PROSTIN_E2- dinoprostone_suppository
Function and Efficacy
PROSTIN E2 Vaginal Suppository administered intravaginally stimulates the myometrium of the gravid uterus to contract in a manner that is similar to the 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 with certainty at this time. Nonetheless, the myometrial contractions induced by the vaginal administration of dinoprostone are sufficient to produce evacuation of the products of conception from the uterus in the majority of cases. 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. In laboratory animals, and also in man, large doses of dinoprostone can lower blood pressure, probably as a consequence of its effect on the smooth muscle of the vascular system. With the doses of dinoprostone used for terminating pregnancy this effect has not been clinically significant. In laboratory animals, and also in man, dinoprostone can elevate body temperature. With the clinical doses of dinoprostone used for the termination of pregnancy some patients do exhibit temperature increases.
Indication
1. 2. 3.
Usage and Dosage
STORE IN A FREEZER NOT ABOVE en dash20°C (en dash4°F) BUT BRING TO ROOM TEMPERATURE JUST PRIOR TO USE. REMOVE FOIL BEFORE USE. A suppository containing 20 mg of dinoprostone should be inserted high into the vagina. The patient should remain in the supine position for ten minutes following insertion. Additional intravaginal administration of each subsequent suppository should be at 3- to 5-hour intervals until abortion occurs. Within the above recommended intervals administration time should be determined by abortifacient progress, uterine contractility response, and by patient tolerance. Continuous administration of the drug for more than 2 days is not recommended.
Label
Adverse Reactions
The most frequent adverse reactions observed with the use of dinoprostone for abortion are related to its contractile effect on smooth muscle. In the patients studied, approximately two-thirds experienced vomiting, one-half temperature elevations, two-fifths diarrhea, one-third some nausea, one-tenth headache, and one-tenth shivering and chills. In addition, approximately one-tenth of the patients studied exhibited transient diastolic blood pressure decreases of greater than 20 mmHg. Two cases of myocardial infarction following the use of dinoprostone have been reported in patients with a history of cardiovascular disease. It is not known whether these events were related to the administration of dinoprostone. Adverse effects in decreasing order of their frequency, observed with the use of dinoprostone, not all of which are clearly drug related include: Vomiting Nocturnal leg cramps Immune system disorders.
Precautions
1. WARNINGS ADVERSE REACTIONS 2. 3.
Special Population Medication
Pregnancy
Animal studies do not indicate that PROSTIN E2 is teratogenic, however, it has been shown to be embryotoxic in rats and rabbits and any dose which produces increased uterine tone could put the embryo or fetus at risk [see WARNINGS
Pediatric use
Safety and effectiveness in pediatric patients have not been established.
Drug Interactions
PROSTIN E2 may augment the activity of other oxytocic drugs. Concomitant use with other oxytocic agents is not recommended.
Other Information
WARNINGS
Dinoprostone, as with other potent oxytocic agents, should be used only with strict adherence to recommended dosages. Dinoprostone should be used by medically trained personnel in a hospital which can provide immediate intensive care and acute surgical facilities. Dinoprostone does not appear to directly affect the fetoplacental unit. Therefore, the possibility does exist that the previable fetus aborted by dinoprostone could exhibit transient life signs. Dinoprostone is not indicated if the fetus in utero has reached the stage of viability. Dinoprostone should not be considered a feticidal agent. Evidence from animal studies has suggested that certain prostaglandins may have some teratogenic potential. Therefore, any failed pregnancy termination with dinoprostone should be completed by some other means. PROSTIN E2 Vaginal Suppository should not be used for extemporaneous preparation of any other dosage form. Neither the PROSTIN E2 Vaginal Suppository, as dispensed nor any extemporaneous formulation made from the PROSTIN E2 Vaginal Suppository should be used for cervical ripening or other indication in the patient with term pregnancy. There have been post-marketing reports of serious and life-threatening hypersensitivity reactions including anaphylaxis and angioedema with PROSTIN E2 Vaginal Suppository (dinoprostone). Onset of these reported reactions occurred within minutes to hours after initiation with PROSTIN E2 Vaginal Suppository (dinoprostone). If a hypersensitivity reaction is suspected, if possible remove PROSTIN E2 Vaginal Suppository (dinoprostone), assess for other potential causes of the event, and institute symptomatic and supportive therapy, as needed.
WARNINGS
Dinoprostone, as with other potent oxytocic agents, should be used only with strict adherence to recommended dosages. Dinoprostone should be used by medically trained personnel in a hospital which can provide immediate intensive care and acute surgical facilities.
Carcinogenesis,mutagenesis, impairment of fertility
Carcinogenic bioassay studies have not been conducted in animals with PROSTIN E2 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
Immune system disorders