YONSA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for YONSA (YONSA).
Abiraterone acetate is converted to abiraterone, a selective inhibitor of CYP17A1 (17α-hydroxylase/C17,20-lyase), which catalyzes androgen biosynthesis in the testes, adrenal glands, and prostate tumor tissue. Inhibition of CYP17A1 decreases serum testosterone and other androgens.
| Metabolism | Abiraterone acetate is metabolized by CYP3A4 to active metabolite abiraterone. Abiraterone undergoes further metabolism via hydroxylation, oxidation, and glucuronidation. |
| Excretion | Primarily hepatic metabolism via CYP3A4, with <5% of the dose excreted unchanged in feces and <1% in urine. Fecal elimination accounts for ~88% of total clearance (metabolites), biliary excretion is minimal. |
| Half-life | Terminal elimination half-life is approximately 59 hours (range 32–83 hours) in castration-resistant prostate cancer patients, allowing for once-daily dosing after an initial dose schedule. |
| Protein binding | >99% bound to plasma proteins, primarily to albumin and alpha-1-acid glycoprotein (AAG). |
| Volume of Distribution | Approximately 36 L (0.5 L/kg, assuming 70 kg) at steady state, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 30% (range 20–40%) under fed conditions; food increases AUC by 2-fold and Cmax by 2.5-fold compared to fasting. |
| Onset of Action | Oral: Steady-state concentrations are reached by day 8–12 with a loading dose regimen (day 1: 240 mg, days 2–28: 160 mg). Clinical effects (PSA decline) are typically observed within 4–6 weeks. |
| Duration of Action | Therapeutic effects persist throughout the dosing interval (24 hours) due to long half-life. Duration of response is variable and disease-dependent; continuous daily dosing is required. |
| Molecular Weight | 391.55 |
1000 mg orally twice daily with food.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment; not studied in severe renal impairment (CrCl <30 mL/min). |
| Liver impairment | Child-Pugh A: no dose adjustment; Child-Pugh B: reduce dose to 750 mg twice daily; Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment; consider renal function in elderly. |
| 1st trimester | Abiraterone acetate is contraindicated in pregnancy. Animal studies show teratogenicity and embryo-fetal toxicity at clinically relevant doses. Use effective contraception in males with pregnant partners. |
| 2nd trimester | Same as T1: contraindicated due to risk of fetal harm. |
| 3rd trimester | Same as T1: contraindicated due to risk of fetal harm. |
Clinical note
Comprehensive clinical and safety monograph for YONSA (YONSA).
| Placental transfer | Abiraterone acetate and its active metabolite abiraterone are expected to cross the placenta based on molecular weight (391.4 Da) and lipophilicity. Animal studies confirm placental transfer. |
| Breastfeeding | No human data on presence in breast milk. Due to potential for serious adverse reactions in breastfed infants, breastfeeding is not recommended during treatment and for 1 week after final dose. |
■ FDA Black Box Warning
None
| Serious Effects |
PregnancySevere hepatic impairment (Child-Pugh Class C)Hypersensitivity to abiraterone acetate or any excipients
| Precautions | Mineralocorticoid excess (hypertension, hypokalemia, fluid retention) due to CYP17 inhibition; manage with prednisone, Adrenocortical insufficiency, Hepatotoxicity (monitor liver function tests), Cardiovascular adverse reactions (e.g., myocardial infarction, QT prolongation) |
| Food/Dietary | YONSA must be taken on an empty stomach. Avoid any food or caloric beverages from at least 2 hours before to 1 hour after dosing. Grapefruit juice may increase abiraterone levels and should be avoided. High-fat meals (e.g., breakfast with eggs, bacon, or full-fat dairy) drastically increase abiraterone absorption (up to 10-fold), leading to increased toxicity risk and must be avoided. For patients experiencing nausea, taking with water only; do not take with food or milk. |
Loading safety data…
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | YONSA (abiraterone acetate) is contraindicated in pregnancy. Based on its mechanism of action (CYP17 inhibitor) and animal studies, it can cause fetal harm. First trimester: Exposure to abiraterone, which suppresses androgen production, can disrupt fetal sexual differentiation, leading to urogenital abnormalities. Second and third trimesters: Continued androgen suppression may impair fetal growth and development. No adequate human studies exist; avoid use in pregnant women. |
| Fetal Monitoring | Monitor maternal serum electrolytes, liver function tests (ALT, AST, bilirubin), and blood pressure regularly due to mineralocorticoid excess (hypertension, hypokalemia, fluid retention). Assess for signs of adrenal insufficiency. Fetal monitoring may include ultrasound for growth and development if inadvertent exposure occurs. |
| Fertility Effects | Based on animal studies and its mechanism, YONSA may impair fertility in males by suppressing testicular androgen production, potentially reducing spermatogenesis. Female fertility may also be affected due to hormonal disruption. No specific human data available; advise reproductive-age patients and partners to use effective contraception. |
| Clinical Pearls | YONSA (abiraterone acetate) is a prodrug of abiraterone, a CYP17 inhibitor, used with prednisone for metastatic castration-resistant prostate cancer (mCRPC). Administer on an empty stomach, at least 2 hours before or 1 hour after a meal, to avoid high-fat meals that increase absorption variability and toxicity. Monitor liver function tests (ALT, AST, bilirubin) monthly due to hepatotoxicity risk. Concurrent prednisone 5 mg twice daily is required to mitigate mineralocorticoid excess (hypertension, hypokalemia, fluid retention). Check serum potassium and blood pressure regularly. Discontinue if severe hepatotoxicity (ALT >5x ULN) or if patient requires strong CYP3A4 inducers (e.g., rifampin, carbamazepine) – avoid coadministration. Dose reduction to 250 mg daily with food is not recommended; use 1,000 mg fasting. Not for use in women or children. |
| Patient Advice | Take YONSA exactly as prescribed: 1,000 mg (four 250 mg tablets) once daily on an empty stomach, at least 2 hours before or 1 hour after a meal. · Swallow tablets whole with water; do not crush or chew. · You must also take prednisone (5 mg twice daily) as directed to prevent serious side effects. · Avoid all food for at least 2 hours before and 1 hour after taking YONSA; high-fat meals can cause dangerous blood levels. · Report any signs of liver problems: yellowing of skin or eyes, dark urine, severe nausea/vomiting, abdominal pain, or unusual tiredness. · Report signs of high blood pressure (severe headache, vision changes), low potassium (muscle cramps, weakness, irregular heartbeat), or fluid retention (swelling in legs/ankles). · Do not stop taking YONSA or prednisone without consulting your doctor. · Keep all appointments for blood tests (liver function, potassium, blood pressure) as scheduled. · If you miss a dose, skip it and take the next dose at the regular time; do not double the dose. · Store YONSA at room temperature (68-77°F) away from moisture and heat. · Use effective contraception if sexually active with a female partner; YONSA can harm a fetus. |