ORSYTHIA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ORSYTHIA (ORSYTHIA).
Nonsteroidal aromatase inhibitor that selectively and reversibly inhibits aromatase, the enzyme responsible for converting androgens to estrogens, thereby reducing estrogen levels in tissues.
| Metabolism | Primarily metabolized by CYP3A4 to active metabolites; hepatic metabolism. |
| Excretion | Primarily renal (≥90% as unchanged drug); <5% biliary/fecal. |
| Half-life | Terminal half-life ~12 hours (range 10-14 h); prolonged in renal impairment (up to 24-30 h). |
| Protein binding | ~70% bound to albumin. |
| Volume of Distribution | Vd ~2.5 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral: 80-90% (fasted); reduced by ~20% with high-fat meal. |
| Onset of Action | Oral: 1-2 hours; IV: within 15-30 minutes. |
| Duration of Action | Approximately 12-24 hours depending on dose and renal function; clinical effect persists for duration of therapy. |
400 mg orally twice daily
| Dosage form | TABLET |
| Renal impairment | GFR 30-89 mL/min: no adjustment. GFR 15-29 mL/min: 200 mg twice daily. GFR <15 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: 200 mg twice daily. Child-Pugh C: not recommended. |
| Pediatric use | <12 years: not established. ≥12 years: weight ≥40 kg: 400 mg twice daily; <40 kg: 8 mg/kg twice daily, max 400 mg/dose. |
| Geriatric use | No specific adjustment; monitor renal function and consider age-related GFR decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ORSYTHIA (ORSYTHIA).
| Breastfeeding | Excreted in human milk; M/P ratio 0.8. Potential for adverse effects in nursing infant (diarrhea, photosensitivity). Contraindicated during breastfeeding. |
| Teratogenic Risk | First trimester: Increased risk of major congenital malformations (cardiac, CNS). Second/third trimester: Risk of oligohydramnios, fetal renal impairment, and skull ossification defects. Avoid throughout pregnancy. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to ORSYTHIA or any of its components; premenopausal women; pregnancy; lactation.
| Precautions | May cause fetal harm if used during pregnancy; risk of osteoporosis due to estrogen suppression; dose reduction recommended in severe hepatic impairment. |
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| Monitor fetal ultrasound for anomalies, amniotic fluid index, and fetal growth. Maternal renal function and liver enzymes every 4 weeks. |
| Fertility Effects | Reversible impairment of spermatogenesis and ovulation in animal studies; no human data. May reduce fertility during use. |