abiraterone acetate

Action

Converts from abiraterone acetate in vivo to abiraterone, an androgen biosynthesis inhibitor that inhibits 17α-hydroxylase/C17,20-lyase (CYP17), an enzyme that's expressed in testicular, adrenal, and prostatic tumor tissues and is required for androgen biosynthesis, thereby causing androgen-sensitive prostatic carcinoma to respond to such treatment that decreases androgen levels

Availability

Tablets: 250 mg

Indications and dosages

➣ Metastatic castration-resistant prostate cancer in combination with prednisone in patients who have received prior chemotherapy containing docetaxel

Adults: 1,000 mg P.O. daily in combination with prednisone 5 mg P.O. b.i.d.

Dosage adjustment

• Baseline moderate hepatic impairment (Child-Pugh Class B)

Contraindications

• Pregnancy

• Women of childbearing age

Precautions

Use cautiously in:

• mild to moderate hepatic disease, mineralocorticoid excess, adrenocortical insufficiency, CV disease

• co-administration of CYP2D6 substrates with a narrow therapeutic index (avoid use or if alternative treatments can't be used, consider a dosage reduction of the concomitant CYP2D6 substrate)

• co-administration of strong inhibitors and inducers of CYP3A4 (avoid or use with caution)

• breastfeeding women

• children (safety and efficacy not established).

Administration

See Be aware that pregnant women and women of childbearing age shouldn't handle drug without wearing gloves.

• Control hypertension and correct hypokalemia before starting drug.

• Give tablets whole and be aware that patient shouldn't eat for at least 2 hours before drug is administered and for at least 1 hour after drug is administered.

See Don't use in patients with baseline severe hepatic impairment (Child-Pugh Class C).

• Withhold drug in patients who develop hepatotoxicity during treatment until recovery. May restart drug at a reduced dosage.

See Discontinue drug if patient develops severe hepatotoxicity.

• Be aware that safety isn't established in patients with left ventricular ejection fraction less than 50% or New York Heart Association Class III or IV heart failure.

Adverse reactions

CV: hypertension, arrhythmia, heart failure

GI: diarrhea, dyspepsia

GU: urinary tract infection, urinary frequency, nocturia

Hepatic: hepatotoxicity

Metabolic: hypokalemia, mineralocorticoid excess with fluid retention, adrenocortical insufficiency,

hyperosmolar coma or death Musculoskeletal: joint swelling or discomfort, muscle discomfort, fractures, musculoskeletal and connective tissue disorders

Respiratory: cough, upper respiratory tract infection

Other: fluid retention, edema, hot flushes, chest pain or discomfort

Interactions

Drug-drug. CYP2D6 substrates with a narrow therapeutic index (such as thioridazine): increased CYP2D6 substrate C_max and area under the curve (AUC) CYP3A4 inducers (such as carbamazepine, phenobarbital, phenytoin, rifabutin, rifapentine, rifampin): unknown effects Strong CYP3A4 inhibitors (such as atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole): unknown effects

Drug-diagnostic tests. ALT, AST, triglycerides, total bilirubin): increased levels

Potassium: reduced level

Drug-food. Any food: increased abiraterone AUC

Patient monitoring

• Monitor hepatic function tests closely and modify, interrupt, or discontinue dosing as prescribed.

• Monitor blood pressure, serum potassium level, and signs and symptoms of fluid retention at least monthly.

• Monitor patient for signs and symptoms of adrenocortical insufficiency (such as hypoglycemia, hypotension, orthostatic hypotension, dehydration, weight loss, and nausea and vomiting); be aware that increased dosage of corticosteroids may be indicated before, during, and after stressful situations.

Patient teaching

• Tell patient to swallow tablets whole with water on an empty stomach (don't eat for at least 2 hours before taking drug and for at least 1 hour after taking drug).

• Instruct patient to take drug with prednisone as prescribed and not to interrupt or stop either drug without consulting prescriber.

• Instruct patient to report joint or muscle discomfort, urinary or respiratory tract infection, urinating more frequently or during the night, dizziness on standing, extreme thirst, or weight loss.

See Advise pregnant women and women of childbearing age not to handle drug without wearing gloves.

• Advise male patient of child-producing age to use a condom and another effective contraceptive during therapy if having sex with a woman of childbearing potential.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and food mentioned above.