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Darolutamide

Medically reviewed by Drugs.com. Last updated on July 25, 2020.

Pronunciation

(DAR oh LOO ta mide)

Index Terms

  • BAY 1841788
  • ODM 201

Dosage Forms

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

Tablet, Oral:

Nubeqa: 300 mg

Brand Names: U.S.

  • Nubeqa

Pharmacologic Category

  • Antineoplastic Agent, Antiandrogen

Pharmacology

Darolutamide is a competitive androgen receptor inhibitor. In addition to androgen binding inhibition, darolutamide also inhibits androgen receptor translocation and androgen receptor-mediated transcription. Keto-darolutamide (active metabolite) has similar in vitro activity to darolutamide. Androgen receptor inhibition results in decreased proliferation of prostate tumor cells and increased apoptosis, leading to a decrease in tumor volume.

Distribution

119 L; darolutamide has low blood-brain barrier penetration (Fizazi 2019).

Metabolism

Primarily metabolized by CYP3A4, as well as by UGT1A9 and UGT1A1; active metabolite is keto-darolutamide.

Excretion

Urine: 63.4% (~7% as unchanged drug); feces: 32.4% (~30% as unchanged drug); Clearance: 116 mL/minute.

Time to Peak

~4 hours.

Half-Life Elimination

~20 hours (darolutamide and keto-darolutamide).

Protein Binding

Darolutamide: 92%; keto-darolutamide (active metabolite): 99.8%; primarily to serum albumin.

Special Populations: Renal Function Impairment

Darolutamide exposure was increased by ~2.5-fold in noncancer subjects with severe renal impairment (eGFR 15 to 29 mL/minute/1.73 m2) not receiving dialysis as compared to healthy subjects.

Special Populations: Hepatic Function Impairment

Darolutamide exposure was increased by ~1.9-fold in noncancer subjects with moderate (Child Pugh class B) hepatic impairment as compared to healthy subjects.

Use: Labeled Indications

Prostate cancer, nonmetastatic, castration-resistant: Treatment of nonmetastatic castration-resistant prostate cancer.

Contraindications

There are no contraindications listed in the US manufacturer's labeling.

Canadian labeling: Hypersensitivity to darolutamide or any component of the formulation.

Dosing: Adult

Prostate cancer, nonmetastatic, castration-resistant: Oral: 600 mg twice daily (in combination with a gonadotropin-releasing hormone analog [if had not received bilateral orchiectomy]); continue until disease progression or unacceptable toxicity (Fizazi 2019).

Missed dose: If a dose is missed, administer as soon as possible prior to the next scheduled dose; do not take 2 doses at the same time to make up for a missed dose.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

Grade 3 or higher toxicity (or intolerable adverse reaction): Withhold darolutamide or reduce dose to 300 mg twice daily until symptoms improve; may then resume therapy at 600 mg twice daily. Dose reduction <300 mg twice daily is not recommended.

Administration

Oral: Administer with food. Swallow tablets whole.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). Keep the bottle tightly closed after initial opening.

Drug Interactions

Alpelisib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions. Consider therapy modification

Asunaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Asunaprevir. Avoid combination

Cladribine: BCRP/ABCG2 Inhibitors may increase the serum concentration of Cladribine. Management: Avoid concomitant use of BCRP inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider dose reduction of the BCRP inhibitor and separation in the timing of administration. Consider therapy modification

CloZAPine: CYP3A4 Inducers (Weak) may decrease the serum concentration of CloZAPine. Monitor therapy

Elagolix: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix. Avoid combination

Elagolix, Estradiol, and Norethindrone: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix, Estradiol, and Norethindrone. Specifically, concentrations of elagolix may be increased. Avoid combination

Eluxadoline: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with OATP1B1/1B3 inhibitors and monitor patients for increased eluxadoline effects/toxicities. Consider therapy modification

Grazoprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Grazoprevir. Avoid combination

Inducers of CYP3A4 (Moderate) and P-glycoprotein: May decrease the serum concentration of Darolutamide. Avoid combination

Inducers of CYP3A4 (Strong) and P-glycoprotein: May decrease the serum concentration of Darolutamide. Avoid combination

Inhibitors of CYP3A4 (Strong) and P-glycoprotein: May increase the serum concentration of Darolutamide. Monitor therapy

NiMODipine: CYP3A4 Inducers (Weak) may decrease the serum concentration of NiMODipine. Monitor therapy

Ozanimod: BCRP/ABCG2 Inhibitors may increase serum concentrations of the active metabolite(s) of Ozanimod. Avoid combination

PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination

Revefenacin: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentrations of the active metabolite(s) of Revefenacin. Avoid combination

Rimegepant: BCRP/ABCG2 Inhibitors may increase the serum concentration of Rimegepant. Avoid combination

Rosuvastatin: Darolutamide may increase the serum concentration of Rosuvastatin. Management: Limit the dose of rosuvastatin to 5 mg daily when combined with darolutamide. Monitor closely for increased rosuvastatin effects/toxicities (eg, myalgias, rhabdomyolysis) when these agents are combined. Consider therapy modification

Selpercatinib: CYP3A4 Inducers (Weak) may decrease the serum concentration of Selpercatinib. Monitor therapy

Tacrolimus (Systemic): CYP3A4 Inducers (Weak) may decrease the serum concentration of Tacrolimus (Systemic). Monitor therapy

Talazoparib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. Monitor therapy

Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. Avoid combination

Ubrogepant: CYP3A4 Inducers (Weak) may decrease the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a weak CYP3A4 inducer. Consider therapy modification

Ubrogepant: BCRP/ABCG2 Inhibitors may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a BCRP inhibitor. Consider therapy modification

Voxilaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Voxilaprevir. Avoid combination

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Central nervous system: Fatigue (16%)

Hematologic & oncologic: Neutropenia (20%; grade 3/4 4%)

Hepatic: Increased serum aspartate aminotransferase (20%), increased serum bilirubin (16%)

Neuromuscular & skeletal: Asthenia (≤16%)

1% to 10%:

Cardiovascular: Ischemic heart disease (4%), cardiac failure (2%)

Dermatologic: Skin rash (3%)

Neuromuscular & skeletal: Limb pain (6%)

Frequency not defined:

Cardiovascular: Hypertension

Genitourinary: Hematuria, urinary retention

Respiratory: Pneumonia

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Neutropenia was observed more frequently with darolutamide than placebo in a clinical trial, although the incidence was not high.

Disease-related concerns:

• Cardiovascular disease: Androgen-deprivation therapy may increase the risk for cardiovascular disease (Levine 2010).

• Hepatic impairment: Patients with moderate hepatic impairment (Child-Pugh class B) have increased darolutamide exposure; dose reduction is recommended.

• Renal impairment: Patients with severe renal impairment (eGFR 15 to 29 mL/minute/1.73 m2) who are not receiving hemodialysis have increased darolutamide exposure; dose reduction is recommended.

Monitoring Parameters

Monitor hepatic and renal function as clinically necessary. Monitor adherence.

Reproductive Considerations

Males with female partners of reproductive potential should use effective contraception during darolutamide treatment and for 1 week after the last darolutamide dose.

Pregnancy Considerations

Based on the mechanism of action, darolutamide may cause fetal harm and pregnancy loss if utero exposure occurs.

Patient Education

What is this drug used for?

• It is used to treat prostate cancer.

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:

• Loss of strength and energy

• Pain in arms or legs

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infection

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.