Abiraterone Acetate

Indications

Abiraterone Acetate 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 is an orally active inhibitor of the steroidal enzyme CYP17A1 (17 alpha-hydroxylase/C17,20 lyase). It inhibits CYP17A1 in a selective and irreversible manner via covalent binding mechanism. CYP17A1 is an enzyme that catalyzes the biosynthesis of androgen and is highly expressed in testicular, adrenal, and prostatic tumor tissue. More specifically, abiraterone inhibits the conversion of 17-hydroxyprognenolone to dehydroepiandrosterone (DHEA) by the enzyme CYP17A1 to decrease serum levels of testosterone and other androgens.

Dosage And Administration

Metastatic castration-resistant prostate cancer: Abiraterone 1,000 mg orally once daily with prednisone 5 mg orally twice daily.

Metastatic castration-sensitive prostate cancer: Abiraterone 1,000 mg orally once daily with prednisone 5 mg orally once daily.

Patients receiving Abiraterone should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy. Abiraterone must be taken on an empty stomach with water at least 1 hour before or 2 hours after a meal. Do not crush or chew tablets.

Dose Modification:

For patients with baseline moderate hepatic impairment (Child-Pugh Class B), reduce the Abiraterone starting dose to 250 mg once daily.
For patients who develop hepatotoxicity during treatment, hold Abiraterone until recovery. Retreatment may be initiated at a reduced dose. Abiraterone should be discontinued if patients develop severe hepatotoxicity.

Interaction

CYP3A4 Inducers: Avoid concomitant strong CYP3A4 inducers during Abiraterone treatment. If a strong CYP3A4 inducer must be co-administered, increase the Abiraterone dosing frequency.

CYP2D6 Substrates: Avoid co-administration of Abiraterone with CYP2D6 substrates that have a narrow therapeutic index. If an alternative treatment cannot be used, exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate.

Contraindications

Hypersensitivity to the Abiraterone acetate or to any of the excipients of Abiraterone.

Side Effects

The most common adverse reactions are fatigue, arthralgia, hypertension, nausea, edema, hypokalemia, hot flush, diarrhea, vomiting, upper respiratory infection, cough, and headache.

Pregnancy And Lactation

The safety and efficacy of Abiraterone have not been established in females. Based on findings from animal studies and the mechanism of action, Abiraterone can cause fetal harm and potential loss of pregnancy. There are no human data on the use of Abiraterone in pregnant women. The safety and efficacy of Abiraterone have not been established in females. There is no information available on the presence of abiraterone acetate in human milk, or on the effects on the breastfed child or milk production.

Precautions And Warnings

Mineralocorticoid excess: Closely monitor patients with cardiovascular disease. Control hypertension and correct hypokalemia before treatment. Monitor blood pressure, serum potassium and symptoms of fluid retention at least monthly.

Adrenocortical insufficiency: Monitor for symptoms and signs of adrenocortical insufficiency. Increased dosage of corticosteroids may be indicated before, during and after stressful situations.

Hepatotoxicity: Can be severe and fatal. Monitor liver function and modify, interrupt, or discontinue Abiraterone dosing as recommended.

Increased fractures and mortality in combination with radium Ra 223 dichloride: Use of Abiraterone plus prednisone/prednisolone in combination with radium Ra 223 dichloride is not recommended.

Embryo-Fetal Toxicity: Abiraterone can cause fetal harm. Advise males with female partners of reproductive potential to use effective contraception.

Overdose Effects

Human experience of overdose with Abiraterone is limited. There is no specific antidote. In the event of an overdose, stop Abiraterone, undertake general supportive measures, including monitoring for arrhythmias and cardiac failure and assess liver function.