Nucala

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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 
 
Nucala 100 mg solution for injection in pre-filled pen  
Nucala 100 mg solution for injection in pre-filled syringe 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Nucala 100 mg solution for injection in pre-filled pen 
 
Each 1 ml pre-filled pen contains 100 mg of mepolizumab. 
 
Nucala 100 mg solution for injection in pre-filled syringe 
 
Each 1 ml pre-filled syringe contains 100 mg of mepolizumab. 
 
Mepolizumab is a humanised monoclonal antibody produced in Chinese hamster ovary cells by recombinant 
DNA technology. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection (injection) 
A clear to opalescent, colourless to pale yellow to pale brown solution 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Nucala is indicated as an add-on treatment for severe refractory eosinophilic asthma in adults, adolescents 
and children aged 6 years and older (see section 5.1). 
 
4.2 Posology and method of administration 
 
Nucala should be prescribed by physicians experienced in the diagnosis and treatment of severe refractory 
eosinophilic asthma. 
 
Posology 
 
Adults and adolescents aged 12 years and over 
The recommended dose of mepolizumab is 100 mg administered subcutaneously once every 4 weeks. 
 
Nucala 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 disease severity and level of control 
of exacerbations. 
 
Special populations 
 



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Elderly patients 
No dose adjustment is required for elderly patients (see section 5.2). 
 
Renal and hepatic impairment 
No dose adjustment is required in patients with renal or hepatic impairment (see section 5.2). 
 
Paediatric population 
 
Children aged 6 to 11 years old 
Nucala 100 mg solution for injection in pre-filled pen and Nucala 100 mg solution for injection in pre-filled 
syringe are not indicated for administration to this population. 
 
The powder for solution for injection presentation is appropriate for administration to this population. The 
recommended dose of mepolizumab is 40 mg administered subcutaneously once every 4 weeks. 
 
Children less than 6 years old 
The safety and efficacy of mepolizumab in children less than 6 years old have not yet been established.  
No data are available. 
 
Method of administration 
 
The Nucala pre-filled pen or pre-filled syringe should be used for subcutaneous injection only. 
 
Nucala may be self-administered by the patient or administered by a caregiver if their healthcare professional 
determines that it is appropriate, and the patient or caregiver are trained in injection techniques. 
 
For self-administration the recommended injection sites are the abdomen or thigh. A caregiver can also inject 
Nucala into the upper arm. 
 
Comprehensive instructions for subcutaneous administration of Nucala in a pre-filled pen or pre-filled 
syringe are provided in the instructions for use 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 
 
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. 
 
Asthma exacerabations 
 
Nucala should not be used to treat acute asthma exacerbations. 
 
Asthma-related adverse symptoms or exacerbations may occur during treatment. Patients should be 
instructed to seek medical advice if their asthma remains uncontrolled or worsens after initiation of 
treatment. 
 
Corticosteroids 
 
Abrupt discontinuation of corticosteroids after initiation of Nucala therapy is not recommended. Reduction 
in corticosteroid doses, if required, should be gradual and performed under the supervision of a physician. 



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Hypersensitivity and administration-related reactions 
 
Acute and delayed systemic reactions, including hypersensitivity reactions (e.g. anaphylaxis, urticaria, 
angioedema, rash, bronchospasm, hypotension), have occurred following administration of Nucala. These 
reactions generally occur within hours of administration, but in some instances have a delayed onset (i.e., 
typically within several days). These reactions may occur for the first time after a long duration of treatment 
(see section 4.8). 
 
Parasitic infections 
 
Eosinophils may be involved in the immunological response to some helminth infections. Patients with pre-
existing helminth infections should be treated before starting therapy. If patients become infected whilst 
receiving treatment with Nucala and do not respond to anti-helminth treatment, temporary discontinuation of 
therapy should be considered. 
 
Excipients 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per 100 mg dose, i.e. essentially “sodium-
free”. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies have been performed. 
 
Cytochrome P450 enzymes, efflux pumps and protein-binding mechanisms are not involved in the clearance 
of mepolizumab. Increased levels of pro-inflammatory cytokines (e.g. IL-6), via interaction with their 
cognate receptors on hepatocytes, have been shown to suppress the formation of CYP450 enzymes and drug 
transporters, however, elevation of systemic pro-inflammatory markers in severe refractory eosinophilic 
asthma is minimal and there is no evidence of IL-5 receptor alpha expression on hepatocytes. The potential 
for interactions with mepolizumab is therefore considered low. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There is a limited amount of data (less than 300 pregnancy outcomes) from the use of mepolizumab in 
pregnant women.  
Mepolizumab crosses the placental barrier in monkeys. Animal studies do not indicate reproductive toxicity 
(see section 5.3). The potential for harm to a human fetus is unknown. 
 
As a precautionary measure, it is preferable to avoid the use of Nucala during pregnancy. Administration of 
Nucala to pregnant women should only be considered if the expected benefit to the mother is greater than 
any possible risk to the fetus. 
 
Breast-feeding 
 
There are no data regarding the excretion of mepolizumab in human milk. However, mepolizumab was 
excreted into the milk of cynomolgous monkeys at concentrations of less than 0.5% of those detected in 
plasma. 
 
A decision must be made whether to discontinue breast-feeding or to discontinue Nucala therapy taking into 
account the benefit of breast-feeding for the child and the benefit of therapy for the woman. 
 
Fertility 
 



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There are no fertility data in humans. Animal studies showed no adverse effects of anti-IL5 treatment on 
fertility (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Nucala has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Adults and adolescents 
In clinical studies in subjects with severe refractory eosinophilic asthma, the most commonly reported 
adverse reactions during treatment were headache, injection site reactions and back pain. 
 
Tabulated list of adverse reactions 
 
A total of 896 adults and 19 adolescent subjects with severe refractory eosinophilic asthma received either a 
subcutaneous or an intravenous dose of mepolizumab during three placebo-controlled clinical studies of 24 
to 52 weeks duration. The table below presents the adverse reactions from the two placebo-controlled studies 
in patients receiving mepolizumab 100 mg subcutaneously (n=263). 
 
The safety profile of mepolizumab in severe refractory eosinophilic asthma patients (n=998) treated for a 
median of 2.8 years (range 4 weeks to 4.5 years) in open-label extension studies was similar to that observed 
in the placebo-controlled studies. 
 
The frequency of adverse reactions is defined using the following convention: very common (≥1/10); 
common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare 
(<1/10,000); and not known (cannot be estimated from available data). Within each frequency grouping, 
adverse reactions are presented in order of decreasing seriousness. 
 

System Organ Class Adverse Reactions Frequency 
Infections and infestations  Lower respiratory tract infection 

Urinary tract infection 
Pharyngitis 
 

Common 
 

Immune system disorders Hypersensitivity reactions (systemic 
allergic)* 
Anaphylaxis** 

Common 
 
Rare 

Nervous system disorders  Headache Very common 
Respiratory, thoracic and 
mediastinal disorders  

Nasal congestion 
 

Common 

Gastrointestinal disorders Abdominal pain upper Common 
Skin and subcutaneous tissue 
disorders 

Eczema Common 

Musculoskeletal and 
connective tissue disorders 

Back pain Common 

General disorders and 
administration site conditions 

Administration-related reactions (systemic 
non allergic)*** 
Local injection site reactions 
Pyrexia 

Common 
 

* Systemic reactions including hypersensitivity have been reported at an overall incidence comparable to that 
of placebo. For examples of the associated manifestations reported and a description of the time to onset, see 
section 4.4. 

**From spontaneous post marketing reporting. 



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*** The most common manifestations associated with reports of systemic non-allergic administration-related 
reactions were rash, flushing and myalgia; these manifestations were reported infrequently and in <1% of 
subjects receiving mepolizumab 100 mg subcutaneously. 
 
Description of selected adverse reaction 
 
Local injection site reactions 
 
In 2 placebo-controlled studies the incidence of local injection site reactions with mepolizumab 100 mg 
subcutaneous and placebo was 8% and 3%, respectively. These events were all non-serious, mild to 
moderate in intensity and the majority resolved within a few days. Local injection site reactions occurred 
mainly at the start of treatment and within the first 3 injections with fewer reports on subsequent injections. 
The most common manifestations reported with these events included pain, erythema, swelling, itching, and 
burning sensation. 
 
Paediatric population 
 
Thirty-seven adolescents (aged 12-17) were enrolled in four placebo-controlled studies (25 mepolizumab 
treated intravenously or subcutaneously) of 24 to 52 weeks duration. Thirty -six paediatric patients (aged 6-
11) received mepolizumab subcutaneously in an open-label study for 12 weeks. After a treatment 
interruption of 8 weeks, 30 of these patients, received mepolizumab for a further 52 weeks. The safety 
profile was similar to that seen in adults. No additional adverse reactions were identified. 
 
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 
 
Single doses of up to 1,500 mg were administered intravenously in a clinical trial to patients with 
eosinophilic disease without evidence of dose-related toxicities. 
 
There is no specific treatment for an overdose with mepolizumab. If overdose occurs, the patient should be 
treated supportively with appropriate monitoring as necessary. 
 
Further management should be as clinically indicated or as recommended by the national poisons centre, 
where available. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs for obstructive airway diseases, other systemic drugs for obstructive 
airway diseases, ATC code: R03DX09. 
 
Mechanism of action 
 
Mepolizumab is a humanised monoclonal antibody (IgG1, kappa), which targets human interleukin-5 (IL-5) 
with high affinity and specificity. IL-5 is the major cytokine responsible for the growth and differentiation, 
recruitment, activation and survival of eosinophils. Mepolizumab inhibits the bioactivity of IL-5 with 
nanomolar potency by blocking the binding of IL-5 to the alpha chain of the IL-5 receptor complex expressed 

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


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on the eosinophil cell surface, thereby inhibiting IL-5 signalling and reducing the production and survival of 
eosinophils. 
 
Pharmacodynamic effects 
 
In patients with severe refractory eosinophilic asthma (adults/adolescents), following a dose of 100 mg 
administered subcutaneously every 4 weeks for 32 weeks, blood eosinophils were reduced from a geometric 
mean count at baseline of 290 to 40 cells/μL at week 32 (n=182), a reduction of 84% compared to placebo. 
This magnitude of blood eosinophils reduction was maintained in severe refractory eosinophilic asthma 
patients (n=998) treated for a median of 2.8 years (range 4 weeks to 4.5 years) in open-label extension 
studies.  
In children aged 6 to 11 years old with severe refractory eosinophilic asthma administered mepolizumab 
subcutaneously every 4 weeks for 52 weeks, blood eosinophils were reduced from a geometric mean count at 
baseline to week 52 of 306 (n=16) to 48 (n=15) following 40 mg (for a weight < 40kg) and 331 to 
44 cells/µL (n=10) following 100 mg (for a weight ≥ 40 kg), a reduction from baseline of 85% and 87%, 
respectively. 
In adults, adolescents and children, this magnitude of reduction was observed within 4 weeks of treatment. 
 
Immunogenicity  
 
Consistent with the potentially immunogenic properties of protein and peptide therapeutics, patients may 
develop antibodies to mepolizumab following treatment. In the placebo-controlled trials, 15/260 (6%) of 
adults and adolescents treated with 100 mg dose subcutaneously had detectable anti-mepolizumab antibodies 
after having received at least one dose of mepolizumab.  
The immunogenicity profile of mepolizumab in severe refractory eosinophilic asthma patients (n=998) 
treated for a median of 2.8 years (range 4 weeks to 4.5 years) in open-label extension studies was similar to 
that observed in the placebo-controlled studies. 
In children aged 6 to 11 years old with severe refractory eosinophilic asthma following either 40 mg 
subcutaneously (for a weight < 40kg) or 100 mg subcutaneously (for a weight ≥ 40 kg), 2/35 (6%) had 
detectable anti-mepolizumab antibodies after having received at least one dose of mepolizumab during the 
initial short phase of the study. No children had detectable anti-mepolizumab antibodies during the long-term 
phase of the study. Neutralising antibodies were detected in one adult subject. Anti-mepolizumab antibodies 
did not discernibly impact the pharmacokinetics and pharmacodynamics of mepolizumab in the majority of 
patients and there was no evidence of a correlation between antibody titres and change in blood eosinophil 
level. 
 
Clinical efficacy  
 
The efficacy of mepolizumab in the treatment of a targeted group of patients with severe refractory 
eosinophilic asthma was evaluated in 3 randomised, double-blind, parallel-group clinical studies of between 
24-52 weeks duration, in patients aged 12 years and older. These patients either remained uncontrolled (at 
least two severe exacerbations in the previous 12 months) on their current standard of care, including at least 
high doses of inhaled corticosteroids (ICS) plus an additional maintenance treatment(s), or were dependent 
on systemic corticosteroids. Additional maintenance treatments included long-acting beta2 -adrenergic 
agonists (LABA), leukotriene modifiers, long-acting muscarinic antagonists (LAMA), theophylline, and oral 
corticosteroids (OCS). 
 
The two exacerbations studies MEA112997 and MEA115588 enrolled a total of 1192 patients, 60% females, 
with a mean age of 49 years (range 12– 82). The proportion of patients on maintenance OCS was 31% and 
24%, respectively. Patients were required to have a history of two or more severe asthma exacerbations 
requiring oral or systemic corticosteroid treatment in the past 12 months and reduced lung function at 
baseline (pre-bronchodilator FEV1<80% in adults and <90% in adolescents). The mean number of 
exacerbations in the previous year was 3.6 and the mean predicted pre-bronchodilator FEV1 was 60%. 
Patients continued to receive their existing asthma medicine during the studies. 
 



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For the oral corticosteroid-sparing study MEA115575, a total of 135 patients were enrolled (55% were 
female; mean age of 50 years) who were being treated daily with OCS (5-35 mg per day), and high-dose ICS 
plus an additional maintenance medicine. 
 
Dose-ranging efficacy MEA112997 (DREAM) study 
 
In MEA112997, a randomised, double-blind, placebo-controlled, parallel-group, multi-centre study of 
52 weeks duration in 616 patients with severe refractory eosinophilic asthma, mepolizumab significantly 
reduced clinically significant asthma exacerbations (defined as worsening of asthma requiring use of 
oral/systemic corticosteroids and/or hospitalisation and/or emergency department visits) when administered 
in doses of 75 mg, 250 mg or 750 mg intravenously compared to placebo (see Table 1). 
 
Table 1: Frequency of clinically significant exacerbations at week 52 in the intent to treat population 

 Intravenous Mepolizumab  Placebo 
75mg 
n=153 

250mg 
n=152 

750mg 
n=156 

 
n= 155 

Exacerbation rate/year 1.24 1.46 1.15 2.40 
Percent reduction 48% 39% 52%  

Rate ratio (95% CI) 0.52 (0.39, 0.69) 0.61(0.46, 0.81) 0.48 (0.36, 0.64)  

p-value <0.001 <0.001 <0.001 - 
 
 
Exacerbation reduction MEA115588 (MENSA) study  
 
MEA115588 was a randomised, double-blind, placebo-controlled, parallel-group, multi-centre study which 
evaluated the efficacy and safety of mepolizumab as add-on therapy in 576 patients with severe refractory 
eosinophilic asthma defined as peripheral blood eosinophils greater than or equal to 150 cells/μL at initiation 
of treatment or greater than or equal to 300 cells/μL within the past 12 months. 
 
Patients received mepolizumab 100 mg administered subcutaneously, mepolizumab 75 mg administered 
intravenously or placebo treatment once every 4 weeks over 32 weeks. The primary endpoint was the 
frequency of clinically significant exacerbations of asthma and the reductions for both mepolizumab 
treatment arms compared to placebo were statistically significant (p<0.001). Table 2 provides the results of 
the primary and secondary endpoints for patients treated with subcutaneous mepolizumab or placebo. 
 
Table 2: Results of primary and secondary endpoints at week 32 in the intent to treat population 
(MEA115588) 

 Mepolizumab 100 mg 
(subcutaneous) 

N= 194 

Placebo 
N= 191 

Primary endpoint 

Frequency of clinically significant exacerbations 

Exacerbation rate per year 0.83 1.74 
Percent reduction 
Rate ratio (95% CI) 

53% 
0.47 (0.35, 0.64) 

- 
 

p-value <0.001  

Secondary endpoints 

Frequency of exacerbations requiring hospitalisations/emergency room visits 

Exacerbation rate per year 0.08 0.20 



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 Mepolizumab 100 mg 
(subcutaneous) 

N= 194 

Placebo 
N= 191 

Percent reduction 
Rate ratio (95% CI) 

61% 
0.39 (0.18, 0.83) 

_ 

p-value 0.015  

Frequency of exacerbations requiring hospitalisation 

Exacerbations rate per year 0.03 0.10 
Percent reduction 
Rate ratio (95% CI) 

69% 
0.31 (0.11, 0.91) 

_ 

p-value 0.034  

Pre-bronchodilator FEV1 (mL) at week 32 

Baseline (SD) 1730 (659) 1860 (631) 
Mean Change from Baseline (SE) 183 (31) 86 (31) 
Difference (mepolizumab vs. placebo) 98  
95% CI (11, 184)  
p-value 0.028  

St. George’s Respiratory Questionnaire (SGRQ) at week 32 

Baseline (SD) 47.9 (19. 5) 46.9 (19.8) 
Mean Change From Baseline (SE) -16.0 (1.1) -9.0 (1.2) 
Difference (mepolizumab vs. placebo) -7.0  
95% CI (-10.2, -3.8)  
p-value <0.001  

 
Reduction of exacerbation rate by baseline blood eosinophil count 
 
Table 3 shows the results of a combined analysis of the two exacerbation studies (MEA112997 and 
MEA115588) by baseline blood eosinophil count. The rate of exacerbations in the placebo arm increased 
with increasing baseline blood eosinophil count. The reduction rate with mepolizumab was greater in 
patients with higher blood eosinophil counts. 
 
Table 3: Combined analysis of the rate of clinically significant exacerbations by baseline blood 
eosinophil count in patients with severe refractory eosinophilic asthma 

 Mepolizumab 
75 mg IV/100 mg SC 

N=538 

Placebo 
N=346 

MEA112997+MEA115588 
<150 cells/µL   
n  123 66 
Exacerbation rate per year 1.16 1.73 
Mepolizumab vs. placebo   
Rate ratio (95% CI) 0.67 (0.46,0.98) --- 
150 to <300 cells/µL   
n  139 86 
Exacerbation rate per year 1.01 1.41 
Mepolizumab vs. placebo   
Rate ratio (95% CI) 0.72 (0.47,1.10) --- 
300 to <500 cells/µL   
n  109 76 
Exacerbation rate per year 1.02 1.64 
Mepolizumab vs. placebo   
Rate ratio (95% CI) 0.62 (0.41,0.93) --- 



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 Mepolizumab 
75 mg IV/100 mg SC 

N=538 

Placebo 
N=346 

≥500 cells/µL   
n  162 116 
Exacerbation rate per year 0.67 2.49 
Mepolizumab vs. placebo   
Rate ratio (95% CI) 0.27 (0.19,0.37) --- 

 
Oral corticosteroid reduction study MEA115575 (SIRIUS) 
 
MEA115575 evaluated the effect of mepolizumab 100 mg administered subcutaneously on reducing the 
requirement for maintenance oral corticosteroids (OCS) while maintaining asthma control in subjects with 
severe refractory eosinophilic asthma. Patients had a blood eosinophil count of ≥150/µL at baseline or a 
blood eosinophil count of ≥300/µL in the 12 months prior to screening. Patients were administered 
mepolizumab or placebo treatment once every 4 weeks over the treatment period. Patients continued to 
receive their existing asthma medicine during the study with the exception of their OCS dose which was 
reduced every 4 weeks during the OCS reduction phase (Weeks 4-20), as long as asthma control was 
maintained. 
 
A total of 135 patients were enrolled: mean age was 50 years, 55% were female, and 48% had been receiving 
oral steroid therapy for at least 5 years. The baseline mean prednisone equivalent dose was approximately 
13 mg per day. 
 
The primary endpoint was the percent reduction in daily OCS dose (weeks 20-24), whilst maintaining 
asthma control by defined dose reduction categories (see Table 4). Predefined categories included percent 
reductions ranging from 90-100% reduction, to no decrease in the prednisone dose from the end of the 
optimisation phase. The comparison between mepolizumab and placebo was statistically significant 
(p=0.008). 
 
Table 4: Results of the primary and secondary endpoints in MEA115575 

 ITT Population 
 Mepolizumab  

100 mg 
(subcutaneous) 

N= 69 

Placebo 
N= 66 

Primary endpoint 

Percent reduction in OCS from baseline (weeks 20-24)  

90% - 100% 
75% - <90% 
50% - <75% 
>0% - <50% 
No decrease in OCS/lack of asthma 
control/ withdrawal from treatment 

16 (23%) 
12 (17%) 
9 (13%) 
7 (10%) 

25 (36%) 

7(11%) 
5 (8%) 

10 (15%) 
7(11%) 

37 (56%) 

Odds ratio (95% CI) 2.39 (1.25, 4.56)  
p-value 0.008  

Secondary endpoints (weeks 20-24) 

Reduction in the daily OCS dose 
to 0 mg/d  

10 (14%) 5 (8%) 

Odds ratio (95% CI) 1.67 (0.49, 5.75)  
p-value 0. 414   



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 ITT Population 
 Mepolizumab  

100 mg 
(subcutaneous) 

N= 69 

Placebo 
N= 66 

Reduction in the daily OCS dose 
to ≤5mg/day 

37 (54%) 21 (32%) 

Odds ratio (95% CI) 2.45 (1.12, 5.37)  
p-value 0.025  
Median % reduction in daily OCS 
dose from baseline (95% CI) 

50.0 (20.0, 75.0) 0.0 (-20.0, 33.3) 

Median difference (95% CI)  -30.0 (-66.7, 0.0)  
p-value 0.007   

 
Open-label extension studies in severe refractory eosinophilic asthma MEA115666 (COLUMBA), 
MEA115661 (COSMOS) and 201312 (COSMEX)  
 
The long-term efficacy profile of Nucala in severe refractory eosinophilic asthma patients (n=998) treated for 
a median of 2.8 years (range 4 weeks to 4.5 years) in open-label extension studies MEA115666, 
MEA115661 and 201312 was generally consistent with the 3 placebo-controlled studies. 
 
Paediatric population 
 
Severe refractory eosinophilic asthma 
In MEA115588 and in the double-blind placebo-controlled study 200862, there were 34 adolescents (12 to 
17 years old). Of these 34 subjects: 12 received placebo, 9 received mepolizumab 75 mg intravenously, and 
13 received 100 mg subcutaneously. In a combined analysis of these studies, a 40% reduction in clinically 
significant exacerbations was observed in adolescents following mepolizumab treatment compared to 
placebo (rate ratio 0.60; 95% CI: 0.17, 2.10). 
 
5.2 Pharmacokinetic properties 
 
Following subcutaneous dosing in patients with asthma, mepolizumab exhibited approximately dose-
proportional pharmacokinetics over a dose range of 12.5 mg to 250 mg. Following administration of a single 
100 mg subcutaneous dose in healthy subjects, mepolizumab systemic exposure was comparable between 
formulations. 
 
Absorption 
 
Following subcutaneous administration to healthy subjects or patients with asthma, mepolizumab was 
absorbed slowly with a median time to reach maximum plasma concentration (Tmax) ranging from 4 to 8 
days. 
Following a single subcutaneous administration in the abdomen, thigh or arm of healthy subjects, 
mepolizumab absolute bioavailability was 64%, 71% and 75%, respectively. In patients with asthma the 
absolute bioavailability of mepolizumab administered subcutaneously in the arm ranged from 74-80%. 
Following repeat subcutaneous administration every 4 weeks, there is approximately a two-fold 
accumulation at steady state. 
 
Distribution 
 
Following a single intravenous administration to patients with asthma, mepolizumab distributes into a mean 
volume of distribution of 55 to 85 mL/kg. 
 
Biotransformation 
 



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Mepolizumab is a humanized IgG1 monoclonal antibody degraded by proteolytic enzymes which are widely 
distributed in the body and not restricted to hepatic tissue. 
 
Elimination 
 
Following a single intravenous administration to patients with asthma, the mean systemic clearance (CL) 
ranged from 1.9 to 3.3 mL/day/kg, with a mean terminal half-life of approximately 20 days. Following 
subcutaneous administration of mepolizumab the mean terminal half-life (t1/2) ranged from 16 to 22 days. In 
the population pharmacokinetic analysis estimated mepolizumab systemic clearance was 3.1 mL/day/kg. 
 
Paediatric population  
 
There are limited pharmacokinetic data available in the paediatric population (59 subjects with eosinophilic 
esophagitis, 55 subjects with severe refractory eosinophilic asthma). Intravenous mepolizumab 
pharmacokinetics was evaluated by population pharmacokinetic analysis in a paediatric study conducted in 
subjects aged 2–17 years old with eosinophilic esophagitis. Paediatric pharmacokinetics was largely 
predictable from adults, after taking into account bodyweight. Mepolizumab pharmacokinetics in adolescent 
subjects with severe refractory eosinophilic asthma included in the phase 3 studies were consistent with 
adults (see section 4.2). 
 
Paediatric pharmacokinetics following subcutaneous administration in subjects 6 to 11 years old with severe 
refractory eosinophilic asthma was investigated in an open label, uncontrolled study of 12-weeks duration. 
Paediatric pharmacokinetics were broadly consistent with adults and adolescents after accounting for 
bodyweight and bioavailability. The absolute subcutaneous bioavailability appears complete compared to 
that observed in adults and adolescents of 76%. Exposure following subcutaneous administration of either 40 
mg (for a weight < 40kg) or 100 mg (for a weight ≥ 40 kg) was 1.32 and 1.97 times of that observed in adults 
at 100 mg. 
Investigation of a 40 mg subcutaneous dosing regimen administered every 4 weeks in children 6 to 11 years 
old over a 15-70 kg broad weight range by PK modelling and simulation predicts that the exposure of this 
dosing regimen would remain on average within 38% of adults at 100 mg. This dosing regimen is considered 
acceptable due to the wide therapeutic index of mepolizumab. 
 
Special populations 
 
Elderly patients (≥65 years old) 
 
There are limited pharmacokinetic data available in elderly patients (≥65 years old) across all clinical studies 
(N=90). However, in the population pharmacokinetic analysis, there were no indications of an effect of age 
on the pharmacokinetics of mepolizumab over the age range of 12 to 82 years. 
 
Renal impairment 
No formal studies have been conducted to investigate the effect of renal impairment on the pharmacokinetics 
of mepolizumab. Based on population pharmacokinetic analyses, no dose adjustment is required in patients 
with creatinine clearance values between 50-80 mL/min. There are limited data available in patients with 
creatinine clearance values <50 mL/min. 
 
Hepatic impairment 
No formal studies have been conducted to investigate the effect of hepatic impairment on the 
pharmacokinetics of mepolizumab. Since mepolizumab is degraded by widely distributed proteolytic 
enzymes, not restricted to hepatic tissue, changes in hepatic function are unlikely to have any effect on the 
elimination of mepolizumab. 
 
5.3 Preclinical safety data 
 
As mepolizumab is a monoclonal antibody, no genotoxicity or carcinogenicity studies have been conducted. 
 



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Animal toxicology and/or pharmacology 
 
Non-clinical data reveal no special hazards for humans based on conventional studies of safety 
pharmacology or repeated dose toxicity studies in monkeys. Intravenous and subcutaneous administration to 
monkeys was associated with reductions in peripheral and lung eosinophil counts, with no toxicological 
findings. 
 
Eosinophils are thought to be associated with immune system responses to some parasitic infections. Studies 
conducted in mice treated with anti-IL-5 antibodies or genetically deficient in IL-5 or eosinophils have not 
shown impaired ability to clear parasitic infections. The relevance of these findings for humans is unknown. 
 
Fertility 
 
No impairment of fertility was observed in a fertility and general reproduction toxicity study in mice 
performed with an analogous antibody that inhibits IL-5 in mice. This study did not include a littering or 
functional offspring assessment. 
 
Pregnancy 
 
In monkeys, mepolizumab had no effect on pregnancy or on embryonic/fetal and postnatal development 
(including immune function) of the offspring. Examinations for internal or skeletal malformations were not 
performed. Data in cynomolgus monkeys demonstrate that mepolizumab crossed the placenta. 
Concentrations of mepolizumab were about 1.2-2.4 times higher in infants than in mothers for several 
months post partum and did not affect the immune system of the infants. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sucrose  
Sodium phosphate dibasic heptahydrate  
Citric acid monohydrate  
Polysorbate 80  
EDTA disodium dihydrate 
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatability studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life 
 
2 years. 
 
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. 
 
If necessary, the Nucala pre-filled pen and pre-filled syringe can be removed from the refrigerator and kept 
in the unopened pack for up to 7 days at room temperature (up to 30°C), when protected from light. The pack 
should be discarded if left out of the refrigerator for more than 7 days. 
 



14 

The pre-filled pen or pre-filled syringe must be administered within 8 hours once the pack is opened. The 
pack should be discarded if not administered within 8 hours. 
 
6.5 Nature and contents of container  
 
Nucala 100 mg solution for injection in pre-filled pen 
 
1 mL solution in a Type 1 glass syringe with a fixed needle (stainless steel) in a pre-filled pen. 
 
Pack sizes:  
1 pre-filled pen 
Multipack comprising 3 (3 packs of 1) pre-filled pens 
 
Not all pack-sizes may be marketed. 
 
Nucala 100 mg solution for injection in pre-filled syringe 
 
1 ml solution in a Type 1 glass syringe with a fixed needle (stainless steel) and passive safety needle guard. 
 
Pack sizes:  
1 pre-filled syringe 
Multipack comprising 3 (3 packs of 1) pre-filled syringe 
 
Not all pack-sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Before administration, the solution should be inspected visually. The liquid should be clear to opalescent, 
colourless to pale yellow to pale brown. If the solution is cloudy, discoloured or contains particles, the 
solution should not be used. 
After removing the pre-filled pen or pre-filled syringe from the refrigerator, allow the pen or syringe to reach 
room temperature for at least 30 minutes before injecting Nucala. 
 
Comprehensive instructions for subcutaneous administration of Nucala in a pre-filled pen or pre-filled syringe 
are provided at the end of the package leaflet. 
 
 
Disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
GlaxoSmithKline Trading Services Limited 
Currabinny 
Carrigaline 
County Cork 
Ireland. 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1043/003 1 pre-filled pen 
EU/1/15/1043/004 3 (3 x 1) pre-filled pens (multipack) 



15 

EU/1/15/1043/005 1 pre-filled syringe 
EU/1/15/1043/006 3 (3 x 1) pre-filled syringes (multipack) 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 02 December 2015 
 
 
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/


16 

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 
 
Nucala 100 mg powder for solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each vial contains 100 mg mepolizumab. After reconstitution, each ml of solution contains 100 mg 
mepolizumab. 
 
Mepolizumab is a humanised monoclonal antibody produced in Chinese hamster ovary cells by recombinant 
DNA technology. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder for solution for injection. 
 
Lyophilised white powder. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Nucala is indicated as an add-on treatment for severe refractory eosinophilic asthma in adults, adolescents 
and children aged 6 years and older (see section 5.1). 
 
4.2 Posology and method of administration 
 
Nucala should be prescribed by physicians experienced in the diagnosis and treatment of severe refractory 
eosinophilic asthma. 
 
Posology 
 
Adults and adolescents aged 12 years and older 
The recommended dose of mepolizumab is 100 mg administered subcutaneously once every 4 weeks. 
 
Children aged 6 to 11 years old 
The recommended dose of mepolizumab is 40 mg administered subcutaneously once every 4 weeks. 
 
Nucala 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 disease severity and level of control 
of exacerbations. 
 
Special populations 
 
Paediatric population 



17 

The posology of Nucala in children and adolescents aged between 6 to 17 years old with severe refractory 
eosinophilic asthma has been determined by limited efficacy, pharmacokinetic and pharmacodynamic studies 
and supported by modelling and simulation data (see sections 5.1 and 5.2). 
 
Elderly patients 
No dose adjustment is required for elderly patients (see section 5.2). 
 
Renal and hepatic impairment 
No dose adjustment is required in patients with renal or hepatic impairment (see section 5.2). 
 
Method of administration 
 
Nucala is for subcutaneous injection only and should be administered by a healthcare professional. It may be 
injected into the upper arm, thigh, or abdomen. 
 
The powder should be reconstituted prior to administration and the reconstituted solution should be used 
immediately. For instructions on the reconstitution of the medicinal product before administration, see 
section 6.6. 
 
Each vial of Nucala should be used for a single patient, and any remainder of the vial should be discarded. 
 
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 
 
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 in the patient file. 
 
Asthma exacerabations 
 
Nucala should not be used to treat acute asthma exacerbations. 
 
Asthma-related adverse symptoms or exacerbations may occur during treatment. Patients should be 
instructed to seek medical advice if their asthma remains uncontrolled or worsens after initiation of 
treatment. 
 
Corticosteroids 
 
Abrupt discontinuation of corticosteroids after initiation of Nucala therapy is not recommended. Reduction 
in corticosteroid doses, if required, should be gradual and performed under the supervision of a physician. 
 
Hypersensitivity and administration-related reactions 
 
Acute and delayed systemic reactions, including hypersensitivity reactions (e.g. anaphylaxis, urticaria, 
angioedema, rash, bronchospasm, hypotension), have occurred following administration of Nucala. These 
reactions generally occur within hours of administration, but in some instances have a delayed onset (i.e., 
typically within several days). These reactions may occur for the first time after a long duration of treatment 
(see section 4.8). 
 
Parasitic infections 
 



18 

Eosinophils may be involved in the immunological response to some helminth infections. Patients with pre-
existing helminth infections should be treated before starting therapy. If patients become infected whilst 
receiving treatment with Nucala and do not respond to anti-helminth treatment, temporary discontinuation of 
therapy should be considered. 
 
Excipients 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per 100 mg dose, i.e. essentially “sodium-
free”. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies have been performed. 
 
Cytochrome P450 enzymes, efflux pumps and protein-binding mechanisms are not involved in the clearance 
of mepolizumab. Increased levels of pro-inflammatory cytokines (e.g. IL-6), via interaction with their 
cognate receptors on hepatocytes, have been shown to suppress the formation of CYP450 enzymes and drug 
transporters, however, elevation of systemic pro-inflammatory markers in severe refractory eosinophilic 
asthma is minimal and there is no evidence of IL-5 receptor alpha expression on hepatocytes. The potential 
for interactions with mepolizumab is therefore considered low. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There is a limited amount of data (less than 300 pregnancy outcomes) from the use of mepolizumab in 
pregnant women.  
Mepolizumab crosses the placental barrier in monkeys. Animal studies do not indicate reproductive toxicity 
(see section 5.3). The potential for harm to a human fetus is unknown. 
 
As a precautionary measure, it is preferable to avoid the use of Nucala during pregnancy. Administration of 
Nucala to pregnant women should only be considered if the expected benefit to the mother is greater than 
any possible risk to the fetus. 
 
Breast-feeding 
 
There are no data regarding the excretion of mepolizumab in human milk. However, mepolizumab was 
excreted into the milk of cynomolgous monkeys at concentrations of less than 0.5% of those detected in 
plasma. 
 
A decision must be made whether to discontinue breast-feeding or to discontinue Nucala therapy taking into 
account the benefit of breast-feeding for the child and the benefit of therapy for the woman. 
 
Fertility 
 
There are no fertility data in humans. Animal studies showed no adverse effects of anti-IL5 treatment on 
fertility (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Nucala has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 



19 

Adults and adolescents 

In clinical studies in subjects with severe refractory eosinophilic asthma, the most commonly reported 
adverse reactions during treatment were headache, injection site reactions and back pain. 
 
Tabulated list of adverse reactions 
 
A total of 896 adults and 19 adolescent subjects with severe refractory eosinophilic asthma received either a 
subcutaneous or an intravenous dose of mepolizumab during three placebo-controlled clinical studies of 24 
to 52 weeks duration. The table below presents the adverse reactions from the two placebo-controlled studies 
in patients receiving mepolizumab 100 mg subcutaneously (n=263). 
 
The safety profile of mepolizumab in severe refractory eosinophilic asthma patients (n=998) treated for a 
median of 2.8 years (range 4 weeks to 4.5 years) in open-label extension studies was similar to that observed 
in the placebo-controlled studies. 
 
The frequency of adverse reactions is defined using the following convention: very common (≥1/10); 
common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare 
(<1/10,000); and not known (cannot be estimated from available data). Within each frequency grouping, 
adverse reactions are presented in order of decreasing seriousness. 
 

System Organ Class Adverse Reactions Frequency 
Infectionsand infestations  Lower respiratory tract infection 

Urinary tract infection 
Pharyngitis 
 

Common 
 

Immune system disorders Hypersensitivity reactions (systemic 
allergic)* 
Anaphylaxis** 

Common 
 
Rare 

Nervous system disorders  Headache Very common 
Respiratory, thoracic and 
mediastinal disorders  

Nasal congestion 
 

Common 

Gastrointestinal disorders Abdominal pain upper Common 
Skin and subcutaneous tissue 
disorders 

Eczema Common 

Musculoskeletal and 
connective tissue disorders 

Back pain Common 

General disorders and 
administration site conditions 

Administration-related reactions (systemic 
non allergic)*** 
Local injection site reactions 
Pyrexia 

Common 
 

* Systemic reactions including hypersensitivity have been reported at an overall incidence comparable to that 
of placebo. For examples of the associated manifestations reported and a description of the time to onset, see 
section 4.4. 

**From spontaneous post marketing reporting. 
 
*** The most common manifestations associated with reports of systemic non-allergic administration-related 
reactions were rash, flushing and myalgia; these manifestations were reported infrequently and in <1% of 
subjects receiving mepolizumab 100 mg subcutaneously. 
 
Description of selected adverse reaction 
 
Local injection site reactions 
 



20 

In 2 placebo-controlled studies the incidence of local injection site reactions with mepolizumab 100 mg 
subcutaneous and placebo was 8% and 3%, respectively. These events were all non-serious, mild to 
moderate in intensity and the majority resolved within a few days. Local injection site reactions occurred 
mainly at the start of treatment and within the first 3 injections with fewer reports on subsequent injections. 
The most common manifestations reported with these events included pain, erythema, swelling, itching, and 
burning sensation. 
 
Paediatric population 
 
Thirty-seven adolescents (aged 12-17) were enrolled in four placebo-controlled studies (25 mepolizumab 
treated intravenously or subcutaneously) of 24 to 52 weeks duration. Thirty -six paediatric patients (aged 6-
11) received mepolizumab subcutaneously in an open-label study for 12 weeks. After a treatment 
interruption of 8 weeks, 30 of these patients, received mepolizumab for a further 52 weeks. The safety 
profile was similar to that seen in adults. No additional adverse reactions were identified. 
 
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 
 
Single doses of up to 1,500 mg were administered intravenously in a clinical trial to patients with 
eosinophilic disease without evidence of dose-related toxicities. 
 
There is no specific treatment for an overdose with mepolizumab. If overdose occurs, the patient should be 
treated supportively with appropriate monitoring as necessary. 
 
Further management should be as clinically indicated or as recommended by the national poisons centre, 
where available. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Drugs for obstructive airway diseases, other systemic drugs for obstructive 
airway diseases, ATC code: R03DX09. 
 
Mechanism of action 
 
Mepolizumab is a humanised monoclonal antibody (IgG1, kappa), which targets human interleukin-5 (IL-5) 
with high affinity and specificity. IL-5 is the major cytokine responsible for the growth and differentiation, 
recruitment, activation and survival of eosinophils. Mepolizumab inhibits the bioactivity of IL-5 with 
nanomolar potency by blocking the binding of IL-5 to the alpha chain of the IL-5 receptor complex expressed 
on the eosinophil cell surface, thereby inhibiting IL-5 signalling and reducing the production and survival of 
eosinophils. 
 
Pharmacodynamic effects 
 
In patients with severe refractory eosinophilic asthma (adults/adolescents), following a dose of 100 mg 
administered subcutaneously every 4 weeks for 32 weeks, blood eosinophils were reduced from a geometric 
mean count at baseline of 290 to 40 cells/µL at week 32 (n=182), a reduction of 84% compared to placebo.  
This magnitude of blood eosinophils reduction was maintained in severe refractory eosinophilic asthma 
patients (n=998) treated for a median of 2.8 years (range 4 weeks to 4.5 years) in open-label extension 
studies. 

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


21 

In children aged 6 to 11 years old with severe refractory eosinophilic asthma administered mepolizumab 
subcutaneously every 4 weeks for 52 weeks, blood eosinophils were reduced from a geometric mean count at 
baseline to week 52 of 306 (n=16) to 48 (n=15) following 40 mg (for a weight < 40kg) and 331 to 
44 cells/µL (n=10) following 100 mg (for a weight ≥ 40 kg), a reduction from baseline of 85% and 87%, 
respectively. 
In adults, adolescents and children, this magnitude of reduction was observed within 4 weeks of treatment. 
 
Immunogenicity  
 
Consistent with the potentially immunogenic properties of protein and peptide therapeutics, patients may 
develop antibodies to mepolizumab following treatment. In the placebo-controlled trials, 15/260 (6%) of 
adults and adolescents treated with 100 mg dose subcutaneously had detectable anti-mepolizumab antibodies 
after having received at least one dose of mepolizumab. 
The immunogenicity profile of mepolizumab in severe refractory eosinophilic asthma patients (n=998) 
treated for a median of 2.8 years (range 4 weeks to 4.5 years) in open-label extension studies was similar to 
that observed in the placebo-controlled studies. 
In children aged 6 to 11 years old with severe refractory eosinophilic asthma following either 40 mg 
subcutaneously (for a weight < 40kg) or 100 mg subcutaneously (for a weight ≥ 40 kg), 2/35 (6%) had 
detectable anti-mepolizumab antibodies after having received at least one dose of mepolizumab during the 
initial short phase of the study. No children had detectable anti-mepolizumab antibodies during the long-term 
phase of the study. Neutralising antibodies were detected in one adult subject. Anti-mepolizumab antibodies 
did not discernibly impact the pharmacokinetics and pharmacodynamics of mepolizumab in the majority of 
patients and there was no evidence of a correlation between antibody titres and change in blood eosinophil 
level. 
 
Clinical efficacy  
 
The efficacy of mepolizumab in the treatment of a targeted group of patients with severe refractory 
eosinophilic asthma was evaluated in 3 randomised, double-blind, parallel-group clinical studies of between 
24-52 weeks duration, in patients aged 12 years and older. These patients either remained uncontrolled (at 
least two severe exacerbations in the previous 12 months) on their current standard of care, including at least 
high doses of inhaled corticosteroids (ICS) plus an additional maintenance treatment(s), or were dependent 
on systemic corticosteroids. Additional maintenance treatments included long-acting beta2 -adrenergic 
agonists (LABA), leukotriene modifiers, long-acting muscarinic antagonists (LAMA), theophylline, and oral 
corticosteroids (OCS). 
 
The two exacerbations studies MEA112997 and MEA115588 enrolled a total of 1192 patients, 60% females, 
with a mean age of 49 years (range 12– 82). The proportion of patients on maintenance OCS was 31% and 
24%, respectively. Patients were required to have a history of two or more severe asthma exacerbations 
requiring oral or systemic corticosteroid treatment in the past 12 months and reduced lung function at 
baseline (pre-bronchodilator FEV1<80% in adults and <90% in adolescents). The mean number of 
exacerbations in the previous year was 3.6 and the mean predicted pre-bronchodilator FEV1 was 60%. 
Patients continued to receive their existing asthma medicine during the studies. 
 
For the oral corticosteroid-sparing study MEA115575, a total of 135 patients were enrolled (55% were 
female; mean age of 50 years) who were being treated daily with OCS (5-35 mg per day), and high-dose ICS 
plus an additional maintenance medicine. 
 
Dose-ranging efficacy MEA112997 (DREAM) study 
 
In MEA112997, a randomised, double-blind, placebo-controlled, parallel-group, multi-centre study of 
52 weeks duration in 616 patients with severe refractory eosinophilic asthma, mepolizumab significantly 
reduced clinically significant asthma exacerbations (defined as worsening of asthma requiring use of 
oral/systemic corticosteroids and/or hospitalisation and/or emergency department visits) when administered 
in doses of 75 mg, 250 mg or 750 mg intravenously compared to placebo (see Table 1). 
 



22 

Table 1: Frequency of clinically significant exacerbations at week 52 in the intent to treat population 
 Intravenous Mepolizumab  Placebo 

75mg 
n=153 

250mg 
n=152 

750mg 
n=156 

 
n= 155 

Exacerbation rate/year 1.24 1.46 1.15 2.40 
Percent reduction 48% 39% 52%  

Rate ratio (95% CI) 0.52 (0.39, 0.69) 0.61(0.46, 0.81) 0.48 (0.36, 0.64)  

p-value <0.001 <0.001 <0.001 - 
 
 
Exacerbation reduction MEA115588 (MENSA) study  
 
MEA115588 was a randomised, double-blind, placebo-controlled, parallel-group, multi-centre study which 
evaluated the efficacy and safety of mepolizumab as add-on therapy in 576 patients with severe refractory 
eosinophilic asthma defined as peripheral blood eosinophils greater than or equal to 150 cells/μL at initiation 
of treatment or greater than or equal to 300 cells/μL within the past 12 months. 
 
Patients received mepolizumab 100 mg administered subcutaneously, mepolizumab 75 mg administered 
intravenously or placebo treatment once every 4 weeks over 32 weeks. The primary endpoint was the 
frequency of clinically significant exacerbations of asthma and the reductions for both mepolizumab 
treatment arms compared to placebo were statistically significant (p<0.001). Table 2 provides the results of 
the primary and secondary endpoints for patients treated with subcutaneous mepolizumab or placebo. 
 
Table 2: Results of primary and secondary endpoints at week 32 in the intent to treat population 
(MEA115588) 

 Mepolizumab 100 mg 
(subcutaneous) 

N= 194 

Placebo 
N= 191 

Primary endpoint 

Frequency of clinically significant exacerbations 

Exacerbation rate per year 0.83 1.74 
Percent reduction 
Rate ratio (95% CI) 

53% 
0.47 (0.35, 0.64) 

- 
 

p-value <0.001  

Secondary endpoints 

Frequency of exacerbations requiring hospitalisations/emergency room visits 

Exacerbation rate per year 0.08 0.20 
Percent reduction 
Rate ratio (95% CI) 

61% 
0.39 (0.18, 0.83) 

_ 

p-value 0.015  

Frequency of exacerbations requiring hospitalisation 

Exacerbations rate per year 0.03 0.10 
Percent reduction 
Rate ratio (95% CI) 

69% 
0.31 (0.11, 0.91) 

_ 

p-value 0.034  

Pre-bronchodilator FEV1 (mL) at week 32 

Baseline (SD) 1730 (659) 1860 (631) 



23 

 Mepolizumab 100 mg 
(subcutaneous) 

N= 194 

Placebo 
N= 191 

Mean Change from Baseline (SE) 183 (31) 86 (31) 
Difference (mepolizumab vs. placebo) 98  
95% CI (11, 184)  
p-value 0.028  

St. George’s Respiratory Questionnaire (SGRQ) at week 32 

Baseline (SD) 47.9 (19. 5) 46.9 (19.8) 
Mean Change From Baseline (SE) -16.0 (1.1) -9.0 (1.2) 
Difference (mepolizumab vs. placebo) -7.0  
95% CI (-10.2, -3.8)  
p-value <0.001  

 
 
Reduction of exacerbation rate by baseline blood eosinophil count 
 
Table 3 shows the results of a combined analysis of the two exacerbation studies (MEA112997 and 
MEA115588) by baseline blood eosinophil count. The rate of exacerbations in the placebo arm increased 
with increasing baseline blood eosinophil count. The reduction rate with mepolizumab was greater in 
patients with higher blood eosinophil counts. 
 
Table 3: Combined analysis of the rate of clinically significant exacerbations by baseline blood 
eosinophil count in patients with severe refractory eosinophilic asthma 

 Mepolizumab 
75 mg IV/100 mg SC 

N=538 

Placebo 
N=346 

MEA112997+MEA115588 
<150 cells/µL   
n  123 66 
Exacerbation rate per year 1.16 1.73 
Mepolizumab vs. placebo   
Rate ratio (95% CI) 0.67 (0.46,0.98) --- 
150 to <300 cells/µL   
n  139 86 
Exacerbation rate per year 1.01 1.41 
Mepolizumab vs. placebo   
Rate ratio (95% CI) 0.72 (0.47,1.10) --- 
300 to <500 cells/µL   
n  109 76 
Exacerbation rate per year 1.02 1.64 
Mepolizumab vs. placebo   
Rate ratio (95% CI) 0.62 (0.41,0.93) --- 
≥500 cells/µL   
n  162 116 
Exacerbation rate per year 0.67 2.49 
Mepolizumab vs. placebo   
Rate ratio (95% CI) 0.27 (0.19,0.37) --- 

 
Oral corticosteroid reduction study MEA115575 (SIRIUS) 
 
MEA115575 evaluated the effect of mepolizumab 100 mg administered subcutaneously on reducing the 
requirement for maintenance oral corticosteroids (OCS) while maintaining asthma control in subjects with 
severe refractory eosinophilic asthma. Patients had a blood eosinophil count of ≥150/µL at baseline or a 



24 

blood eosinophil count of ≥300/µL in the 12 months prior to screening. Patients were administered 
mepolizumab or placebo treatment once every 4 weeks over the treatment period. Patients continued to 
receive their existing asthma medicine during the study with the exception of their OCS dose which was 
reduced every 4 weeks during the OCS reduction phase (Weeks 4-20), as long as asthma control was 
maintained. 
 
A total of 135 patients were enrolled: mean age was 50 years, 55% were female, and 48% had been receiving 
oral steroid therapy for at least 5 years. The baseline mean prednisone equivalent dose was approximately 
13 mg per day. 
 
The primary endpoint was the percent reduction in daily OCS dose (weeks 20-24), whilst maintaining 
asthma control by defined dose reduction categories (see Table 4). Predefined categories included percent 
reductions ranging from 90-100% reduction, to no decrease in the prednisone dose from the end of the 
optimisation phase. The comparison between mepolizumab and placebo was statistically significant 
(p=0.008). 
 
Table 4: Results of the primary and secondary endpoints in MEA115575 

 ITT Population 
 Mepolizumab  

100 mg 
(subcutaneous) 

N= 69 

Placebo 
N= 66 

Primary endpoint 

Percent reduction in OCS from baseline (weeks 20-24)  

90% - 100% 
75% - <90% 
50% - <75% 
>0% - <50% 
No decrease in OCS/lack of asthma 
control/ withdrawal from treatment 

16 (23%) 
12 (17%) 
9 (13%) 
7 (10%) 

25 (36%) 

7(11%) 
5 (8%) 

10 (15%) 
7(11%) 

37 (56%) 

Odds ratio (95% CI) 2.39 (1.25, 4.56)  
p-value 0.008  

Secondary endpoints (weeks 20-24) 

Reduction in the daily OCS dose 
to 0 mg/d  

10 (14%) 5 (8%) 

Odds ratio (95% CI) 1.67 (0.49, 5.75)  
p-value 0. 414   
Reduction in the daily OCS dose 
to ≤5mg/day 

37 (54%) 21 (32%) 

Odds ratio (95% CI) 2.45 (1.12, 5.37)  
p-value 0.025  
Median % reduction in daily OCS 
dose from baseline (95% CI) 

50.0 (20.0, 75.0) 0.0 (-20.0, 33.3) 

Median difference (95% CI)  -30.0 (-66.7, 0.0)  
p-value 0.007   

 
Open-label extension studies in severe refractory eosinophilic asthma MEA115666 (COLUMBA), 
MEA115661 (COSMOS) and 201312 (COSMEX) 
 
The long-term efficacy profile of Nucala in severe refractory eosinophilic asthma patients (n=998) treated for 
a median of 2.8 years (range 4 weeks to 4.5 years) in open-label extension studies MEA115666, 
MEA115661 and 201312  was generally consistent with the 3 placebo-controlled studies. 



25 

 
Paediatric population 
 
Severe refractory eosinophilic asthma 
In MEA115588 and in the double-blind placebo-controlled study 200862, there were 34 adolescents (12 to 
17 years old). Of these 34 subjects: 12 received placebo, 9 received mepolizumab 75 mg intravenously, and 
13 received 100 mg subcutaneously. In a combined analysis of these studies, a 40% reduction in clinically 
significant exacerbations was observed in adolescents following mepolizumab treatment compared to 
placebo (rate ratio 0.60; 95% CI: 0.17, 2.10). 
 
5.2 Pharmacokinetic properties 
 
Following subcutaneous dosing in patients with asthma, mepolizumab exhibited approximately dose-
proportional pharmacokinetics over a dose range of 12.5 mg to 250 mg. 
 
Absorption 
 
Following subcutaneous administration to healthy subjects or patients with asthma, mepolizumab was 
absorbed slowly with a median time to reach maximum plasma concentration (Tmax) ranging from 4 to 8 
days. 
Following a single subcutaneous administration in the abdomen, thigh or arm of healthy subjects, 
mepolizumab absolute bioavailability was 64%, 71% and 75%, respectively. In patients with asthma the 
absolute bioavailability of mepolizumab administered subcutaneously in the arm ranged from 74-80%. 
Following repeat subcutaneous administration every 4 weeks, there is approximately a two-fold 
accumulation at steady state. 
 
Distribution 
 
Following a single intravenous administration to patients with asthma, mepolizumab distributes into a mean 
volume of distribution of 55 to 85 mL/kg. 
 
Biotransformation 
 
Mepolizumab is a humanized IgG1 monoclonal antibody degraded by proteolytic enzymes which are widely 
distributed in the body and not restricted to hepatic tissue. 
 
Elimination 
 
Following a single intravenous administration to patients with asthma, the mean systemic clearance (CL) 
ranged from 1.9 to 3.3 mL/day/kg, with a mean terminal half-life of approximately 20 days. Following 
subcutaneous administration of mepolizumab the mean terminal half-life (t1/2) ranged from 16 to 22 days. In 
the population pharmacokinetic analysis estimated mepolizumab systemic clearance was 3.1 mL/day/kg. 
 
Paediatric population  
 
There are limited pharmacokinetic data available in the paediatric population (59 subjects with eosinophilic 
esophagitis, 55 subjects with severe refractory eosinophilic asthma). Intravenous mepolizumab 
pharmacokinetics was evaluated by population pharmacokinetic analysis in a paediatric study conducted in 
subjects aged 2–17 years old with eosinophilic esophagitis. Paediatric pharmacokinetics was largely 
predictable from adults, after taking into account bodyweight. Mepolizumab pharmacokinetics in adolescent 
subjects with severe refractory eosinophilic asthma included in the phase 3 studies were consistent with 
adults (see section 4.2). 
 
Paediatric pharmacokinetics following subcutaneous administration in subjects 6 to 11 years old with severe 
refractory eosinophilic asthma was investigated in an open label, uncontrolled study of 12-weeks duration. 
Paediatric pharmacokinetics were broadly consistent with adults and adolescents after accounting for 



26 

bodyweight and bioavailability. The absolute subcutaneous bioavailability appears complete compared to 
that observed in adults and adolescents of 76%. Exposure following subcutaneous administration of either 40 
mg (for a weight < 40kg) or 100 mg (for a weight ≥ 40 kg) was 1.32 and 1.97 times of that observed in adults 
at 100 mg. 
Investigation of a 40 mg subcutaneous dosing regimen administered every 4 weeks in children 6 to 11 years 
old over a 15-70 kg broad weight range by PK modelling and simulation predicts that the exposure of this 
dosing regimen would remain on average within 38% of adults at 100 mg. This dosing regimen is considered 
acceptable due to the wide therapeutic index of mepolizumab. 
 
Special populations 
 
Elderly patients (≥65 years old) 
 
There are limited pharmacokinetic data available in elderly patients (≥65 years old) across all clinical studies 
(N=90). However, in the population pharmacokinetic analysis, there were no indications of an effect of age 
on the pharmacokinetics of mepolizumab over the age range of 12 to 82 years. 
 
Renal impairment 
No formal studies have been conducted to investigate the effect of renal impairment on the pharmacokinetics 
of mepolizumab. Based on population pharmacokinetic analyses, no dose adjustment is required in patients 
with creatinine clearance values between 50-80 mL/min. There are limited data available in patients with 
creatinine clearance values <50 mL/min. 
 
Hepatic impairment 
No formal studies have been conducted to investigate the effect of hepatic impairment on the 
pharmacokinetics of mepolizumab. Since mepolizumab is degraded by widely distributed proteolytic 
enzymes, not restricted to hepatic tissue, changes in hepatic function are unlikely to have any effect on the 
elimination of mepolizumab. 
 
5.3 Preclinical safety data 
 
As mepolizumab is a monoclonal antibody, no genotoxicity or carcinogenicity studies have been conducted. 
 
Animal toxicology and/or pharmacology 
 
Non-clinical data reveal no special hazards for humans based on conventional studies of safety 
pharmacology or repeated dose toxicity studies in monkeys. Intravenous and subcutaneous administration to 
monkeys was associated with reductions in peripheral and lung eosinophil counts, with no toxicological 
findings. 
 
Eosinophils are thought to be associated with immune system responses to some parasitic infections. Studies 
conducted in mice treated with anti-IL-5 antibodies or genetically deficient in IL-5 or eosinophils have not 
shown impaired ability to clear parasitic infections. The relevance of these findings for humans is unknown. 
 
Fertility 
 
No impairment of fertility was observed in a fertility and general reproduction toxicity study in mice 
performed with an analogous antibody that inhibits IL-5 in mice. This study did not include a littering or 
functional offspring assessment. 
 
Pregnancy 
 
In monkeys, mepolizumab had no effect on pregnancy or on embryonic/fetal and postnatal development 
(including immune function) of the offspring. Examinations for internal or skeletal malformations were not 
performed. Data in cynomolgus monkeys demonstrate that mepolizumab crossed the placenta. 



27 

Concentrations of mepolizumab were about 1.2-2.4 times higher in infants than in mothers for several 
months post partum and did not affect the immune system of the infants. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sucrose 
Sodium phosphate dibasic heptahydrate 
Polysorbate 80 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products. 
 
6.3 Shelf life 
 
4 years. 
 
After reconstitution  
 
Chemical and physical stability of the reconstituted medicinal product have been demonstrated for 8 hours 
when stored below 30°C. 
 
From a microbiological point of view, unless the method of reconstitution precludes the risk of microbial 
contamination, the product should be used immediately. If not used immediately, in-use storage times and 
conditions are the responsibility of user. 
 
6.4 Special precautions for storage 
 
Store below 25°C. 
Do not freeze. 
Keep the vial in the outer carton in order to protect from light. 
 
For storage conditions after reconstitution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container  
 
Clear, colourless 10 mL type I glass vial, with bromobutyl rubber stopper and a grey aluminium overseal 
with a plastic flip-cap containing 100 mg powder for solution for injection. 
 
Pack sizes:  
1 vial 
Multipack comprising 3 (3 packs of 1) vials 
 
Not all pack-sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Reconstitution should be carried out under aseptic conditions.  
 
Instructions for reconstitution for each vial 
1. Reconstitute the contents of the vial with 1.2 mL of sterile water for injections preferably using a 2 

to 3 mL syringe and a 21 gauge needle. The stream of sterile water should be directed vertically, onto the 



28 

centre of the lyophilised cake. Allow the vial to sit at room temperature during reconstitution, gently 
swirling the vial for 10 seconds with circular motion at 15-second intervals until the powder is dissolved. 
 
Note: The reconstituted solution must not be shaken during the procedure as this may lead to product 
foaming or precipitation. Reconstitution is typically complete within 5 minutes after the sterile water has 
been added, but it may take additional time.  
 

2. If a mechanical reconstitution device (swirler) is used to reconstitute Nucala, reconstitution can be 
accomplished by swirling at 450 rpm for no longer than 10 minutes. Alternatively, swirling at 1000 rpm 
for no longer than 5 minutes is acceptable. 

3. Following reconstitution, Nucala should be visually inspected for particulate matter and clarity prior to 
use.  The solution should be clear to opalescent, and colourless to pale yellow or pale brown, free of 
visible particles. Small air bubbles, however, are expected and acceptable. If particulate matter remains 
in the solution or if the solution appears cloudy or milky, the solution must not be used.  

4. The reconstituted solution, if not used immediately must be: 
• Protected from sunlight  
• Stored below 30°C, not frozen 
• Discarded if not used within 8 hours of reconstitution 

 
Instructions for administration of 100 mg dose 
1. For subcutaneous administration, a 1 mL polypropylene syringe fitted with a disposable needle 21 gauge 

to 27 gauge x 0.5 inch (13 mm) should preferably be used. 
2. Just prior to administration, remove 1 mL of reconstituted Nucala. Do not shake the reconstituted 

solution during the procedure as this could lead to product foaming or precipitation. 
3. Administer the 1 mL injection (equivalent to 100 mg mepolizumab) subcutaneously into the upper arm, 

thigh, or abdomen. 
 

Instructions for administration of 40 mg dose 
1. For subcutaneous administration, a 1 mL polypropylene syringe fitted with a disposable needle 21 gauge 

to 27 gauge x 0.5 inch (13 mm) should preferably be used. 
2. Just prior to administration, remove 0.4mL of reconstituted Nucala. Do not shake the reconstituted 

solution during the procedure as this could lead to product foaming or precipitation. Dispose of the 
remaining solution. 

3. Administer the 0.4mL injection (equivalent to 40 mg mepolizumab) subcutaneously into the upper arm, 
thigh, or abdomen.  

 
Disposal 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
GlaxoSmithKline Trading Services Limited 
Currabinny 
Carrigaline 
County Cork 
Ireland. 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1043/001 
EU/1/15/1043/002 
 
 



29 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 02 December 2015 
 
 
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/


30 

  
  
  
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 

 

A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURERS 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 
 

 



31 

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

 
Name and address of the manufacturers of the biological active substance  
 
GlaxoSmithKline LLC 
893 River Road 
Conshohocken,  
PA 19428 
United States 
 
Or 
 
Human Genome Sciences, Inc. 
9911 Belward Campus Drive 
Rockville, MD 20850  
United States 
 
Name and address of the manufacturers responsible for batch release 
 
GlaxoSmithKline Manufacturing S.P.A. 
Strada Provinciale Asolana No. 90, 
Torrile, 43056, Parma, 
Italy 
 
Or 

 
Glaxo Operations UK Ltd 
Harmire Road 
Barnard Castle 
County Durham, DL12 8DT  
United Kingdom 
 
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  
 
The requirements for submission of periodic safety update reports for this medicinal product are set out in 
the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC 
and any subsequent updates published on the European medicines web-portal. 
The marketing authorisation holder shall submit the first periodic safety update report for this product 
within 6 months following authorisation. 
 



32 

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

USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the agreed 
RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent updates of the 
RMP. 
An updated RMP should be submitted: 

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

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

 
  



33 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
LABELLING AND PACKAGE LEAFLET  

  



34 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



35 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON – PRE-FILLED PEN 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Nucala 100 mg solution for injection in pre-filled pen 
 
mepolizumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 1 ml pre-filled pen contains 100 mg mepolizumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: sucrose, sodium phosphate dibasic heptahydrate, citric acid monohydrate, polysorbate 80, 
EDTA disodium dihydrate, water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in pre-filled pen. 
 
1 pre-filled pen. 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Read the package leaflet before use. 
Subcutaneous use. 
For single use only. 
 
PRESS HERE TO OPEN 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

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



36 

Store in a refrigerator. 
Do not freeze. 
Store pen in the original carton in order to protect from light. 
Time out of refrigeration should not exceed a maximum of 7 days when protected from light and stored 
below 30°C. 
 
 
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 
 
GlaxoSmithKline Trading Services Ltd, Currabinny, Co. Cork, Ireland. 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1043/003 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
nucala pen 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 



37 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER LABEL FOR PRE-FILLED PEN MULTIPACK (WITH BLUE BOX)  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Nucala 100 mg solution for injection in pre-filled pen  
 
mepolizumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 1 ml pre-filled pen contains 100 mg mepolizumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: sucrose, sodium phosphate dibasic heptahydrate, citric acid monohydrate, polysorbate 80, 
EDTA disodium dihydrate, water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in pre-filled pen 
Multipack: 3 pre-filled pens (3 packs of 1 pre-filled pen). 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Subcutaneous use. 
For single use only. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 



38 

Store pen in the original carton in order to protect from light. 
Time out of refrigeration should not exceed a maximum of 7 days when protected from light and stored 
below 30°C. 
 
 
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 
 
GlaxoSmithKline Trading Services Ltd, Currabinny, Co. Cork, Ireland. 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1043/004 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
nucala pen 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
  



39 

 
 
PARTICULARS TO APPEAR ON INTERMEDIATE PACKAGING 
 
INTERMEDIATE CARTON - PRE-FILLED PEN MULTIPACK (WITHOUT BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Nucala 100 mg solution for injection in pre-filled pen  
 
mepolizumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 1 ml pre-filled pen contains 100 mg mepolizumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: sucrose, sodium phosphate dibasic heptahydrate, citric acid monohydrate, polysorbate 80, 
EDTA disodium dihydrate, water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in pre-filled pen. 
 
1 pre-filled pen. Component of a multipack, can’t be sold separately.  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Subcutaneous use. 
For single use only. 
 
PRESS HERE TO OPEN 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

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



40 

 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Store pen in the original carton in order to protect from light. 
Time out of refrigeration should not exceed a maximum of 7 days when protected from light and stored 
below 30°C. 
 
 
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 
 
GlaxoSmithKline Trading Services Ltd, Currabinny, Co. Cork, Ireland. 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
nucala pen 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
 
  



41 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PRE-FILLED PEN LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Nucala 100 mg injection 
mepolizumab 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 ml 
 
 
6. OTHER 
 

 
  



42 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON - PRE-FILLED SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Nucala 100 mg solution for injection in pre-filled syringe 
mepolizumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 1 ml pre-filled syringe contains 100 mg mepolizumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: sucrose, sodium phosphate dibasic heptahydrate, citric acid monohydrate, polysorbate 80, 
EDTA disodium dihydrate, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in pre-filled syringe. 
 
1 pre-filled syringe. 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Read the package leaflet before use. 
Subcutaneous use. 
For single use only. 
 
PRESS HERE TO OPEN 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

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



43 

Do not freeze. 
Store syringe in the original carton in order to protect from light. 
Time out of refrigeration should not exceed a maximum of 7 days when protected from light and stored 
below 30°C. 
 
 
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 
 
GlaxoSmithKline Trading Services Ltd, Currabinny, Co. Cork, Ireland. 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1043/005 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
nucala syringe 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 
  



44 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER LABEL – FOR PRE-FILLED SYRINGE MULTIPACK (WITH BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Nucala 100 mg solution for injection in pre-filled syringe  
mepolizumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 1 ml pre-filled syringe contains 100 mg mepolizumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: sucrose, sodium phosphate dibasic heptahydrate, citric acid monohydrate, polysorbate 80, 
EDTA disodium dihydrate, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in pre-filled syringe. 
 
Multipack: 3 pre-filled syringes (3 packs of 1 pre-filled syringe). 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Subcutaneous use. 
For single use only. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 



45 

Store syringe in the original carton in order to protect from light. 
Time out of refrigeration should not exceed a maximum of 7 days when protected from light and stored 
below 30°C. 
 
 
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 
 
GlaxoSmithKline Trading Services Ltd, Currabinny, Co. Cork, Ireland. 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1043/006 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
nucala syringe 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
  



46 

PARTICULARS TO APPEAR ON INTERMEDIATE PACKAGING 
 
INTERMEDIATE CARTON – PRE-FILLED SYRINGE MULTIPACK (WITHOUT BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Nucala 100 mg solution for injection in pre-filled syringe  
mepolizumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 1 ml pre-filled syringe contains 100 mg mepolizumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: sucrose, sodium phosphate dibasic heptahydrate, citric acid monohydrate, polysorbate 80, 
EDTA disodium dihydrate, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in pre-filled syringe. 
 
1 pre-filled syringe. Component of a multipack, can’t be sold separately. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Subcutaneous use. 
For single use only. 
 
PRESS HERE TO OPEN 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

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



47 

Store in a refrigerator. 
Do not freeze. 
Store syringe in the original carton in order to protect from light. 
Time out of refrigeration should not exceed a maximum of 7 days when protected from light and stored 
below 30°C. 
 
 
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 
 
GlaxoSmithKline Trading Services Ltd, Currabinny, Co. Cork, Ireland. 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
nucala syringe 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
 
  



48 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PRE-FILLED SYRINGE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Nucala 100 mg injection 
mepolizumab 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 ml 
 
 
6. OTHER 
 
 
  



49 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON (INDIVIDUAL PACKS INCLUDING BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Nucala 100 mg powder for solution for injection 
mepolizumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains 100 mg mepolizumab (100 mg/ml after reconstitution)  
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: Sucrose, sodium phosphate dibasic heptahydrate and polysorbate 80 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for solution for injection 
1 vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use after reconstitution. 
Read the package leaflet before use. 
 
PRESS HERE TO OPEN 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
For single use only. 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store below 25°C. 



50 

Do not freeze. 
Store in the original container 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 
 
GlaxoSmithKline Trading Services Ltd. 
Currabinny 
Co. Cork 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1043/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
  



51 

PARTICULARS TO APPEAR ON OUTER PACKAGING 
 
MULTIPACK CARTON (3 PACKS OF 1 VIAL – WITH BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Nucala 100 mg powder for solution for injection 
mepolizumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains 100 mg mepolizumab (100 mg/ml after reconstitution)  
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: Sucrose, sodium phosphate dibasic heptahydrate and polysorbate 80 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for solution for injection 
Multipack: 3 (3 packs of 1) vials  
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use after reconstitution. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store below 25°C. 
Do not freeze. 
Store in the original container to protect from light. 
 



52 

 
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 
 
GlaxoSmithKline Trading Services Ltd. 
Currabinny 
Co. Cork 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1043/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
  



53 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON (MULTIPACK ONLY WITHOUT BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Nucala 100 mg powder for solution for injection 
mepolizumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains 100 mg mepolizumab (100 mg/ml after reconstitution)  
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: Sucrose, sodium phosphate dibasic heptahydrate and polysorbate 80 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Component of a multipack, can’t be sold separately. 
Powder for solution for injection 
1vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Subcutaneous use after reconstitution. 
Read the package leaflet before use. 
 
PRESS HERE TO OPEN 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
For single use only. 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store below 25°C. 



54 

Do not freeze. 
Store in the original container 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 
 
GlaxoSmithKline Trading Services Ltd. 
Currabinny 
Co. Cork 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/15/1043/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
 
  



55 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Nucala 100 mg powder for solution for injection 
mepolizumab 
SC  
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
100 mg 
 
 
6. OTHER 
 
 

  



56 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 
  



57 

Package leaflet: Information for the user  
 

Nucala 100 mg solution for injection in pre-filled pen 
 

mepolizumab 
 

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. 
- 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 Nucala is and what it is used for  
2. What you need to know before you use Nucala  
3. How to use Nucala 
4. Possible side effects  
5. How to store Nucala 
6. Contents of the pack and other information 
7. Step-by-step instructions for use 
 
1. What Nucala is and what it is used for 
 
Nucala contains the active substance mepolizumab, a monoclonal antibody, a type of protein designed to 
recognise a specific target substance in the body. It is used to treat severe asthma in adults, adolescents and 
children aged 6 years and older. 
 
Some people with severe asthma have too many eosinophils (a type of white blood cell) in the blood and 
lungs. This condition is called eosinophilic asthma – the type of asthma Nucala can treat. 
 
Nucala can reduce your number of asthma attacks, if you or your child are already using medicines such as 
high dose inhalers, but your asthma is not well controlled by these medicines.  
If you are taking medicines called oral corticosteroids, Nucala can also help reduce the daily dose you need 
to control your asthma. 
 
Mepolizumab, the active substance in Nucala, blocks a protein called interleukin-5. By blocking the action of 
this protein, it limits the production of more eosinophils from the bone marrow and lowers the number of 
eosinophils in the bloodstream and the lungs. 
 
2. What you need to know before you use Nucala 
 
Do not use Nucala: 
- if you are allergic to mepolizumab or any of the other ingredients of this medicine (listed in section 6). 

 Check with your doctor if you think this applies to you. 
 

Warnings and precautions 
Talk to your doctor before using this medicine. 
 
Worsening asthma 



58 

Some people get asthma-related side effects, or their asthma may become worse, during treatment with 
Nucala. 

 Tell your doctor or nurse if your asthma remains uncontrolled, or gets worse, after you start 
Nucala treatment. 

 
Allergic and injection site reactions 
Medicines of this type (monoclonal antibodies) can cause severe allergic reactions when injected into the 
body (see section 4, ‘Possible side effects’).  
 If you may have had a similar reaction to any injection or medicine: 

 Tell your doctor before you are given Nucala. 
 
Parasitic infections 
Nucala 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 Nucala. If you live in a region where these 
infections are common or if you are travelling to such a region: 

 Check with your doctor if you think any of these may apply to you. 
 
Children and adolescents 
The pre-filled pen is not intended for use in children below 12 years of age. 
For children aged 6-11 years, contact your doctor who will prescribe the recommended dose of Nucala which 
will be administered by a nurse or doctor. 
 
Other medicines and Nucala 
Tell your doctor if you are taking, have recently taken or might take any other medicines. 
 
Other medicines for asthma 

 Don’t suddenly stop taking your preventer medicines for your asthma once you have started 
Nucala. These medicines (especially ones called corticosteroids) must be stopped gradually, under 
the direct supervision of your doctor and dependant on your response to Nucala. 

 
Pregnancy and breast-feeding  
If you are pregnant, if you think you may be pregnant or are planning to have a baby, ask your doctor for 
advice before using this medicine.  
 
It is not known whether the ingredients of Nucala can pass into breast milk. If you are breast-feeding, you 
must check with your doctor before you use Nucala. 
 
Driving and using machines 
The possible side effects of Nucala are unlikely to affect your ability to drive or use machines. 
 
Nucala contains sodium  
This medicine contains less than 1 mmol sodium (23 mg) per 100 mg dose, i.e., it is essentially “sodium-
free”. 
 
3. How to use Nucala 
 
Nucala is given by injection just under the skin (subcutaneous injection).   
 
Your doctor or nurse will decide if you or your caregiver can inject Nucala. If appropriate, they will then 
provide training to show you or your caregiver the correct way to use Nucala.  
 
The recommended dose for adults and adolescents aged 12 years and older is 100 mg. You will have 1 
injection every four weeks. 
 
Instructions for using the pre-filled pen are given on the other side of this leaflet. 



59 

 
 
If you use more Nucala than you should 
If you think you have injected too much Nucala, contact your doctor for advice.  
 
If a dose of Nucala is missed 
You or your caregiver should inject the next dose of Nucala as soon as you remember. If you do not notice 
that you have missed a dose until it is already time for your next dose, then just inject the next dose as 
planned. If you are not sure what to do, ask your doctor, pharmacist or nurse. 
 
Stopping treatment with Nucala 
Do not stop injections of Nucala unless your doctor advises you to. Interrupting or stopping the treatment 
with Nucala may cause your asthma symptoms and attacks to come back. 

 
If your asthma symptoms get worse while receiving injections of Nucala  
 Call your doctor. 
 

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. The side effects 
caused by Nucala are usually mild to moderate but can occasionally be serious. 
 
Allergic reactions 
Some people may have allergic or allergic-like reactions. These reactions may be common (they can affect 
up to 1 in 10 people). They usually occur within minutes to hours after the injection, but sometimes 
symptoms can start up to several days later. 

Symptoms can include: 
• chest tightness, cough, difficulty breathing  
• fainting, dizziness, feeling lightheaded (due to a drop in blood pressure)  
• swelling of eyelids, face, lips, tongue or mouth  
• hives 
• rash 

 
 Seek medical attention immediately if you think you or your child may be having a reaction. 

 
If you may have had a similar reaction to any injection or medicine:  

 Tell your doctor before you or your child are given Nucala. 
 
Other side effects include: 
 
Very common side effects 
These may affect more than 1 in 10 people:  

• headache 
 
Common side effects 
These may affect up to 1 in 10 people:  

• chest infection - symptoms of which may include cough and fever (high temperature) 
• urinary tract infection (blood in urine, painful and frequent urination, fever, pain in lower back) 
• upper abdominal pain (stomach pain or discomfort in the upper area of the stomach) 
• fever (high temperature) 
• eczema (itchy red patches on the skin) 
• injection-site reaction (pain, redness, swelling, itching, and burning sensation of the skin near where 

the injection was given) 



60 

• back pain 
• pharyngitis (sore throat) 
• nasal congestion (stuffy nose) 

 
Rare side effects  
These may affect up to 1 in 1,000 people:  

• severe allergic reactions (anaphylaxis) 
 

 Tell your doctor or a nurse immediately if you get any of these symptoms. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor 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 Nucala 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use Nucala 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). 
 
Do not freeze. 
 
Store in the original package in order to protect from light. 
 
The Nucala pre-filled pen can be removed from the refrigerator and kept in its unopened carton for up to 7 
days at room temperature (up to 30°C), when protected from light. Discard if left out of the refrigerator for 
more than 7 days. 
 
6. Contents of the pack and other information 
 
What Nucala contains 
The active substance is mepolizumab.  
 
Each 1 mL pre-filled pen contains 100 mg of mepolizumab. 
The other ingredients are sucrose, sodium phosphate dibasic heptahydrate, citric acid monohydrate, 
polysorbate 80, EDTA disodium dihydrate, water for injections. 
 
What Nucala looks like and contents of the pack 
 
Nucala is supplied as a 1 mL clear to opalescent, colourless to pale yellow to pale brown solution in a single 
use pre-filled pen. 
 
Nucala is available in a pack containing 1 pre-filled pen, or in a multipack comprised of 3 x 1 pre-filled pen. 
 
Marketing Authorisation Holder 
GlaxoSmithKline Trading Services Limited 
Currabinny 
Carrigaline 
County Cork 
Ireland  
 
Manufacturer 

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


61 

GlaxoSmithKline Manufacturing S.P.A 
Strada Provinciale Asolana, No 90 
43056 San Polo di Torrile, Parma 
Italy 
 
Or 
 
Glaxo Operations UK Ltd 
Harmire Road 
Barnard Castle 
County Durham, DL12 8DT  
United Kingdom 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
GlaxoSmithKline Pharmaceuticals s.a./n.v. 
Tél/Tel: + 32 (0) 10 85 52 00 
 

Lietuva 
GlaxoSmithKline Lietuva UAB 
Tel: + 370 5 264 90 00 
info.lt@gsk.com 
 

България 
ГлаксоСмитКлайн ЕООД  
Teл.: + 359 2 953 10 34 
 

Luxembourg/Luxemburg 
GlaxoSmithKline Pharmaceuticals s.a./n.v. 
Belgique/Belgien 
Tél/Tel: + 32 (0) 10 85 52 00 
 

Česká republika 
GlaxoSmithKline, s.r.o. 
Tel: + 420 222 001 111 
cz.info@gsk.com 

Magyarország 
GlaxoSmithKline Kft. 
Tel.: + 36 1 225 5300 
 

Danmark 
GlaxoSmithKline Pharma A/S 
Tlf: + 45 36 35 91 00 
dk-info@gsk.com 
 

Malta 
GlaxoSmithKline (Malta) Limited 
Tel: + 356 21 238131 

Deutschland 
GlaxoSmithKline GmbH & Co. KG 
Tel.: + 49 (0)89 36044 8701 
produkt.info@gsk.com 
 

Nederland 
GlaxoSmithKline BV 
Tel: + 31 (0)30 6938100 
nlinfo@gsk.com  

Eesti 
GlaxoSmithKline Eesti OÜ 
Tel: + 372 6676 900 
estonia@gsk.com  

Norge 
GlaxoSmithKline AS 
Tlf: + 47 22 70 20 00 
 
 

Ελλάδα 
GlaxoSmithKline A.E.B.E. 
Τηλ: + 30 210 68 82 100 
 

Österreich 
GlaxoSmithKline Pharma GmbH 
Tel: + 43 (0)1 97075 0 
at.info@gsk.com 
 

España 
GlaxoSmithKline, S.A. 
Tel: + 34 902 202 700 
es-ci@gsk.com 
 

Polska 
GSK Services Sp. z o.o. 
Tel.: + 48 (0)22 576 9000 



62 

France 
Laboratoire GlaxoSmithKline 
Tél: + 33 (0)1 39 17 84 44 
diam@gsk.com 
 

Portugal 
GlaxoSmithKline – Produtos Farmacêuticos, Lda. 
Tel: + 351 21 412 95 00 
FI.PT@gsk.com  

Hrvatska 
GlaxoSmithKline d.o.o. 
Tel: +385 1 6051999 
 

România 
GlaxoSmithKline (GSK) S.R.L.  
Tel: + 4021 3028 208 

Ireland 
GlaxoSmithKline (Ireland) Limited 
Tel: + 353 (0)1 4955000 
 

Slovenija 
GlaxoSmithKline d.o.o. 
Tel: + 386 (0)1 280 25 00 
medical.x.si@gsk.com 
 

Ísland 
Vistor hf. 
Sími: + 354 535 7000 
 

Slovenská republika 
GlaxoSmithKline Slovakia s. r. o. 
Tel: + 421 (0)2 48 26 11 11 
recepcia.sk@gsk.com 
 

Italia 
GlaxoSmithKline S.p.A. 
Tel: + 39 (0)45 9218 111 

Suomi/Finland 
GlaxoSmithKline Oy 
Puh/Tel: + 358 (0)10 30 30 30 
Finland.tuoteinfo@gsk.com 
 

Κύπρος 
GlaxoSmithKline (Cyprus) Ltd 
Τηλ: + 357 22 39 70 00 
gskcyprus@gsk.com  

Sverige 
GlaxoSmithKline AB 
Tel: + 46 (0)8 638 93 00 
info.produkt@gsk.com 
 

Latvija 
GlaxoSmithKline Latvia SIA 
Tel: + 371 67312687 
lv-epasts@gsk.com 
 

United Kingdom 
GlaxoSmithKline UK Ltd 
Tel: + 44 (0)800 221441 
customercontactuk@gsk.com 
 

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

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


63 

7. Step by step instructions for using the pre-filled pen 
 

Administer once every four weeks. 
 
Follow these instructions on how to use the pre-filled pen. Failure to follow these instructions may affect 
proper function of the pre-filled pen. You should also receive training on how to use the pre-filled pen. 
Nucala pre-filled pen is for use under the skin only (subcutaneous). 

 

How to store Nucala  
• Keep refrigerated before use. 
• Do not freeze 
• Keep in the carton to protect from light. 
• Keep out of the sight and reach of children. 
• If necessary, the pre-filled pen may be kept at room temperature, up to 30°C, for no more than 

7 days, when stored in the original carton. Safely, throw the pen away if it has been kept out of the 
refrigerator for more than 7 days. 

• Do not store it above 30°C. 

Before you use Nucala 
The pre-filled pen should be used only once and then discarded. 
• Do not share your Nucala pre-filled pen with another person. 
• Do not shake the pen. 
• Do not use the pen if dropped onto a hard surface. 
• Do not use the pen if it appears damaged.  
• Do not remove the needle cap until just before your injection. 

 

Know your pre-filled pen  

 

 

Clear  
needle cap 

Before use After use 

Label 

Stopper 

Inspection 
window 
(medicine inside) 

Yellow needle 
guard 
(needle inside) 

Yellow indicator 
(becomes visible when the  
injection is complete) 



64 

Prepare  

1.Get ready what you need 

Find a comfortable, well-lit and clean surface. Make sure you have within reach: 

• Nucala pre-filled pen 

• Alcohol wipe (not included) 

• Gauze pad or cotton wool ball (not included) 

Do not perform the injection if you do not have all these. 

2. Take out your pre-filled pen 

   

• Take the carton out of the refrigerator. Check the security seals are not broken. 

• Remove the tray from the carton. 

• Peel back the film cover from the tray.  

• Holding the middle of the pen, carefully take it out of the tray. 

• Place the pen on a clean, flat surface, at room temperature, away from direct sunlight and out of 
the reach of children. 

Do not use the pen if the security seal on the carton is broken. 

Do not remove the needle cap at this stage. 

Security 
seals 

Make sure the security seals are 
not broken 

Peel off the 
plastic cover 

Take the pen out of the tray  



65 

3. Inspect and wait 30 minutes before use 

 

• Check the expiry date on the label of the pen. 
• Look in the inspection window to check that the liquid is clear (free from cloudiness or particles) 

and colourless to pale yellow to pale brown. 
• It is normal to see one or more air bubbles. 
• Wait 30 minutes (and no more than 8 hours) before use.  

 
Do not use if the expiry date has passed. 
Do not warm the pen in a microwave, hot water, or direct sunlight. 
Do not inject if the solution looks cloudy or discoloured, or has particles. 
Do not use the pen if left out of the carton for more than 8 hours. 
Do not remove the needle cap during this step. 

4. Choose your injection site  

 
• You can inject Nucala into your thighs or abdomen. 

• If someone else gives you the injection, they can also use your upper arm. 

Do not inject where your skin is bruised, tender, red or hard. 

Check the 
expiry date 

Check the medicine 

Wait 30 minutes  
Exp: Month-Year 

Inject yourself in 
thighs or 
abdomen 

Alternatively, another 
person  
can inject in your upper 
arm 



66 

Do not inject within 5 cm of your navel (belly button).  

5. Clean your injection site 

 

• Wash your hands with soap and water. 

• Clean your injection site by wiping the skin with an alcohol wipe and allowing the skin to air dry. 

Do not touch your injection site again until you have finished your injection. 

Inject 

6. Remove the clear needle cap 

 

• Remove the clear needle cap from the pen by firmly pulling it straight off. 

• Do not worry if you see a drop of liquid at the end of the needle. This is normal. 

• Inject straight after removing the needle cap, and always within 5 minutes. 
Do not touch the yellow needle guard with your fingers. This could activate the pen too soon and 
may cause a needle injury. 

Pull off the clear  
needle cap 



67 

After removal, do not put the needle cap back onto the pen, as it may accidentally start the 
injection. 

7. Start your injection 

 

• Hold the pen with its inspection window facing towards you, so you can see it, and with the 
yellow needle guard facing down. 

• Place the pen straight onto your injection site with the yellow needle guard flat against the 
surface of your skin, as shown. 

• To start your injection, push the pen down all the way and keep it held down against your skin. 
The yellow needle guard will slide up into the pen. 

• You should hear the 1st “click” to tell you your injection has started. 

• The yellow indicator will move down through the inspection window as you receive your dose. 

Do not lift the pen from your skin at this stage, as that may mean you don’t get your full dose of 
medicine. Your injection may take up to 15 seconds to complete. 
Do not use the pen if the yellow needle guard doesn’t slide up as described. Dispose of it (see 
Step 9), and start again with a new pen. 

Inspection 
window 

Needle 
guard 

Press down 

1st 
“Click” 



68 

8. Hold the pen in place to complete your injection 

 
 
 
 
 
 
 
 
 
 
 

• Continue to hold the pen down until you hear the 2nd “click”, and the stopper and yellow 
indicator have stopped moving and fill the inspection window. 

• Continue to hold the pen in place while you count to 5. Then lift the pen away from your skin. 

• If you do not hear the 2nd “click”: 
 – Check that the inspection window is filled with the yellow indicator. 
 – If you are not sure, hold the pen down for another 15 seconds to make sure the injection is 

complete. 

Do not lift the pen until you are sure you have completed your injection. 

• You may notice a small drop of blood at the injection site. This is normal. Press a cotton wool 
ball or gauze on the area for a few moments if necessary.  

Do not rub your injection site. 

Dispose 

9. Dispose of the used pen  

• Dispose of the used pen and needle cap according to local requirements. Ask your doctor or 
pharmacist for advice if necessary. 

• Keep your used pens and needle caps out of the reach of children. 
 

2nd 
“Click” 

Continue to  
hold down  
as you count to 5, 
then lift off 



69 

Package leaflet: Information for the user  
 

Nucala 100 mg solution for injection in pre-filled syringe 
 

mepolizumab 
 

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. 
- 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 Nucala is and what it is used for  
2. What you need to know before you use Nucala  
3. How to use Nucala 
4. Possible side effects  
5. How to store Nucala 
6. Contents of the pack and other information 
7. Step-by-step instructions for use 
 
1. What Nucala is and what it is used for 
 
Nucala contains the active substance mepolizumab, a monoclonal antibody, a type of protein designed to 
recognise a specific target substance in the body. It is used to treat severe asthma in adults, adolescents and 
children aged 6 years and older. 
 
Some people with severe asthma have too many eosinophils (a type of white blood cell) in the blood and 
lungs. This condition is called eosinophilic asthma – the type of asthma Nucala can treat. 
 
Nucala can reduce your number of asthma attacks, if you or your child are already using medicines such as 
high dose inhalers, but your asthma is not well controlled by these medicines.  
If you are taking medicines called oral corticosteroids, Nucala can also help reduce the daily dose you need 
to control your asthma. 
 
Mepolizumab, the active substance in Nucala, blocks a protein called interleukin-5. By blocking the action of 
this protein, it limits the production of more eosinophils from the bone marrow and lowers the number of 
eosinophils in the bloodstream and the lungs. 
 
2. What you need to know before you use Nucala 
 
Do not use Nucala: 
- if you are allergic to mepolizumab or any of the other ingredients of this medicine (listed in section 6). 

 Check with your doctor if you think this applies to you. 
 

Warnings and precautions 
Talk to your doctor before using this medicine. 
 
Worsening asthma 



70 

Some people get asthma-related side effects, or their asthma may become worse, during treatment with 
Nucala. 

 Tell your doctor or nurse if your asthma remains uncontrolled, or gets worse, after you start 
Nucala treatment. 

 
Allergic and injection site reactions 
Medicines of this type (monoclonal antibodies) can cause severe allergic reactions when injected into the 
body (see section 4, ‘Possible side effects’).  
 If you may have had a similar reaction to any injection or medicine: 

 Tell your doctor before you are given Nucala. 
 
Parasitic infections 
Nucala 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 Nucala. If you live in a region where these 
infections are common or if you are travelling to such a region: 

 Check with your doctor if you think any of these may apply to you. 
 
Children and adolescents 
The pre-filled syringe is not intended for use in children below 12 years of age. 
For children aged 6-11 years, contact your doctor who will prescribe the recommended dose of Nucala which 
will be administered by a nurse or doctor. 
 
Other medicines and Nucala 
Tell your doctor if you are taking, have recently taken or might take any other medicines. 
 
Other medicines for asthma 

 Don’t suddenly stop taking your preventer medicines for your asthma once you have started 
Nucala. These medicines (especially ones called corticosteroids) must be stopped gradually, under 
the direct supervision of your doctor and dependant on your response to Nucala. 

 
Pregnancy and breast-feeding  
If you are pregnant, if you think you may be pregnant or are planning to have a baby, ask your doctor for 
advice before using this medicine.  
 
It is not known whether the ingredients of Nucala can pass into breast milk. If you are breast-feeding, you 
must check with your doctor before you use Nucala. 
 
Driving and using machines 
The possible side effects of Nucala are unlikely to affect your ability to drive or use machines. 
 
Nucala contains sodium  
This medicine contains less than 1 mmol sodium (23 mg) per 100 mg dose, i.e., it is essentially “sodium-
free”. 
 
3. How to use Nucala 
 
Nucala is given by injection just under the skin (subcutaneous injection).   
 
Your doctor or nurse will decide if you or your caregiver can inject Nucala. If appropriate, they will then 
provide training to show you or your caregiver the correct way to use Nucala. 
 
The recommended dose for adults and adolescents aged 12 years and older is 100 mg. You will have 1 
injection every four weeks. 
 
Instructions for using the pre-filled syringe are given on the other side of this leaflet. 



71 

 
If you use more Nucala than you should 
If you think you have injected too much Nucala, contact your doctor for advice.  
 
If a dose of Nucala is missed 
You or your caregiver should inject the next dose of Nucala as soon as you remember. If you do not notice 
that you have missed a dose until it is already time for your next dose, then just inject the next dose as 
planned. If you are not sure what to do, ask your doctor, pharmacist or nurse. 
 
Stopping treatment with Nucala 
Do not stop injections of Nucala unless your doctor advises you to. Interrupting or stopping the treatment 
with Nucala may cause your asthma symptoms and attacks to come back. 

 
If your asthma symptoms get worse while receiving injections of Nucala:  

 Call your doctor 
 

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. The side effects 
caused by Nucala are usually mild to moderate but can occasionally be serious. 
 
Allergic reactions 
Some people may have allergic or allergic-like reactions.  These reactions may be common (they can affect 
up to 1 in 10 people). They usually occur within minutes to hours after the injection, but sometimes 
symptoms can start up to several days later. 

Symptoms can include: 
• chest tightness, cough, difficulty breathing  
• fainting, dizziness, feeling lightheaded (due to a drop in blood pressure)  
• swelling of eyelids, face, lips, tongue or mouth  
• hives 
• rash 

 
 Seek medical attention immediately if you think you or your child may be having a reaction. 

 
If you may have had a similar reaction to any injection or medicine:  

 Tell your doctor before you or your child are given Nucala 
 
Other side effects include: 
 
Very common side effects 
These may affect more than 1 in 10 people:  

• headache 
 
Common side effects 
These may affect up to 1 in 10 people:  

• chest infection - symptoms of which may include cough and fever (high temperature) 
• urinary tract infection (blood in urine, painful and frequent urination, fever, pain in lower back) 
• upper abdominal pain (stomach pain or discomfort in the upper area of the stomach) 
• fever (high temperature) 
• eczema (itchy red patches on the skin) 
• injection-site reaction (pain, redness, swelling, itching, and burning sensation of the skin near where 

the injection was given) 
• back pain 



72 

• pharyngitis (sore throat) 
• nasal congestion (stuffy nose) 

 
Rare side effects  
These may affect up to 1 in 1,000 people:  

• Severe allergic reactions (anaphylaxis) 
 

 Tell your doctor or a nurse immediately if you get any of these symptoms. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor 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 Nucala 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use Nucala 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). 
 
Do not freeze. 
 
Store in the original package in order to protect from light. 
 
The Nucala pre-filled syringe can be removed from the refrigerator and kept in its unopened carton for up to 
7 days at room temperature (up to 30°C), when protected from light. Discard if left out of the refrigerator for 
more than 7 days. 
 
6. Contents of the pack and other information 
 
What Nucala contains 
The active substance is mepolizumab.  
 
Each 1 mL pre-filled syringe contains 100 mg of mepolizumab. 
The other ingredients are sucrose, sodium phosphate dibasic heptahydrate, citric acid monohydrate, 
polysorbate 80, EDTA disodium dihydrate, water for injections. 
 
What Nucala looks like and contents of the pack 
 
Nucala is supplied as a 1 mL clear to opalescent, colourless to pale yellow to pale brown solution in a single 
use pre-filled syringe. 
 
Nucala is available in a pack containing 1 pre-filled syringe or in multipacks comprised of 3 x 1 pre-filled 
syringes. 
 
Marketing Authorisation Holder 
GlaxoSmithKline Trading Services Limited 
Currabinny 
Carrigaline 
County Cork 
Ireland  
 
Manufacturer 

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


73 

GlaxoSmithKline Manufacturing S.P.A 
Strada Provinciale Asolana, No 90 
43056 San Polo di Torrile, Parma 
Italy 
 
Or 
 
Glaxo Operations UK Ltd 
Harmire Road 
Barnard Castle 
County Durham, DL12 8DT  
United Kingdom 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
GlaxoSmithKline Pharmaceuticals s.a./n.v. 
Tél/Tel: + 32 (0) 10 85 52 00 
 

Lietuva 
GlaxoSmithKline Lietuva UAB 
Tel: + 370 5 264 90 00 
info.lt@gsk.com 
 

България 
ГлаксоСмитКлайн ЕООД  
Teл.: + 359 2 953 10 34 
 

Luxembourg/Luxemburg 
GlaxoSmithKline Pharmaceuticals s.a./n.v. 
Belgique/Belgien 
Tél/Tel: + 32 (0) 10 85 52 00 
 

Česká republika 
GlaxoSmithKline, s.r.o. 
Tel: + 420 222 001 111 
cz.info@gsk.com 

Magyarország 
GlaxoSmithKline Kft. 
Tel.: + 36 1 225 5300 
 

Danmark 
GlaxoSmithKline Pharma A/S 
Tlf: + 45 36 35 91 00 
dk-info@gsk.com 
 

Malta 
GlaxoSmithKline (Malta) Limited 
Tel: + 356 21 238131 

Deutschland 
GlaxoSmithKline GmbH & Co. KG 
Tel.: + 49 (0)89 36044 8701 
produkt.info@gsk.com 
 

Nederland 
GlaxoSmithKline BV 
Tel: + 31 (0)30 6938100 
nlinfo@gsk.com  

Eesti 
GlaxoSmithKline Eesti OÜ 
Tel: + 372 6676 900 
estonia@gsk.com  

Norge 
GlaxoSmithKline AS 
Tlf: + 47 22 70 20 00 
 
 

Ελλάδα 
GlaxoSmithKline A.E.B.E. 
Τηλ: + 30 210 68 82 100 
 

Österreich 
GlaxoSmithKline Pharma GmbH 
Tel: + 43 (0)1 97075 0 
at.info@gsk.com 
 

España 
GlaxoSmithKline, S.A. 
Tel: + 34 902 202 700 
es-ci@gsk.com 
 

Polska 
GSK Services Sp. z o.o. 
Tel.: + 48 (0)22 576 9000 



74 

France 
Laboratoire GlaxoSmithKline 
Tél: + 33 (0)1 39 17 84 44 
diam@gsk.com 
 

Portugal 
GlaxoSmithKline – Produtos Farmacêuticos, Lda. 
Tel: + 351 21 412 95 00 
FI.PT@gsk.com  

Hrvatska 
GlaxoSmithKline d.o.o. 
Tel: +385 1 6051999 
 

România 
GlaxoSmithKline (GSK) S.R.L.  
Tel: + 4021 3028 208 

Ireland 
GlaxoSmithKline (Ireland) Limited 
Tel: + 353 (0)1 4955000 
 

Slovenija 
GlaxoSmithKline d.o.o. 
Tel: + 386 (0)1 280 25 00 
medical.x.si@gsk.com 
 

Ísland 
Vistor hf. 
Sími: + 354 535 7000 
 

Slovenská republika 
GlaxoSmithKline Slovakia s. r. o. 
Tel: + 421 (0)2 48 26 11 11 
recepcia.sk@gsk.com 
 

Italia 
GlaxoSmithKline S.p.A. 
Tel: + 39 (0)45 9218 111 

Suomi/Finland 
GlaxoSmithKline Oy 
Puh/Tel: + 358 (0)10 30 30 30 
Finland.tuoteinfo@gsk.com 
 

Κύπρος 
GlaxoSmithKline (Cyprus) Ltd 
Τηλ: + 357 22 39 70 00 
gskcyprus@gsk.com  

Sverige 
GlaxoSmithKline AB 
Tel: + 46 (0)8 638 93 00 
info.produkt@gsk.com 
 

Latvija 
GlaxoSmithKline Latvia SIA 
Tel: + 371 67312687 
lv-epasts@gsk.com 
 

United Kingdom 
GlaxoSmithKline UK Ltd 
Tel: + 44 (0)800 221441 
customercontactuk@gsk.com 
 

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

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


75 

 
7. Step by step instructions for using the pre-filled syringe 

Administer once every four weeks. 

Follow these instructions on how to use the pre-filled syringe. Failure to follow these instructions may affect 
proper function of the pre-filled syringe. You should also receive training on how to use the pre-filled 
syringe. Nucala pre-filled syringe is for use under the skin only (subcutaneous). 

 
How to store Nucala  

• Keep refrigerated before use. 

• Do not freeze. 

• Keep in the carton to protect from light. 

• Keep out of the sight and reach of children. 

• If necessary, the pre-filled syringe may be kept at room temperature, up to 30°C, for no more than 
7 days, when stored in the original carton. Safely, throw the pre-filled syringe away if it has been 
kept out of the refrigerator for more than 7 days. 

• Do not store it above 30°C. 

Before you use Nucala 
The pre-filled syringe should be used only once and then discarded. 

• Do not share your Nucala pre-filled syringe with another person. 

• Do not shake the syringe. 

• Do not use the syringe if dropped onto a hard surface. 

• Do not use the syringe if it appears damaged.  

• Do not remove the needle cap until just before your injection. 



76 

Know your pre-filled syringe  

            

 

Prepare  

1. Get ready what you need 
Find a comfortable, well-lit and clean surface. Make sure you have within reach: 

• Nucala pre-filled syringe 

• Alcohol wipe (not included) 

• Gauze pad or cotton wool ball (not included) 

Do not perform the injection if you do not have all these. 

Before use After use 

After use, the automatic needle 
guard is activated and pulls up 
(retracts) the needle. 

Automatic 
needle guard 

Inspection 
window 
(medicine 

 

Stopper 

White 
finger grip 

White 
plunge
 

Needle cap 
(needle inside) 



77 

2. Take out your pre-filled syringe 

   

• Take the carton out of the refrigerator. Check the security seals are not broken. 

• Remove the tray from the carton. 

• Peel back the film cover from the tray.  

• Holding the middle of the syringe, carefully take it out of the tray. 

• Place the syringe on a clean, flat surface, at room temperature, away from direct 
sunlight and out of the reach of children. 

Do not use the syringe if the security seal on the carton is broken. 
Do not remove the needle cap at this stage. 

3. Inspect and wait 30 minutes before use 

  

 

• Check the expiry date on the label of the syringe. 
• Look in the inspection window to check that the liquid is clear (free from cloudiness or 

particles) and colourless to pale yellow to pale brown. 
• It is normal to see one or more air bubbles. 
• Wait 30 minutes (and no more than 8 hours) before use.  

 

Check the 
expiry date 

Check the medicine 

Wait 30 minutes  

Exp: Month-Year 
 

Security 
seals 

Make sure the security seals 
are not broken 

Peel off the 
plastic cover 

Take the syringe out of the tray 



78 

Do not use if the expiry date has passed. 
Do not warm the syringe in a microwave, hot water, or direct sunlight. 
Do not inject if the solution looks cloudy or discoloured, or has particles. 
Do not use the syringe if left out of the carton for more than 8 hours. 
Do not remove the needle cap during this step 

4. Choose your injection site  

   

• You can inject Nucala into your thighs or abdomen. 

• If someone else gives you the injection, they can also use your upper arm. 
Do not inject where your skin is bruised, tender, red or hard. 
Do not inject within 5 cm of your navel (belly button). 

5. Clean your injection site 

 
• Wash your hands with soap and water. 
• Clean your injection site by wiping the skin with an alcohol wipe and allowing the skin 

to air dry. 

Do not touch your injection site again until you have finished your injection. 

Inject yourself in 
thighs or 
abdomen 

Alternatively, another 
person can inject in 
your upper arm 



79 

Inject 

6. Remove the needle cap 

 

• Remove the needle cap from the syringe by firmly pulling it straight off, extending your 
hand away from the needle end (as shown). You may need to pull the needle cap quite 
firmly to remove it. 

• Do not worry if you see a drop of liquid at the end of the needle. This is normal. 

• Inject straight after removing the needle cap, and always within 5 minutes.  

Do not let the needle touch any surface. 

Do not touch the needle. 

Do not touch the plunger at this stage, as you can accidentally push liquid out and will not 
receive your full dose.  

Do not expel any air bubbles from the syringe.  

Do not put the needle cap back onto the syringe. This could cause a needle injury. 

7. Start your injection 

 

Pull off the 
needle cap 

Slowly 
push down  



80 

• Use your free hand to pinch the skin around your injection site. Keep the skin pinched 
throughout your injection. 

• Insert the entire needle into the pinched skin at a 45° angle, as shown. 

• Move your thumb to the plunger and place your fingers on the white finger grip, as 
shown. 

• Slowly push down on the plunger to inject your full dose. 

8. Complete your injection 

 

• Make sure the plunger is pushed all the way down, until the stopper reaches the bottom 
of the syringe and all of the solution is injected. 

• Slowly lift your thumb up. This will allow the plunger to come up and the needle to 
retract (rise up) into the body of the syringe. 

• Once complete, release the pinched skin. 

• You may notice a small drop of blood at the injection site. This is normal. Press a 
cotton wool ball or gauze on the area for a few moments if necessary. 

• Do not put the needle cap back onto the syringe. 

• Do not rub your injection site. 

Dispose 

9. Dispose of the used syringe  

• Dispose of the used syringe and needle cap according to local requirements. Ask your 
doctor or pharmacist for advice if necessary. 

• Keep your used syringes and needle caps out of the reach of children. 

Make sure the 
white plunger is 
fully down Slowly raise 

your thumb 



81 

Package leaflet: Information for the user  
 

Nucala 100 mg powder for solution for injection 
mepolizumab 

 
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. 
- 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 Nucala is and what it is used for  
2. What you need to know before you use Nucala  
3. How to use Nucala 
4. Possible side effects  
5. How to store Nucala 
6. Contents of the pack and other information 
 Step-by-step instructions for use 
 
1. What Nucala is and what it is used for 
 
Nucala contains the active substance mepolizumab, a monoclonal antibody, a type of protein designed to 
recognise a specific target substance in the body. It is used to treat severe asthma in adults, adolescents and 
children aged 6 and over. 
 
Some people with severe asthma have too many eosinophils (a type of white blood cell) in the blood and 
lungs. This condition is called eosinophilic asthma – the type of asthma Nucala can treat. 
 
Nucala can reduce your number of asthma attacks, if you or your child are already using medicines such as 
high dose inhalers, but your asthma is not well controlled by these medicines.  
If you are taking medicines called oral corticosteroids, Nucala can also help reduce the daily dose you need 
to control your asthma. 
 
Mepolizumab, the active substance in Nucala, blocks a protein called interleukin-5. By blocking the action of 
this protein, it limits the production of more eosinophils from the bone marrow and lowers the number of 
eosinophils in the bloodstream and the lungs. 
 
2. What you need to know before you use Nucala 
 
Do not use Nucala: 
- if you are allergic to mepolizumab or any of the other ingredients of this medicine (listed in section 6). 

 Check with your doctor if you think this applies to you. 
 

Warnings and precautions 
Talk to your doctor before using this medicine. 
 
Worsening asthma 



82 

Some people get asthma-related side effects, or their asthma may become worse, during treatment with 
Nucala. 

 Tell your doctor or nurse if your asthma remains uncontrolled, or gets worse, after you start 
Nucala treatment. 

 
Allergic and injection site reactions 
Medicines of this type (monoclonal antibodies) can cause severe allergic reactions when injected into the 
body (see section 4, ‘Possible side effects’).  
 If you may have had a similar reaction to any injection or medicine, 

 Tell your doctor before you are given Nucala. 
 
Parasitic infections 
Nucala 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 Nucala. If you live in a region where these 
infections are common or if you are travelling to such a region: 

 Check with your doctor if you think any of these may apply to you. 
 
Children  
This medicine is not intended for use in children below 6 years of age. 
 
Other medicines and Nucala 
Tell your doctor if you are taking, have recently taken or might take any other medicines. 
 
Other medicines for asthma 

 Don’t suddenly stop taking your preventer medicines for your asthma once you have started 
Nucala. These medicines (especially ones called corticosteriods) must be stopped gradually, under 
the direct supervision of your doctor and dependant on your response to Nucala. 

 
Pregnancy and breast-feeding  
If you are pregnant, if you think you may be pregnant or are planning to have a baby, ask your doctor for 
advice before using this medicine.  
 
It is not known whether the ingredients of Nucala can pass into breast milk. If you are breast-feeding, you 
must check with your doctor before you use Nucala. 
 
Driving and using machines 
The possible side effects of Nucala are unlikely to affect your ability to drive or use machines. 
 
Nucala contains sodium  
This medicine contains less than 1 mmol sodium (23 mg) per 100 mg dose, i.e., it is essentially “sodium-
free”. 
 
3. How to use Nucala 
 
Nucala is given to you by a doctor, nurse or healthcare professional, as an injection just under the skin 
(subcutaneously). 
 
Adults and adolescents aged 12 years and over 
 The recommended dose for adults and adolescents is 100 mg. You will be given 1 injection every 
four weeks. 
 
Children aged 6 to 11 years old  
 The recommended dose is 40 mg. You will be given 1 injection every four weeks. 
 



83 

If a dose of Nucala is missed 
 Contact your doctor or hospital as soon as possible to re-schedule your appointment. 
 
Stopping treatment with Nucala 
Do not stop receiving injections of Nucala unless your doctor advises you to. Interrupting or stopping the 
treatment with Nucala may cause your asthma symptoms and attacks to come back. 

 
If your asthma symptoms get worse while receiving injections of Nucala  
 Call your doctor. 
 
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. The side effects 
caused by Nucala are usually mild to moderate but can occasionally be serious. 
 
Allergic reactions 
Some people may have allergic or allergic-like reactions.  These reactions may be common (they can affect 
up to 1 in 10 people). They usually occur within minutes to hours after the injection, but sometimes 
symptoms can start up to several days later. 

Symptoms can include: 
• chest tightness, cough, difficulty breathing  
• fainting, dizziness, feeling lightheaded (due to a drop in blood pressure)  
• swelling of eyelids, face, lips, tongue or mouth  
• hives 
• rash 

 
 Seek medical attention immediately if you think you (or your child) may be having a reaction. 

 
If you (or your child) may have had a similar reaction to any injection or medicine:  
 Tell your doctor before you are given Nucala. 

 
Other side effects include: 
 
Very common side effects 
These may affect more than 1 in 10 people:  

• headache 
 
Common side effects 
These may affect up to 1 in 10 people:  

• chest infection - symptoms of which may include cough and fever (high temperature) 
• urinary tract infection (blood in urine, painful and frequent urination, fever, pain in lower back) 
• upper abdominal pain (stomach pain or discomfort in the upper area of the stomach) 
• fever (high temperature) 
• eczema (itchy red patches on the skin) 
• injection-site reaction (pain, redness, swelling, itching, and burning sensation of the skin near where 

the injection was given) 
• back pain 
• pharyngitis (sore throat) 
• nasal congestion (stuffy nose) 

 
Rare side effects  
These may affect up to 1 in 1,000 people:  

• Severe allergic reactions (anaphylaxis) 



84 

 
 Tell your doctor or a nurse immediately if you get any of these symptoms. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor 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 Nucala 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use Nucala 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 below 25°C. 
Do not freeze. 
Store in the original package to protect from light. 
 
6. Contents of the pack and other information 
 
What Nucala contains 
The active substance is mepolizumab. Each vial contains 100 mg of mepolizumab. 
After reconstitution, each ml of solution contains 100 mg mepolizumab. 
 
The other ingredients are sucrose, sodium phosphate dibasic heptahydrate and polysorbate 80. 
 
What Nucala looks like and contents of the pack 
 
Nucala is a lyophilised white powder supplied in a clear, colourless glass vial with a rubber stopper. 
 
Nucala is available in a pack containing 1 vial, or in multipacks with 3 individual vials. 
 
Marketing Authorisation Holder 
GlaxoSmithKline Trading Services Limited 
Currabinny 
Carrigaline 
County Cork 
Ireland 
 
Manufacturer 
GlaxoSmithKline Manufacturing S.P.A 
Strada Provinciale Asolana, No 90 
43056 San Polo di Torrile, Parma 
Italy 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
GlaxoSmithKline Pharmaceuticals s.a./n.v. 
Tél/Tel: + 32 (0) 10 85 52 00 
 

Lietuva 
GlaxoSmithKline Lietuva UAB 
Tel: + 370 5 264 90 00 
info.lt@gsk.com 
 

България 
ГлаксоСмитКлайн ЕООД  

Luxembourg/Luxemburg 
GlaxoSmithKline Pharmaceuticals s.a./n.v. 

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


85 

Teл.: + 359 2 953 10 34 
 

Belgique/Belgien 
Tél/Tel: + 32 (0) 10 85 52 00 
 

Česká republika 
GlaxoSmithKline, s.r.o. 
Tel: + 420 222 001 111 
cz.info@gsk.com 

Magyarország 
GlaxoSmithKline Kft. 
Tel.: + 36 1 225 5300 
 

Danmark 
GlaxoSmithKline Pharma A/S 
Tlf: + 45 36 35 91 00 
dk-info@gsk.com 
 

Malta 
GlaxoSmithKline (Malta) Limited 
Tel: + 356 21 238131 

Deutschland 
GlaxoSmithKline GmbH & Co. KG 
Tel.: + 49 (0)89 36044 8701 
produkt.info@gsk.com 
 

Nederland 
GlaxoSmithKline BV 
Tel: + 31 (0)30 6938100 
nlinfo@gsk.com  

Eesti 
GlaxoSmithKline Eesti OÜ 
Tel: + 372 6676 900 
estonia@gsk.com  

Norge 
GlaxoSmithKline AS 
Tlf: + 47 22 70 20 00 
 
 

Ελλάδα 
GlaxoSmithKline A.E.B.E. 
Τηλ: + 30 210 68 82 100 
 

Österreich 
GlaxoSmithKline Pharma GmbH 
Tel: + 43 (0)1 97075 0 
at.info@gsk.com 
 

España 
GlaxoSmithKline, S.A. 
Tel: + 34 902 202 700 
es-ci@gsk.com 
 

Polska 
GSK Services Sp. z o.o. 
Tel.: + 48 (0)22 576 9000 

France 
Laboratoire GlaxoSmithKline 
Tél: + 33 (0)1 39 17 84 44 
diam@gsk.com 
 

Portugal 
GlaxoSmithKline – Produtos Farmacêuticos, Lda. 
Tel: + 351 21 412 95 00 
FI.PT@gsk.com  

Hrvatska 
GlaxoSmithKline d.o.o. 
Tel: +385 1 6051999 
 

România 
GlaxoSmithKline (GSK) S.R.L.  
Tel: + 4021 3028 208 

Ireland 
GlaxoSmithKline (Ireland) Limited 
Tel: + 353 (0)1 4955000 
 

Slovenija 
GlaxoSmithKline d.o.o. 
Tel: + 386 (0)1 280 25 00 
medical.x.si@gsk.com 
 

Ísland 
Vistor hf. 
Sími: + 354 535 7000 
 

Slovenská republika 
GlaxoSmithKline Slovakia s. r. o. 
Tel: + 421 (0)2 48 26 11 11 
recepcia.sk@gsk.com 
 

Italia 
GlaxoSmithKline S.p.A. 
Tel: + 39 (0)45 9218 111 

Suomi/Finland 
GlaxoSmithKline Oy 
Puh/Tel: + 358 (0)10 30 30 30 
Finland.tuoteinfo@gsk.com 



86 

 
Κύπρος 
GlaxoSmithKline (Cyprus) Ltd 
Τηλ: + 357 22 39 70 00 
gskcyprus@gsk.com  

Sverige 
GlaxoSmithKline AB 
Tel: + 46 (0)8 638 93 00 
info.produkt@gsk.com 
 

Latvija 
GlaxoSmithKline Latvia SIA 
Tel: + 371 67312687 
lv-epasts@gsk.com 
 

United Kingdom 
GlaxoSmithKline UK Ltd 
Tel: + 44 (0)800 221441 
customercontactuk@gsk.com 
 

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

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


87 

The following information is intended for healthcare professionals only: 
 
Step-by-step instructions for use and handling, reconstitution, and administration 
Nucala is provided as a lyophilised, white powder in a single-use vial for subcutaneous injection only. 
Reconstitution should be carried out under aseptic conditions.  
 
Once reconstituted, Nucala will contain a concentration of 100 mg/mL mepolizumab. The solution for 
injection can be stored between 2°C to 30°C for no more than 8 hours. Any unused concentrate or solution 
remaining after 8 hours must be discarded. 
 
The trade name (Nucala) and batch number of the administered product should be clearly recorded in the 
patient file. 
 
Instructions for reconstitution for each vial 
1. Reconstitute the contents of the vial with 1.2 mL of sterile water for injections preferably using a 2 

to 3 ml syringe and a 21 gauge needle. The stream of sterile water should be directed vertically, onto the 
centre of the lyophilised cake. Allow the vial to sit at room temperature during reconstitution, gently 
swirling the vial for 10 seconds with circular motion at 15-second intervals until the powder is dissolved. 
 
Note: The reconstituted solution must not be shaken during the procedure as this may lead to product 
foaming or precipitation. Reconstitution is typically complete within 5 minutes after the sterile water has 
been added, but it may take additional time.  
 

2. If a mechanical reconstitution device (swirler) is used to reconstitute Nucala, reconstitution can be 
accomplished by swirling at 450 rpm for no longer than 10 minutes. Alternatively, swirling at 1000 rpm 
for no longer than 5 minutes is acceptable. 

3. Following reconstitution, Nucala should be visually inspected for particulate matter and clarity prior to 
use.  The solution should be clear to opalescent, and colourless to pale yellow or pale brown, free of 
visible particles. Small air bubbles, however, are expected and acceptable. If particulate matter remains 
in the solution or if the solution appears cloudy or milky, the solution must not be used.  

4. The reconstituted solution, if not used immediately must be: 
• Protected from sunlight  
• Stored below 30°C, not frozen 
• Discarded if not used within 8 hours of reconstitution 

 
Instructions for administration of 100 mg dose 
1. For subcutaneous administration, a 1 mL polypropylene syringe fitted with a disposable needle 21 gauge 

to 27 gauge x 0.5 inch (13 mm) should preferably be used. 
2. Just prior to administration, remove 1 mL of reconstituted Nucala.  Do not shake the reconstituted 

solution during the procedure as this could lead to product foaming or precipitation. 
3. Administer the 1 mL injection (equivalent to 100 mg mepolizumab) subcutaneously into the upper arm, 

thigh, or abdomen. 
 

Instructions for administration of 40 mg dose 
1. For subcutaneous administration, a 1 mL polypropylene syringe fitted with a disposable needle 21 gauge 

to 27 gauge x 0.5 inch (13 mm) should preferably be used. 
2. Just prior to administration, remove 0.4mL of reconstituted Nucala.  Do not shake the reconstituted 

solution during the procedure as this could lead to product foaming or precipitation. Dispose of the 
remaining solution. 

3. Administer the 0.4mL injection (equivalent to 40 mg mepolizumab) subcutaneously into the upper arm, 
thigh, or abdomen.  
 

 
Disposal 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURERS 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