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

Active substanceEtanerceptEtanercept

Similar drugsTo uncover

Enbrel®

lyophilizate PC

Pfizer Inc. USA

Enbrel®

solution PC

Pfizer Inc. USA

Enbrel®

lyophilizate PC

Pfizer Inc. USA

Dosage form: & nbsphypodermic solution

Composition:

1 ml of the solution contains:

active substance: etanercept 50.0 mg;

Excipients: arginine hydrochloride 5.3 mg, sodium chloride 5.8 mg, sucrose 10.0 mg, sodium hydrogen phosphate dihydrate 1.2 mg, sodium dihydrogen phosphate dihydrate 2.9 mg, water for inventory up to 1.0 ml.

Description:

Transparent or slightly opalescent colorless or light yellow liquid. It is allowed to have small amorphous protein inclusions that are transparent to white.

Pharmacotherapeutic group:immunosuppressive agent

ATX: & nbsp

L.04.A.B.01 Etanercept

Pharmacodynamics:

Tumor Necrosis Factor (TNF-α, TNF) is the main cytokine that supports the inflammatory process in rheumatoid arthritis. An increase in the concentration of TNF is also found in synovial membranes and psoriatic plaques in patients with psoriatic arthritis, as well as in blood plasma and synovial tissues of patients with ankylosing spondylitis. Etanercept is a competitive inhibitor of the binding of TNF to its receptors on the cell surface and, thus, inhibits the biological activity of TNF.TNF and lymphotoxin relate to pro-inflammatory cytokines that bind to two distinct receptors of tumor necrosis factor (TNFR) on the cell surface: 55-kilodalton (p55) and 75-kilodalton (p75). Both PNOM are present in the body in membrane-bound and free forms. Soluble FNOR regulate the biological activity of TNF.

TNF and lymphotoxin exist predominantly as homotrimers, their biological activity depends on the cross-linking of the TNFR on the surface of the cell. Dimeric soluble receptors, such as etanercept, have a greater affinity for TNF than monomeric receptors, and therefore are significantly stronger competitive inhibitors of TNFα binding to their cellular receptors. In addition, the use of Fc-fragment of the immunoglobulin as a binding element in the dimeric receptor structure prolongs the half-life of serum.

A significant part of the pathological changes in joints with rheumatoid arthritis and ankylosing spondylitis, as well as changes in the skin in the form of psoriatic plaques, arise due to the action of pro-inflammatory molecules involved in a system controlled by TNF.The mechanism of action of etanercept appears to be a competitive inhibition of the binding of TNF to TNF receptors on the cell surface. In this way, etanercept prevents the cellular response mediated by TNF, facilitating the biological inactivation of TNF. Etanercept can also modulate biological responses controlled by additional molecules that transmit the signal downward (for example, cytokines, adhesion molecules or proteinases). And these answers can either stimulate or control TNF.

In patients with active psoriatic arthritis Enbrel® inhibits the progression of structural damage, improves physical activity and reduces the likelihood of developing peripheral joint damage.

After discontinuation of drug therapy Enbrel® within a month, an exacerbation of the disease is possible. The effectiveness of re-appointment of the drug within 24 months after discontinuation of therapy is comparable to that for patients who did not interrupt treatment.

Pharmacokinetics:

Etanercept is slowly absorbed from the subcutaneous injection site, reaching a maximum concentration approximately 48 hours after a single dose of the drug Enbrel®. Absolute bioavailability is 76%. With the administration of a dose Enbrel® twice a week, twice higher concentrations are reached than those observed after a single dose. After a single subcutaneous injection of 25 mg of the drug Enbrel® the mean maximum concentration of etanercept in the blood plasma was 1.65 ± 0.66 μg / ml, the area under the concentration-time curve (AUC) - 235 ± 96.6 μg-hour / ml. Visible saturation of clearance in the dose limits was not observed.

The dependence of the ethanercept concentration on time is described by the biexponential curve. The average value of the volume of distribution is 7.6 liters, while the volume of distribution at the equilibrium state is 10.4 liters.

From the body etanercept output slowly. Half-life (T_1/2) is about 70 hours. In patients with rheumatoid arthritis, clearance is approximately 0.066 L / h, which is somewhat lower than its value of 0.11 L / h in healthy volunteers. The pharmacokinetic characteristics of etanercept in patients with rheumatoid arthritis, ankylosing spondylitis and psoriasis are similar.

The dose of Enbrel® 50 mg, administered once, is bioequivalent to the dose obtained by two injections of 25 mg of the drug, made almost simultaneously.Despite the fact that in patients and healthy volunteers after the introduction of labeled etanercept, the radioactive label is eliminated through the kidneys, in patients with acute renal or hepatic insufficiency, there was no increase in the concentration of etanercept in the blood plasma. In patients with acute renal or hepatic insufficiency, an increase in the concentration of etanercept is not observed.

There are no obvious differences in the pharmacokinetics of etanercept in men and women.

Elderly patients

The clearance and apparent volumes of etanercept distribution in the group of patients from 65 to 87 years are similar to those in patients younger than 65 years.

Children

Juvenile idiopathic polyarthritis

The serum concentration profile is similar to that in adult patients with rheumatoid arthritis. Modeling suggests that in older children (10-17 years) and in adult patients, the concentration of etanercept in serum is approximately the same, and in younger children it will be significantly lower.

Psoriasis

Equilibrium concentrations of etanercept in the blood serum of children aged 4 to 17 years with psoriasis and children with juvenile idiopathic polyarthritis who received Enbrel®, respectively, at a dose of 0.8 mg / kg once a week (maximum dose of 50 mg per week) and 0.4 mg / kg 2 times a week (maximum dose of 50 mg per week) for 48 and 12 weeks, were similar (1.6-2.1 μg / ml). The value of this indicator coincided with that in adult patients with psoriasis, which Enbrel® was administered at a dose of 25 mg twice a week.

Indications:

Rheumatoid arthritis

In combination with methotrexate Enbrel® is prescribed to adults in the treatment of active rheumatoid arthritis of medium and high severity, when the response to basic anti-inflammatory drugs (BPBP), including methotrexate, was inadequate. Enbrel® can be prescribed as a monotherapy in the case of ineffectiveness or intolerance to methotrexate.

Enbrel® is indicated for the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate.

Juvenile idiopathic polyarthritis

Treatment of active juvenile idiopathic polyarthritis (seropositive and seronegative) in children and adolescents over the age of 12 and with a body weight of more than 62.5 kg (for the drug Enbrel in the dosage form "subcutaneous injection solution"), in whom there was insufficient efficiency or intolerance methotrexate.

Treatment of advanced oligoarthritis in children and adolescents over the age of 12 and with a goal weight of more than 62.5 kg (for the drug Enbrel® in a dosage form "solution for subcutaneous administration"), in whom insufficient efficacy or intolerance to methotrexate was observed.

Treatment of psoriatic arthritis in adolescents over the age of 12 and body weight of more than 62.5 kg (for the drug Enbrel® in the dosage form "solution for subcutaneous administration"), in whom there was insufficient efficacy or intolerance to methotrexate.

Treatment of arthritis associated with enthesitis in adolescents over the age of 12 and weighing more than 62.5 kg (for the drug Enbrel® in a dosage form, "a solution for subcutaneous administration"), in whom insufficient efficiency or intolerance to standard therapy was observed.

Psoriatic arthritis

Treatment of active and progressive psoriatic arthritis in adults, when the response to therapy with BPVP was inadequate.

Axial form of spondyloarthritis

Ankylosing spondylitis

Treatment of adults with severe active ankylosing spondylitis, in whom traditional therapy did not lead to significant improvement.

Dorsiatological stage of axial form of spondyloarthritis

Etanercept is indicated for the treatment of adult patients with severe course of the dorotgenological stage of the axial form of spondyloarthritis who have an inadequate response or resistance to standard therapy, and there are objective signs of disease activity confirmed by an increase in C-reactive protein (CRP) and / or MRI- scanning.

Psoriasis

Treatment of adults with psoriasis of moderate and severe severity, who have contraindications or intolerance to other systemic therapy, including ciclosporin, methotrexate or PUVA-therapy.

Treatment of children over the age of 12 and weighing more than 62.5 kg (for the drug Enbrel® in a dosage form, "subcutaneous administration solution") with chronic severe psoriasis, in whom intolerance or insufficient response to other systemic or phototherapy was observed.

Contraindications:

Hypersensitivity to etanercept or any other component of the drug.

Sepsis or the risk of sepsis.

Active infection, including chronic or localized infections.

Pregnancy and the period of breastfeeding.

Patients younger than 12 years of age and weighing less than 62.5 kg (for the drug Enbrel® in a dosage form "solution for subcutaneous administration").

Carefully:

Demyelinating disease, chronic heart failure (CHF), conditions of immunodeficiency diseases that predispose to the development or activation infections (diabetes, hepatitis), alcoholic hepatitis moderate and severe, hepatitis C, dyscrasia blood, nervous diseases (multiple sclerosis, optic neuritis , transverse myelitis).

Pregnancy and lactation:

Application of the drug Enbrel® contraindicated during pregnancy and in women planning pregnancy, since there is no experience of using this drug in pregnant women.

Etanercept penetrates into the placenta.

In newborns whose mothers received etanercept therapy during pregnancy, they detected it in blood plasma. The clinical significance of this is unknown, but such children may have increased sensitivity to infections. It is not recommended to administer live vaccines to newborns within 16 weeks after their mothers received the last dose of etanercept.

Women of childbearing age should use a reliable method of contraception during drug therapy Enbrel®, and also within three weeks after its cancellation. Etanercept is excreted in breast milk after subcutaneous injection. Since immunoglobulins, like many other drugs, can be released from human milk, either stop breastfeeding or stop taking Enbrel® during breastfeeding, taking into account the importance of therapy for the mother and the risk to the baby.

Dosing and Administration:

Subcutaneously.

Treatment with drug Enbrel® should be appointed and monitored by a physician experienced in the diagnosis and treatment of rheumatoid arthritis, juvenile idiopathic polyarthritis, psoriatic arthritis, ankylosing spondylitis, or psoriasis. Enbrel® in the form of a ready-made solution of 25 mg (a disposable syringe containing 0.5 ml of the drug) and 50 mg (a disposable syringe containing 1.0 ml of the drug) or 50 mg (a pen containing 1 ml of the drug) is used for patients who have a mass body more than 62.5 kg. In patients with a body weight of less than 62.5 kg, lyophilizate should be used to prepare the solution.

Before the introduction of the drug, you should carefully study the instructions for its use, which is at the end of this section.

Adults

Rheumatoid arthritis

The recommended dose is 25 mg of the drug Enbrel® twice a week with an interval of 3-4 days. Alternative dose - 50 mg once a week, which can be administered by a single subcutaneous injection of 50 mg or two injections of 25 mg drug made almost simultaneously.

Psoriatic arthritis

Ankylosing spondylitis

Dorsiatological stage of axial form of spondyloarthritis

The recommended dose is 25 mg of the drug Enbrel® twice a week with an interval of 3-4 days. An alternative dose is 50 mg once a week, which can be administered by a single subcutaneous injection of 50 mg or two injections of 25 mg of the drug taken almost simultaneously.

Psoriasis

The recommended dose is 25 mg of the drug Enbrel® twice a week with an interval of 3-4 days. It is possible to administer 50 mg of the drug once a week by a single subcutaneous injection or two injections of 25 mg of the drug taken almost simultaneously. Alternatively, you can apply Enbrel® 50 mg twice a week for no more than 12 weeks. If it is necessary to continue treatment Enbrel® should be administered at a dose of 25 mg twice weekly or 50 mg once a week. Therapy should be performed before remission is achieved and, as a rule, not more than 24 weeks. The drug should be discontinued if there is no positive symptom dynamics after 12 weeks of treatment. In some cases, the duration of treatment may be more than 24 weeks.

In adult patients, depending on the evaluation of the doctor and the individual characteristics of the patient, therapy can be carried out continuously or intermittently.

If it is necessary to re-administer the drug Enbrel® the duration of treatment indicated above should be observed. It is recommended to prescribe a dose of 25 mg twice a week or 50 mg once a week.

The duration of therapy in some patients may exceed 24 weeks.

Elderly patients (65 years and older)

There is no need to adjust the dose or method of administration.

Children (over 12 years of age and having a body weight of 62.5 kg or more)

Children under the age of 12 years and weighing less than 62.5 kg (see the section "Contraindications") should apply Enbrel® in a dosage form, a lyophilizate for preparing a solution for subcutaneous administration, which allows a dose of less than 25 mg to be administered.

Children over the age of 12 and weighing more than 62.5 kg can apply Enbrel® in the form of a solution for subcutaneous administration in the form of syringes or disposable syringes.

Juvenile idiopathic polyarthritis (children over the age of 12 and weighing more than 62.5 kg (for the drug Enbrel® in the dosage form "solution for subcutaneous administration"))

In this group of patients, the drug Enbrel® in a dosage form, "a solution for subcutaneous administration" is used as in adults: a single dose of 25 mg.The drug is administered twice a week at intervals of 3-4 days. Treatment with the drug should be discontinued if after 4 months of therapy there is no positive dynamics of symptoms.

It is possible to administer a dose of 50 mg once a week.

Common oligoarthritis (children over the age of 12 and weighing more than 62.5 kg (for the drug Enbrel® in the dosage form "solution for subcutaneous administration"))

In this group of patients, the drug Enbrel® in a dosage form, "a solution for subcutaneous administration" is used as in adults: a single dose of 25 mg. The drug is administered twice a week at intervals of 3-4 days. Treatment with the drug should be discontinued if after 4 months of therapy there is no positive dynamics of symptoms.

It is possible to administer 50 mg once a week.

Psoriatic arthritis (adolescents older than 12 years and weighing more than 62.5 kg (for the drug Enbrel® in the dosage form "solution for subcutaneous administration"))

In this group of patients, the drug Enbrel® in a dosage form, "a solution for subcutaneous administration" is used as in adults: a single dose of 25 mg. The drug is administered twice a week at intervals of 3-4 days. Treatment with the drug should be discontinued if after 4 months of therapy there is no positive dynamics of symptoms.

It is possible to administer 50 mg once a week.

Arthritis associated with enthesitis (adolescents over 12 years of age and weighing more than 62.5 kg (for the drug Enbrel® in a dosage form "solution for subcutaneous administration"))

In this group of patients, the drug Enbrel® in the dosage form "solution for subcutaneous administration" is used as in adults: a single dose of 25 mg. The drug is administered twice a week at intervals of 3-4 days. Treatment with the drug should be discontinued if after 4 months of therapy there is no positive dynamics of symptoms.

It is possible to administer 50 mg once a week.

Psoriasis (children over the age of 12 and weighing more than 62.5 kg (for the drug Enbrel® in a dosage form "solution for subcutaneous administration"))

A single dose of the drug is 50 mg. The drug is administered once a week, the duration of therapy is no more than 24 weeks. The drug should be discontinued if, after 12 weeks of treatment, there is no response to ongoing therapy. If it is necessary to re-administer the drug Enbless®, the duration of treatment indicated above should be followed. A single dose of the drug is 50 mg once a week.

In case of missing the dose at the due time, it is necessary to apply the drug immediately, as soon as this is remembered, but provided that the next injection should be no earlier than a day later. Otherwise, you must skip the forgotten injection and make another injection in time.

Impaired liver and kidney function: there is no need to adjust the dose.

Below are the instructions for the preparation and administration of a solution for subcutaneous administration of the drug Enbrel® in syringes and in syringes-pens.

Selection of injection site

- Three places are recommended for drug administration Enbrel®: (1) the anterior surface of the middle third of the thigh; (2) the stomach, except for a 5 cm area around the navel; (3) the outer surface of the shoulder (see Figure 1). If you are injecting yourself, do not use the outer surface of the shoulder.

- Each injection should be performed in a new location. The location of each new injection should be at least 3 cm away from the site of previous injections. DO NOT inject the drug into areas where there is soreness, redness of the skin, bruising, or constriction. Do not enter into areas with scars or stretch marks. (It may be useful to record the places of previous injections).

- If the child is ill with psoriasis, try not to inject the drug directly into the areas raised above the surface of the skin, thickened, reddened or in the hearths with peeling ("psoriatic plaques").

1) INSTRUCTION FOR THE PREPARATION AND INTRODUCTION OF A SOLUTION FOR THE SUBSTITUTIONAL ADMINISTRATION OF THE PREPARATION Enbrel® IN THE SYRINGE

Patients or their parents / caregivers who will inject should be informed about how to properly administer the injection. In the event that further injections are carried out by the patient or his parents / guardian, the first administration should be carried out under the supervision of qualified medical personnel.

Preparation for injection

This drug should not be mixed in one syringe or vial with any other drugs!

- Remove the cardboard box with the pre-filled syringes with the Enbrel® preparation from the refrigerator and place it on a clean, well-lit and level surface. Take one pre-filled syringe. Do not shake the syringe. Place the cardboard box with the remaining syringes back into the refrigerator.

- Leave the syringe with the solution Enbrel® for 15-30 minutes, so that it warms up to room temperature. DO NOT remove the cap from the syringe needle until it reaches room temperature. Do not heat Enbrel® in any other way (for example, in a microwave oven or in hot water).

- Wash your hands with soap and warm water.

- Make sure that the solution in the syringe is transparent or slightly opalescent, colorless or light yellow, and may contain small translucent or white particles of protein nature. Otherwise, do not enter the solution. Use another syringe pre-filled with Enbrel®.

- You will also need: an alcoholic napkin, it is included in the set, and a cotton ball or gauze napkin.

Preparation of the skin site and introduction of Enbrel solution®

- In a circular motion, wipe the skin area into which you will inject Enbrel®, with a clean alcohol sponge. DO NOT KASS this area before the injection.

- Remove the cap from the needle, pulling it with force from the syringe (see Figure 2). Be careful not to bend or twist the cap during removal, so as not to damage the needle.

- When removing the cap at the end of the needle, a drop of liquid may appear; this is permissible.

- Do not touch the needle and avoid touching it with any other surface. Do not touch the piston and do not apply pressure to it. This can lead to fluid leakage from the syringe.

- When the cleared area of the skin is completely dry, with one hand, assemble the skin into the crease and hold it. With the second hand, hold the syringe like a pencil.

- With a quick short movement, direct the needle into the skin at an angle of 45 ° to 90 ° (see Fig. Fig. 3). Over time, you will find the angle that is most comfortable with the introduction. Try not to inject the needle into the skin too slowly or with excessive force.

- After the needle has completely entered the skin, release the fold of the skin that you were holding. Hold the base of the syringe with your free hand to stabilize the position of the syringe. Then push the plunger to enter the entire solution at a slow constant rate (see Figure 4).

- When the syringe becomes empty, remove the needle from the skin; try to keep it under the same angle at which it was injected.

- Press the cotton ball or gauze pad onto the injection site for 10 seconds. There may be slight bleeding. DO NOT wipe the injection site. You can impose a bandage.

Recycling

- PrevThe augmented syringe is only for single use. NEVER use the syringe and needle again, NEVER reattach the cap on the needle. Dispose of the needle and syringe as directed by your doctor or nurse.

If you have network questions, please contact your doctor or nurse who work with Enbrel®.

2) INSTRUCTION FOR THE PREPARATION AND INTRODUCTION OF THE SOLUTION FOR THE SUBORDINATE ADMINISTRATION OF THE ENBREL PREPARATION® In the SPRITS-HANDLE

- He try to inject yourself if you do not understand how to properly use the syringe pen. If you have questions regarding injection, please ask your doctor or nurse.

Step 1. Preparation for the administration of Enbrel®

- Select a clean, well-lit, flat working surface.

Collect the following items that are necessary for the injection, and place them on the work surface (see Figure 5):

a. One pre-filled syringe pen and one alcoholic napkin (remove them from a cardboard bundle with syringes, which you store in the refrigerator). Do not shake the syringe pen.

b.One cotton ball or gauze.

- Assess the condition of the solution in the syringe-pen through the transparent inspection window. It is permissible to introduce only a transparent or slightly opalescent, colorless or pale yellow solution that does not contain visible particles. Otherwise, use another syringe pen, and then seek help from a pharmacist.

- Without removing the white needle cap, wait approximately 15-30 minutes for the Enbrel® solution in the syringe to warm to room temperature. This will increase the comfort of injection. Do not heat the syringe handle in any other way. Always put the pen in a place that children can not reach.

- While the solution in the syringe pen is warmed to room temperature, read the details of the Step 2 activities (listed below), and select the place of introduction.

Step 2. Introduction of Enbrel®

- After warming the solution to room temperature for about 15-30 minutes, wash your hands with soap and water.

- In a circular motion, wipe the skin area into which you will inject Enbrel®, with a clean alcohol sponge and allow to dry. DO NOT KASS this area before the injection.

- Remove the syringe handle, remove the white cap from it, pulling it straight towards yourself (see Figure 7). To avoid damaging the needle with the cap closed, do not tilt the cap, taking it off, and do not attempt to re-attach it after removal. After removing the needle cap, you will see a purple protective screen, slightly protruding from the edge of the pen syringe. The needle itself will remain inside the syringe pen until the moment of activation.

- Carefully collect the skin in the fold between the thumb and forefinger of the free hand - this will simplify the introduction of the drug and make it more comfortable. Try not to touch the cleaned surface of the skin.

- Without exerting pressure on the green activation button located at the top of the syringe pen, place it at a right angle (90 °) to the insertion point and tightly Press its open end against the skin so that the protective screen completely goes inside the syringe pen. This will determine the slight pressure of the skin (see Figure 8). It must be remembered that the green activation button will remain locked, which will not allow activating the syringe pen until the violet protective screen is completely inside the syringe pen.

- Firmly press the syringe handle against the skin and make sure that the purple protective screen has fully entered into it. To perform the injection, press and immediately release the green button located at the top of the pen syringe (see Figure 9). After releasing the button, you will hear a click. Continue to hold the syringe-pen tightly pressed to the skin either to the second click, or within 10 seconds after the first click (the earliest of the events is taken into account).

Note: after the first click, remove the finger from the activation button, otherwise you will not hear a second click after the injection is completed. To fully administer Enbrel®, you do not need to hold the button down.

- After the second click (or after 10 seconds), the injection is completed (see Figure 10), and you can relax the pressure on the skin (see Figure 11), as the purple protective screen automatically extends and closes the needle.

In this case, the color of the inspection window of the syringe-pen will change to violet, which is confirmation of the correctness of the dose of the drug. If this does not happen, you should seek help from a doctor, nurse or pharmacist, because in such a situation, the full dose of Enbrel® can not be guaranteed.Do not try to use this syringe pen again, also do not start using a new syringe pen without consulting a nurse or pharmacist.

- When blood drops appear at the injection site, squeeze the cotton ball or gauze pad to the injection site and hold them for 10 seconds. Do not rub the injection site.

Step 3. Disposal of used syringe pen

- The syringe pen is intended for single use only, therefore its repeated use is not allowed. Dispose of used syringes-pens in accordance with the instructions of a doctor, nurse or pharmacist.

If you have any questions, please ask your doctor, nurse or pharmacist who has experience with Enbrel^®.

Side effects:

Adverse reactions, depending on the frequency of occurrence, were grouped as follows: very often (≥1 / 10); often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); rarely (≥1 / 10000, <1/1000); very rarely (<1/10000), isolated cases (it is impossible to determine the frequency).

Infectious and parasitic diseases: very often - infections (including upper respiratory tract infections, bronchitis, cystitis, skin infections); infrequently - serious infections (including pneumonia, phlegmon,septic arthritis, sepsis and parasitic infections); rarely - mycobacterial infections, including tuberculosis, opportunistic infections (including invasive fungal, protozoal, bacterial, atypical mycobacterial, viral infections and diseases caused by Legionella): single cases - infections caused by Listeria, activation of hepatitis B.

Benign, malignant and unspecified neoplasms (including cysts and polyps): infrequently - Skin cancer not related to melanoma (FCNM); rarely - lymphoma, melanoma; isolated cases - leukemia, Merkel's carcinoma.

Violations from the blood and lymphatic system: infrequently - thrombocytopenia; rarely - anemia, leukopenia, neutropenia, pancytopenia; very rarely - aplastic anemia.

Immune system disorders: often - allergic reactions (see subsection "disorders of the skin and subcutaneous tissue"), the formation of autoantibodies; infrequently - systemic vasculitis (including ANCA-associated vasculitis); rarely serious allergic / anaphylactic reactions (including bronchospasm), sarcoidosis; single cases - macrophage activation syndrome.

Disturbances from the nervous system: rarely - convulsions, demyelination in the central nervous system (CNS), similar to those observed with multiple sclerosis or local demyelination, such as optic neuritis and transverse myelitis (see section "Special instructions"); very rarely - peripheral demyelinating diseases (including Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy).

Disturbances on the part of the organ of sight: infrequently - uveitis, scleritis.

Disturbances from the respiratory system, chest and mediastinal organs: infrequently - interstitial lung diseases (including pneumonitis and pulmonary fibrosis).

Disorders from the liver and bile ducts: rarely - increased activity of "hepatic" enzymes, autoimmune hepatitis.

Disturbances from the skin and subcutaneous tissues: often - itchy skin; infrequently - angioedema, urticaria, rash, psoriasis-like rash, psoriasis (including a debut of the disease or worsening and pustular lesions, mostly soles and palms); rarely - cutaneous vasculitis, Stevens-Johnson syndrome, erythema multiforme; very rarely - toxic epidermal necrolysis.

Disturbances from musculoskeletal system and connective tissue: rarely - cutaneous manifestations of subacute lupus erythematosus, discoid lupus erythematosus, lupus-like syndrome.

General disorders and disorders at the site of administration: very often - local reactions after injection (including bleeding, the formation of subcutaneous hematoma, erythema, itching, pain, swelling); often a fever.

Disorders from the cardiovascular system: rarely - worsening of XCN flow (see section "Special instructions").

Additional Information

Adverse reactions in adults

The frequency of drug withdrawal due to the development of adverse reactions during controlled clinical trials in patients with rheumatoid arthritis was similar in patients receiving Enbrel® and receiving placebo. Against the background of treatment with the drug Enbrel® the most common were the reactions at the site of administration of the drug. The frequency of these reactions reached a peak in the first month of application of the drug, and then gradually decreased. In clinical studies, these reactions were predominantly transient and lasted for an average of 4 days. In some patients who experienced the development of the reaction at the site of administration, reactions were also noted at the sites of the previous administration.During postregistration observations of the drug Enbrel®, the development of bleeding and the appearance of hematomas at the injection sites were noted.

Adverse reactions in children

In general, the frequency and types of adverse reactions in children were similar to those observed in adult patients. Infections were the most frequent adverse reactions. Infections that were observed in clinical studies in children with juvenile idiopathic polyarthritis aged 2 to 18 years were of mild to moderate severity, and their species did not conflict with those commonly found among outpatients. Reports of serious adverse events reported included varicella with symptoms of aseptic meningitis, which resolved without sequelae (see. Section "Special instructions"), appendicitis, gastroenteritis, depression / personality disorder, skin ulcer, esophagitis / gastritis, septic shock, caused by group A streptococcus , type I diabetes mellitus and soft tissue infections and postoperative wounds.

4 reports on macrophage activation syndrome were recorded in these patients. The development of reactions at the site of administration during controlled clinical trials in children with juvenile idiopathic polyarthritis was higher in patients receiving Enbrel® than in placebo.

Cases of inflammatory bowel disease have been reported in patients with juvenile idiopathic polyarthritis receiving Enbrel® therapy, including a very small number of observations of recurrence of symptoms upon resumption of therapy. There was no clear cause-effect relationship, since cases of inflammatory bowel disease were also seen in patients with juvenile idiopathic arthritis who were not treated.

The frequency and types of adverse reactions in children with psoriasis were similar to those observed in adult patients.

Overdose:

With an overdose of Enbrel® immediately inform your doctor or pharmacist.

Keep the carton pack of Enbrel® even if it is empty.

The maximum dose of Enbrel® is not established. In the clinical study, healthy volunteers received a dose of 60 mg / m², once, which did not lead to the development of a dose-limiting toxicity.

In the treatment of patients with rheumatoid arthritis, there were no cases of excess of the toxic dose limit. The highest dose administered intravenously was 32 mg / m² with subsequent subcutaneous injection of 16 mg / m² twice a week.

The specific antidote for the drug Enbrel® is unknown.

Interaction:

Anakinra

Against the background of combined therapy with etanercept and anakin, there was a significant increase in the incidence of serious infections and neutropenia compared to patients who received only etanercept or just anakinru.

The combined use of etanercept and anakinra has not shown clinical benefit and is therefore not recommended.

Abatacept

The simultaneous use of abatacept and etanercept was accompanied by an increase in the incidence of serious adverse events. This combination of drugs has not demonstrated clinical benefits and is therefore not recommended.

Sulfasalazine

In patients who were treated with sulfasalazine etanercept, a significant decrease in the number of white blood cells is described compared with those who took only etanercept or only sulfasalazine.

Lack of interaction

There were no undesirable interactions with the simultaneous use of etanercept with glucocorticosteroids,salicylates (with the exception of sulfasalazine), nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics or methotrexate.

Methotrexate

Methotrexate has no effect on pharmacokinetics of etanercept. The effect of etanercept on the pharmacokinetics of methotrexate in humans has not been studied.

Digoxin

There was no clinically significant mutual effect on the pharmacokinetics of etanercept.

Warfarin

There was no clinically significant mutual effect on the pharmacokinetics of etanercept.

Vaccination

Live vaccines should not be administered against the background of etanercept treatment. There is no evidence of secondary transmission of infection through live vaccine to patients receiving etanercept. It is recommended that before the initiation of treatment with etanercept, children and adolescents, if possible, receive all the necessary vaccinations in accordance with the current national vaccination calendar.

Most patients with psoriatic arthritis who receive etanercept, there was an increase in the B-cell immune response to the pneumococcal polysaccharide vaccine, but the titres were generally somewhat lower, a two-fold increase in titers was observed in fewer patients than in patients who did not receive etanercept.

Special instructions:

After discontinuation of Enbrel®, the symptoms of the disease may recur.

Infections

Patients should be screened for infections prior to the use of Enbrel®, during treatment and after the course of therapy, taking into account the average duration of the half-life of etanercept, equal to approximately 70 hours (7-300 hours).

With the use of the drug Enbrel®, sepsis, tuberculosis, parasitic infections (including those caused by protozoan organisms) and severe infections, including opportunistic infections, including invasive fungal infections, listeriosis and legionellosis (some with fatal outcome), viral infections (including those caused by Herpes Zoster). The most frequently reported invasive fungal infections were caused by Candida Pneumocystis, Aspergillus and Histoplasma. Incorrect diagnosis of these infections, especially fungal and other opportunistic infections, resulted in a delay in the appointment of treatment and, in some cases, death. In many cases, patients received therapy with other drugs, including immunosuppressants.When examining patients, it is necessary to take into account the possibility of developing opportunistic infections, for example, endemic mycoses. Patients in whom new infections develop against the background of Enbrel® treatment should be carefully monitored. The use of Enbrel® should be discontinued if the patient develops a severe infection. The use of Enbrel® requires caution in patients with frequent or chronic infections in the anamnesis or having co-morbidities that may contribute to the development of infections (eg, severe or poorly controlled diabetes mellitus).

The safety and efficacy of Enbrel® in patients with chronic infections have not been evaluated.

Tuberculosis

Against the background of therapy with the drug Enbrel®, cases of active tuberculosis, including miliary tuberculosis and tuberculosis of extrapulmonary localization, were reported. Among patients with rheumatoid arthritis, there appears to be a higher incidence of tuberculosis infection.

The development of tuberculosis infection can be associated with the reactivation of a latent infection, as well as the development of a new infection.

Before the start of therapy, all patients should be examined for active or latent tuberculosis. Examination should include a detailed study of history in relation to tuberculosis or having contact with TB patients in the past and data about previous or current immunosuppressive therapy. All patients should have the necessary screening tests that meet local requirements, and necessarily include: tuberculin skin test and lung radiography. The possibility of a false-negative tuberculin test should be considered, especially in patients in serious condition or in patients with impaired immunity. It is also necessary to take into account the possibility of developing tuberculosis in patients who had no evidence of tuberculosis infection prior to initiation of Enbrel® therapy. The attending physician should monitor the patient's condition for signs of tuberculosis, incl. In patients with initially negative results of tests for the presence of tuberculosis infection.

Do not use Enbrel® if the patient has active tuberculosis.If there is inactive tuberculosis before starting therapy with Enbrel® It is necessary to prescribe standard anti-tuberculosis therapy in accordance with local recommendations. In this case, the relationship between the benefits and risks of treatment with Enbrel® should be carefully analyzed.

Weight patients should be informed of the need to see a doctor when they appear on the background of treatment with the drug Enbrel® or after it complaints or symptoms characteristic of tuberculosis (for example, persistent cough, weight loss, subfebrile condition).

Activation of the hepatitis B virus

There have been reports of cases of activation of the hepatitis B virus in carrier patients who received TNF inhibitors, including Enbrel®. Most of these cases have occurred in patients who simultaneously receive other drugs that suppress the immune system, which can also contribute to the reactivation of the hepatitis B virus. Before using Enbrel® in patients at high risk for hepatitis B, it is necessary to conduct an appropriate diagnostic search . Despite the fact that communication with the use of the drug Enbrel® is not proven,should be especially careful when using Enbrel® in patients with hepatitis B virus. Patients should be monitored for signs of hepatitis B. If they develop symptoms of this disease, the possibility of specific therapy should be discussed.

Exacerbation of hepatitis C

The cases of exacerbation of hepatitis C in patients receiving Enbrel® therapy are reported, but the causal relationship with the use of etanercept is not proved. Nevertheless, caution should be exercised when using Enbrel® in patients with history of hepatitis C.

Allergic reactions

Allergic reactions are often accompanied by the ingestion of Enbrel®. For any severe allergic or anaphylactic reactions, stop taking the drug immediately Enbrel® and begin appropriate treatment.

Immunosuppression

In patients with FN inhibitorsO, including the drug Enbrel®, there is the possibility of inhibiting the protective mechanisms of the human body against infections and malignant tumors, as TNF is involved in inflammation processes and modulates the cellular immune response.but the of adult patients with rheumatoid arthritis on the background of treatment with the drug Enbrel®, there were no cases of oppression of the reactions of delayed hypersensitivity, a decrease in the level of immunoglobulin or a change in the number of the population of effector cells.

In children with juvenile idiopathic polyarthritis, chicken pox and the symptoms of aseptic meningitis rarely resolved, which were resolved without complications. Patients who were in contact with patients with chickenpox should temporarily stop taking Enbrell® and prescribe prophylactic immunoglobulin against the virus Varicella Zoster.

The efficacy and safety of Enbrel® treatment in patients with immunosuppression have not been studied.

Malignant and lymphoproliferative diseases

In the postmarketing period (see the "Side effect" section), reports were received of various malignant neoplasms (including breast and lung carcinomas, as well as lymphoma).

In a number of controlled clinical trials, lymphoma was more often diagnosed in patients taking TNF inhibitors than in patients who had theme received.On the other hand, these cases were rare, and the observation period for patients from the placebo group was shorter than for patients receiving treatment with TNF inhibitors.

There have been reports of the development of leukemia in the background of therapy with TNF inhibitors. There is a high risk of lymphoma and leukemia in patients with rheumatoid arthritis, which is a long-term disease characterized by active inflammation, which in itself complicates the risk assessment. The subsequent analysis of clinical studies of etanercept in patients with rheumatoid arthritis did not confirm and did not rule out an increased risk of oncological diseases when etanercept is used. In accordance with modern data, the possible risk of developing lymphoma, leukemia or other malignancies in patients receiving TNF inhibitors can not be ruled out.

There are reports of the development of malignant neoplasms (half the cases of Hodgkin's and non-Hodgkin's lymphomas), some of which were fatal, in children and adolescents treated with TNF inhibitors, including Enbrel®. Most patients received concomitant therapy with immunosuppressants.In other cases, there were various malignant neoplasms, including rare variants associated with immunosuppression. When using the drug, it is necessary to take into account the risk of developing malignant neoplasms.

Skin cancer

Melanoma and non-melanoma skin cancer (FCNM) have been reported in patients treated with TNF inhibitors, including Enbrel®. Most often, the FCNM is diagnosed in patients with psoriasis. There are reports of the development of Merkel's carcinoma. For all patients at risk, a periodic examination of the skin is recommended.

Formation of autoimmune antibodies

Treatment with the drug Enbrel® can be accompanied by the formation of autoimmune antibodies (see section "Side effect"). These antibodies do not belong to neutralizers and usually disappear quickly. There was no correlation between the formation of antibodies and the clinical efficacy of the drug, as well as the incidence of adverse reactions. Single cases of formation of additional autoantibodies in combination with lupus-like syndrome or a rash similar to a subacute form of lupus erythematosus or a discoid form of lupus erythematosus (clinical examination and biopsy data),were observed in patients, including patients with rheumatoid arthritis with a positive rheumatoid factor.

Hematologic reactions

There have been reports of rare cases of pancytopenia and very rare cases of aplastic anemia, including fatal cases, in patients receiving Enbrel®. Caution should be exercised when using Enbrel® in patients with an indication of a history of blood disease. All patients, their relatives / caregivers should be aware that if the patient develops signs and symptoms characteristic of infection or hematologic disorders (eg, prolonged fever, sore throat, bruises, bleeding, pallor) while taking Enbrell®. they should immediately seek medical help. In such patients, it is recommended that an examination be performed urgently, including a complete blood test. When confirming the diagnosis of hematologic disease, treatment with the drug Enbrel® should be discontinued.

Defeat of CNC

There are rare reports of the development of demyelinating CNS diseases in patients receiving etanercept therapy.There were also very rare reports of the development of peripheral demyelinating polyneuropathies (including Guillain-Barre syndrome). Studies of Enbrel® in patients with multiple sclerosis have not been conducted, but studies of other TNF inhibitors in this disease have shown the possibility of exacerbation. Before the initiation of therapy with the drug Enbrel®, it is recommended that the risk / benefit ratio, neurological status in patients with demyelinating diseases, including newly developed ones, as well as in patients who have an increased risk of developing a demyelinating disease, be carefully assessed.

Exacerbation of cholesterolH

Caution should be exercised with regard to the appointment of Enbrel® in patients with XCH. Data from a number of studies suggest a possible deterioration in the flow XCH in patients receiving Enbrel®.

Combination Therapy

The combination of Enbrel® and methotrexate did not give unexpected results in a safety study. Long-term study of this indicator continues. The safety data for the Enbrel® preparation, which was prescribed in combination with methotrexate, were similar to those reported for the use of Enbrel® and methotrexate alone.The long-term safety of Enbrel® in combination with other basic anti-inflammatory drugs has not been investigated. Studies of the use of Enbrel® in combination with other systemic therapy or phototherapy for psoriasis have not been conducted.

DWegener's rheulomatosis

The incidence of various types of malignant tumors in the subcutaneous localization was significantly higher in patients with Wegener's granulomatosis who received Enbrel® than in the control group.

Therefore, Enbrel® is not recommended for the treatment of patients with Wegener's granulomatosis.

Alcoholic Hepatitis

The use of etanercept for the treatment of alcoholic hepatitis is not recommended.

Hypoglycemia in patients with diabetes mellitus

There have been reports of hypoglycemia in combination with Enbrel® in patients taking hypoglycemic drugs, which required correction of their dose.

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

The study of the effect on the ability to drive a car and use complex techniques with Enbrel® was not carried out. In this regard, to drive a car or use sophisticated technology should be carefully.

Form release / dosage:

Solution for subcutaneous administration, 50 mg / ml.

Packaging:

1) 0.5 ml (25 mg) or 1.0 ml (50 mg) of the drug in disposable syringes of colorless glass (type I) equipped with a stainless steel needle, closed with a two-layer cap, plastic finger rest and a stem - a piston with a rubber sealant.

For 4 syringes complete with 4 individually packaged alcohol napkins in plastic packaging, sealed with adhesive paper.

For 1, 2 or 6 plastic packages (25 mg) or 1, 2 or 3 plastic bags (50 mg) together with instructions for use in a cardboard pack.

2) For 1.0 ml (50 mg) of the drug in a disposable syringe pen with a white plastic needle cap and a purple protective screen. A syringe inside the handle of a colorless glass (type I), equipped with a needle made of stainless steel.

By 4 syringes-handles complete with 4 individually packed alcoholic napkins in plastic packing, sealed with adhesive paper. 1 plastic bag together with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature of 2 to 8 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-006652/09

Date of registration:19.08.2009

The owner of the registration certificate: Pfizer Inc. Pfizer Inc. USA

Manufacturer: & nbsp

WYETH PHARMACEUTICALS United Kingdom