Kineret

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Kineret 100 mg/0.67 ml solution for injection in pre-filled syringe. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each graduated pre-filled syringe contains 100 mg of anakinra* per 0.67 ml (150 mg/ml). 
 
* Human interleukin-1 receptor antagonist (r-metHuIL-1ra) produced in Escherichia coli cells by 
recombinant DNA technology. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection (injection). 
 
Clear, colourless-to-white solution for injection that may contain some product-related translucent-
to-white amorphous particles. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Rheumatoid Arthritis (RA) 
Kineret is indicated in adults for the treatment of the signs and symptoms of RA in combination with 
methotrexate, with an inadequate response to methotrexate alone. 
 
Periodic fever syndromes 
Kineret is indicated for the treatment of the following autoinflammatory periodic fever syndromes in 
adults, adolescents, children and infants aged 8 months and older with a body weight of 10 kg or 
above: 
 
Cryopyrin-Associated Periodic Syndromes (CAPS) 
Kineret is indicated for the treatment of CAPS, including: 
- Neonatal-Onset Multisystem Inflammatory Disease (NOMID) / Chronic Infantile Neurological, 

Cutaneous, Articular Syndrome (CINCA) 
- Muckle-Wells Syndrome (MWS) 
- Familial Cold Autoinflammatory Syndrome (FCAS) 
 
Familial Mediterranean Fever (FMF) 
Kineret is indicated for the treatment of Familial Mediterranean Fever (FMF). Kineret should be given 
in combination with colchicine, if appropriate. 
 
Still’s Disease 
Kineret is indicated in adults, adolescents, children and infants aged 8 months and older with a body 
weight of 10 kg or above for the treatment of Still’s disease, including Systemic Juvenile Idiopathic 
Arthritis (SJIA) and Adult-Onset Still’s Disease (AOSD), with active systemic features of moderate to 
high disease activity, or in patients with continued disease activity after treatment with non-steroidal 
anti-inflammatory drugs (NSAIDs) or glucocorticoids. 
 
Kineret can be given as monotherapy or in combination with other anti-inflammatory drugs and 
disease-modifying antirheumatic drugs (DMARDs). 
 



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4.2 Posology and method of administration 
 
Kineret treatment should be initiated and supervised by specialist physicians experienced in the 
diagnosis and treatment of RA, CAPS, FMF and Still’s disease, respectively. 
 
Posology 
 
RA: Adults 
The recommended dose of Kineret is 100 mg administered once a day by subcutaneous injection. The 
dose should be administered at approximately the same time each day. 
 
CAPS: Adults, adolescents, children and infants aged 8 months and older with a body weight of 10 kg 
or above 
 
Starting dose 
The recommended starting dose in all CAPS subtypes is 1-2 mg/kg/day by subcutaneous injection. 
The therapeutic response is primarily reflected by reduction in clinical symptoms such as fever, rash, 
joint pain, and headache, but also in inflammatory serum markers (CRP/SAA levels), or occurrence of 
flares. 
 
Maintenance dose in mild CAPS (FCAS, mild MWS) 
Patients are usually well-controlled by maintaining the recommended starting dose (1-2 mg/kg/day). 
 
Maintenance dose in severe CAPS (MWS and NOMID/CINCA) 
Dose increases may become necessary within 1-2 months based on therapeutic response. The usual 
maintenance dose in severe CAPS is 3-4 mg/kg/day, which can be adjusted to a maximum of 
8 mg/kg/day. 
 
In addition to the evaluation of clinical symptoms and inflammatory markers in severe CAPS, 
assessments of inflammation of the CNS, including the inner ear (MRI or CT, lumbar puncture, and 
audiology) and eyes (ophthalmological assessments) are recommended after an initial 3 months of 
treatment, and thereafter every 6 months, until effective treatment doses have been identified. When 
patients are clinically well-controlled, CNS and ophthalmological monitoring may be conducted 
yearly. 
 
FMF 
The recommended dose for patients weighing 50 kg or more is 100 mg/day by subcutaneous injection. 
Patients weighing less than 50 kg should be dosed by body weight with a recommended dose of 1-
2 mg/kg/day. 
 
Still’s disease 
The recommended dose for patients weighing 50 kg or more is 100 mg/ day by subcutaneous injection. 
Patients weighing less than 50 kg should be dosed by body weight with a starting dose of 
1-2 mg/kg/day. 
 
Response to treatment should be evaluated after 1 month: In case of persistent systemic manifestations 
dose may be adjusted in children or continued treatment with Kineret should be reconsidered by the 
treating physician. 
 
Elderly population (≥ 65 years) 
RA: No dose adjustment is required. Posology and administration are the same as for adults 18 to 
64 years of age. 
 
CAPS: Data in elderly patients are limited. No dose adjustments are expected to be required. 
 
Still’s disease: Data in elderly patients are limited. No dose adjustment are expected to be required. 
 



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Paediatric population (< 18 years) 
No data are available in children under the age of 8 months. 
 
RA: The efficacy of Kineret in children with RA (JIA) aged 0 to 18 years has not been established. 
 
CAPS: Posology and administration in children and infants aged 8 months and older with a body 
weight of 10 kg or above are the same as for adult CAPS patients, based on body weight. 
 
FMF: Children weighing less than 50 kg are dosed by body weight with a recommended dose of 
1-2 mg/kg/day, patients weighing 50 kg or more are dosed with 100 mg/day. In children with 
inadequate response the dose can be escalated up to 4 mg/kg/day. 
 
The efficacy data of Kineret in children under 2 years of age with FMF are limited. 
 
Still’s disease: Children weighing less than 50 kg are dosed by body weight with a starting dose of 
1-2 mg/kg/day, patients weighing 50 kg or more are dosed with 100 mg/day. In children with 
inadequate response the dose can be escalated up to 4 mg/kg/day. 
 
Hepatic impairment 
No dose adjustment is required for patients with moderate hepatic impairment (Child-Pugh Class B). 
Kineret should be used with caution in patients with severe hepatic impairment. 
 
Renal impairment 
No dose adjustment is needed for patients with mild renal impairment (CLcr 60 to 89 ml/min). Kineret 
should be used with caution in patients with moderate renal impairment (CLcr 30 to 59 ml/min). In 
patients with severe renal impairment (CLcr < 30 ml/min) or end stage renal disease, including 
dialysis, administration of the prescribed dose of Kineret every other day should be considered. 
 
Method of administration 
Kineret is administered by subcutaneous injection. 
 
Kineret is supplied ready for use in a graduated pre-filled syringe. The graduated pre-filled syringe 
allows for doses between 20 and 100 mg. As the minimum dose is 20 mg the syringe is not suitable for 
paediatric patients with a body weight below 10 kg. The pre-filled syringe should not be shaken. The 
instructions for use and handling are given in section 6.6. 
 
Alternating the injection site is recommended to avoid discomfort at the site of injection. Cooling of 
the injection site, warming the injection liquid to room temperature, use of cold packs (before and after 
the injection), and use of topical glucocorticoids and antihistamines after the injection can alleviate the 
signs and symptoms of injection site reactions. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to to any of the excipients listed in section 6.1 or to E. coli 
derived proteins. 
 
Kineret treatment must not be initiated in patients with neutropenia (ANC <1.5 x 109/l) (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. 
 



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Allergic reactions 
Allergic reactions, including anaphylactic reactions and angioedema have been reported uncommonly. 
The majority of these reactions were maculopapular or urticarial rashes. 
 
If a severe allergic reaction occurs, administration of Kineret should be discontinued and appropriate 
treatment initiated. 
 
Hepatic Events 
In clinical studies transient elevations of liver enzymes have been seen. These elevations have not 
been associated with signs or symptoms of hepatocellular damage, except for one patient with SJIA 
that developed a serious hepatitis in connection with a cytomegalovirus infection. 
 
During post-marketing use hepatic events, not affecting liver function, have been reported. The 
majority of patients have been treated for Still’s disease or have had predisposing factors, e.g. a history 
of transaminase elevations. In addition cases of non-infectious hepatitis, including occasional events of 
acute liver failure, have been reported in patients with Still’s disease during Kineret treatment. 
 
Hepatic events in patients with Still’s disease predominantly occur during the first month of Kineret 
treatment. Routine testing of hepatic enzymes during the first month should be considered, especially 
if the patient has pre-disposing factors or develops symptoms indicating liver dysfunction. 
The efficacy and safety of Kineret in patients with AST/ALT ≥ 1.5 x upper level of normal have not 
been evaluated. 
 
Serious infections 
Kineret has been associated with an increased incidence of serious infections (1.8%) vs. placebo 
(0.7%) in RA patients. For a small number of patients with asthma, the incidence of serious infection 
was higher in Kineret-treated patients (4.5%) vs. placebo-treated patients (0%), these infections were 
mainly related to the respiratory tract. 
 
The safety and efficacy of Kineret treatment in patients with chronic and serious infections have not 
been evaluated. 
 
Kineret treatment should not be initiated in patients with active infections. Kineret treatment should be 
discontinued in RA patients if a serious infection develops. In Kineret treated CAPS or FMF patients, 
there is a risk for disease flares when discontinuing Kineret treatment. With careful monitoring, 
Kineret treatment can be continued also during a serious infection. 
 
Macrophage activation syndrome (MAS) is a known, life-threatening disorder that may develop in 
patients with Still’s disease. If MAS occurs, or is suspected, evaluation and appropriate 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. Available data is limited regarding 
whether Kineret can be continued during serious infections in patients with Still’s disease. If Kineret 
treatment is continued during serious infections to reduce the risk for a disease flare, careful 
monitoring is required. 
 
During post-marketing use case reports of MAS in Kineret treated patients with Still’s disease have 
been received. Patients with Still’s disease have an increased risk of spontaneous development of 
MAS. A causal relationship between Kineret and MAS has not been established. 
 
Physicians should exercise caution when administering Kineret to patients with a history of recurring 
infections or with underlying conditions which may predispose them to infections. 
 
The safety of Kineret in individuals with latent tuberculosis is unknown. There have been reports of 
tuberculosis in patients receiving several biological anti-inflammatory treatment regimens. Patients 
should be screened for latent tuberculosis prior to initiating Kineret. The available medical guidelines 
should also be taken into account. 
 



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Other anti-rheumatic therapies have been associated with hepatitis B reactivation. Therefore, screening 
for viral hepatitis should be performed in accordance with published guidelines also before starting 
therapy with Kineret. 
 
Renal impairment 
Kineret is eliminated by glomerular filtration and subsequent tubular metabolism. Consequently 
plasma clearance of Kineret decreases with decreasing renal function. 
 
No dose adjustment is needed for patients with mild renal impairment (CLcr 60 to 89 ml/min). Kineret 
should be used with caution in patients with moderate renal impairment (CLcr 30 to 59 ml/min). In 
patients with severe renal impairment (CLcr <30 ml/min) or end stage renal disease, including 
dialysis, administration of the prescribed dose of Kineret every other day should be considered. 
 
Neutropenia 
Kineret was commonly associated with neutropenia (ANC < 1.5 x 109/l) in placebo-controlled studies 
in RA and cases of neutropenia have been observed in patients with CAPS and Still’s disease. For 
more information on neutropenia see section 4.8. 
 
Kineret treatment should not be initiated in patients with neutropenia (ANC < 1.5 x 109/l). It is 
recommended that neutrophil counts be assessed prior to initiating Kineret treatment, and while 
receiving Kineret, monthly during the first 6 months of treatment and quarterly hereafter. In patients 
who become neutropenic (ANC < 1.5 x 109/l) the ANC should be monitored closely and Kineret 
treatment should be discontinued. The safety and efficacy of Kineret in patients with neutropenia have 
not been evaluated. 
 
Pulmonary Events 
During post-marketing use events of interstitial lung disease, pulmonary alveolar proteinosis and 
pulmonary hypertension have been reported mainly in paediatric patients with Still’s disease treated 
with IL-6 and IL-1 inhibitors, including Kineret. Patients with trisomy 21 seem to be overrepresented. 
A causal relationship with Kineret has not been established. 
 
Immunosuppression 
The impact of treatment with Kineret on pre-existing malignancy has not been studied. Therefore the 
use of Kineret in patients with pre-existing malignancy is not recommended. 
 
Malignancies 
RA patients may be at a higher risk (on average 2-3 fold) for the development of lymphoma. In 
clinical trials, whilst patients treated with Kineret had a higher incidence of lymphoma than the 
expected rate in the general population, this rate is consistent with rates reported in general for RA 
patients. 
 
In clinical trials, the crude incidence rate of malignancy was the same in the Kineret-treated patients 
and the placebo-treated patients and did not differ from that in the general population. Furthermore, 
the overall incidence of malignancies was not increased during 3 years of patient exposure to Kineret. 
 
Vaccinations 
In a placebo-controlled clinical trial (n = 126), no difference was detected in anti-tetanus antibody 
response between the Kineret and placebo treatment groups when a tetanus/diphtheria toxoid vaccine 
was administered concurrently with Kineret. No data are available on the effects of vaccination with 
other inactivated antigens in patients receiving Kineret. 
 
No data are available on either the effects of live vaccination or on the secondary transmission of 
infection by live vaccines in patients receiving Kineret. Therefore, live vaccines should not be given 
concurrently with Kineret. 
 



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Elderly population (≥ 65 years) 
A total of 752 RA patients ≥ 65 years of age, including 163 patients ≥ 75 years of age, were studied in 
clinical trials. No overall differences in safety or effectiveness were observed between these patients 
and younger patients. There is limited experience in treating elderly CAPS, FMF and Still’s disease 
patients. Because there is a higher incidence of infections in the elderly population in general, caution 
should be used in treating elderly patients. 
 
Concurrent Kineret and TNF-α antagonist treatment 
Concurrent administration of Kineret and etanercept has been associated with an increased risk of 
serious infections and neutropenia compared to etanercept alone in RA patients. This treatment 
combination has not demonstrated increased clinical benefit. 
 
The concurrent administration of Kineret and etanercept or other TNF-α antagonists is not 
recommended (see section 4.5). 
 
Sodium content 
This medicinal product contains less than 1 mmol sodium (23 mg) per 100 mg dose, that is to say 
essentially ‘sodium-free’. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Interactions between Kineret and other medicinal products have not been investigated in formal 
studies. In clinical trials, interactions between Kineret and other medicinal products (including 
nonsteroidal anti-inflammatory medicinal products, glucocorticoids, and DMARDs) have not been 
observed. 
 
Concurrent Kineret and TNF-α antagonist treatment 
In a clinical trial with RA patients receiving background methotrexate, patients treated with Kineret 
and etanercept were observed to have a higher rate of serious infections (7%) and neutropenia than 
patients treated with etanercept alone and higher than observed in previous trials where Kineret was 
used alone. Concurrent Kineret and etanercept treatment has not demonstrated increased clinical 
benefit. 
 
The concurrent use of Kineret with etanercept or any other TNF-α antagonist is not recommended (see 
section 4.4). 
 
Cytochrome P450 Substrates 
The formation of CYP450 enzymes is suppressed by increased levels of cytokines (e.g., IL-1) during 
chronic inflammation. Thus, it may be expected that for an IL-1 receptor antagonist, such as anakinra, 
the formation of CYP450 enzymes could be normalized during treatment. This would be clinically 
relevant for CYP450 substrates with a narrow therapeutic index (e.g. warfarin and phenytoin). Upon 
start or end of Kineret treatment in patients on these types of medicinal products, it may be relevant to 
consider therapeutic monitoring of the effect or concentration of these products and the individual 
dose of the medicinal product may need to be adjusted. 
 
For information on vaccinations see section 4.4. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
There are limited amount of data from the use of anakinra in pregnant women. Animal studies do not 
indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a 
precautionary measure, it is preferable to avoid the use of anakinra during pregnancy and in woman of 
childbearing potential not using contraception. 
 



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Breast-feeding 
It is unknown whether anakinra/metabolites are excreted in human milk. A risk to the newborns/ 
infants cannot be excluded. Breast-feeding should be discontinued during treatment with Kineret. 
 
4.7 Effects on ability to drive and use machines 
 
Not relevant. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
In placebo-controlled studies in RA patients, the most frequently reported adverse reactions with 
Kineret were injection site reactions (ISRs), which were mild to moderate in the majority of patients. 
The most common reason for withdrawal from study in Kineret-treated RA patients was injection site 
reaction. The subject incidence of serious adverse reactions in RA studies at the recommended dose of 
Kineret (100 mg/day) was comparable with placebo (7.1% compared with 6.5% in the placebo group). 
The incidence of serious infection was higher in Kineret-treated patients compared to patients 
receiving placebo (1.8% vs. 0.7%). Neutrophil decreases occurred more frequently in patients 
receiving Kineret compared with placebo.  
 
Adverse reactions data in CAPS patients are based on an open-label study of 43 patients with 
NOMID/CINCA treated with Kineret for up to 5 years, with a total Kineret exposure of 159.8 patient 
years. During the 5-year study 14 patients (32.6%) reported 24 serious events. Eleven serious events in 
4 (9.3%) patients were considered related to Kineret. No patient withdrew from Kineret treatment due 
to adverse reactions.  
 
Adverse events data in patients with Still's disease is based on a partially open-label and partially 
blinded, placebo-controlled study of 15 SJIA patients, treated for up to 1.5 years. In addition, post-
marketing adverse event reports and published studies constitute supporting data. 
 
Adverse events data in patients with FMF are based on post-marketing adverse event reports and 
published studies. 
 
There are no indications either from these studies or from post-marketing adverse reaction reports that 
the overall safety profile in patients with CAPS, FMF or Still’s disease is different from that in 
patients with RA, with the exception of the risk for development of MAS in patients with Still’s 
disease. The adverse reactions table below therefore applies to Kineret treatment of RA, CAPS, FMF 
and Still’s disease.  
 
Tabulated list of adverse reactions 
Adverse reactions are listed according to MedDRA system organ class and frequency category. 
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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MedDRA Organ System Frequency Undesirable Effect 
Infections and infestations Common (≥ 1/100 to < 1/10) Serious infections 
Blood and lymphatic system 
disorders 

Common (≥ 1/100 to < 1/10) Neutropenia 
Thrombocytopenia 

Immune system disorders Uncommon (≥ 1/1,000 to < 1/100) Allergic reactions including 
anaphylactic reactions, 
angioedema, urticaria and 
pruritus 

Nervous system disorders Very common (≥ 1/10) Headache  
Hepatobiliary disorders Uncommon (≥ 1/1,000 to < 1/100) Hepatic enzyme increased 

Not known 
(cannot be estimated from the 
available data) 

Non-infectious hepatitis 

Skin and subcutaneous tissue 
disorders 

Very common (≥ 1/10) Injection site reaction 
Uncommon (≥ 1/1,000 to < 1/100) Rash  

Investigations Very common (≥ 1/10) Blood cholesterol increased 
 
Serious infections 
The incidence of serious infections in RA studies conducted at the recommended dose (100 mg/day) 
was 1.8% in Kineret treated patients and 0.7% in placebo-treated patients. In observations up to 
3 years, the serious infection rate remained stable over time. The infections observed consisted 
primarily of bacterial events such as cellulitis, pneumonia, and bone and joint infections. Most patients 
continued on study medicinal product after the infection resolved. 
 
In 43 CAPS patients followed for up to 5 years the frequency of serious infections was 0.1/year, the 
most common being pneumonia and gastroenteritis. Kineret was temporarily stopped in one patient, 
all other patients continued Kineret treatment during the infections. 
 
In 15 SJIA patients followed for up to 1.5 years, one patient developed a serious hepatitis in 
connection with a cytomegalovirus infection. There are no indications from post-marketing experience 
that types and severity of infections in patients with Still’s disease differ from those in RA or CAPS 
patients. 
 
In clinical studies and during post-marketing use, rare cases of opportunistic infections have been 
observed and have included fungal, mycobacterial, bacterial, and viral pathogens. Infections have been 
noted in all organ systems and have been reported in patients receiving Kineret alone or in 
combination with immunosuppressive agents. 
 
Neutropenia 
In placebo-controlled RA studies with Kineret, treatment was associated with small reductions in the 
mean values for total white blood count and absolute neutrophil count (ANC). Neutropenia 
(ANC < 1.5 x 109/l) was reported in 2.4% patients receiving Kineret compared with 0.4% of placebo 
patients. None of these patients had serious infections associated with the neutropenia. 
 
In 43 CAPS patients followed for up to 5 years neutropenia was reported in 2 patients. Both episodes 
of neutropenia resolved over time with continued Kineret treatment. 
 
In 15 SJIA patients followed for up to 1.5 years, one event of transient neutropenia was reported. 
 
Thrombocytopenia 
In clinical studies in RA patients, thrombocytopenia has been reported in 1.9% of treated patients 
compared to 0.3% in the placebo group. The thrombocytopenias have been mild, i.e. platelet counts 
have been > 75 x109/l. Mild thrombocytopenia has also been observed in CAPS patients. 
 
During post-marketing use of Kineret, thrombocytopenia has been reported, including occasional case 
reports indicating severe thrombocytopenia (i.e. platelet counts <10 x109/l). 



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Allergic reactions 
Allergic reactions including anaphylactic reactions, angioedema, urticaria, rash, and pruritus have 
been reported uncommonly with Kineret. The majority of these reactions were maculopapular or 
urticarial rashes. 
 
In 43 CAPS patients followed for up to 5 years, no allergic event was serious and no event required 
discontinuation of Kineret treatment. 
 
In 15 SJIA patients followed for up to 1.5 years, no allergic event was serious and no event required 
discontinuation of Kineret. 
 
In 12 FMF patients treated 4 months with Kineret in a published randomized controlled study no 
allergic event was reported as serious and no event required discontinuation of Kineret. 
 
Immunogenicity 
In clinical trials in RA, up to 3% of adult patients tested seropositive at least once during the study for 
neutralizing anti-anakinra antibodies. The occurrence of antibodies was typically transient and not 
associated with clinical adverse reactions or diminished efficacy. In addition, in a clinical trial 6% of 
86 paediatric patients with JIA, whereof none of the 15 SJIA subtype patients, tested seropositive at 
least once during the study for neutralizing anti-anakinra antibodies. 
 
The majority of CAPS patients in Study 03-AR-0298 developed anakinra anti-drug antibodies. This 
was not associated with any clinically significant effects on pharmacokinetics, efficacy, or safety. 
 
Hepatic Events 
In clinical studies transient elevations of liver enzymes have been seen. These elevations have not 
been associated with signs or symptoms of hepatocellular damage, except for one patient with SJIA 
that developed serious hepatitis in connection with a cytomegalovirus infection. 
 
During post-marketing use isolated case reports indicating non-infectious hepatitis have been received. 
Hepatic events during post-marketing use have mainly been reported in patients that have been treated 
for Still’s disease and in patients with predisposing factors, e.g. a history of transaminase elevations 
before start of Kineret treatment. 
 
Injection site reactions 
ISRs typically appear within 2 weeks of therapy and disappear within 4-6 weeks. The development of 
ISRs in patients who had not previously experienced ISRs was uncommon after the first month of 
therapy. 
 
In RA patients the most common and consistently reported treatment-related adverse reactions 
associated with Kineret were ISRs. The majority (95%) of ISRs were reported as mild to moderate. 
These were typically characterised by 1 or more of the following: erythaema, ecchymosis, 
inflammation, and pain. At a dose of 100 mg/day, 71% of RA patients developed an ISR compared to 
28% of the placebo treated patients.  
 
In 43 CAPS patients followed for up to 5 years no patient permanently or temporarily discontinued 
Kineret treatment due to injection site reactions. 
 
In 15 SJIA patients followed for up to 1.5 years, the most common and consistently reported 
treatment-related adverse reactions associated with Kineret treatment were ISRs. One out of the 
15 patients discontinued due to ISRs.  
 
In patients with FMF the types and frequencies of ISRs are similar to those seen in RA and SJIA. 
Discontinuations due to ISRs have occurred also in patients with FMF. 
 



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Blood cholesterol increase 
In clinical studies of RA, 775 patients treated with daily Kineret doses of 30 mg, 75 mg, 150 mg, 
1 mg/kg or 2 mg/kg, there was an increase of 2.4% to 5.3% in total cholesterol levels 2 weeks after 
start of Kineret treatment, without a dose-response relationship. A similar pattern was seen after 
24 weeks Kineret treatment. Placebo treatment (n=213) resulted in a decrease of approximately 2.2% 
in total cholesterol levels at week 2 and 2.3% at week 24. No data are available on LDL or HDL 
cholesterol. 
 
Paediatric population 
Kineret has been studied in 36 CAPS patients, 15 SJIA patients and 71 patients with other forms of 
JIA, aged 8 months to <18 years, for up to 5 years. With the exception of infections and related 
symptoms that were more frequently reported in patients <2 years of age, the safety profile was similar 
in all paediatric age groups. The safety profile in paediatric patients was similar to that seen in adult 
populations and no clinically relevant new adverse reactions were seen. 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
No dose-limiting toxicities were observed during clinical studies. 
In studies of sepsis, 1,015 patients received Kineret at doses up to 2 mg/kg/hour i.v. (~35 times the 
recommended dose in RA) over a 72 hour treatment period. The adverse event profile from these 
studies show no overall difference from that seen in the rheumatoid arthritis studies. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Immunosuppressants, Interleukin inhibitors, ATC code: L04AC03 
 
Mechanism of action 
Anakinra neutralises the biologic activity of interleukin-1α (IL-1α) and interleukin-1β (IL-1β) by 
competitively inhibiting their binding to interleukin-1 type I receptor (IL-1RI). Interleukin-1 (IL-1) is 
a pivotal pro-inflammatory cytokine mediating many cellular responses including those important in 
synovial inflammation. 
 
Pharmacodynamic effects 
IL-1 is found in the plasma and synovial fluid of patients with rheumatoid arthritis, and a correlation 
has been reported between IL-1 concentrations in the plasma and the activity of the disease. 
Anakinra inhibits responses elicited by IL-1 in vitro, including the induction of nitric oxide and 
prostaglandin E2 and/or collagenase production by synovial cells, fibroblasts, and chondrocytes. 
 
Spontaneous mutations in the CIAS1/NLRP3 gene have been identified in a majority of patients with 
CAPS. CIAS1/NLRP3 encodes for cryopyrin, a component of the inflammasome. The activated 
inflammasome results in proteolytic maturation and secretion of IL-1β, which has a broad range of 
effects including systemic inflammation. Untreated CAPS patients are characterized by increased 
CRP, SAA and IL-6 relative to normal serum levels. Administration of Kineret results in a decrease in 
the acute phase reactants and a decrease in IL-6 expression level has been observed. Decreased acute 
phase protein levels are noted within the first weeks of treatment. 
 
In patients with FMF, mutation of the MEFV gene encoding for pyrin is leading to malfunctioning and 
overproduction of interleukin-1β (IL-1β) in the FMF inflammasome. Untreated FMF is characterized 

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


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by increased CRP and SAA. Administration of Kineret results in a decrease in acute phase reactants 
(e.g. CRP and SAA). 
 
Still’s disease, in addition to various degrees of arthritis, is characterised by systemic inflammatory 
features such as spiking fever, skin rash, hepatosplenomegaly, serositis, and increased acute phase 
reactants driven by IL-1 activity. Systemically, IL-1 is known to cause the hypothalamic fever 
response and promote hyperalgesia. The role of IL-1 in the pathogenesis of Still’s disease has been 
demonstrated by ex vivo and gene expression studies. 
 
Clinical efficacy and safety in RA 
The safety and efficacy of anakinra in combination with methotrexate have been demonstrated in 
1,790 RA patients ≥ 18 years of age with varying degrees of disease severity. 
 
A clinical response to anakinra generally appeared within 2 weeks of initiation of treatment and was 
sustained with continued administration of anakinra. Maximal clinical response was generally seen 
within 12 weeks after starting treatment. 
 
Combined anakinra and methotrexate treatment demonstrates a statistically and clinically significant 
reduction in the severity of the signs and symptoms of RA in patients who have had an inadequate 
response to methotrexate alone (38% vs. 22% responders as measured by ACR20 criteria). Significant 
improvements are seen in the pain, tender joint count, physical function (HAQ score), acute phase 
reactants and in the patient’s and physician’s global assessment. 
 
X-ray examinations have been undertaken in one clinical study with anakinra. These have shown no 
deleterious effect on joint cartilage. 
 
Clinical efficacy and safety in CAPS 
The safety and efficacy of Kineret have been demonstrated in CAPS patients with varying degrees of 
disease severity. In a clinical study including 43 adult and paediatric patients (36 patients aged 
8 months to < 18 years) with severe CAPS (NOMID/CINCA and MWS), a clinical response to 
anakinra was seen within 10 days after initiation of treatment in all patients and was sustained for up 
to 5 years with the continued administration of Kineret. 
 
Kineret treatment significantly decreases the manifestations of CAPS, including a reduction in 
frequently occurring symptoms as fever, rash, joint pain, headache, fatigue, and eye redness. A rapid 
and sustained decrease in the levels of the inflammatory biomarkers; serum amyloid A (SAA), 
C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and a normalization of 
inflammatory hematological changes are seen. In the severe form of CAPS, long-term treatment 
improves the systemic inflammatory organ manifestations of the eye, inner ear, and CNS. Hearing and 
visual acuity did not deteriorate further during anakinra treatment. 
 
Analysis of treatment-emergent AEs classified by presence of CIAS1 mutation showed that there were 
no major differences between the CIAS1 and non-CIAS1 groups in overall AE reporting rates, 7.4 and 
9.2, respectively. Similar rates were obtained for the groups on the SOC level, except for eye disorders 
with 55 AEs (rate 0.5), whereof 35 ocular hyperemia (which could also be a symptom of CAPS) in the 
CIAS1 group, and 4 AEs in the non-CIAS1 group (rate 0.1). 
 
Clinical efficacy and safety in FMF 
The safety and efficacy of Kineret in the treatment of patients with colchicine resistant FMF has been 
demonstrated in a randomized, double-blind, and placebo-controlled published study with a treatment 
period of 4 months. Primary efficacy outcomes were number of attacks per month, and number of 
patients with a mean of <1 attack per month. 25 patients with colchicine resistant FMF were enrolled; 
12 randomized to receive Kineret and 13 to receive placebo. The mean number of attacks per patient 
per month was significantly lower in those receiving Kineret (1.7) compared to placebo (3.5). The 
number of patients with <1 attack per month was significantly higher in the Kineret group; 6 patients, 
compared to none in the placebo group. 
 



13 

Additional published data in patients with FMF, intolerant to colchicine or with colchicine resistant 
FMF, demonstrate that the clinical effect of Kineret is evident in both clinical symptoms of attacks as 
well as in reduced levels of inflammatory markers, such as CRP and SAA. In the published studies the 
safety profile of anakinra in patients with FMF was generally similar to that in other indications. 
 
Clinical efficacy and safety in Still’s disease 
The safety and efficacy have been demonstrated in a published randomized controlled study in 
24 SJIA patients treated with Kineret for up to 1 year. After a 1-month blinded phase, 8 of 12 patients 
in the Kineret treated group were identified as modified ACRpedi30 responders compared to 1 of 12 in 
the placebo group. At the same time point, 7 of 12 in the Kineret treated group were classified as 
ACRpedi50 and 5 of 12 as ACRpedi70 responders compared to none in the placebo group. 16 patients 
completed the subsequent open label phase and among 7 responders at month 12, 6 had stopped 
glucocorticoid treatment and 5 of them had inactive disease. 
 
In a published prospective, uncontrolled, observational cohort study of 20 patients with new-onset 
SJIA Kineret was used as initial therapy after failure to respond to NSAIDs, but before the use of 
DMARDs, systemic glucocorticoids, or other biologic agents. Treatment with Kineret resulted in 
normalization of body temperature in 18 of 20 patients. At 1 year follow-up, 18 of 20 patients showed 
at least an adapted ACRpedi 70 response, and 17 of 20 patients reached an adapted ACRpedi 90 
response as well as inactive disease. 
 
The safety and efficacy of Kineret versus DMARD have been reported in a published 24-week 
multicenter, randomized, open-label study of 22 patients with glucocorticoid-dependent refractory 
AOSD. At Week 24, 6 of 12 patients on anakinra were in remission versus 2 of 10 patients on 
DMARDs. During an open-label extension phase, switching or add-on treatment with the comparator 
drug was possible if improvement did not occur within 24 weeks. 17 patients completed the open-label 
extension phase (Week 52), of which 7 of 14 Kineret-treated patients, and 2 of 3 patients on 
DMARDs, were in remission at that time point. 
 
Additional published data in Still’s disease indicate that Kineret induces a rapid resolution of systemic 
features such as fever, rash, and elevation of acute phase reactants. Glucocorticoid doses can in many 
cases be reduced after initiation of Kineret therapy. 
 
Paediatric population 
Overall, the efficacy and safety profile of Kineret is comparable in adult and paediatric patients with 
CAPS or Still’s disease. 
 
The European Medicines Agency has waived the obligation to submit the results of studies with 
Kineret in one or more subsets of the paediatric population in CAPS and RA (JIA) (see section 4.2 for 
information on paediatric use). 
 
Safety in paediatric RA (JIA) patients 
Kineret was studied in a single randomized, blinded multi-center trial in 86 patients with polyarticular 
course JIA (ages 2-17 years) receiving a dose of 1 mg/kg subcutaneously daily, up to a maximum dose 
of 100 mg. The 50 patients who achieved a clinical response after a 12-week open-label run-in were 
randomized to Kineret (25 patients) or placebo (25 patients), administered daily for an additional 
16 weeks. A subset of these patients continued open-label treatment with Kineret for up to 1 year in a 
companion extension study. An adverse event profile similar to that seen in adult RA patients was 
observed in these studies. These study data are insufficient to demonstrate efficacy and, therefore, 
Kineret is not recommended for paediatric use in JIA. 
 
Immunogenicity 
See section 4.8. 
 



14 

5.2 Pharmacokinetic properties 
 
The absolute bioavailability of anakinra after a 70 mg subcutaneous bolus injection in healthy subjects 
(n = 11) is 95%. The absorption process is the rate-limiting factor for the disappearance of anakinra 
from the plasma after subcutaneous injection. In subjects with RA, maximum plasma concentrations 
of anakinra occurred at 3 to 7 hours after subcutaneous administration of anakinra at clinically relevant 
doses (1 to 2 mg/kg; n = 18). The plasma concentration decreased with no discernible distribution 
phase and the terminal half-life ranged from 4 to 6 hours. In RA patients, no unexpected accumulation 
of anakinra was observed after daily subcutaneous doses for up to 24 weeks. Mean (SD) estimates of 
clearance (CL/F) and volume of distribution (Vd/F) by population analysis of data from two PK 
studies in 35 RA patients were 105(27) ml/min and 18.5(11) l, respectively. Human and animal data 
demonstrated that the kidney is the major organ responsible for elimination of anakinra. The clearance 
of anakinra in RA patients increased with increasing creatinine clearance. 
 
The influence of demographic covariates on the pharmacokinetics of anakinra was studied using 
population pharmacokinetic analysis encompassing 341 patients receiving daily subcutaneous 
injection of anakinra at doses of 30, 75, and 150 mg for up to 24 weeks. The estimated anakinra 
clearance increased with increasing creatinine clearance and body weight. Population pharmacokinetic 
analysis demonstrated that the mean plasma clearance value after subcutaneous bolus administration 
was approximately 14% higher in men than in women and approximately 10% higher in subjects 
< 65 years than in subjects ≥ 65 years. However, after adjusting for creatinine clearance and body 
weight, gender and age were not significant factors for mean plasma clearance. No dose adjustment is 
required based on age or gender. 
 
In general the pharmacokinetics in CAPS patients is similar to that in RA patients. In CAPS patients 
approximate dose linearity with a slight tendency to higher than proportional increase has been noted. 
Pharmacokinetic data in children < 4 years are lacking, but clinical experience is available from 8 
months of age, and when started at the recommended daily dose of 1-2 mg/kg, no safety concerns have 
been identified. Pharmacokinetic data are lacking in older CAPS patients. Distribution into the 
cerebrospinal fluid has been demonstrated. 
 
The median steady-state dose-normalized anakinra concentration in SJIA patients over 28 weeks was 
comparable to that observed in RA patients.  
 
Hepatic impairment 
A study including 12 patients with hepatic dysfunction (Child-Pugh Class B) given a single 1mg/kg 
intravenous dose has been performed. Pharmacokinetic parameters were not substantially different 
from healthy volunteers, other than a decrease in clearance of approximately 30% in comparison with 
data from a study with healthy volunteers. A corresponding decrease in creatinine clearance was seen 
in the hepatic failure population. Accordingly, the decrease in clearance is most likely explained by a 
decrease in renal function in this population. These data support that no dose adjustment is required 
for patients with hepatic dysfunction of Child-Pugh Class B. See section 4.2. 
 
Renal impairment 
The mean plasma clearance of Kineret in subjects with mild (creatinine clearance 50-80 ml / min) and 
moderate (creatinine clearance 30-49 ml/min) renal insufficiency was reduced by 16% and 50%, 
respectively. In severe renal insufficiency and end stage renal disease (creatinine clearance 
< 30 ml/min), mean plasma clearance declined by 70% and 75%, respectively. Less than 2.5% of the 
administered dose of Kineret was removed by hemodialysis or continuous ambulatory peritoneal 
dialysis. These data support that no dose adjustment is needed for patients with mild renal impairment 
(CLcr 50 to 80 ml/minute). See section 4.2. 
 
5.3 Preclinical safety data 
 
Anakinra had no observed effect on the fertility, early development, embryo-foetal development, or 
peri- and postnatal development in the rat at doses up to 100 times the human dose (2 mg/kg/day). No 
effects on embryo-foetal development in the rabbit were observed at doses 100 times the human dose. 



15 

 
In a standard battery of tests designed to identify hazards with respect to DNA, anakinra did not 
induce bacterial or mammalian cell gene mutations. Neither did anakinra increase the incidence of 
chromosomal abnormalities or micronuclei in bone marrow cells in mice. Long-term studies have not 
been performed to evaluate the carcinogenic potential of anakinra. Data from mice over expressing 
IL-1ra and IL-1ra mutant knock-out mice, did not indicate an increased risk of tumour development. 
 
A formal toxicologic and toxicokinetic interaction study in rats revealed no evidence that Kineret 
alters the toxicologic or pharmacokinetic profile of methotrexate. 
 
Juvenile rats treated at doses up to 100 times the human dose from day 7 postparturition up to 
adolescence did not show any signs of adverse effects of the treatment. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Citric acid, anhydrous 
Sodium chloride 
Disodium edetate dihydrate 
Polysorbate 80 
Sodium hydroxide 
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. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2 °C – 8 °C). 
Do not freeze. 
Store in the original container in order to protect from light. 
 
For the purpose of ambulatory use, Kineret may be removed from the refrigerator for 12 hours at 
temperature not above 25 °C, without exceeding the expiry date. At the end of this period, the product 
must not be put back in the refrigerator and must be disposed of. 
 
6.5 Nature and contents of container 
 
0.67 ml of solution for injection in a graduated pre-filled syringe (Type I glass) with a plunger stopper 
(bromobutyl rubber) and 29 gauge needle. The pre-filled syringe has an outer rigid plastic needle 
shield attached to an inner needle cover. None of the syringe or needle shield components are made 
with natural rubber latex. 
 
Pack sizes of 1, 7 or 28 (multipack containing 4 packs of 7 pre-filled syringes) pre-filled syringes. 
 
Not all pack sizes may be marketed. 
 



16 

6.6 Special precautions for disposal and other handling 
 
Kineret is a sterile unpreserved solution. For single use only. 
 
Do not shake. Allow the pre-filled syringe to reach room temperature before injecting. 
 
Before administration, visually inspect the solution for particulate matter and discolouration. Only 
clear, colourless-to-white solutions that may contain some product-related translucent-to-white 
amorphous particles should be injected. 
 
The presence of these particles does not affect the quality of the product. 
 
The pre-filled syringe is for single use only. Discard any unused medicinal product. 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Swedish Orphan Biovitrum AB (publ) 
SE-112 76 Stockholm 
Sweden 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/02/203/005 – 1-pack  
EU/1/02/203/006 – 7-pack  
EU/1/02/203/007 – 28-pack  
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 8 March 2002 
Date of latest renewal: 20 March 2007 
 
 
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/


17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 

 



18 

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

 
Name and address of the manufacturer of the biological active substance 
 
Boehringer Ingelheim RCV GmbH & Co KG 
Dr. Boehringer-Gasse 5-11 
A-1121 Vienna 
Austria 
 
Pfizer Health AB 
Mariefredsvägen 37 
SE-645 41 Strängnäs 
Sweden 
 
Name and address of the manufacturer responsible for batch release 
 
Swedish Orphan Biovitrum AB (publ) 
SE-112 76 Stockholm 
Sweden 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2) 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic safety update reports (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk management plan (RMP) 
 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities 
and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation 
and any agreed subsequent updates of the RMP. 
 
An updated RMP should be submitted: 

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

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

 
• Additional risk minimisation measures 
 
Prior to launch of the new indication Still’s disease for Kineret in each Member State the Marketing 
Authorisation Holder (MAH) must agree about the content and format of the educational programme, 



19 

including communication media, distribution modalities, and any other aspects of the programme, 
with the National Competent Authority. 
 
The main objectives of the programme are to provide information on the method of administration, 
raise awareness on the potential risk of macrophage activation syndrome (MAS) and on the potential 
risk of serious infections. 
 
The MAH shall ensure that in each Member State where Kineret is marketed, all healthcare 
professionals and patients/caregivers who are expected to prescribe or use Kineret have access to/are 
provided with the following educational package: 

• Physician educational material 
• Patient and caregiver information pack 

 
The physician educational material should contain: 

• The Summary of Product Characteristics 
• Guide for healthcare professionals 

 
The Guide for healthcare professionals shall contain the following key elements: 

• The importance of explaining the use of the syringe and correct injection technique to patients 
and/or caregivers 

• That it is not recommended to start treatment with Kineret in patients with an ongoing infection 
• Information on macrophage activation syndrome (MAS) in patients receiving the product for 

the treatment of Still’s disease 
• The importance of providing patients and/or caregivers with the educational material 

 
The patient and caregiver information pack should contain: 

• Patient information leaflet 
• The patient and caregiver guide 
• The patient reminder card 

 
The patient and caregiver guide shall contain the following key elements: 

• Instructions on use of the syringe 
• Instructions on correct injection procedures and disposal of used syringes 
• How to manage injection site reactions 

 
The patient reminder card shall contain the following key messages: 

• Patient identification 
• Contact details of their physician 
• The prescribed dose of Kineret 
• The early signs indicative of MAS 
• A description of the signs of serious infections 



20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 



21 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 



22 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
PRE-FILLED SYRINGE CARTON (CONTAINS BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Kineret 100 mg/0.67 ml solution for injection in pre-filled syringe 
Anakinra 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 0.67 ml graduated pre-filled syringe contains 100 mg of anakinra. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: anhydrous citric acid, sodium chloride, disodium edetate dihydrate, polysorbate 80, 
sodium hydroxide, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in pre-filled syringe 
1 GRADUATED pre-filled syringe 
7 GRADUATED pre-filled syringes 
Multipack: 28 (4 x 7) GRADUATED pre-filled syringes 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Single use. 
For subcutaneous use. 
Read the package leaflet before 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 
 
 



23 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze. 
Store in the original container 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 
 
Swedish Orphan Biovitrum AB (publ) 
SE-112 76 Stockholm 
Sweden 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/02/203/005 – 1-pack 
EU/1/02/203/006 – 7-pack 
EU/1/02/203/007 – 28-pack 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Kineret 100 mg 0.67 ml 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC {number} 
SN {number} 
NN {number} 
 



24 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON OF 7 PRE-FILLED SYRINGES AS AN INTERMEDIATE PACK (WITHOUT 
BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Kineret 100 mg/0.67 ml solution for injection in pre-filled syringe 
Anakinra 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each 0.67 ml graduated pre-filled syringe contains 100 mg of anakinra. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: anhydrous citric acid, sodium chloride, disodium edetate dihydrate, polysorbate 80, 
sodium hydroxide, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection in pre-filled syringe 
7 GRADUATED pre-filled syringes 
This box containing 7 pre-filled syringes is part of a 28-multipack. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Single use. 
For subcutaneous use. 
Read the package leaflet before 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 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze. 
Store in the original container in order to protect from light. 



25 

 
 
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 
 
Swedish Orphan Biovitrum AB (publ) 
SE-112 76 Stockholm 
Sweden 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/02/203/007 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Kineret 100 mg 0.67 ml 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC {number} 
SN {number} 
NN {number} 
 



26 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PRE-FILLED SYRINGES 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Kineret 100 mg/0.67 ml injection 
Anakinra 
 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
0.67 ml 
 
 
6. OTHER 
 
 



27 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 



28 

Package leaflet: Information for the user 
 

Kineret 100 mg/0.67 ml solution for injection in pre-filled syringe 
Anakinra 

 
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 or pharmacist. 
- 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 or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Kineret is and what it is used for 
2. What you need to know before you use Kineret 
3. How to use Kineret 
4. Possible side effects 
5. How to store Kineret 
6. Contents of the pack and other information 
 
 
1. What Kineret is and what it is used for 
 
Kineret contains the active substance anakinra. This is a type of cytokine (an immunosuppressive 
agent) that is used to treat: 
- Rheumatoid Arthritis (RA) 
- Periodic fever syndromes: 

- Cryopyrin-Associated Periodic Syndromes (CAPS) 
o Neonatal-Onset Multisystem Inflammatory Disease (NOMID), also called Chronic 

Infantile Neurological, Cutaneous, Articular Syndrome (CINCA), 
o Muckle-Wells Syndrome (MWS), 
o Familial Cold Autoinflammatory Syndrome (FCAS) 

- Familial Mediterranean Fever (FMF) 
- Still´s disease including Systemic Juvenile Idiopathic Arthritis (SJIA) and Adult-Onset Still’s 

Disease (AOSD) 
 
Cytokines are proteins made by your body that co-ordinate communication between cells and help 
control cell activity. In RA, CAPS, FMF and in Still’s disease, your body produces too much of a 
cytokine called interleukin-1. This results in harmful effects leading to inflammation, causing the 
symptoms of the disease. Normally, your body produces a protein that blocks the harmful effects of 
interleukin-1. The active substance of Kineret is anakinra, this works in the same way as your natural 
interleukin-1 blocking protein. Anakinra is produced by DNA technology using the micro-organism 
E. coli. 
 
For RA, Kineret is used to treat the signs and symptoms of the disease in adults (age 18 years and 
over) in combination with another medicine called methotrexate. Kineret is for patients whose 
response to methotrexate on its own is not good enough to control the rheumatoid arthritis. 
 
For CAPS, Kineret is used to treat the signs and symptoms of inflammation associated with the 
disease such as rash, joint pain, fever, headache and fatigue in adults and children (age 8 months and 
older). 
 



29 

For FMF, Kineret is used to treat the signs and symptoms of inflammation associated with the disease 
such as recurrent fever, fatigue, abdominal pain, muscle or joint pain and rash. Kineret can be used 
together with colchicine, if appropriate. 
 
For Still´s disease, Kineret is used to treat the signs and symptoms of inflammation associated with the 
disease such as rash, joint pain and fever. 
 
 
2. What you need to know before you use Kineret 
 
Do not use Kineret 
- if you are allergic to anakinra or any of the other ingredients of this medicine, listed in section 6; 
- if you are allergic to other products that are produced by DNA technology using the micro-

organism E. coli; 
- if you have neutropenia (low white blood cell count) determined after a blood test. 
 
Contact your doctor immediately 
- if you get a rash all over your body, shortness of breath, wheezing, fast pulse or sweating after 

your Kineret injection. These may be signs that you are allergic to Kineret. 
 
Warnings and precautions 
Talk to your doctor before using Kineret: 
- if you have a history of recurring infections, or if you suffer from asthma. Kineret may worsen 

these conditions; 
- if you have cancer. Your doctor will have to decide if you can still be given Kineret; 
- if you have a history of increased levels of liver enzymes; 
- if you require vaccinations. You must not be given live vaccines while being treated with 

Kineret. 
 
Still’s disease 
- Patients with Still’s disease may develop a condition called macrophage activation syndrome 

(MAS), which can be life-threatening. The risk for developing MAS is increased if you have an 
infection or if your Still’s disease symptoms are poorly controlled. Symptoms of MAS can be 
e.g. persistent high fever, swelling of lymph nodes, and persistent rash. If you develop signs of 
an infection or worsening of your Still’s disease symptoms you should contact your health care 
provider as soon as possible. 

- In rare cases patients with Still's disease, mainly children, may develop lung disease, also during 
Kineret treatment. The risk may be increased in patients with Down's syndrome (trisomy 21). 
Symptoms of lung disease can be e.g. shortness of breath during light exercise, morning cough, 
and difficulties breathing. If you develop signs of lung disease you should contact your health 
care provider as soon as possible.  

 
Children and adolescents 
- RA: Use of Kineret in children and adolescents with Rheumatoid Arthritis has not been fully 

investigated and therefore cannot be recommended. 
- CAPS, FMF, Still´s disease: Kineret is not recommended for children younger than 8 months of 

age because there is no data in this age group. 
 
Other medicines and Kineret 
Tell your doctor if you are taking, have recently taken or might take any other medicines. 
 
Medicines called tumour necrosis factor (TNF-α) inhibitors, such as etanercept should not be used 
with Kineret because this may increase the risk of infections. 
 
When you start taking Kineret the chronic inflammation in your body will decrease. This could mean 
that the doses of some other medicines, e.g. warfarin or phenytoin, have to be adjusted. 
 



30 

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 for advice before taking this medicine. 
 
Kineret has not been tested in pregnant women. Use of Kineret is not recommended during pregnancy 
and in women of childbearing potential not using contraception. 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 Kineret during pregnancy. 
 
It is not known whether anakinra is excreted in human milk. You must not breast-feed if you use 
Kineret. 
 
Kineret contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per 100 mg dose, that is to say essentially 
‘sodium-free’. 
 
 
3. How to use Kineret 
 
Always use this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if 
you are not sure. Kineret must be injected under your skin (subcutaneous) daily. You should try to 
have the injection at the same time each day. 
 
The recommended dose is either 20 to 90 mg or 100 mg. Your doctor will tell you the dose that you 
need or whether you need a dose higher than 100 mg. 
 
Injecting Kineret yourself 
Your doctor may decide that it would be more convenient for you to inject Kineret yourself. Your 
doctor or nurse will show you how to inject yourself. Do not try to inject yourself if you have not been 
trained. 
 
For instructions on how to inject yourself or your child with Kineret, please read the “Instructions for 
preparing and giving an injection of Kineret” section at the end of this leaflet. 
 
If you use more Kineret than you should 
You should have no serious problems if you accidentally take more Kineret than you need. However, 
you should contact your doctor, nurse or pharmacist if this does happen. If you feel unwell in any way 
you should contact your doctor or nurse immediately. 
 
If you forget to use Kineret 
If you have forgotten to take a dose of Kineret, you should contact your doctor to discuss when you 
should take the next dose. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Possible side effects are similar regardless if you are treated with Kineret for RA, CAPS, FMF or 
Still’s disease. 
 
If any of the following happen, tell your doctor immediately: 
 
- Serious infections such as pneumonia (a chest infection) or infections of the skin can occur during 

Kineret treatment. Symptoms might be persistent high fever, shivers, cough, headache, and 
redness and tenderness of the skin. Also persistent low-grade fever, weight loss, and persistent 
cough can be signs of an infection. 



31 

 
- Serious allergic reactions are uncommon. However, any of the following symptoms may 

indicate an allergic reaction to Kineret, so you should seek immediate medical attention. Do not 
inject more Kineret. 
- Swelling of the face, tongue or throat 
- Trouble swallowing or breathing 
- Suddenly feeling fast pulse or sweating 
- Itchy skin or rash 

 
Very common side effects (may affect more than 1 in 10 people): 
- Redness, swelling, bruising or itching at the injection site. These symptoms are generally mild 

to moderate and are more common at the start of your treatment. 
- Headaches. 
- Increased total blood cholesterol levels. 
 
Common side effects (may affect up to 1 in 10 people): 
- Neutropenia (low white blood cell count) determined after a blood test. This might increase the 

risk of you getting an infection. Symptoms of infection might include a fever or a sore throat. 
- Serious infections such as pneumonia (a chest infection) or infections of the skin. 
- Thrombocytopenia (low level of blood platelets). 
 
Uncommon side effects (may affect up to 1 in 100 people): 
- Serious allergic reactions including swelling of the face, tongue or throat, trouble swallowing or 

breathing, suddenly feeling fast pulse or sweating and itchy skin or rash. 
- Elevated levels of liver enzymes determined after a blood test. 
 
Side effects with frequency not known (frequency cannot be estimated from the available data): 
- Signs of liver disorders such as yellow skin and eyes, nausea, loss of appetite, dark-coloured 

urine and light-coloured stools. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Kineret 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The 
expiry date refers to the last day of that month. 
Store in a refrigerator (2 °C to 8 °C). Do not freeze. 
Store in original carton in order to protect from light. 
 
Do not use Kineret if you think it has been frozen. Once a syringe has been removed from the 
refrigerator and has reached room temperature (up to 25 °C) it must either be used within 12 hours or 
disposed of. 
 
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. 
 
 

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


32 

6. Contents of the pack and other information 
 
What Kineret contains 
- The active substance is anakinra. Each graduated pre-filled syringe contains 100 mg of 

anakinra. 
- The other ingredients are anhydrous citric acid, sodium chloride, disodium edetate dihydrate, 

polysorbate 80 and sodium hydroxide and water for injections. 
 
What Kineret looks like and contents of the pack 
Kineret is a clear, colourless-to-white solution for injection and is supplied ready for use in a pre-filled 
syringe. It may contain some translucent-to-white particles of protein. The presence of these particles 
does not affect the quality of the product. 
 
Pack sizes of 1, 7 or 28 (multipack containing 4 packs of 7 pre-filled syringes) pre-filled syringes. 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
Swedish Orphan Biovitrum AB (publ) 
SE-112 76 Stockholm 
Sweden 
 
 
This leaflet was last revised in  
 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
--------------------------------------------------------------------------------------------------------------------------- 
 

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


33 

INSTRUCTIONS FOR PREPARING AND GIVING AN INJECTION OF KINERET 
 
This section contains information on how to give yourself or your child an injection of Kineret. It is 
important that you do not try to give yourself or your child the injection unless you have received 
training from a doctor, nurse or pharmacist. If you have questions about how to inject, please ask your 
doctor, nurse or pharmacist for assistance. 
 
How do you or the person injecting you, use the Kineret pre-filled syringe? 
 
You will need to give yourself or your child an injection at the same time every day. Kineret is 
injected just under the skin. This is called a subcutaneous injection. 
 

 
 
Equipment: 
 
To give yourself or your child a subcutaneous injection you will need: 
 
• a pre-filled syringe of Kineret 
 
• alcohol wipes or similar; and 
 
• a sterile gauze or tissue 
 
What should you do before you give yourself or your child a subcutaneous injection of Kineret? 
 
1. Take your Kineret pre-filled syringe out of the refrigerator. 
 
2. Do not shake the pre-filled syringe. 
 
3. Check the expiry date on the pre-filled syringe label (EXP). Do not use it if the date has passed 

the last day of the month shown. 
 
4. Check the appearance of Kineret. It must be a clear, colourless-to-white solution. There may be 

some translucent-to-white particles of protein in the solution. The presence of these particles 
does not affect the quality of the product. The solution should not be used if it is discoloured or 
cloudy, or if any particles other than translucent-to-white particles are present. 

 
5. For a more comfortable injection, leave at room temperature for approximately 30 minutes or 

hold the pre-filled syringe gently in your hand for a few minutes. Do not warm Kineret in any 
other way (for example, do not warm it in a microwave or in hot water). 

 
6. Do not remove the cover from the syringe until you are ready to inject. 
 
7. Wash your hands thoroughly. 
 
8. Find a comfortable, well-lit, clean surface and put all the equipment you need within reach. 
 



34 

9. Make sure you know what Kineret dose your doctor has prescribed; 20 to 90 mg, 100 mg or 
higher.  

• If your doctor has prescribed a 100 mg dose you should continue to the “How to prepare a 
100 mg dose” section. 

• If your doctor has prescribed a lower dose you should continue to the “How to prepare a 20 to 
90 mg dose” section. 

 
How to prepare a 100 mg dose 
 
Before you inject Kineret you must do the following: 
 
1. Hold the syringe barrel and gently remove the cover 

from the needle without twisting. Pull straight as 
shown in Figure A. Do not touch the needle or push 
the plunger. Immediately discard the needle cover. 

 
2. You may notice a small air bubble in the pre-filled 

syringe. You do not have to remove the air bubble 
before injecting. Injecting the solution with the air 
bubble is harmless. 

 
3. You can now use the pre-filled syringe as described in the “Where should you give your 

injection?” section and “How do you give your injection?” section.  
 
How to prepare a 20 to 90 mg dose 
 
Before you inject Kineret you must do the following: 
 
1. Hold the syringe barrel and gently remove the cover from the 

needle without twisting. Pull straight as shown in Figure A. Do 
not touch the needle or push the plunger. Immediately discard the 
needle cover. 

 
2. You should position the syringe in one hand with the needle 

pointing straight upwards as shown in Figure B. Put your thumb 
on the plunger rod and push slowly until you see a tiny liquid drop 
at the tip of the needle. 

 
3. Turn the syringe so that the needle is now pointing 

downwards. Place a sterile gauze or tissue on a flat surface and 
hold the syringe above it with the needle pointing towards the 
gauze or tissue, as shown in Figure C. Make sure the needle 
does not touch the gauze or tissue. 
 

4. Put your thumb on the plunger rod and push slowly until the 
plunger front has reached the scale mark of your Kineret dose. 
(Your doctor will have told you what dose you need to use.) 
The ejected liquid will be absorbed by the gauze or tissue as 
shown in Figure C. 

 
5. If you are not able to set the correct dose, dispose of the 

syringe and use a new one. 
 

6. You can now use the pre-filled syringe as described in the 
“Where should you give your injection?” section and the 
“How do you give your injection?” section. 
 

Figure A 
 



35 

Where should you give your injection? 
 
The most suitable places to inject yourself or your child are (See Figure D): 
 
• the abdomen (except for the area around the navel) 
• the top of the thighs 
• the upper outer areas of the buttocks; and 
• the outer area of the upper arms 
 

Adult        Child 
 

 
 

 
Change the place that you inject each time so you don’t become sore in one area. If someone else is 
injecting for you, they can also use the back of your arms. 
 
How do you give your injection? 
 
1. Disinfect the skin by using the alcohol wipe and pinch the skin between your thumb and 

forefinger, without squeezing it. 
 
2. Put the needle fully into the skin as shown by your nurse or doctor. 
 
3. Inject the liquid slowly and evenly, always keeping the skin pinched as in Figure E. 
 

 
4. After injecting the liquid, remove the needle and let go of the skin. 
 
5. Any unused medicine must be discarded. Only use each syringe for one injection. Do not reuse 

a syringe as this can cause infection. 
 
Remember 
 
If you have any problems, please do not be afraid to ask your doctor or nurse for help and advice. 

Figure D 
 

Figure E  



36 

 
Disposing of used syringes and supplies 
 
• Do not put the cover back on used needles. 
 
• Keep used syringes out of reach and sight of children. 
 
• Never put the pre-filled syringes that you have used into your normal household rubbish bin. 

 
• If you had a dose lower than 100 mg you will have been told to eject liquid from the syringe 

onto a gauze or tissue. After your injection discard the wet gauze or tissue with your syringe and 
clean the surface with a fresh tissue. 

 
• The used pre-filled syringe and any gauze or tissue with Kineret solution should be disposed of 

in accordance with local requirements. Ask your pharmacist how to dispose of medicines no 
longer required. These measures will help to protect the environment. 

 


	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