abiraterone

High Alert

Zytiga

Treatment of metastatic castration-resistant prostate cancer (in combination with prednisone).

Zytiga

Treatment of metastatic high-risk castration-sensitive prostate cancer (in combination with prednisone).

Yonsa

Treatment of metastatic castration-resistant prostate cancer (in combination with methylprednisolone).

Action ⬆ ⬇

Inhibits the enzyme 17α-hydroxylase/C17,20–lyase (CYP17), which is required for androgen production. May also result in increased mineralocortocoid production.

Therapeutic effects:

Decreased androgen production with decreased spread of androgen-sensitive prostate cancer.

Pharmacokinetics ⬆ ⬇

Absorption: Hydrolyzed to its active compound following oral administration.

Distribution: Widely distributed to tissues.

Protein Binding: >99%.

Metabolism/Excretion: Metabolized by esterases to inactive compounds; eliminated primarily in feces as unchanged drug and metabolites; 5% excreted in urine.

Half-Life: 12 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	2 hr	12 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Severe hepatic impairment;
Concurrent use of radium Ra 223 dichloride (↑ risk of fractures and mortality).

Use Cautiously in:

HF, recent MI, other cardiovascular disease, ventricular arrhythmias;
Electrolyte abnormalities or hypertension (correct/treat prior to initiation);
Moderate hepatic impairment;
Stress, infection, trauma, acute disease process (may result in adrenocortical insufficiency requiring additional corticosteroids);
Rep: Men with female partners of reproductive potential

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, arrhythmia, edema, QT interval prolongation (in presence of hypokalemia), TORSADES DE POINTES (IN PRESENCE OF HYPOKALEMIA)

Derm: hot flush

Endo: adrenocortical insufficiency (due to concurrent corticosteroid), hypoglycemia

F and E: hypokalemia

GI: diarrhea, dyspepsia, HEPATOTOXICITY

GU: ↓fertility, nocturia, urinary frequency

MS: fracture, joint pain/discomfort

Resp: cough

Interactions ⬆ ⬇

Drug-drug:

May ↑ levels of and risk of toxicity from CYP2D6 substrates, including thioridazine and dextromethorphan; if concurrent use necessary, ↓ dose of CYP2D6 substrate. may be required.
May ↑ levels of and risk of toxicity from CYP2C8 substrates, including pioglitazone; if concurrent use necessary, ↓ dose of CYP2C8 substrate may be required.
Strong CYP3A4 inducers, including carbamazepine, phenobarbital, phenytoin, rifabutin, rifapentine, or rifampin may ↓ levels and effectiveness; avoid concurrent use.
May ↑ risk of hypoglycemia when used with pioglitazone or repaglinide.

Route/Dosage ⬆ ⬇

Zytiga and Yonsa are not interchangeable.

Zytiga

PO (Adults ): 1000 mg once daily; Concurrent use with strong CYP3A4 inducer: 1000 mg twice daily.

Hepatic Impairment

PO (Adults ): Moderate hepatic impairment: 250 mg once daily.

Yonsa

PO (Adults ): 500 mg once daily; Concurrent use with strong CYP3A4 inducer: 500 mg twice daily.

Hepatic Impairment

PO (Adults ): Moderate hepatic impairment: 125 mg once daily.

Availability ⬆ ⬇

(Generic available)

Tablets (Zytiga): 250 mg; 500 mg
Tablets (Yonsa): 125 mg

Assessment ⬆ ⬇

Monitor BP and assess for fluid retention at least monthly. Control hypertension during therapy.
Monitor for signs and symptoms of adrenocortical insufficiency (hypotension, weight loss, weakness, nausea, vomiting, anorexia, lethargy, confusion, restlessness), especially in patients under stress or who are withdrawn from or have decreased prednisone dose. Symptoms may be masked by abiraterone.

Lab Test Considerations:

Monitor AST, ALT, and bilirubin prior to starting therapy, every 2 wk for 3 mo, and monthly thereafter. Administer reduced dose to patients with baseline moderate hepatic impairment and monitor AST, ALT, and bilirubin prior to starting therapy, every wk for first mo, every 2 wk for 2 mo, and monthly thereafter. If clinical signs of hepatic toxicity occur, measure serum bilirubin, AST, and ALT promptly; monitor frequently if ↑ levels. If AST and/or ALT ↑ >5 times upper limit of normal (ULN) or bilirubin ↑ >3 times ULN in patients with baseline moderate hepatic impairment, interrupt abiraterone. Following return of liver function to baseline or AST and ALT ↑>2.5 times ULN or bilirubin ↑ >1.5 times ULN may restart at a reduced dose of 750 mg once daily. Monitor serum transaminases and bilirubin every 2 wk for 3 mo and monthly thereafter. If hepatotoxicity recurs, may restart at 500 mg once daily following return to baseline or AST and ALT ↑>2.5 times ULN or bilirubin ↑ >1.5 times ULN. If hepatotoxicity recurs at 500 mg dose, discontinue therapy. If concurrent ↑ ALT >3 times ULN and total bilirubin ↑>2 times ULN without biliary obstruction or other causes, permanently discontinue therapy.
- Monitor serum potassium and sodium at least monthly during therapy. May cause hypokalemia; control during therapy.
- May cause ↑ triglycerides and ↓ phosphorous.

Implementation ⬆ ⬇

Control hypertension and correct hypokalemia prior to starting therapy.
Patients should also receive a gonadotropin-releasing hormone analog concurrently or should have had bilateral orchiectomy.
Zytiga: For castration-resistant prostate cancer: Administer once daily with twice daily prednisone 5 mg on an empty stomach at least 1 hr before or 2 hr after meals; food increases absorption and adverse reactions. Swallow tablets whole with water; do not crush, break, or chew. For castration-sensitive prostate cancer: Administer once daily with once daily prednisone 5 mg on an empty stomach at least 1 hr before or 2 hr after meals; food increases absorption. Swallow tablets whole with water; do not crush, break, or chew.
Yonsa: Administer orally once daily in combination with methylprednisolone 4 mg administered orally twice daily. Administer without regard to meals. DNC: Swallow tablets whole; do not crush, break, or chew.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medications as directed and not to stop abiraterone, prednisone or methylprednisolone, or gonadotropin-releasing hormone analog without consulting health care professional. If a dose is missed, take the following day. If more than 1 dose is missed, consult health care professional. Do not share medication with others, even if they have the same symptoms; may be dangerous. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
Advise patient to notify health care professional if signs and symptoms of high blood pressure, low potassium, and fluid retention (dizziness, fast heartbeats, feel faint or lightheaded, headache, confusion, muscle weakness, pain in legs, swelling in legs or feet), adrenal insufficiency, or hepatotoxicity (yellowing of skin and eyes, dark urine, pain in upper right quadrant, severe nausea or vomiting, difficulty concentrating, disorientation, confusion) occur or of side effects that are bothersome or persistent.
Advise parents to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Rep: Male patients should use a condom and another form of contraception during sex with a women of reproductive potential during and for 3 wk after therapy. Pregnant women and women of reproductive potential should not touch tablets without wearing gloves. May impair reproductive function and fertility in males of reproductive potential.
Explain need for continued follow-up exams and lab tests to assess possible side effects.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆