abiraterone (a-bi-ra-te-rone), Zytiga

 Classification

Therapeutic: antineoplastics

Pharmacologic: enzyme inhibitors

Indications

With prednisone in the treatment of metastatic castration-

resistant prostate cancer.

Action

Inhibits the enzyme 17-hydroxylase/C17,20–lyase,

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: Unknown.

Protein Binding: 99%.

Metabolism and 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 (blood level)

ROUTE ONSET PEAK DURATION

PO unknown 2 hr 12 hr

Contraindications/Precautions

Contraindicated in: Severe hepatic impairment

(Child-Pugh Class C); OB: Pregnancy or potential to become

pregnant (may cause fetal harm); Lactation: Lactation.

Use Cautiously in: Cardiovascular disease (safety

not established if LVEF 50% or NYHA Class III or IV

heart failure; Recent myocardial infarction; Ventricular

arrhythmias; Electrolyte abnormalities or hypertension

(correct/treat prior to initiation); Pre-existing liver disease

(dose modification required for Child-Pugh Class

B); Stress, infection, trauma, acute disease process

(may result in adrenocortical insufficiency requiring

additional corticosteroids).

Adverse Reactions/Side Effects A

Noted for combination treatment with prednisone.

Resp: cough. CV: arrhythmia, edema, hypertension.

GI: HEPATOTOXICITY, diarrhea, dyspepsia. Derm: hot

flush. Endo: adrenocortical insufficiency (due to concurrent

prednisone). F and E: hypokalemia. GU:

nocturia, urinary frequency. MS: fracture, joint pain/

discomfort.

Interactions

Drug-Drug: Acts as an inhibitor of the CYP2D6 and

CYP2C8 enzyme system; avoid concurrent use with

agents that are substrates of CYP2D6, especially those

with narrow therapeutic indices, including thioridazine

and dextromethorphan (CYP2D6 substrates) as

well as pioglitazone (CYP2C8 substrate); if concurrent

use is necessary, dosepof substrate may be required.

Abiraterone is a substrate of the CYP3A4 enzyme

system. Concurrent use of strong CYP3A4

inducers including carbamazepine, phenobarbital,

phenytoin, rifabutin, rifapentine, or rifampin

should be avoided or undertaken with caution.

Route/Dosage

PO (Adults): 1000 mg once daily used in combination

with 5 mg prednisone twice daily; Concurrent use of

strong CYP3A4 inducer—1000 mg twice daily.

Hepatic Impairment

PO (Adults): Child-Pugh Class B—250 mg once

daily with 5 mg prednisone twice daily.

Availability

Tablets: 250 mg, 500 mg.