darolutamide

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)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	4 hr	unknown

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