ZYTIGA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZYTIGA (ZYTIGA).
Abiraterone acetate is converted in vivo to abiraterone, an androgen biosynthesis inhibitor that selectively inhibits the enzyme CYP17 (17α-hydroxylase/C17,20-lyase). This inhibition blocks androgen production in the testes, adrenal glands, and prostate tumor tissue.
| Metabolism | Primarily metabolized by CYP3A4 and to a lesser extent by CYP2D6 and CYP1A2 after hydrolysis to abiraterone. |
| Excretion | Abiraterone is primarily eliminated via hepatic metabolism with less than 1% excreted unchanged in urine. Approximately 88% of a radiolabeled dose is recovered in feces (mainly as metabolites) and about 5% in urine. |
| Half-life | The terminal elimination half-life of abiraterone is approximately 12 hours (range 9–18 hours) following oral administration, supporting twice-daily dosing. |
| Protein binding | Abiraterone is highly bound to human plasma proteins (99.8%), primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | The apparent volume of distribution (Vd/F) is approximately 14,000 L (about 200 L/kg for a 70 kg patient), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is increased approximately 5-fold when administered with a high-fat meal compared to fasting; it is recommended to be taken on an empty stomach for consistent exposure. |
| Onset of Action | Oral administration: Reduction of serum androgen levels occurs within days, but maximal clinical effect (e.g., PSA decline) may take weeks to months. |
| Duration of Action | The pharmacodynamic effect (androgen suppression) persists for the dosing interval of 12 hours; continuous therapy is required for sustained effect. |
| Action Class | Anticancer-others |
| Brand Substitutes | Zelgor 250mg Tablet, Abitate 250mg Tablet, Xbira 250mg Tablet, Zecyte 250mg Tablet, Mytera 250 Tablet |
1000 mg orally once daily on an empty stomach, at least 1 hour before or 2 hours after a meal, in combination with prednisone 5 mg orally twice daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (GFR ≥30 mL/min). Not studied in severe renal impairment (GFR <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. Child-Pugh C: Do not use. |
| Pediatric use | Not indicated for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; monitor for fluid retention, hypertension, and hypokalemia, which may be more common in elderly. Use with caution in patients with cardiovascular disease. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZYTIGA (ZYTIGA).
| Breastfeeding | No data are available on the presence of abiraterone acetate or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. The molecular weight (391.5 Da for abiraterone) suggests potential for excretion into breast milk. Due to the potential for serious adverse reactions in the breastfed infant, including androgen inhibition, women should not breastfeed during treatment and for at least 1 week after the last dose. M/P ratio is unknown. |
| Teratogenic Risk | ZYTIGA (abiraterone acetate) is contraindicated in pregnancy. Based on its mechanism of action and animal studies, it can cause fetal harm if administered to pregnant women. There are no adequate and well-controlled studies in pregnant women. Abiraterone acetate is an androgen biosynthesis inhibitor; inhibition of androgen production may cause adverse effects on fetal development, particularly male external genitalia differentiation. The highest risk is during the first trimester when organogenesis occurs, but risks persist throughout pregnancy. Pregnancy should be excluded before starting therapy. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Women who are or may become pregnant","Severe hepatic impairment (Child-Pugh class C)"]
| Precautions | ["Mineralocorticoid excess (hypertension, hypokalemia, fluid retention) due to CYP17 inhibition","Adrenocortical insufficiency","Hepatotoxicity (monitor liver function)","Increased risk of fractures and falls","Use in pregnancy: can cause fetal harm"] |
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| Fetal Monitoring | If inadvertent exposure during pregnancy occurs, fetal monitoring with ultrasound for assessment of external genitalia and overall development is recommended. Maternal monitoring includes serum blood pressure, electrolytes (particularly potassium), liver function tests (ALT, AST, bilirubin), and signs of adrenocortical insufficiency (since abiraterone increases mineralocorticoid levels). Pregnancy testing should be performed in females of reproductive potential prior to initiating therapy. |
| Fertility Effects | Abiraterone acetate may impair fertility in males based on animal studies showing reductions in sperm count and motility, and effects on male reproductive organs. In females, the drug is not indicated for use in premenopausal women, but based on its mechanism (androgen deprivation), it may disrupt ovarian function and reduce fertility. Human data are lacking; however, reversible effects on spermatogenesis and ovulation are possible. |