Androgen Receptor Antagonist (Second-Generation) Pregnancy: US label §8.1: 'The safety and efficacy of NUBEQA have not been established in females. Based on its mechanism of action, NUBEQA can cause fetal harm and loss of pregnancy.' Animal embryo-fetal developmental toxicology studies were not conducted with darolutamide and there are no human data in pregnant females. §5.3 embryo-fetal toxicity: advise males with female partners of reproductive potential to use effective contraception.

Darolutamide

Brand names: Nubeqa

Darolutamide is an oral second-generation androgen-receptor inhibitor used in prostate cancer, including non-metastatic castration-resistant disease and, with chemotherapy, metastatic hormone-sensitive disease. It is always combined with ongoing androgen-deprivation therapy.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: 600 mg (two 300 mg tablets) twice daily

Route: Oral — swallow tablets whole, taken with food

Frequency: Twice daily, continued until disease progression or unacceptable toxicity

Max: 600 mg twice daily (1200 mg/day) is the recommended dose; the label states no separate ceiling above this

SOURCE CAVEAT: providers.emc is null in this bundle — NO UK SPC was fetched. All figures below are verbatim from the US prescribing information for NUBEQA (Bayer HealthCare Pharmaceuticals Inc., label date 2025-06-03) §2.1–2.4; the clinician must verify against the UK SPC before publication. VERBATIM §2.1: 'The recommended dose of NUBEQA is 600 mg (two 300 mg tablets) taken orally, twice daily, with food.' 'Continue treatment until disease progression or unacceptable toxicity occurs.' ANDROGEN DEPRIVATION: 'Patients receiving NUBEQA should also receive a gonadotropin-releasing hormone (GnRH) agonist or antagonist concurrently or have had a bilateral orchiectomy.' WITH DOCETAXEL (mCSPC): 'administer the first of 6 cycles of docetaxel within 6 weeks after the start of NUBEQA treatment'; refer to the docetaxel prescribing information for its own dosing; NUBEQA may be continued even if a docetaxel cycle is delayed, interrupted or discontinued. MISSED DOSE: take as soon as remembered prior to the next scheduled dose; do not take two doses together to make up for a missed dose. DOSE MODIFICATION §2.2: for a ≥ Grade 3 or an intolerable adverse reaction, withhold NUBEQA or reduce the dose to 300 mg twice daily until symptoms improve; NUBEQA may be resumed at 600 mg twice daily when the adverse reaction returns to baseline. 'Dosage reduction below 300 mg twice daily is not recommended.' Additional dose modifications may be required for ischaemic heart disease or seizure. HEPATIC IMPAIRMENT §2.4: for moderate hepatic impairment (Child-Pugh Class B) the recommended dose is 300 mg twice daily; the fetched label states no recommendation for severe hepatic impairment. PAEDIATRIC §8.4: 'Safety and effectiveness of NUBEQA in pediatric patients have not been established' — verify any under-18 use against a children's formulary. ELDERLY §8.5: no overall differences in safety or efficacy were observed between older and younger patients. Sections 5, 6 and 7 of the fetched label were truncated at the source-fetch limit.

Dose adjustments

Renal

US label §2.3: for patients with severe renal impairment (eGFR 15–29 mL/min/1.73 m2) not receiving haemodialysis, the recommended dose is 300 mg twice daily. No recommendation is given in the fetched label for patients on haemodialysis.

Dose auto-extracted from US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

None — US label §4 states 'None.' (no contraindications are listed in the fetched labelling; the UK SPC §4.3 was not fetched and must be checked)

Side effects

In nmCRPC and mCSPC, the most common adverse reactions (>10% with a ≥2% increase over placebo), including laboratory abnormalities: increased AST, decreased neutrophil count, increased bilirubin, fatigue and increased ALT
In mCSPC in combination with docetaxel, the most common adverse reactions (≥10% with a ≥2% increase over placebo): constipation, rash, decreased appetite, haemorrhage, increased weight and hypertension
In mCSPC with docetaxel, the most common laboratory abnormalities (≥30%): anaemia, hyperglycaemia, decreased lymphocyte count, decreased neutrophil count, increased AST, increased ALT and hypocalcaemia
Ischaemic heart disease, including fatal cases (3.4% vs 2.2% placebo in the pooled ARAMIS/ARANOTE analysis; Grade 3–4 in 1.4% vs 0.3%) — monitor and optimise cardiovascular risk factors; discontinue for Grade 3–4 events (§5.1)
Seizure — consider discontinuation in patients who develop a seizure during treatment (§5.2)

Interactions

Combined P-gp and strong or moderate CYP3A4 inducers — avoid concomitant use; they decrease darolutamide exposure, which may decrease NUBEQA activity (§7.1)
Combined P-gp and strong CYP3A4 inhibitors — increase darolutamide exposure; monitor patients more frequently for NUBEQA adverse reactions (§7.1)
BCRP substrates — avoid concomitant use where possible; if used together, monitor more frequently for adverse reactions and consider dose reduction of the BCRP substrate (§7.2)
OATP1B1 and OATP1B3 substrates — concomitant NUBEQA may increase their plasma concentrations; monitor more frequently and consider dose reduction of these drugs (§7.2)
NOTE: §7 was truncated at the source-fetch limit — clinician to review the full interaction section

Clinical monograph

How it works

It binds the androgen receptor with high affinity and blocks its nuclear translocation and signalling, suppressing androgen-driven prostate cancer growth.

Prescribing in practice

Fatigue, fractures, and ischaemic cardiovascular events are recognised risks, so cardiovascular risk factors and bone health should be assessed and managed.
Continue concurrent GnRH analogue therapy (or maintain surgical castration) throughout treatment.
It has clinically relevant interactions via transporters and CYP3A4, so review co-medications against the SPC.

Monitoring

Monitor PSA and clinical response, and review for cardiovascular events, fractures, and significant fatigue during therapy.

Counselling the patient

Take the tablets with food as directed.
Report chest pain, breathlessness, or new bone pain promptly.
Do not stop your other prostate (hormone) injections without advice.

Evidence & guidelines

Supported by randomised trials showing improved metastasis-free and overall survival in castration-resistant and hormone-sensitive prostate cancer.

Reference: NICE TA660 (Darolutamide for nmCRPC); ARAMIS Trial; ARASENS Trial; EAU Guidelines 2024; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways