General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Pronunciation:
dar-oh-loo-ta-mide

Trade Name(s)

• Nubeqa

Ther. Class.

antineoplastics

Pharm. Class.

androgen receptor inhibitors

Indications

• Nonmetastatic castration resistant prostate cancer.
• Metastatic hormone-sensitive prostate cancer (in combination with docetaxel).

Action

Acts as an androgen receptor inhibitor, preventing the binding of androgen; decreases proliferation and induces cell death of prostate cancer cells.

Therapeutic Effect(s):

Decreased growth and spread of prostate cancer.

Pharmacokinetics

Absorption: 30% absorbed following oral administration; absorption ↑ with food.

Distribution: Extensively distributed to tissues.

Protein Binding: Darolutamide: 92%;  Keto-darolutamide: 99.8%.

Metabolism and Excretion: Primarily metabolized in the liver by the CYP3A4 isoenzyme as well as by UGT1A1 and UGT1A9 to an active metabolite (keto-darolutamide). Primarily excreted in urine (63%, 7% as unchanged drug) and 32% excreted in feces (30% as unchanged drug).

Half-life: 20 hr.

TIME/ACTION PROFILE (plasma concentrations)

Contraindication/Precautions

Contraindicated in:

• End-stage renal disease;
• Severe hepatic impairment.

Use Cautiously in:

• Severe renal impairment (↓ dose);
• Moderate hepatic impairment (↓ dose);
• Rep:  Men with female partners of reproductive potential;
• Pedi:  Safety and effectiveness not established in children.

Adverse Reactions/Side Effects

CV: ISCHEMIC HEART DISEASE, HF

Derm: rash

GI: hyperbilirubinemia, ↑ liver enzymes

Hemat: NEUTROPENIA

Neuro: fatigue, SEIZURES

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

• Concurrent use with a  combined P-glycoprotein and strong or moderate CYP3A4 inducer, including  rifampin, may ↓ levels and effectiveness; avoid concurrent use.
• Concurrent use with a  combined P-glycoprotein and strong CYP3A4 inhibitor, including  itraconazole, may ↑ levels and the risk of toxicity; avoid concurrent use.
• May ↑ levels of  BCRP substrates, including  rosuvastatin ; avoid concurrent use.

Route/Dosage

Patients should also be taking a gonadotropin-releasing hormone (GnRH) analog or should have undergone a bilateral orchiectomy.

PO (Adults): 600 mg twice daily until disease progression or unacceptable toxicity.

Renal Impairment 
PO (Adults): CCr 15–29 mL/min: 300 mg twice daily.

Hepatic Impairment 
PO (Adults): Moderate hepatic impairment: 300 mg twice daily.

Availability

Tablets: 300 mg

Assessment

• Monitor for pain in extremities during therapy.
• Monitor for signs and symptoms of ischemic heart disease (chest pain or discomfort at rest or with activity, or shortness of breath) during therapy.

Lab Test Considerations:

May cause neutropenia, and increased AST and bilirubin.

Implementation

• Patients should also be taking a GnRH analog concurrently if they have had a bilateral orchiectomy.
• PO Administer twice daily with food.  DNC: Swallow tablets whole; do not crush, break, or chew. 

Patient/Family Teaching

• Instruct patient to take darolutamide as directed. Take missed doses as soon as remembered, but do not take two doses together to make up for a missed dose. Advise patient to read  Patient Information  before starting therapy and with each Rx refill in case of changes.
• Inform patient of importance of continuing therapy with gonadotropin-releasing hormone during therapy with darolutamide.
• Advise patient darolutamide may increase risk for seizures. Avoid activities where a sudden loss of consciousness could cause serious harm to yourself or others. Tell your health care professional right away if you have loss of consciousness or seizure.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
• Rep:  May cause fetal harm. Advise male patients with female partners of reproductive potential to use effective contraception and avoid breastfeeding during and for 1 wk after last dose. Inform patient that darolutamide may impair fertility.

Evaluation/Desired Outcomes

Decreased growth and spread of prostate cancer.