PREPIDIL- dinoprostone_gel

PREPIDIL Gel (dinoprostone) administered endocervically may stimulate the myometrium of the gravid uterus to contract in a manner similar to contractions seen in the term uterus during labor. Whether or not this action results from a direct effect of dinoprostone on the myometrium has not been determined. Dinoprostone is also capable of stimulating smooth muscle of the gastrointestinal tract in humans. This activity may be responsible for the vomiting and/or diarrhea that is occasionally seen when dinoprostone is used for preinduction cervical ripening. In laboratory animals, and also in humans, large doses of dinoprostone can lower blood pressure, probably as a result of its effect on smooth muscle of the vascular system. With the doses of dinoprostone used for cervical ripening this effect has not been seen. In laboratory animals, and also in humans, dinoprostone can elevate body temperature; however, with the dosing used for cervical ripening this effect has not been seen. In addition to an oxytocic effect, there is evidence suggesting that this agent has a local cervical effect in initiating softening, effacement, and dilation. These changes, referred to as cervical ripening, occur spontaneously as the normal pregnancy progresses toward term and allow evacuation of uterine contents by decreasing cervical resistance at the same time that myometrial activity increases. While not completely understood, biochemical changes within the cervix during natural cervical ripening are similar to those following PGE 2 2 2 Using an unvalidated assay, the following information was determined. When PREPIDIL Gel was administered endocervically to women undergoing preinduction ripening, results from measurement of plasma levels of the metabolite 13,14-dihydro-15-keto-PGE 2 2 2 max max max 2 PGE 2 2 2

PREPIDIL Gel is indicated for ripening an unfavorable cervix in pregnant women at or near term with a medical or obstetrical need for labor induction.

NOTE: USE CAUTION IN HANDLING THIS PRODUCT TO PREVENT CONTACT WITH SKIN. WASH HANDS THOROUGHLY WITH SOAP AND WATER AFTER ADMINISTRATION. PREPIDIL 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 15en dash30 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 6en dash12 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).

PREPIDIL Gel is generally well-tolerated. In controlled trials, in which 1731 women were entered, the following events were reported at an occurrence of >= 1%: Adverse Reaction PGE 2 (N = 884) Control placebo gel or no treatment (N = 847) Maternal N (%) N (%) Uterine contractile abnormality 58 (6. 0) Any gastrointestinal effect 50 (5. 6) Back pain 27 (3. 1) 0 (0) Warm feeling in vagina 13 (1. 5) 0 (0) Fever 12 (1. 2) Fetal Any fetal heart rate abnormality 150 (17. 5) Bradycardia 36 (4. 1) Deceleration Late 25 (2. 1) Variable 38 (4. 4) Unspecified 19 (2. 2) In addition, in other trials amnionitis and intrauterine fetal sepsis have been associated with extra-amniotic intrauterine administration of PGE 2 An increased risk of post-partum disseminated intravascular coagulation has been described in patients whose labor was induced by pharmacological means, either with dinoprostone or oxytocin (see WARNINGS Hypersensitivity reactions (e. , Anaphylactic reaction, Anaphylactic shock, Anaphylactoid reaction).

Endocervically administered PREPIDIL Gel is not recommended for the following: o o o o o o o WARNINGS Error! Hyperlink reference not valid.

Pregnancy,
Prostaglandin 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. PREPIDIL 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 Precautions
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.

PREPIDIL Gel may augment the activity of other oxytocic agents and their concomitant use is not recommended. For the sequential use of oxytocin following PREPIDIL Gel administration, a dosing interval of 6en dash12 hours is recommended.

NDC 0009-3359-01 Prepidil registered dinoprostone cervical gel For endocervical administration DOSAGE AND USE: Store in a refrigerator 2° to 8°C (36° to 46°F). Distributed by Rx only PRINCIPAL DISPLAY PANEL - 3 g Syringe Applicator Label.

WARNINGS
FOR HOSPITAL USE ONLY 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 The 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.
Carcinogenesis,Mutagenesis, Impairment of Fertility
Carcinogenic bioassay studies have not been conducted in animals with PREPIDIL Gel due to the limited indications for use and short duration of administration. No evidence of mutagenicity was observed in the Micronucleus Test or Ames Assay.
Post-marketing surveillance
An increased risk of post-partum disseminated intravascular coagulation has been described in patients whose labor was induced by pharmacological means, either with dinoprostone or oxytocin (see WARNINGS Hypersensitivity reactions (e. , Anaphylactic reaction, Anaphylactic shock, Anaphylactoid reaction).
OVERDOSAGE
Overdosage with PREPIDIL Gel may be expressed by uterine hypercontractility and uterine hypertonus. Because of the transient nature of PGE 2 2

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PREPIDIL- dinoprostone_gel Product manual source documgent