H.R.-50
Clinical safety rating: caution
Comprehensive clinical and safety monograph for H.R.-50 (H.R.-50).
Selective estrogen receptor degrader (SERD); binds to estrogen receptor alpha, inducing degradation and inhibiting estrogen signaling.
| Metabolism | Primarily metabolized by CYP3A4 and CYP2C9. |
| Excretion | Renal excretion of unchanged drug accounts for 60-70%; biliary/fecal excretion accounts for 20-30%; <10% metabolized. |
| Half-life | Terminal elimination half-life is 4-6 hours in adults with normal renal function; prolonged to 10-12 hours in moderate renal impairment (CrCl <50 mL/min). |
| Protein binding | Approximately 85-90% bound to serum albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.8-1.2 L/kg; indicates extensive tissue distribution with moderate penetration into CNS. |
| Bioavailability | Oral: 60-70% (first-pass metabolism reduces bioavailability); no data for other routes. |
| Onset of Action | Intravenous: 5-10 minutes; Oral: 30-60 minutes on empty stomach. |
| Duration of Action | Intravenous: 3-4 hours; Oral: 4-6 hours; duration may be extended in hepatic impairment. |
12.5 mg orally twice daily
| Dosage form | TABLET |
| Renal impairment | GFR >60 mL/min: no adjustment; GFR 30-60 mL/min: 12.5 mg once daily; GFR 15-29 mL/min: 12.5 mg every other day; GFR <15 mL/min: not recommended |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated |
| Pediatric use | Not established for patients <18 years |
| Geriatric use | Start at 6.25 mg twice daily; titrate cautiously due to increased risk of hypotension and renal impairment |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for H.R.-50 (H.R.-50).
| Breastfeeding | No human data on excretion in breast milk. Based on molecular weight and lipophilicity, likely to be present. M/P ratio unknown. Not recommended during breastfeeding due to potential for serious adverse reactions in the infant. |
| Teratogenic Risk | H.R.-50 is contraindicated in pregnancy. First trimester: high risk of major congenital malformations including neural tube defects and craniofacial anomalies. Second and third trimesters: risk of fetal growth restriction and oligohydramnios. Animal studies show embryo-fetal lethality. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Pregnancy","History of thromboembolic disorders","Known hypersensitivity to H.R.-50"]
| Precautions | ["Embryo-fetal toxicity","Increased risk of thromboembolic events","Hypertriglyceridemia","Bone fractures","Ocular toxicity"] |
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| Fetal Monitoring |
| Pregnancy test before initiation. During pregnancy, monitor fetal growth by ultrasound every 4 weeks. Assess amniotic fluid volume. Monitor for maternal hepatotoxicity and renal function monthly. |
| Fertility Effects | Reversible impairment of spermatogenesis in males. In females, may cause anovulation and menstrual irregularities. Fertility may be reduced during therapy; normalizes after discontinuation. |