dinoprostone (prostaglandin E₂, PGE₂)
Cervidil, Prepidil, Prostin E₂

Available forms
Available by prescription only
Vaginal gel: 0.5 mg
Vaginal insert: 10 mg
Vaginal suppositories: 20 mg

Indications and dosages
 Abort second-trimester pregnancy, evacuate uterus in cases of missed abortion, intrauterine fetal deaths up to 28 weeks of gestation, benign hydatidiform mole. Adults: Insert 20-mg suppository high into posterior vaginal fornix. Repeat q 3 to 5 hours until abortion is complete. Don’t exceed 240 mg.
 Ripening of an unfavorable cervix in pregnant patients at or near term (gel or insert). Adults: Insert one applicator (0.5 mg) of gel into vagina. May repeat dose in 6 hours if no response. Maximum recommended dose in 24 hours is 1.5 mg. Or, one 10-mg insert into posterior vaginal fornix. Have patient remain supine for 2 hours. Remove insert upon onset of active labor or 12 hours after insertion.

Pharmacodynamics
Oxytocic action: Exact mechanism unknown. Stimulates myometrial contractions in the gravid uterus similar to the contractions of term labor. Its action may result from one or more of the following: direct stimulation, regulation of cellular calcium transport, or regulation of intracellular levels of cyclic 3,5-adenosine monophosphate. Reductions in plasma estrogen and progesterone levels play a role in drug’s uterine action, but this effect doesn’t occur consistently. Drug facilitates cervical dilations by directly softening the cervix.

Pharmacokinetics
Absorption: Following vaginal insertion, drug diffuses slowly into maternal blood. Some local absorption into uterus through cervix or local vascular and lymphatic channels, but accounts for only small portion of dose. Contractions appear within 10 minutes of dosing, with peak effect in 17 hours. No correlation of activity with plasma levels.
Distribution: Distributed widely in mother.
Metabolism: Metabolized in lungs, liver, kidneys, spleen, and other maternal tissues. At least nine inactive metabolites.
Excretion: Drug and metabolites excreted primarily in urine, with small amounts in feces.

Contraindications and precautions
Gel form is contraindicated when prolonged contractions of the uterus are considered inappropriate and in patients hypersensitive to prostaglandins or constituents of the gel. Also contraindicated in patients with placenta previa or unexplained vaginal bleeding during pregnancy and in whom vaginal delivery isn’t indicated (because of vasa previa or active herpes genitalia).
  Suppository form is contraindicated in patients hypersensitive to drug and in those with acute pelvic inflammatory disease or active cardiac, pulmonary, renal, or hepatic disease.
 Vaginal insert is contraindicated in patients hypersensitive to prostaglandins or when there’s suspicion or definite evidence of marked cephalopelvic disproportion or fetal distress where delivery isn’t imminent. The insert is also contraindicated in patients with unexplained vaginal bleeding during pregnancy, multiparity with six or more previous term pregnancies, and when oxytocics are contraindicated or the patient is already receiving I.V. oxytocic drugs.
 Use suppository form cautiously in patients with asthma, seizure disorders, anemia, diabetes, hypertension or hypotension, jaundice, scarred uterus, cervicitis, acute vaginitis, and CV, renal, or hepatic disease. Use gel form cautiously in patients with asthma or history of asthma, glaucoma or raised intraocular pressure, or renal or hepatic dysfunction and in those with ruptured membranes. Insert should be used cautiously in patients with nonvertex presentation and in those with ruptured membranes or history of previous uterine hypertonia, glaucoma, or childhood asthma.

Interactions
Drug-drug. Oxytocics (oxytocin): Enhances effects of these drugs. When using gel for cervical ripening, concomitant use isn’t recommended because cervical laceration and trauma may occur. Allow dosing interval of 6 to 12 hours after the gel or 30 minutes after removing the insert before starting oxytocin treatment.
Drug-lifestyle. Alcohol use: Inhibits effectiveness of drug with high doses. Discourage alcohol use.

Adverse reactions
Maternal
CNS: headache, dizziness, anxiety, hot flashes, paresthesia, weakness, syncope, fever.
CV: chest pain, arrhythmias.
EENT: blurred vision, eye pain.
GI: nausea, vomiting, diarrhea.
GU: vaginal pain, vaginitis, endometritis.
Musculoskeletal: nocturnal leg cramps, backache, muscle cramps.
Respiratory: cough, dyspnea.
Skin: diaphoresis, rash.
Other: shivering, chills, breast tenderness.
Fetal
CNS: fetal depression, hyperstimulation with or without fetal distress.
CV: bradycardia.
Metabolic: fetal acidosis.
Other: amnionitis, intrauterine fetal sepsis.

Effects on lab test results
None reported.

Overdose and treatment
Overdose causes extensions of adverse reactions.
 Because drug is rapidly metabolized, treatment involves discontinuing drug and providing supportive treatment. Beta adrenergics may be used to treat hyperstimulation caused by drug.

Special considerations
• Store suppositories in freezer at -4° F (-20°C); warm to room temperature (in foil) just before use.
• To prevent absorption through skin, use gloves and keep drug handling to a minimum.
• Premedicate patient with an antiemetic and antidiarrheal to minimize GI effects.
• Abortion should be complete within 30 hours.
• Drug-induced fever is self-limiting and transient. Sponge baths or increased fluid intake usually corrects problem.
• Fetal death must be confirmed before administration when used for missed abortion or intrauterine fetal death.

Patient education
• Advise patient of expected adverse reactions, especially fever, nausea, vomiting (occurs in two-thirds of patients), and diarrhea (occurs in about half of patients), all of which are self-limiting.
• Instruct patient to remain in prone position for 10 minutes after insertion of drug.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use