Stelara - instructions for use, doses, side effects, contraindications

Active substanceUstekinumabUstekinumab

Similar drugsTo uncover

Stelara®

solution PC

Johnson & Johnson, LLC Russia

Stelara®

solution PC

Johnson & Johnson, LLC Russia

Dosage form: & nbsphypodermic solution

Composition:

One vial contains 45 mg (45 mg / 0.5 mL) or 90 mg (90 mg / 1.0 mL) of ustekinumab.

Excipients: sucrose, L-gystidine (including L-histidine hydrochloride monohydrate), polysorbate 80, water for injection.

Description:

Opalescent solution from colorless to light yellow color. The solution can contain single transparent protein particles.

Pharmacotherapeutic group:Interleukin Inhibitors

ATX: & nbsp

L.04.A Immunosuppressive drugs

L.04.A. C.05 Ustekinumab

Pharmacodynamics:

Mechanism of action

Ustekinumab is a fully human monoclonal antibody of class IgGlk with a molecular weight of about 148600 daltons, produced by a recombinant cell line and undergoing multistage purification, including inactivation and removal of viral particles. Ustekinumab has a high specificity for the p40 subunit of interleukins (IL) of human IL-12 and IL-23. The drug blocks the biological activity of IL-12 and IL-23, preventing the binding of p40 to the IL-12 receptorR-β1, expressed on the surface of immune cells. Ustekinumab can not communicate with IL-12 and IL-23, already associated with the IL- 12R-β1. Therefore, the drug is unlikely to affect the complement or antibody-dependent cytotoxicity of cells expressing receptors for IL-12 and / or IL-23.

IL-12 and IL-23 are heterodimeric cytokines, which are secreted by activated antigen-presenting cells, in particular macrophages and dendritic cells. IL-12 activates NKcells, stimulates differentiation Cd⁴⁺ T-cells up to T-helpers 1 (Th1), as well as increases the production of interferon gamma (IFNy). IL-23 stimulates the formation of T-helpers 17 (Th17) and increases the secretion of IL-17A, IL-21 and IL-22. Levels of IL-12 and IL-23 are elevated in blood and skin in patients with psoriasis.

Concentration of IL12 / 23p40 at serum is a fact of differentiation of patients with psoriatic arthritis, which confirms the participation of IL-12 and IL-23 in the pathogenesis of psoriatic diseases. Polymorphism of genes encoding IL-23A, IL-23R and IL-12B, determines the predisposition to such diseases. In addition, IL-12 and IL-23 genes have increased expression in psoriatic affected skin, and the IL-12-induced IFNγ production is directly proportional to the severity of the psoriatic disease. IL-23 sensitive T cells were detected in enteroses on mouse models of inflammatory arthritis, in which IL-23 caused enteric inflammation.

The drug Stelara® shows clinical efficacy in psoriasis and psoriatic arthritis, by binding the p40 subunit of IL-12 and IL-23 and disturbing the production of cytokines Th1 and Th17, which are the key links in the pathogenesis of these diseases.

Pharmacodynamics

Application of Stelar® leads to a significant weakening of histological manifestations of psoriasis, including hyperplasia and proliferation of epidermal cells. These data are consistent with clinical efficacy.

In patients with psoriasis and / or psoriatic arthritis ustekinumab does not have a significant effect on the ratio of circulating immune cells in the blood, including memory cells and non-activated T cells, as well as the concentration of cytokines in the blood. Concentration systemic markers of inflammation in patients taking ustekinumab, is within the limits of the norm, and the indicators of 4 markers (MDC, VEGF, MCSF-1 b YKL-40) slightly differ in patients taking the drug Stelara ®, compared with the placebo group.

Analysis of mRNA isolated from biopsy samples of skin lesions of psoriasis initially and after 2 weeks of treatment,that the use of the drug Stelar® led to a decrease in the expression of genes encoding its molecular targets-IL-12 and IL-23, as well as genes encoding inflammatory cytokines and chemokines-monocyte chemotactic factor (MCP) -1, tumor necrosis factor (TNF) -alpha, interferon-gamma-inducible protein (IP)-10 and IL-8. These data are consistent with the significant clinical effect of treatment in patients with psoriasis.

The clinical effect of treatment of psoriasis and psoriatic arthritis, apparently, depends on the concentration of ustekinumab in the blood plasma. In patients with psoriasis with the best result in the scale of assessment of the area and severity of psoriasis PASI mean concentration ustekinumab in the blood plasma was higher than in patients with less clinical effect. In general, the proportion of patients who improve on a scale PASI reached 75%, increased as the concentration of ustekinumab increased in plasma. In patients with psoriatic arthritis, ACR 20, there is a higher average concentration of ustekinumab in the blood plasma compared to patients who did not respond to treatment. Number of patients with psoriatic arthritis who achieved an improvement on the scale ACR 20 and ACR 50, increased as the concentration of ustekinumab in the blood plasma increased.

Immunization

In a long-term clinical study of Phase 3, patients receiving Stelar® for at least 3.5 years developed an immune response similar to that of a control group of patients with psoriasis but not undergoing systematic treatment, with the introduction of a vaccine containing pneumococcal polysaccharide or tetanus vaccine.

Approximately the same number (%) of patients treated with Stelar® and patients in the control group achieved a protective concentration of anti-pneumococcal and tetanus antibodies. The antibody titres were also approximately the same.

Pharmacokinetics:

Suction

The mean time to reach the maximum concentration in the blood plasma (Tmah) after a single subcutaneous injection of 90 mg of ustekinumab to healthy volunteers was 8.5 days. In patients with psoriasis, this value at doses of the drug 45 or 90 mg was comparable to that of healthy volunteers.

Absolute bioavailability of ustekinumab after a single subcutaneous injection of psoriasis patients was 57.2%.

Distribution

The mean value of the volume distribution of ustekinumab in the terminal phase of excretion after single intravenous administration of psoriasis patients ranged from 57 to 83 ml / kg.

Metabolism

The metabolic path of ustekinumab is not known.

Excretion

The average value of the systemic clearance of уetkinumab after single intravenous administration of psoriasis patients ranged from 1.99 to 2.34 ml / day / kg. The mean half-life (T_1/2) ustekinumab in patients with psoriasis and / or psoriatic arthritis was approximately 3 weeks, and varied from 15 to 32 days in different studies.

Linearity

System exposure ustekinumab (FROMmOh and area under the curve "concentration-time", AUC) in patients with psoriasis increased in proportion to the administered doses after a single intravenous dose in the range from 0,09 mg / kg up to 4,5 mg / kg, as well as after a single subcutaneous dose administration in the range from 24 mg to 240 mg.

The change in the concentration of ustekinumab in the blood plasma over time after single or repeated repeated administration of the drug was basically predictable. The equilibrium concentration of ustekinumab in the blood plasma is reached by the 28th week with the proposed regimen of therapy (second injection 4 weeks after the first application, then every 12 weeks). On average, the equilibrium concentration of the drug in patients with psoriasis is 0.21-0.26 μg / ml for a dose of 45 mg and 0.47-0.49 μg / ml for a dose of 90 mg. Cumulation of the drug in the serum was not observed during the treatment with the dosing regimen 1 injection every 12 weeks.

The influence of the patient's body weight on the pharmacokinetics of the drug

The concentration of the drug in the blood plasma depends on the body weight of the patient with psoriasis and / or psoriatic arthritis. When administered the same dose (45 mg or 90 mg), patients weighing over 100 kg ustekinumab mean concentration in the plasma was less than in patients weighing less than 100 kg. However, the mean minimum concentration of ustekinumab in the blood plasma of patients weighing more than 100 kg administered with 90 mg of the drug was comparable to that in the group of patients weighing less than 100 kg administered with 45 mg of the drug.

Population pharmacokinetic analysis

Apparent ground clearance (CL/F) and volume of distribution (V/F) were 0.465 l / day and 15.7 l, respectively, according to data obtained from patients with psoriasis. The half-life (T₁/₂) of the drug was approximately 3 weeks. Sex, age and race did not affect the apparent clearance of ustekinumab. Ha apparent clearance (CL/F) of the drug was influenced by the body weight of patients, while in patients with a larger body weight the magnitude CL/F was more. The average apparent clearance in patients with a body weight of more than 100 kg was approximately 55% higher than that in patients with a lower body weight. Volume of distribution (V/F) in patients with a body weight of more than 100 kg was approximately 37% higher than that in patients with a lower body weight. Similar results were obtained with confirmatory analysis of population data among patients with psoriatic arthritis.

The effect of comorbid conditions (diabetes mellitus, hypertension, hyperlipidemia) on the pharmacokinetics of the drug in patients with psoriasis was analyzed. In patients with diabetes, the magnitude CL/F was on average 29% higher than in healthy patients.

Population pharmacokinetic analysis showed that there is a tendency to increase the clearance of ustekinumab in patients with a positive immune response.

Special patient groups

Children (from 12 to 18 years)

The pharmacokinetics of ustekinumab in children aged 12 to 18 years with psoriasis, taking the recommended dose, is comparable to the pharmacokinetics in adult patients with psoriasis.

Elderly patients (65 years and over)

Studies of pharmacokinetics in elderly patients have not been conducted. Population pharmacokinetic analysis among patients older than 65 years did not reveal the effect of age on the apparent apparent clearance (CL/F) and volume of distribution (V/F).

Patients with impaired renal function

Data on the pharmacokinetics of the drug in patients with impaired renal function are absent.

Patients with impaired hepatic function

Data on the pharmacokinetics of the drug in patients with impaired liver function are absent.

Other patient groups

The pharmacokinetics of ustekinumab is comparable in patients of Asian descent with psoriasis and in non-Asian patients with psoriasis. The use of alcohol or tobacco did not affect the pharmacokinetics of utekinumab.

Indications:

Plaque psoriasis

Adult patients

Treatment of patients older than 18 years with moderate or severe degree of plaque psoriasis in the absence of treatment effect or in the presence of contraindications, or with intolerance to other methods of systemic therapy or phototherapy.

Children

Treatment of children aged 12 to 18 years with moderate or severe degree of plaque psoriasis in the absence of the effect of treatment or in the presence of contraindications,or with intolerance to other methods of systemic therapy or phototherapy.

Psoriatic arthritis

Treatment of patients older than 18 years with active psoriatic arthritis (PsA) as a monotherapy or in combination with methotrexate.

Contraindications:

- Clinically significant hypersensitivity to ustekinumab or any auxiliary substance of the drug;

- Children under 12 years (according to the indication of "plaque psoriasis"), up to 18 years (according to the indication of "psoriatic arthritis");

- Pregnancy and lactation;

- Serious infectious diseases in the acute phase, including tuberculosis;

- Malignant neoplasms.

Carefully:

- Chronic or recurrent parasitic and infectious diseases of a viral, fungal or bacterial nature.

- Malignant tumors in the anamnesis.

- Elderly age.

Pregnancy and lactation:

Pregnancy

During the study of the drug, a dose of 45 times the recommended clinical dose for a person, with no evidence of teratogenicity, congenital anomalies, or developmental lag. However, the results of animal studies are not always applicable to humans.

It is not known whether ustekinumab when used in pregnant women result in adverse effects on the fetus or affect reproductive function. Adequate and strictly controlled studies in pregnant women were not conducted. Do not use the drug during pregnancy, effective methods of contraception during and for 15 weeks after treatment with the drug should be used.

Lactation

Studies in monkeys have shown that ustekinumab excreted in breast milk. It is not known whether the drug is absorbed systematically after absorption. Because many drugs and immunoglobulins are excreted in breast milk, and because Stelara® drug can cause adverse reactions in infants, should decide to breast-feed while taking the drug, or the abolition of ustekinumab therapy.

Dosing and Administration:

The drug Stelara® is intended for subcutaneous injections.

Adult patients

Plaque psoriasis

The recommended dose is 45 mg. The second injection is done 4 weeks after the first application, then every 12 weeks. In patients with a body weight of more than 100 kg, the drug is recommended to be used in a dose of 90 mg.

If the therapy is ineffective for 28 weeks, it is recommended to consider the feasibility application of the drug.

Correction of dose

Patients in whom the clinical efficacy of the drug every 12 weeks is not enough, the dose should be increased to 90 mg every 12 weeks. If such a dosing regimen is not effective, a dose of 90 mg should be given every 8 weeks.

Resumption of treatment

It was shown that the resumption of therapy according to the scheme: the second injection 4 weeks after the first application, and then every 12 weeks, is effective and safe.

Psoriatic arthritis

Children

Plaque psoriasis

The recommended dose depends on the patient's body weight, as shown in Table 1. The second injection is done 4 weeks after the first application, then every 12 weeks.

Table 1. Recommended dose of Stelar® in children with plaque psoriasis

Body mass	The recommended dose	The form release of
Less than 60 kg	0.75 mg / kg *	Bottles
From 60 kg to 100 kg	45 mg	Syringes, bottles
More than 100 kg	90 mg	Syringes, bottles

* - to calculate the required volume of the drug (ml) for patients with a body weight of less than 60 kg, the following formula is used: body weight (kg) x 0.0083 (ml / kg). The calculated volume of the preparation is rounded to the one hundredth part of ml (0.01 ml). Injection is carried out by a graduated syringe with a capacity of 1 ml. For patients who require a dose of less than 45 mg, the preparation Stelara ® is available in vials with a dosage of 45 mg.

For children, the drug is used in conditions of the hospital.

If the therapy is ineffective for 28 weeks, it is recommended to consider the expediency of using the drug.

Special patient groups

Application in elderly patients (over 65 years)

Of the 4135 patients who received Stelara®, 252 were patients over the age of 65 (183 patients with psoriasis and 69 with psoriatic arthritis). In clinical trials, no effect of age on clearance or volume of drug distribution was found. Despite the fact that during the study of the drug there was no difference in the safety and efficacy of the drug for elderly patients older than 65 years compared with younger patients,the number of elderly patients is not sufficient for the final conclusion about the effect of age (or lack of influence) on clinical efficacy.

Use in children

The safety and efficacy of ustekinumab in children younger than 12 years of age have not been studied.

Application in renal and hepatic insufficiency

Studies of the drug in patients with renal or hepatic insufficiency have not been conducted.

Instructions for the administration of the drug

The drug is intended for subcutaneous administration.

The drug should not be mixed with other injectable liquids. If 2 bottles of 45 mg of the drug are used to administer a dose of 90 mg, two consecutive injections should be made. The second injection should be done immediately after the first injection. Injections should be done in different areas. Do not shake the drug. Prolonged vigorous shaking can damage the drug. Do not use if it is shaken. At the beginning of the treatment, Stelara® should be injected only by medical personnel, however, if the doctor deems it possible, then the patient can inject himself with Stelara® on his own, observing all necessary precautions and having passed mandatory training in the hypodermic injection technique, doctor.In children aged 12 to 18 years, all injections should be performed by medical personnel.

Recommended places for injections are the upper part of the thigh or abdomen about 5 cm below the navel. You can also use the shoulder area (see Figure 1). Avoid injections into the area affected by psoriasis.

Before the introduction carefully examine the contents of the vial. The solution should be opalescent from colorless to light yellow color, can contain single transparent protein particles. When the color changes, turbidity or the presence of solid particles, the solution can not be used. Wash your hands thoroughly and treat the injection site with a cotton swab dipped in antiseptic.

Remove the protective cap from the bottle with the preparation (Fig. 2). Do not remove the rubber cap. Wipe the rubber cap with a cotton swab soaked in an antiseptic. Remove the protective cap from the needle of the syringe (the syringe is not included in the package of the preparation). Do not allow the needle to come into contact with foreign objects and do not touch the needle. Place the vial of the drug on a flat surface and insert the needle of the syringe into the rubber cap of the vial.Turn over the vial with the drug and the syringe stuck into it as shown in Figure 3.

For the introduction of adult patients or children aged 12 to 18 years with a body weight of more than 60 kg, dial the entire contents of the vial into the syringe. The volume of the drug for administration to children aged 12 to 18 years with a body weight of less than 60 kg should be tentative medical staff.

To avoid air bubbles entering the syringe, the tip of the needle, while you are taking the drug into the syringe, should always be in the liquid.

Remove the syringe from the vial. Hold the syringe with the needle in the direction away from you and check for air bubbles. If there are air bubbles in the syringe, gently tap the syringe wall until the air bubbles move upwards (Fig. 4).

Press the plunger of the syringe to release air bubbles. Do not put a syringe and do not allow the needle to come into contact with foreign objects.

Gently pinch the skin in the area of injection between the thumb and forefinger, insert the needle into the skin and slowly lower the syringe piston to the limit (Fig. 5).

After that, release the skin and gently remove the needle. A small amount of blood can be released from the injection site. This is normal. Apply a cotton swab moistened with antiseptic to the injection site and hold for a few seconds.Do not rub the injection site. If necessary, cover with adhesive tape. Unused amount the drug should be destroyed. The used syringe, needle and bottle should be disposed of in accordance with local regulations. requirements for the destruction of such wastes. Re-use of the syringe, needle or bottle is prohibited. Vials can be discarded with conventional garbage.

Side effects:

Adverse effects in adult patients

The most frequent adverse events (> 5%) in controlled clinical trials of the drug in psoriasis and psoriatic arthritis were nasopharyngitis, headache and upper respiratory tract infections. Most of these events were mild and did not require discontinuation of treatment.

Side effects of the drug are systematized relative to each of the organ systems depending on the frequency of occurrence using the following classification: very often (≥ 1/10), often (≥ 1/100, <1/10), infrequently (≥ 1/1000, <1 / 100), rarely (≥ 1/10000, <1/1000), very rarely (<1/10000), including isolated cases.

Infectious and parasitic diseases:

Often: odontogenic infections, upper respiratory tract infections, nasopharyngitis.

Infrequently: inflammation of subcutaneous fat, shingles, viral infections of the upper respiratory tract.

In placebo-controlled studies in patients with psoriasis and / or psoriatic arthritis, the incidence of infection and serious infection with Stelar® and placebo was the same (incidence of 1.27 and 1.17 cases per person-year of treatment, infections - respectively 0.01 (5/616) and 0.01 (4/287) cases per person-year of treatment).

In controlled and uncontrolled clinical trials in patients with psoriasis and psoriatic arthritis, the incidence of infections with Stelar® was 0.86 cases per person-year of treatment. The incidence of serious infection was 0.01 cases per person-year of treatment (107/9848). Serious infections included diverticulitis, inflammation of subcutaneous fat, appendicitis, cholecystitis and sepsis.

Mental disorders:

Infrequently: depression.

Impaired nervous system:

Often: dizziness, headache.

Infrequently: defeat of the facial nerve.

Disturbances from the respiratory system, chest and mediastinal organs:

Often: pain in the throat and larynx.

Infrequently: nasal congestion.

Disorders from the gastrointestinal tract:

Often: diarrhea, vomiting, nausea.

Disturbances from the skin and subcutaneous tissues:

Often: itching.

Infrequently: peeling of the skin.

Rarely: exfoliative dermatitis.

Disorders from the musculoskeletal system and connective tissue:

Often: back pain, myalgia, arthralgia.

General disorders and reactions at the injection site:

Often: fatigue, erythema at the injection site, pain at the injection site.

Infrequently: reactions at the site of administration (including hemorrhage, hematoma, compaction, swelling and itching).

Description of some adverse reactions

Malignant tumors

In 3 clinical placebo-controlled trials in patients with psoriasis and psoriatic arthritis, the incidence of malignant tumors (not including non-melanoma skin cancer) in patients receiving ustekinumab and placebo, was acc. 0.16 (1/615) and 0.35 (1/287) cases per 100 people / year. The frequency of development of other forms of skin cancer than melanoma with the use of the drug Stelar® and placebo was acc. 0.65 (4/615) and 0.70 (2/287) cases per 100 people / year.The frequency of malignant tumors in patients treated with Stelar® was comparable to the incidence of tumors in the general population.

Most often, in addition to non-melanoma skin cancer, malignant tumors of the prostate, intestines, mammary glands and melanoma were observed.

The incidence of non-melanoma skin cancer in patients receiving Stelar® was 0.61 cases per 100 people / year (41/6770).

Hypersensitivity reactions

In clinical trials, rash and urticaria were observed in less than 1% of patients.

Immunogenicity

Approximately 6% of patients with psoriasis and psoriatic arthritis who received Stelar® received antibodies to ustekinumab, which usually had a low titer. There was no clear correlation between the formation of antibodies and the presence of reactions at the injection site. In the presence of antibodies to ustekinumab, patients often had a lower efficacy of the drug, although the presence of antibodies does not exclude the achievement of a clinical effect.

Most patients with psoriasis who had antibodies to ustekinumab also had antibodies that neutralized such antibodies.

Side effects in children

The safety of Stelar® was studied in 110 patients aged 12 to 18 years with a duration of therapy up to 60 weeks. Undesirable reactions observed in children are similar to those in adults.

Undesirable phenomena revealed in the post-marketing application of Stelar®

From the immune system:

Infrequently: hypersensitivity reactions (including rash and hives).

Rarely: severe hypersensitivity reactions (including anaphylaxis and angioedema).

From the skin and subcutaneous tissue:

Infrequently: pustular psoriasis.

Rarely: psoriatic erythroderma.

Overdose:

During clinical trials, patients were injected intravenously with doses of up to 6 mg / kg without development of dose-limiting toxicity. In case of an overdose, it is recommended to monitor the patient's condition to identify signs and symptoms of side effects and, when they develop, immediately begin appropriate symptomatic therapy.

Interaction:

Studies of drug interactions in humans have not been conducted.

Effects of IL-12 and IL-23 on enzymes CYP450 were studied in vitro on human hepatocytes.The study showed that IL-12 and / or IL-23 at a concentration of 10 ng / ml did not affect enzymes CYP450 (CYP1A2, 2B6, 2C9, 2C19, 2D6 or 3A4). The results obtained do not imply the need for dose adjustment in patients taking drugs with Stelar® simultaneously, metabolized by enzymes CYP450.

Do not use vaccines containing weakened pathogens of infectious diseases, concomitantly with ustekinumab.

With the joint use of the drug Stelar® and such drugs as paracetamol (acetaminophen), ibuprofen, acetylsalicylic acid, metformin, atorvastatin, naproxen, levothyroxine and hydrochlorothiazide interaction was not revealed. The safety and efficacy of the joint use of Stelar® with other immunosuppressants (methotrexate, ciclosporin) or biological agents for the treatment of psoriasis has not been evaluated.

Special instructions:

Infections

Ustekinumab is a selective immunosuppressant and may increase the risk of infections and the reactivation of infections in the latent phase.

In clinical trials with the use of the drug Stelara ® in patients there were serious bacterial, fungal and viral infections. Ustekinumab Do not use in patients with clinically relevant, active infections. Care should be taken when using the drug in patients with chronic infections or the presence of recurrent infections in the anamnesis.

Before beginning of application the patient should be tested for tuberculosis. Do not use ustekinumab in patients with active tuberculosis. In the presence of latent or active tuberculosis (including history), it should be started before the use of the drug Stelar®. Also, it is necessary to begin treatment of tuberculosis in patients who have not had sufficient effect from their previous treatment. During the treatment with usekinumab and after that, we should carefully monitor the patients to identify signs and symptoms of active tuberculosis. Patients should be warned about the need to see a doctor if signs and symptoms appear that suggest infection. With the development of a serious infection, the use of Stelar® should be canceled, the patient must be under the supervision of medical personnel. Do not use ustekinumab before the end of infection treatment.

Malignant neoplasms

The drug Stelara ® is a selective immunosuppressant. Immunosuppressants can increase the risk of developing malignant tumors. In some patients who received ustekinumab in clinical studies, the emergence of malignant neoplasms (cutaneous and non-dermal forms). The use of Stelar® is not was studied in patients with malignant tumors in history. Caution should be exercised in prescribing patients with malignant tumors in an anamnesis, and also when considering the continuation of treatment with Stelar® for patients with diagnosed malignancies.

In all patients over the age of 60 years, as well as in patients who received long-term therapy with immunosuppressants or UV radiation, it is necessary to conduct a test for the presence of non-melanoma skin cancer.

Hypersensitivity reactions

In the post-marketing application of Stelar®, cases of serious hypersensitivity reactions are known, including angioedema and anaphylaxis.With the development of anaphylactic and other serious hypersensitivity reactions, the use of ustekinumab should be stopped immediately, and appropriate treatment should be prescribed.

Vaccination

Do not vaccinate the patient with live vaccines during treatment with Stelar®, and 15 weeks before vaccination (after the last dose of Stelar®) and 2 weeks after vaccination.

Data on secondary infection with live vaccines in patients, who receive the drug Stelara ®, are absent. Caution should be exercised when using live vaccines to immunize family members of the patient receiving Stelar®, as there is a risk of viral or bacterial excretion and transmission of infection from these persons to patients. Long-term treatment with Stelar® does not inhibit the humoral immune response to vaccines containing pneumococcal polysaccharide and tetanus toxoid vaccine.

With usxinumab, vaccines containing inactivated microorganisms can be used, but the induced immune response may not be sufficient to prevent the disease.

Concomitant immunosuppressive therapy

The safety and efficacy of Stelar® in combination with immunosuppressive drugs and phototherapy has not been studied in patients with psoriasis. In studies in patients with psoriatic arthritis, co-administration with methotrexate did not affect the safety and efficacy of Stelar®. Care should be exercised when considering the possibility simultaneous use of other immunosuppressants and utekinumab, as well as during the transition from therapy to other antipsoriasis Biological preparation for therapy with ustekinumab.

Immunotherapy

The safety and efficacy of Stelar® in patients who underwent immunotherapy for allergic diseases have not been established. Caution should be exercised in patients currently receiving or undergoing immunotherapy for allergic diseases, especially anaphylactic conditions.

Effect on the ability to drive transp. cf. and fur:No studies have been conducted.

Form release / dosage:

Solution for subcutaneous administration.

Packaging:

Each vial contains 45 mg (45 mg / 0.5 mL) or 90 mg (90 mg / 1.0 mL) of ustekinumab.

For 0.5 ml or 1.0 ml in bottles of borosilicate glass (type I), a capacity of 2 ml, sealed with a rubber stopper, crimped aluminum cap, and fitted with a lid type flip-off.

On 1 bottle together with the instruction on medical application place in a pack a cardboard.

Storage conditions:

Store in the original packaging in a dark place at a temperature of 2 to 8 ° C. Do not freeze.

Do not shake. Keep out of the reach of children.

Shelf life:2 years.
Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-006465/09

Date of registration:13.08.2009

Expiration Date:Unlimited

The owner of the registration certificate:Johnson & Johnson, LLC Johnson & Johnson, LLC Russia

Manufacturer: & nbsp

CILAG, AG Switzerland