darolutamide
General
Pronunciation:
dar-oh-loo-ta-mide
Trade Name(s)
- Nubeqa
Ther. Class.
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
Decreased growth and spread of prostate cancer.