Dupixent
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ANNEX I  
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 

  



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Dupixent 300 mg solution for injection in pre-filled syringe 
Dupixent 300 mg solution for injection in pre-filled pen 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Dupilumab 300 mg solution for injection in pre-filled syringe 
 
Each single-use pre-filled syringe contains 300 mg of dupilumab in 2 ml solution (150 mg/ml). 
 
Dupilumab 300 mg solution for injection in pre-filled pen 
 
Each single-use pre-filled pen contains 300 mg of dupilumab in 2 ml solution (150 mg/ml). 
 
Dupilumab is a fully human monoclonal antibody against interleukin (IL)-4 receptor alpha that inhibits 
IL-4/IL-13 signalling, produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA 
technology. 
 
For the full list of excipients, see section 6.1.  
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection (injection) 
 
Clear to slightly opalescent, colourless to pale yellow sterile solution, which is free from visible 
particulates, with a pH of approximately 5.9. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications  
 
Atopic dermatitis 
 
Adults and adolescents 
Dupixent is indicated for the treatment of moderate-to-severe atopic dermatitis in adults and 
adolescents 12 years and older who are candidates for systemic therapy. 
 
Children 6 to 11 years of age 
Dupixent is indicated for the treatment of severe atopic dermatitis in children 6 to 11 years old who are 
candidates for systemic therapy. 
 
Asthma 
 
Dupixent is indicated in adults and adolescents 12 years and older as add-on maintenance treatment for 
severe asthma with type 2 inflammation characterised by raised blood eosinophils and/or raised 
fraction of exhaled nitric oxide (FeNO), see section 5.1, who are inadequately controlled with high 
dose ICS plus another medicinal product for maintenance treatment.  



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Chronic rhinosinusitis with nasal polyposis (CRSwNP)  
 
Dupixent is indicated as an add-on therapy with intranasal corticosteroids for the treatment of adults 
with severe CRSwNP for whom therapy with systemic corticosteroids and/or surgery do not provide 
adequate disease control. 
 
4.2 Posology and method of administration  
 
Treatment should be initiated by healthcare professionals experienced in the diagnosis and treatment of 
conditions for which dupilumab is indicated (see section 4.1). 
 
Posology 
 
Atopic Dermatitis 
 
Adults 
The recommended dose of dupilumab for adult patients is an initial dose of 600 mg (two 300 mg 
injections), followed by 300 mg given every other week administered as subcutaneous injection. 
 
Adolescents (12 to 17 years of age) 
The recommended dose of dupilumab for adolescent patients 12 to 17 years of age is specified in 
Table 1. 
 
Table 1: Dose of dupilumab for subcutaneous administration in adolescent patients 12 to 17 
years of age with atopic dermatitis 

Body Weight of 
Patient 

Initial Dose Subsequent Doses 
(every other week) 

less than 60 kg 400 mg (two 200 mg injections) 200 mg 
60 kg or more 600 mg (two 300 mg injections) 300 mg 

 
Children 6 to 11 years of age 
The recommended dose of dupilumab for children 6 to 11 years of age is specified in Table 2. 
 
Table 2: Dose of dupilumab for subcutaneous administration in children 6 to 11 years of age 
with atopic dermatitis 

Body Weight of 
Patient 

Initial Dose Subsequent Doses 
 

 
 

 

15 kg to  
less than 60 kg 

300 mg (one 300 mg injection) on Day 1, 
followed by 300 mg on Day 15 

300 mg every 4 weeks (Q4W)*, 
starting 4 weeks after Day 15 dose  

60 kg or more 600 mg (two 300 mg injections) 300 mg every other week (Q2W) 

* The dose may be increased to 200 mg Q2W in patients with body weight of 15 kg to less than 60 kg 
based on physician’s assessment. 
 
Dupilumab can be used with or without topical corticosteroids. Topical calcineurin inhibitors may be 
used, but should be reserved for problem areas only, such as the face, neck, intertriginous and genital 
areas. 
 
Consideration should be given to discontinuing treatment in patients who have shown no response 
after 16 weeks of treatment for atopic dermatitis. Some patients with initial partial response may 
subsequently improve with continued treatment beyond 16 weeks. If dupilumab treatment interruption 
becomes necessary, patients can still be successfully re-treated. 
 



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Asthma 
 
The recommended dose of dupilumab for adults and adolescents (12 years of age and older) is: 

• For patients with severe asthma and who are on oral corticosteroids or for patients with severe 
asthma and co-morbid moderate-to-severe atopic dermatitis or adults with co-morbid severe 
chronic rhinosinusitis with nasal polyposis, an initial dose of 600 mg (two 300 mg injections), 
followed by 300 mg every other week administered as subcutaneous injection. 

• For all other patients, an initial dose of 400 mg (two 200 mg injections), followed by 200 mg 
every other week administered as subcutaneous injection.  

Patients receiving concomitant oral corticosteroids may reduce their steroid dose once clinical 
improvement with dupilumab has occurred (see section 5.1). Steroid reductions should be 
accomplished gradually (see section 4.4). 
 
Dupilumab is intended for long-term treatment. The need for continued therapy should be considered 
at least on an annual basis as determined by physician assessment of the patient’s level of asthma 
control. 
 
Chronic rhinosinusitis with nasal polyposis (CRSwNP)  
 
The recommended dose of dupilumab for adult patients is an initial dose of 300 mg followed by 
300 mg given every other week. 
 
Dupilumab is intended for long-term treatment. Consideration should be given to discontinuing 
treatment in patients who have shown no response after 24 weeks of treatment for CRSwNP. Some 
patients with initial partial response may subsequently improve with continued treatment beyond 24 
weeks. 
 
Missed dose  
 
If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular 
scheduled time. 
 
Special populations 
 
Elderly (≥ 65 years) 
No dose adjustment is recommended for elderly patients (see section 5.2). 
 
Renal impairment 
No dose adjustment is needed in patients with mild or moderate renal impairment. Very limited data 
are available in patients with severe renal impairment (see section 5.2). 
 
Hepatic impairment 
No data are available in patients with hepatic impairment (see section 5.2). 
 
Body weight 
No dose adjustment for body weight is recommended for patients with asthma 12 years of age and 
older or in adults with atopic dermatitis or CRSwNP (see section 5.2). 
 
For patients 12 to 17 years of age with atopic dermatitis, the recommended every other week dose is 
200 mg (< 60 kg) or 300 mg (≥ 60 kg). 
 
For patients 6 to 11 years of age with atopic dermatitis, the recommended doses are 300 mg Q4W with 
the possibility to increase to 200 mg Q2W (15 kg to < 60 kg), and 300 mg Q2W (≥ 60 kg). 
 
Paediatric patients 



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The safety and efficacy of dupilumab in children with atopic dermatitis below the age of 6 years have 
not been established. The safety and efficacy of dupilumab in children with a body weight < 15 kg 
have not been established (see section 5.2). No data are available. 
 
The safety and efficacy of dupilumab in children with severe asthma below the age of 12 years have 
not been established (see section 5.2). No data are available. 
 
CRSwNP does not normally occur in children. The safety and efficacy in children with CRSwNP 
below the age of 18 years have not been established (see section 5.2). No data are available. 
 
Method of administration 
 
Subcutaneous use 
 
The dupilumab pre-filled pen is not intended for use in children below 12 years of age. For children 6 
to 11 years of age with atopic dermatitis, the dupilumab pre-filled syringe is the presentation 
appropriate for administration to this population. 
 
Dupilumab is administered by subcutaneous injection into the thigh or abdomen, except for the 5 cm 
around the navel.  If somebody else administers the injection, the upper arm can also be used. 
 
For the initial 600 mg dose, two 300 mg injections should be administered consecutively in different 
injection sites. 
 
It is recommended to rotate the injection site with each injection. Dupilumab should not be injected 
into skin that is tender, damaged or has bruises or scars. 
 
A patient may self-inject dupilumab or the patient's caregiver may administer dupilumab if their 
healthcare professional determines that this is appropriate. Proper training should be provided to 
patients and/or caregivers on the preparation and administration of dupilumab prior to use according to 
the Instructions for Use (IFU) section in the package leaflet. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Dupilumab should not be used to treat acute asthma symptoms or acute exacerbations. Dupilumab 
should not be used to treat acute bronchospasm or status asthmaticus. 
 
Systemic, topical, or inhaled corticosteroids should not be discontinued abruptly upon initiation of 
therapy with dupilumab. Reductions in corticosteroid dose, if appropriate, should be gradual and 
performed under the direct supervision of a physician. Reduction in corticosteroid dose may be 
associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by 
systemic corticosteroid therapy. 
 
Biomarkers of type 2 inflammation may be suppressed by systemic corticosteroid use. This should be 
taken into consideration to determine type 2 status in patients taking oral corticosteroids (see section 
5.1). 
 
Traceability 
 
In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
Hypersensitivity 



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If a systemic hypersensitivity reaction (immediate or delayed) occurs, administration of dupilumab 
should be discontinued immediately and appropriate therapy initiated. Cases of anaphylactic reaction, 
angioedema, and serum sickness/serum sickness-like reaction have been reported. Anaphylactic 
reactions and angioedema have occurred from minutes to up to seven days after the dupilumab 
injection (section 4.8). 
 
Eosinophilic conditions 
 
Cases of eosinophilic pneumonia and cases of vasculitis consistent with eosinophilic granulomatosis 
with polyangiitis (EGPA) have been reported with dupilumab in adult patients who participated in the 
asthma development program. Cases of vasculitis consistent with EGPA have been reported with 
dupilumab and placebo in adult patients with co-morbid asthma in the CRSwNP development 
program. Physicians should be alert to vasculitic rash, worsening pulmonary symptoms, cardiac 
complications, and/or neuropathy presenting in their patients with eosinophilia. Patients being treated 
for asthma may present with serious systemic eosinophilia sometimes presenting with clinical features 
of eosinophilic pneumonia or vasculitis consistent with eosinophilic granulomatosis with polyangiitis, 
conditions which are often treated with systemic corticosteroid therapy. These events usually, but not 
always, may be associated with the reduction of oral corticosteroid therapy. 
 
Helminth infection 
 
Patients with known helminth infections were excluded from participation in clinical studies. 
Dupilumab may influence the immune response against helminth infections by inhibiting IL-4/IL-13 
signaling. Patients with pre-existing helminth infections should be treated before initiating dupilumab. 
If patients become infected while receiving treatment with dupilumab and do not respond to anti-
helminth treatment, treatment with dupilumab should be discontinued until infection resolves. 
 
Conjunctivitis and keratitis related events 
 
Conjunctivitis and keratitis related events have been reported with dupilumab, predominantly in atopic 
dermatitis patients. Some patients reported visual disturbances (e.g. blurred vision) associated with 
conjunctivitis or keratitis (section 4.8). 
 
Patients should be advised to report new onset or worsening eye symptoms to their healthcare 
provider. Patients treated with dupilumab who develop conjunctivitis that does not resolve following 
standard treatment or signs and symptoms suggestive of keratitis should undergo ophthalmological 
examination, as appropriate (section 4.8).  
 
Atopic dermatitis or CRSwNP patients with comorbid asthma 
 
Patients on dupilumab for moderate-to-severe atopic dermatitis or severe CRSwNP who also have co-
morbid asthma should not adjust or stop their asthma treatments without consultation with their 
physicians. Patients with comorbid asthma should be monitored carefully following discontinuation of 
dupilumab. 
 
Vaccinations 
 
Live and live attenuated vaccines should not be given concurrently with dupilumab as clinical safety 
and efficacy has not been established. Immune responses to TdaP vaccine and meningococcal 
polysaccharide vaccine were assessed, see section 4.5. It is recommended that patients should be 
brought up to date with live and live attenuated immunisations in agreement with current 
immunisation guidelines prior to treatment with dupilumab. 
 
Sodium content  
 



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This medicinal product contains less than 1 mmol sodium (23 mg) per 300 mg dose, i.e. essentially 
“sodium-free”.  
 
4.5 Interaction with other medicinal products and other forms of interaction  
 
Immune responses to vaccination were assessed in a study in which patients with atopic dermatitis 
were treated once weekly for 16 weeks with 300 mg of dupilumab. After 12 weeks of dupilumab 
administration, patients were vaccinated with a Tdap vaccine (T cell-dependent), and a meningococcal 
polysaccharide vaccine (T cell-independent) and immune responses were assessed 4 weeks later. 
Antibody responses to both tetanus vaccine and meningococcal polysaccharide vaccine were similar in 
dupilumab-treated and placebo-treated patients. No adverse interactions between either of the non-live 
vaccines and dupilumab were noted in the study.  
 
Therefore, patients receiving dupilumab may receive concurrent inactivated or non-live vaccinations. 
For information on live vaccines see section 4.4. 
 
In a clinical study of AD patients, the effects of dupilumab on the pharmacokinetics (PK) of CYP 
substrates were evaluated. The data gathered from this study did not indicate clinically relevant effects 
of dupilumab on CYP1A2, CYP3A, CYP2C19, CYP2D6, or CYP2C9 activity. 
 
An effect of dupilumab on the PK of co-administered medications is not expected. Based on the 
population analysis, commonly co-administered medications had no effect on dupilumab 
pharmacokinetics on patients with moderate to severe asthma. 
 
4.6 Fertility, pregnancy and lactation  
 
Pregnancy 
 
There are limited amount of data from the use of dupilumab in pregnant women. Animal studies do not 
indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). 
Dupilumab should be used during pregnancy only if the potential benefit justifies the potential risk to 
the foetus. 
 
Breast-feeding 
 
It is unknown whether dupilumab is excreted in human milk or absorbed systemically after ingestion. 
A decision must be made whether to discontinue breast-feeding or to discontinue dupilumab therapy 
taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman. 
 
Fertility 
 
Animal studies showed no impairment of fertility (see section 5.3). 
 
4.7 Effects on ability to drive and use machines  
 
Dupilumab has no or negligible influence on the ability to drive or operate machinery. 
 



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4.8 Undesirable effects  
 
Atopic dermatitis 
 
Adults with atopic dermatitis 
 
Summary of the safety profile 
 
The most common adverse reactions were injection site reactions, conjunctivitis, blepharitis, and oral 
herpes. Very rare cases of serum sickness/serum sickness-like reaction have been reported in the 
atopic dermatitis development program (see section 4.4). 
 
In the monotherapy adult studies, the proportion of patients who discontinued treatment due to adverse 
events was 1.9 % of the placebo group, 1.9 % of the dupilumab 300 mg Q2W group, 1.5 % of the 
dupilumab 300 mg QW group. In the concomitant TCS adult study, the proportion of patients who 
discontinued treatment due to adverse events was 7.6 % of the placebo + TCS group, 1.8 % of the 
dupilumab 300 mg Q2W + TCS group, and 2.9 % of the dupilumab 300 mg QW + TCS group. 
 
Tabulated list of adverse reactions 
 
The safety of dupilumab was evaluated in four randomized, double-blind, placebo-controlled studies 
and one dose-ranging study in patients with moderate-to-severe atopic dermatitis. In these 5 trials, 1,689 
subjects were treated with subcutaneous injections of dupilumab, with or without concomitant topical 
corticosteroids (TCS). A total of 305 patients were treated with dupilumab for at least 1 year. 
 
Listed in Table 3 are adverse reactions observed in atopic dermatitis clinical trials and/or postmarketing 
setting presented by system organ class and frequency, using the following categories: very common 
(≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); 
very rare (< 1/10,000). Within each frequency grouping, undesirable effects are presented in order of 
decreasing seriousness. 
 
Table 3: List of adverse reactions in atopic dermatitis 

MedDRA System 
Organ Class 

Frequency Adverse Reaction 

Infections and 
infestations 

Common Conjunctivitis 
Oral herpes 

Blood and lymphatic 
system disorders 

Common Eosinophilia 

Immune system 
disorders 

Very rare 
Not known 

 

Serum sickness/serum sickness-like reactions 
Anaphylactic reaction* 
Angioedema* 

Nervous system 
disorders 

Common Headache 

Eye disorders Common 
 
 
Uncommon 

Conjunctivitis allergic 
Eye pruritus  
Blepharitis 
Keratitis 
Ulcerative keratitis 

Musculoskeletal and 
connective tissue 
disorders 

Not known Arthralgia* 

General disorders 
and administration 
site conditions 

Very common Injection site reactions 

* From postmarketing reporting. 
 



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Adolescents with atopic dermatitis (12 to 17 years of age) 
 
The safety of dupilumab was assessed in a study of 250 patients 12 to 17 years of age with moderate-
to-severe atopic dermatitis (AD-1526). The safety profile of dupilumab in these patients followed 
through week 16 was similar to the safety profile from studies in adults with atopic dermatitis. 
 
Paediatric patients with atopic dermatitis (6 to 11 years of age) 
 
The safety of dupilumab was assessed in a trial of 367 patients 6 to 11 years of age with severe atopic 
dermatitis (AD-1652). The safety profile of dupilumab + TCS in these patients through week 16 was 
similar to the safety profile from studies in adults and adolescents with atopic dermatitis. The long-term 
safety profile of dupilumab observed in children and adolescents was consistent with that seen in adults 
with atopic dermatitis. 
 
 
Asthma 
 
Summary of the safety profile 
 
The most common adverse reaction was injection site erythema. Anaphylactic reaction has been reported 
very rarely in the asthma development program (see section 4.4). 
 
In DRI12544 and QUEST studies, the proportion of patients who discontinued treatment due to 
adverse events was 4.3 % of the placebo group, 3.2 % of the dupilumab 200 mg Q2W group, and 
6.1 % of the dupilumab 300 mg Q2W group. 
 
Tabulated list of adverse reactions 
 
A total of 2,888 adult and adolescent patients with moderate-to-severe asthma were evaluated in 3 
randomised, placebo-controlled, multicentre trials of 24 to 52 weeks duration (DRI12544, QUEST, 
and VENTURE). Of these, 2,678 had a history of 1 or more severe exacerbations in the year prior to 
enrolment despite regular use of medium-to-high dose inhaled corticosteroids plus an additional 
controller(s) (DRI12544 and QUEST). A total of 210 patients with oral corticosteroid-dependent 
asthma receiving high-dose inhaled corticosteroids plus up to two additional controllers were enrolled 
(VENTURE).  
 
The safety profile of dupilumab in the 96 weeks long term safety study (TRAVERSE) was consistent 
with the safety profile observed in pivotal asthma studies for up to 52 weeks of treatment. 
 
Listed in Table 4 are adverse reactions observed in asthma clinical trials and/or postmarketing setting 
presented by system organ class and frequency, using the following categories: very common (≥ 1/10); 
common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very 
rare (< 1/10,000). Within each frequency grouping, undesirable effects are presented in order of 
decreasing seriousness. 
 
Table 4: List of adverse reactions in asthma 

MedDRA System 
Organ Class 

Frequency Adverse Reaction 

Immune system 
disorders 

Very rare 
Not known 

Anaphylactic reaction 
Angioedema* 

Eye disorders Rare Keratitis 

Musculoskeletal and 
connective tissue 
disorders 

Not known Arthralgia* 



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General disorders 
and administration 
site conditions 

Very common 
Common 
Common 
Common 

Injection site erythema 
Injection site oedema 
Injection site pain  
Injection site pruritus 

* From postmarketing reporting. 
 
Chronic rhinosinusitis with nasal polyposis (CRSwNP) 
 
Summary of the safety profile 
 
The most common adverse reactions were injection site reaction and injection site swelling. 
 
In the safety pool, the proportion of patients who discontinued treatment due to adverse events was 2.0 % 
of the dupilumab 300 mg Q2W group and 4.6 % of the placebo group. 
 
Tabulated list of adverse reactions 
 
A total of 722 adult patients with CRSwNP were evaluated in 2 randomised, placebo-controlled, 
multicentre trials of 24 to 52 weeks duration (SINUS-24 and SINUS-52). The safety pool consisted of 
data from the first 24 weeks of treatment. 
 
Listed in Table 5 are adverse reactions observed in CRSwNP clinical trials and/or postmarketing 
setting presented by system organ class and frequency, using the following categories: very common 
(≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to 
< 1/1,000); very rare (< 1/10,000). Within each frequency grouping, undesirable effects are presented 
in the order of decreasing seriousness. 
 
Table 5. List of adverse reactions in CRSwNP 

MedDRA System 
Organ Class 

Frequency Adverse Reaction 

Infections and 
infestations 

Common Conjunctivitis  

Blood and lymphatic 
system disorders 

Common Eosinophilia 

Immune system 
disorders 

Not known 
 

Anaphylactic reaction* 
Angioedema* 

Musculoskeletal and 
connective tissue 
disorders 

Not known Arthralgia* 

General disorders 
and administration 
site conditions 

Common Injection site reaction 
Injection site swelling 

* From postmarketing reporting. 
 
Description of selected adverse reactions in atopic dermatitis, asthma, and CRSwNP indications 
 
Hypersensitivity 
Cases of anaphylactic reaction, angioedema, and serum sickness/serum sickness-like reaction have been 
reported following administration of dupilumab (see section 4.4). 
 
Conjunctivitis and keratitis related events 
Conjunctivitis and keratitis occurred more frequently in atopic dermatitis patients who received 
dupilumab. Most patients with conjunctivitis or keratitis recovered or were recovering during the 
treatment period. Among asthma patients frequency of conjunctivitis and keratitis was low and similar 
between dupilumab and placebo. Among CRSwNP patients the frequency of conjunctivitis was higher 



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in dupilumab than placebo, though lower than that observed in atopic dermatitis patients. There were 
no cases of keratitis reported in the CRSwNP development program (see section 4.4). 
 
Eczema herpeticum 
Eczema herpeticum was reported in < 1% of the dupilumab groups and in < 1 % of the placebo group 
in the 16-week atopic dermatitis monotherapy studies. In the 52-week atopic dermatitis dupilumab + 
TCS study, eczema herpeticum was reported in 0.2 % of the dupilumab + TCS group and 1.9 % of the 
placebo + TCS group. 
 
Eosinophilia 
Dupilumab-treated patients had a greater mean initial increase from baseline in eosinophil count 
compared to patients treated with placebo. Eosinophil counts declined to near baseline levels during 
study treatment and returned to baseline during the asthma open-label extension safety study 
(TRAVERSE). 
 
Treatment-emergent eosinophilia (≥ 5,000 cells/mcL) was reported in < 2 % of dupilumab-treated 
patients and < 0.5 % in placebo-treated patients. 
 
Infections 
In the 16-week atopic dermatitis monotherapy clinical studies, serious infections were reported in 1.0 % 
of patients treated with placebo and 0.5 % of patients treated with dupilumab. In the 52-week atopic 
dermatitis CHRONOS study, serious infections were reported in 0.6 % of patients treated with placebo 
and 0.2 % of patients treated with dupilumab. 
 
No increase was observed in the overall incidence of infections with dupilumab compared to placebo in 
the safety pool for CRSwNP clinical studies. In the 52-week SINUS-52 study, serious infections were 
reported in 1.3 % of patients treated with dupilumab and 1.3 % of patients treated with placebo. 
 
 
Immunogenicity 
As with all therapeutic proteins, there is a potential for immunogenicity with dupilumab. 
 
Anti-Drug-Antibodies (ADA) responses were not generally associated with impact on dupilumab 
exposure, safety, or efficacy. 
 
Approximately 5 % of patients with atopic dermatitis, asthma, or CRSwNP who received dupilumab 
300 mg Q2W for 52 weeks developed ADA to dupilumab; approximately 2 % exhibited persistent 
ADA responses and approximately 2 % had neutralizing antibodies. Similar results were observed in 
paediatric patients (6 to 11 years of age) with atopic dermatitis who received dupilumab 200 mg Q2W 
or 300 mg Q4W for 16 weeks. 
 
Approximately 16 % of adolescent patients with atopic dermatitis who received dupilumab 300 mg or 
200 mg Q2W for 16 weeks developed antibodies to dupilumab; approximately 3 % exhibited 
persistent ADA responses, and approximately 5 % had neutralizing antibodies. 
 
Approximately 9 % of patients with asthma who received dupilumab 200 mg Q2W for 52 weeks 
developed antibodies to dupilumab; approximately 4 % exhibited persistent ADA responses and 
approximately 4 % had neutralizing antibodies. 
 
Regardless of age or population, approximately 2 to 4 % of patients in the placebo groups were 
positive for antibodies to dupilumab; approximately 2 % exhibited persistent ADA response and 
approximately 1 % had neutralizing antibodies. 
 
Less than 1 % of patients who received dupilumab at approved dosing regimens exhibited high titer 
ADA responses associated with reduced exposure and efficacy. In addition, there was one patient with 
serum sickness and one with serum sickness-like reaction (< 0.1 %) associated with high ADA titers 
(see section 4.4). 



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Paediatric population 
 
The safety profile observed in children with atopic dermatitis aged 6 to 11 years and in adolescents 
aged 12 to 17 years in atopic dermatitis and asthma clinical trials was similar to that seen in adults. 
 
The long-term safety of dupilumab was assessed in 89 adolescent patients who were enrolled in an 
open-label extension study in moderate-to-severe asthma (TRAVERSE). In this study, patients were 
followed for up to 96 weeks. The safety profile of dupilumab in TRAVERSE was consistent with the 
safety profile observed in pivotal asthma studies for up to 52 weeks of treatment. 
 
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  
 
There is no specific treatment for dupilumab overdose. In the event of overdosage, monitor the patient 
for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment 
immediately. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties  
 
Pharmacotherapeutic group: Other dermatological preparations, agents for dermatitis, excluding 
corticosteroids, ATC code: D11AH05  
 
Mechanism of action 
 
Dupilumab is a recombinant human IgG4 monoclonal antibody that inhibits interleukin-4 and 
interleukin-13 signaling. Dupilumab inhibits IL-4 signaling via the Type I receptor (IL-4Rα/γc), and 
both IL-4 and IL-13 signaling through the Type II receptor (IL-4Rα/IL-13Rα). IL-4 and IL-13 are 
major drivers of human type 2 inflammatory disease, such as atopic dermatitis, asthma, and CRSwNP. 
Blocking the IL-4/IL-13 pathway with dupilumab in patients decreases many of the mediators of type 
2 inflammation.  
 
Pharmacodynamic effects 
 
In atopic dermatitis clinical trials, treatment with dupilumab was associated with decreases from 
baseline in concentrations of type 2 immunity biomarkers, such as thymus and activation-regulated 
chemokine (TARC/CCL17), total serum IgE and allergen-specific IgE in serum. A reduction of lactate 
dehydrogenase (LDH), a biomarker associated with AD disease activity and severity, was observed 
with dupilumab treatment in adults and adolescents with atopic dermatitis. 
 
In asthma clinical trials, dupilumab treatment markedly decreased FeNO and circulating 
concentrations of eotaxin-3, total IgE, allergen specific IgE, TARC, and periostin in asthma subjects 
relative to placebo.  These reductions in type 2 inflammatory biomarkers were comparable for the 
200 mg Q2W and 300 mg Q2W regimens. These markers were near maximal suppression after 2 
weeks of treatment, except for IgE which declined more slowly. These effects were sustained 
throughout treatment. 
 
Clinical efficacy and safety in atopic dermatitis  

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


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Adults with atopic dermatitis 
 
The efficacy and safety of dupilumab as monotherapy and with concomitant topical corticosteroids 
were evaluated in three pivotal randomised, double-blind, placebo-controlled studies (SOLO 1, 
SOLO 2, and CHRONOS) in 2,119 patients 18 years of age and older with moderate to severe atopic 
dermatitis (AD) defined by Investigator’s Global Assessment (IGA) score ≥ 3, an Eczema Area and 
Severity Index (EASI) score ≥ 16, and a minimum body surface area (BSA) involvement of ≥ 10 %. 
Eligible patients enrolled into the three studies had previous inadequate response to topical medication. 
 
In all three studies, patients received 1) an initial dose of 600 mg dupilumab (two 300 mg injections) 
on day 1, followed by 300 mg once every two weeks (Q2W); 2) an initial dose of 600 mg dupilumab 
on day 1, followed by 300 mg once weekly (QW); or 3) matching placebo. Dupilumab was 
administered by subcutaneous (SC) injection in all studies. If needed to control intolerable symptoms 
of atopic dermatitis, patients were permitted to receive rescue treatment (which included higher 
potency topical steroids or systemic immunosuppressants) at the discretion of the investigator. Patients 
who received rescue treatment were considered non-responders. 
 
SOLO 1 enrolled 671 patients (224 to placebo, 224 to dupilumab 300 mg Q2W, and 223 to dupilumab 
300 mg QW) and had a treatment period of 16 weeks. 
 
SOLO 2 enrolled 708 patients (236 to placebo, 233 to dupilumab 300 mg Q2W, and 239 to dupilumab 
300 mg QW) and had a treatment period of 16 weeks. 
 
CHRONOS enrolled 740 patients (315 to placebo + topical corticosteroid (TCS), 106 to dupilumab 
300 mg Q2W + TCS, and 319 to dupilumab 300 mg QW + TCS) and had a treatment period of 
52 weeks. Patients received dupilumab or placebo with concomitant use of TCS starting at baseline 
using a standardized regimen. Patients were also permitted to use topical calcineurin inhibitors (TCI). 
 
Endpoints 
In all three pivotal studies, the co-primary endpoints were the proportion of patients with IGA 0 or 1 
(“clear” or “almost clear”) with a reduction of ≥ 2 points on a 0-4 IGA scale and the proportion of 
patients with improvement of at least 75 % in EASI (EASI-75) from baseline to week 16. Other 
evaluated outcomes included the proportion of patients with improvement of at least 50 % and 90 % in 
EASI (EASI-50 and EASI-90, respectively), reduction in itch as measured by the peak pruritus 
Numerical Rating Scale (NRS), and percent change in the SCORing Atopic Dermatitis (SCORAD) 
scale from baseline to week 16. Additional secondary endpoints included mean change from baseline 
to week 16 in the Patient Oriented Eczema Measure (POEM), Dermatology Life Quality Index 
(DLQI), and Hospital Anxiety and Depression Scale (HADS) scores. In CHRONOS, efficacy was also 
evaluated at week 52. 
 
Baseline Characteristics 
In the monotherapy studies (SOLO 1 and SOLO 2), across all treatment groups, the mean age was 
38.3, the mean weight was 76.9 kg, 42.1 % were female, 68.1 % were white, 21.8 % were Asian, and 
6.8  % were black. In these studies, 51.6 % of patients had a baseline IGA score of 3 (moderate AD), 
48.3 % of patients had a baseline IGA of 4 (severe AD) and 32.4 % of patients had received prior 
systemic immunosuppressants. The baseline mean EASI score was 33.0, the baseline weekly averaged 
pruritus NRS was 7.4, the baseline mean SCORAD score was 67.8, the baseline mean POEM score 
was 20.5, the baseline mean DLQI was 15.0, and the baseline mean HADS total score was 13.3. 
In the concomitant TCS study (CHRONOS), across all treatment groups, the mean age was 37.1, the 
mean weight was 74.5 kg, 39.7 % were female, 66.2 % were white, 27.2 % were Asian, and 4.6 % 
were black. In this study, 53.1 % of patients had a baseline IGA score of 3 and 46.9 % of patients had 
a baseline IGA of 4 and 33.6 % of patients received prior systemic immunosuppressants. The baseline 
mean EASI score was 32.5, the baseline weekly pruritus NRS was 7.3, the baseline mean SCORAD 
score was 66.4, the baseline mean POEM score was 20.1, the baseline mean DLQI was 14.5, and the 
baseline mean HADS total score was 12.7. 
 



14 

Clinical Response 
 
16-Week Monotherapy Studies (SOLO 1 and SOLO 2) 
 
In SOLO 1 and SOLO 2, from baseline to week 16, a significantly greater proportion of patients 
randomized to dupilumab achieved an IGA 0 or 1 response, EASI-75, and/or an improvement of > 4 
points on the pruritus NRS compared to placebo (see Table 6). 
 
A significantly greater proportion of patients randomized to dupilumab achieved a rapid improvement 
in the pruritus NRS compared to placebo (defined as ≥ 4-point improvement as early as week 2; 
p < 0.01) and the proportion of patients responding on the pruritus NRS continued to increase through 
the treatment period. The improvement in pruritus NRS occurred in conjunction with the improvement 
of objective signs of atopic dermatitis. 
 
Figure 1 and Figure 2 show the mean percent change from baseline in EASI and the mean percent 
change from baseline in NRS, respectively up to week 16. 
 
Table 6: Efficacy results of dupilumab monotherapy at week 16 (FAS) 

 SOLO 1 (FAS)a SOLO 2 (FAS)a 

 Placebo 
 

Dupilumab 
300 mg Q2W 

Dupilumab 
300 mg QW 

Placebo Dupilumab 
300 mg Q2W 

Dupilumab 
300 mg QW 

Patients 
randomised 

224 224 223 236 233 239 

IGA 0 or 1b, 
% respondersc 

10.3 % 37.9 %e 37.2 %e 8.5 % 36.1 %e 36.4 %e 

EASI-50, 
% respondersc 

24.6 % 68.8 %e 61.0 %e 22.0 % 65.2 %e 61.1 %e 

EASI-75, 
% respondersc 

14.7 % 51.3 %e 52.5 %e 11.9 % 44.2 %e 48.1 %e 

EASI-90, 
% respondersc 

7.6 % 35.7 %e 33.2 %e 7.2 % 30.0 %e 30.5 %e 

EASI, LS 
mean % 
change from 
baseline (+/-
SE) 

-37.6 % 
(3.28) 

-72.3 %e 
(2.63) 

-72.0 %e 
(2.56) 

-30.9 % 
(2.97) 

-67.1 %e 

(2.52) 
-69.1 %e 

(2.49) 

SCORAD, LS 
mean % 
change from 
baseline (+/- 
SE) 

-29.0 % 
(3.21) 

-57.7 %e  
(2.11) 

-57.0 %e 
(2.11) 

-19.7 % 
(2.52) 

-51.1 %e 
(2.02) 

-53.5 %e 
(2.03) 

Pruritus NRS, 
LS mean % 
change from 
baseline (+/- 
SE) 

-26.1 % 
(3.02) 

-51.0 %e 
(2.50) 

-48.9 %e 
(2.60) 

-15.4 % 
(2.98) 

-44.3 %e 
(2.28) 

-48.3 %e 
(2.35) 

Number of 
patients with 
baseline 
pruritus NRS 
score > 4 

212 213 201 221 225 228 

Pruritus NRS 
(> 4-point 
improvement)

12.3 % 
 

40.8 %e 
 

40.3 %e  9.5% 
 

36.0  %e 
 

39.0 %e 



15 

 SOLO 1 (FAS)a SOLO 2 (FAS)a 

 Placebo 
 

Dupilumab 
300 mg Q2W 

Dupilumab 
300 mg QW 

Placebo Dupilumab 
300 mg Q2W 

Dupilumab 
300 mg QW 

, % 
respondersc, d  

LS = least squares; SE= standard error 
a Full analysis set (FAS) includes all patients randomized. 
b Responder was defined as a patient with IGA 0 or 1 (“clear” or “almost clear”) with a reduction 
of > 2 points on a 0-4 IGA scale. 
c Patients who received rescue treatment or with missing data were considered as non-responders. 
d a significantly greater proportion of patients on dupilumab had improvement in pruritus NRS of ≥ 4 
points compared to placebo at week 2 (p < 0.01). 
e p-value < 0.0001 
 
Figure 1: Mean percent change from baseline in EASI in SOLO 1a and SOLO 2a (FAS)b 
 
 

 
 
LS = least squares  

a In the primary analyses of the efficacy endpoints, patients who received rescue treatment or with 
missing data were considered non-responders. 
b Full analysis set (FAS) includes all patients randomized. 
 
  

SOLO 1 SOLO 2 



16 

Figure 2: Mean percent change from baseline in NRS in SOLO 1a and SOLO 2a (FAS)b 

 

 

 
LS = least squares  

a In the primary analyses of the efficacy endpoints, patients who received rescue treatment or with 
missing data were considered non-responders 
b Full analysis set (FAS) includes all patients randomized. 
 
Treatment effects in subgroups (weight, age, gender, race, and background treatment, including 
immunosuppressants) in SOLO 1 and SOLO 2 were consistent with the results in the overall study 
population. 
 
52-Week Concomitant TCS Study (CHRONOS) 
 
In CHRONOS, a significantly greater proportion of patients randomized to dupilumab 300 mg Q2W + 
TCS achieved an IGA 0 or 1 response, EASI-75, and/or an improvement of > 4 points on the pruritis 
NRS from baseline to week 16 and week 52 compared to placebo + TCS (see Table 7). 
 
A significantly greater proportion of patients randomized to dupilumab + TCS achieved a rapid 
improvement in the pruritus NRS compared to placebo + TCS (defined as > 4-point improvement as 
early as week 2; p < 0.05) and the proportion of patients responding on the pruritus NRS continued to 
increase through the treatment period. The improvement in pruritus NRS occurred in conjunction with 
the improvement of objective signs of atopic dermatitis. 
  

Figure 3 and Figure 4 show the mean percent change from baseline in EASI and the mean percent 
change from baseline in NRS, respectively, up to week 52 in CHRONOS. 
 
Table 7: Efficacy results of dupilumab with concomitant TCSa at Week 16 and Week 52 in 
CHRONOS 

 Week 16 (FAS)b Week 52 (FAS Week 52)b 

 Placebo + 
TCS 

Dupilumab 
300 mg Q2W + 

TCS 

Dupilumab 
300 mg QW + 

TCS 

Placebo +  
TCS 

Dupilumab 
300 mg 

Q2W + TCS 

Dupilumab 
300 mg QW + 

TCS 
Patients 
randomized 

315 106 319 264 89 270 

IGA 0 or 1c, 
% respondersd 

12.4 % 38.7 %f 39.2 %f 12.5 % 36.0 %f 40.0 %f 

EASI-50, 
% respondersd 

37.5 % 80.2 %f 78.1 %f 29.9 % 78.7 %f 70.0 %f 

EASI-75, 
% respondersd 

23.2 % 68.9 %f 63.9 %f 21.6 % 65.2 %f 64.1 %f 

SOLO 1 SOLO 2 



17 

LS = least squares; SE = standard error 
a All patients were on background topical corticosteroids therapy and patients were permitted to use 
topical calcineurin inhibitors. 
b Full analysis set (FAS) includes all patients randomized. FAS week 52 includes all patients 
randomized at least one year before the cutoff date of the primary analysis. 
c Responder was defined as a patient with IGA 0 or 1 (“clear” or “almost clear”) with a reduction of 
≥ 2 points on a 0-4 IGA scale. 
d Patients who received rescue treatment or with missing data were considered as non-responders. 
e a significantly greater proportion of patients on dupilumab had improvement in pruritus NRS of ≥ 4 
points compared to placebo at week 2 (p < 0.05). 
f p-value < 0.0001 
g p-value = 0.0015 
h p-value = 0.0003 
i p-value = 0.0005 
 
 
  

EASI-90, 
% respondersd 

11.1 % 39.6 %f 43.3 %f 15.5 % 50.6 %f 50.7 %f 

EASI, LS 
mean % 
change from 
baseline (+/- 
SE) 

-48.4 % 
(3.82) 

-80.5 %f 
(6.34) 

-81.5 %f 

(5.78) 
-60.9 % 
(4.29) 

-84.9 %g 
(6.73) 

-87.8 %h 
(6.19) 

SCORAD, LS 
mean % 
change from 
baseline (+/- 
SE) 

-36.2 % 
(1.66) 

-63.9 %f 
(2.52) 

-65.9 %f 
(1.49) 

-47.3 % 
(2.18) 

-69.7 %f 
(3.06) 

-70.4 %f 
(1.72) 

Pruritus NRS, 
LS mean % 
change from 
baseline (+/- 
SE) 

-30.3 % 
(2.36) 

-56.6 %f 
(3.95) 

-57.1 %f 
(2.11) 

-31.7 % 
(3.95) 

-57.0 %i 

(6.17) 
-56.5 %f 

(3.26) 

Number of 
patients with 
baseline 
pruritus NRS 
score ≥ 4 

299 102 295 249 86 249 

Pruritus NRS 
(≥ 4-point 
improvement)
, % 
respondersd, e 

19.7 % 58.8 %f 50.8 %f  12.9 % 51.2 %f 39.0 %f 



18 

Figure 3: Mean percent change from baseline in EASI in CHRONOSa (FAS Week 52)b 
 
 

 
LS = least squares 
a In the primary analyses of the efficacy endpoints, patients who received rescue treatment or with 
missing data were considered non-responders. 
b FAS week 52 includes all patients randomized at least one year before the cutoff date of the primary 
analysis. 
 
Figure 4: Mean percent change from baseline in NRS in CHRONOSa (FAS Week 52)b 
 
 

 
LS = least squares 
aIn the primary analyses of the efficacy endpoints, patients who received rescue treatment or with 
missing data were considered non-responders. 
bFAS week 52 includes all patients randomized at least one year before the cutoff date of the primary 
analysis. 
 
Treatment effects in subgroups (weight, age, gender, race, and background treatment, including 
immunosuppressants) in CHRONOS were consistent with the results in the overall study population. 
 

CHRONOS
 

CHRONOS
 



19 

Clinical Response in Patients Not Adequately Controlled with, Intolerant to, or for whom Ciclosporin 
Treatment was Inadvisable (CAFE study) 

CAFE study evaluated the efficacy of dupilumab compared to placebo during a 16-week treatment 
period, administered with concomitant TCS, in adult patients with AD who are not adequately 
controlled with, or are intolerant to, oral ciclosporin, or when this treatment is currently 
contraindicated or not medically advisable. 
 
A total of 325 patients were enrolled, with 210 patients who were previously exposed to ciclosporin 
and 115 patients who have never been exposed to ciclosporin because ciclosporin treatment was 
medically inadvisable. The mean age was 38.4 years, 38.8 % were female, the baseline mean EASI 
score was 33.1, the mean BSA was 55.7, the baseline weekly average pruritis NRS was 6.4, the 
baseline mean SCORAD score was 67.2, and the baseline mean DLQI was 13.8. 
 
The primary endpoint was the proportion of patients with EASI-75 at week 16. 
Primary and secondary endpoints for the 16 week CAFE study are summarized in table 8. 
 
Table 8: Results of the primary and secondary endpoints in CAFE study 

 Placebo + 
TCS 

Dupilumab 
300 mg Q2W + TCS 

Dupilumab 
300 mg QW+TCS 

Patients randomised 108 107 110 
EASI-75, % responders 29.6 % 62.6 % 59.1 % 
EASI, LS mean % change 
from baseline (+/- SE) 

-46.6 
(2.76) 

-79.8 
(2.59) 

-78.2 
(2.55) 

Pruritus NRS, LS mean % 
change from baseline (+/- SE) 

-25.4 % 
(3.39) 

-53.9 % 
(3.14) 

-51.7 % 
(3.09) 

SCORAD, LS mean % change 
from baseline (+/- SE) 

-29.5 % 
(2.55) 

-62.4 % 
(2.48) 

-58.3 % 
(2.45) 

DLQI, LS mean change from 
baseline (SE) 

-4.5 
(0.49) 

-9.5 
(0.46) 

-8.8 
(0.45) 

(all p-values <0.0001) 
In the subgroup of patients resembling the CAFE study population within the 52 week CHRONOS 
study, 69.6 % of dupilumab 300 mg Q2W-treated patients reached EASI-75 vs 18.0 % placebo-treated 
patients at week 16, and 52.4 % of dupilumab 300 mg Q2W-treated vs 18.6 % placebo-treated at 
week 52. In this subset, the percent change of pruritus NRS from baseline was -51.4 % vs -30.2 % at 
week 16 and -54.8 % vs -30.9 % at week 52, for the dupilumab 300 mg Q2W and placebo groups 
respectively. 

Maintenance and Durability of Response (SOLO CONTINUE study) 

To evaluate maintenance and durability of response, subjects treated with dupilumab for 16 weeks in 
SOLO 1 and SOLO 2 studies who achieved IGA 0 or 1 or EASI-75 were re-randomized in SOLO 
CONTINUE study to an additional 36-week treatment of dupilumab or placebo, for a cumulative 52-
week study treatment. Endpoints were assessed at weeks 51 or 52. 
 
The co-primary endpoints were the difference between baseline (week 0) and week 36 in percent 
change in EASI from SOLO 1 and SOLO 2 studies baseline and percentage of patients with EASI-75 
at week 36 in patients with EASI-75 at baseline. 
 
Patients who continued on the same dose regimen received in the SOLO 1 and SOLO 2 studies (300 
mg Q2W or 300 mg QW) showed the optimal effect in maintaining clinical response while efficacy for 
other dose regimens diminished in a dose-dependent manner. 
 
Primary and secondary endpoints for the 52 week SOLO CONTINUE study are summarized in 
table 9. 
  



20 

Table 9: Results of the primary and secondary endpoints in SOLO CONTINUE study 
 Placebo Dupilumab 300 mg 
 

N=83 
Q8W 
N=84 

Q4W 
N=86 

Q2W/QW 
N=169 

Co-Primary Endpoints     
LS mean change (SE) between baseline 
and week 36 in percent change in EASI 
Score from Parent Study baseline 

21.7 
(3.13) 

6.8*** 
(2.43) 

3.8*** 

(2.28) 
0.1*** 
(1.74) 

Percent of patients with EASI-75 at 
week 36 for patients with EASI-75 at 
baseline, n (%) 

24/79 
(30.4 %) 

45/82* 
(54.9 %) 

49/84** 
(58.3 %) 

116/162*** 

(71.6 %) 

Key Secondary Endpoints     
Percent of patients whose IGA 
response at week 36 was maintained 
within 1 point of baseline in the subset 
of patients with IGA (0,1) at baseline, n 
(%) 

18/63 
(28.6) 

32/64† 
(50.0) 

41/66** 
(62.1) 

89/126*** 

(70.6) 

Percent of patients with IGA (0,1) at 
week 36 in the subset of patients with 
IGA (0,1) at baseline, n (%) 

9/63 
(14.3) 

21/64† 
(32.8) 

29/66**  
(43.9) 

68/126*** 
(54.0) 

Percent of patients whose peak pruritus 
NRS increased by ≥ 3 points from 
baseline to week 35 in the subset of 
patients with peak pruritus NRS ≤ 7 at 
baseline, n (%) 

56/80 
(70.0) 

45/81 
(55.6) 

41/83† 
(49.4) 

57/168*** 

(33.9) 

†P< 0.05, *P< 0.01, **P< 0.001, ***P≤ 0.0001 
 
In SOLO CONTINUE, a trend for increased treatment-emergent ADA positivity with increased dosing 
intervals was observed. Treatment-emergent ADA: QW: 1.2 %; Q2W: 4.3 %; Q4W: 6.0 %; Q8W: 
11.7 %. ADA responses lasting more than 12 weeks: QW: 0.0 %; Q2W: 1.4 %; Q4W: 0.0 %; Q8W: 
2.6 %. 
 
Quality of Life/Patient-Reported Outcomes in Atopic Dermatitis 
 
In both monotherapy studies (SOLO 1 and SOLO 2), both dupilumab 300 mg Q2W and 300 mg QW 
groups significantly improved patient-reported symptoms and the impact of AD on sleep and health-
related quality of life as measured by POEM and DLQI total scores, respectively, at 16 weeks 
compared to placebo. A significantly larger proportion of patients administered dupilumab groups had 
clinically meaningful reductions in POEM and DLQI total score (each defined as ≥ 4 points 
improvement) from baseline to week 16 compared to placebo group. In addition, anxiety and 
depression symptoms as measured by the HADS total score were significantly reduced in the 
dupilumab groups compared to placebo at 16 weeks. In a subset of patients with HADS-anxiety or 
HADS-depression subscale scores ≥ 8 at baseline (the cut-off value for anxiety or depression), a larger 
proportion of patients in the dupilumab groups achieved HADS-anxiety and HADS-depression scores 
< 8 at week 16 compared to placebo (See Table 10). 
 
Table 10: Additional secondary endpoint results of dupilumab monotherapy at Week 16 

 Monotherapy 
 SOLO 1 at Week 16 SOLO 2 at Week 16 
 Placebo  Dupilumab 

300 mg Q2W  
Dupilumab 
300 mg QW 

Placebo  Dupilumab 
300 mg Q2W  

Dupilumab 
300 mg QW 

 
Patients 
randomized 224 224 223 236 233 239 



21 

DLQI, LS mean 
change from 
baseline (SE) 

-5.3 
(0.50)  

-9.3a 
(0.40) 

-9.0a 
(0.40)  

-3.6 
(0.50) 

-9.3a 
(0.38) 

-9.5a 
(0.39) 

POEM, LS 
mean change 
from baseline 
(SE) 

-5.1 
(0.67) 

-11.6a 
(0.49) 

-11.0a 
(0.50) 

-3.3 
(0.55) 

-10.2a 
(0.49) 

-11.3a 
(0.52) 

HADS, LS 
mean change 
from baseline 
(SE) 

-3.0 
(0.65) 

-5.2b 
(0.54) 

-5.2b 
(0.51) 

-0.8 
(0.44) 

-5.1a 
(0.39) 

-5.8a 
(0.38) 

 
Number of 
patients with 
DLQI ≥4 at 
baseline  

213 209 209 225 223 234 

DLQI 
(≥ 4-point 
improvement), 
% responders 

30.5 % 64.1 %a 58.4 %a 27.6 % 73.1 %a 62.0 %a 

 
Number of 
patients with 
POEM ≥4 at 
baseline 

223 222 222 234 233 239 

POEM 
(≥ 4-point 
improvement), 
% responders 

26.9 % 67.6 %a 63.1 %a 24.4 % 71.7 %a 64.0 %a 

 
Number of 
patients with 
HADS-anxiety 
≥ 8 or HADS-
depression ≥ 8 
at baseline 

97 100 102 115 129 136 

Patients 
achieving 
HADS-anxiety 
and HADS-
depression score 
< 8, % 

12.4 % 41.0 %a 36.3 %b 6.1 % 39.5 %a 41.2 %a 

LS = least squares; SE = standard error 
a p-value < 0.0001 
b p-value < 0.001 
 
In the concomitant TCS study (CHRONOS), dupilumab 300 mg Q2W + TCS and dupilumab 300 mg 
QW + TCS improved patient-reported symptoms and the impact of AD on sleep and health-related 
quality of life as measured by POEM and DLQI total scores, respectively, at 52 weeks compared to 
placebo + TCS. A larger proportion of patients administered dupilumab 300 mg Q2W + TCS and 
300 mg QW + TCS had clinically meaningful reductions in POEM and DLQI total score (each defined 
as ≥ 4-point improvement) from baseline to week 52 compared to the placebo + TCS. In addition, 
dupilumab 300 mg Q2W + TCS and 300 mg QW + TCS reduced anxiety and depression as measured 
by the HADS total score at 52 weeks compared to placebo + TCS. In a post-hoc analysis in a subset of 
patients with HADS-anxiety or HADS-depression subscale scores ≥ 8 at baseline (the cut-off value for 
anxiety or depression), a larger proportion of patients in the dupilumab 300 mg Q2W + TCS and 
300 mg QW + TCS groups achieved HADS-anxiety and HADS-depression scores < 8 at week 52 
compared to placebo + TCS (See Table 11). 
 



22 

Table 11: Other secondary endpoint results of dupilumab with concomitant TCS at Week 16 and 
Week 52 in CHRONOS  

 Concomitant Use of TCS 
 CHRONOS at Week 16 CHRONOS at Week 52 
 Placebo  Dupilumab 

300 mg Q2W + 
TCS  

Dupilumab 
300 mg QW + 

TCS 
 

Placebo 
+TCS  

Dupilumab 
300 mg Q2W 

+ TCS  

Dupilumab 
300 mg QW 

+ TCS 

Patients 
randomized 

315 106 319 264 89 270 

DLQI, LS mean 
change from 
baseline (SE) 

-5.8 
(0.34) 

-10.0a 
(0.50) 

-10.7a 
(0.31) 

-7.2 
(0.40) 

-11.4a 
(0.57) 

-11.1a 
(0.36) 

POEM, LS 
mean change 
from baseline 
(SE) 

-5.3 
(0.41) 

-12.7a 
(0.64) 

-12.9a 
(0.37) 

-7.0 
(0.57) 

-14.2a 
(0.78) 

-13.2a 
(0.45) 

HADS, LS 
mean change 
from baseline 
(SE) 

-4.0 
(0.37) 

-4.9 
(0.58) 

-5.4c 
(0.35)  

-3.8 
(0.47) 

-5.5c 
(0.71)  

-5.9b 
(0.42)  

       
Number of 
patients with 
DLQI ≥ 4 at 
baseline 

300 100 311 254 85 264 

DLQI 
(≥ 4-point 
improvement), 
% responders 

43.0 % 81.0 %a 74.3 %a 30.3 % 80.0 %a 63.3 %a 

       
Number of 
patients with 
POEM ≥4 at 
baseline  

312 106 318 261 89 269 

POEM 
(≥ 4-point 
improvement), 
% responders 

36.9 % 77.4 %a 77.4 %a 26.1 % 76.4 %a 64.7 %a 

       
Number of 
patients with 
HADS-anxiety 
≥ 8 or HADS-
depression ≥ 8 
at baseline  

148 59 154 133 53 138 

Patients 
achieving 
HADS-anxiety 
and HADS-
depression < 8, 
% 

26.4 % 47.5 %c 47.4 %b 18.0 % 43.4 %b 44.9 %a 

LS = least squares; SE = standard error 
a p-value < 0.0001 
b p-value < 0.001 



23 

c p-value < 0.05 
 
Adolescents with atopic dermatitis (12 to 17 years of age) 
 
The efficacy and safety of dupilumab monotherapy in adolescent patients was evaluated in a 
multicentre, randomised, double-blind, placebo-controlled study (AD-1526) in 251 adolescent 
patients 12 to 17 years of age with moderate-to-severe atopic dermatitis (AD) defined by 
Investigator’s Global Assessment (IGA) score ≥ 3 in the overall assessment of AD lesions on a 
severity scale of 0 to 4, an Eczema Area and Severity Index (EASI) score ≥ 16 on a scale of 0 to 
72, and a minimum body surface area (BSA) involvement of ≥10 %. Eligible patients enrolled into 
this study had previous inadequate response to topical medication. 
 
Patients received 1) an initial dose of 400 mg dupilumab (two 200 mg injections) on day 1, 
followed by 200 mg once every other week (Q2W) for patients with baseline weight of < 60 kg or 
an initial dose of 600 mg dupilumab (two 300 mg injections) on day 1, followed by 300 mg Q2W 
for patients with baseline weight of ≥ 60 kg; 2) an initial dose of 600 mg dupilumab (two 300 mg 
injections) on day 1, followed by 300 mg every 4 weeks (Q4W) regardless of baseline body 
weight; or 3) matching placebo. Dupilumab was administered by subcutaneous (SC) injection. If 
needed to control intolerable symptoms, patients were permitted to receive rescue treatment at the 
discretion of the investigator. Patients who received rescue treatment were considered non-
responders. 
 
In this study, the mean age was 14.5 years, the median weight was 59.4 kg, 41.0 % were female, 
62.5 % were White, 15.1 % were Asian, and 12.0 % were Black. At baseline 46.2 % of patients 
had a baseline IGA score of 3 (moderate AD), 53.8 % of patients had a baseline IGA of 4 (severe 
AD), the mean BSA involvement was 56.5 %, and 42.4 % of patients had received prior systemic 
immunosuppressants. Also at baseline the mean Eczema Area and Severity Index (EASI) score 
was 35.5, the baseline weekly averaged pruritus Numerical Rating Scale (NRS) was 7.6, the 
baseline mean SCORing Atopic Dermatitis (SCORAD) score was 70.3, the baseline mean Patient 
Oriented Eczema Measure (POEM) score was 21.0, and the baseline mean Children Dermatology 
Life Quality Index (CDLQI) was 13.6. Overall, 92.0 % of patients had at least one co-morbid 
allergic condition; 65.6 % had allergic rhinitis, 53.6 % had asthma, and 60.8 % had food allergies. 
The co-primary endpoint was the proportion of patients with IGA 0 or 1 (“clear” or “almost 
clear”) least a 2-point improvement and the proportion of patients with EASI-75 (improvement 
of at least 75 % in EASI), from baseline to week 16. Other evaluated outcomes included the 
proportion of subjects with EASI-50 or EASI-90 (improvement of at least 50 % or 90 % in EASI 
from baseline respectively), reduction in itch as measured by the peak pruritus NRS, and percent 
change in the SCORAD scale from baseline to week 16. Additional secondary endpoints 
included mean change from baseline to week 16 in the POEM and CDLQI scores. 

Clinical Response 
 
The efficacy results at week 16 for adolescent atopic dermatitis study are presented in Table 12. 
 
Table 12: Efficacy results of dupilumab in the adolescent atopic dermatitis study at Week 16 (FAS) 

 AD-1526(FAS)a 

 Placebo 
 

Dupilumab  
200 mg (<60 kg) and  

300 mg (≥60 kg)  
Q2W 

Patients randomised 85a 82a 

IGA 0 or 1b, % respondersc 2.4 % 24.4 % 
EASI-50, % respondersc 12.9 % 61.0 % 

EASI-75, % respondersc 8.2 % 41.5 % 
EASI-90, % respondersc 2.4 % 23.2 % 



24 

EASI, LS mean % change from baseline (+/-SE) -23.6 % 
(5.49) 

-65.9 % 
(3.99) 

SCORAD, LS mean % change from baseline 
(+/- SE) 

-17.6 % 
(3.76) 

-51.6 % 
(3.23) 

Pruritus NRS, LS mean % change from baseline 
(+/- SE) 

-19.0 % 
(4.09) 

-47.9 % 
(3.43) 

Pruritus NRS (> 4-point improvement), % 
respondersc  

4.8 % 36.6 % 

BSA LS mean % change from baseline  
(+/- SE) 

-11.7 % 
(2.72) 

-30.1 % 
(2.34) 

CDLQI, LS mean change from baseline  
(+/-SE) 

-5.1 
(0.62) 

-8.5 
(0.50) 

CDLQI, (≥ 6-point improvement), % responders 19.7 % 60.6 % 
POEM, LS mean change from baseline  
(+/- SE) 

-3.8 
(0.96) 

-10.1 
(0.76) 

POEM, (≥ 6-point improvement), % responders 9.5 % 63.4 % 
a Full Analysis Set (FAS) includes all patients randomised. 
b Responder was defined as a subject with IGA 0 or 1 (“clear” or “almost clear”) with a reduction of ≥ 2 points 

on a 0-4 IGA scale. 
c Patients who received rescue treatment or with missing data were considered as non-responders (58.8 % and 

20.7 % in the placebo and dupilumab arms, respectively).  
All p–values < 0.0001 
 
A larger percentage of patients randomised to placebo needed rescue treatment (topical corticosteroids, 
systemic corticosteroids, or systemic non-steroidal immunosuppressants) as compared to the 
dupilumab group (58.8 % and 20.7 %, respectively). 
 
A significantly greater proportion of patients randomised to dupilumab achieved a rapid improvement 
in the pruritus NRS compared to placebo (defined as > 4-point improvement as early as week 4; 
nominal p< 0.001) and the proportion of patients responding on the pruritus NRS continued to increase 
through the treatment period (see Figure 5). The improvement in pruritus NRS occurred in conjunction 
with the improvement of objective signs of atopic dermatitis. 
 
Figure 5: Proportion of adolescent patients with ≥ 4-point improvement on the pruritus NRS in 
AD-1526 studya (FAS)b 

 
a In the primary analyses of the efficacy endpoints, subjects who received rescue treatment or with missing data 
were considered non-responders. 
b Full Analysis Set (FAS) includes all subjects randomised. 
 



25 

The dupilumab group significantly improved patient-reported symptoms, the impact of AD on sleep 
and health-related quality of life as measured by POEM, SCORAD, and CDLQI scores at 16 weeks 
compared to placebo. 
 
The long-term efficacy of dupilumab in adolescent patients with moderate-to-severe AD who had 
participated in previous clinical trials of dupilumab was assessed in open-label extension study (AD-
1434). Efficacy data from this study suggests that clinical benefit provided at week 16 was sustained 
through week 52. 
 
Paediatrics (6 to 11 years of age) 
 
The efficacy and safety of dupilumab in paediatric patients concomitantly with TCS was evaluated in a 
multicentre, randomised, double-blind, placebo-controlled study (AD-1652) in 367 subjects 6 to 11 
years of age, with AD defined by an IGA score of 4 (scale of 0 to 4), an EASI score ≥ 21 (scale of 0 to 
72), and a minimum BSA involvement of ≥ 15 %. Eligible patients enrolled into this trial had previous 
inadequate response to topical medication. Enrollment was stratified by baseline weight (< 30 kg; ≥ 30 
kg). 
 

Patients in the dupilumab Q2W + TCS group with baseline weight of < 30 kg received an initial dose 
of 200 mg on Day 1, followed by 100 mg Q2W from week 2 to week 14, and patients with baseline 
weight of ≥ 30 kg received an initial dose of 400 mg on Day 1, followed by 200 mg Q2W from week 2 
to week 14. Patients in the dupilumab Q4W + TCS group received an initial dose of 600 mg on Day 1, 
followed by 300 mg Q4W from week 4 to week 12, regardless of weight. Patients were permitted to 
receive rescue treatment at the discretion of the investigator. Patients who received rescue treatment 
were considered non-responders. 
 
In this study, the mean age was 8.5 years, the median weight was 29.8 kg, 50.1 % of patients were 
female, 69.2 % were White, 16.9 % were Black, and 7.6 % were Asian. At baseline, the mean BSA 
involvement was 57.6 %, and 16.9 % had received prior systemic non-steroidal immunosuppressants. 
Also, at baseline the mean EASI score was 37.9, and the weekly average of daily worst itch score was 
7.8 on a scale of 0-10, the baseline mean SCORAD score was 73.6, the baseline POEM score was 
20.9, and the baseline mean CDLQI was 15.1. Overall, 91.7 % of subjects had at least one co-morbid 
allergic condition; 64.4 % had food allergies, 62.7 % had other allergies, 60.2 % had allergic rhinitis, 
and 46.7 % had asthma. 
 
The co-primary endpoint was the proportion of patients with IGA 0 or 1 (“clear” or “almost clear”) at 
least a 2-point improvement and the proportion of patients with EASI-75 (improvement of at least 
75 % in EASI), from baseline to week 16. Other evaluated outcomes included the proportion of 
patients with EASI-50 and EASI-90 (improvement of at least 50 % and 90 % in EASI from baseline, 
respectively), percent change in EASI score from baseline to week 16, and reduction in itch as 
measured by the peak pruritus NRS (≥ 4-point improvement). Additional secondary endpoints 
included mean change from baseline to week 16 in the POEM and CDLQI scores. 
 
Clinical Response 
 
Table 13 presents the results by baseline weight strata for the approved dose regimens. 
 
TABLE 13: Efficacy Results of Dupilumab with Concomitant TCS in AD-1652 at Week 16 
(FAS)a 

 Dupilumab 
300 mg Q4Wd 

+ TCS 

Placebo 
+TCS 

Dupilumab 
200 mg Q2We 

+ TCS 

Placebo 
+ TCS 

(N=122) (N=123) (N=59) (N=62) 
 ≥ 15 kg ≥ 15 kg ≥ 30 kg ≥ 30 kg 
IGA 0 or 1b, % respondersc 32.8 % 11.4 % 39.0 % 9.7 % 
EASI-50, % respondersc 91.0 % 43.1 % 86.4 % 43.5 % 



26 

EASI-75, % respondersc 69.7 % 26.8 % 74.6 % 25.8 % 
EASI-90, % respondersc 41.8 % 7.3 % 35.6 % 8.1 % 
EASI, LS mean % change from 
baseline (+/-SE) 

-82.1 %
(2.37)

-48.6 %
(2.46)

-80.4 %
(3.61)

-48.3 %
(3.63)

SCORAD, LS mean % change 
from baseline (+/- SE) 

-62.4 %
(2.13)

-29.8 %
(2.26)

-62.7 %
(3.14)

-30.7 %
(3.28)

Pruritus NRS, LS mean % change 
from baseline (+/- SE) 

-54.6 %
(2.89)

-25.9 %
(2.90)

-58.2 %
(4.01)

-25.0 %
(3.95)

Pruritus NRS (≥4-point 
improvement), % respondersc 50.8 % 12.3 % 61.4 % 12.9 % 

BSA LS mean change from 
baseline (+/- SE) 

-40.5
(1.65)

-21.7
(1.72)

-38.4
(2.47)

-19.8
(2.50)

CDLQI, LS mean change from 
baseline (+/-SE) 

-10.6
(0.47)

-6.4
(0.51)

-9.8
(0.63)

-5.6
(0.66)

CDLQI, (≥ 6-point improvement), 
% responders 77.3 % 38.8 % 80.8 % 35.8 % 

POEM, LS mean change from 
baseline (+/- SE) 

-13.6
(0.65)

-5.3
(0.69)

-13.6
(0.90)

-4.7
(0.91)

POEM, (≥ 6-point improvement), 
% responders 81.7 % 32.0 % 79.3 % 31.1 % 

Full Analysis Set (FAS) includes all patients randomised. 
b Responder was defined as a patient with an IGA 0 or 1 (“clear” or “almost clear”). 
c Patients who received rescue treatment or with missing data were considered as non-responders. 
d At Day 1, patients received 600 mg of dupilumab (see section 5.2). 
e At Day 1, patients received 400 mg (baseline weight ≥ 30 kg) of dupilumab. 

A greater proportion of patients randomised to dupilumab + TCS achieved an improvement in the peak 
pruritus NRS compared to placebo + TCS (defined as ≥4-point improvement at week 4). See Figure 6. 

Figure 6: Proportion of Paediatric Subjects with ≥4-point Improvement on the Peak Pruritus 
NRS in AD-1652a (FAS)b

a  In the primary analyses of the efficacy endpoints, patients who received rescue treatment or with missing data 
were considered non-responders.  

b  Full Analysis Set (FAS) includes all patients randomised. 
c At Day 1, patients received 600 mg of dupilumab (see section 5.2) 
d At Day 1, patients received 400 mg (baseline weight ≥ 30 kg) of dupilumab 

The dupilumab groups significantly improved patient-reported symptoms, the impact of AD on sleep 
and health-related quality of life as measured by POEM, SCORAD, and CDLQI scores at 16 weeks 
compared to placebo. 



27 

 
The long-term efficacy and safety of dupilumab + TCS in paediatric patients with moderate to severe 
atopic dermatitis who had participated in the previous clinical trials of dupilumab + TCS was assessed 
in an open-label extension study (AD-1434). Efficacy data from this trial suggests that clinical benefit 
provided at week 16 was sustained through week 52. Some patients receiving dupilumab 300 mg Q4W 
+ TCS showed further clinical benefit when escalated to dupilumab 200 mg Q2W + TCS. The safety 
profile of dupilumab in patients followed through week 52 was similar to the safety profile observed at 
week 16 in the AD-1526 and AD-1652 studies. 
 
Clinical efficacy and safety in asthma  
 
The asthma development program included three randomised, double-blind, placebo-controlled, 
parallel-group, multi-centre studies (DRI12544, QUEST, and VENTURE) of 24 to 52 weeks in 
treatment duration which enrolled a total of 2,888 patients (12 years of age and older). Patients were 
enrolled without requiring a minimum baseline blood eosinophil or other type 2 inflammatory 
biomarker (e.g. FeNO or IgE) level. Asthma treatment guidelines define type 2 inflammation as 
eosinophilia ≥ 150 cells/mcL and/or FeNO ≥ 20 ppb. In DRI12544 and QUEST, the pre-specified 
subgroup analyses included blood eosinophils ≥ 150 and ≥ 300 cells/mcL, FeNO ≥ 25 and ≥ 50 ppb.  
 
DRI12544 was a 24-week dose-ranging study which included 776 patients (18 years of age and older). 
Dupilumab compared with placebo was evaluated in adult patients with moderate to severe asthma on 
a medium-to-high dose inhaled corticosteroid and a long acting beta agonist. The primary endpoint 
was change from baseline to week 12 in FEV1 (L). Annualized rate of severe asthma exacerbation 
events during the 24-week placebo controlled treatment period was also determined. Results were 
evaluated in the overall population (unrestricted by minimum baseline eosinophils or other type 2 
inflammatory biomarkers) and subgroups based on baseline blood eosinophil count. 
 
QUEST was a 52-week confirmatory study which included 1,902 patients (12 years of age and older). 
Dupilumab compared with placebo was evaluated in 107 adolescent and 1,795 adult patients with 
persistent asthma on a medium-to-high dose inhaled corticosteroid (ICS) and a second controller 
medication. Patients requiring a third controller were allowed to participate in this trial. Patients were 
randomised to receive either 200 mg (N=631) or 300 mg (N=633) Dupixent every other week (or 
matching placebo for either 200 mg (N = 317) or 300 mg (N= 321) every other week) following an 
initial dose of 400 mg, 600 mg or placebo respectively. The primary endpoints were the annualized 
rate of severe exacerbation events during the 52-week placebo controlled period and change from 
baseline in pre-bronchodilator FEV1 at week 12 in the overall population (unrestricted by minimum 
baseline eosinophils or other type 2 inflammatory biomarkers) and subgroups based on baseline blood 
eosinophils count and FeNO.  
 
VENTURE was a 24-week oral corticosteroid-reduction study in 210 patients with asthma unrestricted 
by baseline type 2 biomarker levels who required daily oral corticosteroids in addition to regular use of 
high dose inhaled corticosteroids plus an additional controller. After optimizing the OCS dose during 
the screening period, patients received 300 mg dupilumab (n=103) or placebo (n=107) once every 
other week for 24 weeks following an initial dose of 600 mg or placebo. Patients continued to receive 
their existing asthma medicine during the study; however their OCS dose was reduced every 4 weeks 
during the OCS reduction phase (week 4-20), as long as asthma control was maintained. The primary 
endpoint was the percent reduction in oral corticosteroid dose assessed in the overall population, based 
on a comparison of the oral corticosteroid dose at weeks 20 to 24 that maintained asthma control with 
the previously optimized (at baseline) oral corticosteroid dose. 
 
The demographics and baseline characteristics of these 3 studies are provided in Table 14 below. 
  



28 

 
Table 14: Demographics and Baseline Characteristics of Asthma Trials 

Parameter DRI12544 
(n = 776) 

QUEST  
(n = 1902) 

VENTURE 
(n=210) 

Mean age (years) (SD) 48.6 (13.0) 47.9 (15.3) 51.3 (12.6) 

% Female 63.1 62.9 60.5 

% White 78.2 82.9 93.8 

Duration of Asthma (years), mean ± SD 22.03 (15.42) 20.94 (15.36) 19.95 (13.90) 

Never smoked, (%) 77.4 80.7 80.5 

Mean exacerbations in previous year ± SD 2.17 (2.14) 2.09 (2.15) 2.09 (2.16) 

High dose ICS use (%)a 49.5 51.5 88.6 

Pre-dose FEV1 (L) at baseline ± SD 1.84 (0.54) 1.78 (0.60) 1.58 (0.57) 

Mean percent predicted FEV1 at baseline 
(%)(± SD) 

60.77 (10.72) 58.43 (13.52) 52.18 (15.18) 

% Reversibility  (± SD) 26.85 (15.43) 26.29 (21.73) 19.47 (23.25) 

Mean ACQ-5 score (± SD) 2.74 (0.81) 2.76 (0.77) 2.50 (1.16) 

Mean AQLQ score (± SD) 4.02 (1.09) 4.29 (1.05) 4.35 (1.17) 

Atopic Medical History % Overall 
(AD %, NP %, AR %) 

72.9 
(8.0, 10.6, 61.7) 

77.7 
(10.3, 12.7, 68.6) 

72.4 
(7.6, 21.0, 55.7) 

Mean FeNO ppb (± SD) 39.10 (35.09) 34.97 (32.85) 37.61 (31.38) 

% patients with FeNO ppb 
≥ 25 
≥ 50 

 
49.9 
21.6 

 
49.6 
20.5 

 
54.3 
25.2 

Mean total IgE IU/ml (± SD) 435.05 (753.88) 432.40 (746.66) 430.58 (775.96) 

Mean baseline Eosinophil count (± SD) 
cells/mcL  

350 (430) 360 (370) 350 (310) 

% patients with EOS  
≥ 150 cells/mcL 
≥ 300 cells/mcL 

 
77.8 
41.9 

 
71.4 
43.7 

 
71.4 
42.4 

ICS = inhaled corticosteroid; FEV1 = Forced expiratory volume in 1 second; ACQ-5 = Asthma Control 
Questionnaire-5; AQLQ = Asthma Quality of Life Questionnaire; AD = atopic dermatitis; NP = nasal polyposis; 
AR = allergic rhinitis; FeNO = fraction of exhaled nitric oxide; EOS = blood eosinophil 
aThe population in dupilumab asthma trials included patients on medium and high dose ICS. The medium ICS 
dose was defined as equal to 500 mcg fluticasone or equivalent per day. 
 
Exacerbations 
 
In the overall population in DRI12544 and QUEST subjects receiving either dupilumab 200 mg or 
300 mg every other week had significant reductions in the rate of severe asthma exacerbations 
compared to placebo. There were greater reductions in exacerbations in subjects with higher baseline 
levels of type 2 inflammatory biomarkers such as blood eosinophils or FeNO (Table 15 and Table 16). 
  



29 

Table 15: Rate of Severe Exacerbations in DRI12544 and QUEST (Baseline Blood Eosinophil 
Levels ≥ 150 and ≥ 300 cells/mcL) 

Treatment Baseline Blood EOS 
 ≥150 cells/mcL ≥300 cells/mcL 

Exacerbations per Year  % 
Reduction 

Exacerbations per Year %  
Reduction N Rate 

(95% CI) 
Rate 
Ratio 

(95%CI) 

N Rate 
(95% CI) 

Rate  
Ratio 

(95%CI) 
All Severe Exacerbations 
DRI12544 study 
Dupilumab 
200 mg Q2W  

120 0.29 
(0.16, 0.53) 

0.28a 

(0.14, 0.55) 
72 % 65 0.30 

(0.13, 0.68) 
0.29c 

(0.11, 0.76) 
71 % 

Dupilumab 
300 mg Q2W 

129 0.28 
(0.16, 0.50) 

0.27b 

(0.14, 0.52) 
73 % 64 0.20 

(0.08, 0.52) 
0.19d 

(0.07, 0.56) 
81 % 

Placebo 
 

127 1.05 
(0.69, 1.60) 

  68 1.04 
(0.57, 1.90) 

  

QUEST study  
Dupilumab 
200 mg Q2W 

437 0.45 
(0.37, 0.54) 

0.44e 
(0.34,0.58) 

56 % 264 0.37 
(0.29, 0.48) 

0.34e 
(0.24,0.48) 

66 % 

Placebo  
 

232 1.01 
(0.81, 1.25) 

  148 1.08 
(0.85, 1.38) 

  

Dupilumab 
300 mg Q2W 

452 0.43 
(0.36, 0.53) 

0.40 e 
(0.31,0.53) 

60 % 277 0.40 
(0.32, 0.51) 

0.33e 
(0.23,0.45) 

67 % 

Placebo  
 

237 1.08 
(0.88, 1.33) 

  142 1.24 
(0.97, 1.57) 

  

ap-value = 0.0003, bp-value = 0.0001, cp-value = 0.0116, dp-value = 0.0024, ep-value < 0.0001 
 
Table 16. Rate of Severe Exacerbations in QUEST Defined by Baseline FeNO Subgroups 

Treatment Exacerbations per Year  Percent Reduction 
 N Rate (95% CI) Rate Ratio (95%CI) 
FeNO ≥ 25 ppb 
Dupilumab 200 mg Q2W 299 0.35 (0.27, 0.45) 0.35 (0.25, 0.50)a 65 % 
Placebo  162 1.00 (0.78, 1.30)   
Dupilumab 300 mg Q2W 310 0.43 (0.35, 0.54) 0.39 (0.28, 0.54) a 61 % 
Placebo 172 1.12 (0.88, 1.43)   
FeNO ≥ 50 ppb 
Dupilumab 200 mg Q2W 119 0.33 (0.22, 0.48) 0.31 (0.18, 0.52) a 69 % 
Placebo  71 1.057 (0.72, 1.55)   
Dupilumab 300 mg Q2W 124 0.39 (0.27, 0.558) 0.31 (0.19, 0.49) a 69 % 
Placebo  75 1.27 (0.90, 1.80)   

ap-value < 0.0001 
 
In the pooled analysis of DRI12544 and QUEST, hospitalizations and/or emergency room visits due to 
severe exacerbations were reduced by 25.5 % and 46.9 % with dupilumab 200 mg or 300 mg every 
other week, respectively. 
 
Lung Function 
 
Clinically significant increases in pre-bronchodilator FEV1 were observed at week 12 for DRI12544 
and QUEST. There were greater improvements in FEV1 in the subjects with higher baseline levels of 
type 2 inflammatory biomarkers such as blood eosinophils or FeNO (Table 17 and Table 18). 
 
Significant improvements in FEV1 were observed as early as week 2 following the first dose of 
dupilumab for both the 200 mg and 300 mg dose strengths and were maintained through week 24 
(DRI12544) and week 52 in QUEST (see Figure 7). 
 



30 

Figure 7: Mean Change from Baseline in Pre-Bronchodilator FEV1 (L) Over Time (Baseline 
Eosinophils ≥ 150 and ≥ 300 cells/mcL and FeNO ≥ 25 ppb) in QUEST 
 

QUEST: Blood Eosinophils  
≥ 150 cells/mcL 

QUEST: Blood Eosinophils 
 ≥ 300 cells/mcL 

QUEST: FeNO ≥ 25 ppb 

 
 
Table 17: Mean Change from Baseline in Pre-Bronchodilator FEV1 at Week 12 in DRI12544 and 
QUEST (Baseline Blood Eosinophil Levels ≥ 150 and ≥ 300 cells/mcL) 

Treatment 
 

Baseline Blood EOS 

 ≥ 150 cells/mcL ≥ 300 cells/mcL 
N LS Mean Δ 

From 
baseline 
L (%) 

LS Mean  
Difference 
vs. placebo 
(95% CI) 

N LS mean Δ 
From 
baseline 
L (%) 

LS Mean  
Difference 
vs. placebo 
(95% CI) 

DRI12544 study 
Dupilumab
200 mg 
Q2W 

120 0.32 (18.25) 0.23a 

(0.13, 0.33) 
65 0.43 (25.9) 0.26c 

(0.11, 0.40) 

Dupilumab
300 mg 
Q2W 

129 0.26 (17.1) 0.18b 

(0.08, 0.27) 
64 0.39 (25.8) 

  
0.21d 

(0.06, 0.36) 

Placebo  127 0.09 (4.36)  68 0.18 (10.2)  
QUEST study 

Dupilumab
200 mg 
Q2W 

437 0.36 (23.6) 0.17e 

(0.11, 0.23) 
 

264 0.43 (29.0) 
 

0.21e 

(0.13, 0.29) 

Placebo  232 0.18 (12.4)  148 0.21 (15.6)  
Dupilumab
300 mg 
Q2W 

452 0.37 (25.3) 0.15e 
(0.09, 0.21) 

277 0.47 (32.5)  
 

0.24e 
(0.16, 0.32) 

Placebo 237 0.22 (14.2)  142 0.22 (14.4)  
ap-value < 0.0001, bp-value = 0.0004, cp-value = 0.0008, dp-value = 0.0063, ep-value < 0.0001 

 

Table 18: Mean Change from Baseline in Pre-Bronchodilator FEV1 at Week 12 and Week 52 in 
QUEST by Baseline FeNO Subgroups 

Treatment  At Week 12 At Week 52 
N LS Mean Δ 

From baseline L 
(%) 

LS Mean Difference 
vs. placebo (95% 
CI) 

LS Mean Δ 
From baseline L 
(%) 

LS Mean Difference 
vs. placebo (95% 
CI) 

FeNO ≥ 25 ppb 
Dupilumab 
200 mg Q2W 

288 0.44 (29.0 %) 0.23 (0.15, 0.31)a 0.49 (31.6 %) 0.30 (0.22, 0.39)a 

Placebo  157 0.21 (14.1 %)  0.18 (13.2 %)  



31 

Dupilumab 
300 mg Q2W 

295 0.45 (29.8 %) 0.24 (0.16, 0.31)a 0.45 (30.5 %) 0.23 (0.15, 0.31)a 

Placebo 167 0.21 (13.7 %)  0.22 (13.6 %)  
FeNO ≥ 50 ppb 
Dupilumab 
200 mg Q2W 

114 0.53 (33.5 %) 0.30 (0.17, 0.44)a 0.59 (36.4 %) 0.38 (0.24, 0.53)a 

Placebo  69 0.23 (14.9 %)  0.21 (14.6 %)  
Dupilumab 
300 mg Q2W 

113 0.59 (37.6 %) 0.39 (0.26, 0.52)a 0.55 (35.8 %) 0.30 (0.16, 0.44)a 

Placebo 73 0.19 (13.0 %)  0.25 (13.6 %)  
ap-value < 0.0001 
 
Quality of Life/Patient-Reported Outcomes in Asthma 
 
Pre-specified secondary endpoint of ACQ-5 and AQLQ(S) responder rates were analysed at 24 weeks 
(DRI12544 and VENTURE) and at 52 weeks (QUEST). The responder rate was defined as an 
improvement in score of 0.5 or more (scale range 0-6 for ACQ-5 and 1-7 for AQLQ(S)). 
Improvements in ACQ-5 and AQLQ(S) were observed as early as week 2 and maintained for 24 
weeks in DRI12544 study and 52 weeks in QUEST study. Similar results were observed in 
VENTURE. The ACQ-5 and AQLQ(S) responder rate results in patients with elevated baseline 
biomarkers of type 2 inflammation in QUEST at week 52 are presented in Table 19. 
 
Table 19: ACQ-5 and AQLQ(S) Responder Rates at Week 52 in QUEST 

PRO Treatment  EOS 
≥ 150 cells/mcL 

 

EOS 
≥ 300 cells/mcL 

 

FeNO 
≥ 25 ppb 

 
N Responder 

rate % 
N Responder 

rate (%) 
N Responder 

rate (%) 
ACQ-5 Dupilumab 

200 mg Q2W 
395 72.9 239 74.5 262 74.4 

Placebo 201 64.2 124 66.9 141 65.2 
Dupilumab 
300 mg Q2W 

408 70.1 248 71.0 277 75.8 

Placebo  217 64.5 129 64.3 159 64.2 
AQLQ(S) Dupilumab 

200 mg Q2W 
395 66.6 239 71.1 262 67.6 

Placebo 201 53.2 124 54.8 141 54.6 
Dupilumab 
300 mg Q2W 

408 62.0 248 64.5 277 65.3 

Placebo  217 53.9 129 55.0 159 58.5 
 
Oral Corticosteroid Reduction Study (VENTURE) 
 
VENTURE evaluated the effect of dupilumab on reducing the use of maintenance oral corticosteroids. 
Baseline characteristics are presented in Table 14. All patients were on oral corticosteroids for at least 
6 months prior to the study initiation. The baseline mean oral corticosteroid use was 11.75 mg in the 
placebo group and 10.75 mg in the group receiving dupilumab. 
 
In this 24-week trial, asthma exacerbations (defined as a temporary increase in oral corticosteroid dose 
for at least 3 days) were reduced by 59 % in subjects receiving dupilumab compared with those 
receiving placebo (annualized rate 0.65 and 1.60 for the dupilumab and placebo group, respectively; 
rate ratio 0.41 [95% CI 0.26, 0.63]) and improvement in pre-bronchodilator FEV1 from baseline to 
week 24 was greater in subjects receiving dupilumab compared with those receiving placebo (LS mean 
difference for dupilumab versus placebo of 0.22 L [95% CI: 0.09 to 0.34 L]). Effects on lung function, 
on oral steroid and exacerbation reduction were similar irrespective of baseline levels of type 2 
inflammatory biomarkers (e.g. blood eosinophils, FeNO). The ACQ-5 and AQLQ(S) were also 
assessed in VENTURE and showed improvements similar to those in QUEST.  



32 

 
The results for VENTURE by baseline biomarkers are presented in the Table 20. 
  
Table 20: Effect of dupilumab on OCS dose reduction, VENTURE (Baseline Blood Eosinophil 
Levels ≥ 150 and ≥ 300 cells/mcL and FeNO ≥ 25 ppb) 

 
Baseline Blood EOS 

≥ 150 cells/mcL 

Baseline Blood EOS 
≥ 300 cells/mcL 

FeNO ≥ 25 ppb 

Dupilumab 
300 mg Q2W 

N=81 

Placebo 
N=69 

Dupilumab 
300 mg Q2W 

N=48 

Placebo 
N=41 

Dupilumab 
300 mg Q2W 

N=57 

Placebo 
N=57 

Primary endpoint (week 24) 
Percent reduction in OCS from baseline  

Mean overall percent reduction 
from baseline (%) 

Difference (% [95% CI]) 
(Dupilumab vs. placebo) 

75.91 
 

29.39b  

(15.67, 43.12) 

46.51 79.54 
 

36.83b 
(18.94, 54.71) 

42.71 77.46 
 

34.53b 

(19.08, 49.97) 

42.93 

Median % reduction in daily 
OCS dose from baseline 

100 50 100 50 100 50 

Percent reduction from baseline  
100% % 
≥ 90 % 
≥ 75 % 
≥ 50 % 
> 0 % 
No reduction or any increase in 
OCS dose, or dropped out of 
study 

 
54.3 
58.0 
72.8 
82.7 
87.7 
12.3 

 
33.3 
34.8 
44.9 
55.1 
66.7 
33.3 

 
60.4 
66.7 
77.1 
85.4 
85.4 
14.6 

 
31.7 
34.1 
41.5 
53.7 
63.4 
36.6 

 
52.6 
54.4 
73.7 
86.0 
89.5 
10.5 

 
28.1 
29.8 
36.8 
50.9 
66.7 
33.3 

Secondary endpoint (week 24)a 
Proportion of patients 
achieving a reduction of OCS 
dose to < 5 mg/day 

77 44 84 40 79 34 

Odds ratio (95% CI) 4.29c 
(2.04, 9.04) 

 8.04d 
(2.71, 23.82) 

 7.21b 

(2.69, 19.28) 
 

aModel estimates by logistic regression 
bp-value < 0.0001  
cp-value = 0.0001 
dp-value = 0.0002 
 
Long-term extension trial (TRAVERSE) 
 
The long-term safety of dupilumab in 2,193 adults and 89 adolescents with moderate-to-severe asthma, 
including 185 adults with oral corticosteroid-dependent asthma, who had participated in previous 
clinical trials of dupilumab (DRI12544, QUEST, and VENTURE), was assessed in the open-label 
extension study (TRAVERSE) (see section 4.8). Efficacy was measured as a secondary endpoint, was 
similar to results observed in the pivotal studies and was sustained up to 96 weeks. In the adults with 
oral-corticosteroid-dependent asthma, there was sustained reduction in exacerbations and improvement 
in lung function up to 96 weeks, despite decrease or discontinuation of oral corticosteroid dose. 
 
Clinical efficacy in chronic rhinosinusitis with nasal polyposis (CRSwNP) 
 
The chronic rhinosinusitis with nasal polyposis (CRSwNP) development program included two 
randomised, double-blind, parallel-group, multicentre, placebo-controlled studies (SINUS-24 and 
SINUS-52) in 724 patients aged 18 years and older on background intranasal corticosteroids (INCS). 
These studies included patients with severe CRSwNP despite prior sino-nasal surgery or treatment 



33 

with, or who were ineligible to receive, systemic corticosteroids in the past 2 years. Rescue with 
systemic corticosteroids or surgery was allowed during the studies at the investigator’s discretion. In 
SINUS-24, a total of 276 patients were randomised to receive either 300 mg dupilumab (N=143) or 
placebo (N=133) every other week for 24 weeks. In SINUS-52, 448 patients were randomised to 
receive either 300 mg dupilumab (N=150) every other week for 52 weeks, 300 mg dupilumab (N=145) 
every other week until week 24 followed by 300 mg dupilumab every 4 weeks until week 52, or 
placebo (N=153). All patients had evidence of sinus opacification on the Lund MacKay (LMK) sinus 
CT scan and 73 % to 90 % of patients had opacification of all sinuses. Patients were stratified based on 
their histories of prior surgery and co-morbid asthma/nonsteroidal anti-inflammatory drug exacerbated 
respiratory disease (NSAID-ERD). 

The co-primary efficacy endpoints were change from baseline to week 24 in bilateral endoscopic nasal 
polyps score (NPS) as graded by central blinded readers, and change from baseline to week 24 in nasal 
congestion/obstruction score averaged over 28 days (NC), as determined by patients using a daily 
diary. For NPS, polyps on each side of the nose were graded on a categorical scale (0=no polyps; 
1=small polyps in the middle meatus not reaching below the inferior border of the middle turbinate; 
2=polyps reaching below the lower border of the middle turbinate; 3=large polyps reaching the lower 
border of the inferior turbinate or polyps medial to the middle turbinate; 4=large polyps causing 
complete obstruction of the inferior nasal cavity). The total score was the sum of the right and left 
scores. Nasal congestion was rated daily by the subjects on a 0 to 3 categorical severity scale (0=no 
symptoms; 1=mild symptoms; 2=moderate symptoms; 3=severe symptoms).  
In both studies, key secondary end-points at week 24 included change from baseline in: LMK sinus CT 
scan score, total symptoms score (TSS), University of Pennsylvania smell identification test (UPSIT), 
daily loss of smell, and 22-item Sino-Nasal Outcome Test (SNOT-22). In the pool of the two studies, 
the reduction in the proportion of patients rescued with systemic corticosteroid and/or sino-nasal 
surgery as well as the improvement in FEV1 in the asthma subgroup were evaluated. Additional 
secondary endpoints included 6-item Asthma Control Questionnaire (ACQ-6) in the co-morbid asthma 
subgroup. 
 
The demographics and baseline characteristics of these 2 studies are provided in Table 21 below. 
 
Table 21: Demographics and Baseline Characteristics of CRSwNP Studies 

Parameter SINUS-24 
(N=276) 

SINUS-52 
(N=448) 

Mean age (years) (SD) 50.49 (13.39) 51.95 (12.45) 
% Male 57.2 62.3 
Mean CRSwNP duration (years)(SD) 11.11 (9.16) 10.94 (9.63) 
Patients with ≥ 1 prior surgery (%) 71.7 58.3 
Patients with systemic corticosteroid use in the previous 2 
years (%) 

64.9 80.1 

Mean Bilateral endoscopic NPSa (SD), range 0–8 5.75 (1.28) 6.10 (1.21) 
Mean Nasal congestion (NC) scorea (SD) range 0–3 2.35 (0.57) 2.43 (0.59) 
Mean LMK sinus CT total scorea(SD), range 0–24  19.03 (4.44) 17.96 (3.76) 
Mean Smell test (UPSIT) scorea (SD), range 0–40 14.56 (8.48) 13.61 (8.02) 
Mean loss of smell scorea (AM), (SD) range 0–3 2.71 (0.54) 2.75 (0.52) 
Mean SNOT-22 total scorea (SD), range 0–110 49.40 (20.20) 51.86 (20.90) 
Mean Rhinosinusitis severity scalea (VAS), (SD) 0–10 cm 7.68 (2.05) 8.00 (2.08) 
Mean blood eosinophils (cells/mcL)(SD) 437 (333) 431 (353) 
Mean total IgE IU/ml (SD) 211.97 

(275.73) 
239.84 

(341.53) 
Atopic (type 2 inflammatory disease)  Medical History  
% Overall 

 
75.4 % 

 
82.4 % 

Asthma (%) 58.3 59.6 



34 

Mean FEV1 (L)(SD) 2.69 (0.96) 2.57 (0.83) 
Mean FEV1 percent predicted (%)(SD) 85.30 (20.23) 83.39 (17.72) 
Mean ACQ-6 scorea (SD) 1.62 (1.14) 1.58 (1.09) 

NSAID-ERD (%) 30.4 26.8 
aHigher scores indicate greater disease severity except UPSIT where higher scores indicate lower disease 
severity; SD=standard deviation; AM = morning; NPS = nasal polyps score; UPSIT = University of 
Pennsylvania smell identification test; SNOT-22 = 22-item Sino-Nasal Outcome Test; VAS = visual analogue 
scale; FEV1 = Forced expiratory volume in 1 second; ACQ-6 = Asthma Control Questionnaire-6; NSAID-ERD= 
aspirin/nonsteroidal anti-inflammatory drug exacerbated respiratory disease  

Clinical Response (SINUS-24 and SINUS-52) 

The results for primary and secondary endpoints in CRSwNP studies are presented in the Table 22. 

Table 22: Results of the Primary and Secondary Endpoints in CRSwNP trials 

SINUS -24 SINUS -52 
Placebo 
(n=133) 

Dupilumab 
 300mg Q2W 

(n=143) 

LS mean 
difference vs. 

Placebo 
(95%CI) 

Placebo 
(n=153) 

Dupilumab 
300mg Q2W 

(n=295) 

LS mean 
difference vs. 

Placebo 
(95%CI) 

Primary Endpoints at Week 24 

Scores 
Baseline 

mean 
LS 

mean 
change 

Baseline 
mean 

LS 
mean 

change 

Baseline 
mean 

LS 
mean 

change 

Baseline 
mean 

LS 
mean 

change 

NPS 5.86 0.17 5.64 -1.89
-2.06

(-2.43, -1.69) 5.96 0.10 6.18 -1.71
-1.80

(-2.10, -1.51) 

NC 2.45 -0.45 2.26 -1.34 -0.89
(-1.07, -0.71) 2.38 -0.38 2.46 -1.25 -0.87

(-1.03, -0.71) 
Key Secondary Endpoints at Week 24 

Scores 
Baseline 

mean 

LS 
mean 

change 

Baseline 
mean 

LS 
mean 

change 

Baseline 
mean 

LS 
mean 

change 

Baseline 
mean 

LS 
mean 

change 
LMK 
sinus CT 
scan  
score 

19.55 -0.74 18.55 -8.18 -7.44
(-8.35, -6.53) 17.65 -0.09 18.12 -5.21 -5.13

(-5.80, -4.46) 

Total 
symptom 
score 

7.28 -1.17 6.82 -3.77 -2.61
(-3.04, -2.17) 7.08 -1.00 7.30 -3.45 -2.44

(-2.87, -2.02) 

UPSIT 14.44 0.70 14.68 11.26 10.56 
(8.79, 12.34) 13.78 -0.81 13.53 9.71 10.52 

(8.98, 12.07) 
Loss of 
smell 

2.73 -0.29 2.70 -1.41 -1.12
(-1.31, -0.93) 

2.72 -0.23 2.77 -1.21 -0.98
(-1.15, -0.81) 

SNOT-22 50.87 -9.31 48.0 -30.43 -21.12
(-25.17, -17.06) 53.48 -10.40 51.02 -27.77 -17.36

(-20.87, -13.85) 

VAS 7.96 -1.34 7.42 -4.54 -3.20
(-3.79, -2.60) 7.98 -1.39 8.01 -4.32 -2.93

(-3.45, -2.40) 

A reduction in score indicates improvement, except UPSIT where an increase indicates improvement. 
Total symptom score is a composite severity score consisting of the sum of daily symptoms of NC, loss of smell, 
and anterior/posterior rhinorrhoea. 
NC = nasal congestion, NPS = nasal polyposis score; LMK = Lund-MacKay total CT score; UPSIT = University 
of Pennsylvania smell identification test; SNOT-22 = 22-item Sino-Nasal Outcome Test; TSS = total symptom 
score; VAS = visual analogue scale for rhinosinusitis 



35 

(all p-values < 0.0001, nominal for VAS) 
 
The results of SINUS-52 study at week 52 are presented in Table 23. 
 
Table 23: Results of the efficacy at week 52 in SINUS-52 study 

 
 

Placebo 
(n=153) 

Dupilumab  
300mg Q2W 

(n=150) 

LS mean 
difference vs. 

Placebo 
(95%CI) 

Dupilumab  
300mg Q2W-Q4W 

(n=145) 

LS mean 
difference vs. 

Placebo 
(95%CI) Baseline 

mean 
LS mean 
change 

Baseline 
mean 

LS mean 
change 

Baseline 
mean 

LS mean 
change 

NPS 5.96 0.15 6.07 -2.24 
-2.40 

(-2.77, -2.02) 
6.29 -2.06 -2.21 

(-2.59, -1.83) 

NC 2.38 -0.37 2.48 -1.35 -0.98 
(-1.17, -0.79) 

2.44 -1.48 -1.10  
(-1.29, -0.91) 

LMK sinus CT 
scan score 17.65 0.11 18.42 -6.83 -6.94  

(-7.87, -6.01) 
17.81 -5.60 -5.71  

(-6.64, -4.77) 
Total symptom 
score 7.08 -0.94 7.31 -3.79 -2.85 

(-3.35, -2.35) 
7.28 -4.16 -3.22 

(-3.73, -2.72) 

UPSIT 13.78 -0.77 13.46 9.53 10.30 
(8.50, 12.10) 

13.60 9.99 10.76 
(8.95, 12.57) 

Loss of Smell 2.72 -0.19 2.81 -1.29 -1.10 
(-1.31, -0.89) 

2.73 -1.49 -1.30 
(-1.51, -1.09) 

SNOT-22 53.48 -8.88 50.16 -29.84 -20.96 
(-25.03, -16.89) 

51.89 -30.52 -21.65 
(-25.71, -

17.58) 

VAS 7.98 -0.93 8.24 -4.74 -3.81 
(-4.46, -3.17) 

7.78 -4.39 -3.46 
(-4.10, -2.81) 

A reduction in score indicates improvement, except UPSIT where an increase indicates improvement. 
Total symptom score is a composite severity score consisting of the sum of daily symptoms of NC, loss of smell, 
and anterior/posterior rhinorrhoea. 
NC = nasal congestion, NPS = nasal polyposis score; LMK = Lund-MacKay total CT score; UPSIT = University 
of Pennsylvania smell identification test; SNOT-22 = 22-item Sino-Nasal Outcome Test; TSS = total symptom 
score; VAS = visual analogue scale for rhinosinusitis 
(all p-values < 0.0001) 
 
Statistically significant and clinically meaningful efficacy was observed in SINUS-24 with regard to 
improvement in bilateral endoscopic NPS score at week 24. In the post-treatment period when patients 
were off dupilumab, the treatment effect diminished over time (see Figure 8a). Similar results were 
also seen in SINUS-52 at both week 24 and week 52 with a progressive improvement over time (see 
Figure 8b). 
  



36 

 
Figure 8. LS mean change from baseline in bilateral nasal polyps score (NPS) in SINUS-24 and 
SINUS-52 - ITT population.  
 

Figure 8a. SINUS-24 Figure 8b. SINUS-52 

  
 
In both studies, significant improvements in NC and daily loss of smell severity were observed as 
early as the first assessment at week 4. The LS mean difference for NC at week 4 in the dupilumab 
group versus placebo was -0.41 (95% CI: -0.52, -0.30) in SINUS-24 and -0.37 (95% CI: -0.46, -0.27) 
in SINUS-52. The LS mean difference for loss of smell at week 4 in the dupilumab group versus 
placebo was -0.34 (95% CI: -0.44, -0.25) in SINUS-24 and -0.31 (95% CI: -0.41, -0.22) in SINUS-52. 
A reduction in the proportion of patients with anosmia was observed in SINUS-24 and SINUS-52. At 
baseline, 74 % to 79 % of patients had anosmia, which was reduced to 24 % in SINUS-24 and 30 % in 
SINUS-52 at week 24, compared to no change in placebo. Improvement in nasal peak inspiratory flow 
(NPIF) was observed in SINUS-24 and SINUS-52 at week 24. The LS mean difference in the 
dupilumab group versus placebo was 40.4 L/min (95% CI: 30.4, 50.4) and 36.6 L/min (95% CI: 28.0, 
45.3), respectively. 
 
Among the patients with rhinosinusitis VAS score > 7 at baseline, a higher percentage of patients 
achieved VAS ≤ 7 in the dupilumab group compared with the placebo group (83.3 % versus 39.4 % in 
SINUS-24 and 75.0 % versus 39.3 % in SINUS-52) at week 24. 
 
In the pre-specified multiplicity-adjusted pooled analysis of two studies, treatment with dupilumab 
resulted in significant reduction of systemic corticosteroid use and need for sino-nasal surgery versus 
placebo (HR of 0.24; 95% CI: 0.17, 0.35) (see Figure 9). The proportion of patients who required 
systemic corticosteroids was reduced by 74 % (HR of 0.26; 95% CI: 0.18, 0.38). The total number of 
systemic corticosteroid courses per year was reduced by 75 % (RR of 0.25; 95% CI: 0.17, 0.37). The 
mean individual annualised prescribed total dose of systemic corticosteroids (in mg) during the 
treatment period was 71 % lower in the pooled dupilumab group compared with the pooled placebo 
group (60.5 [531.3] mg versus 209.5 [497.2] mg, respectively). The proportion of patients who 
required surgery was reduced by 83 % (HR of 0.17; 95% CI: 0.07, 0.46). 
 
  



37 

Figure 9. Kaplan Meier Curve for time to first systemic corticosteroid use and/or sino-nasal 
surgery during treatment period - ITT population [SINUS-24 and SINUS-52 pooled] 

 

 

The effects of dupilumab on the primary endpoints of NPS and nasal congestion and the key secondary 
endpoint of LMK sinus CT scan score were consistent in patients with prior surgery and without prior 
surgery. 
 
In patients with co-morbid asthma, significant improvements in FEV1 and ACQ-6 were observed at 
week 24 irrespective of baseline blood eosinophils levels. The pooled LS Mean change from baseline 
in FEV1 at week 24 for dupilumab 300 mg Q2W was 0.14 vs -0.07 L for placebo, for a difference of 
0.21 L (95% CI: 0.13, 0.29). In addition, improvements in FEV1 were noted from the first 
post-baseline assessment, at week 8 in SINUS-24 and week 4 in SINUS-52. Improvements in ACQ-6 
in patients with co-morbid asthma were observed in both studies. A response was defined as an 
improvement in score of 0.5 or more. The LS mean difference in the dupilumab group versus placebo 
at week 24 was -0.76 (95% CI: -1.00 to -0.51) in SINUS-24 and -0.94 (95% CI: -1.19, -0.69) in 
SINUS-52. 

The ACQ-6 responder rate for dupilumab 300 mg Q2W for SINUS-24 at week 24 was 56 % versus 
28 % in placebo (odds ratio 3.17; 95% CI: 1.65, 6.09). The ACQ-6 responder rate for dupilumab 300 
mg Q2W for SINUS-52 was 46 % versus 14 % placebo at week 52 (odds ratio 7.02; 95% CI: 3.10, 
15.90). 
In patients with NSAID-ERD, the effects of dupilumab on the primary endpoints of NPS and NC and 
the key secondary endpoint of LMK sinus CT scan score were consistent with that observed in the 
overall CRSwNP population. 
 
Paediatric population 
 
Atopic dermatitis  
The safety and efficacy of dupilumab have been established in 12 to 17 years old with moderate-to-
severe atopic dermatitis in study AD-1526 which included 251 adolescents. The safety and efficacy of 
dupilumab have been established in 6 to 11 years old with severe atopic dermatitis in study AD-1652 
which included 367 paediatric patients. Use is supported by study AD-1434 which enrolled patients 
who had completed AD-1526 (136 moderate and 64 severe at the time of enrolment in study AD-
1434) and patients who had completed study AD-1652 (110 moderate and 72 severe at the time of 
enrolment in in study AD-1434). The safety and efficacy were generally consistent between children 6 
to 11 years old, adolescent, and adult patients with atopic dermatitis (see section 4.8). Safety and 
efficacy in paediatric patients < 6 years of age with atopic dermatitis have not been established. 
 



38 

Asthma 
A total of 107 adolescents aged 12 to 17 years with moderate to severe asthma were enrolled in 
QUEST study and received either 200 mg (N=21) or 300 mg (N=18) dupilumab (or matching placebo 
either 200 mg [N=34] or 300 mg [N=34]) every other week. Efficacy with respect to severe asthma 
exacerbations and lung function was observed in both adolescents and adults. For both the 200 mg and 
300 mg every other week doses, significant improvements in FEV1 (LS mean change from baseline at 
eek 12) were observed (0.36 L and 0.27 L, respectively). For the 200 mg every other week dose, 
patients had a reduction in the rate of severe exacerbations that was consistent with adults. Safety and 
efficacy in paediatric patients (< 12 years of age) with severe asthma have not been established. The 
adverse event profile in adolescents was generally similar to the adults. 
 
A total of 89 adolescents aged 12 to 17 years with moderate-to-severe asthma were enrolled in the 
open label long-term study (TRAVERSE). In this study, efficacy was measured as a secondary 
endpoint, was similar to results observed in the pivotal studies and was sustained up to 96 weeks. 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
dupilumab in one or more subset of the paediatric population in atopic dermatitis and asthma (see 
section 4.2 for information on paediatric use). The European Medicines Agency has waived the 
obligation to submit the results of studies with dupilumab in all subsets of the paediatric population in 
the treatment of nasal polyposis (see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties  
 
The pharmacokinetics of dupilumab is similar in patients with atopic dermatitis, asthma, and 
CRSwNP. 
 
Absorption 
 
After a single subcutaneous (SC) dose of 75-600 mg dupilumab to adults, median times to maximum 
concentration in serum (tmax) were 3-7 days. The absolute bioavailability of dupilumab following a SC 
dose is similar between AD, asthma, and CRSwNP patients, ranging between 61 % and 64 %, as 
determined by a population pharmacokinetics (PK) analysis. 
 
Steady-state concentrations were achieved by week 16 following the administration of 600 mg starting 
dose and 300 mg dose every other week or 300 mg dose every other week without a loading dose. 
Across clinical trials, the mean ±SD steady-state trough concentrations ranged from 69.2±36.9 mcg/ml 
to 80.2±35.3 mcg/ml for 300 mg dose and from 29.2±18.7 to 36.5±22.2 mcg/ml for 200 mg dose 
administered every other week to adults. 
 
Distribution 
 
A volume of distribution for dupilumab of approximately 4.6 L was estimated by population PK 
analysis, indicating that dupilumab is distributed primarily in the vascular system. 
 
Biotransformation 
 
Specific metabolism studies were not conducted because dupilumab is a protein. Dupilumab is 
expected to degrade to small peptides and individual amino acids. 
 
Elimination 
 
Dupilumab elimination is mediated by parallel linear and nonlinear pathways. At higher 
concentrations, dupilumab elimination is primarily through a non-saturable proteolytic pathway, while 
at lower concentrations, the non-linear saturable IL-4R α target-mediated elimination predominates. 
After the last steady state dose, the median time for dupilumab concentrations to decrease below the 
lower limit of detection, estimated by population PK analysis, was 6-7 weeks for the 300 mg Q4W 



39 

regimen, 9 weeks for the 200 mg Q2W regimen, 10-11 weeks for the 300 mg Q2W regimen, and 13 
weeks for the 300 mg QW regimen. 
 
Linearity/non-linearity 
 
Due to nonlinear clearance, dupilumab exposure, as measured by area under the concentration-time 
curve, increases with dose in a greater than proportional manner following single SC doses from 75-
600 mg. 
 
Special populations 
 
Gender 
Gender was not found to be associated with any clinically meaningful impact on the systemic exposure 
of dupilumab determined by population PK analysis. 
 
Elderly 
Of the 1,472 patients with atopic dermatitis exposed to dupilumab in a phase 2 dose-ranging study or 
phase 3 placebo-controlled studies, a total of 67 were 65 years or older. Although no differences in 
safety or efficacy were observed between older and younger adult atopic dermatitis patients, the 
number of patients aged 65 and over is not sufficient to determine whether they respond differently 
from younger patients. 
 
Age was not found to be associated with any clinically meaningful impact on the systemic exposure of 
dupilumab determined by population PK analysis. However, there were only 61 patients over 65 years 
of age included in this analysis. 
 
Of the 1,977 patients with asthma exposed to dupilumab, a total of 240 patients were 65 years or older 
and 39 patients were 75 years or older. Efficacy and safety in this age group were similar to the overall 
study population. 
 
There were only 79 patients older than 65 years with CRSwNP exposed to dupilumab among them 11 
patients were 75 years and older. 
 
Race 
Race was not found to be associated with any clinically meaningful impact on the systemic exposure 
of dupilumab by population PK analysis. 
 
Hepatic impairment 
Dupilumab, as a monoclonal antibody, is not expected to undergo significant hepatic elimination. No 
clinical studies have been conducted to evaluate the effect of hepatic impairment on the 
pharmacokinetics of dupilumab. 
 
Renal impairment 
Dupilumab, as a monoclonal antibody, is not expected to undergo significant renal elimination. No 
clinical studies have been conducted to evaluate the effect of renal impairment on the 
pharmacokinetics of dupilumab.  Population PK analysis did not identify mild or moderate renal 
impairment as having a clinically meaningful influence on the systemic exposure of dupilumab. Very 
limited data are available in patients with severe renal impairment. 
 
Body Weight 
Dupilumab trough concentrations were lower in subjects with higher body weight with no meaningful 
impact on efficacy. There were only 6 patients exposed to dupilumab with body weight ≥130 kg in 
CRSwNP clinical studies. 
 
Paediatric population 
 
Atopic dermatitis 



40 

The pharmacokinetics of dupilumab in paediatric patients (< 6 years of age) or body weight < 15 kg 
with atopic dermatitis has not been studied. 
 
For adolescents 12 to 17 years of age with atopic dermatitis receiving every other week dosing (Q2W) 
with either 200 mg (< 60 kg) or 300 mg (≥ 60 kg), the mean ±SD steady state trough concentration of 
dupilumab was 54.5±27.0 mcg/ml. 
 
For children 6 to 11 years of age with atopic dermatitis receiving every four week dosing (Q4W) with 
300 mg (≥ 15 kg) in AD-1652, the mean ± SD steady-state trough concentration was 76.3±37.2 
mcg/ml. At week 16 in AD-1434 in children 6 to 11 years of age who initiated every four week dosing 
(Q4W) with 300 mg (≥ 15 kg), and whose dose was increased to every other week dosing (Q2W) with 
200 mg (≥ 15 to < 60 kg) or 300 mg (≥ 60 kg), the mean±SD steady-state trough concentration was 
108±53.8 mcg/ml. For children 6 to 11 years of age receiving 300 mg Q4W, initial doses of 300 mg on 
Days 1 and 15 produce similar steady-state exposure as an initial dose of 600 mg on Day 1, based on 
PK simulations 
 
Asthma  
A total of 107 adolescents aged 12 to 17 years with asthma were enrolled in QUEST study. The mean 
±SD steady-state trough concentrations of dupilumab were 107±51.6 mcg/ml and 46.7±26.9 mcg/ml, 
respectively, for 300 mg or 200 mg administered every other week. No age-related pharmacokinetic 
difference was observed in adolescent patients after correction for body weight. 
 
CRSwNP 
CRSwNP does not normally occur in children. The pharmacokinetics of dupilumab in paediatric 
patients (< 18 years of age) with CRSwNP has not been studied. 
 
5.3 Preclinical safety data  
 
Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dose 
toxicity (including safety pharmacology endpoints) and toxicity to reproduction and development. 
 
The mutagenic potential of dupilumab has not been evaluated; however monoclonal antibodies are not 
expected to alter DNA or chromosomes. 
 
Carcinogenicity studies have not been conducted with dupilumab. An evaluation of the available 
evidence related to IL-4Rα inhibition and animal toxicology data with surrogate antibodies does not 
suggest an increased carcinogenic potential for dupilumab. 
 
During a reproductive toxicology study conducted in monkeys, using a surrogate antibody specific to 
the monkey IL-4Rα, no fetal abnormalities were observed at dosages that saturate the IL-4Rα.  
 
An enhanced pre- and post-natal developmental study revealed no adverse effects in maternal animals 
or their offspring up to 6 months post-partum/post-birth. 
 
Fertility studies conducted in male and female mice using a surrogate antibody against IL-4Rα showed 
no impairment of fertility (see section 4.6). 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients  
 
arginine hydrochloride 
histidine 
polysorbate 80 (E433) 
sodium acetate trihydrate 
glacial acetic acid (E260) 



41 

sucrose 
water for injections 
 
6.2 Incompatibilities  
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life  
 
3 years.  
 
If necessary, pre-filled syringes or pre-filled pens may be kept at room temperature up to 25°C for a 
maximum of 14 days. Do not store above 25°C. If the carton needs to be removed permanently from 
refrigerator, the date of removal may be recorded on the outer carton. After removal from the 
refrigerator, Dupixent must be used within 14 days or discarded.  
 
6.4 Special precautions for storage  
 
Store in a refrigerator (2°C - 8°C). 
 
Do not freeze. 
 
Store in the original carton in order to protect from light. 
 
6.5 Nature and contents of container  
 
Dupixent 300 mg solution for injection in pre-filled syringe  
2 ml solution in a siliconised type-1 clear glass pre-filled syringe with or without needle shield, with a 
fixed 27 gauge 12.7 mm (½ inch), thin wall stainless steel staked needle.  
 
Pack size:  
• 1 pre-filled syringe  
• 2 pre-filled syringes  
• Multipack containing 3 (3 packs of 1) pre-filled syringes  
• Multipack containing 6 (3 packs of 2) pre-filled syringes  
 
Dupixent 300 mg solution for injection in pre-filled pen  
2 ml solution in a siliconised type-1 clear glass syringe in a pre-filled pen, with a fixed 27 gauge 12.7 
mm (½ inch), thin wall stainless steel staked needle.  
 
Pack size:  
• 1 pre-filled pen  
• 2 pre-filled pens  
• 3 pre-filled pens  
• 6 pre-filled pens  
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
The instructions for the preparation and administration of Dupixent in a pre-filled syringe or in a pre-
filled pen are given in the package leaflet. 
 
The solution should be clear to slightly opalescent, colourless to pale yellow. If the solution is cloudy, 
discoloured or contains visible particulate matter, the solution should not be used. 



42 

 
After removing the 300 mg pre-filled syringe or pre-filled pen from the refrigerator, it should be 
allowed to reach room temperature up to 25°C by waiting for 45 min before injecting Dupixent. 
 
The pre-filled syringe or pre-filled pen should not be exposed to heat or direct sunlight and should not 
be shaken. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. After use, place the pre-filled syringe or the pre-filled pen into a puncture-resistant 
container and discard as required by local regulations. Do not recycle the container. Keep the container 
out of sight and reach of children. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
sanofi-aventis groupe 
54, rue La Boétie 
75008 Paris 
France 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/17/1229/001 
EU/1/17/1229/002 
EU/1/17/1229/003 
EU/1/17/1229/004 
EU/1/17/1229/005 
EU/1/17/1229/006 
EU/1/17/1229/007 
EU/1/17/1229/008 
EU/1/17/1229/017 
EU/1/17/1229/018 
EU/1/17/1229/019 
EU/1/17/1229/020 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 26 September 2017 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 

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


43 

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 
 
Dupixent 200 mg solution for injection in pre-filled syringe 
Dupixent 200 mg solution for injection in pre-filled pen 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Dupilumab 200 mg solution for injection in pre-filled syringe 
 
Each single-use pre-filled syringe contains 200 mg of dupilumab in 1.14 ml solution (175 mg/ml). 
 
Dupilumab 200 mg solution for injection in pre-filled pen 
 
Each single-use pre-filled pen contains 200 mg of dupilumab in 1.14 ml solution (175 mg/ml). 
 
Dupilumab is a fully human monoclonal antibody against interleukin (IL)-4 receptor alpha that inhibits 
IL-4/IL-13 signalling, produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA 
technology. 
 
For the full list of excipients, see section 6.1.  
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection (injection) 
 
Clear to slightly opalescent, colourless to pale yellow sterile solution, which is free from visible 
particulates, with a pH of approximately 5.9. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications  
 
Atopic dermatitis 
 
Adults and adolescents 
Dupixent is indicated for the treatment of moderate-to-severe atopic dermatitis in adults and 
adolescents 12 years and older who are candidates for systemic therapy. 
 
Children 6 to 11 years of age 
Dupixent is indicated for the treatment of severe atopic dermatitis in children 6 to 11 years old who are 
candidates for systemic therapy. 
 
Asthma 
 
Dupixent is indicated in adults and adolescents 12 years and older as add-on maintenance treatment for 
severe asthma with type 2 inflammation characterised by raised blood eosinophils and/or raised 
fraction of exhaled nitric oxide (FeNO), see section 5.1, who are inadequately controlled with high 
dose ICS plus another medicinal product for maintenance treatment.  
 



44 

4.2 Posology and method of administration  
 
Treatment should be initiated by healthcare professionals experienced in the diagnosis and treatment of 
conditions for which dupilumab is indicated (see section 4.1). 
 
Posology 
 
Atopic Dermatitis 
 
Adolescents(12 to 17 years of age) 
The recommended dose of dupilumab for adolescent patients 12 to 17 years of age is specified in 
Table 1. 
 
Table 1: Dose of dupilumab for subcutaneous administration in adolescent patients 12 years to 
17 years of age with atopic dermatitis 

Body Weight of 
Patient 

Initial Dose Subsequent Doses 
(every other week) 

less than 60 kg 400 mg (two 200 mg injections) 200 mg 
60 kg or more 600 mg (two 300 mg injections) 300 mg 

 
Children 6 to 11 years of age 
The recommended dose of dupilumab for children 6 to 11 years of age is specified in Table 2. 
 
Table 2: Dose of dupilumab for subcutaneous administration in children 6 to 11 years of age 
with atopic dermatitis 

Body Weight of 
Patient 

Initial Dose Subsequent Doses 
 

 
 

 

15 kg to  
less than 60 kg 

300 mg (one 300 mg injection) on Day 1, 
followed by 300 mg on Day 15 

300 mg every 4 weeks (Q4W)*, 
starting 4 weeks after Day 15 dose 

60 kg or more 600 mg (two 300 mg injections) 300 mg every other week (Q2W) 

* The dose may be increased to 200 mg Q2W in patients with body weight of 15 kg to less than 60 kg 
based on physician’s assessment. 
 
Adults 
The recommended dose of dupilumab for adult patients is an initial dose of 600 mg (two 300 mg 
injections), followed by 300 mg given every other week administered as subcutaneous injection. 
 
Dupilumab can be used with or without topical corticosteroids. Topical calcineurin inhibitors may be 
used, but should be reserved for problem areas only, such as the face, neck, intertriginous and genital 
areas. 
 
Consideration should be given to discontinuing treatment in patients who have shown no response 
after 16 weeks of treatment for atopic dermatitis. Some patients with initial partial response may 
subsequently improve with continued treatment beyond 16 weeks. If dupilumab treatment interruption 
becomes necessary, patients can still be successfully re-treated. 
 
Asthma 
 
The recommended dose of dupilumab for adults and adolescents (12 years of age and older) is: 
• An initial dose of 400 mg (two 200 mg injections), followed by 200 mg given every other week 

administered as subcutaneous injection.  
• For patients with severe asthma and who are on oral corticosteroids or for patients with severe 

asthma and co-morbid moderate-to-severe atopic dermatitis or adults with co-morbid severe 



45 

chronic rhinosinusitis with nasal polyposis, an initial dose of 600 mg (two 300 mg injections), 
followed by 300 mg every other week administered as subcutaneous injection. 
 

Patients receiving concomitant oral corticosteroids may reduce their steroid dose once clinical 
improvement with dupilumab has occurred (see section 5.1). Steroid reductions should be 
accomplished gradually (see section 4.4). 
 
Dupilumab is intended for long-term treatment. The need for continued therapy should be considered 
at least on an annual basis as determined by physician assessment of the patient’s level of asthma 
control. 
 
Missed dose  
 
If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular 
scheduled time. 
 
Special populations 
 
Elderly (≥ 65 years) 
No dose adjustment is recommended for elderly patients (see section 5.2). 
 
Renal impairment 
No dose adjustment is needed in patients with mild or moderate renal impairment. Very limited data 
are available in patients with severe renal impairment (see section 5.2). 
 
Hepatic impairment 
No data are available in patients with hepatic impairment (see section 5.2). 
 
Body weight 
No dose adjustment for body weight is recommended for patients with asthma 12 years of age and 
older or in adults with atopic dermatitis (see section 5.2). 
 
For patients 12 to 17 years of age with atopic dermatitis, the recommended every other week dose is 
200 mg (< 60 kg) or 300 mg (≥ 60 kg). 
 
For patients 6 to 11 years of age with atopic dermatitis, the recommended doses are 300 mg Q4W with 
the possibility to increase to 200 mg Q2W (15 kg to < 60 kg), and 300 mg Q2W (≥ 60 kg). 
 
Paediatric patients 
The safety and efficacy of dupilumab in children with atopic dermatitis below the age of 6 years have 
not been established. The safety and efficacy of dupilumab in children with a body weight < 15 kg 
have not been established (see section 5.2). No data are available. 
 
The safety and efficacy of dupilumab in children with severe asthma below the age of 12 years have 
not been established (see section 5.2). No data are available. 
 
Method of administration 
 
Subcutaneous use 
 
The dupilumab pre-filled pen is not intended for use in children below 12 years of age. For children 6 
to 11 years of age with atopic dermatitis, the dupilumab pre-filled syringe is the presentation 
appropriate for administration to this population. 
 
Dupilumab is administered by subcutaneous injection into the thigh or abdomen, except for the 5 cm 
around the navel.  If somebody else administers the injection, the upper arm can also be used. 
 



46 

For the initial 400 mg dose, two 200 mg injections should be administered consecutively in different 
injection sites. 
 
It is recommended to rotate the injection site with each injection. Dupilumab should not be injected 
into skin that is tender, damaged or has bruises or scars. 
 
A patient may self-inject dupilumab or the patient's caregiver may administer dupilumab if their 
healthcare professional determines that this is appropriate. Proper training should be provided to 
patients and/or caregivers on the preparation and administration of dupilumab prior to use according to 
the Instructions for Use (IFU) section in the package leaflet. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Dupilumab should not be used to treat acute asthma symptoms or acute exacerbations. Dupilumab 
should not be used to treat acute bronchospasm or status asthmaticus. 
 
Systemic, topical, or inhaled corticosteroids should not be discontinued abruptly upon initiation of 
therapy with dupilumab. Reductions in corticosteroid dose, if appropriate, should be gradual and 
performed under the direct supervision of a physician. Reduction in corticosteroid dose may be 
associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by 
systemic corticosteroid therapy. 
 
Biomarkers of type 2 inflammation may be suppressed by systemic corticosteroid use. This should be 
taken into consideration to determine type 2 status in patients taking oral corticosteroids (see section 
5.1). 
 
Traceability 
 
In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
Hypersensitivity 
 
If a systemic hypersensitivity reaction (immediate or delayed) occurs, administration of dupilumab 
should be discontinued immediately and appropriate therapy initiated. Cases of anaphylactic reaction, 
angioedema, and serum sickness/serum sickness-like reaction have been reported. Anaphylactic 
reactions and angioedema have occurred from minutes to up to seven days after the dupilumab 
injection (section 4.8). 
 
Eosinophilic conditions 
 
Cases of eosinophilic pneumonia and cases of vasculitis consistent with eosinophilic granulomatosis 
with polyangiitis have been reported with dupilumab in adult patients who participated in the asthma 
development program. Physicians should be alert to vasculitic rash, worsening pulmonary symptoms, 
cardiac complications, and/or neuropathy presenting in their patients with eosinophilia. Patients being 
treated for asthma may present with serious systemic eosinophilia sometimes presenting with clinical 
features of eosinophilic pneumonia or vasculitis consistent with eosinophilic granulomatosis with 
polyangiitis, conditions which are often treated with systemic corticosteroid therapy. These events 
usually, but not always, may be associated with the reduction of oral corticosteroid therapy. 
 
Helminth infection 
 



47 

Patients with known helminth infections were excluded from participation in clinical studies. 
Dupilumab may influence the immune response against helminth infections by inhibiting IL-4/IL-13 
signaling. Patients with pre-existing helminth infections should be treated before initiating dupilumab. 
If patients become infected while receiving treatment with dupilumab and do not respond to anti-
helminth treatment, treatment with dupilumab should be discontinued until infection resolves. 
 
Conjunctivitis and keratitis related events 
 
Conjunctivitis and keratitis related events have been reported with dupilumab, predominantly in atopic 
dermatitis patients. Some patients reported visual disturbances (e.g. blurred vision) associated with 
conjunctivitis or keratitis (section 4.8). 
 
Patients should be advised to report new onset or worsening eye symptoms to their healthcare 
provider. Patients treated with dupilumab who develop conjunctivitis that does not resolve following 
standard treatment or signs and symptoms suggestive of keratitis should undergo ophthalmological 
examination, as appropriate (section 4.8).  
 
Atopic dermatitis patients with comorbid asthma 
 
Patients on dupilumab for moderate-to-severe atopic dermatitis who also have comorbid asthma 
should not adjust or stop their asthma treatments without consultation with their physicians. Patients 
with comorbid asthma should be monitored carefully following discontinuation of dupilumab.  
 
Vaccinations 
 
Live and live attenuated vaccines should not be given concurrently with dupilumab as clinical safety 
and efficacy has not been established. Immune responses to TdaP vaccine and meningococcal 
polysaccharide vaccine were assessed, see section 4.5. It is recommended that patients should be 
brought up to date with live and live attenuated immunisations in agreement with current 
immunisation guidelines prior to treatment with dupilumab. 
 
Sodium content  
 
This medicinal product contains less than 1 mmol sodium (23 mg) per 200 mg dose, i.e. essentially 
“sodium-free”.  
 
4.5 Interaction with other medicinal products and other forms of interaction  
 
Immune responses to vaccination were assessed in a study in which patients with atopic dermatitis 
were treated once weekly for 16 weeks with 300 mg of dupilumab. After 12 weeks of dupilumab 
administration, patients were vaccinated with a Tdap vaccine (T cell-dependent), and a meningococcal 
polysaccharide vaccine (T cell-independent) and immune responses were assessed 4 weeks later. 
Antibody responses to both tetanus vaccine and meningococcal polysaccharide vaccine were similar in 
dupilumab-treated and placebo-treated patients. No adverse interactions between either of the non-live 
vaccines and dupilumab were noted in the study.  
 
Therefore, patients receiving dupilumab may receive concurrent inactivated or non-live vaccinations. 
For information on live vaccines see section 4.4. 
 
In a clinical study of AD patients, the effects of dupilumab on the pharmacokinetics (PK) of CYP 
substrates were evaluated. The data gathered from this study did not indicate clinically relevant effects 
of dupilumab on CYP1A2, CYP3A, CYP2C19, CYP2D6, or CYP2C9 activity. 
 
An effect of dupilumab on the PK of co-administered medications is not expected. Based on the 
population analysis, commonly co-administered medications had no effect on dupilumab 
pharmacokinetics on patients with moderate to severe asthma. 
 



48 

4.6 Fertility, pregnancy and lactation  
 
Pregnancy 
 
There are limited amount of data from the use of dupilumab in pregnant women. Animal studies do not 
indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). 
Dupilumab should be used during pregnancy only if the potential benefit justifies the potential risk to 
the foetus. 
 
Breast-feeding 
 
It is unknown whether dupilumab is excreted in human milk or absorbed systemically after ingestion. 
A decision must be made whether to discontinue breast-feeding or to discontinue dupilumab therapy 
taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman. 
 
Fertility 
 
Animal studies showed no impairment of fertility (see section 5.3). 
 
4.7 Effects on ability to drive and use machines  
 
Dupilumab has no or negligible influence on the ability to drive or operate machinery. 
 
4.8 Undesirable effects  
 
Atopic dermatitis 
 
Adults with atopic dermatitis 
 
Summary of the safety profile 
 
The most common adverse reactions were injection site reactions, conjunctivitis, blepharitis, and oral 
herpes. Very rare cases of serum sickness/serum sickness-like reaction have been reported in the atopic 
dermatitis development program (see section 4.4). 
 
In the monotherapy adult studies, the proportion of patients who discontinued treatment due to adverse 
events was 1.9 % of the placebo group, 1.9 % of the dupilumab 300 mg Q2W group, 1.5 % of the 
dupilumab 300 mg QW group. In the concomitant TCS adult study, the proportion of patients who 
discontinued treatment due to adverse events was 7.6 % of the placebo + TCS group, 1.8 % of the 
dupilumab 300 mg Q2W + TCS group, and 2.9 % of the dupilumab 300 mg QW + TCS group. 
 
Tabulated list of adverse reactions 
 
The safety of dupilumab was evaluated in four randomized, double-blind, placebo-controlled studies 
and one dose-ranging study in patients with moderate-to-severe atopic dermatitis. In these 5 trials, 1,689 
subjects were treated with subcutaneous injections of dupilumab, with or without concomitant topical 
corticosteroids (TCS). A total of 305 patients were treated with dupilumab for at least 1 year. 
 
Listed in Table 3 are adverse reactions observed in atopic dermatitis clinical trials and/or postmarketing 
setting presented by system organ class and frequency, using the following categories: very common 
(≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); 
very rare (< 1/10,000). Within each frequency grouping, undesirable effects are presented in order of 
decreasing seriousness. 
 
Table 3: List of adverse reactions in atopic dermatitis 

MedDRA System 
Organ Class 

Frequency Adverse Reaction 



49 

Infections and 
infestations 

Common Conjunctivitis 
Oral herpes 

Blood and lymphatic 
system disorders 

Common Eosinophilia 

Immune system 
disorders 

Very rare 
Not known 
 

Serum sickness/serum sickness-like reactions 
Anaphylactic reaction* 
Angioedema* 

Nervous system 
disorders 

Common Headache 

Eye disorders Common 
 
 
Uncommon 

Conjunctivitis allergic 
Eye pruritus  
Blepharitis 
Keratitis 
Ulcerative keratitis 

Musculoskeletal and 
connective tissue 
disorders 

Not known Arthralgia* 

General disorders 
and administration 
site conditions 

Very common Injection site reactions 

* From postmarketing reporting. 
 
Adolescents with atopic dermatitis (12 to 17 years of age) 
 
The safety of dupilumab was assessed in a study of 250 patients 12 to 17 years of age with moderate-
to-severe atopic dermatitis (AD-1526). The safety profile of dupilumab in these patients followed 
through week 16 was similar to the safety profile from studies in adults with atopic dermatitis. 
 
Paediatric patients with atopic dermatitis (6 to 11 years of age) 
 
The safety of dupilumab was assessed in a trial of 367 patients 6 to 11 years of age with severe atopic 
dermatitis (AD-1652). The safety profile of dupilumab + TCS in these patients through week 16 was 
similar to the safety profile from studies in adults and adolescents with atopic dermatitis. The long-term 
safety profile of dupilumab observed in children and adolescents was consistent with that seen in adults 
with atopic dermatitis. 
 
Asthma 
 
Summary of the safety profile 
 
The most common adverse reaction was injection site erythema. Anaphylactic reaction has been reported 
very rarely in the asthma development program (see section 4.4). 
 
In DRI12544 and QUEST studies, the proportion of patients who discontinued treatment due to 
adverse events was 4.3 % of the placebo group, 3.2 % of the dupilumab 200 mg Q2W group, and 
6.1 % of the dupilumab 300 mg Q2W group. 
 



50 

Tabulated list of adverse reactions 
 
A total of 2,888 adult and adolescent patients with moderate-to-severe asthma were evaluated in 3 
randomised, placebo-controlled, multicentre trials of 24 to 52 weeks duration (DRI12544, QUEST, 
and VENTURE). Of these, 2,678 had a history of 1 or more severe exacerbations in the year prior to 
enrolment despite regular use of medium-to-high dose inhaled corticosteroids plus an additional 
controller(s) (DRI12544 and QUEST). A total of 210 patients with oral corticosteroid-dependent 
asthma receiving high-dose inhaled corticosteroids plus up to two additional controllers were enrolled 
(VENTURE).  
 
The safety profile of dupilumab in the 96 weeks long term safety study (TRAVERSE) was consistent 
with the safety profile observed in pivotal asthma studies for up to 52 weeks of treatment. 
 
Listed in Table 4 are adverse reactions observed in asthma clinical trials and/or postmarketing setting 
presented by system organ class and frequency, using the following categories: very common (≥ 1/10); 
common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very 
rare (< 1/10,000). Within each frequency grouping, undesirable effects are presented in order of 
decreasing seriousness. 
 
Table 4: List of adverse reactions in asthma 

MedDRA System 
Organ Class 

Frequency Adverse Reaction 

Immune system 
disorders 

Very rare 
Not known 

Anaphylactic reaction 
Angioedema* 

Eye disorders Rare Keratitis 

Musculoskeletal and 
connective tissue 
disorders 

Not known Arthralgia* 

General disorders 
and administration 
site conditions 

Very common 
Common 
Common 
Common 

Injection site erythema 
Injection site oedema 
Injection site pain 
Injection site pruritus 

* From postmarketing reporting. 
 
Description of selected adverse reactions in atopic dermatitis and asthma indications 
 
Hypersensitivity 
Cases of anaphylactic reaction, angioedema, and serum sickness/serum sickness-like reaction have been 
reported following administration of dupilumab (see section 4.4). 
 
Conjunctivitis and keratitis related events 
Conjunctivitis and keratitis occurred more frequently in atopic dermatitis patients who received 
dupilumab. Most patients with conjunctivitis or keratitis recovered or were recovering during the 
treatment period. Among asthma patients frequency of conjunctivitis and keratitis was low and similar 
between dupilumab and placebo (see section 4.4). 
 
Eczema herpeticum 
Eczema herpeticum was reported in < 1 % of the dupilumab groups and in < 1 % of the placebo group 
in the 16-week atopic dermatitis monotherapy studies. In the 52-week atopic dermatitis dupilumab + 
TCS study, eczema herpeticum was reported in 0.2 % of the dupilumab + TCS group and 1.9 % of the 
placebo + TCS group. 
 
Eosinophilia 
Dupilumab-treated patients had a greater mean initial increase from baseline in eosinophil count 
compared to patients treated with placebo. Eosinophil counts declined to near baseline levels during 



51 

study treatment and returned to baseline during the asthma open-label extension safety study 
(TRAVERSE). 
 
Treatment-emergent eosinophilia (≥ 5,000 cells/mcL) was reported in < 2 % of dupilumab-treated 
patients and < 0.5 % in placebo-treated patients. 
 
Infections 
In the 16-week atopic dermatitis monotherapy clinical studies, serious infections were reported in 1.0 % 
of patients treated with placebo and 0.5 % of patients treated with dupilumab. In the 52-week atopic 
dermatitis CHRONOS study, serious infections were reported in 0.6 % of patients treated with placebo 
and 0.2 % of patients treated with dupilumab. 
 
 
Immunogenicity 
As with all therapeutic proteins, there is a potential for immunogenicity with dupilumab. 
 
Anti-Drug-Antibodies (ADA) responses were not generally associated with impact on dupilumab 
exposure, safety, or efficacy. 
 
Approximately 6 % of patients with atopic dermatitis or asthma who received dupilumab 300 mg 
Q2W for 52 weeks developed ADA to dupilumab; approximately 2 % exhibited persistent ADA 
responses and approximately 2 % had neutralizing antibodies. Similar results were observed in 
paediatric patients (6 to 11 years of age) with atopic dermatitis who received dupilumab 200 mg Q2W 
or 300 mg Q4W for 16 weeks. 
 
Approximately 16 % of adolescent patients with atopic dermatitis who received dupilumab 300 mg or 
200 mg Q2W for 16 weeks developed antibodies to dupilumab; approximately 3 % exhibited 
persistent ADA responses, and approximately 5 % had neutralizing antibodies 
 
Approximately 9 % of patients with asthma who received dupilumab 200 mg Q2W for 52 weeks 
developed antibodies to dupilumab; approximately 4 % exhibited persistent ADA responses and 
approximately 4 % had neutralizing antibodies. 
 
Regardless of age or population, approximately 2 to 4 % of patients in the placebo groups were 
positive for antibodies to dupilumab; approximately 2 % exhibited persistent ADA response and 
approximately 1 % had neutralizing antibodies. 
 
Less than 1 % of patients who received dupilumab at approved dosing regimens exhibited high titer 
ADA responses associated with reduced exposure and efficacy. In addition, there was one patient with 
serum sickness and one with serum sickness-like reaction (< 0.1 %) associated with high ADA titers 
(see section 4.4). 
 
Paediatric population 
 
The safety profile observed in children with atopic dermatitis aged 6 to 11 years and in adolescents 
aged 12 to 17 years in atopic dermatitis and asthma clinical trials was similar to that seen in adults. 
 
The long-term safety of dupilumab was assessed in 89 adolescent patients who were enrolled in an 
open-label extension study in moderate-to-severe asthma (TRAVERSE). In this study, patients were 
followed for up to 96 weeks. The safety profile of dupilumab in TRAVERSE was consistent with the 
safety profile observed in pivotal asthma studies for up to 52 weeks of treatment.  
 
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 



52 

professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose  
 
There is no specific treatment for dupilumab overdose. In the event of overdosage, monitor the patient 
for any signs or symptoms of adverse reactions and institute appropriate symptomatic treatment 
immediately. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties  
 
Pharmacotherapeutic group: Other dermatological preparations, agents for dermatitis, excluding 
corticosteroids, ATC code: D11AH05  
 
Mechanism of action 
 
Dupilumab is a recombinant human IgG4 monoclonal antibody that inhibits interleukin-4 and 
interleukin-13 signaling. Dupilumab inhibits IL-4 signaling via the Type I receptor (IL-4Rα/γc), and 
both IL-4 and IL-13 signaling through the Type II receptor (IL-4Rα/IL-13Rα). IL-4 and IL-13 are 
major drivers of human type 2 inflammatory disease, such as atopic dermatitis and asthma. Blocking 
the IL-4/IL-13 pathway with dupilumab in patients decreases many of the mediators of type 2 
inflammation.  
 
Pharmacodynamic effects 
 
In atopic dermatitis clinical trials, treatment with dupilumab was associated with decreases from 
baseline in concentrations of type 2 immunity biomarkers, such as thymus and activation-regulated 
chemokine (TARC/CCL17), total serum IgE and allergen-specific IgE in serum. A reduction of lactate 
dehydrogenase (LDH), a biomarker associated with AD disease activity and severity, was observed 
with dupilumab treatment in adults and adolescents with atopic dermatitis. 
 
In asthma clinical trials, dupilumab treatment markedly decreased FeNO and circulating 
concentrations of eotaxin-3, total IgE, allergen specific IgE, TARC, and periostin in asthma subjects 
relative to placebo.  These reductions in type 2 inflammatory biomarkers were comparable for the 
200 mg Q2W and 300 mg Q2W regimens. These markers were near maximal suppression after 2 
weeks of treatment, except for IgE which declined more slowly. These effects were sustained 
throughout treatment. 
 
Clinical efficacy and safety in atopic dermatitis 
 
Adolescents with atopic dermatitis (12 to 17 years of age) 
 
The efficacy and safety of dupilumab monotherapy in adolescent patients was evaluated in a 
multicentre, randomised, double-blind, placebo-controlled study (AD-1526) in 251 adolescent 
patients 12 to 17 years of age with moderate-to-severe atopic dermatitis (AD) defined by 
Investigator’s Global Assessment (IGA) score ≥3 in the overall assessment of AD lesions on a 
severity scale of 0 to 4, an Eczema Area and Severity Index (EASI) score ≥ 16 on a scale of 0 to 
72, and a minimum body surface area (BSA) involvement of ≥10 %. Eligible patients enrolled into 
this study had previous inadequate response to topical medication. 
 
Patients received 1) an initial dose of 400 mg dupilumab (two 200 mg injections) on day 1, 
followed by 200 mg once every other week (Q2W) for patients with baseline weight of < 60 kg or 
an initial dose of 600 mg dupilumab (two 300 mg injections) on day 1, followed by 300 mg Q2W 

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


53 

for patients with baseline weight of ≥ 60 kg; 2) an initial dose of 600 mg dupilumab (two 300 mg 
injections) on day 1, followed by 300 mg every 4 weeks (Q4W) regardless of baseline body 
weight; or 3) matching placebo. Dupilumab was administered by subcutaneous (SC) injection. If 
needed to control intolerable symptoms, patients were permitted to receive rescue treatment at the 
discretion of the investigator. Patients who received rescue treatment were considered non-
responders. 
 
In this study, the mean age was 14.5 years, the median weight was 59.4 kg, 41.0 % were female, 
62.5 % were White, 15.1 % were Asian, and 12.0 % were Black. At baseline 46.2 % of patients 
had a baseline IGA score of 3 (moderate AD), 53.8 % of patients had a baseline IGA of 4 (severe 
AD), the mean BSA involvement was 56.5 %, and 42.4  % of patients had received prior 
systemic immunosuppressants. Also at baseline the mean Eczema Area and Severity Index 
(EASI) score was 35.5, the baseline weekly averaged pruritus Numerical Rating Scale (NRS) was 
7.6, the baseline mean SCORing Atopic Dermatitis (SCORAD) score was 70.3, the baseline 
mean Patient Oriented Eczema Measure (POEM) score was 21.0, and the baseline mean Children 
Dermatology Life Quality Index (CDLQI) was 13.6. Overall, 92.0 % of patients had at least one 
co-morbid allergic condition; 65.6 % had allergic rhinitis, 53.6 % had asthma, and 60.8 % had 
food allergies. 
The co-primary endpoint was the proportion of patients with IGA 0 or 1 (“clear” or “almost 
clear”) least a 2-point improvement and the proportion of patients with EASI-75 (improvement 
of at least 75 % in EASI), from baseline to week 16. Other evaluated outcomes included the 
proportion of subjects with EASI-50 or EASI-90 (improvement of at least 50 % or 90 % in EASI 
from baseline respectively), reduction in itch as measured by the peak pruritus NRS, and percent 
change in the SCORAD scale from baseline to week 16. Additional secondary endpoints 
included mean change from baseline to week 16 in the POEM and CDLQI scores. 

Clinical Response 
 
The efficacy results at week 16 for adolescent atopic dermatitis study are presented in Table 5. 
 
Table 5: Efficacy results of dupilumab in the adolescent atopic dermatitis study at Week 16 (FAS) 

 AD-1526(FAS)a 

 Placebo 
 

Dupilumab 
200 mg (< 60 kg) and  

300 mg (≥ 60 kg)  
Q2W 

Patients randomised 85a 82a 

IGA 0 or 1b, % respondersc 2.4 % 24.4 % 
EASI-50, % respondersc 12.9 % 61.0 % 

EASI-75, % respondersc 8.2 % 41.5 % 
EASI-90, % respondersc 2.4 % 23.2 % 
EASI, LS mean % change from baseline (+/-SE) -23.6 % 

(5.49) 
-65.9 % 
(3.99) 

SCORAD, LS mean % change from baseline 
(+/- SE) 

-17.6 % 
(3.76) 

-51.6 % 
(3.23) 

Pruritus NRS, LS mean % change from baseline 
(+/- SE) 

-19.0 % 
(4.09) 

-47.9 % 
(3.43) 

Pruritus NRS (> 4-point improvement), % 
respondersc  

4.8 % 36.6 % 

BSA LS mean % change from baseline  
(+/- SE) 

-11.7 % 
(2.72) 

-30.1 % 
(2.34) 

CDLQI, LS mean change from baseline  
(+/-SE) 

-5.1 
(0.62) 

-8.5 
(0.50) 

CDLQI, (≥ 6-point improvement), % responders 19.7 % 60.6 % 
POEM, LS mean change from baseline  -3.8 -10.1 



54 

 AD-1526(FAS)a 

 Placebo 
 

Dupilumab 
200 mg (< 60 kg) and  

300 mg (≥ 60 kg)  
Q2W 

(+/- SE) (0.96) (0.76) 
POEM, (≥ 6-point improvement), % responders 9.5 % 63.4 % 

a Full Analysis Set (FAS) includes all patients randomised. 
b Responder was defined as a subject with IGA 0 or 1 (“clear” or “almost clear”) with a reduction of ≥ 2 points 

on a 0-4 IGA scale. 
c Patients who received rescue treatment or with missing data were considered as non-responders (58.8 % and 

20.7 % in the placebo and dupilumab arms, respectively).  
All p –values < 0.0001 
 
A larger percentage of patients randomised to placebo needed rescue treatment (topical corticosteroids, 
systemic corticosteroids, or systemic non-steroidal immunosuppressants) as compared to the 
dupilumab group (58.8 % and 20.7 %, respectively). 
 
A significantly greater proportion of patients randomised to dupilumab achieved a rapid improvement 
in the pruritus NRS compared to placebo (defined as > 4-point improvement as early as week 4; 
nominal p< 0.001) and the proportion of patients responding on the pruritus NRS continued to increase 
through the treatment period (see Figure 1). The improvement in pruritus NRS occurred in conjunction 
with the improvement of objective signs of atopic dermatitis. 
 
Figure 1: Proportion of adolescent patients with ≥ 4-point improvement on the pruritus NRS in 
AD-1526 studya (FAS)b 

 
a In the primary analyses of the efficacy endpoints, subjects who received rescue treatment or with missing data 
were considered non-responders. 
b Full Analysis Set (FAS) includes all subjects randomised. 
 
The dupilumab group significantly improved patient-reported symptoms, the impact of AD on sleep 
and health-related quality of life as measured by POEM, SCORAD, and CDLQI scores at 16 weeks 
compared to placebo. 
 
The long-term efficacy of dupilumab in adolescent patients with moderate-to-severe AD who had 
participated in previous clinical trials of dupilumab was assessed in open-label extension study (AD-
1434). Efficacy data from this study suggests that clinical benefit provided at week 16 was sustained 
through week 52. 
 



55 

Paediatrics (6 to 11 years of age) 

The efficacy and safety of dupilumab in paediatric patients concomitantly with TCS was evaluated in a 
multicentre, randomised, double-blind, placebo-controlled study (AD-1652) in 367 subjects 6 to 11 
years of age, with AD defined by an IGA score of 4 (scale of 0 to 4), an EASI score ≥ 21 (scale of 0 to 
72), and a minimum BSA involvement of ≥ 15 %. Eligible patients enrolled into this trial had previous 
inadequate response to topical medication. Enrollment was stratified by baseline weight (< 30 kg; ≥ 30 
kg). 

Patients in the dupilumab Q2W + TCS group with baseline weight of < 30 kg received an initial dose 
of 200 mg on Day 1, followed by 100 mg Q2W from week 2 to week 14, and patients with baseline 
weight of ≥ 30 kg received an initial dose of 400 mg on Day 1, followed by 200 mg Q2W from week 2 
to week 14. Patients in the dupilumab Q4W + TCS group received an initial dose of 600 mg on Day 1, 
followed by 300 mg Q4W from week 4 to week 12, regardless of weight. Patients were permitted to 
receive rescue treatment at the discretion of the investigator. Patients who received rescue treatment 
were considered non-responders. 

In this study, the mean age was 8.5 years, the median weight was 29.8 kg, 50.1 % of patients were 
female, 69.2 % were White, 16.9 % were Black, and 7.6 % were Asian. At baseline, the mean BSA 
involvement was 57.6 %, and 16.9 % had received prior systemic non-steroidal immunosuppressants. 
Also, at baseline the mean EASI score was 37.9, and the weekly average of daily worst itch score was 
7.8 on a scale of 0-10, the baseline mean SCORAD score was 73.6, the baseline POEM score was 
20.9, and the baseline mean CDLQI was 15.1. Overall, 91.7 % of subjects had at least one co-morbid 
allergic condition; 64.4 % had food allergies, 62.7 % had other allergies, 60.2 % had allergic rhinitis, 
and 46.7 % had asthma. 

The co-primary endpoint was the proportion of patients with IGA 0 or 1 (“clear” or “almost clear”) at 
least a 2-point improvement and the proportion of patients with EASI-75 (improvement of at least 
75 % in EASI), from baseline to week 16. Other evaluated outcomes included the proportion of 
patients with EASI-50 and EASI-90 (improvement of at least 50 % and 90 % in EASI from baseline, 
respectively), percent change in EASI score from baseline to week 16, and reduction in itch as 
measured by the peak pruritus NRS (≥ 4-point improvement). Additional secondary endpoints 
included mean change from baseline to week 16 in the POEM and CDLQI scores. 

Clinical Response 

Table 6 presents the results by baseline weight strata for the approved dose regimens. 

TABLE 6: Efficacy Results of Dupilumab with Concomitant TCS in AD-1652 at Week 16 (FAS)a 

Dupilumab 
300 mg Q4Wd 

+ TCS

Placebo 
+TCS

Dupilumab 
200 mg Q2We 

+ TCS

Placebo 
+ TCS

(N=122) (N=123) (N=59) (N=62) 
≥ 15 kg ≥ 15 kg ≥ 30 kg ≥ 30 kg 

IGA 0 or 1b,  % respondersc 32.8 % 11.4 % 39.0 % 9.7 % 

EASI-50,  % respondersc 91.0 % 43.1 % 86.4 % 43.5 % 
EASI-75,  % respondersc 69.7 % 26.8 % 74.6 % 25.8 % 
EASI-90,  % respondersc 41.8 % 7.3 % 35.6 % 8.1 % 
EASI, LS mean  % change from 
baseline (+/-SE) 

-82.1 %
(2.37)

-48.6 %
(2.46)

-80.4 %
(3.61)

-48.3 %
(3.63)



56 

SCORAD, LS mean  % change 
from baseline (+/- SE) 

-62.4 % 
(2.13) 

-29.8 % 
(2.26) 

-62.7 % 
(3.14) 

-30.7 % 
(3.28) 

Pruritus NRS, LS mean  % change 
from baseline (+/- SE) 

-54.6 % 
(2.89) 

-25.9 % 
(2.90) 

-58.2 % 
(4.01) 

-25.0 % 
(3.95) 

Pruritus NRS (≥ 4-point 
improvement),  % respondersc 50.8 % 12.3 % 61.4 % 12.9 % 

BSA LS mean change from 
baseline (+/- SE) 

-40.5 
(1.65) 

-21.7 
(1.72) 

-38.4 
(2.47) 

-19.8 
(2.50) 

CDLQI, LS mean change from 
baseline (+/-SE) 

-10.6 
(0.47) 

-6.4 
(0.51) 

-9.8 
(0.63) 

-5.6 
(0.66) 

CDLQI, (≥ 6-point 
improvement),  % responders 77.3 % 38.8 % 80.8 % 35.8 % 

POEM, LS mean change from 
baseline (+/- SE) 

-13.6 
(0.65) 

-5.3 
(0.69) 

-13.6 
(0.90) 

-4.7 
(0.91) 

POEM, (≥ 6-point 
improvement),  % responders 81.7  % 32.0  % 79.3 % 31.1 % 

Full Analysis Set (FAS) includes all patients randomised. 
b Responder was defined as a patient with an IGA 0 or 1 (“clear” or “almost clear”). 
c Patients who received rescue treatment or with missing data were considered as non-responders.  
d At Day 1, patients received 600 mg of dupilumab (see section 5.2). 
e At Day 1, patients received 400 mg (baseline weight ≥ 30 kg) of dupilumab. 
 
A greater proportion of patients randomised to dupilumab + TCS achieved an improvement in the peak 
pruritus NRS compared to placebo + TCS (defined as ≥4-point improvement at week 4). See Figure 2. 
 
Figure 2: Proportion of Paediatric Subjects with ≥ 4-point Improvement on the Peak Pruritus 
NRS in AD-1652a (FAS)b 

 

 
a  In the primary analyses of the efficacy endpoints, patients who received rescue treatment or with missing data 

were considered non-responders.  
b  Full Analysis Set (FAS) includes all patients randomised. 
c At Day 1, patients received 600 mg of dupilumab (see section 5.2) 
d At Day 1, patients received 400 mg (baseline weight ≥ 30 kg) of dupilumab 
 
The dupilumab groups significantly improved patient-reported symptoms, the impact of AD on sleep 
and health-related quality of life as measured by POEM, SCORAD, and CDLQI scores at 16 weeks 
compared to placebo. 
 



57 

The long-term efficacy and safety of dupilumab + TCS in paediatric patients with moderate to severe 
atopic dermatitis who had participated in the previous clinical trials of dupilumab + TCS was assessed 
in an open-label extension study (AD-1434). Efficacy data from this trial suggests that clinical benefit 
provided at week 16 was sustained through week 52. Some patients receiving dupilumab 300 mg Q4W 
+ TCS showed further clinical benefit when escalated to dupilumab 200 mg Q2W + TCS. The safety 
profile of dupilumab in patients followed through week 52 was similar to the safety profile observed at 
week 16 in the AD-1526 and AD-1652 studies. 
 
Adults with atopic dermatitis 
 
For clinical data in adults with atopic dermatitis please refer to the dupilumab 300 mg Summary of 
Product Characteristics. 
 
Clinical efficacy and safety in asthma  
 
The asthma development program included three randomised, double-blind, placebo-controlled, 
parallel-group, multi-centre studies (DRI12544, QUEST, and VENTURE) of 24 to 52 weeks in 
treatment duration which enrolled a total of 2,888 patients (12 years of age and older). Patients were 
enrolled without requiring a minimum baseline blood eosinophil or other type 2 inflammatory 
biomarkers (e.g. FeNO or IgE) level. Asthma treatment guidelines define type 2 inflammation as 
eosinophilia ≥ 150 cells/mcL and/or FeNO ≥ 20 ppb. In DRI12544 and QUEST, the pre-specified 
subgroup analyses included blood eosinophils ≥ 150 and ≥ 300 cells/mcL, FeNO ≥ 25 and ≥ 50 ppb. 
 
DRI12544 was a 24-week dose-ranging study which included 776 patients (18 years of age and older). 
Dupilumab compared with placebo was evaluated in adult patients with moderate to severe asthma on 
a medium-to-high dose inhaled corticosteroid and a long acting beta agonist. The primary endpoint 
was change from baseline to week 12 in FEV1 (L). Annualized rate of severe asthma exacerbation 
events during the 24-week placebo controlled treatment period was also determined. Results were 
evaluated in the overall population (unrestricted by minimum baseline eosinophils or other type 2 
inflammatory biomarkers) and subgroups based on baseline blood eosinophil count.  
 
QUEST was a 52-week confirmatory study which included 1,902 patients (12 years of age and older). 
Dupilumab compared with placebo was evaluated in 107 adolescent and 1,795 adult patients with 
persistent asthma on a medium-to-high dose inhaled corticosteroid (ICS) and a second controller 
medication. Patients requiring a third controller were allowed to participate in this trial. Patients were 
randomised to receive either 200 mg (N=631) or 300 mg (N=633) Dupixent every other week (or 
matching placebo for either 200 mg (N = 317) or 300 mg (N= 321) every other week) following an 
initial dose of 400 mg, 600 mg or placebo respectively. The primary endpoints were the annualized 
rate of severe exacerbation events during the 52-week placebo controlled period and change from 
baseline in pre-bronchodilator FEV1 at week 12 in the overall population (unrestricted by minimum 
baseline eosinophils or other type 2 inflammatory biomarkers) and subgroups based on baseline blood 
eosinophils count and FeNO. 
 
VENTURE was a 24-week oral corticosteroid-reduction study in 210 patients with asthma unrestricted 
by baseline type 2 biomarker levels who required daily oral corticosteroids in addition to regular use of 
high dose inhaled corticosteroids plus an additional controller. After optimizing the OCS dose during 
the screening period, patients received 300 mg dupilumab (n=103) or placebo (n=107) once every 
other week for 24 weeks following an initial dose of 600 mg or placebo. Patients continued to receive 
their existing asthma medicine during the study; however their OCS dose was reduced every 4 weeks 
during the OCS reduction phase (week 4-20), as long as asthma control was maintained. The primary 
endpoint was the percent reduction in oral corticosteroid dose assessed in the overall population, based 
on a comparison of the oral corticosteroid dose at weeks 20 to 24 that maintained asthma control with 
the previously optimized (at baseline) oral corticosteroid dose. 
 
The demographics and baseline characteristics of these 3 studies are provided in Table 7 below. 
 



58 

Table 7: Demographics and Baseline Characteristics of Asthma Trials 
Parameter DRI12544 

(n = 776) 
QUEST  

(n = 1902) 
VENTURE 

(n=210) 

Mean age (years) (SD) 48.6 (13.0) 47.9 (15.3) 51.3 (12.6) 

% Female 63.1 62.9 60.5 

% White 78.2 82.9 93.8 

Duration of Asthma (years), mean ± SD 22.03 (15.42) 20.94 (15.36) 19.95 (13.90) 

Never smoked, (%) 77.4 80.7 80.5 

Mean exacerbations in previous year  ± SD 2.17 (2.14) 2.09 (2.15) 2.09 (2.16) 

High dose ICS use (%)a 49.5 51.5 88.6 

Pre-dose FEV1 (L) at baseline  ± SD 1.84 (0.54) 1.78 (0.60) 1.58 (0.57) 

Mean percent predicted FEV1 at baseline 
(%)(± SD) 

60.77 (10.72) 58.43 (13.52) 52.18 (15.18) 

% Reversibility  (± SD) 26.85 (15.43) 26.29 (21.73) 19.47 (23.25) 

Mean ACQ-5 score (± SD) 2.74 (0.81) 2.76 (0.77) 2.50 (1.16) 

Mean AQLQ score (± SD) 4.02 (1.09) 4.29 (1.05) 4.35 (1.17) 

Atopic Medical History % Overall 
(AD %, NP %, AR %) 

72.9 
(8.0, 10.6, 61.7) 

77.7 
(10.3, 12.7, 68.6) 

72.4 
(7.6, 21.0, 55.7) 

Mean FeNO ppb (± SD) 39.10 (35.09) 34.97 (32.85) 37.61 (31.38) 

% patients with FeNO ppb 
≥ 25 
≥ 50 

 
49.9 
21.6 

 
49.6 
20.5 

 
54.3 
25.2 

Mean total IgE IU/ml (± SD) 435.05 (753.88) 432.40 (746.66) 430.58 (775.96) 

Mean baseline Eosinophil count (± SD) 
cells/mcL  

350 (430) 360 (370) 350 (310) 

% patients with EOS  
≥ 150 cells/mcL 
≥ 300 cells/mcL 

 
77.8 
41.9 

 
71.4 
43.7 

 
71.4 
42.4 

ICS = inhaled corticosteroid; FEV1 = Forced expiratory volume in 1 second; ACQ-5 = Asthma Control 
Questionnaire-5; AQLQ = Asthma Quality of Life Questionnaire; AD = atopic dermatitis; NP = nasal polyposis; 
AR = allergic rhinitis; FeNO = fraction of exhaled nitric oxide; EOS = blood eosinophil 
aThe population in dupilumab asthma trials included patients on medium and high dose ICS. The medium ICS 
dose was defined as equal to 500 mcg fluticasone or equivalent per day. 
 
Exacerbations 
 
In the overall population in DRI12544 and QUEST subjects receiving either dupilumab 200 mg or 
300 mg every other week had significant reductions in the rate of severe asthma exacerbations 
compared to placebo. There were greater reductions in exacerbations in subjects with higher baseline 
levels of type 2 inflammatory biomarkers such as blood eosinophils or FeNO (Table 8 and Table 9). 
 
Table 8: Rate of Severe Exacerbations in DRI12544 and QUEST (Baseline Blood Eosinophil 
Levels ≥ 150 and ≥ 300 cells/mcL) 

Treatment Baseline Blood EOS 
 ≥150 cells/mcL ≥300 cells/mcL 

Exacerbations per Year  % 
Reduction 

Exacerbations per Year %  
Reduction N Rate Rate N Rate Rate  



59 

(95% CI) Ratio 
(95%CI) 

(95% CI) Ratio 
(95%CI) 

All Severe Exacerbations 
DRI12544 study 
Dupilumab 
200 mg Q2W  

120 0.29 
(0.16, 0.53) 

0.28a 

(0.14, 0.55) 
72 % 65 0.30 

(0.13, 0.68) 
0.29c 

(0.11, 0.76) 
71 % 

Dupilumab 
300 mg Q2W 

129 0.28 
(0.16, 0.50) 

0.27b 

(0.14, 0.52) 
73 % 64 0.20 

(0.08, 0.52) 
0.19d 

(0.07, 0.56) 
81 % 

Placebo 
 

127 1.05 
(0.69, 1.60) 

  68 1.04 
(0.57, 1.90) 

  

QUEST study  
Dupilumab 
200 mg Q2W 

437 0.45 
(0.37, 0.54) 

0.44e 
(0.34,0.58) 

56 % 264 0.37 
(0.29, 0.48) 

0.34e 
(0.24,0.48) 

66 % 

Placebo  
 

232 1.01 
(0.81, 1.25) 

  148 1.08 
(0.85, 1.38) 

  

Dupilumab 
300 mg Q2W 

452 0.43 
(0.36, 0.53) 

0.40 e 
(0.31,0.53) 

60 % 277 0.40 
(0.32, 0.51) 

0.33e 
(0.23,0.45) 

67 % 

Placebo  
 

237 1.08 
(0.88, 1.33) 

  142 1.24 
(0.97, 1.57) 

  

ap-value = 0.0003, bp-value = 0.0001, cp-value = 0.0116, dp-value = 0.0024, ep-value < 0.0001 
 
Table 9: Rate of Severe Exacerbations in QUEST Defined by Baseline FeNO Subgroups 

Treatment Exacerbations per Year  Percent Reduction 
 N Rate (95% CI) Rate Ratio (95%CI) 
FeNO ≥ 25 ppb 
Dupilumab 200 mg Q2W 299 0.35 (0.27, 0.45) 0.35 (0.25, 0.50)a 65 % 
Placebo  162 1.00 (0.78, 1.30)   
Dupilumab 300 mg Q2W 310 0.43 (0.35, 0.54) 0.39 (0.28, 0.54) a 61 % 
Placebo 172 1.12 (0.88, 1.43)   
FeNO ≥ 50 ppb 
Dupilumab 200 mg Q2W 119 0.33 (0.22, 0.48) 0.31 (0.18, 0.52) a 69 % 
Placebo  71 1.057 (0.72, 1.55)   
Dupilumab 300 mg Q2W 124 0.39 (0.27, 0.558) 0.31 (0.19, 0.49) a 69 % 
Placebo  75 1.27 (0.90, 1.80)   

ap-value < 0.0001 
 
In the pooled analysis of DRI12544 and QUEST, hospitalizations and/or emergency room visits due to 
severe exacerbations were reduced by 25.5 % and 46.9 % with dupilumab 200 mg or 300 mg every 
other week, respectively. 
 
Lung Function 
 
Clinically significant increases in pre-bronchodilator FEV1 were observed at week 12 for DRI12544 
and QUEST. There were greater improvements in FEV1 in the subjects with higher baseline levels of 
type 2 inflammatory biomarkers such as blood eosinophils or FeNO (Table 10 and Table 11). 
 
Significant improvements in FEV1 were observed as early as week 2 following the first dose of 
dupilumab for both the 200 mg and 300 mg dose strengths and were maintained through week 24 
(DRI12544) and week 52 in QUEST (see Figure 3). 
 
  



60 

Figure 3: Mean Change from Baseline in Pre-Bronchodilator FEV1 (L) Over Time (Baseline 
Eosinophils ≥ 150 and ≥ 300 cells/mcL and FeNO ≥25 ppb) in QUEST 

QUEST: Blood Eosinophils  
≥ 150 cells/mcL 

QUEST: Blood Eosinophils 
 ≥ 300 cells/mcL 

QUEST: FeNO ≥ 25 ppb 

 

 
Table 10: Mean Change from Baseline in Pre-Bronchodilator FEV1 at Week 12 in DRI12544 and 
QUEST (Baseline Blood Eosinophil Levels ≥ 150 and ≥ 300 cells/mcL) 

Treatment 
 

Baseline Blood EOS 

 ≥ 150 cells/mcL ≥ 300 cells/mcL 
N LS Mean Δ 

From 
baseline 
L (%) 

LS Mean  
Difference 
vs. placebo 
(95% CI) 

N LS mean Δ 
From 
baseline 
L (%) 

LS Mean  
Difference 
vs. placebo 
(95% CI) 

DRI12544 study 
Dupilumab
200 mg 
Q2W 

120 0.32 (18.25) 0.23a 

(0.13, 0.33) 
65 0.43 (25.9) 0.26c 

(0.11, 0.40) 

Dupilumab
300 mg 
Q2W 

129 0.26 (17.1) 0.18b 

(0.08, 0.27) 
64 0.39 (25.8) 

  
0.21d 

(0.06, 0.36) 

Placebo  127 0.09 (4.36)  68 0.18 (10.2)  
QUEST study 

Dupilumab
200 mg 
Q2W 

437 0.36 (23.6) 0.17e 

(0.11, 0.23) 
 

264 0.43 (29.0) 
 

0.21e 

(0.13, 0.29) 

Placebo  232 0.18 (12.4)  148 0.21 (15.6)  
Dupilumab
300 mg 
Q2W 

452 0.37 (25.3) 0.15e 
(0.09, 0.21) 

277 0.47 (32.5)  
 

0.24e 
(0.16, 0.32) 

Placebo 237 0.22 (14.2)  142 0.22 (14.4)  
ap-value < 0.0001, bp-value = 0.0004, cp-value = 0.0008, dp-value = 0.0063, ep-value < 0.0001 
 
Table 11: Mean Change from Baseline in Pre-Bronchodilator FEV1 at Week 12 and Week 52 in 
QUEST by Baseline FeNO Subgroups 

Treatment  At Week 12 At Week 52 
N LS Mean Δ 

From baseline L 
(%) 

LS Mean Difference 
vs. placebo (95% 
CI) 

LS Mean Δ 
From baseline L 
(%) 

LS Mean Difference 
vs. placebo (95% 
CI) 

FeNO ≥ 25 ppb 
Dupilumab 
200 mg Q2W 

288 0.44 (29.0 %) 0.23 (0.15, 0.31)a 0.49 (31.6 %) 0.30 (0.22, 0.39)a 

Placebo  157 0.21 (14.1 %)  0.18 (13.2 %)  



61 

Dupilumab 
300 mg Q2W 

295 0.45 (29.8 %) 0.24 (0.16, 0.31)a 0.45 (30.5 %) 0.23 (0.15, 0.31)a 

Placebo 167 0.21 (13.7 %)  0.22 (13.6 %)  
FeNO ≥ 50 ppb 
Dupilumab 
200 mg Q2W 

114 0.53 (33.5 %) 0.30 (0.17, 0.44)a 0.59 (36.4 %) 0.38 (0.24, 0.53)a 

Placebo  69 0.23 (14.9 %)  0.21 (14.6 %)  
Dupilumab 
300 mg Q2W 

113 0.59 (37.6 %) 0.39 (0.26, 0.52)a 0.55 (35.8 %) 0.30 (0.16, 0.44)a 

Placebo 73 0.19 (13.0 %)  0.25 (13.6 %)  
ap-value < 0.0001 
 
Quality of Life/Patient-Reported Outcomes in Asthma 
 
Pre-specified secondary endpoint of ACQ-5 and AQLQ(S) responder rates were analysed at 24 weeks 
(DRI12544 and VENTURE) and at 52 weeks (QUEST). The responder rate was defined as an 
improvement in score of 0.5 or more (scale range 0-6 for ACQ-5 and 1-7 for AQLQ(S)). 
Improvements in ACQ-5 and AQLQ(S) were observed as early as week 2 and maintained for 24 
weeks in DRI12544 study and 52 weeks in QUEST study. Similar results were observed in 
VENTURE. The ACQ-5 and AQLQ(S) responder rate results in patients with elevated baseline 
biomarkers of type 2 inflammation in QUEST at week 52 are presented in Table 12. 
 
Table 12: ACQ-5 and AQLQ(S) Responder Rates at Week 52 in QUEST 

PRO Treatment  EOS 
≥ 150 cells/mcL 

 

EOS 
≥ 300 cells/mcL 

 

FeNO 
≥ 25 ppb 

 
N Responder 

rate % 
N Responder 

rate (%) 
N Responder 

rate (%) 
ACQ-5 Dupilumab 

200 mg Q2W 
395 72.9 239 74.5 262 74.4 

Placebo 201 64.2 124 66.9 141 65.2 
Dupilumab 
300 mg Q2W 

408 70.1 248 71.0 277 75.8 

Placebo  217 64.5 129 64.3 159 64.2 
AQLQ(S) Dupilumab 

200 mg Q2W 
395 66.6 239 71.1 262 67.6 

Placebo 201 53.2 124 54.8 141 54.6 
Dupilumab 
300 mg Q2W 

408 62.0 248 64.5 277 65.3 

Placebo  217 53.9 129 55.0 159 58.5 



62 

Oral Corticosteroid Reduction Study (VENTURE) 
 
VENTURE evaluated the effect of dupilumab on reducing the use of maintenance oral corticosteroids. 
Baseline characteristics are presented in Table 7. All patients were on oral corticosteroids for at least 6 
months prior to the study initiation. The baseline mean oral corticosteroid use was 11.75 mg in the 
placebo group and 10.75 mg in the group receiving dupilumab. 
 
In this 24-week trial, asthma exacerbations (defined as a temporary increase in oral corticosteroid dose 
for at least 3 days) were reduced by 59 % in subjects receiving dupilumab compared with those 
receiving placebo (annualized rate 0.65 and 1.60 for the dupilumab and placebo group, respectively; 
rate ratio 0.41 [95% CI 0.26, 0.63]) and improvement in pre-bronchodilator FEV1 from baseline to 
week 24 was greater in subjects receiving dupilumab compared with those receiving placebo (LS mean 
difference for dupilumab versus placebo of 0.22 L [95% CI: 0.09 to 0.34 L]). Effects on lung function, 
on oral steroid and exacerbation reduction were similar irrespective of baseline levels of type 2 
inflammatory biomarkers (e.g. blood eosinophils, FeNO). The ACQ-5 and AQLQ(S) were also 
assessed in VENTURE and showed improvements similar to those in QUEST. 
 
The results for VENTURE by baseline biomarkers are presented in the Table 13. 
  
Table 13: Effect of dupilumab on OCS dose reduction, VENTURE (Baseline Blood Eosinophil 
Levels ≥ 150 and ≥ 300 cells/mcL and FeNO ≥ 25 ppb) 

 
Baseline Blood EOS 

≥ 150 cells/mcL 

Baseline Blood EOS 
≥ 300 cells/mcL 

FeNO ≥ 25 ppb 

Dupilumab 
300 mg Q2W 

N=81 

Placebo 
N=69 

Dupilumab 
300 mg Q2W 

N=48 

Placebo 
N=41 

Dupilumab 
300 mg Q2W 

N=57 

Placebo 
N=57 

Primary endpoint (week 24) 
Percent reduction in OCS from baseline  

Mean overall percent reduction 
from baseline (%) 

Difference (% [95% CI]) 
(Dupilumab vs. placebo) 

75.91 
 

29.39b  

(15.67, 43.12) 

46.51 79.54 
 

36.83b 
(18.94, 54.71) 

42.71 77.46 
 

34.53b 

(19.08, 49.97) 

42.93 

Median % reduction in daily 
OCS dose from baseline 

100 50 100 50 100 50 

Percent reduction from baseline  
100% % 
≥ 90 % 
≥ 75 % 
≥ 50 % 
> 0 % 
No reduction or any increase in 
OCS dose, or dropped out of 
study 

 
54.3 
58.0 
72.8 
82.7 
87.7 
12.3 

 
33.3 
34.8 
44.9 
55.1 
66.7 
33.3 

 
60.4 
66.7 
77.1 
85.4 
85.4 
14.6 

 
31.7 
34.1 
41.5 
53.7 
63.4 
36.6 

 
52.6 
54.4 
73.7 
86.0 
89.5 
10.5 

 
28.1 
29.8 
36.8 
50.9 
66.7 
33.3 

Secondary endpoint (week 24)a 
Proportion of patients 
achieving a reduction of OCS 
dose to < 5 mg/day 

77 44 84 40 79 34 

Odds ratio (95% CI) 4.29c 
(2.04, 9.04) 

 8.04d 
(2.71, 23.82) 

 7.21b 

(2.69, 19.28) 
 

aModel estimates by logistic regression 
bp-value < 0.0001  
cp-value = 0.0001 
dp-value = 0.0002 
 



63 

Long-term extension trial (TRAVERSE) 
 
The long-term safety of dupilumab in 2,193 adults and 89 adolescents with moderate-to-severe asthma, 
including 185 adults with oral corticosteroid-dependent asthma, who had participated in previous 
clinical trials of dupilumab (DRI12544, QUEST, and VENTURE), was assessed in the open-label 
extension study (TRAVERSE) (see section 4.8). Efficacy was measured as a secondary endpoint, was 
similar to results observed in the pivotal studies and was sustained up to 96 weeks. In the adults with 
oral-corticosteroid-dependent asthma, there was sustained reduction in exacerbations and improvement 
in lung function up to 96 weeks, despite decrease or discontinuation of oral corticosteroid dose. 
 
Paediatric population 
 
Atopic dermatitis  
The safety and efficacy of dupilumab have been established in 12 to 17 years old with moderate-to-
severe atopic dermatitis in study AD-1526 which included 251 adolescents. The safety and efficacy of 
dupilumab have been established in 6 to 11 years old with severe atopic dermatitis in study AD-1652 
which included 367 paediatric patients. Use is supported by study AD-1434 which enrolled patients 
who had completed AD-1526 (136 moderate and 64 severe at the time of enrolment in study AD-
1434) and patients who had completed study AD-1652 (110 moderate and 72 severe at the time of 
enrolment in in study AD-1434). The safety and efficacy were generally consistent between children 6 
to 11 years old, adolescent, and adult patients with atopic dermatitis (see section 4.8). Safety and 
efficacy in paediatric patients < 6 years of age with atopic dermatitis have not been established. 
 
Asthma 
A total of 107 adolescents aged 12 to 17 years with moderate to severe asthma were enrolled in 
QUEST study and received either 200 mg (N=21) or 300 mg (N=18) dupilumab (or matching placebo 
either 200 mg [N=34] or 300 mg [N=34]) every other week. Efficacy with respect to severe asthma 
exacerbations and lung function was observed in both adolescents and adults.  For both the 200 mg 
and 300 mg every other week doses, significant improvements in FEV1 (LS mean change from 
baseline at week 12) were observed (0.36 L and 0.27 L, respectively). For the 200 mg every other 
week dose, patients had a reduction in the rate of severe exacerbations that was consistent with adults. 
Safety and efficacy in paediatric patients (< 12 years of age) with severe asthma have not been 
established. The adverse event profile in adolescents was generally similar to the adults. 
 
A total of 89 adolescents aged 12 to 17 years with moderate-to-severe asthma were enrolled in the 
open label long-term study (TRAVERSE). In this study, efficacy was measured as a secondary 
endpoint, was similar to results observed in the pivotal studies and was sustained up to 96 weeks. 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
dupilumab in one or more subset of the paediatric population in atopic dermatitis and asthma (see 
section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties  
 
The pharmacokinetics of dupilumab is similar in patients with atopic dermatitis and asthma. 
 
Absorption 
 
After a single subcutaneous (SC) dose of 75-600 mg dupilumab to adults, median times to maximum 
concentration in serum (tmax) were 3-7 days. The absolute bioavailability of dupilumab following a SC 
dose is similar between AD and asthma patients, ranging between 61 % and 64  %, as determined by a 
population pharmacokinetics (PK) analysis. 
 
Steady-state concentrations were achieved by week 16 following the administration of 600 mg starting 
dose and 300 mg dose every other week. Across clinical trials, the mean ±SD steady-state trough 



64 

concentrations ranged from 60.3±35.1 mcg/ml to 79.9±41.4 mcg/ml for 300 mg dose and from 
29.2±18.7 to 36.5±22.2 mcg/ml for 200 mg dose administered every other week to adults. 
 
Distribution 
 
A volume of distribution for dupilumab of approximately 4.6 L was estimated by population PK 
analysis, indicating that dupilumab is distributed primarily in the vascular system. 
 
Biotransformation 
 
Specific metabolism studies were not conducted because dupilumab is a protein. Dupilumab is 
expected to degrade to small peptides and individual amino acids. 
 
Elimination 
 
Dupilumab elimination is mediated by parallel linear and nonlinear pathways. At higher 
concentrations, dupilumab elimination is primarily through a non-saturable proteolytic pathway, while 
at lower concentrations, the non-linear saturable IL-4R α target-mediated elimination predominates. 
After the last steady state dose, the median time for dupilumab concentrations to decrease below the 
lower limit of detection, estimated by population PK analysis, was 6-7 weeks for the 300 mg Q4W 
regimen, 9 weeks for the 200 mg Q2W regimen, 10-11 weeks for the 300 mg Q2W regimen, and 13 
weeks for the 300 mg QW regimen. 
 
Linearity/non-linearity 
 
Due to nonlinear clearance, dupilumab exposure, as measured by area under the concentration-time 
curve, increases with dose in a greater than proportional manner following single SC doses from 75-
600 mg. 
 
Special populations 
 
Gender 
Gender was not found to be associated with any clinically meaningful impact on the systemic exposure 
of dupilumab determined by population PK analysis. 
 
Elderly 
Of the 1,472 patients with atopic dermatitis exposed to dupilumab in a phase 2 dose-ranging study or 
phase 3 placebo-controlled studies, a total of 67 were 65 years or older. Although no differences in 
safety or efficacy were observed between older and younger adult atopic dermatitis patients, the 
number of patients aged 65 and over is not sufficient to determine whether they respond differently 
from younger patients. 
 
Age was not found to be associated with any clinically meaningful impact on the systemic exposure of 
dupilumab determined by population PK analysis. However, there were only 61 patients over 65 years 
of age included in this analysis. 
 
Of the 1,977 patients with asthma exposed to dupilumab, a total of 240 patients were 65 years or older 
and 39 patients were 75 years or older. Efficacy and safety in this age group were similar to the overall 
study population. 
 
Race 
Race was not found to be associated with any clinically meaningful impact on the systemic exposure 
of dupilumab by population PK analysis. 
 
Hepatic impairment 



65 

Dupilumab, as a monoclonal antibody, is not expected to undergo significant hepatic elimination. No 
clinical studies have been conducted to evaluate the effect of hepatic impairment on the 
pharmacokinetics of dupilumab. 
 
Renal impairment 
Dupilumab, as a monoclonal antibody, is not expected to undergo significant renal elimination. No 
clinical studies have been conducted to evaluate the effect of renal impairment on the 
pharmacokinetics of dupilumab.  Population PK analysis did not identify mild or moderate renal 
impairment as having a clinically meaningful influence on the systemic exposure of dupilumab. Very 
limited data are available in patients with severe renal impairment. 
 
Body Weight 
Dupilumab trough concentrations were lower in subjects with higher body weight with no meaningful 
impact on efficacy. 
 
Paediatric population 
 
Atopic dermatitis 
The pharmacokinetics of dupilumab in paediatric patients (< 6 years of age) or body weight < 15 kg 
with atopic dermatitis has not been studied. 
 
For adolescents 12 to 17 years of age with atopic dermatitis receiving every other week dosing (Q2W) 
with either 200 mg (<60 kg) or 300 mg (≥60 kg), the mean ±SD steady state trough concentration of 
dupilumab was 54.5±27.0 mcg/ml. 
 
For children 6 to 11 years of age with atopic dermatitis receiving every four week dosing (Q4W) with 
300 mg (≥ 15 kg) in AD-1652, the mean ± SD steady-state trough concentration was 76.3±37.2 
mcg/ml. At week 16 in AD-1434 in children 6 to 11 years of age who initiated every four week dosing 
(Q4W) with 300 mg (≥ 15 kg), and whose dose was increased to every other week dosing (Q2W) with 
200 mg (≥ 15 to < 60 kg) or 300 mg (≥ 60 kg), the mean±SD steady-state trough concentration was 
108±53.8 mcg/ml. For children 6 to 11 years of age receiving 300 mg Q4W, initial doses of 300 mg on 
Days 1 and 15 produce similar steady-state exposure as an initial dose of 600 mg on Day 1, based on 
PK simulations. 
 
Asthma 
A total of 107 adolescents aged 12 to 17 years with asthma were enrolled in QUEST study. The mean 
±SD steady-state trough concentrations of dupilumab were 107±51.6 mcg/ml and 46.7±26.9 mcg/ml, 
respectively, for 300 mg or 200 mg administered every other week. No age-related pharmacokinetic 
difference was observed in adolescent patients after correction for body weight. 
 
5.3 Preclinical safety data  
 
Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dose 
toxicity (including safety pharmacology endpoints) and toxicity to reproduction and development. 
 
The mutagenic potential of dupilumab has not been evaluated; however monoclonal antibodies are not 
expected to alter DNA or chromosomes. 
 
Carcinogenicity studies have not been conducted with dupilumab. An evaluation of the available 
evidence related to IL-4Rα inhibition and animal toxicology data with surrogate antibodies does not 
suggest an increased carcinogenic potential for dupilumab. 
 
During a reproductive toxicology study conducted in monkeys, using a surrogate antibody specific to 
the monkey IL-4Rα, no fetal abnormalities were observed at dosages that saturate the IL-4Rα.  
 
An enhanced pre- and post-natal developmental study revealed no adverse effects in maternal animals 
or their offspring up to 6 months post-partum/post-birth. 



66 

Fertility studies conducted in male and female mice using a surrogate antibody against IL-4Rα showed 
no impairment of fertility (see section 4.6). 

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients 

arginine hydrochloride 
histidine 
polysorbate 80 (E433) 
sodium acetate trihydrate 
glacial acetic acid (E260) 
sucrose 
water for injections 

6.2 Incompatibilities 

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 

6.3 Shelf life 

3 years. 

If necessary, pre-filled syringes or pre-filled pens may be kept at room temperature up to 25°C for a 
maximum of 14 days. Do not store above 25°C. If the carton needs to be removed permanently from 
refrigerator, the date of removal may be recorded on the outer carton. After removal from the 
refrigerator, Dupixent must be used within 14 days or discarded.  

6.4 Special precautions for storage 

Store in a refrigerator (2°C - 8°C). 

Do not freeze. 

Store in the original carton in order to protect from light. 

6.5 Nature and contents of container 

Dupixent 200 mg solution for injection in pre-filled syringe  
1.14 ml solution in a siliconised type-1 clear glass pre-filled syringe with needle shield, with a fixed 27 
gauge 12.7 mm (½ inch), thin wall stainless steel staked needle.  

Pack size: 
• 1 pre-filled syringe
• 2 pre-filled syringes
• Multipack containing 3 (3 packs of 1) pre-filled syringes
• Multipack containing 6 (3 packs of 2) pre-filled syringes

Dupixent 200 mg solution for injection in pre-filled pen  
1.14 ml solution in a siliconised type-1 clear glass syringe in a pre-filled pen, with a fixed 27 gauge 
12.7 mm (½ inch), thin wall stainless steel staked needle.  

Pack size: 
• 1 pre-filled pen



67 

• 2 pre-filled pens  
• 3 pre-filled pens  
• 6 pre-filled pens  
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
The instructions for the preparation and administration of Dupixent in a pre-filled syringe or in a pre-
filled pen are given in the package leaflet. 
 
The solution should be clear to slightly opalescent, colourless to pale yellow. If the solution is cloudy, 
discoloured or contains visible particulate matter, the solution should not be used. 
 
After removing the 200 mg pre-filled syringe or pre-filled pen from the refrigerator, it should be 
allowed to reach room temperature up to 25°C by waiting for 30 min before injecting Dupixent. 
 
The pre-filled syringe or the pre-filled pen should not be exposed to heat or direct sunlight and should 
not be shaken. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. After use, place the pre-filled syringe or the pre-filled pen into a puncture-resistant 
container and discard as required by local regulations. Do not recycle the container. Keep the container 
out of sight and reach of children. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
sanofi-aventis groupe 
54, rue La Boétie 
75008 Paris 
France 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/17/1229/009 
EU/1/17/1229/010 
EU/1/17/1229/011 
EU/1/17/1229/012 
EU/1/17/1229/013 
EU/1/17/1229/014 
EU/1/17/1229/015 
EU/1/17/1229/016 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 26 September 2017 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 
  

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


68 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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

MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE  
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

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

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 

 



69 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S)  AND 
MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) of the biological active substance(s)  
REGENERON PHARMACEUTICALS INC. 
81 Columbia Turnpike 
RENSSELAER 
NEW YORK 12144 
UNITED STATES 
 
Regeneron Ireland Designated Activity Company (DAC) 
Ballycummin 
Raheen Business Park 
Limerick 
Ireland 
 
Genzyme Flanders BVBA 
Cipalstraat 8, 
B-2440 Geel 
Belgium 
 
Name and address of the manufacturer(s) responsible for batch release 
 
SANOFI WINTHROP INDUSTRIE 
1051 Boulevard Industriel,  
76580 LE TRAIT, 
FRANCE 
 
Sanofi-Aventis Deutschland GmbH 
Brüningstrasse 50 
Industriepark Hoechst 
65926 FRANKFURT AM MAIN 
GERMANY 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  
 
• Periodic Safety Update Reports (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of 
Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and 
any subsequent updates published on the European medicines web-portal. 
The marketing authorisation holder (MAH) shall submit the first PSUR for this product within 6 
months following authorisation. 



70 

 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP) 

 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities 
and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing 
authorisation and any agreed subsequent updates of the RMP. 
An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new 

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

 
 
 
  



71 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III  
 

LABELLING AND PACKAGE LEAFLET  
  



72 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING  
 
 
 

  



73 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
OUTER CARTON 
Pre-filled syringe 300 mg 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Dupixent 300 mg solution for injection in pre-filled syringe 
dupilumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S)  
 
Each pre-filled syringe contains 300 mg of dupilumab in 2 ml solution (150 mg/ml). 
 
 
3. LIST OF EXCIPIENTS  
 
Excipients: arginine hydrochloride, histidine, polysorbate 80 (E433), sodium acetate, glacial acetic 
acid (E260), sucrose, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS  
 
Solution for injection 
 
1 pre-filled syringe 
2 pre-filled syringes 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION  
 
For single use only 
Read the package leaflet before use. 
Subcutaneous use 
Do not shake 
Open 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  
 
 
8. EXPIRY DATE  
 
EXP 
Date of removal from the refrigerator:   /  /  /   
 
 



74 

9. SPECIAL STORAGE CONDITIONS  
 
Store in a refrigerator. Do not freeze. 
Time out of refrigeration should not exceed a maximum of 14 days at temperature below 25 °C. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE  

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER  
 
sanofi-aventis groupe  
54, rue La Boétie 
75008 Paris  
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1229/001 1 pre-filled syringe 
EU/1/17/1229/002 2 pre-filled syringes 
 
 
13. BATCH NUMBER  
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY  
 
 
15. INSTRUCTIONS ON USE  
 
 
16. INFORMATION IN BRAILLE 
 
Dupixent 300 mg syringe 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
  



75 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
OUTER CARTON 
Pre-filled syringe 300 mg - Multipack (contains Blue Box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Dupixent 300 mg solution for injection in pre-filled syringe 
dupilumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S)  
 
Each pre-filled syringe contains 300 mg of dupilumab in 2 ml solution (150 mg/ml). 
 
 
3. LIST OF EXCIPIENTS  
 
Excipients: arginine hydrochloride, histidine, polysorbate 80 (E433), sodium acetate, glacial acetic 
acid (E260), sucrose, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS  
 
Solution for injection 
 
Multipack: 3 (3 packs of 1) pre-filled syringes 
Multipack: 6 (3 packs of 2) pre-filled syringes 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION  
 
For single use only 
Read the package leaflet before use. 
Subcutaneous use 
Do not shake 
Open 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  
 
 
8. EXPIRY DATE  
 
EXP 
Date of removal from the refrigerator:   /  /  /   
 
 



76 

9. SPECIAL STORAGE CONDITIONS  
 
Store in a refrigerator. Do not freeze. 
Time out of refrigeration should not exceed a maximum of 14 days at temperature below 25 °C. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE  

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER  
 
sanofi-aventis groupe  
54, rue La Boétie 
75008 Paris 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1229/003 3 pre-filled syringes (3 packs of 1) 
EU/1/17/1229/004 6 pre-filled syringes (3 packs of 2) 
 
 
13. BATCH NUMBER  
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY  
 
 
15. INSTRUCTIONS ON USE  
 
 
16. INFORMATION IN BRAILLE 
 
Dupixent 300 mg syringe 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
  



77 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
INNER CARTON 
Pre-filled syringe 300 mg - Multipack (without Blue Box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Dupixent 300 mg solution for injection in pre-filled syringe 
dupilumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S)  
 
Each pre-filled syringe contains 300 mg of dupilumab in 2 ml solution (150 mg/ml). 
 
 
3. LIST OF EXCIPIENTS  
 
Excipients: arginine hydrochloride, histidine, polysorbate 80 (E433), sodium acetate, glacial acetic 
acid (E260), sucrose, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS  
 
Solution for injection 
 
1 pre-filled syringe 
2 pre-filled syringes 
Component of a multipack, can’t be sold separately. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION  
 
For single use only 
Read the package leaflet before use. 
Subcutaneous use 
Do not shake 
Open 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  
 
 
8. EXPIRY DATE  
 
EXP 
Date of removal from the refrigerator:   /  /  /   
 
 



78 

9. SPECIAL STORAGE CONDITIONS  
 
Store in a refrigerator. Do not freeze. 
Time out of refrigeration should not exceed a maximum of 14 days at temperature below 25 °C. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE  

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER  
 
sanofi-aventis groupe  
54, rue La Boétie 
75008 Paris 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1229/003 3 pre-filled syringes (3 packs of 1) 
EU/1/17/1229/004 6 pre-filled syringes (3 packs of 2) 
 
 
13. BATCH NUMBER  
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY  
 
Medicinal product subject to medical prescription. 
 
15. INSTRUCTIONS ON USE  
 
 
16. INFORMATION IN BRAILLE 
 
Dupixent 300 mg syringe 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
  



79 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
LABEL 
Pre-filled syringe 300 mg 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION  
 
Dupixent 300 mg injection 
dupilumab 
Subcutaneous use 
 
 
2. METHOD OF ADMINISTRATION  
 
 
3. EXPIRY DATE  
 
EXP 
 
 
4. BATCH NUMBER  
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT  
 
300 mg/2 ml 
 
 
6. OTHER  
 
 
  



80 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
OUTER CARTON 
Pre-filled syringe with needle shield 300 mg 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Dupixent 300 mg solution for injection in pre-filled syringe 
dupilumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S)  
 
Each pre-filled syringe contains 300 mg of dupilumab in 2 ml solution (150 mg/ml). 
 
 
3. LIST OF EXCIPIENTS  
 
Excipients: arginine hydrochloride, histidine, polysorbate 80 (E433), sodium acetate, glacial acetic 
acid (E260), sucrose, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS  
 
Solution for injection 
 
1 pre-filled syringe with needle shield 
2 pre-filled syringes with needle shield 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION  
 
Read the package leaflet before use. 
For single use only 
Subcutaneous use 
Do not shake 
Open 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  
 
 
8. EXPIRY DATE  
 
EXP 
Date of removal from the refrigerator:   /  /  /   
 
 



81 

9. SPECIAL STORAGE CONDITIONS  
 
Store in a refrigerator. Do not freeze. 
Time out of refrigeration should not exceed a maximum of 14 days at temperature below 25 °C. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE  

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER  
 
sanofi-aventis groupe  
54, rue La Boétie 
75008 Paris 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1229/005 1 pre-filled syringe with needle shield 
EU/1/17/1229/006 2 pre-filled syringes with needle shield 
 
 
13. BATCH NUMBER  
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY  
 
 
15. INSTRUCTIONS ON USE  
 
 
16. INFORMATION IN BRAILLE 
 
Dupixent 300 mg syringe 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
  



82 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
OUTER CARTON 
Pre-filled syringe with needle shield 300 mg - Multipack (contains Blue Box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Dupixent 300 mg solution for injection in pre-filled syringe 
dupilumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S)  
 
Each pre-filled syringe contains 300 mg of dupilumab in 2 ml solution (150 mg/ml). 
 
 
3. LIST OF EXCIPIENTS  
 
Excipients: arginine hydrochloride, histidine, polysorbate 80 (E433), sodium acetate, glacial acetic 
acid (E260), sucrose, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS  
 
Solution for injection 
 
Multipack: 3 (3 packs of 1) pre-filled syringes with needle shield 
Multipack: 6 (3 packs of 2) pre-filled syringes with needle shield 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION  
 
For single use only 
Read the package leaflet before use. 
Subcutaneous use 
Do not shake 
Open 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  
 
 
8. EXPIRY DATE  
 
EXP 
Date of removal from the refrigerator:   /  /  /   
 
 



83 

9. SPECIAL STORAGE CONDITIONS  
 
Store in a refrigerator. Do not freeze. 
Time out of refrigeration should not exceed a maximum of 14 days at temperature below 25 °C. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE  

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER  
 
sanofi-aventis groupe  
54, rue La Boétie 
75008 Paris 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1229/007 3 pre-filled syringes with needle shield (3 packs of 1) 
EU/1/17/1229/008 6 pre-filled syringes with needle shield (3 packs of 2) 
 
 
13. BATCH NUMBER  
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY  
 
 
15. INSTRUCTIONS ON USE  
 
 
16. INFORMATION IN BRAILLE 
 
Dupixent 300 mg syringe 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
  



84 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
INNER CARTON 
Pre-filled syringe with needle shield 300 mg - Multipack (without Blue Box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Dupixent 300 mg solution for injection in pre-filled syringe 
dupilumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S)  
 
Each pre-filled syringe contains 300 mg of dupilumab in 2 ml solution (150 mg/ml). 
 
 
3. LIST OF EXCIPIENTS  
 
Excipients: arginine hydrochloride, histidine, polysorbate 80 (E433), sodium acetate, glacial acetic 
acid (E260), sucrose, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS  
 
Solution for injection 
 
1 pre-filled syringe with needle shield 
2 pre-filled syringes with needle shield 
Component of a multipack, can’t be sold separately. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION  
 
For single use only 
Read the package leaflet before use. 
Subcutaneous use 
Do not shake 
Open 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  
 
 
8. EXPIRY DATE  
 
EXP 
Date of removal from the refrigerator:   /  /  /   
 
 



85 

9. SPECIAL STORAGE CONDITIONS  
 
Store in a refrigerator. Do not freeze. 
Time out of refrigeration should not exceed a maximum of 14 days at temperature below 25 °C. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE  

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER  
 
sanofi-aventis groupe  
54, rue La Boétie 
75008 Paris  
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1229/007 3 pre-filled syringes with needle shield (3 packs of 1) 
EU/1/17/1229/008 6 pre-filled syringes with needle shield (3 packs of 2) 
 
 
13. BATCH NUMBER  
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY  
 
Medicinal product subject to medical prescription. 
 
15. INSTRUCTIONS ON USE  
 
 
16. INFORMATION IN BRAILLE 
 
Dupixent 300 mg syringe 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
  



86 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
LABEL 
Pre-filled syringe with needle shield 300 mg 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION  
 
Dupixent 300 mg injection 
dupilumab 
Subcutaneous use 
 
 
2. METHOD OF ADMINISTRATION  
 
 
3. EXPIRY DATE  
 
EXP 
 
 
4. BATCH NUMBER  
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT  
 
300 mg/2 ml 
 
 
6. OTHER  
  



87 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
Pre-filled pen 300 mg 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Dupixent 300 mg solution for injection in pre-filled pen 
dupilumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S)  
 
Each pre-filled pen contains 300 mg of dupilumab in 2 ml solution (150 mg/ml). 
 
 
3. LIST OF EXCIPIENTS  
 
Excipients: arginine hydrochloride, histidine, polysorbate 80 (E433), sodium acetate, glacial acetic 
acid (E260), sucrose, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS  
 
Solution for injection 
 
1 pre-filled pen 
2 pre-filled pens 
3 pre-filled pens 
6 pre-filled pens 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION  
 
For single use only 
Read the package leaflet before use. 
Subcutaneous use 
Do not shake 
Open 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  
 
 



88 

8. EXPIRY DATE  
 
EXP 
Date of removal from the refrigerator:   /  /  /   
 
 
9. SPECIAL STORAGE CONDITIONS  
 
Store in a refrigerator. Do not freeze. 
Time out of refrigeration should not exceed a maximum of 14 days at temperature below 25 °C. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE  

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER  
 
sanofi-aventis groupe  
54, rue La Boétie 
75008 Paris 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1229/017 1 pre-filled pen 
EU/1/17/1229/018 2 pre-filled pens 
EU/1/17/1229/019 3 pre-filled pens 
EU/1/17/1229/020 6 pre-filled pens 
 
 
13. BATCH NUMBER  
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY  
 
 
15. INSTRUCTIONS ON USE  
 
 
16. INFORMATION IN BRAILLE 
 
Dupixent 300 mg pen 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 



89 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
  



90 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
LABEL 
 
Pre-filled pen 300 mg 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION  
 
Dupixent 300 mg injection 
dupilumab 
Subcutaneous use 
 
 
2. METHOD OF ADMINISTRATION  
 
 
3. EXPIRY DATE  
 
EXP 
 
 
4. BATCH NUMBER  
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT  
 
300 mg/2 ml 
 
 
6. OTHER  



91 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
Pre-filled syringe with needle shield 200 mg 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Dupixent 200 mg solution for injection in pre-filled syringe 
dupilumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S)  
 
Each pre-filled syringe contains 200 mg of dupilumab in 1.14 ml solution (175 mg/ml). 
 
 
3. LIST OF EXCIPIENTS  
 
Excipients: arginine hydrochloride, histidine, polysorbate 80 (E433), sodium acetate, glacial acetic 
acid (E260), sucrose, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS  
 
Solution for injection 
 
1 pre-filled syringe with needle shield 
2 pre-filled syringes with needle shield 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION  
 
Read the package leaflet before use. 
For single use only 
Subcutaneous use 
Do not shake 
Open 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  
 
 
8. EXPIRY DATE  
 
EXP 
Date of removal from the refrigerator:   /  /  /   
 
 



92 

9. SPECIAL STORAGE CONDITIONS  
 
Store in a refrigerator. Do not freeze. 
Time out of refrigeration should not exceed a maximum of 14 days at temperature below 25 °C. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE  

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER  
 
sanofi-aventis groupe  
54, rue La Boétie 
75008 Paris 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1229/009 1 pre-filled syringe with needle shield 
EU/1/17/1229/010 2 pre-filled syringes with needle shield 
 
 
 
13. BATCH NUMBER  
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY  
 
 
15. INSTRUCTIONS ON USE  
 
 
16. INFORMATION IN BRAILLE 
 
Dupixent 200 mg syringe 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
  



93 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
OUTER CARTON 
Pre-filled syringe with needle shield 200 mg - Multipack (contains Blue Box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Dupixent 200 mg solution for injection in pre-filled syringe 
dupilumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S)  
 
Each pre-filled syringe contains 200 mg of dupilumab in 1.14 ml solution (175 mg/ml). 
 
 
3. LIST OF EXCIPIENTS  
 
Excipients: arginine hydrochloride, histidine, polysorbate 80 (E433), sodium acetate, glacial acetic 
acid (E260), sucrose, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS  
 
Solution for injection 
 
Multipack: 3 (3 packs of 1) pre-filled syringes with needle shield 
Multipack: 6 (3 packs of 2) pre-filled syringes with needle shield 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION  
 
Read the package leaflet before use. 
For single use only 
Subcutaneous use 
Do not shake 
Open 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  
 
 
8. EXPIRY DATE  
 
EXP 
Date of removal from the refrigerator:   /  /  /   
 
 



94 

9. SPECIAL STORAGE CONDITIONS  
 
Store in a refrigerator. Do not freeze. 
Time out of refrigeration should not exceed a maximum of 14 days at temperature below 25 °C. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE  

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER  
 
sanofi-aventis groupe  
54, rue La Boétie 
75008 Paris 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1229/011 3 pre-filled syringes with needle shield (3 packs of 1) 
EU/1/17/1229/012 6 pre-filled syringes with needle shield (3 packs of 2) 
 
 
13. BATCH NUMBER  
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY  
 
 
15. INSTRUCTIONS ON USE  
 
 
16. INFORMATION IN BRAILLE 
 
Dupixent 200 mg syringe 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
  



95 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
INNER CARTON 
Pre-filled syringe with needle shield 200 mg - Multipack (without Blue Box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Dupixent 200 mg solution for injection in pre-filled syringe 
dupilumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S)  
 
Each pre-filled syringe contains 200 mg of dupilumab in 1.14 ml solution (175 mg/ml). 
 
 
3. LIST OF EXCIPIENTS  
 
Excipients: arginine hydrochloride, histidine, polysorbate 80 (E433), sodium acetate, glacial acetic 
acid (E260), sucrose, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS  
 
Solution for injection 
 
1 pre-filled syringe with needle shield 
2 pre-filled syringes with needle shield 
Component of a multipack, can’t be sold separately. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION  
 
Read the package leaflet before use. 
For single use only 
Subcutaneous use 
Do not shake 
Open 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  
 
 
8. EXPIRY DATE  
 
EXP 
Date of removal from the refrigerator:   /  /  /   
 
 



96 

9. SPECIAL STORAGE CONDITIONS  
 
Store in a refrigerator. Do not freeze. 
Time out of refrigeration should not exceed a maximum of 14 days at temperature below 25 °C. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE  

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER  
 
sanofi-aventis groupe  
54, rue La Boétie 
75008 Paris 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1229/011 3 pre-filled syringes with needle shield (3 packs of 1) 
EU/1/17/1229/012 6 pre-filled syringes with needle shield (3 packs of 2) 
 
 
13. BATCH NUMBER  
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY  
 
Medicinal product subject to medical prescription. 
 
15. INSTRUCTIONS ON USE  
 
 
16. INFORMATION IN BRAILLE 
 
Dupixent 200 mg syringe 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
  



97 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
LABEL 
Pre-filled syringe with needle shield 200 mg 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION  
 
Dupixent 200 mg injection 
dupilumab 
Subcutaneous use 
 
 
2. METHOD OF ADMINISTRATION  
 
 
3. EXPIRY DATE  
 
EXP 
 
 
4. BATCH NUMBER  
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT  
 
200 mg/1.14 ml 
 
 
6. OTHER  
  



98 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
Pre-filled pen 200 mg 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
Dupixent 200 mg solution for injection in pre-filled pen 
dupilumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S)  
 
Each pre-filled pen contains 200 mg of dupilumab in 1.14 ml solution (175 mg/ml). 
 
 
3. LIST OF EXCIPIENTS  
 
Excipients: arginine hydrochloride, histidine, polysorbate 80 (E433), sodium acetate, glacial acetic 
acid (E260), sucrose, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS  
 
Solution for injection 
 
1 pre-filled pen 
2 pre-filled pens 
3 pre-filled pens 
6 pre-filled pens 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION  
 
Read the package leaflet before use. 
For single use only 
Subcutaneous use 
Do not shake 
Open 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  
 
 
8. EXPIRY DATE  
 
EXP 
Date of removal from the refrigerator:   /  /  /   



99 

 
 
9. SPECIAL STORAGE CONDITIONS  
 
Store in a refrigerator. Do not freeze. 
Time out of refrigeration should not exceed a maximum of 14 days at temperature below 25 °C. 
Store in the original carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE  

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER  
 
sanofi-aventis groupe  
54, rue La Boétie 
75008 Paris 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1229/013 1 pre-filled pen 
EU/1/17/1229/014 2 pre-filled pens 
EU/1/17/1229/015 3 pre-filled pens 
EU/1/17/1229/016 6 pre-filled pens 
 
 
13. BATCH NUMBER  
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY  
 
 
15. INSTRUCTIONS ON USE  
 
 
16. INFORMATION IN BRAILLE 
 
Dupixent 200 mg pen 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 



100 

NN: 
  



101 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
LABEL 
Pre-filled pen 200 mg 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION  
 
Dupixent 200 mg injection 
dupilumab 
Subcutaneous use 
 
 
2. METHOD OF ADMINISTRATION  
 
 
3. EXPIRY DATE  
 
EXP 
 
 
4. BATCH NUMBER  
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT  
 
200 mg/1.14 ml 
 
 
6. OTHER  
  



102 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET  
 
 



103 

Package leaflet: Information for the user  
 

Dupixent 300 mg solution for injection in pre-filled syringe  
 

dupilumab 
 

This medicine is subject to additional monitoring. This will allow quick identification of new 
safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- 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, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What Dupixent is and what it is used for 
2. What you need to know before you use Dupixent 
3. How to use Dupixent 
4. Possible side effects 
5. How to store Dupixent 
6. Contents of the pack and other information 
 
 
1. What Dupixent is and what it is used for 
 
What Dupixent is 
Dupixent contains the active substance dupilumab. 
 
Dupilumab is a monoclonal antibody (a type of specialised protein) that blocks the action of proteins 
called IL-4 and IL-13. Both play a major role in causing the signs and symptoms of atopic dermatitis, 
asthma, and chronic rhinosinusitis with nasal polyposis (CRSwNP). 
 
What Dupixent is used for 
Dupixent is used to treat adults and adolescents 12 years and older with moderate-to-severe atopic 
dermatitis, also known as atopic eczema. Dupixent is also used to treat children 6 to 11 years old with 
severe atopic dermatitis. Dupixent may be used with eczema medicines that you apply to the skin or it 
may be used on its own.  
 
Dupixent is also used with other asthma medicines for the maintenance treatment of severe asthma in 
adults and adolescents (12 years of age and older) whose asthma is not controlled with their current 
asthma medicines. 
 
Dupixent is also used with other medicines for the maintenance treatment of CRSwNP in adults whose 
disease is not controlled with their current CRSwNP medicines. Dupixent can also reduce the need for 
surgery and the need for systemic corticosteroid use. 
 
How Dupixent works 
Using Dupixent for atopic dermatitis (atopic eczema) can improve the condition of your skin and 
reduce itching. Dupixent has also been shown to improve symptoms of pain, anxiety, and depression 
associated with atopic dermatitis. In addition, Dupixent helps improve your sleep disturbance and 
overall quality of life. 
 



104 

Dupixent helps prevent severe asthma attacks (exacerbations) and can improve your breathing. 
Dupixent may also help reduce the amount of another group of medicines you need to control your 
asthma, called oral corticosteroids, while preventing severe asthma attacks and improving your 
breathing. 
 
 
2. What you need to know before you use Dupixent 
 
Do not use Dupixent  
• if you are allergic to dupilumab or any of the other ingredients of this medicine (listed in 

section 6). 
• if you think you may be allergic, or you are not sure, ask your doctor, pharmacist or nurse for 

advice before using Dupixent. 
 
Warnings and precautions  
Talk to your doctor, pharmacist or nurse before using Dupixent: 
 
Dupixent is not a rescue medicine and should not be used to treat a sudden asthma attack. 
 
Allergic reactions 
• Very rarely, Dupixent can cause serious side effects, including allergic (hypersensitivity) reactions 

and anaphylactic reaction and angioedema. These reactions can occur from minutes until seven 
days after Dupixent administration. You must look out for signs of these conditions (i.e. breathing 
problems, swelling of the face, lips, mouth, throat or tongue, fainting, dizziness, feeling 
lightheaded (low blood pressure), fever, general ill feeling, swollen lymph nodes, hives, itching, 
joint pain, skin rash) while you are taking Dupixent. Such signs are listed under “Serious side 
effects” in section 4. 

• Stop using Dupixent and tell your doctor or get medical help immediately if you notice any signs 
of an allergic reaction. 
 

Eosinophilic conditions 
• Rarely patients taking an asthma medicine may develop inflammation of blood vessels or lungs 

due to an increase of certain white blood cells (eosinophilia). 
• It is not known whether this is caused by Dupixent. This usually, but not always, happens in 

people who also take a steroid medicine which is being stopped or for which the dose is being 
lowered. 

• Tell your doctor immediately if you develop a combination of symptoms such as a flu-like illness, 
pins and needles or numbness of arms or legs, worsening of pulmonary symptoms, and/or rash. 
 

Parasitic (intestinal parasites) infection 
• Dupixent may weaken your resistance to infections caused by parasites. If you already have a 

parasitic infection it should be treated before you start treatment with Dupixent. 
• Check with your doctor if you have diarrhoea, gas, upset stomach, greasy stools, and dehydration 

which could be a sign of a parasitic infection. 
• If you live in a region where these infections are common or if you are travelling to such a region 

check with your doctor. 
 
Asthma 
If you have asthma and are taking asthma medicines, do not change or stop your asthma medicine 
without talking to your doctor. Talk to your doctor before you stop Dupixent or if your asthma remains 
uncontrolled or worsens during treatment with this medicine. 
 
Eye problems 
Talk to your doctor if you have any new or worsening eye problems, including eye pain or changes in 
vision. 
 



105 

Children and adolescents 
• The safety and benefits of Dupixent are not yet known in children with atopic dermatitis below the 

age of 6. 
• The safety and benefits of Dupixent are not yet known in children with asthma below the age of 

12. 
• CRSwNP does not normally occur in children. The safety and benefits of Dupixent are not yet 

known in children with CRSwNP below the age of 18 years. 
 
Other medicines and Dupixent 
Tell your doctor or pharmacist  
• if you are using, have recently used or might use any other medicines. 
• if you have recently had or are due to have a vaccination. 
 
Other medicines for asthma 
Do not stop or reduce your asthma medicines, unless instructed by your doctor. 
• These medicines (especially ones called corticosteroids) must be stopped gradually. 
• This must be done under the direct supervision of your doctor and dependent on your response to 

Dupixent. 
 
Pregnancy and breast-feeding 
• If you are pregnant, think you may be pregnant, or are planning to have a baby, ask your doctor for 

advice before using this medicine. The effects of this medicine in pregnant women are not known; 
therefore it is preferable to avoid the use of Dupixent in pregnancy unless your doctor advises to 
use it. 

• If you are breast-feeding or are planning to breast-feed, talk to your doctor before using this 
medicine. You and your doctor should decide if you will breast-feed or use Dupixent. You should 
not do both. 

 
Driving and using machines  
Dupixent is unlikely to influence your ability to drive and use machines. 
 
Dupixent contains sodium  
This medicine contains less than 1 mmol sodium (23 mg) per 300 mg dose, i.e., it is essentially 
“sodium-free”. 
 
 
3. How to use Dupixent 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or 
pharmacist if you are not sure. 
 
How Dupixent is given 
Dupixent is given by injection under the skin (subcutaneous injection). 
 
How much Dupixent you will receive 
Your doctor will decide which dose of Dupixent is right for you. 
 
Recommended dose in adults with atopic dermatitis 
For patients with atopic dermatitis, the recommended dose of Dupixent is: 
• An initial dose of 600 mg (two 300 mg injections) 
• Followed by 300 mg given every other week by subcutaneous injection. 
 
Recommended dose in adolescents with atopic dermatitis 
The recommended dose of Dupixent for adolescents (12 to 17 years of age) with atopic dermatitis is 
based on body weight: 
 



106 

Body Weight of 
Patient 

Initial Dose Subsequent Doses 
(every other week) 

less than 60 kg 400 mg (two 200 mg injections) 200 mg 
60 kg or more 600 mg (two 300 mg injections) 300 mg 

 
Recommended dose in children with atopic dermatitis 
The recommended dose of Dupixent for children (6 to 11 years of age) with atopic dermatitis is based 
on body weight: 
 

Body Weight of 
Patient 

Initial Dose Subsequent Doses 
 

 
 

 

15 kg to 
less than 60 kg 

300 mg (one 300 mg injection) on Day 1, 
followed by 300 mg on Day 15 

300 mg every 4 weeks*,  
starting 4 weeks after Day 15 dose 

60 kg or more 600 mg (two 300 mg injections) 300 mg every other week  

* The dose may be increased to 200 mg every other week based on the doctor’s opinion. 
 
Recommended dose in adult and adolescent patients with asthma (12 years of age and older) 
For patients with severe asthma and who are on oral corticosteroids or for patients with severe asthma 
and co-morbid moderate-to-severe atopic dermatitis or adults with co-morbid severe chronic 
rhinosinusitis with nasal polyposis, the recommended dose of Dupixent is: 
• An initial dose of 600 mg (two 300 mg injections) 
• Followed by 300 mg given every other week administered as subcutaneous injection. 

 
For all other patients with severe asthma, the recommended dose of Dupixent is: 
• An initial dose of 400 mg (two 200 mg injections) 
• Followed by 200 mg given every other week administered as subcutaneous injection. 

 
Recommended dose in adults with chronic rhinosinusitis with nasal polyposis (CRSwNP) 
In CRSwNP, the recommended first dose of Dupixent is 300 mg followed by 300 mg given every two 
weeks by subcutaneous injection. 
 
Injecting Dupixent 
Dupixent is given by injection under your skin (subcutaneous injection). You and your doctor or nurse 
should decide if you should inject Dupixent yourself. 
 
Before injecting Dupixent yourself you must have been properly trained by your doctor or nurse. Your 
Dupixent injection may also be given by a caregiver after proper training by a doctor or nurse. 
 
Each pre-filled syringe contains one dose of Dupixent (300 mg). Do not shake the pre-filled syringe. 
 
Read the “Instructions for Use” for the pre-filled syringe carefully before using Dupixent. 
 
If you use more Dupixent than you should  
If you use more Dupixent than you should or the dose has been given too early, talk to your doctor, 
pharmacist or nurse.  
 
If you forget to use Dupixent  
If you have forgotten to inject a dose of Dupixent, talk to your doctor, pharmacist or nurse. 
 
If you stop using Dupixent  
Do not stop using Dupixent without speaking to your doctor first.  
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 



107 

 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Dupixent can cause serious side effects, including very rare allergic (hypersensitivity) reactions, 
including anaphylactic reaction; the signs of allergic reaction or anaphylactic reaction may include: 

• breathing problems 
• swelling of the face, lips, mouth, throat or tongue (angioedema) 
• fainting, dizziness, feeling lightheaded (low blood pressure) 
• fever 
• general ill feeling 
• swollen lymph nodes 
• hives 
• itching 
• joint pain 
• skin rash 

 
If you develop an allergic reaction, stop using Dupixent and talk to your doctor right away. 
 
Other side effects 
Very Common (may affect more than 1 in 10 people) atopic dermatitis and asthma: 

• injection site reactions (i.e. redness, swelling, and itching) 
 
Common (may affect up to 1 in 10 people) atopic dermatitis only: 

• headache  
• eye dryness, redness and itching  
• eyelid itching, redness and swelling  
• eye infection 
• cold sores (on lips and skin) 

 
Uncommon (may affect up to 1 in 100 people):  

• inflammation of the eye surface, sometimes with blurred vision (keratitis, ulcerative keratitis) 
 
Not known 
The following side effects have been reported since the marketing of Dupixent, but how often they 
occur is not known: 

• joint pain (arthralgia) 
 

Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Dupixent 
 
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 label and carton after EXP. The 
expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C to 8°C). If necessary, pre-filled syringes may be kept at room temperature 
up to 25°C for a maximum of 14 days. Do not store above 25°C. If you need to permanently remove 

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


108 

the carton from the refrigerator, write down the date of removal in the space provided on the outer 
carton, and use Dupixent within 14 days. 
 
Store in the original carton to protect from light. 
 
Do not use this medicine if you notice that the medicine is cloudy, discoloured, or has particles in it. 
Do not throw away any medicines via wastewater or household waste. Ask your doctor, pharmacist or 
nurse how to throw away medicines you no longer use. These measures will help protect the 
environment. 
 
 
6. Contents of the pack and other information 
 
What Dupixent contains 
• The active substance is dupilumab. 
• Each pre-filled syringe contains 300 mg of dupilumab in 2 ml solution for injection (injection). 
• The other ingredients are arginine hydrochloride, histidine, polysorbate 80 (E433), sodium acetate, 

glacial acetic acid (E260), sucrose, water for injections. 
 
What Dupixent looks like and contents of the pack 
Dupixent is a clear to slightly opalescent, colourless to pale yellow solution supplied in a glass pre-
filled syringe with or without needle shield. 
 
Dupixent is available as 300 mg pre-filled syringes in a pack containing 1 or 2 pre-filled syringes or in 
a pack containing 3 (3 packs of 1) or 6 (3 packs of 2) pre-filled syringes.  
 
Not all pack sizes may be marketed.  
 
Marketing Authorisation Holder 
sanofi-aventis groupe 
54, rue La Boétie 
75008 Paris 
France 
 
Manufacturer 
SANOFI WINTHROP INDUSTRIE 
1051 Boulevard Industriel,  
76580 LE TRAIT, 
FRANCE 
 
Sanofi-Aventis Deutschland GmbH 
Brüningstrasse 50 
Industriepark Hoechst 
65926 FRANKFURT AM MAIN 
GERMANY 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB "SANOFI-AVENTIS LIETUVA"  
Tel: +370 5 2755224 
 

България 
SANOFI BULGARIA EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 



109 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
Sanofi A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi S.r.l. 
Tel: +39 02 39394275 

Deutschland 
Sanofi-Aventis Deutschland GmbH 
Tel.: 0800 04 36 996 
Tel. aus dem Ausland: +49 69 305 70 13 
 

Nederland 
Genzyme Europe B.V. 
Tel: + 31 20 245 4000 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
sanofi-aventis Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

España 
sanofi-aventis, S.A.  
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis france 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda 
Tel: +351 21 35 89 400 
 

Hrvatska  
sanofi-aventis Croatia d.o.o.  
Tel: +385 1 600 34 00 
 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

 
Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.r.l. 
Tel: 800 536389 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

  
This leaflet was last revised in  



110 

 
Detailed information on this medicine is available on the European Medicines Agency web site:  
http://www.ema.europa.eu 
 
 
<------------------------------------------------------------------------------------------------------------------------> 

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


111 

Dupixent 300 mg solution for injection in a pre-filled syringe with needle shield 
dupilumab 
 
Instructions for use 
 
The parts of the Dupixent pre-filled syringe with needle shield are shown in this picture.  
 

 

 
Important information 
This device is a single-use pre-filled syringe. It contains 300 mg of Dupixent for injection under the 
skin (subcutaneous injection). 
 
You must not try to give yourself or someone else the injection unless you have received training from 
your healthcare professional. In adolescents 12 years and older, it is recommended that Dupixent be 
administered by or under supervision of an adult. In children less than 12 years of age, Dupixent 
should be given by a caregiver. 
 

• Read all of the instructions carefully before using the syringe. 
• Check with your healthcare professional how often you will need to inject the medicine. 
• Ask your healthcare professional to show you the right way to use the syringe before you 

inject for the first time. 
•  Change the injection site for each injection. 
• Do not use the syringe if it has been dropped on a hard surface or damaged. 
• Do not use the syringe if the needle cap is missing or not securely attached. 
• Do not touch the plunger rod until you are ready to inject. 
• Do not inject through clothes. 
• Do not get rid of any air bubbles in the syringe.  
• To help prevent accidental needle injury, each pre-filled syringe has a needle shield that is 

automatically activated to cover the needle after you have given your injection. 
• Never pull back on the plunger rod. 
• Do not re-use the syringe. 

 
How to Store Dupixent 
 

• Keep the syringe(s) out of the reach of children. 
• Keep unused syringes in the original carton and store in the refrigerator between 2ºC and 8ºC. 



112 

• Do not keep Dupixent at room temperature (< 25ºC) for more than 14 days. If you need to 
permanently remove the carton from the refrigerator, write down the date of removal in the 
space provided on the outer carton, and use Dupixent within 14 days. 

• Do not shake the syringe at any time. 
• Do not heat the syringe. 
• Do not freeze the syringe. 
• Do not place the syringe into direct sunlight. 

 
Step 1: Remove 
 
Remove the syringe from the carton by holding the middle of the syringe body. 

Do not pull off the needle cap until you are ready to inject. 

Do not use the syringe if it has been dropped on a hard surface or damaged. 

 
 
Step 2: Prepare 
 
Ensure you have the following: 

• the Dupixent pre-filled syringe 
• 1 alcohol wipe* 
• 1 cotton ball or gauze* 
• a puncture-resistant container* (See Step 12) 

 
*Items not included in the carton 
 
Look at the label: 

• Check the expiry date. 
• Check that you have the correct product and dose. 

Do not use the syringe if the expiry date has passed. 

Do not keep Dupixent at room temperature for more than 14 days. 
 

 
 
Step 3: Inspect 



113 

 
Look at the medicine through the viewing window on the syringe: 
 
Check if the liquid is clear and colourless to pale yellow. 
 
Note: You may see an air bubble; this is normal. 
 

Do not use the syringe if the liquid is discoloured or cloudy, or if it contains flakes or 
particles. 

 
 
Step 4: Wait 45 minutes 
 
Lay the syringe on a flat surface for at least 45 minutes and let it get to room temperature naturally. 
 

Do not warm the syringe in a microwave, hot water, or direct sunlight. 

Do not place the syringe in direct sunlight. 

Do not keep Dupixent at room temperature for more than 14 days. 

 
 
 
Step 5: Choose 
 
Select the injection site. 

• You can inject into your thigh or belly (stomach), except for the 5 cm around your navel. 
• If somebody else gives you the injection, they can also use your upper arm. 
• Change the injection site for each injection. 



114 

 

Do not inject into skin that is tender, damaged or has bruises or scars. 
 

 
 
Step 6: Clean 
 
Wash your hands. 
 
Clean the injection site with an alcohol wipe. 
 
Let your skin dry before injecting. 
 

Do not touch the injection site again or blow on it before the injection. 
 

 
 
Step 7: Pull 
 
Hold the syringe in the middle of the syringe body with the needle pointing away from you and pull 
off the needle cap. 
 



115 

Do not put the needle cap back on. 

Do not touch the needle. 
 
Inject your medicine immediately after removing the needle cap. 
 

 
 
Step 8: Pinch 
 
Pinch a fold of skin at the injection site, as shown in the picture. 
 

 
 
Step 9: Insert 
 
Insert the Needle completely into the fold of skin at roughly a 45º angle. 



116 

 
 
Step 10: Push 
 
Relax the pinch. 
 
Push the plunger rod down slowly and steadily as far as it will go until the syringe is empty. 
 
Note: You will feel some resistance. This is normal. 
 

 

Step 11: Release and Remove  
 

Lift your thumb to release the plunger rod until the needle is covered by the needle shield and then 
remove the syringe from the injection site. 
Lightly press a cotton ball or gauze on the injection site if you see any blood. 
 

Do not put the needle cap back on. 

Do not rub your skin after the injection. 
 

 



117 

 
 
Step 12: Dispose 
 
Dispose of the syringe and the needle cap in a puncture-resistant container. 
 

Do not put the needle cap back on. 
 

Always keep the container out of the reach of children. 

 

 



118 

 Dupixent 300 mg solution for injection in a pre-filled syringe 
dupilumab 
 
Instructions for use 
 
The parts of the Dupixent pre-filled syringe are shown in this picture.  
 

 
Important information 
 
This device is a single-use pre-filled syringe. It contains 300 mg of Dupixent for injection under the 
skin (subcutaneous injection). 
You must not try to give yourself or someone else the injection unless you have received training from 
your healthcare professional. In adolescents 12 years and older, it is recommended that Dupixent be 
administered by or under supervision of an adult. In children less than 12 years of age, Dupixent 
should be given by a caregiver. 

• Read all of the instructions carefully before using the syringe. 
• Check with your healthcare professional how often you will need to inject the medicine. 
• Ask your healthcare professional to show you the right way to use the syringe before you 

inject for the first time. 
• Change the injection site for each injection. 
• Do not use the syringe if it has been damaged. 
• Do not use the syringe if the needle cap is missing or not securely attached. 
• Do not touch the plunger rod until you are ready to inject. 
• Do not inject through clothes. 
• Do not get rid of any air bubbles in the syringe. 
• Never pull back on the plunger rod. 
• Do not re-use the syringe. 

 
How to Store Dupixent 
 

• Keep the syringe(s) out of the reach of children. 
• Keep unused syringes in the original carton and store in the refrigerator between 2ºC and 8ºC. 
• Do not keep Dupixent at room temperature (< 25°C) for more than 14 days. If you need to 

permanently remove the carton from the refrigerator, write down the date of removal in the 
space provided on the outer carton, and use Dupixent within 14 days. 

• Do not shake the syringe at any time. 
• Do not heat the syringe. 



119 

• Do not freeze the syringe. 
• Do not place the syringe into direct sunlight. 

 
Step 1: Remove 
 
Remove the syringe from the carton by holding the middle of the syringe body. 

Do not pull off the needle cap until you are ready to inject. 

Do not use the syringe if it has been damaged. 
 

 

Step 2: Prepare 
 
Ensure you have the following: 

• the Dupixent pre-filled syringe 
• 1 alcohol wipe* 
• 1 cotton ball or gauze* 
• a puncture-resistant container* (See Step 12) 

 
*Items not included in the carton 
 
Look at the label: 

• Check the expiry date. 
• Check that you have the correct product and dose. 

Do not use the syringe if the expiry date has passed. 

Do not keep Dupixent at room temperature for more than 14 days. 
 

 
 
Step 3: Inspect 
 
Look at the medicine in the syringe: 
 



120 

Check if the liquid is clear and colourless to pale yellow. 
 
Note: You may see an air bubble; this is normal. 

Do not use the syringe if the liquid is discoloured or cloudy, or if it contains flakes or 
particles. 

 
 
Step 4: Wait 45 minutes 
 
Lay the syringe on a flat surface for at least 45 minutes and let it get to room temperature naturally. 

Do not warm the syringe in a microwave, hot water, or direct sunlight. 

Do not place the syringe in direct sunlight. 

Do not keep Dupixent at room temperature for more than 14 days. 
 

 
 
Step 5: Choose 
 
Select the injection site. 

• You can inject into your thigh or belly (stomach), except for the 5 cm around your navel. 
• If somebody else gives you the injection, they can also use your upper arm. 
• Change the injection site for each injection. 

Do not inject into skin that is tender, damaged or has bruises or scars. 
 



121 

 
 
Step 6: Clean 
 
Wash your hands. 
 
Clean the injection site with an alcohol wipe. 
 
Let your skin dry before injecting. 

 Do not touch the injection site again or blow on it before the injection. 

 
 
Step 7: Pull 
 
Hold the syringe in the middle of the syringe body with the needle pointing away from you and pull 
off the needle cap. 

Do not put the needle cap back on. 

Do not touch the needle. 
 
Inject your medicine immediately after removing the needle cap. 
 



122 

 
 
Step 8: Pinch 
 
Pinch a fold of skin at the injection site, as shown in the picture. 

 
 
Step 9: Insert 
 
Insert the needle into the fold of skin at roughly a 45º angle. 

 
 
Step 10: Push 
 
Relax the pinch. 



123 

 
Push the plunger rod down slowly and steadily as far as it will go until the syringe is empty. 
 
Note: You will feel some resistance. This is normal. 

 
 
Step 11: Remove 
 
Pull the needle out of the skin at the same angle it was inserted. 

Do not put the needle cap back on. 
 
Lightly press a cotton ball or gauze on the injection site if you see any blood. 

Do not rub your skin after the injection. 

 
 
Step 12: Dispose 
 
Dispose of the syringe and the needle cap in a puncture-resistant container. 

Do not put the needle cap back on. 
 
Always keep the container out of the reach of children. 

 



124 

 

 

 

 

 

 

 
 

 



125 

Package leaflet: Information for the user  
 

Dupixent 300 mg solution for injection in pre-filled pen  
 

dupilumab 
 

This medicine is subject to additional monitoring. This will allow quick identification of new 
safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- 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, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What Dupixent is and what it is used for 
2. What you need to know before you use Dupixent 
3. How to use Dupixent 
4. Possible side effects 
5. How to store Dupixent 
6. Contents of the pack and other information 
 
 
1. What Dupixent is and what it is used for 
 
What Dupixent is 
Dupixent contains the active substance dupilumab. 
 
Dupilumab is a monoclonal antibody (a type of specialised protein) that blocks the action of proteins 
called IL-4 and IL-13. Both play a major role in causing the signs and symptoms of atopic dermatitis, 
asthma and chronic rhinosinusitis with nasal polyposis (CRSwNP). 
 
What Dupixent is used for 
Dupixent is used to treat adults and adolescents 12 years and older with moderate-to-severe atopic 
dermatitis, also known as atopic eczema. Dupixent is also used to treat children 6 to 11 years old with 
severe atopic dermatitis (see section Children and adolescents). Dupixent may be used with eczema 
medicines that you apply to the skin or it may be used on its own.  
 
Dupixent is also used with other asthma medicines for the maintenance treatment of severe asthma in 
adults and adolescents (12 years of age and older) whose asthma is not controlled with their current 
asthma medicines. 
 
Dupixent is also used with other medicines for the maintenance treatment of CRSwNP in adults whose 
disease is not controlled with their current CRSwNP medicines. Dupixent can also reduce the need for 
surgery and the need for systemic corticosteroid use. 
 
How Dupixent works 
Using Dupixent for atopic dermatitis (atopic eczema) can improve the condition of your skin and 
reduce itching. Dupixent has also been shown to improve symptoms of pain, anxiety, and depression 
associated with atopic dermatitis. In addition, Dupixent helps improve your sleep disturbance and 
overall quality of life. 
 



126 

Dupixent helps prevent severe asthma attacks (exacerbations) and can improve your breathing. 
Dupixent may also help reduce the amount of another group of medicines you need to control your 
asthma, called oral corticosteroids, while preventing severe asthma attacks and improving your 
breathing. 
 
 
2. What you need to know before you use Dupixent 
 
Do not use Dupixent  
• if you are allergic to dupilumab or any of the other ingredients of this medicine (listed in 

section 6). 
• if you think you may be allergic, or you are not sure, ask your doctor, pharmacist or nurse for 

advice before using Dupixent. 
 
Warnings and precautions  
Talk to your doctor, pharmacist or nurse before using Dupixent: 
 
Dupixent is not a rescue medicine and should not be used to treat a sudden asthma attack. 
 
Allergic reactions 
• Very rarely, Dupixent can cause serious side effects, including allergic (hypersensitivity) reactions 

and anaphylactic reaction and angioedema. These reactions can occur from minutes until seven 
days after Dupixent administration. You must look out for signs of these conditions (i.e. breathing 
problems, swelling of the face, lips, mouth, throat or tongue, fainting, dizziness, feeling 
lightheaded (low blood pressure), fever, general ill feeling, swollen lymph nodes, hives, itching, 
joint pain, skin rash) while you are taking Dupixent. Such signs are listed under “Serious side 
effects” in section 4. 

• Stop using Dupixent and tell your doctor or get medical help immediately if you notice any signs 
of an allergic reaction.  
 

Eosinophilic conditions 
• Rarely patients taking an asthma medicine may develop inflammation of blood vessels or lungs 

due to an increase of certain white blood cells (eosinophilia). 
• It is not known whether this is caused by Dupixent. This usually, but not always, happens in 

people who also take a steroid medicine which is being stopped or for which the dose is being 
lowered. 

• Tell your doctor immediately if you develop a combination of symptoms such as a flu-like illness, 
pins and needles or numbness of arms or legs, worsening of pulmonary symptoms, and/or rash. 
 

Parasitic (intestinal parasites) infection 
• Dupixent may weaken your resistance to infections caused by parasites. If you already have a 

parasitic infection it should be treated before you start treatment with Dupixent. 
• Check with your doctor if you have diarrhoea, gas, upset stomach, greasy stools, and dehydration 

which could be a sign of a parasitic infection. 
• If you live in a region where these infections are common or if you are travelling to such a region 

check with your doctor. 
 
Asthma 
If you have asthma and are taking asthma medicines, do not change or stop your asthma medicine 
without talking to your doctor. Talk to your doctor before you stop Dupixent or if your asthma remains 
uncontrolled or worsens during treatment with this medicine. 
 
Eye problems 
Talk to your doctor if you have any new or worsening eye problems, including eye pain or changes in 
vision. 
 



127 

Children and adolescents 
• The Dupixent pre-filled pen is not intended for use in children below 12 years of age. For 

children aged 6-11 years with atopic dermatitis, contact your doctor who will prescribe the 
appropriate Dupixent pre-filled syringe. 

• The safety and benefits of Dupixent are not yet known in children with atopic dermatitis below the 
age of 6. 

• The safety and benefits of Dupixent are not yet known in children with asthma below the age of 
12. 

• CRSwNP does not normally occur in children. The safety and benefits of Dupixent are not yet 
known in children with CRSwNP below the age of 18 years. 

 
Other medicines and Dupixent 
Tell your doctor or pharmacist  
• if you are using, have recently used or might use any other medicines. 
• if you have recently had or are due to have a vaccination. 
 
Other medicines for asthma 
Do not stop or reduce your asthma medicines, unless instructed by your doctor. 
• These medicines (especially ones called corticosteroids) must be stopped gradually. 
• This must be done under the direct supervision of your doctor and dependent on your response to 

Dupixent. 
 
Pregnancy and breast-feeding 
• If you are pregnant, think you may be pregnant, or are planning to have a baby, ask your doctor for 

advice before using this medicine. The effects of this medicine in pregnant women are not known; 
therefore it is preferable to avoid the use of Dupixent in pregnancy unless your doctor advises to 
use it. 

• If you are breast-feeding or are planning to breast-feed, talk to your doctor before using this 
medicine. You and your doctor should decide if you will breast-feed or use Dupixent. You should 
not do both. 

 
Driving and using machines  
Dupixent is unlikely to influence your ability to drive and use machines. 
 
Dupixent contains sodium  
This medicine contains less than 1 mmol sodium (23 mg) per 300 mg dose, i.e., it is essentially 
“sodium-free”. 
 
 
3. How to use Dupixent 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or 
pharmacist if you are not sure. 
 
How Dupixent is given 
Dupixent is given by injection under the skin (subcutaneous injection). 
 
How much Dupixent you will receive 
Your doctor will decide which dose of Dupixent is right for you. 
 
Recommended dose in adults with atopic dermatitis 
For patients with atopic dermatitis, the recommended dose of Dupixent is: 
• An initial dose of 600 mg (two 300 mg injections) 
• Followed by 300 mg given every other week by subcutaneous injection. 
 
Recommended dose in adolescents with atopic dermatitis 



128 

The recommended dose of Dupixent for adolescents (12 to 17 years of age) with atopic dermatitis is 
based on body weight: 
 

Body Weight of 
Patient 

Initial Dose Subsequent Doses 
(every other week) 

less than 60 kg 400 mg (two 200 mg injections) 200 mg 
60 kg or more 600 mg (two 300 mg injections) 300 mg 

 
Recommended dose in children with atopic dermatitis 
The recommended dose of Dupixent for children (6 to 11 years of age) with atopic dermatitis is based 
on body weight: 
 

Body Weight of 
Patient 

Initial Dose Subsequent Doses 
 

 
 

 

15 kg to 
less than 60 kg 

300 mg (one 300 mg injection) on Day 1, 
followed by 300 mg on Day 15 

300 mg every 4 weeks*,  
starting 4 weeks after Day 15 dose 

60 kg or more 600 mg (two 300 mg injections) 300 mg every other week  

* The dose may be increased to 200 mg every other week based on the doctor’s opinion. 
 
Recommended dose in adult and adolescent patients with asthma (12 years of age and older) 
For patients with severe asthma and who are on oral corticosteroids or for patients with severe asthma 
and co-morbid moderate-to-severe atopic dermatitis or adults with co-morbid severe chronic 
rhinosinusitis with nasal polyposis, the recommended dose of Dupixent is: 
• An initial dose of 600 mg (two 300 mg injections) 
• Followed by 300 mg given every other week administered as subcutaneous injection. 
 
For all other patients with severe asthma, the recommended dose of Dupixent is: 
• An initial dose of 400 mg (two 200 mg injections) 
• Followed by 200 mg given every other week administered as subcutaneous injection. 
 
Recommended dose in adults with chronic rhinosinusitis with nasal polyposis (CRSwNP) 
In CRSwNP, the recommended first dose of Dupixent is 300 mg followed by 300 mg given every two 
weeks by subcutaneous injection. 
 
Injecting Dupixent 
Dupixent is given by injection under your skin (subcutaneous injection). You and your doctor or nurse 
should decide if you should inject Dupixent yourself. 
 
Before injecting Dupixent yourself you must have been properly trained by your doctor or nurse. Your 
Dupixent injection may also be given by a caregiver after proper training by a doctor or nurse. 
 
Each pre-filled pen contains one dose of Dupixent (300 mg). Do not shake the pre-filled pen. 
 
Read the “Instructions for Use” for the pre-filled pen carefully before using Dupixent. 
 
If you use more Dupixent than you should  
If you use more Dupixent than you should or the dose has been given too early, talk to your doctor, 
pharmacist or nurse.  
 
If you forget to use Dupixent  
If you have forgotten to inject a dose of Dupixent, talk to your doctor, pharmacist or nurse. 
 
If you stop using Dupixent  



129 

Do not stop using Dupixent without speaking to your doctor first.  
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Dupixent can cause serious side effects, including very rare allergic (hypersensitivity) reactions, 
including anaphylactic reaction; the signs of allergic reaction or anaphylactic reaction may include: 

• breathing problems 
• swelling of the face, lips, mouth, throat or tongue (angioedema) 
• fainting, dizziness, feeling lightheaded (low blood pressure) 
• fever 
• general ill feeling 
• swollen lymph nodes 
• hives 
• itching 
• joint pain 
• skin rash 

 
If you develop an allergic reaction, stop using Dupixent and talk to your doctor right away. 
 
Other side effects 
Very Common (may affect more than 1 in 10 people) atopic dermatitis and asthma: 

• injection site reactions (i.e. redness, swelling, and itching) 
 
Common (may affect up to 1 in 10 people) atopic dermatitis only: 

• headache 
• eye dryness, redness and itching  
• eyelid itching, redness and swelling  
• eye infection 
• cold sores (on lips and skin) 

 
Uncommon (may affect up to 1 in 100 people):  

• inflammation of the eye surface, sometimes with blurred vision (keratitis, ulcerative keratitis) 
 
Not known 
The following side effects have been reported since the marketing of Dupixent, but how often they 
occur is not known: 

• joint pain (arthralgia) 
 

Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Dupixent 
 
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 label and carton after EXP. The 
expiry date refers to the last day of that month. 

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


130 

 
Store in a refrigerator (2°C to 8°C). If necessary, pre-filled pens may be kept at room temperature up 
to 25°C for a maximum of 14 days. Do not store above 25°C. If you need to permanently remove the 
carton from the refrigerator, write down the date of removal in the space provided on the outer carton, 
and use Dupixent within 14 days. 
 
Store in the original carton to protect from light. 
 
Do not use this medicine if you notice that the medicine is cloudy, discoloured, or has particles in it. 
Do not throw away any medicines via wastewater or household waste. Ask your doctor, pharmacist or 
nurse how to throw away medicines you no longer use. These measures will help protect the 
environment. 
 
 
6. Contents of the pack and other information 
 
What Dupixent contains 
• The active substance is dupilumab. 
• Each pre-filled pen contains 300 mg of dupilumab in 2 ml solution for injection (injection). 
• The other ingredients are arginine hydrochloride, histidine, polysorbate 80 (E433), sodium acetate, 

glacial acetic acid (E260), sucrose, water for injections. 
 
What Dupixent looks like and contents of the pack 
Dupixent is a clear to slightly opalescent, colourless to pale yellow solution supplied in a pre-filled 
pen. 
 
Dupixent is available as 300 mg pre-filled pens in a pack containing 1, 2, 3, or 6 pre-filled pens.  
 
Not all pack sizes may be marketed.  
 
Marketing Authorisation Holder 
sanofi-aventis groupe 
54, rue La Boétie 
75008 Paris 
France 
 
Manufacturer 
SANOFI WINTHROP INDUSTRIE 
1051 Boulevard Industriel,  
76580 LE TRAIT, 
FRANCE 
 
Sanofi-Aventis Deutschland GmbH 
Brüningstrasse 50 
Industriepark Hoechst 
65926 FRANKFURT AM MAIN 
GERMANY 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB "SANOFI-AVENTIS LIETUVA"  
Tel: +370 5 2755224 
 

България 
SANOFI BULGARIA EOOD 

Luxembourg/Luxemburg 
Sanofi Belgium  



131 

Тел.: +359 (0)2 970 53 00 
 

Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
Sanofi A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi S.r.l. 
Tel: +39 02 39394275 
 

Deutschland 
Sanofi-Aventis Deutschland GmbH 
Tel.: 0800 04 36 996 
Tel. aus dem Ausland: +49 69 305 70 13 
 

Nederland 
Genzyme Europe B.V. 
Tel: +31 20 245 4000 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
sanofi-aventis Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

España 
sanofi-aventis, S.A.  
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis france 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda 
Tel: +351 21 35 89 400 
 

Hrvatska  
sanofi-aventis Croatia d.o.o.  
Tel: +385 1 600 34 00 
 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

 
Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.r.l. 
Tel: 800 536389 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 



132 

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

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


133 

Dupixent 300 mg solution for injection in a pre-filled pen 
Dupilumab 
 
Instructions for use 
 
The parts of the Dupixent pre-filled pen are shown in this picture.  
 

 

Important information 
This device is a single-use pre-filled pen. It contains 300 mg of Dupixent for injection under the skin 
(subcutaneous injection). 
 
You must not try to give yourself or someone else the injection unless you have received training from 
your healthcare professional. In adolescents 12 years and older, it is recommended that Dupixent be 
administered by or under supervision of an adult. The Dupixent pre-filled pen is only for use in adults 
and children aged 12 years and older. 
 

• Read all of the instructions carefully before using the pre-filled pen. 
• Ask your healthcare professional how often you will need to inject the medicine. 
• Choose a different injection site for each injection 
• Do not use the pre-filled pen if it has been damaged. 
• Do not use the pre-filled pen if the green cap is missing or not securely attached. 
• Do not press or touch the yellow needle cover with your fingers. 
• Do not inject through clothes. 
• Do not remove the green cap until just before you give the injection.  
• Do not try to put the green cap back on the pre-filled pen. 
• Do not re-use the pre-filled pen. 

 
How to Store Dupixent 
 

• Keep the pre-filled pen(s) and all medicines out of the reach of children. 
• Keep unused pre-filled pens in the original carton and store in the refrigerator between 2ºC 

and 8ºC. 
• Store pre-filled pens in the original carton to protect it from light. 
• Do not keep pre-filled pens at room temperature (<25ºC) for more than 14 days. If you need to 

permanently remove the carton from the refrigerator, write down the date of removal in the 
space provided on the outer carton, and use Dupixent within 14 days. 

• Do not shake the pre-filled pen at any time. 
• Do not heat the pre-filled pen. 
• Do not freeze the pre-filled pen. 
• Do not place the pre-filled pen into direct sunlight. 

 
 

A: Prepare 
A1. Gather supplies 



134 

 
Ensure you have the following: 

• the Dupixent pre-filled pen 
• 1 alcohol wipe* 
• 1 cotton ball or gauze* 
• a puncture-resistant container* (See Step D) 

 
*Items not included in the carton 
 
A2. Look at the label  
 

• Confirm that you have the correct product and dose. 
 

 
 
A3. Check expiration date 
 

• Check the expiration date.  
 

Do not use the pre-filled pen if the expiration date has passed. 

Do not keep Dupixent at room temperature for more than 14 days. 
 

 
 
 
A4. Check the medicine 
 
Look at the medicine through the window on the pre-filled pen. 
 
Check if the liquid is clear and colourless to pale yellow. 
 
Note: You may see an air bubble; this is normal. 

Do not use the pre-filled pen if the liquid is discolored or cloudy, or if it contains visible 
flakes or particles. 

Do not use the pre-filled pen if the window is yellow. 



135 

 
 
A5: Wait 45 minutes 
 
Lay the pre-filled pen on a flat surface and let it naturally warm up at room temperature (less than 
25ºC) for at least 45 minutes. 
 

Do not warm the pre-filled pen in a microwave, hot water, or direct sunlight. 

Do not put the pre-filled pen into direct sunlight. 

Do not keep Dupixent at room temperature for more than 14 days. 
 

 
 
B. Choose your injection site 
B1. Recommended injection sites are: 
 

• Thigh 
• Stomach except for the 5 cm around your belly button (navel). 
• Upper Arm If a caregiver gives your dose, they can also use the outer area of the upper arm. 

 
Choose a different injection site for each Dupixent injection. 

Do not inject through clothes. 

Do not inject into skin that is tender, damaged, bruised or scarred. 
 



136 

 
 
 
B2. Wash your hands 
 

 
 
B3. Prepare the injection site 
 

• Clean the injection site with an alcohol wipe. 

• Let your skin dry before injecting. 

Do not touch the injection site again or blow on it before the injection. 
 

 
 
C. Give injection 
C1. Remove green cap 
 
Pull the green cap straight off 
 
Do not twist the green cap off. 
 
Do not remove the green cap until you are ready to inject. 
 
Do not press or touch the yellow needle cover with your fingers. The needle is inside. 
 

Do not put the green cap back on the pre-filled pen after you have removed it. 



137 

 

 
 
C2. Place 
 

• When placing the yellow needle cover on your skin, hold the pre-filled pen so that you can see 
the window.  

 
• Place the yellow needle cover on your skin at approximately a 90-degree angle. 

 

Do not press or touch the yellow needle cover with your fingers. The needle is inside. 
 

 
 
C3. Press down 
 
 
Press the pre-filled pen firmly against your skin until you cannot see the yellow needle cover, and 
hold. 
 

• There will be a “click” when the injection starts. 

• The window will start to turn yellow. 
 
The injection can take up to 20 seconds. 
 



138 

 
 

 
C4. Hold firmly  
 
Keep holding the pre-filled pen firmly against your skin. 

 
• You may hear a second click. 
• Check that the entire window has turned to yellow. 
• Then slowly count to 5. 
• Then lift the pen up off the skin, your injection is complete. 

 
If the window does not turn completely yellow, remove the pen and call your healthcare provider. 
 

Do not give yourself a second dose without speaking to your healthcare provider. 
 

 
 
C5. Remove 
 

• After you have completed your injection pull straight up to remove pre-filled pen from the skin 
and dispose of immediately as described in section D. 
 

• If you see any blood at the site, lightly dab a cotton ball or gauze pad. 

Do not rub your skin after the injection. 
 



139 

 
 
 
 
D. Dispose 
 

• Dispose of the pre-filled pens, (needle inside), and green caps in a puncture resistant container 
right away after use. 

Do not dispose of (throw away) pre-filled pens (needle inside), and green caps in your household 
trash. 
 

Do not put the green cap back on. 
 
 

 
  



140 

 
Package leaflet: Information for the user  

 
Dupixent 200 mg solution for injection in pre-filled syringe  

dupilumab 
 

This medicine is subject to additional monitoring. This will allow quick identification of new 
safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- 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, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What Dupixent is and what it is used for 
2. What you need to know before you use Dupixent 
3. How to use Dupixent 
4. Possible side effects 
5. How to store Dupixent 
6. Contents of the pack and other information 
 
 
1. What Dupixent is and what it is used for 
 
What Dupixent is 
Dupixent contains the active substance dupilumab. 
 
Dupilumab is a monoclonal antibody (a type of specialised protein) that blocks the action of proteins 
called IL-4 and IL-13. Both play a major role in causing the signs and symptoms of asthma. 
 
What Dupixent is used for 
Dupixent is used to treat adults and adolescents 12 years and older with moderate-to-severe atopic 
dermatitis, also known as atopic eczema. Dupixent is also used to treat children 6 to 11 years old with 
severe atopic dermatitis. Dupixent may be used with eczema medicines that you apply to the skin or it 
may be used on its own.  
 
Dupixent is used with other asthma medicines for the maintenance treatment of severe asthma in adults 
and adolescents (12 years of age and older) whose asthma is not controlled with their current asthma 
medicines. 
 
How Dupixent works 
Using Dupixent for atopic dermatitis (atopic eczema) can improve the condition of your skin and 
reduce itching. Dupixent has also been shown to improve symptoms of pain, anxiety, and depression 
associated with atopic dermatitis. In addition, Dupixent helps improve your sleep disturbance and 
overall quality of life. 
 
Dupixent helps prevent severe asthma attacks (exacerbations) and can improve your breathing. 
Dupixent may also help reduce the amount of another group of medicines you need to control your 
asthma, called oral corticosteroids, while preventing severe asthma attacks and improving your 
breathing. 
 



141 

 
2. What you need to know before you use Dupixent 
 
Do not use Dupixent  
• if you are allergic to dupilumab or any of the other ingredients of this medicine (listed in 

section 6). 
• if you think you may be allergic, or you are not sure, ask your doctor, pharmacist or nurse for 

advice before using Dupixent. 
 
Warnings and precautions  
Talk to your doctor, pharmacist or nurse before using Dupixent: 
 
Dupixent is not a rescue medicine and should not be used to treat a sudden asthma attack. 
 
Allergic reactions 
• Very rarely, Dupixent can cause serious side effects, including allergic (hypersensitivity) reactions 

and anaphylactic reaction and angioedema. These reactions can occur from minutes until seven 
days after Dupixent administration. You must look out for signs of these conditions (i.e. breathing 
problems, swelling of the face, lips, mouth, throat or tongue, fainting, dizziness, feeling 
lightheaded (low blood pressure), fever, general ill feeling, swollen lymph nodes, hives, itching, 
joint pain, skin rash) while you are taking Dupixent. Such signs are listed under “Serious side 
effects” in section 4. 

• Stop using Dupixent and tell your doctor or get medical help immediately if you notice any signs 
of an allergic reaction. 

 
Eosinophilic conditions 
• Rarely patients taking an asthma medicine may develop inflammation of blood vessels or lungs 

due to an increase of certain white blood cells (eosinophilia). 
• It is not known whether this is caused by Dupixent. This usually, but not always, happens in 

people who also take a steroid medicine which is being stopped or for which the dose is being 
lowered. 

• Tell your doctor immediately if you develop a combination of symptoms such as a flu-like illness, 
pins and needles or numbness of arms or legs, worsening of pulmonary symptoms, and/or rash. 

 
Parasitic (intestinal parasites) infection 
• Dupixent may weaken your resistance to infections caused by parasites. If you already have a 

parasitic infection it should be treated before you start treatment with Dupixent. 
• Check with your doctor if you have diarrhoea, gas, upset stomach, greasy stools, and dehydration 

which could be a sign of a parasitic infection. 
• If you live in a region where these infections are common or if you are travelling to such a region 

check with your doctor. 
 
Asthma 
If you have asthma and are taking asthma medicines, do not change or stop your asthma medicine 
without talking to your doctor. Talk to your doctor before you stop Dupixent or if your asthma remains 
uncontrolled or worsens during treatment with this medicine. 
 
Eye problems 
Talk to your doctor if you have any new or worsening eye problems, including eye pain or changes in 
vision. 
 
Children and adolescents 
• The safety and benefits of Dupixent are not yet known in children with atopic dermatitis below the 

age of 6. 
• The safety and benefits of Dupixent are not yet known in children with asthma below the age of 

12. 
 



142 

Other medicines and Dupixent 
Tell your doctor or pharmacist  
• if you are using, have recently used or might use any other medicines. 
• if you have recently had or are due to have a vaccination. 

 
Other medicines for asthma 
Do not stop or reduce your asthma medicines, unless instructed by your doctor. 
• These medicines (especially ones called corticosteroids) must be stopped gradually. 
• This must be done under the direct supervision of your doctor and dependent on your response to 

Dupixent. 
 
Pregnancy and breast-feeding  
• If you are pregnant, think you may be pregnant, or are planning to have a baby, ask your doctor for 

advice before using this medicine. The effects of this medicine in pregnant women are not known; 
therefore it is preferable to avoid the use of Dupixent in pregnancy unless your doctor advises to 
use it. 

• If you are breast-feeding or are planning to breast-feed, talk to your doctor before using this 
medicine. You and your doctor should decide if you will breast-feed or use Dupixent. You should 
not do both. 

 
Driving and using machines  
Dupixent is unlikely to influence your ability to drive and use machines. 
 
Dupixent contains sodium  
This medicine contains less than 1 mmol sodium (23 mg) per 200 mg dose, i.e., it is essentially 
“sodium-free”. 
 
 
3. How to use Dupixent 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or 
pharmacist if you are not sure. 
 
How Dupixent is given 
Dupixent is given by injection under the skin (subcutaneous injection). 
 
How much Dupixent you will receive 
Your doctor will decide which dose of Dupixent is right for you. 
 
Recommended dose in adolescents with atopic dermatitis 
The recommended dose of Dupixent for adolescents (12 to 17 years of age) with atopic dermatitis is 
based on body weight: 
 

Body Weight of 
Patient 

Initial Dose Subsequent Doses 
(every other week) 

less than 60 kg 400 mg (two 200 mg injections) 200 mg 
60 kg or more 600 mg (two 300 mg injections) 300 mg 

 
Recommended dose in children with atopic dermatitis 
The recommended dose of Dupixent for children (6 to 11 years of age) with atopic dermatitis is based 
on body weight: 
  



143 

 
Body Weight of 

Patient 
Initial Dose Subsequent Doses 

 
 
 

 

15 kg to 
less than 60 kg 

300 mg (one 300 mg injection) on Day 1, 
followed by 300 mg on Day 15 

300 mg every 4 weeks*,  
starting 4 weeks after Day 15 dose 

60 kg or more 600 mg (two 300 mg injections) 300 mg every other week  

* The dose may be increased to 200 mg every other week based on the doctor’s opinion. 
 
Recommended dose in adult and adolescent patients with asthma (12 years of age and older) 
For most patients with severe asthma, the recommended dose of Dupixent is: 
• An initial dose of 400 mg (two 200 mg injections) 
• Followed by 200 mg given every other week administered as subcutaneous injection. 
 
For patients with severe asthma and who are on oral corticosteroids or for patients with severe asthma 
and co-morbid moderate-to-severe atopic dermatitis or adults with co-morbid severe chronic 
rhinosinusitis with nasal polyposis, the recommended dose of Dupixent is: 
• An initial dose of 600 mg (two 300 mg injections) 
• Followed by 300 mg given every other week administered as subcutaneous injection. 

 
Injecting Dupixent 
Dupixent is given by injection under your skin (subcutaneous injection). You and your doctor or nurse 
should decide if you should inject Dupixent yourself. 
 
Before injecting Dupixent yourself you must have been properly trained by your doctor or nurse. Your 
Dupixent injection may also be given by a caregiver after proper training by a doctor or nurse. 
 
Each pre-filled syringe contains one dose of Dupixent (200 mg). Do not shake the pre-filled syringe. 
 
Read the “Instructions for Use” for the pre-filled syringe carefully before using Dupixent. 
 
If you use more Dupixent than you should  
If you use more Dupixent than you should or the dose has been given too early, talk to your doctor, 
pharmacist or nurse.  
 
If you forget to use Dupixent  
If you have forgotten to inject a dose of Dupixent, talk to your doctor, pharmacist or nurse. 
 
If you stop using Dupixent  
Do not stop using Dupixent without speaking to your doctor first.  
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Dupixent can cause serious side effects, including very rare allergic (hypersensitivity) reactions, 
including anaphylactic reaction; the signs of allergic reaction or anaphylactic reaction may include: 

• breathing problems 
• swelling of the face, lips, mouth, throat or tongue (angioedema) 
• fainting, dizziness, feeling lightheaded (low blood pressure) 
• fever 



144 

• general ill feeling 
• swollen lymph nodes 
• hives 
• itching 
• joint pain 
• skin rash 

 
If you develop an allergic reaction, stop using Dupixent and talk to your doctor right away. 
 
Other side effects 
Very Common (may affect more than 1 in 10 people) atopic dermatitis and asthma: 

• injection site reactions (i.e. redness, swelling, and itching) 
 
Common (may affect up to 1 in 10 people) atopic dermatitis only: 

• headache 
• eye dryness, redness and itching  
• eyelid itching, redness and swelling  
• eye infection 
• cold sores (on lips and skin) 

 
Uncommon (may affect up to 1 in 100 people):  

• inflammation of the eye surface, sometimes with blurred vision (keratitis, ulcerative keratitis) 
 
Not known 
The following side effects have been reported since the marketing of Dupixent, but how often they 
occur is not known: 

• joint pain (arthralgia) 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Dupixent 
 
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 label and carton after EXP. The 
expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C to 8°C). If necessary, pre-filled syringes may be kept at room temperature 
up to 25°C for a maximum of 14 days. Do not store above 25°C. If you need to permanently remove 
the carton from the refrigerator, write down the date of removal in the space provided on the outer 
carton, and use Dupixent within 14 days. 
 
Store in the original carton to protect from light. 
 
Do not use this medicine if you notice that the medicine is cloudy, discoloured, or has particles in it. 
Do not throw away any medicines via wastewater or household waste. Ask your doctor, pharmacist or 
nurse how to throw away medicines you no longer use. These measures will help protect the 
environment. 
 
 

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


145 

6. Contents of the pack and other information 
 
What Dupixent contains 
• The active substance is dupilumab. 
• Each pre-filled syringe contains 200 mg of dupilumab in 1.14 ml solution for injection (injection). 
• The other ingredients are arginine hydrochloride, histidine, polysorbate 80 (E433), sodium acetate, 

glacial acetic acid (E260), sucrose, water for injections. 
 
What Dupixent looks like and contents of the pack 
Dupixent is a clear to slightly opalescent, colourless to pale yellow solution supplied in a glass pre-
filled syringe. 
 
Dupixent is available as 200 mg pre-filled syringes in a pack containing 1 or 2 pre-filled syringes or in 
a pack containing 3 (3 packs of 1) or 6 (3 packs of 2) pre-filled syringes.  
 
Not all pack sizes may be marketed.  
 
Marketing Authorisation Holder 
sanofi-aventis groupe 
54, rue La Boétie 
75008 Paris 
France 
 
Manufacturer 
SANOFI WINTHROP INDUSTRIE 
1051 Boulevard Industriel,  
76580 LE TRAIT, 
FRANCE 
 
Sanofi-Aventis Deutschland GmbH 
Brüningstrasse 50 
Industriepark Hoechst 
65926 FRANKFURT AM MAIN 
GERMANY 
 



146 

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB "SANOFI-AVENTIS LIETUVA"  
Tel: +370 5 2755224 
 

България 
SANOFI BULGARIA EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
Sanofi A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi S.r.l. 
Tel: +39 02 39394275 
 

Deutschland 
Sanofi-Aventis Deutschland GmbH 
Tel.: 0800 04 36 996 
Tel. aus dem Ausland: +49 69 305 70 13 
 

Nederland 
Genzyme Europe B.V. 
Tel: + 31 20 245 4000 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
sanofi-aventis Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

España 
sanofi-aventis, S.A.  
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis france 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda 
Tel: +351 21 35 89 400 
 

Hrvatska  
sanofi-aventis Croatia d.o.o.  
Tel: +385 1 600 34 00 
 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.r.l. 
Tel: 800 536389 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 



147 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

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

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


148 

Dupixent 200 mg solution for injection in a pre-filled syringe with needle shield 
dupilumab 
 
Instructions for use 
 
The parts of the Dupixent pre-filled syringe with needle shield are shown in this picture.  
 

 

Important information 
This device is a single-use pre-filled syringe. It contains 200 mg of Dupixent for injection under the 
skin (subcutaneous injection). 
 
You must not try to give yourself or someone else the injection unless you have received training from 
your healthcare professional. In adolescents 12 years and older, it is recommended that Dupixent be 
administered by or under supervision of an adult. In children less than 12 years of age, Dupixent 
should be given by a caregiver. 
 

• Read all of the instructions carefully before using the syringe. 
• Check with your healthcare professional how often you will need to inject the medicine. 
• Ask your healthcare professional to show you the right way to use the syringe before you 

inject for the first time. 
• Change the injection site for each injection. 
• Do not use the syringe if it has been dropped on a hard surface or damaged. 
• Do not use the syringe if the needle cap is missing or not securely attached. 
• Do not touch the plunger rod until you are ready to inject. 
• Do not inject through clothes. 
• Do not get rid of any air bubbles in the syringe.  
• To help prevent accidental needle injury, each pre-filled syringe has a needle shield that is 

automatically activated to cover the needle after you have given your injection. 
• Never pull back on the plunger rod. 
• Do not re-use the syringe. 

 
How to Store Dupixent 
 

• Keep the syringe(s) out of the reach of children. 



149 

• Keep unused syringes in the original carton and store in the refrigerator between 2ºC and 8ºC. 
• Do not keep Dupixent at room temperature (< 25ºC) for more than 14 days. If you need to 

permanently remove the carton from the refrigerator, write down the date of removal in the 
space provided on the outer carton, and use Dupixent within 14 days. 

• Do not shake the syringe at any time. 
• Do not heat the syringe. 
• Do not freeze the syringe. 
• Do not place the syringe into direct sunlight. 

 
Step 1: Remove 
 
Remove the syringe from the carton by holding the middle of the syringe body. 

Do not pull off the needle cap until you are ready to inject. 

Do not use the syringe if it has been dropped on a hard surface or damaged. 

 
 
Step 2: Prepare 
 
Ensure you have the following: 

• the Dupixent pre-filled syringe 
• 1 alcohol wipe* 
• 1 cotton ball or gauze* 
• a puncture-resistant container* (See Step 12) 

 
*Items not included in the carton 
 
Look at the label: 

• Check the expiry date. 
• Check that you have the correct product and dose. 

Do not use the syringe if the expiry date has passed. 

Do not keep Dupixent at room temperature for more than 14 days. 
 

 



150 

 
Step 3: Inspect 
 
Look at the medicine through the viewing window on the syringe: 
 
Check if the liquid is clear and colourless to pale yellow. 
 
Note: You may see an air bubble; this is normal. 
 

Do not use the syringe if the liquid is discoloured or cloudy, or if it contains flakes or 
particles. 

 

 
 
 
Step 4: Wait 30 minutes 
 
Lay the syringe on a flat surface for at least 30 minutes and let it get to room temperature naturally. 
 

Do not warm the syringe in a microwave, hot water, or direct sunlight. 

Do not place the syringe in direct sunlight. 

Do not keep Dupixent at room temperature for more than 14 days. 
 

 
 
Step 5: Choose 
 
Select the injection site. 

• You can inject into your thigh or belly (stomach), except for the 5 cm around your navel. 
• If somebody else gives you the injection, they can also use your upper arm. 
• Change the injection site for each injection. 



151 

 

Do not inject into skin that is tender, damaged or has bruises or scars. 
 

 
 
Step 6: Clean 
 
Wash your hands. 
 
Clean the injection site with an alcohol wipe. 
 
Let your skin dry before injecting. 
 

Do not touch the injection site again or blow on it before the injection. 
 

 
 
Step 7: Pull 
 
Hold the syringe in the middle of the syringe body with the needle pointing away from you and pull 
off the needle cap. 
 



152 

Do not put the needle cap back on. 

Do not touch the needle. 
 
Inject your medicine immediately after removing the needle cap. 
 

 
 
Step 8: Pinch 
 
Pinch a fold of skin at the injection site, as shown in the picture. 
 

 
Step 9: Insert 
 
Insert the Needle completely into the fold of skin at roughly a 45º angle. 
 

 



153 

 
Step 10: Push 
 
Relax the pinch. 
 
Push the plunger rod down slowly and steadily as far as it will go until the syringe is empty. 
 
Note: You will feel some resistance. This is normal. 
 

 

Step 11: Release and Remove 
 

Lift your thumb to release the plunger rod until the needle is covered by the needle shield and then 
remove the syringe from the injection site. 
 

Lightly press a cotton ball or gauze on the injection site if you see any blood. 

 

Do not put the needle cap back on. 

Do not rub your skin after the injection. 
 

 
 
Step 12: Dispose 



154 

 
Dispose of the syringe and the needle cap in a puncture-resistant container. 
 

Do not put the needle cap back on. 
 

Always keep the container out of the reach of children. 

 

 



155 

Package leaflet: Information for the user  
 

Dupixent 200 mg solution for injection in pre-filled pen  
dupilumab 

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

safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- 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, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What Dupixent is and what it is used for 
2. What you need to know before you use Dupixent 
3. How to use Dupixent 
4. Possible side effects 
5. How to store Dupixent 
6. Contents of the pack and other information 
 
 
1. What Dupixent is and what it is used for 
 
What Dupixent is 
Dupixent contains the active substance dupilumab. 
 
Dupilumab is a monoclonal antibody (a type of specialised protein) that blocks the action of proteins 
called IL-4 and IL-13. Both play a major role in causing the signs and symptoms of asthma. 
 
What Dupixent is used for 
Dupixent is used to treat adults and adolescents 12 years and older with moderate-to-severe atopic 
dermatitis, also known as atopic eczema. Dupixent is also used to treat children 6 to 11 years old with 
severe atopic dermatitis (see section Children and adolescents). Dupixent may be used with eczema 
medicines that you apply to the skin or it may be used on its own.  
 
Dupixent is used with other asthma medicines for the maintenance treatment of severe asthma in adults 
and adolescents (12 years of age and older) whose asthma is not controlled with their current asthma 
medicines. 
 
How Dupixent works 
Using Dupixent for atopic dermatitis (atopic eczema) can improve the condition of your skin and 
reduce itching. Dupixent has also been shown to improve symptoms of pain, anxiety, and depression 
associated with atopic dermatitis. In addition, Dupixent helps improve your sleep disturbance and 
overall quality of life. 
 
Dupixent helps prevent severe asthma attacks (exacerbations) and can improve your breathing. 
Dupixent may also help reduce the amount of another group of medicines you need to control your 
asthma, called oral corticosteroids, while preventing severe asthma attacks and improving your 
breathing. 
 
 



156 

2. What you need to know before you use Dupixent 
 
Do not use Dupixent  
• if you are allergic to dupilumab or any of the other ingredients of this medicine (listed in 

section 6). 
• if you think you may be allergic, or you are not sure, ask your doctor, pharmacist or nurse for 

advice before using Dupixent. 
 
Warnings and precautions  
Talk to your doctor, pharmacist or nurse before using Dupixent: 
 
Dupixent is not a rescue medicine and should not be used to treat a sudden asthma attack. 
 
Allergic reactions 
• Very rarely, Dupixent can cause serious side effects, including allergic (hypersensitivity) reactions 

and anaphylactic reaction and angioedema. These reactions can occur from minutes until seven 
days after Dupixent administration. You must look out for signs of these conditions (i.e. breathing 
problems, swelling of the face, lips, mouth, throat or tongue, fainting, dizziness, feeling 
lightheaded (low blood pressure), fever, general ill feeling, swollen lymph nodes, hives, itching, 
joint pain, skin rash) while you are taking Dupixent. Such signs are listed under “Serious side 
effects” in section 4. 

• Stop using Dupixent and tell your doctor or get medical help immediately if you notice any signs 
of an allergic reaction. 

 
Eosinophilic conditions 
• Rarely patients taking an asthma medicine may develop inflammation of blood vessels or lungs 

due to an increase of certain white blood cells (eosinophilia). 
• It is not known whether this is caused by Dupixent. This usually, but not always, happens in 

people who also take a steroid medicine which is being stopped or for which the dose is being 
lowered. 

• Tell your doctor immediately if you develop a combination of symptoms such as a flu-like illness, 
pins and needles or numbness of arms or legs, worsening of pulmonary symptoms, and/or rash. 

 
Parasitic (intestinal parasites) infection 
• Dupixent may weaken your resistance to infections caused by parasites. If you already have a 

parasitic infection it should be treated before you start treatment with Dupixent. 
• Check with your doctor if you have diarrhoea, gas, upset stomach, greasy stools, and dehydration 

which could be a sign of a parasitic infection. 
• If you live in a region where these infections are common or if you are travelling to such a region 

check with your doctor. 
 
Asthma 
If you have asthma and are taking asthma medicines, do not change or stop your asthma medicine 
without talking to your doctor. Talk to your doctor before you stop Dupixent or if your asthma remains 
uncontrolled or worsens during treatment with this medicine. 
 
Eye problems 
Talk to your doctor if you have any new or worsening eye problems, including eye pain or changes in 
vision. 
 
Children and adolescents 



157 

• The Dupixent pre-filled pen is not intended for use in children below 12 years of age. For 
children aged 6-11 years with atopic dermatitis, contact your doctor who will prescribe the 
appropriate Dupixent pre-filled syringe. 

• The safety and benefits of Dupixent are not yet known in children with atopic dermatitis below the 
age of 6. 

• The safety and benefits of Dupixent are not yet known in children with asthma below the age of 
12. 

 
Other medicines and Dupixent 
Tell your doctor or pharmacist  
• if you are using, have recently used or might use any other medicines. 
• if you have recently had or are due to have a vaccination. 

 
Other medicines for asthma 
Do not stop or reduce your asthma medicines, unless instructed by your doctor. 
• These medicines (especially ones called corticosteroids) must be stopped gradually. 
• This must be done under the direct supervision of your doctor and dependent on your response to 

Dupixent. 
 
Pregnancy and breast-feeding  
• If you are pregnant, think you may be pregnant, or are planning to have a baby, ask your doctor for 

advice before using this medicine. The effects of this medicine in pregnant women are not known; 
therefore it is preferable to avoid the use of Dupixent in pregnancy unless your doctor advises to 
use it. 

• If you are breast-feeding or are planning to breast-feed, talk to your doctor before using this 
medicine. You and your doctor should decide if you will breast-feed or use Dupixent. You should 
not do both. 

 
Driving and using machines  
Dupixent is unlikely to influence your ability to drive and use machines. 
 
Dupixent contains sodium  
This medicine contains less than 1 mmol sodium (23 mg) per 200 mg dose, i.e., it is essentially 
“sodium-free”. 
 
 
3. How to use Dupixent 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or 
pharmacist if you are not sure. 
 
How Dupixent is given Dupixent is given by injection under the skin (subcutaneous injection). 
 
How much Dupixent you will receive 
Your doctor will decide which dose of Dupixent is right for you. 
 
Recommended dose in adolescents with atopic dermatitis 
The recommended dose of Dupixent for adolescents (12 to 17 years of age) with atopic dermatitis is 
based on body weight: 
 

Body Weight of 
Patient 

Initial Dose Subsequent Doses 
(every other week) 

less than 60 kg 400 mg (two 200 mg injections) 200 mg 
60 kg or more 600 mg (two 300 mg injections) 300 mg 

 



158 

Recommended dose in children with atopic dermatitis 
The recommended dose of Dupixent for children (6 to 11 years of age) with atopic dermatitis is based 
on body weight: 
 

Body Weight of 
Patient 

Initial Dose Subsequent Doses 
 

 
 

 

15 kg to 
less than 60 kg 

300 mg (one 300 mg injection) on Day 1, 
followed by 300 mg on Day 15 

300 mg every 4 weeks*,  
starting 4 weeks after Day 15 dose 

60 kg or more 600 mg (two 300 mg injections) 300 mg every other week  

* The dose may be increased to 200 mg every other week based on the doctor’s opinion. 
 
Recommended dose in adult and adolescent patients with asthma (12 years of age and older) 
For most patients with severe asthma, the recommended dose of Dupixent is: 
• An initial dose of 400 mg (two 200 mg injections) 
• Followed by 200 mg given every other week administered as subcutaneous injection. 

 
For patients with severe asthma and who are on oral corticosteroids or for patients with severe asthma 
and co-morbid moderate-to-severe atopic dermatitis or adults with co-morbid severe chronic 
rhinosinusitis with nasal polyposis, the recommended dose of Dupixent is: 
• An initial dose of 600 mg (two 300 mg injections) 
• Followed by 300 mg given every other week administered as subcutaneous injection. 
 
Injecting Dupixent 
Dupixent is given by injection under your skin (subcutaneous injection). You and your doctor or nurse 
should decide if you should inject Dupixent yourself. 
 
Before injecting Dupixent yourself you must have been properly trained by your doctor or nurse. Your 
Dupixent injection may also be given by a caregiver after proper training by a doctor or nurse. 
 
Each pre-filled pen contains one dose of Dupixent (200 mg). Do not shake the pre-filled pen. 
 
Read the “Instructions for Use” for the pre-filled pen carefully before using Dupixent. 
 
If you use more Dupixent than you should  
If you use more Dupixent than you should or the dose has been given too early, talk to your doctor, 
pharmacist or nurse.  
 
If you forget to use Dupixent  
If you have forgotten to inject a dose of Dupixent, talk to your doctor, pharmacist or nurse. 
 
If you stop using Dupixent  
Do not stop using Dupixent without speaking to your doctor first.  
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Dupixent can cause serious side effects, including very rare allergic (hypersensitivity) reactions, 
including anaphylactic reaction; the signs of allergic reaction or anaphylactic reaction may include: 

• breathing problems 
• swelling of the face, lips, mouth, throat or tongue (angioedema) 



159 

• fainting, dizziness, feeling lightheaded (low blood pressure) 
• fever 
• general ill feeling 
• swollen lymph nodes 
• hives 
• itching 
• joint pain 
• skin rash 

 
If you develop an allergic reaction, stop using Dupixent and talk to your doctor right away. 
 
Other side effects 
 
Very Common (may affect more than 1 in 10 people) atopic dermatitis and asthma: 

• injection site reactions (i.e. redness, swelling, and itching) 
 
Common (may affect up to 1 in 10 people) atopic dermatitis only: 

• headache 
• eye dryness, redness and itching  
• eyelid itching, redness and swelling  
• eye infection 
• cold sores (on lips and skin) 

 
Uncommon (may affect up to 1 in 100 people):  

• inflammation of the eye surface, sometimes with blurred vision (keratitis, ulcerative keratitis) 
 
Not known 
The following side effects have been reported since the marketing of Dupixent, but how often they 
occur is not known: 

• joint pain (arthralgia) 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Dupixent 
 
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 label and carton after EXP. The 
expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C to 8°C). If necessary, pre-filled pens may be kept at room temperature up 
to 25°C for a maximum of 14 days. Do not store above 25°C. If you need to permanently remove the 
carton from the refrigerator, write down the date of removal in the space provided on the outer carton, 
and use Dupixent within 14 days. 
 
Store in the original carton to protect from light. 
 
Do not use this medicine if you notice that the medicine is cloudy, discoloured, or has particles in it. 
Do not throw away any medicines via wastewater or household waste. Ask your doctor, pharmacist or 
nurse how to throw away medicines you no longer use. These measures will help protect the 
environment. 

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


160 

 
 
6. Contents of the pack and other information 
 
What Dupixent contains 
• The active substance is dupilumab. 
• Each pre-filled pen contains 200 mg of dupilumab in 1.14 ml solution for injection (injection). 
• The other ingredients are arginine hydrochloride, histidine, polysorbate 80 (E433), sodium 

acetate, glacial acetic acid (E260), sucrose, water for injections. 
 
What Dupixent looks like and contents of the pack 
Dupixent is a clear to slightly opalescent, colourless to pale yellow solution supplied in a pre-filled 
pen. 
 
Dupixent is available as 200 mg pre-filled pens in a pack containing 1, 2, 3, or 6 pre-filled pens.  
 
Not all pack sizes may be marketed.  
 
Marketing Authorisation Holder 
sanofi-aventis groupe 
54, rue La Boétie 
75008 Paris 
France 
 
Manufacturer 
SANOFI WINTHROP INDUSTRIE 
1051 Boulevard Industriel,  
76580 LE TRAIT, 
FRANCE 
 
Sanofi-Aventis Deutschland GmbH 
Brüningstrasse 50 
Industriepark Hoechst 
65926 FRANKFURT AM MAIN 
GERMANY 
 



161 

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 
 

Lietuva 
UAB "SANOFI-AVENTIS LIETUVA"  
Tel: +370 5 2755224 
 

България 
SANOFI BULGARIA EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 
 

Danmark 
Sanofi A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi S.r.l. 
Tel: +39 02 39394275 
 

Deutschland 
Sanofi-Aventis Deutschland GmbH 
Tel.: 0800 04 36 996 
Tel. aus dem Ausland: +49 69 305 70 13 
 

Nederland 
Genzyme Europe B.V. 
Tel: + 31 20 245 4000 
 

Eesti 
sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

Norge 
sanofi-aventis Norge AS 
Tlf: +47 67 10 71 00 
 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 
 

España 
sanofi-aventis, S.A.  
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 
 

France 
sanofi-aventis france 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda 
Tel: +351 21 35 89 400 
 

Hrvatska  
sanofi-aventis Croatia d.o.o.  
Tel: +385 1 600 34 00 
 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 

Ireland 
sanofi-aventis Ireland Ltd. T/A SANOFI 
Tel: +353 (0) 1 403 56 00 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.r.l. 
Tel: 800 536389 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 
 



162 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 
 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 
 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 
 

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

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


163 

  

Dupixent 200 mg solution for injection in a pre-filled pen 
Dupilumab 
 
Instructions for use 
 
The parts of the Dupixent pre-filled pen are shown in this picture.  
 

 

Important information 
This device is a single-use pre-filled pen. It contains 200 mg of Dupixent for injection under the skin 
(subcutaneous injection). 
 
You must not try to give yourself or someone else the injection unless you have received training from 
your healthcare professional. In adolescents 12 years and older, it is recommended that Dupixent be 
administered by or under supervision of an adult. The Dupixent pre-filled pen is only for use in adults 
and children aged 12 years and older. 
 

• Read all of the instructions carefully before using the pre-filled pen. 
• Ask your healthcare professional how often you will need to inject the medicine. 
• Choose a different injection site for each injection 
• Do not use the pre-filled pen if it has been damaged. 
• Do not use the pre-filled pen if the yellow cap is missing or not securely attached. 
• Do not press or touch the orange needle cover with your fingers. 
• Do not inject through clothes. 
• Do not remove the yellow cap until just before you give the injection.  
• Do not try to put the yellow cap back on the pre-filled pen. 
• Do not re-use the pre-filled pen. 

 
How to Store Dupixent 
 

• Keep the pre-filled pen(s) and all medicines out of the reach of children. 
• Keep unused pre-filled pens in the original carton and store in the refrigerator between 2ºC 

and 8ºC. 
• Store pre-filled pens in the original carton to protect it from light. 
• Do not keep pre-filled pens at room temperature (<25ºC) for more than 14 days. If you need to 

permanently remove the carton from the refrigerator, write down the date of removal in the 
space provided on the outer carton, and use Dupixent within 14 days. 

• Do not shake the pre-filled pen at any time. 
• Do not heat the pre-filled pen. 
• Do not freeze the pre-filled pen. 
• Do not place the pre-filled pen into direct sunlight. 

 
 



164 

A: Prepare 
A1. Gather supplies 
 
Ensure you have the following: 

• the Dupixent pre-filled pen 
• 1 alcohol wipe* 
• 1 cotton ball or gauze* 
• a puncture-resistant container* (See Step D) 

 
*Items not included in the carton 
 
A2. Look at the label  
 

• Confirm that you have the correct product and dose. 
 

 
 
A3. Check expiration date 
 

• Check the expiration date. 
 

Do not use the pre-filled pen if the expiration date has passed. 

Do not keep Dupixent at room temperature for more than 14 days. 
 
 
 

 
A4. Check the medicine 
 
Look at the medicine through the window on the pre-filled pen. 
 
Check if the liquid is clear and colourless to pale yellow. 
 
Note: You may see an air bubble; this is normal. 

Do not use the pre-filled pen if the liquid is discolored or cloudy, or if it contains visible 
flakes or particles. 

Do not use the pre-filled pen if the window is yellow. 



165 

 
 
A5: Wait 30 minutes 
 
Lay the pre-filled pen on a flat surface and let it naturally warm up at room temperature (less than 
25ºC) for at least 30 minutes. 
 

Do not warm the pre-filled pen in a microwave, hot water, or direct sunlight. 

Do not put the pre-filled pen into direct sunlight. 

Do not keep Dupixent at room temperature for more than 14 days. 
 

 
 
B. Choose your injection site 
B1. Recommended injection sites are: 
 

• Thigh 
• Stomach except for the 5 cm around your belly button (navel). 
• Upper Arm If a caregiver gives your dose, they can also use the outer area of the upper arm. 

 
Choose a different injection site for each Dupixent injection. 

Do not inject through clothes. 

Do not inject into skin that is tender, damaged, bruised or scarred. 
 



166 

 
 
 
B2. Wash your hands 
 

 
 
B3. Prepare the injection site 
 

• Clean the injection site with an alcohol wipe. 

• Let your skin dry before injecting. 

Do not touch the injection site again or blow on it before the injection. 
 

 
 
C. Give injection 
C1. Remove yellow cap 
 
Pull the yellow cap straight off. 
 
Do not twist the yellow cap off. 
 
Do not remove the yellow cap until you are ready to inject. 
 
Do not press or touch the orange needle cover with your fingers. The needle is inside. 
 

Do not put the yellow cap back on the pre-filled pen after you have removed it. 



167 

 

 
 
C2. Place 
 

• When placing the orange needle cover on your skin, hold the pre-filled pen so that you can see 
the window.  

 
• Place the orange needle cover on your skin at approximately a 90-degree angle. 

 

Do not press or touch the orange needle cover with your fingers. The needle is inside. 
 

 
 
C3. Press down 
 
 
Press the pre-filled pen firmly against your skin until you cannot see the orange needle cover, and 
hold. 
 

• There will be a “click” when the injection starts. 

• The window will start to turn yellow. 
 
The injection can take up to 20 seconds. 
 



168 

 
 

 
C4. Hold firmly  
 
Keep holding the pre-filled pen firmly against your skin. 

 
• You may hear a second click. 
• Check that the entire window has turned to yellow. 
• Then slowly count to 5. 
• Then lift the pen up off the skin, your injection is complete. 

 
If the window does not turn completely yellow, remove the pen and call your healthcare provider. 
 

Do not give yourself a second dose without speaking to your healthcare provider. 
 

 
 
C5. Remove 
 

• After you have completed your injection pull straight up to remove pre-filled pen from the skin 
and dispose of immediately as described in section D. 
 

• If you see any blood at the site, lightly dab a cotton ball or gauze pad. 

Do not rub your skin after the injection. 
 



169 

 
 
 
 
D. Dispose 
 

• Dispose of the pre-filled pens, (needle inside), and yellow caps in a puncture resistant container 
right away after use. 

Do not dispose of (throw away) pre-filled pens (needle inside), and yellow caps in your household 
trash. 
 

Do not put the yellow cap back on. 
 
 

 
  



170 

 

 

 

 

 

 

 

 

 

 

 

 

Annex IV 

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

 
 
 
 
 

 



171 

Scientific conclusions 

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

In view of available data on keratitis from clinical trials, literature, spontaneous reports including 
cases with close temporal relationship, positive re-challenge, the PRAC considers that a causal 
relationship between dupilumab and keratitis is a reasonable possibility at least in atopic dermatitis 
and asthma conditions. 

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

 

Grounds for the variation to the terms of the marketing authorisation 

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

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

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET
	Scientific conclusions and grounds for the variation to the terms of the marketing authorisation
{'Title': '1. what dupixent is and what it is used for', 'Section_Content': 'what dupixent is dupixent contains the active substance dupilumab. dupilumab is a monoclonal antibody (a type of specialised protein) that blocks the action of proteins called il-4 and il-13. both play a major role in causing the signs and symptoms of atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis (crswnp). what dupixent is used for dupixent is used to treat adults and adolescents 12 years and older with moderate-to-severe atopic dermatitis, also known as atopic eczema. dupixent is also used to treat children 6 to 11 years old with severe atopic dermatitis. dupixent may be used with eczema medicines that you apply to the skin or it may be used on its own. dupixent is also used with other asthma medicines for the maintenance treatment of severe asthma in adults and adolescents (12 years of age and older) whose asthma is not controlled with their current asthma medicines. dupixent is also used with other medicines for the maintenance treatment of crswnp in adults whose disease is not controlled with their current crswnp medicines. dupixent can also reduce the need for surgery and the need for systemic corticosteroid use. how dupixent works using dupixent for atopic dermatitis (atopic eczema) can improve the condition of your skin and reduce itching. dupixent has also been shown to improve symptoms of pain, anxiety, and depression associated with atopic dermatitis. in addition, dupixent helps improve your sleep disturbance and overall quality of life. dupixent helps prevent severe asthma attacks (exacerbations) and can improve your breathing. dupixent may also help reduce the amount of another group of medicines you need to control your asthma, called oral corticosteroids, while preventing severe asthma attacks and improving your breathing.', 'Entity_Recognition': [{'Text': 'dupixent', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Id': 2, 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{'Title': '2. what you need to know before you use dupixent', 'Section_Content': 'do not use dupixent if you are allergic to dupilumab or any of the other ingredients of this medicine (listed in section 6). if you think you may be allergic, or you are not sure, ask your doctor, pharmacist or nurse for advice before using dupixent. warnings and precautions talk to your doctor, pharmacist or nurse before using dupixent: dupixent is not a rescue medicine and should not be used to treat a sudden asthma attack. allergic reactions very rarely, dupixent can cause serious side effects, including allergic (hypersensitivity) reactions and anaphylactic reaction and angioedema. these reactions can occur from minutes until seven days after dupixent administration. you must look out for signs of these conditions (i.e. breathing problems, swelling of the face, lips, mouth, throat or tongue, fainting, dizziness, feeling lightheaded (low blood pressure), fever, general ill feeling, swollen lymph nodes, hives, itching, joint pain, skin rash) while you are taking dupixent. such signs are listed under "serious side effects" in section 4. stop using dupixent and tell your doctor or get medical help immediately if you notice any signs of an allergic reaction. eosinophilic conditions rarely patients taking an asthma medicine may develop inflammation of blood vessels or lungs due to an increase of certain white blood cells (eosinophilia). it is not known whether this is caused by dupixent. this usually, but not always, happens in people who also take a steroid medicine which is being stopped or for which the dose is being lowered. tell your doctor immediately if you develop a combination of symptoms such as a flu-like illness, pins and needles or numbness of arms or legs, worsening of pulmonary symptoms, and/or rash. parasitic (intestinal parasites) infection dupixent may weaken your resistance to infections caused by parasites. if you already have a parasitic infection it should be treated before you start treatment with dupixent. check with your doctor if you have diarrhoea, gas, upset stomach, greasy stools, and dehydration which could be a sign of a parasitic infection. if you live in a region where these infections are common or if you are travelling to such a region check with your doctor. asthma if you have asthma and are taking asthma medicines, do not change or stop your asthma medicine without talking to your doctor. talk to your doctor before you stop dupixent or if your asthma remains uncontrolled or worsens during treatment with this medicine. eye problems talk to your doctor if you have any new or worsening eye problems, including eye pain or changes in vision. children and adolescents the safety and benefits of dupixent are not yet known in children with atopic dermatitis below the age of 6. the safety and benefits of dupixent are not yet known in children with asthma below the age of 12. crswnp does not normally occur in children. the safety and benefits of dupixent are not yet known in children with crswnp below the age of 18 years. other medicines and dupixent tell your doctor or pharmacist if you are using, have recently used or might use any other medicines. if you have recently had or are due to have a vaccination. other medicines for asthma do not stop or reduce your asthma medicines, unless instructed by your doctor. these medicines (especially ones called corticosteroids) must be stopped gradually. this must be done under the direct supervision of your doctor and dependent on your response to dupixent. pregnancy and breast-feeding if you are pregnant, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before using this medicine. the effects of this medicine in pregnant women are not known; therefore it is preferable to avoid the use of dupixent in pregnancy unless your doctor advises to use it. if you are breast-feeding or are planning to breast-feed, talk to your doctor before using this medicine. you and your doctor should decide if you will breast-feed or use dupixent. you should not do both. driving and using machines dupixent is unlikely to influence your ability to drive and use machines. dupixent contains sodium this medicine contains less than 1 mmol sodium (23 mg) per 300 mg dose, i.e., it is essentially "sodium-free".', 'Entity_Recognition': [{'Text': 'dupixent', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Id': 13, 'BeginOffset': 11, 'EndOffset': 19, 'Score': 0.4136806130409241, 'Text': 'dupixent', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': [{'Name': 'NEGATION', 'Score': 0.7354276776313782}]}, {'Text': 'allergic', 'Type': 'PROBLEM', 'BeginOffset': 31, 'EndOffset': 39}, {'Id': 14, 'BeginOffset': 43, 'EndOffset': 52, 'Score': 0.9554928541183472, 'Text': 'dupilumab', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 88, 'EndOffset': 101}, {'Text': '6.', 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{'Title': '3. how to use dupixent', 'Section_Content': 'always use this medicine exactly as your doctor or pharmacist has told you. check with your doctor or pharmacist if you are not sure. how dupixent is given dupixent is given by injection under the skin (subcutaneous injection). how much dupixent you will receive your doctor will decide which dose of dupixent is right for you. recommended dose in adults with atopic dermatitis for patients with atopic dermatitis, the recommended dose of dupixent is: an initial dose of 600 mg (two 300 mg injections) followed by 300 mg given every other week by subcutaneous injection. recommended dose in adolescents with atopic dermatitis the recommended dose of dupixent for adolescents (12 to 17 years of age) with atopic dermatitis is based on body weight: 106 body weight of patient initial dose subsequent doses (every other week) less than 60 kg 400 mg (two 200 mg injections) 200 mg 60 kg or more 600 mg (two 300 mg injections) 300 mg recommended dose in children with atopic dermatitis the recommended dose of dupixent for children (6 to 11 years of age) with atopic dermatitis is based on body weight: body weight of patient initial dose subsequent doses 15 kg to less than 60 kg 300 mg (one 300 mg injection) on day 1, followed by 300 mg on day 15 300 mg every 4 weeks*, starting 4 weeks after day 15 dose 60 kg or more 600 mg (two 300 mg injections) 300 mg every other week * the dose may be increased to 200 mg every other week based on the doctor\'s opinion. recommended dose in adult and adolescent patients with asthma (12 years of age and older) for patients with severe asthma and who are on oral corticosteroids or for patients with severe asthma and co-morbid moderate-to-severe atopic dermatitis or adults with co-morbid severe chronic rhinosinusitis with nasal polyposis, the recommended dose of dupixent is: an initial dose of 600 mg (two 300 mg injections) followed by 300 mg given every other week administered as subcutaneous injection. for all other patients with severe asthma, the recommended dose of dupixent is: an initial dose of 400 mg (two 200 mg injections) followed by 200 mg given every other week administered as subcutaneous injection. recommended dose in adults with chronic rhinosinusitis with nasal polyposis (crswnp) in crswnp, the recommended first dose of dupixent is 300 mg followed by 300 mg given every two weeks by subcutaneous injection. injecting dupixent dupixent is given by injection under your skin (subcutaneous injection). you and your doctor or nurse should decide if you should inject dupixent yourself. before injecting dupixent yourself you must have been properly trained by your doctor or nurse. your dupixent injection may also be given by a caregiver after proper training by a doctor or nurse. each pre-filled syringe contains one dose of dupixent (300 mg). do not shake the pre-filled syringe. read the "instructions for use" for the pre-filled syringe carefully before using dupixent. if you use more dupixent than you should if you use more dupixent than you should or the dose has been given too early, talk to your doctor, pharmacist or nurse. if you forget to use dupixent if you have forgotten to inject a dose of dupixent, talk to your doctor, pharmacist or nurse. if you stop using dupixent do not stop using dupixent without speaking to your doctor first. if you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.', 'Entity_Recognition': [{'Text': 'dupixent', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 11, 'EndOffset': 24}, {'Id': 1, 'BeginOffset': 156, 'EndOffset': 164, 'Score': 0.5431966781616211, 'Text': 'dupixent', 'Category': 'MEDICATION', 'Type': 'BRAND_NAME', 'Traits': [], 'Attributes': [{'Type': 'ROUTE_OR_MODE', 'Score': 0.39820802211761475, 'RelationshipScore': 0.9999970197677612, 'RelationshipType': 'ROUTE_OR_MODE', 'Id': 2, 'BeginOffset': 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{'Title': '4. possible side effects', 'Section_Content': 'like all medicines, this medicine can cause side effects, although not everybody gets them. dupixent can cause serious side effects, including very rare allergic (hypersensitivity) reactions, including anaphylactic reaction; the signs of allergic reaction or anaphylactic reaction may include: breathing problems swelling of the face, lips, mouth, throat or tongue (angioedema) fainting, dizziness, feeling lightheaded (low blood pressure) fever general ill feeling swollen lymph nodes hives itching joint pain skin rash if you develop an allergic reaction, stop using dupixent and talk to your doctor right away. other side effects very common (may affect more than 1 in 10 people) atopic dermatitis and asthma: injection site reactions (i.e. redness, swelling, and itching) common (may affect up to 1 in 10 people) atopic dermatitis only: headache eye dryness, redness and itching eyelid itching, redness and swelling eye infection cold sores (on lips and skin) uncommon (may affect up to 1 in 100 people): inflammation of the eye surface, sometimes with blurred vision (keratitis, ulcerative keratitis) not known the following side effects have been reported since the marketing of dupixent, but how often they occur is not known: joint pain (arthralgia) reporting of side effects if you get any side effects, talk to your doctor, pharmacist or nurse. this includes any possible side effects not listed in this leaflet. you can also report side effects directly via the national reporting system listed in appendix v. by reporting side effects you can help provide more information on the safety of this medicine.', 'Entity_Recognition': [{'Text': 'dupixent', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'all medicines', 'Type': 'TREATMENT', 'BeginOffset': 5, 'EndOffset': 18}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 20, 'EndOffset': 33}, {'Id': 20, 'BeginOffset': 44, 'EndOffset': 56, 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{'Title': '5. how to store dupixent', 'Section_Content': '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 label and carton after exp. the expiry date refers to the last day of that month. store in a refrigerator (2 to 8). if necessary, pre-filled syringes may be kept at room temperature up to 25 for a maximum of 14 days. do not store above 25. if you need to permanently remove 108 the carton from the refrigerator, write down the date of removal in the space provided on the outer carton, and use dupixent within 14 days. store in the original carton to protect from light. do not use this medicine if you notice that the medicine is cloudy, discoloured, or has particles in it. do not throw away any medicines via wastewater or household waste. ask your doctor, pharmacist or nurse how to throw away medicines you no longer use. these measures will help protect the environment.', 'Entity_Recognition': [{'Text': 'dupixent', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 70, 'EndOffset': 83}, {'Text': 'pre-filled syringes', 'Type': 'TREATMENT', 'BeginOffset': 259, 'EndOffset': 278}, {'Text': '25', 'Type': 'NUMBER', 'BeginOffset': 317, 'EndOffset': 319}, {'Text': '14', 'Type': 'NUMBER', 'BeginOffset': 337, 'EndOffset': 339}, {'Text': '25.', 'Type': 'NUMBER', 'BeginOffset': 365, 'EndOffset': 368}, {'Text': '108', 'Type': 'NUMBER', 'BeginOffset': 403, 'EndOffset': 406}, {'Text': 'removal', 'Type': 'TREATMENT', 'BeginOffset': 464, 'EndOffset': 471}, {'Text': '14', 'Type': 'NUMBER', 'BeginOffset': 539, 'EndOffset': 541}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 611, 'EndOffset': 624}, {'Text': 'cloudy', 'Type': 'PROBLEM', 'BeginOffset': 660, 'EndOffset': 666}]}
{'Title': '6. contents of the pack and other information', 'Section_Content': 'what dupixent contains the active substance is dupilumab. each pre-filled syringe contains 300 mg of dupilumab in 2 ml solution for injection (injection). the other ingredients are arginine hydrochloride, histidine, polysorbate 80 (e433), sodium acetate, glacial acetic acid (e260), sucrose, water for injections. what dupixent looks like and contents of the pack dupixent is a clear to slightly opalescent, colourless to pale yellow solution supplied in a glass pre- filled syringe with or without needle shield. dupixent is available as 300 mg pre-filled syringes in a pack containing 1 or 2 pre-filled syringes or in a pack containing 3 (3 packs of 1) or 6 (3 packs of 2) pre-filled syringes. not all pack sizes may be marketed.', 'Entity_Recognition': [{'Text': 'dupixent', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Id': 0, 'BeginOffset': 47, 'EndOffset': 56, 'Score': 0.9829769134521484, 'Text': 'dupilumab', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': [], 'Attributes': [{'Type': 'FORM', 'Score': 0.42253008484840393, 'RelationshipScore': 0.9953966736793518, 'RelationshipType': 'FORM', 'Id': 1, 'BeginOffset': 63, 'EndOffset': 90, 'Text': 'pre-filled syringe contains', 'Category': 'MEDICATION', 'Traits': []}, {'Type': 'DOSAGE', 'Score': 0.5404363870620728, 'RelationshipScore': 0.9290792346000671, 'RelationshipType': 'DOSAGE', 'Id': 4, 'BeginOffset': 114, 'EndOffset': 118, 'Text': '2 ml', 'Category': 'MEDICATION', 'Traits': []}, {'Type': 'ROUTE_OR_MODE', 'Score': 0.6001837253570557, 'RelationshipScore': 0.5998608469963074, 'RelationshipType': 'ROUTE_OR_MODE', 'Id': 6, 'BeginOffset': 132, 'EndOffset': 141, 'Text': 'injection', 'Category': 'MEDICATION', 'Traits': []}]}, {'Text': 'each pre-filled syringe', 'Type': 'TREATMENT', 'BeginOffset': 58, 'EndOffset': 81}, {'Text': '300', 'Type': 'NUMBER', 'BeginOffset': 91, 'EndOffset': 94}, {'Id': 3, 'BeginOffset': 101, 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'Text': 'solution', 'Category': 'MEDICATION', 'Traits': []}, {'Type': 'ROUTE_OR_MODE', 'Score': 0.6001837253570557, 'RelationshipScore': 0.9989645481109619, 'RelationshipType': 'ROUTE_OR_MODE', 'Id': 6, 'BeginOffset': 132, 'EndOffset': 141, 'Text': 'injection', 'Category': 'MEDICATION', 'Traits': []}]}, {'Text': '2', 'Type': 'NUMBER', 'BeginOffset': 114, 'EndOffset': 115}, {'Id': 8, 'BeginOffset': 181, 'EndOffset': 203, 'Score': 0.9964262843132019, 'Text': 'arginine hydrochloride', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Text': 'histidine, polysorbate', 'Type': 'TREATMENT', 'BeginOffset': 205, 'EndOffset': 227}, {'Text': '80', 'Type': 'NUMBER', 'BeginOffset': 228, 'EndOffset': 230}, {'Id': 11, 'BeginOffset': 239, 'EndOffset': 253, 'Score': 0.9995794892311096, 'Text': 'sodium acetate', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Id': 12, 'BeginOffset': 255, 'EndOffset': 274, 'Score': 0.9836779832839966, 'Text': 'glacial acetic acid', 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