INDICATIONS AND USAGE Carboprost tromethamine injection USP is indicated for aborting pregnancy between the 13th and 20th weeks of gestation as calculated from the first day of the last normal menstrual period and in the following conditions related to second trimester abortion: 1.

Failure of expulsion of the fetus during the course of treatment by another method; 2.

Premature rupture of membranes in intrauterine methods with loss of drug and insufficient or absent uterine activity; 3.

Requirement of a repeat intrauterine instillation of drug for expulsion of the fetus; 4.

Inadvertent or spontaneous rupture of membranes in the presence of a previable fetus and absence of adequate activity for expulsion.

Carboprost tromethamine injection USP is indicated for the treatment of postpartum hemorrhage due to uterine atony which has not responded to conventional methods of management.

Prior treatment should include the use of intravenously administered oxytocin, manipulative techniques such as uterine massage and, unless contraindicated, intramuscular ergot preparations.

Studies have shown that in such cases, the use of carboprost tromethamine injection USP has resulted in satisfactory control of hemorrhage, although it is unclear whether or not ongoing or delayed effects of previously administered ecbolic agents have contributed to the outcome.

In a high proportion of cases, carboprost tromethamine injection USP used in this manner has resulted in the cessation of life threatening bleeding and the avoidance of emergency surgical intervention.

WARNINGS Carboprost tromethamine injection sterile solution (carboprost tromethamine), like other potent oxytocic agents, should be used only with strict adherence to recommended dosages.

Carboprost tromethamine injection should be used by medically trained personnel in a hospital which can provide immediate intensive care and acute surgical facilities.

Carboprost tromethamine injection does not appear to directly affect the fetoplacental unit.

Therefore, the possibility does exist that the previable fetus aborted by carboprost tromethamine injection could exhibit transient life signs.

Carboprost tromethamine injection is not indicated if the fetus in utero has reached the stage of viability.

Carboprost tromethamine injection should not be considered a feticidal agent.

Evidence from animal studies has suggested that certain other prostaglandins have some teratogenic potential.

Although these studies do not indicate that carboprost tromethamine injection is teratogenic, any pregnancy termination with carboprost tromethamine injection that fails should be completed by some other means.

This product contains benzyl alcohol.

Benzyl alcohol has been reported to be associated with a fatal "Gasping Syndrome" in premature infants.

ADVERSE REACTIONS The adverse effects of carboprost tromethamine injection sterile solution are generally transient and reversible when therapy ends.

The most frequent adverse reactions observed are related to its contractile effect on smooth muscle.

In patients studied, approximately two-thirds experienced vomiting and diarrhea, approximately one-third had nausea, one-eighth had a temperature increase greater than 2° F, and one-fourteenth experienced flushing.

The pretreatment or concurrent administration of antiemetic and antidiarrheal drugs decreases considerably the very high incidence of gastrointestinal effects common with all prostaglandins used for abortion.

Their use should be considered an integral part of the management of patients undergoing abortion with carboprost tromethamine injection.

Of those patients experiencing a temperature elevation, approximately one-sixteenth had a clinical diagnosis of endometritis.

The remaining temperature elevations returned to normal within several hours after the last injection.

Adverse effects observed during the use of carboprost tromethamine injection for abortion and for hemorrhage, not all of which are clearly drug related, in decreasing order of frequency include: Vomiting Diarrhea Nausea Flushing or hot flashes Chills or shivering Coughing Headaches Endometritis Hiccough Dysmenorrhea-like pain Paresthesia Backache Muscular pain Breast tenderness Eye pain Drowsiness Dystonia Asthma Injection site pain Tinnitus Vertigo Vaso-vagal syndrome Dryness of mouth Hyperventilation Respiratory distress Hematemesis Taste alterations Urinary tract infection Septic shock Torticollis Lethargy Hypertension Tachycardia Pulmonary edema Endometritis from IUCD Nervousness Nosebleed Sleep disorders Dyspnea Tightness in chest Wheezing Posterior cervical perforation Weakness Diaphoresis Dizziness Blurred vision Epigastric pain Excessive thirst Twitching eyelids Gagging, retching Dry throat Sensation of choking Thyroid storm Syncope Palpitations Rash Upper respiratory infection Leg cramps Perforated uterus Anxiety Chest pain Retained placental fragment Shortness of breath Fullness of throat Uterine sacculation Faintness, light- headedness Uterine rupture The most common complications when carboprost tromethamine injection was utilized for abortion requiring additional treatment after discharge from the hospital were endometritis, retained placental fragments, and excessive uterine bleeding, occurring in about one in every 50 patients.

Post-marketing experience: Hypersensitivity reactions (e.g.

Anaphylactic reaction, Anaphylactic shock, Anaphylactoid reaction, Angioedema).

To report SUSPECTED ADVERSE REACTIONS, contact ANI Pharmaceuticals, Inc.

at 1-800-308-6755 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.