Dinoprostone
FDA Drug Information • Also known as: Cervidil, Prepidil
- Brand Names
- Cervidil, Prepidil
- Dosage Form
- POWDER
- Product Type
- BULK INGREDIENT
Description
DESCRIPTION PREPIDIL Gel contains dinoprostone as the naturally occurring form of prostaglandin E 2 (PGE 2 ) and is designated chemically as (5Z, 11a, 13E, 15S)-11,15-Dihydroxy-9-oxo-prosta-5,13-dien-1-oic acid. The molecular formula is C 20 H 32 O 5 and the molecular weight is 352.5. Dinoprostone occurs as a white to off-white crystalline powder with a melting point within the range of 65° to 69°C. It is soluble in ethanol, in 25% ethanol in water, and in water to the extent of 130 mg/100 mL. The active constituent of PREPIDIL Gel is dinoprostone 0.5 mg/3 g (2.5 mL gel); other constituents are colloidal silicon dioxide NF (240 mg/3 g) and triacetin USP (2760 mg/3 g). The structural formula is represented below: Chemical Structure
What Is Dinoprostone Used For?
INDICATIONS AND USAGE 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.
Dosage and Administration
DOSAGE AND ADMINISTRATION 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 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). Figure
Side Effects (Adverse Reactions)
ADVERSE REACTIONS 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 (6.6) 34 (4.0) Any gastrointestinal effect 50 (5.7) 22 (2.6) Back pain 27 (3.1) 0 (0) Warm feeling in vagina 13 (1.5) 0 (0) Fever 12 (1.4) 10 (1.2) Fetal Any fetal heart rate abnormality 150 (17.0) 123 (14.5) Bradycardia 36 (4.1) 26 (3.1) Deceleration Late 25 (2.8) 18 (2.1) Variable 38 (4.3) 29 (3.4) Unspecified 19 (2.1) 19 (2.2) In addition, in other trials amnionitis and intrauterine fetal sepsis have been associated with extra-amniotic intrauterine administration of PGE 2 . Uterine rupture has been reported in association with the use of PREPIDIL Gel intracervically. Additional events reported in the literature, associated by the authors with the use of PREPIDIL Gel, included premature rupture of membranes, fetal depression (1 min Apgar < 7), and fetal acidosis (umbilical artery pH < 7.15). Post-marketing surveillance Blood and lymphatic system disorders 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 ) . The frequency of this adverse event, however, appears to be rare (<1 per 1,000 labors). Immune system disorders Hypersensitivity reactions (e.g., Anaphylactic reaction, Anaphylactic shock, Anaphylactoid reaction).
Warnings and Precautions
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 ). 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. 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.
Drug Interactions
3. Drug Interactions 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 6–12 hours is recommended.
Contraindications
CONTRAINDICATIONS Endocervically administered PREPIDIL Gel is not recommended for the following: a. Patients in whom oxytocic drugs are generally contraindicated or where prolonged contractions of the uterus are considered inappropriate, such as:
Pregnancy and Breastfeeding
5. Pregnancy Teratogenic Effects 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 .
Overdosage
OVERDOSAGE Overdosage with PREPIDIL Gel may be expressed by uterine hypercontractility and uterine hypertonus. Because of the transient nature of PGE 2 -induced myometrial hyperstimulation, nonspecific, conservative management was found to be effective in the vast majority of the cases; i.e., maternal position change and administration of oxygen to the mother. β-adrenergic drugs may be used as a treatment of hyperstimulation following the administration of PGE 2 for cervical ripening.
How Supplied
HOW SUPPLIED PREPIDIL 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).
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.