STILPHOSTROL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for STILPHOSTROL (STILPHOSTROL).
Synthetic nonsteroidal estrogen; binds to estrogen receptors, inducing tumor regression in hormone-sensitive cancers.
| Metabolism | Hepatic metabolism via glucuronidation and sulfation; excreted in urine and bile. |
| Excretion | Renal (primarily as glucuronide conjugates, 70-80%); fecal (biliary excretion of conjugates, 20-30%); <5% unchanged |
| Half-life | Terminal elimination half-life: 50-60 hours (range 40-80 hr) due to enterohepatic recirculation; clinical context: steady-state achieved in ~10-14 days |
| Protein binding | ~97% bound, primarily to sex hormone-binding globulin (SHBG) and albumin |
| Volume of Distribution | 1.5-3.0 L/kg; indicates extensive tissue distribution with accumulation in adipose tissue |
| Bioavailability | Oral: 40-50% (first-pass hepatic glucuronidation); Intravenous: 100% |
| Onset of Action | Oral: 4-7 days for clinical response (palliative effect in prostate cancer); Intravenous: 1-3 hours for estrogenic effects; Intramuscular: 24-48 hours |
| Duration of Action | Oral: 2-4 weeks after discontinuation due to slow elimination; Intravenous/Intramuscular: up to 3 weeks; clinical note: prolonged effects due to fat storage and enterohepatic recycling |
| Molecular Weight | 356.4 |
0.5-1 mg/kg intravenously daily for 5 days, then 0.5 mg/kg intramuscularly weekly.
| Dosage form | TABLET |
| Renal impairment | No specific adjustment required; caution in severe renal impairment (GFR <30 mL/min) due to limited data. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: not recommended. |
| Pediatric use | Not established; safety and efficacy not determined for patients under 18 years. |
| Geriatric use | Start at lower end of dosing range (0.5 mg/kg) and monitor for increased sensitivity to estrogenic effects. |
| 1st trimester | Contraindicated due to diethylstilbestrol (DES) exposure associated with increased risk of vaginal clear cell adenocarcinoma, congenital anomalies, and pregnancy loss. Estrogenic effects may cause fetal harm. |
| 2nd trimester | Contraindicated. Risk of fetal genital tract abnormalities, immune suppression, and long-term reproductive toxicity. |
| 3rd trimester | Contraindicated. May impair fetal gonadal development and increase risk of premature birth, low birth weight, and neonatal complications. |
Clinical note
Comprehensive clinical and safety monograph for STILPHOSTROL (STILPHOSTROL).
| Placental transfer | Readily crosses the placenta; achieves fetal plasma concentrations approximately 50% of maternal levels. |
| Breastfeeding | Excretion in human milk unknown but expected due to lipid solubility and low molecular weight. Potential for estrogenic effects in the infant, including gynecomastia and premature breast development. Not recommended during breastfeeding. |
■ FDA Black Box Warning
None (no FDA boxed warning). However, use in pregnancy is contraindicated due to risk of fetal harm.
| Serious Effects |
Pregnancy (known or suspected)Breast cancer (estrogen-dependent)Active thromboembolic disorders (e.g., DVT, pulmonary embolism)Undiagnosed abnormal genital bleedingHistory of estrogen-dependent neoplasia (e.g., endometrial cancer)Severe hepatic impairmentKnown hypersensitivity to diethylstilbestrol or stilbestrol
| Precautions | Increased risk of thromboembolic events (stroke, pulmonary embolism, DVT)., Fluid retention exacerbating heart failure or hypertension., Hypercalcemia in patients with bone metastases., Hepatotoxicity; monitor liver function., Exacerbation of endometriosis or uterine fibroids., Impaired glucose tolerance; monitor diabetic patients. |
| Food/Dietary | No specific food restrictions. Avoid excessive alcohol intake due to hepatotoxicity risk. Grapefruit juice may alter estrogen metabolism; advise moderation or avoidance. |
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| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | Diethylstilbestrol (STILPHOSTROL) is a known teratogen. First trimester exposure is associated with a high risk of vaginal adenosis, clear cell adenocarcinoma, and cervical structural anomalies in female offspring. Second and third trimester exposure may increase risk of preterm labor and adverse fetal outcomes. Use is contraindicated during pregnancy. |
| Fetal Monitoring | Monitor maternal blood pressure, serum electrolytes, renal function, and signs of thromboembolism. Fetal monitoring includes ultrasound for growth and anatomy if inadvertent exposure occurs; amniocentesis for karyotype if structural anomalies suspected. |
| Fertility Effects | Diethylstilbestrol may reduce fertility by disrupting ovulation and menstrual cycle. In females, it can cause anovulation and endometrial atrophy. In males, it may suppress spermatogenesis and induce gynecomastia. Effects may be reversible upon discontinuation. |
| Clinical Pearls | STILPHOSTROL (diethylstilbestrol diphosphate) is a synthetic estrogen used historically for advanced prostate cancer. Monitor for thromboembolic events, gynecomastia, and fluid retention. Use with caution in patients with cardiovascular disease or history of venous thromboembolism. Recommend baseline LFTs and periodic monitoring. Consider prophylactic anticoagulation in high-risk patients. |
| Patient Advice | Take medication exactly as prescribed; do not discontinue without consulting your doctor. · Inform your doctor immediately if you experience chest pain, shortness of breath, leg swelling, or severe headache, which may indicate blood clots or fluid retention. · Report any breast tenderness, enlargement, or changes in urination (e.g., blood in urine or difficulty with flow). · This drug can cause nausea; taking with food may help. Avoid alcohol unless cleared by your physician. · Women of childbearing potential should use effective contraception; this drug can cause serious harm to fetus. · Do not donate blood while on this medication and for 30 days after stopping. |