Abiraterone Acetate

Introduction Overview

Generic Name

abiraterone acetate

Brand Name

Zytiga; Yonsa; generic abiraterone acetate products

Dosage Form

Oral tablets. Zytiga and many generics are available as 250 mg and 500 mg tablets; Yonsa is a micronized abiraterone acetate tablet available as 125 mg.

Drug Class

Androgen biosynthesis inhibitor; CYP17 inhibitor; antineoplastic hormonal therapy for prostate cancer.

Pharmacokinetics

Absorption:
Abiraterone acetate is taken by mouth and converted to active abiraterone. Food can greatly increase abiraterone exposure with Zytiga-type tablets, so those products must be taken on an empty stomach: no food for at least 2 hours before the dose and at least 1 hour after the dose. Yonsa is a different micronized formulation and may be taken with or without food. These formulations are not interchangeable milligram-for-milligram.

Distribution:
Abiraterone is highly bound to plasma proteins, including albumin and alpha-1 acid glycoprotein, and distributes beyond the bloodstream into tissues relevant to prostate cancer treatment.

Metabolism:
Abiraterone acetate is a prodrug hydrolyzed to abiraterone. Abiraterone is then metabolized mainly in the liver. It is also a clinically important inhibitor of CYP2D6 and CYP2C8, which explains some drug interaction risks.

Elimination:
Most drug-related material is eliminated in feces, with little urinary elimination. Because hepatic metabolism is important, liver impairment and liver toxicity are central safety concerns. Severe baseline hepatic impairment is a do-not-use situation in current labeling.

Dosage Forms

Formulation-specific dosing:
- Zytiga-type abiraterone acetate tablets: 1000 mg by mouth once daily on an empty stomach.
- Yonsa: 500 mg by mouth once daily, with or without food.

Corticosteroid coadministration:
Abiraterone must be given with a corticosteroid to reduce mineralocorticoid excess and adrenal insufficiency risk. Zytiga-type products are used with prednisone. Yonsa is used with methylprednisolone 4 mg twice daily.

Common adult regimens:
- Metastatic castration-resistant prostate cancer: Zytiga-type product 1000 mg once daily with prednisone 5 mg twice daily, or Yonsa 500 mg once daily with methylprednisolone 4 mg twice daily.
- Metastatic high-risk castration-sensitive prostate cancer: Zytiga-type product 1000 mg once daily with prednisone 5 mg once daily.

Androgen deprivation therapy:
Patients receiving abiraterone should also receive a GnRH analog or have had bilateral orchiectomy unless a clinician documents another appropriate castration strategy.

Administration:
Swallow tablets whole with water. Do not crush or chew. Pregnant patients or people who may become pregnant should not handle crushed, broken, or damaged tablets without protection.

Mechanism Of Action

Abiraterone acetate is converted to abiraterone, which inhibits CYP17A1. CYP17A1 has 17 alpha-hydroxylase and C17,20-lyase activities that are needed for androgen production in the testes, adrenal glands, and prostate tumor tissue.

By blocking CYP17A1, abiraterone lowers production of testosterone and other androgens that activate the androgen receptor. Prostate cancer cells often depend on androgen receptor signaling for growth and survival, even after standard medical or surgical castration.

For students, the key idea is: standard androgen deprivation lowers testicular androgen production, while abiraterone further blocks androgen synthesis from adrenal and tumor sources. The corticosteroid is not optional; it helps control the mineralocorticoid imbalance caused by upstream CYP17 blockade.

Pharmacological Actions

Inhibits CYP17A1, an enzyme required for androgen biosynthesis.
Reduces testosterone and other androgen levels from testicular, adrenal, and intratumoral sources.
Decreases androgen receptor stimulation in prostate cancer cells.
Improves outcomes in metastatic castration-resistant prostate cancer when combined with corticosteroid therapy.
Improves outcomes in metastatic high-risk castration-sensitive prostate cancer when combined with androgen deprivation therapy and prednisone.
Can cause mineralocorticoid excess because steroid precursors are redirected upstream of CYP17 blockade.

Therapeutic Or Clinical Uses

Metastatic castration-resistant prostate cancer, in combination with prednisone or methylprednisolone depending on formulation.
Metastatic high-risk castration-sensitive prostate cancer, in combination with prednisone and ongoing androgen deprivation therapy.
Used in adults with prostate cancer; safety and effectiveness are not established in pediatric patients.
Not used as monotherapy because corticosteroid coadministration is needed to reduce predictable endocrine toxicities.

Side Or Adverse Effects

Hypertension, hypokalemia, and fluid retention from mineralocorticoid excess.
Peripheral edema, hot flushes, fatigue, weakness, and joint or muscle discomfort.
Nausea, vomiting, diarrhea, dyspepsia, or abdominal discomfort.
Elevated liver enzymes and hepatotoxicity, including rare severe liver injury.
Adrenocortical insufficiency, especially if corticosteroids are interrupted or during infection, surgery, or other stress.
Cardiac events such as arrhythmia, heart failure, or ischemic heart disease in susceptible patients.
Urinary tract infection, cough, upper respiratory symptoms, headache, and anemia may occur.
Severe hypoglycemia has been reported when abiraterone is used with some antidiabetic drugs such as pioglitazone or repaglinide.
Fracture risk increases when abiraterone plus prednisone is used with radium Ra 223 dichloride; this combination is not recommended outside clinical trials.

Precautions

Check blood pressure, serum potassium, and fluid status before treatment and monitor at least monthly.
Control hypertension and correct hypokalemia before and during therapy.
Monitor liver function tests before treatment, every 2 weeks for the first 3 months, monthly thereafter, and promptly if symptoms suggest liver injury.
Use caution in patients with heart failure, recent myocardial infarction, ventricular arrhythmia, or other significant cardiovascular disease.
Do not use in severe hepatic impairment. Use formulation-specific dose adjustment and close monitoring in moderate hepatic impairment if treatment is appropriate.
Do not substitute Yonsa and Zytiga-type tablets milligram-for-milligram because exposure differs.
Review all medicines for CYP3A inducer, CYP2D6 substrate, and CYP2C8 substrate interactions.
Use effective contraception if a male patient with a female partner of reproductive potential is taking abiraterone.
Do not stop the corticosteroid suddenly unless directed; adrenal insufficiency can occur.

Warnings

Mineralocorticoid excess can cause hypertension, hypokalemia, and fluid retention.
Adrenocortical insufficiency can occur, especially after steroid interruption or during physiologic stress.
Hepatotoxicity can be severe; treatment interruption, dose reduction, or discontinuation may be required.
Severe hypoglycemia can occur in patients with diabetes taking certain antidiabetic drugs.
Increased fractures and mortality were seen when abiraterone plus prednisone was combined with radium Ra 223 dichloride; use together is not recommended outside clinical trials.
Abiraterone can cause fetal harm based on its mechanism of action and animal data.
Zytiga-type tablets must be taken on an empty stomach because food can markedly increase exposure and toxicity risk.

Contraindication

Pregnancy. Abiraterone acetate can cause fetal harm and is not indicated for use in females.

Other situations, such as severe hepatic impairment, strong interacting medicines, cardiovascular disease, or radium Ra 223 combination, are serious warnings, precautions, or not-recommended uses rather than the main label-listed formal contraindication.

Drug Interactions

Strong CYP3A inducers, such as rifampin, carbamazepine, phenytoin, phenobarbital, or St. John's wort, can lower abiraterone exposure and should generally be avoided.
Abiraterone inhibits CYP2D6; use caution with CYP2D6 substrates that have a narrow therapeutic index.
Abiraterone inhibits CYP2C8; avoid or closely monitor CYP2C8 substrates with narrow therapeutic index.
Pioglitazone and repaglinide may increase severe hypoglycemia risk when used with abiraterone.
Radium Ra 223 dichloride with abiraterone plus prednisone is not recommended outside clinical trials because of fracture and mortality risk.
Mineralocorticoid effects may complicate therapy with drugs affected by potassium changes, blood pressure, or fluid balance.

Preparations Of The Drug

Zytiga tablets: abiraterone acetate 250 mg and 500 mg.
Generic abiraterone acetate tablets: product-specific 250 mg and/or 500 mg strengths depending on manufacturer.
Yonsa tablets: micronized abiraterone acetate 125 mg.
Zytiga-type tablets are taken fasting; Yonsa may be taken with or without food.
Yonsa and Zytiga-type products are not interchangeable because dosage and systemic exposure differ.
Store according to product labeling and keep tablets out of reach of children and pregnant individuals.

Student Key Points

Abiraterone blocks CYP17, lowering androgen production beyond standard castration.
Always pair it with the correct corticosteroid for the formulation.
Zytiga-type products are fasting-only; Yonsa can be taken with or without food.
Do not swap Yonsa and Zytiga milligram-for-milligram.
Watch the triad of mineralocorticoid excess: hypertension, hypokalemia, and fluid retention.
Liver tests, potassium, blood pressure, and fluid status are core monitoring items.