Ilaris® (Ilaris®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceKanakinumabKanakinumab
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  • Ilaris®
    lyophilizate PC 
    Novartis Pharma AG     Switzerland
    • Dosage form: & nbsplyophilizate for the preparation of a solution for subcutaneous administration
    Composition:

    1 a vial of lyophilizate for the preparation of a solution for subcutaneous administration comprises:

    active substance: Kanakinumab 150 mg;

    Excipients: L-histidine 2,801 mg, L-histidine hydrochloride monohydrate 1.673 mg, polysorbate-80 0.60 mg, sucrose 92.35 mg, hydrochloric acid 1 M to pH 6.5.

    If completeness involves the inclusion of a solvent: 1 bottle of solvent contains: water for injection - 5 ml.

    Description:

    Lyophilizate: lyophilized white powder.

    Solvent: Clear, colorless liquid.

    Pharmacotherapeutic group:Immunosuppressive agent, monoclonal antibodies to interleukin-1β
    ATX: & nbsp

    L.04.A.C.08   Kanakinumab

    Pharmacodynamics:
    Kanakinumab is a fully human monoclonal antibody IgG1 / kappa isotype to interleukin-1β (IL-1β). Kanakinumab with high affinity binds to human IL-1β, thus neutralizing its biological effect by blocking the interaction of IL-1β with its receptors, IL-1β-induced gene activation and the production of inflammatory mediators such as IL-6 and cyclooxygenase-2.
    In the treatment of patients with systemic juvenile idiopathic arthritis (sIIA), there was a rapid and continued improvement in the joint and systemic manifestations of the disease: a significant reduction in the number of inflamed joints, rapid disappearance of fever, and reduction of acute phase reactants in the majority patients.
    In 33% of patients on day 29 of the therapy, there was an improvement in the course of the disease by 100% according to the pediatric criteria of the American College of Rheumatology compared with no effect in the placebo group. The use of kanakinumab significantly reduces or eliminates the use of glucocorticosteroids in the treatment of SJUIA. Kanakinumab allows to extend the time interval until the disease worsens, improve the quality of life of patients and perform their daily tasks.

    In patients with gouty arthritis and various phenotypes of cryopyrin-associated periodic syndrome (cryopyrin-associated periodic syndrome, CAPS) including family cold auto-inflammatory syndrome / family cold urticaria (Familial Cold Autoinflammatory Syndrome/ Familial Cold Urticaria, FCAS/FCU), McLean-Wales Syndrome (Muckle-Wells Syndrome, MWS) and multisystem infantile inflammatory disease / chronic infant neurologic skin-articular syndrome (Neonatal onset multisystemic inflammatory disease/Chronic infantile neurological cutaneous and articular, NOMID/CINCA), kanakinumab reduces the severity of local and systemic inflammatory reactions caused by excessive production of IL-1β. When using the drug in patients with acute attacks of gouty arthritis, the concentration of laboratory markers of inflammation (C reactive protein (SRV), serum amyloid A (CAA)) decreases, symptoms of inflammation of the affected joint (pain, swelling, redness) disappear for a short time.

    Against the background of the drug Ilaris® 150 mg subcutaneously in patients with frequent exacerbations of gout attacks (at least 3 attacks throughout the year), a statistically significant reduction in pain intensity (on the VAS scale) was observed compared to the control group (triamcinalone 40 mg). Against the background of the drug Ilaris® decreased pain intensity from 24 hours after the administration of the drugs and within 7 days after the administration.

    When Ilaris® was used, a statistically significant reduction in the risk of a new attack of gout at 62% within 12 weeks of therapy and 56% during 24 weeks of therapy compared with the control group was demonstrated.

    The effectiveness of Ilaris® gouty arthritis was comparable in patients at the age of> 65 and <65 years.

    When using kanakinumab in patients with different phenotypes CAPS there is a decrease in the following manifestations of the disease during the first day: fever, increased fatigue, skin rashes, arthralgia, myalgia, headache / migraine, conjunctivitis, weakness, and a decrease (within a few days) of inflammatory markers, including both SRV and CAA , and leads to normalization of the number of leukocytes and platelets (in case of their increase).

    With prolonged use of kanakinumab (within 48 weeks) in patients with CAPS the complete response to therapy, defined as the combination of a decrease (to a minimal extent or complete disappearance) of the symptoms of auto-inflammatory disease and skin lesions (rash like urticaria), and a decrease in SRV and CAA <10 mg / l, was observed in 97% of cases for 7 days after the start of therapy. With the use of kanakinumab, the patients did not develop recurrences of the disease (in the group of patients treated with placebo, relapses were observed in 81% of cases).

    Pharmacokinetics:

    Absorption

    In adults with different phenotypes CAPS after a single subcutaneous injection of 150 mg of the drug, the time to reach the maximum concentration (C max) of kanakinumab is about 7 days. Average the final half-life is 26 days. With subcutaneous administration of kanakinumab, absolute bioavailability is 66% (population pharmacokinetic analysis in patients with CAPS, including children at the age of 2 years).

    Parameters of pharmacokinetics (area under the curve "concentration-time" (AUC) and the maximum concentration (Сmах) increase in proportion to the dose in the range doses from 0.30 to 10.0 mg / kg with intravenous infusion or with subcutaneous administration (in a dose of 150 to 600 mg).

    Distribution

    Kanakinumab binds to serum IL-1β. Volume of distribution (Vss) varies with body weight.

    Have patients with CAPS Vss is 6.2 liters with a body weight of 70 kg, in patients with SUIA - 3.2 liters with a body weight of 33 kg and in patients with gouty arthritis - 7.9 liters with a body weight of 93 kg. With subcutaneous administration of the drug for 6 months at a dose of 150 mg every 8 weeks, at a dose of 4 mg / kg every 4 weeks, 150 mg every 12 weeks, the cumulative concentration of kanakinumab is 1.3.1.6 and 1.1, respectively.

    Excretion

    The clearance (C1) varies with body weight. For patients with CAPS this figure is 0.17 l / day with a body weight of 70 kg, in a patient with SJUIA 0.11 l / day with a body weight of 33 kg, in a patient with gouty arthritis 0.23 l / day with a body weight of 93 kg. After taking into account weight differences, a significant difference in the pharmacokinetic properties of cannacinumab in patients with gouty arthritis, various phenotypes CAPS and the SJUIA was not detected.

    With repeated use of the drug, there is no increase in O or changes in any other time-dependent pharmacokinetic parameters of kanakinumab. When the drug is administered with taking into account the body weight, the sex and age of the patients do not affect the pharmacokinetics of the drug.

    Pharmacokinetics in special clinical cases

    Patients aged < 18 years

    In patients aged 4 years and older after subcutaneous single administration of the drug at a dose of 150 mg or 2 mg / kg, the time to achieve Cmax kanakinumab is 2-7 days. The final half-life of kanakinumab in this category of patients is similar to that in adults and ranges from 22.9 to 25.7 days. The results of a population analysis of the pharmacokinetics of cannacinumab in children aged 2 to 4 years are similar to those in patients 4 years and older.Pharmacokinetic characteristics in patients with CAPS and the SJUA are similar. With subcutaneous administration of cannacinumab at a dose of 4 mg / kg every 4 weeks in patients with SUAI values AUC and Cmax were similar in the age group from 2 to under 20 years.

    Patients aged> 65 years

    There was no difference in pharmacokinetic parameters based on C1 and Vss, in patients of the older age group and patients aged less than 65 years.

    Indications:

    Acute gouty arthritis

    Treatment of frequent acute attacks of gouty arthritis and prevention of the development of new seizures with inefficiency, intolerance or in the presence of contraindications to the use of non-steroidal anti-inflammatory drugs and / or colchicine and when it is not possible to carry out therapy with repeated courses of glucocorticosteroids.

    Cryopyrin-associated Periodic Syndrome (CAPS) in adults and children> 2 years of age and older, including:

    - family cold auto-inflammatory syndrome (FCAS) / Family cold urticaria (FCU);

    - fromMcLean Wales (MWS);

    - mThe multi-system inflammatory disease (NOMID) / chronic infant neurological skin-articular syndrome (CINCA).

    Active phase systemic juvenile idiopathic arthritis (sJIA) in children> 2 years of age and older.

    Contraindications:

    - Hypersensitivity to the active substance or other components of the drug in the history;

    - aboutacute infectious diseases;

    - bVariability and the period of breastfeeding;

    - Children under 2 years of age (safety and efficacy for this category of patients have not been adequately studied).

    Carefully:

    The drug should be used with caution in elderly patients; if there are any relapsing infections in the patients or any conditions predisposing to the development of the infection.

    Pregnancy and lactation:There are limited data on the use of Ilaris® in patients of reproductive age and in pregnant women. In animal studies, the drug did not show any reproductive toxicity. Women should use reliable methods of contraception during therapy with Ilaris® and within 3 months after the last dose of the drug.

    It is not known whether the kanakinumab in breast milk. If it is necessary to use the preparation breast Feeding should be discontinued.

    Dosing and Administration:

    The drug (lyophilizate) is dissolved in 1 ml of water for injection (see section "Instructions for use").

    Injections are conducted subcutaneously in those parts of the body where there is subcutaneous fat: in the abdomen, the front surface of the thighs, the posterolateral surface of the shoulders.

    Gouty Arthritis

    The recommended dose of the drug in adults is 150 mg, the drug is administered during an attack of gouty arthritis, concurrently subcutaneously. To achieve maximum effectiveness, the drug should be administered as soon as possible after the onset of an attack of gouty arthritis.

    Patients who did not respond to the first injection of Ilaris® should not be re-injected. For patients who responded to treatment, the repeated administration of Ilaris® is possible at least 12 weeks after the previous injection.

    Apply the drug Ilaris ® for the treatment of attacks of gouty arthritis should be as necessary. Optimization of hyper-drug control should be carried out with appropriate anti-gouty drugs.

    The drug therapy can be initiated and performed only by a doctor who has experience in diagnosing and treating patients with gouty arthritis.

    Cryopyrin-associated Periodic Syndrome

    The recommended starting dose of Ilaris® for patients with cryopyrin-associated periodic syndrome:

    Adults and children> 4 years of age, depending on body weight, are prescribed:

    - patients with a body weight> 40 kg - 150 mg;

    - patients with body weight> 15 kg and <40kg - 2 mg / kg;

    patients with a body weight> 7.5 kg and <15kg - 4 mg / kg.

    For children aged 2 years and <4 years with a body weight> 7.5 kg, the drug is used at a rate of 4 mg / kg.

    The drug is administered subcutaneously (SC) 1 injection at intervals of 8 weeks.

    If a satisfactory clinical response is not obtained in patients with a starting dose of 150 mg or 2 mg / kg, namely the process of resolution of rash and other symptoms of inflammation is not observed within 7 days after the first injection of Ilaris®, it is possible to carry out a second injection of the drug in a dose 150 mg (with a body weight> 40 kg) and 2 mg / kg (with a body weight> 15 kg and <40 kg).

    If the subsequent complete clinical response is achieved in these patients, maintenance therapy with Ilaris® at a dose of 300 mg 1 injection at an interval of 8 weeks (with a body weight> 40 kg) and 4 mg / kg 1 injection at an interval of 8 weeks (with a body weight> 15 kg and <40 kg).

    If a satisfactory clinical effect is not observed within 7 days after increasing the dose, it is possible to conduct a third injection of Ilaris® at a dose of 300 mg 1 injection at an interval of 8 weeks (with a body weight> 40 kg) or 4 mg / kg (body weight> 15 kg and <40 kg). When the complete clinical response is subsequently reached, these patients are recommended maintenance therapy with Ilaris® at a dose of 600 mg 1 injection at an interval of 8 weeks (at a body weight> 40 kg) or 8 mg / kg (body weight> 15 kg and <40 kg) 1 injection at an interval of 8 weeks.

    If a satisfactory clinical effect is not observed in patients with a starting dose of 4 mg / kg within 7 days after the first injection, a second injection of Ilaris® in a dose of 4 mg / kg is possible. When the subsequent complete clinical response is achieved in these patients, maintenance therapy with a drug of 8 mg / kg 1 injection at an interval of 8 weeks is recommended.

    The clinical experience of using the drug with a dosing interval of less than 4 weeks or at a dose of more than 600 mg or 8 mg / kg is limited.

    Increasing the dose of Ilaris® was required most often for patients with NOMID / CINCA compared with FCAS or MWS.

    Therapy with the drug can be initiated and performed only by a doctor who has experience in diagnosing and treating patients with CAPS.

    SJUIA

    In SJUIA, the recommended dose for patients with a body weight> 7.5 kg is 4 mg / kg (with increase to 300 mg) for four weeks as a subcutaneous injection.

    After training in the hypodermic injection technique, patients or persons caring for them can independently administer the drug under proper supervision (if the doctor deems it necessary). Patients or persons caring for them should be instructed in the technique of preparing the solution, syringes and needles suitable for injection.

    Use in different patient groups

    Patients aged> 65 years

    No dose adjustment is required in patients aged> 65 years.

    Patients aged <18 years

    Gouty Arthritis

    There is no data on the use of Ilaris ® for the treatment of gouty arthritis in children and adolescents <18 years.

    Cryopyrin-associated periodical syndrome with JIA

    The experience of using kanakinumab in children under 2 years is limited.

    Patients with impaired renal function

    No dose adjustment is required in patients with impaired renal function (clinical experience in these patients is limited).

    Patients with impaired hepatic function

    In patients with impaired hepatic function, the efficacy and safety of the drug have not been studied. Since Ilaris® is a human IgG, it is believed that liver failure does not affect the pharmacokinetics of this drug.

    Side effects:

    With the use of Ilaris ®, clinical trials have shown an increased incidence of infectious diseases, mainly upper respiratory tract infections. The course of infectious diseases most often was of mild or moderate severity, but there were also cases of a serious course of infectious diseases. Isolated cases of development of rare or opportunistic infections were observed against the background of Ilaris®, however, the association of these diseases with the drug intake is not known.

    To assess the incidence of adverse events (AEs) detected in placebo-controlled clinical trials (when the drug is used to treat cryopirin-associated periodic syndrome at a dose of 150 mg with a body weight> 40 kg and 2 mg / kg with a body weight> 15 kg and < 40 kg and in the treatment of SJUA in patients aged 2 to 20 years) and for the treatment of acute attacks of gouty arthritis in doses of 10 mg to 300 mg in actively controlled trials, the following criteria were used (according to WHO classification): very frequent (> 1/10 appointments); frequent (> 1/100, <1/10); infrequent (> 1/1000, <1/100); rare (> 1/10000, <1/1000); very rare (<1/10000), the frequency is unknown (insufficient data to estimate the frequency of development). **

    Gouty Arthritis

    Infectious and parasitic diseases: very often - infections (in particular, nasopharyngitis, sinusitis, upper respiratory tract infections, bronchitis, pneumonia, pharyngitis, influenza, urinary tract infections, ear infections, gastroenteritis, panniculitis).

    Disturbances from the nervous system: often - dizziness / vertigo.

    Disturbances from the musculoskeletal system: often - backache.

    Disorders from the digestive system: infrequently gastroesophageal reflux disease.

    General disorders and reactions at the site of administration: often - general weakness /increased fatigue.

    Reactions at the injection site were observed in 1.2% of patients treated with Ilaris ® in clinical trials.

    Changes in laboratory indicators

    General blood analysis

    Reducing the number of leukocytes <0.8 × 109/ l of the lower limit of the norm was noted in 6.7% of patients treated with Ilaris ®, compared with 1.4% of patients who received triamcinolone. Reduction of the absolute number of neutrophils below 1 x 109 / l was observed in 2% of patients in comparative studies on gouty arthritis. There were also isolated cases of a decrease in the number of neutrophils below 0.5 x 109 / l.

    In 12.7% of cases, against the background of Kanakinumab therapy, there was a slight and transient decrease in the number of platelets (ranging from 75 x 109/ l) to the lower limit of the norm (in the reference drug, this decrease was observed in 7.7% of cases).

    Uric acid

    On the background of therapy with kanakinumab, there is a transient increase in the concentration of uric acid (by about 0.6 mg / dL). Ilaris® does not reduce the ability of antidotal drugs to reduce the concentration of uric acid when combined.

    Aspartate aminotransferase / alanine aminotransferase (AST / ALT)

    On the background of Kanakinumab therapy, it is possible to develop a mild to moderate increase in AST / ALT activity.

    Triglycerides

    On the background of therapy with kanakinumab, on average, there is an increase in concentration triglycerides in blood plasma at 33.5 mg / dl, and in the group of triamcinolone - a slight decrease of 3.1 mg / dl.Increase in triglyceride concentration by more than 5 times (compared with the upper limit of normal) was observed in 2.4% of cases in the group of application of kanakinumab and in 0.7% of cases in the group of triamcinolone. The clinical significance of this observation is unknown.

    Cryopyrin-associated Periodic Syndrome

    Infectious and parasitic diseases: very often - nasopharyngitis; often - urinary tract infections; infection of the upper respiratory tract, viral infection.

    Disturbances from the nervous system: Often dizziness / vertigo.

    Disturbances from the skin and subcutaneous tissues: Often - reaction in place administration of the drug **.

    * Vertigo symptoms, in some cases, were considered as serious AEs, all episodes of vertigo were resolved, despite continued therapy with the drug.

    ** An adverse event (AE) was detected using a questionnaire for a doctor.

    In the course of long, open studies with escalation of the dose, there was an increase in the incidence of infectious diseases (gastroenteritis, respiratory tract infections and upper respiratory tract infections), nausea and dizziness in a group of patients receiving doses of 600 mg or 8 mg / kg, compared with groups receiving other doses of the drug.

    Changes in laboratory indicators

    General blood analysis

    When using the drug in clinical studies in patients with CAPS there was an increase in hemoglobin and a decrease in the number of leukocytes, neutrophils and platelets. However, these changes were probably associated with a decrease the severity of the inflammatory process against the background of drug therapy and did not have clinical significance.

    Enzymes of the liver

    In rare cases in patients with CAPS, who received treatment with the drug, there was an increase in the activity of "liver" transaminases.

    Bilirubin

    In a number of cases, against the background of drug therapy in patients with CAPS There was an asymptomatic insignificant increase in serum bilirubin, not accompanied by an increase in the activity of "liver" transaminases.

    SJUIA

    Infectious and parasitic diseases: very often - infections (in particular, nasopharyngitis, viral infections of the upper respiratory tract, pneumonia, rhinitis, pharyngitis, tonsillitis, sinusitis, urinary tract infections, gastroenteritis, viral infection).

    Disorders from the digestive system: very often - pain in the upper abdomen.

    Disturbances from the skin and subcutaneous tissues: very often - a reaction at the site of administration of the drug of mild severity *, often - a reaction at the site of administration of the drug of moderate severity *.

    * - did not lead to the termination of the study.

    Changes in laboratory indicators

    General blood analysis

    Decrease in the number of leukocytes <0.8 × 109/ l of the lower limit of normal was observed in 10.4% of patients treated with Ilaris®, compared to 4.0% in the placebo group.

    Transient decrease in the absolute number of neutrophils <1x109/ l was observed in 6.0% of patients treated with Ilaris®, compared with 2.0% in the placebo group. There was only one case of a decrease in the absolute number of neutrophils <0.5x109/ l when treated with Ilaris®.

    Moderate and transient decrease in the range from 75 х109/ l to the lower limit of the norm thrombocytes was noted in 6.3% of patients receiving Ilaris®, compared with 2.0% in the placebo group.

    Enzymes of the liver

    Three-fold increase in ALT and / or ACT in comparison with the upper limit of the norm was noted in 4.1 % patients, who received treatment with Ilaris®, compared with 2.0% in the placebo group. At the subsequent examination normalization of parameters was noted.

    Hypersensitivity reactions

    When Ilaris ® was used in clinical trials, adverse events were reported by doctors as hypersensitivity reactions. In most cases, these reactions were mild. When using the drug, there was no development of anaphylactoid or anaphylactic reactions. However, when prescribing Ilaris®, one can not exclude the risk of developing severe hypersensitivity reactions that can occur when injected with preparations of protein origin. Patients treated with Ilaris® about gouty arthritis, CAPS and SJUIA antibodies to the drug were detected in 1.5%, 3% and 2% of cases, respectively. Interrelations between the formation of antibodies, clinical response and the development of adverse events have not been identified.

    Application in patients aged < 18 years (patients with CAPS)

    Children aged 2-17 years did not have clinically significant differences in the safety and tolerability of Ilaris®, including the overall incidence and severity of infections, compared with the general population of patients.Most often, children had upper respiratory tract infections.

    Use in patients > 65 years old

    There were no differences in the safety profile of the drug in this group of patients.

    The patient should be informed of the need to consult a doctor if severe adverse reactions develop, including those not specified in the instructions.

    Overdose:No confirmed cases of drug overdose have been reported. In case of an overdose of Ilaris®, patients should be monitored to identify possible adverse events and, if necessary, to prescribe appropriate symptomatic therapy.
    Interaction:

    There were no special studies on the interaction of Ilaris® with other drugs. Since the expression in the liver of the isoenzymes of the cytochrome P450 system can be suppressed by cytokines that stimulate chronic inflammation, such as IL-1β, then in the appointment of potent inhibitors of cytokines, the expression in the liver of the isoenzymes of the cytochrome P450 system can be normalized. This is clinically significant for drugs metabolized by isoenzymes of the cytochrome P450 system and having a narrow therapeutic index when the dose of the drug is selected individually.When administering Ilaris® to patients taking such drugs, their dose should be adjusted if necessary (depending on their clinical effect and concentration of the active substance in the blood plasma).

    In clinical studies, the safe use of Ilaris with antidotal agents was noted. The drug is not recommended to be administered simultaneously with TNF inhibitors and other blockers IL-1, as their use against the background of the Ilaris® drug increases the risk of developing severe infections.

    Data on the effect of vaccination on live vaccines, as well as on the possible secondary transmission of infection, to patients receiving treatment with the drug are not available. Vaccinate patients treated with Ilaris® with live vaccines only if the benefits of vaccination exceed the possible risk. It is recommended that immunization be carried out (according to the vaccination schedule) before initiating therapy with Ilaris® (including pneumococcal vaccine and inactivated influenza vaccine).

    If necessary, vaccination with live vaccines is carried out after initiation of therapy with the drug (at least 3 months after the last injection of the drug and 3 months before the next).Data from clinical studies conducted in adult healthy volunteers show that a single administration of Ilaris 300 mg does not affect the onset of antibody production and the persistence of the post-vaccination response when vaccinated against influenza and meningococcal infection (glycosylated protein vaccine).

    Special instructions:

    The experience of using Ilaris® in patients with CAPS without an established mutation in NLRP3 gene is limited.

    Neutropenia

    Against the background of therapy with inhibitors of IL-1, including the preparation Ilaris®, neutropenia (the absolute number of neutrophils (ACH) is lower 1.5х109) was mainly observed in patients with other diseases, and not in patients with different phenotypes of CAPS. Before the beginning of treatment with the drug, 1-2 months after the beginning and periodically during the therapy with the drug, it is necessary to conduct a standard general clinical analysis of the blood in order to detect neutropenia. In patients with neutropenia, treatment with Ilaris® should be started only after the normalization of the number of neutrophils. If there is a decrease in ASC during the treatment with the drug, it is necessary to ensure proper control of the patients' condition and, if necessary, consider stopping the treatment with the drug.

    Malignant neoplasms

    There have been reports of cases of development of malignant neoplasms in patients receiving Ilaris®, but the risk of developing malignant tumors with antibodies binding IL-1 is unknown.

    Infectious diseases

    The use of Ilaris® can be accompanied by an increase in the incidence of serious infections, so patients should be under the supervision of a doctor to identify symptoms of infection during and after therapy with the drug.

    Treatment with drug Ilaris® should not be started or continued in patients with active infection. When using Ilaris ®, isolated cases of opportunistic infections (including aspergillosis, atypical infectious diseases of mycobacterial etiology, shingles) were noted. It is impossible to exclude a causal relationship between these phenomena and the use of the drug.

    When using the drug in approximately 12% of patients with different phenotypes CAPS positive tuberculin test results were observed without any signs of tuberculosis infection (latent or active).There is no evidence of an increased risk of reactivation of tuberculosis infection when treated with monoclonal antibodies to IL-1 (eg Ilaris®). Before using Ilaris®, all patients should be examined in order to identify an active or latent tuberculosis infection (including the collection of anamnesis and the conduct of appropriate screening tests, such as tuberculin test, tests IGRA (Interferon-Gamma-Release-Assay) or chest X-ray. During treatment, the patient should carefully monitor the status of patients with a view to detecting a tuberculosis infection. It is recommended to inform patients about the need to consult a doctor if the following symptoms appear on the background and after therapy with Ilaris® (long-persistent cough, weight loss, low-grade fever). In the case of the conversion of the tuberculin test from negative to positive, especially in high-risk patients, alternative screening tests should be performed. If tuberculosis infection is detected, treatment with Ilaris® should not be started or continued.

    Syndrome of activation of macrophages in patients with SJUIA

    The macrophage activation syndrome is a known life-threatening condition that can develop in patients with rheumatic diseases, in particular in patients with SJUA and require intensive therapy. Physicians should carefully consider the symptoms of infection or worsening of the course of SJIA, known as the trigger mechanism for the macrophage activation syndrome. Clinical studies indicate that Ilaris® probably does not increase the risk of developing macrophage activation syndrome in patients with SJUI, however, it does not allow for final conclusions.

    Effect on the ability to drive transp. cf. and fur:

    Patients who have a vertigo when the Ilaris® drug is used should refrain from controlling vehicles or mechanisms until this undesirable phenomenon disappears completely.

    Form release / dosage:

    Lyophilizate for the preparation of a solution for subcutaneous administration, 150 mg.

    Packaging:

    I. Lyophilizate for the preparation of a solution for subcutaneous administration

    Lyophilizate for the preparation of a solution for subcutaneous administration of 150 mg in a vial of clear glass with a capacity of 6 ml, corked with a rubber stopper,coated with an aluminum cap with a plastic lid. One bottle together with the instruction for use is placed in a pack.

    OR

    II. Lyophilizate for the preparation of a solution for subcutaneous administration with a solvent - water for injection

    1. The first plastic pallet contains:

    Bottle with lyophilizate. 150 mg of active ingredient per bottle of colorless glass (type 1, Hebrew F / F USA) with a capacity of 6 ml, corked with a rubber stopper, covered with an aluminum cap with a plastic flip-off cover ("flip-off" device).

    Vial with solvent. 5 ml of water for injection into a colorless glass bottle (type 1, Hebrew F./F. USA) with a capacity of 6 ml, sealed with a rubber stopper, covered with an aluminum cap with a plastic flip-off cover ("flip-off" device).

    2. The second plastic pallet contains a set of devices for injections: one sterile syringe with the Luer-Lock system, one safe sterile injection needle, two Luer-Lock adapters to the bottle, four alcohol wipes.

    Two plastic pallets, together with instructions for use, are placed in a bundle.

    Storage conditions:
    Store at a temperature of 2 to 8 ° C in a dark place.
    Do not freeze.
    The drug should be stored out of the reach of children.
    Shelf life:

    Lyophilizate-3 years.

    Solvent - 5 years.

    Expiration date of the kit is determined from an earlier date expiration of the component, included in the kit.

    The drug should not be used after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-001414
    Date of registration:11.01.2012
    The owner of the registration certificate:Novartis Pharma AGNovartis Pharma AG Switzerland
    Manufacturer: & nbsp
    Representation: & nbspNOVARTIS PHARMA LLCNOVARTIS PHARMA LLC
    Information update date: & nbsp25.02.15
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