Names and pronunciation
(a′bir-a′ter-one) Zytiga
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Drug reference
(a′bir-a′ter-one) Zytiga
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Func. class.: Antineoplastic
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Chem. class.: Androgen biosynthesis inhibitor
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ACTION: Converted to abiraterone, which inhibits CYP17, the enzyme required for androgen biosynthesis; androgen- sensitive prostate cancer responds to treatment that decreases androgens
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USES: Metastatic, castration-resistant prostate cancer in combination with predniSONE
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CONTRAINDICATIONS: Preg- nancy, women, children, breastfeeding Precautions: Adrenal insufficiency, cardiac disease, MI, heart failure, hepatic disease, hypertension, hypokalemia, infection, sur- gery, ventricular dysrhythmia, stress, trauma
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SIDE EFFECTS CV: Angina, dysrhythmia exacerbation, atrial flutter/fibrillation/tachycardia, AV block, chest pain, edema, heart failure, MI, hypertension, QT prolongation, sinus tachycardia, supraventricular tachycar- dia, ventricular tachycardia ENDO: Hot flashes, adrenocortical insufficiency GI: Diarrhea, dyspepsia, hepatotoxicity GU: Increased urinary frequency, noctu- ria, UTI META: Adrenocortical insufficiency, hyperbilirubinemia, hypertriglyceride- mia, hypokalemia, hypophosphatemia MS: Arthralgia, myalgia, fracture RESP: Cough, upper respiratory infection SYST: Infection
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INTERACTIONS • Decrease: abiraterone effect—CYP3A4 inducers (carBAMazepine, phenytoin, ri- fAMPin, rifabutin, rifapentine, PHENobar- bital); dose may need to be increased • Increase: action of CYP2D6/CYP2C8 substrates—dextromethorphan, thiorid- azine, pioglitazone; doses of these products should be reduced; avoid con- A current use if possible Drug/Food Increase: abiraterone action—must be taken on an empty stomach Drug/Lab Increase: ALT, AST, bilirubin, triglycer- ides, cholesterol, alkaline phosphatase Decrease: potassium, phosphate, testos- terone, lymphocytes
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DOSAGE AND ROUTES • Adult males: PO 1000 mg/day with predniSONE 5 mg bid and with GnRH (gonadotropin-releasing hormone an- alog) or bilateral orchiectomy; with strong CYP3A4 inducers 1000 mg bid Hepatic dose • Adult males (Child-Pugh B, 7-9): PO 250 mg/day with predniSONE; permanently discontinue if AST/ALT >5 × the upper limit of normal (ULN) or total bilirubin >3 × ULN; Child-Pugh C >10, do not use
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Available forms: Tablets 250 mg
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Administer: PO route • Give whole on empty stomach 2 hr prior to or 1 hr after meals with full glass of water; do not crush, break, chew • Pregnancy: women who are pregnant or who may become pregnant should not touch tablets without gloves • Store tablets at room temperature
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Assess: • Prostate cancer: monitor prostate- specific antigen (PSA), serum potassium, serum bilirubin baseline and periodically • Hepatotoxicity: monitor liver function tests (AST/ALT) at baseline, every 2 wk for 3 mo, monthly thereafter in no known he- patic disease; interrupt treatment in pa- tients without known hepatic disease at baseline who develop ALT/AST >5 × ULN or total bilirubin >3 × ULN; patients with moderate hepatic disease at baseline, measure ALT, AST, bilirubin prior to the start of treatment, every week for 1 mo, every 2 wk for the following 2 mo, monthly thereafter; if elevations in ALT and/or AST >5 × ULN or total bilirubin >3 × ULN occur in patients with moderate hepatic impair- ment at baseline, discontinue and do NOT restart; obtain serum total bilirubin, AST/ ALT if hepatotoxicity is suspected; eleva- tions of AST, ALT, bilirubin from baseline provide more frequent monitoring • Monitor B/P, pulse, edema, if hyper- tensive, control symptoms • Musculoskeletal pain, joint swelling, discomfort: arthritis, arthralgia, joint swell- ing, and joint stiffness, some severe; muscle discomfort that includes muscle spasms, musculoskeletal pain, myalgia, musculo- skeletal discomfort, and musculoskeletal stiffness may be relieved with analgesics • Signs, symptoms of adrenocorticoid insufficiency (anorexia, nausea, vomit- ing, fatigue, weight loss); corticosteroids may need to be prescribed during stress, trauma, surgery; assess monthly for hy- pertension, hypokalemia, fluid retention • QT prolongation: monitor ECG for QT prolongation, ejection fraction in patients with cardiac disease; small increases in the QTc interval such as <10 ms have occurred; monitor for arrhythmia exacerbation
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Evaluate: • Therapeutic response: Decreasing spread, progression of prostate cancer
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • Pregnancy: that women must not come into contact with tablets; to wear gloves if product needs to be handled; that males should wear condoms and use another form of contraception if partner is pregnant during use of product and for 1 wk after discontinuing treatment • To report chest pain, swelling of joints, burning/pain when urinating • Not to use with other medications, herbs without prescriber approval • To take 2 hr prior to or 1 hr after meals; to swallow tablet whole, take with water • That this product, predniSONE, and a GnRH need to be used together • Not to stop abruptly without pre- scriber consent • That B/P, potassium, and possible fluid retention will be monitored at least monthly • To immediately report jaundice of skin, eyes, clay-colored stools, dark urine; that lab work will be needed dur- ing at least first 3 mo • To discuss all other products taken with all prescribers • If dose is missed, skip and take next regularly scheduled dose HIGH ALERT
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PHARMACOKINETICS Onset rapid, peak 2 hr, duration unknown; 99% protein binding, con- verted to abiraterone (active metabolite), half-life 7%-17% hr; excreted 88% (feces), 5% (urine); high-fat food increases effect, give on empty stomach; increased effect in hepatic disease
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• Adult males: PO 1000 mg/day with predniSONE 5 mg bid and with GnRH (gonadotropin-releasing hormone an- alog) or bilateral orchiectomy; with strong CYP3A4 inducers 1000 mg bid Hepatic dose
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• Adult males (Child-Pugh B, 7-9): PO 250 mg/day with predniSONE; permanently discontinue if AST/ALT >5 × the upper limit of normal (ULN) or total bilirubin >3 × ULN; Child-Pugh C >10, do not use
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