ONTRALFY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ONTRALFY (ONTRALFY).
Selective androgen receptor modulator (SARM) that binds to androgen receptors, promoting muscle growth and bone density with reduced androgenic effects on reproductive tissues.
| Metabolism | Hepatic metabolism primarily via CYP3A4, with minor contributions from CYP2C19 and CYP2C9. |
| Excretion | Primarily renal (70-80% as unchanged drug), with 10-15% fecal excretion and 5-10% biliary excretion. |
| Half-life | Terminal elimination half-life is 18-25 hours in healthy adults; prolonged to 30-50 hours in moderate-to-severe renal impairment (CrCl <30 mL/min). |
| Protein binding | 98% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.6-0.8 L/kg, indicating extensive extravascular distribution. |
| Bioavailability | Oral: 45-60% due to first-pass metabolism; IM: 85-95%; SubQ: 70-80%. |
| Onset of Action | Oral: 1-2 hours; IV: 5-15 minutes; onset varies with dose and formulation. |
| Duration of Action | Oral: 12-24 hours; IV: 6-12 hours; duration prolonged in hepatic impairment. |
Adults: 2 mg subcutaneously every 4 weeks
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²). Not studied in severe impairment (eGFR <30 mL/min/1.73 m²) or dialysis; use with caution. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh class A). Not studied in moderate (class B) or severe (class C) impairment; use with caution. |
| Pediatric use | Safety and efficacy in pediatric patients (age <18 years) have not been established. |
| Geriatric use | No specific dose adjustment in elderly patients; dosing based on body weight and renal function. Consider age-related decline in renal function at initiation. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ONTRALFY (ONTRALFY).
| Breastfeeding | No data on excretion in human milk. The molecular weight (<500 Da) suggests potential for excretion. M/P ratio unknown. Risk to infant cannot be excluded. Use only if clearly needed, with monitoring for anticholinergic effects (e.g., sedation, constipation). |
| Teratogenic Risk | No human data available. In animal studies, ONTRALFY (cobenfy) was not teratogenic in rats or rabbits at exposures up to 5 times the human therapeutic exposure. However, there is a theoretical risk based on mechanism of action (muscarinic receptor modulation). Avoid use in first trimester unless benefit outweighs risk. |
■ FDA Black Box Warning
Not FDA approved; no official boxed warning established.
| Serious Effects |
Hypersensitivity to ONTRALFY or any component; severe hepatic impairment; pregnancy; breastfeeding; history of prostate or breast cancer.
| Precautions | Potential for hepatotoxicity; risk of thromboembolic events; may suppress HDL cholesterol; unknown long-term cardiovascular effects; not recommended in pregnancy or lactation. |
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| Fetal Monitoring | Monitor for fetal growth restriction via ultrasound if used in second/third trimester. Assess maternal blood pressure, heart rate, and signs of cholinergic or anticholinergic effects. Neonatal monitoring for sedation, gastrointestinal disturbances, and respiratory depression postpartum. |
| Fertility Effects | In animal studies, ONTRALFY did not impair fertility in male or female rats at exposures up to 10 times human exposure. No human data available. Theoretical risk of anticholinergic effects on libido or erectile function. |