Introduction
Zytiga (abiraterone acetate) is an oral antiandrogen medication used in the treatment of prostate cancer. It represents a significant advancement in the management of castration-resistant prostate cancer (CRPC) by targeting androgen biosynthesis at its source. Approved by the FDA in 2011, Zytiga has become a cornerstone therapy for advanced prostate cancer patients.
Mechanism of Action
Abiraterone acetate is a prodrug that is hydrolyzed to abiraterone, a potent and selective inhibitor of cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17). This enzyme system is required for androgen biosynthesis in the testes, adrenal glands, and prostate tumor tissue. By inhibiting CYP17, Zytiga significantly reduces testosterone production throughout the body, depriving prostate cancer cells of the androgens they require for growth and survival.
Indications
- Metastatic castration-resistant prostate cancer (mCRPC) in combination with prednisone
- High-risk castration-sensitive prostate cancer (CSPC) in combination with prednisone
Dosage and Administration
Standard dosing: 1000 mg (four 250 mg tablets) orally once daily in combination with prednisone 5 mg orally twice daily Administration:- Take on an empty stomach (at least 1 hour before or 2 hours after food)
- Swallow tablets whole with water
- Dosing should be consistent with regard to timing
- Hepatic impairment: Not recommended in moderate or severe hepatic impairment
- Renal impairment: No dosage adjustment necessary
- Elderly: No dosage adjustment necessary
Pharmacokinetics
Absorption: Abiraterone acetate is hydrolyzed to abiraterone (active moiety) with increased exposure when taken with food Distribution: Highly protein-bound (>99%) to albumin and alpha-1 acid glycoprotein Metabolism: Primarily metabolized in the liver via CYP3A4 and SULT2A1 Elimination: Mean elimination half-life of 12 hours; primarily fecal excretion (88%) with minor renal excretion (5%)Contraindications
- Pregnancy (may cause fetal harm)
- Women who are or may become pregnant
- Patients with baseline severe hepatic impairment (Child-Pugh Class C)
- Hypersensitivity to abiraterone acetate or any component of the formulation
Warnings and Precautions
Hypertension, hypokalemia, and fluid retention: Due to mineralocorticoid excess; monitor blood pressure, serum potassium, and fluid retention symptoms Adrenal insufficiency: Monitor for symptoms, especially in stress situations Hepatotoxicity: Monitor liver function tests regularly Cardiovascular risk: Increased risk of cardiovascular events; assess cardiovascular risk before initiation Bone marrow suppression: May cause anemia and other cytopeniasDrug Interactions
Strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine): May decrease abiraterone concentrations; avoid concomitant use Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole): May increase abiraterone concentrations; avoid or use with caution Drugs that prolong QT interval: Abiraterone may cause QT prolongation; use caution with concomitant drugs that prolong QT intervalAdverse Effects
Very common (>10%):- Fatigue (39%)
- Arthralgia (28%)
- Hypertension (27%)
- Nausea (23%)
- Edema (27%)
- Hypokalemia (17%)
- Hot flush (19%)
- Diarrhea (18%)
- Vomiting (12%)
- Cough (11%)
- Adrenal insufficiency
- Severe hepatic toxicity
- Cardiovascular events (myocardial infarction, heart failure)
- Severe hypokalemia
- fractures
Monitoring Parameters
- Serum prostate-specific antigen (PSA) levels regularly
- Liver function tests at baseline, every 2 weeks for first 3 months, then monthly
- Blood pressure weekly for first 2 months, then at least monthly
- Serum potassium monthly or as clinically indicated
- Signs and symptoms of fluid retention
- Adrenal function in stress situations
- Complete blood count regularly
- ECG for QT prolongation in susceptible patients
Patient Education
- Take medication exactly as prescribed on an empty stomach
- Do not crush or chew tablets
- Report any signs of liver problems (yellowing skin/eyes, dark urine, fatigue)
- Monitor blood pressure regularly as advised by healthcare provider
- Report symptoms of low potassium (muscle weakness, cramps, irregular heartbeat)
- Inform all healthcare providers about Zytiga use
- Use effective contraception if partner is pregnant or may become pregnant
- Report any new symptoms or side effects promptly
- Do not stop prednisone without medical supervision
References
1. de Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364(21):1995-2005. 2. Fizazi K, Tran N, Fein L, et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med. 2017;377(4):352-360. 3. Zytiga [package insert]. Horsham, PA: Janssen Biotech, Inc.; 2021. 4. Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368(2):138-148. 5. National Comprehensive Cancer Network. Prostate Cancer (Version 4.2022). Accessed [date].