darolutamide (Rx)

Brand and Other Names:Nubeqa
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 300mg

Prostate Cancer

Indicated for nonmetastatic castration-resistant prostate cancer (nmCRPC)

600 mg PO BID

Patients should also receive a gonadotropin-releasing hormone analog concurrently or should have had a bilateral orchiectomy

Dosage Modifications

Grade ≥3 toxicity or an intolerable adverse reaction

  • Withhold dose or reduce to 300 mg PO BID until symptoms improve
  • Resume at 600 mg PO BID
  • Do not reduce dose below 300 mg BID

Renal impairment

  • Mild or moderate (eGFR 30-89 mL/min/1.73 m2): No dosage adjustment necessary
  • Severe (eGFR 15-29 mL/min/1.73 m2) who are not receiving hemodialysis: Reduce to 300 mg PO BID
  • End-stage renal disease (eGFR ≤15 mL/min/1.73 m2): Pharmacokinetics unknown

Hepatic impairment

  • Mild (Child-Pugh Class A): No dosage adjustment necessary
  • Moderate (Child-Pugh Class B): Reduce to 300 mg PO BID
  • Severe (Child-Pugh Class C): Pharmacokinetics unknown

Safety and efficacy not established

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Interactions

Interaction Checker

and darolutamide

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            All grades of severity are listed unless otherwise indicated

            >10%

            AST increased (23%)

            Decreased neutrophil count (20%)

            Fatigue (16%)

            Bilirubin increased (16%

            1-10%

            Pain in extremity (6%)

            Ischemic heart disease (4%)

            Rash (3%)

            Heart failure (2.1%)

            Grade ≥3

            • Neutrophil count decreased (4%)

            <1%

            Grade ≥3

            • Fatigue (0.6%)
            • AST increased (0.5%)
            • Rash (0.1%)
            • Bilirubin increased (0.1%)
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            Warnings

            Contraindications

            None

            Cautions

            Based on its mechanism of action, fetal harm and loss of pregnancy may occur when administered to a pregnant women

            Drug interaction overview

            • Darolutamide is a P-gp and CYP3A4 substrate; BCRP transporter inhibitor; OATP1B1 and OATP1B3 inhibitor
            • Combined P-gp and strong or moderate CYP3A4 inducers
              • Avoid coadministration
              • Coadministration of darolutamide with a combined P-gp and strong or moderate CYP3A4 inducer decreases darolutamide exposure, which may decrease darolutamide activity
            • Combined P-gp and strong CYP3A4 inhibitors
              • Concomitant use of darolutamide with a combined P-gp and strong CYP3A4 inhibitor increases darolutamide exposure which may increase the risk of darolutamide adverse reactions
              • Monitor more frequently for darolutamide adverse reactions and modify darolutamide dosage as needed
            • Breast cancer resistance protein (BCRP) substrates
              • Concomitant use of darolutamide increases the AUC and peak plasma concentration of BCRP substrates, which may increase the risk of BCRP substrate-related toxicities
              • Avoid use with drugs that are BCRP substrates where possible
              • If used together, monitor more frequently for adverse reactions, and consider dose reduction of the BCRP substrate drug; refer to the prescribing information of the BCRP substrate when used concomitantly with darolutamide
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            Pregnancy & Lactation

            Pregnancy

            Safety and efficacy have not been established in females

            Based on its mechanism of action, fetal harm and loss of pregnancy may occur

            Animal embryofetal developmental toxicology studies were not conducted with darolutamide

            There are no human data on the use in pregnant females

            Contraception

            • Males: Based on the mechanism of action, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 1 week after the last dose

            Infertility

            • Males: Based on animal studies, fertility may be impaired in males of reproductive potential

            Lactation

            Safety and efficacy have not been established in females

            There are no data on the presence of darolutamide or its metabolites in human milk, the effect on the breastfed child, or the effect 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; competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription

            Keto-darolutamide (major metabolite) exhibited similar in vitro activity

            In addition, darolutamide functioned as a progesterone receptor (PR) antagonist in vitro

            Also, decreases prostate cancer cell proliferation in vitro and tumor volume in mouse xenograft models of prostate cancer

            Absorption

            Steady-state peak plasma concentration: 4.79 mg/L

            Peak plasma time: ~4 hr (after single 600-mg dose)

            Absolute bioavailability: ~30% (after 300-mg dose under fasted conditions)

            AUC: 52.82 mcg⋅hr/mL

            Steady-state is reached 2-5 days after repeated dosing with food, with a ~2-fold accumulation

            Effect of food

            • Bioavailability of darolutamide increased by 2- to 2.5-fold when administered with food
            • Similar increase of exposure was observed for the active metabolite keto-darolutamide

            Distribution

            Vd: 119 L (IV)

            Protein bound: 92% (darolutamide); 99.8% (active metabolite, keto-darolutamide)

            Serum albumin is main binding protein for darolutamide and keto-darolutamide

            Metabolism

            Primarily metabolized CYP3A4, as well as by UGT1A9 and UGT1A1

            Keto-darolutamide total exposure in plasma is 1.7-fold higher compared with darolutamide

            Elimination

            Half-life: ~20 hr

            Clearance: 116 mL/min

            Excretion

            • Urine: 63.4%, ~7% unchanged
            • Feces 32.4%; ~30% unchanged
            • >95% of dose recovered within 7 days after administration
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            Administration

            Oral Administration

            Swallow tablets whole with food

            Missed dose

            • Take missed dose as soon as remembered before next scheduled dose; do not take 2 doses together to make up for a missed dose

            Storage

            Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)

            Keep bottle tightly closed after opening

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            Images

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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.

            Adding plans allows you to:

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