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.

reful 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. placement of prepidil gel into the extra-amniotic space has been associated with uterine hyperstimulation. as prepidil gel is extensively metabolized in the lung, liver, and kidney, and the major route of elimination is the kidney, prepidil gel should be used with caution in patients with renal and hepatic dysfunction.

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

uded 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).

t 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 -induced ripening. further, it has been shown that these changes can take place independent of myometrial activity; however, it is quite likely that pge 2 administered endocervically produces effacement and softening by combined contraction-inducing and cervical-ripening properties. there is evidence to suggest that the changes that take place within the cervix are due to collagen degradation resulting from collagenase secretion as a response, at least in part, to pge 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 (dhk-pge 2 ) showed that pge 2 was relatively rapidly absorbed and the t max was 0.5 to 0.75 hours. plasma mean c max for gel-treated subjects was 433 ± 51 pg/ml versus 137 ± 24 pg/ml for untreated controls. in those subjects in which a clinical response was observed, mean c max was 484 ± 57 pg/ml versus 213 ± 69 pg/ml in nonresponders and 219 ± 92 pg/ml in control subjects who had positive clinical progression toward normal labor. these elevated levels in gel-treated subjects appear to be largely a result of absorption of pge 2 from the gel rather than from endogenous sources. pge 2 is completely metabolized in humans. pge 2 is extensively metabolized in the lungs, and the resulting metabolites are further metabolized in the liver and kidney. the major route of elimination of the products of pge 2 metabolism is the kidneys.