Zytix
Generic Name : Abiraterone Acetate
Indications
Zytix is a CYP17 inhibitor indicated in combination with prednisone for the treatment of patients with
- Metastatic castration-resistant prostate cancer (CRPC).
- Metastatic high-risk castration-sensitive prostate cancer (CSPC).
Pharmacology
Abiraterone Acetate is converted in vivo to Abiraterone, an androgen biosynthesis inhibitor, 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. CYP17 catalyzes two sequential reactions:
1. The conversion of pregnenolone and progesterone to their 17 α-hydroxy derivatives by 17 α-hydroxylase activity and
2. The subsequent formation of dehydroepiandrosterone (DHEA) and androstenedione, respectively, by C17, 20 lyase activity. DHEA and androstenedione are androgens and are precursors of testosterone. Inhibition of CYP17 by Abiraterone can also result in increased mineralocorticoid production by the adrenals. Androgen sensitive prostatic carcinoma responds to treatment that decreases androgen levels. Androgen deprivation therapies, such as treatment with GnRH agonists or orchiectomy, decrease androgen production in the testes but do not affect androgen production by the adrenals or in the tumor.
Abiraterone Acetate decreased serum testosterone and other androgens in patients in the placebo-controlled clinical trial. It is not necessary to monitor the effect of Abiraterone Acetate on serum testosterone levels. Changes in serum prostate specific antigen (PSA) levels may be observed but have not been shown to correlate with clinical benefit in individual patients.
Dosage & Administration
Recommended Dose For Metastatic CRPC: The recommended dose of Abiraterone Acetate is 1,000 mg (two 500 mg tablets or four 250 mg tablets) orally once daily with Prednisone 5 mg orally twice daily.
Recommended Dose For Metastatic High-Risk CSPC: The recommended dose of Abiraterone Acetate is 1,000 mg (two 500 mg tablets or four 250 mg tablets) orally once daily with Prednisone 5 mg administered orally once daily.
Patients receiving Abiraterone Acetate should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy. Abiraterone Acetate must be taken on an empty stomach, at least one hour before or at least two hours atier a meal. The tablets should be swallowed whole with water. Do not crush or chew tablets.
Dose Modification:
- For patients with baseline moderate hepatic impairment (Child-Pugh Class B), reduce the Abiraterone Acetate starting dose to 250 mg once daily.
- For patients who develop hepatotoxicity during treatment, hold Abiraterone Acetate until recovery. Retreatment may be initated at a reduced dose. Abiraterone Acetate should be discontinued if patients develop severe hepatotoxicity.
- Avoid concomitant strong CYP3A4 inducers (e.g., Phenytoin, Carbamazepine, Rifampin, Rifabutin, Rifapentine, Phenobarbital) during Abiraterone Acetate treatment. If a strong CYP3A4 inducer must be co-administered, increase the Abiraterone Acetate dosing frequency to twice a day only during the co-administration period (e.g., from 1,000 mg once daily to 1,000 mg twice a day). Reduce the dose back to the previous dose and frequency, if the concomitant strong CYP3A4 inducer is discontinued. Or, as directed by the registered physician.
Pediatric Use: The safety and effectiveness in pediatric patients have not been established.
