Instruction for use: Etanercept

Trade name of the drug – Enbrel

The Latin name of the substance Etanercept

Etanerceptum (genus. Etanercepti)

Gross formula

C₂₂₂₄H₃₄₇₅N₆₂₁O₆₉₈S₃₆

Pharmacological group:

Immunosuppressive drugs

The nosological classification (ICD-10)

L40 Psoriasis: Chronic plaque psoriasis with diffuse; generalized psoriasis; Psoriasis of the scalp; hairy parts of the skin; A generalized form of psoriasis; Psoriazoformny dermatitis; Psoriasis complicated with erythroderma; disabling psoriasis; Isolated psoriatic plaque; Eksfolliativny psoriasis; psoriatic erythroderma; Psoriasis with eczematization; Hyperkeratosis in psoriasis; Inverse psoriasis; Psoriasis ekzemopodobnye; dermatoses psoriazoformny; Psoriasis genitals; Psoriasis lesions with hairy areas of the skin; erythrodermic psoriasis; Chronic psoriasis of the scalp; Chronic psoriasis; ordinary psoriasis; refractory psoriasis; Koebner phenomenon; psoriasis

M06.9 Rheumatoid arthritis, unspecified: Rheumatoid arthritis; Pain syndrome in rheumatic diseases; Pain in rheumatoid arthritis; Inflammation in rheumatoid arthritis; Degenerative forms of rheumatoid arthritis; Children's rheumatoid arthritis; Exacerbation of rheumatoid arthritis; Acute articular rheumatism; Rheumatic arthritis; Rheumatic polyarthritis; Rheumatoid arthritis; Rheumatic polyarthritis; Rheumatoid arthritis; Rheumatoid arthritis; Rheumatoid arthritis of active course; Rheumatoid periarthritis; Rheumatoid polyarthritis; Acute rheumatoid arthritis; Acute rheumatism

M07.3 Other psoriatic arthropathies (L40.5 +): Psoriatic arthritis; Generalized form of psoriatic arthritis; Psoriatic arthritis

M08 Juvenile [juvenile] arthritis: Juvenile arthritis; Juvenile chronic polyarthritis; Juvenile chronic arthritis; Juvenile rheumatoid arthritis; Arthritis Juvenile chronic

M45 Ankylosing spondylitis: Ankylosing spondylarthrosis; Marie-Strumpel disease; Ankylosing spondylitis; Ankylosing spondylitis; Pain syndrome in acute inflammatory diseases of the musculoskeletal system; Pain syndrome in chronic inflammatory diseases of the musculoskeletal system; Bechterew's disease; Ankylosing spondylitis; Diseases of the spinal column; Rheumatic spondylitis; Bechterew-Marie-Strumpel disease

CAS Code

185243-69-0

Pharmacology

Mode action - Immunosuppressive.

Pharmacodynamics

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 TNF receptors on the cell surface-55-kDa (p55) and 75-kDa (p75). Both receptors are present in the body in membrane-bound and free forms. Soluble TNF receptors regulate its biological activity.

TNF and lymphotoxin exist primarily as homotrimers, their biological activity depends on the cross-linking of TNF receptors located on the cell surface. Dimeric soluble receptors, such as etanercept, have a greater affinity for TNF than monomeric ones, and therefore are significantly stronger competitive inhibitors of TNF-binding to their cellular receptors. In addition, the use of the Fc fragment of Ig as a binding element in the dimeric receptor structure prolongs T1 / 2 from 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 its receptors on the cell surface. Thus, etanercept prevents the cellular response mediated by TNF, promoting the biological inactivation of TNF. Etanercept can also modulate biological responses controlled by additional molecules that transmit the signal downward (eg, cytokines, adhesion molecules or proteinases). And these answers can either stimulate or control TNF.

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

After discontinuing therapy with etanercept during the month, the disease may worsen. The effectiveness of re-appointment 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 injection site, reaching Cmax approximately 48 hours after a single dose. Absolute bioavailability is 76%. When a dose of ethanercept is administered 2 times a week, the Css is twice as high as that observed after a single dose. After a single administration of 25 mg, the average Cmax etanercept in the blood plasma was (1.65 ± 0.66) μg / ml, AUC - (235 ± 96.6) μg · h / ml. Apparent saturation of clearance in the dose limits was not observed.

The dependence of the etanercept concentration on time is described by the biexponential curve. The average value of Vd is 7.6 liters, while Vss is 10.4 liters.

From the body etanercept is withdrawn slowly. T1 / 2 is about 70 hours. In patients with rheumatoid arthritis, clearance is approximately 0.066 l / h, slightly 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 etanercept 50 mg, administered once, is bioequivalent to the dose obtained by two 25 mg injections done 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 is 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 clear differences in the pharmacokinetics of etanercept in men and women.

Elderly patients. The clearance and apparent Vd etanercept in the group of patients 65 to 87 years old were similar to those in patients younger than 65 years of age.

Children

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

Psoriasis. Css etanercept in the blood serum in children aged 4 to 17 years with psoriasis and children with juvenile idiopathic polyarthritis who received etanercept respectively at a dose of 0.8 mg / kg once a week and 0.4 mg / kg 2 times a week (Maximum dose of 50 mg / 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 etanercept was administered at a dose of 25 mg twice a week.

Application of the substance Etanercept

Rheumatoid arthritis:

- in combination with methotrexate in the treatment of active rheumatoid arthritis of medium and high severity, when the response to basic anti-inflammatory drugs, including methotrexate, was inadequate;

- in the form of monotherapy in case of ineffectiveness or intolerance of methotrexate;

- severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate.

Juvenile idiopathic polyarthritis:

- active juvenile idiopathic polyarthritis (seropositive and seronegative) in children and adolescents who have had insufficient efficiency or intolerance to methotrexate;

- common oligoarthritis in children and adolescents who have had insufficient effectiveness or intolerance to methotrexate;

- psoriatic arthritis in adolescents over the age of 12 years who have had insufficient efficacy or intolerance to methotrexate;

- Arthritis associated with enthesitis, in adolescents over the age of 12 years, who have had insufficient efficacy or intolerance to standard therapy.

Psoriatic arthritis:

- active and progressive psoriatic arthritis in adults with inadequate response to treatment with basic anti-inflammatory drugs.

Axial form of spondyloarthritis:

- severe active ankylosing spondylitis in adults in the absence of significant improvement as a result of traditional therapy;

- severe course of the dorotgenologic stage of the axial form of spondyloarthritis in adult patients who had an inadequate response or resistance to standard therapy, and there are objective signs of disease activity confirmed by an increase in C-reactive protein concentration and / or MRI scan data.

Psoriasis:

- moderate to severe psoriasis, in adult patients with contraindications or intolerance to other systemic therapy, including cyclosporine, methotrexate, or PUVA therapy;

- chronic psoriasis of severe severity in children and adolescents who experienced intolerance or insufficient response to other systemic or phototherapy.

Contraindications

Hypersensitivity to etanercept; Sepsis or risk of sepsis; Active infections, including chronic or localized; Pregnancy and the period of breastfeeding.

Efficacy and safety of etanercept for the treatment of juvenile idiopathic polyarthritis (seropositive and seronegative) and advanced oligoarthritis in children under 2 years of age have not been studied.

The efficacy and safety of the use of etanercept for the treatment of psoriasis in children under the age of 6 years has not been studied.

The efficacy and safety of the use of etanercept for the treatment of psoriatic arthritis and arthritis associated with enthesitis in children under the age of 12 has not been studied.

Restrictions

Demyelinating diseases; CHF; State of immunodeficiency; Diseases predisposing to the development or activation of infections (diabetes, hepatitis); Alcoholic hepatitis of moderate and severe course; Hepatitis C; Blood dissociation; Nerve diseases (multiple sclerosis, optic neuritis, transverse myelitis).

Application of pregnancy and breastfeeding

The safety of etanercept during pregnancy is not established. The available data did not show an increase in the frequency of congenital malformations of the fetus. In addition, there was no increase in the incidence of intrauterine or postnatal growth deficits or postnatal developmental delays in children. The use of etanercept is contraindicated during pregnancy and in women planning pregnancy, because there is no experience of its use 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. The introduction of live vaccines to newborns is not recommended for 16 weeks after their mothers received the last dose of etanercept. Women of childbearing age should use a reliable method of contraception during therapy, and also within 3 weeks after its cancellation.

Etanercept is excreted in breast milk after SC injection. You should either stop breastfeeding or take etanercept during breastfeeding, taking into account the importance of therapy for the mother and the risk to the baby.

Side effects of the substance Etanercept

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), single cases (the frequency cannot be determined).

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; Single cases - leukemia, Merkel's carcinoma.

From the blood and lymphatic system: infrequently - thrombocytopenia; Rarely - anemia, leukopenia, neutropenia, pancytopenia; Very rarely - aplastic anemia.

On the part of the immune system: often - allergic reactions (see "From the skin and subcutaneous tissues"), the formation of autoantibodies; Infrequently - systemic vasculitis (including ANCA-associated); Rarely serious allergic / anaphylactic reactions (including bronchospasm), sarcoidosis; Single cases - the syndrome of activation of macrophages.

From the side of the nervous system: rarely - convulsions, demyelination in the CNS, similar to those observed with multiple sclerosis or local demyelination, such as optic neuritis and transverse myelitis (see "Precautions"); Very rarely - peripheral demyelinating diseases (including Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, demyelinating polyneuropathy, multifocal motor neuropathy).

From the side of the organ of vision: rarely - uveitis, scleritis.

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

From the liver and bile ducts: rarely - increased activity of liver enzymes, autoimmune hepatitis.

From the skin and subcutaneous tissues: often - skin itching; 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 forms of vasculitis, Stevens-Johnson syndrome, erythema multiforme; Very rarely - toxic epidermal necrolysis.

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

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

On the part of the CAS: rarely - worsening of the course of CHF (see "Precautions").

Additional Information

Adverse reactions in adults. The frequency of withdrawal due to the development of adverse reactions during controlled clinical trials in patients with rheumatoid arthritis was similar in patients receiving etanercept and placebo. Against the background of etanercept therapy, the most common reactions were at the injection site. The frequency of these reactions reached a peak in the first month of use, and then gradually decreased. In clinical trials, these reactions were predominantly transient and lasted 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 the post-trend observation of etanercept, 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 severe adverse events included chicken pox with symptoms of aseptic meningitis that resolved without complications (see "Precautions"), appendicitis, gastroenteritis, depression / personality disorders, skin ulcers, esophagitis / gastritis, septic shock caused by group A streptococci, Type 1 diabetes mellitus and soft tissue infections and postoperative wounds.

4 reports on macrophage activation syndrome were recorded in these patients.

Cases of inflammatory bowel disease have been reported in patients with juvenile idiopathic polyarthritis who are receiving etanercite therapy, including a very small number of observations of recurrence of symptoms upon resumption of therapy. There was no clear causal relationship, because Cases of inflammatory bowel diseases have also occurred in patients with juvenile idiopathic arthritis who have not been treated.

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

Interaction

Anakinra. Against the background of combined therapy with ethanercent and anakin, there was a significant increase in the incidence of serious infections and neutropenia compared with patients who were given only etanercept or anakinru alone.

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

Abatacept. 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. Patients who received etanercept during the treatment with sulfasalazine reported a significant decrease in the number of white blood cells compared to patients who took only etanercept or only sulfasalazine.

Lack of interaction. No undesirable interactions were observed with the simultaneous use of etanercept with GCS, salicylates (excluding sulfasalazine), NSAIDs, analgesics or methotrexate.

Methotrexate. Methotrexate does not affect the 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 and digoxin.

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

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.

In most patients with psoriatic arthritis receiving etanercept, an increase in the B-cell immune response to the pneumococcal polysaccharide vaccine was observed, but the titres were generally somewhat lower; A double increase in titers was observed in fewer patients than in patients not receiving etanercept.

Overdose

The maximum dose of etanercept is not established. In a 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 followed by SC administration of 16 mg / m2 twice a week.

The specific antidote for etanercept is unknown.

Routes of administration

SC.

Precautions for the substance Etanercept

After the termination of the use of etanercept, the symptoms of the disease may recur.

Infections. Patients should be screened for infections prior to initiating the use of etanercept, during treatment and after the course of therapy, taking into account the average duration of T1 / 2 etanercept, equal to about 70 hours (7-300 hours).

When etanercept was used, it was reported about sepsis, tuberculosis, parasitic infections (including those caused by protozoan organisms) and severe infections, incl. Opportunistic (including invasive fungal infections), listeriosis and legionellosis (some with a fatal outcome), viral infections (including those caused by Herpes zoster). The most frequently recorded invasive fungal infections were caused by Candida, Pneumocystis, Aspergillus and Histoplasma. Incorrect diagnosis of these infections, especially fungal and other opportunistic infections, led to a belated appointment of necessary treatment and in some cases - a fatal outcome. In many cases, patients received therapy with other drugs, including. Immunosuppressive drugs. 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 etanercept therapy should be carefully monitored. The use of etanercept should be discontinued if the patient develops a severe infection. The use of etanercept requires caution in patients with frequent or chronic infections in the history or having co-morbidities that can contribute to the development of infections (eg severe or poorly controlled diabetes mellitus).

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

Tuberculosis. On the background of etanercept therapy, cases of active tuberculosis, including miliary and extra-pulmonary 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. The examination should include a detailed history of tuberculosis disease or contacts with TB patients in the past and data on previous or current immunosuppressive therapy. All patients must have the necessary screening tests that meet local requirements and necessarily include a tuberculin skin test and lung radiography. The possibility of a false-negative tuberculin test should be taken into account, especially in patients with a severe condition or patients with impaired immunity. It is also necessary to take into account the possibility of developing tuberculosis in patients who did not have signs of tuberculosis infection before initiation of etanercept 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 etanercept if the patient has active tuberculosis. In the presence of inactive tuberculosis before the initiation of therapy with etanercept, standard antituberculous therapy should be prescribed in accordance with local recommendations. In this case, it is necessary to carefully analyze the relationship between the benefits and risks of treatment with etanercept.

All patients should be informed of the need to see a doctor if etanercept or treatment with symptoms or symptoms characteristic of tuberculosis (for example, persistent cough, weight loss, subfebrile condition) appear against the background of treatment with etanercept or after the withdrawal of therapy.

Activation of the hepatitis B virus. There have been reports of cases of activation of the hepatitis B virus in patient carriers who received TNF inhibitors, including etanercept. Most of these cases have been observed in patients who simultaneously receive other drugs that suppress the immune system, which can also contribute to the reactivation of hepatitis B virus. Before using etanercept in patients at high risk for hepatitis B, an appropriate diagnostic search should be carried out. Despite the fact that the connection with the use of etanercept is not proven, special care should be taken when using it in patients with hepatitis B virus. It is necessary to monitor the status of patients for the presence of signs of hepatitis B. When they have symptoms of this disease, the possibility of conducting a specific Therapy.

Exacerbation of hepatitis C. There have been reported cases of exacerbation of hepatitis C in patients who received etanercept therapy, but the causal relationship is not proven. Nevertheless, caution should be exercised when using etanercept in patients with hepatitis C in a history.

Allergic reactions. Allergic reactions often accompany the use of etanercept. For any severe allergic or anaphylactic reactions, the use of etanercept should be immediately discontinued and appropriate treatment initiated.

Immunosuppression. With therapy with TNF inhibitors, incl. Etanercept, 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. However, in adults with rheumatoid arthritis, etanercept was not associated with depression of delayed hypersensitivity reactions, a decrease in Ig level, or a change in 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 had contact with patients with chickenpox should temporarily stop the use of etanercept and prescribe a prophylactic treatment of Ig against the virus Varicella Zoster.

The efficacy and safety of etanercept therapy in patients with immunosuppression has not been studied.

Malignant and lymphoproliferative diseases. In the postmarketing period (see "Side effects"), 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 patients who did not receive them. On the other hand, these cases were rare, and the observation period in patients in the placebo group was shorter than in patients treated with TNF inhibitors. There are reports of the development of leukemia against the background of therapy with TNF inhibitors. There is a high risk of lymphoma and leukemia in patients with rheumatoid arthritis, a long-term disease characterized by active inflammation, which in itself complicates risk assessment. The subsequent analysis of clinical studies of etanercept in patients with rheumatoid arthritis did not confirm or rule out an increased risk of developing cancer due to the use of etanercept. According to modern data, the possible risk of developing lymphoma, leukemia or other malignancies in patients receiving TNF inhibitors cannot be ruled out.

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

Skin cancer. Melanoma and FCNM have been reported in patients treated with TNF inhibitors, including etanercept. 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.

The formation of autoimmune antibodies. Treatment with etanercept can be accompanied by the formation of autoimmune antibodies (see "Side effects"). 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 etanercept, and the incidence of adverse reactions. Single cases of formation of additional autoantibodies in combination with lupus-like syndrome or a rash similar to subacute or discoid form of lupus erythematosus (clinical examination and biopsy data) were noted 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, incl. With a fatal outcome, in patients receiving etanercept. Caution should be exercised when using etanercept in patients with indications of blood diseases in the history. All patients, their relatives / caregivers should be warned that if a patient develops signs and symptoms that are typical for infection or hematologic disorders (eg, prolonged fever, sore throat, bruises, bleeding, pallor) during the use of etanercept, they should immediately Seek medical attention. 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 etanercept should be discontinued.

Defeat of the central nervous system. There are rare reports of the development of demyelinating CNS diseases in patients who received etanercept therapy. There are also very rare reports of the development of peripheral demyelinating polyneuropathies (including Guillain-Barre syndrome). Studies of the use of etanercept in patients with multiple sclerosis have not been conducted, but studies of the use of other TNF inhibitors in this disease have shown the possibility of exacerbation. Before starting therapy with etanercept, it is recommended to carefully evaluate the risk / benefit ratio, neurological status in patients with demyelinating diseases, incl. Recently emerged, as well as in patients who have an increased risk of developing a demyelinating disease.

Exacerbation of CHF. Caution should be exercised in prescribing etanercept to patients with CHF. Data from various studies suggest a possible worsening of CHF in patients receiving etanercept.

Combined therapy. The use of a combination of etanercept and methotrexate did not lead to unexpected results in a safety study. Long-term study of this combination continues. Data on the safety of etanercept, which was prescribed in combination with methotrexate, were similar to those from reports on the use of etanercept and methotrexate alone. Long-term safety of the use of etanercept in combination with other basic anti-inflammatory drugs has not been investigated. The use of etanercept 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 in the subcutaneous localization was significantly higher in patients with Wegener's granulomatosis who received etanercept than in the control group. Etanercept is not recommended for the treatment of patients with Wegener's granulomatosis.

Alcoholic Hepatitis. The use of etanercept in patients with alcoholic hepatitis is not recommended.

Hypoglycemia in patients with diabetes mellitus. There have been reports of cases of hypoglycemia with etanercept therapy in patients taking hypoglycemic drugs, which required correction of their dose.

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