Progesterone (vaginal)

Drugs known to induce the hepatic cytochrome-P450-3A4 system may increase the elimination of progesterone, lower progesterone exposure in ENDOMETRIN-treated women, and reduce the efficacy of ENDOMETRIN. 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 ENDOMETRIN vaginal insert. CYP3A4 Inducers: May increase the elimination of progesterone and may reduce the efficacy of ENDOMETRIN. ( 7 ) Other Vaginal Products: Avoid use of ENDOMETRIN with other vaginal products. ( 7 )

8.1 Pregnancy Risk Summary ENDOMETRIN is indicated, as part of an Assisted Reproductive Technology (ART) treatment program, to support embryo implantation in infertile women less than 35 years of age by supplementation of corpus luteal function and to maintain pregnancy after implantation up to 10 weeks. Maternal risks of ENDOMETRIN use during pregnancy are discussed throughout the labeling. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data Human Data: In one clinical study [see Clinical Studies (14)], ENDOMETRIN was vaginally administered to support embryo implantation during the first trimester of pregnancy and to maintain clinical pregnancy through week 10 of pregnancy when the placenta takes over production of progesterone. The live birth outcomes of these pregnancies were as follows: • Among the 404 women treated with ENDOMETRIN twice daily, 143 (35%) women had live births consisting of 85 (59%) singletons, 56 (39%) twins, and 2 (1%) triplets.

In this treatment group, 13 (3%) women had a spontaneous abortion, 1 (0.2%) woman had an ectopic pregnancy, and neonatal birth defects were reported in 7 infants (3% based on 203 live births). • Among the 404 women treated with ENDOMETRIN three times daily, 155 (38%) women had live births consisting of 91 (59%) singletons, 60 (39%) twins, and 4 (3%) triplets. In this treatment group, 22 (5%) women had a spontaneous abortion, 4 (1%) women had an ectopic pregnancy, and neonatal birth defects were reported in 7 infants (3% based on 223 live births).

Birth defects reported in the ENDOMETRIN: Twice daily group included one neonate with a cleft palate and intrauterine growth retardation, one with spina bifida, three with congenital heart defects, one with an umbilical hernia, and one with an intestinal anomaly. Three times daily group included one neonate with an esophageal fistula, one with hypospadias and an underdeveloped right ear, one with Down Syndrome and an atrial septal defect, one with congenital heart anomalies, one with DiGeorge’s syndrome, one fetus with a hand deformity, and one with cleft palate.

For additional information on the pharmacology of ENDOMETRIN and pregnancy outcome information [see Clinical Pharmacology (12) and Clinical Studies (14) ] .