Oral High-risk hormone sensitive metastatic prostate cancer
Adult: In combination with prednisone or prednisolone, and androgen deprivation therapy: 1,000 mg once daily. Dose reduction, dosing interruption or discontinuation may be required according to individual safety or tolerability (refer to detailed product guideline).
Oral Metastatic castration-resistant prostate cancer
Adult: In patients with disease progression after docetaxel-based chemotherapy, or after failure of androgen deprivation therapy whom chemotherapy is not yet indicated: As conventional tab: In combination with prednisone or prednisolone: 1,000 mg once daily. As micronised tab: In combination methylprednisolone: 500 mg once daily. Dose reduction, dosing interruption or discontinuation may be required according to individual safety or tolerability (refer to detailed product guideline).
Special Patient Group
Patients taking potent CYP3A4 inducers: As conventional tab: Increase dose to 1,000 mg bid. As micronised tab: Increase dose to 500 mg bid.
Hepatic Impairment
High-risk hormone sensitive metastatic prostate cancer
Moderate (Child-Pugh Class B): 250 mg once daily. Permanently discontinue if ALT/AST increase to >5x the upper limit of normal (ULN) or total bilirubin increase to >3x ULN. Severe (Child-Pugh Class C): Contraindicated.
Metastatic castration-resistant prostate cancer
Moderate (Child-Pugh Class B): As conventional tab: 250 mg once daily. As micronised tab: 125 mg once daily. Permanently discontinue if ALT/AST increase to >5x the upper limit of normal (ULN) or total bilirubin increase to >3x ULN. Severe (Child-Pugh Class C): Contraindicated.
Administration
Should be taken on an empty stomach. Take at least 1 hr before or 2 hr after meals. Swallow whole, do not chew/crush.
Contraindications
Severe hepatic impairment. Pregnancy and lactation. Women who may become pregnant. Concomitant use with radium Ra-223.
Special Precautions
Patient with CV disease (e.g. heart failure, severe or unstable angina pectoris, recent MI, ventricular arrhythmia), diabetes. Patient subjected to unusual stress. Abiraterone formulations are not interchangeable, do not switch between products or formulations. Renal and moderate hepatic impairment.
Adverse Reactions
Significant: Increased liver enzymes (including grade 3 and 4 events); mineralocorticoid excess, hypertension, hypokalaemia, fluid retention, hypo-hyper-glycaemia, decreased bone density, myopathy, rhabdomyolysis, anaemia, sexual dysfunction. Rarely, adrenocortical insufficiency (upon withdrawal from corticosteroid combination therapy); QT prolongation, torsades de pointes. Cardiac disorders: Tachycardia, atrial fibrillation, cardiac failure, angina pectoris. Gastrointestinal disorders: Diarrhoea, dyspepsia. General disorders and administration site conditions: Peripheral oedema. Infections and infestations: Sepsis. Injury, poisoning and procedural complications: Fractures. Metabolism and nutrition disorders: Hypertriglyceridaemia. Renal and urinary disorders: Haematuria, UTI. Skin and subcutaneous tissue disorders: Rash. Potentially Fatal: Rarely, severe hepatotoxicity (e.g. fulminant hepatitis, acute liver failure).
Patients with female partners of childbearing potential must use effective birth control methods during therapy and for 3 weeks after stopping the treatment.
Monitoring Parameters
Monitor ALT, AST, and bilirubin before treatment, every 2 weeks for 3 months, and monthly thereafter. Monitor LFTs (for patient with moderate hepatic impairment) weekly for the 1st month, every 2 weeks for 2 months, and monthly thereafter. Monitor blood glucose (in patients with diabetes) during and after treatment discontinuation; serum K, blood pressure, fluid retention before treatment and monthly as necessary. Assess for signs and symptoms of adrenocorticoid insufficiency, hepatotoxicity.
Drug Interactions
Decreased serum concentration with potent CYP3A4 inducers (e.g. rifampicin, phenytoin, carbamazepine, rifapentine, rifabutin, phenobarbital). May increase the serum concentration of drugs metabolised by CYP2D6 (e.g. dextromethorphan, thioridazine, codeine, oxycodone, tramadol, metoprolol, desipramine, venlafaxine, haloperidol, propafenone, risperidone, flecainide). Increased risk of QT prolongation with class IA antiarrhythmics (e.g. quinidine, disopyramide), class III antiarrhythmics (e.g. amiodarone, sotalol, dofetilide, ibutilide), methadone, moxifloxacin, antipsychotics. Decreased therapeutic effect with spironolactone. Potentially Fatal: Increased risk of fractures and mortality with radium Ra 223.
Food Interaction
High-fat meals may increase the systemic exposure of abiraterone. Decreased serum concentration with St. John’s wort.
Action
Description: Mechanism of Action: Abiraterone, the active metabolite of abiraterone acetate, is an androgen biosynthesis inhibitor. It selectively and irreversibly inhibits 17α-hydroxylase/C17,20-lyase (CYP17), an enzyme expressed in the testicular, adrenal, and prostatic tumour tissues, which is vital for androgen biosynthesis. It inhibits the formation of the various testosterone precursors (e.g. dehydroepiandrosterone [DHEA] and androstenedione). Pharmacokinetics: Absorption: Increased systemic exposure with food. Time to peak plasma concentration: Approx 2 hours. Distribution: Volume of distribution: 19,669 ± 13,358 L. Plasma protein binding: >99% to albumin and α1-acid glycoprotein. Metabolism: Metabolised in the liver via hydroxylation into active metabolite abiraterone; further metabolised by CYP3A4 and SULT2A1 into inactive metabolites abiraterone sulfate and N-oxide abiraterone sulfate, respectively. Excretion: Mainly via faeces (approx 88%; 55% as abiraterone acetate, 22% as abiraterone); urine (approx 5%). Elimination half-life: 14.4-16.5 hours.
Chemical Structure
Abiraterone Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 132971, Abiraterone. https://pubchem.ncbi.nlm.nih.gov/compound/Abiraterone. Accessed Apr. 27, 2023.
Storage
Store below 30°C. Follow applicable procedures for receiving, handling, administration, and disposal.
L02BX03 - abiraterone ; Belongs to the class of other hormone antagonists and related agents. Used in the treatment of metastatic castration-resistant prostate cancer.
References
Abiraterone 250 mg Tablets (Axunio Pharma GmbH). MHRA. https://products.mhra.gov.uk. Accessed 07/07/2022.Abiraterone 500 mg Film-coated Tablets (Torrent Pharma [UK] Ltd.). MHRA. https://products.mhra.gov.uk. Accessed 07/07/2022.Abiraterone Sandoz 1,000 mg Film-coated Tablets (Sandoz Limited). MHRA. https://products.mhra.gov.uk. Accessed 07/07/2022.Anon. Abiraterone Acetate. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 14/03/2023.Buckingham R (ed). Abiraterone Acetate. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/07/2022.Janssen-Cilag (New Zealand) Ltd. Zytiga 250 mg, 500 mg Film-coated Tablets data sheet 15 September 2021. Medsafe. http://www.medsafe.govt.nz. Accessed 07/07/2022.Joint Formulary Committee. Abiraterone Acetate. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/07/2022.Yonsa Tablet (Sun Pharmaceuticals Industries, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 07/07/2022.Zytiga 250 mg, 500 mg Film-coated Tablets (Johnson & Johnson Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 07/07/2022.Zytiga Tablet, Film Coated (Janssen Biotech, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 07/07/2022.
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