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. |
| Molecular Weight | 303.25 |
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 | Avoid use; animal studies show teratogenicity and embryotoxicity. No adequate human data. |
| 2nd trimester | Avoid use; potential for fetal harm. Risk of oligohydramnios and fetal renal impairment. |
| 3rd trimester | Avoid use; may cause premature closure of ductus arteriosus and oligohydramnios. |
Clinical note
Comprehensive clinical and safety monograph for YESAFILI (YESAFILI).
| Placental transfer | Crosses placenta in animal studies; human data limited but expected due to low molecular weight. |
| Breastfeeding | Excreted in human milk in low levels; however, due to potential for serious adverse reactions in nursing infants, consider discontinuing drug or breastfeeding. |
| Lactation Rating |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to YESAFILI or any excipientConcurrent use with nitrates or nitric oxide donorsConcurrent use with guanylate cyclase stimulators (e.g., riociguat)
| 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 |
| Food/Dietary | YESAFILI has no known direct food interactions, but grapefruit juice is contraindicated due to CYP3A4 inhibition, increasing finerenone levels and risk of adverse effects. |
Loading safety data…
| L4 - Possibly Hazardous |
| 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. |
| 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. |
| Clinical Pearls |
| YESAFILI (finerenone) is a nonsteroidal mineralocorticoid receptor antagonist indicated for chronic kidney disease associated with type 2 diabetes. Monitor serum potassium regularly; discontinue if potassium >5.5 mEq/L. Avoid concomitant use with strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole) as they increase finerenone exposure. |
| Patient Advice | Take YESAFILI once daily, with or without food, at the same time each day. · Do not take potassium supplements or salt substitutes containing potassium. · Report symptoms of hyperkalemia (e.g., muscle weakness, heart palpitations) immediately. · Avoid grapefruit or grapefruit juice while taking this medication. · Regular blood tests are required to monitor kidney function and potassium levels. |