Abiraterone Acetate

Registered South African indications:

• Metastatic advanced prostate cancer (castration resistant prostate cancer)

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy or potential pregnancy
• Severe hepatic impairment
• Coadministration with prednisone or prednisolone in combination with Ra-223 (see additional prescribing points)

Cautions

• Severe renal impairment
• Moderate hepatic impairment
• Patients whose underlying medical conditions might be compromised by increases in blood pressure
• History of cardiovascular disease
• Uncontrolled hypertension
• Hypokalaemia
• Pre-existing fluid retention
• Severe or unstable angina pectoris
• Recent myocardial infarction
• Ventricular arrhythmia
• Clinically significant heart disease
• Myocardial infarction or arterial thrombotic events within last 6 months
• New York Heart Association Class III or IV heart failure
• New York Heart Association Class II-IV heart failure
• Cardiac ejection fraction <50% (e.g left ventricular ejection fraction (LVEF) <50%)
• Atrial fibrillation or other cardiac arrhythmia requiring medical therapy
• Significant risk for congestive cardiac failure
  - History of cardiac failure
  - Uncontrolled hypertension
  - Ischaemic heart disease
• Active or symptomatic viral hepatitis
• Patients who are withdrawn from prednisone or prednisolone
• Previous treatment with ketoconazole for prostate cancer
• Diabetes  
• Bone density disorders
• Anaemia  
• Sexual dysfunction  
• Myopathy and/or history of rhabdomyolysis
• Coadministration with chemotherapy
• Sodium controlled diet
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption

Forms avail. in SA and covered in this monograph: tab

Used for the treatment of

• Metastatic advanced prostate cancer (additional agent required) 
  - Newly diagnosed high risk metastatic hormone sensitive prostate cancer in combination with androgen deprivation therapy
  - Metastatic castration resistant prostate cancer in patients who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom combination chemotherapy is not yet clinically indicated
  - Metastatic castration resistant prostate cancer whose disease has progressed on or after a docetaxel-based chemotherapy regimen

Consult specialist for dosages and regimens

Not indicated for use in children

Pregnancy

• Contraindicated
• Abiraterone acetate is not for use in women and is contraindicated in women who are or may potentially be pregnant. There is no human data on the use of abiraterone acetate in pregnancy and this medicine is not for use in women of childbearing potential. Studies in animals have shown reproductive toxicity
• It is not known whether abiraterone or its metabolites are present in semen. A condom is required if the patient is engaged in sexual activity with a pregnant woman. If the patient is engaged in sex with a woman of childbearing potential, a condom is required along with another effective contraception method

Breastfeeding

• Not indicated for use in women
• Abiraterone acetate is not indicated for use in women

Fertility

• Abiraterone affected fertility in male and female rats, but these effects were fully reversible

Renal Impairment

• Mild to moderate: No dose adjustment recommended
• Severe: Caution; no information available
  There is no clinical experience in patients with prostate cancer and severe renal impairment

Hepatic Impairment

• Mild (Child-Pugh Class A): No dose adjustment necessary
  Moderate (Child-Pugh Class B): Caution; no information available
  No dose adjustment can be predicted as there is no data on the clinical safety and efficacy of abiraterone in these patients. Use of abiraterone in moderate hepatic impairment should be cautiously assessed and the benefit should outweigh the possible risks
• Severe (Child-Pugh Class C): Contraindicated

Elderly

• No dose adjustment recommended
  Incidence and severity of adverse effects may be increased in patients ≥75 years

Porphyria Information

• Not yet classified (NC)

Drugs in Sport

• Permitted - No warnings

Cardiovascular Disorders

• Cardiac failure
  - Congestive heart failure
  - Left ventricular dysfunction
  - Decreased ejection fraction
• Angina pectoris
• Arrhythmia
• Atrial fibrillation
• Tachycardia
• Myocardial infarction
• QT prolongation
• Hypertension

Respiratory Disorders

• Allergic alveolitis

Gastrointestinal Disorders

• Diarrhoea
• Dyspepsia

Hepatobiliary Disorders

• Increased alanine aminotransferase  
• Increased aspartate aminotransferase
• Abnormal hepatic function
• Hepatitis fulminant
• Acute hepatic failure

Genitourinary Disorders

• Urinary tract infection
• Haematuria
• Sexual dysfunction

Endocrine and Metabolic Disorders

• Adrenal insufficiency
• Hypokalaemia
• Hypertriglyceridaemia

Musculoskeletal Disorders

• Myopathy
• Rhabdomyolysis
• Fractures
• Osteoporosis

Skin and Subcutaneous Tissue Disorders

• Rash

Immune, Blood and Lymphatic System Disorders

• Sepsis
• Peripheral oedema
• Anaemia

• Prednisone/prednisolone in combination with Ra-223 (see additional prescribing points)
• CYP3A4 inducers 
• Phenytoin
• Carbamazepine
• Rifampicin
• Rifabutin
• Rifapentine
• Phenobarbital
• St John's wort (Hypericum perforatum)
• CYP3A4 inhibitor
• CYP2D6 substrates
• Dextromethorphan
• Metoprolol
• Propranolol
• Desipramine
• Venlafaxine
• Haloperidol
• Risperidone
• Propafenone
• Flecainide
• Codeine
• Oxycodone
• Tramadol
• CYP2C8 substrates
• Pioglitazone
• Repaglinide
• OATP1B1 substrates
• QT-prolonging agents
• Agents able to induce torsades de pointes
• Class IA antiarrhythmics
• Quinidine
• Disopyramide
• Class III antiarrhythmics
• Amiodarone
• Sotalol
• Dofetilide
• Ibutilide
• Methadone
• Moxifloxacin
• Antipsychotics
• Spironolactone 
• Coadministration with agents known to be associated with myopathy/rhabdomyolysis
• Cardiac glycosides
• Food

• Hepatic function
• Serum potassium
• Blood pressure

None routine. Specific cases may require

• Blood glucose
• ECG

Combination of abiraterone and prednisone/prednisolone with Ra-223

• Treatment with abiraterone and prednisone/prednisolone in combination with Ra-223 is contraindicated due to an increased risk of fractures and a trend for increased mortality among asymptomatic or mildly symptomatic prostate cancer patients as observed in clinical trials
• It is recommended that subsequent treatment with Ra-223 is not initiated for at least 5 days after the last administration of abiraterone acetate in combination with prednisone/prednisolone

Abiraterone acetate is converted in vivo to abiraterone, an androgen biosynthesis inhibitor. Specifically, abiraterone selectively inhibits the enzyme 17α-hydroxylase/C17,20-lyase (CYP17). This enzyme is expressed in and is required for androgen biosynthesis in testicular, adrenal and prostatic tumour tissues. CYP17 catalyses the conversion of pregnenolone and progesterone into testosterone precursors, DHEA and androstenedione, respectively, by 17α-hydroxylation and cleavage of the C17,20 bond. CYP17 inhibition also results in increased mineralocorticoid production by the adrenals. Androgen-sensitive prostatic carcinoma responds to treatment that decreases androgen levels. Androgen deprivation therapies, such as treatment with LHRH analogues or orchiectomy, decrease androgen production in the testes but do not affect androgen production by the adrenals or in the tumour. Treatment with abiraterone acetate decreases serum testosterone to undetectable levels (using commercial assays) when given with LHRH analogues (or orchiectomy).

Tablet 250mg

• Abiraterone Cipla (Cipla Medpro)
• Abitig (Ranbaxy Pharmaceuticals)
• Heteran 250 (Hetero Drugs SA)
• Protyga (Forrester Pharma)
• Teronred 250 (Dr Reddy's Laboratories)
• Zytiga (Janssen) originator

Tablet 500mg

• Zytiga 500mg (Janssen) originator