Introduction
Abiraterone acetate is an oral antiandrogen medication used primarily in the treatment of prostate cancer. It represents a significant advancement in hormonal therapy for advanced prostate cancer by targeting androgen biosynthesis at its source. Marketed under the brand name Zytiga®, abiraterone was approved by the FDA in 2011 and has since become a cornerstone in the management of metastatic castration-resistant prostate cancer.
Mechanism of Action
Abiraterone is a selective inhibitor of cytochrome P450 17A1 (CYP17A1), a critical enzyme in androgen biosynthesis. CYP17A1 mediates two essential reactions: 17α-hydroxylase and 17,20-lyase activities. By inhibiting this enzyme, abiraterone effectively blocks the conversion of pregnenolone and progesterone to their 17α-hydroxy derivatives and subsequent conversion to dehydroepiandrosterone (DHEA) and androstenedione, which are precursors to testosterone and dihydrotestosterone (DHT). This action suppresses androgen production not only in the testes but also in adrenal glands and prostate cancer tissues themselves.
Indications
- Metastatic castration-resistant prostate cancer (mCRPC) in combination with prednisone
- Metastatic high-risk castration-sensitive prostate cancer (mCSPC) 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 guidelines:- Take on an empty stomach (at least 1 hour before or 2 hours after meals)
- Swallow tablets whole with water
- Do not crush or chew tablets
- Hepatic impairment: Reduce dose to 250 mg daily for moderate impairment (Child-Pugh Class B)
- Severe hepatic impairment: Use is not recommended
- Renal impairment: No dosage adjustment necessary
Pharmacokinetics
Absorption: Time to peak plasma concentration: 2 hours; increased exposure when taken with food Distribution: >99% bound to human plasma proteins; apparent volume of distribution: 19,669 L Metabolism: Extensive hepatic metabolism via CYP3A4 (major) and SULT2A1; active metabolite: Δ(4)-abiraterone (N-abiraterone) Elimination: Half-life: 12 hours; fecal excretion (88%; 55% as unchanged drug); renal excretion (5%)Contraindications
- Pregnancy (may cause fetal harm)
- Women who are or may become pregnant
- Severe hepatic impairment (Child-Pugh Class C)
- Hypersensitivity to abiraterone or any component of the formulation
Warnings and Precautions
Cardiovascular effects: Hypertension, hypokalemia, and fluid retention due to mineralocorticoid excess; monitor blood pressure and serum potassium regularly Hepatotoxicity: Can cause serious liver injury; monitor liver function tests at baseline, every two weeks for first three months, and monthly thereafter Adrenal insufficiency: May occur with concomitant corticosteroid withdrawal or stress Skeletal muscle effects: Myopathy and rhabdomyolysis have been reported QTc prolongation: May occur at supratherapeutic dosesDrug 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; use with caution and monitor for toxicity Drugs that prolong QTc interval: Additive effects possible; use with caution Corticosteroids: Synergistic effects when used with prednisone as indicatedAdverse Effects
Very common (≥10%):- Fatigue (39%)
- Arthralgia (28%)
- Hypertension (27%)
- Nausea (22%)
- Edema (27%)
- Hypokalemia (17%)
- Elevated ALT/AST (11%)
- Hot flush (19%)
- Hepatotoxicity
- Cardiac failure
- Adrenal insufficiency
- Severe hypokalemia
- Rhabdomyolysis
- QT prolongation
Monitoring Parameters
Baseline:- Liver function tests (ALT, AST, bilirubin)
- Serum electrolytes (especially potassium)
- Blood pressure
- ECG (if risk factors for QTc prolongation)
- PSA levels
- Testosterone levels
- Liver function: Every 2 weeks for first 3 months, then monthly
- Serum potassium: Weekly for first month, then monthly
- Blood pressure: Weekly for first month, then monthly
- PSA: Every 3-4 months
- Symptoms of adrenal insufficiency
- Signs of fluid retention
Patient Education
- Take medication on an empty stomach as directed
- Do not stop prednisone unless instructed by your healthcare provider
- Report any signs of liver problems (yellowing of skin/eyes, dark urine, abdominal pain)
- Monitor blood pressure regularly if advised by your doctor
- Report muscle pain, weakness, or cramps immediately
- Use effective contraception during treatment and for 3 weeks after discontinuation
- Inform all healthcare providers about abiraterone use before starting new medications
- Keep all scheduled follow-up appointments for monitoring
References
1. Ryan CJ, Smith MR, Fizazi K, et al. Abiraterone acetate for metastatic prostate cancer progressing after docetaxel chemotherapy: a multinational, randomized, double-blind, placebo-controlled phase 3 study. Lancet. 2011;377(9764):813-822.
2. Fizazi K, Scher HI, Molina A, et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012;13(10):983-992.
3. US Food and Drug Administration. Zytiga (abiraterone acetate) prescribing information. Revised 2022.
4. National Comprehensive Cancer Network. Prostate Cancer Guidelines. Version 4.2023.
5. Attard G, Reid AHM, Yap TA, et al. Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. J Clin Oncol. 2008;26(28):4563-4571.
6. Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2019;381(1):13-24.
This information is intended for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for personalized medical guidance.