ENDOMETRIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ENDOMETRIN (ENDOMETRIN).
Progesterone is a steroid hormone that binds to progesterone receptors in the endometrium, inducing secretory changes, decreasing uterine contractility, and supporting pregnancy maintenance.
| Metabolism | Hepatic via CYP3A4 and CYP2C19; metabolites include pregnanediols. |
| Excretion | Primarily renal (50-60% as metabolites, <10% unchanged); fecal (20-30%) via biliary excretion. |
| Half-life | Terminal elimination half-life is approximately 12-15 hours, supporting twice-daily dosing for endometrial support. |
| Protein binding | 96-99% bound to serum albumin and corticosteroid-binding globulin. |
| Volume of Distribution | Apparent volume of distribution is 1.1 L/kg, indicating extensive distribution into tissues. |
| Bioavailability | Intravaginal: ~10% due to first-pass uterine effect and hepatic metabolism; oral bioavailability is <5%. |
| Onset of Action | Intravaginal: Onset within 2-4 hours, with peak plasma levels achieved in 6-8 hours. |
| Duration of Action | Duration of action for secretory transformation of endometrium is approximately 12-24 hours, requiring continuous exposure for adequate luteal phase support. |
Vaginal tablet: 100 mg twice daily starting on day 15 of a 28-day cycle for 12 weeks.
| Dosage form | INSERT |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment; not studied in severe impairment (GFR <30 mL/min). |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A); not studied in moderate or severe impairment (Child-Pugh B or C). |
| Pediatric use | Not indicated for use in pediatric patients. |
| Geriatric use | No specific dose adjustment; caution due to increased risk of thromboembolic events in elderly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ENDOMETRIN (ENDOMETRIN).
| Breastfeeding | Progesterone is excreted into human breast milk in small amounts. The M/P ratio is approximately 0.6-1.0. No adverse effects on the nursing infant have been reported. Use with caution in breastfeeding women. |
| Teratogenic Risk | Progesterone (active ingredient in ENDOMETRIN) is not associated with major congenital malformations based on available data. However, animal studies have shown reproductive toxicity at high doses. Use during the first trimester should be limited to luteal phase support. No known risks during second and third trimesters, but use only if clearly needed as progesterone is critical for maintaining pregnancy. |
■ FDA Black Box Warning
None
| Serious Effects |
["Known hypersensitivity to progesterone or any component","Undiagnosed vaginal bleeding","Known or suspected pregnancy (for non-pregnancy indications)","Active thrombophlebitis or thromboembolic disorders","History of thromboembolic disease","Known or suspected breast cancer","Severe hepatic impairment"]
| Precautions | ["Thromboembolic disorders: discontinue if thrombosis occurs","Cardiovascular disease: increased risk in postmenopausal women","Breast cancer: avoid use in women with history of breast cancer","Hepatic impairment: use with caution","Depression: monitor mood changes","Ophthalmic effects: discontinue if sudden vision loss occurs"] |
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| Fetal Monitoring | Monitor for signs of pregnancy complications such as preterm labor, gestational hypertension, and glucose intolerance. No specific fetal monitoring required beyond standard prenatal care. In patients with history of preterm birth, monitor cervical length. Assess liver function if prolonged use. |
| Fertility Effects | ENDOMETRIN is used for luteal phase support in assisted reproductive technology and does not impair fertility. It may improve fertility by supporting implantation. No negative impact on future fertility. |