Enbrel, lyophilizate 10 mg 4 pcs

A drug with anti-inflammatory action. Tumor necrosis factor alpha (TNF-α) inhibitor

Indications

Juvenile idiopathic polyarthritis

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

Psoriasis

Treatment of children 6 years of age and older with severe chronic psoriasis who have had intolerance or inadequate response to other systemic or phototherapies.

Active ingredient

Composition

1 vial etanercept 10 mg

Supplementary substances:

Mannitol 40 mg,

sucrose 10 mg,

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

How to take, the dosage

Subcutaneously.

The treatment with Enbrel should be prescribed and monitored by a physician experienced in the diagnosis and treatment of juvenile idiopathic polyarthritis, psoriasis.

Juvenile idiopathic polyarthritis (children 2 years and older

The dose is based on 0.4 mg/kg body weight (maximum single dose 25 mg). The drug is administered twice a week at intervals of 3-4 days. Treatment with the drug should be stopped if after 4 months of therapy no positive dynamics of symptoms are observed.

Psoriasis (children 6 years and older)

The dose is determined at the rate of 0.8 mg/kg of body weight (maximum single dose of 50 mg). The drug is administered once a week, the duration of therapy is not more than 24 weeks. Administration of the drug should be stopped if after 12 weeks of treatment there is no response to the therapy.

If repeated administration of Enbrel is necessary, the treatment duration stated above should be observed. The drug dose is 0.8 mg/kg body weight (maximum single dose 50 mg) once a week.

If a dose is missed at the proper time, the drug should be administered as soon as remembered, provided that the next injection is not earlier than the day after. Otherwise, the forgotten injection must be skipped and the next injection given on time.

Hepatic and renal dysfunction

There is no need to adjust the dose.

Instructions for preparation and administration of Enbrel subcutaneous solution

Interaction

Anakinra

The combined therapy of Enbrel and anakinra showed a significant increase in the incidence of serious infections and neutropenia compared to patients who received Enbrel alone or anakinra alone. Co-administration of Enbrel and anakinra showed no clinical benefit and therefore is not recommended.

Abatacept

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

Sulfasalazine

A significant decrease in leukocyte counts has been described in patients who received Enbrel alone or sulfasalazine alone during treatment with sulfasalazine.

No interactions

No adverse interactions have been observed when Enbrel is used simultaneously 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 has been no clinically significant reciprocal effect on the pharmacokinetics of etanercept.

Warfarin

No clinically significant reciprocal effect on the pharmacokinetics of etanercept has been found.

Vaccination

Live vaccines should not be administered in the foyer of treatment with Enbrel. There is no evidence of secondary transmission through live vaccine in patients receiving Enbrel. It is recommended that prior to treatment with Enbrel, patients with juvenile idiopathic polyarthritis should receive all necessary vaccinations, if possible, in accordance with the current national vaccination calendar.

Special Instructions

After discontinuation of Enbrel, symptoms may recur.

Infections

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

Sepsis, tuberculosis, parasitic infections (including protozoa) and severe infections, including opportunistic infections, including invasive fungal infections, listeriosis and legionellosis have been reported with Enbrel. Misdiagnosis of these infections, especially of fungal and other opportunistic infections, resulted in delayed prescription of necessary treatment and, in some cases, death.

The possibility of opportunistic infections, such as endemic mycoses, should be taken into account when examining patients. 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 with great caution in patients with a history of frequent or chronic infections or who have an underlying medical condition, such as advanced or poorly controlled diabetes, which may contribute to the development of infections.

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

Tuberculosis

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

Before initiating therapy, all patients should be examined for active or latent tuberculosis. The examination should include a detailed history of tuberculosis or past contact with tuberculosis patients and evidence of prior or current immunosuppressive therapy. All patients should have appropriate screening procedures performed (according to local requirements), namely, tuberculin skin test and pulmonary radiography. The possibility of a false-negative tuberculin test should be considered, especially in critically ill or immunocompromised patients.

Enbrel should not be used in patients with active tuberculosis. The diagnosis of inactive tuberculosis suggests prescription of standard antituberculosis therapy before starting Enbrel therapy. In this case, the benefit-risk ratio of treatment with Enbrel should be carefully analyzed.

All patients should be informed to seek medical attention if, during or after treatment with Enbrel, they have complaints or symptoms characteristic of tuberculosis (e.g., persistent cough, weight loss, subfebrile fever).

Hepatitis B virus activation

Hepatitis B virus activation has been reported in carrier patients who received TNF inhibitors, including Enbrel. Before using Enbrel in patients at high risk for hepatitis B, an appropriate diagnostic search should be performed. Particular caution should be observed when using Enbrel in patients who are carriers of hepatitis B virus. If they have symptoms of the disease, specific therapy should be discussed.

Hepatitis C exacerbation

Cases of hepatitis C exacerbation have been reported in patients treated with Enbrel. Caution should be used with Enbrel in patients with a history of hepatitis C.

Allergic reactions

Allergic reactions often accompany the use of Enbrel. Any severe allergic or anaphylactic reactions should immediately discontinue Enbrel and begin appropriate treatment.

Immunosuppression

When treated with TNF inhibitors, including Enbrel, there is a possibility of inhibiting the body’s defense mechanisms against infections and malignancies, since TNF is involved in inflammatory processes and modulates the cellular immune response. However, in adult patients with rheumatoid arthritis no cases of inhibition of delayed hypersensitivity reactions, decrease in immunoglobulin levels or changes in the number of effector cells have been found during treatment with Enbrel.

Children with juvenile idiopathic polyarthritis rarely developed chickenpox and symptoms of aseptic meningitis, which resolved without complications. Patients who have been in contact with patients with varicella zoster should temporarily discontinue Enbrel and be given prophylactic treatment with immunoglobulin against Varicella zoster virus.

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

Malignant and lymphoproliferative diseases

A variety of malignancies (including breast and lung carcinoma and lymphoma) have been reported in the post-marketing period (see side effects section).

Lymphoma was diagnosed more often 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 lymphoma and leukemia in patients with rheumatoid arthritis, which is a long-term disease characterized by active inflammation, which in itself complicates risk assessment. At the same time, according to current data, the possible risk of lymphoma, leukemia or other malignancies cannot be excluded in patients receiving TNF inhibitors either.

There have been reports of malignancies, some of which have been fatal, in children and adolescents treated with TNF inhibitors, including Enbrel. Approximately half of these cases developed lymphoma. In other cases, various malignancies occurred, including rare variants associated with immunosuppression. The risk of malignancy in children and adolescents should be considered when using the drug.

Skin cancer

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

Autoimmune antibody formation

The treatment with Enbrel may be accompanied by the formation of autoimmune antibodies (see side effects section). These antibodies are not neutralizing and usually disappear quickly. No correlation between the formation of antibodies and the clinical efficacy of the drug, as well as the frequency of adverse reactions, has been noted. Single cases of additional autoantibodies formation in combination with lupus-like syndrome or rash similar to subacute form of lupus erythematosus or discoid lupus (data of clinical examination and biopsy) were noted in patients, including rheumatoid arthritis patients with positive rheumatoid factor.

Hematological reactions

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

CNS damage

While Enbrel has not been studied in patients with multiple sclerosis, studies of other TNF inhibitors in this comorbid disease have shown the potential for exacerbation.

Before initiating therapy with Enbrel, a careful assessment of the risk/benefit ratio, neurologic status in patients with a previous exacerbation of demyelinating disease, and in patients who are at increased risk for demyelinating disease is recommended.

Combination therapy

The combination of Enbrel and methotrexate produced no unexpected results in the safety study. Long-term studies of this indication are ongoing. The safety data for Enbrel prescribed with methotrexate were similar to those reported for Enbrel and methotrexate alone. The long-term safety of Enbrel with other baseline 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 malignant tumors of extracutaneous localization was significantly higher in patients with Wegener’s granulomatosis who received Enbrel® than in the control group.

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

Hypoglycemia in patients with diabetes mellitus

Hypoglycemia has been reported with Enbrel therapy in patients taking antidiabetic drugs, which required adjustment of their dose.

Influence on the ability to drive and use complex equipment

The study of the effect on the ability to drive and use complex equipment during the use of Enbrel has not been conducted. In this regard, caution should be exercised while driving a vehicle or using complex equipment.

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 breastfeeding.

The efficacy and safety of Enbrel for the treatment of juvenile idiopathic polyarthritis in children under 2 years of age has 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.

Cautions

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

Side effects

The adverse reactions based on frequency of occurrence were grouped as follows: very common (≥1/10); common (≥1/100, < 1/10); infrequent (≥1/1000, < 1/100); rare (≥1/10,000, < 1/1000); very rare (< 1/10000), isolated cases (frequency cannot be determined).

Infectious and parasitic diseases:very common–infections (including upper respiratory tract infections, bronchitis, cystitis, skin infections); infrequent–severe infections (including pneumonia, phlegmon, septic arthritis, sepsis and parasitic infections); rare – tuberculosis, opportunistic infections (including invasive fungal, protozoal, bacterial and atypical mycobacterial infections and diseases caused by Legionella); single cases – infections caused by Listeria.

Malignant, malignant and unspecified neoplasms (including cysts and polyps): infrequent – non-melanoma skin cancer (RCNM); rare – lymphoma, melanoma; single cases – leukemia, Merkel carcinoma.

Blood and lymphatic system disorders: infrequent – thrombocytopenia; rare – anemia, leukopenia, neutroia, pancytopenia; very rare – anelastic anemia.

Disorders of the immune system:often – allergic reactions (see. Skin and subcutaneous tissue” subsection), formation of autoantibodies; infrequent – systemic vasculitis (including ANCA-associated vasculitis); rare – serious allergic/anaphylactic reactions (including angioedema, bronchospasm), sarcoidosis; single cases – macrophage activation syndrome.

Nervous system disorders: seldom – seizures, phenomena of demyelination in CNS, similar to those observed in multiple sclerosis or the condition of local demyelination, such as optic neuritis and transverse myelitis (see “Special indications”). section “Special Indications”); very rarely – peripheral demyelinating diseases (including Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, demyelinating polyneuropathy, multifocal motor neuropathy).

Visual disorders: infrequently – uveitis.

Disorders of the respiratory system, thorax and mediastinum:infrequent – interstitial lung disease (including pneumonitis and pulmonary fibrosis).

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

Dermatological and subcutaneous tissue disorders: often – skin itching; infrequent – angioneurotic edema, urticaria, rash, psoriasis-like rash, psoriasis (including debut or worsening and pustular lesions, mainly of the soles and palms); rare – cutaneous forms of vasculitis, Stevens-Johnson syndrome, erythema multiforme; very rare – toxic epidermal necrolysis.

Muscular and connective tissue disorders: frequently – skin 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, formation of subcutaneous hematoma, erythema, skin itching, pain, swelling); often – fever.

Cardiovascular system disorders: seldom – worsening of the course of congestive heart failure (CHF) (see section “Special indications”).

Infections in children

The frequency and types of adverse reactions in children with juvenile idiopathic polyarthritis were similar to those seen in adult patients with rheumatoid arthritis. The infections observed in clinical trials in children with juvenile idiopathic polyarthritis aged 2 to 18 years were mild to moderate in severity, and their types were not inconsistent with those commonly seen in ambulatory patients. Reports of severe adverse events included varicella with aseptic meningitis symptoms that resolved without complications (see Special Indications), appendicitis, gastroenteritis, depression/personality disorders, skin ulcers, esophagitis/gastritis, aseptic shock caused by group A streptocococci, type I diabetes and soft tissue and postoperative wound infections.

There have been 4 reports of macrophage activation syndrome in these patients. Inflammatory bowel disease has been reported in patients with juvenile idiopathic polyarthritis receiving Enbrel therapy in the post-marketing period, including cases with recurrent bowel disease. No clear causal relationship was established, as cases of inflammatory bowel disease also occurred in patients with untreated juvenile idiopathic polyarthritis.

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

Overdose

If you overdose on Enbrel, tell your doctor or pharmacist immediately. Save the carton 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 dose administered intravenously was 32 mg/m2 followed by subcutaneous administration of 16 mg/m twice weekly.

One patient with rheumatoid arthritis mistakenly self-administered 62 mg of Enbrel subcutaneously twice weekly for 3 weeks with no adverse effects. A specific antidote for Enbrel is not known.