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Darolutamide

Medically reviewed by Drugs.com. Last updated on Aug 5, 2019.

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 manufacturer's labeling.

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.

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

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

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

Rosuvastatin: Darolutamide may increase the serum concentration of Rosuvastatin. Management: Avoid coadministration of darolutamide and rosuvastatin if possible. If combined, monitor for increased rosuvastatin effects/toxicities and consider a rosuvastatin dose reduction. Consider therapy modification

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

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

Adverse Reactions

>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.

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.

Monitoring Parameters

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

Pregnancy Considerations

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

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

Patient Education

What is this drug used for?

• It is used to treat prostate cancer.

Frequently reported side effects of this drug

• Loss of strength and energy

• Pain in arms or legs

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Infection

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of 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 brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Further information

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

More about darolutamide

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