Abiraterone

ABIRATERONE ACETATE — CLINICIAN SUMMARY

🔴 RED FLAG (IMPORTANT) INFORMATION

(Main things to consider when using this drug)

• Must be co-prescribed with prednisone/prednisolone (10 mg daily) → prevents mineralocorticoid excess and adrenal insufficiency.

• Take on an empty stomach → food increases absorption up to 10×, markedly increasing toxicity.

• Monitor liver function closely, especially in the first 3 months → risk of severe hepatotoxicity.

• Monitor potassium and blood pressure regularly → risk of hypertension, hypokalaemia, and fluid retention.

• Avoid in severe hepatic impairment.

1. BASIC INFORMATION

Generic name: Abiraterone acetate
Formulation: Uncoated oral tablets
Strength: 250 mg

Mechanism of action:
Selective inhibition of CYP17 (17α-hydroxylase/C17,20-lyase) → suppression of androgen synthesis in adrenal glands, testes, and prostate tumour tissue → reduced testosterone levels and tumour control.

2. INDICATIONS

Prostate cancer

• Metastatic castration-resistant prostate cancer (mCRPC) — with prednisone/prednisolone

• Metastatic hormone-sensitive prostate cancer (mHSPC) — with ADT ± prednisone

• Pre- or post-chemotherapy settings depending on disease course

3. DOSING & ADMINISTRATION

Dose:

• 1000 mg once daily (4 × 250 mg tablets)

Route:

• Oral

Administration:

• Take on an empty stomach (≥1 hour before or ≥2 hours after food)

• Swallow tablets whole with water

• Must be given with prednisone/prednisolone 10 mg daily

• Do not take with food

• Continue until disease progression or unacceptable toxicity

Initiation and supervision by a clinician experienced in prostate cancer management.

4. DOSE MODIFICATIONS

Hepatic toxicity:

• ALT/AST >5 × ULN or bilirubin >3 × ULN → withhold

• Resume at 500 mg daily only once LFTs normalise

• Permanently discontinue if severe or recurrent

Mineralocorticoid excess (hypertension, hypokalaemia, oedema):

• Optimise BP and potassium before resuming

• Potassium supplementation and antihypertensives may be required

• Avoid spironolactone

Severe adverse events (e.g. acute liver failure, serious cardiac events):

• Permanently discontinue

5. CO-MEDICATIONS / INTERACTIONS

Required:

• Prednisone or prednisolone 10 mg daily

Avoid or use with caution:

• Strong CYP3A4 inducers (rifampicin, carbamazepine, phenytoin)

• CYP2D6 substrates with narrow therapeutic index (e.g. metoprolol, codeine, tramadol)

• Spironolactone (androgen receptor agonist activity)

• St John’s Wort

• Food intake around dosing

6. CONTRAINDICATIONS

• Hypersensitivity to abiraterone or excipients

• Severe hepatic impairment

• Concomitant use with Radium-223

• Paediatric patients (<18 years)

7. MONITORING REQUIREMENTS

Baseline and ongoing:

• Blood pressure, weight, oedema — each visit

• Serum potassium — baseline and monthly (target ≥4.0 mmol/L)

• Liver function tests — baseline, every 2 weeks for first 3 months, then monthly

• Renal function — baseline and periodically

• FBC — periodically

• Blood glucose — especially if diabetic or steroid-treated

• PSA and clinical response — every 1–3 months

8. SIDE EFFECTS & MANAGEMENT

Very common (>10%):

• Hypertension

• Hypokalaemia

• Oedema

• Elevated liver enzymes

• Fatigue

• Diarrhoea, dyspepsia

Common (1–10%):

• Rash

• Arthralgia

• Urinary tract infection

• Hypertriglyceridaemia

• Fluid retention

• Bone fractures

Serious (<5%):

• Acute liver failure

• Cardiac failure, arrhythmia, myocardial infarction

• Severe hypokalaemia

• Sepsis

• Severe allergic reactions

Rare / uncommon:

• Adrenal insufficiency

• Non-alcoholic fatty liver disease

• Interstitial pneumonitis

9. USE IN SPECIAL POPULATIONS

Hepatic impairment:

• Contraindicated if severe

• Dose reduction required if moderate

Renal impairment:

• No adjustment for mild–moderate impairment

• Use caution in severe impairment

Elderly:

• No dose adjustment required

Cardiovascular disease:

• Use with caution; close monitoring recommended

10. DURATION OF USE / WHEN TO STOP

Continue until:

• Disease progression (clinical or radiographic), or

• Unacceptable toxicity

Permanently discontinue if:

• ALT/AST >5 × ULN or bilirubin >3 × ULN despite dose interruption

• Life-threatening hepatic or cardiac events

• Recurrent severe toxicity despite optimal management

https://pi-pil-repository.sahpra.org.za/wp-content/uploads/2023/08/pil-protyga-21072023.pdf https://activo.co.za/downloads/pi/Protyga-PI.pdf