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. |
| Molecular Weight | 250.34 |
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 | No adequate human studies; animal data suggest risk. Use only if clearly needed. |
| 2nd trimester | No adequate studies; unknown fetal risk. Use only if benefit outweighs risk. |
| 3rd trimester | Potential neonatal adverse effects (e.g., respiratory depression, withdrawal). Avoid near term. |
Clinical note
Comprehensive clinical and safety monograph for H.R.-50 (H.R.-50).
| Placental transfer | Crosses placenta; fetal concentrations approximately 50-80% of maternal |
| Breastfeeding | Excreted in human milk in low amounts; monitor infant for sedation and feeding difficulties. Use with caution. |
| Lactation Rating |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to H.R.-50Severe hepatic impairmentConcomitant MAO inhibitor useHistory of neuroleptic malignant syndrome
| Precautions | Embryo-fetal toxicity, Increased risk of thromboembolic events, Hypertriglyceridemia, Bone fractures, Ocular toxicity |
| Food/Dietary | Avoid grapefruit juice and grapefruit products, as they can increase H.R.-50 concentrations. No other significant food interactions known; maintain consistent vitamin K intake if on warfarin, but H.R.-50 is not vitamin K-dependent. |
| Clinical Pearls |
Loading safety data…
| L3 (Moderately Safe) |
| 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. |
| 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. |
| H.R.-50 is a novel oral anticoagulant; avoid use in patients with mechanical heart valves or moderate-to-severe mitral stenosis. Monitor renal function before initiation and periodically thereafter, as clearance is renally dependent. No routine coagulation monitoring required; if necessary, measure anti-factor Xa activity calibrated to H.R.-50. Reversal agent available only in specialized centers. |
| Patient Advice | Take this medication exactly as prescribed, at the same time each day. · Do not skip doses; if you miss a dose, take it as soon as you remember on the same day. Do not double the next dose. · Inform your doctor before any surgery or dental procedure; you may need to stop this medication temporarily. · Watch for signs of bleeding: unusual bruising, pink or brown urine, red or black stools, coughing up blood, or prolonged bleeding from cuts. · Avoid aspirin, NSAIDs, and other blood thinners unless specifically prescribed by your doctor. · Store at room temperature away from moisture and heat. |