Abiraterone Acetate

Indications

Abiraterone is a CYP17 inhibitor indicated in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer.

Therapeutic Class

Cytotoxic Chemotherapy

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 & Administration

The recommended dose of Abiraterone is 1,000 mg (four 250 mg tablets) administered orally once daily in combination with prednisone 5 mg administered orally twice daily. Abiraterone must be taken on an empty stomach. No food should be consumed for at least two hours before the dose of Abiraterone is taken and for at least one hour after the dose of Abiraterone is taken. The tablets should be swallowed whole with water. Do not crush or chew tablets.

Contraindications

Hypersensitivity to the Abiraterone acetate or to any of the excipients of Abiraterone. Women who may potentially be pregnant.

Side Effects

Hypertension, Hypokalemia, and Fluid Retention due to Mineralocorticoid Excess, Adrenocortical Insufficiency  Hepatotoxicity

Pregnancy & Lactation

There are no human data on the use of Abiraterone in pregnancy and it is not for use in women of childbearing potential. Maternal use of a CYP17 inhibitor is expected to produce changes in hormone levels that could affect development of the foetus.

Pregnancy: Abiraterone is not for use in women. Abiraterone acetate is contraindicated in women who are or may potentially by pregnant (see Pharmacology: Toxicology: Preclinical Safety Data under Actions and Contraindications).

Breast feeding: Abiraterone is not for use in women. It is not known if either abiraterone acetate or its metabolites are excreted in human milk

Precautions

Abiraterone may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition. In the two randomized clinical trials, grade 3 to 4 hypertension occurred in 2% of patients, grade 3 to 4 hypokalemia in 4% of patients, and grade 3 to 4 edema in 1% of patients treated with Abiraterone

Overdose Effects

There have been no reports of overdose during clinical studies. There is no specific antidote. In the event of an overdose, administration should be withheld and general supportive measures undertaken, including monitoring for arrhythmias, hypokalaemia and for signs and symptoms of fluid retention. Liver function also should be assessed.

Storage Conditions

Store below 30°C.

Available Brand Names