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Etanercept for injection, with indications for moderate to severe active rheumatoid arthritis (RA) in adult patients. DMARD including methotrexate (if not contraindicated) Antirheumatic drugs) are ineffective, can be treated with combination of etanercept and methotrexate. Etanercept has been shown to reduce the rate of joint damage progression and improve joint function when used alone or in combination with methotrexate. Adult patients with ankylosing spondylitis (AS) with severe active ankylosing spondylitis can be treated with etanercept when they fail to respond to conventional treatment.

Drug Name: Etanercept for injection

Drug type: prescription

Etanercept warnings for injection

WARNING Serious Infections Patients treated with Enley® are at increased risk of developing a serious infection, which may result in hospitalization or death (see Warnings and Adverse Reactions). The vast majority of patients with the above-mentioned conditions also take immunosuppressants, such as methotrexate or corticosteroids. Enley should be discontinued in patients with severe infections or sepsis.
Reported infections include:
Active TB infections, including recurrent latent TB infections. Disseminated or extrapulmonary lesions occur repeatedly in patients with tuberculosis infection. Patients should be tested for latent tuberculosis infection before and during use of Enley. Latent tuberculosis infection must be treated before treatment with Enley®.
Invasive fungal infections, including histoplasmosis, coccidiosis, candidiasis, aspergillosis, blastomycosis, and pneumocystis. Patients with histoplasmosis or other invasive fungal infections may present disseminated rather than localized lesions. Antigens and antibodies to histoplasmosis may be negative in some patients with active infection. Empiric antifungal therapy should be considered when the patient's invasive fungal infection is at risk of developing severe systemic disease.
Bacterial, viral and other infections caused by opportunistic pathogens, including Legionella and Listeria.
Patients with chronic or recurrent infections should be carefully evaluated for risks and benefits before using Enley.
Patients should be closely monitored for changes in infection symptoms and signs during and after treatment with Enley, including those who have a negative test for latent tuberculosis infection before treatment and may develop tuberculosis infection.
Malignancies have reported the use of TNF-inhibitors, including Enley, in treating children and adolescents with lymphomas and other malignancies, some of which are fatal.

Etanercept for injection

Main ingredients: etanercept excipients: mannitol, sucrose and tromethamine (Tris).
Source of active ingredients: Etanercept is a human tumor necrosis factor receptor p75 Fc fusion protein produced by the Chinese hamster ovary (CHO) cell expression system. The dimer consists of the extracellular ligand binding site of human tumor necrosis factor receptor 2 (TNFR2 / p75) and the Fc fragment of human IgG1. The Fc that makes up etanercept includes CH2, CH3, and the linker, but does not include the CH1 portion of IgG1. The efficacy of etanercept was determined by detecting the inhibitory effect of etanercept on TNF-mediated growth of A375 cells. The activity of etanercept was 1.7 × 106 units / mg.
Molecular weight: Etanercept includes 934 amino acids and a molecular weight of approximately 150 kD

Etanercept traits for injection

White lyophilized powder. The solvent is a clear, colorless liquid.

Etanercept for injection

Rheumatoid arthritis (RA)
Adult patients with moderate to severe active rheumatoid arthritis who do not respond to DMARD, including methotrexate (if not contraindicated), can use etanercept and methotrexate Combination therapy.
Etanercept has been shown to reduce the rate of joint damage progression and improve joint function when used alone or in combination with methotrexate.
Ankylosing spondylitis (AS)
Adult patients with severe active ankylosing spondylitis can be treated with etanercept when they fail to respond to conventional treatment.

Etanercept for injection

25mg / bottle.

Etanercept for injection

This product should be used under the guidance of a specialist with experience in the diagnosis and treatment of rheumatoid arthritis and ankylosing spondylitis.
No drug compatibility studies have been conducted and the use of etanercept in combination with other drugs is prohibited.
For the preparation and use of this product, please refer to the "Instruction Manual of Etanercept (Enley®) for Injection" in the instructions.
Adult (18-64 years)
[u] Rheumatoid arthritis [/ u]
The recommended dose is 25 mg twice a week (72-96 hours apart) or 50 mg once a week. The 50 mg once a week dosing regimen has been proven to be safe and effective (see the Pharmacology and Toxicology section).
[u] Ankylosing spondylitis [/ u]
The recommended dose is 25 mg twice a week (72-96 hours apart) or 50 mg once a week.
Elderly patients (65 years)
No dose adjustment is required. Dosage is the same as for adults aged 18-64.
Patients with impaired liver and kidney function < br No dose adjustment is required.
Injection site < br The injection site of this product is thigh, abdomen and upper arm. The injection method is subcutaneous injection. Each injection is in a different location, at least 3 cm away from the previous injection site. Do not inject on soft, bruised, red or hard parts of the skin. For detailed information on the choice of injection site and injection method, please refer to the "Instruction Manual of Etanercept (Enley) for Injection".
Disposal < br Filoxacin lyophilized powder must be stored in a refrigerator at 2 ° C-8 ° C before use. Do not freeze. This product should be used immediately after dissolution. If not used immediately, the dissolved etanercept injection in a vial should be stored in a refrigerator at 2 ° C 8 ° C for a maximum of 6 hours. If not used within 6 hours, the solution should be discarded. Before injection, the refrigerated solution should be allowed to reach room temperature. Solvent pre-filled syringe rubber stopper contains rubber (dry natural rubber). Before touching or using etanercept, patients or caregivers should contact a doctor to ask how to deal with allergic reactions (allergic reactions) known or likely to occur with rubber.

Etanercept for injection adverse reactions

Safety information summary The most common adverse reactions reported are injection site reactions (such as pain, swelling, itching, erythema, and injection site bleeding), infections (such as upper respiratory infections, bronchitis, bladder infections, and skin infections), allergies, autoantibodies Formation, itching and fever.
There are also reports of serious adverse reactions to etanercept. Tumor necrosis factor inhibitors, such as etanercept, affect the immune system, and their use may affect patients' own resistance to infections and tumors. Fewer than 1 in 100 patients develop severe infections after etanercept treatment. Safety reports also include fatal or life-threatening infections and sepsis. Patients using etanercept have also reported various malignancies, including breast cancer, skin cancer, and lymphoma.
There have also been reports of severe blood system, nervous system abnormalities, and autoimmune reactions. These include rare pancytopenia and very rare aplastic anemia. Patients using etanercept have also reported demyelination of the central and peripheral nervous systems, which are rare and very rare, respectively. There are also reports of rare lupus, lupus-related manifestations, and vasculitis.
Adverse reactions are summarized in the following list. The following adverse reactions are based on clinical trial reports and post-marketing monitoring reports performed in adults.
In each organ system, the adverse reactions are listed according to the incidence rate (number of patients who may have the adverse reaction). The classification criteria are as follows: very common (> 1/10); common (> 1/100, <1 / 10); rare (> 1/1000, <1/100); rare (> 1/10000, <1/1000); very rare (<1/10000); unknown: (the incidence cannot be accurately evaluated in clinical trials) .
Benign, malignant, and unknown tumors (including cysts and polyps)
Rare: Non-melanoma skin cancer Rare: Melanoma; Lymphoma Unknown: Merkel cell carcinoma; Leukemia <br Infection and infection:
Very common: infections (including upper respiratory infections, bronchitis, cystitis, skin infections) *
Rare: severe infections (including pneumonia, cellulitis, septic arthritis, sepsis and parasitic infections) *
Rare: tuberculosis, opportunistic infections (including invasive fungi, protozoa, bacteria and atypical mycobacterial infections and Legionella) *
Unknown: Listeria spp. abnormalities of blood and lymphatic system Immune system abnormalities < br Common: Allergic reactions (see "Skin and subcutaneous tissue abnormalities"), autoantibody formation *
Rare: Systemic vasculitis (including anti-neutrophil cytoplasmic antibody (ANCA) positive vasculitis)
Rare: Severe allergies / allergic reactions (including angioedema, bronchospasm), sarcoidosis unknown: Macrophage activation syndrome <br Symptoms of the sacral nervous system < br Rare: Seizures of the central nervous system Myelinating lesions, including multiple sclerosis or local neurodemyelinating lesions such as optic neuritis and transmyelitis (see "Precautions")
Very rare: Peripheral nerve demyelinating lesions, including Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, demyelinating polyneuropathy, and multifocal motor neuropathy.
Respiratory, thoracic, and mediastinal abnormalities < br Rare: Interstitial lung disease (including pneumonia and pulmonary fibrosis) *
Hepatobiliary abnormalities < br rare: elevated liver enzymes, autoimmune hepatitis <br skin and subcutaneous tissue abnormalities < br common: pruritus rare: angioedema, urticaria, rash, psoriasis-like rash, Psoriasis (including new or worsening and pustules, mainly in the palm or sole)
Rare: cutaneous vasculitis (including leukocyte rupturing vasculitis), Stevens-Johnson syndrome, and erythema polymorpha are very rare: toxic epidermal necrolysis <br br musculoskeletal, connective tissue, and skeletal abnormalities < br br rare : Subacute cutaneous lupus erythematosus, discoid lupus erythematosus, lupus-like syndrome <br Systemic abnormalities and injection site reactions < br are common: injection site reactions (including bleeding, congestion, erythema, itching, pain, swelling)*
Common: Fever <br Abnormal heart <br Rare: Congestive heart failure worsens (see "Precautions")
Eye abnormalities < br Rarely: uveitis, scleritis * See "Other adverse effects" below.
Other adverse reactions < br Malignant tumors and lymphoproliferative diseases In 4114 patients with rheumatoid arthritis who have used this product for 6 years in clinical trials, 129 neonatal malignancies have been observed, including combined methotrexate And etanercept for 231 patients in a 2-year active controlled trial. The rates and morbidity observed in these clinical trials are the same as those expected for the entire population. In a study of 351 patients with ankylosing spondylitis treated with etanercept for more than 2 years, the etanercept group reported 6 malignancies. Among patients treated for other indications, 32 malignancies and 43 non-melanoma skin cancers were reported.
In a clinical trial of etanercept for rheumatoid arthritis, ankylosing spondylitis, and other indications, a total of 18 lymphomas were reported in 7,416 patients.
Various tumors have also been reported after listing, including breast cancer, lung cancer, and lymphoma (see "Special Warnings").
In a clinical trial, malignancies have been reported in patients with Wegener's granulomatosis (see Clinical Trials).
Injection-site response Compared with placebo, the incidence of injection-site reactions was significantly higher in patients with rheumatism treated with etanercept (36% in the etanercept group and 9% in the placebo group, including erythema and / or pruritus, Pain or swelling). Injection site reactions usually occur in the first month and occur most frequently in the first month, and then gradually decrease. The average duration of the injection site response was 3-5 days. Most of the patients in the etanercept group who experienced injection site reactions were untreated, and most of the patients who received the treatment received topical medications, such as glucocorticoids or oral antihistamines. In addition, some patients also experienced injection site reactions, that is, skin reactions at the most recent injection site and injection site reactions at most of the previous injection sites. This response is usually transient and does not recur after treatment.
Controlled trials in patients with plaque-type psoriasis have shown that approximately 13.6% of patients in the etanercept-treated group and 3.4% of placebo-treated patients experienced injection site reactions within the first 12 weeks of dosing.
Hemorrhage and stasis at the injection site associated with etanercept treatment have been observed after marketing.
Severe infection In a controlled trial in patients with rheumatoid arthritis, when the etanercept and placebo groups received the same treatment exposure, the two groups reported severe infections (fatal, life-threatening, hospitalization, or antibiotics). Intravenous) and non-severe infections are comparable. The most common non-serious infection is an upper respiratory infection. The proportion of severe infections in rheumatoid arthritis patients treated with etanercept for 48 months was 6.3%, including abscesses (various parts), bacteremia, bronchitis, bursitis, cellulitis, and cholecystitis , Diarrhea, diverticulitis, endocarditis (suspected), gastroenteritis, hepatitis B, shingles, leg ulcers, oral infections, osteomyelitis, otitis, peritonitis, pneumonia, pyelonephritis, sepsis , Septic arthritis, sinusitis, skin infections, skin ulcers, urethral infections, vasculitis, and wound infections. Subjects were given etanercept, methotrexate, or combination of etanercept and methotrexate in a two-year activity-controlled trial. The incidence of severe infections was similar in the three treatment groups, but not Excluding the combination of etanercept with methotrexate was associated with an increased incidence of infection.
In a 24-week placebo-controlled trial in patients with plaque psoriasis, infection rates were similar in the etanercept-treated and placebo-treated groups. Severe infections in patients treated with etanercept include cellulitis, gastroenteritis, pneumonia, cholecystitis, osteomyelitis, gastritis, appendicitis, fasciitis caused by streptococcus, myositis, and septic shock , Diverticulitis, and abscesses. In a double-blind open-label psoriatic arthritis trial, one patient reported severe infection (pneumonia).
Serious and fatal infections have been reported with etanercept. The reported pathogens include bacteria, mycobacteria (including tuberculosis), viruses and fungi. Some cases occurred within a few weeks of starting etanercept, and these patients had a basic disease (diabetes, congestive heart failure, active or chronic infection) in addition to rheumatoid arthritis (see "Precautions "). A clinical trial has shown that etanercept treatment may increase mortality in patients with sepsis.
Opportunistic pathogenic infections have been reported, including invasive fungal infections, parasitic (including protozoan) infections, bacterial infections (including Listeria and Legionella), and atypical mycobacterial infections. In a comprehensive clinical trial data, the overall incidence of opportunistic pathogenic infections in 15,402 etanercept-treated patients was 0.09%. The adjusted exposure rate was 0.06 events per 100 patient years. After marketing, about half of all cases of opportunistic pathogenic infections worldwide are invasive fungal infections. The most commonly reported invasive fungal infections are Pneumocystis and Aspergillus. Invasive fungal infections kill more than half of patients with opportunistic pathogenic infections. The main fatal results appear in patients with pneumocystis pneumonia, unidentified systemic fungal infections, and aspergillosis (see "Precautions").
Autoantibodies Autoantibody tests are performed on patient serum samples at multiple time points. The positive rate (11%) of antinuclear antibodies (ANA) (titer 1: 40) in rheumatoid arthritis patients in the etanercept group was greater than in the placebo group (5%). Yield was measured by radioimmunoassay (15% in the etanercept-treated group and 4% in the placebo-treated group) and green leafworm short-membrane analysis (3% in the etanercept-treated group and 0% in the placebo-treated group). A higher proportion of patients with nascept were positive for anti-double-stranded DNA antibodies. The rate of increase in anticardiolipin antibodies in etanercept-treated patients was similar to that in the placebo group. The effect of long-term use of etanercept on autoantibody production is unknown.
Rarely reported patients (including rheumatoid factor-positive patients) develop other autoantibodies and develop lupus-like syndrome or rashes that are similar to the clinical manifestations and biopsies of subacute skin lupus erythematosus or discoid lupus erythematosus.
Cases of pancytopenia and aplastic anemia have been reported since the introduction of pancytopenia and aplastic anemia, and some have resulted in death (see "Precautions").
Cases of interstitial lung disease (including pneumonia and pulmonary fibrosis) have been reported after marketing of interstitial lung disease, and some have resulted in death.
Laboratory evaluations Based on the results of clinical studies, special laboratory evaluations of patients are usually not required except for careful medical treatment and monitoring.
The combination of etanercept and anakinra in a study of patients receiving both etanercept and anakinra found that compared with etanercept alone, etanercept and Severe infections were more frequent during anakinra treatment, and neutropenia was reported in 2% (3/139) of patients (absolute neutrophil count <1000 / mm ³ ). One patient had cellulitis and recovered after hospitalization (see "Precautions" and "Drug Interactions").

Etanercept for injection

Those who are allergic to the active ingredients or any other ingredients in this product.
Patients with or at risk for sepsis.
This product cannot be used for patients with severe active infections including chronic or local infections.

Precautions for etanercept for injection

Special warnings < br There have been reports of severe infections (including sepsis and tuberculosis) with etanercept, some of which are fatal. These infections are caused by bacteria, mycobacteria, fungi, viruses and parasites (including protozoa). There have also been reports of opportunities for pathogenic infections (including Legionella and Listeria). Close monitoring of patients with new infections during treatment with etanercept is needed. If a patient develops a severe infection, etanercept must be discontinued. Patients with recurrent or chronic infections or the presence of potential conditions that may make patients susceptible to infections should be used with caution when considering the use of etanercept.
The combination of etanercept and Anakinra is associated with an increased risk of severe infections and neutropenia. Since it has not been proven that this combination therapy can increase clinical efficacy, the combination of etanercept and anakinra is not recommended.
A placebo-controlled study of 180 patients with Wegener's granulomatosis plus etanercept in standard treatments (including cyclophosphamide and high-dose hormones) compared with standard therapy alone Patients in the group had better clinical symptoms. Patients in the etanercept group had more non-epithelial malignancies of various types compared to the placebo group. Egenercept is not recommended for patients with Wegener's granulomatosis.
A trial in 48 inpatients with moderate to severe alcoholic hepatitis treated with etanercept or placebo showed that etanercept treatment was ineffective and 6 months after treatment in the etanercept group Patient mortality is significantly higher. Etanercept is not recommended for patients with alcoholic hepatitis. Doctors should use caution when using etanercept in patients with moderate to severe alcoholic hepatitis.
Solvent pre-filled syringe rubber stopper contains rubber (dry natural rubber). Before touching or using etanercept, patients or caregivers should contact a doctor to ask how to deal with a hypersensitivity (allergic reaction) known or possible to rubber.
General Precautions < br Infection <br Since the average elimination half-life of etanercept is approximately 70 hours (range: 7-300 hours), before, during, and after treatment with etanercept, The patient's infection status must be evaluated.
Serious infections, sepsis, tuberculosis, and opportunistic bacterial infections (including invasive fungal infections) have been reported with etanercept (see "Adverse Reactions"). These infections are caused by bacteria, mycobacteria, fungi and viruses. In some cases, delays in treatment and sometimes death due to the inability to identify fungi and other opportunistic pathogens. In many reports, patients are also treated with drugs including immunosuppressants. In assessing the patient's infection status, the risk of the opportunistic pathogen to the patient should also be considered (eg endemic fungal disease).
Close monitoring of patients with new infections during treatment with etanercept is needed. If a patient develops a severe infection, etanercept must be discontinued. There is no assessment of the safety and effectiveness of etanercept in patients with chronic infection. Patients with recurrent or chronic infections or the presence of potential conditions that may make them susceptible to infection (such as advanced diabetes or poorly controlled diabetes) should be used with caution when considering treatment with etanercept.
Tuberculosis (TB)
Tuberculosis, including diffuse tuberculosis and extrapulmonary manifestations, have been reported in patients using TNF inhibitors, including etanercept. The emergence of tuberculosis may be due to a recurrence of latent tuberculosis infection or a new infection.
Before initiating treatment with etanercept, patients with a high TB risk must be evaluated for active or latent TB infection. The assessment includes personal information and detailed medical history of TB patients, past contact with TB patients, and past and / or current immunosuppressive therapies. All patients need to be screened appropriately, such as a combined bacteriocin skin test and a chest X-ray (see local recommendations). Prescribers should be aware of false negative results from tuberculin skin tests, especially those with severe illness or immunodeficiency.
If the patient is diagnosed with active TB infection, the use of etanercept is prohibited. Before initiating treatment with etanercept, latent tuberculosis infection must be prevented. Some patients who tested negative for latent TB infection before treatment developed active TB infection after using etanercept. Doctors should monitor patients for signs and symptoms of active tuberculosis infection during use of etanercept, including those with a negative test for latent infection. You should also refer to applicable local treatment guidelines. If the patient is diagnosed with latent tuberculosis, antituberculosis treatment must be performed in accordance with local recommendations before starting etanercept. In this case, the benefit / risk balance of using etanercept should be carefully considered. People with rheumatoid arthritis are more likely to be infected with tuberculosis.
Patients should be advised to seek medical guidance for signs / symptoms of tuberculosis (eg, persistent cough, weight loss and low fever) during or after treatment with etanercept.
Hepatitis B virus activation Hepatitis B virus (HBV) activation has been reported in carriers of chronic hepatitis B virus who received TNF inhibitors including etanercept. Patients at risk for HBV infection must evaluate prior HBV infection before starting anti-TNF therapy. The causal relationship between etanercept and HBV activation is not clear. Patients who have been diagnosed with HBV carriers should use etanercept with caution. If HBV carriers are treated with etanercept, they should be monitored for signs and symptoms of HBV infection activation and appropriate treatment should be taken if necessary.
Hepatitis C exacerbation < br There have been reports of exacerbation of hepatitis C in patients treated with etanercept, but the causal relationship between etanercept and exacerbation of hepatitis C is unknown.
Hypoglycemia in diabetics <br There have been reports of hypoglycemia in patients treated with etanercept after using diabetes medications, some of whom had to reduce their use of antidiabetic medications.
Combined etanercept and anakinra therapy < br Compared with etanercept alone, etanercept and anakinra combined with increased risk of severe infection and neutropenia . It has not been proven that this combination therapy can increase clinical effects. Therefore, the combined use of etanercept and anakin is not recommended (see "Drug Interactions" and "Adverse Reactions").
Combination of etanercept and abatacepte < br In clinical studies, the combination of etanercept and abatacepte resulted in an increased incidence of serious adverse events, and it has not been proven that this combination therapy can increase clinical Effect, so it is not recommended.
Allergies < br Allergies related to the use of etanercept are often reported. Allergic reactions include angioedema and urticaria, and severe such reactions have occurred. If any severe allergies or allergic reactions occur, the use of etanercept must be stopped immediately and treated appropriately.
Immunosuppression < br Since tumor necrosis factor (TNF) can mediate inflammatory responses and regulate cellular immune responses, TNF inhibitors (including etanercept) can affect patients' resistance to infections and malignancies. In a study of 49 patients with rheumatoid arthritis treated with etanercept, there was no evidence that it might inhibit delayed hypersensitivity, reduce immunoglobulin levels, or change the number of effector cell populations.
The use of etanercept should be suspended when patients are significantly exposed to chickenpox-zoster virus, and the use of varicella-zoster immunoglobulin prophylaxis should be considered.
The safety and effectiveness of etanercept in immunosuppressed or chronically infected patients is unknown.
Malignant tumors and lymphoproliferative diseases < br Solid tumors and malignant hematological diseases (excluding skin cancer)
There have been reports of malignant tumors that have invaded different sites after marketing (see "Adverse Reactions").
In clinical trials of TNF inhibitors, there were more cases of lymphoma in patients treated with TNF inhibitors compared with the control group, but they were rare, and the follow-up period of patients treated with placebo was shorter than that of patients treated with TNF inhibitors. Post-marketing observations have reported reports of leukemia in patients using TNF-inhibitors. In addition, the risk of lymphoma in rheumatoid arthritis patients who have been in the state of highly active inflammatory diseases for a long time increases the risk assessment.
As far as is known, the risk of lymphoma or other malignancies in patients treated with TNF inhibitors cannot be ruled out. Patients with a history of malignant tumors or malignant tumors who are considering continuing treatment should be vigilant when considering treatment with TNF-inhibitors.
Post-marketing observations of fatal malignancies (especially Hodgkin's and non-Hodgkin's lymph) in children, adolescents and adults (greater than 22 years) treated with TNF-inhibitors, including etanercept Tumors) (initial treatment less than 18 years of age). About half of the reports are lymphoma. It also includes various other malignancies and rare malignancies typically associated with immunosuppression. The risk of malignancy in children and adolescents cannot be ruled out using TNF-inhibitors.
Skin cancer < br Patients treated with TNF inhibitors, including etanercept, have reported melanoma skin cancer and non-melanoma skin cancer (NMSC). Postmarketing report of very rare Merkel cell carcinoma in etanercept-treated patients. Periodic skin tests are recommended for all patients with an increased risk of skin cancer.
The results of the comprehensive control part of the clinical trial of etanercept found that compared with the control group, patients in the etanercept treatment group produced more NMSC cases, especially in patients with psoriasis.
Vaccinations < br Live vaccines are strictly prohibited during the treatment of etanercept. There are no data on secondary transmission infections in patients receiving etanercept as a result of receiving live vaccines. In a double-blind, placebo-controlled, randomized clinical trial, 184 adult patients with psoriatic arthritis received a polyvalent pneumococcal polysaccharide vaccine at week 4, and most received psoriatic arthritis treated with etanercept. Patients were able to produce an effective B-cell immune response to the pneumococcal polysaccharide vaccine, but compared with patients who did not receive etanercept, the total titer was slightly lower, but a few patients increased the titer by 2 times, but its clinical significance was not clear. .
Autoantibody formation The treatment with etanercept may produce autoantibodies (see "Adverse Reactions").
Hematological reactions < br Patients receiving etanercept rarely report whole blood cell reduction, very rarely report aplastic anemia, and some cause death. Patients with a history of blood cachexia should be treated with caution when using etanercept. All patients who develop symptoms of blood cachexia or infection (such as persistent fever, sore throat, congestion, bleeding, paleness) during the use of etanercept should seek medical advice immediately. The above patients should be checked immediately including a complete blood count; if a blood cachexia is diagnosed, etanercept must be discontinued.
Diseases of the central nervous system < br Rarely reported denervation of the central nervous system in patients treated with etanercept (see "Adverse Reactions"). In addition, there are very rare reports of peripheral demyelinating polyneuropathy (including Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, demyelinating polyneuropathy, and multifocal motor neuropathy). Although there are no clinical trials of etanercept in patients with multiple sclerosis, clinical trials of other TNF inhibitors in patients with multiple sclerosis have shown increased disease activity. When prescribing patients who have or are suffering from demyelinating disease or who are considered to have an increased risk of developing demyelinating disease, a detailed risk / benefit assessment including neurological assessment should be recommended.
A 2-year controlled clinical trial in rheumatoid arthritis patients shows that the combination of etanercept and methotrexate does not cause unexpected safety events, and the combination of etanercept and methotrexate The safety characteristics are similar to those reported for etanercept or methotrexate alone. An assessment of the safety profile of long-term combination use is currently underway. When etanercept is used in conjunction with other anti-rheumatic drugs (DMARD) that improve the condition, Enli's long-term safety has not been determined.
Etanercept has not been studied in conjunction with other systemic or light therapies for psoriasis.
Renal and liver impairment < br According to pharmacokinetic data (see "Pharmacokinetics"), there is no need for dose adjustments for patients with liver or renal impairment; clinical experience in these patients is limited.
Congestive heart failure < br Physicians should exercise extreme caution when using etanercept in patients with congestive heart failure (CHF). There have been reports of exacerbations of congestive heart failure in patients with etanercept after marketing, with or without significant triggers. Two large-scale clinical trials evaluating etanercept in patients with congestive heart failure were terminated due to lack of efficacy. Although not final, data from one of these trials suggest that patients treated with etanercept may be predisposed to exacerbate congestive heart failure.
Alcoholic hepatitis < br In a phase II randomized placebo-controlled study, 48 inpatients with moderate or severe alcoholic hepatitis were treated with etanercept or placebo. The results showed that etanercept treatment was ineffective, and the mortality of the etanercept group was significantly higher after 6 months of treatment. Therefore, etanercept is not recommended for patients with alcoholic hepatitis. Doctors should use caution when using etanercept in patients with moderate or severe alcoholic hepatitis.
Wegener's Granuloma < br In a placebo-controlled trial with an average duration of 25 months, 89 adult patients received etanercept and standard therapies (including cyclophosphamide, methotrexate, and glucocorticoids) ), The results did not show that etanercept was effective in treating Wegener's granulomatosis. The incidence of various types of non-cutaneous malignant tumors in the etanercept group was significantly higher than that in the control group. The use of etanercept is not recommended for Wegener's granuloma.
Treatment of hypoglycemia in diabetic patients There are reports that for patients receiving diabetes treatment, the use of etanercept will be accompanied by hypoglycemia, and some patients need to reduce the use of medications for diabetes.

Etanercept for injection for pregnant and lactating women

There are no studies on the use of etanercept in pregnant women, so the safety of etanercept in pregnant women has not been established. Developmental toxicity studies in rats and rabbits have not found damage to fetuses by etanercept. There are no preclinical data on the perinatal and postpartum toxicity of etanercept and the effect of etanercept on fertility and reproductive capacity, and animal reproduction studies do not predict the results in humans well. Therefore, etanercept is not recommended for pregnant women, and women of childbearing age are advised not to get pregnant during etanercept treatment. Etanercept should be given to pregnant women only when clearly needed.
The use of lactation has not yet established the safety of etanercept in lactating women, and it is not clear whether etanercept is secreted by human milk. After subcutaneous injection in lactating rats, etanercept can be excreted through milk, and etanercept can be detected in fetal serum. Because many drugs and immunoglobulins can be secreted from human milk, women who are breastfeeding need to consider whether to stop breastfeeding or discontinue etanercept.

Etanercept for injection for children

Not applicable

Etanercept for injection

No dose adjustment is required based on patient age.

Interaction of etanercept for injection

Combined treatment with etanercept and anakinra Compared with patients treated with etanercept or anakinra alone, the incidence of severe infections is higher in patients treated with both drugs ( historical data).
In addition, in a double-blind placebo-controlled trial, patients receiving basal methotrexate treated with etanercept and anakinra were more severe than patients receiving etanercept Increased incidence of infections (7%) and neutropenia (see "Precautions" and "Adverse Reactions").
 
 
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12AS660881A1-322-CN50mg
1527478147686.5%64/74ASAS20[]95%[78.7~94.3%]57%95%[44.2~69.8%]245.3%95%12+MTX

TNFTNFTNFTNFTNFTNFTNF
TNF55p5575p75(TNFR)TNFRTNFRTNF
TNFTNFRTNFTNFFc

2000mg/kg1000mg/kg42615mg/kgAUC25mgAUC27

The serum concentration of etanercept is determined by ELISA method, which can detect the degradation products and its prototype components that react with ELISA.
Etanercept is slowly absorbed from the site of subcutaneous injection, reaching a peak concentration approximately 48 hours after a single dose. The absolute bioavailability is 76%. In the case of a twice weekly dose, the expected steady-state concentration is approximately twice the value observed after a single dose. After a single subcutaneous injection of 25 mg of etanercept, the average peak serum concentration measured in healthy volunteers was 1.65 ± 0.66 g / ml, and the area under the curve was 235 ± 96.6 g.hr / ml. The dose-response ratio was not formally measured, but within the observed dose range, no clear clearance saturation phenomenon was found.
The concentration-time curve of etanercept is a double exponential curve. The median distribution volume of etanercept is 7.6L, while the steady-state distribution volume is 10.4L.
Etanercept is slowly cleared from the body. Long half-life, about 70 hours. The clearance rate of rheumatoid arthritis patients is about 0.066 L / hr, which is slightly lower than the observed value of 0.11 L / hr in healthy volunteers. In addition, the pharmacokinetics of etanercept are similar in patients with rheumatoid arthritis and ankylosing spondylitis.
The steady-state mean serum concentrations in rheumatoid arthritis patients treated with 50 mg etanercept once a week (n = 21) and 25 mg etanercept twice a week (n = 16) were: Cmax was 2.4 mg / l and 2.6 mg / l; Cmin was 1.2 mg / l and 1.4 mg / l, respectively; some AUCs were 297 mgh / l and 316 mgh / l, respectively. In open, single-dose, two-treatment, and crossover trials in healthy volunteers, a single injection of etanercept 50 mg / ml and two 25 mg / ml simultaneous injections were bioequivalent.
In a population pharmacokinetic analysis of patients with ankylosing spondylitis, 50 mg etanercept once a week (N = 154) and 25 mg twice weekly (N = 148). They were 466 g.hr / ml and 474 g.h / ml, respectively.
Although radioactive excretion can be measured in urine after injecting radiolabeled etanercept to patients and volunteers, patients with acute kidney or liver failure have not observed elevated serum etanercept . Kidney or liver insufficiency requires no dose adjustment. There were no significant pharmacokinetic differences between men and women.
Methotrexate has no effect on the pharmacokinetics of etanercept. The effect of etanercept on the pharmacokinetics of methotrexate in humans has not been studied.
The effect of pharmacokinetic analysis of etanercept serum concentration on elderly patients in the elderly patient population was studied. Estimates of clearance and volume of distribution for patients 65 to 87 years are the same as for patients under 65 years.

Etanercept for injection

Store this product in a refrigerator at 2 ° C-8 ° C before use. Do not freeze.
This product should be used immediately after dissolution. It has been proven to be chemically and physically stable for 48 hours at 2 ° C-8 ° C. However, from a microbiological point of view, this product should be used immediately. If it cannot be used in time, the dissolved etanercept injection in a vial should be stored in a refrigerator at 2 ° C-8 ° C for a maximum of 6 hours. If not used within 6 hours, the solution should be discarded. Before injection, the refrigerated solution should be allowed to reach room temperature.

Etanercept for injection

Transparent glass bottle with rubber stopper (4ml, type I glass), aluminum seal and plastic easy-open cap. This product comes with a syringe pre-filled with water for injection. The syringe is made of type I glass and is equipped with a stainless steel needle.
The two packaging specifications are as follows:
Each box contains 2 bottles of etanercept (25mg / bottle) and 2 water-filled pre-filled syringes, 2 needles, 2 adapters, and 4 alcohol swabs.
Each box contains 4 bottles of etanercept (25mg / bottle) and 4 pre-filled syringes for water for injection, 4 needles, 4 adapters and 8 alcohol swabs.