Cousentix (Cosentyx)

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

    Active substance: secuquinumab 150.00 mg;

    Excipients: sucrose 92.43 mg, histidine / histidine hydrochloride monohydrate 4.666 mg, polysorbage 80 0.60 mg.

    Description:BA white powder or amorphous mass.
    Pharmacotherapeutic group:interleukin inhibitor
    ATX: & nbsp

    L.04.A.C.10   Secukinumab

    Pharmacodynamics:

    Mechanism of action

    Sekokinumab is a completely human antibody (immunoglobulin G1 (IgGl), which selectively binds and neutralizes the pro-inflammatory cytokine-interleukin-17A (IL-17A). Secukinumab has a direct effect on IL-17 and inhibition of its interaction with the IL-17 receptor, which is expressed by different types of cells, including keratinocytes and synoviocytes. As a result secuquinumab inhibits the release of pro-inflammatory cytokines, chemokines and mediators of tissue damage and reduces the contribution of IL-17A to autoimmune and inflammatory diseases. In clinically significant concentrations secuquinumab reaches the skin and reduces the concentration of local inflammatory markers.A direct consequence of secotinumab treatment is a reduction in the redness, densification and flaking of the skin that result from psoriatic lesions.

    IL-17A is a natural cytokine that participates in normally occurring inflammatory and immune responses. IL-17A plays a key role in the pathogenesis of plaque psoriasis, psoriatic arthritis and ankylosing spondylitis. An increase in the concentration of IL-17A produced by lymphocytes and congenital immune cells was found in the blood and affected areas of the skin in patients with plaque psoriasis, psoriatic arthritis and ankylosing spondylitis. The production of IL-17A is high in the affected skin compared to intact skin in patients with plaque psoriasis. In the synovial fluid of patients with psoriatic arthritis and in the subchondral bone marrow of the facet joint bones of patients with ankylosing spondylitis, a high concentration of cells producing IL-17A is found. IL-17A also contributes to the development of tissue inflammation, neutrophil infiltration, destruction of bones and tissues, as well as tissue remodeling, including angiogenesis and fibrosis.

    Pharmacodynamics

    The concentration of total IL-17A (free and associated with secinumab) is increased due to a decrease in clearance of sec-neuron-associated IL-17A for 2-7 days in patients receiving secuquinumab, pointing out that secuquinumab selectively captures free IL-17A, which plays a key role in the pathogenesis of plaque psoriasis.

    In a study with sekichinumab, infiltration of epidermal neutrophils and various neutrophil-associated markers that are elevated in injured skin in patients with plaque psoriasis have been significantly reduced after one to two weeks of treatment.

    Against the background of secotinumab therapy in patients with psoriatic arthritis and ankylosing spondylitis, the concentration of C-reactive protein, which is a marker of inflammation, was observed within 1-2 weeks.

    Pharmacokinetics:

    Suction

    After a single subcutaneous dose of 150 mg or 300 mg with plaque psoriasis, the maximum serum concentration of sekichinumab was 13.7 ± 4.8 μg / ml, or 27.3 ± 9.5 μg / ml, between 5 and 6 days after introduction.

    After the initial weekly administration during the first month, the time to reach the maximum concentration was between 31 and 34 in the afternoon.

    The maximum concentration in the equilibrium state (Cmax,ss) after subcutaneous administration, 150 mg or 300 mg were 27.6 μg / ml and 55.2 μg / ml, respectively. The equilibrium state is achieved after 20 weeks with a monthly mode of administration.

    In comparison with the exposure after a single dose, a twofold increase in the maximum concentration and area under the concentration-time curve (AUC) after repeated monthly administration during maintenance therapy. Secukinumab Absorbed with an average absolute bioavailability of 73%.

    Distribution

    The average volume of distribution in the terminal phase (Vz) after a single intravenous administration varied between 7.10 and 8.60 L in patients with plaque psoriasis; probably, secuquinumab is distributed on the periphery.

    Sekinumab concentrations in the intercellular fluid of the skin in patients with plaque psoriasis ranged from 28% to 39% of that in the blood serum at 1-2 weeks after a single subcutaneous injection of 300 mg sec.

    Excretion

    Average system clearance (CL) in patients with plaque psoriasis was 0.19 l / day. The clearance was dose-and time-dependent, as was for the therapeutic IgGl a monoclonal antibody interacting with a soluble cytokine target, such as IL-17A.

    The average half-life in patients with plaque psoriasis was 27 days. The half-life in individual patients with psoriasis ranged from 17 to 41 days.

    Linearity / nonlinearity

    Pharmacokinetic parameters for single and multiple injection of secinucinum in patients with plaque psoriasis were determined in separate studies with intravenous doses varying from 1x0.3 mg / kg up to 3x10 mg / kg and with subcutaneous administration of doses varying from 1x25 mg to a multiple dose of 300 mg. For all dosing regimens, the exposure was proportional to the dose.

    The pharmacokinetic parameters of secuinumab in patients with psoriatic arthritis, ankylosing arthritis and plaque psoriasis are the same.

    Pharmacokinetics in special clinical cases

    Patients over 65 years of age

    Based on a population analysis of pharmacokinetic parameters, the clearance in patients older than 65 years and patients younger than this age group was similar.

    Patients with impaired hepatic or renal function

    Available data on pharmacokinetics in patients with impaired hepatic or renal function are absent.

    Indications:

    - Treatment of moderate to severe psoriasis in adult patients who are shown systemic therapy or phototherapy.

    - Treatment of active psoriatic arthritis in monotherapy or in combination with methotrexate in adult patients with inadequate response to prior therapy with basic medications.

    - Treatment of active ankylosing spondylitis in adult patients with insufficient response to standard therapy.

    Contraindications:

    - Severe hypersensitivity reactions to secaquinumab or to other auxiliary components of the drug.

    - Clinically significant infections in the stage of exacerbation (eg, active tuberculosis).

    - Age to 18 years due to lack of data on efficiency and safety.

    - Pregnancy and the period of breastfeeding.

    Carefully:

    Caution should be exercised when prescribing Cozentix to patients with chronic infections or with anamnestic indications due to an increased risk of infection, as well as to patients with active Crohn's disease.

    Patients receiving Cozentix can be vaccinated with inactivated or killed vaccines, administration of live vaccines should not be performed.

    Pregnancy and lactation:

    Studies in laboratory animals showed no direct or indirect adverse effects on pregnancy, embryonic / fetal development, childbirth, or postnatal development. Since there are no adequate data on the use of COSENTEX in pregnant women, its use in this category of patients is not recommended.

    It is not known whether the secuquinumab in human milk. Since immunoglobulins are excreted in human breast milk, it is not recommended to use Cosentix during breastfeeding.

    There is no information on the influence of Cosentix on the fertility of men and women. In the studies of COSENTEX in animals, there was no decrease in fertility.

    Dosing and Administration:

    COSENTEX is administered by subcutaneous injection. If possible, avoid as an injection site for skin lesions affected by psoriasis.

    Treatment of psoriasis of moderate to severe severity in adult patients who are shown systemic therapy or phototherapy: the recommended dose is 300 mg as the initial dose at 0, 1, 2 and 3 weeks in the form of a subcutaneous injection, which is subsequently administered monthly as a maintenance dose, starting at week 4. Each dose of 300 mg is administered as two separate subcutaneous injections of 150 mg.

    Treatment of active psoriatic arthritis in monotherapy or in combination with methotrexate in adult patients, with insufficient response to prior therapy with basic drugsand: the recommended dose is 150 mg as the initial dose at 0, 1, 2 and 3 weeks by subcutaneous injection, which is subsequently administered monthly as a maintenance dose, starting at week 4. For patients with an inadequate response to anti-TNFα therapy (tumor necrosis factor a) or for patients with moderate to severe psoriasis, the recommended dose is 300 mg as the initial dose at 0, 1, 2 and 3 weeks by subcutaneous injection, which in the subsequent it is entered monthly as a maintenance dose, starting from the 4th week.Each dose of 300 mg is administered as two separate subcutaneous injections of 150 mg.

    Treatment of active ankylosing spondylitis in adult patients with insufficient response to standard therapy: The recommended dose is 150 mg as the initial dose at 0, 1, 2 and 3 weeks by subcutaneous injection, which is subsequently administered monthly as a maintenance dose starting at week 4.

    Special patient groups

    Patients with impaired hepatic or renal function

    There are no data on the use of Cosentix in this group of patients.

    Patients under the age of 18 years

    The effectiveness and safety of the drug in children under 18 years of age is not established.

    Patients over 65 years of age

    Correction of the dose is not required.

    Instructions for use

    Instructions for the use of COSENTEX, lyophilizate for the preparation of a solution for injection, 150 mg

    The following information is only for health care professionals or health care workers.

    Bottle with lyophilizate for solution for injection must be stored in the refrigerator at a temperature of 2 ° C to 8 ° C.

    A single-use vial contains 150 mg of Coenzentix for reconstitution with sterile water for injection.Do not use the vial after the expiration date indicated on the package or vial.

    In order to comply with aseptic rules, the preparation of a solution of the drug for subcutaneous injection should be carried out without interruptions.

    The preparation time from the moment of opening the plug to the final recovery takes on average 20 minutes, and should not exceed 90 minutes.

    To prepare the preparation COSENTEX, lyophilizate for the preparation of solution for injection, 150 mg, please follow the instructions below.

    Instructions for preparing a solution of COSENTEX

    1. Bring a bottle of COSENTEX, lyophilizate for the injection solution, 150 mg, and sterile water for injection to room temperature.

    2. Collect a little more than 1.0 ml of sterile water for injection into a disposable syringe with a 1 ml graduation and level it at 1.0 ml.

    3. Remove the plastic cap from the vial.

    4. Insert the needle of the syringe into the bottle containing the lyophilizate of the Cosentix preparation, through the center of the rubber plug and restore the lyophilisate by slowly injecting 1.0 ml of sterile water for injection into the vial. A stream of sterile water for injection should be directed to the lyophilizate.

    Tilt the bottle at an angle of about 45 ° and, holding it with your fingertips, gently rotate for about 1 minute. Do not shake or flip the bottle.

    Leave the vial to stand at room temperature for at least 10 minutes to achieve complete dissolution. Foaming of the solution may occur.

    Tilt the bottle at an angle of about 45 ° and, holding it with your fingertips, gently rotate for about 1 minute. Do not shake or flip the bottle.

    Leave the vial in an upright position at room temperature for about 5 minutes. The resulting solution should be clear or opalescent. Its color can vary from colorless to light yellow.

    Do not use the drug if the lyophilizate is not completely soluble, or if the liquid contains easily visible particles, and if it is cloudy or brown. Prepare the required number of vials (1 vial for a dose of 150 mg, 2 vials for doses of 300 mg).

    After preparation, the hypodermic injection solution can be administered immediately or it can be stored at a temperature of 2 ° C to 8 ° C for a maximum of 24 hours. Do not freeze.After storage at a temperature of 2 ° C to 8 ° C, the solution should be left to stand at room temperature for about 20 minutes before use. The solution should be used within 1 hour after removal from storage conditions at a temperature of 2 ° C to 8 ° C.

    Instructions for the administration of a solution of COSENTEX

    Tilt the bottle at an angle of approximately 45 ° and place the tip of the needle on the bottom of the vial with the solution when typed into the syringe. Do not turn the vial over.

    Carefully take a little more than 1.0 ml of the subcutaneous injection solution from the vial into a disposable syringe with a 1 ml graduation and with a needle of suitable size (for example, "21G x 2 "). This needle is used only for sampling Kozentiks drug in a disposable syringe. Prepare the required number of syringes (syringe 1 for a dose of 150 mg, a syringe 2 for the dose 300 mg).

    Holding the syringe with the needle up, gently tap on the syringe to move the air bubbles up.

    Replace the needle used to take the drug to another size "27G x 1/2".

    Remove the air bubbles and push the piston to the 1.0 ml mark.

    Disinfect the injection site with an alcohol swab.

    Enter the solution of COSENTEX subcutaneously in the antero-lateralHip surface or lower abdomen (with the exception of a five-centimeter area around the navel) or the outer surface of the shoulder. Place the injection every time you change. Do not enter into the area of ​​damaged skin (thinning, redness, irritation, densification, peeling). Avoid insertion into places with the presence of scars and stretch marks.

    The remaining solution in the vial should not be used and should be disposed of. Vials are for single use only. Dispose of the used syringe in a sharps container (lockable, puncture resistant container). For your safety and the health of others, needles and used syringes in no case should reused.

    Side effects:

    The most common adverse events (AEs) with the use of COSENTEX were infections of the upper respiratory tract (most often nasopharyngitis, rhinitis). Most of them were mild or moderate.

    NIs are listed in accordance with the system-organ class of the medical vocabulary for regulatory activities MedDRA. Within each system-organ class, AEs are distributed according to the frequency of occurrence in order of decreasing importance. To estimate the frequency, the following criteria were used: very often (≥1 / 10); often (from ≥1 / 100 to <1/10); infrequently (from ≥1 / 1000 to <1/100); rarely (from ≥1 / 10000 to <1/1000); very rarely (<1/10000), including individual messages.

    Infectious and parasitic diseases: very often - nasopharyngitis, upper respiratory tract infection; often - rhinitis, pharyngitis, herpetic infection of the oral mucosa; infrequently - sinusitis, tonsillitis, candidal infection of the oral cavity, fungal skin damage, inflammation of the external ear.

    Violations of the blood and lymphatic system: infrequently - neutropenia.

    Disorders from the organs of vision: infrequently - conjunctivitis.

    Disturbances from the respiratory system, chest and mediastinal organs: often - rhinorrhea.

    Disorders from the gastrointestinal tract: often diarrhea.

    Disturbances from the skin and subcutaneous tissues: often - hives; rarely anaphylactic reactions.

    Immunogenicity

    According to clinical studies of COSENTEX in <1% of cases, antibodies to secaquinumab were observed, which did not affect the effectiveness of therapy and pharmacokinetic parameters.

    If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, inform the doctor about it.

    Overdose:

    In the course of clinical studies of COSENTEX, there were no reports of cases of overdose.

    In clinical trials, intravenous doses of up to 30 mg / kg (ie, approximately 2000-3000 mg) were not associated with the development of dose-limiting toxicity. In case of an overdose, it is recommended to observe the patient to identify signs and symptoms of AEs. If necessary, symptomatic treatment should be performed immediately.

    Interaction:

    The drug can not be administered with live vaccines. There are no data on the interaction of Cosentix with other drugs in humans.

    There is no direct evidence of the involvement of IL-17A in the expression of cytochrome system isoenzymes CYP450. Increased concentration of cytokines in conditions of chronic inflammatory process suppresses the formation of certain isoenzymes of the cytochrome system. Thus, anti-inflammatory therapy, incl.secinukinab, an inhibitor of IL-17A, may lead to a normalization of the activity of cytochrome isoenzymes CYP450, accompanied by a decrease in the exposure of concomitantly used drugs, the metabolism of which is carried out with the participation of these isoenzymes. Thus. a clinically significant effect on drugs with a narrow therapeutic index, which are substrates of the cytochrome system isoenzymes, and whose dosage is selected individually (for example, warfarin). Consideration should be given to the possibility of therapeutic control in the initiation of sekicinumab therapy in patients receiving treatment with the drugs of the above groups.

    With the use of Coenzentix simultaneously with methotrexate and / or glucocorticosteroids in patients with psoriatic arthritis and ankylosing spondylitis, no drug interactions were identified.

    COSENTEX should not be mixed with any medications or solvents, except for water for injection.

    Special instructions:

    Infections

    The drug COSENTEX may increase the risk of infection.In clinical trials, patients who received the drug COSENTEX, there were cases of infection, most of which were mild or moderate severity. Caution should be exercised when deciding whether to use Cosentix in patients with chronic infections or with a history of recurrent infection.

    Patients should be informed of the need to see a doctor if signs and symptoms suggest infection. If a serious infection develops, the patient should be monitored, the Cosentix preparation should not be administered until the infection is resolved.

    In clinical trials, there was no reported increased susceptibility to tuberculosis, however, COSENTHEX should not be given to patients with active tuberculosis. Before the start of treatment with Cozentix, a decision must be made to conduct anti-tuberculosis therapy in patients with latent forms of tuberculosis.

    Crohn's disease

    Caution should be exercised when prescribing Cozentix to patients with exacerbation of Crohn's disease, since clinical studies have exacerbated the course of Crohn's disease, in some cases severe.Patients with an exacerbation of Crohn's disease on the background of treatment with Coenzentix should be carefully observed.

    Hypersensitivity reactions

    If anaphylactic or other serious allergic reactions occur, use of COSENTEX should be stopped immediately, and appropriate symptomatic therapy should be started immediately.

    Vaccination

    Vaccination with live vaccines should not be carried out against the background of treatment with Cozentix.

    Patients receiving Cozentix can be vaccinated with inactivated or killed vaccines. After vaccination with the inactivated meningococcal and influenza vaccine, patients receiving the Cosentix preparation had an adequate immune response in the form of at least a fourfold increase in the titer of antibodies to the meningococcal and influenza vaccine. These data indicate that the COSENTEX drug does not inhibit the development of an immune response to the administration of meningococcal and influenza vaccines.

    Impact on fertility

    Women with preserved reproductive potential should use reliable contraceptive methods during treatment with the drug and for at least 20 weeks after discontinuation of therapy.

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

    There are no data on the effect of the drug on the ability to drive vehicles and / or mechanisms.

    Form release / dosage:Lyophilizate for the preparation of a solution for subcutaneous administration, 150 mg.
    Packaging:

    150 mg in a bottle of colorless glass class I with a capacity of 6 ml, sealed with a gray rubber stopper, coated with an aluminum cap with a snap-off cap made of polypropylene.

    For 1 bottle together with instructions for medical use in a pack.

    Storage conditions:

    Keep out of reach of children, at a temperature of 2 to 8 ° C.

    Shelf life:

    3 years.

    The drug should not be used after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-003715
    Date of registration:07.07.2016
    Expiration Date:07.07.2021
    The owner of the registration certificate:Novartis Pharma AGNovartis Pharma AG Switzerland
    Manufacturer: & nbsp
    Representation: & nbspNOVATOR PHARMA, LLCNOVATOR PHARMA, LLCRussia
    Information update date: & nbsp01.09.2016
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