PROMETRIUM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROMETRIUM (PROMETRIUM).
Progesterone binds to progesterone receptors in target tissues, promoting endometrial maturation, reducing uterine contractility, and suppressing ovulation.
| Metabolism | Primarily hepatic via CYP3A4 to metabolites, predominantly 3-alpha-hydroxy-progesterone and 20-alpha-dihydroprogesterone; undergoes conjugation and renal excretion. |
| Excretion | Urine (50-60% as metabolites, <1% unchanged); feces (20-30% as metabolites); minor biliary elimination. |
| Half-life | Terminal half-life: Approximately 16-18 hours for oral micronized progesterone (Prometrium); permits twice-daily dosing for luteal phase support. |
| Protein binding | 96-99% bound, primarily to albumin and corticosteroid-binding globulin (CBG). |
| Volume of Distribution | Vd: 17-29 L (approximately 0.25-0.4 L/kg), indicating extensive distribution into tissues including breast, uterus, and adipose. |
| Bioavailability | Oral: <10% (extensive first-pass metabolism); Intravaginal: ~25-30% (higher bioavailability due to uterine first-pass effect). |
| Onset of Action | Oral: 1-2 hours (serum progesterone rise); Intravaginal: 2-4 hours (local endometrial effect). |
| Duration of Action | Oral: 12-24 hours (sustained progesterone levels); Intravaginal: 24 hours (local endometrial support); clinical effect persists with continued dosing. |
Oral: 200 mg once daily at bedtime for 12 consecutive days per 28-day cycle in combination with conjugated estrogens 0.625 mg daily. For secondary amenorrhea: 400 mg once daily at bedtime for 10 days. Intravaginal: 4% gel (90 mg) or 8% gel (180 mg) applied every other day for 6 doses in postmenopausal women with intact uterus on estrogen therapy.
| Dosage form | CAPSULE |
| Renal impairment | No specific dosage adjustment is recommended for renal impairment. Use caution in patients with renal disease due to potential accumulation of metabolites. |
| Liver impairment | Contraindicated in patients with severe hepatic disease (Child-Pugh class C). For mild to moderate impairment (Child-Pugh A or B), use with caution; no specific dose recommendations available. Monitor for adverse effects. |
| Pediatric use | Safety and effectiveness in pediatric patients have not been established. Not indicated for use in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended based on age alone. Consider lower starting doses due to potential increased sensitivity to progesterone effects (e.g., dizziness, drowsiness). Monitor cognitive function and risk of falls. Use with caution in patients with cardiovascular risk factors. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PROMETRIUM (PROMETRIUM).
| Breastfeeding | Progesterone is excreted into breast milk in small amounts. The milk-to-plasma ratio is approximately 0.5. Administration to nursing mothers is not expected to cause adverse effects in the infant due to low levels. Caution advised with high doses. |
| Teratogenic Risk | PROMETRIUM (progesterone) is not associated with increased risk of major congenital malformations when used during early pregnancy. First trimester exposure does not elevate teratogenic risk. Second and third trimester use is generally safe; however, high doses may cause fetal harm such as hypospadias in male infants, though evidence is limited. No known risk of miscarriage or preterm birth with use. |
■ FDA Black Box Warning
Progestins should not be used during the first four months of pregnancy.
| Serious Effects |
Known or suspected pregnancy, undiagnosed vaginal bleeding, known or suspected malignancy of the breast or genital organs, active thrombophlebitis or thromboembolic disorders, history of thromboembolic disorders, severe hepatic impairment, and known hypersensitivity to progesterone or any excipients.
| Precautions | Cardiovascular disorders, elevated blood pressure, thrombophlebitis, thromboembolic disorders, cerebrovascular disease, lipid changes, fluid retention, depression, glucose tolerance, and potential risk of breast cancer. |
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| Fetal Monitoring | Monitor for signs of thromboembolic disorders, hypertension, and fluid retention. In pregnancy, assess fetal growth and well-being with ultrasound if used for luteal phase support or preterm birth prevention. Also monitor liver function, lipid profile, and blood glucose periodically. |
| Fertility Effects | Progesterone is essential for ovulation and implantation. PROMETRIUM is used to support luteal phase in fertility treatments. It does not impair fertility; rather, it is indicated as part of assisted reproductive technology. Can also be used to treat secondary amenorrhea, restoring menstrual cycles and fertility. |