Nubeqa
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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
NUBEQA 300 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 300 mg of darolutamide. 
 
Excipient with known effect 
 
Each film-coated tablet contains 186 mg of lactose monohydrate (see section 4.4). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet (tablet). 
 
White to off-white, oval tablets with a length of 16 mm and a width of 8 mm, marked with “300” on 
one side, and “BAYER” on the other side. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
NUBEQA is indicated for the treatment of adult men with non-metastatic castration resistant prostate 
cancer (nmCRPC) who are at high risk of developing metastatic disease (see section 5.1). 
 
4.2 Posology and method of administration 
 
Treatment should be initiated and supervised by a specialist physician experienced in treatment of 
prostate cancer. 
 
Posology 
 
The recommended dose is 600 mg darolutamide (two tablets of 300 mg) taken twice daily, equivalent 
to a total daily dose of 1200 mg (see section 5.2). 
 
Medical castration with a luteinising hormone-releasing hormone (LHRH) analogue should be 
continued during treatment of patients not surgically castrated. 
 
Missed dose 
If a dose is missed, the dose should be taken as soon as the patient remembers prior to the next 
scheduled dose. The patient should not take two doses together to make up for a missed dose. 
 



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Dose modification 
If a patient experiences a ≥ Grade 3 toxicity or an intolerable adverse reaction (see section 4.8), dosing 
should be withheld or reduced to 300 mg twice daily until symptoms improve. Treatment may then be 
resumed at a dose of 600 mg twice daily. 
 
Dose reduction below 300 mg twice daily is not recommended, because efficacy has not been 
established. 
 
Special populations 
 
Elderly 
No dose adjustment is necessary in elderly patients (see section 5.2). 
 
Renal impairment 
No dose adjustment is necessary for patients with mild or moderate renal impairment. 
For patients with severe renal impairment (eGFR 15-29 mL/min/1.73 m2) not receiving haemodialysis, 
the recommended starting dose is 300 mg twice daily (see sections 4.4 and 5.2). 
 
Hepatic impairment 
No dose adjustment is necessary for patients with mild hepatic impairment. 
The available data on darolutamide pharmacokinetics in moderate hepatic impairment is limited. 
Darolutamide has not been studied in patients with severe hepatic impairment. 
For patients with moderate and severe hepatic impairment (Child-Pugh Classes B and C), the 
recommended starting dose is 300 mg twice daily (see sections 4.4 and 5.2.). 
 
Paediatric population 
There is no relevant use of darolutamide in the paediatric population for the indication of treatment of 
nmCRPC. 
 
Method of administration 
 
NUBEQA is for oral use. 
 
The tablets should be taken whole with food (see section 5.2). 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
Women who are or may become pregnant (see section 4.6). 
 
4.4 Special warnings and precautions for use 
 
Renal impairment 
 
The available data in patients with severe renal impairment are limited. 
As exposure might be increased those patients should be closely monitored for adverse reactions (see 
sections 4.2 and 5.2). 
 
Hepatic impairment 
 
The available data in patients with moderate hepatic impairment are limited, and darolutamide has not 
been studied in patients with severe hepatic impairment. 
As exposure might be increased those patients should be closely monitored for adverse reactions (see 
sections 4.2 and 5.2). 
 



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Recent cardiovascular disease 
 
Patients with clinically significant cardiovascular disease in the past 6 months including stroke, 
myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, and 
symptomatic congestive heart failure were excluded from the clinical studies. Therefore, the safety of 
darolutamide in these patients has not been established. 
If NUBEQA is prescribed, patients with clinically significant cardiovascular disease should be treated 
for these conditions according to established guidelines. 
 
Concomitant use with other medicinal products 
 
Use of strong CYP3A4 and P-gp inducers during treatment with darolutamide may decrease the 
plasma concentration of darolutamide and is not recommended, unless there is no therapeutic 
alternative. Selection of an alternate concomitant medicinal product with less potential to induce 
CYP3A4 or P-gp should be considered (see section 4.5). 
 
Patients should be monitored for adverse reactions of BCRP, OATP1B1 and OATP1B3 substrates as 
co-administration with darolutamide may increase the plasma concentrations of these substrates. 
Co-administration with rosuvastatin should be avoided unless there is no therapeutic alternative (see 
section 4.5). 
 
Androgen deprivation therapy 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 (see section 4.5), physicians should assess the 
benefit-risk ratio including the potential for Torsade de pointes prior to initiating NUBEQA. 
 
Information about excipients 
 
NUBEQA contains lactose. Patients with rare hereditary problems of galactose intolerance, total 
lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Effects of other medicinal products on darolutamide 
 
CYP3A4 and P-gp inducers 
Darolutamide is a substrate of CYP3A4 and P-glycoprotein (P-gp). 
Use of strong and moderate CYP3A4 inducers and P-gp inducers (e.g. carbamazepine, phenobarbital, 
St. John's Wort, phenytoin, and rifampicin) during treatment with darolutamide is not recommended, 
unless there is no therapeutic alternative. Selection of an alternate concomitant medicinal product, 
with no or weak potential to induce CYP3A4 or P-gp should be considered. 
Repeated administration of rifampicin (600 mg), a strong CYP3A4 and a P-gp inducer, with a single 
dose of darolutamide (600 mg) together with food, resulted in a decrease of 72% in mean exposure 
(AUC0-72) and a decrease of 52% in Cmax of darolutamide. 
 
CYP3A4, P-gp and BCRP inhibitors 
Darolutamide is a substrate of CYP3A4, P-gp and breast cancer resistance protein (BCRP). 
No clinically relevant drug-drug interaction is expected in case of CYP3A4, P-gp or BCRP inhibitor 
administration. Darolutamide may be given concomitantly with CYP3A4, P-gp or BCRP inhibitors. 
Concomitant use of darolutamide with a combined P-gp and strong CYP3A4 inhibitor increases 
darolutamide exposure which may increase the risk of darolutamide adverse reactions. It is 
recommended to monitor patients more frequently for darolutamide adverse reactions and modify 
darolutamide dose as needed. 



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Administration of itraconazole (200 mg twice daily on day 1 and once daily on the following 7 days), 
a strong CYP3A4, P-gp and BCRP inhibitor, with a single dose of darolutamide (600 mg on day 5 
together with food) resulted in a 1.7-fold increase in mean exposure (AUC0-72) and a 1.4-fold increase 
of Cmax of darolutamide. 
 
UGT1A9 inhibitors 
Darolutamide is a substrate of UGT1A9. 
No clinically relevant drug-drug interaction is expected in case of UGT1A9 inhibitor administration.  
Darolutamide may be given concomitantly with UGT1A9 inhibitors. 
A population pharmacokinetic analysis showed that co-administration of UGT1A9 inhibitors with 
darolutamide resulted in a 1.2-fold increase in exposure (AUC0-72) of darolutamide. 
 
Effects of darolutamide on other medicinal products 
 
BCRP, OATP1B1 and OATP1B3 substrates 
Darolutamide is an inhibitor of breast cancer resistance protein (BCRP) and Organic Anion 
Transporting Polypeptides (OATP) 1B1 and 1B3. 
Co-administration of rosuvastatin should be avoided unless there is no therapeutic alternative. 
Selection of an alternative concomitant medicinal product with less potential to inhibit BCRP, 
OATP1B1 and OATP1B3 should be considered. 
Administration of darolutamide (600 mg twice daily for 5 days) prior to co-administration of a single 
dose of rosuvastatin (5 mg) together with food resulted in approximately 5-fold increase in mean 
exposure (AUC) and Cmax of rosuvastatin. 
Co-administration of darolutamide with other BCRP substrates should be avoided where possible. 
Co-administration of darolutamide may increase the plasma concentrations of other concomitant 
BCRP, OATP1B1 and OATP1B3 substrates (e.g. methotrexate, sulfasalazine, fluvastatin, atorvastatin, 
pitavastatin). Therefore, it is recommended to monitor patients for adverse reactions of BCRP, 
OATP1B1 and OATP1B3 substrates. In addition, the related recommendation in the product 
information of these substrates should be followed when co-administered with darolutamide. 
 
P-gp substrates 
No clinically relevant drug-drug interaction is expected in case of P-gp substrate administration. 
Darolutamide may be given concomitantly with P-gp substrates (e.g. digoxin, verapamil or 
nifedipine). Co-administration of darolutamide together with the sensitive P-gp substrate dabigatran 
etexilate did not reveal any increase in exposure (AUC and Cmax) of dabigatran. 
 
CYP3A4 substrates 
Darolutamide is a mild inducer of CYP3A4. 
No clinically relevant drug-drug interaction is expected in case of CYP substrate administration. 
Darolutamide may be given concomitantly with CYP substrates (e.g. warfarin, L-thyroxine, 
omeprazole). 
Administration of darolutamide (600 mg twice daily for 9 days) prior to co-administration of a single 
dose of the sensitive CYP3A4 substrate midazolam (1 mg) together with food, decreased the mean 
exposure (AUC) and Cmax of midazolam by 29% and 32%, respectively. 
Darolutamide did not inhibit the metabolism of selected CYP substrates in vitro at clinically relevant 
concentrations. 
 
Medicinal products that prolong the QT interval 
Since androgen deprivation treatment may prolong the QT interval, the co-administration with 
medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de 
pointes should be carefully evaluated. These include medicinal products such as class IA (e.g., 
quinidine, disopyramide) or class III (e.g., amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmic 
medicinal products, methadone, moxifloxacin, and antipsychotics (e.g. haloperidol). 
 



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4.6 Fertility, pregnancy and lactation 
 
This medicinal product is not indicated in women of childbearing potential. It is not to be used in 
women who are, or may be, pregnant or breast-feeding (see sections 4.1 and 4.3). 
 
Women of childbearing potential / contraception in males and females 
 
It is not known whether darolutamide or its metabolites are present in semen. If the patient is engaged 
in sexual activity with a woman of childbearing potential, a highly effective contraceptive 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, darolutamide may cause foetal harm. No non-clinical reproductive 
toxicity studies have been conducted (see section 5.3). 
It is not known whether darolutamide or its metabolites are present in semen. 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. Exposure of the foetus to an androgen receptor inhibitor 
through seminal transfer to the pregnant woman has to be avoided, as this could affect development of 
the foetus. 
 
Breast-feeding 
 
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 
(see section 5.3). A risk to the breast-fed child cannot be excluded. 
 
Fertility 
 
There are no human data on the effect of darolutamide on fertility. 
Based on animal studies, NUBEQA may impair fertility in males of reproductive potential (see 
section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
NUBEQA has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most frequently observed adverse reaction is fatigue/asthenic conditions (15.8%). 
 
Tabulated list of adverse reactions 
 
The adverse reactions observed are listed in Table 1 below. They are classified according to System 
Organ Class. 
Adverse reactions are grouped according to their frequencies. Frequency groups are defined by the 
following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to 
< 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from 
the available data). 
Within each frequency group, adverse reactions are presented in order of decreasing seriousness. 
 



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Table 1: Adverse reactions reported in the ARAMIS study 
System organ class 
(MedDRA) 

Very common Common 

Cardiac disorders  Ischaemic heart diseaseb 
Heart failurec 

Skin and subcutaneous tissue 
disorders 

 Rash 

Musculoskeletal and connective 
tissue disorders 

 Pain in extremity 
Musculoskeletal pain 
Fractures 

General disorders and administration 
site conditions 

Fatigue/asthenic conditionsa  

Investigationsd Neutrophil count decreased 
Bilirubin increased 
AST increased 

 

a Includes fatigue and asthenia, lethargy and malaise. 
b Includes arteriosclerosis coronary artery, coronary artery disease, coronary artery occlusion, coronary 

artery stenosis, acute coronary syndrome, acute myocardial infarction, angina pectoris, angina unstable, 
myocardial infarction, myocardial ischaemia. 

c Includes cardiac failure, cardiac failure acute, cardiac failure chronic, cardiac failure congestive, 
cardiogenic shock. 

d Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. 
 
Description of selected adverse reactions 
 
Fatigue 
Fatigue/asthenic conditions were reported in 15.8% of patients treated with darolutamide and in 11.4% 
of patients treated with placebo. Events with worst grade of 3 were reported in 0.6% of patients treated 
with darolutamide and in 1.1% of patients treated with placebo. Fatigue (not including asthenia, 
lethargy or malaise) occurred in the majority of patients (12.1% of patients treated with darolutamide 
and 8.7% of patients treated with placebo). 
 
Fractures 
Fractures occurred in 4.2% of patients treated with darolutamide and in 3.6% of patients treated with 
placebo. 
 
Ischaemic heart disease and heart failure 
Ischaemic heart disease occurred in 3.2% of patients treated with darolutamide and in 2.5% of patients 
treated with placebo. Grade 5 events occurred in 0.3% of patients treated with darolutamide and 0.2% 
of patients treated with placebo. Heart failure occurred in 1.9% of patients treated with darolutamide 
and in 0.9% of patients treated with placebo. 
 
Neutrophil count decreased 
Neutrophil count decreased was reported as a laboratory abnormality in 19.6% of patients treated with 
darolutamide and in 9.4% of patients treated with placebo. The median time to nadir was 256 days. 
The laboratory tests abnormalities manifested predominantly as grade 1 or 2 intensity. Neutrophil 
count decreased of grade 3 and 4 was reported in 3.5% and 0.5% of patients, respectively. Only one 
patient permanently discontinued darolutamide due to neutropenia. Neutropenia was either transient or 
reversible (88% of patients) and were not associated with any clinically relevant signs or symptoms. 
 



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Bilirubin increased 
Bilirubin increased was reported as a laboratory abnormality in 16.4% of patients treated with 
darolutamide and in 6.9% of patients treated with placebo. The episodes were predominantly of 
grade 1 or 2 intensity, not associated with any clinically relevant signs or symptoms, and reversible 
after darolutamide was discontinued. Bilirubin increased of grade 3 was reported in 0.1% of patients 
treated with darolutamide and in 0% of patients treated with placebo. In the darolutamide arm, the 
mean time to first onset of increased bilirubin was 153 days, and the mean duration of the first episode 
was 182 days. No patients were discontinued from treatment due to increase in bilirubin. 
 
AST increased 
AST increased was reported as a laboratory abnormality in 22.5% of patients treated with 
darolutamide and in 13.6% of patients treated with placebo. The episodes were predominantly of 
grade 1 or 2 intensity, not associated with any clinically relevant signs or symptoms, and reversible 
after darolutamide was discontinued. AST increased of grade 3 was reported in 0.5% of patients 
treated with darolutamide and in 0.2% of patients treated with placebo. In the darolutamide arm, the 
mean time to first onset of increased AST was 258 days, and the mean duration of the first episode 
was 118 days. No patients were discontinued from treatment due to increase in AST. 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
The highest dose of darolutamide studied clinically was 900 mg twice daily, equivalent to a total daily 
dose of 1800 mg. No dose limiting toxicities were observed with this dose. 
Considering the saturable absorption (see section 5.2) and the absence of evidence for acute toxicity, 
an intake of a higher than recommended dose of darolutamide is not expected to lead to toxicity. 
In the event of intake of a higher than recommended dose, treatment with darolutamide can be 
continued with the next dose as scheduled. 
There is no specific antidote for darolutamide and symptoms of overdose are not established. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Endocrine therapy, anti-androgens; ATC code: L02BB06 
 
Mechanism of action 
 
Darolutamide is an androgen receptor (AR) inhibitor with a flexible polar-substituted pyrazole 
structure that binds with high affinity directly to the receptor ligand binding domain. 
Darolutamide competitively inhibits androgen binding, AR nuclear translocation, and AR mediated 
transcription. A major metabolite, keto-darolutamide, exhibited similar in vitro activity to 
darolutamide. Darolutamide treatment decreases prostate tumour cell proliferation leading to potent 
antitumour activity. 
 
Pharmacodynamic effects 
 
No prolongation of the mean QTcF interval (i.e., greater than 10 ms) was observed after oral 
administration of 600 mg darolutamide twice daily compared to placebo. 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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Clinical efficacy and safety 
 
The efficacy and safety of darolutamide was assessed in a randomised, double-blind, 
placebo-controlled multicentre phase III study (ARAMIS) in patients with non-metastatic (as assessed 
by conventional imaging CT, bone scan, MRI) castration resistant prostate cancer with a 
prostate-specific antigen doubling time (PSADT) of ≤ 10 months.  
Patients were included in the trial if they had 3 rising prostate-specific antigen (PSA) levels after the 
nadir taken at least 1 week apart during androgen deprivation therapy, PSA ≥ 2 ng/mL at screening 
and castrate level of serum testosterone < 1.7 nmol/L. 
Patients with a medical history of seizure were allowed to enter the study. There were 12 patients 
(0.21%) enrolled on the darolutamide arm with a history of seizure. 
Patients with uncontrolled hypertension or recent (in the past 6 months) stroke, myocardial infarction, 
severe/unstable angina pectoris, coronary/peripheral artery bypass graft, congestive heart failure New 
York Heart Association (NYHA) Class III or IV were excluded from the study. 
Patients with prior treatment with second generation AR inhibitors such as enzalutamide, apalutamide 
and darolutamide, or CYP17 enzyme inhibitors such as abiraterone acetate as well as patients 
receiving systemic corticosteroid with dose greater than the equivalent 10 mg of prednisone/day 
within 28 days before randomisation were excluded from the study. 
In total, 1509 patients were randomized 2:1 to receive either 600 mg darolutamide orally twice daily 
(n=955) or matching placebo (n=554). 
All patients received a gonadotropin-releasing hormone (GnRH) analogue concurrently or had a 
bilateral orchiectomy. Patients with presence of pelvic lymph nodes < 2 cm in short axis below the 
aortic bifurcation were allowed to enter the study. Absence or presence of metastasis was assessed by 
independent central radiological review. Included in these analyses were 89 patients that were 
retrospectively identified with metastasis at baseline. Randomization was stratified by PSADT 
(≤ 6 months or > 6 months) and use of osteoclast-targeted therapy at study entry (yes or no). 
 
The following patient demographics and disease characteristics were balanced between treatment 
arms. The median age was 74 years (range 48-95) and 9% of patients were 85 years of age or older. 
The racial distribution was 79% White, 13% Asian, and 3% Black. A majority of patients had a 
Gleason score of 7 or higher at diagnosis (73%). The median PSADT was 4.5 months. Nine percent 
(9%) of patients had prior orchiectomy, 25% of patients had prior prostatectomy and 50% of patients 
had at least one prior radiotherapy. Seventy-six percent (76%) of patients received more than one prior 
anti-hormonal treatment. Patients had an Eastern Cooperative Oncology Group Performance Status 
(ECOG PS) score of 0 (69%) or 1 (31%) at study entry. 
 
Treatment with darolutamide continued until radiographic disease progression as assessed by 
conventional imaging (CT, bone scan, MRI) by blinded central review, unacceptable toxicity or 
withdrawal. 
The primary efficacy endpoint was metastasis free survival (MFS). Secondary endpoints were overall 
survival (OS), time to pain progression, time to initiation of first cytotoxic chemotherapy for prostate 
cancer, and time to first symptomatic skeletal events (defined as occurrence of any of the following: 
external beam radiotherapy to relieve skeletal symptoms, new symptomatic pathologic bone fracture, 
spinal cord compression, or tumour-related orthopaedic surgical intervention). 
 
Treatment with darolutamide resulted in an improvement in MFS compared to placebo (see Table 2 
and Figure 1). 
MFS results were consistent across patient subgroups regardless of PSADT, prior use of 
bone-targeting agents or loco-regional disease. Additional subgroups with consistent MFS results 
included PSA at baseline, Gleason score at diagnosis, age, geographical region, ECOG PS at baseline, 
race, and number of prior hormonal therapies. 
Treatment with darolutamide also resulted in a positive trend in overall survival (median was not 
reached in either arm at the time of the interim OS analysis) and a delay in time to pain progression 
compared to placebo (see Table 2 and Figure 2). Time to initiation of first cytotoxic chemotherapy and 
time to first symptomatic skeletal event were not mature at the time of primary analyses (see Table 2). 
 



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Table 2: Efficacy results from the ARAMIS study 

Efficacy 
parameter 

Number of events (%) Median (95% CI) 

Hazard Ratioa  
(95% Confidence 

Interval [CI]) 
p-value 

(two-sided) 
Darolutamide 

(n=955) 
Placebo 
(n=554) 

Darolutamide 
(n=955) 

Placebo 
(n=554)  

Metastasis 
free survival  

221 (23.1%) 216 (39.0%) 40.4 months 
(34.3, NR) 

18.4 months 
(15.5, 22.3) 

0.413 
(0.341, 0.500) 

<0.000001 
Overall 
survival 

78 (8.2%) 58 (10.5%) NR 
(44.5, NR) 

NR 
(NR, NR) 

0.706 
(0.501, 0.994) 

0.045210b 
Time to pain 
progressionc 

251 (26.3%) 178 (32.1%) 40.3 months 
(33.2, 41.2) 

25.4 months 
(19.1, 29.6) 

0.647 
(0.533, 0.785) 

0.000008b 
Time to 
initiation of 
first cytotoxic 
chemotherapy 

73 (7.6%) 79 (14.3%) NR 
(NR, NR) 

38.2 months 
(35.6, 41.9) 0.433 (0.314, 0.595) 

<0.000001b 

Time to first 
symptomatic 
skeletal event 

16 (1.7%) 18 (3.2%) NR 
(NR, NR) 

NR 
(NR, NR) 

0.428 
(0.218, 0.842) 

0.011262b 
a Hazard ratio < 1 favours darolutamide 
b The p-value for OS did not reach the pre-defined threshold for statistical significance at the time of the 

interim OS analysis. Therefore (as per hierarchical methodology) a formal testing for significance of the 
remaining three secondary endpoints was not conducted.  

c Patient reported outcome as evaluated by Brief Pain Inventory-Short Form questionnaire 
NR: Not reached. 
 
Treatment with darolutamide also resulted in a longer progression free survival (PFS, median 36.8 vs 
14.8 months, HR=0.380, nominal p<0.000001) and time to PSA progression (median 33.2 vs 
7.3 months, HR=0.130, nominal p<0.000001). Consistency of effect was observed across all measures 
of survival (MFS, OS and PFS). 
 



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Figure 1: Kaplan-Meier curves of metastasis free survival 

 
 
Figure 2: Kaplan-Meier curves of overall survival 

 
 
Patients receiving darolutamide in the ARAMIS study demonstrated a significantly higher confirmed 
PSA response rate (defined as a ≥ 50% reduction from baseline), compared with patients receiving 
placebo, 83.6% vs 7.6% (difference = 76%, p<0.000001). 
 
Paediatric population 
 
The European Medicines Agency has waived the obligation to submit the results of studies with 
darolutamide in all subsets of the paediatric population in prostate malignant neoplasms (see 
section 4.2 for information on paediatric use). 
 

Darolutamide 

Placebo 

M
et

as
ta

si
s 

Fr
ee

 S
ur

vi
va

l P
ro

ba
bi

lit
y 

(%
) 

Months from Randomization Patients at risk 

Darolutamide (N = 955) 
     Placebo (N = 554) 

Darolutamide (N = 955) 
     Placebo (N = 554) 

Months from Randomization 

Darolutamide 

Placebo 

O
ve

ra
ll 

Su
rv

iv
al

 P
ro

ba
bi

lit
y 

(%
) 

Patients at risk 



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5.2 Pharmacokinetic properties 
 
General introduction 
 
Darolutamide consists of two diastereomers [(S,R)-darolutamide and (S,S)-darolutamide] which 
interconvert via the main circulating metabolite called keto-darolutamide. In vitro, all three substances 
show similar pharmacological activity. Darolutamide is poorly soluble in aqueous solvents over a 
large pH range and generally more soluble in organic solvents. 
 
Absorption 
 
Following oral administration of 600 mg (2 tablets of 300 mg), peak plasma concentrations of 
darolutamide of 4.79 mg/L (coefficient of variation: 30.9%) are usually reached around 4 hours after 
administration. The ratio of the two diastereomers, (S,R)-darolutamide to (S,S)-darolutamide, changed 
from a 1:1 ratio in the tablet to an approximately 1:9 ratio in plasma based on AUC0-12 data at 
steady-state. Following oral administration together with food, steady-state is reached after 2-5 days of 
repeated twice-daily dosing. 
The absolute bioavailability compared to an intravenous injection is approximately 30% following oral 
administration of a NUBEQA tablet containing 300 mg darolutamide under fasted conditions. 
Bioavailability of darolutamide was enhanced by 2.0- to 2.5-fold when administered with food. A 
similar increase of exposure was observed for the major metabolite keto-darolutamide.  
 
Distribution 
 
The apparent volume of distribution of darolutamide after intravenous administration is 119 L 
indicating that darolutamide is widely distributed throughout the body to both intracellular and 
extracellular fluid spaces. 
Darolutamide is moderately (92%) bound to human plasma proteins without any difference between 
the two diastereomers. The major metabolite of darolutamide, keto-darolutamide, is highly (99.8%) 
bound to plasma proteins.  
Passage of darolutamide across the blood-brain barrier has not been studied clinically. However, brain 
exposures to darolutamide in terms of AUC0-24 are very low with 4.5% of plasma exposure after single 
dose in rats and 1.9-3.9% after repeated dose in mice. This indicates low passage of darolutamide 
across the intact blood-brain barrier in rats and mice and a low likelihood that darolutamide crosses the 
intact blood-brain barrier in humans to a clinically relevant extent. 
 
Biotransformation 
 
The diastereomers (S,R)-darolutamide and (S,S)-darolutamide are able to interconvert via the 
metabolite keto-darolutamide with a preference for (S,S)-darolutamide.  
Following single oral administration of 300 mg14 C-darolutamide given as an oral solution, 
keto-darolutamide is the only major metabolite with about 2-fold higher total exposure in plasma 
compared to darolutamide. Darolutamide and keto-darolutamide accounted together for 87.4% of 
the 14 C-radioactivity in plasma indicating that all other metabolites are of minor importance.  
Darolutamide is metabolised primarily by oxidative metabolism mediated mainly by CYP3A4, as well 
as by direct glucuronidation mediated preferentially by UGT1A9 and UGT1A1. In addition, mainly 
the AKR1C isoforms were shown to catalyse the reduction of keto-darolutamide to the substance 
diastereomers. 
 



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Elimination 
 
The effective half-life of darolutamide and keto-darolutamide in plasma of patients is approximately 
20 hours. Of the two diastereomers comprising darolutamide, (S,R)-darolutamide has a shorter 
effective half-life of 9 hours compared to (S,S)-darolutamide with an effective half-life of 22 hours. 
The clearance of darolutamide following intravenous administration was 116 mL/min (CV: 39.7%). A 
total of 63.4% of substance-related material is excreted in the urine (approximately 7% unchanged), 
32.4% is excreted in the faeces. More than 95% of the dose was recovered within 7 days after 
administration. 
 
Linearity / Non-linearity 
 
In the dose range of 100 to 700 mg (after single dose and at steady state), the exposure to the two 
diastereomers and the major metabolite keto-darolutamide increases linearly in a nearly dose-related 
manner. Based on a saturated absorption, no further increase in exposure to darolutamide was 
observed at 900 mg twice daily.  
 
Special populations 
 
Elderly 
No clinically relevant differences in the pharmacokinetics of darolutamide were observed 
(65-95 years). 
 
Renal impairment 
In a clinical pharmacokinetic study, AUC and Cmax for darolutamide were 2.5 and 1.6-fold higher in 
patients with severe renal impairment (estimated Glomerular Filtration Rate [eGFR] 15 to 
29 mL/min/1.73 m2) compared to healthy volunteers. 
A population pharmacokinetic analysis indicates a 1.1-, 1.3- and an approximately 1.5-fold higher 
exposure (AUC) of darolutamide in patients with mild, moderate and severe renal impairment (eGFR 
15 to 89 mL/min/1.73 m2) compared to patients with normal renal function. 
The pharmacokinetics of darolutamide has not been studied in patients with end-stage renal disease 
receiving dialysis (eGFR < 15 mL/min/1.73 m2). 
 
Hepatic impairment 
In a clinical pharmacokinetic study, Cmax and AUC for darolutamide were 1.5 and 1.9-fold higher in 
patients with moderate hepatic impairment (Child-Pugh B) compared to healthy volunteers. There are 
no data for patients with severe hepatic impairment (Child-Pugh C). 
 
Ethnic differences 
No clinically relevant differences in the pharmacokinetics of darolutamide were observed based on 
ethnicity (White, Japanese, non-Japanese Asian, Black or African American). A population 
pharmacokinetic analysis indicated a 1.4-fold increase in exposure (AUC) in Japanese patients 
compared to patients from all other regions. 
 



14 

5.3 Preclinical safety data 
 
Systemic toxicity 
 
In repeated dose toxicity studies in rats and dogs, the main findings were changes in the male 
reproductive organs (decreases in organ weight with atrophy of the prostate and epididymides). These 
effects occurred at systemic exposures in the range of or below the anticipated human exposure (based 
on AUC comparison). Additional changes to reproductive tissues included minimal increase in 
vacuolation of the pituitary gland, atrophy and secretory reduction in seminal vesicles and mammary 
glands in rats as well as testicular hypospermia, seminiferous tubule dilatation and degeneration in 
dogs. Changes in the male reproductive organs in both species were consistent with the 
pharmacological activity of darolutamide and reversed or partially resolved after 4- to 8-week 
recovery periods. 
 
Embryotoxicity / teratogenicity 
 
Studies on developmental toxicity have not been performed. 
 
Reproduction toxicity 
 
Studies on reproductive toxicity have not been performed. However, male fertility is likely to be 
impaired based on the findings in repeat-dose toxicity studies in rats and dogs, which are consistent 
with the pharmacological activity of darolutamide. 
 
Genotoxicity and carcinogenicity  
 
Darolutamide did not induce mutations in the microbial mutagenesis (Ames) assay. At high 
concentrations, darolutamide did induce structural chromosome aberrations in vitro in cultured human 
lymphocytes. However, in the in vivo combined bone marrow micronucleus test and the Comet assay 
in the liver and duodenum of the rat, no genotoxicity was observed at exposures in excess of the 
maximum human exposure. Long-term animal studies to evaluate the carcinogenic potential of 
darolutamide have not been conducted. 
 
Safety pharmacology 
 
In vitro, darolutamide weakly inhibited the hERG potassium current and the L-type calcium channel. 
In vivo, in anaesthetised dogs, darolutamide slightly decreased the QT interval duration, but this effect 
was not found in conscious dogs. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core 
Calcium hydrogen phosphate (E 341) 
Croscarmellose sodium 
Lactose monohydrate 
Magnesium stearate (E 470b) 
Povidone (E 1201) 
 
Film-coating 
Hypromellose 
Lactose monohydrate 
Macrogol (E 1521) 
Titanium dioxide (E 171) 
 



15 

6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5 Nature and contents of container  
 
PVC/Aluminium foil blisters containing 16 film-coated tablets. 
Each pack contains 96 or 112 film-coated tablets. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal  
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
7. MARKETING AUTHORISATION HOLDER 
 
Bayer AG  
51368 Leverkusen 
Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/20/1432/001 112 film-coated tablets 
EU/1/20/1432/002 96 film-coated tablets 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 27 March 2020 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

http://www.ema.europa.eu/
http://www.ema.europa.eu/


16 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE 

 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 
THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 



17 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
 
Orion Corporation, Orion Pharma 
24100 Salo 
Finland 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic safety update reports (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of 
Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC 
and any subsequent updates published on the European medicines web-portal. 
 
The marketing authorisation holder (MAH) shall submit the first PSUR for this product within 
6 months following authorisation. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk management plan (RMP) 
 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities 
and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation 
and any agreed subsequent updates of the RMP. 
 
An updated RMP should be submitted: 
• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
• Obligation to conduct post-authorisation measures 
 
The MAH shall complete, within the stated timeframe, the below measures: 
 
Description Due date 
Post-authorisation efficacy study (PAES): In order to further investigate the 
efficacy of darolutamide in adult men with non-metastatic castration resistant 
prostate cancer who are at high risk of developing metastatic disease, the MAH 
should submit the final study report, including overall survival results, from 
study ARAMIS 17712. 

30 June 2020 

 



18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



19 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



20 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
NUBEQA 300 mg film-coated tablets 
darolutamide 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
Each film-coated tablet contains 300 mg of darolutamide. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. Read the package leaflet before use. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
96 film-coated tablets 
112 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
 



21 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Bayer AG 
51368 Leverkusen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/20/1432/001 112 film-coated tablets 
EU/1/20/1432/002 96 film-coated tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
NUBEQA 300 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 



22 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
NUBEQA 300 mg tablets  
darolutamide 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Bayer (logo) 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 



23 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



24 

Package leaflet: Information for the patient 
 

NUBEQA 300 mg film-coated tablets 
darolutamide 

 
This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.  
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
 
What is in this leaflet 
 
1. What NUBEQA is and what it is used for 
2. What you need to know before you take NUBEQA 
3. How to take NUBEQA 
4. Possible side effects 
5. How to store NUBEQA 
6. Contents of the pack and other information 
 
 
1. What NUBEQA is and what it is used for 
 
NUBEQA contains the active substance darolutamide. It is used to treat adult men with prostate 
cancer that has not spread to other parts of the body and no longer responds to medical or surgical 
treatment that lowers testosterone (also called castration-resistant prostate cancer). 
 
How NUBEQA works 
NUBEQA blocks the activity of male sex hormones called androgens, such as testosterone. By 
blocking these hormones, darolutamide stops prostate cancer cells from growing and dividing. 
 
 
2. What you need to know before you take NUBEQA 
 
Do not take NUBEQA if 
- you are allergic to darolutamide or any of the other ingredients of this medicine (listed in 

section 6) 
- you are a woman who is or may become pregnant. 
 
Warnings and precautions 
Talk to your doctor or pharmacist before taking NUBEQA if 
- you have problems with your kidneys 
- you have problems with your liver 
- you have any heart conditions including heart rhythm problems or if you are using medicines 

for these conditions 
- you had a surgery to treat blood vessel conditions. 
 



25 

Children and adolescents 
This medicine is not for use in children and adolescents under 18 years. Prostate cancer does not occur 
in this age group. 
 
Other medicines and NUBEQA 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
The following medicines may influence the effect of NUBEQA, or NUBEQA may influence the effect 
of these medicines to treat: 
- bacterial infections, such as rifampicin 
- epilepsy, such as carbamazepine, phenobarbital, phenytoin 
- symptoms of slightly low mood and mild anxiety: St. John's wort (a herbal medicine) 
- high cholesterol, such as rosuvastatin, fluvastatin, atorvastatin, pitavastatin 
- severe joint inflammation, severe cases of the skin disease psoriasis, and cancers: methotrexate 
- inflammatory bowel diseases: sulfasalazine 
 
Your doctor may therefore change the dose of the medicines that you are taking. 
 
Pregnancy, breast-feeding and fertility 
NUBEQA is not for use in women. 
This medicine could possibly have an effect on male fertility. 
Follow these advices during and for 1 week after stopping: 
- use a highly effective method of contraception to prevent pregnancy, if you are having sex with 

a woman who can become pregnant. 
- use a condom to protect the unborn baby, if you are having sex with a pregnant woman. 
 
Driving and using machines 
This medicine is unlikely to affect your ability to drive and use machines. 
 
NUBEQA contains lactose 
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor 
before taking this medicine. 
 
 
3. How to take NUBEQA 
 
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.  
 
The recommended dose is 
2 tablets 2 times daily 
 
Your doctor may reduce your dose to 1 tablet 2 times daily, if you have problems with your liver or 
kidneys. 
 
Method of use 
Swallow the tablets whole, take them with food and a glass of water. 
 
Your doctor may also prescribe other medicines while you are taking NUBEQA. 
 
If you take more NUBEQA than you should 
Continue the treatment with the next dose as scheduled. 
 



26 

If you forget to take NUBEQA 
Take your missed dose as soon as you remember before the next scheduled dose. Do not take a double 
dose to make up for 1 or more forgotten tablets. 
 
If you stop taking NUBEQA 
Do not stop taking this medicine unless your doctor tells you to. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Side effects of NUBEQA with the following frequencies: 
Very common side effects (may affect more than 1 in 10 people): 
- tiredness 
 
Common side effects (may affect up to 1 in 10 people): 
- blockage of the arteries in the heart 
- heart failure 
- rash 
- pain in arms and legs 
- pain in muscles and bones 
- broken bones 
 
Very common side effects that may show up in blood tests: 
- reduced number of a white blood cell type called neutrophils 
- increased blood levels of substances produced by the liver: bilirubin, aspartate transaminase 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects, you can help provide more information on the safety 
of this medicine. 
 
 
5. How to store NUBEQA 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and on each blister after 
EXP. The expiry date refers to the last day of that month. 
 
This medicine does not require any special storage conditions. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


27 

6. Contents of the pack and other information 
 
What NUBEQA contains 
The active substance is darolutamide. Each film-coated tablet contains 300 mg of darolutamide. 
The other ingredients are: 
- calcium hydrogen phosphate (E 341) 
- croscarmellose sodium 
- hypromellose 
- lactose monohydrate 
- macrogol (E 1521) 
- magnesium stearate (E 470b) 
- povidone (E 1201) 
- titanium dioxide (E 171) 
 
See “NUBEQA contains lactose” in section 2 for more information. 
 
What NUBEQA looks like and contents of the pack 
The film-coated tablets (tablets) are white to off-white, oval with a length of 16 mm and a width of 
8 mm. They are marked with “300” on one side, and “BAYER” on the other side. 
 
Each carton contains: 
- 96 film-coated tablets consisting of 6 blisters or 
- 112 film-coated tablets consisting of 7 blisters 
 
Each blister contains 16 film-coated tablets. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
Bayer AG 
51368 Leverkusen 
Germany 
 
Manufacturer 
Orion Corporation, Orion Pharma 
24100 Salo 
Finland 
 



28 

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Bayer SA-NV 
Tél/Tel: +32-(0)2-5356311 

Lietuva 
UAB Bayer 
Tel. +37 05 23 36 868 

България 
Байер България ЕООД 
Tел.: +359 02 424 72 80 

Luxembourg/Luxemburg 
Bayer SA-NV 
Tél/Tel: +32-(0)2-535 63 11 

Česká republika 
Bayer s.r.o. 
Tel: +420 266 101 111 

Magyarország 
Bayer Hungária KFT 
Tel:+36 14 87-41 00 

Danmark 
Bayer A/S 
Tlf: +45 45 23 50 00 

Malta 
Alfred Gera and Sons Ltd. 
Tel: +35 621 44 62 05 

Deutschland 
Bayer Vital GmbH 
Tel: +49 (0)214-30 513 48 

Nederland 
Bayer B.V. 
Tel: +31-(0)297-28 06 66 

Eesti 
Bayer OÜ 
Tel: +372 655 8565 

Norge 
Bayer AS 
Tlf: +47 24 11 18 00 

Ελλάδα 
Bayer Ελλάς ΑΒΕΕ 
Τηλ: +30 210-618 75 00 

Österreich 
Bayer Austria Ges.m.b.H. 
Tel: +43-(0)1-711 46-0 

España 
Bayer Hispania S.L. 
Tel: +34-93-495 65 00 

Polska 
Bayer Sp. z.o.o. 
Tel: +48 22 572 35 00 

France 
Bayer HealthCare 
Tél (N° vert): +33-(0)800 87 54 54 

Portugal 
Bayer Portugal, Lda. 
Tel: +351 21 416 42 00 

Hrvatska 
Bayer d.o.o. 
Tel: +385-(0)1-6599 900 

România 
SC Bayer s.r.l. 
Tel: +40 21 529 59 00 

Ireland 
Bayer Limited 
Tel: +353 1 216 3300 

Slovenija 
Bayer d. o. o. 
Tel: +386 1 58 14 400 

Ísland 
Icepharma hf. 
Sími: +354 540 8000 

Slovenská republika 
Bayer spol. s r.o. 
Tel. +421 2 59 21 31 11 

Italia 
Bayer S.p.A. 
Tel: +39 02 397 81 

Suomi/Finland 
Bayer Oy 
Puh/Tel: +358 20 785 21 

Κύπρος 
NOVAGEM Limited 
Tηλ: +357 22 48 38 58 

Sverige 
Bayer AB 
Tel: +46 (0) 8 580 223 00 

Latvija 
SIA Bayer 
Tel: +371 67 84 55 63 

United Kingdom 
Bayer plc 
Tel: +44-(0)118 206 3000 

 
 
This leaflet was last revised in 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET
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{'Title': '3. how to take nubeqa', 'Section_Content': 'always take this medicine exactly as your doctor or pharmacist has told you. check with your doctor or pharmacist if you are not sure. the recommended dose is 2 tablets 2 times daily your doctor may reduce your dose to 1 tablet 2 times daily, if you have problems with your liver or kidneys. method of use swallow the tablets whole, take them with food and a glass of water. your doctor may also prescribe other medicines while you are taking nubeqa. if you take more nubeqa than you should continue the treatment with the next dose as scheduled. if you forget to take nubeqa take your missed dose as soon as you remember before the next scheduled dose. do not take a double dose to make up for 1 or more forgotten tablets. if you stop taking nubeqa do not stop taking this medicine unless your doctor tells you to. if you have any further questions on the use of this medicine, ask your doctor or pharmacist.', 'Entity_Recognition': [{'Text': 'nubeqa', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 12, 'EndOffset': 25}, {'Text': '2', 'Type': 'NUMBER', 'BeginOffset': 159, 'EndOffset': 160}, {'Text': '2', 'Type': 'NUMBER', 'BeginOffset': 169, 'EndOffset': 170}, {'Text': '1', 'Type': 'NUMBER', 'BeginOffset': 219, 'EndOffset': 220}, {'Text': '2', 'Type': 'NUMBER', 'BeginOffset': 228, 'EndOffset': 229}, {'Text': 'problems with your liver or kidneys', 'Type': 'PROBLEM', 'BeginOffset': 255, 'EndOffset': 290}, {'Text': 'swallow', 'Type': 'TREATMENT', 'BeginOffset': 306, 'EndOffset': 313}, {'Text': 'other medicines', 'Type': 'TREATMENT', 'BeginOffset': 406, 'EndOffset': 421}, {'Id': 6, 'BeginOffset': 443, 'EndOffset': 449, 'Score': 0.3870333433151245, 'Text': 'nubeqa', 'Category': 'MEDICATION', 'Type': 'BRAND_NAME', 'Traits': []}, {'Text': 'the treatment', 'Type': 'TREATMENT', 'BeginOffset': 500, 'EndOffset': 513}, {'Text': 'a double dose', 'Type': 'TREATMENT', 'BeginOffset': 666, 'EndOffset': 679}, {'Text': '1', 'Type': 'NUMBER', 'BeginOffset': 695, 'EndOffset': 696}, {'Id': 7, 'BeginOffset': 743, 'EndOffset': 749, 'Score': 0.4884839653968811, 'Text': 'nubeqa', 'Category': 'MEDICATION', 'Type': 'BRAND_NAME', 'Traits': []}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 769, 'EndOffset': 782}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 864, 'EndOffset': 877}]}
{'Title': '4. possible side effects', 'Section_Content': 'like all medicines, this medicine can cause side effects, although not everybody gets them. side effects of nubeqa with the following frequencies: very common side effects (may affect more than 1 in 10 people): - tiredness common side effects (may affect up to 1 in 10 people): - blockage of the arteries in the heart - heart failure - rash - pain in arms and legs - pain in muscles and bones - broken bones very common side effects that may show up in blood tests: - reduced number of a white blood cell type called neutrophils - increased blood levels of substances produced by the liver: bilirubin, aspartate transaminase reporting of side effects if you get any side effects, talk to your doctor or pharmacist. this includes any possible side effects not listed in this leaflet. you can also report side effects directly via the national reporting system listed in appendix v. by reporting side effects, you can help provide more information on the safety of this medicine.', 'Entity_Recognition': [{'Text': 'nubeqa', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'all medicines', 'Type': 'TREATMENT', 'BeginOffset': 5, 'EndOffset': 18}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 20, 'EndOffset': 33}, {'Id': 10, 'BeginOffset': 44, 'EndOffset': 56, 'Score': 0.9675427079200745, 'Text': 'side effects', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.7401847839355469}]}, {'Id': 11, 'BeginOffset': 92, 'EndOffset': 104, 'Score': 0.8187174797058105, 'Text': 'side effects', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.5045716762542725}]}, {'Text': 'nubeqa', 'Type': 'TREATMENT', 'BeginOffset': 108, 'EndOffset': 114}, {'Id': 12, 'BeginOffset': 159, 'EndOffset': 171, 'Score': 0.8901721239089966, 'Text': 'side effects', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 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894, 'EndOffset': 906, 'Score': 0.9223865866661072, 'Text': 'side effects', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.736994206905365}]}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 963, 'EndOffset': 976}]}
{'Title': '5. how to store nubeqa', 'Section_Content': None, 'Entity_Recognition': None}
{'Title': '6. contents of the pack and other information', 'Section_Content': 'what nubeqa contains the active substance is darolutamide. each film-coated tablet contains 300 mg of darolutamide. the other ingredients are: - calcium hydrogen phosphate (e 341) - croscarmellose sodium - hypromellose - lactose monohydrate - macrogol (e 1521) - magnesium stearate (e 470b) - povidone (e 1201) - titanium dioxide (e 171) see "nubeqa contains lactose" in section 2 for more information. what nubeqa looks like and contents of the pack the film-coated tablets (tablets) are white to off-white, oval with a length of 16 mm and a width of 8 mm. they are marked with "300" on one side, and "bayer" on the other side. each carton contains: - 96 film-coated tablets consisting of 6 blisters or - 112 film-coated tablets consisting of 7 blisters each blister contains 16 film-coated tablets. not all pack sizes may be marketed.', 'Entity_Recognition': [{'Text': 'nubeqa', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Id': 0, 'BeginOffset': 45, 'EndOffset': 57, 'Score': 0.9894618391990662, 'Text': 'darolutamide', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': [], 'Attributes': [{'Type': 'FORM', 'Score': 0.3205307126045227, 'RelationshipScore': 0.9998408555984497, 'RelationshipType': 'FORM', 'Id': 1, 'BeginOffset': 64, 'EndOffset': 68, 'Text': 'film', 'Category': 'MEDICATION', 'Traits': []}, {'Type': 'FORM', 'Score': 0.3798767328262329, 'RelationshipScore': 0.9994753003120422, 'RelationshipType': 'FORM', 'Id': 2, 'BeginOffset': 69, 'EndOffset': 82, 'Text': 'coated tablet', 'Category': 'MEDICATION', 'Traits': []}]}, {'Text': 'each film', 'Type': 'TEST', 'BeginOffset': 59, 'EndOffset': 68}, {'Text': '300', 'Type': 'NUMBER', 'BeginOffset': 92, 'EndOffset': 95}, {'Id': 4, 'BeginOffset': 102, 'EndOffset': 114, 'Score': 0.9949618577957153, 'Text': 'darolutamide', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': [], 'Attributes': [{'Type': 'FORM', 'Score': 0.3205307126045227, 'RelationshipScore': 0.5005988478660583, 'RelationshipType': 'FORM', 'Id': 1, 'BeginOffset': 64, 'EndOffset': 68, 'Text': 'film', 'Category': 'MEDICATION', 'Traits': []}, {'Type': 'DOSAGE', 'Score': 0.9843452572822571, 'RelationshipScore': 0.9999959468841553, 'RelationshipType': 'DOSAGE', 'Id': 3, 'BeginOffset': 92, 'EndOffset': 98, 'Text': '300 mg', 'Category': 'MEDICATION', 'Traits': []}]}, {'Id': 5, 'BeginOffset': 145, 'EndOffset': 171, 'Score': 0.997516393661499, 'Text': 'calcium hydrogen phosphate', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Id': 6, 'BeginOffset': 173, 'EndOffset': 178, 'Score': 0.6275148391723633, 'Text': 'e 341', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Id': 7, 'BeginOffset': 182, 'EndOffset': 251, 'Score': 0.9894872903823853, 'Text': 'croscarmellose sodium - hypromellose - lactose monohydrate - macrogol', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Text': '1521', 'Type': 'NUMBER', 'BeginOffset': 255, 'EndOffset': 259}, {'Id': 8, 'BeginOffset': 263, 'EndOffset': 281, 'Score': 0.9944169521331787, 'Text': 'magnesium stearate', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Id': 9, 'BeginOffset': 283, 'EndOffset': 301, 'Score': 0.5073292851448059, 'Text': 'e 470b) - povidone', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Id': 10, 'BeginOffset': 303, 'EndOffset': 309, 'Score': 0.47243747115135193, 'Text': 'e 1201', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Id': 11, 'BeginOffset': 313, 'EndOffset': 329, 'Score': 0.9986500144004822, 'Text': 'titanium dioxide', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Id': 12, 'BeginOffset': 331, 'EndOffset': 336, 'Score': 0.31382638216018677, 'Text': 'e 171', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Text': '2', 'Type': 'NUMBER', 'BeginOffset': 379, 'EndOffset': 380}, {'Text': 'the pack the film-coated tablets (tablets)', 'Type': 'TREATMENT', 'BeginOffset': 442, 'EndOffset': 484}, {'Text': '16', 'Type': 'NUMBER', 'BeginOffset': 531, 'EndOffset': 533}, {'Text': '8', 'Type': 'NUMBER', 'BeginOffset': 552, 'EndOffset': 553}, {'Text': '300', 'Type': 'NUMBER', 'BeginOffset': 580, 'EndOffset': 583}, {'Text': '96', 'Type': 'NUMBER', 'BeginOffset': 653, 'EndOffset': 655}, {'Text': 'film-coated tablets', 'Type': 'TREATMENT', 'BeginOffset': 656, 'EndOffset': 675}, {'Text': '6 blisters', 'Type': 'PROBLEM', 'BeginOffset': 690, 'EndOffset': 700}, {'Text': '112', 'Type': 'NUMBER', 'BeginOffset': 706, 'EndOffset': 709}, {'Text': 'film-coated tablets', 'Type': 'TREATMENT', 'BeginOffset': 710, 'EndOffset': 729}, {'Text': '7 blisters each blister', 'Type': 'PROBLEM', 'BeginOffset': 744, 'EndOffset': 767}, {'Text': '16 film-coated tablets', 'Type': 'TREATMENT', 'BeginOffset': 777, 'EndOffset': 799}]}