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

Active substanceSecukinumabSecukinumab

Similar drugsTo uncover

Cousentix

lyophilizate PC

Novartis Pharma AG Switzerland

Cousentix

solution PC

Novartis Pharma AG Switzerland

Dosage form: & nbspRAsterol for subcutaneous administration

Composition:

Active component: secuquinumab 150.00 mg;

Excipients: trehalose dihydrate 75.67 mg, histidine / histidine hydrochloride monohydrate 3,103 mg, methionine 0.774 mg, polysorbate-80 0.200 mg, water for injection 1069 mg.

Description:From colorless to light yellow color, transparent or opalescent solution.

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 the treatment with sekikinumab is the reduction in the redness, densification and flaking that are the result of 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 in patients with psoriatic arthritis and in the subchondral bone marrow of the facet joint bones in 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 sec -kinumab IL-17A) is increased due to a decrease in the 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 sec-neumab was 13.7 ± 4.8 μg / ml, or 27.3 ± 9.5 μg / ml, respectively, between 5 and 6 in the afternoon after administration.

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 (C_{max, ss}) after subcutaneous administration of 150 mg or 300 mg was 27.6 μg / ml and 55.2 μg / ml, respectively. The equilibrium state is achieved after 20 weeks with a monthly mode of administration.

Compared with exposure after a single dose, there was 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, it is likely that 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 ranging from 1 x 0.3 mg / kg to 3 × 10 mg / kg and with subcutaneous administration of doses ranging from 1 x 25 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.

Since the removable cap of the pre-filled syringe with the device for passive needle protection / pre-filled syringe in the auto injector contains derivatives of natural rubber latex, care must be taken when using COSENTEX in patients with individual latex intolerance.

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

If you have any of these diseases, consult a doctor before taking the drug.

Pregnancy and lactation:

Pregnancy

Risk Summary

There is insufficient data on the use of the drug in pregnant women.

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, the areas of skin affected by psoriasis should be avoided as an injection site.

Treatment of moderate to severe psoriasis 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 by subcutaneous injection, which is subsequently administered monthly as a maintenance dose, starting with the 4th week. 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 medications: 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-TNF-α therapy (tumor necrosis factor α) 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.

At the discretion of the attending physician, after appropriate training in the technique of subcutaneous injection, patients can independently administer COSENTEX, but the physician must ensure appropriate monitoring of the patient. Patients should be instructed to fully comply with all instructions for the administration of Cosentix in accordance with the Directions for Use.

Instructions for use

Instructions for the use of the preparation COSENTEX pre-filled syringe with a device for passive needle protection

Read the instructions completely before injection. Do not attempt to administer the drug yourself unless you are trained with your doctor. The pack contains 1 or 2 pre-filled syringes with a device for passive needle protection in the blister.

Your COSENTEX preparation is a pre-filled syringe with a device for passive needle protection - see Fig. 1.

After the drug has been injected, the automatic syringe protective device activates and hides the needle.This pre-filled syringe with a device for passive needle protection provides additional protection against accidental pricks needle of medical workers, patients who independently administer the drug at the prescription of a doctor, as well as persons who help administer the drug to patients.

What you need in addition for the injection:

- Alcohol tampon.

- Wadded or gauze swab.

- Container for the disposal of sharp objects.

Important Safety Information

Attention: store Cozentix pre-filled syringe with device for passive needle protection out of the reach of children.

The needle cap of the syringe may contain dry rubber (latex), which is not recommended for use by persons with hypersensitivity to this substance.

Do not open the sealed pack until you are ready to use the COSENTEX preparation pre-filled syringe with a device for passive needle protection.

Do not use COSENTEX pre-filled syringe with a device for passive needle protection if the integrity of the pack or blister is violated, as the application is unsafe in this case.

Never leave the COSENTEX product pre-filled with a syringe with a device for passive needle protection, in places accessible to others.

Do not shake the COSENTEX product pre-filled syringe with a device for passive needle protection.

Be careful not to touch the protective tabs of the syringe before use. Touching them can cause premature activation of the automatic syringe safety device.

Do not remove the cap from the needle until the moment of injection.

The COSENTEX preparation is a pre-filled syringe with a device for passive needle protection, should not be reused. Dispose of the used pre-filled syringe with the passive needle protection device immediately after use in the sharps container.

Kozentix pre-filled syringe with passive needle protection device

Store the COSENTEX preparation pre-filled syringe with a device for passive needle protection, in sealed packaging to protect from light. Keep in the refrigerator at a temperature of 2 ° C to 8 ° C. Do not freeze!

Before the injection, take the COSENTEX drug pre-filled syringe with a device for passive needle protection from the refrigerator and allow it to warm to room temperature (15 to 30 minutes).

Do not use a prefilled syringe with a passive needle protection device with COSENTEX after the expiry date printed on the package or label of the syringe.

Places for Injection

- Recommended injection areas are located on the front of the thighs. You can also inject the drug into the lower third of the abdomen, avoiding the five-centimeter area around the navel. If the injection is carried out by the caregiver, the injection can be carried out to the outer surface of the shoulder.

Each time, change the injection site.

Do not inject into areas with skin lesions (thinning, redness, irritation, densification, peeling). Avoid insertion into places with the presence of scars and stretch marks.

Preparation for use of COSENTEX preparation of a pre-filled syringe with device for passive needle protection

Remove the package from the refrigerator and leave it open for 15-30 minutes to warm it to room temperature.

Wash hands thoroughly with soap and water before use.

Wipe the injection site with an alcohol swab.

Remove the pre-filled syringe with a device for passive protection of the needle from the bundle, and then from the blister.

Examine the pre-filled syringe. The liquid in it must be transparent. Its color can vary from colorless to slightly yellowish. You can see a small air bubble. DO NOT USE the drug if the liquid contains visible particles, cloudy or obviously brown. DO NOT USE the drug if the integrity of the pre-filled syringe is broken. In all cases, consult a doctor.

How to use the COSENTEX preparation pre-filled syringe with a device for passive needle protection

Carefully remove the needle cap from the pre-filled syringe and discard it. You can see a drop of liquid on the end of the needle. This is normal.

Gently collect the skin fold between the fingers at the injection site and insert the needle as shown. Insert the entire length of the needle to ensure that the drug is completely inserted.

While holding the syringe, as shown in the figure, slowly push the plunger until, The base of the piston will not be between the protective side tabs.

Hold the piston fully depressed with the syringe for 5 seconds.

Disposal Instructions

Hold the piston pressed all the way to the stop, While you remove the needle from the injection site. Slowly release the piston and allow the automatic protective device to hide the needle.

At the injection site, a small amount of blood can be observed. You can apply a cotton or gauze swab to the injection site and hold it for 10 seconds. Do not rub the injection site. If necessary, you can close the injection site with a small patch.

Place the used pre-filled syringe into the sharps container (lockable, puncture resistant container). For your safety and the health of others, the needles and used syringes should never be reused.

Instruction for the use of the COSENTEX preparation of a pre-filled syringe in an autoinjector

Before injection:

Your COSENTEX preparation is a pre-filled syringe in the autoinjector

The pre-filled syringe in the autoinjector is shown with the cap removed - see Fig. 8.

Do not remove the cap until you are ready to administer the drug. Store the COSENTEX package of the pre-filled syringe in the autoinjector in the refrigerator at a temperature of 2 ° C to 8 ° C, in places not accessible to children.

Do not freeze COSENTEX preparation pre-filled syringe in an auto injector.

Do not shake COSENTEX preparation pre-filled syringe in the autoinjector. Do not use the COSENTEX preparation pre-filled syringe in the auto injector, if at the opening of the package the cover is removed.

To avoid discomfort during administration, first remove the Cosentix preparation with a prefilled syringe in the autoinjector from the refrigerator and leave it at room temperature for 15-30 minutes before the introduction.

What you need for the injection:

Included in the package:

- New COSENTEX preparation pre-filled syringe in the auto-injector (see Figure 9).

Not included in the package:

- An alcohol swab.

- Wadded or gauze swab.

- Container for the disposal of sharp objects.

What you need to check for safe injection:

The liquid must be clear.Its color can vary from colorless to slightly yellowish.

Do not use a preparation if the liquid contains easily visible particles, cloudy or obviously brown. You can see a small air bubble, which is normal.

Do not use COSENTEX preparation pre-filled syringe in the auto injector, if the expiration date has expired.

Do not use, if the integrity safety shutter is broken.

Contact your pharmacist if there is at least one of the above listed violations.

2a. Choose a place for injection:

Recommended places are located on the front of the thighs. You can also inject the drug into the lower third of the abdomen, avoiding the five-centimeter area around the navel.

Each time, change the injection site.

Do not inject into areas with skin lesions (thinning, redness, irritation, densification, peeling). Avoid insertion into places with the presence of scars and stretch marks.

2b. Only for carers and medical personnel:

If the injection is a medical worker or a person caring for a sick person, injection can be carried out in the outer surface of the shoulder.

3. Treatment of the injection site:

Wash your hands with hot soapy water.

In a circular motion, wipe the injection site with an alcohol swab. Leave it to dry before injection.

Do not touch the pre-treated area prior to injection.

Injection:

4. Removing the cap:

When you are ready to use the COSENTEX preparation pre-filled syringe in the auto injector, remove only the cap.

Unscrew the cap in the direction of the arrow.

After removal, discard the cap. Do not attempt to re-attach the cap.

Use the drug for 5 minutes after removing the cap.

5. Position of the preparation COSENTEX pre-filled syringe in the auto-injector:

Keep the COSENTEX preparation pre-filled with a syringe in the auto injector, at an angle of 90 degrees to the treated injection site.

YOU MUST READ THIS BEFORE INJECTION:

During the injection, you will hear 2 loud clicks.

The 1st click means the injection begins. After a few seconds, the second click will indicate that the injection is almost over.

You must continue to hold the COSENTEX drug pre-filled with the syringe in the auto-injector that fits snugly against the skin until you see the green indicator window,and stop manipulation.

6. Start of injection:

Press the COSENTEX drug pre-filled with the syringe in the auto injector, tightly to the skin to begin the injection.

1st click means that the injection has started.

Continue to hold the Cosentix preparation is a pre-filled syringe in an auto-injector that fits snugly against the skin.

Green indicator shows the progress of the injection.

7. Completion of injection:

Listen carefully to the 2nd click. He points out that the injection nearly completed.

Check that green indicator filled the window and stopped moving.

Now the drug COSENTEX pre-filled syringe in the autoinjector can be removed.

After injection:

8. Check that the green indicator is filled in the window:

This means that the medicine has been administered. Consult a doctor if the green indicator is not visible.

At the injection site, a small amount of blood may be present. You can apply a cotton or gauze swab to the injection site and hold it for 10 seconds. Do not rub the injection site. If necessary, you can close the injection site with a small patch.

9. Disposal:

Place the used Cosentix drug pre-filled syringe in the auto injector, into the sharps container (lockable, puncture-resistant container).

Do not ever try to reuse your COSENTEX preparation with a pre-filled syringe in the auto injector.

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 / 1,000 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.

Vision disorders: 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 indicated in the instruction are aggravated, or you notice Any other side effects not listed in the instructions should be reported to the doctor.

Overdose:

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

In clinical trials, doses up to 30 mg / kg (i.e.approximately 2000-3000 mg) were administered intravenously without development of dose-limiting toxicity.

In case of an overdose, it is recommended that patients be monitored to identify signs and symptoms of AEs. If necessary, symptomatic treatment should be performed immediately.

Interaction:

The drug COSENTEX 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. the clinically significant effect on preparations that are substrates of the cytochrome system isoenzymes with a narrow therapeutic index, whose dose is selected individually (for example, warfarin).

Consideration should be given to the possibility of therapeutic control at the beginning of sekicinumab therapy in patients receiving treatment with the drugs of the above groups.

With the appointment of Coenzentix simultaneously with methotrexate and / or glucocorticosteroids in patients with psoriatic arthritis and ankylosing spondylitis, drug interactions were not identified.

The drug COSENTEX should not be mixed with any medications.

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.

Patients with hypersensitivity to latex

The removable cap of the pre-filled syringe with the device for passive needle protection / pre-filled syringe in the autoinjector contains derivatives of natural rubber latex.Although natural rubber latex is not found in the cap, the safety of using COSENTEX in a pre-filled syringe with a device for passive needle protection / pre-filled syringe in the autoinjector has not been studied in patients with hypersensitivity to latex.

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, the 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:A solution for subcutaneous administration, 150 mg / ml.

Packaging:

1 ml in a glass syringe with a fixed needle with a protective cap.

For 1 or 2 pre-filled syringes with device for passive protection of the needle in the blister, pasted with a label, together with instructions for use in a pack of cardboard.

For 1 or 2 pre-filled syringes in autoinjectors (handles), together with instructions for use in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of 2 to 8 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:

2 years.

The drug should not be used after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003780

Date of registration:12.08.2016

Expiration Date:12.08.2021

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