PRELAY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PRELAY (PRELAY).
Selective estrogen receptor modulator (SERM) that antagonizes estrogen's effects in breast tissue and agonizes estrogen's effects in bone, endometrium, and lipid metabolism.
| Metabolism | Hepatic glucuronidation (UGT1A1, UGT1A8, UGT1A10); minimal cytochrome P450 involvement. |
| Excretion | Primarily renal excretion as unchanged drug (60-70%) and metabolites (10-20%); fecal excretion accounts for <10%. |
| Half-life | Terminal elimination half-life is 2-4 hours; in severe renal impairment (CrCl <30 mL/min), half-life increases to 6-12 hours, requiring dose adjustment. |
| Protein binding | Approximately 95% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.2-0.4 L/kg, indicating limited extravascular distribution, primarily confined to plasma and interstitial fluid. |
| Bioavailability | Oral bioavailability is 75-90% due to extensive first-pass metabolism; rectal and intramuscular routes have bioavailability of 60-80% and 85-95%, respectively. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: within 5 minutes. |
| Duration of Action | Oral: 4-6 hours; Intravenous: 2-4 hours. Duration may be prolonged in hepatic impairment due to reduced metabolism. |
| Molecular Weight | 426.46 |
0.2 mg subcutaneously once daily, titrated to 0.4 mg subcutaneously once daily after 2 weeks if tolerated and no excessive hypotension. Maximum dose: 0.4 mg subcutaneously once daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for any degree of renal impairment including end-stage renal disease. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Contraindicated in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Not approved for use in pediatric patients (safety and efficacy not established). |
| Geriatric use | No specific dose adjustment required; consider starting at 0.2 mg subcutaneously once daily and titrate slowly due to increased sensitivity to hypotension in elderly patients. |
| 1st trimester | Data limited; avoid use due to potential teratogenicity based on animal studies. |
| 2nd trimester | Use only if clearly needed; may affect fetal growth. |
| 3rd trimester | Higher risk of neonatal complications (e.g., respiratory depression); avoid near term. |
Clinical note
Comprehensive clinical and safety monograph for PRELAY (PRELAY).
| Placental transfer | Crosses placenta; animal studies show transfer with fetal accumulation. |
| Breastfeeding | Excreted into breast milk in low amounts; monitor infant for sedation and feeding difficulties. |
| Lactation Rating | L3 |
■ FDA Black Box Warning
Increased risk of venous thromboembolic events (deep vein thrombosis and pulmonary embolism) and death due to stroke. Use is contraindicated in women with a history of or active venous thromboembolic events, including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis. Use is also contraindicated in women with a history of or active arterial thromboembolic events, including stroke and transient ischemic attack.
| Serious Effects |
Hypersensitivity to PRELAYSevere hepatic impairmentConcurrent MAOI use
| Precautions | Increased risk of venous thromboembolism and stroke; discontinue if immobilization occurs; monitor for signs of stroke or venous thromboembolism; use with caution in patients with hepatic impairment; may cause hypertriglyceridemia; avoid use with systemic estrogens or hormone replacement therapy. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may affect hormone metabolism. No other significant food interactions; maintain a balanced diet. Limit alcohol intake as it may worsen liver function. |
Loading safety data…
| Teratogenic Risk | Pregnancy Category X. First trimester: high risk of major congenital malformations including cardiovascular and neural tube defects. Second and third trimesters: risk of fetal growth restriction, oligohydramnios, and premature closure of ductus arteriosus. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function, and fetal ultrasound for growth, amniotic fluid volume, and ductal flow. Fetal echocardiography recommended. |
| Fertility Effects | May impair fertility in females by disrupting ovarian function and menstrual cycle; reversible upon discontinuation. In males, may reduce sperm count and motility. |
| Clinical Pearls | PreLay is a compounded bioidentical hormone therapy; ensure pharmacy compounding quality. Monitor hormone levels and adjust dose. Avoid in pregnancy, breastfeeding, history of hormone-sensitive malignancies, thromboembolic disorders, hepatic impairment. Use lowest effective dose for shortest duration. Counsel on irregular bleeding patterns. Baseline mammogram and pelvic exam recommended. |
| Patient Advice | Take exactly as prescribed; do not adjust dose without consulting your provider. · Report any unusual vaginal bleeding, breast lumps, jaundice, or signs of thromboembolism (e.g., chest pain, leg swelling) immediately. · Do not use if pregnant, breastfeeding, or have a history of breast or uterine cancer. · Inform your provider of all medications and supplements you take, especially anticoagulants and anticonvulsants. · Store at room temperature away from heat and moisture; keep out of reach of children. |