Abiraterone Acetate

Abiraterone acetate is an orally administered androgen biosynthesis inhibitor used in the treatment of selected advanced prostate cancers. It is a prodrug that is converted in the body to abiraterone, which inhibits CYP17, an enzyme involved in androgen production in the testes, adrenal glands and tumor tissue. By reducing androgen synthesis, abiraterone can decrease hormonal stimulation of prostate cancer cells and slow disease progression. It is generally administered together with prednisone or prednisolone, or with another corticosteroid regimen specified for the particular formulation, because inhibition of CYP17 can increase mineralocorticoid activity and lead to hypertension, low potassium and fluid retention. Abiraterone acetate is available as oral tablets, including conventional formulations and micronized formulations with different food requirements. It is used in selected patients with metastatic castration-resistant prostate cancer and, in appropriate treatment settings, metastatic high-risk castration-sensitive or hormone-sensitive prostate cancer. The medicine is usually given alongside androgen deprivation therapy when indicated. Treatment requires monitoring of liver function, blood pressure, serum potassium and signs of fluid retention. Because abiraterone can affect steroid hormone synthesis and hepatic drug metabolism, careful attention to concomitant medicines and corticosteroid administration is important.

Abiraterone acetate was developed as a targeted inhibitor of androgen biosynthesis after research demonstrated the importance of CYP17-mediated steroid production in prostate cancer progression. The U.S. Food and Drug Administration granted initial approval for Zytiga in April 2011 for metastatic castration-resistant prostate cancer in patients previously treated with docetaxel, based on the COU-AA-301 clinical programme. In 2012, FDA expanded the indication to include metastatic castration-resistant prostate cancer in patients who had not received prior chemotherapy based on the COU-AA-302 study. Subsequent regulatory developments expanded its use to selected metastatic hormone-sensitive or castration-sensitive prostate cancer settings. The European Commission granted marketing authorisation for Zytiga on 5 September 2011, with subsequent variations expanding and updating its indications. Current European product information includes newly diagnosed high-risk metastatic hormone-sensitive prostate cancer in combination with androgen deprivation therapy and metastatic castration-resistant prostate cancer in specified treatment settings. Indian regulatory records include abiraterone acetate tablets and more recent regulatory consideration of an oral suspension formulation. Multiple generic abiraterone acetate products have also received regulatory approvals in different jurisdictions. Key clinical programmes include COU-AA-301, COU-AA-302, LATITUDE and STAMPEDE.

Abiraterone acetate is used with appropriate corticosteroid therapy for selected adult men with advanced prostate cancer. In metastatic castration-resistant prostate cancer, it is used in patients whose disease has progressed despite androgen deprivation therapy, including patients who are asymptomatic or mildly symptomatic and have not yet received chemotherapy in applicable treatment settings, as well as patients whose disease has progressed during or after docetaxel-based chemotherapy. In selected newly diagnosed high-risk metastatic hormone-sensitive or castration-sensitive prostate cancer settings, abiraterone may be combined with androgen deprivation therapy and prednisone or prednisolone. The precise approved indication varies between regulatory jurisdictions and product formulations. Abiraterone is generally used as part of androgen-deprivation treatment rather than as a replacement for medical or surgical castration when continued androgen suppression is required. Treatment selection should consider disease stage, prior therapies, symptoms, comorbidities, laboratory findings and the approved indication applicable to the specific product.

Abiraterone acetate conventional tablets are commonly administered at a total dose of 1,000 mg once daily together with prednisone or prednisolone according to the approved indication. Conventional abiraterone acetate tablets should be taken on an empty stomach, generally at least two hours after food and with no food for at least one hour after administration, because food can substantially increase abiraterone exposure. The micronized formulation has different administration requirements and may be taken with or without food according to its specific prescribing information. The accompanying corticosteroid regimen varies according to the indication and product. Abiraterone should generally be continued while clinical benefit is maintained and unacceptable toxicity has not developed, with androgen deprivation therapy continued when required for the treatment setting. Dose interruption or reduction may be necessary for clinically significant liver toxicity. Patients with moderate hepatic impairment require specific dose considerations, while severe hepatic impairment is generally a contraindication for conventional abiraterone acetate. Liver function should be assessed before treatment and monitored regularly during therapy.

Common adverse effects of abiraterone acetate include fatigue, joint or muscle discomfort, hot flushes, hypertension, low potassium levels, peripheral edema and increases in liver enzymes. Other reactions may include diarrhea, nausea, vomiting, urinary tract infection, headache and changes in blood glucose or other laboratory parameters. Because abiraterone suppresses cortisol production and increases mineralocorticoid activity, some adverse effects are related to fluid retention, elevated blood pressure and electrolyte abnormalities. The accompanying corticosteroid reduces these effects but does not eliminate the need for monitoring. The frequency and severity of adverse reactions may vary according to the cancer setting, treatment combination, duration of therapy and individual patient factors. Clinically significant laboratory abnormalities or persistent symptoms may require medical evaluation, supportive treatment or adjustment of therapy.

Important serious risks associated with abiraterone acetate include severe hepatotoxicity, significant hypertension, hypokalemia, fluid retention and cardiovascular complications. Liver injury can occasionally be severe, including marked elevation of transaminases or acute liver failure, and requires prompt evaluation and appropriate treatment interruption. Mineralocorticoid excess can lead to substantial blood pressure elevation, low serum potassium and fluid accumulation, which may worsen underlying cardiovascular disease. Patients with a history of cardiovascular conditions require appropriate clinical assessment and monitoring. Abiraterone can also cause adrenal insufficiency, particularly when corticosteroid therapy is interrupted, reduced or withdrawn during physiological stress. Corticosteroid withdrawal or inadequate replacement may produce clinically significant symptoms. Rare respiratory complications and severe hypersensitivity reactions have also been reported. Treatment should be interrupted or permanently discontinued when clinically significant toxicity occurs according to the severity and applicable prescribing information.

Before starting treatment, healthcare professionals should assess liver function, blood pressure, serum potassium, fluid status and relevant cardiovascular history. Liver tests should be monitored regularly during treatment, particularly during the early months of therapy. Abiraterone inhibits CYP2D6 and CYP2C8 and can therefore increase exposure to medicines that are sensitive substrates of these enzymes, making medication review important before and during treatment. Strong CYP3A4 inducers can reduce abiraterone exposure and should generally be avoided when possible; if unavoidable, the applicable product information should be followed. Patients receiving medicines that can prolong QT interval or increase the risk of arrhythmia should be assessed carefully when hypokalemia may occur. Abiraterone should be used with the required corticosteroid regimen to reduce the consequences of mineralocorticoid excess. It is not intended for use in women, and exposure during pregnancy may cause fetal harm. Women who are pregnant or may become pregnant should not handle conventional tablets without appropriate protection. Patients should also inform healthcare professionals about all prescription medicines, supplements and other anticancer treatments.

Prescribers should confirm the exact prostate cancer setting, formulation, corticosteroid regimen and need for continued androgen deprivation therapy before initiating abiraterone acetate. Baseline evaluation should include liver function, serum potassium, blood pressure, fluid status and cardiovascular history. Liver enzymes and bilirubin should be monitored regularly, particularly during the first months of treatment, and potassium and blood pressure should be followed throughout therapy. Pharmacists should verify whether the prescribed formulation is a conventional or micronized abiraterone product because food instructions and dosing recommendations can differ. Medication reconciliation is important because abiraterone can inhibit CYP2D6 and CYP2C8 and may interact with clinically important substrates. Patients should understand the importance of taking the prescribed corticosteroid consistently and should not stop corticosteroid therapy abruptly without medical guidance. New or worsening swelling, shortness of breath, palpitations, severe weakness, jaundice or significant blood-pressure changes should prompt clinical assessment. Coordination between oncology, urology, pharmacy and laboratory teams helps maintain appropriate monitoring and management.