PROSTIN E2 Vaginal Suppository, an oxytocic, contains dinoprostone as the naturally occurring prostaglandin E2 (PGE2).

Its chemical name is (5Z,11α,13E,15S)-11,15-Dihydroxy-9-oxo-prosta-5,13-dien-1-oic acid and the structural formula is represented below:

The molecular formula is C₂₀H₃₂O₅. The molecular weight of dinoprostone is 352.5.

Dinoprostone occurs as a white crystalline powder. It has a melting point within the range of 64° to 71°C. Dinoprostone is soluble in ethanol and in 25% ethanol in water. It is soluble in water to the extent of 130 mg/100 mL.

Each suppository contains 20 mg of dinoprostone in a mixture of glycerides of fatty acids.

Last updated on RxList: 10/7/2008

1. PROSTIN E2 Vaginal Suppository is indicated for the termination of pregnancy from the 12th through the 20th gestational week as calculated from the first day of the last normal menstrual period.
2. PROSTIN E2 is also indicated for evacuation of the uterine contents in the management of missed abortion or intrauterine fetal death up to 28 weeks of gestational age as calculated from the first day of the last normal menstrual period.
3. PROSTIN E2 is indicated in the management of nonmetastatic gestational trophoblastic disease (benign hydatidiform mole).

STORE IN A FREEZER NOT ABOVE –20°C (–4°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.

PROSTIN E2 Vaginal Suppositories are available in foil strips of 5 individually sealed suppositories, NDC 0009-0827-03. Each suppository contains 20 mg of dinoprostone in a mixture of glycerides of fatty acids.

STORE IN A FREEZER NOT ABOVE –20°C (–4°F).

Distributed by: Pharmacia and Upjohn Company, Division of Pfizer Inc, NY, NY 10017. Revised April 2006. FDA Rev date: 11/19/1997

Last updated on RxList: 10/7/2008

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
Diarrhea	Uterine rupture
Nausea	Breast tenderness
Fever	Blurred vision
Headache	Coughing
Chills or shivering	Rash
Backache	Myalgia
Joint inflammation or	Stiff neck
pain new or	Dehydration
exacerbated	Tremor
Flushing or hot flashes	Paresthesia
Dizziness	Hearing impairment
Arthralgia	Urine retention
Vaginal pain	Pharyngitis
Chest pain	Laryngitis
Dyspnea	Diaphoresis
Endometritis	Eye pain
Syncope or fainting	Wheezing
sensation	Cardiac arrhythmia
Vaginitis or vulvitis	Skin discoloration
Weakness	Vaginismus
Muscular cramp or pain	Tension
Tightness in chest

PROSTIN E2 may augment the activity of other oxytocic drugs. Concomitant use with other oxytocic agents is not recommended.

Last updated on RxList: 10/7/2008

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.

General precautions

Animal studies lasting several weeks at high doses have shown that prostaglandins of the E and F series can induce proliferation of bone. Such effects have also been noted in newborn infants who have received prostaglandin E1 during prolonged treatment.

There is no evidence that short term administration of PROSTIN E2 Vaginal Suppository can cause similar bone effects.

As in spontaneous abortion, where the process is sometimes incomplete, abortion induced by PROSTIN E2 may sometimes be incomplete. In such cases, other measures should be taken to assure complete abortion.

In patients with a history of asthma, hypo-or hypertension, cardiovascular disease, renal disease, hepatic disease, anemia, jaundice, diabetes or history of epilepsy, dinoprostone should be used with caution.

Dinoprostone administered by the vaginal route should be used with caution in the presence of cervicitis, infected endocervical lesions, or acute vaginitis.

As with any oxytocic agent, dinoprostone should be used with caution in patients with compromised (scarred) uteri.

Dinoprostone vaginal therapy is associated with transient pyrexia that may be due to its effect on hypothalamic thermoregulation. In the patients studied, temperature elevations in excess of 2°F (1.1°C) were observed in approximately one-half of the patients on the recommended dosage regimen. In all cases, temperature returned to normal on discontinuation of therapy. Differentiation of post-abortion endometritis from drug-induced temperature elevations is difficult, but with increasing clinical exposure and experience with PGE2 vaginal therapy the distinctions become more obviously apparent and are summarized below:

Endometritis pyrexia	PGE2 induced pyrexia
a. Time of onset: Typically, on third post- abortional day (38°C or higher).	Within 15–45 minutes of suppository administration.
b.Duration: Untreated pyrexia and infection continue and may give rise to other infective pelvic pathology.	Elevations revert to pretreatment levels within 2– 6 hours after discontinuation of therapy or removal of suppository from vagina without any other treatment.
c. Retention: Products of conception are often retained in the cervical os or uterine cavity.	Elevation occurs irrespective of any retained tissue.
d.Histology:Endometrium shows evidence of inflammatory lymphocytic infiltration with areas of necrotic hemorrhagic tissue.	Although the endometrial stroma may be edematous and vascular, there is relative absence of inflammatory reaction.
e. The uterus: Often remains boggy and soft with tenderness over the fundus, and pain on moving the cervix, on bimanual examination.	Normal uterine involution not tender.
f.Discharge: Often associated foul-smelling lochia and leukorrhea. lochia and leukorrhea Cervical culture.	Lochia normal.
g. Cervical culture The culture of pathological organisms from the cervix or uterine cavity after abortion does not, of itself, warrant the diagnosis of septic abortion in the absence of clinical evidence of sepsis. It is not uncommon to culture pathogens from cases of recent abortion not clinically infected. Persistent positive culture with clear clinical signs of infection are significant in the differential diagnosis.
h.Blood count Leukocytosis and differential white cell counts are not of major clinical importance in distinguishing between the two conditions, since total WBC's may be increased as a result of infection and transient leukocytosis may also be drug induced.

In the absence of clinical or bacteriological evidence of intrauterine infection, supportive therapy for drug induced fevers includes the forcing of fluids. As all PGE2-induced fevers have been found to be transient or self-limiting, it is doubtful if any simple empirical measures for temperature reduction are indicated.

Laboratory tests

When a pregnancy diagnosed as missed abortion is electively interrupted with intravaginal administration of dinoprostone, confirmation of intrauterine fetal death should be obtained in respect to a negative pregnancy test for chorionic gonadotropic activity (U.C.G. test or equivalent). When a pregnancy with late fetal intrauterine death is interrupted with intravaginal administration of dinoprostone, confirmation of intrauterine fetal death should be obtained prior to treatment.

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.

Pregnancy: Teratogenic Effects: Pregnancy Category C

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 section.

Pediatric use

Safety and effectiveness in pediatric patients have not been established.

Last updated on RxList: 10/7/2008

No information provided.

1. Hypersensitivity to dinoprostone
2. Acute pelvic inflammatory disease
3. Patients with active cardiac, pulmonary, renal, or hepatic disease

Last updated on RxList: 10/7/2008

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.

Last updated on RxList: 10/7/2008

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Last updated on RxList: 10/7/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

DINOPROSTONE SUPPOSITORY - VAGINAL

(dye-no-PROST-own)

COMMON BRAND NAME(S): Prostin E2

USES: This medication is used to cause an abortion during weeks 12-20 of pregnancy. It is also used up to week 28 of pregnancy to help vaginally remove any remaining material in the womb from a miscarriage/missed abortion. This medication causes the womb to contract and push out its contents, including the placenta and the fetus/unborn baby, whether living or not. Dinoprostone is a natural substance (prostaglandin) that your body makes in preparation for labor. It softens and widens the opening of the womb and increases contractions.

It is also used to treat a certain type of womb problem (benign hydatiform mole). This medication should not be used for cervical ripening or any other use in a pregnancy that is near the time of delivery.

HOW TO USE: This drug is used vaginally. Allow the suppository to warm to room temperature and remove the foil before use. The suppository is inserted high in the vagina by a health care professional, and you must remain in a reclined or lying-down position for at least 10 minutes after insertion. More doses may be used every 3-5 hours until the desired effect occurs. Do not use for more than 48 hours.

This medication should only be used in a hospital setting with trained medical care available. You will be monitored for changes in your womb (e.g., water breaking, strong/long-lasting contractions). If the desired result has not occurred in 48 hours, or if the abortion is not complete, other treatment (e.g., surgical removal) may be needed. This medication may be used with a medication given by vein (oxytocin) to help strengthen the contractions. It is very important that all of the products of pregnancy are removed (e.g., fetal/unborn baby tissue, placenta) to prevent serious, rarely fatal problems such as severe infection and bleeding.

SIDE EFFECTS: Nausea, vomiting, diarrhea, fever, chills, abdominal pain, flushing, and dizziness may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Most women will experience a fever 15-45 minutes after the suppository is inserted. Sponge baths and drinking lots of fluids may help lower the fever. Aspirin will not usually lower the fever. The fever usually goes away within 6 hours after the last dose. Seek immediate medical attention if you have a high fever (e.g., higher than 101 degrees F or 38 degrees C) after the abortion. Fever may be a sign of a serious infection.

Tell your doctor immediately if any of these rare but very serious side effects occur: fainting, strong contractions that are very close together (uterine overstimulation), severe abdominal pain.

Seek immediate medical attention if this rare but very serious side effect occurs: chest pain.

This drug has rarely caused injury to the womb (uterine rupture), which may require emergency surgery. Your doctor will be monitoring you for signs of uterine overstimulation.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using this medication, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: severe breathing problem (e.g., uncontrolled asthma), current pelvic problem (active pelvic inflammatory disease), current heart disease (e.g., uncontrolled angina, recent heart attack), liver disease, kidney disease.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: anemia, asthma, high or low blood pressure, diabetes, glaucoma, heart disease (e.g., angina, heart attack), infections in the vaginal/pelvic area (e.g., cervicitis, vaginal infection, genital herpes, pelvic inflammatory disease), seizure disorder, uterine surgery including previous cesarean section (c-section) birth, pelvic problems (e.g., womb scarring, fibroids, cervical stenosis).

This medication should not be used if the unborn baby is mature enough to survive outside the womb. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: other prostaglandins (e.g., misoprostol).

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: Not applicable.

NOTES: Use under direct medical supervision.

MISSED DOSE: Not applicable.

STORAGE: Store in a freezer at or below -4 degrees F (-20 degrees C) away from light and moisture. Bring to room temperature just before use. Keep wrapped in foil until just before use.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.