ENDOMETRIN

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE ENDOMETRIN ® (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. (1) Dosage and administration 2 DOSAGE AND ADMINISTRATION 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. ( 2.1 ) 2.1 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. Warnings and cautions 5 WARNINGS AND PRECAUTIONS Life-threatening arterial or venous thromboembolic disorders may occur during hormone treatment, including treatment with ENDOMETRIN. Discontinue ENDOMETRIN if any of these are suspected. ( 5.1 ) Observe patients with a history of depression closely. Consider discontinuation if symptoms worsen. ( 5.2 ) 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. ( 5.3 ) 5.1 Cardiovascular or Cerebrovascular Disorders The physician should be alert to earliest signs of myocardial infarction, cerebrovascular disorders, arterial or venous thromboembolism (venous thromboembolism or pulmonary embolism), thrombophlebitis, or retinal thrombosis. ENDOMETRIN should be discontinued if any of these are suspected. 5.2 Depression Patients with a history of depression need to be closely observed. Consider discontinuation if symptoms worsen. 5.3 Use of Other Vaginal Products ENDOMETRIN should not be recommended for use with other vaginal products (such as antifungal products) as this may alter progesterone release and absorption from the vaginal insert [ see Drug Interactions (7) ]. Drug interactions 7 DRUG INTERACTIONS 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 [ see Warnings and Precautions (5.3) ]. Pregnancy 8.1 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 [ see Clinical Pharmacology (12) and Clinical Studies Sections (14) ].