1. Clinical Overview
Abiraterone acetate is a prodrug of abiraterone, a potent, selective, and irreversible inhibitor of cytochrome P450 17A1 (CYP17A1), an enzyme critical for androgen biosynthesis in the testes, adrenal glands, and prostate tumor tissue. It is a cornerstone of treatment for metastatic castration-resistant prostate cancer (mCRPC) and metastatic castration-sensitive prostate cancer (mCSPC) in the Indian context, used in combination with prednisone/prednisolone and androgen deprivation therapy (ADT).
| Onset | Duration | Bioavailability |
|---|---|---|
| The onset of action is not immediate; a significant reduction in serum testosterone to castrate levels (<50 ng/dL) is typically achieved within 2-4 weeks of continuous dosing. | The pharmacological effect persists as long as the drug is administered, with a terminal half-life of approximately 12-16 hours, necessitating daily dosing. | Approximately 10% under fasting conditions. Bioavailability increases significantly (up to 10-fold) when taken with a meal, especially a high-fat meal, which is why it must be taken on an empty stomach. |
2. Mechanism of Action
Abiraterone acetate is a prodrug converted to abiraterone, which irreversibly inhibits the enzyme cytochrome P450 17A1 (CYP17A1). This enzyme is expressed in testicular, adrenal, and prostatic tumor tissues and has two key activities: 17α-hydroxylase and C17,20-lyase. Inhibition of C17,20-lyase is particularly crucial as it blocks the conversion of pregnenolone and progesterone precursors into dehydroepiandrosterone (DHEA) and androstenedione, the immediate precursors to testosterone and dihydrotestosterone (DHT). This results in a profound suppression of androgen synthesis from all sources.
3. Indications & Uses
- Metastatic Castration-Resistant Prostate Cancer (mCRPC) in combination with prednisone/prednisolone.
- Metastatic Castration-Sensitive Prostate Cancer (mCSPC) (also known as metastatic hormone-sensitive prostate cancer, mHSPC) in combination with prednisone/prednisolone and androgen deprivation therapy (ADT).
4. Dosage & Administration
Adult Dosage: 1000 mg (four 250 mg tablets) orally once daily, in combination with prednisone 5 mg orally twice daily or prednisolone 5 mg orally twice daily.
Administration: Swallow tablets whole with water. Do not crush or chew. Must be taken on an EMPTY STOMACH. No food should be consumed for at least 2 hours before and at least 1 hour after taking abiraterone acetate. Dosing should be consistent with respect to food (always fasting).
5. Side Effects
Common side effects may include:
- Peripheral edema
- Hypokalemia
- Hypertension
- Fatigue/asthenia
- Arthralgia
- Hot flush
- Diarrhea
- Nausea
- Increased liver function tests (ALT, AST)
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Strong CYP3A4 Inducers (e.g., Rifampicin, Phenytoin, Carbamazepine, St. John's Wort) | Decrease abiraterone exposure significantly, potentially reducing efficacy. Coadministration is contraindicated. | Major |
| Strong CYP3A4 Inhibitors (e.g., Ketoconazole, Itraconazole, Clarithromycin, Ritonavir) | Increase abiraterone exposure. If coadministration is necessary, reduce abiraterone dose to 250 mg once daily with close monitoring. | Major |
| Drugs that lower serum potassium (e.g., Diuretics, Amphotericin B) | Increased risk of severe hypokalemia. Monitor potassium levels closely. | Moderate |
| Corticosteroids (Prednisone/Prednisolone) | Concomitant use is required. Be aware of additive immunosuppressive and hyperglycemic effects. | Moderate (Therapeutic) |
7. Patient Counselling
- DO take the tablets exactly as prescribed, usually 4 tablets (1000 mg) once daily.
- DO take it on an empty stomach. No food for 2 hours before and 1 hour after the dose.
- DO take your prescribed corticosteroid (prednisone/prednisolone) exactly as directed, usually 5 mg twice daily.
- DO NOT crush, chew, or break the tablets. Swallow whole with water.
- DO NOT take with food or a high-fat meal.
- DO NOT stop any medication without consulting your doctor.
8. Toxicology & Storage
Overdose: Limited data. Expected symptoms would be an exaggeration of known adverse effects: severe hypertension, hypokalemia, cardiac arrhythmias, and hepatotoxicity.
Storage: Store at room temperature (15°C to 30°C). Keep in the original blister pack or container to protect from moisture. Keep out of reach of children.