Abiraterone Acetate

Name: Abiraterone Acetate

Introduction

Antineoplastic agent; inhibitor of 17α-hydroxylase/C17,20-lyase (CYP17).1 5 6 10 13

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Abiraterone Acetate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

250 mg

Zytiga

Centocor Ortho Biotech

What are some other side effects of Abiraterone Acetate?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Flushing.
  • Muscle pain.
  • Joint pain or swelling.
  • Heartburn.
  • Cough.
  • Loose stools (diarrhea).
  • Feeling tired or weak.
  • Throwing up.
  • Signs of a common cold.
  • Nose or throat irritation.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Zytiga: 250 mg, 500 mg

Pharmacologic Category

  • Antiandrogen
  • Antineoplastic Agent, Antiandrogen

Special Populations Hepatic Function Impairment

Systemic exposure increased approximately 1.1- and 3.6-fold in subjects with mild and moderate hepatic impairment, respectively. Systemic exposure of abiraterone increased by 7- fold and the fraction of free drug increased by 2-fold in subjects with severe baseline hepatic impairment.

Dosing Geriatric

Refer to adult dosing.

Dosing Hepatic Impairment

Hepatic impairment prior to treatment initiation:

Mild (Child-Pugh class A): No dosage adjustment necessary.

Moderate (Child-Pugh class B): 250 mg once daily. Permanently discontinue if ALT and/or AST >5 times the upper limit of normal (ULN) or total bilirubin >3 times ULN occur during treatment in patients with baseline moderate hepatic impairment.

Severe (Child-Pugh class C): Do not use.

Hepatotoxicity during treatment:

ALT and/or AST >5 times ULN or total bilirubin >3 times ULN: Withhold treatment until liver function tests return to baseline or ALT and AST ≤2.5 times ULN and total bilirubin ≤1.5 times ULN, then reinitiate at 750 mg once daily.

Recurrent hepatotoxicity on 750 mg/day: Withhold treatment until liver function tests return to baseline or ALT and AST ≤2.5 times ULN and total bilirubin ≤1.5 times ULN, then reinitiate at 500 mg once daily.

Recurrent hepatotoxicity on 500 mg once daily: Discontinue treatment

ALT >3 times ULN and total bilirubin >2 times ULN (in the absence of biliary obstruction or other contributing cause responsible for concurrent elevation): Permanently discontinue treatment

Warnings/Precautions

Concerns related to adverse effects:

• Adrenocortical insufficiency: Concurrent infection, stress, or interruption of daily corticosteroids is associated with reports of adrenocortical insufficiency. Monitor closely for signs and symptoms of adrenocorticoid insufficiency, which could be masked by adverse events associated with mineralocorticoid excess. Diagnostic testing for adrenal insufficiency may be clinically indicated. Increased corticosteroid doses may be required before, during, and after stress.

• Hepatotoxicity: Severe hepatotoxicity (eg, fulminant hepatitis, acute liver failure, and death) has been reported. Significant increases in liver enzymes have also been observed (higher likelihood in patients with baseline elevations), generally occurring in the first 3 months of treatment. May require dosage reduction, treatment interruption, and/or discontinuation. ALT, AST, and bilirubin should be monitored prior to treatment, every 2 weeks for 3 months and monthly thereafter; patients with hepatic impairment, elevations in liver function tests, or experiencing hepatotoxicity require more frequent monitoring (see dosage adjustment for hepatic impairment and monitoring parameters). Evaluate liver function promptly with signs or symptoms of hepatotoxicity. The safety of retreatment after significant elevations (ALT or AST ≥20 times the upper limit of normal [ULN] and/or total bilirubin ≥10 times ULN) has not been evaluated.

• Mineralocorticoid excess: Increased mineralocorticoids due to CYP17 inhibition may result in hypertension, hypokalemia, and fluid retention (including grade 3 and 4 events). Monitor at least monthly for hypertension, hypokalemia, and fluid retention. Concomitant administration with corticosteroids reduces the incidence and severity of these adverse events.

Disease-related concerns:

• Cardiovascular disease: May cause hypertension, hypokalemia, and fluid retention. Control hypertension and correct hypokalemia prior to and during treatment. Use with caution in patients with cardiovascular disease, particularly with heart failure, recent MI, or ventricular arrhythmia. Patients with left ventricular ejection fraction (LVEF) <50% or NYHA class II, III, or IV heart failure were excluded from clinical trials. Monitor at least monthly for hypertension, hypokalemia, and fluid retention.

• Hepatic impairment: Do not use in patients with preexisting severe hepatic impairment (Child-Pugh class C); dosage reduction is recommended in patients with baseline moderate impairment.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Food: Abiraterone must be administered on an empty stomach (administer at least 1 hour before and 2 hours after any food); abiraterone AUC (exposure) may be increased up to 10-fold if administered with a meal.

Pregnancy Risk Factor X Pregnancy Considerations

Adverse effects were observed in animal reproduction studies at doses resulting in less systemic exposure than in humans. Adverse effects were also observed in the reproductive system of animals during toxicology and pharmacology studies. Based on the mechanism of action, abiraterone may cause fetal harm or fetal loss if administered during pregnancy. Abiraterone is not indicated for use in women and is specifically contraindicated in women who are or may become pregnant. It is not known if abiraterone is excreted in semen, therefore, men should use a condom and another method of birth control during treatment and for 1 week following therapy if having intercourse with a woman of reproductive age. Women who are or may become pregnant should wear gloves if contact with tablets may occur.

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