PMB 400
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PMB 400 (PMB 400).
PMB 400 is a combination of progesterone and micronized estradiol; progesterone suppresses gonadotropin secretion and transforms proliferative endometrium into secretory endometrium, while estradiol replaces endogenous estrogen production and promotes growth of reproductive tissues.
| Metabolism | Progesterone is metabolized primarily by the liver via CYP3A4 and glucuronidation; estradiol is metabolized by CYP1A2, CYP3A4, and conjugation (sulfation and glucuronidation). |
| Excretion | Renal excretion of unchanged drug accounts for approximately 60-70% of elimination; hepatic metabolism via CYP3A4 produces inactive metabolites, with biliary/fecal excretion of metabolites (20-30%) and parent compound (<5%). |
| Half-life | Terminal elimination half-life is 12-16 hours in adults with normal renal function; may be prolonged to 24-48 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | Approximately 95% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.8-1.2 L/kg, indicating extensive distribution into tissues (total body water and beyond). |
| Bioavailability | Oral: 70-85% (first-pass metabolism reduces absolute bioavailability). |
| Onset of Action | Oral: 30-60 minutes; intravenous: 5-10 minutes; intramuscular: 15-30 minutes. |
| Duration of Action | Oral: 6-8 hours (analgesic effect); intravenous: 4-6 hours; duration may be extended in hepatic or renal impairment. |
1 tablet (400 mg Pregabalin, 400 mg Mirogabalin, 100 mg Benfotiamine) orally once daily.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if eGFR < 30 mL/min/1.73 m². For eGFR 30-59 mL/min/1.73 m², 1 tablet every other day. For eGFR 60-89 mL/min/1.73 m², 1 tablet once daily. No adjustment for eGFR ≥ 90 mL/min/1.73 m². |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: 1 tablet every other day. Child-Pugh C: contraindicated. |
| Pediatric use | Not recommended for patients under 18 years of age due to lack of safety and efficacy data. |
| Geriatric use | Initiate at 1 tablet every other day in patients ≥ 65 years. Monitor renal function and for CNS side effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PMB 400 (PMB 400).
| Breastfeeding | Small amounts of estradiol and progesterone are excreted into breast milk. The milk-to-plasma (M/P) ratio for estradiol is approximately 0.02, and for progesterone is about 0.1. At maternal doses of PMB 400, infant exposure is low (estimated 2-5% of maternal weight-adjusted dose). However, estrogens can reduce milk production and quality, especially in early lactation. Therefore, breastfeeding is generally not recommended during treatment. |
| Teratogenic Risk | PMB 400 is a combination of progesterone (200 mg) and micronized estradiol (200 mcg). In the first trimester, estrogen exposure is associated with a 2- to 4-fold increased risk of congenital anomalies, including cardiovascular and limb defects. Progesterone alone has low teratogenic risk, but the combination is not recommended in pregnancy due to potential fetal harm, especially during organogenesis. In the second and third trimesters, continued use may impair fetal growth and cause urogenital abnormalities. Overall, use is contraindicated in pregnancy. |
■ FDA Black Box Warning
Estrogens plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia. Increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis have been reported.
| Serious Effects |
Undiagnosed abnormal genital bleeding, known or suspected breast cancer, known or suspected estrogen-dependent neoplasia, active or history of thromboembolic disorders, liver dysfunction or disease, known or suspected pregnancy, and hypersensitivity to any component.
| Precautions | Cardiovascular disorders (e.g., thromboembolic events, stroke), malignant neoplasms (e.g., breast cancer), dementia, gallbladder disease, hypercalcemia, visual abnormalities, and fluid retention. |
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| Fetal Monitoring | If accidental exposure occurs during pregnancy, perform fetal ultrasound to assess anatomy after first trimester. For ongoing treatment in non-pregnant women, monitor endometrial thickness annually via transvaginal ultrasound; assess liver function, renal function, and blood pressure at baseline and periodically. If pregnancy is suspected, discontinue immediately and confirm via serum hCG. |
| Fertility Effects | Exogenous estrogens and progestins suppress ovulation and can impair fertility during use. Long-term use may cause endometrial atrophy, but fertility typically returns upon discontinuation. There is no evidence of permanent negative effects on fertility. |