PROPESS

Dinoprostone is a naturally occurring prostaglandin

E2 (PGE2).

It has important effects in labour.

It also stimulates osteoblasts to release factors which stimualtes bone resorption by osteoclasts.

As a prescription drug it is used as a vaginal suppository, to prepare the cervix for labour and to induce labour.

For the termination of pregnancy during the second trimester (from the 12th through the 20th gestational week as calculated from the first day of the last normal menstrual period), as well as for evacuation of the uterine contents in the management of missed abortion or intrauterine fetal death up to 28 weeks of gestational age as calculated from the first day of the last normal menstrual period.

Also used in the management of nonmetastatic gestational trophoblastic disease (benign hydatidiform mole).

Other indications include improving the cervical inducibility (cervical "ripening") in pregnant women at or near term with a medical or obstetrical need for labor induction, and the management of postpartum hemorrhage.

Dinoprostone is equivalent to prostaglandin

E2 (PGE2).

It stimulates labor and delivery by stimulating the uterine, and thus terminates pregnancy.

Dinoprostone is also capable of stimulating the smooth muscle of the gastrointestinal tract of man.

This activity may be responsible for the vomiting and/or diarrhea that is not uncommon when dinoprostone is used to terminate pregnancy.

E2 receptor EP2 subtype Agonist Prostaglandin E2 receptor EP1 subtype Agonist Prostaglandin E2 receptor EP3 subtype Agonist + 1 more target.

Absorbed at a rate of 0.3 mg per hour over 12 hours while the vaginal system is in place.

Rapid metabolism of dinoprostone occurs primarily in the local tissues; any systemic absorption of the medication is cleared mainly in the maternal lungs and, secondarily, at sites such as the liver and kidneys.

The major route of elimination of the products of PGE2 metabolism is the kidneys.

Less than 5 minutes.

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Oral, mouse: LD 50 = 750 mg/kg; Oral, rat: LD 50 = 500 mg/kg.

Dinoprostone, as with other potent oxytocic agents, should be used only with strict adherence to recommended dosages.

Dinoprostone should be administered by physicians in a hospital that can provide immediate intensive care and acute surgical facilities.

Women aged 30 years or older, those with complications during pregnancy and those with a gestational age over 40 weeks have been shown to have an increased risk of post-partum disseminated intravascular coagulation.

In addition, these factors may further increase the risk associated with labor induction See ADVERSE REACTIONS.

Therefore, in these women, use of dinoprostone should be undertaken with caution.

Measures should be applied to detect as soon as possible an evolving fibrinolysis in the immediate post-partum phase.

Clinician should be alert that the intracervical placement of dinoprostone gel 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).

There have been post-marketing reports of serious and life-threatening hypersensitivity reactions including anaphylaxis and angioedema with PREPIDIL Gel (dinoprostone).

Onset of these reported reactions occurred within minutes to hours after initiation with PREPIDIL Gel (dinoprostone).

If a hypersensitivity reaction is suspected, if possible remove PREPIDIL Gel (dinoprostone).

Assess for other potential causes of the event, and institute symptomatic and supportive therapy, as needed.

Endocervically administered PREPIDIL

Gel is not recommended for the following: a.

• cases with a history of cesarean section or major uterine surgery.

• cases in which cephalopelvic disproportion is present.

• cases in which there is a history of difficult labor and/or traumatic delivery.

• grand multiparae with six or more previous term pregnancies cases with non-vertex presentation.

• cases with hyperactive or hypertonic uterine patterns.

• cases of fetal distress where delivery is not imminent.

• in obstetric emergencies where the benefit-to-risk ratio for either the fetus or the mother favors surgical intervention b.

Patients with hypersensitivity to prostaglandins or constituents of the gel See WARNINGS and ADVERSE REACTIONS. c.

Patients with placenta previa or unexplained vaginal bleeding during this pregnancy. d.

Patients for whom vaginal delivery is not indicated, such as vasa previa or active herpes genitalia.

Gel should be brought to room temperature (59° to 86°F; 15° to 30°C) just prior to administration.

Do not force the warming process by using a water bath or other source of external heat (eg, microwave oven).

To prepare the product for use remove the protective end cap (to serve as plunger extension) and insert the protective end cap into the plunger stopper assembly in the barrel of syringe.

Choose the appropriate length shielded catheter (10 mm or 20 mm) and aseptically remove the sterile shielded catheter from the package.

Careful vaginal examination will reveal the degree of effacement which will regulate the size of the shielded endocervical catheter to be used.

That is, the 20 mm endocervical catheter should be used if no effacement is present, and the 10 mm catheter should be used if the cervix is 50% effaced.

Firmly attach the catheter hub to the syringe tip as evidenced by a distinct click.

Fill the catheter with sterile gel by pushing the plunger assembly to expel air from the catheter prior to administration to the patient.

Proper assembly of the dosing apparatus is shown below.

To properly administer the product, the patient should be in a dorsal position with the cervix visualized using a speculum.

Using sterile technique, introduce the gel with the catheter provided into the cervical canal just below the level of the internal os.

Administer the contents of the syringe by gentle expulsion and then remove the catheter.

The gel is easily extrudable from the syringe.

Use the contents of one syringe for one patient only.

No attempt should be made to administer the small amount of gel remaining in the catheter.

The syringe, catheter, and any unused package contents should be discarded after use.

Following administration of PREPIDIL

Gel, the patient should remain in the supine position for at least 15–30 minutes to minimize leakage from the cervical canal.

If the desired response is obtained from PREPIDIL Gel, the recommended interval before giving intravenous oxytocin is 6–12 hours.

If there is no cervical/uterine response to the initial dose of PREPIDIL Gel, repeat dosing may be given.

The recommended repeat dose is 0.5 mg dinoprostone with a dosing interval of 6 hours.

The need for additional dosing and the interval must be determined by the attending physician based on the course of clinical events.

The maximum recommended cumulative dose for a 24-hour period is 1.5 mg of dinoprostone (7.5 mL PREPIDIL Gel).

Gel is available as a sterile semitranslucent viscous preparation for endocervical application: 0.5 mg PGE 2 per 3.0 g (2.5 mL) in syringe.

In addition, each package contains two shielded catheters (10 mm and 20 mm tip) enclosed in sterile envelopes.

The contents are not guaranteed sterile if envelopes are not intact.

Each 3 gram syringe applicator contains: dinoprostone, 0.5 mg; colloidal silicon dioxide, 240 mg; triacetin, 2760 mg. 1 × 3 gram syringe NDC 0009-3359-01 5 × 3 gram syringes NDC 0009-3359-02 PREPIDIL Gel needs to be stored under continuous refrigeration (36° to 46°F; 2° to 8°C).

Gel needs to be stored under continuous refrigeration (36° to 46°F; 2° to 8°C).

E2 produced an increase in skeletal anomalies in rats and rabbits.

No effect would be expected clinically, when used as indicated, since PREPIDIL Gel is administered after the period of organogenesis.

Gel 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.

See statements under General

Safety and effectiveness in pediatric patients have not been established.