Abiraterone acetate (brand name Zytiga®)
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What it is
Abiraterone acetate is a pro‑drug that is converted in the body to the active compound abiraterone. The active drug blocks the enzyme CYP17A1 (17α‑hydroxylase/17,20‑lyase), which is essential for the synthesis of androgens (testosterone and dihydrotestosterone) in the testes, adrenal glands, and the tumor itself. By shutting down androgen production, it helps slow the growth of prostate cancer cells that rely on these hormones.
Primary indications
| Condition | Typical regimen (per FDA) |
|-----------|---------------------------|
| Metastatic castration‑resistant prostate cancer (mCRPC) after androgen‑deprivation therapy (ADT) | 1 g orally once daily with food plus prednisone 5 mg orally twice daily |
| Non‑metastatic castration‑resistant prostate cancer (nmCRPC) with rising PSA | 1 g orally once daily with food plus prednisone 5 mg twice daily |
| Newly diagnosed metastatic castration‑resistant prostate cancer (mCRPC) in combination with ADT | Same as above (often added earlier) |
The prednisone is essential to counteract the mineralocorticoid excess that abiraterone can cause.
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How it works (mechanism)
- Inhibits CYP17A1 → ↓ production of androgens in adrenal cortex and tumor.
- Results in reduced levels of testosterone and dihydrotestosterone in the circulation and tumor microenvironment.
- The drug has a long half‑life (≈60 h), allowing once‑daily dosing.
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Common side‑effects
| Symptom | Frequency (approx.) | How it’s managed |
|---------|---------------------|------------------|
| Hypotension, dizziness | ≤ 10 % | Monitor BP; adjust fluid status |
| Hyperkalemia / hypokalemia | ≤ 5 % | Check electrolytes weekly; give potassium supplements or diuretics |
| Fluid retention / edema | ≤ 20 % | Diuretics (e.g., furosemide) if needed |
| Elevated liver enzymes (ALT/AST) | < 5 % | Periodic LFTs; hold dose if >3× upper limit normal (ULN) |
| Fatigue, abdominal pain, nausea | ≤ 15 % | Supportive measures, anti‑emetics, dose hold if severe |
| Cataract formation (rare) | < 1 % | Ophthalmologic monitoring if symptomatic |
Black‑box warning: Severe hepatotoxicity (including fatal liver failure) has been reported, especially when drug is given with other hepatotoxic agents. Monitor liver enzymes; discontinue if ≥3 × ULN (or >2 × ULN if baseline >1.5 × ULN).
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Contraindications / cautions
- Pregnancy – teratogenic; contraindicated.
- Severe hepatic impairment (Child‑Pugh C).
- Uncontrolled hypertension or severe cardiac disease.
- Active severe infection (e.g., hepatitis B/C).
| Drug Interaction | Effect | Management |
|------------------|--------|------------|
| CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin) | ↑ abiraterone levels → ↑ toxicity | Reduce dose or monitor closely |
| CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin) | ↓ abiraterone levels → ↓ efficacy | Consider dose adjustment or alternative therapy |
| Steroids (e.g., prednisone, dexamethasone) | Prednisone is part of the regimen; other steroids may affect mineralocorticoid balance | Maintain prescribed prednisone dose |
| Anticoagulants (e.g., warfarin) | Minimal interaction | Monitor INR if on warfarin |
| Antiepileptics (e.g., valproate) | Minimal interaction | Standard monitoring |
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Practical points for patients
- Take with food (preferably a meal) to improve absorption.
- Take the same time daily; use a pill organizer or phone alarm.
- Prednisone: Take at the same times each day (usually 2–4 h after abiraterone).
- Hydration: Drink adequate fluids, but avoid excess salt if fluid retention is an issue.
- Monitoring:
- Blood pressure, weight, and edema daily for the first 4–6 weeks.
- Serum potassium and liver enzymes every 2–4 weeks during the first 3 months, then every 3 months.
- PSA levels and imaging per oncologist’s schedule.
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Frequently asked questions
| Q | A |
|---|---|
| Will it cure prostate cancer? | No, it is a palliative therapy that slows disease progression. |
| Can I skip doses? | No. Skipping can reduce effectiveness and increase risk of adrenal insufficiency. |
| Do I need to stop the drug if I feel sick? | Do not stop abruptly. Contact your oncologist or pharmacist if severe side‑effects appear. |
| Is the drug safe during breastfeeding? | Not studied; avoid if possible. |
| Can it interact with my other medications (e.g., statins, antihypertensives)? | Statins are generally safe; antihypertensives may need dose adjustment due to fluid retention/hypertension. |
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Bottom line
Abiraterone acetate (Zytiga) is a key drug in the modern management of advanced prostate cancer. By dramatically cutting androgen production, it helps control tumor growth. Success hinges on strict adherence, regular monitoring, and managing side‑effects—especially those related to mineralocorticoid excess and liver function. Always discuss any concerns or new symptoms with your oncology team before making changes to your regimen.