Ilaris

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 

Ilaris 150 mg powder for solution for injection 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

One vial contains 150 mg of canakinumab*. 

 

After reconstitution, each ml of solution contains 150 mg canakinumab. 

 

* human monoclonal antibody produced in mouse myeloma Sp2/0 cells by recombinant DNA 

technology 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Powder for solution for injection. 

 

The powder is white. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Periodic fever syndromes 

 

Ilaris is indicated for the treatment of the following autoinflammatory periodic fever syndromes in 

adults, adolescents and children aged 2 years and older: 

 

Cryopyrin-associated periodic syndromes 

Ilaris is indicated for the treatment of cryopyrin-associated periodic syndromes (CAPS) including: 

 Muckle-Wells syndrome (MWS), 

 Neonatal-onset multisystem inflammatory disease (NOMID) / chronic infantile neurological, 
cutaneous, articular syndrome (CINCA), 

 Severe forms of familial cold autoinflammatory syndrome (FCAS) / familial cold urticaria 
(FCU) presenting with signs and symptoms beyond cold-induced urticarial skin rash. 

 

Tumour necrosis factor receptor associated periodic syndrome (TRAPS) 

Ilaris is indicated for the treatment of tumour necrosis factor (TNF) receptor associated periodic 

syndrome (TRAPS). 

 

Hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD) 

Ilaris is indicated for the treatment of hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase 

deficiency (MKD). 

 

Familial Mediterranean fever (FMF) 

Ilaris is indicated for the treatment of Familial Mediterranean Fever (FMF). Ilaris should be given in 

combination with colchicine, if appropriate. 

 



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Ilaris is also indicated for the treatment of: 

 

Still’s disease 

 

Ilaris is indicated for the treatment of active Still’s disease including adult-onset Still’s disease 

(AOSD) and systemic juvenile idiopathic arthritis (SJIA) in patients aged 2 years and older who have 

responded inadequately to previous therapy with non-steroidal anti-inflammatory drugs (NSAIDs) and 

systemic corticosteroids. Ilaris can be given as monotherapy or in combination with methotrexate. 

 

Gouty arthritis 

 

Ilaris is indicated for the symptomatic treatment of adult patients with frequent gouty arthritis attacks 

(at least 3 attacks in the previous 12 months) in whom non-steroidal anti-inflammatory drugs 

(NSAIDs) and colchicine are contraindicated, are not tolerated, or do not provide an adequate 

response, and in whom repeated courses of corticosteroids are not appropriate (see section 5.1). 

 

4.2 Posology and method of administration 

 

For CAPS, TRAPS, HIDS/MKD, FMF and Still’s disease, the treatment should be initiated and 

supervised by a specialist physician experienced in the diagnosis and treatment of the relevant 

indication. 

 

For gouty arthritis, the physician should be experienced in the use of biologics and Ilaris should be 

administered by a healthcare professional. 

 

Posology 

 

CAPS: Adults, adolescents and children aged 2 years and older 

The recommended starting dose of canakinumab for CAPS patients is: 

Adults, adolescents and children ≥ 4 years of age: 

 150 mg for patients with body weight > 40 kg 

 2 mg/kg for patients with body weight ≥ 15 kg and ≤ 40 kg 

 4 mg/kg for patients with body weight ≥ 7.5 kg and < 15 kg 
Children 2 to < 4 years of age: 

 4 mg/kg for patients with body weight ≥ 7.5 kg 
 

This is administered every eight weeks as a single dose via subcutaneous injection. 

 

For patients with a starting dose of 150 mg or 2 mg/kg, if a satisfactory clinical response (resolution of 

rash and other generalised inflammatory symptoms) has not been achieved 7 days after treatment start, 

a second dose of canakinumab at 150 mg or 2 mg/kg can be considered. If a full treatment response is 

subsequently achieved, the intensified dosing regimen of 300 mg or 4 mg/kg every 8 weeks should be 

maintained. If a satisfactory clinical response has not been achieved 7 days after this increased dose, a 

third dose of canakinumab at 300 mg or 4 mg/kg can be considered. If a full treatment response is 

subsequently achieved, maintaining the intensified dosing regimen of 600 mg or 8 mg/kg every 

8 weeks should be considered, based on individual clinical judgement. 

 

  



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For patients with a starting dose of 4 mg/kg, if a satisfactory clinical response has not been achieved 

7 days after treatment start, a second dose of canakinumab 4 mg/kg can be considered. If a full 

treatment response is subsequently achieved, maintaining the intensified dosing regimen of 8 mg/kg 

every 8 weeks should be considered, based on individual clinical judgement. 

 

Clinical experience with dosing at intervals of less than 4 weeks or at doses above 600 mg or 8 mg/kg 

is limited. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

  

CAPS in adults and children  4 years of age 
 15 kg 

Maintenance dose: 
150 mg or 2 mg/kg 

every 8 weeks 

Additional dose of 
150 mg or 2 mg/kg 
can be considered 

150 mg or 2 mg/kg 

Additional dose of 
300 mg or 4 mg/kg can 

be considered 

Maintenance 
dose 4 mg/kg 
every 8 weeks 

Additional dose 
of 4 mg/kg can 
be considered 

Satisfactory clinical response after 
7 days? 

Satisfactory clinical 
response after 7 days? 

Maintenance dose: 
300 mg or 4 mg/kg 

every 8 weeks 

If full treatment response after 
7 days, maintenance dose: 
600 mg or 8 mg/kg every 

8 weeks 

Satisfactory clinical 
response after 7 days? 

4 mg/kg 

CAPS in children 2-< 4 years of age or  

children  4 years of age  7.5 kg and < 15 kg 

If full treatment 
response after 7 days, 

maintenance dose: 
8 mg/kg every 8 weeks 

Yes No 

No 
No Yes Yes 



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TRAPS, HIDS/MKD and FMF: Adults, adolescents and children aged 2 years and older 

The recommended starting dose of canakinumab in TRAPS, HIDS/MKD and FMF patients is: 

 150 mg for patients with body weight > 40 kg 

 2 mg/kg for patients with body weight ≥ 7.5 kg and ≤ 40 kg 
 

This is administered every four weeks as a single dose via subcutaneous injection. 

 

If a satisfactory clinical response has not been achieved 7 days after treatment start, a second dose of 

canakinumab at 150 mg or 2 mg/kg can be considered. If a full treatment response is subsequently 

achieved, the intensified dosing regimen of 300 mg (or 4 mg/kg for patients weighing ≤ 40 kg) every 

4 weeks should be maintained. 

 

Continued treatment with canakinumab in patients without clinical improvement should be 

reconsidered by the treating physician. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Still’s disease (SJIA and AOSD) 

The recommended dose of canakinumab for patients with Still’s disease with body weight ≥ 7.5 kg is 

4 mg/kg (up to a maximum of 300 mg) administered every four weeks via subcutaneous injection. 

Continued treatment with canakinumab in patients without clinical improvement should be 

reconsidered by the treating physician. 

 

Gouty arthritis 

Management of hyperuricaemia with appropriate urate lowering therapy (ULT) should be instituted or 

optimised. Canakinumab should be used as an on-demand therapy to treat gouty arthritis attacks. 

 

The recommended dose of canakinumab for adult patients with gouty arthritis is 150 mg administered 

subcutaneously as a single dose during an attack. For maximum effect, canakinumab should be 

administered as soon as possible after the onset of a gouty arthritis attack. 

 

TRAPS, HIDS/MKD and FMF patients  
with body weight > 40 kg 

Maintenance 
dose: 150 mg 
every 4 weeks 

Additional dose of 
150 mg can be 

considered 

150 mg 

Maintenance 
dose 2 mg/kg 
every 4 weeks 

Additional dose 
of 2 mg/kg can 
be considered 

Satisfactory clinical 
response after 7 days? 

Satisfactory clinical 
response after 7 days? 

2 mg/kg 

TRAPS, HIDS/MKD and FMF patients  

with body weight  7.5 kg and ≤ 40 kg 

If full treatment response is 
achieved, maintenance dose: 

4 mg/kg every 4 weeks 

No 
 

No Yes Yes 
 

If full treatment response is 
achieved, maintenance dose: 

300 mg every 4 weeks 



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Patients who do not respond to initial treatment should not be re-treated with canakinumab. In patients 

who respond and require re-treatment, there should be an interval of at least 12 weeks before a new 

dose of canakinumab may be administered (see section 5.2). 

 

Special populations 

 

Paediatric population 

CAPS, TRAPS, HIDS/MKD and FMF 

The safety and efficacy of canakinumab in CAPS, TRAPS, HIDS/MKD and FMF patients under 

2 years of age have not been established. Currently available data are described in sections 4.8, 5.1 and 

5.2 but no recommendation on a posology can be made. 

 

SJIA 

The safety and efficacy of canakinumab in SJIA patients under 2 years of age have not been 

established. No data are available. 

 

Gouty arthritis 

There is no relevant use of canakinumab in the paediatric population in the indication gouty arthritis. 

 

Elderly 

No dose adjustment is required. 

 

Hepatic impairment 

Canakinumab has not been studied in patients with hepatic impairment. No recommendation on a 

posology can be made. 

 

Renal impairment 

No dose adjustment is needed in patients with renal impairment. However, clinical experience in such 

patients is limited. 

 

Method of administration 

 

For subcutaneous use. 

The following are suitable injection sites: upper thigh, abdomen, upper arm or buttocks. It is 

recommended to select a different injection site each time the product is injected to avoid soreness. 

Broken skin and areas which are bruised or covered by a rash should be avoided. Injection into scar 

tissue should be avoided as this may result in insufficient exposure to canakinumab. 

 

Each vial is for single use in a single patient, for a single dose. 

 

After proper training in the correct injection technique, patients or their caregivers may inject 

canakinumab if the physician determines that it is appropriate and with medical follow-up as necessary 

(see section 6.6). 

 

For instructions on reconstitution of the medicinal product before administration, see section 6.6. 

 

4.3 Contraindications 
 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 

Active, severe infections (see section 4.4). 

 

  



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4.4 Special warnings and precautions for use 

 

Traceability 

 

In order to improve the traceability of biological medicinal products, the name and the batch number 

of the administered product should be clearly recorded. 

 

Infections 

 

Canakinumab is associated with an increased incidence of serious infections. Therefore patients 

should be monitored carefully for signs and symptoms of infections during and after treatment with 

canakinumab. Physicians should exercise caution when administering canakinumab to patients with 

infections, a history of recurring infections, or underlying conditions which may predispose them to 

infections. 

 

Treatment of CAPS, TRAPS, HIDS/MKD, FMF and Still’s disease (SJIA and AOSD) 

Canakinumab should not be initiated or continued in patients during an active infection requiring 

medical intervention. 

 

Treatment of gouty arthritis 

Canakinumab should not be administered during an active infection. 

Concomitant use of canakinumab with tumour necrosis factor (TNF) inhibitors is not recommended 

because this may increase the risk of serious infections (see section 4.5). 

 

Isolated cases of unusual or opportunistic infections (including aspergillosis, atypical mycobacterial 

infections, herpes zoster) have been reported during canakinumab treatment. The causal relationship of 

canakinumab to these events cannot be excluded. 

 

Tuberculosis screening 

 

In approximately 12% of CAPS patients tested with a PPD (purified protein derivative) skin test in 

clinical trials, follow-up testing yielded a positive test result while treated with canakinumab without 

clinical evidence of a latent or active tuberculosis infection. 

 

It is unknown whether the use of interleukin-1 (IL-1) inhibitors such as canakinumab increases the risk 

of reactivation of tuberculosis. Before initiation of therapy, all patients must be evaluated for both 

active and latent tuberculosis infection. Particularly in adult patients, this evaluation should include a 

detailed medical history. Appropriate screening tests (e.g. tuberculin skin test, interferon gamma 

release assay or chest X-ray) should be performed in all patients (local recommendations may apply). 

Patients must be monitored closely for signs and symptoms of tuberculosis during and after treatment 

with canakinumab. All patients should be instructed to seek medical advice if signs or symptoms 

suggestive of tuberculosis (e.g. persistent cough, weight loss, subfebrile temperature) appear during 

canakinumab therapy. In the event of conversion from a negative to a positive PPD test, especially in 

high-risk patients, alternative means of screening for a tuberculosis infection should be considered. 

 

Neutropenia and leukopenia 

 

Neutropenia (absolute neutrophil count [ANC] < 1.5 x 109/l) and leukopenia have been observed with 

medicinal products that inhibit IL-1, including canakinumab. Treatment with canakinumab should not 

be initiated in patients with neutropenia or leukopenia. It is recommended that white blood cell (WBC) 

counts including neutrophil counts be assessed prior to initiating treatment and again after 1 to 

2 months. For chronic or repeated therapies, it is also recommended to assess WBC counts 

periodically during treatment. If a patient becomes neutropenic or leukopenic, the WBC counts should 

be monitored closely and treatment discontinuation should be considered. 

 



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Malignancies 

 

Malignancy events have been reported in patients treated with canakinumab. The risk for the 

development of malignancies with anti-interleukin (IL)-1 therapy is unknown. 

 

Hypersensitivity reactions 

 

Hypersensitivity reactions with canakinumab therapy have been reported. The majority of these events 

were mild in severity. During clinical development of canakinumab in over 2,600 patients, no 

anaphylactoid or anaphylactic reactions attributable to treatment with canakinumab were reported. 

However, the risk of severe hypersensitivity reactions, which is not uncommon for injectable proteins, 

cannot be excluded (see section 4.3). 

 

Hepatic function 

 

Transient and asymptomatic cases of elevations of serum transaminases or bilirubin have been 

reported in clinical trials (see section 4.8). 

 

Vaccinations 

 

No data are available on the risk of secondary transmission of infection by live (attenuated) vaccines 

in patients receiving canakinumab. Therefore, live vaccines should not be given concurrently with 

canakinumab unless the benefits clearly outweigh the risks (see section 4.5). 

 

Prior to initiation of canakinumab therapy it is recommended that adult and paediatric patients receive 

all vaccinations, as appropriate, including pneumococcal vaccine and inactivated influenza vaccine 

(see section 4.5). 

 

Mutation in NLRP3 gene in CAPS patients 

 

Clinical experience in CAPS patients without a confirmed mutation in the NLRP3 gene is limited. 

 

Macrophage activation syndrome in patients with Still’s disease (SJIA and AOSD) 

 

Macrophage activation syndrome (MAS) is a known, life-threatening disorder that may develop in 

patients with rheumatic conditions, in particular Still’s disease. If MAS occurs, or is suspected, 

evaluation and treatment should be started as early as possible. Physicians should be attentive to 

symptoms of infection or worsening of Still’s disease, as these are known triggers for MAS. Based on 

clinical trial experience, canakinumab does not appear to increase the incidence of MAS in Still’s 

disease patients, but no definitive conclusion can be made. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Interactions between canakinumab and other medicinal products have not been investigated in formal 

studies. 

 

An increased incidence of serious infections has been associated with administration of another IL-1 

blocker in combination with TNF inhibitors. Use of canakinumab with TNF inhibitors is not 

recommended because this may increase the risk of serious infections. 

 

The expression of hepatic CYP450 enzymes may be suppressed by the cytokines that stimulate 

chronic inflammation, such as interleukin-1 beta (IL-1 beta). Thus, CYP450 expression may be 

reversed when potent cytokine inhibitory therapy, such as canakinumab, is introduced. This is 

clinically relevant for CYP450 substrates with a narrow therapeutic index where the dose is 

individually adjusted. On initiation of canakinumab in patients being treated with this type of 

medicinal product, therapeutic monitoring of the effect or of the active substance concentration should 

be performed and the individual dose of the medicinal product adjusted as necessary. 



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No data are available on either the effects of live vaccination or the secondary transmission of 

infection by live vaccines in patients receiving canakinumab. Therefore, live vaccines should not be 

given concurrently with canakinumab unless the benefits clearly outweigh the risks. Should 

vaccination with live vaccines be indicated after initiation of canakinumab treatment, the 

recommendation is to wait for at least 3 months after the last canakinumab injection and before the 

next one (see section 4.4). 

 

The results of a study in healthy adult subjects demonstrated that a single dose of canakinumab 

300 mg did not affect the induction and persistence of antibody responses after vaccination with 

influenza or glycosylated protein based meningococcus vaccines. 

 

The results of a 56-week, open label study in CAPS patients aged 4 years and younger demonstrated 

that all patients who received non-live, standard of care childhood vaccinations developed protective 

antibody levels. 

 

4.6 Fertility, pregnancy and lactation 

 

Women of childbearing potential / Contraception in males and females 

 

Women should use effective contraceptives during treatment with canakinumab and for up to 

3 months after the last dose. 

 

Pregnancy 

 

There is a limited amount of data from the use of canakinumab in pregnant women. Animal studies do 

not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). 

The risk for the foetus/mother is unknown. Women who are pregnant or who desire to become 

pregnant should therefore only be treated after a thorough benefit-risk evaluation. 

 

Animal studies indicate that canakinumab crosses the placenta and is detectable in the foetus. No 

human data are available, but as canakinumab is an immunoglobulin of the G class (IgG1), human 

transplacental transfer is expected. The clinical impact of this is unknown. However, administration of 

live vaccines to newborn infants exposed to canakinumab in utero is not recommended for 16 weeks 

following the mother’s last dose of canakinumab before childbirth. Women who received 

canakinumab during pregnancy should be instructed to inform the baby’s healthcare professional 

before any vaccinations are given to their newborn infant. 

 

Breast-feeding 

 

It is unknown whether canakinumab is excreted in human milk. The decision whether to breast-feed 

during canakinumab therapy should therefore only be taken after a thorough benefit-risk evaluation. 

 

Animal studies have shown that a murine anti-murine IL-1 beta antibody had no undesirable effects on 

development in nursing mouse pups and that the antibody was transferred to them (see section 5.3). 

 

Fertility 

 

Formal studies of the potential effect of canakinumab on human fertility have not been conducted. 

Canakinumab had no effect on male fertility parameters in marmosets (C. jacchus). A murine anti-

murine IL-1 beta antibody had no undesirable effects on fertility in male or female mice (see 

section 5.3). 

 

  



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4.7 Effects on ability to drive and use machines 
 

Ilaris has minor influence on the ability to drive and use machines. Treatment with Ilaris may result in 

dizziness/vertigo or asthenia (see section 4.8). Patients who experience such symptoms during Ilaris 

treatment should wait for this to resolve completely before driving or operating machines. 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

The most frequent adverse drug reactions were infections predominantly of the upper respiratory tract. 

No impact on the type or frequency of adverse drug reactions was seen with longer-term treatment. 

 

Hypersensitivity reactions have been reported in patients treated with canakinumab (see sections 4.3 

and 4.4). 

 

Opportunistic infections have been reported in patients treated with canakinumab (see section 4.4). 

 

Tabulated list of adverse reactions 

 

Adverse reactions are listed according to MedDRA system organ class. Within each system organ 

class, the adverse reactions are ranked by frequency category with the most common first. Frequency 

categories are 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); not 

known (cannot be estimated from the available data). Within each frequency grouping, adverse 

reactions are presented in order of decreasing seriousness. 



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Table 1 Tabulated list of adverse reactions 

 

MedDRA 

System Organ 

Class 

Indications: 

CAPS, TRAPS, HIDS/MKD, FMF, SJIA, gouty arthritis 

Infections and infestations 

Very common Respiratory tract infections (including pneumonia, bronchitis, influenza, viral 

infection, sinusitis, rhinitis, pharyngitis, tonsillitis, nasopharyngitis, upper 

respiratory tract infection) 

Ear infection 

Cellulitis 

Gastroenteritis 

Urinary tract infection 

Common Vulvovaginal candidiasis 

Nervous system disorders 

Common Dizziness/vertigo 

Gastrointestinal disorders 

Very common Upper abdominal pain 1 

Uncommon Gastro-oesophageal reflux disease 2 

Skin and subcutaneous tissue disorders 

Very common Injection site reaction 

Musculoskeletal and connective tissue disorders 

Very common Arthralgia 1 

Common Musculoskeletal pain 1 

Back pain 2 

General disorders and administration site conditions 

Common Fatigue/asthenia 2 

Investigations 

Very common Creatinine renal clearance decreased 1,3 

Proteinuria 1,4 

Leukopenia 1,5 

Common Neutropenia 5 

Uncommon Platelet count decreased 5 
1 In SJIA 
2 In gouty arthritis 
3 Based on estimated creatinine clearance, most were transient 
4 Most represented transient trace to 1+ positive urinary protein by dipstick 
5 See further information below 

 

  



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Still’s Disease (SJIA and AOSD) 

 

SJIA pooled analysis and AOSD 

A total of 445 SJIA patients aged 2 to < 20 years received canakinumab in clinical trials, including 

321 patients aged 2 to < 12 years, 88 patients aged 12 to < 16 years, and 36 patients aged 16 to 

< 20 years. A pooled safety analysis of all SJIA patients showed that in the subset of young adult SJIA 

patients aged 16 to < 20 years, the safety profile of canakinumab was consistent with what was 

observed in SJIA patients less than 16 years of age. The safety profile of canakinumab in AOSD 

patients in a randomised, double blind placebo-controlled study (GDE01T) in 36 adult patients (aged 

22 to 70 years) was similar to what was observed in SJIA patients. 

 
Description of selected adverse reactions 

 

Long-term data and laboratory abnormalities in CAPS patients 

During clinical trials with canakinumab in CAPS patients mean values for haemoglobin increased and 

those for white blood cell, neutrophils and platelets decreased. 

 

Elevations of transaminases have been observed rarely in CAPS patients. 

 

Asymptomatic and mild elevations of serum bilirubin have been observed in CAPS patients treated 

with canakinumab without concomitant elevations of transaminases. 

 

In the long-term, open-label studies with dose escalation, events of infections (gastroenteritis, 

respiratory tract infection, upper respiratory tract infection), vomiting and dizziness were more 

frequently reported in the 600 mg or 8 mg/kg dose group than in other dose groups. 

 

Laboratory abnormalities in TRAPS, HIDS/MKD and FMF patients 

Neutrophils 

Although ≥ Grade 2 reductions in neutrophil count occurred in 6.5% of patients (common) and 

Grade 1 reductions occurred in 9.5% of patients, the reductions are generally transient and 

neutropenia-associated infection has not been identified as an adverse reaction. 

 

Platelets 

Although reductions in platelet count (≥ Grade 2) occurred in 0.6% of patients, bleeding has not been 

identified as an adverse reaction. Mild and transient Grade 1 reduction in platelets occurred in 15.9% 

of patients without any associated bleeding adverse events. 

 

Laboratory abnormalities in SJIA patients 

Haematology 

In the overall SJIA programme, transient decreased white blood cell (WBC) counts ≤ 0.8 x LLN were 

reported in 33 patients (16.5%). 

 

In the overall SJIA programme, transient decreases in absolute neutrophil count (ANC) to less than 1 x 

109/l were reported in 12 patients (6.0%). 

 

In the overall SJIA programme, transient decreases in platelet counts (< LLN) were observed in 

19 patients (9.5%). 

 

ALT/AST 

In the overall SJIA programme, high ALT and/or AST > 3 x upper limit of normal (ULN) were 

reported in 19 patients (9.5%). 

 



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Laboratory abnormalities in gouty arthritis patients 

Haematology 

Decreased white blood cell counts (WBC) ≤ 0.8 x lower limit of normal (LLN) were reported in 6.7% 

of patients treated with canakinumab compared to 1.4% treated with triamcinolone acetonide. 

Decreases in absolute neutrophil counts (ANC) to less than 1 x 109/l were reported in 2% of patients in 

the comparative trials. Isolated cases of ANC counts < 0.5 x 109/l were also observed (see section 4.4). 

 

Mild (< LLN and > 75 x 109/l) and transient decreases in platelet counts were observed at a higher 

incidence (12.7%) with canakinumab in the active-controlled clinical studies versus the comparator 

(7.7%) in gouty arthritis patients. 

 

Uric acid 

Increases in uric acid level (0.7 mg/dl at 12 weeks and 0.5 mg/dl at 24 weeks) were observed after 

canakinumab treatment in comparative trials in gouty arthritis. In another study, among patients who 

were starting on ULT, increases in uric acid were not observed. Uric acid increases were not observed 

in clinical trials in non-gouty arthritis populations (see section 5.1). 

 

ALT/AST 

Mean and median increases in alanine transaminase (ALT) of 3.0 U/l and 2.0 U/l, respectively, and in 

aspartate transaminase (AST) of 2.7 U/l and 2.0 U/l, respectively, from baseline to end of study were 

seen in the canakinumab-treated groups versus the triamcinolone acetonide-treated group(s), however 

the incidence of clinically significant changes (≥ 3 x the upper limit of normal) was greater for patients 

treated with triamcinolone acetonide (2.5% for both AST and ALT) compared with canakinumab-

treated patients (1.6% for ALT and 0.8% for AST). 

 

Triglycerides 

In active-controlled gouty arthritis trials, there was a mean increase in triglycerides of 33.5 mg/dl in 

canakinumab-treated patients compared with a modest decrease of -3.1 mg/dl with triamcinolone 

acetonide. The incidence of patients with triglyceride elevations > 5 x upper limit of normal (ULN) 

was 2.4% with canakinumab and 0.7% with triamcinolone acetonide. The clinical significance of this 

observation is unknown. 

 

Long term data from observational study 

 

A total of 243 CAPS patients (85 paediatric patients aged ≥ 2 to ≤ 17 years and 158 adult patients aged 

≥ 18 years) were treated with canakinumab in routine clinical practice in a long-term registry study 

(mean of 3.8 years of canakinumab exposure). The safety profile of canakinumab observed following 

long-term treatment in this setting was consistent with what has been observed in interventional 

studies in CAPS patients. 

 

Paediatric population 

 

There were 80 paediatric CAPS patients (2-17 years of age) who received canakinumab in the 

interventional studies. Overall, there were no clinically meaningful differences in the safety and 

tolerability profile of canakinumab in paediatric patients compared to the overall CAPS population 

(comprised of adult and paediatric patients, N=211), including the overall frequency and severity of 

infectious episodes. Infections of the upper respiratory tract were the most frequently reported 

infection events. 

 

Additionally, 6 paediatric patients under the age of 2 years were evaluated in a small open-label 

clinical study. The safety profile of canakinumab appeared similar to that in patients aged 2 years and 

above. 

 

There were 102 TRAPS, HIDS/MKD and FMF patients (2-17 years of age) who received 

canakinumab in a 16-week study. Overall, there were no clinically meaningful differences in the safety 

and tolerability profile of canakinumab in paediatric patients compared to the overall population. 

 



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Elderly population 

 

There is no significant difference in safety profile observed in patients ≥ 65 years of age. 

 

Reporting of suspected adverse reactions 

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 

4.9 Overdose 
 

Reported experience with overdose is limited. In early clinical trials, patients and healthy volunteers 

received doses as high as 10 mg/kg, administered intravenously or subcutaneously, without evidence 

of acute toxicity. 

 

In case of overdose, it is recommended for the patient to be monitored for any signs or symptoms of 

adverse reactions, and appropriate symptomatic treatment instituted immediately. 

 

 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: Immunosuppressants, interleukin inhibitors, ATC code: L04AC08 

 

Mechanism of action 

 

Canakinumab is a human monoclonal anti-human interleukin-1 beta (IL-1 beta) antibody of the 

IgG1/κ isotype. Canakinumab binds with high affinity specifically to human IL-1 beta and neutralises 

the biological activity of human IL-1 beta by blocking its interaction with IL-1 receptors, thereby 

preventing IL-1 beta-induced gene activation and the production of inflammatory mediators. 

 

Pharmacodynamic effects 

 

CAPS, TRAPS, HIDS/MKD and FMF 

In clinical studies, CAPS, TRAPS, HIDS/MKD and FMF patients who have uncontrolled over-

production of IL-1 beta show a rapid and sustained response to therapy with canakinumab, i.e. 

laboratory parameters such as high C-reactive protein (CRP) and serum amyloid A (SAA), high 

neutrophil and platelet counts, and leukocytosis rapidly returned to normal. 

 

Still’s disease (SJIA and AOSD) 

Adult-onset Still’s disease and systemic juvenile idiopathic arthritis are severe autoinflammatory 

diseases, driven by innate immunity by means of pro-inflammatory cytokines, a key one being IL-1-

beta. 

 

Common features of SJIA and AOSD include fever, rash, hepatosplenomegaly, lymphadenopathy, 

polyserositis and arthritis. Treatment with canakinumab resulted in a rapid and sustained improvement 

of both the articular and the systemic features of SJIA with significant reduction of the number of 

inflamed joints, prompt resolution of fever and reduction of acute phase reactants in the majority of 

patients (see Clinical efficacy and safety). 

 

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


15 

Gouty arthritis 

A gouty arthritis attack is caused by urate (monosodium urate monohydrate) crystals in the joint and 

surrounding tissue, which trigger resident macrophages to produce IL-1 beta via the “NALP3 

inflammasome” complex. Activation of macrophages and concomitant over-production of IL-1 beta 

results in an acute painful inflammatory response. Other activators of the innate immune system, such 

as endogenous agonists of toll-like receptors, may contribute to the transcriptional activation of the IL-

1 beta gene, initiating a gouty arthritis attack. Following canakinumab treatment, the inflammatory 

markers CRP or SAA and signs of acute inflammation (e.g. pain, swelling, redness) in the affected 

joint subside rapidly. 

 

Clinical efficacy and safety 

 

CAPS 

The efficacy and safety of canakinumab have been demonstrated in a total of 211 adult and paediatric 

patients with varying degrees of disease severity and different CAPS phenotypes (including 

FCAS/FCU, MWS, and NOMID/CINCA). Only patients with confirmed NLRP3 mutation were 

included in the pivotal study. 

 

In the Phase I/II study, treatment with canakinumab had a rapid onset of action, with disappearance or 

clinically significant improvement of symptoms within one day after dosing. Laboratory parameters 

such as high CRP and SAA, high neutrophils and platelet counts normalised rapidly within days of 

canakinumab injection. 

 

The pivotal study consisted of a 48-week three-part multicentre study, i.e. an 8-week open-label period 

(Part I), a 24-week randomised, double-blind, placebo-controlled withdrawal period (Part II), followed 

by a 16-week open-label period (Part III). The aim of the study was to assess efficacy, safety, and 

tolerability of canakinumab (150 mg or 2 mg/kg every 8 weeks) in patients with CAPS. 

 

 Part I: A complete clinical and biomarker response to canakinumab (defined as composite of 
physician’s global assessment on autoinflammatory and on skin disease ≤ minimal and CRP or 

SAA values < 10 mg/litre) was observed in 97% of patients and appeared within 7 days of 

initiation of treatment. Significant improvements were seen in physician’s clinical assessment of 

autoinflammatory disease activity: global assessment of autoinflammatory disease activity, 

assessment of skin disease (urticarial skin rash), arthralgia, myalgia, headache/migraine, 

conjunctivitis, fatigue/malaise, assessment of other related symptoms, and patient’s assessment 

of symptoms. 

 

 Part II: In the withdrawal period of the pivotal study, the primary endpoint was defined as the 
proportion of patients with a disease relapse/flare: none (0%) of the patients randomised to 

canakinumab flared, compared with 81% of the patients randomised to placebo. 

 

 Part III: Patients treated with placebo in Part II who flared regained and maintained clinical and 
serological response following entry into the open-label canakinumab extension. 

 



16 

Table 2 Tabulated summary of efficacy in Phase III trial, pivotal placebo-controlled 

withdrawal period (Part II) 

 

Phase III trial, pivotal placebo-controlled withdrawal period (Part II) 

 Canakinumab 

N=15 

n(%) 

Placebo 

N=16 

n(%) 

 

p-value 

 

Primary endpoint (flare) 
 Proportion of patients with disease flare in Part II 0 (0%) 13 (81%) < 0.001 

 

Inflammatory markers* 
 C-reactive protein, mg/l 1.10 (0.40) 19.93 (10.50) < 0.001 

 Serum amyloid A, mg/l 2.27 (-0.20) 71.09 (14.35) 0.002 

* mean (median) change from beginning of Part II 

 

Two open-label, uncontrolled, long-term phase III studies were performed. One was a safety, 

tolerability, and efficacy study of canakinumab in patients with CAPS. The total treatment duration 

ranged from 6 months to 2 years. The other was an open-label study with canakinumab to evaluate the 

efficacy and safety in Japanese CAPS patients for 24 weeks, with an extension phase up to 48 weeks. 

The primary objective was to assess the proportion of patients who were free of relapse at week 24, 

including those patients whose dose was increased. 

 

In the pooled efficacy analysis for these two studies, 65.6% of patients who had not previously been 

treated with canakinumab achieved complete response at 150 mg or 2 mg/kg, while 85.2% of patients 

achieved complete response at any dose. Of the patients treated with 600 mg or 8 mg/kg (or even 

higher), 43.8% achieved complete response. Fewer patients aged 2 to < 4 years achieved complete 

response (57.1%) than older paediatric and adult patients. Of the patients who had achieved a 

complete response, 89.3% maintained response without relapsing. 

 

Experience from individual patients who achieved a complete response following dose escalation to 

600 mg (8 mg/kg) every 8 weeks suggests that a higher dose may be beneficial in patients not 

achieving complete response or not maintaining complete response with the recommended doses 

(150 mg or 2 mg/kg for patients ≥ 15 kg and ≤ 40 kg). An increased dose was administered more 

frequently to patients aged 2 to < 4 years and to patients with NOMID/CINCA symptoms compared 

with FCAS or MWS. 

 

A 6-year observational registry study was conducted to provide data on the long-term safety and 

effectiveness of canakinumab treatment in paediatric and adult CAPS patients in routine clinical 

practice. The study included 243 CAPS patients (including 85 patients less than 18 years of age). 

Disease activity was rated as absent or mild/moderate in more than 90% of patients at all post-baseline 

time points in the study, and median serological markers of inflammation (CRP and SAA) were 

normal (< 10 mg/litre) at all post-baseline time points. Although approximately 22% of patients 

receiving canakinumab required dose adjustment, only a small percentage of patients (1.2%) 

discontinued canakinumab due to lack of therapeutic effect. 

 

  



17 

Paediatric population 

The CAPS interventional trials with canakinumab included a total of 80 paediatric patients with an age 

range from 2 to 17 years (approximately half of them treated on an mg/kg basis). Overall, there were 

no clinically meaningful differences in the efficacy, safety and tolerability profile of canakinumab in 

paediatric patients compared to the overall CAPS population. The majority of paediatric patients 

achieved improvement in clinical symptoms and objective markers of inflammation (e.g. SAA and 

CRP). 

 

A 56-week, open-label study was conducted to assess the efficacy, safety and tolerability of 

canakinumab in paediatric CAPS patients ≤ 4 years of age. Seventeen patients (including 6 patients 

under the age of 2 years) were evaluated, using weight-based starting doses of 2-8 mg/kg. The study 

also evaluated the effect of canakinumab on the development of antibodies to standard childhood 

vaccines. No differences in safety or efficacy were observed in patients under the age of 2 years 

compared with patients aged 2 years and above. All patients who received non-live, standard of care 

childhood vaccinations (N=7) developed protective antibody levels. 

 

TRAPS, HIDS/MKD and FMF 

The efficacy and safety of canakinumab for the treatment of TRAPS, HIDS/MKD and FMF were 

demonstrated in a single, pivotal, phase III, 4-part study (N2301) consisting of three separate disease 

cohorts. 

- Part I: Patients in each disease cohort aged 2 years and older entered a 12-week screening period 
during which they were evaluated for the onset of disease flare. 

- Part II: Patients at flare onset were randomised into a 16-week double-blind, placebo-controlled 
treatment period during which they received either 150 mg canakinumab (2 mg/kg for patients 

with body weight ≤ 40 kg) subcutaneous (s.c.) or placebo every 4 weeks. Patients > 28 days but 

< 2 years of age were allowed to enter the study directly into an open-arm of Part II as non-

randomised patients (and were excluded from the primary efficacy analysis). 

- Part III: Patients who completed 16 weeks of treatment and were classified as responders were 
re-randomised into a 24-week, double-blind withdrawal period during which they received 

canakinumab 150 mg (2 mg/kg for patients ≤ 40 kg) s.c. or placebo every 8 weeks. 

- Part IV: All Part III patients treated with canakinumab were eligible to enter into a 72-week 
open-label treatment extension period. 

 

A total of 185 patients aged 28 days and above were enrolled and a total of 181 patients aged 2 years 

and above were randomised in part II of the study. 

 

The primary efficacy endpoint of the randomised treatment period (Part II) was the proportion of 

responders within each cohort who had resolution of their index disease flare at day 15 and did not 

experience a new flare during the remainder of the 16-week treatment period (defined as complete 

response). Resolution of the index disease flare was defined as having a Physician’s Global 

Assessment (PGA) of Disease Activity score < 2 (“minimal or no disease”) and CRP within normal 

range (≤ 10 mg/l) or reduction ≥ 70% from baseline. A new flare was defined as a PGA score ≥ 2 

(“mild, moderate, or severe disease”) and CRP ≥ 30 mg/l. Secondary endpoints, all based on week 16 

results (end of Part II), included the proportion of patients who achieved a PGA score of < 2, the 

proportion of patients with serological remission (defined as CRP ≤ 10 mg/l), and the proportion of 

patients with a normalised SAA level (defined as SAA ≤ 10 mg/l). 

 

For the primary efficacy endpoint, canakinumab was superior to placebo for all three disease cohorts. 

Canakinumab also demonstrated superior efficacy compared to placebo on the secondary endpoints of 
PGA < 2 and CRP ≤ 10 mg/l in all three cohorts. Higher proportions of patients had normalised SAA 

(≤ 10 mg/l) at week 16 with canakinumab treatment compared to placebo in all three cohorts, with a 

statistically significant difference observed in TRAPS patients (see Table 3 with study results below). 

 



18 

Table 3 Tabulated summary of efficacy in Phase III trial, pivotal, randomised, placebo-

controlled treatment period (Part II) 

 

Phase III trial, pivotal, randomised placebo-controlled treatment period (Part II) 

 Canakinumab 

n/N (%) 

Placebo 

n/N (%) 

 

p-value 

Primary endpoint (disease flare) - Proportion of patients who had index disease flare resolution at 

day 15 and did not experience a new flare during the remainder of the 16-week treatment period 

FMF 19/31 (61.29) 2/32 (6.25) < 0.0001* 

HIDS/MKD 13/37 (35.14) 2/35 (5.71) 0.0020* 

TRAPS 10/22 (45.45) 2/24 (8.33) 0.0050* 

Secondary endpoints (disease and inflammatory markers) 
 Physician Global Assessment < 2    

FMF 20/31 (64.52) 3/32 (9.38) < 0.0001** 

HIDS/MKD 17/37 (45.95) 2/35 (5.71) 0.0006** 

TRAPS 10/22 (45.45) 1/24 (4.17) 0.0028** 

 C-reactive protein ≤ 10 mg/l    

FMF 21/31 (67.74) 2/32 (6.25) < 0.0001** 

HIDS/MKD 15/37 (40.54) 2/35 (5.71) 0.0010** 

TRAPS 8/22 (36.36) 2/24 (8.33) 0.0149** 

 Serum amyloid A ≤ 10 mg/l    

FMF 8/31 (25.81) 0/32 (0.00) 0.0286 

HIDS/MKD 5/37 (13.51) 1/35 (2.86) 0.0778 

TRAPS 6/22 (27.27) 0/24 (0.00) 0.0235** 

n=number of responders; N=number of evaluable patients 

* indicates statistical significance (one-sided) at the 0.025 level based on Fisher exact test 

** Indicates statistical significance (one-sided) at the 0.025 level based on the logistic regression model 

with treatment group and baseline PGA, CRP or SAA respectively, as explanatory variables for each 

cohort 

 

Up-titration 

In Part II of the study, patients treated with canakinumab who had persistent disease activity received 

an additional dose of 150 mg (or 2 mg/kg for patients ≤ 40 kg) within the first month. This additional 

dose could be provided as early as 7 days after the first treatment dose. All up-titrated patients 

remained at the increased dose of 300 mg (or 4 mg/kg for patients ≤ 40 kg) every 4 weeks. 

 

In an exploratory analysis of the primary endpoint, it was observed that in patients with an inadequate 

response after the first dose, an up-titration within the first month to a dose of 300 mg (or 4 mg/kg) 

every 4 weeks further improved flare control, reduced disease activity and normalised CRP and SAA 

levels. 

 

Paediatric patients: 

Two non-randomised HIDS/MKD patients aged > 28 days but < 2 years were included in the study 

and received canakinumab. One patient had resolution of index flare by day 15 after receiving one 

single dose of canakinumab 2 mg/kg, but discontinued treatment after this first dose due to serious 

adverse events (pancytopenia and hepatic failure). This patient presented at study entry with a history 

of immune thrombocytopenic purpura and an active medical condition of abnormal hepatic function. 

The second patient received a starting dose of canakinumab 2 mg/kg and an add-on dose of 2 mg/kg at 

week 3, and was up-titrated at week 5 to receive a dose of 4 mg/kg administered every 4 weeks until 

the end of Part II of the study. Resolution of disease flare was achieved by week 5 and the patient had 

not experienced any new flare at the end of Part II of the study (week 16). 

 



19 

Still’s disease (SJIA and AOSD) 

SJIA 

The efficacy of canakinumab for the treatment of active SJIA was assessed in two pivotal phase III 

studies (G2305 and G2301). Patients enrolled were aged 2 to < 20 years (mean age of 8.5 years and 

mean disease duration of 3.5 years at baseline) and had active disease defined as ≥ 2 joints with active 

arthritis, fever and elevated CRP. 

 

Study G2305 

Study G2305 was a randomised, double-blind, placebo-controlled, 4-week study assessing the short-

term efficacy of canakinumab in 84 patients randomised to receive a single dose of 4 mg/kg (up to 

300 mg) canakinumab or placebo. The primary objective was the proportion of patients at day 15 who 

achieved a minimum 30% improvement in the paediatric American College of Rheumatology (ACR) 

response criterion adapted to include absence of fever. Canakinumab treatment improved all paediatric 

ACR response scores as compared to placebo at days 15 and 29 (Table 4). 

 

Table 4 Paediatric ACR response and disease status at days 15 and 29 

 

 Day 15 Day 29 

 Canakinumab 

N=43 

Placebo 

N=41 

Canakinumab

N=43 

Placebo 

N=41 

ACR30 84% 10% 81% 10% 

ACR50 67% 5% 79% 5% 

ACR70 61% 2% 67% 2% 

ACR90 42% 0% 47% 2% 

ACR100 33% 0% 33% 2% 

Inactive disease 33% 0% 30% 0% 

Treatment difference for all ACR scores was significant (p ≤ 0.0001) 

 

Results for the components of the adapted paediatric ACR which included systemic and arthritic 

components, were consistent with the overall ACR response results. At day 15, the median change 

from baseline in the number of joints with active arthritis and limited range of motion were -67% 

and -73% for canakinumab (N=43), respectively, compared to a median change of 0% and 0% for 

placebo (N=41). The mean change in patient pain score (0-100 mm visual analogue scale) at day 15 

was -50.0 mm for canakinumab (N=43), as compared to +4.5 mm for placebo (N=25). The mean 

change in pain score among canakinumab treated patients was consistent at day 29. 

 

Study G2301 

Study G2301 was a randomised, double-blind, placebo-controlled withdrawal study of flare prevention 

by canakinumab. The study consisted of two parts with two independent primary endpoints (successful 

steroid taper and time to flare). In Part I (open label) 177 patients were enrolled and received 4 mg/kg 

(up to 300 mg) canakinumab administered every 4 weeks for up to 32 weeks. Patients in Part II 

(double-blind) received either canakinumab 4 mg/kg or placebo every 4 weeks until 37 flare events 

occurred. 

 

Corticosteroid dose tapering: 

Of the total 128 patients who entered Part I taking corticosteroids, 92 attempted corticosteroid 

tapering. Fifty-seven (62%) of the 92 patients who attempted to taper were able to successfully taper 

their corticosteroid dose and 42 (46%) discontinued corticosteroids. 

 

Time to flare: 

Patients taking canakinumab in Part II had a 64% reduced risk of a flare event as compared to the 

placebo group (hazard ratio of 0.36; 95% CI: 0.17 to 0.75; p=0.0032). Sixty-three of the 100 patients 

entering Part II, whether assigned to placebo or canakinumab, did not experience a flare over the 

observation period (up to a maximum of 80 weeks). 

 



20 

Health-related and quality of life outcomes in studies G2305 and G2301 

Treatment with canakinumab resulted in clinically relevant improvements in patients’ physical 

function and quality of life. In study G2305, the Childhood Health Assessment Questionnaire Least 

Squares means improvement was 0.69 for canakinumab vs placebo representing 3.6 times the minimal 

clinically important difference of 0.19 (p=0.0002). The median improvement from baseline to end of 

Part I of study G2301 was 0.88 (79%). Statistically significant improvements in the Child Health 

Questionnaire-PF50 scores were reported for canakinumab vs placebo in study G2305 (physical 

p=0.0012; psychosocial well-being p=0.0017). 

 

Pooled efficacy analysis 

Data from the first 12 weeks of canakinumab treatment from studies G2305, G2301 and the extension 

study were pooled to assess maintenance of efficacy. These data showed similar improvements from 

baseline to week 12 in the adapted paediatric ACR responses and its components to those observed in 

the placebo controlled study (G2305). At week 12, the adapted paediatric ACR30, 50, 70, 90 and 100 

responses were: 70%, 69%, 61%, 49% and 30%, respectively and 28% of patients had inactive disease 

(N=178). 

 

Although limited, evidence from the clinical trials suggests that patients not responding to tocilizumab 

or anakinra may respond to canakinumab. 

 

Study G2301E1 

The efficacy observed in the studies G2305 and G2301 was maintained in the open-label long-term 

extension study G2301E1. Of the 270 SJIA patients in the study, 147 patients had received treatment 

with canakinumab in studies G2305 or G2301 (Cohort I), and 123 patients were canakinumab-naive 

patients (Cohort II). Patients in Cohort I were treated for a median duration of 3.2 years (up to 

5.2 years), and patients in Cohort II were treated for a median duration of 1.8 years (up to 2.8 years). 

In the extension study, all patients received canakinumab 4 mg/kg (up to maximum 300 mg) every 

4 weeks. In both cohorts, patients who were well-controlled responders (retrospectively defined as 

adapted paediatric ACR ≥ 90) and who did not require a concomitant corticosteroid were permitted to 

reduce their canakinumab dose to 2 mg/kg every 4 weeks (62/270; 23%). 

 

Study G2306 

Study G2306 was an open-label study to assess maintenance of treatment response with canakinumab 

dose reduction (2 mg/kg every 4 weeks) or dose interval prolongation (4 mg/kg every 8 weeks) in 

SJIA patients who were receiving canakinumab 4 mg/kg every 4 weeks. Seventy five patients aged 2 

to 22 years who maintained inactive disease status for at least 6 consecutive months (clinical 

remission) with canakinumab monotherapy, including patients who were able to maintain inactive 

disease status with discontinuation of concomitant corticosteroid and/or methotrexate use for at least 

4 weeks, were randomised to receive canakinumab 2 mg/kg every 4 weeks (N=38) or canakinumab 

4 mg/kg every 8 weeks (N=37). After 24 weeks, 71% (27/38) of patients who received the reduced 

dose (2 mg/kg every 4 weeks) and 84% (31/37) of patients who received the prolonged dosing interval 

(4 mg/kg every 8 weeks) were able to maintain inactive disease status for 6 months. Of the patients in 

clinical remission who continued with further dose reduction (1 mg/kg every 4 weeks) or dose interval 

prolongation (4 mg/kg every 12 weeks), 93% (26/28) and 91% (30/33) of patients, respectively, were 

able to maintain inactive disease status for 6 months. Patients who maintained inactive disease status 

for 6 additional months at this lowest dose regimen were allowed to discontinue canakinumab. 

Overall, 33% (25/75) of patients randomised to dose reduction or dose interval prolongation arms 

were able to discontinue treatment with canakinumab and maintain inactive disease status for 

6 months. The rate of adverse events in both treatment arms was similar to the rate seen in patients 

treated with canakinumab 4 mg/kg every 4 weeks. 

 



21 

AOSD 

The efficacy of canakinumab 4 mg/kg (up to maximum 300 mg) administered every 4 weeks in AOSD 

patients in a randomised, double-blind placebo-controlled study in 36 patients (22 to 70 years old) was 

comparable to that observed in SJIA patients. In study GDE01T, a higher proportion of patients 

(12/18, 66.7%) in the canakinumab group than in the placebo group (7/17, 41.2%) demonstrated an 

improvement from baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28-

ESR) of > 1.2 at week 12, which failed to reach statistical significance (odds ratio 2.86, treatment 

difference [%] 25.49 [95% CI: 9.43, 55.80]). By week 4, 7 of 18 patients (38.9%) treated with 

canakinumab had already achieved DAS28-ESR remission versus 2 of 17 patients (11.8%) on placebo. 

These data are consistent with the results of a pooled efficacy analysis of 418 SJIA patients which 

showed that the efficacy of canakinumab in a subset of SJIA patients aged 16 to < 20 years (n=34) was 

consistent with the efficacy observed in patients less than 16 years of age (n=384). 

 

Gouty arthritis 

The efficacy of canakinumab for the treatment of acute gouty arthritis attacks was demonstrated in two 

multicentre, randomised, double-blind, active-controlled studies in patients with frequent gouty 

arthritis (≥ 3 attacks in the previous 12 months) unable to use NSAIDs or colchicine (due to 

contraindication, intolerance or lack of efficacy). The studies were 12 weeks followed by 12-week 

double-blind extension. A total of 225 patients were treated with subcutaneous canakinumab 150 mg 

and 229 patients were treated with intramuscular triamcinolone acetonide (TA) 40 mg at study entry, 

and when experiencing a new attack thereafter. The mean number of gouty arthritis attacks in the 

previous 12 months was 6.5. Over 85% of patients had comorbidity, including hypertension (60%), 

diabetes (15%), ischaemic heart disease (12%), and stage ≥ 3 chronic kidney disease (25%). 

Approximately one-third of the patients enrolled (76 [33.8%] in the canakinumab group and 84 

[36.7%] in the triamcinolone acetonide group) had documented inability (intolerance, contraindication 

or lack of response) to use both NSAIDs and colchicine. Concomitant treatment with ULTs was 

reported by 42% of patients at entry. 

 

The co-primary endpoints were: (i) gouty arthritis pain intensity (visual analogue scale, VAS) at 

72 hours post-dose, and (ii) time to first new gouty arthritis attack. 

 

For the overall study population, pain intensity was statistically significantly lower for canakinumab 

150 mg compared with triamcinolone acetonide at 72 hours. Canakinumab also reduced the risk of 

subsequent attacks (see Table 5). 

 

Efficacy results in a subgroup of patients unable to use both NSAIDs and colchicine and who were on 

ULT, failed ULT or had a contraindication to ULT (N=101) were consistent with the overall study 

population with a statistically significant difference compared to triamcinolone acetonide in pain 

intensity at 72 hours (-10.2 mm, p=0.0208) and in reduction of risk of subsequent attacks (Hazard ratio 

0.39, p=0.0047 at 24 weeks). 

 

Efficacy results for a more stringent subgroup limited to current users of ULT (N=62) are presented in 

Table 5. Treatment with canakinumab induced a reduction of pain and reduced the risk of subsequent 

attacks in patients using ULT and unable to use both NSAIDs and colchicine, although the observed 

treatment difference compared to triamcinolone acetonide was less pronounced than with the overall 

study population. 

 



22 

Table 5 Efficacy for the overall study population and in a subgroup of patients currently 

using ULT and unable to use both NSAIDs and colchicine 

 

Efficacy endpoint Overall study population;  

N=454 

Unable to use both NSAIDs 

and colchicine; on ULT 

N=62 

Treatment of gouty arthritis attacks as measured by pain intensity (VAS) at 72 h 

Least Squares mean estimated 

difference to triamcinolone acetonide 

CI 

p-value, 1-sided 

-10.7 

 

(-15.4, -6.0) 

p < 0.0001* 

-3.8 

 

(-16.7, 9.1) 

p=0.2798 

Risk reduction of subsequent gouty arthritis attacks as measured by time to first new flare 

(24 weeks) 

Hazard ratio to triamcinolone 

acetonide 

CI 

p-value, 1-sided 

0.44 

 

(0.32, 0.60) 

p < 0.0001* 

0.71 

 

(0.29, 1.77) 

p=0.2337 

* Denotes significant p-value ≤ 0.025 

 

Safety results showed an increased incidence of adverse events for canakinumab compared to 

triamcinolone acetonide, with 66% vs 53% of patients reporting any adverse event and 20% vs 10% of 

patients reporting an infection adverse event over 24 weeks. 

 

Elderly population 

Overall, the efficacy, safety and tolerability profile of canakinumab in elderly patients ≥ 65 years of 

age was comparable to patients < 65 years of age. 

 

Patients on urate lowering therapy (ULT) 

In clinical studies, canakinumab has been safely administered with ULT. In the overall study 

population, patients on ULT had a less pronounced treatment difference in both pain reduction and 

reduction in the risk of subsequent gouty arthritis attacks compared to patients not on ULT. 

 

Immunogenicity 

 

Antibodies against canakinumab were observed in approximately 1.5%, 3% and 2% of the patients 

treated with canakinumab for CAPS, SJIA and gouty arthritis, respectively. No neutralising antibodies 

were detected. No apparent correlation of antibody development to clinical response or adverse events 

was observed. 

 

There were no antibodies against canakinumab observed in TRAPS, HIDS/MKD and FMF patients 

treated with doses of 150 mg and 300 mg over 16 weeks of treatment. 

 

Paediatric population 

 

The Marketing Authorisation Holder has completed four Paediatric Investigation Plans for 

canakinumab (for CAPS, SJIA, FMF – HIDS/MKD and TRAPS respectively). This product 

information has been updated to include the results of studies with canakinumab in the paediatric 

population. 

 

The European Medicines Agency has waived the obligation to submit the results of studies with 

canakinumab in all subsets of the paediatric population in gouty arthritis (see section 4.2 for 

information on paediatric use). 

 



23 

5.2 Pharmacokinetic properties 
 

CAPS 

 

Absorption 

The peak serum canakinumab concentration (Cmax) occurred approximately 7 days following single 

subcutaneous administration of 150 mg in adult CAPS patients. The mean terminal half-life was 

26 days. Mean values for Cmax and AUCinf after a single subcutaneous dose of 150 mg in a typical 

adult CAPS patient (70 kg) were 15.9 µg/ml and 708 µg*d/ml. The absolute bioavailability of 

subcutaneously administered canakinumab was estimated to be 66%. Exposure parameters (such as 

AUC and Cmax) increased in proportion to dose over the dose range of 0.30 to 10.0 mg/kg given as 

intravenous infusion or from 150 to 600 mg as subcutaneous injection. Predicted steady-state exposure 

values (Cmin,ss, Cmax,ss, AUC,ss,8w) after 150 mg subcutaneous administration (or 2 mg/kg, respectively) 

every 8 weeks were slightly higher in the weight category 40-70 kg (6.6 µg/ml, 24.3 µg/ml, 

767 µg*d/ml) compared to the weight categories < 40 kg (4.0 µg/ml, 19.9 µg/ml, 566 µg*d/ml) and 

> 70 kg (4.6 µg/ml, 17.8 µg/ml, 545 µg*d/ml). The expected accumulation ratio was 1.3-fold 

following 6 months of subcutaneous administration of 150 mg canakinumab every 8 weeks. 

 

Distribution 

Canakinumab binds to serum IL-1 beta. The distribution volume (Vss) of canakinumab varied 

according to body weight. It was estimated to be 6.2 litres in a CAPS patient of body weight 70 kg. 

 

Elimination 

The apparent clearance (CL/F) of canakinumab increases with body weight. It was estimated to be 

0.17 l/d in a CAPS patient of body weight 70 kg and 0.11 l/d in a SJIA patient of body weight 33 kg. 

After accounting for body weight differences, no clinically significant differences in the 

pharmacokinetic properties of canakinumab were observed between CAPS and SJIA patients. 

 

There was no indication of accelerated clearance or time-dependent change in the pharmacokinetic 

properties of canakinumab following repeated administration. No gender or age-related 

pharmacokinetic differences were observed after correction for body weight. 

 

TRAPS, HIDS/MKD and FMF 

 

Bioavailability in TRAPS, HIDS/MKD and FMF patients has not been determined independently. 

Apparent clearance (CL/F) in the TRAPS, HIDS/MKD and FMF population at body weight of 55 kg 

(0.14 l/d) was comparable to CAPS population at body weight of 70 kg (0.17 l/d). The apparent 

volume of distribution (V/F) was 4.96 l at body weight of 55 kg. 

 

After repeated subcutaneous administration of 150 mg every 4 weeks, canakinumab minimal 

concentration at week 16 (Cmin) was estimated to be 15.4 ± 6.6 g/ml. The estimated steady state 

AUCtau was 636.7 ± 260.2 μg*d/ml. 

 

Still’s disease (SJIA and AOSD) 

 

Bioavailability in SJIA patients has not been determined independently. Apparent clearance per kg 

body weight (CL/F per kg) was comparable between the SJIA and CAPS population (0.004 l/d per 

kg). The apparent volume of distribution per kg (V/F per kg) was 0.14 l/kg. Sparse pharmacokinetics 

(PK) data in AOSD patients suggest similar PK of canakinumab as compared to SJIA and other patient 

populations. 

 

After repeated administration of 4 mg/kg every 4 weeks the accumulation ratio of canakinumab was 

1.6 fold in SJIA patients. Steady state was reached after 110 days. The overall predicted mean (±SD) 

for Cmin,ss, Cmax,ss and AUC,ss4w were 14.7±8.8 μg/ml, 36.5 ± 14.9 μg/ml and 696.1 ± 326.5 μg*d/ml, 

respectively. 

 



24 

The AUCss4w in each age group was 692, 615, 707 and 742 µg*d/ml for 2-3, 4-5, 6-11, and 12-19 years 

old, respectively. When stratified by weight, a lower (30-40%) median of exposure for Cmin,ss (11.4 vs 

19 µg/ml) and AUCss (594 vs 880 µg*d/ml) for the lower bodyweight category (≤ 40 kg) vs the higher 

bodyweight category (> 40 kg) was observed. 

 

Based on the population pharmacokinetic modelling analysis, the pharmacokinetics of canakinumab in 

young adult SJIA patients aged 16 to 20 years were similar to those in patients less than 16 years of 

age. Predicted canakinumab steady state exposures at a dose level of 4 mg/kg (maximum 300 mg) in 

patients over the age of 20 years were comparable to those in SJIA patients younger than 20 years of 

age. 

 

Gouty arthritis population 

 

Bioavailability in gouty arthritis patients has not been determined independently. Apparent clearance 

per kg body weight (CL/F per kg) was comparable between the gouty arthritis and CAPS population 

(0.004 l/d/kg). Mean exposure in a typical gouty arthritis patient (93 kg) after a single subcutaneous 

150 mg dose (Cmax: 10.8 µg/ml and AUCinf: 495 µg*d/ml) was lower than in a typical 70 kg CAPS 

patient (15.9 µg/ml and 708 µg*d/ml). This is consistent with the observed increase in CL/F with body 

weight. 

 

The expected accumulation ratio was 1.1-fold following subcutaneous administration of 150 mg 

canakinumab every 12 weeks. 

 

Paediatric population 

 

Peak concentrations of canakinumab occurred between 2 to 7 days (Tmax) following single 

subcutaneous administration of canakinumab 150 mg or 2 mg/kg in paediatric patients 4 years of age 

and older. The terminal half-life ranged from 22.9 to 25.7 days, similar to the pharmacokinetic 

properties observed in adults. Based on the population pharmacokinetic modelling analysis, the 

pharmacokinetics of canakinumab in children aged 2 to < 4 years were similar to those in patients 

4 years of age and older. Subcutaneous absorption rate was estimated to decrease with age and 

appeared to be fastest in the youngest patients. Accordingly, Tmax was shorter (3.6 days) in younger 

SJIA patients (2-3 years) compared to older SJIA patients (12-19 years; Tmax 6 days). Bioavailability 

(AUCss) was not affected. 

 

An additional pharmacokinetics analysis showed that the pharmacokinetics of canakinumab in 

6 paediatric CAPS patients under the age of 2 years were similar to the pharmacokinetics in paediatric 

patients 2-4 years of age. Based on the population pharmacokinetic modelling analysis, the expected 

exposures after a dose of 2 mg/kg were comparable across the CAPS paediatric age groups, but were 

approximately 40% lower in paediatric patients of very low body weight (e.g. 10 kg) than in adult 

patients (150 mg dose). This is consistent with the observations of higher exposure in higher body 

weight groups in CAPS patients. 

 

In TRAPS, HIDS/MKD and FMF, exposure parameters (trough concentrations) were comparable 

across age groups from 2 to < 20 years old following subcutaneous administration of canakinumab 

2 mg/kg every 4 weeks. 

 

Pharmacokinetic properties are similar in CAPS, TRAPS, HIDS/MKD, FMF and SJIA paediatric 

populations. 

 

Elderly population 

 

No change in pharmacokinetic parameters based on clearance or volume of distribution were observed 

between elderly patients and adult patients < 65 years of age. 

 



25 

5.3 Preclinical safety data 
 

Non-clinical data reveal no special hazard for humans based on conventional studies of cross-

reactivity, repeated dose toxicity, immunotoxicity, toxicity to reproduction and development. 

 

Formal carcinogenicity studies have not been conducted with canakinumab. 

 

 

6. PHARMACEUTICAL PARTICULARS 
 

6.1 List of excipients 
 

Sucrose 

Histidine 

Histidine hydrochloride monohydrate 

Polysorbate 80 

 

6.2 Incompatibilities 
 

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

products. 

 

6.3 Shelf life 
 

3 years. 

 

After reconstitution, from a microbiological point of view, the product should be used immediately. If 

not used immediately, in-use storage times and conditions prior to use are the responsibility of the user 

and would normally not be longer than 24 hours at 2°C - 8°C. 

 

6.4 Special precautions for storage 
 

Store in a refrigerator (2°C - 8°C). 

Do not freeze. 

Store in the original package 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 
 

Powder for solution for injection in a vial (type I glass) with a stopper (coated chlorobutyl rubber) and 

flip-off cap (aluminium). 

 

Packs containing 1 vial or multipacks containing 4 (4x1) vials. 

 

Not all pack sizes may be marketed. 

 

  



26 

6.6 Special precautions for disposal and other handling 
 

Ilaris 150 mg powder for solution for injection is supplied in a single-use vial for individual use. 

 

Instructions for reconstitution 

 

Using aseptic technique, reconstitute each vial of canakinumab at room temperature (typically 15°C to 

25°C) by slowly injecting 1 ml water for injections with a 1 ml syringe and an 

18 G x 2 inch (50 mm) needle. Swirl the vial slowly at an angle of about 45° for approximately 

1 minute and allow to stand for about 5 minutes. Then gently turn the vial upside down and back again 

ten times. If possible, avoid touching the rubber stopper with your fingers. Allow to stand for about 

15 minutes at room temperature to obtain a clear to opalescent solution. Do not shake. Do not use if 

particles are present in the solution. 

 

Tap the side of the vial to remove any residual liquid from the stopper. The solution should be free of 

visible particles and clear to opalescent. The solution should be colourless or may have a slight 

brownish-yellow tint. If the solution has a distinctly brown discolouration it should not be used. If not 

used immediately after reconstitution, the solution should be kept at 2°C to 8°C and used within 

24 hours. 

 

Instructions for administration 

 

Carefully withdraw the required volume depending on the dose to be administered (0.1 ml to 1 ml) and 

subcutaneously inject using a 27 G x 0.5 inch (13 mm) needle. 

 

Disposal 

 

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

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/564/001-002 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 23 October 2009 

Date of latest renewal: 06 June 2019 

 

 

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/


27 

1. NAME OF THE MEDICINAL PRODUCT 
 

Ilaris 150 mg/ml solution for injection 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

One vial contains 150 mg of canakinumab*. 

 

Each ml of solution contains 150 mg canakinumab. 

 

* human monoclonal antibody produced in mouse myeloma Sp2/0 cells by recombinant DNA 

technology 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Solution for injection (injection). 

 

The solution is clear to opalescent and colourless to slightly brownish yellow. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

Periodic fever syndromes 

 

Ilaris is indicated for the treatment of the following autoinflammatory periodic fever syndromes in 

adults, adolescents and children aged 2 years and older: 

 

Cryopyrin-associated periodic syndromes 

Ilaris is indicated for the treatment of cryopyrin-associated periodic syndromes (CAPS) including: 

 Muckle-Wells syndrome (MWS), 

 Neonatal-onset multisystem inflammatory disease (NOMID) / chronic infantile neurological, 
cutaneous, articular syndrome (CINCA), 

 Severe forms of familial cold autoinflammatory syndrome (FCAS) / familial cold urticaria 
(FCU) presenting with signs and symptoms beyond cold-induced urticarial skin rash. 

 

Tumour necrosis factor receptor associated periodic syndrome (TRAPS) 

Ilaris is indicated for the treatment of tumour necrosis factor (TNF) receptor associated periodic 

syndrome (TRAPS). 

 

Hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD) 

Ilaris is indicated for the treatment of hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase 

deficiency (MKD). 

 

Familial Mediterranean fever (FMF) 

Ilaris is indicated for the treatment of Familial Mediterranean Fever (FMF). Ilaris should be given in 

combination with colchicine, if appropriate. 

 



28 

Ilaris is also indicated for the treatment of: 

 

Still’s disease 

 

Ilaris is indicated for the treatment of active Still’s disease including adult-onset Still’s disease 

(AOSD) and systemic juvenile idiopathic arthritis (SJIA) in patients aged 2 years and older who have 

responded inadequately to previous therapy with non-steroidal anti-inflammatory drugs (NSAIDs) and 

systemic corticosteroids. Ilaris can be given as monotherapy or in combination with methotrexate. 

 

Gouty arthritis 

 

Ilaris is indicated for the symptomatic treatment of adult patients with frequent gouty arthritis attacks 

(at least 3 attacks in the previous 12 months) in whom non-steroidal anti-inflammatory drugs 

(NSAIDs) and colchicine are contraindicated, are not tolerated, or do not provide an adequate 

response, and in whom repeated courses of corticosteroids are not appropriate (see section 5.1). 

 

4.2 Posology and method of administration 

 

For CAPS, TRAPS, HIDS/MKD, FMF and Still’s disease, the treatment should be initiated and 

supervised by a specialist physician experienced in the diagnosis and treatment of the relevant 

indication. 

 

For gouty arthritis, the physician should be experienced in the use of biologics and Ilaris should be 

administered by a healthcare professional. 

 

Posology 

 

CAPS: Adults, adolescents and children aged 2 years and older 

The recommended starting dose of canakinumab for CAPS patients is: 

Adults, adolescents and children ≥ 4 years of age: 

 150 mg for patients with body weight > 40 kg 

 2 mg/kg for patients with body weight ≥ 15 kg and ≤ 40 kg 

 4 mg/kg for patients with body weight ≥ 7.5 kg and < 15 kg 
Children 2 to < 4 years of age: 

 4 mg/kg for patients with body weight ≥ 7.5 kg 
 

This is administered every eight weeks as a single dose via subcutaneous injection. 

 

For patients with a starting dose of 150 mg or 2 mg/kg, if a satisfactory clinical response (resolution of 

rash and other generalised inflammatory symptoms) has not been achieved 7 days after treatment start, 

a second dose of canakinumab at 150 mg or 2 mg/kg can be considered. If a full treatment response is 

subsequently achieved, the intensified dosing regimen of 300 mg or 4 mg/kg every 8 weeks should be 

maintained. If a satisfactory clinical response has not been achieved 7 days after this increased dose, a 

third dose of canakinumab at 300 mg or 4 mg/kg can be considered. If a full treatment response is 

subsequently achieved, maintaining the intensified dosing regimen of 600 mg or 8 mg/kg every 

8 weeks should be considered, based on individual clinical judgement. 

 

  



29 

For patients with a starting dose of 4 mg/kg, if a satisfactory clinical response has not been achieved 

7 days after treatment start, a second dose of canakinumab 4 mg/kg can be considered. If a full 

treatment response is subsequently achieved, maintaining the intensified dosing regimen of 8 mg/kg 

every 8 weeks should be considered, based on individual clinical judgement. 

 

Clinical experience with dosing at intervals of less than 4 weeks or at doses above 600 mg or 8 mg/kg 

is limited. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

  

CAPS in adults and children  4 years of age 
 15 kg 

Maintenance dose: 
150 mg or 2 mg/kg 

every 8 weeks 

Additional dose of 
150 mg or 2 mg/kg 
can be considered 

150 mg or 2 mg/kg 

Additional dose of 
300 mg or 4 mg/kg can 

be considered 

Maintenance 
dose 4 mg/kg 
every 8 weeks 

Additional dose 
of 4 mg/kg can 
be considered 

Satisfactory clinical response after 
7 days? 

Satisfactory clinical 
response after 7 days? 

Maintenance dose: 
300 mg or 4 mg/kg 

every 8 weeks 

If full treatment response after 
7 days, maintenance dose: 
600 mg or 8 mg/kg every 

8 weeks 

Satisfactory clinical 
response after 7 days? 

4 mg/kg 

CAPS in children 2-< 4 years of age or  

children  4 years of age  7.5 kg and < 15 kg 

If full treatment 
response after 7 days, 

maintenance dose: 
8 mg/kg every 8 weeks 

Yes No 

No 
No Yes Yes 



30 

TRAPS, HIDS/MKD and FMF: Adults, adolescents and children aged 2 years and older 

The recommended starting dose of canakinumab in TRAPS, HIDS/MKD and FMF patients is: 

 150 mg for patients with body weight > 40 kg 

 2 mg/kg for patients with body weight ≥ 7.5 kg and ≤ 40 kg 
 

This is administered every four weeks as a single dose via subcutaneous injection. 

 

If a satisfactory clinical response has not been achieved 7 days after treatment start, a second dose of 

canakinumab at 150 mg or 2 mg/kg can be considered. If a full treatment response is subsequently 

achieved, the intensified dosing regimen of 300 mg (or 4 mg/kg for patients weighing ≤ 40 kg) every 

4 weeks should be maintained. 

 

Continued treatment with canakinumab in patients without clinical improvement should be 

reconsidered by the treating physician. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Still’s disease (SJIA and AOSD) 

The recommended dose of canakinumab for patients with Still’s disease with body weight ≥ 7.5 kg is 

4 mg/kg (up to a maximum of 300 mg) administered every four weeks via subcutaneous injection. 

Continued treatment with canakinumab in patients without clinical improvement should be 

reconsidered by the treating physician. 

 

Gouty arthritis 

Management of hyperuricaemia with appropriate urate lowering therapy (ULT) should be instituted or 

optimised. Canakinumab should be used as an on-demand therapy to treat gouty arthritis attacks. 

 

The recommended dose of canakinumab for adult patients with gouty arthritis is 150 mg administered 

subcutaneously as a single dose during an attack. For maximum effect, canakinumab should be 

administered as soon as possible after the onset of a gouty arthritis attack. 

 

TRAPS, HIDS/MKD and FMF patients  
with body weight > 40 kg 

Maintenance 
dose: 150 mg 
every 4 weeks 

Additional dose of 
150 mg can be 

considered 

150 mg 

Maintenance 
dose 2 mg/kg 
every 4 weeks 

Additional dose 
of 2 mg/kg can 
be considered 

Satisfactory clinical 
response after 7 days? 

Satisfactory clinical 
response after 7 days? 

2 mg/kg 

TRAPS, HIDS/MKD and FMF patients  

with body weight  7.5 kg and ≤ 40 kg 

If full treatment response is 
achieved, maintenance dose: 

4 mg/kg every 4 weeks 

No 
 

No Yes Yes 
 

If full treatment response is 
achieved, maintenance dose: 

300 mg every 4 weeks 



31 

Patients who do not respond to initial treatment should not be re-treated with canakinumab. In patients 

who respond and require re-treatment, there should be an interval of at least 12 weeks before a new 

dose of canakinumab may be administered (see section 5.2). 

 

Special populations 

 

Paediatric population 

CAPS, TRAPS, HIDS/MKD and FMF 

The safety and efficacy of canakinumab in CAPS, TRAPS, HIDS/MKD and FMF patients under 

2 years of age have not been established. Currently available data are described in sections 4.8, 5.1 and 

5.2 but no recommendation on a posology can be made. 

 

SJIA 

The safety and efficacy of canakinumab in SJIA patients under 2 years of age have not been 

established. No data are available. 

 

Gouty arthritis 

There is no relevant use of canakinumab in the paediatric population in the indication gouty arthritis. 

 

Elderly 

No dose adjustment is required. 

 

Hepatic impairment 

Canakinumab has not been studied in patients with hepatic impairment. No recommendation on a 

posology can be made. 

 

Renal impairment 

No dose adjustment is needed in patients with renal impairment. However, clinical experience in such 

patients is limited. 

 

Method of administration 

 

For subcutaneous use. 

The following are suitable injection sites: upper thigh, abdomen, upper arm or buttocks. It is 

recommended to select a different injection site each time the product is injected to avoid soreness. 

Broken skin and areas which are bruised or covered by a rash should be avoided. Injection into scar 

tissue should be avoided as this may result in insufficient exposure to canakinumab. 

 

Each vial is for single use in a single patient, for a single dose. 

 

After proper training in the correct injection technique, patients or their caregivers may inject 

canakinumab if the physician determines that it is appropriate and with medical follow-up as necessary 

(see section 6.6). 

 

4.3 Contraindications 
 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 

Active, severe infections (see section 4.4). 

 

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. 

 



32 

Infections 

 

Canakinumab is associated with an increased incidence of serious infections. Therefore patients 

should be monitored carefully for signs and symptoms of infections during and after treatment with 

canakinumab. Physicians should exercise caution when administering canakinumab to patients with 

infections, a history of recurring infections, or underlying conditions which may predispose them to 

infections. 

 

Treatment of CAPS, TRAPS, HIDS/MKD, FMF and Still’s disease (SJIA and AOSD) 

Canakinumab should not be initiated or continued in patients during an active infection requiring 

medical intervention. 

 

Treatment of gouty arthritis 

Canakinumab should not be administered during an active infection. 

Concomitant use of canakinumab with tumour necrosis factor (TNF) inhibitors is not recommended 

because this may increase the risk of serious infections (see section 4.5). 

 

Isolated cases of unusual or opportunistic infections (including aspergillosis, atypical mycobacterial 

infections, herpes zoster) have been reported during canakinumab treatment. The causal relationship of 

canakinumab to these events cannot be excluded. 

 

Tuberculosis screening 

 

In approximately 12% of CAPS patients tested with a PPD (purified protein derivative) skin test in 

clinical trials, follow-up testing yielded a positive test result while treated with canakinumab without 

clinical evidence of a latent or active tuberculosis infection. 

 

It is unknown whether the use of interleukin-1 (IL-1) inhibitors such as canakinumab increases the risk 

of reactivation of tuberculosis. Before initiation of therapy, all patients must be evaluated for both 

active and latent tuberculosis infection. Particularly in adult patients, this evaluation should include a 

detailed medical history. Appropriate screening tests (e.g. tuberculin skin test, interferon gamma 

release assay or chest X-ray) should be performed in all patients (local recommendations may apply). 

Patients must be monitored closely for signs and symptoms of tuberculosis during and after treatment 

with canakinumab. All patients should be instructed to seek medical advice if signs or symptoms 

suggestive of tuberculosis (e.g. persistent cough, weight loss, subfebrile temperature) appear during 

canakinumab therapy. In the event of conversion from a negative to a positive PPD test, especially in 

high-risk patients, alternative means of screening for a tuberculosis infection should be considered. 

 

Neutropenia and leukopenia 

 

Neutropenia (absolute neutrophil count [ANC] < 1.5 x 109/l) and leukopenia have been observed with 

medicinal products that inhibit IL-1, including canakinumab. Treatment with canakinumab should not 

be initiated in patients with neutropenia or leukopenia. It is recommended that white blood cell (WBC) 

counts including neutrophil counts be assessed prior to initiating treatment and again after 1 to 

2 months. For chronic or repeated therapies, it is also recommended to assess WBC counts 

periodically during treatment. If a patient becomes neutropenic or leukopenic, the WBC counts should 

be monitored closely and treatment discontinuation should be considered. 

 

Malignancies 

 

Malignancy events have been reported in patients treated with canakinumab. The risk for the 

development of malignancies with anti-interleukin (IL)-1 therapy is unknown. 

 



33 

Hypersensitivity reactions 

 

Hypersensitivity reactions with canakinumab therapy have been reported. The majority of these events 

were mild in severity. During clinical development of canakinumab in over 2,600 patients, no 

anaphylactoid or anaphylactic reactions attributable to treatment with canakinumab were reported. 

However, the risk of severe hypersensitivity reactions, which is not uncommon for injectable proteins, 

cannot be excluded (see section 4.3). 

 

Hepatic function 

 

Transient and asymptomatic cases of elevations of serum transaminases or bilirubin have been 

reported in clinical trials (see section 4.8). 

 

Vaccinations 

 

No data are available on the risk of secondary transmission of infection by live (attenuated) vaccines 

in patients receiving canakinumab. Therefore, live vaccines should not be given concurrently with 

canakinumab unless the benefits clearly outweigh the risks (see section 4.5). 

 

Prior to initiation of canakinumab therapy it is recommended that adult and paediatric patients receive 

all vaccinations, as appropriate, including pneumococcal vaccine and inactivated influenza vaccine 

(see section 4.5). 

 

Mutation in NLRP3 gene in CAPS patients 

 

Clinical experience in CAPS patients without a confirmed mutation in the NLRP3 gene is limited. 

 

Macrophage activation syndrome in patients with Still’s disease (SJIA and AOSD) 

 

Macrophage activation syndrome (MAS) is a known, life-threatening disorder that may develop in 

patients with rheumatic conditions, in particular Still’s disease. If MAS occurs, or is suspected, 

evaluation and treatment should be started as early as possible. Physicians should be attentive to 

symptoms of infection or worsening of Still’s disease, as these are known triggers for MAS. Based on 

clinical trial experience, canakinumab does not appear to increase the incidence of MAS in Still’s 

disease patients, but no definitive conclusion can be made. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Interactions between canakinumab and other medicinal products have not been investigated in formal 

studies. 

 

An increased incidence of serious infections has been associated with administration of another IL-1 

blocker in combination with TNF inhibitors. Use of canakinumab with TNF inhibitors is not 

recommended because this may increase the risk of serious infections. 

 

The expression of hepatic CYP450 enzymes may be suppressed by the cytokines that stimulate 

chronic inflammation, such as interleukin-1 beta (IL-1 beta). Thus, CYP450 expression may be 

reversed when potent cytokine inhibitory therapy, such as canakinumab, is introduced. This is 

clinically relevant for CYP450 substrates with a narrow therapeutic index where the dose is 

individually adjusted. On initiation of canakinumab in patients being treated with this type of 

medicinal product, therapeutic monitoring of the effect or of the active substance concentration should 

be performed and the individual dose of the medicinal product adjusted as necessary. 

 



34 

No data are available on either the effects of live vaccination or the secondary transmission of 

infection by live vaccines in patients receiving canakinumab. Therefore, live vaccines should not be 

given concurrently with canakinumab unless the benefits clearly outweigh the risks. Should 

vaccination with live vaccines be indicated after initiation of canakinumab treatment, the 

recommendation is to wait for at least 3 months after the last canakinumab injection and before the 

next one (see section 4.4). 

 

The results of a study in healthy adult subjects demonstrated that a single dose of canakinumab 

300 mg did not affect the induction and persistence of antibody responses after vaccination with 

influenza or glycosylated protein based meningococcus vaccines. 

 

The results of a 56-week, open label study in CAPS patients aged 4 years and younger demonstrated 

that all patients who received non-live, standard of care childhood vaccinations developed protective 

antibody levels. 

 

4.6 Fertility, pregnancy and lactation 

 

Women of childbearing potential / Contraception in males and females 

 

Women should use effective contraceptives during treatment with canakinumab and for up to 

3 months after the last dose. 

 

Pregnancy 

 

There is a limited amount of data from the use of canakinumab in pregnant women. Animal studies do 

not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). 

The risk for the foetus/mother is unknown. Women who are pregnant or who desire to become 

pregnant should therefore only be treated after a thorough benefit-risk evaluation. 

 

Animal studies indicate that canakinumab crosses the placenta and is detectable in the foetus. No 

human data are available, but as canakinumab is an immunoglobulin of the G class (IgG1), human 

transplacental transfer is expected. The clinical impact of this is unknown. However, administration of 

live vaccines to newborn infants exposed to canakinumab in utero is not recommended for 16 weeks 

following the mother’s last dose of canakinumab before childbirth. Women who received 

canakinumab during pregnancy should be instructed to inform the baby’s healthcare professional 

before any vaccinations are given to their newborn infant. 

 

Breast-feeding 

 

It is unknown whether canakinumab is excreted in human milk. The decision whether to breast-feed 

during canakinumab therapy should therefore only be taken after a thorough benefit-risk evaluation. 

 

Animal studies have shown that a murine anti-murine IL-1 beta antibody had no undesirable effects on 

development in nursing mouse pups and that the antibody was transferred to them (see section 5.3). 

 

Fertility 

 

Formal studies of the potential effect of canakinumab on human fertility have not been conducted. 

Canakinumab had no effect on male fertility parameters in marmosets (C. jacchus). A murine anti-

murine IL-1 beta antibody had no undesirable effects on fertility in male or female mice (see 

section 5.3). 

 

  



35 

4.7 Effects on ability to drive and use machines 
 

Ilaris has minor influence on the ability to drive and use machines. Treatment with Ilaris may result in 

dizziness/vertigo or asthenia (see section 4.8). Patients who experience such symptoms during Ilaris 

treatment should wait for this to resolve completely before driving or operating machines. 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

The most frequent adverse drug reactions were infections predominantly of the upper respiratory tract. 

No impact on the type or frequency of adverse drug reactions was seen with longer-term treatment. 

 

Hypersensitivity reactions have been reported in patients treated with canakinumab (see sections 4.3 

and 4.4). 

 

Opportunistic infections have been reported in patients treated with canakinumab (see section 4.4). 

 

Tabulated list of adverse reactions 

 

Adverse reactions are listed according to MedDRA system organ class. Within each system organ 

class, the adverse reactions are ranked by frequency category with the most common first. Frequency 

categories are 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); not 

known (cannot be estimated from the available data). Within each frequency grouping, adverse 

reactions are presented in order of decreasing seriousness. 

 



36 

Table 1 Tabulated list of adverse reactions 

 

MedDRA 

System Organ 

Class 

Indications: 

CAPS, TRAPS, HIDS/MKD, FMF, SJIA, gouty arthritis 

Infections and infestations 

Very common Respiratory tract infections (including pneumonia, bronchitis, influenza, viral 

infection, sinusitis, rhinitis, pharyngitis, tonsillitis, nasopharyngitis, upper 

respiratory tract infection) 

Ear infection 

Cellulitis 

Gastroenteritis 

Urinary tract infection 

Common Vulvovaginal candidiasis 

Nervous system disorders 

Common Dizziness/vertigo 

Gastrointestinal disorders 

Very common Upper abdominal pain 1 

Uncommon Gastro-oesophageal reflux disease 2 

Skin and subcutaneous tissue disorders 

Very common Injection site reaction 

Musculoskeletal and connective tissue disorders 

Very common Arthralgia 1 

Common Musculoskeletal pain 1 

Back pain 2 

General disorders and administration site conditions 

Common Fatigue/asthenia 2 

Investigations 

Very common Creatinine renal clearance decreased 1,3 

Proteinuria 1,4 

Leukopenia 1,5 

Common Neutropenia 5 

Uncommon Platelet count decreased 5 
1 In SJIA 
2 In gouty arthritis 
3 Based on estimated creatinine clearance, most were transient 
4 Most represented transient trace to 1+ positive urinary protein by dipstick 
5 See further information below 

 

  



37 

Still’s Disease (SJIA and AOSD) 

 

SJIA pooled analysis and AOSD 

A total of 445 SJIA patients aged 2 to < 20 years received canakinumab in clinical trials, including 

321 patients aged 2 to < 12 years, 88 patients aged 12 to < 16 years, and 36 patients aged 16 to 

< 20 years. A pooled safety analysis of all SJIA patients showed that in the subset of young adult SJIA 

patients aged 16 to < 20 years, the safety profile of canakinumab was consistent with what was 

observed in SJIA patients less than 16 years of age. The safety profile of canakinumab in AOSD 

patients in a randomised, double blind placebo-controlled study (GDE01T) in 36 adult patients (aged 

22 to 70 years) was similar to what was observed in SJIA patients. 

 

Description of selected adverse reactions 

 

Long-term data and laboratory abnormalities in CAPS patients 

During clinical trials with canakinumab in CAPS patients mean values for haemoglobin increased and 

those for white blood cell, neutrophils and platelets decreased. 

 

Elevations of transaminases have been observed rarely in CAPS patients. 

 

Asymptomatic and mild elevations of serum bilirubin have been observed in CAPS patients treated 

with canakinumab without concomitant elevations of transaminases. 

 

In the long-term, open-label studies with dose escalation, events of infections (gastroenteritis, 

respiratory tract infection, upper respiratory tract infection), vomiting and dizziness were more 

frequently reported in the 600 mg or 8 mg/kg dose group than in other dose groups. 

 

Laboratory abnormalities in TRAPS, HIDS/MKD and FMF patients 

Neutrophils 

Although ≥ Grade 2 reductions in neutrophil count occurred in 6.5% of patients (common) and 

Grade 1 reductions occurred in 9.5% of patients, the reductions are generally transient and 

neutropenia-associated infection has not been identified as an adverse reaction. 

 

Platelets 

Although reductions in platelet count (≥ Grade 2) occurred in 0.6% of patients, bleeding has not been 

identified as an adverse reaction. Mild and transient Grade 1 reduction in platelets occurred in 15.9% 

of patients without any associated bleeding adverse events. 

 

Laboratory abnormalities in SJIA patients 

Haematology 

In the overall SJIA programme, transient decreased white blood cell (WBC) counts ≤ 0.8 x LLN were 

reported in 33 patients (16.5%). 

 

In the overall SJIA programme, transient decreases in absolute neutrophil count (ANC) to less than 1 x 

109/l were reported in 12 patients (6.0%). 

 

In the overall SJIA programme, transient decreases in platelet counts (< LLN) were observed in 

19 patients (9.5%). 

 

ALT/AST 

In the overall SJIA programme, high ALT and/or AST > 3 x upper limit of normal (ULN) were 

reported in 19 patients (9.5%). 

  



38 

Laboratory abnormalities in gouty arthritis patients 

Haematology 

Decreased white blood cell counts (WBC) ≤ 0.8 x lower limit of normal (LLN) were reported in 6.7% 

of patients treated with canakinumab compared to 1.4% treated with triamcinolone acetonide. 

Decreases in absolute neutrophil counts (ANC) to less than 1 x 109/l were reported in 2% of patients in 

the comparative trials. Isolated cases of ANC counts < 0.5 x 109/l were also observed (see section 4.4). 

 

Mild (< LLN and > 75 x 109/l) and transient decreases in platelet counts were observed at a higher 

incidence (12.7%) with canakinumab in the active-controlled clinical studies versus the comparator 

(7.7%) in gouty arthritis patients. 

 

Uric acid 

Increases in uric acid level (0.7 mg/dl at 12 weeks and 0.5 mg/dl at 24 weeks) were observed after 

canakinumab treatment in comparative trials in gouty arthritis. In another study, among patients who 

were starting on ULT, increases in uric acid were not observed. Uric acid increases were not observed 

in clinical trials in non-gouty arthritis populations (see section 5.1). 

 

ALT/AST 

Mean and median increases in alanine transaminase (ALT) of 3.0 U/l and 2.0 U/l, respectively, and in 

aspartate transaminase (AST) of 2.7 U/l and 2.0 U/l, respectively, from baseline to end of study were 

seen in the canakinumab-treated groups versus the triamcinolone acetonide-treated group(s), however 

the incidence of clinically significant changes (≥ 3 x the upper limit of normal) was greater for patients 

treated with triamcinolone acetonide (2.5% for both AST and ALT) compared with canakinumab-

treated patients (1.6% for ALT and 0.8% for AST). 

 

Triglycerides 

In active-controlled gouty arthritis trials, there was a mean increase in triglycerides of 33.5 mg/dl in 

canakinumab-treated patients compared with a modest decrease of -3.1 mg/dl with triamcinolone 

acetonide. The incidence of patients with triglyceride elevations > 5 x upper limit of normal (ULN) 

was 2.4% with canakinumab and 0.7% with triamcinolone acetonide. The clinical significance of this 

observation is unknown. 

 

Long term data from observational study 

 

A total of 243 CAPS patients (85 paediatric patients aged ≥ 2 to ≤ 17 years and 158 adult patients aged 

≥ 18 years) were treated with canakinumab in routine clinical practice in a long-term registry study 

(mean of 3.8 years of canakinumab exposure). The safety profile of canakinumab observed following 

long-term treatment in this setting was consistent with what has been observed in interventional 

studies in CAPS patients. 

 

Paediatric population 

 

There were 80 paediatric CAPS patients (2-17 years of age) who received canakinumab in the 

interventional studies. Overall, there were no clinically meaningful differences in the safety and 

tolerability profile of canakinumab in paediatric patients compared to the overall CAPS population 

(comprised of adult and paediatric patients, N=211), including the overall frequency and severity of 

infectious episodes. Infections of the upper respiratory tract were the most frequently reported 

infection events. 

 

Additionally, 6 paediatric patients under the age of 2 years were evaluated in a small open-label 

clinical study. The safety profile of canakinumab appeared similar to that in patients aged 2 years and 

above. 

 

There were 102 TRAPS, HIDS/MKD and FMF patients (2-17 years of age) who received 

canakinumab in a 16-week study. Overall, there were no clinically meaningful differences in the safety 

and tolerability profile of canakinumab in paediatric patients compared to the overall population. 

 



39 

Elderly population 

 

There is no significant difference in safety profile observed in patients ≥ 65 years of age. 

 

Reporting of suspected adverse reactions 

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 

4.9 Overdose 
 

Reported experience with overdose is limited. In early clinical trials, patients and healthy volunteers 

received doses as high as 10 mg/kg, administered intravenously or subcutaneously, without evidence 

of acute toxicity. 

 

In case of overdose, it is recommended for the patient to be monitored for any signs or symptoms of 

adverse reactions, and appropriate symptomatic treatment instituted immediately. 

 

 

5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: Immunosuppressants, interleukin inhibitors, ATC code: L04AC08 

 

Mechanism of action 

 

Canakinumab is a human monoclonal anti-human interleukin-1 beta (IL-1 beta) antibody of the 

IgG1/κ isotype. Canakinumab binds with high affinity specifically to human IL-1 beta and neutralises 

the biological activity of human IL-1 beta by blocking its interaction with IL-1 receptors, thereby 

preventing IL-1 beta-induced gene activation and the production of inflammatory mediators. 

 

Pharmacodynamic effects 

 

CAPS, TRAPS, HIDS/MKD and FMF 

In clinical studies, CAPS, TRAPS, HIDS/MKD and FMF patients who have uncontrolled over-

production of IL-1 beta show a rapid and sustained response to therapy with canakinumab, i.e. 

laboratory parameters such as high C-reactive protein (CRP) and serum amyloid A (SAA), high 

neutrophil and platelet counts, and leukocytosis rapidly returned to normal. 

 

Still’s disease (SJIA and AOSD) 

Adult-onset Still’s disease and systemic juvenile idiopathic arthritis are severe autoinflammatory 

diseases, driven by innate immunity by means of pro-inflammatory cytokines, a key one being IL-1-

beta. 

 

Common features of SJIA and AOSD include fever, rash, hepatosplenomegaly, lymphadenopathy, 

polyserositis and arthritis. Treatment with canakinumab resulted in a rapid and sustained improvement 

of both the articular and the systemic features of SJIA with significant reduction of the number of 

inflamed joints, prompt resolution of fever and reduction of acute phase reactants in the majority of 

patients (see Clinical efficacy and safety). 

 

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


40 

Gouty arthritis 

A gouty arthritis attack is caused by urate (monosodium urate monohydrate) crystals in the joint and 

surrounding tissue, which trigger resident macrophages to produce IL-1 beta via the “NALP3 

inflammasome” complex. Activation of macrophages and concomitant over-production of IL-1 beta 

results in an acute painful inflammatory response. Other activators of the innate immune system, such 

as endogenous agonists of toll-like receptors, may contribute to the transcriptional activation of the IL-

1 beta gene, initiating a gouty arthritis attack. Following canakinumab treatment, the inflammatory 

markers CRP or SAA and signs of acute inflammation (e.g. pain, swelling, redness) in the affected 

joint subside rapidly. 

 

Clinical efficacy and safety 

 

CAPS 

The efficacy and safety of canakinumab have been demonstrated in a total of 211 adult and paediatric 

patients with varying degrees of disease severity and different CAPS phenotypes (including 

FCAS/FCU, MWS, and NOMID/CINCA). Only patients with confirmed NLRP3 mutation were 

included in the pivotal study. 

 

In the Phase I/II study, treatment with canakinumab had a rapid onset of action, with disappearance or 

clinically significant improvement of symptoms within one day after dosing. Laboratory parameters 

such as high CRP and SAA, high neutrophils and platelet counts normalised rapidly within days of 

canakinumab injection. 

 

The pivotal study consisted of a 48-week three-part multicentre study, i.e. an 8-week open-label period 

(Part I), a 24-week randomised, double-blind, placebo-controlled withdrawal period (Part II), followed 

by a 16-week open-label period (Part III). The aim of the study was to assess efficacy, safety, and 

tolerability of canakinumab (150 mg or 2 mg/kg every 8 weeks) in patients with CAPS. 

 

 Part I: A complete clinical and biomarker response to canakinumab (defined as composite of 
physician’s global assessment on autoinflammatory and on skin disease ≤ minimal and CRP or 

SAA values < 10 mg/litre) was observed in 97% of patients and appeared within 7 days of 

initiation of treatment. Significant improvements were seen in physician’s clinical assessment of 

autoinflammatory disease activity: global assessment of autoinflammatory disease activity, 

assessment of skin disease (urticarial skin rash), arthralgia, myalgia, headache/migraine, 

conjunctivitis, fatigue/malaise, assessment of other related symptoms, and patient’s assessment 

of symptoms. 

 

 Part II: In the withdrawal period of the pivotal study, the primary endpoint was defined as the 
proportion of patients with a disease relapse/flare: none (0%) of the patients randomised to 

canakinumab flared, compared with 81% of the patients randomised to placebo. 

 

 Part III: Patients treated with placebo in Part II who flared regained and maintained clinical and 
serological response following entry into the open-label canakinumab extension. 

 



41 

Table 2 Tabulated summary of efficacy in Phase III trial, pivotal placebo-controlled 

withdrawal period (Part II) 

 

Phase III trial, pivotal placebo-controlled withdrawal period (Part II) 

 Canakinumab 

N=15 

n(%) 

Placebo 

N=16 

n(%) 

 

p-value 

 

Primary endpoint (flare) 
 Proportion of patients with disease flare in Part II 0 (0%) 13 (81%) < 0.001 

 

Inflammatory markers* 
 C-reactive protein, mg/l 1.10 (0.40) 19.93 (10.50) < 0.001 

 Serum amyloid A, mg/l 2.27 (-0.20) 71.09 (14.35) 0.002 

* mean (median) change from beginning of Part II 

 

Two open-label, uncontrolled, long-term phase III studies were performed. One was a safety, 

tolerability, and efficacy study of canakinumab in patients with CAPS. The total treatment duration 

ranged from 6 months to 2 years. The other was an open-label study with canakinumab to evaluate the 

efficacy and safety in Japanese CAPS patients for 24 weeks, with an extension phase up to 48 weeks. 

The primary objective was to assess the proportion of patients who were free of relapse at week 24, 

including those patients whose dose was increased. 

 

In the pooled efficacy analysis for these two studies, 65.6% of patients who had not previously been 

treated with canakinumab achieved complete response at 150 mg or 2 mg/kg, while 85.2% of patients 

achieved complete response at any dose. Of the patients treated with 600 mg or 8 mg/kg (or even 

higher), 43.8% achieved complete response. Fewer patients aged 2 to < 4 years achieved complete 

response (57.1%) than older paediatric and adult patients. Of the patients who had achieved a 

complete response, 89.3% maintained response without relapsing. 

 

Experience from individual patients who achieved a complete response following dose escalation to 

600 mg (8 mg/kg) every 8 weeks suggests that a higher dose may be beneficial in patients not 

achieving complete response or not maintaining complete response with the recommended doses 

(150 mg or 2 mg/kg for patients ≥ 15 kg and ≤ 40 kg). An increased dose was administered more 

frequently to patients aged 2 to < 4 years and to patients with NOMID/CINCA symptoms compared 

with FCAS or MWS. 

 

A 6-year observational registry study was conducted to provide data on the long-term safety and 

effectiveness of canakinumab treatment in paediatric and adult CAPS patients in routine clinical 

practice. The study included 243 CAPS patients (including 85 patients less than 18 years of age). 

Disease activity was rated as absent or mild/moderate in more than 90% of patients at all post-baseline 

time points in the study, and median serological markers of inflammation (CRP and SAA) were 

normal (< 10 mg/litre) at all post-baseline time points. Although approximately 22% of patients 

receiving canakinumab required dose adjustment, only a small percentage of patients (1.2%) 

discontinued canakinumab due to lack of therapeutic effect. 

 

Paediatric population 

The CAPS interventional trials with canakinumab included a total of 80 paediatric patients with an age 

range from 2 to 17 years (approximately half of them treated on an mg/kg basis). Overall, there were 

no clinically meaningful differences in the efficacy, safety and tolerability profile of canakinumab in 

paediatric patients compared to the overall CAPS population. The majority of paediatric patients 

achieved improvement in clinical symptoms and objective markers of inflammation (e.g. SAA and 

CRP). 

 



42 

A 56-week, open-label study was conducted to assess the efficacy, safety and tolerability of 

canakinumab in paediatric CAPS patients ≤ 4 years of age. Seventeen patients (including 6 patients 

under the age of 2 years) were evaluated, using weight-based starting doses of 2-8 mg/kg. The study 

also evaluated the effect of canakinumab on the development of antibodies to standard childhood 

vaccines. No differences in safety or efficacy were observed in patients under the age of 2 years 

compared with patients aged 2 years and above. All patients who received non-live, standard of care 

childhood vaccinations (N=7) developed protective antibody levels. 

 

TRAPS, HIDS/MKD and FMF 

The efficacy and safety of canakinumab for the treatment of TRAPS, HIDS/MKD and FMF were 

demonstrated in a single, pivotal, phase III, 4-part study (N2301) consisting of three separate disease 

cohorts. 

- Part I: Patients in each disease cohort aged 2 years and older entered a 12-week screening period 
during which they were evaluated for the onset of disease flare. 

- Part II: Patients at flare onset were randomised into a 16-week double-blind, placebo-controlled 
treatment period during which they received either 150 mg canakinumab (2 mg/kg for patients 

with body weight ≤ 40 kg) subcutaneous (s.c.) or placebo every 4 weeks. Patients > 28 days but 

< 2 years of age were allowed to enter the study directly into an open-arm of Part II as non-

randomised patients (and were excluded from the primary efficacy analysis). 

- Part III: Patients who completed 16 weeks of treatment and were classified as responders were 
re-randomised into a 24-week, double-blind withdrawal period during which they received 

canakinumab 150 mg (2 mg/kg for patients ≤ 40 kg) s.c. or placebo every 8 weeks. 

- Part IV: All Part III patients treated with canakinumab were eligible to enter into a 72-week 
open-label treatment extension period. 

 

A total of 185 patients aged 28 days and above were enrolled and a total of 181 patients aged 2 years 

and above were randomised in part II of the study. 

 

The primary efficacy endpoint of the randomised treatment period (Part II) was the proportion of 

responders within each cohort who had resolution of their index disease flare at Day 15 and did not 

experience a new flare during the remainder of the 16-week treatment period (defined as complete 

response). Resolution of the index disease flare was defined as having a Physician’s Global 

Assessment (PGA) of Disease Activity score < 2 (“minimal or no disease”) and CRP within normal 

range (≤ 10 mg/l) or reduction ≥ 70% from baseline. A new flare was defined as a PGA score ≥ 2 

(“mild, moderate, or severe disease”) and CRP ≥ 30 mg/l. Secondary endpoints, all based on week 16 

results (end of Part II), included the proportion of patients who achieved a PGA score of < 2, the 

proportion of patients with serological remission (defined as CRP ≤ 10 mg/l), and the proportion of 

patients with a normalised SAA level (defined as SAA ≤ 10 mg/l). 

 

For the primary efficacy endpoint, canakinumab was superior to placebo for all three disease cohorts. 

Canakinumab also demonstrated superior efficacy compared to placebo on the secondary endpoints of 

PGA < 2 and CRP ≤ 10 mg/l in all three cohorts. Higher proportions of patients had normalised SAA 

(≤ 10 mg/l) at week 16 with canakinumab treatment compared to placebo in all three cohorts, with a 

statistically significant difference observed in TRAPS patients (see Table 3 with study results below). 

 



43 

Table 3 Tabulated summary of efficacy in Phase III trial, pivotal, randomised, placebo-

controlled treatment period (Part II) 

 

Phase III trial, pivotal, randomised placebo-controlled treatment period (Part II) 

 Canakinumab 

n/N (%) 

Placebo 

n/N (%) 

 

p-value 

Primary endpoint (disease flare) - Proportion of patients who had index disease flare resolution at 

day 15 and did not experience a new flare during the remainder of the 16-week treatment period 

FMF 19/31 (61.29) 2/32 (6.25) < 0.0001* 

HIDS/MKD 13/37 (35.14) 2/35 (5.71) 0.0020* 

TRAPS 10/22 (45.45) 2/24 (8.33) 0.0050* 

Secondary endpoints (disease and inflammatory markers) 
 Physician Global Assessment < 2    

FMF 20/31 (64.52) 3/32 (9.38) < 0.0001** 

HIDS/MKD 17/37 (45.95) 2/35 (5.71) 0.0006** 

TRAPS 10/22 (45.45) 1/24 (4.17) 0.0028** 

 C-reactive protein ≤ 10 mg/l    

FMF 21/31 (67.74) 2/32 (6.25) < 0.0001** 

HIDS/MKD 15/37 (40.54) 2/35 (5.71) 0.0010** 

TRAPS 8/22 (36.36) 2/24 (8.33) 0.0149** 

 Serum amyloid A ≤ 10 mg/l    

FMF 8/31 (25.81) 0/32 (0.00) 0.0286 

HIDS/MKD 5/37 (13.51) 1/35 (2.86) 0.0778 

TRAPS 6/22 (27.27) 0/24 (0.00) 0.0235** 

n=number of responders; N=number of evaluable patients 

* indicates statistical significance (one-sided) at the 0.025 level based on Fisher exact test 

**Indicates statistical significance (one-sided) at the 0.025 level based on the logistic regression model 

with treatment group and baseline PGA, CRP or SAA respectively, as explanatory variables for each 

cohort 

 

Up-titration 

In Part II of the study, patients treated with canakinumab who had persistent disease activity received 

an additional dose of 150 mg (or 2 mg/kg for patients ≤ 40 kg) within the first month. This additional 

dose could be provided as early as 7 days after the first treatment dose. All up-titrated patients 

remained at the increased dose of 300 mg (or 4 mg/kg for patients ≤ 40 kg) every 4 weeks. 

 

In an exploratory analysis of the primary endpoint, it was observed that in patients with an inadequate 

response after the first dose, an up-titration within the first month to a dose of 300 mg (or 4 mg/kg) 

every 4 weeks further improved flare control, reduced disease activity and normalised CRP and SAA 

levels. 

 

Paediatric patients: 

Two non-randomised HIDS/MKD patients aged > 28 days but < 2 years were included in the study 

and received canakinumab. One patient had resolution of index flare by day 15 after receiving one 

single dose of canakinumab 2 mg/kg, but discontinued treatment after this first dose due to serious 

adverse events (pancytopenia and hepatic failure). This patient presented at study entry with a history 

of immune thrombocytopenic purpura and an active medical condition of abnormal hepatic function. 

The second patient received a starting dose of canakinumab 2 mg/kg and an add-on dose of 2 mg/kg at 

week 3, and was up-titrated at week 5 to receive a dose of 4 mg/kg administered every 4 weeks until 

the end of Part II of the study. Resolution of disease flare was achieved by week 5 and the patient had 

not experienced any new flare at the end of Part II of the study (week 16). 

 



44 

Still’s disease (SJIA and AOSD) 

SJIA 

The efficacy of canakinumab for the treatment of active SJIA was assessed in two pivotal phase III 

studies (G2305 and G2301). Patients enrolled were aged 2 to < 20 years (mean age of 8.5 years and 

mean disease duration of 3.5 years at baseline) and had active disease defined as ≥ 2 joints with active 

arthritis, fever and elevated CRP. 

 

Study G2305 

Study G2305 was a randomised, double-blind, placebo-controlled, 4-week study assessing the short-

term efficacy of canakinumab in 84 patients randomised to receive a single dose of 4 mg/kg (up to 

300 mg) canakinumab or placebo. The primary objective was the proportion of patients at day 15 who 

achieved a minimum 30% improvement in the paediatric American College of Rheumatology (ACR) 

response criterion adapted to include absence of fever. Canakinumab treatment improved all paediatric 

ACR response scores as compared to placebo at days 15 and 29 (Table 4). 

 

Table 4 Paediatric ACR response and disease status at days 15 and 29 

 

 Day 15 Day 29 

 Canakinumab 

N=43 

Placebo 

N=41 

Canakinumab 

N=43 

Placebo 

N=41 

ACR30 84% 10% 81% 10% 

ACR50 67% 5% 79% 5% 

ACR70 61% 2% 67% 2% 

ACR90 42% 0% 47% 2% 

ACR100 33% 0% 33% 2% 

Inactive disease 33% 0% 30% 0% 

Treatment difference for all ACR scores was significant (p ≤ 0.0001) 

 

Results for the components of the adapted paediatric ACR which included systemic and arthritic 

components, were consistent with the overall ACR response results. At day 15, the median change 

from baseline in the number of joints with active arthritis and limited range of motion were -67% 

and -73% for canakinumab (N=43), respectively, compared to a median change of 0% and 0% for 

placebo (N=41). The mean change in patient pain score (0-100 mm visual analogue scale) at day 15 

was -50.0 mm for canakinumab (N=43), as compared to +4.5 mm for placebo (N=25). The mean 

change in pain score among canakinumab treated patients was consistent at day 29. 

 

Study G2301 

Study G2301 was a randomised, double-blind, placebo-controlled withdrawal study of flare prevention 

by canakinumab. The study consisted of two parts with two independent primary endpoints (successful 

steroid taper and time to flare). In Part I (open label) 177 patients were enrolled and received 4 mg/kg 

(up to 300 mg) canakinumab administered every 4 weeks for up to 32 weeks. Patients in Part II 

(double-blind) received either canakinumab 4 mg/kg or placebo every 4 weeks until 37 flare events 

occurred. 

 

Corticosteroid dose tapering: 

Of the total 128 patients who entered Part I taking corticosteroids, 92 attempted corticosteroid 

tapering. Fifty-seven (62%) of the 92 patients who attempted to taper were able to successfully taper 

their corticosteroid dose and 42 (46%) discontinued corticosteroids. 

 

Time to flare: 

Patients taking canakinumab in Part II had a 64% reduced risk of a flare event as compared to the 

placebo group (hazard ratio of 0.36; 95% CI: 0.17 to 0.75; p=0.0032). Sixty-three of the 100 patients 

entering Part II, whether assigned to placebo or canakinumab, did not experience a flare over the 

observation period (up to a maximum of 80 weeks). 

 



45 

Health-related and quality of life outcomes in studies G2305 and G2301 

Treatment with canakinumab resulted in clinically relevant improvements in patients’ physical 

function and quality of life. In study G2305, the Childhood Health Assessment Questionnaire Least 

Squares means improvement was 0.69 for canakinumab vs placebo representing 3.6 times the minimal 

clinically important difference of 0.19 (p=0.0002). The median improvement from baseline to end of 

Part I of study G2301 was 0.88 (79%). Statistically significant improvements in the Child Health 

Questionnaire-PF50 scores were reported for canakinumab vs placebo in study G2305 (physical 

p=0.0012; psychosocial well-being p=0.0017). 

 

Pooled efficacy analysis 

Data from the first 12 weeks of canakinumab treatment from studies G2305, G2301 and the extension 

study were pooled to assess maintenance of efficacy. These data showed similar improvements from 

baseline to week 12 in the adapted paediatric ACR responses and its components to those observed in 

the placebo controlled study (G2305). At week 12, the adapted paediatric ACR30, 50, 70, 90 and 100 

responses were: 70%, 69%, 61%, 49% and 30%, respectively and 28% of patients had inactive disease 

(N=178). 

 

Although limited, evidence from the clinical trials suggests that patients not responding to tocilizumab 

or anakinra may respond to canakinumab. 

 

Study G2301E1 

The efficacy observed in the studies G2305 and G2301 was maintained in the open-label long-term 

extension study G2301E1. Of the 270 SJIA patients in the study, 147 patients had received treatment 

with canakinumab in studies G2305 or G2301 (Cohort I), and 123 patients were canakinumab-naive 

patients (Cohort II). Patients in Cohort I were treated for a median duration of 3.2 years (up to 

5.2 years), and patients in Cohort II were treated for a median duration of 1.8 years (up to 2.8 years). 

In the extension study, all patients received canakinumab 4 mg/kg (up to maximum 300 mg) every 

4 weeks. In both cohorts, patients who were well-controlled responders (retrospectively defined as 

adapted paediatric ACR ≥ 90) and who did not require a concomitant corticosteroid were permitted to 

reduce their canakinumab dose to 2 mg/kg every 4 weeks (62/270; 23%). 

 

Study G2306 

Study G2306 was an open-label study to assess maintenance of treatment response with canakinumab 

dose reduction (2 mg/kg every 4 weeks) or dose interval prolongation (4 mg/kg every 8 weeks) in 

SJIA patients who were receiving canakinumab 4 mg/kg every 4 weeks. Seventy five patients aged 2 

to 22 years who maintained inactive disease status for at least 6 consecutive months (clinical 

remission) with canakinumab monotherapy, including patients who were able to maintain inactive 

disease status with discontinuation of concomitant corticosteroid and/or methotrexate use for at least 

4 weeks, were randomised to receive canakinumab 2 mg/kg every 4 weeks (N=38) or canakinumab 

4 mg/kg every 8 weeks (N=37). After 24 weeks, 71% (27/38) of patients who received the reduced 

dose (2 mg/kg every 4 weeks) and 84% (31/37) of patients who received the prolonged dosing interval 

(4 mg/kg every 8 weeks) were able to maintain inactive disease status for 6 months. Of the patients in 

clinical remission who continued with further dose reduction (1 mg/kg every 4 weeks) or dose interval 

prolongation (4 mg/kg every 12 weeks), 93% (26/28) and 91% (30/33) of patients, respectively, were 

able to maintain inactive disease status for 6 months. Patients who maintained inactive disease status 

for 6 additional months at this lowest dose regimen were allowed to discontinue canakinumab. 

Overall, 33% (25/75) of patients randomised to dose reduction or dose interval prolongation arms 

were able to discontinue treatment with canakinumab and maintain inactive disease status for 

6 months. The rate of adverse events in both treatment arms was similar to the rate seen in patients 

treated with canakinumab 4 mg/kg every 4 weeks. 

 



46 

AOSD 

The efficacy of canakinumab 4 mg/kg (up to maximum 300 mg) administered every 4 weeks in AOSD 

patients in a randomised, double-blind placebo-controlled study in 36 patients (22 to 70 years old) was 

comparable to that observed in SJIA patients. In study GDE01T, a higher proportion of patients 

(12/18, 66.7%) in the canakinumab group than in the placebo group (7/17, 41.2%) demonstrated an 

improvement from baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28-

ESR) of > 1.2 at week 12, which failed to reach statistical significance (odds ratio 2.86, treatment 

difference [%] 25.49 [95% CI: 9.43, 55.80]). By week 4, 7 of 18 patients (38.9%) treated with 

canakinumab had already achieved DAS28-ESR remission versus 2 of 17 patients (11.8%) on placebo. 

These data are consistent with the results of a pooled efficacy analysis of 418 SJIA patients which 

showed that the efficacy of canakinumab in a subset of SJIA patients aged 16 to < 20 years (n=34) was 

consistent with the efficacy observed in patients less than 16 years of age (n=384). 

 

Gouty arthritis 

The efficacy of canakinumab for the treatment of acute gouty arthritis attacks was demonstrated in two 

multicentre, randomised, double-blind, active-controlled studies in patients with frequent gouty 

arthritis (≥ 3 attacks in the previous 12 months) unable to use NSAIDs or colchicine (due to 

contraindication, intolerance or lack of efficacy). The studies were 12 weeks followed by 12-week 

double-blind extension. A total of 225 patients were treated with subcutaneous canakinumab 150 mg 

and 229 patients were treated with intramuscular triamcinolone acetonide (TA) 40 mg at study entry, 

and when experiencing a new attack thereafter. The mean number of gouty arthritis attacks in the 

previous 12 months was 6.5. Over 85% of patients had comorbidity, including hypertension (60%), 

diabetes (15%), ischaemic heart disease (12%), and stage ≥ 3 chronic kidney disease (25%). 

Approximately one-third of the patients enrolled (76 [33.8%] in the canakinumab group and 84 

[36.7%] in the triamcinolone acetonide group) had documented inability (intolerance, contraindication 

or lack of response) to use both NSAIDs and colchicine. Concomitant treatment with ULTs was 

reported by 42% of patients at entry. 

 

The co-primary endpoints were: (i) gouty arthritis pain intensity (visual analogue scale, VAS) at 

72 hours post-dose, and (ii) time to first new gouty arthritis attack. 

 

For the overall study population, pain intensity was statistically significantly lower for canakinumab 

150 mg compared with triamcinolone acetonide at 72 hours. Canakinumab also reduced the risk of 

subsequent attacks (see Table 5). 

 

Efficacy results in a subgroup of patients unable to use both NSAIDs and colchicine and who were on 

ULT, failed ULT or had a contraindication to ULT (N=101) were consistent with the overall study 

population with a statistically significant difference compared to triamcinolone acetonide in pain 

intensity at 72 hours (-10.2 mm, p=0.0208) and in reduction of risk of subsequent attacks (Hazard ratio 

0.39, p=0.0047 at 24 weeks). 

 

Efficacy results for a more stringent subgroup limited to current users of ULT (N=62) are presented in 

Table 5. Treatment with canakinumab induced a reduction of pain and reduced the risk of subsequent 

attacks in patients using ULT and unable to use both NSAIDs and colchicine, although the observed 

treatment difference compared to triamcinolone acetonide was less pronounced than with the overall 

study population. 

 



47 

Table 5 Efficacy for the overall study population and in a subgroup of patients currently 

using ULT and unable to use both NSAIDs and colchicine 

 

Efficacy endpoint Overall study population;  

N=454 

Unable to use both NSAIDs 

and colchicine; on ULT 

N=62 

Treatment of gouty arthritis attacks as measured by pain intensity (VAS) at 72 h 

Least Squares mean estimated 

difference to triamcinolone acetonide 

CI 

p-value, 1-sided 

-10.7 

 

(-15.4, -6.0) 

p < 0.0001* 

-3.8 

 

(-16.7, 9.1) 

p=0.2798 

Risk reduction of subsequent gouty arthritis attacks as measured by time to first new flare 

(24 weeks) 

Hazard ratio to triamcinolone 

acetonide 

CI 

p-value, 1-sided 

0.44 

 

(0.32, 0.60) 

p < 0.0001* 

0.71 

 

(0.29, 1.77) 

p=0.2337 

* Denotes significant p-value ≤ 0.025 

 

Safety results showed an increased incidence of adverse events for canakinumab compared to 

triamcinolone acetonide, with 66% vs 53% of patients reporting any adverse event and 20% vs 10% of 

patients reporting an infection adverse event over 24 weeks. 

 

Elderly population 

Overall, the efficacy, safety and tolerability profile of canakinumab in elderly patients ≥ 65 years of 

age was comparable to patients < 65 years of age. 

 

Patients on urate lowering therapy (ULT) 

In clinical studies, canakinumab has been safely administered with ULT. In the overall study 

population, patients on ULT had a less pronounced treatment difference in both pain reduction and 

reduction in the risk of subsequent gouty arthritis attacks compared to patients not on ULT. 

 

Immunogenicity 

 

Antibodies against canakinumab were observed in approximately 1.5%, 3% and 2% of the patients 

treated with canakinumab for CAPS, SJIA and gouty arthritis, respectively. No neutralising antibodies 

were detected. No apparent correlation of antibody development to clinical response or adverse events 

was observed. 

 

There were no antibodies against canakinumab observed in TRAPS, HIDS/MKD and FMF patients 

treated with doses of 150 mg and 300 mg over 16 weeks of treatment. 

 

Paediatric population 

 

The Marketing Authorisation Holder has completed four Paediatric Investigation Plans for 

canakinumab (for CAPS, SJIA, FMF – HIDS/MKD and TRAPS respectively). This product 

information has been updated to include the results of studies with canakinumab in the paediatric 

population. 

 

The European Medicines Agency has waived the obligation to submit the results of studies with 

canakinumab in all subsets of the paediatric population in gouty arthritis (see section 4.2 for 

information on paediatric use). 

 



48 

5.2 Pharmacokinetic properties 
 

CAPS 

 

Absorption 

The peak serum canakinumab concentration (Cmax) occurred approximately 7 days following single 

subcutaneous administration of 150 mg in adult CAPS patients. The mean terminal half-life was 

26 days. Mean values for Cmax and AUCinf after a single subcutaneous dose of 150 mg in a typical 

adult CAPS patient (70 kg) were 15.9 µg/ml and 708 µg*d/ml. The absolute bioavailability of 

subcutaneously administered canakinumab was estimated to be 66%. Exposure parameters (such as 

AUC and Cmax) increased in proportion to dose over the dose range of 0.30 to 10.0 mg/kg given as 

intravenous infusion or from 150 to 600 mg as subcutaneous injection. Predicted steady-state exposure 

values (Cmin,ss, Cmax,ss, AUC,ss,8w) after 150 mg subcutaneous administration (or 2 mg/kg, respectively) 

every 8 weeks were slightly higher in the weight category 40-70 kg (6.6 µg/ml, 24.3 µg/ml, 

767 µg*d/ml) compared to the weight categories < 40 kg (4.0 µg/ml, 19.9 µg/ml, 566 µg*d/ml) and 

> 70 kg (4.6 µg/ml, 17.8 µg/ml, 545 µg*d/ml). The expected accumulation ratio was 1.3-fold 

following 6 months of subcutaneous administration of 150 mg canakinumab every 8 weeks. 

 

Distribution 

Canakinumab binds to serum IL-1 beta. The distribution volume (Vss) of canakinumab varied 

according to body weight. It was estimated to be 6.2 litres in a CAPS patient of body weight 70 kg. 

 

Elimination 

The apparent clearance (CL/F) of canakinumab increases with body weight. It was estimated to be 

0.17 l/d in a CAPS patient of body weight 70 kg and 0.11 l/d in a SJIA patient of body weight 33 kg. 

After accounting for body weight differences, no clinically significant differences in the 

pharmacokinetic properties of canakinumab were observed between CAPS and SJIA patients. 

 

There was no indication of accelerated clearance or time-dependent change in the pharmacokinetic 

properties of canakinumab following repeated administration. No gender or age-related 

pharmacokinetic differences were observed after correction for body weight. 

 

TRAPS, HIDS/MKD and FMF 

 

Bioavailability in TRAPS, HIDS/MKD and FMF patients has not been determined independently. 

Apparent clearance (CL/F) in the TRAPS, HIDS/MKD and FMF population at body weight of 55 kg 

(0.14 l/d) was comparable to CAPS population at body weight of 70 kg (0.17 l/d). The apparent 

volume of distribution (V/F) was 4.96 l at body weight of 55 kg. 

 

After repeated subcutaneous administration of 150 mg every 4 weeks, canakinumab minimal 

concentration at week 16 (Cmin) was estimated to be 15.4 ± 6.6 g/ml. The estimated steady state 

AUCtau was 636.7 ± 260.2 μg*d/ml. 

 

Still’s disease (SJIA and AOSD) 

 

Bioavailability in SJIA patients has not been determined independently. Apparent clearance per kg 

body weight (CL/F per kg) was comparable between the SJIA and CAPS population (0.004 l/d per 

kg). The apparent volume of distribution per kg (V/F per kg) was 0.14 l/kg. Sparse pharmacokinetics 

(PK) data in AOSD patients suggest similar PK of canakinumab as compared to SJIA and other patient 

populations. 

 

After repeated administration of 4 mg/kg every 4 weeks the accumulation ratio of canakinumab was 

1.6 fold in SJIA patients. Steady state was reached after 110 days. The overall predicted mean (±SD) 

for Cmin,ss, Cmax,ss and AUC,ss4w were 14.7±8.8 μg/ml, 36.5 ± 14.9 μg/ml and 696.1 ± 326.5 μg*d/ml, 

respectively. 

 



49 

The AUCss4w in each age group was 692, 615, 707 and 742 µg*d/ml for 2-3, 4-5, 6-11, and 12-19 years 

old, respectively. When stratified by weight, a lower (30-40%) median of exposure for Cmin,ss (11.4 vs 

19 µg/ml) and AUCss (594 vs 880 µg*d/ml) for the lower bodyweight category (≤ 40 kg) vs the higher 

bodyweight category (> 40 kg) was observed. 

 

Based on the population pharmacokinetic modelling analysis, the pharmacokinetics of canakinumab in 

young adult SJIA patients aged 16 to 20 years were similar to those in patients less than 16 years of 

age. Predicted canakinumab steady state exposures at a dose level of 4 mg/kg (maximum 300 mg) in 

patients over the age of 20 years were comparable to those in SJIA patients younger than 20 years of 

age. 

 

Gouty arthritis population 

 

Bioavailability in gouty arthritis patients has not been determined independently. Apparent clearance 

per kg body weight (CL/F per kg) was comparable between the gouty arthritis and CAPS population 

(0.004 l/d/kg). Mean exposure in a typical gouty arthritis patient (93 kg) after a single subcutaneous 

150 mg dose (Cmax: 10.8 µg/ml and AUCinf: 495 µg*d/ml) was lower than in a typical 70 kg CAPS 

patient (15.9 µg/ml and 708 µg*d/ml). This is consistent with the observed increase in CL/F with body 

weight. 

 

The expected accumulation ratio was 1.1-fold following subcutaneous administration of 150 mg 

canakinumab every 12 weeks. 

 

Paediatric population 

 

Peak concentrations of canakinumab occurred between 2 to 7 days (Tmax) following single 

subcutaneous administration of canakinumab 150 mg or 2 mg/kg in paediatric patients 4 years of age 

and older. The terminal half-life ranged from 22.9 to 25.7 days, similar to the pharmacokinetic 

properties observed in adults. Based on the population pharmacokinetic modelling analysis, the 

pharmacokinetics of canakinumab in children aged 2 to < 4 years were similar to those in patients 

4 years of age and older. Subcutaneous absorption rate was estimated to decrease with age and 

appeared to be fastest in the youngest patients. Accordingly, Tmax was shorter (3.6 days) in younger 

SJIA patients (2-3 years) compared to older SJIA patients (12-19 years; Tmax 6 days). Bioavailability 

(AUCss) was not affected. 

 

An additional pharmacokinetics analysis showed that the pharmacokinetics of canakinumab in 

6 paediatric CAPS patients under the age of 2 years were similar to the pharmacokinetics in paediatric 

patients 2-4 years of age. Based on the population pharmacokinetic modelling analysis, the expected 

exposures after a dose of 2 mg/kg were comparable across the CAPS paediatric age groups, but were 

approximately 40% lower in paediatric patients of very low body weight (e.g. 10 kg) than in adult 

patients (150 mg dose). This is consistent with the observations of higher exposure in higher body 

weight groups in CAPS patients. 

 

In TRAPS, HIDS/MKD and FMF, exposure parameters (trough concentrations) were comparable 

across age groups from 2 to < 20 years old following subcutaneous administration of canakinumab 

2 mg/kg every 4 weeks. 

 

Pharmacokinetic properties are similar in CAPS, TRAPS, HIDS/MKD, FMF and SJIA paediatric 

populations. 

 

Elderly population 

 

No change in pharmacokinetic parameters based on clearance or volume of distribution were observed 

between elderly patients and adult patients < 65 years of age. 

 



50 

5.3 Preclinical safety data 
 

Non-clinical data reveal no special hazard for humans based on conventional studies of cross-

reactivity, repeated dose toxicity, immunotoxicity, toxicity to reproduce and development. 

 

Formal carcinogenicity studies have not been conducted with canakinumab. 

 

 

6. PHARMACEUTICAL PARTICULARS 
 

6.1 List of excipients 
 

Mannitol 

Histidine 

Histidine hydrochloride monohydrate 

Polysorbate 80 

Water for injections 

 

6.2 Incompatibilities 
 

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

products. 

 

6.3 Shelf life 
 

3 years. 

 

From a microbiological point of view, the product should be used immediately after first opening. 

 

6.4 Special precautions for storage 
 

Store in a refrigerator (2°C - 8°C). 

Do not freeze. 

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

 

6.5 Nature and contents of container 
 

Solution for injection in a vial (type I glass) with a stopper (laminated chlorobutyl rubber) and flip-off 

cap (aluminium). 

 

Packs containing 1 vial. 

 

Not all pack sizes may be marketed. 

 

  



51 

6.6 Special precautions for disposal and other handling 
 

Ilaris 150 mg/ml solution for injection is supplied in a single-use vial for individual use. 

 

Instructions for administration 

 

Allow the vial to warm to room temperature before injection. The solution should be practically free 

of visible particles and clear to opalescent. The solution should be colourless or may have a slight 

brownish-yellow tint. Using an 18 G or 21 G x 2 inch needle (or similar as available on the market) 

and a 1 ml syringe, carefully withdraw the required volume depending on the dose to be administered. 

Once the required volume is withdrawn, recap and remove the withdrawal needle from the syringe and 

attach a 27 G x 0.5 inch needle (or similar as available on the market) to immediately inject the 

solution subcutaneously. 

 

Disposal 

 

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

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/564/004 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 23 October 2009 

Date of latest renewal: 06 June 2019 

 

 

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/


52 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 
 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE 

SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR 

BATCH RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 

PRODUCT 

 



53 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 

MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 

Name and address of the manufacturer of the biological active substance 

 

Novartis Pharma S.A.S. 

Centre de Biotechnologie 

8, rue de l’Industrie 

68330 Huningue 

France 

 

Name and address of the manufacturer responsible for batch release 

 

Novartis Pharma GmbH 

Roonstrasse 25 

D-90429 Nürnberg 

Germany 

 

 

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 PSURs for this medicinal product are set out in the list of 

Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC 

and any subsequent updates published on the European medicines web-portal. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

 Risk management plan (RMP) 
 

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance 

activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the 

marketing authorisation and any agreed subsequent updates of the RMP. 

 

An updated RMP should be submitted: 

 At the request of the European Medicines Agency; 

 Whenever the risk management system is modified, especially as the result of new 
information being received that may lead to a significant change to the benefit/risk profile 

or as the result of an important (pharmacovigilance or risk minimisation) milestone being 

reached. 

 



54 

 Additional risk minimisation measures 
 

The Marketing Authorisation Holder (MAH) shall ensure that, prior to launch, all physicians who are 

expected to prescribe/use Ilaris are provided with a physician information pack containing the 

following: 

 The Summary of Product Characteristics 

 Patient Reminder Card 
 

  



55 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

  



56 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 
  



57 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

UNIT PACK CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Ilaris 150 mg powder for solution for injection 

canakinumab 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One vial contains 150 mg canakinumab. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: sucrose, histidine, histidine hydrochloride monohydrate, polysorbate 80. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder for solution for injection 

 

1 vial 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Subcutaneous use. 

Single use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

The reconstituted solution should ideally be used immediately, but can still be used for up to 24 hours 

if stored in a refrigerator. 

 

 



58 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/564/001 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Ilaris 150 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

  



59 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON OF MULTIPACK (INCLUDING BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Ilaris 150 mg powder for solution for injection 

canakinumab 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One vial contains 150 mg canakinumab. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: sucrose, histidine, histidine hydrochloride monohydrate, polysorbate 80. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder for solution for injection 

 

Multipack: 4 (4x1) vials. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Subcutaneous use. 

Single use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

The reconstituted solution should ideally be used immediately, but can still be used for up to 24 hours 

if stored in a refrigerator. 

 

 



60 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/564/002 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Ilaris 150 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

  



61 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Ilaris 150 mg powder for solution for injection 

canakinumab 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One vial contains 150 mg canakinumab. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: sucrose, histidine, histidine hydrochloride monohydrate, polysorbate 80. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder for solution for injection 

 

1 vial. Component of a multipack. Not to be sold separately. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Subcutaneous use. 

Single use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

The reconstituted solution should ideally be used immediately, but can still be used for up to 24 hours 

if stored in a refrigerator. 

 

 



62 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/564/002 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Ilaris 150 mg 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

  



63 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Ilaris 150 mg powder for solution for injection 

canakinumab 

SC after reconstitution 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

150 mg 

 

 

6. OTHER 

 

  



64 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

UNIT PACK CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Ilaris 150 mg/ml solution for injection 

canakinumab 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One vial contains 150 mg canakinumab in 1 ml of solution. 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: mannitol, histidine, histidine hydrochloride monohydrate, polysorbate 80, water for 

injections. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for injection 

 

1 vial 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Subcutaneous use 

Single use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

Use immediately after first opening. 

 

 



65 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

Keep the vial in the outer carton in order to protect from light. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/09/564/004 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Ilaris 150 mg/ml 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

  



66 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Ilaris 150 mg/ml injection 

canakinumab 

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 

 

 

  



67 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



68 

Package leaflet: Information for the user 

 

Ilaris 150 mg powder for solution for injection 

canakinumab 

 

Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 

- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 
side effects not listed in this leaflet. See section 4. 

 

 

What is in this leaflet: 

1. What Ilaris is and what it is used for 

2. What you need to know before you use Ilaris 

3. How to use Ilaris 

4. Possible side effects 

5. How to store Ilaris 

6. Contents of the pack and other information 

 

 

1. What Ilaris is and what it is used for 

 

What Ilaris is 

Ilaris contains the active substance canakinumab, a monoclonal antibody that belongs to a group of 

medicines called interleukin inhibitors. It blocks the activity of a substance called interleukin-1 beta 

(IL-1 beta) in the body, which is present at increased levels in inflammatory diseases. 

 

What Ilaris is used for 

Ilaris is used for treatment of the following inflammatory diseases: 

- Periodic fever syndromes: 

 Cryopyrin-associated periodic syndromes (CAPS), 

 Tumour necrosis factor receptor associated periodic syndrome (TRAPS), 

 Hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD), 

 Familial Mediterranean fever (FMF). 
- Still’s disease including adult onset Still’s disease (AOSD) and systemic juvenile idiopathic 

arthritis (SJIA) 

- Gouty arthritis 
 

More information on each of these diseases is given below. 

 

  



69 

Periodic fever syndromes 

Ilaris is used in adults and children aged 2 years and older to treat the following: 

- Cryopyrin-associated periodic syndromes (CAPS) – this is a group of auto-inflammatory 
diseases, which include: 

 Muckle-Wells syndrome (MWS), 

 Neonatal-onset multisystem inflammatory disease (NOMID), also called chronic infantile 
neurological, cutaneous, articular syndrome (CINCA), 

 Severe forms of familial cold auto-inflammatory syndrome (FCAS) / familial cold 
urticaria (FCU) presenting with signs and symptoms beyond cold-induced urticarial skin 

rash. 

- Tumour necrosis factor receptor associated periodic syndrome (TRAPS) 
- Hyperimmunoglobulin D syndrome (HIDS) also known as mevalonate kinase deficiency 

(MKD) 

- Familial Mediterranean fever (FMF): Ilaris is used to treat FMF. Ilaris can be used together with 
colchicine, if appropriate. 

 

In patients with periodic fever syndromes (CAPS, TRAPS, HIDS/MKD and FMF), the body produces 

too much IL-1 beta. This may cause fever, headache, fatigue, skin rash, or painful joints and muscles. 

By blocking the activity of IL-1 beta, Ilaris may improve these symptoms. 

 

Still’s disease 

Ilaris is used in adults, adolescents and children to treat active Still’s disease including adult-onset 

Still’s disease (AOSD) and systemic juvenile idiopathic arthritis (SJIA) in patients aged 2 years and 

older if other treatments have not worked well enough. Ilaris can be used alone or in combination with 

methotrexate. 

 

Still’s disease including SJIA and AOSD is an inflammatory disease that can cause pain, swelling and 

inflammation of one or more joints, as well as rash and fever. A pro-inflammatory protein called IL-1 

beta plays an important role in Still’s disease inflammation. Ilaris blocks the activity of IL-1 beta, 

which may improve the signs and symptoms of Still’s disease. 

 

Gouty arthritis 

Ilaris is used in adults to treat the symptoms of frequent gouty arthritis attacks if other treatments have 

not worked well enough. 

 

Gouty arthritis is caused by the formation of urate crystals. These crystals cause excessive production 

of IL-1 beta, which in turn can lead to sudden, severe pain, redness, warmth and swelling in a joint 

(known as a gouty arthritis attack). By blocking the activity of IL-1 beta, Ilaris may lead to an 

improvement in these symptoms. 

 

 

  



70 

2. What you need to know before you use Ilaris 

 

Do not use Ilaris 

- if you are allergic to canakinumab or any of the other ingredients of this medicine (listed in 

section 6). 

- if you have, or suspect you have, an active and severe infection. 
 

Warning and precautions 

Talk to your doctor before using Ilaris if any of the following applies to you: 

 if you currently have an infection or if you have had repeated infections or a condition such as a 
known low level of white blood cells which makes you more likely to get infections. 

 if you have or have ever had tuberculosis or direct contact with a person with an active 
tuberculosis infection. Your doctor may check whether you have tuberculosis using a specific 

test. 

 if you have signs of a liver disorder such as yellow skin and eyes, nausea, loss of appetite, dark-
coloured urine and light-coloured stools. 

 if you need to have any vaccinations. You are advised to avoid being vaccinated with a type of 
vaccine called a live vaccine while being treated with Ilaris (see also “Other medicines and 

Ilaris”). 

 

Still’s disease 

 Patients with Still’s disease may develop a condition called macrophage activation syndrome 
(MAS), which can be life-threatening. Your doctor will monitor you for potential triggering 

factors of MAS that include infections and re-activation of the underlying Still’s disease (flare). 

 

Children and adolescents 

 CAPS, TRAPS, HIDS/MKD, FMF and SJIA: Ilaris can be used in children aged 2 years and 
older. 

 Gouty arthritis: Ilaris is not recommended for children or adolescents under 18 years of age. 
 

Other medicines and Ilaris 

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other 

medicines. 

 Live vaccines: You are advised to avoid being vaccinated with a type of vaccine called a live 
vaccine while you are being treated with Ilaris. Your doctor may want to check your vaccination 

history and give you any vaccinations that you have missed before you start treatment with 

Ilaris. If you need to be given a live vaccine after starting treatment with Ilaris, discuss this with 

your doctor. A live vaccine should normally be given 3 months after your last injection of Ilaris 

and 3 months before the next one. 

 Medicines called tumour necrosis factor (TNF) inhibitors, such as etanercept, adalimumab or 
infliximab. These are used mainly in rheumatic and autoimmune diseases. They should not be 

used with Ilaris because this may increase the risk of infections. 

 

Pregnancy and breast-feeding 

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 

your doctor or pharmacist for advice before taking this medicine. 

 You are advised to avoid becoming pregnant and must use adequate contraception while using 
Ilaris and for at least 3 months after the last Ilaris treatment. It is important to tell your doctor if 

you are pregnant, if you think you may be pregnant or are planning to have a baby. Your doctor 

will discuss with you the potential risks of taking Ilaris during pregnancy. 

 If you received canakinumab while you were pregnant, it is important that you inform the 
baby’s doctor or nurse before any vaccinations are given to your baby. Your baby should not 

receive live vaccines until at least 16 weeks after you received your last dose of canakinumab 

before giving birth. 

 It is not known whether Ilaris passes into human milk. Your doctor will discuss with you the 
potential risks of taking Ilaris before breast-feeding. 



71 

 

Driving and using machines 

Ilaris treatment may give you a spinning sensation (dizziness or vertigo) or intense tiredness 

(asthenia). This may affect your ability to drive or use tools or machines. If you feel a spinning 

sensation or feel tired, do not drive or use any tools or machines until you are feeling normal again. 

 

 

3. How to use Ilaris 
 

Always use this medicine exactly as your doctor has told you. Check with your doctor, pharmacist or 

nurse if you are not sure. 

 

Keep your doctor informed of your condition and any symptoms before you use or are given Ilaris (see 

section 2). Your doctor may decide to delay or interrupt your treatment, but only if necessary. 

 

Ilaris is intended for subcutaneous use. This means that it is injected through a short needle into the 

fatty tissue just under the skin. 

 

If you have gouty arthritis, your treatment will be overseen by a doctor with specialist training. Ilaris 

should be injected by a healthcare professional only. 

 

If you have CAPS, TRAPS, HIDS/MKD, FMF or Still’s disease (AOSD or SJIA), you may inject 

yourself with Ilaris after proper training, or a caregiver may inject it for you. 

 

How much Ilaris to use 

Cryopyrin-associated periodic syndromes (CAPS) 

The recommended starting dose of Ilaris is: 

- Adults and children aged 4 years or more 

 150 mg for patients who weigh more than 40 kg 

 2 mg/kg for patients who weigh between 15 kg and 40 kg 

 4 mg/kg for patients who weigh between 7.5 kg and less than 15 kg 
- Children aged 2 or 3 years 

 4 mg/kg for patients with body weight of 7.5 kg or more 
 

Ilaris is injected every 8 weeks as a single dose. 

 

 If you have not responded well enough to the treatment after 7 days, your doctor may give you 
another dose of 150 mg or 2 mg/kg. 

 If you respond well enough to the second dose, your treatment will be continued with 300 mg or 
4 mg/kg every 8 weeks. 

 If you do not respond well enough to the second dose, a third dose of Ilaris at 300 mg or 
4 mg/kg may be given. 

 If you respond well enough to the third dose, your treatment will be continued at 600 mg or 
8 mg/kg every 8 weeks. 

 

For children given a starting dose of 4 mg/kg who have not responded well enough after 7 days, the 

doctor may give a second dose of 4 mg/kg. If the child responds well enough to this, treatment may be 

continued with a dose of 8 mg/kg every 8 weeks. 

 



72 

Tumour necrosis factor receptor associated periodic syndrome (TRAPS), hyperimmunoglobulin D 

syndrome (HIDS)/mevalonate kinase deficiency (MKD) and familial Mediterranean fever (FMF) 

The recommended starting dose of Ilaris is: 

- Adults and children aged 2 years or more 

 150 mg for patients who weigh more than 40 kg 

 2 mg/kg for patients who weigh between 7.5 kg and less than 40 kg 
 

Ilaris is injected every 4 weeks as a single dose. 

 

- If you have not responded well enough to the treatment after 7 days, your doctor may give you 
another dose of 150 mg or 2 mg/kg. 

- If you respond well enough to this, your treatment will be continued with 300 mg or 4 mg/kg 
every 4 weeks. 

 

Still’s disease (SJIA and AOSD) 

The recommended dose of Ilaris for patients with Still’s disease with body weight of 7.5 kg and above 

is 4 mg/kg (up to a maximum of 300 mg). Ilaris is injected every 4 weeks as a single dose. 

 

Gouty arthritis 

Your doctor will discuss with you the need to start or adjust a urate lowering therapy to lower the uric 

acid level in your blood. 

 

The recommended dose of Ilaris for adult gouty arthritis patients is 150 mg given as a single dose at 

the time of a gouty arthritis attack. 

 

If you need another treatment with Ilaris, and got relief from the last dose, you must wait at least 

12 weeks before the next dose. 

 

Injecting Ilaris yourself or injecting a patient with Ilaris 

If you are a patient with CAPS, TRAPS, HIDS/MKD, FMF or Still’s disease (AOSD or SJIA), or a 

caregiver of a patient with one of these conditions, you may administer Ilaris injections yourself after 

proper training in the correct injection technique. 

 The patient or caregiver and the doctor should decide together who will administer the Ilaris 
injections. 

 The doctor or nurse will demonstrate how to administer Ilaris injections. 

 Do not try to administer an injection yourself if you have not been properly trained or if you are 
not sure how to do it. 

 Ilaris 150 mg powder for solution for injection is supplied in a single-use vial for individual use. 

 Never re-use the leftover solution. 
 

For instructions on how to administer Ilaris injections, please read the section “Instructions for use” at 

the end of this leaflet. If you have any questions, talk to your doctor, pharmacist or nurse. 

 

How long to use Ilaris 

 CAPS, TRAPS, HIDS/MKD, FMF or Still’s disease (AOSD or SJIA): You should continue 
using Ilaris for as long as the doctor tells you. 

 Gouty arthritis: If you have a gouty arthritis attack, you will be given a single dose of Ilaris. If 
you experience a new attack, your doctor may consider giving you a new dose of Ilaris but not 

earlier than 12 weeks from the previous dose. 

 

If you use more Ilaris than you should 

If you accidentally inject more Ilaris than the recommended dose, it is unlikely to be serious, but you 

should inform your doctor, pharmacist or nurse as soon as possible. 

 



73 

If you forget to use Ilaris 

If you have CAPS, TRAPS, HIDS/MKD, FMF or Still’s disease (AOSD or SJIA) and have forgotten 

to inject a dose of Ilaris, inject the next dose as soon as you remember. Then talk to the doctor to 

discuss when you should inject the next dose. You should then continue with injections at the 

recommended intervals as before. 

 

If you stop using Ilaris 

Stopping your treatment with Ilaris may cause your condition to get worse. Do not stop taking Ilaris 

unless your doctor tells you to. 

 

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. 

 

Some side effects could be serious. Tell your doctor immediately, if you notice any of the side 

effects below: 

 Fever lasting longer than 3 days or any other symptoms that might suggest a serious infection. 
These include shivering, chills, malaise, loss of appetite, body aches, typically in connection 

with a sudden onset of illness, sore throat or mouth ulcers, cough, phlegm, chest pain, difficulty 

breathing, ear pain, prolonged headache or localised redness, warmth or swelling of your skin or 

inflammation of connective tissue (cellulitis). These symptoms could be due to a serious 

infection, an unusual infection (opportunistic infection) or be related to low levels of white 

blood cells (called leukopenia or neutropenia). Your doctor may check your blood regularly if 

considered necessary. 

 Allergic reactions with rash and itching and possibly also hives, difficulty breathing or 
swallowing, dizziness, unusual awareness of your heart beat (palpitations) or low blood 

pressure. 

 

Other side effects of Ilaris include: 

Very common (may affect more than 1 in 10 people): 

 Infections of any kind. These can include: 

 Respiratory infections such as chest infection, flu, sore throat, runny nose, blocked nose, 
sneezing, feeling of pressure or pain in the cheeks or forehead with or without fever 

(pneumonia, bronchitis, influenza, sinusitis, rhinitis, pharyngitis, tonsilitis, 

nasopharyngitis, upper respiratory tract infection). 

 Other infections such as ear infection, skin infection (cellulitis), stomach pain and feeling 
sick (gastroenteritis) and painful and frequent urination with or without fever (urinary 

tract infection). 

 Upper abdominal pain. 

 Pain in joints (arthralgia). 

 Drop in level of white blood cells (leukopenia). 

 Abnormal kidney function test results (creatinine renal clearance decreased, proteinuria). 

 Injection site reaction (such as redness, swelling, warmth and itching). 
 

Common (may affect up to 1 in 10 people): 

 Candida - vaginal yeast infection (vulvovaginal candidiasis). 

 Feeling dizzy, spinning sensation (dizziness or vertigo). 

 Pain in the back or muscles. 

 Feeling weak or very tired (fatigue, asthenia). 

 Drop in level of white blood cells which help prevent infection (neutropenia). 

 Abnormal levels of triglycerides in your blood (lipid metabolism disorder). 

 Abnormal liver function test results (transaminases increased) or high level of bilirubin in the 
blood, with or without yellow skin and eyes (hyperbilirubinaemia). 



74 

 

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

 Heartburn (gastro-oesophageal reflux disease). 

 Drop in level of blood cells which help prevent bleeding (platelets). 
 

Tell your doctor or your child’s doctor immediately if you notice any of these symptoms. 

 

Reporting of side effects 

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 

effects not listed in this leaflet. You can also report side effects directly via the national reporting 

system listed in Appendix V. By reporting side effects you can help provide more information on the 

safety of this medicine. 

 

 

5. How to store Ilaris 
 

- Keep this medicine out of the sight and reach of children. 
 

- Do not use this medicine after the expiry date which is stated on the label and carton. The expiry 
date refers to the last day of that month. 

 

- Store in a refrigerator (2°C - 8°C). Do not freeze. 
 

- Store in the original package in order to protect from light. 
 

- After mixing (reconstitution) the medicine should be used immediately. If not used 
immediately, the solution should be stored in the refrigerator (2°C - 8°C) and used within 

24 hours. 

 

- Do not use this medicine if you notice that the solution is not clear to opalescent or contains 
particles. 

 

- Any unused medicine must be discarded after the dose has been injected. 
 

- Do not throw away any medicines via wastewater or household waste. Ask your pharmacist 
how to throw away medicines you no longer use. These measures will help protect the 

environment. 

 

 

6. Contents of the pack and other information 

 

What Ilaris contains 

 The active substance is canakinumab. One vial of powder contains 150 mg canakinumab. After 
reconstitution, each ml of solution contains 150 mg canakinumab. 

 The other ingredients are: sucrose, histidine, histidine hydrochloride monohydrate, polysorbate 
80. 

 

What Ilaris looks like and contents of the pack 

 Ilaris is supplied as a powder for solution for injection (150 mg in a 6 ml glass vial). 

 The powder is white. 

 Ilaris is available in packs containing one vial or multipacks comprising four intermediate 
packs, each containing one vial. Not all pack sizes may be marketed in your country. 

 

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


75 

Marketing Authorisation Holder 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 

Novartis Pharma GmbH 

Roonstrasse 25 

D-90429 Nuremberg 

Germany 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 
SIA Novartis Baltics Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел.: +359 2 489 98 28 

 

Luxembourg/Luxemburg 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Česká republika 
Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

Danmark 
Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Deutschland 
Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 
Novartis Pharma B.V. 

Tel: +31 88 04 52 111 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 
Novartis Norge AS 

Tlf: +47 23 05 20 00 

Ελλάδα 
Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 
Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

Novartis Farmacéutica, S.A. 

Tel: +34 93 306 42 00 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

Portugal 
Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 



76 

Ireland 
Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 
Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 
Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 
Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

SIA Novartis Baltics 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

 

This leaflet was last revised in 
 

 

Other sources of information 

Detailed information on this medicine is available on the European Medicines Agency website: 

http://www.ema.europa.eu 

 

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


77 

Instructions for use of Ilaris powder for solution for injection 

 

Please note that the preparation of the injection takes about 30 minutes. 

See also section 3, “Injecting Ilaris yourself or injecting a patient with Ilaris”. 

 

Read these instructions all the way through before beginning. 

 

Essential preparation 

 Find a clean place in which to prepare and administer the injection. 

 Wash your hands with soap and water. 

 Check the expiry dates on the vial and syringes. Do not use after the expiry date which is stated 
on the label and carton. The expiry date refers to the last day of that month. 

 Always use new, unopened needles and syringes. Avoid touching the needles and the tops of the 
vials. 

 

Gather together the necessary items 

Included in the pack 

- one vial of Ilaris powder for solution for injection (keep refrigerated) 
 

Not included in the pack 

 one vial (or ampoule) of sterile water for injections (“water”) (at room temperature) 

 one 1.0 ml syringe 

 one 18 G x 2 inch (50 mm) needle for reconstituting the powder (“transfer needle”) 

 one 27 G x 0.5 inch (13 mm) needle for injecting (“injection needle”) 

 alcohol swabs 

 clean, dry cotton swabs 

 an adhesive plaster 

 a proper disposal container for used needles, syringe and vials (sharps container) 
 

 

Mixing Ilaris 

 

 

1. Remove the caps from the Ilaris and water vials. 
Do not touch the vial stoppers. Clean the stoppers 

with the alcohol swab. 

2. Open the wrappers containing the syringe and the 
transfer needle (the 50 mm needle) and attach the 

needle to the syringe. 

3. Carefully remove the cap from the transfer needle 
and set the cap aside. Pull the plunger all the way 

down to the 1.0 ml mark, filling the syringe with 

air. Insert the needle into the water vial through the 

centre of the rubber stopper. 

4. Gently push the plunger all the way down until air 
is in the vial. 



78 

 

5. Turn the vial and syringe upside down and bring to 
eye level. 

6. Make sure the tip of the transfer needle is covered 
by the water and slowly pull the syringe plunger 

down to slightly past the 1.0 ml mark. If you see 

bubbles in the syringe, remove bubbles as 

instructed by your healthcare professional or 

pharmacist. 

7. Make sure 1.0 ml of water is in the syringe, then 
take the needle out of the vial. (There will be water 

remaining in the vial.) 

 

8. Insert the transfer needle through the centre of the 
stopper of the vial of Ilaris powder, taking care not 

to touch the needle or the stopper. Slowly inject the 

water into the vial containing the Ilaris powder. 

9. Carefully remove the transfer needle from the vial 
and recap the needle as instructed by your 

healthcare provider or pharmacist. 

 

10. Without touching the rubber stopper, swirl (do not 
shake) the vial slowly at an angle of about 

45 degrees for about 1 minute. Allow to stand for 

5 minutes. 



79 

 

11. Now, gently turn the vial upside down and back 
again ten times, again taking care not to touch the 

rubber stopper. 

12. Allow to stand for about 15 minutes at room 
temperature to get a clear to opalescent solution. 

Do not shake. Do not use if particles are present in 

the solution. 

13. Make sure all of the solution is in the bottom of the 
vial. If drops remain on the stopper, tap the side of 

the vial to remove them. The solution should be 

clear to opalescent and free of visible particles. The 

solution should be colourless or may have a slight 

brownish-yellow tint. 

- If not used immediately after mixing, the 
solution should be stored in the refrigerator 

(2°C to 8°C) and used within 24 hours. 

 

 

Preparing the injection 

 

 

14. Clean the rubber stopper of the vial containing the 
Ilaris solution with a new alcohol swab. 

15. Uncap the transfer needle again. Pull the plunger of 
the syringe all the way down to the 1.0 ml mark, 

filling the syringe with air. Insert the syringe 

needle into the vial of Ilaris solution through the 

centre of the rubber stopper. The needle should not 

be in the liquid at this point. Gently push the 

plunger all the way down until all of the air is 

injected into the vial. Do not inject air into the 

liquid. 

 

16. Do not turn the vial and syringe upside down, the 
vial should stay upright. Insert the needle all the 

way into the vial until it reaches the bottom edge. 



80 

 

17. Tip the vial to ensure that the required amount of 
solution can be drawn into the syringe 

18. NOTE: The required amount depends on the dose 
to be administered. Your healthcare provider will 

instruct you on the right amount for you. 

19. Slowly pull the syringe plunger up to the correct 
mark (amount to be given), filling the syringe with 

Ilaris solution. If there are air bubbles in the 

syringe, remove bubbles as instructed by your 

healthcare provider. Ensure that the correct amount 

of solution is in the syringe. 

20. Remove the syringe and needle from the vial. 
(There may be solution remaining in the vial.) 

Recap the transfer needle as instructed by your 

healthcare provider or pharmacist. Remove the 

transfer needle from the syringe. Place the transfer 

needle in the sharps container. 

21. Open the wrapper containing the injection needle 
and attach the needle to the syringe. Set the syringe 

aside. 

 

 

Giving the injection 

 

 

22. Choose an injection site on the upper thigh, 
abdomen, upper arm or buttocks. Do not use an 

area that has a rash or broken skin, or is bruised or 

lumpy. Do not inject into scar-tissue as this may 

mean you do not get all of your medicine. Avoid 

injecting into a vein. 

23. Clean the injection site with a new alcohol swab. 
Allow the area to dry. Uncap the injection needle. 

24. Gently pinch the skin up at the injection site. Hold 
the syringe at a 90-degree angle and in a single, 

smooth motion, push the needle straight down 

completely into the skin. 

 

25. Keep the needle all the way in the skin while 
slowly pushing the syringe plunger down until the 

barrel is empty. Release the pinched skin and pull 

the needle straight out. Dispose of the needle and 

syringe in the sharps container without recapping 

or removing the needle. 

 

 



81 

After the injection 

 

 

26. Do not rub the injection area. If bleeding occurs, 
apply a clean, dry cotton swab over the area, and 

press gently for 1 to 2 minutes, or until bleeding 

stops. Then apply an adhesive plaster. 

 

 

27. Safely dispose of needles and syringe in the sharps 
container or as directed by your healthcare provider 

or pharmacist. Never re-use syringes or needles. 

28. Properly dispose of vials containing remaining 
water and Ilaris solution (if any) as directed by 

your healthcare provider or pharmacist. Any 

unused product or waste material should be 

disposed of in accordance with local requirements. 

 

Keep the sharps container out of reach of children. 

 

Dispose of it as directed by your healthcare provider or 

pharmacist. 

 



82 

Package leaflet: Information for the user 

 

Ilaris 150 mg/ml solution for injection 

canakinumab 

 

Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 

- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 
side effects not listed in this leaflet. See section 4. 

 

 

What is in this leaflet: 

1. What Ilaris is and what it is used for 

2. What you need to know before you use Ilaris 

3. How to use Ilaris 

4. Possible side effects 

5. How to store Ilaris 

6. Contents of the pack and other information 

 

 

1. What Ilaris is and what it is used for 

 

What Ilaris is 

Ilaris contains the active substance canakinumab, a monoclonal antibody that belongs to a group of 

medicines called interleukin inhibitors. It blocks the activity of a substance called interleukin-1 beta 

(IL-1 beta) in the body, which is present at increased levels in inflammatory diseases. 

 

What Ilaris is used for 

Ilaris is used for treatment of the following inflammatory diseases: 

- Periodic fever syndromes: 

 Cryopyrin-associated periodic syndromes (CAPS), 

 Tumour necrosis factor receptor associated periodic syndrome (TRAPS), 

 Hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD), 

 Familial Mediterranean fever (FMF). 
- Still’s disease including adult onset Still’s disease (AOSD) and systemic juvenile idiopathic 

arthritis (SJIA) 

- Gouty arthritis 
 

More information on each of these diseases is given below. 

 

  



83 

Periodic fever syndromes 

Ilaris is used in adults and children aged 2 years and older to treat the following: 

- Cryopyrin-associated periodic syndromes (CAPS) – this is a group of auto-inflammatory 
diseases, which include: 

 Muckle-Wells syndrome (MWS), 

 Neonatal-onset multisystem inflammatory disease (NOMID), also called chronic infantile 
neurological, cutaneous, articular syndrome (CINCA), 

 Severe forms of familial cold auto-inflammatory syndrome (FCAS) / familial cold 
urticaria (FCU) presenting with signs and symptoms beyond cold-induced urticarial skin 

rash. 

- Tumour necrosis factor receptor associated periodic syndrome (TRAPS) 
- Hyperimmunoglobulin D syndrome (HIDS) also known as mevalonate kinase deficiency 

(MKD) 

- Familial Mediterranean fever (FMF): Ilaris is used to treat FMF. Ilaris can be used together with 
colchicine, if appropriate. 

 

In patients with periodic fever syndromes (CAPS, TRAPS, HIDS/MKD and FMF), the body produces 

too much IL-1 beta. This may cause fever, headache, fatigue, skin rash, or painful joints and muscles. 

By blocking the activity of IL-1 beta, Ilaris may improve these symptoms. 

 

Still’s disease 

Ilaris is used in adults, adolescents and children to treat active Still’s disease including adult-onset 

Still’s disease (AOSD) and systemic juvenile idiopathic arthritis (SJIA) in patients aged 2 years and 

older if other treatments have not worked well enough. Ilaris can be used alone or in combination with 

methotrexate. 

 

Still’s disease including SJIA and AOSD is an inflammatory disease that can cause pain, swelling and 

inflammation of one or more joints, as well as rash and fever. A pro-inflammatory protein called IL-1 

beta plays an important role in Still’s disease inflammation. Ilaris blocks the activity of IL-1 beta, 

which may improve the signs and symptoms of Still’s disease. 

 

Gouty arthritis 

Ilaris is used in adults to treat the symptoms of frequent gouty arthritis attacks if other treatments have 

not worked well enough. 

 

Gouty arthritis is caused by the formation of urate crystals. These crystals cause excessive production 

of IL-1 beta, which in turn can lead to sudden, severe pain, redness, warmth and swelling in a joint 

(known as a gouty arthritis attack). By blocking the activity of IL-1 beta, Ilaris may lead to an 

improvement in these symptoms. 

 

 

  



84 

2. What you need to know before you use Ilaris 

 

Do not use Ilaris 

- if you are allergic to canakinumab or any of the other ingredients of this medicine (listed in 

section 6). 

- if you have, or suspect you have, an active and severe infection. 
 

Warning and precautions 

Talk to your doctor before using Ilaris if any of the following applies to you: 

 if you currently have an infection or if you have had repeated infections or a condition such as a 
known low level of white blood cells which makes you more likely to get infections. 

 if you have or have ever had tuberculosis or direct contact with a person with an active 
tuberculosis infection. Your doctor may check whether you have tuberculosis using a specific 

test. 

 if you have signs of a liver disorder such as yellow skin and eyes, nausea, loss of appetite, dark-
coloured urine and light-coloured stools. 

 if you need to have any vaccinations. You are advised to avoid being vaccinated with a type of 
vaccine called a live vaccine while being treated with Ilaris (see also “Other medicines and 

Ilaris”). 

 

Still’s disease 

 Patients with Still’s disease may develop a condition called macrophage activation syndrome 
(MAS), which can be life-threatening. Your doctor will monitor you for potential triggering 

factors of MAS that include infections and re-activation of the underlying Still’s disease (flare). 

 

Children and adolescents 

 CAPS, TRAPS, HIDS/MKD, FMF and SJIA: Ilaris can be used in children aged 2 years and 
older. 

 Gouty arthritis: Ilaris is not recommended for children or adolescents under 18 years of age. 
 

Other medicines and Ilaris 

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other 

medicines. 

 Live vaccines: You are advised to avoid being vaccinated with a type of vaccine called a live 
vaccine while you are being treated with Ilaris. Your doctor may want to check your vaccination 

history and give you any vaccinations that you have missed before you start treatment with 

Ilaris. If you need to be given a live vaccine after starting treatment with Ilaris, discuss this with 

your doctor. A live vaccine should normally be given 3 months after your last injection of Ilaris 

and 3 months before the next one. 

 Medicines called tumour necrosis factor (TNF) inhibitors, such as etanercept, adalimumab or 
infliximab. These are used mainly in rheumatic and autoimmune diseases. They should not be 

used with Ilaris because this may increase the risk of infections. 

 

Pregnancy and breast-feeding 

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 

your doctor or pharmacist for advice before taking this medicine. 

 You are advised to avoid becoming pregnant and must use adequate contraception while using 
Ilaris and for at least 3 months after the last Ilaris treatment. It is important to tell your doctor if 

you are pregnant, if you think you may be pregnant or are planning to have a baby. Your doctor 

will discuss with you the potential risks of taking Ilaris during pregnancy. 

 If you received canakinumab while you were pregnant, it is important that you inform the 
baby’s doctor or nurse before any vaccinations are given to your baby. Your baby should not 

receive live vaccines until at least 16 weeks after you received your last dose of canakinumab 

before giving birth. 

 It is not known whether Ilaris passes into human milk. Your doctor will discuss with you the 
potential risks of taking Ilaris before breast-feeding. 



85 

 

Driving and using machines 

Ilaris treatment may give you a spinning sensation (dizziness or vertigo) or intense tiredness 

(asthenia). This may affect your ability to drive or use tools or machines. If you feel a spinning 

sensation or feel tired, do not drive or use any tools or machines until you are feeling normal again. 

 

 

3. How to use Ilaris 
 

Always use this medicine exactly as your doctor has told you. Check with your doctor, pharmacist or 

nurse if you are not sure. 

 

Keep your doctor informed of your condition and any symptoms before you use or are given Ilaris (see 

section 2). Your doctor may decide to delay or interrupt your treatment, but only if necessary. 

 

Ilaris is intended for subcutaneous use. This means that it is injected through a short needle into the 

fatty tissue just under the skin. 

 

If you have gouty arthritis, your treatment will be overseen by a doctor with specialist training. Ilaris 

should be injected by a healthcare professional only. 

 

If you have CAPS, TRAPS, HIDS/MKD, FMF or Still’s disease (AOSD or SJIA), you may inject 

yourself with Ilaris after proper training, or a caregiver may inject it for you. 

 

How much Ilaris to use 

Cryopyrin- associated periodic syndromes (CAPS) 

The recommended starting dose of Ilaris is: 

- Adults and children aged 4 years or more 

 150 mg for patients who weigh more than 40 kg 

 2 mg/kg for patients who weigh between 15 kg and 40 kg 

 4 mg/kg for patients who weigh between 7.5 kg and less than 15 kg 
- Children aged 2 or 3 years 

 4 mg/kg for patients with body weight of 7.5 kg or more 
 

Ilaris is injected every 8 weeks as a single dose. 

 

 If you have not responded well enough to the treatment after 7 days, your doctor may give you 
another dose of 150 mg or 2 mg/kg. 

 If you respond well enough to the second dose, your treatment will be continued with 300 mg or 
4 mg/kg every 8 weeks. 

 If you do not respond well enough to the second dose, a third dose of Ilaris at 300 mg or 
4 mg/kg may be given. 

 If you respond well enough to the third dose, your treatment will be continued at 600 mg or 
8 mg/kg every 8 weeks. 

 

For children given a starting dose of 4 mg/kg who have not responded well enough after 7 days, the 

doctor may give a second dose of 4 mg/kg. If the child responds well enough to this, treatment may be 

continued with a dose of 8 mg/kg every 8 weeks. 

 



86 

Tumour necrosis factor receptor associated periodic syndrome (TRAPS), hyperimmunoglobulin D 

syndrome (HIDS)/mevalonate kinase deficiency (MKD) and familial Mediterranean fever (FMF) 

The recommended starting dose of Ilaris is: 

- Adults and children aged 2 years or more 

 150 mg for patients who weigh more than 40 kg 

 2 mg/kg for patients who weigh between 7.5 kg and less than 40 kg 
 

Ilaris is injected every 4 weeks as a single dose. 

 

- If you have not responded well enough to the treatment after 7 days, your doctor may give you 
another dose of 150 mg or 2 mg/kg. 

- If you respond well enough to this, your treatment will be continued with 300 mg or 4 mg/kg 
every 4 weeks. 

 

Still’s disease (SJIA and AOSD) 

The recommended dose of Ilaris for patients with Still’s disease with body weight of 7.5 kg and above 

is 4 mg/kg (up to a maximum of 300 mg). Ilaris is injected every 4 weeks as a single dose. 

 

Gouty arthritis 

Your doctor will discuss with you the need to start or adjust a urate lowering therapy to lower the uric 

acid level in your blood. 

 

The recommended dose of Ilaris for adult gouty arthritis patients is 150 mg given as a single dose at 

the time of a gouty arthritis attack. 

 

If you need another treatment with Ilaris, and got relief from the last dose, you must wait at least 

12 weeks before the next dose. 

 

Injecting Ilaris yourself or injecting a patient with Ilaris 

If you are a patient with CAPS, TRAPS, HIDS/MKD, FMF or Still’s disease (AOSD or SJIA), or a 

caregiver of a patient with one of these conditions, you may administer Ilaris injections yourself after 

proper training in the correct injection technique. 

 The patient or caregiver and the doctor should decide together who will administer the Ilaris 
injections. 

 The doctor or nurse will demonstrate how to administer Ilaris injections. 

 Do not try to administer an injection yourself if you have not been properly trained or if you are 
not sure how to do it. 

 Ilaris 150 mg/ml solution for injection is supplied in a single-use vial for individual use. 

 Never re-use the leftover solution. 
 

For instructions on how to administer Ilaris injections, please read the section “Instructions for use” at 

the end of this leaflet. If you have any questions, talk to your doctor, pharmacist or nurse. 

 

How long to use Ilaris 

 CAPS, TRAPS, HIDS/MKD, FMF or Still’s disease (AOSD or SJIA): You should continue 
using Ilaris for as long as the doctor tells you. 

 Gouty arthritis: If you have a gouty arthritis attack, you will be given a single dose of Ilaris. If 
you experience a new attack, your doctor may consider giving you a new dose of Ilaris but not 

earlier than 12 weeks from the previous dose. 

 

If you use more Ilaris than you should 

If you accidentally inject more Ilaris than the recommended dose, it is unlikely to be serious, but you 

should inform your doctor, pharmacist or nurse as soon as possible. 

 



87 

If you forget to use Ilaris 

If you have CAPS, TRAPS, HIDS/MKD, FMF or Still’s disease (AOSD or SJIA) and have forgotten 

to inject a dose of Ilaris, inject the next dose as soon as you remember. Then talk to the doctor to 

discuss when you should inject the next dose. You should then continue with injections at the 

recommended intervals as before. 

 

If you stop using Ilaris 

Stopping your treatment with Ilaris may cause your condition to get worse. Do not stop taking Ilaris 

unless your doctor tells you to. 

 

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. 

 

Some side effects could be serious. Tell your doctor immediately, if you notice any of the side 

effects below: 

 Fever lasting longer than 3 days or any other symptoms that might suggest a serious infection. 
These include shivering, chills, malaise, loss of appetite, body aches, typically in connection 

with a sudden onset of illness, sore throat or mouth ulcers, cough, phlegm, chest pain, difficulty 

breathing, ear pain, prolonged headache or localised redness, warmth or swelling of your skin or 

inflammation of connective tissue (cellulitis). These symptoms could be due to a serious 

infection, an unusual infection (opportunistic infection) or be related to low levels of white 

blood cells (called leukopenia or neutropenia). Your doctor may check your blood regularly if 

considered necessary. 

 Allergic reactions with rash and itching and possibly also hives, difficulty breathing or 
swallowing, dizziness, unusual awareness of your heart beat (palpitations) or low blood 

pressure. 

 

Other side effects of Ilaris include: 

Very common (may affect more than 1 in 10 people): 

 Infections of any kind. These can include: 

 Respiratory infections such as chest infection, flu, sore throat, runny nose, blocked nose, 
sneezing, feeling of pressure or pain in the cheeks or forehead with or without fever 

(pneumonia, bronchitis, influenza, sinusitis, rhinitis, pharyngitis, tonsilitis, 

nasopharyngitis, upper respiratory tract infection). 

 Other infections such as ear infection, skin infection (cellulitis), stomach pain and feeling 
sick (gastroenteritis) and painful and frequent urination with or without fever (urinary 

tract infection). 

 Upper abdominal pain. 

 Pain in joints (arthralgia). 

 Drop in level of white blood cells (leukopenia). 

 Abnormal kidney function test results (creatinine renal clearance decreased, proteinuria). 

 Injection site reaction (such as redness, swelling, warmth and itching). 
 

Common (may affect up to 1 in 10 people): 

 Candida - vaginal yeast infection (vulvovaginal candidiasis). 

 Feeling dizzy, spinning sensation (dizziness or vertigo). 

 Pain in the back or muscles. 

 Feeling weak or very tired (fatigue, asthenia). 

 Drop in level of white blood cells which help prevent infection (neutropenia). 

 Abnormal levels of triglycerides in your blood (lipid metabolism disorder). 

 Abnormal liver function test results (transaminases increased) or high level of bilirubin in the 
blood, with or without yellow skin and eyes (hyperbilirubinaemia). 



88 

 

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

 Heartburn (gastro-oesophageal reflux disease). 

 Drop in level of blood cells which help prevent bleeding (platelets). 
 

Tell your doctor or your child’s doctor immediately if you notice any of these symptoms. 

 

Reporting of side effects 

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 

effects not listed in this leaflet. You can also report side effects directly via the national reporting 

system listed in Appendix V. By reporting side effects you can help provide more information on the 

safety of this medicine. 

 

 

5. How to store Ilaris 
 

- Keep this medicine out of the sight and reach of children. 
 

- Do not use this medicine after the expiry date which is stated on the label and carton. The expiry 
date refers to the last day of that month. 

 

- Store in a refrigerator (2°C - 8°C). Do not freeze. 
 

- Keep the vial in the outer carton in order to protect from light. 
 

- The solution should be used immediately after first piercing the vial stopper to prepare the 
injection. 

 

- Do not use this medicine if you notice that the solution is not clear to opalescent or contains 
particles. 

 

- Any unused medicine must be discarded after withdrawal of the dose. 
 

- Do not throw away any medicines via wastewater or household waste. Ask your pharmacist 
how to throw away medicines you no longer use. These measures will help protect the 

environment. 

 

 

6. Contents of the pack and other information 

 

What Ilaris contains 

 The active substance is canakinumab. One vial contains 150 mg canakinumab in 1 ml of 
solution. 

 The other ingredients are mannitol, histidine, histidine hydrochloride monohydrate, polysorbate 
80, water for injections. 

 

What Ilaris looks like and contents of the pack 

 Ilaris is supplied as a solution for injection in a 2 ml glass vial. 

 The solution is a clear to opalescent liquid. It is colourless to slightly brownish-yellow. Do not 
use if the liquid contains easily visible particles, is cloudy or is distinctly brown. 

 Ilaris is available in packs containing one vial. 
 

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


89 

Marketing Authorisation Holder 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

Manufacturer 

Novartis Pharma GmbH 

Roonstrasse 25 

D-90429 Nuremberg 

Germany 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 
SIA Novartis Baltics Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел.: +359 2 489 98 28 

 

Luxembourg/Luxemburg 
Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Česká republika 
Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

Danmark 
Novartis Healthcare A/S 

Tlf: +45 39 16 84 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Deutschland 
Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 
Novartis Pharma B.V. 

Tel: +31 88 04 52 111 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 
Novartis Norge AS 

Tlf: +47 23 05 20 00 

Ελλάδα 
Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 
Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

Novartis Farmacéutica, S.A. 

Tel: +34 93 306 42 00 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

France 

Novartis Pharma S.A.S. 

Tél: +33 1 55 47 66 00 

 

Portugal 
Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

România 

Novartis Pharma Services Romania SRL 

Tel: +40 21 31299 01 



90 

Ireland 
Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 
Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 
Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 
Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Novartis Sverige AB 

Tel: +46 8 732 32 00 

 

Latvija 

SIA Novartis Baltics 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

 

This leaflet was last revised in 
 

 

Other sources of information 

Detailed information on this medicine is available on the European Medicines Agency website: 

http://www.ema.europa.eu 

 



91 

Instructions for use of Ilaris solution for injection 

 

Read all the way through these instructions before injecting. 

- It is important not to try to inject yourself until you have been trained by your healthcare 
professional. 

- See also section 3, “Injecting Ilaris yourself or injecting a patient with Ilaris”. 
 

Essential preparation 

 Find a clean place in which to prepare and give yourself the injection. 

 Wash your hands with soap and water, then dry them on a clean towel. 

 After removing the vial from the refrigerator, check the expiry date on the vial. Do not use after 
the expiry date which is stated on the label and carton. The expiry date refers to the last day of 

that month. 

 Let the vial stand unopened for 10 minutes to bring the contents to room temperature. Do not try 
to heat the vial. Let it warm up on its own. 

 Always use new, unopened needles and syringes. Do not touch the needles or the top of the vial. 
 

Gather together the necessary items 

Included in the pack 

- one vial of Ilaris solution for injection (keep refrigerated) 
 

Not included in the pack 

 one 1.0 ml syringe 

 one needle (such as 18 G or 21 G x 2 inch or similar, as available on the market) to draw up the 
solution from the vial (“withdrawal needle”). 

 one 27 G x 0.5 inch (or similar, as available on the market) needle for injecting (“injection 
needle”) 

 alcohol swabs 

 clean, dry cotton swabs 

 an adhesive plaster 

 a proper disposal container for used needles, syringe and vial (sharps container) 
 

 

Preparing the injection 

 

 

1. Take off the protective cap from the Ilaris vial. Do 
not touch the vial stopper. Clean the rubber stopper 

of the vial with an alcohol swab. 

 

Open the wrappers containing the syringe and the 

withdrawal needle. 

- Put the withdrawal needle on the syringe. 
- Take off the cap from the withdrawal needle. 
- Push the withdrawal needle into the vial of 

Ilaris solution through the centre of the rubber 

stopper. 



92 

 

2. Tip the vial to ensure that the required amount of 
solution can be drawn into the syringe. 

NOTE: The required amount depends on the dose 

to be administered. Your healthcare provider will 

instruct you on the right amount for you. 

3. Slowly pull the syringe plunger up to the correct 
mark (amount to be given as per healthcare 

provider’s instructions), filling the syringe with 

Ilaris solution. If there are air bubbles in the 

syringe, remove bubbles as instructed by your 

healthcare provider. Ensure that the correct amount 

of solution is in the syringe. 

4. Remove the syringe and withdrawal needle from 
the vial. (There may be solution remaining in the 

vial.) Recap the withdrawal needle as instructed by 

your healthcare provider or pharmacist. Remove 

the withdrawal needle from the syringe and place it 

in the sharps container. 

5. Open the wrapper containing the injection needle 
and attach the needle to the syringe. Immediately 

proceed to administering the injection. 

 

 

Giving the injection 

 

 

6. Choose an injection site on the upper thigh, 
abdomen, upper arm or buttocks. Do not use an 

area that has a rash or broken skin, or is bruised or 

lumpy. Do not inject into scar tissue as this may 

mean you do not get all of your medicine. Avoid 

injecting into a vein. 

7. Clean the injection site with a new alcohol swab. 
Allow the area to dry. Uncap the injection needle. 

8. Gently pinch the skin up at the injection site. Hold 
the syringe at a 90-degree angle and in a single, 

smooth motion, push the needle straight down 

completely into the skin. 

 

9. Keep the needle all the way in the skin while 
slowly pushing the syringe plunger down until the 

barrel is empty. Release the pinched skin and pull 

the needle straight out. Dispose of the needle and 

syringe in the sharps container without recapping 

or removing the needle. 

 

 



93 

After the injection 

 

 

10. Do not rub the injection area. If bleeding occurs, 
apply a clean, dry cotton swab over the area, and 

press gently for 1 to 2 minutes, or until bleeding 

stops. Then apply an adhesive plaster. 

 

 

11. Safely dispose of needles and syringe in the sharps 
container or as directed by your healthcare provider 

or pharmacist. Never re-use syringes or needles. 

12. Properly dispose of vials containing remaining 
Ilaris solution (if any) as directed by your 

healthcare provider or pharmacist. Any unused 

product or waste material should be disposed of in 

accordance with local requirements. Never re-use 

the leftover solution. 

 

Keep the sharps container out of reach of children. 

 

Dispose of it as directed by your healthcare provider or 

pharmacist. 

 


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