Xolar - instructions for use, dose, side effects, contraindications

Active substanceOmalizumabOmalizumab

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Xolar

lyophilizate PC

Novartis Pharma AG Switzerland

Xolar®

solution PC

Novartis Pharma AG Switzerland

Dosage form: & nbsplyophilizate for the preparation of a solution for subcutaneous administration

Composition:1 bottle contains: active substance - omalizumab - 150 mg, as well as auxiliary substances: sucrose - 108.0 mg, L-histidine-1.3 mg, L-histidine hydrochloride monohydrate - 2.1 mg, polysorbate 20 - 0.4 mg.

Solvent: water for injection - 2.0 ml.

Description:

Lyophilizate: white or almost white.

Solvent: clear, colorless liquid.

Pharmacotherapeutic group:Other means for systemic use in obstructive airways diseases

ATX: & nbsp

R.03.D.X.05 Omalizumab

Pharmacodynamics:Omalizumab is a humanized monoclonal antibody derived from recombinant DNA selectively binding to immunoglobulin (IgE). Omalizumab is a IgG₁kappa antibody containing a human structural basis with complementarity determining regions of murine antibody binding IgE.

Patients with atopic bronchial asthma

Omalizumab binds to IgE and prevents its interaction with high-affinity FcɛRIreceptor. Thus, there is a decrease in the amount of free IgE, which is the starting factor for a cascade of allergic reactions.

When using the drug in patients with atopic bronchial asthma (BA), there is a marked decrease in the number FcɛRIreceptors on the surface of basophils.

In clinical trials in patients with asthma, the concentration of free IgE in blood serum was dose-dependent decreased within 1 hour after the administration of the first dose of Xolar and remained at the reached level during the period between the introduction of subsequent doses. When used at recommended doses, the average decrease in the concentration of free IgE in the serum was more than 96%. The total concentration IgE (bound and unbound) in the serum increased after the first dose due to the formation of the omalizumab complex-IgE, characterized by a slower rate of excretion compared to free IgE. At 16 weeks after the first dose, the average concentration of the total IgE in the serum was 5 times higher compared with that before treatment. After the withdrawal of treatment by the drug, the increase in the concentration of the total IgE and a decrease in the concentration of free IgE were reversible.After complete excretion of omalizumab, no increase in concentration was observed from the body IgE in the blood serum. Concentration of total IgE remained high for 1 year after the Xolar drug was discontinued.

With the use of Xolar in patients with moderate and severe atopic BA, there was a significant decrease in the frequency of exacerbations of asthma (defined as worsening of asthma, requiring the use of systemic glucocorticosteroids (GCS) or doubling the initial dose of inhaled glucocorticosteroids) and a decrease in the need for inhaled glucocorticosteroids compared with placebo.

With the use of the drug Xolar for 16 weeks against a background of a gradual decrease in the dose of inhaled or oral GCS, there was also a significant decrease in the frequency of exacerbations of asthma and a decrease in the need for inhaled glucocorticosteroids compared with placebo.

In patients with asthma and all-the-year-round allergic rhinitis who received SCS therapy, when omalizumab was used for 28 weeks, there was a decrease in the severity of BA symptoms and allergic rhinitis all year round, as well as an improvement in pulmonary function parameters. Reducing the frequency of exacerbations of asthma and improving the quality of life of patients (according tocertified quality of life questionnaire) against the background of therapy with Xolar drug persisted for a long time compared with placebo. With the use of Xolar in children from 6 to 12 years for 52 weeks, there was a decrease in the frequency of exacerbations of asthma compared with the group of patients who received placebo. In another study, when Xolar was used for 28 weeks in children aged 6-12 years, there was a decrease in the frequency and severity of exacerbations of asthma, and a reduction in the dose of inhaled glucocorticosteroids by the end of the 28th week of therapy compared with the placebo group.

Patients with chronic idiopathic urticaria

In some patients with chronic idiopathic urticaria (HIC), serum autoimmune antibodies were isolated from serum IgE and FceRIreceptor. These antibodies are capable of activating basophils or mast cells, which leads to the release of histamine.

One of the hypotheses of the mechanism of the action of omalizumab in patients with CRC is to reduce the concentration of free IgE in the blood, and then in the skin. As a result, the transmission of the signal by FcsRIreceptors and, consequently, the activation of cells participating in the inflammatory reaction is suppressed. Thus, the incidence and severity of the symptoms of CIC is reduced.

In addition, it is believed that a decrease in the concentration of circulating IgE leads to rapid nonspecific desensitization of mast cells in the skin, and FcsRI-receptors through negative feedback support this reaction.

In clinical studies in patients with HIC, as well as in patients with atopic asthma, the use of omalizumab led to a dose-dependent decrease in the concentration of free IgE and increasing the concentration of total IgE. The maximum decrease in the concentration of free IgE was observed 3 days after subcutaneous (SC) administration of the first dose of Xolar.

After repeated administration of the drug 1 time every 4 weeks, the concentration of free IgE in the blood serum before the introduction of the next dose was maintained at the reached level between 12 and 24 weeks of treatment. Concentration of total IgE in the blood serum was increased after the first dose due to the formation of a complex of omalizumab-IgE, characterized by a slower rate of excretion compared to free IgE. After repeated administration of the drug 1 time every 4 weeks at a dose of 75 mg to 300 mg, the concentration of the total IgE in the blood serum at 12 weeks from the start of treatment was 2-3 times higher compared to that before treatment and remained at the reached level between 12 and 24 weeks of treatment. After the Xolar drug was discontinued for 16 weeks of follow-up, the total IgE decreased, and the concentration of free IgE Increasing, approaching the original values.

When Xolar was used at doses of 150 and 300 mg every 4 weeks, patients with CIC exhibited reproducible and statistically significant therapeutic effects in reducing the severity of the itching. The effect peaked at week 12 of treatment and persisted throughout the observation period.

In addition, the Xolar drug at a dose of 300 mg had a reproducible and statistically significant effect on urticaria activity index (UAS), the proportion of days without angioedema, a weekly index of sleep disorders and the quality of life of patients assessed by the questionnaire Cu-Q2oL (questionnaire for studying the quality of life in patients with HIC), as well as an index DLQI (Dermatological index of quality of life).

Pharmacokinetics:

Suction

After SC administration in patients with BA, the absolute bioavailability of omalizumab is on average 62%. When used in doses of more than 0.5 mg / kg, the pharmacokinetics of omalizumab is linear.

Patients with atopic asthma

After a single SC administration in adults and adolescents with BA, the absorption of omalizumab is slow, the peak concentration in serum is achieved on average after 7-8 days.

After repeated administration of omalizumab, the area under the concentration-time curve (AUC) during the period from 0 to 14 days in the equilibrium state was 6 times higher than after the administration of a single dose.

Patients with HIC

After a single SC administration in adults and adolescents with HIC, the absorption of omalizumab is slow, the peak concentration in serum is achieved on average after 6-8 days. When omalizumab is used in patients with HIC in the dose range from 75 mg to 600 mg as a single injection, pharmacokinetics is linear. The minimum concentration of omalizumab in the serum increases in proportion to the increase in dose with 75 mg, 150 mg or 300 mg every 4 weeks.

Distribution

In vitro omalizumab c IgE forms a complex of a certain size. In vitro or in vivo there was no formation of precipitating complexes and complexes, the molecular weight of which exceeded 1 million daltons.

In clinical studies, there was no specific accumulation of omalizumab in any organs and tissues.

Patients with atopic asthma

In patients with atopic asthma, after the sc administration, the apparent volume of omalizumab distribution was 78 ± 32 ml / kg.

Patients with HIC

Based on the population pharmacokinetic model, it was shown that the distribution of omalizumab in patients with CIC was similar to that in patients with atopic asthma.

Excretion

The clearance of omalizumab includes both the clearance itself IgG, and clearance by specific binding and formation of complexes with the target ligand - free IgE blood serum.

Hepatic elimination IgG includes degradation in the reticuloendothelial system of the liver and endothelial cells of the liver. Intact IgG also excreted with bile.

Patients with atopic asthma

In patients with asthma, the half-life of omalizumab from serum averaged 26 days, the apparent clearance was 2.4 ± 1.1 ml / kg / day on average.In addition, with an increase in body weight, a doubling of the apparent apparent clearance was observed twice.

Patients with HIC

Based on the population pharmacokinetic model in patients with HIC, the half-life of omalizumab from serum at an equilibrium concentration averaged 24 days, the apparent clearance at an average concentration was 240 ml / day (corresponding to 3.0 ml / kg / day for the patient with body weight of 80 kg).

Pharmacokinetics in special clinical cases

Age, race / ethnicity, gender, body weight, body mass index, baseline concentration IgE, autoimmune antibodies to FceRI-receptor, the simultaneous use of drugs.

Patients with atopic asthma

Patients with asthma do not require a dose adjustment for omalizumab, depending on the age (6-76 years), race or ethnicity, gender and body mass index.

Patients with HIC

Patients with CIC do not require a dose adjustment for omalizumab, depending on age (12-75 years), race or ethnicity, the patient's sex, body weight, body mass index, baseline concentration IgE, autoimmune antibodies to FceRI-receptor or simultaneous use of H2-histamine receptor blockers and leukotriene receptor antagonists.

Impaired kidney and liver function

Pharmacokinetic and pharmacodynamic parameters of omalizumab in patients with atopic asthma or CHC and impaired renal or hepatic function have not been studied.

Since the metabolism of the drug is carried out mainly reticuloendothelial system, a violation of the liver and kidneys have no effect on it. Despite the fact that correction of the dose of omalizumab is not required, the drug should be used with caution in patients in this category.

Indications:

- Treatment of persistent atopic bronchial asthma of moderate and severe course, the symptoms of which are not adequately controlled by the use of inhaled glucocorticosteroids in patients 6 years and older. The drug Xolar should be used in patients with initial concentration IgE and body weight corresponding to those listed in the table for the selection of the dosing regimen (see section "Method of administration and dose").

- Treatment of chronic idiopathic urticaria, resistant to therapy with blockers H₁-gistamine receptors, in patients 12 years and older.

Contraindications:Hypersensitivity to omalizumab or to another component of the drug. Children under 6 years of age in patients with atopic asthma and up to 12 years of age in patients with HIC due to lack of relevant data on efficacy and safety.

Carefully:Caution should be used in patients with impaired liver and / or kidney function, with autoimmune diseases or diseases associated with the accumulation of immune complexes.

Pregnancy and lactation:

Special studies on the use of omalizumab in pregnant women have not been conducted.In experimental studies, there was no direct or indirect adverse effect of the drug on the course of pregnancy, development of the embryo and fetus, the course of labor and the development of newborns. It is known that molecules IgG penetrate the hemato-placental barrier. The use of the drug during pregnancy is possible only if the benefit to the mother exceeds the potential risk to the fetus.

Human IgG excreted in breast milk. It is not known whether omalizumab with human breast milk. It is impossible to exclude the risk for newborns / infants who are breastfed, so omalizumab should not be used during breastfeeding. If necessary, breast-feeding should be discontinued.

Impact on fertility

There is no data on the effect of omalizumab on fertility in humans. Studies have shown no violation of male and female fertility in animals with multiple doses exceeding 75 mg / kg.

Dosing and Administration:Only for subcutaneous injection! The drug can not be administered intravenously or intramuscularly.

Atopic asthma

The dose of Xolar and the periodicity of administration are determined based on the initial concentration IgE (IU / ml), measured before the start of treatment, as well as body weight (kg).

Depending on the initial concentration IgE (IU / mL) and body weight (kg), the recommended dose is 75 to 600 mg once every 2 or 4 weeks (see Tables 3 and 4).

Xolar should not be used in patients with initial concentration IgE and body weight that do not correspond to those listed in the table for the selection of the dosing regimen.

Determination of the number of vials, injections and total volume of Xolar drug solution as a function of the dose, see table 1.

Table 1. Number of vials, number of injections and total volume of solution drug depending on the dose

Dose (mg)	amount vials	Number of injections	Total solution volume (ml)
75	1	1	0,6
150	1	1	1,2
225	2	2	1,8
300	2	2	2,4
375	3	3	3,0
450	3	3	3,6
525	3	4	4,2
600	4	4	4.8

Calculation of the volume of the drug for each dose

Mri dilution of one vial of Xolar preparation yields 1.2 ml of a solution for subcutaneous administration. The algorithm for calculating the dose per injection is presented in Table 2 below.

Table 2. Algorithm for calculating the volume of solution per injection as a function of dose

Dose (mg)	Number of injections	Scope solution (ml)
75	one injection	0.6 m
150	one injection	1,2
225	first injection	1,2
225	second injection	0,6
300	first injection	1,2
300	second injection	1,2
375	first injection	1,2
	second injection	1,2
	third injection	0,6
450	first injection	1,2
	second injection	1,2
	third injection	1,2
525	first injection	1,2
	second injection	1,2
	third injection	1,2
	fourth injection	0,6
600	first injection	1,2
	second injection	1,2
	third injection	1,2
	fourth injection	1,2

Duration of treatment, monitoring and dose adjustment

Doses of Xolar should be adjusted for significant changes in body weight (see Tables 3, 4).

For dose determination schemes, see tables 3 and 4.

Table 3. Calculation of the dose of Xolar (mg) for the sc administration every 4 weeks

	Body weight (kg)
Initial concentration IgE (IU / ml)	>20- 25	>25- 30	>30- 40	>40- 50	>50- 60	>60- 70	>70- 80	>80- 90	>90- 125	>125- 150
>30-100	75	75	75	150	150	150	150	150	300	300
>100-200	150	150	150	300	300	300	300	300	450	600
>200-300	150	150	225	300	300	450	450	450	600
>300-400	225	225	300	450	450	450	600	600
>400-500	225	300	450	450	600	600	Applicable once in 2 weeks
>500-600	300	300	450	600	600		See Table 4
>600-700	300		450	600

Table 4. Calculation of the dose of Xolar (mg) for the sc administration every 2 weeks

	Body weight (kg)
Initial	>20-	>25-	>30-	>40-	>50-	>60-	>70-	>80-	>90-	>125-	>150-
concentration	25	30	40	50	60	70	80	90	125	150	200
IgE (IU / ml)
>30-100			Applicable every 4 weeks								225
>100-200					See Table 3						375
>200-300										375	525
>300-400									450	525
>400-500							375	375	525	600
>500-600						375	450	450	600
>600-700		225			375	450	450	525
>700-800	225	225	300	375	450	450	525	600
>800-900	225	225	300	375	450	525	600
>900-1000	225	300	375	450	525	600
>1000-1100	225	300	375	450	600
>1100-1200	300	300	450	525	600			Not Applicable
>1200-1300	300	375	450	525
>1300-1500	300	375	525	600

With the use of Xolar during the first 16 weeks in clinical trials, there was a decrease in the incidence of exacerbations of asthma, a reduction in the number of cases of emergency therapy, and improvement in the symptoms of the disease.Evaluation of the effectiveness of Xolar therapy should be performed after at least 12 weeks of treatment with the drug.

The drug Xolar is intended for long-term therapy. The abolition of the drug, as a rule, leads to the restoration of an increased concentration of free IgE and development of the corresponding symptoms.

Concentration of total IgE increases during treatment and remains elevated within one year after cessation of therapy. Thus, the concentration IgE when re-defined on the background of therapy with the drug Xolar can not serve as a guide for selecting the dose of the drug. To select the dose after suspension of treatment for a period of less than 1 year should be guided by concentration IgE in the serum, established before the introduction of the initial dose of the drug.

If treatment with Xolar has been suspended for 1 year or more in order to select a dose of Xolar, the concentration IgE in the blood serum.

Chronic idiopathic urticaria

The recommended dose of Xolar is 300 mg every 4 weeks as a sc injection. The treating physician should periodically re-evaluate the need for continued therapy with the drug.

The long-term experience with omalizumab in clinical trials in patients with HIC is limited.

Application in children and adolescents

Xolar is not recommended for use in patients with atopic asthma before the age of 6 years and in patients with CRC at the age of 12 years due to lack of data on efficacy and safety.

Use in elderly patients

There is limited experience in the use of Xolar in patients older than 65 years. However, there is no evidence of the need for dose adjustment in patients of this age.

Rules for the preparation and administration of a solution

When preparing a solution for subcutaneous administration of Xolar, follow the instructions below.

- Using a syringe with an 18 gauge needle, 1.4 ml of water for injections is drawn from the ampoule to prepare a solution.

- Having established a bottle with a drug vertically, it pierce a needle in accordance with the rules of asepsis and inject water for injections directly into the dry substance of the preparation.

- While keeping the bottle in an upright position, the bottle is gently rotated (not shaking) for 1 minute to evenly impregnate the dry matter with water for injection.

- To facilitate dissolution, the vial is rotated for about 5-10 seconds approximately every 5 minutes, until all solids are completely dissolved. In some cases, it may take more than 20 minutes to completely dissolve the dry matter. In this case, repeat the above steps until dissolution of the visible gel-like particles.

After complete dissolution of the dry matter in the solution, there should be no visible gel-like particles. It is acceptable to have small bubbles or foam on the walls of the bottle. The resulting solution should be clear or slightly opalescent, colorless or light yellowish in color. Do not use the solution if foreign particles are found in it.

- After removing the needle, flip the bottle for 15 seconds to allow the solution to flow towards the plug. Using a new 3 cm syringe equipped with an 18 gauge needle with a wide lumen, insert the needle into the inverted vial. Place the end of the needle at the lowest point of the solution that has accumulated in the vial, and put the solution into the syringe. Before removing the needle, pull the plunger completely back to the end of the syringe barrel to remove all solution from the inverted vial.

- Replace the 18 gauge needle with a 25 gauge needle for subcutaneous injection.

- Let out excess air, large bubbles and excess solution to get the required dose (volume 1.2 ml). A thin layer of small bubbles may remain on top of the solution in the syringe.

Since the solution has a certain viscosity, the duration of the injection can be 5-10 seconds.

- The drug solution is injected subcutaneously into the deltoid muscle region or into the anterolateral region of the thigh, avoiding the rash area with hives.

The drug Xolar should not be mixed with any other medicinal products or solutions other than water for injection.

The solution should be used immediately after preparation, since the preparation does not contain antibacterial preservatives.

If necessary, it is allowed to store the solution for 8 hours at a temperature of 2 to 8 ° C and for 4 hours at 30 ° C.

Unused residue and packaging waste are disposed of in accordance with local regulations.

Side effects:

Atopic asthma

The most frequent adverse events (AEs) with Xolar are headache, reactions at the injection site, including pain, swelling, erythema and pruritus at the site of injection.Most AEs were mild to moderate in severity. The following criteria were used to determine the frequency of unwanted reactions detected during clinical trials: very often (≥1/10), often (> 1/100, <1/10), infrequently (> 1/1000, <1 / 100), rarely (<1/1000).

Infectious and parasitic diseases: infrequently - pharyngitis; rarely - parasitic infestations.

Immune system disorders: rarely - anaphylactic reactions and other allergic conditions, including angioedema, the emergence of antibodies to omalizumab.

Impaired nervous system: often - headache; infrequently - dizziness, drowsiness, paresthesia, syncopal conditions.

Vascular disorders: infrequently - postural hypotension, "hot flashes".

Disturbances from the respiratory system, chest and mediastinal organs: infrequently - cough, allergic bronchospasm; rarely - a laryngeal edema.

Disorders from the gastrointestinal tract: infrequently - nausea, diarrhea, dyspepsia.

Disturbances from the skin and subcutaneous tissues: infrequently - hives, rash, itching, photosensitivity; rarely - angioedema.

General disorders and disorders at the site of administration: often - reactions at the injection site, such as pain, erythema, pruritus, puffiness; infrequently - weight gain, fatigue, swelling of the hands, flu-like condition.

On the background of therapy with Xolar during the postgistrict period, the following AEs were observed in clinical practice, whose frequency is unknown, due to the fact that spontaneous reports of AEs are received voluntarily from a population of undetermined size.

Immune system disorders: anaphylaxis and anaphylactoid reactions (noted both with the first and repeated use of the drug in most cases within 2 hours after SC injection, in some patients more than 2 hours after the administration of Xolar), serum sickness may include an increase body temperature, lymphadenopathy.

Disturbances from the skin and subcutaneous tissues: alopecia.

Violations of the blood and lymphatic system: severe idiopathic thrombocytopenia.

Disturbances from the respiratory system, chest and mediastinal organs: allergic granulomatous vasculitis (Charga-Strauss syndrome).

Disturbances from musculoskeletal and connective tissue: arthralgia, myalgia, swelling of the joints.

In typical studies in children aged 6-12 years, the following AEs were noted:

Impaired nervous system: very often - a headache.

Disorders from the gastrointestinal tract: often - pain in the upper abdomen.

General disorders and disorders at the site of administration: very often - an increase in body temperature.

HIC

The most frequent AEs with the use of Xolar drug in patients 12 years and older are headache and nasopharyngitis.

The following AEs were reported in> 1% of patients in all treatment groups and at least 2% more often in patients receiving Xolar at recommended doses (150 mg and 300 mg), compared with the placebo group.

HI grouped in accordance with the classification of organs and systems of organs MedDRA, within each group are listed in order of decreasing frequency of occurrence. To determine the frequency of occurrence, the following criteria were used: very often (≥1/10), often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (<1/1000) , very rarely (<1/10000).

Infectious and parasitic diseases: often - nasopharyngitis, sinusitis, upper respiratory tract infections, including viral etiology, urinary tract infection.

Impaired nervous system: very often - headache; often a headache in the sinuses of the sinuses.

Disturbances from the musculoskeletal and connective tissue: often - arthralgia, myalgia, pain in the extremities, bone and muscle pain.

General disorders and disorders at the site of administration: often - increased body temperature, reactions at the injection site, such as puffiness, erythema, pain, bruising, itching, bleeding, urticaria.

Anaphylaxis

In the post-marketing period, the incidence of anaphylactic reactions with the Xolar drug was approximately 0.2% (of all cases of anaphylactic reactions per 500,000 patient-years).

Anaphylactic reactions in the anamnesis not associated with the use of omalizumab may be a risk factor for the development of an anaphylactic reaction to the administration of Xolar.

Malignization

The overall incidence of neoplasia with Xolar in clinical trials was similar to that in the general population.The incidence of malignant neoplasms in the group of patients receiving the Xolar drug and in the control group was estimated to be <1/100. In the observational study of comparison of patients treated with Xolar and patients who received other treatment for up to 5 years, there was no increased risk of developing malignant tumors.

In children aged 6-12 years, there were no cases of development of malignant neoplasms in the group of patients receiving Xolar.

Thromboembolic complications

In controlled clinical trials, patients who received Xolar treatment experienced development of thromboembolic complications, including stroke, transient ischemic attacks, myocardial infarction, unstable angina, death from cardiovascular causes (including fatal outcome for unknown reasons).

When analyzing the main factors of cardiovascular risk, the risk ratio was 1.32.

Helminth infestations

Possible participation IgE in the immune response in the development of helminthic invasions. In placebo-controlled studies in patients with allergicdiseases and the risk of helminthic invasion with the use of the drug Xolar, there was a slight increase in the incidence of helminthiasis (however, the course, severity of the disease and response to therapy did not change). The overall frequency of helminth invasion in all clinical trials was less than 1 in 1000 (the design of the studies did not include a special study of the incidence of helminth diseases).

Change in the number of blood platelets

With the use of Xolar in clinical trials, few patients had a lower platelet count than normal, which was not accompanied by hemorrhage or a decrease in hemoglobin concentration.

In the course of clinical studies, there was no evidence of a continuous decrease in the number of platelets.

Data from other laboratory studies

Significant changes in laboratory parameters during clinical trials have not been revealed.

Overdose:

No cases of omalizumab overdose have been reported to date. The maximum tolerated dose of Xolar has not been determined to date.With a single intravenous dose of up to 4000 mg, there were no signs of dose-limiting toxicity. With the introduction of the highest cumulative dose of the drug-44,000 mg for 20 weeks, no severe acute AEs developed.

Interaction:

Because the IgE can participate in the formation of an immune response to some helminthic infestations, the drug Xolar can indirectly reduce the effectiveness of drugs for the treatment of helminth and other parasitic infestations. Since cytochrome P450 enzymes, energy release system mechanisms (efflux pumps) and protein binding do not play a role in omalizumab clearance, the likelihood of drug interaction with other drugs is low. Special studies on the interaction of Xolar with drugs, including vaccines, have not been conducted. The interaction of omalizumab with drugs used to treat asthma or HIC is unlikely.

Atopic asthma

In clinical trials, Xolar was widely used in combination with inhaled and oral glucocorticosteroids, short-acting and long-acting inhaled beta2-adrenomimetics, leukotriene antagonists, theophylline and oral antihistamines.The above preparations do not affect the safety of Xolar.

Currently, data on the use of Xolar in combination with specific immunotherapy (hyposensitizing therapy) are limited.

HIC

In clinical trials, the Xolar drug was used in combination with antihistamines (H1 and H2-histamine receptor blockers), leukotriene receptor antagonists. The effect of the above preparations on the safety profile of Xolar preparation was not revealed. As a result of population pharmacokinetic analysis, the effect of H2-histamine receptor blockers and leukotriene receptor antagonists on the pharmacokinetics of omalizumab was also not revealed. The use of Xolar in combination with immunosuppressive agents has not been studied.

The drug Xolar should not be mixed with any other medicinal products or solutions other than water for injection.

Special instructions:Allergic reactions

When applying the drug Xolar, as with any other protein-containing drugs, there may be local or systemic allergic reactions, including anaphylactic reactions.Before the introduction of the drug Xolar, it is necessary to prepare in advance the appropriate resuscitation equipment and medicines needed to stop the hypersensitivity reactions. Patients should be informed of the possibility of developing anaphylactic reactions and provide appropriate medical supervision. In clinical trials, the development of anaphylaxis and anaphylactoid reactions was noted with the use of both the first and repeated doses of Xolar. In most cases, the occurrence of such reactions was noted within 2 hours after the administration of the drug.

Just as with the application of other humanized monoclonal antibodies - derivatives of recombinant DNA, in rare cases, the formation of antibodies to omalizumab is possible.

Serum sickness

In patients treated with humanized monoclonal antibodies, including omalizumab, in rare cases, there was a development of serum sickness and similar conditions that are a manifestation of delayed allergic reactions of type 3. The onset of development of such conditions was usually noted on the 1-5 day after the first or subsequent injections, as well as with prolonged therapy.Symptoms that allow suspected development of serum sickness include: arthritis / arthralgia, rash (urticaria or other forms), fever and lymphadenopathy. As the prevention and treatment of this pathology, it is possible to use antihistamines and glucocorticosteroids. It is necessary to inform the patient about the possibility of developing this condition and to warn about the need to consult a doctor if any symptoms appear.

Charge-Strauss syndrome and hypereosinophilic syndrome

In patients with asthma of severe severity, in rare cases, a systemic hypereosinophilic syndrome or allergic eosinophilic granulomatous vasculitis (Charga-Strauss syndrome) can be developed, which are usually treated with systemic glucocorticosteroids (SCS).

In rare cases, patients receiving antiasthmatic medications, including omalizumab, systemic eosinophilia or vasculitis may or may not develop. These cases, as a rule, are associated with a decrease in the dose of oral GCS.

The doctor should be wary of the development of severe eosinophilia, vasculitic rash, worsening of the course of pulmonary symptoms,pathology of the paranasal sinuses, complications from the heart and / or nephropathy in such patients.

In the case of the development of the above-mentioned severe disorders by the immune system, the possibility of abolishing omalizumab should be considered.

General instructions

The drug should not be used to treat acute attacks of asthma, acute bronchospasm or asthmatic status.

The use of Xolar in patients with the syndrome of increased concentration has not been studied IgE, with allergic bronchopulmonary aspergillosis, for the prevention of anaphylactic reactions, with atopic dermatitis, allergic rhinitis or with food allergies.

The use of Xolar in patients with impaired hepatic and / or renal function, autoimmune diseases or diseases associated with the accumulation of immune complexes has not been studied. Care should be taken when using the drug in such patients.

Do not abruptly discontinue therapy with systemic or inhaled glucocorticosteroids after starting treatment with Xolar. The dose of these drugs, applied simultaneously with the drug Xolar, is reduced gradually under the supervision of a doctor.

The content of sucrose in the preparation does not have a clinically significant effect on the concentration of glucose in the blood serum in patients with diabetes mellitus, therefore dosage correction of Xolar and hypoglycemic drugs is not required.

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

Patients who experience dizziness, fatigue, syncopal conditions, or drowsiness, should refrain from controlling vehicles and mechanisms when using Xolar.

Form release / dosage:

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

Packaging:Lyophilizate for the preparation of a solution for subcutaneous administration, 150 mg, in a 6 ml bottle of colorless glass, sealed with a rubber stopper and an aluminum lid with a plastic "snap-off" top.

Solvent - water for injection 2 ml in an ampoule of colorless glass of hydrolytic class I.

One vial with lyophilizate complete with one ampoule with a solvent and with instructions for use in a cardboard pack.

Storage conditions:

Store at 2-8 ° C. Do not freeze.

The drug should be stored out of the reach of children.

Shelf life:Lyophilizate - 4 years;

Solvent - 5 years.

The expiration date of the kit is determined by the earlier expiry date 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:LSR-000082

Date of registration:29.05.2007

Expiration Date:Unlimited

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

Manufacturer: & nbsp

NOVARTIS PHARMA, AG Switzerland

Representation: & nbspNOVARTIS PHARMA LLCNOVARTIS PHARMA LLC

Information update date: & nbsp28.03.2017

Illustrated instructions

Instructions

Table 1

table 2

table 3

Xolar (Holair)