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NUBEQA (darolutamide) Side Effects & Safety

^{Proven Tolerability}^|^{NUBEQA Side Effects and Safety Profile in mHSPC: ARANOTE Study}^|^{NUBEQA Triplet Safety and Side Effects Profile in mHSPC: ARASENS Study}^|^{NUBEQA Side Effects and Safety Profile in nmCRPC: ARAMIS Study}^|^{NUBEQA: Contraindications}^|^{NUBEQA: Fertility, Pregnancy and Breastfeeding}

Choose NUBEQA for efficacy that doesn’t compromise your patients’ QoL. Clinically proven in Phase 3 studies across three indications in mHSPC and nmCRPC.

Refer to full

Summary of Product Characteristics (SmPC)

before prescribing.

NUBEQA (darolutamide) Safety and Side Effects: Tolerability

NUBEQA (darolutamide) safety and tolerability is well-documented across three clinical trials: ARANOTE, ARASENS, and ARAMIS, and supports its suitability for a wide range of mHSPC and nmCRPC patient populations.
NUBEQA offers a distinct molecular structure, reduced blood–brain barrier penetration^* and fewer drug–drug interactions versus other second-generation ARIs.
NUBEQA’s proven tolerability, helps patients continue treatment without further impacting their QoL and daily routines.

^{* Versus apalutamide and enzalutamide in a preclinical model.}

Explore the ARANOTE Clinical Trial

NUBEQA (darolutamide) Side effects and Safety: ARANOTE Study

The ARANOTE Phase III clinical trial investigated the efficacy and safety of NUBEQA in combination with ADT in metastatic hormone-sensitive prostate cancer (mHSPC) patients.
Patients randomised in a 2:1 ratio (N=669) were administered either NUBEQA + ADT doublet therapy (n=446) or placebo + ADT (n=223), with a primary endpoint of radiographic progression-free survival.
The well-established and consistent NUBEQA safety profile was demonstrated in ARANOTE, adding to the body of evidence from ARASENS (mHSPC) and ARAMIS (nmCRPC) clinical trials.

Explore the ARANOTE Clinical Trial

ARANOTE: Occurrence of Adverse Events (AEs) with NUBEQA + ADT vs Placebo + ADT

Most adverse events were grade 1 and 2,

with no significant differences in grade 3, 4, and 5 adverse events in the treatment groups.

^{a : Two patients who were randomly assigned to the placebo group but received NUBEQA are analysed in the NUBEQA group for the safety analysis set.}

Maintain your patients’ QoL with NUBEQA

The only second-generation ARI in mHSPC with lower levels of fatigue and fewer discontinuations versus placebo when added to ADT in a Phase III clinical trial.

ARANOTE: AEs of special interest common to the ARI class

In ARANOTE, burdensome adverse events commonly associated with second-generation ARIs, including rash, occurred at low or similar incidences in the NUBEQA + ADT and placebo + ADT groups.
NUBEQA is the only second-generation ARI with lower rate of fatigue when added to ADT versus placebo + ADT in a Phase III clinical trial (5.6% vs 8.1%).

Image Footnotes:

^{*This category combines the following MedDRA terms: rash, maculopapular rash, popular rash, pustular rash, and dermatitis. †This category is a MedDRA High-Level Group Term. ‡Excluding pathologic fractures. This category combines the following MedDRA terms: any fractures and dislocations, limb fractures and dislocations, pelvic fractures and dislocations, spinal fractures and dislocations, and thoracic cage fractures and dislocations.}

NUBEQA + ADT displayed a consistent tolerability profile, with low discontinuation rates and extended time on therapy vs placebo +ADT.

Median duration of treatment at time of data cut off

Patients on NUBEQA +ADT experienced median treatment durations that were approximately 7 months longer than those of patients with placebo + ADT (24.2 months vs 17.3 months).

Discontinuation rates in ARANOTE

Discontinuation rates due to adverse events in ARANOTE were lower in the NUBEQA + ADT group (6.1%) than in the placebo + ADT group (9.0%).

^{ARANOTE: NUBEQA + ADT (6.1%, n=445) vs placebo + ADT (9.0%, n=221)}

^{* ARANOTE: NUBEQA +ADT vs Placebo +ADT}

NUBEQA (darolutamide) Summary of the Safety Profile and Side Effects - nmCRPC and mHSPC

In a pooled analysis of NUBEQA + ADT (ARAMIS and ARANOTE), the most common adverse reactions in patients receiving NUBEQA
were fatigue/asthenic conditions (13.7%). The most common serious adverse reactions were ischaemic heart disease (1.9%), cardiac arrhythmias (1.8%), pneumonia (1.5%), urinary retention (1.3%), urinary tract infection (1.1%) and fractures (1.0%).
The most common adverse reactions in patients receiving NUBEQA in combination with docetaxel (ARASENS)
were rash (17.3%) alanine aminotransferase (ALT) increased (15.8%), aspartate aminotransferase (AST) increased (14.0%) and hypertension (13.8%). The most common serious adverse reactions in patients receiving darolutamide in combination with docetaxel were febrile neutropenia (6.1%), neutrophil count decreased (2.8%) and pneumonia (2.5%).
For further information on the NUBEQA (darolutamide) safety profile and full list of adverse events, please refer to the Summary of Product Characteristics (SmPC).

NUBEQA (darolutamide) Contraindications, Special Warnings and Precautions

Contraindications

Contraindications
:

Women who are or may become pregnant, and in patients with known hypersensitivity to the active substance or to any of the excipients listed:

Calcium hydrogen phosphate (E 341)
Croscarmellose sodium
Lactose monohydrate
Magnesium stearate (E 470b)
Povidone (E 1201)
Hypromellose
Lactose monohydrate
Macrogol (E 1521)
Titanium dioxide (E 171)

NUBEQA contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose‑galactose malabsorption should not take this medicinal product.

For further information, please refer to the

Summary of Product Characteristics.

Ischaemic heart disease

Ischaemic heart disease
:

Ischaemic heart disease, including fatal cases, occurred in patients receiving NUBEQA in the clinical studies ARAMIS and ARASENS.
Monitor for signs and symptoms of ischaemic heart disease. Optimise management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidaemia.
Discontinue NUBEQA for Grade 3-4 ischaemic heart disease.

Seizure

Seizure
:

Seizure occurred in patients receiving NUBEQA in the clinical studies ARAMIS and ARASENS. It is unknown whether anti-epileptic medications will prevent seizures with NUBEQA.
Advise patients of the risk of developing a seizure while receiving NUBEQA and of engaging in any activity where sudden loss of consciousness could cause harm to themselves or others.
Consider discontinuation of NUBEQA in patients who develop a seizure during treatment.

Hepatotoxicity

Hepatotoxicity
:

Cases of idiosyncratic drug-induced liver injury (DILI) with increases in alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) to ≥5 and ≥20 x upper limit of normal (ULN) have been reported in NUBEQA clinical trials and post-marketing settings.
In case of liver function test abnormalities suggestive of idiosyncratic drug-induced liver injury, permanently discontinue NUBEQA.

Renal impairment

Renal impairment
:

Available data in patients with severe renal impairment are limited, therefore, patients with renal impairment should be closely monitored for adverse reactions.

Hepatic impairment

Hepatic impairment
:

Available data in patients with moderate hepatic impairment is limited, and NUBEQA has not been studied in patients with severe hepatic impairment.
Therefore, due to potential increased exposure, such patients should be closely monitored for adverse reactions.

Recent cardiovascular disease

Recent cardiovascular disease
:

Safety of NUBEQA in patients with significant cardiovascular disease in the past six months is not established, as these patients were excluded from clinical studies.
If NUBEQA is prescribed, patients with clinically significant cardiovascular disease should be treated for these conditions according to established guidelines.

Drug-drug interactions (DDIs): Concomitant use with other medicinal products

Drug-drug interactions (DDIs): Concomitant use with other medicinal products:

Prostate cancer patients are often managing multiple comorbidities and complex polypharmacy.

NUBEQA interacts with fewer medications versus other second-generation ARIs, offering confidence when treating patients who required concomitant medications

Number of medicines listed as an interaction in the BNF (as of August 2025)

Number of medicines listed as an interaction graph

DDIs may cause treatment and/or management complexities, such as: Reduced efficacy of ARI and other prescribed medications; dose adjustment, discontinuation or switching; increased risk, incidence and severity of AEs; increased stress, confusion and anxiety for patients and caregivers; and increased healthcare burden
Use of strong CYP3A4 and P‑gp inducers during treatment with NUBEQA may decrease the plasma concentration of NUBEQA and is not recommended, unless there is no therapeutic alternative.
Patients should be monitored for adverse reactions of BCRP, OATP1B1 and OATP1B3 substrates as co‑administration with NUBEQA may increase the plasma concentrations of these substrates.
Co‑administration of NUBEQA and rosuvastatin should be avoided unless there is no therapeutic alternative.

Deepen your learning of second-generation ARI DDIs:

View this Learning Module on DDIs

ADT may prolong the QT interval

ADT may prolong the QT interval
:

In patients with a history of risk factors for QT prolongation and in patients receiving concomitant medicinal products that might prolong the QT interval, physicians should assess the benefit‑risk ratio including the potential for Torsade de pointes prior to initiating NUBEQA.

NUBEQA (darolutamide): fertility, pregnancy and breastfeeding

NUBEQA is not indicated in women of childbearing potential and is not to be used in women who are, or may be, pregnant or breastfeeding.

Fertility

There are no human data on the effect of NUBEQA on fertility.
Based on animal studies, NUBEQA may impair fertility in males of reproductive potential.
It is not known whether NUBEQA or its metabolites are present in semen.
If the patient is engaged in sexual activity with a women of childbearing potential, a highly effective contraception method (<1% failure rate per year) should be used during and for 1 week after completion of treatment with NUBEQA to prevent pregnancy.

Pregnancy

Based on its mechanism of action, NUBEQA may cause foetal harm. No non-clinical reproductive toxicity studies have been conducted.
Exposure of the foetus to an androgen receptor inhibitor through seminal transfer to the pregnant women has to be avoided, as this could affect development of the foetus.
If the patient is engaged in sexual activity with a pregnant woman, a condom should be used during and for 1 week after completion of treatment with NUBEQA.

Breastfeeding

It is unknown whether darolutamide or its metabolites are excreted in human milk. No studies in animals have been conducted to evaluate the excretion of darolutamide or its metabolites into milk. A risk to the breastfed child cannot be excluded.

Where can I find summary resources about NUBEQA’s tolerability in nmCRPC and mHSPC?

Discover these Quick Hit Summary resources

Download Resources

Abbreviations

^{ADT, androgen deprivation therapy; AEs, adverse events; ALT, alanine aminotransferase; AR, androgen receptor; ARI, androgen receptor inhibitor; AST, aspartate aminotransferase; BCRP, breast cancer resistance protein; DILI, drug-induced liver injury; MedDRA, medical directory for regulatory activities; mHSPC, metastatic hormone-sensitive prostate cancer; nmCRPC, non-metastatic castration-resistant prostate cancer; OATP1B1/3, organic anion transporting polypeptide 1B1/1B3; QoL, quality of life; SPC, summary of product characteristics; TEAEs, treatment emergent adverse events; ULN, upper limit of normal.}

PP-NUB-GB-2547 | August 2025

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