Composition, form of production and packaging
Liofilizate for the preparation of a solution for s / c injection in the form of a white powder; The applied solvent is a clear, colorless liquid.
1 f.
cannacinumab 150 mg
Excipients: L-histidine - 2.801 mg, L-histidine hydrochloride monohydrate - 1.673 mg, polysorbate 80 - 0.6 mg, sucrose - 92.35 mg, hydrochloric acid 1M - up to pH 6.5.
Solvent: water d / u - 5 ml.
Vials of colorless glass with a capacity of 6 ml (1) complete with a solvent (1 pc.) - plastic pallets (1) with a device d / and in a pallet plastic - packs cardboard.
Liofilizate for the preparation of a solution for s / c injection in the form of a white powder.
1 f.
cannacinumab 150 mg
Excipients: L-histidine - 2.801 mg, L-histidine hydrochloride monohydrate - 1.673 mg, polysorbate 80 - 0.6 mg, sucrose - 92.35 mg, hydrochloric acid 1M - up to pH 6.5.
Vials of colorless glass with a capacity of 6 ml (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
PHARMACHOLOGIC EFFECT
Immunosuppressant, monoclonal antibodies to interleukin-1 ?.
Kanakinumab is a fully human monoclonal antibody IgG1 / kappa isotype to interleukin-1? (IL-1?). Kanakinumab binds to human IL-1 with high affinity, thus neutralizing its biologic action, blocking the interaction of IL-1? with its receptors, IL-1? -induced activation of genes and production of inflammatory mediators, such as IL-6 and COX-2.
In the treatment of patients with systemic juvenile idiopathic arthritis (sIIA), there was rapid rapid improvement in 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 most patients. In 33% of patients on 29 laziness of therapy, there was an improvement in the course of the disease by 100% do with the pediatric criteria of the American College of Rheumatology compared with no effect in the placebo group. The use of puma aba can significantly reduce or eliminate the use of glucocorticosteroid in the treatment of SJUIA. Kanakinumab allows to extend the time interval to exacerbate the disease, 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 autoinflammatory syndrome / familial cold urticaria (FCAS / FCU), the McLean- (Muckle-Wells Syndrome, MWS) and multisystem infantile inflammatory disease / chronic neonatal neurological skin-articular syndrome (NOMID / CINCA), cannacinumab reduces local severity x and systemic inflammatory reactions caused by excessive production of IL-1 ?.When using the drug in patients with acute attacks of gouty arthritis, the concentration of laboratory markers of inflammation (C-reactive protein (CRP), serum amyloid A (CAA)) decreases, signs of inflammation of the affected joint (pain, swelling, redness) disappear for a short time.
On the background of 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 a visual analogue scale) was observed compared to the control group. Against the backdrop of the use of Ilaris В®, a decrease in the intensity of pain is observed 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 was observed at 62% during the 12 weeks of therapy and at 56% for 24 weeks of therapy compared with the control group.
Efficacy of Ilaris in gouty arthritis was comparable in patients aged ≥65 and ≥65 years. When using kanakinumab in patients with different phenotypes of CAPS, the following manifestations of the disease have already been observed during the first day: fever, increased fatigue, skin rash, arthralgia, myalgia, headache / migraine, conjunctivitis, weakness, and a decrease (for several days) production of inflammatory markers, including both 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 decrease (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 develop recurrences of the disease (in the group of patients who did not receive the drug, relapses were observed in 81% of cases).
PHARMACOKINETICS
Absorption
In adult patients with different phenotypes of CAPS after a single subcutaneous injection of 150 mg of the drug
TC max kanakinumab is about 7 days. The average final half-life is 26 days. With subcutaneous administration of kanakinumab, absolute bioavailability is 66% (population pharmacokinetic analysis in patients with CAPS, including children aged 2 years). Parameters of the kinetics kinetics (the area under the concentration-time curve (AUC) and C max increase in proportion to the dose in the dose range from 0.30 lO 10.0 mg / kg with intravenous infusion or with subcutaneous injection (in a dose of 150 to 600 mg).
Distribution
Kanakinumab binds to serum IL-1 ?. The volume of distribution (Vss) varies with body weight. V 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 patients with gouty arthritis - 7.9 liters with a body weight of 93 kg. When subcutaneously injected for 6 months in a vine 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
Clearance (Cl) 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 with a body weight of 93 kg. After accounting for weight differences, there was no significant difference in the pharmacokinetic properties of cannacinumab in patients with gouty arthritis, with various phenotypes of CAPS to the SUIA.
With repeated use of the drug, there is no increase in Cl 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 the patients do not affect the drug's makokinetics.
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 C max 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. The pharmacokinetic characteristics in patients with CAPS and SJUIA are similar. With subcutaneous administration of kakakinumab at a dose of 4 mg / kg every 4 weeks in patients with SUAA, the values ​​of AUC and C max were similar in the age group 2 to 20 years.
Patients aged> 65 years
There was no difference in the pharmacokinetic parameters based on Cl 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 ineffectiveness, intolerance or in the presence of contraindications to the use of NSAIDs and / or colchicine and when it is not possible to conduct therapy with repeated courses of GCS;
Cryopyrin-associated Periodic Syndrome (CAPS) in adults and children aged 2 years and older, including:
- Family cold auto-inflammatory syndrome (FCAS) / Family cold urticaria (FCU);
- Macle-Wales Syndrome (MWS);
- Infant multisystem inflammatory disease (NOMID) / chronic infant neurologic skin-articular syndrome (CINCA).
The active phase of systemic juvenile idiopathic arthritis (sIIA) in children aged 2 years and older.
DOSING MODE
The drug (lyophilizate) is dissolved in 1 ml of water for injection. Injections are conducted subcutaneously in those parts of the body where there is subcutaneous fatty tissue: in the stomach, the anterior surface of the bender, the posterolateral surface of the shoulders.
Gouty Arthritis
The recommended dose of the drug for adults is 150 mg, the drug is administered during an attack of gouty arthritis one-time sc. 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 В® should not be re-injected. Repeated administration of Ilaris is possible, at least 12 weeks after the previous injection.
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 В® for patients with cryopyrin-associated periodic syndrome:
Adults and children? 4 years , depending on body weight appoint:
- patients with a body weight of? 40 kg - 150 mg;
- patients with a body weight of? 15 kg and <40kg - 2 mg / kg;
- patients with a body weight of? 7.5 kg and <15kg? 4 mg / kg.
Children aged 2 years and < 4 years with a body weight of? 7.5 kg are prescribed 4 mg / kg. The drug is injected n / a 1 injection at an interval 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 ) and 2 mg / kg (with a body weight of? 15 kg and? 40 kg ). When the complete clinical response is achieved in the future, these patients recommend 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 ( body weight ≥15 kg and ≥40 kg ) - 1 injection at an interval of 8 weeks.
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 the drug Ilaris В® in a dose of 300 mg 1 injection at an interval of 8 weeks (with a body weight> 40 kg) or 4 mg / kg (with a body weight of? 15 kg and? 40 kg). When a complete clinical response is achieved in the future, these patients recommend maintenance therapy with Ilaris В® in a dose of 600 mg 1 injection at an interval of 8 weeks (with 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 patients with a starting dose of 4 mg / kg satisfactory clinical effect is not observed within 7 days after the first injection, it is possible to conduct a second injection of Ilaris В® in a dose of 4 mg / kg. 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 an interval of less than 4 weeks is limited.
Increasing the dose of Ilaris В® 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.
With 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 subcutaneous 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 preparing the solution, syringes and needles suitable for injection.
To patients of advanced age? 65 years do not require dose adjustment.
Children and adolescents aged 18 years or older do not have data on the use of Ilaris В® for the treatment of gouty arthritis.
Since the experience of using kanakinumab for the treatment of cryopirin-associated periodic syndrome in children younger than 2 years is limited, the drug is not recommended for this category of patients.
Patients with impaired renal function do not need dose adjustment. It should be borne in mind that the experience of clinical use in this category of patients is limited.
In patients with impaired hepatic function, the efficacy and safety of the drug have not been studied. Because Ilaris В® is a human IgG, it is suggested that liver failure does not affect the pharmacokinetics of this drug.
Instructions for use
For injection, you need:
A. one ampoule / vial of water for injection
B. one syringe (1.0 ml volume)
C. one large needle (50 mm) for solution preparation
D. one small needle for SC injection (13 mm)
E. alcohol swabs
F. clean, dry tampons
G. Adhesive plaster
H. container for used needles and syringes
Preparation of solution of Ilaris В®
1. Remove the protective cover from the bottle with Ilaris В® , without touching the stopper of the vial. Wipe it with alcohol
tampon. Also wipe and vial / ampoule with water for injection (A).
2. Open the package with a syringe (B) and a large needle (C). Put the needle on the syringe.
3. Carefully remove the protective cap from the needle and set it aside.
4. Collect 1.0 ml of water for injection into the syringe.
5. Insert the needle with the syringe into the center of the vial plug with Ilaris В® and slowly release all the water (1.0 ml) from the syringe into the vial.
6. Remove the syringe from the needle from the vial, put a protective cap on the needle.
7. Without touching the rubber stopper of the vial, tilt it at an angle of 45 В° and rotate for 1 minute. Not
shake. Then put the bottle for 5 minutes.
8. Then gently turn the bottle down and back 10 times, without touching the rubber stopper.
9. 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 in it.
10. Make sure that the entire solution is at the bottom of the vial. If drops of solution remain on the plug, you should tap the bottle slightly. The solution should be transparent and free from foreign visible particles.
If it is not necessary to use the prepared solution immediately, it should be placed in the refrigerator (at a temperature of 2 В° to 8 В° C) and used within 24 hours.
Preparation for injection
1. Wipe the rubber stopper of the vial with the prepared solution of Ilaris В® with a new alcohol swab.
2. Remove the protective cap from the needle (the needle for solution preparation), pull the syringe piston to the 1.0 ml mark, thereby tying air into it. Insert the needle into the center of the rubber bottle stopper with Ilaris В® and release all air from the syringe into it (do not let the air directly into the solution).
3. Do not turn the vial with the syringe. Insert the needle to the bottom of the vial.
4. Tilt the bottle so that you can collect the required amount of solution. The required amount corresponds to the prescribed dose (from 0.2 ml to 1.0 ml). Slowly pulling the piston back to the required mark (from 0.2 ml to 1.0 ml), dial the required amount of the prepared solution of Ilaris В® . Care should be taken so that air does not get into the syringe with the solution. It should be ensured that the amount of solution needed for injection is in the syringe. Remove the syringe from the needle from the vial. Put the protective cap on the needle with which the drug was taken and remove it from the syringe. Remove it in a special container.
5. Open the package with the injection needle and put it on the syringe. Put the syringe aside.
Injection
1. Choose a site for injection: upper arm, upper thigh, abdomen or buttock. Do not inject into a place where redness is observed, a rash in the hematoma, a violation of the integrity of the skin or the surface of the skin is uneven. Avoid injection into scar tissue, because this can cause insufficient exposure of kanakinumab. Avoid getting into a blood vessel. It is necessary to 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.
2. Carefully squeeze the skin over the injection site. Take the syringe at an angle of 90 В° and gently push it completely into the skin.
3. 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. The used needles and syringe should be put in a special container.
After injection
1.Do not wipe the injection site. If bleeding noted at the injection site, with a dry swab to push lightly on the injection site and to hold it in this position for 1-2 minutes or until until bleeding stops. Followed seal adhesive injection site.
2. Harvesting the used needle and syringe into a special container for subsequent disposal. Never reuse a syringe and needle.
No residues of the solution nor the remaining water for injection may not be used again. Each time make sure that the container with water remains injectable and drug Ilaris В® (if it is) thrown out. Make sure that children can not reach the container with used needles and syringes.
SIDE EFFECT
In applying the drug Ilaris В® in clinical studies showed an increase in infectious diseases, preferably nasopharyngitis and upper respiratory tract infections. For infectious diseases often it was mild or moderate severity, but were also observed cases of severe infectious diseases. As a rule, the infection were stopped after the standard anti-infective therapy. There were isolated or rare cases of opportunistic infections in patients receiving prerarata Ilaris В® , however, the relationship of these diseases with taking the drug is not known.
To assess the frequency of adverse reactions identified in the placebo-controlled clinical trials (using a preparation for the treatment kriopirin-associated periodic syndrome at a dose of 150 mg if body weight> 40 kg and 2 mg / kg body weight of? 15 kg? 40 kg and sJIA in the treatment in patients aged 2 to 20 years), and for treatment of acute attacks of gouty arthritis at doses of from 10 mg to 300 mg active-controlled trial, the following criteria are used (according to WHO classification): very often (1/10? ), often (? 1/100, <1/10), uncommon (? 1/1000, <1/100) rare (? 1/10 000, <1/1000), very rare (<1/10 000), the frequency is unknown (not enough data to assess the incidence).
Gouty arthritis is
infectious and parasitic diseases:very often - infection, in particular, nasopharyngitis, sinusitis (viral), upper respiratory tract infections, bronchitis, influenza, urinary tract infections, gastroenteritis, panniculitis, pneumonia, pharyngitis, ear infections.
From the nervous system: often - dizziness / vertigo.
On the part of the musculoskeletal system: often - pain in the back.
From hemopoiesis system: often - thrombocytopenia, leukopenia; rarely - neutropenia.
From a metabolism: often - dyslipidemia.
On the part of the ear and labyrinth disorders: often - dizziness.
From the digestive system: often - vomiting; infrequently - gastroesophageal reflux disease.
Of the liver and biliary tract: often - increase in bilirubin, increase in ACT activity.
General reactions: rarely - weakness.
Local reactions: often - a reaction to the injection site. Reactions at the site of injection were observed in 1.2% of patients receiving treatment with Ilaris В® in clinical studies.
Changes in laboratory parameters
Complete blood count: ? Reduction in the number of white blood cells is equal to or less than 0.8 lower limit of normal was observed in 6.7% of patients receiving treatment with Ilaris В® compared to 1.4% of patients treated with triamcinolone. Reduction in the absolute neutrophil count is less than 1 Г— 10 9/ l was observed in 2% of patients in comparative studies of gouty arthritis. There were also isolated cases of reducing the number of neutrophils below 0.5 Г— 10 9 / L. In 12.7% of the therapy kanakinumabom observed mild and transient decrease in the number of platelets (in the range of 75 Г— 10 9 / l) to the lower limit of normal (the reference drug, this decrease was observed in 7.7% of cases).
Uric acid: the therapy kanakinumabom observed a transient increase in the concentration of uric acid (approximately 0.6 mg / dl). Preparation Ilaris В® does not reduce the ability protivopodagricakih means to reduce the concentration of uric acid in the combined use.
AST / ALT:kanakinumabom the therapy may develop mild to moderate severity increasing the activity of AST / ALT.
Triglycerides: the therapy kanakinumabom, on average, increase in the concentration of TG in the blood plasma by 33.8 mg / dl and group application triamcinolone - slight decrease by 3.1 mg / dl. Increased TG concentration is more than 5 times compared to the ULN is marked in 2.4% of cases in the group of application kanakinumaba in 0.7% of cases in the application of triamcinolone group. The clinical relevance of this observation is unknown.
Kriopirin-associated periodic syndrome
Infectious and parasitic diseases: very often - nasopharyngitis; often - urinary tract infection; upper respiratory tract infection, viral infection.
On the part of the organ of hearing and labyrinth disorders: very often - vertigo *.
Local reactions: often - a reaction at the site of drug **.
* Symptom of vertigo, in some cases, seen as a serious adverse reaction; all the episodes of vertigo resolved despite continued drug therapy.
** adverse reaction was identified using a questionnaire to the physician.
During the long, open-label trials with escalating doses noted an increased frequency of infections (gastroenteritis, respiratory tract infection and upper respiratory tract infections), nausea and dizziness in the group of patients receiving doses of 600 mg of the drug or 8 mg / kg, compared with the groups gets another dose.
Changes in laboratory parameters
Complete blood analysis
Using the drug in clinical trials with CAPS patients showed an increase in hemoglobin and reduced the number of leukocytes, neutrophils and platelets. However, these changes were probably associated with reduced severity of inflammatory process on a background of drug therapy and had no clinical significance.
Liver Enzymes
In rare cases, patients with the CAPS, treated with the drug, there was an increase in liver transaminases.
Bilirubin
In some cases during therapy with the drug in patients with CAPS patients had asymptomatic slight increase of serum bilirubin, is not accompanied by an increase in liver transaminases.
sJIA
Infectious and parasitic diseases:
very often - infection (for example, nasopharyngitis, viral upper respiratory tract infection, pneumonia, rhinitis, pharyngitis, tonsillitis, sinusitis, urinary tract infections vodatih, gastroenteritis, viral infection).
Violations of the digestive system:
very often - pain in the upper abdomen.
Violations of the skin and subcutaneous tissue disorders:
very often - reactions at the injection site mild drug *.
often - a reaction at the site of moderate severity of the drug *.
* - did not lead to the termination of the study.
Changes in laboratory parameters
Complete blood count
Reducing the number of leukocytes <0.8x the lower limit of normal was observed in 10.4% of patients receiving treatment with Ilaris В® , compared with 4.0% in the placebo group. A transient decrease in absolute neutrophil count <1x10 9 / l was observed in 6.0% of patients receiving treatment with Ilaris В® , compared with 2.0% in the placebo group. Said one case reducing the absolute neutrophil count <0,5h10 9 / l in the treatment of drug Ilaris В® . Mild and transient decrease in the range of 75 Г— 10 9 L to the lower limit platelet rules observed in 6.3% of patients receiving drug Ilaris В® , compared with 2.0% in the placebo group.
Liver enzymes
threefold increase in ALT and / or ACT as compared with the upper limit of normal was observed in 4.1% of patients receiving treatment with Ilaris В® , compared with 2.0% in the placebo group. Upon subsequent examination showed normalization of indicators.
Hypersensitivity reactions
In applying the drug Ilaris В® in clinical studies reported adverse events regarded by physicians as a hypersensitivity reaction. In most cases these reactions have been expressed in mild. In applying the drug was observed of anaphylactoid or anaphylactic reactions. However for a drug Ilaris В®we can not exclude the risk of severe hypersensitivity reactions, which may occur when injected, drugs of protein origin. At 1% of patients treated with the drug Ilaris В® over CAPS, gouty arthritis and sJIA detected antibodies to the drug in the 1.5%, 3% and 2%, respectively. The relationship between the formation of antibodies, clinical response and the development of adverse events have been detected.
Use in children and adolescents under the age of 18 years (patients with CAPS)
in children aged 2 to 17 years are no clinically significant differences in safety and tolerability of the drug Ilaris В®Including a common frequency and tyazhetst infections, compared with the general population of patients. The most common in this group of patients had an upper respiratory infection.
In applying the drug Ilaris В® children overall frequency and severity of infections corresponded to those of adults.
Use in patients? 65
There were no differences in the safety profile of the drug in these patients.
The patient should be informed of the need to see a doctor in case of any adverse reactions.
CONTRAINDICATIONS
- acute infectious diseases;
- Pregnancy;
- Lactation (breast-feeding)
- Children under 2 years of age (safety and efficacy for this category of patients studied is not enough);
- Hypersensitivity to the components of the drug.
With caution should use the drug in elderly patients; When specifying a history of recurrent infections or any conditions that predispose to the development of infection.
PREGNANCY AND LACTATION
There is limited information on the use of the drug Ilaris В® in pregnancy.
Women must use effective contraception during therapy with Ilaris В® and within 3 months after the application of the last dose.
It is unknown whether kanakinumab excreted in breast milk. If necessary, use of the mother during lactation should stop breastfeeding.
In experimental studies on animals have revealed the drug was not a reproductive toxicant.
APPLICATION FOR FUNCTIONS OF THE LIVER
Patients with impaired renal function dose adjustment is required. It should be borne in mind that the clinical application experience is limited in these patients.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
In patients with impaired hepatic function efficacy and safety of the drug has not been studied. Because Ilaris В® - human IgG, it is assumed that hepatic failure does not affect the pharmacokinetics of the drug.
APPLICATION FOR CHILDREN
Contraindicated: children under 4 years of age and weighing less than 15 kg (safety and efficacy have not been studied sufficiently specified category of patients).
APPLICATION IN ELDERLY PATIENTS
With caution should be used in elderly patients.
SPECIAL INSTRUCTIONS
Previous applications Ilaris drug В® patients without established mutations in gene NLRP3 limited.
Neutropenia
The therapy inhibitors of IL-1 ?, including drug Ilaris В® , neutropenia (absolute neutrophil count (ANC) less than 1.5? 10%) generally observed in patients with other diseases, but not in patients with different phenotypes CAPS. Prior to the beginning of treatment, 1-2 months after the start and periodically during drug therapy should be carried out by standard clinical blood analysis to identify neutropenia. Patients with neutropenia treatment with Ilaris В®should start only after normalization of the number of neutrophils. In identifying the decrease in the ANC drug therapy should ensure proper control over the patient's condition and consider discontinuing treatment with the drug if necessary.
Malignancies
have been reported cases of malignancies in patients receiving therapy with Ilaris В® , but the risk of malignancies during therapy with antibodies that bind to IL-1 is unknown.
Infectious disease
The use Ilaris preparation В®It may be associated with an increased incidence of serious infections, so patients should be under the supervision of a doctor, in order to identify symptoms of infection during and after treatment with the drug. With the development of severe infections, treatment with Ilaris В® should not be initiated or continued.
The development of serious and systemic infections during therapy with the drug was accompanied by clinical symptoms (fever) and increased production of inflammatory markers (C-reactive protein in serum). However, since we can not exclude the possibility of infectious processes without these manifestations, when using the drug should ensure proper monitoring of patients.
In applying the drug in approximately 12% of patients with different phenotypes observed positive results of CAPS tuberculin test without any sign of TB infection (latent or active). No data on increased risk of reactivation of tuberculosis or in the treatment of opportunistic infections of monoclonal antibodies to IL-1 (e.g., drug Ilaris В® ). Before the appointment of the drug Ilaris В®you need to conduct a survey of all patients in order to identify active or latent tuberculosis infection (including medical history and conduct appropriate screening tests, eg tuberculin skin test, test IGRA (Interferon-Gamma-Release- Assay) or chest x-ray. During treatment should be carefully monitor the status of patients in order to detect TB infection. It is recommended to inform patients about the need to consult a doctor if the following symptoms on a background after therapy with Ilaris В®: Long-lasting cough, weight loss, low-grade fever. In the case of conversion from a negative tuberculin test in a positive, especially in high-risk patients, it is necessary to carry out alternative screening tests. In identifying TB infection treatment with Ilaris В®should not be initiated or continued.
Activation of macrophages syndrome in patients with sJIA. Macrophage activation syndrome - known life-threatening condition can develop in patients with rheumatic diseases, in particular in patients with sJIA and requires intensive care. Physicians should be alert to the symptoms of infection or worsening of sJIA known as a trigger for the macrophage activation syndrome. According to clinical studies of the drug IlarisВ® probably does not increase the risk of macrophage activation syndrome in patients with JIA.
Impact on the ability to drive vehicles and manage mechanisms
Patients who against application Ilaris preparation В® occurs vertigo should not drive vehicles or mechanisms to work with complete disappearance of the side reaction.
OVERDOSE
Cases of confirmed drug overdose with
