without the use of a retrieval system
^† Trial 3 (101-801) evaluated the dinoprostone insert with the retrieval system.

Drug related fever, nausea, vomiting, diarrhea, and abdominal pain occurred in less than 1% of CERVIDIL-treated patients.

In Trial 3 (with the retrieval system) cases of tachysystole uterine hyperstimulation reversed within 2 to 13 minutes of removal of CERVIDIL. Tocolytics were required in one of the five cases.

The following adverse reactions have been identified during postapproval use of CERVIDIL or other dinoprostone products. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Blood and lymphatic system disorders: Disseminated Intravascular Coagulation

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

Immune system disorders: Hypersensitivity

Nervous system disorders: Headache

Pregnancy, puerperium and perinatal conditions: Amniotic fluid embolism

Reproductive system: reports of uterine rupture have been reported in association with use of CERVIDIL. Some required a hysterectomy and others resulted in subsequent fetal or neonatal death. Uterine hypertonus

Vascular disorders: Hypotension

7.1 Oxytocic Agents

CERVIDIL is contraindicated in patients receiving intravenous oxytocic agents because CERVIDIL may augment the activity of oxytocic agents. A dosing interval of at least 30 minutes is recommended for the sequential use of an oxytocic agent following the removal of CERVIDIL.

Risk Summary

CERVIDIL is indicated for the initiation and/or continuation of cervical ripening in pregnant women at or near term in whom there is a medical or obstetrical indication for the induction of labor. Fetal, neonatal, and maternal risks are discussed throughout the labeling. Limited available data with CERVIDIL use in pregnant women do not show a clear association with adverse developmental outcomes. Relevant animal reproduction data with dinoprostone is not available.

Data

Human Data

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 CERVIDIL.

Clinical Considerations

Fetal/Neonatal Adverse Reactions

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

Risk Summary

Concomitant administration of CERVIDIL is not indicated in breastfeeding women. There is no information on the effects of maternal CERVIDIL administration on the breastfed child. Insufficient information is available on the effects of maternal CERVIDIL administration on milk production.

The safety and effectiveness of CERVIDIL have not been established in pregnant girls.