YESAFILI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for YESAFILI (YESAFILI).
Selective estrogen receptor degrader (SERD) that binds to estrogen receptors (ER), inducing a conformational change leading to receptor degradation and inhibition of estrogen-dependent tumor growth.
| Metabolism | Primarily metabolized by CYP3A4 and to a minor extent by CYP2C8 and CYP2C9. |
| Excretion | Primarily hepatic metabolism; renal excretion of unchanged drug accounts for approximately 2% of the dose, with biliary/fecal elimination as the major route. |
| Half-life | Terminal elimination half-life of 3–5 hours in healthy adults; prolonged in hepatic impairment (up to 8–10 hours), requiring dose adjustment. |
| Protein binding | Approximately 96% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 1.5–2.0 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 40–50% due to first-pass metabolism. |
| Onset of Action | Oral: 30–60 minutes; peak effect at 1–2 hours post-dose. |
| Duration of Action | 4–6 hours; clinical effect persists as long as adequate plasma concentrations are maintained, typically until drug is cleared. |
10 mg orally once daily.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). For severe renal impairment (CrCl <30 mL/min), use is not recommended. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). For moderate to severe hepatic impairment (Child-Pugh B or C), use is contraindicated. |
| Pediatric use | Safety and efficacy in pediatric patients have not been established. |
| Geriatric use | No specific dose adjustment recommended; however, monitor for increased sensitivity due to age-related changes in renal and hepatic function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for YESAFILI (YESAFILI).
| Breastfeeding | No human data. Excretion in animal milk unknown. M/P ratio not available. Caution due to risk of adverse effects in nursing infant, including hypotension and prolonged erection. Consider alternative agents. |
| Teratogenic Risk | YESAFILI (avanafil) is FDA Pregnancy Category B. No fetal harm observed in animal studies at doses up to 32 times the MRHD. No adequate human studies; use only if clearly needed. Risks in first trimester: theoretical based on PDE5 inhibition; no specific malformation signal. Second/third trimester: potential for uterine relaxation and hypotension; avoid near term due to risk of neonatal hypotension. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to yesafili or any of its excipients","Pregnancy","Lactation"]
| Precautions | ["Embryo-fetal toxicity","Increased risk of thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism)","Hypertriglyceridemia","Mild to moderate elevation of liver enzymes","Dizziness, fatigue, and other CNS effects that may impair driving ability"] |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate during therapy. Assess for signs of hypotension, syncope, or priapism. In pregnancy: monitor fetal heart rate and uterine activity if near term. Evaluate for evidence of preterm labor if used in third trimester. |
| Fertility Effects | No human studies. Animal studies: no effect on fertility or reproductive function at doses up to 32 mg/kg/day. Theoretical concern with PDE5 inhibition on spermatogenesis or sperm motility, but clinical significance unknown. |