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

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