Instructions Enbrel solution for injection 50 mg syringe 1 ml syringe pen No. 4
Composition
active ingredient: etanercept;
1 ml of solution contains 50 mg of etanercept;
1 pre-filled syringe contains 50 mg of etanercept; 1 pre-filled pen contains 50 mg of etanercept;
Excipients: sucrose, water for injection, sodium phosphate dibasic dihydrate, sodium phosphate monobasic dihydrate, L-arginine hydrochloride, sodium chloride.
Dosage form
Solution for injection.
Main physicochemical properties: colorless to yellow or pale brown liquid, transparent or opalescent; may contain a small amount of translucent or white amorphous particles.
Pharmacotherapeutic group
Immunosuppressants, tumor necrosis factor-a inhibitors. Etanercept. ATC code L04A B01.
Pharmacological properties
Pharmacodynamics
Etanercept is a chimeric protein of human tumor necrosis factor receptor and p75Fc, produced by recombinant DNA technology using mammalian cells (Chinese hamster ovary cells) as an expression system.
Tumor necrosis factor (TNF) is a cytokine that plays a major role in the inflammatory process in rheumatoid arthritis. Elevated levels of TNF are also found in the synovium and psoriatic plaques of patients with psoriatic arthritis, and in the serum and synovial tissue of patients with ankylosing spondylitis. Infiltration of psoriatic plaques by inflammatory cells, including T cells, results in increased levels of TNF at sites of psoriatic lesions compared with unaffected skin. Etanercept is a competitive inhibitor of TNF binding to its cell surface receptors and, therefore, inhibits the biological activity of TNF. TNF and lymphotoxin are pro-inflammatory cytokines that bind to two distinct cell surface receptors for tumor necrosis factor (TNF): 55 kDa (p55) and 75 kDa (p75). Both TNF-α and TNF-α exist in the body in membrane-bound and soluble forms. Soluble TNF-α regulates the biological activity of TNF.
TNF and lymphotoxin exist primarily as homotrimers, and their biological activity depends on cross-linking of TNF receptors on the cell surface. Dimeric soluble receptors, such as etanercept, have a higher affinity for TNF than monomeric receptors and are therefore much more potent competitive inhibitors of TNF binding to its cellular receptors. In addition, the use of the Fc fragment of immunoglobulin as a binding element in the dimeric receptor structure prolongs the serum half-life of the drug.
Thus, etanercept prevents the emergence of a cellular response mediated by TNF by biological inactivation of TNF. Etanercept is also able to modulate biological responses controlled by additional downstream signaling molecules (e.g., cytokines, adhesion molecules, or proteinases) that are stimulated or regulated by TNF.
Pharmacokinetics
Absorption
Etanercept is slowly absorbed from the subcutaneous injection site, reaching peak concentrations approximately 48 hours after a single dose. Absolute bioavailability is 76%. When administered twice weekly, steady-state concentrations are expected to be twice those observed after single doses. After a single subcutaneous injection of 25 mg etanercept in healthy volunteers, the mean peak plasma concentration was 1.65 ± 0.66 μg/mL, and the area under the concentration-time curve (AUC) was 235 ± 96.6 μg h/mL.
Distribution
The concentration-time curve of etanercept is described by a biexponential curve. The central volume of distribution is 7.6 L, while the volume of distribution at steady state is 10.41 L.
Breeding
Etanercept is slowly eliminated from the body. The elimination half-life is long, approximately 70 hours. In patients with rheumatoid arthritis, clearance is approximately 0.066 l/h, which is slightly lower than in healthy volunteers (0.11 l/h). The pharmacokinetics of etanercept in patients with rheumatoid arthritis, ankylosing spondylitis, and plaque psoriasis are similar.
There are no clear differences in the pharmacokinetics of etanercept in men and women.
Linearity
Dose proportionality has not been formally studied, but there is no apparent saturation of clearance for any dosage.
Special populations
Patients with renal failure
Although excretion of radioactivity following administration of radiolabeled etanercept to patients and healthy volunteers occurs in the urine, no increase in plasma concentrations of etanercept was observed in patients with acute renal failure. Impaired renal function does not require dose adjustment.
Patients with hepatic insufficiency
Increased etanercept concentrations were not observed in patients with acute hepatic impairment. Impaired hepatic function does not require dose adjustment.
Elderly patients
Estimated clearance and volume of distribution in patients aged 65 to 87 years were similar to those in patients under 65 years of age.
The serum concentration profiles of etanercept in children with polyarticular juvenile idiopathic arthritis are similar to those in adult patients with rheumatoid arthritis. In the youngest children studied (4 years of age), clearance was reduced (clearance was increased when standardized for body weight) compared with older children (12 years of age) and adults. Dosing modeling suggests that plasma concentrations of etanercept are approximately the same in older children (10–17 years of age) and adults, and are substantially lower in younger children.
Children with psoriasis
Children with plaque psoriasis (aged 4 to 17 years) received etanercept at a dose of 0.8 mg/kg body weight (maximum dose 50 mg per week) once weekly for up to 48 weeks. Mean steady-state plasma concentrations of etanercept ranged from 1.6 to 2.1 μg/mL at weeks 12, 24, and 48. The above mean concentrations in children with plaque psoriasis were similar to those observed in children with juvenile idiopathic arthritis when etanercept was administered at a dose of 0.4 mg/kg twice weekly (maximum dose 50 mg per week). These values were similar to those in adult patients with plaque psoriasis who received etanercept at a dose of 25 mg twice weekly.
Indication
Rheumatoid arthritis
Enbrel® in combination with methotrexate is indicated for the treatment of moderate to severe active rheumatoid arthritis in adults when the response to basic antirheumatic drugs, including methotrexate (in the absence of contraindications), is inadequate.
Enbrel® can be prescribed as monotherapy in case of intolerance to methotrexate or in cases where long-term treatment with methotrexate is inappropriate.
Enbrel® is also indicated for the treatment of severe, active and progressive rheumatoid arthritis in adult patients who have not previously received methotrexate therapy.
Juvenile idiopathic arthritis
Treatment of polyarthritis (rheumatoid factor positive or negative) and widespread oligoarthritis in children and adolescents from 2 years of age who have a known intolerance to or inadequate response to methotrexate therapy.
Treatment of psoriatic arthritis in children aged 12 years and older with known intolerance to or inadequate response to methotrexate therapy.
Treatment of enthesitis-related arthritis in children aged 12 years and older with known intolerance to or inadequate response to conventional therapy.
Psoriatic arthritis
Treatment of active and progressive psoriatic arthritis in adults who have had an inadequate response to therapy with basic antirheumatic drugs.
Axial spondyloarthritis
Ankylosing spondylitis
Treatment of adults with severe active ankylosing spondylitis when conventional therapy has failed.
Non-radiographic axial spondyloarthritis.
Treatment of adult patients with severe non-radiographic axial spondyloarthritis with objective signs of inflammation as evidenced by elevated C-reactive protein and/or MRI findings who have had an inadequate response to non-steroidal anti-inflammatory drugs (NSAIDs).
Plaque psoriasis
Treatment of adult patients with moderate to severe plaque psoriasis who have contraindications to or intolerance to other systemic therapies including ciclosporin, methotrexate, psoralen and ultraviolet A (PUVA) therapy, or who have failed such therapies.
Plaque psoriasis in children
Treatment of chronic severe plaque psoriasis in children aged 6 years and older who are inadequately controlled on other systemic therapies or phototherapy or who are intolerant to such treatments.
Contraindication
Hypersensitivity to the active substance or to any of the excipients. Sepsis or risk of sepsis. Patients with active infections, including chronic or local infections, at the time of initiation of treatment with Enbrel®.
Interaction with other medicinal products and other types of interactions
Concomitant use of anakinra
In adult patients treated with Enbrel® and anakinra, an increased incidence of serious infections was observed compared to patients treated with Enbrel® or anakinra alone (based on history).
In addition, in a double-blind, placebo-controlled study in adult patients receiving Enbrel and anakinra in combination with methotrexate, an increased incidence of serious infections (7%) and neutropenia was observed compared to patients receiving Enbrel alone (see sections 4.4 and 4.8).
The combination of Enbrel® and anakinra has not demonstrated increased clinical benefit and is therefore not recommended for use.
Concomitant use of abatacept
In clinical trials, concomitant use of abatacept and Enbrel® resulted in an increased incidence of serious adverse reactions. This combination has not demonstrated increased clinical benefit and is therefore not recommended for use.
In a clinical study of adult patients receiving Enbrel® in addition to standard doses of sulfasalazine, a statistically significant decrease in mean white blood cell count was observed in patients receiving the combination compared to patients receiving Enbrel® or sulfasalazine alone. The clinical significance of this combination is unknown. Physicians should exercise caution when prescribing the above combination.
Lack of interaction
In clinical studies, no interactions were observed with the concomitant use of Enbrel® with glucocorticosteroids, salicylates (except sulfasalazine), nonsteroidal anti-inflammatory drugs, analgesics, or methotrexate. Vaccination recommendations are provided in the section "Special Instructions for Use".
No clinically significant drug-drug pharmacokinetic interactions were observed in studies with methotrexate, digoxin, or warfarin.
Application features
To facilitate traceability of biological medicinal products, the trade name and batch number of the administered product should be clearly recorded (or noted) in the patient record.
Enbrel®, both as monotherapy and in combination with methotrexate, has been shown to slow the progression of joint damage (as assessed by X-ray) and improve joint function.
Enbrel® has been shown to improve the physical condition of patients with psoriatic arthritis and to slow the progression of peripheral joint damage (as measured by X-ray) in patients with polyarticular symmetrical subtypes of the disease.
Infections
Patients should be evaluated for infection before initiating Enbrel®, during treatment, and after discontinuation of therapy, given that the mean half-life of etanercept is approximately 70 hours (range 7–300 hours).
Serious infections, sepsis, tuberculosis, and opportunistic infections, including invasive fungal infections, listeriosis, and legionellosis (see Adverse Reactions), have been reported with Enbrel®, and have been caused by bacteria, mycobacteria, fungi, viruses, and parasites (including protozoa). In some cases, the specific type of fungal or other opportunistic infection was not identified, which resulted in delays in appropriate treatment and sometimes death. When evaluating patients for infections, the risk of certain opportunistic infections (e.g., exposure to endemic mycoses) should be considered.
Patients who develop new infections while receiving Enbrel® should be closely monitored. If a serious infection develops, Enbrel® should be discontinued. The efficacy and safety of Enbrel® in patients with chronic infections have not been evaluated. Enbrel® should be used with caution in patients with a history of recurrent or chronic infections or in patients whose underlying medical conditions (e.g., complicated or poorly controlled diabetes) may predispose them to infection.
Tuberculosis
Cases of active tuberculosis, including miliary tuberculosis and extrapulmonary tuberculosis, have been reported in patients receiving Enbrel.
Before initiating treatment with Enbrel®, all patients should be evaluated for both active and inactive (latent) tuberculosis. This evaluation should include a detailed medical history, including a personal history of tuberculosis or possible past exposure to tuberculosis, and information on previous or current immunosuppressive therapy. All patients should undergo the necessary screening tests, i.e., tuberculin skin test and chest x-ray (local guidelines may be used). It is recommended that these tests be recorded in the patient's chart. Physicians should be aware of the risk of false-negative tuberculin skin test results, especially in critically ill or immunocompromised patients.
If active tuberculosis is diagnosed, Enbrel® should not be used. If inactive (“latent”) tuberculosis is diagnosed, anti-tuberculosis therapy should be initiated according to local guidelines before starting Enbrel®. In such situations, the benefit/risk ratio of treatment with the drug should be carefully considered.
All patients should be advised to seek medical advice if signs or symptoms suggestive of tuberculosis (such as persistent cough, fatigue/weight loss, low-grade fever) develop during or after treatment with Enbrel.
Cases of hepatitis B reactivation have been reported in patients previously infected with hepatitis B virus and receiving concomitant treatment with TNF-antagonists, including Enbrel®. Hepatitis B reactivation has also been reported in patients who tested positive for anti-HBs antibodies but were negative for HBsAg. Patients should be evaluated for hepatitis B virus infection before initiating treatment with Enbrel®. Patients who test positive for hepatitis B virus infection are advised to consult a physician experienced in the management of hepatitis B. Enbrel® should be used with caution in patients previously infected with hepatitis B virus. Such patients should be closely monitored for signs and symptoms of acute hepatitis B virus infection throughout treatment and for several weeks after discontinuation of treatment. There are no adequate data on the treatment of patients infected with hepatitis B virus with combinations of antiviral agents and TNF-antagonists. If hepatitis B virus infection develops, Enbrel should be discontinued and effective antiviral treatment should be initiated along with appropriate supportive care.
Hepatitis C exacerbation
Cases of exacerbation of hepatitis C have been reported in patients taking Enbrel®. Therefore, it should be prescribed with caution to patients with a history of hepatitis C.
Concomitant use of anakinra
Concomitant use of Enbrel® and anakinra was associated with an increased risk of serious infections and neutropenia compared to Enbrel® alone. This combination has not demonstrated increased clinical benefit and is therefore not recommended (see sections 4.8 and 4.5).
Concomitant use of abatacept
In clinical trials, concomitant use of Enbrel® and abatacept resulted in an increased incidence of serious adverse reactions. This combination has not shown increased clinical benefit and is therefore not recommended (see section 4.5).
Allergic reactions
The needle cap of the pre-filled syringe/pen contains latex (dry natural rubber) which may cause hypersensitivity reactions in individuals with known or possible sensitivity to latex.
The administration of Enbrel® was often accompanied by the occurrence of allergic reactions.
Allergic reactions have included angioedema and urticaria; severe reactions have been reported. If any severe allergic or anaphylactic reactions occur, Enbrel® therapy should be discontinued immediately and appropriate treatment initiated.
Immunosuppression
It is possible that TNF antagonists, including Enbrel®, affect the human body's defense mechanisms against infections and malignancies, since TNF is involved in inflammation and modulates the cellular immune response. In a study of 49 adult patients with rheumatoid arthritis who received Enbrel®, there were no cases of suppression of delayed-type hypersensitivity reactions, decreases in immunoglobulin levels, or changes in the number of effector cell populations.
Two patients with juvenile idiopathic arthritis developed varicella and signs and symptoms of aseptic meningitis, which resolved without complications. Patients who have been in contact with varicella should temporarily discontinue Enbrel® therapy and receive prophylactic treatment with Varicella Zoster Immune Globulin.
The efficacy and safety of Enbrel® in patients with immunosuppression or chronic infections have not been evaluated.
Malignant and lymphoproliferative diseases
Solid and oncohematological malignant neoplasms (excluding skin cancer).
In the post-marketing period (see section "Adverse reactions"), various malignancies (including breast and lung carcinoma, as well as lymphoma) have been reported.
In controlled clinical trials of TNF antagonists, a higher incidence of lymphoma was observed in patients treated with TNF inhibitors than in control patients. However, these cases were isolated and the follow-up period for patients treated with placebo was shorter than for patients treated with TNF inhibitors. In the post-marketing period, cases of leukemia have been reported in patients treated with TNF antagonists. Patients with rheumatoid arthritis with long-standing, highly active inflammatory disease have an increased baseline risk of lymphoma or leukemia, making risk assessment difficult.
In the post-marketing period, reports of malignancies, sometimes fatal, have been received in children, adolescents and young adults (up to 22 years of age) treated with TNF-antagonists (treatment initiated before the age of 18 years), including Enbrel. In approximately half of the cases, lymphoma was reported. Other reports received concerned a variety of malignancies and included isolated cases of typical malignancies associated with immunosuppression. The risk of malignancies in children and adolescents treated with TNF-antagonists cannot be excluded.
Skin cancer
Melanoma and non-melanoma skin cancers have been reported in patients treated with TNF-antagonists, including Enbrel. Merkel cell carcinoma has been reported in post-marketing experience in patients treated with Enbrel (very rare). Periodic skin examinations are recommended for all patients, especially those with risk factors for skin cancer.
Pooled results from controlled clinical trials showed that the incidence of non-melanoma skin cancer was higher in patients treated with Enbrel, particularly in patients with psoriasis, compared with the control group.
Vaccinations
Live vaccines should not be administered concomitantly with Enbrel®. There are no data on secondary transmission of infection by live vaccines in patients receiving Enbrel®. In a double-blind, placebo-controlled, randomized clinical trial in adult patients with psoriatic arthritis, 184 patients also received pneumococcal polyvalent polysaccharide vaccine at week 4 of the study. Most patients receiving Enbrel® were able to mount an effective humoral immune response to pneumococcal polysaccharide vaccine, but titers were generally somewhat lower, and only a few patients had antibody titers twice as high as those observed in patients not receiving Enbrel®. The clinical significance of this finding is unknown.
Formation of autoimmune antibodies
Treatment with Enbrel® may lead to the formation of autoimmune antibodies (see section “Adverse reactions”).
Hematological reactions
Cases of pancytopenia (rare) and aplastic anemia (very rare), including fatal cases, have been reported in patients receiving Enbrel®. Caution should be exercised when prescribing Enbrel® to patients with a history of hematological disorders (blood dyscrasias). All patients and caregivers should be informed that they should seek immediate medical attention if signs and symptoms suggestive of blood disorders or infections (e.g., persistent fever, sore throat, bruising, bleeding, pallor) develop during treatment with Enbrel®. Such patients should be evaluated promptly, including a complete blood count; if a hematological disorder is confirmed, treatment with the drug should be discontinued.
Neurological disorders
In isolated cases, CNS demyelinating diseases have been reported in patients receiving Enbrel (see section 4.8). Peripheral demyelinating polyneuropathies (including Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, demyelinating polyneuropathy, and multifocal motor neuropathy) have also been reported rarely. Although clinical trials of Enbrel in patients with multiple sclerosis have not been conducted, clinical trials of other TNF inhibitors have shown an increase in disease activity (multiple sclerosis). Before prescribing Enbrel to patients with a previously diagnosed or newly diagnosed demyelinating disease, as well as to patients who are at increased risk of developing such a disease, a careful benefit-risk assessment, including neurological status, is recommended.
Combination therapy
A two-year controlled clinical trial of the combination of Enbrel® and methotrexate in patients with rheumatoid arthritis did not reveal any unexpected safety findings. The safety profile of Enbrel® (when used in combination with methotrexate) was similar to that observed in studies of the two drugs alone. Long-term safety studies of this combination are ongoing. The safety of long-term use of Enbrel® in combination with other basic antirheumatic drugs has not been established.
The use of etanercept in combination with other systemic treatments for psoriasis or phototherapy has not been studied.
Renal and hepatic failure
Pharmacokinetic data suggest that there is no need to adjust the dose for patients with renal or hepatic impairment; clinical experience in such patients is limited.
Caution should be exercised when prescribing Enbrel® to patients with congestive heart failure (CHF). In the post-marketing period, there have been reports of worsening CHF in patients treated with Enbrel®, although precipitating factors have not always been identified. In addition, isolated cases (< 0.1%) of new CHF have been reported, including CHF in patients with no known underlying cardiovascular disease. Some of these patients were under 50 years of age. Two large clinical trials evaluating the use of Enbrel® in the treatment of CHF were terminated early due to lack of efficacy. Data from one of these trials, although not conclusive, suggest the possibility of worsening CHF in patients treated with Enbrel®.
Alcoholic hepatitis
In a phase II randomized placebo-controlled trial of 48 hospitalized patients treated with Enbrel® or placebo for the treatment of moderate to severe alcoholic hepatitis, Enbrel® was ineffective and mortality was significantly higher in patients treated with Enbrel® at 6 months. Therefore, Enbrel® should not be used in patients for the treatment of alcoholic hepatitis. Enbrel® should be used with caution in patients with moderate to severe alcoholic hepatitis.
Wegener's granulomatosis
A placebo-controlled study in which 89 adult patients received Enbrel® in addition to standard therapy (including cyclophosphamide or methotrexate and glucocorticoids) for a mean duration of 25 months did not demonstrate the efficacy of Enbrel® in the treatment of Wegener's granulomatosis. The incidence of non-cutaneous malignancies of various types was significantly higher in patients treated with Enbrel® compared with control patients. Therefore, Enbrel® is not recommended for the treatment of Wegener's granulomatosis.
Hypoglycemia in patients receiving treatment with antidiabetic drugs.
Cases of hypoglycemia have been reported after initiation of Enbrel in patients receiving antidiabetic medications, necessitating a dose reduction of antidiabetic medications in some of these patients.
Special populations
Elderly patients.
In phase III studies in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, the overall incidence of adverse reactions, serious adverse reactions, and serious infections in patients aged 65 years and older receiving Enbrel® was similar to that observed in younger patients. However, caution should be exercised when treating elderly patients; special attention should be paid to monitoring for infections.
Children
Vaccinations
It is recommended that, if possible, pediatric patients should be brought up to date with all vaccinations according to the current national vaccination schedule (see Vaccinations above) before starting treatment with Enbrel®.
Inflammatory diseases of the digestive tract in patients with juvenile idiopathic arthritis.
Gastrointestinal inflammatory diseases and uveitis have been reported in patients with juvenile idiopathic arthritis treated with Enbrel (see Adverse Reactions).
Ability to influence reaction speed when driving vehicles or other mechanisms
Studies on the effect of the drug on the ability to drive vehicles and operate other mechanisms have not been conducted.
Use during pregnancy or breastfeeding
Women of reproductive age
Women of childbearing potential should use adequate contraception to avoid pregnancy while taking Enbrel® and for 3 weeks after stopping therapy.
Animal studies of fetal toxicity have not revealed any evidence of harmful effects of etanercept on the fetus or newborns. The effects of etanercept on pregnancy have been studied in two observational cohort studies. In one observational study comparing pregnant patients exposed to etanercept during the first trimester (n=370) with pregnant patients not exposed to etanercept or other TNF-antagonists (n=164), an increased incidence of major congenital malformations was reported (adjusted odds ratio 2.4, 95% CI: 1.0-5.5). The types of major congenital malformations were consistent with those most commonly seen in the general population, and no specific patterns of malformations were observed. No changes in the incidence of spontaneous abortions, stillbirths, or minor malformations were observed. Another observational international registry study comparing the risks of adverse pregnancy outcomes among women exposed to etanercept during the first 90 days of pregnancy (n=425) and those exposed to nonbiologic agents (n=3497) found no increased risk of major congenital anomalies (overall odds ratio (OR) = 1.22; 95% CI: 0.79–1.90; after adjusting for country, maternal disease, prior number of deliveries, maternal age, and smoking in early pregnancy, OR = 0.96; 95% CI: 0.58–1.60). This study also found no increased risk of minor birth defects, preterm birth, stillbirth, or infections in the first year of life in women exposed to etanercept during pregnancy. Enbrel® should be used during pregnancy only if clearly needed.
Etanercept crosses the placenta and is detected in the serum of infants born to mothers treated with Enbrel® during pregnancy. The clinical significance of this finding is unknown, but infants may be at increased risk of infection. In general, infants should not be vaccinated with live vaccines for 16 weeks after the mother's last dose of Enbrel®.
Breast-feeding
Etanercept has been reported to be excreted in human milk following subcutaneous administration. Etanercept was excreted in milk and detected in the plasma of rat pups following subcutaneous administration to lactating animals. Because immunoglobulins, like many other drugs, are excreted in human milk, a decision should be made whether to discontinue breast-feeding or to discontinue Enbrel® therapy. This decision should take into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Fertility
Preclinical data on peri- and postnatal toxicity of etanercept and the effects of etanercept on fertility and general reproductive performance are not available.
Method of administration and doses
Treatment with Enbrel® should be initiated and supervised by a physician experienced in the diagnosis and treatment of rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, plaque psoriasis, and pediatric plaque psoriasis.
Dosage
Rheumatoid arthritis
The recommended dose is 25 mg twice weekly. Alternatively, a dose of 50 mg once weekly has been shown to be safe and effective.
Psoriatic arthritis, ankylosing spondylitis, and non-radiographic axial spondyloarthritis.
The recommended dose is 25 mg 2 times a week or 50 mg 1 time a week.
For all of the above indications, available data suggest that clinical response to the drug usually occurs within 12 weeks of initiation of treatment. If a patient does not respond to treatment within this time period, continued therapy should be carefully reconsidered.
Plaque psoriasis
The recommended dose is 25 mg twice weekly or 50 mg once weekly. Alternatively, Enbrel® can be administered at 50 mg twice weekly for up to 12 weeks. Thereafter, if necessary, treatment may be continued at 25 mg twice weekly or 50 mg once weekly.
Enbrel® therapy should be continued until remission is achieved, for a period not exceeding 24 weeks. For some adult patients, treatment lasting more than 24 weeks may be appropriate (see section "Pharmacodynamics"). Therapy should be discontinued if there is no effect after 12 weeks of use. If re-administration of the drug is necessary, the recommendations for the duration of treatment specified above should be followed. The dose should be 25 mg of the drug 2 times a week or 50 mg 1 time a week.
Special patient groups
Patients with renal and hepatic insufficiency
There is no need for dose adjustment.
Elderly patients
The dose of Enbrel® for children is calculated based on the child's body weight. Patients weighing less than 62.5 kg should receive the exact dose (calculated in mg/kg) of Enbrel® in the form of a lyophilisate with a solvent (dosage information for specific diseases is provided below). Children weighing 62.5 kg or more can receive a fixed dose of Enbrel® in the form of a solution for injection in pre-filled syringes or pens.
Juvenile
