apalutamide (Rx)

Brand and Other Names:Erleada
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 60mg

Prostate Cancer

Indicated for metastatic castration-sensitive prostate cancer (mCSPC) or nonmetastatic, castration-resistant prostate cancer (nmCRPC)

240 mg PO qDay

Dosage Modifications

Grade ≥3 toxicity or intolerable adverse effect

  • Hold dosing until symptoms improve to Grade ≤1 or baseline, THEN
  • Resume at the same dose or a reduced dose (180 mg or 120 mg), if warranted

Renal impairment

  • Mild-to-moderate (eGFR 30-89 mL/min/1.73 m2): No clinical significant difference in pharmacokinetics
  • Severe (eGFR ≤30 mL/min/1.73 m2): Pharmacokinetics unknown

Hepatic impairment

  • Mild-to-moderate (Child-Pugh A or B): No clinical significant difference in pharmacokinetics
  • Severe (Child-Pugh C): Pharmacokinetics unknown

Dosing Considerations

Patients receiving antiandrogens (eg, apalutamide) should also receive a gonadotropin-releasing hormone (GnRH) analog (eg, leuprolide, triptorelin, goserelin, histrelin) concurrently or should have had a bilateral orchiectomy

Safety and efficacy not established

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Interactions

Interaction Checker

and apalutamide

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10% (All Grades)

            nmCRPC

            • Hypercholesterolemia, nonfasting (76%)
            • Anemia (70%)
            • Hyperglycemia (70%)
            • Hypertriglyceridemia, nonfasting (67%)
            • Leukopenia (47%)
            • Lymphopenia (41%)
            • Fatigue (39%)
            • Hyperkalemia (32%)
            • Hypertension (25%)
            • Rash (24%)
            • Diarrhea (20%)
            • Nausea (18%)
            • Arthralgia (16%)
            • Fall (16%)
            • Weight decreased (16%)
            • Hot flush (14%)
            • Fracture (12%)
            • Decreased appetite (12%)
            • Peripheral edema (11%)

            mCSPC

            • Rash (28%)
            • Decreased WBC (27%)
            • Fatigue (26%)
            • Hot flush (23%)
            • Hypertension (18%)
            • Arthralgia (17%)
            • Pruritus (11%)

            >10% (Grades 3-4)

            nmCRPC

            • Hypertension (14%)

            1-10% (All Grades)

            nmCRPC

            • Hypothyroidism (8%)
            • Pruritus (6.2%)
            • Ischemic heart disease (3.7%)
            • Heart failure (2.2%)

            1-10% (Grades 3-4)

            nmCRPC

            • Rash (5%)
            • Fracture (3%)
            • Fall (2%)
            • Hypertriglyceridemia, nonfasting (2%)
            • Lymphopenia (2%)
            • Hyperkalemia (2%)
            • Hyperglycemia (2%)
            • Fatigue (1%)
            • Weight decreased (1%)
            • Diarrhea (1%)
            • mCSPC H4
            • Hypertension (8%)
            • Rash (6%)
            • Fatigue (3%)
            • Hypertriglyceridemia (3%)

            <1% (Grades 3-4)

            nmCRPC

            • Anemia (0.4%)
            • Leukopenia (0.3%)
            • Appetite decreased (0.1%)
            • Hypercholesterolemia, nonfasting (0.1%)

            mCSPC

            • Pruritus (<1%)
            • Arthralgia (0.4%)
            • Decreased WBC (0.4%)
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            Warnings

            Contraindications

            None

            Cautions

            Ischemic cardiovascular events, including events leading to death reported; monitor for signs and symptoms of ischemic heart disease; consider discontinuing if Grade 3 or 4 events occur

            Falls and fractures reported; evaluate patient for risk; monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone-targeted agents; falls were not associated with loss of consciousness or seizure

            Seizures reported; permanently discontinue if a seizure occurs during treatment; unknown whether anticonvulsants will prevent seizures with apalutamide; there is no clinical experience in re-administering therapy to patients who experienced seizure

            Advise patients of risk of developing a seizure while on therapy and harm, to themselves or others, that could occur from sudden loss of memory while engaging in activities

            Based on its mechanism of action, apalutamide can cause fetal harm and loss of pregnancy if administered to pregnant women

            Drug interaction overview

            • Strong CYP2C8 or CYP3A4 inhibitors
              • Coadministration with strong CYP2C8 or CYP3A4 inhibitors is predicted to increase the steady-state exposure of the active apalutamide moieties
              • No initial dose adjustment is necessary; however, reduce dose based on tolerability
              • Mild or moderate CYP2C8 or CYP3A4 inhibitors are not expected to affect apalutamide levels
            • CYP3A4, CYP2C9, CYP2C19, and UGT substrates
              • Apalutamide is a strong inducer of CYP3A4 and CYP2C19, a weak inducer of CYP2C9, and it induces UDP-glucuronosyltransferase (UGT)
              • Drugs primarily metabolized by CYP3A4, CYP2C19, or CYP2C9 can result in lower exposure to these medications; use alternate medications when possible or evaluate for loss of activity if medication is continued
              • Caution if UGT substrates must be coadministered with apalutamide and evaluate for loss of activity
            • P-gp, BCRP, or OATP1B1 substrates
              • Apalutamide is a weak inducer of P-gp, BCRP, and OATP1B1 clinically
              • Coadministration of apalutamide with these substrates can result in lower exposure of these drugs; caution if these substrates must be coadministered with apalutamide and evaluate for loss of activity
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            Pregnancy

            Pregnancy

            Based on its mechanism of action, the drug can cause fetal harm and potential loss of pregnancy

            There are no available data regarding use in pregnant women

            The drug is not indicated for use in females, so animal embryo-fetal developmental toxicology studies were not conducted

            Contraception

            • Based on the mechanism of action and findings in an animal reproduction study, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 3 months after the last dose

            Infertility

            • Based on animal studies, may impair fertility in males of reproductive potential

            Lactation

            Not indicated for use in females

            No data are available on presence in human milk or effect on the breastfed child or on 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 receptor (AR) inhibitor that binds directly to the ligand-binding domain of the AR; inhibits AR nuclear translocation, inhibits DNA binding, and impedes AR-mediated transcription

            Administration caused decreased tumor cell proliferation and increased apoptosis, leading to decreased tumor volume in mouse xenograft models of prostate cancer

            Absorption

            Oral bioavailability: 100%

            Peak plasma time: 2 hr; delayed by ~2 hr with food

            Peak plasma concentration: 6 mcg/mL; 5.9 mcg/mL (active metabolite)

            AUC: 100 mcg·h/mL; 124 mcg·h/mL (active metabolite)

            Steady-state achieved: 4 weeks

            Distribution

            Protein bound: 96% (apalutamide); 95% (N-desmethyl apalutamide)

            Vd: ~276 L

            Metabolism

            Metabolism is the main route of elimination

            Primarily metabolized by CYP2C8 and CYP3A4 to form active metabolite, N-desmethyl apalutamide

            The contribution of CYP2C8 and CYP3A4 in the metabolism of apalutamide is estimated to be 58% and 13% following single dose, but changes to 40% and 37%, respectively, at steady-state

            Apalutamide represented 45% and N-desmethyl apalutamide represented 44% of the total AUC following a single oral dose

            Elimination

            Half-life: 3 days

            CL/F: 1.3 L/hr (single dose); 2 L/hr (steady-state)

            Excretion: 65% urine; 24% feces

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            Administration

            Oral Administration

            May take with or without food

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

            Storage

            Store at controlled room temperature (20-25ºC [68-77ºF]); excursions permitted to 15-30ºC (59-86ºF)

            Store in the original package

            Do not discard desiccant

            Protect from light and moisture

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            Formulary

            FormularyPatient Discounts

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            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.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.