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. |
| Molecular Weight | 583.22 |
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 | Avoid due to known teratogenic effects; associated with Ebstein's anomaly and other congenital defects. |
| 2nd trimester | Use only if benefit outweighs risk; risk of fetal arrhythmias and electrolyte disturbances. |
| 3rd trimester | Avoid near term; risk of neonatal arrhythmias, hypotonia, and respiratory depression. |
Clinical note
Comprehensive clinical and safety monograph for PMB 400 (PMB 400).
| Placental transfer | Complete placental transfer; fetal serum levels approach maternal levels. |
| Breastfeeding | Breastfeeding is contraindicated due to high concentration in breast milk and risk of neonatal electrolyte disturbances and arrhythmias. |
| Lactation Rating |
■ 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 |
Severe renal impairmentHypercalcemiaDigitalis toxicityVentricular fibrillationHypersensitivity 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. |
| Food/Dietary | No significant food interactions reported. However, taking with food may help reduce gastrointestinal upset. Avoid grapefruit juice as it may interfere with estrogen metabolism. |
Loading safety data…
| L5 - Contraindicated |
| 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. |
| 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. |
| Clinical Pearls | PMB 400 is a combination of progesterone and estradiol used for menopausal hormone therapy. Dosing should be individualized based on symptom severity and patient history. Assess thromboembolic risk prior to initiation; avoid in patients with history of DVT/PE or active thrombophlebitis. Monitor for endometrial hyperplasia if using unopposed estrogen; PMB 400 includes progesterone to mitigate this risk. Reassess need for therapy periodically. |
| Patient Advice | Take this medication at the same time each day, preferably with food to reduce nausea. · Attend all scheduled check-ups including breast exams, mammograms, and pelvic exams. · Report any signs of blood clots such as leg swelling, chest pain, or sudden shortness of breath immediately. · Do not smoke while using this medication as it increases the risk of serious cardiovascular side effects. · If you miss a dose, take it as soon as you remember unless it is close to the next dose; do not double the dose. |