Drug interactions (critical):
Avoid strong CYP3A4/P-gp inducers (rifampicin, carbamazepine, phenytoin, phenobarbital, St John's Wort) → severe drop in drug levels.
Avoid rosuvastatin and other BCRP/OATP1B1/1B3 substrates (atorvastatin, fluvastatin, methotrexate) unless no alternative → risk of toxicity.
Cardiovascular caution:
Patients with recent MI, stroke, unstable angina, or NYHA III–IV heart failure were excluded from trials.
Use carefully and treat CV disease optimally before starting.
Renal/hepatic dysfunction:
Severe renal impairment (eGFR 15–29) → increase exposure; dose should be reduced.
Limited data in moderate hepatic impairment; avoid in severe hepatic impairment.
Neutropenia and LFT changes:
Neutrophil count decrease (commonly lab-based, may reach grade 3–4).
Bilirubin and AST increases possible; monitor.
QT prolongation risk:
Androgen deprivation therapy can prolong QT; caution when using with other QT-prolonging drugs (amiodarone, sotalol, moxifloxacin, methadone, antipsychotics).
Contains lactose:
Contraindicated in patients with galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption.
Generic name: Darolutamide
Brand name: Nubeqa
Drug class: Androgen Receptor Inhibitor
Formulation: Film-coated tablets
Strength: 300 mg
Use: Non-metastatic castration-resistant prostate cancer (nmCRPC) at high risk of metastasis.
Non-metastatic castration-resistant prostate cancer (nmCRPC)
For adult men with nmCRPC and high risk of developing metastatic disease.
Must be used with ongoing androgen deprivation therapy (LHRH agonist) unless surgically castrated.
Standard dose:
600 mg twice daily (2 × 300 mg tablets twice daily)
Total: 1200 mg/day
Administration:
Take with food.
Swallow tablets whole.
Missed dose:
Take as soon as remembered before the next dose.
Do NOT double dose.
Dose modification:
For ≥ Grade 3 toxicity, hold or reduce to 300 mg twice daily until recovery, then return to full dose.
Do not reduce below 300 mg twice daily.
Special populations:
Severe renal impairment (eGFR 15–29): Start with 300 mg twice daily.
Moderate hepatic impairment (Child-Pugh B): Start with 300 mg twice daily.
Not studied in severe hepatic impairment or patients on dialysis.
Hypersensitivity to darolutamide or components.
Women who are or may become pregnant (drug is teratogenic).
Lactose intolerance syndromes (contains lactose).
Avoid / use alternatives for:
Strong CYP3A4/P-gp inducers:
Rifampicin, carbamazepine, phenobarbital, phenytoin, St John’s Wort → ↓ darolutamide levels by up to 70%.
BCRP / OATP1B1/1B3 substrates:
Rosuvastatin (↑ exposure 5-fold), methotrexate, fluvastatin, atorvastatin → risk of toxicity.
Caution with QT-prolonging medications:
Amiodarone, sotalol, methadone, haloperidol, quinidine, moxifloxacin, etc.
Safe:
CYP3A4 inhibitors (e.g., itraconazole) → may ↑ darolutamide modestly; monitor.
P-gp substrates (digoxin, verapamil, nifedipine) → no major interaction.
Before starting & ongoing:
FBC: neutrophil counts (risk of decreases).
Liver function: ALT, AST, bilirubin.
Renal function: baseline; more often in renal impairment.
CV assessment: for patients with cardiac history.
QT-risk assessment if on QT-prolonging meds.
Clinical monitoring:
Symptoms of cardiovascular disease.
Bone health (fracture risk slightly increased).
Fatigue levels.
Very Common / Common
Fatigue / asthenia (15.8%)
→ supportive care.
Rash
→ antihistamines / topical steroids if needed.
Musculoskeletal pain / extremity pain
Fractures (4.2%)
→ assess for osteoporosis; consider bone protective agents.
Bilirubin or AST elevation (lab-based)
→ usually grade 1–2; continue with monitoring.
Neutrophil decrease (19.6% lab-based)
→ mostly mild; rarely leads to discontinuation.
Serious but less common
Ischemic heart disease (3.2%)
Heart failure (1.9%)
→ stop drug, treat per cardiology guidelines.
Rare
Severe neutropenia
Significant hepatic injury (rare but reported)
Elderly:
No dose adjustment needed.
Renal impairment:
Mild/moderate: no change
Severe (eGFR 15–29): start 300 mg BID
ESRD/dialysis: not studied.
Hepatic impairment:
Mild: no change
Moderate (Child-Pugh B): start 300 mg BID
Severe: not studied/avoid.
Continue until:
Radiographic or clinical disease progression
OR
Unacceptable toxicity
Stop immediately if:
Life-threatening cardiac events
Severe hepatic injury
Severe intolerance even after dose reduction
https://pi-pil-repository.sahpra.org.za/wp-content/uploads/2022/11/NUBEQA_EN_PI.pdf
| Generic Name | Darolutamide |
|---|---|
| Drug Class | Androgen Receptor Inhibitor (ARI) |
| Cost | |
| Company | |
|---|---|
| Drug Rep | Admin |
| Indications | Prostate Cancer |
| Dosage |