Products
Abiraterone is commercially available in the form of film-coated tablets (Zytiga). It has been approved in many countries since 2011.
Structure and properties
Abiraterone acetate (C26H33NO2, Mr = 391.5 g/mol) exists as a white crystalline powder that is practically insoluble in water. It is a prodrug and is rapidly biotransformed in the body to the active metabolite abiraterone. The reason for administering the prodrug is the increased bioavailability of the precursor.
Effects
Abiraterone (ATC L02BX03) inhibits CYP17 in the testes, adrenals, and prostate tumor tissue, leading to blockade of the synthesis of androgens such as testosterone and dihydrotestosterone. Unlike ketoconazole, it is more selective. Androgens provide a growth stimulus for tumor cells. Abiraterone inhibits hormone-dependent tumor growth.
Indications
For the treatment of advanced metastatic prostate cancer. Abiraterone acetate is administered in combination with glucocorticoids.
Dosage
According to the SmPC. Abiraterone acetate is taken once daily. It is mandatory that it be administered fasting because food greatly increases bioavailability. It should be taken no earlier than two hours after a meal. No food should be eaten for at least one hour after taking it.
Contraindications
- Hypersensitivity
- Heart failure (NYHA III and IV)
When having sexual intercourse with a woman of childbearing potential, both a condom and another reliable method of contraception are required. Refer to the drug label for complete precautions.
Interactions
Abiraterone acetate should not be taken with food (see above). It strongly inhibits CYP1A2 and CYP2D6 and weakly inhibits CYP3A4. Concentrations of the CYP2D6 substrate dextromethorphan are greatly increased when combined.
Adverse effects
Abiraterone acetate increases mineralocorticoid levels and causes hypertension, hypokalemia, and fluid retention, among other effects. Concurrently administered glucocorticoids such as prednisone and prednisolone may reduce these side effects (hence the combination). The most common potential adverse effects include urinary tract infection, hypokalemia, hypertension, peripheral edema, hypertriglyceridemia, heart failure, angina, arrhythmia, atrial fibrillation, tachycardia, and elevated liver enzymes.
