Calcent

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).

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.

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.

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

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.

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.

Cytotoxic Chemotherapy

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.

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.