Pharmacia & Upjohn
Action And Clinical Pharmacology: Dinoprostone gel, which contains a prostaglandin E2 analogue as the active ingredient, causes cervical ripening preparatory to the onset of labor when it is administered endocervically. Although the local effects of prostaglandin E2 on cervical maturation is not specifically known, experimental data indicates the drug enhances cervical hemodynamics which in turn promotes ripening of the cervix.
Indications And Clinical Uses: Administered to the cervical canal, for inducing cervical softening and dilatation of the cervix in pregnant women at or near term, where cervical features are not conducive to induction.
The use of the gel in this manner, in patients with unfavorable induction features prior to labor induction by conventional methods, has been shown to improve the overall outcome of labor induction attempt.
Contra-Indications: Endocervically administered dinoprostone gel is not recommended for use in the following: patients in whom oxytocic drugs are generally contraindicated or where prolonged contractions of the uterus are considered inappropriate. These include the following situations: patients with a history of cesarean section or major uterine surgery; patients with a major degree of cephalopelvic disproportion; patients with a history of difficult labor and/or traumatic delivery; grand multiparae with 6 or more previous term pregnancies; patients with suspected or clinically evident pre-existing fetal distress; patients with overdistention of the uterus (multiple pregnancy, polyhydramnios). Patients with ruptured membranes. Patients with known hypersensitivity to the prostaglandins. Patients with unexplained vaginal bleeding during this pregnancy. Patients with fetal malpresentation. Patients with gynecological, obstetrical or medical conditions that preclude vaginal delivery.
Dinoprostone gel should not be used simultaneously with other oxytocics (see Warnings).
Dinoprostone gel should not be used in patients with a history of epilepsy.
Manufacturers’ Warnings In Clinical States: Dinoprostone, like other effective oxytocic agents, should be used with strict adherence to recommended dosages, by medically trained personnel in hospital surroundings with appropriate obstetrical care facilities.
The use of oxytocin following pre-induction cervical ripening with dinoprostone gel has been studied. Prostaglandins may potentiate the effect of oxytocin on the uterus. Therefore, to preclude inappropriate augmentation of one oxytocic agent with another, it is recommended that induction with an oxytocic agent not be implemented until 6 to 12 hours after application of the gel for cervical ripening. Patients requiring oxytocin induction after administration should be carefully monitored.
Precautions: Prior to and during the use of dinoprostone uterine activity, fetal status and the character of the cervix (dilatation and effacement) should be carefully monitored to detect possible evidence of undesired responses. These include hypertonus, sustained uterine contractility or fetal distress. In cases where there is a known history of hypertonic uterine contractility or tetanic uterine contractions, it is recommended that uterine activity and the state of the fetus should be continuously monitored. The possibility of uterine rupture and/or cervical laceration should be born in mind where high-tone myometrial contractions are sustained.
Cephalopelvic relationships should be carefully evaluated before the use of dinoprostone.
Caution should be exercised in the administration of the gel in patients with the following medical conditions: asthma or a history of asthma; glaucoma or raised intraocular pressure.
Prolonged treatment of newborn infants with prostaglandin E1 can induce proliferation of bone. There is no evidence that short-term administration of prostaglandin E2 can cause similar bone effects.
Caution should be taken not to administer dinoprostone gel above the level of the internal os. Placement of the gel into the extra-amniotic space has been associated with uterine hyperstimulation.
Patients with severe renal disease and/or severe hepatic disease accompanied by metabolic aberrations should be dosed with caution.
Drug Interactions: Dinoprostone, like all prostaglandins, may potentiate the uterine response to oxytocin. Patients requiring oxytocin induction, after pre-induction cervical ripening with dinoprostone, should be carefully monitored (see Warnings).
Adverse Reactions: In clinical trials of dinoprostone gel the most commonly seen reactions were intrapartum fetal heart rate changes and unclassified fetal distress during or subsequent to gel administration. The adverse reaction incidences reported below are from the clinical trials (0.5 mg administered endocervically) in which oxytocin was used as the control. The control group had comparable incidences of adverse events.
Fetal Effects (16%): intrapartum fetal heart rate changes and unclassified fetal distress during or subsequent to dinoprostone treatment (13%); uterine contractile abnormalities with fetal heart rate changes (3%); depressed neonates at birth (Apgar Scores below 7): 1 minute (13%) and 5 minutes (1%).
Maternal Effects (10%): uterine contractile abnormalities without fetal heart rate changes (5%); vomiting and/or diarrhea (5%).
Symptoms And Treatment Of Overdose: Symptoms and Treatment: No cases of overdose have been reported. Should an overdose occur, any of the listed adverse reactions would be anticipated. Treatment of overdosage must be symptomatic at this time, since clinical studies with prostaglandin antagonists have not progressed to the point where recommendations may be made.
Dosage And Administration: The recommended dose is 0.5 mg. Each prefilled syringe contains 3 g (2.5 mL) of gel which, in turn contains 0.5 mg dinoprostone.
This product is intended for single dose administration.
Utilizing the catheter provided, administer the entire contents of the syringe by gentle expulsion into the cervical canal-just below the level of the internal cervical os. Care should be taken not to administer the gel above the level of the internal os. Placement of the gel into the amniotic space has been associated with uterine hyperstimulation (see Precautions).
After placement of the gel, the patient should be instructed to remain in the dorsal position for 10 to 15 minutes to minimize gel leakage.
Availability And Storage: Each prefilled syringe of translucent sterile gel with an accompanying catheter contains: dinoprostone 0.5 mg. Syringes of 3 g (2.5 mL). Nonmedicinal ingredients: colloidal silicon dioxide and triacetin. Available to hospitals only. This product has a shelf life of 24 months when stored at 4°C, under continuous refrigeration. (Shown in Product Recognition Section)
PREPIDIL® GEL Pharmacia & Upjohn Dinoprostone Prostaglandin