darolutamide

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)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	4 hr	unknown

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

Combined P-glycoprotein and strong or moderate CYP3A4 inducers, including rifampin, may ↓ levels and effectiveness; avoid concurrent use.
Combined P-glycoprotein and strong CYP3A4 inhibitors, including itraconazole, may ↑ levels and risk of toxicity; avoid concurrent use.
May ↑ levels and risk of toxicity of breast cancer resistance protein 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 fatigue, pain in extremities, and rash during therapy.
Monitor for signs and symptoms of ischemic heart disease. Optimally manage hypertension, diabetes, and dyslipidemia. If Grade 3–4 ischemic heart disease occurs, permanently discontinue darolutamide.

Lab Test Considerations:

May cause neutropenia, ↑ AST, and ↑ bilirubin.

Implementation

Patients with bilateral orchiectomy should take a GnRH analog concurrently.
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.
Advise patient darolutamide may ↑ risk of seizures. Avoid activities where a sudden loss of consciousness could cause serious harm to self or others. Notify health care professional immediately if seizure symptoms occur.
Advise patient to immediately notify health care professional of chest pain or difficulty breathing.
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