ABIRATERONE ACETATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ABIRATERONE ACETATE (ABIRATERONE ACETATE).
Abiraterone acetate is a prodrug of abiraterone, a selective and irreversible inhibitor of cytochrome P450 17A1 (CYP17A1), an enzyme with 17α-hydroxylase and 17,20-lyase activities expressed in testicular, adrenal, and prostatic tumor tissues. Inhibition of CYP17A1 blocks androgen biosynthesis at two steps: conversion of pregnenolone and progesterone to their 17α-hydroxy derivatives (17α-hydroxylase activity) and subsequent formation of dehydroepiandrosterone (DHEA) and androstenedione (17,20-lyase activity), thereby suppressing production of androgens in the testes, adrenal glands, and prostate cancer cells.
| Metabolism | Abiraterone acetate is hydrolyzed to abiraterone (active metabolite) by esterases in the gastrointestinal tract and liver. Abiraterone is further metabolized primarily via CYP3A4 and to a lesser extent by CYP1A2 and CYP2D6, producing inactive metabolites such as abiraterone sulfate and N-oxide abiraterone sulfate. |
| Excretion | Approximately 88% of the dose is eliminated in feces (primarily as unchanged drug and metabolites) and about 5% in urine. Less than 1% is excreted unchanged in urine. |
| Half-life | Median terminal elimination half-life is 12 hours (range 8.5–17 hours) in patients with metastatic castration-resistant prostate cancer. After multiple doses, half-life supports once-daily dosing on an empty stomach. |
| Protein binding | Abiraterone is highly protein bound (>99%) to human plasma proteins, including albumin and alpha-1-acid glycoprotein (AAG). |
| Volume of Distribution | Mean apparent volume of distribution is approximately 19,669 L (or ~281 L/kg for a 70 kg individual), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is low (approximately 10%) when administered as abiraterone acetate tablets; bioavailability is increased approximately 5-fold when taken with a high-fat meal, but labeling recommends administration on an empty stomach to reduce variability. |
| Onset of Action | Onset of clinical effect is not immediate; requires continuous daily dosing. Serum testosterone suppression (to castrate levels) occurs within 2–4 weeks of starting therapy. |
| Duration of Action | Sustained androgen suppression persists as long as treatment continues. Clinical benefit duration is variable and disease-dependent; typically several months to years. |
1000 mg orally once daily on an empty stomach, at least 1 hour before or 2 hours after a meal. Administered in combination with prednisone 5 mg orally twice daily or prednisolone 5 mg orally twice daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease; use with caution. |
| Liver impairment | Child-Pugh A: 1000 mg once daily. Child-Pugh B: 250 mg once daily (reduce dose from 1000 mg to 250 mg). Child-Pugh C: Avoid use (not studied). |
| Pediatric use | Safety and efficacy not established in pediatric patients; no approved dosing available. |
| Geriatric use | No specific dose adjustment required. Greater sensitivity in elderly patients may necessitate monitoring for adverse effects such as hypertension, hypokalemia, and fluid retention. Select dose cautiously, starting at the low end of the dosing range due to potential age-related decreases in hepatic, renal, or cardiac function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ABIRATERONE ACETATE (ABIRATERONE ACETATE).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. Because of potential for serious adverse reactions in breastfed infants, women should not breastfeed during treatment and for 1 week after the last dose. M/P ratio is unknown. |
| Teratogenic Risk | Pregnancy Category X. Abiraterone acetate is contraindicated in pregnancy. In animal studies, it caused developmental toxicity including fetal malformations and embryo-fetal lethality. In humans, no controlled studies exist, but based on mechanism of action (CYP17 inhibition reducing androgen and estrogen synthesis), it is expected to cause fetal harm. Use in pregnant women is contraindicated, and females of reproductive potential must use effective contraception during treatment and for 1 week after the last dose. |
■ FDA Black Box Warning
None
| Serious Effects |
["Pregnancy (teratogenic potential)","Severe hepatic impairment (Child-Pugh class C)","Use of radium-223 dichloride concurrently or within 5 days (increased risk of fracture and mortality)"]
| Precautions | ["Mineralocorticoid excess due to increased adrenocorticotropic hormone (ACTH) feedback: hypertension, hypokalemia, fluid retention (managed by concomitant prednisone)","Adrenocortical insufficiency","Hepatotoxicity: monitor liver function tests before and during treatment","Increased risk of fractures and bone density loss due to androgen deprivation","Cardiovascular events including myocardial infarction and QT prolongation: caution in patients with history of cardiovascular disease","Urinary tract infections and hematuria","Use caution in patients with moderate to severe hepatic impairment (Child-Pugh class B or C)"] |
| Food/Dietary | Take on an empty stomach: no food should be consumed for at least 2 hours before and 1 hour after dosing. Avoid grapefruit and grapefruit juice due to potential CYP3A4 inhibition increasing drug exposure. |
Loading safety data…
| Fetal Monitoring | Monitor liver function tests (ALT, AST, bilirubin) before starting, every 2 weeks for first 3 months, and monthly thereafter. Monitor serum potassium and phosphate periodically due to mineralocorticoid excess. Monitor blood pressure and fluid balance. In pregnancy, consider fetal ultrasound for developmental assessment if exposure occurs, though drug is contraindicated. |
| Fertility Effects | Abiraterone acetate may impair fertility in males based on animal studies showing reduced spermatogenesis and effects on male reproductive organs. In humans, no specific fertility studies; however, as an androgen synthesis inhibitor, it may adversely affect spermatogenesis. Females of reproductive potential should use effective contraception. |
| Clinical Pearls | Administer on an empty stomach, at least 1 hour before or 2 hours after a meal, to avoid increased systemic exposure. Coadministration with corticosteroids (prednisone 5 mg BID) is required to mitigate mineralocorticoid excess syndrome (hypertension, hypokalemia, fluid retention). Monitor serum potassium, blood pressure, and liver function tests monthly. Discontinue if ALT >5x ULN or bilirubin >3x ULN. Avoid use with strong CYP3A4 inducers (e.g., phenytoin, rifampin). |
| Patient Advice | Take abiraterone acetate exactly as prescribed on an empty stomach; do not take with food. · You must also take prednisone twice daily as directed to prevent serious side effects. · Report symptoms of high blood pressure, fast or irregular heartbeat, leg swelling, or muscle weakness immediately. · Your liver function will be monitored with blood tests regularly; inform your doctor if you notice yellowing of skin or eyes, dark urine, or severe nausea. · Avoid grapefruit and grapefruit juice during treatment. · Men of childbearing potential must use effective contraception during and for at least 2 weeks after treatment. |