Erelzi

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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 
 
Erelzi 25 mg solution for injection in pre-filled syringe. 
 
Erelzi 50 mg solution for injection in pre-filled syringe. 
 
Erelzi 50 mg solution for injection in pre-filled pen. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Erelzi 25 mg solution for injection in pre-filled syringe 
Each pre-filled syringe contains 25 mg of etanercept. 
 
Erelzi 50 mg solution for injection in pre-filled syringe 
Each pre-filled syringe contains 50 mg of etanercept. 
 
Erelzi 50 mg solution for injection in pre-filled pen 
Each pre-filled pen contains 50 mg of etanercept. 
 
Etanercept is a human tumour necrosis factor receptor p75 Fc fusion protein produced by recombinant 
DNA technology in a Chinese hamster ovary (CHO) mammalian expression system. Etanercept is a 
dimer of a chimeric protein genetically engineered by fusing the extracellular ligand binding domain of 
human tumour necrosis factor receptor-2 (TNFR2/p75) to the Fc domain of human IgG1. This Fc 
component contains the hinge, CH2 and CH3 regions, but not the CH1 region of IgG1. Etanercept 
contains 934 amino acids and has an apparent molecular weight of approximately 150 kilodaltons. The 
specific activity of etanercept is 1.7 x 106 units/mg. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection (injection) 
 
The solution is clear or slightly opalescent, colourless to slightly yellowish. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Rheumatoid arthritis  
Erelzi in combination with methotrexate is indicated for the treatment of moderate to severe active 
rheumatoid arthritis in adults when the response to disease-modifying antirheumatic drugs, including 
methotrexate (unless contraindicated), has been inadequate. 
 
Erelzi can be given as monotherapy in case of intolerance to methotrexate or when continued treatment 
with methotrexate is inappropriate. 
 



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Erelzi is also indicated in the treatment of severe, active and progressive rheumatoid arthritis in adults 
not previously treated with methotrexate. 
 
Etanercept, alone or in combination with methotrexate, has been shown to reduce the rate of progression 
of joint damage as measured by X-ray and to improve physical function. 
 
Juvenile idiopathic arthritis 
Treatment of polyarthritis (rheumatoid factor positive or negative) and extended oligoarthritis in 
children and adolescents from the age of 2 years who have had an inadequate response to, or who have 
proved intolerant of, methotrexate. 
 
Treatment of psoriatic arthritis in adolescents from the age of 12 years who have had an inadequate 
response to, or who have proved intolerant of, methotrexate. 
 
Treatment of enthesitis-related arthritis in adolescents from the age of 12 years who have had an 
inadequate response to, or who have proved intolerant of, conventional therapy. 
 
Etanercept has not been studied in children aged less than 2 years. 
 
Psoriatic arthritis 
Treatment of active and progressive psoriatic arthritis in adults when the response to previous 
disease-modifying antirheumatic drug therapy has been inadequate. Etanercept has been shown to 
improve physical function in patients with psoriatic arthritis, and to reduce the rate of progression of 
peripheral joint damage as measured by X-ray in patients with polyarticular symmetrical subtypes of the 
disease. 
 
Axial spondyloarthritis 
 
Ankylosing spondylitis (AS) 
Treatment of adults with severe active ankylosing spondylitis who have had an inadequate response to 
conventional therapy. 
 
Non-radiographic axial spondyloarthritis 
Treatment of adults with severe non-radiographic axial spondyloarthritis with objective signs of 
inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging 
(MRI) evidence, who have had an inadequate response to non-steroidal anti-inflammatory drugs 
(NSAIDs). 
 
Plaque psoriasis 
Treatment of adults with moderate to severe plaque psoriasis who failed to respond to, or who have a 
contraindication to, or are intolerant to other systemic therapy, including ciclosporin, methotrexate or 
psoralen and ultraviolet-A light (PUVA) (see section 5.1). 
 
Paediatric plaque psoriasis 
Treatment of chronic severe plaque psoriasis in children and adolescents from the age of 6 years who 
are inadequately controlled by, or are intolerant to, other systemic therapies or phototherapies. 
 
4.2 Posology and method of administration 
 
Erelzi treatment should be initiated and supervised by specialist physicians experienced in the diagnosis 
and treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing 
spondylitis, non-radiographic axial spondyloarthritis, plaque psoriasis or paediatric plaque psoriasis. 
Patients treated with Erelzi should be given the Patient Alert Card. 
 
Erelzi is available in strengths of 25 mg and 50 mg. 
 



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Posology 
 
Rheumatoid arthritis 
25 mg etanercept administered twice weekly is the recommended dose. Alternatively, 50 mg 
administered once weekly has been shown to be safe and effective (see section 5.1). 
 
Psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondyloarthritis 
The recommended dose is 25 mg etanercept administered twice weekly, or 50 mg administered once 
weekly. 
 
For all of the above indications, available data suggest that a clinical response is usually achieved within 
12 weeks of treatment. Continued therapy should be carefully reconsidered in a patient not responding 
within this time period. 
 
Plaque psoriasis 
The recommended dose of etanercept is 25 mg administered twice weekly or 50 mg administered once 
weekly. Alternatively, 50 mg given twice weekly may be used for up to 12 weeks followed, if 
necessary, by a dose of 25 mg twice weekly or 50 mg once weekly. Treatment with etanercept should 
continue until remission is achieved, for up to 24 weeks. Continuous therapy beyond 24 weeks may be 
appropriate for some adult patients (see section 5.1). Treatment should be discontinued in patients who 
show no response after 12 weeks. If re-treatment with etanercept is indicated, the same guidance on 
treatment duration should be followed. The dose should be 25 mg twice weekly or 50 mg once weekly. 
 
Special populations 
 
Renal and hepatic impairment 
No dose adjustment is required. 
 
Elderly  
No dose adjustment is required. Posology and administration are the same as for adults 18–64 years of 
age. 
 
Paediatric population 
Erelzi is only available as 25 mg pre-filled syringe and 50 mg pre-filled syringe and pre-filled pen. 
Thus, it is not possible to administer Erelzi to paediatric patients that require less than a full 25 mg or 
50 mg dose. Paediatric patients who require a dose other than a full 25 mg or 50 mg should not receive 
Erelzi. If an alternate dose is required, other etanercept products offering such an option should be used. 
The dosage of etanercept is based on body weight for paediatric patients. Patients weighing less than 
62.5 kg should be accurately dosed on a mg/kg basis using the powder and solvent for solution for 
injection presentations or the powder for solution for injection presentations (see below for dosing for 
specific indications). Patients weighing 62.5 kg or more may be dosed using a fixed-dose pre-filled 
syringe or pre-filled pen. 
 
Juvenile idiopathic arthritis 
The recommended dose is 0.4 mg/kg (up to a maximum of 25 mg per dose), given twice weekly as a 
subcutaneous injection with an interval of 3–4 days between doses or 0.8 mg/kg (up to a maximum of 
50 mg per dose) given once weekly. Discontinuation of treatment should be considered in patients who 
show no response after 4 months. 
 
A 10 mg vial strength may be more appropriate for administration to children with JIA below the 
weight of 25 kg. 
 
No formal clinical trials have been conducted in children aged 2 to 3 years. However, limited safety 
data from a patient registry suggest that the safety profile in children from 2 to 3 years of age is similar 
to that seen in adults and children aged 4 years and older, when dosed every week with 0.8 mg/kg 
subcutaneously (see section 5.1). 



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There is generally no applicable use of etanercept in children aged below 2 years in the indication 
juvenile idiopathic arthritis. 
 
Paediatric plaque psoriasis (age 6 years and above) 
The recommended dose is 0.8 mg/kg (up to a maximum of 50 mg per dose) once weekly for up to 
24 weeks. Treatment should be discontinued in patients who show no response after 12 weeks. 
 
If re-treatment with etanercept is indicated, the above guidance on treatment duration should be 
followed. The dose should be 0.8 mg/kg (up to a maximum of 50 mg per dose) once weekly. 
 
There is generally no applicable use of etanercept in children aged below 6 years in the indication 
plaque psoriasis. 
 
Method of administration 
 
Erelzi is administered by subcutaneous injection (see section 6.6). 
 
Comprehensive instructions for administration are given in the package leaflet, section 7, "Instructions 
for use of the Erelzi pre-filled syringe” or “Instructions for use of the Erelzi SensoReady pen”. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.  
 
Sepsis or risk of sepsis. 
 
Treatment with Erelzi should not be initiated in patients with active infections, including chronic or 
localised infections. 
 
4.4 Special warnings and precautions for use 
 
Traceability 
 
In order to improve the traceability of biological medicinal products, the name and the batch number of 
the administered product should be clearly recorded. 
 
Infections 
Patients should be evaluated for infections before, during, and after treatment with Erelzi, taking into 
consideration that the mean elimination half-life of etanercept is approximately 70 hours (range 7 to 
300 hours). 
 
Serious infections, sepsis, tuberculosis, and opportunistic infections, including invasive fungal 
infections, listeriosis and legionellosis, have been reported with the use of etanercept (see section 4.8). 
These infections were due to bacteria, mycobacteria, fungi, viruses and parasites (including protozoa). 
In some cases, particular fungal and other opportunistic infections have not been recognised, resulting in 
delay of appropriate treatment and sometimes death. In evaluating patients for infections, the patient’s 
risk for relevant opportunistic infections (e.g., exposure to endemic mycoses) should be considered. 
 
Patients who develop a new infection while undergoing treatment with Erelzi should be monitored 
closely. Administration of Erelzi should be discontinued if a patient develops a serious infection. The 
safety and efficacy of etanercept in patients with chronic infections have not been evaluated. Physicians 
should exercise caution when considering the use of Erelzi in patients with a history of recurring or 
chronic infections or with underlying conditions that may predispose patients to infections, such as 
advanced or poorly controlled diabetes. 
 



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Tuberculosis 
Cases of active tuberculosis, including miliary tuberculosis and tuberculosis with extra-pulmonary 
location, have been reported in patients treated with etanercept. 
 
Before starting treatment with Erelzi, all patients must be evaluated for both active and inactive 
(‘latent’) tuberculosis. This evaluation should include a detailed medical history with personal history of 
tuberculosis or possible previous contact with tuberculosis and previous and/or current 
immunosuppressive therapy. Appropriate screening tests, i.e., tuberculin skin test and chest X-ray, 
should be performed in all patients (local recommendations may apply). It is recommended that the 
conduct of these tests should be recorded in the Patient’s Alert Card. Prescribers are reminded of the 
risk of false negative tuberculin skin test results, especially in patients who are severely ill or 
immunocompromised. 
 
If active tuberculosis is diagnosed, Erelzi therapy must not be initiated. If inactive (‘latent’) tuberculosis 
is diagnosed, treatment for latent tuberculosis must be started with anti-tuberculosis therapy before the 
initiation of Erelzi, and in accordance with local recommendations. In this situation, the benefit/risk 
balance of Erelzi therapy should be very carefully considered. 
 
All patients should be informed to seek medical advice if signs/symptoms suggestive of tuberculosis 
(e.g., persistent cough, wasting/weight loss, low-grade fever) appear during or after Erelzi treatment. 
 
Hepatitis B reactivation 
Reactivation of hepatitis B in patients who were previously infected with the hepatitis B virus (HBV) 
and had received concomitant TNF-antagonists, including etanercept, has been reported. This includes 
reports of reactivation of hepatitis B in patients who were anti-HBc positive but HBsAg negative. 
Patients should be tested for HBV infection before initiating treatment with Erelzi. For patients who test 
positive for HBV infection, consultation with a physician with expertise in the treatment of hepatitis B 
is recommended. Caution should be exercised when administering Erelzi in patients previously infected 
with HBV. These patients should be monitored for signs and symptoms of active HBV infection 
throughout therapy and for several weeks following termination of therapy. Adequate data from treating 
patients infected with HBV with anti-viral therapy in conjunction with TNF-antagonist therapy are not 
available. In patients who develop HBV infection, Erelzi should be stopped and effective anti-viral 
therapy with appropriate supportive treatment should be initiated. 
 
Worsening of hepatitis C 
There have been reports of worsening of hepatitis C in patients receiving etanercept. Erelzi should be 
used with caution in patients with a history of hepatitis C. 
 
Concurrent treatment with anakinra 
Concurrent administration of etanercept and anakinra has been associated with an increased risk of 
serious infections and neutropenia compared to etanercept alone. This combination has not 
demonstrated increased clinical benefit. Thus, the combined use of Erelzi and anakinra is not 
recommended (see sections 4.5 and 4.8). 
 
Concurrent treatment with abatacept 
In clinical studies, concurrent administration of abatacept and etanercept resulted in increased 
incidences of serious adverse events. This combination has not demonstrated increased clinical benefit; 
such use is not recommended (see section 4.5). 
 
Allergic reactions 
Allergic reactions associated with etanercept administration have been reported commonly. Allergic 
reactions have included angioedema and urticaria; serious reactions have occurred. If any serious 
allergic or anaphylactic reaction occurs, Erelzi therapy should be discontinued immediately and 
appropriate therapy initiated. 
 



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Immunosuppression 
The possibility exists for TNF-antagonists, including Erelzi, to affect host defences against infections 
and malignancies since TNF mediates inflammation and modulates cellular immune responses. In a 
study of 49 adult patients with rheumatoid arthritis treated with etanercept, there was no evidence of 
depression of delayed-type hypersensitivity, depression of immunoglobulin levels, or change in 
enumeration of effector cell populations. 
 
Two juvenile idiopathic arthritis patients developed varicella infection and signs and symptoms of 
aseptic meningitis, which resolved without sequelae. Patients with a significant exposure to varicella 
virus should temporarily discontinue Erelzi therapy and be considered for prophylactic treatment with 
Varicella Zoster Immune Globulin. 
 
The safety and efficacy of etanercept in patients with immunosuppression have not been evaluated.  
 
Malignancies and lymphoproliferative disorders 
 
Solid and haematopoietic malignancies (excluding skin cancers) 
 
Reports of various malignancies (including breast and lung carcinoma and lymphoma) have been 
received in the post-marketing period (see section 4.8). 
 
In the controlled portions of clinical trials of TNF-antagonists, more cases of lymphoma have been 
observed among patients receiving a TNF-antagonist compared with control patients. However, the 
occurrence was rare, and the follow-up period of placebo patients was shorter than for patients receiving 
TNF-antagonist therapy. In the post-marketing setting, cases of leukaemia have been reported in 
patients treated with TNF-antagonists. There is an increased background risk for lymphoma and 
leukaemia in rheumatoid arthritis patients with long-standing, highly active, inflammatory disease, 
which complicates risk estimation. 
 
Based on current knowledge, a possible risk for the development of lymphomas, leukaemia or other 
haematopoietic or solid malignancies in patients treated with a TNF-antagonist cannot be excluded. 
Caution should be exercised when considering TNF-antagonist therapy for patients with a history of 
malignancy or when considering continuing treatment in patients who develop a malignancy. 
 
Malignancies, some fatal, have been reported among children, adolescents and young adults (up to 
22 years of age) treated with TNF-antagonists (initiation of therapy ≤ 18 years of age), including 
etanercept, in the post-marketing setting. Approximately half the cases were lymphomas. The other 
cases represented a variety of different malignancies and included rare malignancies typically associated 
with immunosuppression. A risk for the development of malignancies in children and adolescents 
treated with TNF-antagonists cannot be excluded. 
 
Skin cancers 
Melanoma and non-melanoma skin cancer (NMSC) have been reported in patients treated with 
TNF-antagonists, including etanercept. Post-marketing cases of Merkel cell carcinoma have been 
reported very infrequently in patients treated with etanercept. Periodic skin examination is 
recommended for all patients, particularly those with risk factors for skin cancer. 
 
Combining the results of controlled clinical trials, more cases of NMSC were observed in patients 
receiving etanercept compared with control patients, particularly in patients with psoriasis. 
 
Vaccinations 
Live vaccines should not be given concurrently with Erelzi. No data are available on the secondary 
transmission of infection by live vaccines in patients receiving etanercept. In a double-blind, 
placebo-controlled, randomised clinical study in adult patients with psoriatic arthritis, 184 patients also 
received a multivalent pneumococcal polysaccharide vaccine at week 4. In this study, most psoriatic 
arthritis patients receiving etanercept were able to mount effective B-cell immune response to 



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pneumococcal polysaccharide vaccine, but titres in aggregate were moderately lower, and few patients 
had two-fold rises in titres compared to patients not receiving etanercept. The clinical significance of 
this is unknown. 
 
Autoantibody formation 
Treatment with Erelzi may result in the formation of autoimmune antibodies (see section 4.8). 
 
Haematologic reactions 
Rare cases of pancytopenia and very rare cases of aplastic anaemia, some with fatal outcome, have been 
reported in patients treated with etanercept. Caution should be exercised in patients being treated with 
Erelzi who have a previous history of blood dyscrasias. All patients and parents/caregivers should be 
advised that if the patient develops signs and symptoms suggestive of blood dyscrasias or infections 
(e.g., persistent fever, sore throat, bruising, bleeding, paleness) whilst on Erelzi, they should seek 
immediate medical advice. Such patients should be investigated urgently, including full blood count; if 
blood dyscrasias are confirmed, Erelzi should be discontinued. 
 
Neurological disorders 
There have been rare reports of CNS demyelinating disorders in patients treated with etanercept (see 
section 4.8). Additionally, there have been rare reports of peripheral demyelinating polyneuropathies 
(including Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, 
demyelinating polyneuropathy, and multifocal motor neuropathy). Although no clinical trials have been 
performed evaluating etanercept therapy in patients with multiple sclerosis, clinical trials of other TNF 
antagonists in patients with multiple sclerosis have shown increases in disease activity. A careful 
risk/benefit evaluation, including a neurologic assessment, is recommended when prescribing Erelzi to 
patients with pre-existing or recent onset of demyelinating disease, or to those who are considered to 
have an increased risk of developing demyelinating disease. 
 
Combination therapy 
In a controlled clinical trial of two years duration in rheumatoid arthritis patients, the combination of 
etanercept and methotrexate did not result in unexpected safety findings, and the safety profile of 
etanercept when given in combination with methotrexate was similar to the profiles reported in studies 
of etanercept and methotrexate alone. Long-term studies to assess the safety of the combination are 
ongoing. The long-term safety of etanercept in combination with other disease-modifying antirheumatic 
drugs (DMARD) has not been established. 
 
The use of etanercept in combination with other systemic therapies or phototherapy for the treatment of 
psoriasis has not been studied. 
 
Renal and hepatic impairment 
Based on pharmacokinetic data (see section 5.2), no dose adjustment is needed in patients with renal or 
hepatic impairment; clinical experience in such patients is limited. 
 
Congestive heart failure (Cardiac failure congestive) 
Physicians should use caution when using Erelzi in patients who have congestive heart failure (CHF). 
There have been post-marketing reports of worsening of CHF, with and without identifiable 
precipitating factors, in patients taking etanercept. There have also been rare (< 0.1%) reports of new 
onset CHF, including CHF in patients without known pre-existing cardiovascular disease. Some of 
these patients have been under 50 years of age. Two large clinical trials evaluating the use of etanercept 
in the treatment of CHF were terminated early due to lack of efficacy. Although not conclusive, data 
from one of these trials suggest a possible tendency toward worsening CHF in those patients assigned to 
etanercept treatment. 
 
Alcoholic hepatitis 
In a phase II randomised placebo-controlled study of 48 hospitalised patients treated with etanercept or 
placebo for moderate to severe alcoholic hepatitis, etanercept was not efficacious, and the mortality rate 
in patients treated with etanercept was significantly higher after 6 months. Consequently, Erelzi should 



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not be used in patients for the treatment of alcoholic hepatitis. Physicians should use caution when using 
Erelzi in patients who also have moderate to severe alcoholic hepatitis. 
 
Wegener's granulomatosis 
A placebo-controlled trial, in which 89 adult patients were treated with etanercept in addition to 
standard therapy (including cyclophosphamide or methotrexate, and glucocorticoids) for a median 
duration of 25 months, has not shown etanercept to be an effective treatment for Wegener’s 
granulomatosis. The incidence of non-cutaneous malignancies of various types was significantly higher 
in patients treated with etanercept than in the control group. Erelzi is not recommended for the treatment 
of Wegener’s granulomatosis. 
 
Hypoglycaemia in patients treated for diabetes 
There have been reports of hypoglycaemia following initiation of etanercept in patients receiving 
medicinal product for diabetes, necessitating a reduction in anti-diabetic medicinal products in some of 
these patients. 
 
Special populations 
 
Elderly  
 
In the Phase 3 studies in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, no overall 
differences in adverse events, serious adverse events, and serious infections in patients age 65 or older 
who received etanercept were observed compared with younger patients. However, caution should be 
exercised when treating the elderly and particular attention paid with respect to occurrence of infections. 
 
Paediatric population 
 
Vaccinations 
It is recommended that paediatric patients, if possible, be brought up to date with all immunisations in 
agreement with current immunisation guidelines prior to initiating Erelzi therapy (see Vaccinations, 
above). 
 
Inflammatory bowel disease (IBD) and uveitis in patients with juvenile idiopathic arthritis (JIA) 
There have been reports of IBD and uveitis in JIA patients being treated with etanercept (see 
section 4.8). 
 
Erelzi contains sodium 
This medicinal product contains less than 1 mmol sodium (23 mg) per 25mg or 50 mg, that is to say 
essentially ‘sodium-free’. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Concurrent treatment with anakinra 
Adult patients treated with etanercept and anakinra were observed to have a higher rate of serious 
infection when compared with patients treated with either etanercept or anakinra alone (historical data). 
 
In addition, in a double-blind, placebo-controlled trial in adult patients receiving background 
methotrexate, patients treated with etanercept and anakinra were observed to have a higher rate of 
serious infections (7%) and neutropenia than patients treated with etanercept (see sections 4.4 and 4.8). 
The combination etanercept and anakinra has not demonstrated increased clinical benefit, and is 
therefore not recommended. 
 
Concurrent treatment with abatacept 
In clinical studies, concurrent administration of abatacept and etanercept resulted in increased 
incidences of serious adverse events. This combination has not demonstrated increased clinical benefit; 
such use is not recommended (see section 4.4). 



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Concurrent treatment with sulfasalazine 
In a clinical study of adult patients who were receiving established doses of sulfasalazine, to which 
etanercept was added, patients in the combination group experienced a statistically significant decrease 
in mean white blood cell counts in comparison to groups treated with etanercept or sulfasalazine alone. 
The clinical significance of this interaction is unknown. Physicians should use caution when considering 
combination therapy with sulfasalazine. 
 
Non-interactions 
In clinical trials, no interactions have been observed when etanercept was administered with 
glucocorticoids, salicylates (except sulfasalazine), non-steroidal anti-inflammatory drugs (NSAIDs), 
analgesics, or methotrexate. See section 4.4 for vaccination advice. 
 
No clinically significant pharmacokinetic drug-drug interactions were observed in studies with 
methotrexate, digoxin or warfarin. 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential 
Women of childbearing potential should consider the use of appropriate contraception to avoid 
becoming pregnant during Erelzi therapy and for three weeks after discontinuation of therapy. 
 
Pregnancy 
Developmental toxicity studies performed in rats and rabbits have revealed no evidence of harm to the 
foetus or neonatal rat due to etanercept. The effects of etanercept on pregnancy outcomes have been 
investigated in two observational cohort studies. A higher rate of major birth defects was observed in 
one observational study comparing pregnancies exposed to etanercept (n = 370) during the first 
trimester with pregnancies not exposed to etanercept or other TNF-antagonists (n = 164) (adjusted odds 
ratio 2.4, 95% CI: 1.0 - 5.5). The types of major birth defects were consistent with those most 
commonly reported in the general population and no particular pattern of abnormalities was identified. 
No change in the rate of spontaneous abortion, stillbirth, or minor malformations was observed. In 
another observational multi-country registry study comparing the risk of adverse pregnancy outcomes in 
women exposed to etanercept during the first 90 days of pregnancy (n = 425) to those exposed to non-
biologic drugs (n = 3497), there was no observed increased risk of major birth defects (crude odds ratio 
[OR] = 1.22, 95% CI: 0.79 - 1.90; adjusted OR = 0.96, 95% CI: 0.58 - 1.60 after adjusting for country, 
maternal disease, parity, maternal age and smoking in early pregnancy). This study also showed no 
increased risks of minor birth defects, preterm birth, stillbirth, or infections in the first year of life for 
infants born to women exposed to etanercept during pregnancy.  Erelzi should only be used during 
pregnancy if clearly needed. 
 
Etanercept crosses the placenta and has been detected in the serum of infants born to female patients 
treated with etanercept during pregnancy. The clinical impact of this is unknown, however, infants may 
be at increased risk of infection. Administration of live vaccines to infants for 16 weeks after the 
mother’s last dose of Erelzi is generally not recommended. 
 
Breast-feeding 
Etanercept has been reported to be excreted in human milk following subcutaneous administration. In 
lactating rats following subcutaneous administration, etanercept was excreted in the milk and detected 
in the serum of pups. Because immunoglobulins, in common with many medicinal products, can be 
excreted in human milk, a decision must be made whether to discontinue breast-feeding or to 
discontinue Erelzi therapy, taking into account the benefit of breast-feeding for the child and the benefit 
of therapy for the woman. 
 
Fertility 
Preclinical data about peri- and postnatal toxicity of etanercept and of effects of etanercept on fertility 
and general reproductive performance are not available. 



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4.7 Effects on ability to drive and use machines 
 
No studies on the effects on the ability to drive and use machines have been performed. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
The most commonly reported adverse reactions are injection site reactions (such as pain, swelling, 
itching, reddening and bleeding at the puncture site), infections (such as upper respiratory infections, 
bronchitis, bladder infections and skin infections), allergic reactions, development of autoantibodies, 
itching, and fever. 
 
Serious adverse reactions have also been reported for etanercept. TNF-antagonists, such as etanercept, 
affect the immune system and their use may affect the body’s defences against infection and cancer. 
Serious infections affect fewer than 1 in 100 patients treated with etanercept. Reports have included 
fatal and life-threatening infections and sepsis. Various malignancies have also been reported with use 
of etanercept, including cancers of the breast, lung, skin and lymph glands (lymphoma). 
 
Serious haematological, neurological and autoimmune reactions have also been reported. These include 
rare reports of pancytopenia and very rare reports of aplastic anaemia. Central and peripheral 
demyelinating events have been seen rarely and very rarely, respectively, with etanercept use. There 
have been rare reports of lupus, lupus-related conditions, and vasculitis. 
 
Tabulated list of adverse reactions 
The following list of adverse reactions is based on experience from clinical trials in adults and on 
post-marketing experience. 
 
Within the system organ classes, adverse reactions are listed under headings of frequency (number of 
patients expected to experience the reaction), using the following categories: 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). 
 

System Organ 
Class 

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 
 

Frequency Not 
Known 
(Cannot be 
Estimated 
from Available 
Data) 

Infections and 
infestations 

Infection 
(including 
upper 
respiratory 
tract 
infection, 
bronchitis, 
cystitis, skin 
infection)* 

 Serious infections 
(including 
pneumonia, 
cellulitis, arthritis 
bacterial, sepsis 
and parasitic 
infection)* 

 

Tuberculosis, 
opportunistic 
infection 
(including 
invasive fungal, 
protozoal, 
bacterial, 
atypical 
mycobacterial, 
viral infections, 
and Legionella)* 

 Hepatitis B 
reactivation, 
listeria 

Neoplasms 
benign, 
malignant and 
unspecified 
(including cysts 
and polyps) 

  Non-melanoma 
skin cancers* (see 
section 4.4) 

Malignant 
melanoma (see 
section 4.4), 
lymphoma, 
leukaemia  

 Merkel cell 
carcinoma (see 
section 4.4) 



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System Organ 
Class 

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 
 

Frequency Not 
Known 
(Cannot be 
Estimated 
from Available 
Data) 

Blood and 
lymphatic 
system disorders 

  Thrombocytopenia, 
anaemia, 
leukopenia, 
neutropenia 

 

Pancytopenia* Aplastic 
anaemia* 

Histiocytosis 
haematophagic 
(macrophage 
activation 
syndrome)* 

Immune system 
disorders 

 Allergic 
reactions (see 
Skin and 
subcutaneous 
tissue disorders), 
autoantibody 
formation* 

Vasculitis 
(including anti-
neutrophilic 
cytoplasmic 
antibody positive 
vasculitis) 

Serious allergic/ 
anaphylactic 
reactions 
(including 
angioedema, 
bronchospasm), 
sarcoidosis 

 Worsening of 
symptoms of 
dermatomyositis 

Nervous system 
disorders  

   CNS 
demyelinating 
events 
suggestive of 
multiple 
sclerosis or 
localised 
demyelinating 
conditions, such 
as optic neuritis 
and transverse 
myelitis (see 
section 4.4), 
peripheral 
demyelinating 
events, including 
Guillain-Barré 
syndrome, 
chronic 
inflammatory 
demyelinating 
polyneuropathy, 
demyelinating 
polyneuropathy, 
and multifocal 
motor 
neuropathy (see 
section 4.4), 
seizure 

  

Eye disorders    Uveitis, scleritis    
Cardiac 
disorders  

  Worsening of 
cardiac failure 
congestive (see 
section 4.4) 

New onset 
cardiac failure 
congestive (see 
section 4.4) 

  

Respiratory, 
thoracic, and 
mediastinal 
disorders  

   Interstitial lung 
disease 
(including 
pneumonitis and 
pulmonary 
fibrosis)* 

  

Hepatobiliary 
disorders  

  Elevated liver 
enzymes* 

Autoimmune 
hepatitis* 

  



13 
 
 

System Organ 
Class 

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 
 

Frequency Not 
Known 
(Cannot be 
Estimated 
from Available 
Data) 

Skin and 
subcutaneous 
tissue disorders  

 Pruritus, rash Angioedema, 
psoriasis (including 
new onset or 
worsening and 
pustular, primarily 
palms and soles), 
urticaria, 
psoriasiform rash 

Stevens-Johnson 
syndrome, 
cutaneous 
vasculitis 
(including 
hypersensitivity 
vasculitis), 
erythema 
multiforme, 
lichenoid 
reactions 

Toxic 
epidermal 
necrolysis 

 

Musculoskeletal 
and connective 
tissue disorders  
 
 
 

   Cutaneous lupus 
erythematosus, 
subacute 
cutaneous lupus 
erythematosus, 
lupus-like 
syndrome 

  

General 
disorders and 
administration 
site conditions  

Injection site 
reactions 
(including 
bleeding, 
bruising, 
erythema, 
itching, 
pain, 
swelling)* 

Pyrexia     

Gastrointestinal 
disorders 

  Inflammatory 
bowel disease 

   

 
*see Description of selected adverse reactions, below. 
 
Description of selected adverse reactions 
 
Malignancies and lymphoproliferative disorders 
One hundred and twenty-nine (129) new malignancies of various types were observed in 
4,114 rheumatoid arthritis patients treated in clinical trials with etanercept for up to approximately 
6 years, including 231 patients treated with etanercept in combination with methotrexate in a 2-year 
active-controlled study. The observed rates and incidences in these clinical trials were similar to those 
expected for the population studied. A total of 2 malignancies were reported in clinical studies of 
approximately 2 years duration involving 240 etanercept-treated psoriatic arthritis patients. In clinical 
studies conducted for more than 2 years with 351 ankylosing spondylitis patients, 6 malignancies were 
reported in etanercept-treated patients. In a group of 2,711 plaque psoriasis patients treated with 
etanercept in double-blind and open-label studies of up to 2.5 years, 30 malignancies and 
43 non-melanoma skin cancers were reported. 
 
In a group of 7,416 patients treated with etanercept in rheumatoid arthritis, psoriatic arthritis, ankylosing 
spondylitis and psoriasis clinical trials, 18 lymphomas were reported. 
 
Reports of various malignancies (including breast and lung carcinoma and lymphoma) have also been 
received in the post-marketing period (see section 4.4). 
 
Injection site reactions 



14 
 
 

Compared to placebo, patients with rheumatic diseases treated with etanercept had a significantly higher 
incidence of injection site reactions (36% vs. 9%). Injection site reactions usually occurred in the first 
month. Mean duration was approximately 3 to 5 days. No treatment was given for the majority of 
injection site reactions in the etanercept treatment groups, and the majority of patients who were given 
treatment received topical preparations, such as corticosteroids, or oral antihistamines. Additionally, 
some patients developed recall injection site reactions characterised by a skin reaction at the most recent 
site of injection, along with the simultaneous appearance of injection site reactions at previous injection 
sites. These reactions were generally transient and did not recur with treatment. 
 
In controlled trials in patients with plaque psoriasis, approximately 13.6% of patients treated with 
etanercept developed injection site reactions compared with 3.4% of placebo-treated patients during the 
first 12 weeks of treatment. 
 
Serious infections 
In placebo-controlled trials, no increase in the incidence of serious infections (fatal, life-threatening, or 
requiring hospitalisation or intravenous antibiotics) was observed. Serious infections occurred in 6.3% 
of rheumatoid arthritis patients treated with etanercept for up to 48 months. These included abscess (at 
various sites), bacteraemia, bronchitis, bursitis, cellulitis, cholecystitis, diarrhoea, diverticulitis, 
endocarditis (suspected), gastroenteritis, hepatitis B, herpes zoster, leg ulcer, mouth infection, 
osteomyelitis, otitis, peritonitis, pneumonia, pyelonephritis, sepsis, septic arthritis, sinusitis, skin 
infection, skin ulcer, urinary tract infection, vasculitis, and wound infection. In a 2-year 
active-controlled study where patients were treated with either etanercept alone, methotrexate alone or 
etanercept in combination with methotrexate, the rates of serious infections were similar among the 
treatment groups. However, it cannot be excluded that the combination of etanercept with methotrexate 
could be associated with an increase in the rate of infections. 
 
There were no differences in rates of infection among patients treated with etanercept and those treated 
with placebo for plaque psoriasis in placebo-controlled trials of up to 24 weeks duration. Serious 
infections experienced by etanercept-treated patients included cellulitis, gastroenteritis, pneumonia, 
cholecystitis, osteomyelitis, gastritis, appendicitis, Streptococcal fasciitis, myositis, septic shock, 
diverticulitis and abscess. In the double-blind and open-label psoriatic arthritis trials, 1 patient reported 
a serious infection (pneumonia). 
 
Serious and fatal infections have been reported during use of etanercept; reported pathogens include 
bacteria, mycobacteria (including tuberculosis), viruses and fungi. Some have occurred within a few 
weeks after initiating treatment with etanercept in patients who have underlying conditions (e.g., 
diabetes, congestive heart failure, history of active or chronic infections) in addition to their rheumatoid 
arthritis (see section 4.4). Etanercept treatment may increase mortality in patients with established 
sepsis. 
 
Opportunistic infections have been reported in association with etanercept, including invasive fungal, 
parasitic (including protozoal), viral (including herpes zoster), bacterial (including Listeria and 
Legionella), and atypical mycobacterial infections. In a pooled data set of clinical trials, the overall 
incidence of opportunistic infections was 0.09% for the 15,402 subjects who received etanercept. The 
exposure-adjusted rate was 0.06 events per 100 patient-years. In post-marketing experience, 
approximately half of all of the case reports of opportunistic infections worldwide were invasive fungal 
infections. The most commonly reported invasive fungal infections included Candida, Pneumocystis, 
Aspergillus and Histoplasma. Invasive fungal infections accounted for more than half of the fatalities 
amongst patients who developed opportunistic infections. The majority of the reports with a fatal 
outcome were in patients with Pneumocystis pneumonia, unspecified systemic fungal infections, and 
aspergillosis (see section 4.4). 
 
Autoantibodies 
Adult patients had serum samples tested for autoantibodies at multiple timepoints. Of the rheumatoid 
arthritis patients evaluated for antinuclear antibodies (ANA), the percentage of patients who developed 
new positive ANA (≥ 1:40) was higher in patients treated with etanercept (11%) than in placebo-treated 



15 
 
 

patients (5%). The percentage of patients who developed new positive anti-double-stranded DNA 
antibodies was also higher by radioimmunoassay (15% of patients treated with etanercept compared to 
4% of placebo-treated patients) and by Crithidia luciliae assay (3% of patients treated with etanercept 
compared to none of placebo-treated patients). The proportion of patients treated with etanercept who 
developed anticardiolipin antibodies was similarly increased compared to placebo-treated patients. The 
impact of long-term treatment with etanercept on the development of autoimmune diseases is unknown. 
 
There have been rare reports of patients, including rheumatoid factor positive patients, who have 
developed other autoantibodies in conjunction with a lupus-like syndrome or rashes that are compatible 
with subacute cutaneous lupus or discoid lupus by clinical presentation and biopsy. 
 
Pancytopenia and aplastic anaemia 
There have been post-marketing reports of pancytopenia and aplastic anaemia, some of which had fatal 
outcomes (see section 4.4). 
 
Interstitial lung disease 
In controlled clinical trials of etanercept across all indications, the frequency (incidence proportion) of 
interstitial lung disease in patients receiving etanercept without concomitant methotrexate was 0.06% 
(frequency rare). In the controlled clinical trials that allowed concomitant treatment with etanercept and 
methotrexate, the frequency (incidence proportion) of interstitial lung disease was 0.47% (frequency 
uncommon). There have been post-marketing reports of interstitial lung disease (including pneumonitis 
and pulmonary fibrosis), some of which had fatal outcomes. 
 
Concurrent treatment with anakinra 
In studies when adult patients received concurrent treatment with etanercept plus anakinra, a higher rate 
of serious infections compared to etanercept alone was observed and 2% of patients (3/139) developed 
neutropenia (absolute neutrophil count ˂ 1,000/mm3). While neutropenic, one patient developed 
cellulitis that resolved after hospitalisation (see sections 4.4 and 4.5). 
 
Elevated liver enzymes 
In the double-blind periods of controlled clinical trials of etanercept across all indications, the frequency 
(incidence proportion) of adverse events of elevated liver enzymes in patients receiving etanercept 
without concomitant methotrexate was 0.54% (frequency uncommon). In the double-blind periods of 
controlled clinical trials that allowed concomitant treatment with etanercept and methotrexate, the 
frequency (incidence proportion) of adverse events of elevated liver enzymes was 4.18% (frequency 
common). 
 
Autoimmune hepatitis 
In controlled clinical trials of etanercept across all indications, the frequency (incidence proportion) of 
autoimmune hepatitis in patients receiving etanercept without concomitant methotrexate was 0.02% 
(frequency rare). In the controlled clinical trials that allowed concomitant treatment with etanercept and 
methotrexate, the frequency (incidence proportion) of autoimmune hepatitis was 0.24% (frequency 
uncommon).  
 
Paediatric population 
 
Undesirable effects in paediatric patients with juvenile idiopathic arthritis  
In general, the adverse events in paediatric patients with juvenile idiopathic arthritis were similar in 
frequency and type to those seen in adult patients. Differences from adults and other special 
considerations are discussed in the following paragraphs. 
 
The types of infections seen in clinical trials in juvenile idiopathic arthritis patients aged 2 to 18 years 
were generally mild to moderate and consistent with those commonly seen in outpatient paediatric 
populations. Severe adverse events reported included varicella with signs and symptoms of aseptic 
meningitis, which resolved without sequelae (see also section 4.4), appendicitis, gastroenteritis, 



16 
 
 

depression/personality disorder, cutaneous ulcer, oesophagitis/gastritis, group A streptococcal septic 
shock, type I diabetes mellitus, and soft tissue and post-operative wound infection. 
 
In one study in children with juvenile idiopathic arthritis aged 4 to 17 years, 43 of 69 (62%) children 
experienced an infection while receiving etanercept during 3 months of the study (part 1, open-label), 
and the frequency and severity of infections was similar in 58 patients completing 12 months of 
open-label extension therapy. The types and proportion of adverse events in juvenile idiopathic arthritis 
patients were similar to those seen in trials of etanercept in adult patients with rheumatoid arthritis, and 
the majority were mild. Several adverse events were reported more commonly in 69 juvenile idiopathic 
arthritis patients receiving 3 months of etanercept compared to the 349 adult rheumatoid arthritis 
patients. These included headache (19% of patients, 1.7 events per patient year), nausea (9%, 1.0 event 
per patient year), abdominal pain (19%, 0.74 events per patient year), and vomiting (13%, 0.74 events 
per patient year). 
 
There were 4 reports of macrophage activation syndrome in juvenile idiopathic arthritis clinical trials.  
 
There have been reports of inflammatory bowel disease and uveitis in JIA patients being treated with 
etanercept from post-marketing sources, including a very small number of cases indicating a positive 
rechallenge (see section 4.4). 
 
Undesirable effects in paediatric patients with plaque psoriasis  
In a 48-week study in 211 children aged 4 to 17 years with paediatric plaque psoriasis, the adverse 
events reported were similar to those seen in previous studies in adults with plaque psoriasis. 
 
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 
 
No dose-limiting toxicities were observed during clinical trials of rheumatoid arthritis patients. The 
highest dose level evaluated has been an intravenous loading dose of 32 mg/m2 followed by 
subcutaneous doses of 16 mg/m2 administered twice weekly. One rheumatoid arthritis patient 
mistakenly self-administered 62 mg etanercept subcutaneously twice weekly for 3 weeks without 
experiencing undesirable effects. There is no known antidote to etanercept. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunosuppressants, tumour necrosis factor alpha (TNF-α) inhibitors, 
ATC code: L04AB01 
 
Erelzi is a biosimilar medicinal product. Detailed information is available on the website of the 
European Medicines Agency http://www.ema.europa.eu. 
 
Tumour necrosis factor (TNF) is a dominant cytokine in the inflammatory process of rheumatoid 
arthritis. Elevated levels of TNF are also found in the synovium and psoriatic plaques of patients with 
psoriatic arthritis and in serum and synovial tissue of patients with ankylosing spondylitis. In plaque 
psoriasis, infiltration by inflammatory cells, including T-cells, leads to increased TNF levels in psoriatic 
lesions compared with levels in uninvolved skin. Etanercept is a competitive inhibitor of TNF binding 
to its cell surface receptors, and thereby inhibits the biological activity of TNF. TNF and lymphotoxin 
are pro-inflammatory cytokines that bind to two distinct cell surface receptors: the 55-kilodalton (p55) 



17 
 
 

and 75-kilodalton (p75) tumour necrosis factor receptors (TNFRs). Both TNFRs exist naturally in 
membrane-bound and soluble forms. Soluble TNFRs are thought to regulate TNF biological activity. 
 
TNF and lymphotoxin exist predominantly as homotrimers, with their biological activity dependent on 
cross-linking of cell surface TNFRs. Dimeric soluble receptors, such as etanercept, possess a higher 
affinity for TNF than monomeric receptors and are considerably more potent competitive inhibitors of 
TNF binding to its cellular receptors. In addition, use of an immunoglobulin Fc region as a fusion 
element in the construction of a dimeric receptor imparts a longer serum half-life. 
 
Mechanism of action 
Much of the joint pathology in rheumatoid arthritis and ankylosing spondylitis and skin pathology in 
plaque psoriasis is mediated by pro-inflammatory molecules that are linked in a network controlled by 
TNF. The mechanism of action of etanercept is thought to be its competitive inhibition of TNF binding 
to cell surface TNFR, preventing TNF-mediated cellular responses by rendering TNF biologically 
inactive. Etanercept may also modulate biologic responses controlled by additional downstream 
molecules (e.g., cytokines, adhesion molecules, or proteinases) that are induced or regulated by TNF. 
 
Clinical efficacy and safety 
This section presents data from four randomised controlled trials in adults with rheumatoid arthritis, one 
study in adults with psoriatic arthritis, one study in adults with ankylosing spondylitis, one study in 
adults with non-radiographic axial spondyloarthritis, four studies in adults with plaque psoriasis, three 
studies in juvenile idiopathic arthritis and one study in paediatric patients with plaque psoriasis. 
 
Adult patients with rheumatoid arthritis 
The efficacy of etanercept was assessed in a randomised, double-blind, placebo-controlled study. The 
study evaluated 234 adult patients with active rheumatoid arthritis who had failed therapy with at least 
one but no more than four disease-modifying antirheumatic drugs (DMARDs). Doses of 10 mg or 
25 mg etanercept or placebo were administered subcutaneously twice a week for 6 consecutive months. 
The results of this controlled trial were expressed in percentage improvement in rheumatoid arthritis 
using American College of Rheumatology (ACR) response criteria. 
 
ACR 20 and 50 responses were higher in patients treated with etanercept at 3 and 6 months than in 
patients treated with placebo (ACR 20: etanercept 62% and 59%, placebo 23% and 11% at 3 and 
6 months, respectively: ACR 50: etanercept 41% and 40%, placebo 8% and 5% at months 3 and 6, 
respectively; p < 0.01 etanercept vs. placebo at all timepoints for both ACR 20 and ACR 50 responses). 
 
Approximately 15% of subjects who received etanercept achieved an ACR 70 response at month 3 and 
month 6 compared to fewer than 5% of subjects in the placebo arm. Among patients receiving 
etanercept, the clinical responses generally appeared within 1 to 2 weeks after initiation of therapy and 
nearly always occurred by 3 months. A dose response was seen; results with 10 mg were intermediate 
between placebo and 25 mg. Etanercept was significantly better than placebo in all components of the 
ACR criteria, as well as other measures of rheumatoid arthritis disease activity not included in the ACR 
response criteria, such as morning stiffness. A Health Assessment Questionnaire (HAQ), which 
included disability, vitality, mental health, general health status, and arthritis-associated health status 
subdomains, was administered every 3 months during the trial. All subdomains of the HAQ were 
improved in patients treated with etanercept compared to controls at 3 and 6 months. 
 
After discontinuation of etanercept, symptoms of arthritis generally returned within a month. 
Re-introduction of treatment with etanercept after discontinuation of up to 24 months resulted in the 
same magnitudes of responses as patients who received etanercept without interruption of therapy based 
on results of open-label studies. Continued durable responses have been seen for up to 10 years in 
open-label extension treatment trials when patients received etanercept without interruption. 
 
The efficacy of etanercept was compared to methotrexate in a randomised, active-controlled study with 
blinded radiographic evaluations as a primary endpoint in 632 adult patients with active rheumatoid 
arthritis (< 3 years duration) who had never received treatment with methotrexate. Doses of 10 mg or 



18 
 
 

25 mg etanercept were administered subcutaneously (SC) twice a week for up to 24 months. 
Methotrexate doses were escalated from 7.5 mg/week to a maximum of 20 mg/week over the first 
8 weeks of the trial and continued for up to 24 months. Clinical improvement, including onset of action 
within 2 weeks with etanercept 25 mg, was similar to that seen in the previous trials and was maintained 
for up to 24 months. At baseline, patients had a moderate degree of disability, with mean HAQ scores of 
1.4 to 1.5. Treatment with etanercept 25 mg resulted in substantial improvement at 12 months, with 
about 44% of patients achieving a normal HAQ score (less than 0.5). This benefit was maintained in 
Year 2 of this study. 
 
In this study, structural joint damage was assessed radiographically and expressed as change in Total 
Sharp Score (TSS) and its components, the erosion score and Joint Space Narrowing (JSN) score. 
Radiographs of hands/wrists and feet were read at baseline and 6, 12, and 24 months. The 10 mg 
etanercept dose had consistently less effect on structural damage than the 25 mg dose. Etanercept 25 mg 
was significantly superior to methotrexate for erosion scores at both 12 and 24 months. The differences 
in TSS and JSN were not statistically significant between methotrexate and etanercept 25 mg. The 
results are shown in the figure below. 
 
Radiographic progression: comparison of etanercept vs. methotrexate in patients with RA of < 3 
years duration 
 

 
 
In another active-controlled, double-blind, randomised study, clinical efficacy, safety, and radiographic 
progression in RA patients treated with etanercept alone (25 mg twice weekly), methotrexate alone (7.5 
to 20 mg weekly, median dose 20 mg), and the combination of etanercept and methotrexate initiated 
concurrently were compared in 682 adult patients with active rheumatoid arthritis of 6 months to 
20 years duration (median 5 years) who had a less than satisfactory response to at least 1 
disease-modifying antirheumatic drug (DMARD) other than methotrexate. 
 
Patients in the etanercept in combination with methotrexate therapy group had significantly higher 
ACR 20, ACR 50, ACR 70 responses and improvement for DAS and HAQ scores at both 24 and 
52 weeks than patients in either of the single therapy groups (results shown in table below). Significant 
advantages for etanercept in combination with methotrexate compared with etanercept monotherapy and 
methotrexate monotherapy were also observed after 24 months. 
 



19 
 
 

 Clinical efficacy results at 12 months: comparison of etanercept vs. methotrexate vs. etanercept in 
combination with methotrexate in patients with RA of 6 months to 20 years duration 
 

Endpoint 
 

Methotrexate 
(n = 228) 

Etanercept 
(n = 223) 

Etanercept + 
Methotrexate 

(n = 231) 
ACR Responsesa  ACR 20 58.8% 65.5% 74.5% †,ϕ 

 ACR 50 36.4% 43.0% 63.2% †, ϕ 
 ACR 70 16.7% 22.0% 39.8% †, ϕ 

DAS  Baseline scoreb 5.5 5.7 5.5 
 Week 52 scoreb 3.0 3.0 2.3 †, ϕ 
 Remissionc 14% 18% 37% †, ϕ 

HAQ  Baseline 1.7 1.7 1.8 
 Week 52 1.1 1.0 0.8 †, ϕ 

 a: Patients who did not complete 12 months in the study were considered to be non-responders. 
b: Values for Disease Activity Score (DAS) are means. 
c: Remission is defined as DAS < 1.6. 
Pairwise comparison p-values: † = p < 0.05 for comparisons of etanercept + methotrexate vs. 
methotrexate and ϕ = p < 0.05 for comparisons of etanercept + methotrexate vs. etanercept. 
 
Radiographic progression at 12 months was significantly less in the etanercept group than in the 
methotrexate group, while the combination was significantly better than either monotherapy at slowing 
radiographic progression (see figure below). 
 
Radiographic progression: comparison of etanercept vs. methotrexate vs. etanercept in 
combination with methotrexate in patients with RA of 6 months to 20 years duration (12 month 
results) 

 
Pairwise comparison p-values: * = p < 0.05 for comparisons of etanercept vs. methotrexate, † = p < 0.05 
for comparisons of etanercept + methotrexate vs. methotrexate and ϕ = p < 0.05 for comparisons of 
etanercept + methotrexate vs. etanercept. 

 
Significant advantages for etanercept in combination with methotrexate compared with etanercept 
monotherapy and methotrexate monotherapy were also observed after 24 months. Similarly, the 
significant advantages for etanercept monotherapy compared with methotrexate monotherapy were also 
observed after 24 months. 
 



20 
 
 

In an analysis in which all patients who dropped out of the study for any reason were considered to have 
progressed, the percentage of patients without progression (TSS change ≤ 0.5) at 24 months was higher 
in the etanercept in combination with methotrexate group compared with the etanercept alone and 
methotrexate alone groups (62%, 50%, and 36%, respectively; p < 0.05). The difference between 
etanercept alone and methotrexate alone was also significant (p < 0.05). Among patients who completed 
a full 24 months of therapy in the study, the non-progression rates were 78%, 70%, and 61%, 
respectively. 
 
The safety and efficacy of 50 mg etanercept (two 25 mg SC injections) administered once weekly were 
evaluated in a double-blind, placebo-controlled study of 420 patients with active RA. In this study, 
53 patients received placebo, 214 patients received 50 mg etanercept once weekly and 153 patients 
received 25 mg etanercept twice weekly. The safety and efficacy profiles of the two etanercept 
treatment regimens were comparable at week 8 in their effect on signs and symptoms of RA; data at 
week 16 did not show comparability (non-inferiority) between the two regimens. A single 50 mg/ml 
injection of etanercept was found to be bioequivalent to two simultaneous injections of 25 mg/ml. 
 
Adult patients with psoriatic arthritis 
The efficacy of etanercept was assessed in a randomised, double-blind, placebo-controlled study in 
205 patients with psoriatic arthritis. Patients were between 18 and 70 years of age and had active 
psoriatic arthritis (≥ 3 swollen joints and ≥ 3 tender joints) in at least one of the following forms: (1) 
distal interphalangeal (DIP) involvement; (2) polyarticular arthritis (absence of rheumatoid nodules and 
presence of psoriasis); (3) arthritis mutilans; (4) asymmetric psoriatic arthritis; or (5) spondylitis-like 
ankylosis. Patients also had plaque psoriasis with a qualifying target lesion ≥ 2 cm in diameter. Patients 
had previously been treated with NSAIDs (86%), DMARDs (80%), and corticosteroids (24%). Patients 
currently on methotrexate therapy (stable for ≥ 2 months) could continue at a stable dose of 
≤ 25 mg/week methotrexate. Doses of 25 mg of etanercept (based on dose-finding studies in patients 
with rheumatoid arthritis) or placebo were administered SC twice a week for 6 months. At the end of 
the double-blind study, patients could enter a long-term open-label extension study for a total duration 
of up to 2 years. 
 
Clinical responses were expressed as percentages of patients achieving the ACR 20, 50, and 70 response 
and percentages with improvement in Psoriatic Arthritis Response Criteria (PsARC). Results are 
summarised in the table below. 
 

 Responses of patients with psoriatic arthritis in a placebo-controlled trial 
  Percent of Patients 
Psoriatic Arthritis Response 
 

Placebo 
n = 104 

Etanercepta 
n = 101 

ACR 20 
 

 Month 3  15  59b 
 Month 6  13  50b 

ACR 50 
 

 Month 3  4  38b 
 Month 6  4  37b 

ACR 70 
 

 Month 3  0  11b 
 Month 6  1  9c 

PsARC   Month 3  31  72b 
  Month 6  23  70b 
 a: 25 mg etanercept SC twice weekly 

b: p < 0.001, etanercept vs. placebo 
c: p < 0.01, etanercept vs. placebo 

 
Among patients with psoriatic arthritis who received etanercept, the clinical responses were apparent at 
the time of the first visit (4 weeks) and were maintained through 6 months of therapy. Etanercept was 
significantly better than placebo in all measures of disease activity (p < 0.001), and responses were 
similar with and without concomitant methotrexate therapy. Quality of life in psoriatic arthritis patients 
was assessed at every timepoint using the disability index of the HAQ. The disability index score was 



21 
 
 

significantly improved at all timepoints in psoriatic arthritis patients treated with etanercept, relative to 
placebo (p < 0.001). 
 
Radiographic changes were assessed in the psoriatic arthritis study. Radiographs of hands and wrists 
were obtained at baseline and months 6, 12, and 24. The modified TSS at 12 months is presented in the 
table below. In an analysis in which all patients who dropped out of the study for any reason were 
considered to have progressed, the percentage of patients without progression (TSS change ≤ 0.5) at 
12 months was higher in the etanercept group compared with the placebo group (73% vs. 47%, 
respectively, p ≤ 0.001). The effect of etanercept on radiographic progression was maintained in 
patients who continued on treatment during the second year. The slowing of peripheral joint damage 
was observed in patients with polyarticular symmetrical joint involvement. 
 

Mean (SE) annualized change from baseline in total sharp score 

Time 
Placebo 
(n = 104) 

Etanercept(n = 101) 

Month 12 1.00 (0.29) -0.03 (0.09)a 
SE = standard error. 
a. p = 0.0001. 
 
Etanercept treatment resulted in improvement in physical function during the double-blind period, and 
this benefit was maintained during the longer-term exposure of up to 2 years. 
 
There is insufficient evidence of the efficacy of etanercept in patients with ankylosing spondylitis-like 
and arthritis mutilans psoriatic arthropathies due to the small number of patients studied. 
 
No study has been performed in patients with psoriatic arthritis using the 50 mg once-weekly dosing 
regimen. Evidence of efficacy for the once-weekly dosing regimen in this patient population has been 
based on data from the study in patients with ankylosing spondylitis. 
 
Adult patients with ankylosing spondylitis 
The efficacy of etanercept in ankylosing spondylitis was assessed in 3 randomised, double-blind studies 
comparing twice-weekly administration of 25 mg etanercept with placebo. A total of 401 patients were 
enrolled, from which 203 were treated with etanercept. The largest of these trials (n = 277) enrolled 
patients who were between 18 and 70 years of age and had active ankylosing spondylitis defined as 
visual analog scale (VAS) scores of ≥ 30 for average of duration and intensity of morning stiffness plus 
VAS scores of ≥ 30 for at least 2 of the following 3 parameters: patient global assessment; average of 
VAS values for nocturnal back pain and total back pain; average of 10 questions on the Bath 
Ankylosing Spondylitis Functional Index (BASFI). Patients receiving DMARDs, NSAIDS, or 
corticosteroids could continue them on stable doses. Patients with complete ankylosis of the spine were 
not included in the study. Doses of 25 mg of etanercept (based on dose-finding studies in patients with 
rheumatoid arthritis) or placebo were administered subcutaneously twice a week for 6 months in 
138 patients. 
 
The primary measure of efficacy (ASAS 20) was a ≥ 20% improvement in at least 3 of the 4 
Assessment in Ankylosing Spondylitis (ASAS) domains (patient global assessments, back pain, BASFI, 
and inflammation) and absence of deterioration in the remaining domain. ASAS 50 and 70 responses 
used the same criteria with a 50% improvement or a 70% improvement, respectively. 
 
Compared to placebo, treatment with etanercept resulted in significant improvements in the ASAS 20, 
ASAS 50 and ASAS 70 as early as 2 weeks after the initiation of therapy. 
 



22 
 
 

Responses of patients with ankylosing spondylitis in 
a placebo-controlled trial 

 Percent of Patients 
Ankylosing Spondylitis 
Response 

Placebo 
N = 139 

Etanercept 
N = 138 

ASAS 20   
2 weeks 22 46a 
3 months 27 60a 
6 months 23 58a 
   

ASAS 50   
2 weeks 7 24a 
3 months 13 45a 
6 months 10 42a 
   

ASAS 70   
2 weeks 2 12b 
3 months 7 29b 
6 months 5 28b 
   

a: p < 0.001, etanercept vs. placebo 
b: p = 0.002, etanercept vs. placebo 

 
Among patients with ankylosing spondylitis who received etanercept, the clinical responses were 
apparent at the time of the first visit (2 weeks) and were maintained through 6 months of therapy. 
Responses were similar in patients who were or were not receiving concomitant therapies at baseline. 
 
Similar results were obtained in the 2 smaller ankylosing spondylitis trials. 
 
In a fourth study, the safety and efficacy of 50 mg etanercept (two 25 mg SC injections) administered 
once weekly vs. 25 mg etanercept administered twice weekly were evaluated in a double-blind, 
placebo-controlled study of 356 patients with active ankylosing spondylitis. The safety and efficacy 
profiles of the 50 mg once-weekly and 25 mg twice-weekly regimens were similar. 
 
Adult patients with non-radiographic axial spondyloarthritis 
The efficacy of etanercept in patients with non-radiographic axial spondyloarthritis (nr-AxSpa) was 
assessed in a randomised, 12-week double-blind, placebo-controlled study. The study evaluated 
215 adult patients (modified intent-to-treat population) with active nr-AxSpa (18 to 49 years of age), 
defined as those patients meeting the ASAS classification criteria of axial spondyloarthritis but did not 
meet the modified New York criteria for AS. Patients were also required to have an inadequate response 
or intolerance to two or more NSAIDs. In the double-blind period, patients received etanercept 50 mg 
weekly or placebo for 12 weeks. The primary measure of efficacy (ASAS 40) was a 40% improvement 
in at least three of the four ASAS domains and absence of deterioration in the remaining domain. The 
double-blind period was followed by an open-label period during which all patients received etanercept 
50 mg weekly for up to an additional 92 weeks. MRIs of the sacroiliac joint and spine were obtained to 
assess inflammation at baseline and at weeks 12 and 104.  
 
Compared to placebo, treatment with etanercept resulted in statistically significant improvement in the 
ASAS 40, ASAS 20 and ASAS 5/6. Significant improvement was also observed for the ASAS partial 
remission and BASDAI 50. Week 12 results are shown in the table below. 
 



23 
 
 

Efficacy response in placebo-controlled nr-AxSpa study: percent of patients achieving 
endpoints 

Double-Blind Clinical  
Responses at Week 12 

Placebo 
N = 106 to 109* 

Etanercept 
N = 103 to 105* 

ASAS** 40 15.7 32.4b 
ASAS 20 36.1 52.4c 
ASAS 5/6 10.4 33.0a 
ASAS partial remission 11.9 24.8c 
BASDAI*** 50 23.9 43.8b 
*Some patients did not provide complete data for each endpoint 
**ASAS = Assessments in Spondyloarthritis International Society 
***Bath Ankylosing Spondylitis Disease Activity Index 
a: p < 0.001, b:< 0.01 and c:< 0.05, respectively between etanercept and placebo 
 
At week 12, there was a statistically significant improvement in the SPARCC (Spondyloarthritis 
Research Consortium of Canada) score for the sacroiliac joint (SIJ) as measured by MRI for patients 
receiving etanercept. Adjusted mean change from baseline was 3.8 for etanercept treated (n = 95) versus 
0.8 for placebo treated (n = 105) patients (p < 0.001). At week 104, the mean change from baseline in 
the SPARCC score measured on MRI for all etanercept-treated subjects was 4.64 for the SIJ (n = 153) 
and 1.40 the spine (n = 154). 
 
Etanercept showed statistically significantly greater improvement from baseline to week 12 compared to 
placebo in most health-related quality of life and physical function assessments, including BASFI (Bath 
Ankylosing Spondylitis Functional Index), EuroQol 5D Overall Health State Score and SF-36 Physical 
Component Score. 
 
Clinical responses among nr-AxSpa patients who received etanercept were apparent at the time of the 
first visit (2 weeks) and were maintained through 2 years of therapy. Improvements in health-related 
quality of life and physical function were also maintained through 2 years of therapy. The 2 year data 
did not reveal any new safety findings. At week 104, 8 subjects had progressed to a score of bilateral 
Grade 2 on spinal X-ray according to the modified New York Radiological Grade, indicative of axial 
spondyloarthropathy. 
 
Adult patients with plaque psoriasis 
Etanercept is recommended for use in patients as defined in section 4.1. Patients who “failed to respond 
to” in the target population is defined by insufficient response (PASI < 50 or PGA less than good), or 
worsening of the disease while on treatment, and who were adequately dosed for a sufficiently long 
duration to assess response with at least each of the three major systemic therapies as available. 
 
The efficacy of etanercept versus other systemic therapies in patients with moderate to severe psoriasis 
(responsive to other systemic therapies) has not been evaluated in studies directly comparing etanercept 
with other systemic therapies. Instead, the safety and efficacy of etanercept were assessed in four 
randomised, double-blind, placebo-controlled studies. The primary efficacy endpoint in all four studies 
was the proportion of patients in each treatment group who achieved the PASI 75 (i.e., at least a 75% 
improvement in the Psoriasis Area and Severity Index score from baseline) at 12 weeks. 
 
Study 1 was a Phase 2 study in patients with active, but clinically stable, plaque psoriasis involving 
≥ 10% of the body surface area who were ≥ 18 years old. One hundred and twelve (112) patients were 
randomised to receive a dose of 25 mg of etanercept (n = 57) or placebo (n = 55) twice a week for 
24 weeks. 
 
Study 2 evaluated 652 patients with chronic plaque psoriasis using the same inclusion criteria as study 1 
with the addition of a minimum psoriasis area and severity index (PASI) of 10 at screening. Etanercept 
was administered at doses of 25 mg once a week, 25 mg twice a week or 50 mg twice a week for 6 
consecutive months. During the first 12 weeks of the double-blind treatment period, patients received 



24 
 
 

placebo or one of the above three etanercept doses. After 12 weeks of treatment, patients in the placebo 
group began treatment with blinded etanercept (25 mg twice a week); patients in the active treatment 
groups continued to week 24 on the dose to which they were originally randomised. 
 
Study 3 evaluated 583 patients and had the same inclusion criteria as study 2. Patients in this study 
received a dose of 25 mg or 50 mg etanercept, or placebo twice a week for 12 weeks and then all 
patients received open-label 25 mg etanercept twice weekly for an additional 24 weeks. 
 
Study 4 evaluated 142 patients and had similar inclusion criteria to studies 2 and 3. Patients in this study 
received a dose of 50 mg etanercept or placebo once weekly for 12 weeks and then all patients received 
open-label 50 mg etanercept once weekly for an additional 12 weeks. 
 
In study 1, the etanercept-treated group had a significantly higher proportion of patients with a PASI 75 
response at week 12 (30%) compared to the placebo-treated group (2%) (p < 0.0001). At 24 weeks, 
56% of patients in the etanercept-treated group had achieved the PASI 75 compared to 5% of 
placebo-treated patients. Key results of studies 2, 3 and 4 are shown below. 
 

Responses of patients with psoriasis in studies 2, 3 and 4 

Response 
(%) 

Study 2 Study 3 Study 4 

Placebo 
--------Etanercept------- 

Placebo 
-----Etanercept----- 

Placebo 
-----Etanercept----- 

25 mg 
BIW 

50 mg 
BIW 

25 mg 
BIW 

50 mg 
BIW 

50 mg 
QW 

50 mg 
QW 

n = 166 n = 162 
n = 
162 

n = 
164 

n = 
164 n = 193 

n = 196 n = 196 n = 46 n = 96 n = 90 

wk 12 wk 12 
wk 
24a 

wk 
12 

wk 
24a wk 12 

wk 12 wk 12 wk 12 wk 12 wk 24
a 

PASI 50 14 58* 70 74* 77 9 64* 77* 9 69* 83 
PASI 75 4 34* 44 49* 59 3 34* 49* 2 38* 71 
DSGAb, 
clear or 
almost 
clear 5 34* 39 49* 55 4 39* 57* 4 39* 64 
*p ≤ 0.0001 compared with placebo 
a. No statistical comparisons to placebo were made at week 24 in studies 2 and 4 because the original 
placebo group began receiving etanercept 25 mg BIW or 50 mg once weekly from week 13 to week 24. 
b. Dermatologist Static Global Assessment. Clear or almost clear defined as 0 or 1 on a 0 to 5 scale. 

 
Among patients with plaque psoriasis who received etanercept, significant responses relative to placebo 
were apparent at the time of the first visit (2 weeks) and were maintained through 24 weeks of therapy. 
 
Study 2 also had a drug withdrawal period during which patients who achieved a PASI improvement of 
at least 50% at week 24 had treatment stopped. Patients were observed off treatment for the occurrence 
of rebound (PASI ≥ 150% of baseline) and for the time to relapse (defined as a loss of at least half of the 
improvement achieved between baseline and week 24). During the withdrawal period, symptoms of 
psoriasis gradually returned, with a median time to disease relapse of 3 months. No rebound flare of 
disease and no psoriasis-related serious adverse events were observed. There was some evidence to 
support a benefit of re-treatment with etanercept in patients initially responding to treatment. 
 
In study 3, the majority of patients (77%) who were initially randomised to 50 mg twice weekly and had 
their etanercept dose decreased at week 12 to 25 mg twice weekly maintained their PASI 75 response 
through week 36. For patients who received 25 mg twice weekly throughout the study, the PASI 75 
response continued to improve between weeks 12 and 36. 
 
In study 4, the etanercept-treated group had a higher proportion of patients with PASI 75 at week 12 
(38%) compared to the placebo-treated group (2%) (p < 0.0001). For patients who received 50 mg once 



25 
 
 

weekly throughout the study, the efficacy responses continued to improve with 71% achieving PASI 75 
at week 24. 
 
In long-term (up to 34 months) open-label studies where etanercept was given without interruption, 
clinical responses were sustained and safety was comparable to shorter-term studies. 
 
An analysis of clinical trial data did not reveal any baseline disease characteristics that would assist 
clinicians in selecting the most appropriate dosing option (intermittent or continuous). Consequently, 
the choice of intermittent or continuous therapy should be based upon physician judgment and 
individual patient needs. 
 
Antibodies to etanercept 
 
Antibodies to etanercept have been detected in the sera of some subjects treated with etanercept. These 
antibodies have all been non-neutralising and are generally transient. There appears to be no correlation 
between antibody development and clinical response or adverse events. 
 
Paediatric population 
 
Paediatric patients with juvenile idiopathic arthritis 
The safety and efficacy of etanercept were assessed in a two-part study in 69 children with 
polyarticular-course juvenile idiopathic arthritis who had a variety of juvenile idiopathic arthritis onset 
types (polyarthritis, pauciarthritis, systemic onset). Patients aged 4 to 17 years with moderately to 
severely active polyarticular-course juvenile idiopathic arthritis refractory to, or intolerant of, 
methotrexate were enrolled; patients remained on a stable dose of a single non-steroidal 
anti-inflammatory drug and/or prednisone (< 0.2 mg/kg/day or 10 mg maximum). In part 1, all patients 
received 0.4 mg/kg (maximum 25 mg per dose) etanercept subcutaneously twice weekly. In part 2, 
patients with a clinical response at day 90 were randomised to remain on etanercept or receive placebo 
for four months and assessed for disease flare. Responses were measured using the ACR Pedi 30, 
defined as ≥ 30% improvement in at least three of six and ≥ 30% worsening in no more than one of six 
JRA core set criteria, including active joint count, limitation of motion, physician and patient/parent 
global assessments, functional assessment, and erythrocyte sedimentation rate (ESR). Disease flare was 
defined as a ≥ 30% worsening in three of six JRA core set criteria and ≥ 30% improvement in not more 
than one of the six JRA core set criteria and a minimum of two active joints. 
 
In part 1 of the study, 51 of 69 (74%) patients demonstrated a clinical response and entered part 2. In 
part 2, 6 of 25 (24%) patients remaining on etanercept experienced a disease flare compared to 20 of 26 
(77%) patients receiving placebo (p = 0.007). From the start of part 2, the median time to flare was 
≥ 116 days for patients who received etanercept and 28 days for patients who received placebo. Of 
patients who demonstrated a clinical response at 90 days and entered part 2 of the study, some of the 
patients remaining on etanercept continued to improve from month 3 through month 7, while those who 
received placebo did not improve. 
 
In an open-label, safety extension study, 58 paediatric patients from the above study (from the age of 
4 years at time of enrolment) continued to receive etanercept for up to 10 years. Rates of serious adverse 
events and serious infections did not increase with long-term exposure. 
 
Long-term safety of etanercept monotherapy (n = 103), etanercept plus methotrexate (n = 294), or 
methotrexate monotherapy (n = 197) were assessed for up to 3 years in a registry of 594 children aged 2 
to 18 years with juvenile idiopathic arthritis, 39 of whom were 2 to 3 years of age. Overall, infections 
were more commonly reported in patients treated with etanercept compared to methotrexate alone (3.8 
versus 2%), and the infections associated with etanercept use were of a more severe nature. 
 
In another open-label single-arm study, 60 patients with extended oligoarthritis (15 patients aged 2 to 4, 
23 patients aged 5 to 11 and 22 patients aged 12 to 17 years old), 38 patients with enthesitis-related 
arthritis (12 to 17 years old), and 29 patients with psoriatic arthritis (12 to 17 years old) were treated 



26 
 
 

with etanercept at a dose of 0.8 mg/kg (up to a maximum of 50 mg per dose) administered weekly for 
12 weeks. In each of the JIA subtypes, the majority of patients met ACR Pedi 30 criteria and 
demonstrated clinical improvement in secondary endpoints such as number of tender joints and 
physician global assessment. The safety profile was consistent with that observed in other JIA studies. 
 
Studies have not been done in patients with juvenile idiopathic arthritis to assess the effects of continued 
etanercept therapy in patients who do not respond within 3 months of initiating etanercept therapy. 
Additionally, studies have not been conducted to assess the effects of discontinuing or reducing the 
recommended dose of etanercept following its long-term use in patients with JIA. 
 
Paediatric patients with plaque psoriasis 
The efficacy of etanercept was assessed in a randomised, double-blind, placebo-controlled study in 
211 paediatric patients aged 4 to 17 years with moderate to severe plaque psoriasis (as defined by an 
sPGA score ≥ 3, involving ≥ 10% of the BSA, and PASI ≥ 12). Eligible patients had a history of 
receiving phototherapy or systemic therapy, or were inadequately controlled on topical therapy. 
 
Patients received etanercept 0.8 mg/kg (up to 50 mg) or placebo once weekly for 12 weeks. At week 12, 
more patients randomised to etanercept had positive efficacy responses (e.g., PASI 75) than those 
randomised to placebo. 
 

Paediatric plaque psoriasis outcomes at 12 weeks 
 Etanercept 

0.8 mg/kg Once Weekly 
(N = 106) 

Placebo 
(N = 105) 

PASI 75, n (%) 60 (57%)a 12 (11%) 
PASI 50, n (%) 79 (75%)a 24 (23%) 
   
sPGA “clear” or “minimal”, n (%) 56 (53%)a 14 (13%) 
Abbreviation: sPGA-static Physician Global Assessment 
a. p < 0.0001 compared with placebo 

 
After the 12-week double-blind treatment period, all patients received etanercept 0.8 mg/kg (up to 
50 mg) once weekly for additional 24 weeks. Responses observed during the open-label period were 
similar to those observed in the double-blind period. 
 
During a randomised withdrawal period, significantly more patients re-randomised to placebo 
experienced disease relapse (loss of PASI 75 response) compared with patients re-randomised to 
etanercept. With continued therapy, responses were maintained up to 48 weeks. 
 
The long-term safety and effectiveness of etanercept 0.8 mg/kg (up to 50 mg) once weekly was assessed 
in an open-label extension study of 181 paediatric subjects with plaque psoriasis for up to 2 years 
beyond the 48 week study discussed above. Long-term experience with etanercept was generally 
comparable to the original 48-week study and did not reveal any new safety findings. 
 
5.2 Pharmacokinetic properties 
 
Etanercept serum values were determined by an Enzyme-Linked Immunosorbent Assay (ELISA) 
method, which may detect ELISA-reactive degradation products, as well as the parent compound. 
 
Absorption 
 
Etanercept is slowly absorbed from the site of subcutaneous injection, reaching maximum concentration 
approximately 48 hours after a single dose. The absolute bioavailability is 76%. With twice-weekly 
doses, it is anticipated that steady-state concentrations are approximately twice as high as those 
observed after single doses. After a single subcutaneous dose of 25 mg etanercept, the average 



27 
 
 

maximum serum concentration observed in healthy volunteers was 1.65 ± 0.66 µg/ml, and the area 
under the curve was 235 ± 96.6 µg•hr/ml. 
 
Mean serum concentration profiles at steady state in treated RA patients were Cmax of 2.4 mg/l vs. 
2.6 mg/l, Cmin of 1.2 mg/l vs. 1.4 mg/l, and partial AUC of 297 mg•hr/l vs. 316 mg•hr/l for 50 mg 
etanercept once weekly (n = 21) vs. 25 mg etanercept twice weekly (n = 16), respectively. In an 
open-label, single-dose, two-treatment, crossover study in healthy volunteers, etanercept administered 
as a single 50 mg/ml injection was found to be bioequivalent to two simultaneous injections of 
25 mg/ml. 
 
In a population pharmacokinetics analysis in ankylosing spondylitis patients, the etanercept steady state 
AUCs were 466 µg•hr/ml and 474 µg•hr/ml for 50 mg etanercept once weekly (N = 154) and 25 mg 
twice weekly (N = 148), respectively. 
 
Distribution 
 
A biexponential curve is required to describe the concentration time curve of etanercept. The central 
volume of distribution of etanercept is 7.6 l, while the volume of distribution at steady-state is 10.4 l. 
 
Elimination 
 
Etanercept is cleared slowly from the body. The half-life is long, approximately 70 hours. Clearance is 
approximately 0.066 l/hr in patients with rheumatoid arthritis, somewhat lower than the value of 
0.11 l/hr observed in healthy volunteers. Additionally, the pharmacokinetics of etanercept in rheumatoid 
arthritis patients, ankylosing spondylitis and plaque psoriasis patients are similar. 
 
There is no apparent pharmacokinetic difference between males and females.  
 
Linearity 
 
Dose proportionality has not been formally evaluated, but there is no apparent saturation of clearance 
across the dosing range. 
 
Special populations 
 
Renal impairment 
 
Although there is elimination of radioactivity in urine after administration of radiolabelled etanercept to 
patients and volunteers, increased etanercept concentrations were not observed in patients with acute 
renal failure. The presence of renal impairment should not require a change in dosage. 
 
Hepatic impairment 
 
Increased etanercept concentrations were not observed in patients with acute hepatic failure. The 
presence of hepatic impairment should not require a change in dosage. 
 
Elderly  
 
The impact of advanced age was studied in the population pharmacokinetic analysis of etanercept serum 
concentrations. Clearance and volume estimates in patients aged 65 to 87 years were similar to 
estimates in patients less than 65 years of age. 
 



28 
 
 

Paediatric population 
 
Paediatric patients with juvenile idiopathic arthritis 
In a polyarticular-course juvenile idiopathic arthritis trial with etanercept, 69 patients (aged 4 to 
17 years) were administered 0.4 mg etanercept/kg twice weekly for three months. Serum concentration 
profiles were similar to those seen in adult rheumatoid arthritis patients. The youngest children (4 years 
of age) had reduced clearance (increased clearance when normalised by weight) compared with older 
children (12 years of age) and adults. Simulation of dosing suggests that while older children (10–
17 years of age) will have serum levels close to those seen in adults, younger children will have 
appreciably lower levels. 
 
Paediatric patients with plaque psoriasis 
Patients with paediatric plaque psoriasis (aged 4 to 17 years) were administered 0.8 mg/kg (up to a 
maximum dose of 50 mg per week) of etanercept once weekly for up to 48 weeks. The mean serum 
steady-state trough concentrations ranged from 1.6 to 2.1 mcg/ml at weeks 12, 24, and 48. These mean 
concentrations in patients with paediatric plaque psoriasis were similar to the concentrations observed in 
patients with juvenile idiopathic arthritis (treated with 0.4 mg/kg etanercept twice weekly, up to 
maximum dose of 50 mg per week). These mean concentrations were similar to those seen in adult 
patients with plaque psoriasis treated with 25 mg etanercept twice-weekly. 
 
5.3 Preclinical safety data 
 
In the toxicological studies with etanercept, no dose-limiting or target organ toxicity was evident. 
Etanercept was considered to be non-genotoxic from a battery of in vitro and in vivo studies. 
Carcinogenicity studies, and standard assessments of fertility and postnatal toxicity, were not performed 
with etanercept due to the development of neutralising antibodies in rodents. 
 
Etanercept did not induce lethality or notable signs of toxicity in mice or rats following a single 
subcutaneous dose of 2,000 mg/kg or a single intravenous dose of 1,000 mg/kg. Etanercept did not elicit 
dose-limiting or target organ toxicity in cynomolgus monkeys following twice weekly subcutaneous 
administration for 4 or 26 consecutive weeks at a dose (15 mg/kg) that resulted in AUC-based serum 
drug concentrations that were over 27-fold higher than that obtained in humans at the recommended 
dose of 25 mg. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Citric acid anhydrous  
Sodium citrate dihydrate  
Sodium chloride  
Sucrose  
L-Lysine hydrochloride  
Sodium hydroxide (for pH adjustment) 
Hydrochloric acid (for pH adjustment) 
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life 
 
30 months 



29 
 
 

 
6.4 Special precautions for storage 
 
Store in a refrigerator (2 °C – 8 °C).  
Do not freeze. 
Keep the pre-filled syringes and the pre-filled pens in the outer carton in order to protect from light. 
 
After taking a syringe from the refrigerator, wait approximately 15-30 minutes to allow the Erelzi 
solution in the syringe to reach room temperature. Do not warm in any other way. Immediate use is then 
recommended. 
 
Erelzi may be stored at temperatures up to a maximum of 25 °C for a single period of up to four weeks; 
after which, it should not be refrigerated again. Erelzi should be discarded if not used within four weeks 
of removal from refrigeration. 
 
6.5 Nature and contents of container 
 
Erelzi solution for injection in pre-filled syringe 
Clear type I glass syringe with a stainless steel 27 gauge ½ inch needle with a needle guard with finger 
flange, rubber needle cap and plastic plunger, containing 0.5 ml or 1.0 ml of solution. 
 
Erelzi 50 mg solution for injection in pre-filled pen 
Erelzi is supplied in a single-use pre-filled syringe assembled into a triangular-shaped pen with 
transparent window and label (SensoReady pen). The syringe inside the pen is made from clear type I 
glass with a stainless steel 27 gauge ½ inch needle and an inner rubber needle cap, containing 1.0 ml of 
solution.  
 
Cartons contain 1, 2 or 4 pre-filled syringes or pre-filled pens of Erelzi. Multipacks contain 12 (3 packs 
of 4) 25 mg or 50 mg pre-filled syringes or pre-filled pens or 8 (2 packs of 4) or 24 (6 packs of 
4) 25 mg pre-filled syringes of Erelzi. Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Instructions for use and handling of the Erelzi pre-filled syringe  
Before injection, Erelzi single-use pre-filled syringe should be allowed to reach room temperature 
(approximately 15 to 30 minutes). The needle cap should not be removed while allowing the pre-filled 
syringe to reach room temperature. The solution should be clear to slightly opalescent, colourless to 
slightly yellowish and may contain small translucent or white particles of protein. 
 
Comprehensive instructions for administration are given in the package leaflet, section 7, "Instructions 
for use of the Erelzi pre-filled syringe". 
 
Instructions for use and handling of the Erelzi pre-filled SensoReady pen 
Before injection, Erelzi single-use pre-filled pens should be allowed to reach room temperature 
(approximately 15 to 30 minutes). The needle cap should not be removed while allowing the pre-filled 
pen to reach room temperature. By looking through the viewing window, the solution should be clear to 
slightly opalescent, colourless to slightly yellowish and may contain small translucent or white particles 
of protein. 
 
Comprehensive instructions for administration are given in the package leaflet, section 7, "Instructions 
for use of the Erelzi SensoReady pen". 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 



30 
 
 

7. MARKETING AUTHORISATION HOLDER 
 
Sandoz GmbH 
Biochemiestr. 10 
A-6250 Kundl 
Austria 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
Erelzi 25 mg solution for injection in pre-filled syringe 
EU/1/17/1195/001 
EU/1/17/1195/002 
EU/1/17/1195/003 
EU/1/17/1195/004 
EU/1/17/1195/013 
EU/1/17/1195/014 
 
Erelzi 50 mg solution for injection in pre-filled syringe 
EU/1/17/1195/005 
EU/1/17/1195/006 
EU/1/17/1195/007 
EU/1/17/1195/008 
 
Erelzi 50 mg solution for injection in pre-filled pen 
EU/1/17/1195/009 
EU/1/17/1195/010 
EU/1/17/1195/011 
EU/1/17/1195/012 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 23 June 2017 
 
 
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. 



31 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE 
SUBSTANCE(S) AND MANUFACTURER(S) 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 



32 
 
 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND 
MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer(s) of the biological active substance(s) 
 
Sandoz GmbH Schaftenau 
Biochemiestrasse 10 
A-6336 Langkampfen 
AUSTRIA 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Sandoz GmbH Schaftenau 
Biochemiestrasse 10 
A-6336 Langkampfen 
AUSTRIA 
 
 
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. 
 
 
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.  

 
• Additional risk minimisation measures  
 
Patient Alert Card  
 
In order to minimize the risk for the most critical side effects “infection” and “worsening of congestive 
heart failure” of Erelzi, a Patient Alert Card has been developed. All healthcare professionals (HCPs) 
who are most likely to prescribe Erelzi for patients with rheumatoid arthritis, psoriatic arthritis, axial 



33 
 
 

spondyloarthritis including ankylosing spondylitis, juvenile idiopathic arthritis, plaque psoriasis and 
paediatric plaque psoriasis are provided with a Patient Alert Card for distribution to patients receiving 
Erelzi. This card provides important safety information for patients, including information relating to 
infections and to worsening of congestive heart failure related to Erelzi.  
 
Key elements of the Erelzi Patient Alert Card  
 
• Brief introduction to the aim of the Patient Alert Card  
• Request to show the Patient Alert Card to any treating doctor  
• Reminder that Erelzi should not be used in children and adolescents weighing less than 62.5 kg.  
• Information that Erelzi can increase risk for getting serious infection:  

• Advice that patients should not be treated with Erelzi in case of infection  
• Instruction to immediately seek for medical attention after detection of symptoms suggestive for 

infection  
• Information regarding the need for evaluation on tuberculosis (TB)  
• Request to ask the doctor to record test, date and results of last TB screening on the alert card  
• Request to ask the doctor to list other medications that may increase the risk of infection on the 

alert card  
• Instruction to immediately seek for medical attention after developing or worsening of symptoms 

for congestive heart failure  
• Free lines for adding additional information:  

• Patient´s name, Doctor´s name and phone number  
• Request to keep the Patient Alert Card during and after treatment  

• Reminder to record brand name and batch number of the medication  
• Free lines to record brand name and batch number  

 
Educational materials  
 
An educational program is developed in order to assist in training and educating HCPs for proper use of 
Erelzi:  
The educational material is intended to prevent or reduce potential medication errors related to improper 
use of Erelzi prefilled-pen (autoinjector (AI):  
 
• A visually engaging instruction guide demonstrating step-by-step procedure for the use of the AI 

will be developed and distributed to nurses and HCPs to facilitate training of patients and staff in 
the prescriber´s office or during a homecare program  

• A needle-free AI device for demonstration will be available for patient practice use. This device 
will be provided to HCPs to support (self-) injection training and is intended to be used and 
trained in the HCP office or during a home care program  

• Any core educational materials for HCPs are subject to country-specific adaptation according to 
local regulatory requirements  

• Educational materials will be constantly updated for further improvements  
• Sandoz staff will be trained on the correct use of Erelzi in order to support HCPs in case of 

questions  
 



34 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



35 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



36 
 
 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON OF UNIT PACK – 25 MG PRE-FILLED SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Erelzi 25 mg solution for injection in pre-filled syringe 
etanercept 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled syringe contains 25 mg etanercept. 
 
 
3. LIST OF EXCIPIENTS 
 
The other ingredients are: 
citric acid anhydrous, sodium citrate dihydrate, sodium chloride, sucrose, L-lysine hydrochloride, 
sodium hydroxide, hydrochloric acid and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
 
1 pre-filled syringe with a needle guard 
 
2 pre-filled syringes with a needle guard 
 
4 pre-filled syringes with a needle guard 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Single use. 
Subcutaneous 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 
 
 



37 
 
 

8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
 
Keep the pre-filled syringe in the outer carton in order to protect from light. 
Keep the pre-filled syringes in the outer carton in order to protect from light. 
 
 
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 
 
Sandoz GmbH 
Biochemiestr. 10 
A-6250 Kundl  
Austria 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/17/1195/001 1 pre-filled syringe 
EU/1/17/1195/002 2 pre-filled syringes 
EU/1/17/1195/003 4 pre-filled syringes 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
‘QR code to be included’ + www.erelzi.eu 
 
 
16. INFORMATION IN BRAILLE 
 
Erelzi 25 mg 
 
 



38 
 
 

17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 



39 
 
 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON OF MULTIPACK (INCLUDING BLUE BOX) – 25 MG PRE-FILLED 
SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Erelzi 25 mg solution for injection in pre-filled syringe 
etanercept 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled syringe contains 25 mg etanercept. 
 
 
3. LIST OF EXCIPIENTS 
 
The other ingredients are: 
citric acid anhydrous, sodium citrate dihydrate, sodium chloride, sucrose, L-lysine hydrochloride, 
sodium hydroxide, hydrochloric acid and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
 
Multipack:   8 (2 packs of 4) pre-filled syringes with a needle guard. 
Multipack: 12 (3 packs of 4) pre-filled syringes with a needle guard. 
Multipack: 24 (6 packs of 4) pre-filled syringes with a needle guard. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Single use. 
Subcutaneous 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 
 
 



40 
 
 

8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
 
Keep the pre-filled syringes in the outer carton in order to protect from light. 
 
 
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 
 
Sandoz GmbH 
Biochemiestr. 10 
A-6250 Kundl 
Austria 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/17/1195/013   8 pre-filled syringes 
EU/1/17/1195/004 12 pre-filled syringes 
EU/1/17/1195/014 24 pre-filled syringes 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
‘QR code to be included’ + www.erelzi.eu 
 
 
16. INFORMATION IN BRAILLE 
 
Erelzi 25 mg 
 
 



41 
 
 

17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 



42 
 
 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX) – 25 MG 
PRE-FILLED SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Erelzi 25 mg solution for injection in pre-filled syringe 
etanercept 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled syringe contains 25 mg etanercept. 
 
 
3. LIST OF EXCIPIENTS 
 
The other ingredients are: 
citric acid anhydrous, sodium citrate dihydrate, sodium chloride, sucrose, L-lysine hydrochloride, 
sodium hydroxide, hydrochloric acid and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
 
4 pre-filled syringes with a needle guard. Component of a multipack, cannot be sold separately. 
 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Single use. 
Subcutaneous 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 
 



43 
 
 

 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
 
Keep the pre-filled syringes in the outer carton in order to protect from light. 
 
 
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 
 
Sandoz GmbH 
Biochemiestr. 10 
A-6250 Kundl 
Austria 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/17/1195/013   8 pre-filled syringes 
EU/1/17/1195/004 12 pre-filled syringes 
EU/1/17/1195/014 24 pre-filled syringes 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
‘QR code to be included’ + www.erelzi.eu 
 
 
16. INFORMATION IN BRAILLE 
 
Erelzi 25 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
 



44 
 
 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 



45 
 
 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TEXT FOR TRAY BACK – 25 MG PRE-FILLED SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Erelzi 25 mg  
injection 
etanercept 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
SC 
25 mg / 0.5 ml 



46 
 
 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
TEXT FOR PRE-FILLED SYRINGE LABEL – 25 MG PRE-FILLED SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Erelzi 25 mg 
injection 
etanercept 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 



47 
 
 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON OF UNIT PACK – 50 MG PRE-FILLED SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Erelzi 50 mg solution for injection in pre-filled syringe 
etanercept 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled syringe contains 50 mg etanercept. 
 
 
3. LIST OF EXCIPIENTS 
 
The other ingredients are: 
citric acid anhydrous, sodium citrate dihydrate, sodium chloride, sucrose, L-lysine hydrochloride, 
sodium hydroxide, hydrochloric acid and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
 
1 pre-filled syringe with a needle guard 
 
2 pre-filled syringes with a needle guard 
 
4 pre-filled syringes with a needle guard 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Single use. 
Subcutaneous 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 
 
 



48 
 
 

8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
 
Keep the pre-filled syringe in the outer carton in order to protect from light. 
Keep the pre-filled syringes in the outer carton in order to protect from light. 
 
 
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 
 
Sandoz GmbH 
Biochemiestr. 10 
A-6250 Kundl 
Austria 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/17/1195/005 1 pre-filled syringe 
EU/1/17/1195/006 2 pre-filled syringes 
EU/1/17/1195/007 4 pre-filled syringes 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
‘QR code to be included’ + www.erelzi.eu 
 
 
16. INFORMATION IN BRAILLE 
 
Erelzi 50 mg 
 
 



49 
 
 

17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 



50 
 
 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON OF MULTIPACK (INCLUDING BLUE BOX) – 50 MG PRE-FILLED 
SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Erelzi 50 mg solution for injection in pre-filled syringe 
etanercept 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled syringe contains 50 mg etanercept. 
 
 
3. LIST OF EXCIPIENTS 
 
The other ingredients are: 
citric acid anhydrous, sodium citrate dihydrate, sodium chloride, sucrose, L-lysine hydrochloride, 
sodium hydroxide, hydrochloric acid and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
 
Multipack: 12 (3 packs of 4) pre-filled syringes with a needle guard. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Single use. 
Subcutaneous 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 
 
 



51 
 
 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
 
Keep the pre-filled syringes in the outer carton in order to protect from light. 
 
 
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 
 
Sandoz GmbH 
Biochemiestr. 10 
A-6250 Kundl 
Austria 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/17/1195/008 12 pre-filled syringes 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
‘QR code to be included’ + www.erelzi.eu 
 
 
16. INFORMATION IN BRAILLE 
 
Erelzi 50 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 



52 
 
 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX) – 50 MG 
PRE-FILLED SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Erelzi 50 mg solution for injection in pre-filled syringe 
etanercept 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled syringe contains 50 mg etanercept. 
 
 
3. LIST OF EXCIPIENTS 
 
The other ingredients are: 
citric acid anhydrous, sodium citrate dihydrate, sodium chloride, sucrose, L-lysine hydrochloride, 
sodium hydroxide, hydrochloric acid and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
 
4 pre-filled syringes with a needle guard. Component of a multipack, cannot be sold separately. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Single use. 
Subcutaneous 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 
 
 



53 
 
 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
 
Keep the pre-filled syringes in the outer carton in order to protect from light. 
 
 
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 
 
Sandoz GmbH 
Biochemiestr. 10 
A-6250 Kundl 
Austria 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/17/1195/008 12 pre-filled syringes 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
‘QR code to be included’ + www.erelzi.eu 
 
 
16. INFORMATION IN BRAILLE 
 
Erelzi 50 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 



54 
 
 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
TEXT FOR TRAY BACK – 50 MG PRE-FILLED SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Erelzi 50 mg  
injection 
etanercept 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
SC 
50 mg / 1.0 ml 



55 
 
 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
TEXT FOR PRE-FILLED SYRINGE LABEL – 50 MG PRE-FILLED SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Erelzi 50 mg 
injection 
etanercept 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 



56 
 
 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON OF UNIT PACK – 50 MG PRE-FILLED PEN 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Erelzi 50 mg solution for injection in pre-filled pen 
etanercept 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled pen contains 50 mg etanercept. 
 
 
3. LIST OF EXCIPIENTS 
 
The other ingredients are: 
citric acid anhydrous, sodium citrate dihydrate, sodium chloride, sucrose, L-lysine hydrochloride, 
sodium hydroxide, hydrochloric acid and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
 
1 pre-filled SensoReady pen 
 
2 pre-filled SensoReady pens 
 
4 pre-filled SensoReady pens 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Single use. 
Subcutaneous 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 
 
 



57 
 
 

8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
 
Keep the pre-filled SensoReady pen in the outer carton in order to protect from light. 
Keep the pre-filled SensoReady pens in the outer carton in order to protect from light. 
 
 
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 
 
Sandoz GmbH 
Biochemiestr. 10 
A-6250 Kundl 
Austria 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/17/1195/009 1 pre-filled SensoReady pen 
EU/1/17/1195/010 2 pre-filled SensoReady pens 
EU/1/17/1195/011 4 pre-filled SensoReady pens 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
‘QR code to be included’ + www.erelzi.eu 
 
 
16. INFORMATION IN BRAILLE 
 
Erelzi 50 mg 
 
 



58 
 
 

17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



59 
 
 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON OF MULTIPACK (INCLUDING BLUE BOX) – 50 MG PRE-FILLED PEN 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Erelzi 50 mg solution for injection in pre-filled pen 
etanercept 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled pen contains 50 mg etanercept. 
 
 
3. LIST OF EXCIPIENTS 
 
The other ingredients are: 
citric acid anhydrous, sodium citrate dihydrate, sodium chloride, sucrose, L-lysine hydrochloride, 
sodium hydroxide, hydrochloric acid and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
 
Multipack: 12 (3 packs of 4) pre-filled SensoReady pens. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Single use. 
Subcutaneous 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 
 
 



60 
 
 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
 
Keep the pre-filled SensoReady pens in the outer carton in order to protect from light. 
 
 
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 
 
Sandoz GmbH 
Biochemiestr. 10 
A-6250 Kundl 
Austria 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/17/1195/012 12 pre-filled SensoReady pens 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
‘QR code to be included’ + www.erelzi.eu 
 
 
16. INFORMATION IN BRAILLE 
 
Erelzi 50 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 



61 
 
 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX) – 50 MG 
PRE-FILLED PEN 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Erelzi 50 mg solution for injection in pre-filled pen 
etanercept 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled pen contains 50 mg etanercept. 
 
 
3. LIST OF EXCIPIENTS 
 
The other ingredients are: 
citric acid anhydrous, sodium citrate dihydrate, sodium chloride, sucrose, L-lysine hydrochloride, 
sodium hydroxide, hydrochloric acid and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
 
4 pre-filled SensoReady pens. Component of a multipack, cannot be sold separately. 
 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Single use. 
Subcutaneous 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 
 



62 
 
 

 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
 
Keep the pre-filled SensoReady pens in the outer carton in order to protect from light. 
 
 
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 
 
Sandoz GmbH 
Biochemiestr. 10 
A-6250 Kundl 
Austria 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/17/1195/012 12 pre-filled SensoReady pens 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
‘QR code to be included’ + www.erelzi.eu 
 
 
16. INFORMATION IN BRAILLE 
 
Erelzi 50 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
 
 



63 
 
 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 



64 
 
 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
TEXT FOR PRE-FILLED PEN LABEL – 50 MG PRE-FILLED PEN 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Erelzi 50 mg 
injection 
etanercept 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
50 mg / 1.0 ml 
 
6. OTHER 
 



65 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



66 
 
 

Package leaflet: Information for the user 
 
 

Erelzi 25 mg solution for injection in pre-filled syringe 
 

Erelzi 50 mg solution for injection in pre-filled syringe 
etanercept 

 

▼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 (both sides) of this leaflet carefully before you start using this medicine because it 
contains important information for you. 
• Keep this leaflet. You may need to read it again. 
• Your doctor will also give you a Patient Alert Card, which contains important safety information 

that you need to be aware of before and during treatment with Erelzi. 
• If you have any further questions, ask your doctor, pharmacist or nurse. 
• This medicine has been prescribed for you or a child in your care. Do not pass it on to others. It 

may harm them, even if their signs of illness are the same as yours or those of the child you are 
caring for. 

• 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 Erelzi is and what it is used for 
2. What you need to know before you use Erelzi 
3. How to use Erelzi 
4. Possible side effects 
5. How to store Erelzi 
6. Contents of the pack and other information 
7. Instructions for Use of the Erelzi pre-filled syringe (see overleaf) 
 
 
1. What Erelzi is and what it is used for 
 
Erelzi is a medicine that is made from two human proteins. It blocks the activity of another protein in 
the body that causes inflammation. Erelzi works by reducing the inflammation associated with certain 
diseases. 
 
In adults (aged 18 and over), Erelzi can be used for moderate or severe rheumatoid arthritis, psoriatic 
arthritis, severe axial spondyloarthritis including ankylosing spondylitis, and moderate or severe 
psoriasis – in each case usually when other widely used treatments have not worked well enough or are 
not suitable for you. 
 
For rheumatoid arthritis, Erelzi is usually used in combination with methotrexate, although it may 
also be used alone if treatment with methotrexate is unsuitable for you. Whether used alone or in 
combination with methotrexate, Erelzi can slow down the damage to your joints caused by the 
rheumatoid arthritis and improve your ability to do normal daily activities. 
 
For psoriatic arthritis patients with multiple joint involvement, Erelzi can improve your ability to do 
normal daily activities.  
 



67 
 
 

For patients with multiple symmetrical painful or swollen joints (e.g., hands, wrists and feet), Erelzi 
can slow down the structural damage to those joints caused by the disease. 
 
Erelzi is also prescribed for the treatment of the following diseases in children and adolescents: 
• For the following types of juvenile idiopathic arthritis when treatment with methotrexate has not 

worked well enough or is not suitable for them: 
• Polyarthritis (rheumatoid factor positive or negative) and extended oligoarthritis in patients 

from the age of 2 years and weighing 62.5 kg or more. 
• Psoriatic arthritis in patients from the age of 12 years and weighing 62.5 kg or more. 

• For enthesitis-related arthritis in patients from the age of 12 years and weighing 62.5 kg or more 
when other widely used treatments have not worked well enough or are not suitable for them. 

• Severe psoriasis in patients from the age of 6 years and weighing 62.5 kg or more who have had 
an inadequate response to (or are unable to take) phototherapies or other systemic therapies. 

 
 
2. What you need to know before you use Erelzi 
 
Do not use Erelzi 
 
• if you, or the child you are caring for, are allergic to etanercept or any of the other ingredients 

of Erelzi (listed in section 6). If you or the child experience allergic reactions such as chest 
tightness, wheezing, dizziness or rash, do not inject more Erelzi, and contact your doctor 
immediately. 

• if you or the child have, or are at risk of developing a serious blood infection called sepsis. If 
you are not sure, please contact your doctor. 

• if you or the child have an infection of any kind. If you are not sure, please talk to your doctor. 
 
Warnings and precautions 
 
Talk to your doctor before taking Erelzi. 
 
• Allergic reactions: If you or the child experience allergic reactions such as chest tightness, 

wheezing, dizziness or rash, do not inject more Erelzi, and contact your doctor immediately. 
• Infections/surgery: If you or the child develop a new infection, or are about to have any major 

surgery, your doctor may wish to monitor the treatment with Erelzi. 
• Infections/diabetes: Tell your doctor if you or the child have a history of recurrent infections or 

suffer from diabetes or other conditions that increase the risk of infection. 
• Infections/monitoring: Tell your doctor of any recent travel outside the European region. If you 

or the child develop symptoms of an infection such as fever, chills or cough, notify your doctor 
immediately. Your doctor may decide to continue to monitor you or the child for the presence of 
infections after you or the child stop using Erelzi. 

• Tuberculosis: As cases of tuberculosis have been reported in patients treated with Erelzi, your 
doctor will check for signs and symptoms of tuberculosis before starting Erelzi. This may include 
a thorough medical history, a chest X-ray and a tuberculin test. The conduct of these tests should 
be recorded on the Patient Alert Card. It is very important that you tell your doctor if you or the 
child have ever had tuberculosis, or have been in close contact with someone who has had 
tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, listlessness, mild 
fever), or any other infection appear during or after therapy, tell your doctor immediately. 

• Hepatitis B: Tell your doctor if you or the child have or have ever had hepatitis B. Your doctor 
should test for the presence of hepatitis B infection before you or the child begin treatment with 
Erelzi. Treatment with Erelzi may result in reactivation of hepatitis B in patients who have 
previously been infected with the hepatitis B virus. If this occurs, you should stop using Erelzi. 

• Hepatitis C: Tell your doctor if you or the child have hepatitis C. Your doctor may wish to 
monitor the treatment with Erelzi in case the infection worsens. 



68 
 
 

• Blood disorders: Seek medical advice immediately if you or the child have any signs or 
symptoms such as persistent fever, sore throat, bruising, bleeding or paleness. Such symptoms 
may point to the existence of potentially life-threatening blood disorders, which may require 
discontinuation of Erelzi. 

• Nervous system and eye disorders: Tell your doctor if you or the child have multiple sclerosis, 
optic neuritis (inflammation of the nerves of the eyes) or transverse myelitis (inflammation of the 
spinal cord). Your doctor will determine if Erelzi is an appropriate treatment. 

• Congestive heart failure: Tell your doctor if you or the child have a history of congestive heart 
failure, because Erelzi needs to be used with caution under these circumstances. 

• Cancer: Tell your doctor if you have or have ever had lymphoma (a type of blood cancer) or any 
other cancer before you are given Erelzi. 
Patients with severe rheumatoid arthritis, who have had the disease for a long time, may be at 
higher than average risk of developing lymphoma. 
Children and adults taking Erelzi may have an increased risk of developing lymphoma or another 
cancer. 
Some children and teenage patients who have received Erelzi or other medicines that work the 
same way as Erelzi have developed cancers, including unusual types, which sometimes resulted 
in death. 
Some patients receiving Erelzi have developed skin cancers. Tell your doctor if you or the child 
develop any change in the appearance of the skin or growths on the skin. 

• Chickenpox: Tell your doctor if you or the child are exposed to chickenpox when using Erelzi. 
Your doctor will determine if preventive treatment for chickenpox is appropriate. 

• Alcohol abuse: Erelzi should not be used for the treatment of hepatitis related to alcohol abuse. 
Please tell your doctor if you or the child in your care have a history of alcohol abuse. 

• Wegener’s granulomatosis: Erelzi is not recommended for the treatment of Wegener’s 
granulomatosis, a rare inflammatory disease. If you or the child in your care have Wegener’s 
granulomatosis, talk to your doctor. 

• Anti-diabetic medicines: Tell your doctor if you or the child have diabetes or are taking 
medicines to treat diabetes. Your doctor may decide if you or the child need less anti-diabetic 
medicine while using Erelzi. 

 
Children and adolescents 
 
Erelzi is not indicated for use in children and adolescents who weigh less than 62.5 kg. 
 
• Vaccinations: If possible, children should be up to date with all vaccinations before using Erelzi. 

Some vaccines, such as oral polio vaccine, should not be given while using Erelzi. Please consult 
your doctor before you or the child receive any vaccines. 

• Inflammatory bowel disease (IBD): There have been cases of IBD in patients with juvenile 
idiopathic arthritis (JIA) treated with Erelzi. Tell the doctor if the child develops any abdominal 
cramps and pain, diarrhoea, weight loss or blood in the stool. 
 

Erelzi should not normally be used in children with polyarthritis or extended oligoarthritis below the 
age of 2 years or weighing less than 62.5 kg, or in children with enthesitis-related arthritis or psoriatic 
arthritis below the age of 12 years or weighing less than 62.5 kg, or in children with psoriasis below the 
age of 6 years or weighing less than 62.5 kg. 
 
Other medicines and Erelzi 
 
Tell your doctor or pharmacist if you or the child are taking, have recently taken or might take any other 
medicines (including anakinra, abatacept or sulfasalazine), even those not prescribed by the doctor.  
 
You or the child should not use Erelzi with medicines that contain the active substance anakinra or 
abatacept. 
 



69 
 
 

Pregnancy and breast-feeding 
 
Erelzi should only be used during pregnancy if clearly needed. You should consult your doctor if you 
become pregnant, think you may be pregnant, or are planning to have a baby. 
 
If you received Erelzi during pregnancy, your baby may have a higher risk of getting an infection. In 
addition, one study found more birth defects when the mother had received etanercept in pregnancy, 
compared with mothers who had not received etanercept or other similar medicines (TNF-antagonists), 
but there was no particular kind of birth defect reported. Another study found no increased risk of birth 
defects when the mother had received etanercept in pregnancy. Your doctor will help you to decide 
whether the benefits of treatment outweigh the potential risk to your baby. It is important that you tell 
the baby’s doctors and other healthcare professionals about the use of Erelzi during pregnancy before 
the baby receives any vaccine (for more information see section 2, “Vaccinations”). 
 
Women using Erelzi should not breast-feed, since Erelzi passes into human breast milk. 
 
Driving and using machines 
 
The use of Erelzi is not expected to affect the ability to drive or use machines. 
 
Erelzi contains sodium 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per 25 mg or 50 mg, that is to say 
essentially ‘sodium-free’. 
 
 
3. How to use Erelzi 
 
Always use this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if 
you are not sure. 
 
If you feel that the effect of Erelzi is too strong or too weak, talk to your doctor or pharmacist. 
 
Erelzi is available as 25 mg strength and 50 mg strength.  
 
Use in adult patients (aged 18 years or over) 
 
Rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis including ankylosing spondylitis 
 
The usual dose is 25 mg given twice a week or 50 mg once a week as an injection under the skin. 
However, your doctor may determine an alternative frequency at which to inject Erelzi. 
 
Plaque psoriasis 
 
The usual dose is 25 mg twice a week or 50 mg once a week. 
 
Alternatively, 50 mg may be given twice a week for up to 12 weeks, followed by 25 mg twice a week or 
50 mg once a week. 
 
Your doctor will decide how long you should use Erelzi and whether retreatment is needed based on 
your response. If Erelzi has no effect on your condition after 12 weeks, your doctor may tell you to stop 
using this medicine. 
 



70 
 
 

Use in children and adolescents 
 
The appropriate dose and frequency of dosing for the child or adolescent will depend on body weight 
and disease. Your doctor will determine the correct dose for the child and will prescribe an appropriate 
strength of etanercept. Paediatric patients weighing 62.5 kg or more can be dosed 25 mg given twice a 
week or 50 mg given once a week using a fixed-dose pre-filled syringe or pre-filled pen. 
 
Other etanercept products with appropriate dosage forms for children are available. 
 
For polyarthritis or extended oligoarthritis in patients from the age of 2 years and weighing 62.5 kg or 
more, or enthesitis-related arthritis or psoriatic arthritis in patients from the age of 12 years and 
weighing 62.5 kg or more, the usual dose is 25 mg given twice a week or 50 mg given once a week. 
 
For psoriasis in patients from the age of 6 years and weighing 62.5 kg or more, the usual dose is 50 mg 
and should be given once weekly. If Erelzi has no effect on the child’s condition after 12 weeks, your 
doctor may tell you to stop using this medicine. 
 
The doctor will provide you with detailed directions for preparing and measuring the appropriate dose. 
 
Method and route of administration 
 
Erelzi is administered by an injection under the skin (by subcutaneous injection). 
 
Erelzi can be taken with or without food or drink. 
 
Detailed instructions on how to inject Erelzi are provided in section 7, “Instructions for use of the 
Erelzi pre-filled syringe”.  
 
Do not mix the Erelzi solution with any other medicine. 
 
To help you remember, it may be helpful to write in a diary which day(s) of the week Erelzi should be 
used. 
 
If you use more Erelzi than you should 
 
If you have used more Erelzi than you should (either by injecting too much on a single occasion or by 
using it too frequently), talk to a doctor or pharmacist immediately. Always have the outer carton of 
the medicine with you, even if it is empty. 
 
If you forget to inject Erelzi 
 
If you forget a dose, you should inject it as soon as you remember, unless the next scheduled dose is the 
next day; in which case you should skip the missed dose. Then continue to inject the medicine on the 
usual day(s). If you do not remember until the day that the next injection is due, do not take a double 
dose (two doses on the same day) to make up for a forgotten dose. 
 
If you stop using Erelzi 
 
Your symptoms may return upon discontinuation. 
 
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. 



71 
 
 

 
Allergic reactions 
 
If any of the following happen, do not inject more Erelzi. Tell your doctor immediately, or go to the 
casualty department at your nearest hospital. 
 
• Trouble swallowing or breathing 
• Swelling of the face, throat, hands, or feet 
• Feeling nervous or anxious, throbbing sensations, sudden reddening of the skin and/or a warm 

feeling 
• Severe rash, itching, or hives (elevated patches of red or pale skin that often itch) 
 
Serious allergic reactions are rare. However, any of the above symptoms may indicate an allergic 
reaction to Erelzi, so you should seek immediate medical attention. 
 
Serious side effects 
 
If you notice any of the following, you or the child may need urgent medical attention. 
 
• Signs of serious infections such as high fever that may be accompanied by cough, shortness of 

breath, chills, weakness, or a hot, red, tender, sore area on the skin or joints; 
• Signs of blood disorders, such as bleeding, bruising, or paleness; 
• Signs of nerve disorders, such as numbness or tingling, changes in vision, eye pain, or onset of 

weakness in an arm or leg; 
• Signs of heart failure or worsening heart failure, such as fatigue or shortness of breath with 

activity, swelling in the ankles, a feeling of fullness in the neck or abdomen, night-time shortness 
of breath or coughing, bluish colour of the nails or the lips; 

• Signs of cancers: cancers may affect any part of the body including the skin and blood, and 
possible signs will depend on the type and location of the cancer. These signs may include weight 
loss, fever, swelling (with or without pain), persistent cough, presence of lumps or growths on the 
skin; 

• Signs of autoimmune reactions (where antibodies are made that may harm normal tissues in the 
body) such as pain, itching, weakness, and abnormal breathing, thinking, sensation, or vision; 

• Signs of lupus or lupus-like syndrome, such as weight changes, persistent rash, fever, joint or 
muscle pain, or fatigue; 

• Signs of inflammation of the blood vessels such as pain, fever, redness or warmth of the skin, or 
itching. 

 
These are rare or uncommon side effects, but are serious conditions (some of which may rarely be 
fatal). If these signs occur, tell your doctor immediately, or visit the casualty department at your nearest 
hospital. 
 
The known side effects of Erelzi include the following in groups of decreasing frequency: 
 
• Very common (may affect more than 1 in 10 people): 

Infections (including colds, sinusitis, bronchitis, urinary tract infections and skin infections); 
injection site reactions (including bleeding, bruising, redness, itching, pain, and swelling). 
Reactions at the injection site (these do not occur as often after the first month of treatment). 
Some patients have developed a reaction at an injection site that was used before. 
 

• Common (may affect up to 1 in 10 people): 
Allergic reactions; fever; rash; itching; antibodies directed against normal tissue (autoantibody 
formation). 
 



72 
 
 

• Uncommon (may affect up to 1 in 100 people): 
Serious infections (including pneumonia, deep skin infections, joint infections, blood infection, 
and infections at various sites); worsening of congestive heart failure; low red blood cell count, 
low white blood cell count, low neutrophil (a type of white blood cell) count; low blood platelet 
count; skin cancer (excluding melanoma); localised swelling of the skin (angioedema); hives 
(elevated patches of red or pale skin that often itch); eye inflammation; psoriasis (new or 
worsening); inflammation of the blood vessels affecting multiple organs; elevated liver blood 
tests (in patients also receiving methotrexate treatment, the frequency of elevated liver blood tests 
is common); abdominal cramps and pain, diarrhoea, weight loss or blood in the stool (signs of 
bowel problems). 
 

• Rare (may affect up to 1 in 1,000 people): 
Serious allergic reactions (including severe localised swelling of the skin and wheezing); 
lymphoma (a type of blood cancer); leukaemia (cancer affecting the blood and bone marrow); 
melanoma (a type of skin cancer); combined low platelet, red, and white blood cell count; 
nervous system disorders (with severe muscle weakness and signs and symptoms similar to those 
of multiple sclerosis or inflammation of the nerves of the eyes or spinal cord); tuberculosis; new 
onset congestive heart failure; seizures; lupus or lupus-like syndrome (symptoms may include 
persistent rash, fever, joint pain, and tiredness); skin rash, which may lead to severe blistering and 
peeling of the skin; lichenoid reactions (itchy reddish-purple skin rash and/or threadlike white-
grey lines on mucous membranes); inflammation of the liver caused by the body's own immune 
system (autoimmune hepatitis; in patients also receiving methotrexate treatment, the frequency is 
uncommon); immune disorder that can affect the lungs, skin and lymph nodes (sarcoidosis); 
inflammation or scarring of the lungs (in patients also receiving methotrexate treatment, the 
frequency of inflammation or scarring of the lungs is uncommon). 
 

• Very rare (may affect up to 1 in 10,000 people):  
Failure of the bone marrow to produce crucial blood cells. 

 
• Not known (frequency cannot be estimated from the available data):  

Merkel cell carcinoma (a type of skin cancer); excessive activation of white blood cells 
associated with inflammation (macrophage activation syndrome); recurrence of hepatitis B (a 
liver infection); worsening of a condition called dermatomyositis (muscle inflammation and 
weakness with an accompanying skin rash). 

 
Side effects in children and adolescents 
 
The side effects and their frequencies seen in children and adolescents are similar to those described 
above. 
 
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 Erelzi 
 
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 the label of the pre-filled 
syringe after EXP. The expiry date refers to the last day of that month. 
 
Store in a refrigerator (2 °C – 8 °C). Do not freeze.  



73 
 
 

 
Keep the pre-filled syringes in the outer carton in order to protect from light. 
 
After taking a syringe from the refrigerator, wait approximately 15-30 minutes to allow the Erelzi 
solution in the syringe to reach room temperature. Do not warm in any other way. Immediate use is 
then recommended. 
 
Erelzi may be stored outside of the refrigerator at temperatures up to a maximum of 25 °C for a single 
period of up to four weeks; after which, it should not be refrigerated again. Erelzi should be discarded if 
not used within four weeks after removal from the refrigerator. It is recommended that you record the 
date that Erelzi is removed from the refrigerator and the date after which Erelzi should be discarded (no 
more than 4 weeks following the removal from the refrigerator). 
 
Inspect the solution in the syringe. It should be clear or slightly opalescent, colourless to slightly 
yellowish, and may contain small white or almost translucent particles of protein. This appearance is 
normal for Erelzi. Do not use the solution if it is discoloured, cloudy, or if particles other than those 
described above are present. If you are concerned with the appearance of the solution, then contact your 
pharmacist for assistance. 
 
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. 
 
 
6. Contents of the pack and other information 
 
What Erelzi contains 
 
The active substance is etanercept.  
Each pre-filled syringe contains 25 mg of etanercept or 50 mg of etanercept. 
 
The other ingredients are citric acid anhydrous, sodium citrate dihydrate, sodium chloride, sucrose, 
L-lysine hydrochloride, sodium hydroxide, hydrochloric acid and water for injections. 
 
What Erelzi looks like and contents of the pack 
 
Erelzi is supplied as a pre-filled syringe containing a clear or slightly opalescent, colourless to slightly 
yellowish solution for injection (injection). Each pack contains 1, 2 or 4 pre-filled syringes with a 
needle guard, multipacks contain 12 (3 packs of 4) 25 mg or 50 mg pre-filled syringes with a needle 
guard or 8 (2 packs of 4) or 24 (6 packs of 4) 25 mg pre-filled syringes with a needle guard. Not all pack 
sizes may be marketed. 
 
Marketing Authorisation Holder 
 
Sandoz GmbH 
Biochemiestr. 10 
A-6250 Kundl 
Austria 
 
Manufacturer 
 
Sandoz GmbH Schaftenau 
Biochemiestr. 10 
A-6336 Langkampfen 
Austria 
 
This leaflet was last revised in  



74 
 
 

 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
 
7. Instructions for use of the Erelzi pre-filled syringe 
 
Read ALL the way through these instructions before injecting. The same information is also 
available on www.erelzi.eu and through the code below. 
 

 
 www.erelzi.eu 
 
It is important not to try to inject yourself until you have been trained by your doctor, nurse or 
pharmacist. The box contains Erelzi pre-filled syringe(s) individually sealed in a plastic blister. 
 
DO NOT USE 
 

In this configuration the needle guard is ACTIVATED – 
DO NOT USE the pre-filled syringe  

 
READY TO BE USED 

  

 
In this configuration the needle guard is NOT 
ACTIVATED and the pre-filled syringe is ready for use  

 
Your Erelzi pre-filled syringe with needle guard and add-on finger flange 
 
 

 
After the medicine has been injected, the needle guard will be activated to cover the needle. This is 
intended to aid in the protection of healthcare professionals, patients who self-inject doctor-prescribed 
medicines and individuals who assist self-injecting patients from accidental needle stick injuries. 



75 
 
 

 
What you additionally need for your injection:  
• Alcohol wipe 
• Cotton ball or gauze 
• Sharps disposal container 

 
 
Important safety information 
 
Caution: Keep the syringe out of the sight and reach of children. 
1. Do not open the outer box until you are ready to use this medicine. 
2. Do not use this medicine if the seal of the blister is broken, as it may not be safe for you to use. 
3. Do not shake the syringe. 
4. Never leave the syringe lying around where others might tamper with it. 
5. The pre-filled syringe has a needle guard that will be activated to cover the needle after the 

injection is finished. The needle guard will help to prevent needle stick injuries to anyone who 
handles the pre-filled syringe. 
Be careful not to touch the needle guard wings before use. By touching them, the needle guard 
may be activated too early. 

6. Do not remove the needle cap until just before you give the injection. 
7. The syringe cannot be re-used. Dispose of the used syringe immediately after use in a sharps 

container. 
 
Storage of the Erelzi pre-filled syringe 
 
1. Store this medicine sealed in its outer box to protect it from light. Store in the refrigerator 

between 2 °C to 8 °C. DO NOT FREEZE. 
2. Remember to take the blister out of the refrigerator and allow it to reach room temperature before 

preparing it for injection (15–30 minutes). 
3. Do not use the syringe after the expiry date which is stated on the outer box or syringe label after 

“EXP”. If it has expired, return the entire pack to the pharmacy. 
 



76 
 
 

The injection site 
 

 

The injection site is the place on the body where you are going to use the 
pre-filled syringe. 
• The recommended site is the front of your thighs. You may also use 

the lower abdomen, but not the area 5 centimetres around the navel 
(belly button).  

• Choose a different site each time you give yourself an injection. 
• Do not inject into areas where the skin is tender, bruised, red, scaly or 

hard. Avoid areas with scars or stretch marks. 
If you have psoriasis, you should NOT inject directly into any raised, 
thick, red, or scaly skin patches or lesions (“psoriasis skin lesions”). 

 

If a caregiver is giving you the injection, the outer upper arms may also 
be used. 

Preparing the Erelzi pre-filled syringe 
 
 
1. Take the blister out of the refrigerator and leave it unopened for about 15–30 minutes so that it 

reaches room temperature. 
2. When you are ready to use the syringe, open the blister and wash your hands thoroughly with 

soap and water. 
3. Clean the injection site with an alcohol swab. 
4. Take the syringe out of the blister. 
5. Inspect the syringe. The liquid should be clear or slightly opalescent, colourless to slightly 

yellowish, and may contain small white or almost translucent particles of protein. This 
appearance is normal for Erelzi. Do not use if the liquid is cloudy, discoloured, or has large 
lumps, flakes, or coloured particles. Do not use if the syringe is broken or the needle guard is 
activated. In all these cases, return the entire product pack to the pharmacy. 

 
How to use the Erelzi pre-filled syringe 
 

 

Carefully remove the needle cap from the syringe. Discard 
the needle cap. You may see a drop of liquid at the end of the 
needle. This is normal. 

 

Gently pinch the skin at the injection site and insert the 
needle as shown. Push the needle all the way in to ensure that 
the medicine can be fully administered. 



77 
 
 

 

Hold the syringe finger flange as shown. Slowly press the 
plunger as far as it will go, so that the plunger head is 
completely between the needle guard wings. 
Keep the plunger pressed fully down while you hold the 
syringe in place for 5 seconds. 

 

Keep the plunger fully depressed while you carefully lift 
the needle straight out from the injection site. 

 

Slowly release the plunger and allow the needle guard to 
automatically cover the exposed needle. 
There may be a small amount of blood at the injection site. 
You can press a cotton ball or gauze over the injection site 
and hold it for 10 seconds. Do not rub the injection site. You 
may cover the injection site with a small adhesive bandage, if 
needed. 

 
Disposal instructions 

 

Dispose of the used syringe in a sharps container (closable, 
puncture-resistant container). For the safety and health of you 
and others, needles and used syringes must never be re-used. 

If you have any questions, please talk to a doctor, nurse or pharmacist who is familiar with Erelzi. 



78 
 
 

Package leaflet: Information for the user 
 
 

Erelzi 50 mg solution for injection in pre-filled pen 
etanercept 

 

▼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 using this medicine because it contains important 
information for you. 
• Keep this leaflet. You may need to read it again. 
• Your doctor will also give you a Patient Alert Card, which contains important safety information 

that you need to be aware of before and during treatment with Erelzi. 
• If you have any further questions, ask your doctor, pharmacist or nurse. 
• This medicine has been prescribed for you or a child in your care. Do not pass it on to others. It 

may harm them, even if their signs of illness are the same as yours or those of the child you are 
caring for. 

• 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 Erelzi is and what it is used for 
2. What you need to know before you use Erelzi 
3. How to use Erelzi 
4. Possible side effects 
5. How to store Erelzi 
6. Contents of the pack and other information 
7. Instructions for Use of the Erelzi SensoReady pen  
 
 
1. What Erelzi is and what it is used for 
 
Erelzi is a medicine that is made from two human proteins. It blocks the activity of another protein in 
the body that causes inflammation. Erelzi works by reducing the inflammation associated with certain 
diseases. 
 
In adults (aged 18 and over), Erelzi can be used for moderate or severe rheumatoid arthritis, psoriatic 
arthritis, severe axial spondyloarthritis including ankylosing spondylitis, and moderate or severe 
psoriasis – in each case usually when other widely used treatments have not worked well enough or are 
not suitable for you. 
 
For rheumatoid arthritis, Erelzi is usually used in combination with methotrexate, although it may 
also be used alone if treatment with methotrexate is unsuitable for you. Whether used alone or in 
combination with methotrexate, Erelzi can slow down the damage to your joints caused by the 
rheumatoid arthritis and improve your ability to do normal daily activities. 
 
For psoriatic arthritis patients with multiple joint involvement, Erelzi can improve your ability to do 
normal daily activities.  
 
For patients with multiple symmetrical painful or swollen joints (e.g., hands, wrists and feet), Erelzi 
can slow down the structural damage to those joints caused by the disease. 
 



79 
 
 

Erelzi is also prescribed for the treatment of the following diseases in children and adolescents: 
• For the following types of juvenile idiopathic arthritis when treatment with methotrexate 

has not worked well enough or is not suitable for them: 
• Polyarthritis (rheumatoid factor positive or negative) and extended oligoarthritis in 

patients from the age of 2 years and weighing 62.5 kg or more. 
• Psoriatic arthritis in patients from the age of 12 years and weighing 62.5 kg or more. 

• For enthesitis-related arthritis in patients from the age of 12 years and weighing 62.5 kg or 
more when other widely used treatments have not worked well enough or are not suitable 
for them. 

• Severe psoriasis in patients from the age of 6 years and weighing 62.5 kg or more who 
have had an inadequate response to (or are unable to take) phototherapies or other systemic 
therapies. 

 
 
2. What you need to know before you use Erelzi 
 
Do not use Erelzi 
 
• if you, or the child you are caring for, are allergic to etanercept or any of the other ingredients 

of Erelzi (listed in section 6). If you or the child experience allergic reactions such as chest 
tightness, wheezing, dizziness or rash, do not inject more Erelzi, and contact your doctor 
immediately. 

• if you or the child have, or are at risk of developing a serious blood infection called sepsis. If 
you are not sure, please contact your doctor. 

• if you or the child have an infection of any kind. If you are not sure, please talk to your doctor. 
 
Warnings and precautions 
 
Talk to your doctor before taking Erelzi. 
 
• Allergic reactions: If you or the child experience allergic reactions such as chest tightness, 

wheezing, dizziness or rash, do not inject more Erelzi, and contact your doctor immediately. 
• Infections/surgery: If you or the child develop a new infection, or are about to have any major 

surgery, your doctor may wish to monitor the treatment with Erelzi. 
• Infections/diabetes: Tell your doctor if you or the child have a history of recurrent infections or 

suffer from diabetes or other conditions that increase the risk of infection. 
• Infections/monitoring: Tell your doctor of any recent travel outside the European region. If you 

or the child develop symptoms of an infection such as fever, chills or cough, notify your doctor 
immediately. Your doctor may decide to continue to monitor you or the child for the presence of 
infections after you or the child stop using Erelzi. 

• Tuberculosis: As cases of tuberculosis have been reported in patients treated with Erelzi, your 
doctor will check for signs and symptoms of tuberculosis before starting Erelzi. This may include 
a thorough medical history, a chest X-ray and a tuberculin test. The conduct of these tests should 
be recorded on the Patient Alert Card. It is very important that you tell your doctor if you or the 
child have ever had tuberculosis, or have been in close contact with someone who has had 
tuberculosis. If symptoms of tuberculosis (such as persistent cough, weight loss, listlessness, mild 
fever), or any other infection appear during or after therapy, tell your doctor immediately. 

• Hepatitis B: Tell your doctor if you or the child have or have ever had hepatitis B. Your doctor 
should test for the presence of hepatitis B infection before you or the child begin treatment with 
Erelzi. Treatment with Erelzi may result in reactivation of hepatitis B in patients who have 
previously been infected with the hepatitis B virus. If this occurs, you should stop using Erelzi. 

• Hepatitis C: Tell your doctor if you or the child have hepatitis C. Your doctor may wish to 
monitor the treatment with Erelzi in case the infection worsens. 

• Blood disorders: Seek medical advice immediately if you or the child have any signs or 
symptoms such as persistent fever, sore throat, bruising, bleeding or paleness. Such symptoms 



80 
 
 

may point to the existence of potentially life-threatening blood disorders, which may require 
discontinuation of Erelzi. 

• Nervous system and eye disorders: Tell your doctor if you or the child have multiple sclerosis, 
optic neuritis (inflammation of the nerves of the eyes) or transverse myelitis (inflammation of the 
spinal cord). Your doctor will determine if Erelzi is an appropriate treatment. 

• Congestive heart failure: Tell your doctor if you or the child have a history of congestive heart 
failure, because Erelzi needs to be used with caution under these circumstances. 

• Cancer: Tell your doctor if you have or have ever had lymphoma (a type of blood cancer) or any 
other cancer before you are given Erelzi.  
Patients with severe rheumatoid arthritis, who have had the disease for a long time, may be at 
higher than average risk of developing lymphoma. 
Children and adults taking Erelzi may have an increased risk of developing lymphoma or another 
cancer. 
Some children and teenage patients who have received Erelzi or other medicines that work the 
same way as Erelzi have developed cancers, including unusual types, which sometimes resulted 
in death. 
Some patients receiving Erelzi have developed skin cancers. Tell your doctor if you or the child 
develop any change in the appearance of the skin or growths on the skin. 

• Chickenpox: Tell your doctor if you or the child are exposed to chickenpox when using Erelzi. 
Your doctor will determine if preventive treatment for chickenpox is appropriate. 

• Alcohol abuse: Erelzi should not be used for the treatment of hepatitis related to alcohol abuse. 
Please tell your doctor if you or the child in your care have a history of alcohol abuse. 

• Wegener’s granulomatosis: Erelzi is not recommended for the treatment of Wegener’s 
granulomatosis, a rare inflammatory disease. If you or the child in your care have Wegener’s 
granulomatosis, talk to your doctor. 

• Anti-diabetic medicines: Tell your doctor if you or the child have diabetes or are taking 
medicines to treat diabetes. Your doctor may decide if you or the child need less anti-diabetic 
medicine while using Erelzi. 

 
Children and adolescents 
 
Erelzi is not indicated for use in children and adolescents who weigh less than 62.5 kg. 
 
• Vaccinations: If possible, children should be up to date with all vaccinations before using Erelzi. 

Some vaccines, such as oral polio vaccine, should not be given while using Erelzi. Please consult 
your doctor before you or the child receive any vaccines. 

• Inflammatory bowel disease (IBD): There have been cases of IBD in patients with juvenile 
idiopathic arthritis (JIA) treated with Erelzi. Tell the doctor if the child develops any abdominal 
cramps and pain, diarrhoea, weight loss or blood in the stool. 

 
Erelzi should not normally be used in children with polyarthritis or extended oligoarthritis below the 
age of 2 years or weighing less than 62.5 kg, or in children with enthesitis-related arthritis or psoriatic 
arthritis below the age of 12 years or weighing less than 62.5 kg, or in children with psoriasis below the 
age of 6 years or weighing less than 62.5 kg. 
 
Other medicines and Erelzi 
 
Tell your doctor or pharmacist if you or the child are taking, have recently taken or might take any other 
medicines (including anakinra, abatacept or sulfasalazine), even those not prescribed by the doctor.  
 
You or the child should not use Erelzi with medicines that contain the active substance anakinra or 
abatacept. 
 



81 
 
 

Pregnancy and breast-feeding 
 
Erelzi should only be used during pregnancy if clearly needed. You should consult your doctor if you 
become pregnant, think you may be pregnant, or are planning to have a baby. 
 
If you received Erelzi during pregnancy, your baby may have a higher risk of getting an infection. In 
addition, one study found more birth defects when the mother had received etanercept in pregnancy, 
compared with mothers who had not received etanercept or other similar medicines (TNF-antagonists), 
but there was no particular kind of birth defect reported. Another study found no increased risk of birth 
defects when the mother had received etanercept in pregnancy. Your doctor will help you to decide 
whether the benefits of treatment outweigh the potential risk to your baby. It is important that you tell 
the baby’s doctors and other healthcare professionals about the use of Erelzi during pregnancy before 
the baby receives any vaccine (for more information see section 2, “Vaccinations”). 
 
Women using Erelzi should not breast-feed, since Erelzi passes into human breast milk. 
 
Driving and using machines 
 
The use of Erelzi is not expected to affect the ability to drive or use machines. 
 
Erelzi contains sodium 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per 50 mg, that is to say essentially 
‘sodium-free’. 
 
 
3. How to use Erelzi 
 
Always use this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if 
you are not sure. 
 
If you feel that the effect of Erelzi is too strong or too weak, talk to your doctor or pharmacist. 
 
You have been prescribed a 50 mg strength of Erelzi. A 25 mg strength of Erelzi is available for doses 
of 25 mg. 
 
Use in adult patients (aged 18 years or over) 
 
Rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis including ankylosing spondylitis 
 
The usual dose is 25 mg given twice a week or 50 mg once a week as an injection under the skin. 
However, your doctor may determine an alternative frequency at which to inject Erelzi. 
 
Plaque psoriasis 
 
The usual dose is 25 mg twice a week or 50 mg once a week. 
 
Alternatively, 50 mg may be given twice a week for up to 12 weeks, followed by 25 mg twice a week or 
50 mg once a week. 
 
Your doctor will decide how long you should use Erelzi and whether retreatment is needed based on 
your response. If Erelzi has no effect on your condition after 12 weeks, your doctor may tell you to stop 
using this medicine. 
 



82 
 
 

Use in children and adolescents 
 
The appropriate dose and frequency of dosing for the child or adolescent will depend on body weight 
and disease. Your doctor will determine the correct dose for the child and will prescribe an appropriate 
strength of etanercept. Paediatric patients weighing 62.5 kg or more can be dosed 25 mg given twice a 
week or 50 mg given once a week using a fixed-dose pre-filled syringe or pre-filled pen. 
 
Other etanercept products with appropriate dosage forms for children are available. 
 
For polyarthritis or extended oligoarthritis in patients from the age of 2 years and weighing 62.5 kg or 
more, or enthesitis-related arthritis or psoriatic arthritis in patients from the age of 12 years and 
weighing 62.5 kg or more, the usual dose is 25 mg given twice a week or 50 mg given once a week. 
 
For psoriasis in patients from the age of 6 years and weighing 62.5 kg or more, the usual dose is 50 mg 
and should be given once weekly. If Erelzi has no effect on the child’s condition after 12 weeks, your 
doctor may tell you to stop using this medicine. 
 
The doctor will provide you with detailed directions for preparing and measuring the appropriate dose. 
 
Method and route of administration 
 
Erelzi is administered by an injection under the skin (by subcutaneous injection). 
 
Erelzi can be taken with or without food or drink. 
 
Detailed instructions on how to inject Erelzi are provided in section 7, “Instructions for use of the 
Erelzi SensoReady pen”.  
 
Do not mix the Erelzi solution with any other medicine. 
 
To help you remember, it may be helpful to write in a diary which day(s) of the week Erelzi should be 
used. 
 
If you use more Erelzi than you should 
 
If you have used more Erelzi than you should (either by injecting too much on a single occasion or by 
using it too frequently), talk to a doctor or pharmacist immediately. Always have the outer carton of 
the medicine with you, even if it is empty. 
 
If you forget to inject Erelzi 
 
If you forget a dose, you should inject it as soon as you remember, unless the next scheduled dose is the 
next day; in which case you should skip the missed dose. Then continue to inject the medicine on the 
usual day(s). If you do not remember until the day that the next injection is due, do not take a double 
dose (two doses on the same day) to make up for a forgotten dose. 
 
If you stop using Erelzi 
 
Your symptoms may return upon discontinuation. 
 
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. 



83 
 
 

 
Allergic reactions 
 
If any of the following happen, do not inject more Erelzi. Tell your doctor immediately, or go to the 
casualty department at your nearest hospital. 
 
• Trouble swallowing or breathing 
• Swelling of the face, throat, hands, or feet 
• Feeling nervous or anxious, throbbing sensations, sudden reddening of the skin and/or a warm 

feeling 
• Severe rash, itching, or hives (elevated patches of red or pale skin that often itch) 
 
Serious allergic reactions are rare. However, any of the above symptoms may indicate an allergic 
reaction to Erelzi, so you should seek immediate medical attention. 
 
Serious side effects 
 
If you notice any of the following, you or the child may need urgent medical attention. 
 
• Signs of serious infections such as high fever that may be accompanied by cough, shortness of 

breath, chills, weakness, or a hot, red, tender, sore area on the skin or joints; 
• Signs of blood disorders, such as bleeding, bruising, or paleness; 
• Signs of nerve disorders, such as numbness or tingling, changes in vision, eye pain, or onset of 

weakness in an arm or leg; 
• Signs of heart failure or worsening heart failure, such as fatigue or shortness of breath with 

activity, swelling in the ankles, a feeling of fullness in the neck or abdomen, night-time shortness 
of breath or coughing, bluish colour of the nails or the lips; 

• Signs of cancers: cancers may affect any part of the body including the skin and blood, and 
possible signs will depend on the type and location of the cancer. These signs may include weight 
loss, fever, swelling (with or without pain), persistent cough, presence of lumps or growths on the 
skin; 

• Signs of autoimmune reactions (where antibodies are made that may harm normal tissues in the 
body) such as pain, itching, weakness, and abnormal breathing, thinking, sensation, or vision; 

• Signs of lupus or lupus-like syndrome, such as weight changes, persistent rash, fever, joint or 
muscle pain, or fatigue; 

• Signs of inflammation of the blood vessels such as pain, fever, redness or warmth of the skin, or 
itching. 

 
These are rare or uncommon side effects, but are serious conditions (some of which may rarely be 
fatal). If these signs occur, tell your doctor immediately, or visit the casualty department at your nearest 
hospital. 
 
The known side effects of Erelzi include the following in groups of decreasing frequency: 
 
• Very common (may affect more than 1 in 10 people): 

Infections (including colds, sinusitis, bronchitis, urinary tract infections and skin infections); 
injection site reactions (including bleeding, bruising, redness, itching, pain, and swelling). 
Reactions at the injection site (these do not occur as often after the first month of treatment). 
Some patients have developed a reaction at an injection site that was used before. 
 

• Common (may affect up to 1 in 10 people): 
Allergic reactions; fever; rash; itching; antibodies directed against normal tissue (autoantibody 
formation). 
 



84 
 
 

• Uncommon (may affect up to 1 in 100 people): 
Serious infections (including pneumonia, deep skin infections, joint infections, blood infection, 
and infections at various sites); worsening of congestive heart failure; low red blood cell count, 
low white blood cell count, low neutrophil (a type of white blood cell) count; low blood platelet 
count; skin cancer (excluding melanoma); localised swelling of the skin (angioedema); hives 
(elevated patches of red or pale skin that often itch); eye inflammation; psoriasis (new or 
worsening); inflammation of the blood vessels affecting multiple organs; elevated liver blood 
tests (in patients also receiving methotrexate treatment, the frequency of elevated liver blood tests 
is common); abdominal cramps and pain, diarrhoea, weight loss or blood in the stool (signs of 
bowel problems). 
 

• Rare (may affect up to 1 in 1,000 people): 
Serious allergic reactions (including severe localised swelling of the skin and wheezing); 
lymphoma (a type of blood cancer); leukaemia (cancer affecting the blood and bone marrow); 
melanoma (a type of skin cancer); combined low platelet, red, and white blood cell count; 
nervous system disorders (with severe muscle weakness and signs and symptoms similar to those 
of multiple sclerosis or inflammation of the nerves of the eyes or spinal cord); tuberculosis; new 
onset congestive heart failure; seizures; lupus or lupus-like syndrome (symptoms may include 
persistent rash, fever, joint pain, and tiredness); skin rash, which may lead to severe blistering and 
peeling of the skin; lichenoid reactions (itchy reddish-purple skin rash and/or threadlike white-
grey lines on mucous membranes); inflammation of the liver caused by the body's own immune 
system (autoimmune hepatitis; in patients also receiving methotrexate treatment, the frequency is 
uncommon); immune disorder that can affect the lungs, skin and lymph nodes (sarcoidosis); 
inflammation or scarring of the lungs (in patients also receiving methotrexate treatment, the 
frequency of inflammation or scarring of the lungs is uncommon). 
 

• Very rare (may affect up to 1 in 10,000 people):  
Failure of the bone marrow to produce crucial blood cells. 
 

• Not known (frequency cannot be estimated from the available data):  
Merkel cell carcinoma (a type of skin cancer); excessive activation of white blood cells 
associated with inflammation (macrophage activation syndrome); recurrence of hepatitis B (a 
liver infection); worsening of a condition called dermatomyositis (muscle inflammation and 
weakness with an accompanying skin rash). 

 
Side effects in children and adolescents 
 
The side effects and their frequencies seen in children and adolescents are similar to those described 
above. 
 
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 Erelzi 
 
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 the label of the pre-filled 
SensoReady pen after EXP. The expiry date refers to the last day of that month. 
 
Store in a refrigerator (2 °C – 8 °C). Do not freeze. 



85 
 
 

 
Keep the pre-filled pens in the outer carton in order to protect from light. 
 
After taking a pre-filled pen from the refrigerator, wait approximately 15-30 minutes to allow the 
Erelzi solution in the pen to reach room temperature. Do not warm in any other way. Immediate use 
is then recommended. 
 
Erelzi may be stored outside of the refrigerator at temperatures up to a maximum of 25 °C for a single 
period of up to four weeks; after which, it should not be refrigerated again. Erelzi should be discarded if 
not used within four weeks after removal from the refrigerator. It is recommended that you record the 
date that Erelzi is removed from the refrigerator and the date after which Erelzi should be discarded (no 
more than 4 weeks following the removal from the refrigerator). 
 
Inspect the solution in the pen by looking through the clear viewing window. The solution should be 
clear or slightly opalescent, colourless to slightly yellowish, and may contain small white or almost 
translucent particles of protein. This appearance is normal for Erelzi. Do not use the solution if it is 
discoloured, cloudy, or if particles other than those described above are present. If you are concerned 
with the appearance of the solution, then contact your pharmacist for assistance. 
 
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. 
 
 
6. Contents of the pack and other information 
 
What Erelzi contains 
 
The active substance is etanercept.  
Each pre-filled pen contains 50 mg of etanercept. 
 
The other ingredients are citric acid anhydrous, sodium citrate dihydrate, sodium chloride, sucrose, 
L-lysine hydrochloride, sodium hydroxide, hydrochloric acid and water for injections. 
 
What Erelzi looks like and contents of the pack 
 
Erelzi is supplied as a solution for injection in a pre-filled pen (SensoReady). The SensoReady pen 
contains a clear or slightly opalescent, colourless to slightly yellowish solution for injection (injection).  
Each pack contains 1, 2 or 4 pens, multipacks contain 12 (3 packs of 4) pens.  
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
 
Sandoz GmbH 
Biochemiestr. 10 
A-6250 Kundl 
Austria 
 
Manufacturer 
 
Sandoz GmbH Schaftenau 
Biochemiestr. 10 
A-6336 Langkampfen 
Austria 
 
This leaflet was last revised in 
 



86 
 
 

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
 
7. Instructions for use of the Erelzi SensoReady pen  
 
 
 

 

Read ALL the way through these instructions before injecting. The same 
information is also available on www.erelzi.eu and through the code below. 
 

 
www.erelzi.eu 

 

These instructions are to help you to inject correctly using the Erelzi 
SensoReady pen. 
It is important not to try to inject yourself until you have been trained by your 
doctor, nurse or pharmacist. 

 
Your Erelzi SensoReady pen: 
 

 
Erelzi SensoReady pen shown with the cap removed. Do 
not remove the cap until you are ready to inject. 

Store your boxed pen in a refrigerator, 
between 2 °C to 8 °C and out of the 
sight and reach of children. 
• Do not freeze the pen. 
• Do not shake the pen. 
• Do not use the pen if it has been 

dropped with the cap removed. 
For a more comfortable injection, take 
the pen out of the refrigerator 
15-30 minutes before injecting to 
allow it to reach room temperature. 

 
What you need for your injection: 
 
Included in the carton:  
 
A new and unused Erelzi SensoReady 
pen. 

Not included in the carton:  
 
• Alcohol wipe 
• Cotton ball or gauze  
• Sharps disposal container 

  
 



87 
 
 

Before your injection:  
 
 

 

1. Important safety checks before you inject: 
The solution should be clear or slightly opalescent, colourless to 
slightly yellowish, and may contain small white or almost translucent 
particles of protein. This appearance is normal for Erelzi. 
Do not use if the liquid is cloudy, discoloured, or has large lumps, 
flakes, or coloured particles. 
Do not use the pen if the expiry date has passed.  
Do not use if the safety seal has been broken. 
Contact your pharmacist if the pen fails any of these checks. 

 

2a. Choose your injection site: 
• The recommended site is the front of the thighs. You may also use 

the lower abdomen, but not the area 5 centimetres around the 
navel (belly button).  

• Choose a different site each time you give yourself an injection.  
• Do not inject into areas where the skin is tender, bruised, red, 

scaly or hard. Avoid areas with scars or stretch marks. If you have 
psoriasis, you should NOT inject directly into any raised, thick, 
red, or scaly skin patches or lesions (“psoriasis skin lesions”). 

 

2b. Caregivers and healthcare professionals only:  
• If a caregiver or healthcare professional is giving you your 

injection, they may also inject into your outer upper arm. 

 

3. Cleaning your injection site: 
• Wash your hands with soap and hot water.  
• Using a circular motion, clean the injection site with the alcohol 

swab. Leave it to dry before injecting.  
• Do not touch the cleaned area again before injecting. 

 



88 
 
 

Your injection: 
 

 

4. Removing the cap:  
• Only remove the cap when you are ready to use the pen. 
• Twist off the cap in the direction of the arrows. 
• Once removed, throw away the cap. Do not try to re-attach the 

cap.  
• Use the pen within 5 minutes of removing the cap. 

 

5. Holding your pen:  
• Hold the pen at 90 degrees to the cleaned injection site. 

 
      Correct         Incorrect 

 

 

YOU MUST READ THIS BEFORE INJECTING. 
 
During the injection you will hear 2 loud clicks.  
 
The 1st click indicates that the injection has started. Several seconds later a 2nd 
click will indicate that the injection is almost finished.  
 
You must keep holding the pen firmly against your skin until you see a green 
indicator fill the window and stop moving. 

 

 

6. Starting your injection:  
• Press the pen firmly against the skin to start the injection. 
• The 1st click indicates the injection has started.  
• Keep holding the pen firmly against your skin.  
• The green indicator shows the progress of the injection. 

 

7. Completing your injection: 
• Listen for the 2nd click. This indicates the injection is almost 

complete.  
• Check the green indicator fills the window and has stopped 

moving. 
• The pen can now be removed. 

 



89 
 
 

After your injection: 

 

8. Check the green indicator fills the window: 
• This means the medicine has been delivered. Contact your doctor if 

the green indicator is not visible.  
• There may be a small amount of blood at the injection site. You can 

press a cotton ball or gauze over the injection site and hold it for 
10 seconds. Do not rub the injection site. You may cover the 
injection site with a small adhesive bandage, if needed. 

 
 
 
 
 

9. Disposing of your Erelzi pen:  
• Dispose of the used pen in a sharps disposal container (i.e. a 

puncture-resistant closable container, or similar). 
• Never try to re-use your pen. 

If you have any questions, please talk to a doctor, nurse or pharmacist who is familiar with Erelzi. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



90 
 
 

 
 

 

 

 

 

 

 

 

 

 

 

 

Annex IV 

Scientific conclusions and grounds for the variation to the terms of the marketing 
authorisation(s) 

 
 
 
 
 

 



91 
 
 

Scientific conclusions 

Taking into account the PRAC Assessment Report on the PSUR(s) for etanercept (biosimilars), the 
scientific conclusions of CHMP are as follows:  

Based on the review of the literature and spontaneous reporting presented in this PSUSA, covering the 
period from 15 July 2018 to 14 January 2019, as well as cumulative data since the European birth date, 
the PRAC considered that a causal relationship between inflammatory bowel disease and etanercept 
cannot be excluded and therefore recommends that the product information of medicinal products 
containing the active substance etanercept should be updated as follows: update of section 4.8 of the 
SmPC to add inflammatory bowel disease with a frequency uncommon. The package leaflet is updated 
accordingly.  

The CHMP agrees with the scientific conclusions made by the PRAC. 

Grounds for the variation to the terms of the marketing authorisation(s) 

On the basis of the scientific conclusions for etanercept (biosimilars) the CHMP is of the opinion that 
the benefit-risk balance of the medicinal product(s) containing etanercept (biosimilars) is unchanged 
subject to the proposed changes to the product information 

The CHMP recommends that the terms of the marketing authorisation(s) should be varied. 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND MANUFACTURER(S) 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
	Scientific conclusions and grounds for the variation to the terms of the marketing authorisation(s)