General

Pronunciation:
dar-oh-loo-ta-mide

Trade Name(s)

• Nubeqa

Ther. Class.

antineoplastics

Pharm. Class.

androgen receptor inhibitors

Indications

Non-metastatic castration resistant prostate cancer.

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 increased 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 (CCr <15 mL/min)
• Severe hepatic impairment;
• OB:   Pregnancy (may cause fetal harm).

Use Cautiously in:

• Severe renal impairment (CCr 15–29 mL/min) (↓ 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: HF, ischemic heart disease

Derm: rash

GI: hyperbilirubinemia, ↑ liver enzymes

Hemat: NEUTROPENIA

Neuro: fatigue

* 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 (2 × 300–mg tablets) twice daily.

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

Hepatic Impairment 
PO (Adults): Moderate hepatic impairment (Child–Pugh Class B)– 300 mg twice daily.

Availability

Film-coated tablets: 300 mg

Assessment

• Monitor for pain in extremities during therapy.

Lab Test Considerations:

May cause neutropenia, and increased AST and bilirubin.

Potential Diagnoses

• Deficient knowledge, related to medication regimen (Patient/Family/Teaching) 

Implementation

• Patients should also be taking a gonadotropin-releasing hormone (GnRH) analog concurrently of have had a bilateral orchiectomy.
• PO Administer twice daily with food. 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 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:  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.