Zinbryta

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 
 
Zinbryta 150 mg solution for injection in pre-filled syringe 
Zinbryta 150 mg solution for injection in pre-filled pen 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each pre-filled syringe contains 150 mg of daclizumab beta in 1 mL solution for injection. 
 
Each pre-filled pen contains a pre-filled syringe, containing 150 mg of daclizumab beta in  
1 mL solution for injection. 
 
Daclizumab beta is produced in a mammalian cell line (NS0) by recombinant DNA technology. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection (injection).  
 
Colourless to slightly yellow, clear to slightly opalescent liquid with pH 6. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Zinbryta is indicated for the treatment of adult patients with relapsing forms of multiple sclerosis 
(RMS) who have had an inadequate response to at least two disease modifying therapies (DMTs) and 
for whom treatment with any other DMT is contraindicated or otherwise unsuitable (see section 4.4). 
 
4.2 Posology and method of administration 
 
Treatment should be initiated by a physician experienced in the management of multiple sclerosis. 
 
Posology 
 
The recommended dose of Zinbryta is 150 mg injected subcutaneously once a month. 
 
In case a dose is missed and it is within 2 weeks of the missed dose, patients should be instructed to 
inject without delay their missed dose and then remain on their original monthly dosing schedule.   
 
If a dose is missed and it is more than 2 weeks from the missed dose, patients should skip the missed 
dose, wait until their next scheduled dose, and then remain on their original monthly dosing schedule.   
 
Only one dose should be administered at a time to make up for a missed dose.  
 

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Special populations 
 
Elderly population 
There was limited exposure in patients over 55 years of age in clinical studies with daclizumab beta. It 
has not been determined whether these patients respond differently compared with younger patients.  
 
Renal impairment 
Daclizumab beta has not been studied in patients with renal impairment. As renal excretion is not a 
major route of elimination, no dose adjustments are considered necessary (see section 5.2). 
 
Hepatic impairment 
Daclizumab beta has not been studied in patients with hepatic impairment. Zinbryta is contraindicated 
in patients with pre-existing hepatic impairment (see sections 4.3 and 4.4). 
 
Paediatric population 
The safety and efficacy of Zinbryta in children and adolescents below 18 years have not been 
established. No data are available.  
 
Method of administration  
 
Zinbryta is for subcutaneous use. 
 
It is recommended that patients should be trained in the proper technique for self-administering 
subcutaneous injection using the pre-filled syringe/pre-filled pen. The usual sites for subcutaneous 
injection include the thigh, abdomen, and back of the upper arm. 
 
Zinbryta is provided with the needle pre-attached. Pre-filled syringes/Pre-filled pens contain a single 
dose only and should be discarded after use.   
 
Precautions to be taken before handling or administering the medicinal product 
Once removed from the refrigerator, Zinbryta should be allowed to warm to room temperature 
(20°C-30°C) (about 30 minutes) prior to injection. External heat sources such as hot water must not be 
used to warm Zinbryta. 
 
This medicinal product should not be used if: 
• the syringe/pen is cracked or broken 
• the solution is cloudy or you can see particles floating in it 
• the solution is any other colour than colourless to slightly yellow 
• the pen has been dropped or is visibly damaged. 
 
4.3 Contraindications 
 
Zinbryta is contraindicated in patients with a history of severe hypersensitivity (e.g. anaphylaxis or 
anaphylactoid reactions) to all forms of daclizumab or to any of the excipients in Zinbryta (see section 
6.1). 
 
Pre-existing hepatic disease or hepatic impairment (see section 4.4). 
 

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4.4 Special warnings and precautions for use 
 
Hepatic injury 
Due to the risk of hepatic injury, the use of Zinbryta is restricted (see section 4.1). 
Serious hepatic injury including elevations of serum transaminases and fatal cases of autoimmune 
hepatitis and fulminant liver failure have occurred in patients treated with Zinbryta (see section 4.8). 
Cases occurred early after treatment initiation, in patients having received repeated treatment courses 
and several months after discontinuation. 
 
Prior to treatment initiation with Zinbryta, serum transaminases (ALT and AST) and total bilirubin 
levels should be obtained, and patients should be screened  for Hepatitis B (HBV) and C (HCV). 
Treatment initiation is not recommended in patients with ALT or AST ≥ 2 times the upper limit of 
normal (ULN) and is contraindicated in patients with pre-existing hepatic impairment (see section 
4.3). For patients who test positive for HBV or HCV infection, consultation with a physician with 
expertise in the treatment of HBV or HCV is recommended. Treatment initiation is not recommended 
in patients with history of concurrent autoimmune conditions other than multiple sclerosis. 
 
Patient serum transaminase and total bilirubin levels should be monitored at least monthly and as close 
as possible before each administration, and more frequently as clinically indicated during treatment 
and up to 6 months after the last dose of Zinbryta. Treatment discontinuation is recommended in 
patients who reach ALT or AST >3 times the ULN regardless of bilirubin levels.  
 
Patients should be informed about the risk of hepatic injury, the need for periodic monitoring and 
warned about signs or symptoms suggestive of hepatic dysfunction. If a patient develops clinical signs 
or symptoms suggestive of hepatic dysfunction (e.g. unexplained nausea, vomiting, abdominal pain, 
fatigue, anorexia, or jaundice and/or dark urine), it is recommended to promptly measure serum 
transaminases, discontinue treatment with Zinbryta, as appropriate, and promptly refer the patient to a 
hepatologist.  
 
Treatment discontinuation should be considered if an adequate response has not been achieved or the 
patient fails to follow the requirement for scheduled liver test monitoring. 
 
Caution should be exercised when administering medicinal products of known hepatotoxic potential, 
including non-prescription products and herbal supplements, concomitantly with Zinbryta (see section 
4.5). 
 
Refer to section below, ‘Educational Guidance’, for details of the Hepatic Risk Management Guide for 
Physicians and Patient Card that are recommended for use with this medicine. 
 
Educational guidance 
All physicians who intend to prescribe Zinbryta must ensure they are familiar with the Hepatic Risk 
Management Guide for Physicians for this medicinal product.  
 
The physician should discuss the risk of hepatic injury with patients and provide them with a Patient 
Card.  
 
The Card informs patients of the risk of serious hepatic injury, and its possible symptoms, so that they 
are aware of situations in which they should contact a healthcare professional in a timely manner. In 
addition, the Card explains the need for monitoring of liver function and educates the patient on the 
importance of adherence to their monthly blood tests. 
 
Skin reactions 
Skin reactions, some serious (e.g. exfoliative rash or dermatitis, toxic skin eruption), have been 
reported with Zinbryta. Skin reactions generally resolved with standard care, including treatment with 
topical or systemic steroids. If a patient develops a diffuse or highly inflammatory rash, referral to a 
dermatologist and discontinuation of Zinbryta may be required (see section 4.8). 

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Depression 
Zinbryta should be administered with caution to patients with previous or current depressive disorders. 
Patients treated with Zinbryta should be advised to report any symptoms of new or worsening 
depression, and/or suicidal ideation immediately to the prescribing physician. If a patient develops 
severe depression, and/or suicidal ideation, discontinuation of Zinbryta should be considered (see 
section 4.8). 
 
Infections  
Infections, some serious (e.g. pneumonia and bronchitis), have been reported with Zinbryta. If serious 
infection develops, it could be necessary to withhold treatment with Zinbryta until the infection 
resolves.  
 
Tuberculosis infections have been reported in patients treated with Zinbryta. In patients who have had 
tuberculosis or who live in endemic areas of the disease, screening for active tuberculosis should be 
performed before starting treatment, and patients should be monitored during treatment. 
 
In patients with severe active infection, a delay in initiation of Zinbryta therapy should be considered 
(see section 4.8). 
 
Zinbryta has not been studied in patients with immunodeficiency syndromes. 
 
Autoimmune haemolytic anaemia  
Autoimmune haemolytic anaemia has been reported in patients treated with Zinbryta which resolved 
with standard treatment and discontinuation of Zinbryta.  
If a patient develops signs or symptoms of autoimmune haemolytic anaemia (e.g. pallor, fatigue, dark 
urine, jaundice, shortness of breath), consider referring to a specialist and discontinuing Zinbryta (see 
section 4.8).  
 
Gastrointestinal disorders 
Colitis has been reported with Zinbryta. The colitis improved with discontinuation of Zinbryta and 
standard treatment. Referring patients who develop symptoms of colitis (e.g. abdominal pain, fever, 
prolonged diarrhoea) to a specialist is advisable (see section 4.8).    
 
Lymphopenia 
When observed during Zinbryta clinical studies, lymphopenia was mostly mild to moderate 
(≥ 500/mm3). Sustained severe lymphopenia (< 500/mm3), was not observed in clinical studies with 
Zinbryta.  However, as a precaution, monitoring of complete blood count is recommended every 
3 months. 
 
The risk of Progressive Multifocal Leukoencephalopathy (PML) associated to the treatment with 
Zinbryta has not been established. 
 
Excipient related considerations 
This medicinal product contains 0.14 mmol sodium per dose. It is essentially ‘sodium-free’ and can be 
used by patients on a sodium-restricted diet. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Zinbryta is not expected to undergo metabolism by hepatic enzymes or renal elimination. There is 
limited data on concomitant use of Zinbryta with MS symptomatic therapies.  
 
Hepatic injury 
Cases of hepatic injury have occurred in patients taking Zinbryta with other hepatotoxic drugs, 
although the role of these medicinal products is uncertain. Caution is recommended when 

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administering medicinal products of known hepatotoxic potential including non-prescription products 
and herbal supplements concomitantly with Zinbryta (see section 4.4).  

 
Immunisations 
The safety of immunisation with live viral vaccines during treatment with Zinbryta has not been 
studied. Vaccination with live vaccines is not advised during treatment and up to 4 months after 
discontinuation. 
 
In a clinical study, patients (n=90) on long-term treatment with Zinbryta mounted appropriate immune 
responses to an inactivated trivalent seasonal influenza vaccine. The magnitude of the immune 
response to the seasonal influenza vaccine, and proportion of patients with seroconversion and 
seroprotection were consistent with those observed in healthy volunteer populations. Patients on 
Zinbryta may receive non-live vaccines. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
There are limited data from the use of Zinbryta in pregnant women. Animal studies do not indicate 
direct or indirect harmful effects with respect to reprotoxicity (see section 5.3). 
 
Zinbryta should be used during pregnancy only if the potential benefit justifies the potential risk to the 
foetus. 
 
Breast-feeding 
Available toxicology data in lactating cynomolgus monkeys have shown excretion of daclizumab beta 
in milk (for details see section 5.3). It is not known whether Zinbryta is secreted in human milk. 
Although human IgG is secreted into human milk, published data suggest that antibodies in breast 
milk do not enter the neonatal and infant circulations in substantial amounts. A risk to 
newborns/infants cannot be excluded. 
 
If a woman wishes to breast-feed during treatment with Zinbryta, the benefit of breast-feeding to the 
child and of therapy to the woman should be considered. 
 
Fertility 
No impact on male or female fertility as assessed by fertility indices was detected in animal studies 
(see section 5.3). There are no data on the effects of Zinbryta on human fertility. 
 
4.7 Effects on ability to drive and use machines 
 
Zinbryta has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
In the placebo-controlled study (the SELECT study), 417 patients received Zinbryta (150 mg, n=208; 
300 mg, n=209; every 4 weeks) for up to 1 year. In the active-controlled study (the DECIDE study), 
919 patients received Zinbryta (150 mg, every 4 weeks) and 922 patients received interferon beta-1a 
intramuscular, (30 microgram weekly) for a minimum of 2 years and up to 3 years.  
 
The most commonly reported adverse reactions leading to discontinuation in patients treated with 
Zinbryta were hepatic reactions, including elevations of serum transaminases (5%), and cutaneous 
reactions (4%) (see section 4.4). 
 

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The most common adverse reactions reported for Zinbryta were rash, increased alanine 
aminotransferase (ALT), depression, nasopharyngitis, upper respiratory tract infection, influenza, 
oropharyngeal pain, and lymphadenopathy.  
 
Tabulated list of adverse reactions 
The adverse reactions are presented as MedDRA preferred terms under the MedDRA System Order 
Class by frequency and incidence. Within each frequency grouping, adverse reactions are presented in 
order of decreasing seriousness. The incidence of the adverse reactions is expressed according to 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) 
 

 
Table 1: Adverse reactions reported for Zinbryta 150mg 
 
System Organ Class Adverse reaction Frequency 
Infections and infestations Upper respiratory tract infection† Very Common 

Nasopharyngitis† Very Common 
Pneumonia Common 
Respiratory tract infection Common 
Bronchitis Common 
Viral infection  Common 
Influenza† Common 
Laryngitis Common 
Tonsillitis† Common 
Pharyngitis Common 
Folliculitis Common 
Rhinitis* Common 

Blood and lymphatic system disorders  Lymphadenopathy† Common 
Lymphadenitis Common 
Anaemia* Common 
Autoimmune haemolytic anaemia Uncommon 

Immune system disorders Sarcoidosis Uncommon 
Psychiatric disorders Depression* Common 
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain† Common 
Gastrointestinal disorders Diarrhoea Common  

Colitis Common 
Skin and subcutaneous tissue disorders  
  

Dermatitis Common 
Dermatitis allergic Common 
Eczema† Common 
Psoriasis Common 
Seborrhoeic dermatitis† Common 
Skin exfoliation Common 
Rash*† Common 
Rash maculopapular Common 
Acne† Common 
Erythema Common 
Pruritus Common 
Dry skin Common 

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Exfoliative rash Uncommon 
Toxic skin eruption Uncommon 
Eczema nummular Uncommon 

General disorders and administration site conditions Pyrexia*  Common 
Hepatobiliary disorders Transaminases increased  Very common 

Autoimmune hepatitis Uncommon 

Fulminant hepatitis Not known 

Investigations 
  

Liver function test abnormal Very common 
Lymphocyte count decreased Common 

*Observed with a ≥2% higher incidence than placebo 
†Observed with a ≥2% higher incidence than interferon beta-1a (intramuscular) 
 
Description of selected adverse reactions 
 
Hepatic injury 
 
Serious hepatic injury, including fatal cases of autoimmune hepatitis and fulminant liver failure have 
occurred in patients treated with Zinbryta. Serious reactions, including autoimmune hepatitis, hepatitis 
and jaundice, were observed in 1.7% of patients in clinical trials.  
 
In clinical studies, serum transaminase elevations occurred at any time during treatment and up to 
6 months after the last dose of Zinbryta. Most patients had mild elevations that were below or up to 
3 x ULN and resolved spontaneously. In clinical trials, an increased incidence of elevations of ALT or 
AST was reported more frequently in Zinbryta-treated patients compared to placebo or interferon beta-
1a (intramuscular). The incidence of discontinuation due to medicine related hepatic disorders was 5% 
in Zinbryta-treated patients and 4% in interferon beta-1a (intramuscular). 
 
Table 2. Cumulative incidences of peak ALT or AST increase (based on laboratory data) observed in 
clinical trials 
 

 
 
Skin reactions 
In clinical studies Zinbryta increased the incidence of skin reactions [18% vs 13% (placebo); 37% vs 
19% (interferon beta-1a (intramuscular))] and serious skin reactions [<1% vs 0% (placebo); 2% vs 
<1% (interferon beta-1a (intramuscular))] compared to placebo and interferon beta-1a (intramuscular).  
 
The most common skin reactions were rash, dermatitis, and eczema. The majority of patients had skin 
reactions that were mild or moderate in severity. Discontinuation due to skin reactions was 4% in 
Zinbryta-treated patients.  

 Daclizumab 150 mg 

(N=1943) 

Interferon beta-1a 

(N=922) 

Placebo 

(N=204) 

Total exposure (subject-years) 7011 1884 210 

≥ 3 x ULN 13.6% 8.5% 3.4% 

> 5 x ULN 9.0% 3.4% 0.5% 

> 10 x ULN 4.3% 1.3% 0.0% 

> 20 x ULN 1.4% 0.4% 0.0% 

AST or ALT ≥ 3 x ULN AND total 
bilirubin ≥ x 2 ULN 

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Depression 
In clinical studies, Zinbryta increased the incidence of depression [5% vs 1% (placebo); 8% vs 6% 
(interferon beta-1a (intramuscular))]; the incidence of serious reactions of depression was <1% with 
Zinbryta.  
 
Infections 
In clinical studies, Zinbryta increased the incidence of infections [50% vs 44% (placebo) and 65% vs 
57% (interferon beta-1a (intramuscular))] and serious infections [3% vs 0% (placebo); 4% vs 2% 
(interferon beta-1a (intramuscular))] compared to placebo and interferon beta-1a (intramuscular). The 
most common types of infections were upper respiratory tract infections and viral infections.  The 
median duration was similar between the treatment groups. The rate of infections and serious 
infections did not increase over time. The majority of patients with infections continued on treatment 
with Zinbryta. Discontinuation of Zinbryta due to infections was <1%. 
 
Autoimmune haemolytic anaemia  
Autoimmune haemolytic anaemia was reported in < 1% of patients treated with Zinbryta in clinical 
studies.  
 
Gastrointestinal disorders 
An increased incidence of serious colitis (<1%) was reported in patients treated with Zinbryta in 
clinical studies.  
 
Lymphadenopathy 
In clinical studies, Zinbryta increased the incidence of lymphadenopathy, with onset occurring 
throughout the treatment period. Discontinuation due to lymphadenopathy was <1% in 
Zinbryta-treated patients. The majority of patients with lymphadenopathy continued on treatment with 
Zinbryta, and the majority of cases resolved within 3 months. 
 
Immunogenicity 
In the DECIDE study (see section 5.1), patients were tested for anti-drug (daclizumab beta) antibodies 
at week 4 and approximately every 3 months thereafter. Treatment-emergent anti-drug antibodies and 
neutralising antibodies were observed in 19% (175/913) and 8% (71/913) of study patients, 
respectively. The majority of the treatment-emergent anti-drug antibodies responses were transient 
(12% [110/913]) and the remaining minority (7% [65/913]) were persistent. Among the evaluable 
patients, the majority of treatment-emergent neutralising antibody responses were transient (6% [56 of 
913]) and 2% of patients (15 of 913) had persistent responses. Treatment-emergent anti-drug 
antibodies and neutralising antibodies responses predominantly occurred during the first year of 
treatment and their frequency declined with continued Zinbryta treatment.  
 
In patients with neutralising antibodies, daclizumab beta clearance was increased on average by 19% 
(see section 5.2). There was no apparent correlation of anti-drug antibodies or neutralising antibodies 
development to clinical response, adverse reactions, or pharmacodynamic profile of daclizumab beta. 
 
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 
 
Reported experience with overdose is limited. The safety of doses above 300 mg administered 
subcutaneously and 400 mg intravenously have not been evaluated. Doses up to this level were well 
tolerated with no evidence of acute toxicity. Potential adverse reactions beyond this level are expected 
to be consistent with the safety profile for daclizumab beta in MS patients. 

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Management 
In case of overdose, patients may require medical attention and appropriate supportive treatment 
should be given. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: immunosuppressants, interleukin inhibitors, ATC code: L04AC01 
 
Mechanism of action 

Daclizumab beta is a humanised IgG1 monoclonal antibody that binds to CD25 (IL-2Rα), and 
prevents IL-2 binding to CD25. Daclizumab beta modulates IL-2 signalling by blocking CD25-
dependent, high-affinity IL-2 receptor signalling, resulting in higher levels of IL-2 available for 
signalling through the intermediate-affinity IL-2 receptor.  Key effects of this IL-2 pathway 
modulation potentially related to the therapeutic effects of daclizumab beta in MS include selective 
antagonism of activated T-cell responses, and expansion of immunoregulatory CD56bright natural killer 
(NK) cells, which have been shown to selectively decrease activated T-cells. Together, these 
immunomodulatory effects of daclizumab beta are believed to reduce CNS pathology in MS and 
thereby reduce the occurrence of relapses and disability progression. 

 
Pharmacodynamic effects 
In clinical studies, the pharmacodynamic effects of Zinbryta 150 mg administered subcutaneously 
every 4 weeks were consistent with modulation of IL-2 signalling as evidenced by the rapid and 
sustained saturation of the target CD25 receptors on circulating T-cells and a sustained approximately 
2-fold increase in serum IL-2 concentration. In addition, an increase in CD56bright NK cells and a 
decrease in regulatory T-cells (defined as CD4+CD127lowFoxP3+ T-cells) was observed within 2 weeks 
after the first dose, with a sustained 5-fold increase in CD56bright NK cells above baseline and an 
approximately 60% decrease in regulatory T-cells in the treatment phase, with a return to baseline 
levels approximately 20-24 weeks after the last dose. During Zinbryta treatment, mean cell counts for 
the major immune subsets (T, B, and NK cells) remained within normal ranges; total lymphocyte, T 
and B cell counts decreased on average ≤10% from baseline during the first year of treatment. Total 
lymphocyte counts returned to baseline levels approximately 8-12 weeks after the last dose of Zinbryta 
(150mg). Total lymphocyte counts <0.8x109 cells/L ([Common Terminology Criteria for Adverse 
Events – CTCAE] Grade 2; at least one measurement) occurred in 4% of placebo-treated and 5% of 
Zinbryta-treated patients in the SELECT study, and 9% of the interferon beta-1a 
(intramuscular)-treated and 8% of Zinbryta-treated patients in the DECIDE study. Total NK cell 
counts increased approximately 1.5-fold as a result of the change in CD56bright NK cells. 
 
Clinical efficacy and safety 

The efficacy of Zinbryta was demonstrated in two studies (SELECT and DECIDE) in patients with 
RMS. The SELECT study was double-blind, randomised, placebo-controlled, with either Zinbryta 
150 mg (n=208), or 300 mg (n=209) versus placebo (n=204) every 4 weeks for 52 weeks. The 
DECIDE study was double-blind, randomised, parallel-group, active-controlled with Zinbryta 150 mg 
every 4 weeks (n=919) versus interferon beta-1a (intramuscular) 30 micrograms weekly (n=922), for a 
minimum of 2 to a maximum of 3 years (96 to 144 weeks). The study designs and baseline 
characteristics are presented in Table 3. 

 

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Table 3: Study design and baseline characteristics for SELECT study and DECIDE study  
 
Study name SELECT DECIDE 
Study design 
Treatment 52 weeks 96 to 144 weeks 
Disease history Patients with RMS, at least 1 relapse (clinical and/or MRI) 

during the year prior to randomisation, and had an EDSS score 
between 0 to 5.0. For DECIDE, at least 2 relapses (one of 
which was a clinical relapse) within the prior 3 years was also 
required 

Baseline characteristics 
Mean age (years) 35.7 36.3 
Mean disease duration (years) 4.1 4.2 
Mean number of relapses within 
12 months prior to study 

1.4 1.6 

Median EDSS score 2.5 2.0 
Percent with EDSS ≥ 3.5 36% 30% 
Percent with ≥ 1 Gd enhancing 
lesion (mean) 

44% (1.8) 46% (2.1) 

Percent ≥ 2 relapses in the year 
prior to study  

31% 46% 

Percent prior DMT use (%) 20% 41% 
 
Results for the SELECT study are shown in Table 4. Treatment with Zinbryta 150 mg every 4 weeks 
versus placebo significantly reduced the annualised relapse rate (ARR) and risk of relapse compared to 
placebo. In addition, there was a statistically significant effect on 24 week confirmed disability 
progression in Zinbryta treated patients with a hazard ratio 0.24  [95% CI: 0.09, 0.63]. The 300 mg 
dose did not provide additional benefit over the 150 mg dose. 
 

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Table 4:  SELECT study clinical and MRI results (at 52 weeks) 
 
 Placebo  Zinbryta 150 mg  p-value 

 
Clinical endpoints 
Number of patients 196 201  
Annualised relapse rate 
 
Rate ratio  
[95% CI] 

0.458 0.211 
 

0.461 
[0.318, 0.668] 

 
 
p<0.0001 

Percentage of patients relapse-free 
 
Hazard ratio*  
[95% CI] 

64% 81% 
 

0.45 
[0.30, 0.67] 

 
 
p<0.0001 

Percentage with 24 weeks confirmed 
disability progression 
 
Hazard ratio  
[95% CI] 

11% 2.6% 
 

 
0.24 

[0.09, 0.63] 

 
 
 
p=0.0037 

Percentage with 12 weeks confirmed 
disability progression 
 
Hazard ratio  
[95% CI] 

13% 
 
 
 

6% 
 
 

0.43 
[0.21, 0.88] 

 
 
 
p=0.0211 

Mean change in MSIS-29 physical 
score 

3.0 point worsening 1.0 point 
improvement 

p=0.0008 

MRI endpoints# 
Mean number of new or newly 
enlarging T2 hyperintense lesions 
 
Lesion mean ratio 
[95% CI] 

8.13 
 

2.4 
 
 

0.30 
[0.22, 0.40] 

 
 
 
p<0.0001 

Mean number of new T1 Gd-
enhancing lesions between 8 and 24 
weeks (on monthly MRI scans) 
 
Lesion mean ratio  
[95% CI] 

4.79 1.46 
 
 
 

0.31 
[0.20, 0.48] 

 
 
 
 
p<0.0001 

*Hazard ratio for the risk of relapse 
#MRI analyses used evaluable dataset for each endpoint; T1 Gd-enhancing: MRI intensive population 
 
Table 5 and Figures 1-2 show the results for the DECIDE study. Zinbryta significantly reduced the 
ARR and the risk of relapse, compared to interferon beta-1a (intramuscular)-treated patients. In 
addition, there was a statistically significant effect on 24 week confirmed disability progression in 
Zinbryta treated patients with a hazard ratio 0.73  [95%  CI: 0.55, 0.98]. At week 96, Zinbryta 
demonstrated a statistically significant reduction in the number of new or newly enlarging T2 
hyperintense lesions, the number of new T1 Gd-enhancing lesions and the mean number of new T1 
hypointense lesions. In addition, Zinbryta reduced clinically meaningful worsening in the patient-
reported physical impact of MS (≥7.5 point worsening from baseline to week 96 in the MSIS-29 
physical score) compared to interferon beta-1a (intramuscular). 
 

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Table 5: DECIDE study clinical and MRI results (96 to 144 weeks) (Values refer to results at 
96 weeks, unless otherwise indicated.)  
 
 Interferon  

beta-1a 
(intramuscular)  
30 micrograms  

Zinbryta 150 mg 
 

p-value 

Clinical endpoints 
Number of patients 922 919  
Annualised relapse rate* 
 
Rate ratio* 
[95% CI] 

0.393 
 

0.216 
 

0.550 
[0.469, 0.645] 

 
 
p<0.0001 

Percentage of patients relapse-free 
 
Hazard ratio# * 
[95% CI] 

59% 
 
 

73% 
 

0.59 
[0.50, 0.69] 

 
 
p<0.0001 

Percentage with 24 weeks confirmed 
disability progression 
 
Hazard ratio*  
[95% CI] 

12% 
 
 
 

9% 
 
 

0.73 
[0.55, 0.98] 

 
 
 
p=0.03 

Percentage with 12 weeks confirmed 
disability progression  
 
Hazard ratio*  
[95% CI] 

14% 
 
 
 

12% 
 
 

0.84 
[0.66, 1.07] 

 
 
 
p=0.16 

Percentage of patients with clinically 
meaningful worsening in MSIS-29 
physical score (≥7.5 point) 
 
Odds ratio 
[95% CI] 

23% 
 
 
 
 

19% 
 
 
 

0.76 
[0.60, 0.95] 

 
 
 
 
p=0.018 

MRI endpoints † 
Mean number of new or newly 
enlarging T2 hyperintense lesions  
 
Lesion mean ratio  
[95% CI] 

9.44 
 
 
 

4.31 
 
 

0.46 
[0.39, 0.53] 

 
 
 
p<0.0001 

Mean number of new T1 Gd-
enhancing lesions  
 
Odds ratio 
[95% CI] 

1.0 
 
 
 

0.4 
 
 

0.25 
[0.20, 0.32] 

 
 
 
p<0.0001 

Mean number of new T1 
hypointense lesions 
 
Lesion mean ratio  
[95% CI]  

4.43 
 
 
 

2.13 
 
 

0.48 
[0.42, 0.55] 

 
 
 
p<0.0001 

* Rates and risk reductions/endpoints are calculated over the treatment period up to 144 weeks. 
# Hazard ratio for the risk of relapse. 
† MRI analyses used evaluable dataset for each MRI endpoint. 
 

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Subgroup analyses of the SELECT and DECIDE studies demonstrated a consistent effect of Zinbryta 
compared to placebo and interferon beta-1a (intramuscular) across subgroups defined by demographic 
and MS disease characteristics.  In the DECIDE study subgroup analysis, there was a statistically 
significant reduction observed compared to interferon beta-1a (intramuscular) on ARR and the number 
of new or newly enlarging T2 hyperintense lesions across subgroups (gender, age, prior MS DMT 
therapy, and disease activity levels). 
 
Although the effect on disability progression was mainly seen in patients with baseline EDSS < 3.5, 
evidence of efficacy was shown in patients with relapsing secondary progressive MS (SPMS) as 
defined by baseline EDSS ≥ 3.5 and at least one of the three: confirmed 24 week worsening of 
EDSS, or ≥ 20% decline on Timed 25-foot Walk (T25FW), or, ≥ 20% decline on 9-Hole Peg Test (9-
HPT). 
 
Efficacy in patients with highly active disease 
Highly active disease was defined as follows: 
 
• Patients with 2 or more relapses in 1 year, and with 1 or more Gd-enhancing lesions on brain 

MRI, or 
• Patients who had failed to respond to a full and adequate course (at least 1 year) of prior DMT 

treatment, having had at least 1 relapse in the previous year while on therapy, and at least 9 T2 
hyperintense lesions in cranial MRI or at least 1 Gd-enhancing lesion, or having an unchanged 
or increased relapse rate in the prior year as compared to the previous 2 years. 

 
Clinical trial data from the DECIDE study demonstrated consistent treatment effects in the highly 
active disease subgroup. Compared with interferon beta-1a intramuscular (n=440), Zinbryta (n=404) 
led to reductions on ARR (rate ratio 0.52 [95% CI: 0.42, 0.64], p<0.0001), number of new or newly 
enlarging T2 hyperintense lesions (lesion mean ratio 0.46 [95% CI: 0.37, 0.57], p<0.0001), and 
24 weeks confirmed disability progression (hazard ratio 0.60 [95% CI: 0.40, 0.89], p=0.012).  
 

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Figure 1: Percentage of patients relapse-free (DECIDE study) 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 2: Proportion of patients with 24 week confirmed disability (DECIDE study) 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Zinbryta in one or more subsets of the paediatric population in treatment of multiple sclerosis (see 
section 4.2 for information on paediatric use). 
 

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Time on study (weeks) 
Number of patients at risk 

Baseline 
IFN beta-1a 

IFN beta-1a 

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Time on study (weeks) 
Average number of patients at risk 

Baseline 
IFN beta-1a 

IFN beta-1a 

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5.2 Pharmacokinetic properties 
 
Daclizumab beta pharmacokinetics are well described by a two-compartment model with first-order 
absorption and elimination. 
 
Absorption 
Following subcutaneous administration of daclizumab beta, the median time to reach maximum serum 
concentrations (Tmax) ranged from 5 to 7 days. The absolute bioavailability of daclizumab beta 150 mg 
subcutaneously administered was approximately 90% based on a cross-study population 
pharmacokinetic analysis of subcutaneous and intravenous dosing. 
 
Distribution 
Following subcutaneous administration of daclizumab beta 150 mg every 4 weeks, steady-state serum 
daclizumab beta concentrations were achieved by the 4th dose and daclizumab beta accumulated to a 
level approximately 2.5-fold compared to a single dose. At steady state, daclizumab beta mean 
maximum serum concentration (Cmax), minimum serum concentration (Cmin) and area under the serum 
concentration-time curve over the dosing interval (AUCtau) values were approximately 
30 micrograms/mL, 15 micrograms/mL and 640  day*micrograms/mL, respectively, with inter-patient 
variability (% CV) of approximately 40%. 
 
Based on the cross-study population pharmacokinetic analysis, the steady-state volume of distribution 
of daclizumab beta is 6.34 L in a patient with a body weight of 68 kg (approximate median of 
evaluated patients). This small volume of distribution indicates that daclizumab beta is primarily 
confined to the vascular and interstitial spaces. 
 
Biotransformation 
The exact metabolic pathway for daclizumab beta has not been characterised. As an IgG1 monoclonal 
antibody, daclizumab beta is expected to undergo catabolism to peptides and amino acids in the same 
manner as endogenous IgG. Daclizumab beta is not expected to undergo metabolism by hepatic 
enzymes such as CYP isoenzymes (see section 4.5). 
 
Elimination 
As an IgG1 monoclonal antibody, daclizumab beta is not expected to undergo renal elimination. 
 
Based on the cross-study population pharmacokinetic analysis, the clearance of daclizumab beta is 
0.212 L/day with a terminal half-life value of approximately 21 days. Daclizumab beta clearance in 
patients who developed neutralising antibodies was, on average, 19% higher (see section 4.8 
Immunogenicity). 
 
Linearity/non-linearity 
Consistent with results from individual studies, a cross-study population pharmacokinetic analysis 
indicated that daclizumab beta exposure is more than dose-proportional in the 50 mg to 100 mg 
subcutaneous dose range and is dose proportional in the 100 mg to 300 mg subcutaneous dose range. 
 
Pharmacokinetic/pharmacodynamic relationship(s) 
Within the studied regimens of daclizumab beta 150 mg and 300 mg administered subcutaneous every 
4 weeks in MS patients, there was no clear relationship between daclizumab beta exposure and clinical 
efficacy endpoints (ARR, T2 lesions and Gd-enhancing lesions) or safety endpoints of interest (serious 
infection status, moderate or severe cutaneous adverse reaction, and AST/ALT > 5 times the ULN). 
 
Special populations 
 
Renal or hepatic impairment 
No studies were conducted to evaluate daclizumab beta pharmacokinetics in patients with renal or 
hepatic impairment. Daclizumab beta is not expected to undergo renal elimination or metabolism by 
hepatic enzymes (see section 4.2). 

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Weight 
Based on the cross-study population pharmacokinetic analysis, body weight accounted for less than 
40% of the inter-patient variability in daclizumab beta clearance. No meaningful differences in clinical 
efficacy or safety were observed among the subgroups of MS patients by weight quartile in the 
DECIDE study. 
 
Age and gender 
Based on the cross-study population pharmacokinetic analysis, daclizumab beta pharmacokinetics 
were not influenced by age (range: 18 to 66 years; n=1670) or gender (n = 567 males and 
1103 females). 
 
Race 
No pharmacokinetic differences were observed between Japanese and Caucasian healthy volunteers. 
 
5.3 Preclinical safety data 
 
Preclinical safety studies were conducted in cynomolgus monkeys due to species specificity of 
daclizumab beta binding only to human or primate CD25. 
 
Carcinogenesis 
Carcinogenicity studies with daclizumab beta have not been conducted.  In two 9 month studies in 
monkeys there were no pre-neoplastic or neoplastic tissue observed. 
 
Mutagenesis 
Genotoxicity studies have not been conducted. 
 
Reproductive toxicity 
Daclizumab beta did not affect reproductive capacity in female and male cynomolgus monkeys (AUC 
in females and males up to 85 and 100 times higher than the exposure at the clinical dose respectively). 
There was no effect on foetal development and no evidence of teratogenicity. Daclizumab beta had no 
effect on peri- and post-natal development from birth to up to 6 months in the offspring. Exposures 
(AUC) in these studies ranged from 55 to 140 times that observed with the clinical 
dose.  Daclizumab beta was detected in the milk of 11/14 lactating monkeys at levels that were 
<0.122% of the maternal serum levels, with no adverse reactions observed in the off-spring.  
 
Toxicology 
In two 9 month studies conducted in cynomolgus monkeys daclizumab beta was subcutaneously 
administered at bi-weekly doses of 10-200 mg/kg. 
Chronic administration of daclizumab beta at all doses increased the incidence of skin findings 
(compared to those observed in control animals). These findings (dry, red raised patchy areas of the 
skin, as compared to controls, that correlated microscopically with acanthosis/hyperkeratosis and sub-
acute to chronic inflammation) were characterised predominantly as mild to moderate, with one case 
assessed as severe. 
 
A dose dependent increase in incidence of microglial aggregates above background was observed in 
the brain and spinal cord of monkeys treated with ≥35 mg/kg, (AUC 27 times higher than the clinical 
dose). Following a recovery period of up to 12 weeks, there was evidence of reversibility. Microglial 
aggregates in monkeys did not increase in incidence or severity with increased duration of dosing and 
were not associated with neuronal damage or neurobehavioral effects. A small subset of microglial 
aggregates were associated with microhaemorrhage but with no evident functional sequelae in 
monkeys. 
 
In vitro investigative studies suggest that microglial aggregates are not due to a direct effect of 
daclizumab beta on microglial cells but are likely to be attributable to an increase in local IL-2 
bioavailability. 

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The clinical relevance of microglial aggregates is unknown, however no deleterious neurologic effects 
attributed to the microscopic change have been observed in monkeys. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sodium succinate 
Succinic acid 
Sodium chloride 
Polysorbate 80 
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product should not be mixed with other 
products. 
 
6.3 Shelf life 
 
3 years. 
 
Zinbryta can be stored at room temperature (up to 30oC) in the original pack for 30 days.  
Do not place Zinbryta back into the refrigerator after warming to room temperature. 
If Zinbryta has been outside of the refrigerator for more than a total of 30 days or if you are not sure 
how long Zinbryta has been at room temperature, it should be discarded. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2oC-8oC).  
Do not freeze.  
Store in the original package in order to protect from light. 
 
For additional information on storage at room temperature, see section 6.3. 
 
6.5 Nature and contents of container 
  
Pre-filled syringe made of glass (Type 1) with a rubber stopper and thermoplastic rigid needle shield 
containing 1 mL of solution. A 29 gauge, 0.5 inch staked needle is pre-affixed to the syringe. 
 
Pack sizes:  
- Pack containing one 150 mg pre-filled syringe. 
- 3 month multipack containing three 150 mg pre-filled syringes (3 boxes containing 1 syringe each).  
 
A pre-filled syringe of Zinbryta is contained within a spring-powered pen injector called Zinbryta Pen. 
The syringe inside the pen is a pre-filled syringe made of glass (Type 1) with a rubber stopper and 
thermoplastic rigid needle shield, containing 1 mL of solution. A 29 gauge, 0.5 inch staked needle is 
pre-affixed to the syringe. 
 
Pack sizes:   
- Pack containing one 150 mg pre-filled pen. 
- 3 month multipack containing three 150 mg pre-filled pens (3 boxes containing 1 pen each). 
 
Not all pack sizes may be marketed. 

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6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
BIOGEN IDEC Limited 
Innovation House 
70 Norden Road 
Maidenhead 
Berkshire 
SL6 4AY 
United Kingdom 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1107/001 
EU/1/16/1107/002 
EU/1/16/1107/003 
EU/1/16/1107/004 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 01 July 2016 
 
 
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. 
 

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


20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 

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

B.  CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 
C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
D.  CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 

 

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

Name and address of the manufacturer of the biological active substance: 

Biogen Inc 
5000 Davis Drive 
Research Triangle Park 
North Carolina 
27709 
UNITED STATES 
 

Name and address of the manufacturer responsible for batch release 

Biogen (Denmark) Manufacturing ApS 
Biogen Allé 1 
Hillerød 
DK-3400 
Denmark 

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  
 

The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 

The marketing authorisation holder shall submit the first periodic safety update report for this 
product within 6 months following authorisation.  

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

• Risk Management Plan (RMP) 
 

The 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.  

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• Additional risk minimisation measures  
 

Hepatic Risk Management Guide for Physicians, Patient Card and Acknowledgment Form 

Prior to launch of Zinbryta in each Member State the Marketing Authorisation Holder (MAH) must 
agree about the content and format of the educational programme, including communication media, 
distribution modalities, and any other aspects of the programme, with the National Competent 
Authority.  

The MAH shall ensure that in each EU MS where Zinbryta is marketed, all prescribers are provided 
with an educational package, aiming at preventing and/or minimising the risk of serious hepatic injury 
(potentially life threatening or fatal) and informing the patients about the unpredictability of these 
events and containing the following elements: 

• Summary of Product Characteristics (SmPC) and Package Leaflet (PL); 

• Hepatic Risk Management Guide for Physicians; 

• Patient Card; 

• Acknowledgment  Form. 

  

 

The Hepatic Risk Management Guide for Physicians should inform HCPs about: 

• The unpredictable risk of serious and potentially fatal hepatic injury at any time during 
treatment and up to several months after the last dose; 

• The contraindication in all patients with pre-existing hepatic disease or hepatic impairment; 

• The recommendation not to initiate treatment in patients with autoimmune disorders (other than 
multiple sclerosis); 

• The need to screen for hepatitis B and C prior to treatment initiation and to recommend patients 
who test positive for HBV or HCV infection to consult with a physician with expertise in the 
treatment of those conditions. 

• The recommendation not to initiate Zinbryta in patients with ALT or AST ≥ 2 times the ULN, 
and to discontinue treatment in patients with ALT or AST > 3 times the ULN; 

• The importance of monitoring the liver function (AST, ALT and total bilirubin levels) at least 
monthly (or more frequently as clinically indicated) as close as possible before each treatment 
administration, and for up to six months after the last dose; 

• The management of patients receiving Zinbryta and presenting with signs and symptoms of 
potential hepatic injury, including treatment discontinuation, potential consideration of 
additional therapy, and prompt referral to a hepatologist; 

• The need to exercise caution regarding concomitant use of other hepatotoxic medications; 

• The need to provide the patient with the Patient Card and the Acknowledgment Form, discuss 
their content before starting Zinbryta treatment, informing patients of the risk of hepatic injury, 
the need for periodic monitoring and the signs or symptoms suggestive of hepatic dysfunction. 

 

 

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The Patient Card should: 

• Be designed to enable physicians to present patient-friendly information; 

• Inform patients about the unpredictable risk of serious and potentially fatal hepatic injury at any 
time during treatment and up to several month after treatment; 

• Inform patients about the need for monitoring of liver function during treatment and for up to 6 
months after the last dose of Zinbryta; 

• Educate the patient on the importance of: 

o Adhering to the monthly liver function tests (or more frequently, as clinically 
indicated during treatment); 

o Recognising the symptoms and signs of possible hepatic injury so that they are aware 
of situations in which they should contact a physician in a timely manner;  

 

The Acknowledgment Form aims at providing information on the risk of serious hepatic injury to 
patients. It should include the following elements: 
 
• Prior to treatment (re)start, confirmation of: 

o A discussion between the physician and the patient about the risk of serious and 
potentially fatal hepatic injury and the unpredictable nature of such reactions and 
about the possibility of having to switch treatment in case of levels of ALT or 
AST > 3 times the ULN; 

o Patient understanding of the risk information provided;  

o Receipt of a copy of the acknowledgement form; 

o Receipt of the Patient Card; 

• The importance of the liver function monitoring, at least monthly during treatment (or more 
frequently as clinically indicated), and for up to 6 months after the last dose; 

• The importance of detecting signs and symptoms which might indicate hepatic injury, and if any 
of these occur, to promptly contact their physician; 

• Patient details, signature and date; 

• Prescriber name, signature and date. 

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ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 

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A. LABELLING 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zinbryta 150 mg solution for injection in pre-filled syringe 
Zinbryta 150 mg solution for injection in pre-filled pen 
daclizumab beta 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled syringe contains 150 mg of daclizumab beta in 1 mL 
Each pre-filled pen contains 150 mg of daclizumab beta in 1 mL 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium succinate, succinic acid, sodium chloride, polysorbate 80, water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection  
 
1 pre-filled syringe  
1 pre-filled pen  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use 
Read the package leaflet before use.  
For single use only. 
 
Open here 
Tear here 
 
 
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 
 

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8. EXPIRY DATE 
 
EXP 
 
Can be stored at room temperature (up to 30°C) for a single period of up to 30 days. Must not be 
returned to refrigerator after storage at room temperature. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Store in the original package 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 
 
Biogen Idec Ltd. 
Innovation House 
70 Norden Road 
Maidenhead 
Berkshire  
SL6 4AY 
United Kingdom 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1107/001 
EU/1/16/1107/003 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Zinbryta 
 
 

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

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
MULTIPACK OUTER CARTON (with blue box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zinbryta 150 mg solution for injection in pre-filled syringe 
Zinbryta 150 mg solution for injection in pre-filled pen 
daclizumab beta 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled syringe contains 150 mg of daclizumab beta in 1 mL 
Each pre-filled pen contains 150 mg of daclizumab beta in 1 mL 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium succinate, succinic acid, sodium chloride, polysorbate 80, water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection  
 
Multipack: 3 (3 packs of 1) pre-filled syringes.  
 
Multipack: 3 (3 packs of 1) pre-filled pens. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use 
Read the package leaflet before use.  
For single use only. 
 
 
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 
 
 

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8. EXPIRY DATE 
 
EXP 
 
Can be stored at room temperature (up to 30°C) for a single period up of to 30 days. Must not be 
returned to refrigerator after storage at room temperature. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Store in the original package 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 
 
Biogen Idec Ltd. 
Innovation House 
70 Norden Road 
Maidenhead 
Berkshire  
SL6 4AY 
United Kingdom 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1107/002 
EU/1/16/1107/004 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Zinbryta 
 
 

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

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
MULTIPACK INNER CARTON (without blue box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zinbryta 150 mg solution for injection in pre-filled syringe 
Zinbryta 150 mg solution for injection in pre-filled pen 
daclizumab beta 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each pre-filled syringe contains 150 mg of daclizumab beta in 1 mL 
Each pre-filled pen contains 150 mg of daclizumab beta in 1 mL 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium succinate, succinic acid, sodium chloride, polysorbate 80, water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection  
 
1 pre-filled syringe. Component of a multipack, cannot be sold separately. 
1 pre-filled pen. Component of a multipack, cannot be sold separately. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use 
Read the package leaflet before use.  
For single use only. 
 
Open here 
Tear here 
 
 
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 
 
 

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8. EXPIRY DATE 
 
EXP 
 
Can be stored at room temperature (up to 30°C) for a single period of up to 30 days. Must not be 
returned to refrigerator after storage at room temperature. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Store in the original package 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 
 
Biogen Idec Ltd. 
Innovation House 
70 Norden Road 
Maidenhead 
Berkshire 
SL6 4AY 
United Kingdom 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1107/002 
EU/1/16/1107/004 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Zinbryta 
 
 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Pre-Filled Syringe Label 
 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Zinbryta 150 mg injection  
daclizumab beta 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 mL 
 
 
6. OTHER 
 
 

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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Pre-Filled Pen Label 
 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Zinbryta 150 mg injection  
daclizumab beta 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 mL 
 
 
6. OTHER 
 
 

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B. PACKAGE LEAFLET 
 

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Package leaflet: Information for the user 
 

Zinbryta 150 mg solution for injection in pre-filled syringe 
Zinbryta 150 mg solution for injection in pre-filled pen 

daclizumab beta 
 

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. 
 
In addition to this leaflet you will be given a Patient Card by your doctor. This has important 
safety information that you need to know before and during treatment with Zinbryta. 
 
• Keep this leaflet and the Patient Card. You may need to read them again. Keep the leaflet and 

Card with you during treatment and for 6 months after the last dose of Zinbryta, since side 
effects may occur even after you have stopped treatment. 

• If you have any further questions, ask your doctor. 
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
• If you get any side effects, talk to your doctor. This includes any possible side effects not listed 

in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Zinbryta is and what it is used for  
2. What you need to know before you use Zinbryta 
3. How to use Zinbryta 
4. Possible side effects 
5. How to store Zinbryta 
6. Contents of the pack and other information 
7.  Instructions for injecting Zinbryta 
 
 
1. What Zinbryta is and what it is used for 
 
The active substance in Zinbryta is daclizumab beta. This is a type of medicine called a monoclonal 
antibody. 
 
What Zinbryta is used for 
Zinbryta is used to treat relapsing forms of multiple sclerosis (MS) in adults who have failed to 
respond despite therapy with at least two MS treatment and who cannot be given other treatments. 

In MS, the body’s immune system causes inflammation which damages the protective sheath (called 
myelin) around the nerves in the central nervous system (including the brain and spinal cord). This 
loss of myelin is called demyelination. This stops nerves from working properly. 

People with relapsing MS have repeated attacks (relapses) of symptoms caused by their nerves not 
working properly. These symptoms vary from patient to patient but usually involve problems such as 
difficulty with walking, vision and balance. 

Symptoms may disappear completely after the relapse is over but, over time, some problems may 
remain between relapses and interfere with daily activities. 
 

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How Zinbryta works 
Zinbryta works by stopping the body’s immune system from damaging your brain and spinal 
cord. This can help to reduce the number of relapses that you have and slow down the disabling 
effects of MS. Treatment with Zinbryta can help to prevent you from getting worse, although it will 
not cure MS. Your doctor will decide whether Zinbryta is the right medicine for you. 
 
 
2. What you need to know before you use Zinbryta 
 
Do not use Zinbryta 
- if you have previously had a serious allergic reaction to any form of daclizumab, or any of the 

other ingredients of this medicine listed in section 6. 
- if you have liver problems.  
 
Warnings and precautions 
Talk to your doctor before using Zinbryta: 
-  if you have any other autoimmune disorders in addition to MS 
- if you are taking, have recently taken or might take any other medicines and herbal 

supplements.  Your doctor will evaluate if any medicines or supplements you are taking have 
liver side effects and whether you should continue these medicines while taking Zinbryta 

- if you have depression or have had it in the past. 
-  if you have a serious infection, such as pneumonia. 
- if you have ever had tuberculosis (also called TB) or live in a region where TB infections are 

common, you may be at greater risk of TB. You may be tested for TB before starting Zinbryta 
and monitored during treatment. 

 

Possible liver problems 

Zinbryta may cause serious liver problems that may be life-threatening or result in death.  Serious liver 
problems can occur both early after starting treatment with Zinbryta, any time during treatment and 
several months after discontinuing treatment. Even if you have had no previous liver problems, your 
doctor will carry out blood tests to test your liver function. You will need: 
-  a blood test before starting treatment to check your liver function and if you have hepatitis B 

and C. If your blood test shows that you have some liver problems, your doctor will decide 
whether to start Zinbryta 

-  at least monthly blood tests during treatment, as close as possible before each dose of 
Zinbryta, and more often if your doctor decides this is necessary 

-  tests for up to 6 months after stopping treatment. Side effects may occur even after stopping 
treatment (see serious side effects in section 4). 

 

It is very important that you have these regular blood tests. If you do not not undergo your 
scheduled blood tests your doctor may decide to stop treatment with Zinbryta. 

You will be given a Patient Card with further information about the things to watch out for while 
taking Zinbryta. Keep this Card with you during treatment and for 6 months afterwards. When you 
have any medical treatment, even if it is not for your MS, show the Patient Card to the doctor, 
pharmacist or nurse. 

If you experience any of the following, contact your doctor immediately: 

• unexplained nausea (feeling sick) 
• vomiting (being sick) 
• stomach pain 
• increased tiredness 
• loss of appetite 
• your skin or the whites of your eyes turn yellow 

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• dark (tea-coloured) urine   
 
These symptoms may suggest problems with your liver. If you do develop liver problems your MS 
doctor may stop your treatment with Zinbryta and refer you to a liver specialist (see section 4, Possible 
side effects). 
 
Children and adolescents 
Zinbryta is not to be used in children and adolescents younger than 18 years old. The safety and 
effectiveness of Zinbryta in this age group are not known. 
 
Elderly 
Zinbryta has had very little testing in people older than 55 years old. If you are over 55 your doctor 
may still prescribe Zinbryta. 
 
Other medicines and Zinbryta 
Tell your doctor if you are taking, have recently taken or might take any other medicines  and herbal 
supplements. Your doctor will evaluate if any medicines or supplements you are taking have liver side 
effects and whether you should continue these medicines while receiving Zinbryta. 
 
Vaccinations 
If you need a vaccination, ask your doctor first because Zinbryta may affect how well vaccines work. 
Seasonal flu vaccines (inactive vaccine) have been shown to be effective when given to patients taking 
Zinbryta. However, Zinbryta’s effect on other vaccines (live vaccines) is not known. 
 
Pregnancy and breast-feeding 
As data on use of Zinbryta during pregnancy are limited, the risk to the baby and benefit to the mother 
should be taken into consideration. If you are pregnant or breast-feeding, think you may be pregnant or 
are planning to have a baby, ask your doctor for advice before taking this medicine. 
 
It is not known whether Zinbryta passes into breast milk. Your doctor will help you decide whether 
you should stop breast-feeding, or stop using Zinbryta.  
 
Driving and using machines 
Zinbryta is not expected to affect your ability to drive and use machines. Your doctor will tell you 
whether your illness allows you to drive vehicles and use machines safely. 
 
Zinbryta contains a small amount of sodium 
Each dose of Zinbryta contains 0.14 mmol sodium. It is essentially ‘sodium-free’ and can be used by 
people on a sodium-restricted diet. 
 
 
3. How to use Zinbryta 
 
Zinbryta will be prescribed to you by a doctor experienced in the treatment of MS. 
 
Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not 
sure. 
 
Recommended dose 
The dose of Zinbryta is 150 mg every month. 
Try to do your injection on the same day each month, to help you remember it. For example, inject on 
the first day of each month.  
 
You will also have a blood test to check your liver every month, as close as possible before each dose 
of Zinbryta, and more often if your doctor decides this is necessary. It is very important that you do 

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not miss this blood test. Try to keep to a set day for it each month. Contact your doctor if you think 
you may have missed a blood test.  
 
Injecting yourself  
Zinbryta is injected under the skin (subcutaneously) into your thigh, stomach or back of your upper 
arm. Detailed instructions for injecting Zinbryta are given in section 7, Instructions for injecting 
Zinbryta. 
 
Your doctor or nurse should train you to give yourself the injections. Read and follow the advice given 
in section 7. 
 
If you have trouble handling the syringe/pen, tell your doctor or nurse who may be able to help. 
 
How long to use Zinbryta 
Your doctor will tell you how long you need to keep using Zinbryta. Do not make changes unless your 
doctor tells you to. 
 
If your doctor has told you to stop using your medicine, do not restart unless your doctor tells you to. 
If your MS does not respond to Zinbryta, your doctor may decide to stop your treatment with Zinbryta. 
 
If you use more Zinbryta than you should 
If you have injected more than your usual dose, and you notice any side effects, or are concerned, 
speak with your doctor or nurse. Patients have received double the recommended dose of Zinbryta 
with no serious extra side effects. 
 
If you forget to take Zinbryta 
Zinbryta is injected monthly. Try to keep to a particular day of the month to help remember your 
injection. 
 
• If you do forget a dose, and it is within 2 weeks of your missed dose, inject as soon as you can. 

Then carry on as normal, sticking to your usual injection day. 
• However, if it is more than 2 weeks from your missed dose, skip the missed dose and take your 

next dose on your usual day.  
 
In either case, do not use two injections to make up for a missed dose. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. Do not try 
to treat any side effects yourself, but contact your doctor or nurse. Some side effects may require 
your doctor to interrupt your treatment and refer you to a specialist. 
 
Serious side effects:  

Liver problems:  

(Common - may affect up to 1 in 10 people) 
• unexplained nausea (feeling sick) 
• vomiting (being sick) 
• stomach pain 
• increased tiredness 
• loss of appetite (anorexia) 
• your skin or the whites of your eyes turn yellow 
• dark (tea-coloured) urine   
 

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(Uncommon – may affect up to  1 in 100 people) 
• Severe inflammation of the liver which might be life-threatening or result in death  
 
Contact your doctor immediately. These may be signs of a serious liver problem. Your 
Patient Card has more information about these side effects. 
 
Skin reactions:  
(Common - may affect up to 1 in 10 people) 
• severe wide-spread rash.  
 
Depression:  
(Uncommon – may affect up to 1 in 100 people) 
• feeling unusually sad, hopeless or bad about yourself  
• irritability, getting upset easily 
• nervousness, anxiety 
• thoughts of hurting yourself or suicide 
 

Lung infections: 

(Common - may affect up to 1 in 10 people) 
• lung infection (e.g. pneumonia, bronchitis) 
 
Low red blood cell counts (autoimmune haemolytic anaemia): 
(Uncommon – may affect up to 1 in 100 people) 
• paleness 
• increased tiredness 
• dark urine 
• shortness of breath 
• your skin or the whites of the eyes turn yellow 
Increased tiredness, dark urine and skin or whites of the eyes turning yellow also may be symptoms of 
liver problems, see section above on liver problems. 
 
Inflammation of the bowel (colitis): 
(Common – may affect up to 1 in 10 people) 
• diarrhoea that does not go away 
• stomach pain 
• fever 
• blood in your stools  
Stomach pain may also be a symptom of liver problems, see section above on liver problems. 
 
Low level of a type of white blood cells (called lymphocytes): 
Zinbryta could reduce your level of these white blood cells so you will have a blood test every 3 months. 

 
Contact your doctor immediately if you get any serious side effects. 
 
Other side effects:  
 
Very common side effects  
(These may affect more than 1 in 10 people) 
• infections of the airways, such as coughs and colds (nasopharyngitis, upper respiratory tract 

infection) 
• increases in liver enzymes in the blood (these will show up in blood tests) 

 
 

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Common side effects   
(These may affect up to 1 in 10 people) 
• flu (influenza) 
• sore throat, tonsillitis (pharyngitis, laryngitis) 
• runny nose (rhinitis) 
• skin rashes, including inflamed, irritated, itchy, dry or peeling skin (dermatitis, eczema, 

psoriasis) 
• skin infection (folliculitis, acne) 
• decreases in the amount of white blood cells (these will show up in blood tests) 
• increases in body temperature (fever) 
• inflamed or enlarged lymph nodes (lymphadenopathy, lymphadenitis) 
• diarrhoea 
• changes in your blood (anaemia) which may make you feel weak 
 
Uncommon side effects 
(These may affect up to 1 in 100 people) 
• Immune disorder that can affect the lungs, skin and lymph nodes (sarcoidosis) 
 
Reporting of side effects 
If you get any side effects, talk to your doctor. This includes any possible side effects not listed in 
this leaflet. Do not try to treat any side effects yourself. 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 Zinbryta 
 
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 after ‘EXP’. 
The expiry date refers to the last day of that month. 
 
• Keep the Zinbryta pre-filled syringe/pen in its original package to protect from light. Keep the 

pack closed until you need to use a new syringe/pen. 
• Store in a refrigerator (2oC to 8oC).  

o Do not freeze. Throw away any Zinbryta that is accidentally frozen. 
• If a refrigerator is not available, Zinbryta syringes/pens can be stored at room temperature (up to 

30oC) in the original pack for up to 30 days.  
o Make sure Zinbryta is out of the refrigerator for no longer than 30 days. 
o If Zinbryta has been outside of the refrigerator for more than a total of 30 days or if you are 
not sure how long Zinbryta has been at room temperature, throw the syringe/pen away (see 
section 7, Instructions for injecting Zinbryta).  

• Do not place Zinbryta back into the refrigerator after warming to room temperature. 
 
Additional information 
Do not use this medicine if you notice that: 
• the syringe/pen is cracked or broken. 
• the solution is cloudy or you can see particles floating in it. 
• the solution is any other colour than colourless to slightly yellow. 
• the pen has been dropped or is visibly damaged. 
 
Disposal 
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. 
 

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43 

 
6. Contents of the pack and other information 
 
What Zinbryta contains  
 
The active substance is daclizumab beta. 
 
Each pre-filled syringe contains 150 mg of daclizumab beta in 1 mL solution for injection. 
Each pre-filled pen contains 150 mg of daclizumab beta in 1 mL solution for injection. 
 
The other ingredients are sodium succinate, succinic acid, sodium chloride, polysorbate 80, water for 
injections (see section 2 ‘Zinbryta contains a small amount of sodium’). 
 
What Zinbryta looks like and contents of the pack 
Zinbryta is a colourless to slightly yellow, clear to opalescent liquid contained within a syringe/pen.  
 
Pack sizes: Each pack contains one pre-filled glass syringe/pre-filled pen with an attached needle, 
ready to inject. A multipack of three packs of one syringe/pen is also available. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder  
Biogen Idec Ltd. 
Innovation House 
70 Norden Road 
Maidenhead 
Berkshire 
SL6 4AY 
United Kingdom 
 
Manufacturer  
Biogen (Denmark) Manufacturing ApS 
Biogen Allé 1 
Hillerød 
DK-3400 
Denmark 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
 
België/Belgique/Belgien  
Biogen Belgium N.V./S.A.  
 +32 2 219 12 18  
 

Lietuva  
UAB "JOHNSON & JOHNSON"  
 +370 5 278 68 88  
 

България  
ТП ЕВОФАРМА  
 +359 2 962 12 00  
 

Luxembourg/Luxemburg 
Biogen Belgium N.V./S.A.  
 +32 2 219 12 18  

Česká republika 
Biogen (Czech Republic) s.r.o.  
 +420 255 706 200  

Magyarország 
Biogen Hungary Kft.  
 +36 (1) 899 9883  

Danmark 
Biogen (Denmark) A/S  
 +45 77 41 57 57  

Malta 
Pharma MT limited  
 +356 213 37008/9  

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Deutschland 
Biogen GmbH  
 +49 (0) 89 99 6170  
 

Nederland 
Biogen Netherlands B.V.  
 +31 20 542 2000  

Eesti 
UAB "JOHNSON & JOHNSON" Eesti filiaal 
 +372 617 7410 
 

Norge  
Biogen Norway AS  
 +47 23 40 01 00  

Ελλάδα  
Genesis Pharma SA  
 +30 210 8771500  
 

Österreich  
Biogen Austria GmbH  
 +43 1 484 46 13  

España  
Biogen Spain SL  
 +34 91 310 7110  
 

Polska  
Biogen Poland Sp. z o.o.  
 +48 22 351 51 00  

France  
Biogen France SAS  
 +33 (0)1 41 37 95 95  
 

Portugal  
Biogen Portugal Sociedade Farmacêutica 
Unipessoal, Lda  
 +351 21 318 8450  

 
Hrvatska  
Medis Adria d.o.o.  
 +385 (0) 1 230 34 46  
 
Ireland  
Biogen Idec (Ireland) Ltd.  
 +353 (0)1 463 7799  
 

România  
Johnson & Johnson Romania S.R.L. 
 +40 21 207 18 00  
 
Slovenija  
Biogen Pharma d.o.o.  
 +386 1 511 02 90  

Ísland  
Icepharma hf  
 +354 540 8000  
 

Slovenská republika  
Biogen Slovakia s.r.o.  
 +421 2 323 340 08  

Italia  
Biogen Italia s.r.l.  
 +39 02 584 9901  

Suomi/Finland  
Biogen Finland Oy  
 +358 207 401 200 
 

Κύπρος  
Genesis Pharma Cyprus Ltd  
 +357 22 769946  
 

Sverige  
Biogen Sweden AB  
 +46 8 594 113 60  

Latvija  
UAB "JOHNSON & JOHNSON" filiāle Latvijā 
 +371 678 93561 
 

United Kingdom  
Biogen Idec Limited  
 +44 (0) 1628 50 1000  
 

  
 
This leaflet was last revised in  
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency website: 
http://www.ema.europa.eu.  
 
 
Instructions overleaf  

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45 

 
 
7. Instructions for injecting Zinbryta 
 
How to inject Zinbryta 
Read the instructions before you start using Zinbryta and each time you get a refill of your 
prescription. There may be new information. This information does not take the place of talking to 
your doctor or nurse about your medical condition or your treatment. 
 
Note: 
• Before you use the Zinbryta pre-filled syringe for the first time, your doctor or nurse should 

show you or your carer how to prepare and inject the Zinbryta pre-filled syringe. 
 Do not use more than one pre-filled syringe per month. 

• Zinbryta pre-filled syringe is for injecting the medicine under the skin only (subcutaneous). 
• Each Zinbryta pre-filled syringe can be used once only. Do not share Zinbryta pre-filled 

syringe with anyone else.   
 
 
 
Supplies needed for your Zinbryta injection 
 
• Zinbryta pre-filled syringe 

 
 
 
 
 
 
 
 
 
 
Additional supplies which are not included in the pack (See Figure B): 
• alcohol wipe 
• gauze pad 
• adhesive bandage or plaster 
 
Ask your doctor, pharmacist, or nurse for instructions on throwing away used syringes. 

 
 

 
 
 
 
 
 
 
 
 
 
 
 

150 mg Prefilled Syringe  

Figure A 

Figure B 

Alcohol 
Wipe 

Gauze 
Pad 

Adhesive 
Bandage 

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Parts of the Zinbryta pre-filled syringe (See Figure C) 
 

 
Needle 
Cover Medicine Plunger 

Finger 
Flange 

Glass 
Barrel 

Figure C 

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Preparing for your injection 
 
Note: 
 
• Before you prepare your injection, take the syringe out of the fridge and let it warm to room 

temperature. This takes around 30 minutes. 
 Do not use external heat sources such as hot water to warm Zinbryta pre-filled 

syringe. 
• The Finger Flange will allow you to better grip the syringe and should remain attached. 
 
Step 1:  Collect your supplies and wash your hands  
• Use a well-lit, clean, flat surface to work on, like a table. Collect all the supplies you will need to 

give yourself or to receive an injection. 
• Wash your hands with soap and water. 

 
Step 2:  Check The Zinbryta Pre-filled Syringe 
 

• Check the expiry date on the Zinbryta pre-
filled syringe (See Figure D). 
  Do not use the Zinbryta pre-filled 

syringe past the expiry date. 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

• Check that the Zinbryta medicine is 
colourless or slightly yellow (See Figure 
E). 

  Do not use the Zinbryta pre-filled 
syringe if the liquid is cloudy, or has 
floating particles in it. 

o You might see air bubbles in the 
Zinbryta medicine. This is normal 
and the bubbles do not need to be 
expelled before your injection. 

 

Figure D 

Figure E 

Medicine 

Expiry 
Date 

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Giving the Injection  
 
Step 3:  Choose and clean your injection site 
 
• Zinbryta pre-filled syringe is for 

subcutaneous injection (injection into skin). 
 

• Zinbryta pre-filled syringe should be 
injected into the abdomen, thigh, or the 
back of the upper arm (see Figure F). 

 
  Do not inject directly into your belly 

button. 
 

  Do not inject into an area of the body 
where the skin is irritated, tender, 
red, bruised, tattooed, infected or 
scarred. 

 
• Choose an injection site and wipe the skin 

with an alcohol wipe. 
 

• Let the injection site dry on its own before 
injecting the dose. 

 
 Do not touch or blow on this area again 

before giving your injection. 
 

 

 
 

Step 4:  Firmly remove the needle cover 
 
• Using one hand, hold the syringe by the 

glass barrel. Be sure that this hand is not 
pushing on the Finger Flange. With your 
other hand, firmly grasp the needle cover 
and pull it straight off the needle (See 
Figure G).   

 
 Use caution when removing the needle 

cover to avoid getting a needle injury. 
 
 Do not touch the needle.  
 
 Caution - do not recap the Zinbryta pre-

filled syringe.  You could get a needle 
injury. 

 
 

Figure F 

Thigh 

Abdomen 

Back of 
Upper  

Arm 

Needle 
Cover 

Needle 

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Step 5:  Gently pinch your injection site 
 
• Gently pinch the skin around the cleaned 

injection site using thumb and forefinger to 
create a slight bulge. (See Figure H.) 

 
 
 
 
 
 
 
 
 
 
 

Step 6:  Inject Medicine 
 
• Hold the Zinbryta pre-filled syringe at a 

45°-90° angle to the injection site (see 
Figure I). Quickly insert the needle straight 
into the skin fold until the needle is fully 
under the skin. (See Figure I.) 

 
• After the needle is in, let go of your skin 

 
 Do not pull back on the plunger.   

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

• Slowly push the plunger all the way down 
until the syringe is empty. (See Figure J.) 

 
 Do not take the Zinbryta pre-filled syringe 

out of the injection site until you have 
pushed the plunger all the way down. 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Figure H 

Figure I 

Figure J 

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50 

 
Step 7:  Remove the pre-filled syringe from your injection site 
 
• Pull the needle straight out. (See Figure K.) 

 
 Caution - do not recap the Zinbryta 

pre-filled syringe. You could get a needle 
injury.   

 
 Do not reuse the Zinbryta pre-filled 

syringe. 

 
 
 
 
 
 
 
 
 
 
 
 
 
 

After your injection 
 
Step 8: Disposing of the used Zinbryta Pre-filled Syringe 
 

• Check with your doctor, pharmacist or nurse about the right way to throw away the used syringe. 
 

Step 9:  Care for your injection site 
 

• If needed, apply the gauze pad, adhesive bandage or plaster to the injection site. 
 

 
General Warnings 

 Do not reuse Zinbryta pre-filled syringe. 
 Do not share Zinbryta pre-filled syringe. 

• Keep Zinbryta pre-filled syringe and all medicines out of reach and sight of children. 
 

Storage 
• Recommended storage is controlled refrigeration 2°C to 8°C in the closed original carton to 

protect from light.  
• If needed, Zinbryta may be stored in the closed original carton without refrigeration up to 30°C 

for up to 30 days. 
 Do not place Zinbryta pre-filled syringe back into the refrigerator after warming to room 

temperature. 
 Do not freeze or expose to high temperatures. 

 

Figure K 

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51 

7. Instructions for injecting Zinbryta 
 

 Caution! Do not remove the cap until you are ready to inject. 
 
Read the instructions before you start using Zinbryta and each time you get a refill of your 
prescription. There may be new information. This information does not take the place of talking to 
your doctor or nurse about your medical condition or your treatment. 
 
Note: 
• Before you use the pen for the first time, your doctor or nurse should show you or your carer 

how to prepare and inject the pen. 
• The pen is for use under the skin only (subcutaneous). 
• Each pen can be used once only.  

 Do not share the pen with anyone else to avoid giving an infection to them or getting an 
infection from them.  

 Do not use more than 1 pen per month. 
 Do not use the pen if it has been dropped or is visibly damaged. 

 
 
Supplies needed for Zinbryta Pen injection: 
 
• 1 Zinbryta 150 mg Pen (see Figure A) 
 
Before Use – Parts of Zinbryta Pen (See Figure A): 
 
 
Figure A 
 
 
 
           Figure A 
 
 
 
 
 

 Caution! Do not remove the cap until you are ready to inject. If you remove the cap, do 
not re-cap the pen. Re-capping could cause the pen to lock. 

 
Additional supplies which are not included in the pack (See Figure B): 
 
 

 
          Figure B 

Green Stripes Visible 

Injection Status 
Window Body 

Medicine Window 

Medicine Visible 

Cap 

Alcohol Wipe Gauze Pad Adhesive Bandage 

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52 

 
Preparing for your injection 
 
Step 1: Remove the pen from the fridge 

a. Remove the pen from the carton in the fridge 30 minutes before giving your injection to allow it 
to warm to room temperature. 

 Do not use external heat sources, such as hot water, to warm the pen. 
 
Step 2: Collect your supplies and wash your hands 

a. Find a well-lit area and a clean, flat surface, like a table, and collect all the supplies you will need 
to give yourself, or to receive, an injection. 
b. Wash your hands with soap and water. 

 
 
Step 3: Check the Zinbryta Pen (Figure C) 
 
a. Check the injection status window. You 

should see green stripes. 
b. Check the expiry date. 
c. Check the medicine window and make sure 

the Zinbryta medicine is colourless to 
slightly yellow.   

 
 Do not use the pen if: 

• You do not see the green stripes in the 
injection status window. 

• It is expired. 
• The liquid is cloudy or contains floating 

particles. 
 
Note: You might see air bubbles in the medicine 
window. This is normal and will not affect your 
dose. 
 

 Do not use the pen if it has been dropped or 
is visibly damaged. 

 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure C 

Step 4: Choose and clean your injection site 
 
a. Choose an injection site in your thigh, 

abdomen, or the back of your upper arm (See 
highlighted areas in Figure D). 
• If some areas are too difficult for you to 

reach, ask a carer who has been trained to 
help you. 

 Do not inject into an area of your body 
where the skin is irritated, red, bruised, 
tattooed, infected, or scarred.   

 Do not inject directly into your belly 
button. 

 
b. Wipe your skin with an alcohol wipe. 

 Note: Do not touch or blow on this area 
before giving your injection. 

c. Let your injection site dry on its own before 
injecting your dose. 

 

 
Figure D 

 

Expiry 
Date 

Injection Status 
Window 

Medicine 
Window 

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53 

 
Giving your injection 
 
Step 5: Remove the Zinbryta Pen cap 
a. Pull the pen cap straight off and set it aside 

(See Figure E). Your pen is now ready to 
inject. 

 Warning! Do not touch, clean or manipulate 
the needle cover. You could get a needle 
injury or the pen may lock. 

 Do not re-cap the pen. This could lock the 
pen. 

 
 
 
 
 
 
 
 
 
 
 
 

Figure E 
Step 6: Give the injection 
a. Hold the pen over your injection site. Make 

sure you can see the green stripes in the 
injection status window (see Figure F). 
• You should hold the pen over your 

injection site at a 90o angle. 
 

Note: Do not rest the pen on the injection site until 
you are ready to inject. This may cause the pen to 
accidentally lock. 
 

 

 

 
Figure F 
 

b. Firmly press and hold down the pen on 
your injection site. You will hear the 
clicking sounds start. 
This tells you that the injection is 
happening (see Figure G). 

 
 
 
 
 
 
 
 
 
 
 
Figure G 
 

c. Continue to hold the pen firmly down on 
your injection site until the clicking sounds 
have stopped (see Figure H). 

 
 Do not lift your pen off your injection site 

until the clicking sounds stop and you see 
green ticks in the injection status window. 

 
 
 
 
 
 
 
 
 
 
 
Figure H 

Clicking  
Starts 

Clicking Clicking  
Stops 

Hold 

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54 

 Warning! If you do not hear clicking sounds 
or you do not see green ticks in the injection  
status window after attempting to inject, the  
pen may have locked and you may not have  
received your injection. You should then  
contact your doctor, nurse or pharmacist. 
 

Step 7: Remove the Zinbryta Pen from your injection site 
 
a. After the clicking sound has stopped, lift the 

pen from your injection site. The needle 
cover will extend to cover the needle and 
will lock (See Figure I).  
 
• If you see blood at your injection site, wipe 

it off with the gauze pad and apply an 
adhesive bandage or plaster. 

 
  

Figure I 
 
Step 8:  Check to make sure you have received your full dose of Zinbryta (see Figure J). 
 
a. Check the injection status window.  

You should see green ticks. 
 
b. Check the medicine window.  

You should see a yellow plunger. 
 
 
 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure J 

 
 

Injection Status 
Window 

Medicine 
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55 

 
After your injection 
 
After Use – Parts of your Zinbryta Pen (see Figure K): 
 
 
 
 
 
 
 
 
 
 

 
Figure K 
 
 
Note: After the pen has been removed from the injection site, the needle cover will lock to protect against 
needle injury. Do not re-cap the pen. 
 
 
Step 9: Disposing of used Zinbryta Pens 
 
• Check with your doctor, pharmacist or nurse about the right way to throw away the used pen. 

 Do not re-cap the pen. 
 

Step 10: Care for your injection site 
 
• If needed, apply a gauze pad, adhesive bandage or plaster to the injection site. 
 
Storage 
• Recommended storage is controlled refrigeration 2°C to 8°C in the closed original carton to 

protect from light.  
• If needed, Zinbryta may be stored in the closed original carton without refrigeration up to 30°C 

for up to 30 days. 
 Do not place Zinbryta pen back into the refrigerator after warming to room temperature. 
 Do not freeze or expose to high temperatures. 

• Keep Zinbryta pen and all medicines out of reach and sight of children. 
 
 

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56 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX IV 

SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS 
OF THE MARKETING AUTHORISATION(S) 

 
 

 
 
 
 

 

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57 

Scientific conclusions 
 
Taking into account the PRAC Assessment Report on the PSUR(s) for daclizumab beta, the scientific 
conclusions of CHMP are as follows:  
 
Sarcoidosis 
 
Twelve cases of sarcoidosis confirmed by health-care professionals were reported from clinical trials 
cumulatively. No risk factors or alternative aetiology have been reported in any of these cases. There 
is also a plausible mechanism of action for the development of sarcoidosis due to the 
immunomodulatory effects of daclizumab beta and involvement of daclizumab beta in the origin of 
other immune-mediated events. The causal relationship between daclizumab beta and sarcoidosis is 
considered possible. 
 
Colitis 
 
Four new serious cases of colitis confirmed by health-care professionals have been received during 
this period. Cumulatively, 24 cases of colitis have been retrieved from clinical trials. There is a 
plausible mechanism of action for the development of this colitis due to immunomodulatory properties 
of daclizumab beta and involvement of daclizumab beta in the origin of other immune-mediated 
events. The causal relationship between daclizumab beta and colitis is possible. 
Section 4.8 of the SmPC has been reviewed to add the adverse reaction sarcoidosis with a frequency 
uncommon and the adverse reaction colitis with a frequency common.  
 
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 daclizumab beta the CHMP is of the opinion that the 
benefit-risk balance of the medicinal product(s) containing daclizumab beta 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. 

 

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	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION 
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET