Enbrel

General characteristics. Structure:

Active agent: Этанерцепт 50,0 mg; excipients: arginine a hydrochloride of 5,3 mg, sodium chloride of 5,8 mg, sucrose of 10,0 mg, hydrophosphate sodium a dihydrate of 1,2 mg, dihydrophosphate sodium a dihydrate of 2,9 mg, water for injections to 1,0 ml.

Pharmacological properties:

Pharmacodynamics. The factor of a necrosis of a tumor (TNF-α, FNO) is the main cytokine supporting inflammatory process at a pseudorheumatism. Increase in the FNO level is also revealed in synovial membranes and psoriasis plaques at patients with psoriasis arthritis, and also in plasma and synovial tissues of patients with an ankylosing spondylitis. Этанерцепт is a competitive inhibitor of linkng of FNO with his receptors on a cell surface, and, thus, inhibits biological activity of FNO. FNO and lymphotoxin belong to pro-inflammatory cytokines which contact two accurately distinguishable receptors of a factor of a necrosis of a tumor (FNOR) on a cell surface: 55-kilodalton (r55) and 75-kilodalton (r75). Both FNOR are present at an organism in membrane-bound and free forms. Soluble FNOR regulate biological activity of FNO.

FNO and lymphotoxin exist preferential as gomotrimer, their biological activity depends on a cross stitching of FNOR which are on a cell surface. Dimeric soluble receptors, such as этанерцепт, have bigger affinity to FNO, than monomeric receptors, and therefore, are much stronger competitive inhibitors of linkng of FNO with their cellular receptors. Besides, use of the Fc area of immunoglobulin as binding element in structure of a dimeric receptor extends an elimination half-life from serum.

Considerable part of pathological changes in joints at a pseudorheumatism and an ankylosing spondylitis, and also changes of skin in the form of psoriasis plaques arise due to influence of the pro-inflammatory molecules involved in the system controlled by FNO. The mechanism of action of an etanertsept, apparently, consists in competitive inhibition of linkng of FNO with FNO receptors on a cell surface. Thus, этанерцепт the cellular answer mediated by FNO warns, promoting a biological inactivation of FNO. Этанерцепт can also modulate the biological answers controlled by the additional molecules transmitting a signal on descending (for example, cytokines, adhesive molecules or proteinases). And these answers can either stimulate, or control FNO.

At patients with psoriasis arthritis Enbrel improves physical activity and reduces probability of development of damage of peripheral joints.

After the therapy termination by drug Enbrel within a month perhaps exacerbations of a disease. Efficiency of repeated purpose of drug within 24 months after the termination of therapy is comparable with that for the patients who were not interrupting treatment.

Pharmacokinetics. Этанерцепт it is slowly absorbed from the place of a subcutaneous injection, reaching the maximum concentration approximately in 48 hours after a single dose of Enbrel. Absolute bioavailability makes 76%. At introduction of a dose of Enbrel higher equilibrium concentration are twice a week reached twice, than those that are observed after a single dose. After single hypodermic introduction of 25 mg Enbrela average maximum concentration in plasma was 1,65 ±0,66 mkg/ml, the area under a curve "concentration – time" (AUC) – 235 ±96,6 mkg · hour/ml. Visible saturation of clearance in borders of a dose was not observed.

Dependence of concentration of an etanertsept on time is described by a bieksponentsialny curve. Average value of volume of distribution makes 7,6 l while distribution volume at an equilibrium state makes 10,4 l.

Out of an organism этанерцепт it is brought slowly. The elimination half-life (T1/2) makes about 80 hours. At patients with a pseudorheumatism the clearance is equal to about 0,066 l/hour that is slightly lower than its value of 0,11 l/hour at healthy volunteers. Pharmacokinetic characteristics of an etanertsept at patients with a pseudorheumatism, ankylosing spondylarthritis and psoriasis are similar.

Enbrel's dose of 50 mg once a week a bioekvivalentna to the dose of 25 mg entered two times a week.

At patients with an acute renal or liver failure of increase of concentration of an etanertsept it is not observed.

In pharmacokinetics of an etanertsept men and women have no explicit distinctions.

Elderly patients
The clearance and the seeming volumes of distribution of an etanertsept in group of patients from 65 to 87 years are similar to those at patients younger 65 years.

Children with juvenile idiopathic polyarthritis
The profile of concentration in serum is similar to that at adult patients with a pseudorheumatism. Modeling allows to assume that at children of advanced age (10–17 years) and adult patients the level of an etanertsept in serum is approximately identical, and at children of younger age it will be significantly lower.

Children with psoriasis

Average concentration of an etanertsept in blood serum of children aged from 4 up to 17 years with psoriasis and children with juvenile idiopathic polyarthritis who received Enbrel, respectively, in a dose of 0,8 mg/kg once a week (the maximum dose of 50 mg a week) and 0,4 mg/kg 2 times a week (the maximum dose of 50 mg a week) for 12-48 weeks, were similar (1,6-2,1 mkg/ml). Value of this indicator matched that at adult patients with psoriasis by which Enbrel was entered in a dose of 25 mg 2 times a week.

Indications to use:

Pseudorheumatism
In a combination with a methotrexate Enbrel is appointed the adult at treatment of an active pseudorheumatism of average and high severity when the answer to basic antiinflammatory drugs (BPVP), including a methotrexate, was inadequate.

Enbrel can be appointed in the form of monotherapy in case of inefficiency or intolerance of a methotrexate.

Enbrel is shown for treatment of the heavy, active and progressing pseudorheumatism at the adults who were not receiving before therapy by a methotrexate.

Juvenile idiopathic polyarthritis

Treatment of active juvenile idiopathic polyarthritis at children and teenagers at the age of 4-17 years at which insufficient efficiency or intolerance of a methotrexate was observed.

Psoriasis arthritis
Treatment of the active and progressing psoriasis arthritis at adults when the response to therapy of BPVP was inadequate.

Ankylosing spondylitis
Treatment of adults with a heavy active ankylosing spondylitis at whom traditional therapy did not give to essential an uluchsheniiya.

Psoriasis
Treatment of adults with psoriasis moderate and heavy degree of manifestation who have contraindications or intolerance of other system therapy including cyclosporine, a methotrexate or PUVA therapy.

Treatment of children of 8 years is also more senior with chronic psoriasis heavy degree of manifestation at which the intolerance or the insufficient answer to another system or phototherapy was observed.

Contraindications
Hypersensitivity to an etanertsept or any other component of a dosage form.

Sepsis or risk of developing of sepsis.

Active infection, including the chronic or localized infections (including tuberculosis).

Pregnancy and period of a lactation.

This dosage form is intended for patients with body weight more than 62,5 kg.
WITH CARE
Demyelinating diseases, congestive heart failure, conditions of an immunodeficiency, a dyscrasia of blood, diseases contributing to development or activation of infections (a diabetes mellitus, hepatitises, etc.),

PREGNANCY AND LACTATION
Therapy by Enbrel as there is no experience of use of this drug for pregnant women is not recommended to pregnant women. Women of childbearing age should not plan pregnancy during treatment by Enbrel.

It is not known whether it can этанерцепт be allocated with breast milk. As immunoglobulins, as well as many other drugs, can be emitted with milk of the person, it is necessary either to stop breastfeeding, or to stop Enbrel's reception during breastfeeding.

Route of administration and doses:

Subcutaneously.

Treatment by Enbrel has to be appointed and controlled by the doctor having experience in diagnosis and treatment of a pseudorheumatism, juvenile idiopathic polyarthritis, psoriasis arthritis, an ankylosing spondylitis or psoriasis.

Enbrel in the form of ready solution of 25 mg (the one-time syringe containing 0,5 ml of drug) and 50 mg (the one-time syringe containing 1,0 ml of drug). it is used for the patients having body weight more than 62,5 kg. At patients with body weight less than 62,5 kg it is necessary to use lyophilisate for solution preparation.

Before administration of drug it is necessary to study attentively the instruction for its application which is found in the end of this section.

Adults
Pseudorheumatism
The recommended dose makes 25 mg of Enbrel twice a week with an interval of 3-4 days. An alternative dose - 50 mg once a week.

Psoriasis arthritis
The recommended dose - 25 mg of Enbrel twice a week with an interval of 3-4 days or 50 mg once a week.

Ankylosing spondylitis
The recommended dose - 25 mg of Enbrel twice a week or 50 mg once a week.

Psoriasis
The recommended dose - 25 mg of Enbrel twice a week or 50 mg once a week. As an alternative it is possible to appoint Enbrel 50 mg twice a week for no more than 12 weeks. In need of treatment continuation Enbrel can be appointed in a dose of 25 mg twice a week or 50 mg once a week. Therapy by Enbrel should be carried out until remission, as a rule, is reached no more than 24 weeks. Administration of drug should be stopped if after 12 weeks of treatment positive dynamics of symptoms is not observed.

In need of repeated appointment of Enbrel, it is necessary to observe the treatment duration stated above. It is recommended to appoint a dose of 25 mg twice a week or 50 mg once a week.

Therapy duration at some patients can exceed 24 weeks.

Elderly patients (65 years are also more senior)
There is no need to adjust neither a dose, nor a route of administration.

The children (having body weight more than 62,5 kg)
At children with body weight less than 62,5 kg should be used Enbrel in a dosage form lyophilisate for preparation of solution for hypodermic introduction which allows to enter a dose less than 25 mg.

Juvenile idiopathic arthritis (children of 4 years are also more senior)
The dose is defined at the rate of 0,4 mg/kg of body weight (the maximum single dose of 25 mg). The drug is administered twice a week bucketed 3-4 days between doses.

Psoriasis (children of 8 years are also more senior)

The dose is defined at the rate of 0,8 mg/kg of body weight (the maximum single dose of 50 mg). The drug is administered once a week until remission, as a rule, is reached no more than 24 weeks. Treatment by drug should be stopped if after 12 weeks of therapy positive dynamics of symptoms is not observed.

In need of repeated appointment of Enbrel, it is necessary to observe the treatment duration stated above. A drug dose - 0,8 mg/kg of body weight (the maximum single dose of 50 mg) once a week. In certain cases duration of treatment can make more than 24 weeks.

Abnormal liver function and kidneys
There is no need to adjust a dose.

THE INSTRUCTION FOR PREPARATION AND ADMINISTRATION OF SOLUTION FOR DRUG ENBREL INJECTIONS

Preparation for an injection

This drug cannot be mixed in one syringe or a bottle with any other drugs!

Take a cardboard box with previously filled syringes with drug Enbrel from the refrigerator and place it on the pure well lit plain working surface. Take one previously filled syringe. Do not stir up the syringe. Place a cardboard box with the remained previously filled syringes back in the refrigerator.

Leave the syringe with solution Enbrel for 15 – 30 minutes that it heated up to room temperature. DO NOT REMOVE a cap from the hypodermic needle until it reaches room temperature. Do not warm up Enbrel otherwise (for example, in the microwave oven or in hot water).

Wash up hands with soap in warm water.

Make sure that solution in the syringe transparent or slightly opalescent, colourless or light yellow, practically without visible particles. Otherwise you do not enter solution. Use other syringe which is previously filled with drug Enbrel.

Also it will be necessary for you: a spirit napkin, it enters set, and a cotton or gauze plug.

Choice of the place of an injection

Enbrel is recommended to administer the drug subcutaneously in the following anatomic zones:

(1)              front surface of an average third of a hip; (2) a front abdominal wall, except area in the diameter of 5 cm from a navel; and (3) outside surface of a shoulder (see fig. 1). If you do an injection independently, it is not necessary to administer the drug in the outside surface of a shoulder.

 Sites of an injection alternate. The distance between places of injections has to be not less than 3 cm. You do not administer the drug to sites where skin is injured or reddened. Exclude areas with fibrous changes of skin (hems, consolidations), striya (extensions) or hematomas (bruises). (It is possible to note places of the previous injections.)

In the presence of psoriasis, it is not necessary to administer the drug directly to sites with the thickened, reddened skin or in the centers with a peeling ("psoriasis plaques").

Preparation of the site of skin and administration of solution of Enbrel

Process a solution injection site Enbrel the tampon moistened with alcohol, making roundabouts. DO NOT TOUCH the processed site of skin until an injection.

Remove a cap from a needle, with a force having pulled it from the syringe (see fig. 2). Be careful, without bending and without overwinding a cap during removal not to damage a needle.

During removal of a cap on the end of a needle the liquid drop can appear; it is admissible. Do not concern a needle and avoid its contact with any other surface. Do not concern the piston and do not press on it. It can lead to a liquid effluence from the syringe.

After the processed surface of skin dried up, one hand take skin pleated, and other hand take the syringe as a pencil.

The Bystry, short movement enter a needle completely subcutaneously at an angle from 45º to 90º. Further you will pick up the most comfortable position of a needle (tilt angle) at introduction (see fig. 3). You do not enter a needle too slowly or with excessive effort.

After the needle completely entered skin, a skin fold which you held, it is possible to release. Hold with the released hand the syringe basis in invariable situation. Then begin to enter slowly solution, with small constant effort pressing on the piston. Enter the solution which is contained in the syringe completely

After solution is completely entered, take a needle from skin. Delete a needle under the same corner under which carried out introduction. In the place of an injection perhaps small bleeding. Apply to the place of an injection a cotton or gauze plug for 10 seconds. Do not wipe an injection site. If necessary it is possible to apply a bandage an injection site.

Recycling

Previously filled syringe is intended only for single application. NEVER reuse the syringe and a needle. NEVER dress a cap on a needle repeatedly. Utilize a needle and the syringe according to instructions of your doctor or nurse.

If you have questions, please, see a doctor or the nurse who work with drug Enbrel.

Features of use:

Infections

Patients have to be inspected on existence of infections before Enbrel's appointment, during treatment and after the termination of a course of therapy by Enbrel, in view of the average duration of an elimination half-life of an etanertsept, to equal about 80 hours (7-300 hours).

When using Enbrel's it was reported about sepsis, tuberculosis and heavy infections, including opportunistic, including invasive fungal infections. At inspection of patients it is necessary to take into account a possibility of development in them of opportunistic infections, for example, of endemic mycoses.

Patients at whom new infections develop against the background of treatment by Enbrel have to be under careful observation. Enbrel's reception should be interrupted if at the patient the heavy infection develops. It is necessary to appoint very carefully Enbrel to patients with frequent or persistent infections in the anamnesis or having a basic disease, for example, the progressing or badly controlled diabetes which can promote development of infections.

Safety and Enbrel's efficiency at patients with persistent infections was not estimated.

Tuberculosis

Cases of active tuberculosis included miliary tuberculosis and tuberculosis of not pulmonary localization.

Before Enbrel's appointment all patients have to be inspected on existence of active or latent tuberculosis. Inspection has to include detailed studying of medical history concerning a disease of tuberculosis or existence of contacts with tubercular patients in the past, and data on the previous or current immunosuppressive therapy. At all patients the corresponding screening procedures (according to local requirements), namely, the tuberkulinovy skin test and a X-ray analysis of lungs have to be performed. It must be kept in mind a possibility of the false-negative tuberkulinovy test, especially at seriously ill or patients with the immuno-compromised status.

In case of diagnosis of active tuberculosis Enbrel should not be appointed. The diagnosis of a healed tuberculosis assumes purpose of standard antitubercular therapy before an initiation of treatment by Enbrel. In this case the ratio of advantage and risk of treatment by Enbrel has to be carefully analyzed.

All patients have to be informed on expediency of the address to the doctor at emergence against the background of treatment by Enbrel or after it the complaints or symptoms characteristic of tuberculosis (for example, persistent cough, loss of weight, subfebrile condition).

Activation of a virus of hepatitis B

It was reported about cases of activation of a virus of hepatitis B at patients carriers who received FNO inhibitors, including Enbrel. Before Enbrel's appointment the patients entering into group of high risk of a disease of hepatitis B need to carry out the corresponding diagnostic search. Extra care should be observed at Enbrel's appointment the patient carriers of a virus of hepatitis B. At emergence of symptoms of this disease in them to discuss a possibility of performing specific therapy.

Exacerbation of hepatitis C

Cases of an exacerbation of hepatitis C at treatment by Enbrel are registered though to accurate relationship of cause and effect it was not established.

Allergic reactions

Allergic reactions often accompany Enbrel's reception. Allergic reactions, including a heavy current, included a Quincke's disease and a small tortoiseshell. At any heavy allergic or anaphylactic reactions it is necessary to stop immediately Enbrel's reception and to begin the corresponding treatment.

Immunosuppression

At ANTI-FNO therapies including the possibility of oppression of protective mechanisms of a human body against infections and malignant new growths as FNO participates in processes of an inflammation exists Enbrel, and are modulated by a cellular immune response. However at adult patients with a pseudorheumatism against the background of treatment by Enbrel cases of oppression of the delayed giperchuvstitelnost, falling of level of immunoglobulin or change of number of population of cells effectors were not revealed.

At children with juvenile idiopathic arthritis chicken pox and symptoms of aseptic meningitis which were resolved without complications in rare instances developed. The patients who were in contact with patients with chicken pox should stop temporarily Enbrel's reception and to appoint preventive treatment Varicella Zoster virus immunoglobulin.

Malignant and limfoproliferativny diseases

In the post-marketing period (watch the section "Side effect") reports on various malignant new growths were received (including a carcinoma of a mammary gland and lung, and also a lymphoma).

More often the lymphoma was diagnosed for the patients accepting FNO inhibitors than for patients who did not receive them. On the other hand, these cases were rare, and the period of observation of patients from placebo group was shorter, than for the patients receiving treatment by FNO inhibitors. Besides, there is a high risk of emergence of a lymphoma at patients with a pseudorheumatism - a long, highly active inflammatory disease which complicates risk assessment. In compliance with modern knowledge it is impossible to exclude possible risk of development of lymphoma or other malignant new growths in the patients receiving FNO inhibitors.

The carcinoma cutaneum who is not relating to a melanoma (RKNM)

RKNM was registered at the patients receiving treatment by FNO inhibitors including Enbrel. Most often RKNM diagnose for patients with psoriasis. For all patients entering into risk group periodic inspections of integuments are recommended.

Formation of autoimmune antibodies

Treatment by Enbrel can be followed by formation of autoimmune antibodies (watch the section "Side effect"). These antibodies do not belong to neutralizing and usually quickly disappear. Correlation between antibody formation and clinical performance of drug, and also frequency of development of side reactions is noted.

Isolated cases of formation of additional autoantibodies in combination with a volchanochnopodobny syndrome or the rash similar to a subacute form of a lupus erythematosus or a diskoidny form of a lupus erythematosus (given clinical inspection and a biopsy) were celebrated at patients, including patients with a pseudorheumatism with a positive rhematoid factor.

Hematologic reactions

It was reported about exceptional cases of a pancytopenia and very exceptional cases of aplastic anemia, including from the death, at the patients receiving Enbrel. It is necessary to show care at Enbrel's appointment to the patients having a blood dyscrasia in the anamnesis. All patients, their relatives / nurses have to be informed that if at the patient during reception Enbrel the signs and symptoms characteristic of an infection develop or hematologic disturbances (for example, long fever, quinsy, bruises, bleeding, pallor), they should ask for medical care immediately. At such patients it is recommended to conduct examination, including an integrated analysis of blood. At confirmation of the diagnosis of a dyscrasia, treatment by Enbrel should be stopped.

Defeat of TsNS

Several cases of disturbances of TsNS caused by demyelination at the adult patients receiving Enbrel are registered. Though Enbrel was not studied at patients with multiple sclerosis, researches of other FNO inhibitors at this associated disease showed a possibility of its aggravation.

It is recommended to estimate carefully before Enbrel's appointment risk/advantage, including the neurologic status, at patients with the previous or recent attack of a demyelinating disease or at for what there is an increased risk of development of a demyelinating disease.

Combination therapy
Enbrel's combination and a methotrexate did not yield unexpected results at a safety research. Long-term studying of this indicator continues. Data on safety of Enbrel who appointed together with a methotrexate were similar to data from periodic reports on Enbrel's safety and a methotrexate separately. Long-term safety at reception Enbrela with other BPVP is not investigated.

Congestive Heart Failure (CHF)
It is necessary to be careful concerning Enbrel's appointment to patients with ZSN. Data of a number of researches allow to assume a possibility of deterioration in a current of ZSN at the patients receiving Enbrel.

Alcoholic hepatitis

It is necessary to show extra care at Enbrel's appointment to patients with alcoholic hepatitis medium-weight and a severe disease.

Wegener's granulomatosis

Frequency of development of malignant tumors of various type of extra skin localization was much higher at the patients receiving Enbrel than in control group. Therefore, Enbrel is not recommended for treatment of patients with Wegener's granulomatosis.
Influence on ability to drive the car and other machines.
Researches of influence on ability to drive the car and difficult mechanisms were not conducted.

Side effects:

Side reactions depending on the frequency of emergence were grouped as follows: very often (> 1/10); often (> 1/100, <1/10); infrequently (> 1/1000, <1/100); seldom (> 1/10.000, <1/1000); very seldom (<1/10.000), isolated cases (frequency cannot be determined).

Infections and invasions

Very often: Infections (including upper respiratory tract infections, cystitis, skin infections).

Infrequently:      Serious infections (including pneumonia, phlegmon, septic arthritis, sepsis).

Seldom:           Tuberculosis, opportunistic infections (including invasive fungal, protozoan, bacterial and atypical mikobakterialny infections).

System of a hemopoiesis and lymphatic system
Infrequently:      Thrombocytopenia.

Seldom:            Anemia, leukopenia, neutropenia, pancytopenia.

Very seldom: Aplastic anemia.

Immune system

Often:          Allergic reactions (look "Skin and hypodermic cellulose), formation of autoantibodies.

Seldom:            Serious allergic/anaphylactic reactions (including a Quincke's disease, a bronchospasm).

Isolated cases: Syndrome of activation of macrophages.

Nervous system
Seldom:            Spasms, the demyelination phenomena in TsNS similar with observed at multiple sclerosis or a condition of local demyelination, such as an optic neuritis and a cross myelitis (watch the section "Special Instructions and Precautionary Measures").

Respiratory organs, thorax and mediastinum

Infrequently:      Intersticial diseases of lungs (including a pneumonitis and a pneumosclerosis).

Gepatobiliarny disturbances
Seldom:            Increase in activity of liver enzymes, autoimmune hepatitis.

Skin and hypodermic cellulose
Often:          Itch.

Infrequently:      The carcinoma cutaneum who is not relating to a melanoma (RKNM), urticaria, rash, psoriasis (including a debut of a disease and pustular defeat, generally soles and palms).

Seldom:           Skin forms of a vasculitis (including a leykotsitoklastichesky vasculitis), Stephens-Johnson's syndrome, a multiformny erythema.

Very seldom: Toxic epidermal necrolysis.

Bone muscular system and connecting fabric

Seldom:           Skin manifestations of a subacute lupus erythematosus, diskoidny lupus erythematosus, volchanochnopodobny syndrome.

The general disturbances and reactions in an injection site

Very often: Local reactions after injections (including bleeding, formation of a hypodermic hematoma, an erythema, an itch, pain, a swelling).

Often:          Fever.

Cardiovascular system
Seldom: deterioration in a course of the congestive heart failure (CHF) (watch "Special instructions and precautionary measures").

Additional information
Side reactions at adults

Drug withdrawal frequency because of development of side reactions during controlled clinical trials at patients with a pseudorheumatism was comparable at the patients receiving Enbrel and placebo. Against the background of treatment by Enbrel reactions in a drug injection site were the most widespread.

Side reactions at children
Frequency and types of side reactions at children with juvenile idiopathic polyarthritis were similar to those which were observed at adult patients with a pseudorheumatism. Differences from adults and additional data are given below.

Infections which were observed in clinical trials at patients with juvenile idiopathic arthritis were soft and moderate degree of manifestation, and their types did not contradict those which usually occur among ambulatories. Messages on the heavy undesirable phenomena included chicken pox with symptoms of aseptic meningitis which were resolved without complications (watch also the section "Special Instructions and Precautionary Measures"), appendicitis, a gastroenteritis, depressions/frustration of the personality, a skin ulcer, esophagitis/gastritis, the aseptic shock caused by group A streptococci, a diabetes mellitus of the I type and an infection of soft tissues and postoperative wounds.

4 messages on a syndrome of activation of macrophages at these patients are registered.

Frequency and types of side reactions at children with psoriasis were similar to those which were observed at adult patients.

Interaction with other medicines:

Enbrel's use in combination with anakinry
At adult patients against the background of a combination therapy Enbrel and anakinry observed substantial increase of frequency of serious infections and a neutropenia in comparison with patients to whom entered only Enbrel.

Joint reception of Enbrel and anakinra did not show clinical advantage and therefore, it is not recommended.

Enbrel's use in combination with abatatsepty
Co-administration of an abatatsept and Enbrel was followed by increase in frequency of the serious undesirable phenomena. This combination of medicines did not show clinical advantages and therefore, it is not recommended.

Enbrel's use in combination with Sulfasalazinum

At patients to whom against the background of treatment by Sulfasalazinum entered Enbrel considerable decrease in average of leukocytes in comparison with those patients who accepted only Enbrel or only Sulfasalazinum is described.

Lack of interaction

Undesirable interactions at joint appointment of Enbrel with glucocorticosteroids, salicylates (except for Sulfasalazinum), non-steroidal anti-inflammatory drugs (NPVP), analgetics were not observed.

Methotrexate

The methotrexate does not exert impact on pharmacokinetics of an etanertsept. Enbrel's influence on methotrexate pharmacokinetics at the person was not studied.

Digoxin

Clinically significant mutual influence on pharmacokinetics is not revealed.

Warfarin

Clinically significant mutual influence on pharmacokinetics is not revealed.

Vaccination
Live vaccines should not be entered against the background of treatment by Enbrel. There are no data on secondary transmission of infection through a live vaccine to the patients receiving Enbrel. It is recommended that prior to treatment by Enbrel patients with juvenile idiopathic arthritis if it is possible, received all inoculations according to the operating national calendar of inoculations.

Contraindications:

Hypersensitivity to an etanertsept or any other component of a dosage form. Sepsis or risk of developing of sepsis. An active infection, including the chronic or localized infections (including tuberculosis). Pregnancy and period of a lactation. This dosage form is intended for patients with body weight more than 62,5 kg.

Overdose:

At treatment of patients with a pseudorheumatism exceeding of a limit toxic dose was not registered. The highest dose entered intravenously made 32 mg/sq.m with the subsequent hypodermic introduction of 16 mg / м2дважды in a week. One patient with a pseudorheumatism mistakenly independently entered 62 mg of Enbrel subcutaneously twice a week for 3 weeks without emergence of undesirable effects. The specific antidote for Enbrel is unknown.

Storage conditions:

To store at a temperature from 2 to 8 to the °sena to freeze. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Solution for hypodermic introduction of 50 mg/ml. On 0,5 ml (25 mg) or 1,0 ml (50 mg) of drug in syringes for disposable of transparent colourless glass (type I), supplied with a needle from the stainless steel closed by a two-layer cap, a plastic emphasis for fingers and a rod piston with a rubber sealant. On 1 syringe complete with 2 individually packed spirit napkins in the plastic packaging sealed by aluminum foil. On 4, 8 or 24 plastic packagings (25 mg) or on 2, 4 or 12 plastic packagings (50 mg) together with the application instruction in a cardboard pack.