Instruction for use: Ilaris

Dosage form: Lyophilizate for the preparation of a solution for subcutaneous administration

Active substance: Canakinumabum

ATX

L04AC08 Kanakinumab

Pharmacological group:

Immunosuppressive agent - monoclonal antibodies to interleukin-1β [Immunodepressants]

The nosological classification (ICD-10)

D84.9 Unspecified Immunodeficiency: Pneumonia in immunodeficient states; Autoimmune disease; Autoimmune diseases; Severe immunodeficiency; immune deficiency; Immunodeficiency; immunodeficiency diseases; Immunodeficiency states due to surgery; Immunotherapy for cancer; Immunomodulation; Infections in patients with weakened immune systems; Correction of immune deficiency; Correction of immunodeficiencies; Correction of a weakened immune system; Correction of a weakened immunity in immunodeficient states; Violation of immunity; Violation of the immune status; Immune System Disorders; Primary immunodeficiency; Maintaining immunity; Lowering the body's defenses; Lowering the immunity; Lowering the immunity of colds and infectious diseases; The decrease of the immune status; Lowered resistance to infections; Lowered resistance to infections and colds; Lowered resistance; Immunosuppression; Predisposition to colds; acquired immune deficiencies; Radiation immunodeficiency; The development of immunodeficiency; Immune dysfunction syndrome; immunodeficiency syndrome; primary immunodeficiency syndrome; Reducing the body's defenses; Immunosuppression; Reduced immune defense; Reducing local immunity; Reducing the total body resistance; The decrease in cell-mediated immunity; Reduced resistance to infections in children; Reducing the body's resistance; Reduced resistance; reduced immunity; Status immunodeficiency; Stimulation of the processes of nonspecific immunity; Heavy selective secondary immunodeficiency; immunity Oppression; Primary immunodeficiency

E85.0 Hereditary family amyloidosis without neuropathy: Armenian disease; The disease is periodic; Sigala-Mamu's disease; Paroxysmal Jaynoye-Mosental syndrome; Periodic peritonitis; Family paroxysmal polyserositis; Reimann's syndrome; Family periodic peritonitis; Peritonitis family periodic

L50.2 Urticaria caused by exposure to low or high temperature: Cold urticarial

M08 Juvenile [juvenile] arthritis: Juvenile arthritis; Juvenile chronic polyarthritis; Juvenile chronic arthritis; Juvenile rheumatoid arthritis; Arthritis Juvenile chronic

M10 Gout: An exacerbation of gout; Acute articular attack with gout; Acute gouty attack; Gouty attack; Recurrent gout attacks; Chronic gout

Composition

Lyophilizate for the preparation of a solution for subcutaneous administration 1 vial.

active substance: Cancinumab 150 mg

Auxiliary substances: L-histidine - 2,801 mg; L-histidine hydrochloride monohydrate - 1.673 mg; Polysorbate 80 - 0.6 mg; Sucrose 92.35 mg; Hydrochloric acid 1 M - up to pH 6.5

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

Descriptionofdosageform

Lyophilizate: lyophilized white powder.

Pharmachologic effect

Mode of action - Immunosuppressive.

Pharmacodynamics

Kanakinumab is a fully human monoclonal antibody IgG1 / kappa isotype to 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 COX-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 decrease in the number of inflamed joints, rapid disappearance of fever, and reduction of acute phase reactants in most patients.

In 33% of patients on the 29th day of 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 GCS in the therapy 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 intermittent syndrome (CAPS) including familial cold auto-inflammatory syndrome / familial cold urticaria (FCAS / FCU), Muckle syndrome -Wells Syndrome, MWS) and multisystem infantile inflammatory disease / chronic neurological neurological skin-articular syndrome (NOMID / CINCA), cannacinumab reduces local severity (Neonatal onset multisystemic inflammatory disease, Chronic infantile neurological cutaneous and articular) X and systemic inflammatory reactions caused by excessive production of IL-1β. When using the drug in patients with a sharp attack of gouty arthritis, the concentration of laboratory markers of inflammation decreases: (C-reactive protein (CRP), serum amyloid A (CAA), signs of inflammation of the affected joint (pain, swelling, redness) for a short time go away.

Against the backdrop of using Ilaris® 150 mg p / c in patients with frequent exacerbations of gout attacks (at least 3 attacks during the year), a statistically significant reduction in pain intensity (on the VAS scale) was observed compared with the control group (triamcinolone 40 mg). Against the backdrop of the use of Ilaris ®, a decrease in the intensity of pain is observed from 24 hours after the administration of the drug and lasts for 7 days after 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 by 56% during 24 weeks of therapy was demonstrated compared to those in the control group.

The effectiveness of Ilaris ® in gouty arthritis was comparable in patients aged ≥65 and ≤65 years.

With the use of Kanakinumab in patients with various phenotypes of CAPS, the following manifestations of the disease have already decreased during the first day: fever, increased fatigue, skin rashes, arthralgia, myalgia, headache / migraine, conjunctivitis, weakness, and a decrease (within a few days) Production of inflammatory markers, including CRP and CAA, and leads to normalization of the number of leukocytes and platelets (in case of their increase).

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

Pharmacokinetics

Absorption. In adult patients with different phenotypes of CAPS after a single administration of 150 mg of Tmax, kanakinumab is about 7 days. The average final T1 / 2 is 26 days. With n / to the introduction of kanakinumab, absolute bioavailability is 66% (population pharmacokinetic analysis in patients with CAPS, including children aged 2 years). The parameters of pharmacokinetics (AUC and Cmax) increase proportionally to the dose in the range from 0.3 to 10 mg / kg with intravenous infusion or p / to administration (in a dose of 150 to 600 mg).

Distribution. Kanakinumab binds to serum IL-1β. Vss varies with body weight. In 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 SC 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 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 SUIA - 0.11 l / day with a body weight of 33 kg, in a patient with gouty arthritis - 0.23 l / day at a mass Body weight 93 kg. After accounting for weight differences, a significant difference in the pharmacokinetic properties of cannacinumab in patients with gouty arthritis, various phenotypes of CAPS and SJUIA has not been identified.

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

Special patient groups

Patients aged ≤18 years. In patients aged 4 years and older, after a single injection of 150 mg or 2 mg / kg, Tmax kanakinumab is 2-7 days. The final T1 / 2 kanakinumab in this category of patients is similar to that in adults and ranges from 22.9 to 25.7 days. The results of the population analysis of the pharmacokinetics of cannacinumab in children aged 2 to 4 years are similar to those in patients 4 years and older. The pharmacokinetic characteristics in patients with CAPS and SJUIA are similar. With the administration of kanakinumab at a dose of 4 mg / kg every 4 weeks in patients with SJUA, the values of 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 clearance and Vss, in patients of the older age group and at the age of less than 65 years.

Indication of the Ilaris

Acute arthritic arthritis:

- treatment of frequent acute attacks of gouty arthritis and prevention of the development of new seizures with ineffectiveness, intolerance or contraindications to the use of NSAIDs and / or colchicine and the inability to carry out therapy with repeated courses of GCS;

Cryopirin-associated periodic syndrome in adults and children aged ≥2 years, including:

- family cold auto-inflammatory syndrome / family cold urticaria;

- McLean-Wales syndrome;

- Infant multisystem inflammatory disease / chronic infant neurologic skin-articular syndrome;

Active phase of systemic juvenile idiopathic arthritis in children ≥2 years of age.

Contraindications

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

Acute infectious diseases;

pregnancy;

The period of breast-feeding;

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

With caution: elderly patients; The presence in the anamnesis of recurrent infections or any conditions predisposing to the development of infection.

Application in pregnancy and breastfeeding

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

It is not known whether Kanakinumab penetrates into breast milk. If it is necessary to use the drug, breastfeeding should be discontinued.

Side effects

With the use of the Ilaris® drug, clinical trials have shown an increase in the incidence of infectious diseases, mainly upper respiratory tract infections. The course of infectious diseases most often was mild or moderate, 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®, but the relationship of these diseases to the drug intake is unknown.

To assess the incidence of adverse events (AEs) detected in placebo-controlled clinical trials (when the drug is used to treat CAPS at a dose of 150 mg with a body weight> 40 kg and 2 mg / kg with a body weight of ≥15 kg and ≤40 kg and Treatment of SJUA in patients aged 2 to 20 years) and for the treatment of acute attacks of gouty arthritis in doses of 10 to 300 mg in actively-controlled studies, the following criteria were used (according to the WHO classification): very often (≥1/10 appointments) ; Often (≥1 / 100, <1/10); Infrequently (≥1 / 1000, <1/100); Rarely (≥1 / 10000, <1/1000); Very rarely (<1/10000); 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).

From the nervous system: often - dizziness / vertigo.

From the musculoskeletal system: often - back pain.

From the side of the digestive system: infrequently - gastroesophageal reflux disease.

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

Reactions at the site of administration 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 equal to or less than 0.8 × the lower limit of the norm was noted in 6.7% of patients treated with Ilaris®, compared with 1.4% of patients receiving triamcinolone. Reduction of the absolute number of neutrophils below 1 × 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 × 109 / L. In 12.7% of cases, a slight and transient decrease in the number of platelets (in the range from 75 × 109 / L) to the lower limit of the norm was observed against the background of therapy with kanakinumab (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.

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

Triglycerides. On the background of therapy with kanakinumab, an average increase in plasma triglyceride concentration by 33.5 mg / dl was observed, and in the triamcinolone group a slight decrease of 3.1 mg / dl was observed. The increase in triglyceride concentration by more than 5-fold (compared with HHV) was observed in 2.4% of cases in the group of application of kanakinumab and in 0.7% of cases in the triamcinolone group. The clinical significance of this observation is unknown.

CAPS

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

From the nervous system: very often - dizziness / vertigo1.

From the skin and subcutaneous tissues: very often - a reaction at the injection site2.

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

2 AE was detected using a questionnaire for a doctor.

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

Changes in laboratory indicators

General blood analysis. When the drug was used 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 in the severity of the inflammatory process against the background of drug therapy and had no 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 hepatic transaminases.

Bilirubin. In some 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 hepatic transaminase activity.

SJUIA

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

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

From the skin and subcutaneous tissues: very often - the reaction at the place of injection of the drug of mild severity 1; Often a reaction at the site of administration of the drug of moderate severity.

1 Did not lead to discontinuation of the study.

Changes in laboratory indicators

General blood analysis. A decrease in the number of leukocytes ≤0.8 × the lower limit of the norm was observed in 10.4% of patients treated with Ilaris®, compared with 4% in the placebo group.

Transient decrease in the absolute number of neutrophils <1 × 109 / l was observed in 6% of patients treated with Ilaris ®, compared with 2% in the placebo group. There was one case of a decrease in the absolute number of neutrophils <0.5 × 109 / l when treated with Ilaris ®.

A moderate and transient decrease in the range from 75 × 109 / L to the lower limit of platelet count was observed in 6.3% of patients receiving Ilaris ®, compared with 2% in the placebo group.

Enzymes of the liver. A threefold increase in ALT and / or ACT compared with IGN was noted in 4.1% of patients treated with Ilaris®, compared with 2% 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 may occur when injected with preparations of protein origin. Patients treated with Ilaris® for CAPS, sJIA and gouty arthritis, antibodies to the drug were detected in 1.5; 3 and 2% of cases, respectively. The relationship between the formation of antibodies, clinical response and development of adverse events is not revealed.

Special patient groups

Use in patients aged ≤18 years (patients with CAPS). In children from 2 to 17 years, there were no 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 of age. 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 in the event of the development of severe adverse reactions, incl. Not specified in the instructions.

Interaction

Special studies on the interaction of Ilaris® with other medications have not been conducted. 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, the expression of the cytochrome P450 isoenzymes in the liver can be normalized by the administration of potent cytokine inhibitors. 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 the concentration of the active substance in the blood plasma).

In clinical trials, the safe use of Ilaris® with antidotal agents has been noted.

The drug is not recommended to be administered simultaneously with TNF inhibitors and other blockers of 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 performed (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 trials conducted in adult healthy volunteers indicate that a single dose of 300 mg of Ilaris® 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).

Dosing and Administration

SC in those parts of the body where there is subcutaneous fat: in the abdomen, the front of the thighs, the posterolateral surface of the shoulders (see instructions for use).

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

Gouty Arthritis

The recommended dose of the drug in adults is 150 mg, the drug is administered during an attack of gouty arthritis, one-time. 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. Patients who responded to the treatment, the repeated administration of Ilaris® is possible at least 12 weeks after the previous injection.

Use Ilaris ® for the treatment of attacks of gouty arthritis should be as necessary. Optimization of hyperuricemia control should be performed with appropriate anti-gouty drugs.

The drug therapy can be initiated and conducted only by a doctor who has experience in the diagnosis and treatment of patients with gouty arthritis.

CAPS

The recommended starting dose of Ilaris® for patients with CAPS:

Adults and children ≥4 years, depending on the weight, the body is appointed:

- body weight> 40 kg - 150 mg;

- body weight ≥15 kg and ≤40 kg - 2 mg / kg;

- body weight ≥ 7.5 kg and <15 kg - 4 mg / kg.

In children from 2 and <4 years with a body weight of ≥ 7.5 kg, the drug is used at a rate of 4 mg / kg.

The drug is given p / k - 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 resolving the rash and other symptoms of inflammation is not observed within 7 days after the first injection of Ilaris®, a second injection of the drug in a dose of 150 mg (With a body weight> 40 kg) or 2 mg / kg (with body weight ≥15 kg and ≤40 kg). If the subsequent complete clinical response is achieved in these patients, maintenance therapy with Ilaris® 300 mg, 1 injection at 8-week intervals (with a body weight> 40 kg) or 4 mg / kg, 1 injection at an interval of 8 weeks (with 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 carry out the third injection of Ilaris® at a dose of 300 mg, 1 injection at an interval of 8 weeks (at a body weight> 40 kg) or 4 mg / kg (body weight ≥ 15 kg and ≤40 kg). If the subsequent complete clinical response is achieved in these patients, maintenance therapy with Ilaris® 600 mg, 1 injection at 8-week intervals (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 intervals of 8 weeks is recommended.

The clinical experience of using the drug with a dosage interval of <4 weeks or a dose> 600 mg or 8 mg / kg is limited.

An increase in 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.

In SJUIA, the recommended dose for patients with a body weight of ≥ 7.5 kg is 4 mg / kg (with an increase to 300 mg) every 4 weeks in the form of a SC injection.

After learning the technique of injections, patients or persons caring for them can independently administer the drug under proper control (if the doctor deems it necessary). Patients or persons caring for them should be instructed in the technique of solution preparation and the rules for using syringes and needles suitable for injection.

Special patient groups

Patients ≥65 years of age. No dose adjustment is required in patients aged ≥65 years.

Patients ≤18 years of age. Gouty arthritis - there is no data on the use of Ilaris ® for the treatment of gouty arthritis in children and adolescents ≤18 years. CAPS and SJUA - the experience of using kanakinumab in children younger than 2 years is limited.

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

Violation of the function of the liver. In patients with impaired liver 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.

Instructions for use

I. Ilaris ® preparation, complete with a vial of lyophilizate without solvent

It should be noted that the preparation for injection is about 30 minutes.

Before the beginning it is necessary: to find a clean, convenient place for the injection; Wash hands with soap; Check expiry date on vials and syringes; Do not use the drug if the expiration date (the last day of the month indicated on the vial); Always use new unopened needles and syringes; Avoid touching the needles and upper parts of the vials.

It is necessary to prepare the necessary materials: 1 fl. With lyophilisate of Ilaris® (stored refrigerated at a temperature of 2 to 8 ° C) is included in the package.

For the injection in addition to the bottle with the preparation Ilaris®, it is necessary: 1 fl. With water for injection; 1 syringe (1 ml volume); 1 large needle (50 mm) for solution (needle for dilution); 1 small needle for injection (13 mm), alcohol tampons; Clean, dry cotton swabs; Sticking plaster; Container for used bottles, needles and syringe.

Preparation of solution of Ilaris® preparation

1. Remove the protective cover from the bottle with the preparation Ilaris® and the solvent, without touching the vials of the vials. Wipe them with an alcohol swab.

2. Open the package with a syringe and a dilution needle. Put the needle on the syringe.

3. Carefully remove the protective cap from the needle and set it aside. Pull the syringe plunger back to the 1 ml mark, filling the syringe with air. Insert the needle into the vial of water for injection through the center of the rubber stopper.

4. Gently push the syringe plunger from top to bottom so that air enters the water bottle.

5. Turn the vial with the needle and syringe inserted into it and bring it to your eyes.

6. Make sure that the end of the needle is covered with water, and slowly move the plunger of the syringe down, slightly below the 1 ml mark. If there are air bubbles in the syringe, remove them, according to the instructions received from the health professional.

7. Make sure that 1 ml of water for injection is in the syringe, and then pull the needle out of the vial (there will be water in the vial - this is normal).

8. Insert the needle with the syringe into the center of the bottle stopper with the Ilaris® preparation, trying not to touch the needle and the stopper of the vial, and slowly release all the water (1 ml) from the syringe into the vial.

9. Carefully remove the syringe from the needle from the vial, place the protective cap on the needle.

10. Do not touch the rubber stopper of the vial, tilt it at an angle of 45 ° and rotate for 1 minute. Do not shake. Then set aside the bottle for 5 minutes.

11. Then gently rotate the bottle in the frontal plane 10 times, without touching the rubber stopper.

12. Remove the vial again for 15 minutes, at room temperature, to obtain a clear solution. Do not shake. Do not use the solution if foreign particles are present.

13. Make sure that the entire solution is at the bottom of the vial. If drops of solution remain on the plug, gently knock on the wall of the vial. The solution should be transparent and free from foreign visible particles. If the prepared solution is not used immediately, it is necessary to put it in the refrigerator (at a temperature of 2-8 ° C) and use within 24 hours.

Preparation for injection

14. Wipe the rubber stopper of the vial with the prepared solution of Ilaris® with a new alcohol swab.

15. Remove the protective cap from the needle (the needle for solution), pull the syringe piston to the 1 ml mark, thereby tying air into it. Insert the needle into the center of the rubber bottle stopper with Ilaris® and release all air from the syringe into it (do not let the air directly into the solution).

16. Do not turn the vial with the syringe. Lower the needle to the bottom of the vial.

17. Tilt the bottle so that it is possible to collect the required amount of solution. Note: the required amount corresponds to the prescribed dose (from 0.2 to 1 ml).

18. Slowly pull the piston to the required mark (from 0.2 to 1 ml), dial the required amount of the prepared solution of Ilaris ®. Care must be taken so that air does not get into the syringe with the solution. Make sure that the amount of solution needed for the injection is in the syringe.

19. Remove the syringe from the needle from the vial (unused solution of Ilaris® may remain in the vial). Put the protective cap on the needle, with which the drug was taken, and remove it from the syringe. Remove the needle in a special container. Open the package with the injection needle and put it on the syringe. Put the syringe aside.

Injection

20. Choose a site for injection: the upper part of the shoulder, the upper part of the hip, abdomen or buttock. Do not inject into a place where redness, rash, bruising, disfiguring of the skin or the surface of the skin are uneven. Avoid injection into scar tissue. This can cause insufficient exposure of kanakinumab. Avoid getting into a blood vessel.

21. Wipe the intended site of injection with a new alcoholic napkin and wait for the surface of the skin to become dry. Remove the protective cap from the injection needle.

22. Gently squeeze the skin above the injection site. Take the syringe at an angle of 90 ° and gently smoothly move the needle completely into the skin.

23. Do not remove the needle until the drug is completely injected. Release the skin fold and remove the needle. Do not use the syringe and needle again. Use the used needles and syringe in a special container.

After injection

24. Do not wipe the injection site. If bleeding is noted at the injection site, use a dry tampon to lightly press the injection site and hold it in this position for 1-2 minutes or until bleeding ceases. Then seal the injection site with a patch.

25. Remove used needles and syringe in a special container for subsequent disposal. Never re-use the syringe and needle. Neither the remnants of the solution nor the remainder of the water for injection can be used again. Every time you need to make sure that the containers with water for injection and Ilaris® (if left) are discarded. Make sure that children can not reach the container with used needles and a syringe.

II. Preparation Ilaris®, complete with a bottle of lyophilizate complete with a solvent

Contents of the ready-made kit: a bottle of powder; A vial of solvent; Syringe for injection per 1 ml; Safety needle; Bottle adapter (2 pcs.); Cleaning (alcohol) wipes (4 pcs.).

Mixing Ilaris® with the solvent

1. Remove the flip cover from the powder vial, then wipe the rubber stopper with a fresh cleaning cloth. Note: do not touch the rubbed rubber stopper.

2. Take one of the blister-trays with the vial adapters and, holding the blister-tray firmly, completely remove the film cover from it. Care must be taken not to touch the bottle adapter. Do not remove the vial adapter from the blister tray.

3. Place the powder bottle on a flat surface. Holding on to the blister tray, place the vial adapter on the top of the vial with the powder and push it all the way down until it clicks into place on the vial.

4. Hold the blister tray by its top, lift it vertically upwards and remove the blister tray from the bottle adapter. Note: If the vial adapter is incorrectly placed, do not touch it. Before correcting the position of the adapter, place the blister tray on it again.

5. To attach the second adapter to the vial containing the solvent containing water for injection, repeat steps 1-4. Note: now both adapters are on both vials, and they are ready for use.

6. After adapters are put on both vials, open the syringe packing, pulling off the film from it, and take out the syringe. Try not to touch the tip of the syringe, pull the piston down, letting in the syringe 1 ml of air. Note: filling the syringe with air (1 ml) facilitates the subsequent intake of water for injection into the syringe and reduces the formation of air bubbles.

7. Take the vial with the solvent and gently screw the syringe onto the vial adapter. Do not make efforts. Note: care must be taken not to touch the tip of the syringe or the bottle adapter. At this stage, the needle is not required.

8. Slowly push the piston down to the very end, to inject 1 ml of air into the vial with the solvent. Hold the piston in this position.

9. Turn the syringe back so that the solvent bottle turns upside down and lift it up to eye level. Slowly pull the piston down so as to take 1 ml of water into the syringe. Continuing to hold the bottle in the direction of the bottom up, check if there are large air bubbles in the syringe.

10. Remove large air bubbles from the syringe by doing the following procedure: tap on the syringe lightly so that large air bubbles rise upward. Carefully push the piston up so that large air bubbles enter the bottle. Again slowly pull the plunger back to the 1 ml mark. Repeat these steps until all of the large bubbles have been removed. Make sure that the syringe contains 1 ml of water. Holding on to the piston, remove the syringe from the vial, previously placed on a clean and level surface to avoid splashing. Note: some of the water will remain in the vial with the solvent.

11. Put a bottle of powder on a clean and level surface. Screw a syringe containing 1 ml of water into the bottle adapter. Do not make efforts. Note: Take care not to touch the tip of the syringe or the top of the bottle with your fingers. At this stage, the needle is not required.

12. Slowly push the piston down to the very end to transfer 1 ml of water from the syringe into the vial of powder. Do not disconnect the syringe yet.

13. While making circular movements, slowly turning the syringe with the flask at an angle of 45 ° for at least 1 minute, do not shake the syringe and the vial.

14. Place the vial with the syringe on a flat surface and leave it for 5 minutes. Note: the piston may rise slightly. This can happen because the pressure in the vial is slightly increased.

15. After 5 minutes, push the syringe piston all the way down again. Carefully turn the vial with the syringe 10 times in a vertical plane. Do not shake the syringe and the bottle.

16. Give the bottle with a syringe to stand for another 15 minutes. After 15 minutes, without shaking the bottle, make sure that the solution is not cloudy and contains no particles. A foam may be present at the top of the solution; This should not be a concern and does not interfere with the next stage. If particles are still present in the solution, repeat step 15 above, then leave the vial with a syringe for another 5 minutes, then check again for any particles in the solution. If the solution is not cloudy and contains no particles, select the assigned dose as described in the next section. Note: If the solution is not used immediately after preparation, it should be placed in the refrigerator (at a temperature of 2-8 ° C) and used within 24 hours.

Preparation for injection

17. Turn the vial with the syringe upside down and gently pull the piston down so that 1 ml of the solution is taken into the syringe. Do not disconnect the syringe yet.

Slowly push the piston to the very end to transfer the entire solution back to the vial. Note: The goal of this stage is to ensure complete mixing of the solution and to reduce the formation of air bubbles.

18. Lift the syringe to eye level and again slowly pull the piston back to select the required volume of solution. Note: The amount required depends on the dose to be administered (from 0.2 to 1 ml). What kind of volume of solution you need to enter, the doctor will say. Continuing to hold the bottle upside down, check to see if there are large air bubbles in the solution drawn into the syringe (some of the solution may remain in the vial).

19. Remove large air bubbles from the solution by doing the following procedure: tap the syringe lightly so that large air bubbles rise up; Gently push the piston up so that large air bubbles enter the vial; Again slowly pull the piston back to the mark corresponding to the prescribed dose. Repeat these steps until all of the large bubbles have been removed. Make sure that the volume of solution in the syringe corresponds to the prescribed dose. Holding on to the piston, remove the syringe from the vial, previously placed on a clean and level surface to avoid splashing. Place the prepared syringe on a clean and level surface. Note: do not touch the tip of the syringe.

20. Remove the safe needle from the blister pack and screw it onto the prepared syringe. Note: Do not touch the tip of the syringe or needle. Move the flap in the direction of the syringe housing.

The technique of injection, the choice of the injection site, the behavior after injection - see above, in section I.

Overdose

No confirmed cases of drug overdose have been reported.

Treatment: care should be taken to identify possible AEs, and if necessary, appropriate symptomatic therapy should be prescribed.

Special instructions

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

Neutropenia

Against the background of therapy with IL-1 inhibitors, including the Ilaris® preparation, neutropenia (absolute neutrophil count (AFN) below 1.5 × 109 / L) was mainly observed in patients with other diseases, rather than with different phenotypes of CAPS. Before the beginning of treatment with the drug, 1-2 months after the beginning and periodically during 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 ACN on the background of drug therapy, it is necessary to ensure proper monitoring of patients' condition and, if necessary, to consider the termination of treatment with the drug.

Malignant neoplasms

There are reports of cases of development of malignant neoplasms in patients receiving Ilaris®, but the risk of developing malignant tumors against antibodies that bind IL-1 is unknown.

Infectious diseases

The use of Ilaris® may be accompanied by an increase in the incidence of serious infections, so patients should be under the supervision of a physician to identify the symptoms of infection during and after therapy with the drug. Treatment with 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 the drug was used, approximately 12% of patients with different CAPS phenotypes had positive tuberculin test results 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 screened for active or latent TB infection, including history and appropriate screening tests, such as tuberculin test, IGRA (Interferon-Gamma-Release-Assay) tests 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 treatment 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 macrophage activation in patients with SJIA

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 flow 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 SJUA, but they do not allow for definitive conclusions.

Influence on the ability to drive vehicles and work with machinery. Patients who, when Ilaris ® is used, get vertigo, it is necessary to refrain from controlling vehicles or mechanisms until this undesirable phenomenon disappears completely.

Release form

Lyophilizate for the preparation of a solution for subcutaneous administration, 150 mg. In a bottle of colorless glass with a capacity of 6 ml, corked with a rubber stopper, covered with an aluminum cap with a plastic lid. On 1 fl. In a pack.

Lyophilizate for the preparation of a solution for subcutaneous administration, 150 mg with a solvent - water for injection.

The 1st plastic tray contains: a vial of lyophilizate - a bottle of colorless glass (type 1, Ph. Eur./USP), a capacity of 6 ml, sealed with a rubber stopper, covered with an aluminum cap with a plastic flip-off cover (flip-off device). Vial with solvent - in a bottle of colorless glass (type 1, Ph. Eur./USP) with a capacity of 6 ml, closed with an aluminum cap with a plastic flip-off cover (flip-off device), 5 ml of water for injection.

The 2nd plastic pallet contains a set of devices for injection: 1 sterile syringe with Luer-Lock system, 1 safe sterile injection needle, 2 Luer-Lock adapters to the bottle, 4 alcohol wipes.

2 plastic pallet in a pack.

Manufacturer

Novartis Pharma Stein AG. Lichtstraße 35, 4056, Basel, Switzerland.

The owner of the registration certificate: Novartis Pharma AG. Switzerland.

Additional information about the drug can be obtained at: 125315, Moscow

Conditions of supply of pharmacies

On prescription.

Storage conditions of the drug Ilaris

In the dark place at a temperature of 2-8 ° C.

Keep out of the reach of children.

Shelf life of the drug Ilaris

Lyophilizate for the preparation of a solution for subcutaneous administration of 150 mg - 3 years. Solvent - 5 years. The expiration date of the kit is determined by the earlier expiry date of the component included in the kit.

Do not use after the expiry date printed on the package.