Abiraterone

Indications

Abiraterone is used for: Prostate cancer

Adult Dose

Oral Prostate cancer Adult: Metastatic, castration-resistant prostate cancer: 1 g (two 500-mg tablets or four 250-mg tablets) once daily, in combination w/ prednisolone (5 mg PO q12hr). Metastatic high-risk castration-sensitive prostate cancer Indicated in combination with prednisone for patients with metastatic high-risk castration-sensitive prostate cancer (CSPC) 1000 mg (two 500-mg tablets or four 250-mg tablets) PO qDay with prednisone 5 mg PO q12hr Hepatic Impairment Moderate (Child-Pugh Class B): 250 mg once daily; permanently discontinue if ALT/AST reaches >5 times the upper limit of normal (ULN) or total bilirubin >3 times ULN during treatment. Severe (Child-Pugh Class C): Contraindicated.

Child Dose

Renal Dose

Renal impairment Mild-to-severe: No dosage adjustment necessary

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.

Contra Indications

Severe hepatic impairment (Child-Pugh Class C). Pregnancy and lactation.

Precautions

Hypertension, hypokalemia, and fluid retention may result from increased mineralocorticoid due to CYP17 inhibition; control hypertension and correct hypokalemia before treatment; monitor blood pressure, serum potassium, and symptoms of fluid retention at least monthly Closely monitor patients with medical conditions that might be compromised by increased blood pressure, hypokalemia, or fluid retention (eg, heart failure, recent MI, cardiovascular disease, ventricular arrhythmia) QT prolongation and Torsades de Pointes observed in patients who develop hypokalemia during postmarketing surveillance and additional clinical trials Adrenocortical insufficiency reported in patients receiving abiraterone in combination with prednisone, following interruption of daily steroids and/or with concurrent infection or stress; monitor for symptoms and signs of adrenocortical insufficiency; increased corticosteroid dosage may be indicated before, during, and after stressful situations; concurrent infection or interruption of daily corticosteroids associated with adrenocortical insufficiency

Pregnancy-Lactation

Pregnancy Based on findings from animal studies and mechanism of action, abiraterone is contraindicated for use in pregnant women because drug can cause fetal harm and potential loss of pregnancy Not indicated for use in females There are no human data regarding use in pregnant women In animal reproduction studies, oral administration of abiraterone acetate to pregnant rats during organogenesis caused adverse developmental effects at maternal exposures ~?0.03 times the human exposure (AUC) at the recommended dose Contraception Advise males with female partners of reproductive potential to use effective contraception during treatment and for 3 weeks after the final dose of abiraterone Infertility Based on animal studies, may impair reproductive function and fertility in males of reproductive potential Lactation Not indicated for women No information available on the presence of abiraterone acetate in human milk, or on the effects on the breastfed child or milk production

Interactions

Increased risk of hypokalaemia w/ K-lowering drugs (e.g. thiazide diuretics). Risk of tumour progression w/ spironolactone. Decreased exposure w/ strong CYP3A4 inducers (e.g. rifampicin). Increased plasma concentration w/ potent CYP3A4 inhibitors e.g. ketoconazole. Increased risk of QT prolongation w/ antiarrhythmics (e.g. quinidine, amiodarone), antipsychotics, moxifloxacin, methadone. May increase exposure to drugs that are metabolised or activated by CYP2D6 (e. g. desipramine, venlafaxine, metoprolol), esp those w/ narrow therapeutic index.

Side Effects

Side effects of Abiraterone : Adverse drug reactions are for abiraterone with prednisone >10% (All grades) Hypertriglyceridemia (63%) Hyperglycemia, nonfasting (57%) Increased ALT (11-46%) Fatigue (39%) Lymphopenia (20-38%) Increased AST (15-37%) Hypertension (8.5-37%) Hypernatremia (33%) Joint swelling/discomfort (30%) Hypokalemia (17-30%) Edema (25-27%) Muscle discomfort (26%) Hypophosphatemia (24%) Constipation (23%) Hot flush (15-22%) Diarrhea (18-22%) Hot flush (19%) Cough (6.5-17%) Increased total bilirubin (6.6-16%) Insomnia (14%) Contusion (13%) Upper respiratory tract infection (5.4-13%) Urinary tract infection (7-12%) Dyspnea (12%) Nasopharyngitis (11%) Dyspepsia (6.1-11%) >10% (Grade 3 or 4) Hypertension (1.3-20%) 1-10% All grades Hematuria (10%) Pyrexia (8.7%) Rash (8.1%) Headache (7.5%) Urinary frequency (7.2%) Arrhythmia (7.2%) Groin pain (6.6%) Nocturia (6.2%) Falls (5.9%) Fractures (5.9%) Chest pain or chest discomfort (3.8%) Cardiac failure (2.3%) Grade 3 or 4 Lymphopenia (4.1-8.7%) Hypophosphatemia (7.2%) Hyperglycemia, nonfasting (6.5%) Increased ALT (1.4-6.1%) Hypokalemia (2.8-10%) Increased AST (2.1-4.4%) Joint swelling/discomfort (2-4.2%) Muscle discomfort (3%) Dyspnea (2.4%) Fatigue (2.2%) Urinary tract infection (1-2.1%) Edema or cardiac failure(1.9%) Fractures (1.4%) Hematuria (1.3%) Arrhythmias (1.1%) <1% Grade 3 or 4 Diarrhea (0.6-0.9%) Pyrexia (0.6%) Chest pain or discomfort (0.5%) Hypertriglyceridemia (0.4%) Groin pain (0.4%) Constipation (0.4%) Edema (0.4%) Hyponatremia (0.4%) Urinary frequency (0.3%) Hot flush (0.2-0.3%) Headache (0.3%) Upper respiratory tract (0.2%) Insomnia (0.2%) Increased total bilirubin (0.1-0.2%)

Mode of Action

Abiraterone suppresses testosterone production through selective and irreversible inhibition of 17 alpha-hydroxylase/C17, 20-lyase (CYP17), an enzyme required for androgen biosynthesis in testicular, adrenal, and prostatic tumour tissues.