Zytiga
Metastatic castration-resistant prostate cancer (mCRPC); Metastatic high-risk castration-sensitive prostate cancer (mCSPC) โ in combination with prednisone.
1,000 mg orally once daily (original tabs, taken on empty stomach)
Must be taken with prednisone 5 mg orally twice daily (mCRPC) or with prednisone 5 mg daily (mCSPC)
Empty stomach: No food 2 hours before and 1 hour after dose
Continue LHRH analogue or have had orchiectomy
Hepatic impairment (Child-Pugh B): 250 mg once daily
Tablets: 250 mg, 500 mg (original formulation); Fine particle tablets: 500 mg (Yonsaยฎ formulation)
Use in pregnant women or women who may become pregnant (contraindicated due to mechanism).
- Mineralocorticoid Excess: Hypertension (22%), hypokalemia (17%), fluid retention/edema (27%). Co-administration with prednisone mitigates these effects. Monitor BP, potassium, and fluid status monthly.
- Adrenocortical Insufficiency: May occur if prednisone is interrupted, during infection/stress, or post-treatment. Monitor for symptoms.
- Hepatotoxicity: Grade 3-4 ALT/AST elevations in 6%. Monitor LFTs every 2 weeks ร 3 months, then monthly. Withhold if ALT/AST >5ร ULN.
- Food Effect: Cmax and AUC increase up to 17-fold and 10-fold with food. MUST be taken fasting.
Fatigue (39%), joint swelling/discomfort (30%), edema (27%), hot flush (22%), diarrhea (22%), hypertension (22%), nausea (22%), hypokalemia (17%), upper respiratory tract infection (13%), cough (11%), headache (12%), urinary tract infection (12%)
Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.
Abiraterone acetate is a prodrug converted to abiraterone, a selective inhibitor of CYP17A1 (17ฮฑ-hydroxylase/C17,20-lyase). CYP17A1 is expressed in testicular, adrenal, and prostatic tumor tissues and is required for androgen biosynthesis. Inhibition of CYP17A1 blocks the conversion of pregnenolone and progesterone to their 17ฮฑ-hydroxy derivatives and subsequently to DHEA and androstenedione, suppressing androgen production from all three sources. Prednisone co-administration compensates for increased mineralocorticoid levels resulting from CYP17A1 blockade.
Tmax (abiraterone): 2 hours after abiraterone acetate. Half-life: approximately 12 hours. Protein binding: >99%. Metabolized by esterases (prodrug โ abiraterone) and CYP3A4/SULT2A1 (abiraterone โ inactive metabolites). Excreted in feces (88%) and urine (5%).
Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.
- COU-AA-301 โ Abiraterone + prednisone vs. placebo + prednisone in post-docetaxel mCRPC. Phase III, n=1195.
- COU-AA-302 โ Abiraterone + prednisone vs. placebo + prednisone in chemo-naรฏve mCRPC. Phase III, n=1088.