abiraterone (Rx)

Brand and Other Names:Zytiga
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 250mg
  • 500mg
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Prostate Cancer

Metastatic castration-resistant prostate cancer

  • Indicated in combination with prednisone for patients with metastatic castration-resistant prostate cancer (CRPC)
  • 1000 mg (two 500-mg tablets or four 250-mg tablets) PO qDay with prednisone 5 mg PO q12hr

Metastatic high-risk castration-sensitive prostate cancer

  • Indicated in combination with prednisone for patients with metastatic high-risk castration-sensitive prostate cancer (CSPC)
  • 1000 mg (two 500-mg tablets or four 250-mg tablets) PO qDay with prednisone 5 mg PO qDay

Dosage Modifications

Strong CYP3A4 inducers

  • Coadministration with strong CYP3A4 inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital): Avoid if possible; if strong CYP3A4 inducer must be administered, increase dosage frequency of abiraterone from qDay to BID (eg, from 1,000 mg qDay to 1,000 mg BID)
  • Reduce dose back to the previous dose and frequency, if the concomitant strong CYP3A4 inducer is discontinued

CYP2D6 and CYP2C8 substrates

  • Avoid coadministration with substrates of CYP2D6 with a narrow therapeutic index (eg, thioridazine); if alternative treatments cannot be used, consider a dose reduction of the concomitant CYP2D6 substrate drug
  • Closely monitor for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly with abiraterone

Hepatic impairment

  • Baseline LFTs
    • Mild (Child-Pugh A): No dosage adjustment necessary
    • Moderate (Child-Pugh B): Reduce starting dose to 250 mg PO qDay; monitor ALT, AST, and bilirubin prior to start of treatment, qWeek for the first month, q2Weeks for the following 2 months of treatment and monthly thereafter
    • If elevations in ALT and/or AST >5x ULN or total bilirubin >3x ULN occur in patients with baseline moderate hepatic impairment, discontinue abiraterone and do not retreat patients
    • Severe (Child-Pugh C): Do not use
  • Increased LFTs during treatment
    • ALT and/or AST >5x ULN or total bilirubin >3x ULN: Interrupt treatment; reinitiate at reduced dose of 750 mg PO qDay following return of LFTs to baseline or to AST/ALT ≤2.5x ULN and total bilirubin ≤1.5x ULN
    • For patients who resume treatment, monitor serum transaminases and bilirubin at least q2Weeks for 3 months, and then monthly thereafter
    • If hepatotoxicity recurs at 750 mg/day, may restart at 500 mg/day (after LFTs decrease as above)
    • If hepatoxicity recurs at reduced dose of 500 mg/day, discontinue treatment
    • Permanently discontinue treatment for patients who develop a concurrent elevation of ALT >3x ULN and total bilirubin >2x ULN in the absence of biliary obstruction or other causes responsible for the concurrent elevation

Renal impairment

  • Mild-to-severe: No dosage adjustment necessary

Safety and efficacy not established

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Interactions

Interaction Checker

and abiraterone

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            Adverse drug reactions are for abiraterone with prednisone

            >10% (All grades)

            Hypertriglyceridemia (63%)

            Hyperglycemia, nonfasting (57%)

            Increased ALT (11-46%)

            Fatigue (39%)

            Lymphopenia (20-38%)

            Increased AST (15-37%)

            Hypertension (8.5-37%)

            Hypernatremia (33%)

            Joint swelling/discomfort (30%)

            Hypokalemia (17-30%)

            Edema (25-27%)

            Muscle discomfort (26%)

            Hypophosphatemia (24%)

            Constipation (23%)

            Hot flush (15-22%)

            Diarrhea (18-22%)

            Hot flush (19%)

            Cough (6.5-17%)

            Increased total bilirubin (6.6-16%)

            Insomnia (14%)

            Contusion (13%)

            Upper respiratory tract infection (5.4-13%)

            Urinary tract infection (7-12%)

            Dyspnea (12%)

            Nasopharyngitis (11%)

            Dyspepsia (6.1-11%)

            >10% (Grade 3 or 4)

            Hypertension (1.3-20%)

            1-10%

            All grades

            • Hematuria (10%)
            • Pyrexia (8.7%)
            • Rash (8.1%)
            • Headache (7.5%)
            • Urinary frequency (7.2%)
            • Arrhythmia (7.2%)
            • Groin pain (6.6%)
            • Nocturia (6.2%)
            • Falls (5.9%)
            • Fractures (5.9%)
            • Chest pain or chest discomfort (3.8%)
            • Cardiac failure (2.3%)

            Grade 3 or 4

            • Lymphopenia (4.1-8.7%)
            • Hypophosphatemia (7.2%)
            • Hyperglycemia, nonfasting (6.5%)
            • Increased ALT (1.4-6.1%)
            • Hypokalemia (2.8-10%)
            • Increased AST (2.1-4.4%)
            • Joint swelling/discomfort (2-4.2%)
            • Muscle discomfort (3%)
            • Dyspnea (2.4%)
            • Fatigue (2.2%)
            • Urinary tract infection (1-2.1%)
            • Edema or cardiac failure(1.9%)
            • Fractures (1.4%)
            • Hematuria (1.3%)
            • Arrhythmias (1.1%)

            <1%

            Grade 3 or 4

            • Diarrhea (0.6-0.9%)
            • Pyrexia (0.6%)
            • Chest pain or discomfort (0.5%)
            • Hypertriglyceridemia (0.4%)
            • Groin pain (0.4%)
            • Constipation (0.4%)
            • Edema (0.4%)
            • Hyponatremia (0.4%)
            • Urinary frequency (0.3%)
            • Hot flush (0.2-0.3%)
            • Headache (0.3%)
            • Upper respiratory tract (0.2%)
            • Insomnia (0.2%)
            • Increased total bilirubin (0.1-0.2%)

            Postmarketing Reports

            Respiratory, thoracic and mediastinal disorders: Noninfectious pneumonitis

            Musculoskeletal and connective tissue disorders: Myopathy, including rhabdomyolysis

            Hepatobiliary disorders: Fulminant hepatitis, including acute hepatic failure and death

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            Warnings

            Contraindications

            Women who are or may become pregnant

            Cautions

            Caution in patients with a history of cardiovascular disease; safety in patients with LVEF <50% or NYHA Class III or IV heart failure is not established

            Hypertension, hypokalemia, and fluid retention may result from increased mineralocorticoid due to CYP17 inhibition; control hypertension and correct hypokalemia before treatment; monitor blood pressure, serum potassium, and symptoms of fluid retention at least monthly

            Adrenocortical insufficiency reported in patients receiving abiraterone in combination with prednisone, following interruption of daily steroids and/or with concurrent infection or stress; monitor for symptoms and signs of adrenocortical insufficiency; increased corticosteroid dosage may be indicated before, during, and after stressful situations; concurrent infection or interruption of daily corticosteroids associated with adrenocortical insufficiency

            In postmarketing experience, severe hepatic toxicity, including fulminant hepatitis, acute liver failure and deaths occurred; increases in liver enzymes have led to drug interruption, dose modification, and/or discontinuation (typically within the first 3 months of treatment); monitor ALT/AST and bilirubin levels prior to starting treatment, q2Weeks for the first 3 months of treatment and monthly thereafter (See Dosage Modifications)

            In a multicenter, open-label, single-arm trial, 33 patients with metastatic CRPC received abiraterone at a dose of 1,000 mg qDay at least 1 hr before or 2 hr after a meal in combination with prednisone 5 mg PO BID; small increases in the QTc interval (eg, <10 ms) due to abiraterone acetate cannot be excluded

            Drug interactions overview

            • See Dosage Modifications
            • Drugs that inhibit or induce CYP3A4
              • Strong CYP3A4 inducers (eg, rifampin) decreased systemic exposure of abiraterone; avoid coadministration; if unable to avoid, increase abiraterone dose frequency
              • Ketoconazole, a strong CYP3A4 inhibitor, had no clinically meaningful effect when coadministered with abiraterone
            • Effects of abiraterone on drug metabolizing enzyme
              • Abiraterone inhibits CYP2D6 and CYP2C8
              • In a CYP2D6 drug-drug interaction trial, peak plasma concentration and AUC of dextromethorphan (CYP2D6 substrate) were increased 2.8- and 2.9-fold, respectively, when dextromethorphan was given with abiraterone acetate 1,000 mg qDay and prednisone 5 mg PO BID
              • In a CYP2C8 drug-drug interaction trial in healthy subjects, the AUC of pioglitazone (CYP2C8 substrate) was increased by 46% when pioglitazone was coadministered with a single dose of 1,000 mg abiraterone
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            Pregnancy & Lactation

            Pregnancy

            Based on findings from animal studies and mechanism of action, abiraterone is contraindicated for use in pregnant women because drug can cause fetal harm and potential loss of pregnancy

            Not indicated for use in females

            There is no human data on abiraterone use in pregnant women

            In animal reproduction studies, oral administration of abiraterone acetate to pregnant rats during organogenesis caused adverse developmental effects at maternal exposures ~≥0.03 times the human exposure (AUC) at the recommended dose

            Contraception

            • Advise males with female partners of reproductive potential to use effective contraception during treatment and for 3 weeks after the final dose of abiraterone
            • Based on animal studies, abiraterone may impair reproductive function and fertility in males of reproductive potential

            Lactation

            Not indicated for women

            No information available on the presence of abiraterone acetate in human milk, or on the effects on the breastfed child or milk production

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Androgen biosynthesis inhibitor that inhibits 17 alpha-hydroxylase/C17, 20-lyase (CYP17); this enzyme is expressed in testicular, adrenal, and prostatic tumor tissues and is required for androgen biosynthesis

            Inhibition of CYP17 by abiraterone can also result in increased mineralocorticoid production by the adrenal glands

            Absorption

            Peak plasma time: 2 hr

            Peak plasma concentration: 226 ng/mL ng/mL (at steady state); increases up to 17-fold when administered with high-fat meal

            AUC: 993 ng·hr/mL; increases up to 10-fold when administered with high-fat meal

            Distribution

            Protein bound: >99% (albumin, alpha-1 acid glycoprotein)

            Vd: 19,669 L (at steady state)

            P-glycoprotein (P-gp) inhibitor

            Metabolism

            Hydrolyzed to abiraterone (active metabolite); hydrolysis is likely via esterase activity and is not CYP mediated

            CYP3A4 and SULT2A1 enzymes are involved in the formation of 2 inactive metabolites, N-oxide abiraterone sulphate and abiraterone sulphate

            Strong inhibitor of CYP1A2 and CYP2D6; moderate inhibitor of CYP2C9, CYP2C19, and CYP3A4

            Excretion

            Excretion: Feces (88%), urine (5%)

            Half-life: 12 hr (prolonged by hepatic impairment to 18-19 hr)

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            Administration

            Oral Administration

            Patients receiving abiraterone should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy

            Take once daily in combination with prednisone

            Take on empty stomach, at least 1 hr before or 2 hr after meals

            Swallow tablets whole with water; do not chew, crush, or split

            Storage

            Tablets: Store at 20-25°C (68-77°F); excursions permitted in the range from 15-30°C (59-86°F)

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

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            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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