Enbrel Lyophilizate for solution for subcutaneous injection 10mg vial 4pcs + 1ml syringe with solvent, pack

Composition

of 1 fl. etanercept 10 mg

Auxiliary substances:

mannitol 40 mg,

sucrose 10 mg,

trometamol (as a mixture of trometamol and trometamol hydrochloride until pH 7.4 is reached) 1.2 mg

Pharmacological action

A drug with an anti-inflammatory effect. Tumor necrosis factor alpha (TNF-alpha)inhibitor

Indications

Juvenile idiopathic polyarthritis

— treatment of active juvenile idiopathic polyarthritis in children and adolescents aged 2-17 years who have experienced insufficient efficacy or intolerance to methotrexate.

Psoriasis

— treatment of children aged 6 years and older with severe chronic psoriasis, who have experienced intolerance or insufficient response to other systemic or phototherapy.

Contraindications

-hypersensitivity to etanercept or any other component of the drug;

– sepsis or risk of sepsis;

– active infection, including chronic or localized infections—

– pregnancy and lactation.

The efficacy and safety of Enbrel for the treatment of juvenile idiopathic polyarthritis in children under 2 years of age have not been studied.

The efficacy and safety of Enbrel for the treatment of psoriasis in children under 6 years of age have not been studied.

With caution

Demyelipating diseases, congestive heart failure( CHF), immunodeficiency states, diseases predisposing to the development or activation of infections (diabetes mellitus, hepatitis), moderate and severe alcoholic hepatitis, hepatitis C, blood dyscrasia, nervous diseases (multiple sclerosis, optic neuritis, transverse myelitis).

Side effects

Adverse reactions were grouped by frequency as follows: very common (≥1/10); common (≥1/100, < 1/10); uncommon (≥ 1/1000, <1/100); rare (≥1/10 000, <1/1000); very rare (

Infectious and parasitic diseases:  very often, infections (including upper respiratory tract infection, bronchitis, cystitis, skin infections); rarely, serious infections (including pneumonia, cellulitis, septic arthritis, sepsis, and parasitic infections); rarely, tuberculosis, opportunistic infections (including invasive fungal, protozoal, bacterial and atypical mycobacterial infection and disease caused by Legionella); isolated cases of infection caused by Listeria.

Benign, malignant, and unspecified neoplasms (including cysts and polyps): infrequently-non-melanoma skin cancer (NSCLC); rarely-lnmfoma, melanoma; isolated cases-leukemia, Merkel cell carcinoma.

Disorders of the blood and lymphatic system: infrequently-thrombocytopenia; rarely-anemia, leukopenia, neutropenia, pancytopenia; very rarely-anaplastic anemia.

Immune system disorders: often-allergic reactions (see section “Skin and subcutaneous tissue”), autoantibody formation; infrequently-systemic vasculitis (including ANCA-associated vasculitis); rarely-serious allergic / anaphylactic reactions (including angioedema, bronchospasm), sarcoidosis; isolated cases-macrophage activation syndrome.

Nervous system disorders: rarely – convulsions, symptoms of demyelination in the CNS similar to that observed in multiple sclerosis or as a local demyelinate, such as optic neuritis and transverse myelitis (see “Special instructions”); very rarely – peripheral demicontinuous diseases (including Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, demyelinating polyneuropathy, multifocal motor neuropathy).

Visual disturbances: infrequently – uveitis.

Respiratory, thoracic and mediastinal disorders: infrequently-interstitial lung diseases (including pneumonitis and pulmonary fibrosis).

Liver and biliary tract disorders: rarely-increased activity of “liver” enzymes, autoimmune hepatitis.

Skin and subcutaneous tissue disorders: often-pruritus of the skin; infrequently-angioedema, urticaria, rash, psoriasis-like rash, psoriasis (including the onset of the disease or worsening and pustular lesion, mainly of the soles and palms); rarely-cutaneous forms of vasculitis, Stevens-Johnson syndrome, erythema multiforme; very rarely-toxic epidermal necrolysis.

Musculoskeletal and connective tissue disorders: rarely-skin manifestations of subacute lupus erythematosus, discoid lupus erythematosus, lupus-like syndrome.

General disorders and disorders at the injection site:  very often – local reactions after injections (including bleeding, subcutaneous hematoma, erythema, pruritus, pain, swelling); often-fever.

Disorders of the cardiovascular system: rarely-worsening of the course of congestive heart failure (CHF) (see the section “Special instructions”).

Adverse reactions in children

The frequency and types of adverse reactions in children with juvenile idiopathic polyarthritis were similar to those observed in adult patients with rheumatoid arthritis. Infections that were observed in clinical studies in children with juvenile idiopathic polyarthritis aged 2 to 18 years were mild to moderate in severity, and their types did not contradict those that are usually found among outpatient patients. Reports of severe adverse events have included chickenpox with symptoms of aseptic meningitis that resolved without complications (see section “Special instructions”), appendicitis, gastroenteritis, depression/personality disorders, skin ulcers, esophagitis/gastritis, aseptic shock caused by Group A streptococci, type I diabetes mellitus, and soft tissue and postoperative wound infections.

There were 4 reports of macrophage activation syndrome in these patients. Cases of inflammatory bowel disease have been reported in patients with juvenile idiopathic polyarthritis treated with Enbrel in the post-marketing period, including cases with recurrent bowel disease. A clear causal relationship was not established, as cases of inflammatory bowel diseases also occurred in patients with juvenile idiopathic polyarthritis who did not receive treatment.

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

Interaction

Anakinra

When combined with Enbrel and anakinra, there was a significant increase in the incidence of serious infections and neutropenia compared to patients treated with Enbrel alone or anakinra alone. The combined use of Enbrel and anakinra has not shown any clinical benefit and is therefore not recommended.

Abatacept

Concomitant use of abatacept and Enbrel was associated with an increased incidence of serious adverse events. This combination of drugs has not demonstrated clinical benefits and is therefore not recommended.

Sulfasalazine

Patients who received Enbrel during treatment with sulfasalazine showed a significant decrease in the number of white blood cells compared to those who received Enbrel alone or sulfasalazine alone.

Lack of interaction

No adverse interactions were observed when Enbrel was co-administered with glucocorticosteroids, salicylates (except for sulfasalazine), NSAIDs, analgesics, or methotrexate.

Methotrexate

Methotrexate has no effect on the pharmacokinetics of etanercept. The effect of Enbrel 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 in the foyer of Enbrel treatment. There are no data on secondary transmission of infection via live vaccine to patients receiving Enbrel. It is recommended that patients with juvenile idiopathic polyarthritis receive all necessary vaccinations in accordance with the current national vaccination calendar before starting treatment with Enbrel.

How to take it, course of administration and dosage

Subcutaneously.

Treatment with Enbrel should be prescribed and supervised by a doctor who has experience in the diagnosis and treatment of juvenile idiopathic polyarthritis, psoriasis.

Juvenile idiopathic polyarthritis (children aged 2 years and older)

The dose is determined at the rate of 0.4 mg / kg of body weight (the maximum single dose is 25 mg). The drug is administered twice a week with an interval of 3-4 days. Treatment with the drug should be discontinued if after 4 months of therapy there is no positive dynamics of symptoms.

Psoriasis (children aged 6 years and older)

The dose is determined at the rate of 0.8 mg / kg of body weight (the maximum single dose 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 there is no response to the therapy after 12 weeks of treatment.

If it is necessary to re-prescribe Enbrel, the duration of treatment indicated above should be observed.The dose of the drug is 0.8 mg / kg of body weight (the maximum single dose is 50 mg) once a week.

If the dose is missed at the prescribed time, the drug should be administered immediately, as soon as it is remembered, but provided that the next injection should be no earlier than a day later. Otherwise, you need to skip the forgotten injection and make the next injection on time.

Impaired liver and kidney function

There is no need to adjust the dose.

Instructions for preparation and use of a solution for subcutaneous use of Enbrel

Introduction

Do not attempt to use Enbrel until you are sure that you understand how to properly prepare and administer it.

Do not mix Enbrel with any other medication in the same syringe or bottle!

The prepared solution should be used within 6 hours.

Preparation for drug use

Wash your hands thoroughly.

Choose a clean, well-lit, flat work surface.

The plastic packaging for the use of a single dose of the drug should contain the items listed below. (If an item is missing from the plastic packaging, do not use it and contact your pharmacist. ) Use only the listed items. Do not use other syringes.

— 1 bottle containing Enbrel lyophilizate

– 1 syringe containing a clear, colorless solvent (water for injection)

— 1 injection needle

— 1 bottle adapter

-2 alcohol wipes

Check the expiration date (month and year) on the label of the bottle and syringe. They should not be used after the specified period.

Preparation of a dose of Enbrel for injection

Remove the contents of the plastic packaging.

Remove the plastic cap from the bottle. Do not remove the rubber stopper or the aluminum ring around the neck of the bottle.

Use a clean alcohol cloth to wipe the rubber stopper on the Enbrel bottle. After processing, do not touch it with your hands and do not allow it to come into contact with any surface.

Place the bottle in an upright position on a clean, flat surface.

Remove the paper cover from the packaging with the bottle adapter.

Without removing the adapter from its plastic packaging, place it on the Enbrel bottle so that the tip of the adapter is in the center of the raised circle on the bottle cap.

Hold the bottle firmly on a flat surface with one hand. With your other hand, push the adapter pack straight down until you feel the tip of the adapter pass through the bottle cap and feel or hear the adapter’s rim slide into place. Do not push the adapter at an angle. It is important that the tip of the adapter passes completely through the bottle cap.

While holding the bottle in one hand, remove the plastic packaging from the bottle adapter.

Remove the protective coating from the tip of the syringe by breaking off the white cap along the perforated line. To do this, hold one end of the cap with one hand and hold the other end of the white cap firmly with the other hand and pull it down until it breaks. Do not remove any part of the white cap remaining on the syringe.

Do not use the syringe if the tip of the cap is already broken off along the perforated line. Take a different package.

Holding the syringe by the glass cylinder (but not the white cap) in one hand and the bottle adapter (but not the bottle itself) in the other, connect the syringe to the bottle adapter by inserting the tip into the hole and turning it clockwise until it is fully connected.

Adding a solvent

While holding the bottle vertically on a flat surface, push the plunger very slowly until all the solvent is in the bottle. This will help reduce the formation of foam (a lot of bubbles).

After adding the solvent to Enbrel, the plunger can rise on its own. This is normal and has to do with air pressure.

Without removing the syringe, gently rotate the bottle to dissolve the powder. Do not shake the bottle. Wait until the powder is completely dissolved (this usually takes less than 10 minutes). The solution should be clear and colorless, without lumps, flakes or particles. There may be some white foam left in the bottle, this is normal.

Do not use Enbrel if the powder in the bottle does not dissolve within 10 minutes. Take a new plastic package with the drug.

How to get a solution of Enbrel from a bottle.

The doctor or his assistant should have informed you how much of the solution should be collected from the bottle. If your doctor has not given you such instructions, please contact them.

Without disconnecting the syringe from the bottle and the bottle adapter, lift the bottle up to eye level, holding it upside down. Push the plunger down until it is fully inserted into the syringe.

Then slowly pull the plunger to draw liquid into the syringe. Take only the necessary part of the solution, as indicated by your child’s doctor. After you have taken the required dose of Enbrel, there may be air left in the syringe. Don’t worry about this as you will remove the air from the syringe later.

While holding the bottle upside down, unscrew the syringe from the adapter by turning it counterclockwise.

Place the filled syringe on a clean, flat surface. Make sure that the tip of the syringe does not touch anything. Be careful not to push on the plunger.

How to put a needle on a syringe

The needle is placed in a plastic container to preserve its sterility.

To open a plastic container, hold the short, wide end in one hand. With the other hand, take the longer part of the container.

To break the seal, pull the longer part down and then up until it breaks off.

Once the seal is broken, remove the short, wide part of the plastic container.

The needle will remain in the long part of the package.

Holding the needle and container in one hand, take the syringe and insert the tip of the syringe into the needle hole.

Attach the syringe to the needle by turning it clockwise until it is fully connected.

Remove the cap from the needle by pulling on it; be careful not to touch the needle or allow the needle to come into contact with anything. Try not to bend or twist the cap when removing it, so as not to damage the needle.

While holding the syringe vertically, remove any air bubbles by slowly pressing the plunger until all the air is out of the syringe.

Choosing the injection site

Three sites for Enbrel use are recommended: (1) the front surface of the middle third of the thigh; (2) the abdomen, except for the 5 cm area around the navel; (3) the outer surface of the shoulder. If you are injecting yourself, do not use the outer surface of the shoulder.

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

If your child has psoriasis, try not to inject the drug directly into areas that are raised above the surface of the skin, thickened, reddened, or in areas with peeling (“psoriatic plaques”).

Preparation of the injection site and use of Enbrel solution

In a circular motion, wipe the area of skin into which you will inject Enbrel with a clean alcohol cloth. Do not touch this area before performing the injection.

When the cleaned area of skin is completely dry, gather the skin into a fold with one hand and hold it. With the other hand, hold the syringe like a pencil.

In a quick, short motion, point the needle into the skin at an angle of 45° to 90°. Over time, you will find the corner that is most comfortable for the child. Try not to insert the needle into the skin too slowly or with excessive force.

Once the needle is fully embedded in the skin, release the fold of skin you were holding. With your free hand, hold the base of the syringe to stabilize it. Then push down on the plunger to inject the entire solution at a slow, constant rate.

When the syringe is empty, remove the needle from the skin; try to hold it at the same angle at which it was inserted.

Apply a cotton swab to the injection site for 10 seconds. Minor bleeding may occur. Do not wipe the injection site. You can apply a bandage.

Disposal of consumables

Never re-use the syringe or needles. Dispose of the needles and syringe as directed by your doctor, nurse, or pharmacist.

If you have any questions, please contact the doctor or nurse who works with Enbrel.

Overdose

If you overdose on Enbrel, tell your doctor or pharmacist immediately. Keep the cardboard package of Enbrel, even if it is empty.

No cases of exceeding the toxic dose limit have been reported in the treatment of patients with rheumatoid arthritis.

The highest intravenous dose was 32 mg / m%^%2, followed by subcutaneous use of 16 mg / m twice a week.

One patient with rheumatoid arthritis mistakenly self-administered 62 mg of Enbrel subcutaneously twice a week for 3 weeks with no adverse effects. The specific antidote for Enbrel is unknown.

Special instructions

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

Infections

Patients should be screened for infections before starting Enbrel, during treatment, and after the end of therapy, taking into account the average etanercept half-life of approximately 70 hours (7-300 hours).

Sepsis, tuberculosis, parasitic infections (including protozoa) and severe infections, including opportunistic ones, including invasive fungal infections, listeriosis and legionellosis, have been reported with Enbrel. Incorrect diagnosis of these infections, especially fungal and other opportunistic infections, led to delayed treatment and, in some cases, death.

When examining patients, it is necessary to take into account the possibility of developing opportunistic infections, for example, endemic mycoses. Patients who develop new infections during treatment with Enbrel should be closely monitored. Enbrel should be discontinued if the patient develops a severe infection. Enbrel should be used very carefully in patients with a history of frequent or chronic infections or an underlying medical condition, such as progressive or poorly controlled diabetes, which may contribute to the development of infections.

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

Tuberculosis

Cases of active tuberculosis, including miliary tuberculosis and extrapulmonary tuberculosis, have been reported with Enbrel therapy.

All patients should be screened for active or latent tuberculosis before starting therapy. The examination should include a detailed history of tuberculosis or previous contact with TB patients, as well as data on previous or ongoing immunosuppressive therapy. All patients should undergo appropriate screening procedures (according to local requirements), namely, a tuberculin skin test and a lung X-ray. The possibility of a false-negative tuberculin test should be considered, especially in patients in serious condition or patients with impaired immunity.

Enbrel should not be used if the patient has active tuberculosis. The diagnosis of inactive tuberculosis involves prescribing standard TB therapy before starting Enbrel therapy. In this case, the benefit-risk ratio of Enbrel treatment should be carefully evaluated.

All patients should be informed about the need to consult a doctor if they develop complaints or symptoms characteristic of tuberculosis (for example, persistent cough, weight loss, subfebrility) during or after treatment with Enbrel.

Hepatitis B virus activation

Cases of hepatitis B virus activation have been reported in carrier patients treated with TNF inhibitors, including Enbrel. Before using Enbrel in patients who are at high risk for hepatitis B, it is necessary to conduct an appropriate diagnostic search. Special care should be taken when using Enbrel in patients with hepatitis B virus carriers. If they develop symptoms of this disease, the possibility of specific therapy should be discussed.

Hepatitis C exacerbation

Cases of hepatitis C exacerbation have been reported in patients receiving Enbrel therapy. Caution should be exercised when using Enbrel in patients with a history of hepatitis C.

Allergic reactions

Allergic reactions often accompany taking Enbrel. In case of any severe allergic or anaphylactic reactions, you should immediately stop taking Enbrel and start appropriate treatment.

Immunosuppression

When treated with TNF inhibitors, including Enbrel, it is possible to inhibit the protective mechanisms of the human body against infections and malignancies, since TNF is involved in inflammatory processes and modulates the cellular immune response. However, in adult patients with rheumatoid arthritis treated with Enbrel, there were no cases of inhibition of delayed hypersensitivity reactions, a drop in the level of immunoglobulin, or changes in the population of effector cells.

Children with juvenile idiopathic polyarthritis rarely developed chickenpox and symptoms of aseptic meningitis, which resolved without complications. Patients who have been in contact with chickenpox patients should temporarily stop taking Enbrel and prescribe preventive treatment with Varicella zoster immunoglobulin.

The efficacy and safety of Enbrel treatment in immunosuppressed patients have not been studied.

Malignant and lymphoproliferative diseases

In the post-marketing period (see the “Side effect” section) various malignancies (including breast and lung carcinoma, as well as lymphoma) were reported.

More often, lymphoma was diagnosed in patients taking TNF inhibitors than in patients who did not receive them. On the other hand, these cases were rare, and the follow-up period for patients in the placebo group was shorter than for patients treated with TNF inhibitors. In addition, there is a high risk of developing lymphoma and leukemia in patients with rheumatoid arthritis, which is a long-term disease characterized by active inflammation, which in itself complicates risk assessment. However, according to current data, it is impossible to exclude the possible risk of developing lymphomas, leukemia, or other malignancies in patients receiving TNF inhibitors.

There are reports of malignancies, some of which were fatal, in children and adolescents treated with TNF inhibitors, including Enbrel. Approximately half of these cases developed lymphoma. In other cases, various malignancies have occurred, including rare variants associated with immunosuppression. When using the drug, it is necessary to take into account the risk of developing malignant neoplasms in children and adolescents.

Skin cancer

Melanoma and non-melanoma skin cancer (NSCLC) have been reported in patients treated with TNF inhibitors, including Enbrel. Most often, PCNM is diagnosed in patients with psoriasis. There are reports of the development of Merkel cell carcinoma. Periodic skin examinations are recommended for all patients at risk.

Formation of autoimmune antibodies

Treatment with Enbrel may be accompanied by the formation of autoimmune antibodies (see section “Side effects”). These antibodies are not neutralizing and usually disappear quickly. There was no correlation between the formation of antibodies and the clinical efficacy of the drug, as well as the frequency of adverse reactions. Isolated cases of formation of additional autoantibodies in combination with lupus-like syndrome or rash similar to subacute lupus erythematosus or discoid lupus erythematosus (data from clinical examination and biopsy) They were observed in patients, including patients with rheumatoid arthritis with a positive rheumatoid factor.

Hematological reactions

Rare cases of pancytopenia and very rare cases of aplastic anemia, including fatal cases, have been reported in patients treated with Enbrel. Caution should be exercised when using Enbrel in patients with a history of blood disorders. All patients and their relatives/caregivers should be informed that if a patient develops signs and symptoms that are characteristic of infection or hematological disorders (for example, prolonged fever, sore throat, bruising, bleeding, pallor) while taking Eibrel, they should immediately seek medical attention. In such patients, it is recommended to conduct an urgent examination, including a complete blood test. If the diagnosis of a hematological disease is confirmed, treatment with Enbrel should be discontinued.

CNS lesion

Although the use of Enbrel in patients with multiple sclerosis has not been studied, studies of other TNF inhibitors in this concomitant disease have shown the possibility of its exacerbation.

Before starting therapy with Enbrel, it is recommended to carefully evaluate the risk / benefit ratio, neurological status in patients with a previous exacerbation of demyelinating disease and in patients with an increased risk of developing demyelinating disease.

Combination therapy

The combination of Enbrel and methotrexate did not produce unexpected results in the safety study. A long-term study of this indicator is ongoing. Data on the safety of Enbrel, which was administered together with methotrexate, were similar to data from reports on the use of Enbrel and methotrexate separately. The long-term safety of Enbrel with other basic anti-inflammatory drugs has not been studied.

The use of Enbrel in combination with other systemic therapy or phototherapy for psoriasis has not been studied.

Wegener’s granulomatosis

The incidence of various types of extracutaneous malignancies was significantly higher in patients with Wegener’s granulomatosis treated with Enbrel than in the control group.

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

Hypoglycemia in patients with diabetes mellitus

Hypoglycaemia has been reported with Enbrel therapy in patients taking antidiabetic medications, which required dose adjustment.

Influence on the ability to drive a car and use complex equipment

The study of the effect on the ability to drive a car and use complex equipment when using Enbrel has not been conducted.In this regard, you should drive a car or use complex equipment with caution.

Form of production

Lyophilizate for the preparation of a solution for subcutaneous use in the form of a white powder or porous mass.

Active ingredient

Etanercept

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection

Purpose

Children as prescribed by a doctor, Adults as prescribed by a doctor

Indications

Cancer