Abiraterone acetate is an androgen biosynthesis inhibitor. It is converted to abiraterone in vivo that inhibits 17 α-hydroxylase/C17,20-lyase (CYP17). This enzyme is expressed in testicular, adrenal, and prostatic tumor tissues and is required for androgen biosynthesis. Androgen sensitive prostatic carcinoma responds to androgen-lowering therapy. Androgen deprivation therapies, such as GnRH agonist treatment or orchiectomy, reduce androgen production in the testes but have no effect on androgen production in the adrenals or the tumor.
Abiraterone acetate is indicated for use in combination with prednisone for the treatment of patients with-
- metastatic castration-resistant prostate cancer who have received prior chemotherapy containing docetaxel.
- Recommended dose: Abiraterone 1,000 mg taken orally once daily in conjunction with prednisone 5 mg taken orally twice daily. Abiraterone should be consumed on an empty stomach. No food should be consumed for at least two hours before the Abiraterone dose and for at least one hour after the Abiraterone dose.
- Reduce the Abiraterone starting dose to 250 mg once daily for patients with baseline moderate hepatic impairment (Child-Pugh Class B).
- Hold Abiraterone for patients who develop hepatotoxicity during treatment until they recover. Retreatment may be started at a lower dose. If patients develop severe hepatotoxicity, Abiraterone should be stopped.
The most common adverse reactions (≥ 5%) are-
- joint swelling or discomfort
- muscle discomfort
- hot flush
- urinary tract infection
- urinary frequency
- upper respiratory tract infection
Mineralocorticoid excess: In patients with a history of cardiovascular disease, use Abiraterone with caution. Abiraterone's safety in patients with LVEF 50% or NYHA Class III or IV heart failure has not been established. Prior to treatment, control hypertension and correct hypokalemia. At least once a month, check your blood pressure, serum potassium, and symptoms of fluid retention.
Adrenocortical insufficiency: Keep an eye out for adrenocortical insufficiency symptoms and signs. Corticosteroid dosage should be increased before, during, and after stressful situations.
Hepatotoxicity: Increases in liver enzymes have resulted in drug discontinuation, dose modification, and/or interruption. Monitor liver function and adjust, interrupt, or stop Abiraterone dosing as needed.
Food Effect: Abiraterone should be consumed on an empty stomach. When abiraterone acetate is taken with meals, the exposure (area under the curve) of abiraterone increases up to tenfold.