Endometrin Drug Information

® (progesterone) is indicated to support embryo implantation and early pregnancy by supplementation of corpus luteal function as part of an Assisted Reproductive Technology (ART) treatment program for infertile women. ENDOMETRIN ® is a progesterone indicated to support embryo implantation and early pregnancy by supplementation of corpus luteal function as part of an Assisted Reproductive Technology (ART) treatment program for infertile women.

General Dosing Information

The dose of ENDOMETRIN is 100 mg administered vaginally two or three times daily starting the day after oocyte retrieval and continuing for up to 10 weeks total duration. Efficacy in women 35 years of age and older has not been clearly established. The appropriate dose of ENDOMETRIN in this age group has not been determined.

Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data reflect exposure to ENDOMETRIN in 808 infertile women (74.9% White, 10.3% Hispanic, 5.4% Black, 5% Asian, and 4.6% Other) in a single Assisted Reproductive Technology 10 week clinical study conducted in the U.S. ENDOMETRIN was studied at doses of 100 mg twice daily and 100 mg three times daily. The adverse reactions that occurred at a rate greater than or equal to 2% in either ENDOMETRIN group are summarized in Table 1. Table 1: Number and Frequency of Reported Adverse Reactions in Women Treated with ENDOMETRIN in an Assisted Reproductive Technology Study Body System ENDOMETRIN 100 mg twice daily (N=404) ENDOMETRIN 100 mg three times daily (N=404) Preferred Term Gastrointestinal Disorders Abdominal pain 50 (12%) 50 (12%) Nausea 32 (8%) 29 (7%) Abdominal distension 18 (4%) 17 (4%) Constipation 9 (2%) 14 (3%) Vomiting 13 (3%) 9 (2%) General Disorders and Administration Site Conditions Fatigue 7 (2%) 12 (3%) Infections and Infestations Urinary tract infection 9 (2%) 4 (1%) Injury, Poisoning and Procedural Complications Post-oocyte retrieval pain 115 (28%) 102 (25%) Nervous System Disorders Headache 15 (4%) 13 (3%) Reproductive System and Breast Disorders Ovarian hyperstimulation syndrome 30 (7%) 27 (7%) Uterine spasm 15 (4%) 11 (3%) Vaginal bleeding 13 (3%) 14 (3%) Other less common reported adverse reactions included vaginal irritation, itching, burning, discomfort, urticaria, and peripheral edema.

Expected Adverse Reaction Profile Seen with Progesterone

ENDOMETRIN is also expected to have adverse reactions similar to other drugs containing progesterone that may include breast tenderness, bloating, mood swings, irritability, and drowsiness.

No formal drug-drug interaction studies have been conducted for ENDOMETRIN. Drugs known to induce the hepatic cytochrome-P450-3A4 system (such as rifampin, carbamazepine) may increase the elimination of progesterone. The effect of concomitant vaginal products on the exposure of progesterone from ENDOMETRIN has not been assessed. ENDOMETRIN is not recommended for use with other vaginal products (such as antifungal products) as this may alter progesterone release and absorption from the vaginal insert.

Pregnancy ENDOMETRIN has been used to support embryo implantation and maintain clinical pregnancy in one clinical study. The live birth outcomes of these pregnancies were as follows: Among the 404 subjects treated with ENDOMETRIN twice daily, 143 subjects had live births consisting of 85 singletons, 56 twins, and 2 triplets. In this treatment group, 13 subjects had a spontaneous abortion, 1 subject had an ectopic pregnancy, and 7 subjects reported fetal birth defects (3.4% based on 203 livebirths). Among the 404 subjects treated with ENDOMETRIN three times daily, 155 subjects had livebirths consisting of 91 singletons, 60 twins, and 4 triplets.

In this treatment group, 22 subjects had a spontaneous abortion, 4 subjects had an ectopic pregnancy, and 7 subjects reported fetal birth defects (3.1% based on 223 livebirths). Birth defects reported in the ENDOMETRIN twice daily group included: one fetus with a cleft palate and intrauterine growth retardation, one fetus with spina bifida, three fetuses with congenital heart defects, one fetus with an umbilical hernia, and one fetus with an intestinal anomaly. Birth defects reported in the ENDOMETRIN three times daily group included: one fetus with an esophageal fistula, one fetus with hypospadias and an underdeveloped right ear, one fetus with Down Syndrome and an atrial septal defect, one fetus with congenital heart anomalies, one fetus with DiGeorge's syndrome, one fetus with a hand deformity, and one fetus with cleft palate. For additional information on the pharmacology of ENDOMETRIN and pregnancy outcome information.

Pediatric Use This drug is not intended for pediatric use and no clinical data have been collected in children. Therefore, the safety and effectiveness of ENDOMETRIN in pediatric patients have not been established.

is contraindicated in individuals with any of the following conditions: Previous allergic reactions to progesterone or any of the ingredients of ENDOMETRIN Undiagnosed vaginal bleeding Known missed abortion or ectopic pregnancy Liver disease Known or suspected malignancy of the breast or genital organs Active arterial or venous thromboembolism or severe thrombophlebitis, or a history of these events Previous allergic reactions to progesterone or any of the ingredients of ENDOMETRIN Vaginal Insert Undiagnosed vaginal bleeding Known missed abortion or ectopic pregnancy Liver disease Known or suspected malignancy of the breast or genital organs Active arterial or venous thromboembolism or severe thrombophlebitis, or a history of these events

Treatment of overdosage consists of discontinuation of ENDOMETRIN together with institution of appropriate symptomatic and supportive care.