Enbrel

Etanercept instructions

Common name: Etanercept for injection

Trade name: Enbrel

All names: Etanercept for injection, Etanercept, Enli, Etanercept, Enbrel

Indications:

Rheumatoid arthritis (RA)

Adult patients with moderately to severely active rheumatoid arthritis who are refractory to DMARDs (disease-modifying antirheumatic drugs) including methotrexate (if their use is not contraindicated) can be treated with etanercept in combination with methotrexate.

Ankylosing spondylitis (AS)

Adult patients with severe active ankylosing spondylitis who fail to respond to conventional treatments can be treated with etanercept.

Usage and dosage:

Adults (18-64 years old)

Rheumatoid arthritis: 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 dosage regimen has been proven to be safe and effective.

Ankylosing spondylitis: The recommended dose is 25 mg twice weekly (72-96 hours apart) or 50 mg once weekly.

Adverse reactions:

The most commonly reported adverse reactions are injection site reactions (such as pain, swelling, itching, erythema and injection site bleeding), infections (such as upper respiratory tract infection, bronchitis, bladder infection and skin infection), allergic reactions, Autoantibody formation, itching and fever.

Serious adverse reactions have also been reported with etanercept. Tumor necrosis factor inhibitors, such as etanercept, affect the immune system, and their use may affect a patient's own ability to fight infections and tumors. Less than 1/100 patients develop serious infection after treatment with etanercept. Fatal or life-threatening infections and sepsis are also included in the safety report. Various malignancies have also been reported in patients taking etanercept, including breast cancer, skin cancer, and lymphoma.

Severe hematological and neurological abnormalities, as well as autoimmune reactions, have also been reported. These include rare pancytopenia and very rare aplastic anemia. Demyelinating lesions of the central and peripheral nervous systems have also been reported, respectively, rarely and very rarely, in patients taking etanercept. There have also been rare reports of lupus, lupus-related manifestations, and vasculitis.

Contraindications:

Those who are allergic to the active ingredients or any other ingredients in this product.

Patients with sepsis or at risk of sepsis.

This product cannot be used to treat patients with severe active infections, including chronic or local infections.

Precautions:

Severe infections (including sepsis and tuberculosis), some fatal, have been reported with etanercept. These infections are caused by bacteria, mycobacteria, fungi, viruses and parasites (including protozoa). Infections with opportunistic pathogens (including Legionella spp. and Listeria spp.) have also been reported. Patients who develop new infections during etanercept treatment require close monitoring. Etanercept must be discontinued if the patient develops a serious infection. Caution should be used when considering treatment with etanercept in patients with recurrent or chronic infections or with underlying conditions that may render the patient susceptible to infection.

Co-treatment with etanercept and anakinra (Anakinra) is associated with an increased risk of serious infections and neutropenia. The combined use of etanercept and anakinra is not recommended as this combination has not been shown to increase clinical efficacy.

In a placebo-controlled study of 180 patients with Wegener's granulomatosis who received etanercept added to standard treatment (including cyclophosphamide and high-dose corticosteroids), patients who received etanercept did not experience better clinical improvement than standard treatment alone. Patients in the etanercept group developed more non-epithelial malignancies of all types compared with those in the placebo group. Treatment with etanercept is not recommended for patients with Wegener's granulomatosis.

In a trial of 48 hospitalized patients with moderate to severe alcoholic hepatitis treated with etanercept or placebo, treatment with etanercept was ineffective and mortality was significantly higher in the etanercept group after 6 months of treatment. Treatment with etanercept is not recommended in patients with alcoholic hepatitis. Physicians should use caution when treating patients with moderate to severe alcoholic hepatitis.

The rubber stopper of the solvent's prefilled syringe contains rubber (dry natural rubber). Before contacting or using etanercept, patients or caregivers should contact their physician to inquire about management of known or possible hypersensitivity (allergy) to rubber.

Infection: Because the mean elimination half-life of etanercept is approximately 70 hours (range: 7-300 hours), patients must be evaluated for infection before, during, and after treatment with etanercept. Serious infections, sepsis, tuberculosis, and opportunistic infections (including invasive fungal infections) have been reported with etanercept. These infections are caused by bacteria, mycobacteria, fungi, and viruses. In some cases, failure to recognize fungi and other opportunistic pathogens results in delays in treatment and sometimes death. In many reports, patients were also treated with concomitant medications including immunosuppressants. When assessing a patient's infection status, the risk to the patient from relevant opportunistic pathogens should also be considered (e.g., endemic mycoses). Patients who develop new infections during etanercept treatment require close monitoring. Etanercept must be discontinued if the patient develops a serious infection. The safety and effectiveness of etanercept in patients with chronic infections have not been evaluated. Caution should be used when considering treatment with etanercept in patients with recurrent or chronic infections or in patients with underlying conditions that may render the patient susceptible to infection (such as advanced diabetes or poorly controlled diabetes).

Tuberculosis (TB): Tuberculosis, including diffuse TB and extrapulmonary manifestations, has been reported in patients taking TNF inhibitors, including etanercept. Tuberculosis may occur due to recurrence of latent tuberculosis infection or new infection. Patients at high risk for tuberculosis must be evaluated for active or latent tuberculosis infection before initiating treatment with etanercept. This assessment includes personal information and detailed medical history of the TB patient, past contact with TB patients, and previous and/or current immunosuppressive therapy. All patients need to undergo appropriate screening tests, such as bindomycin skin test and chest X-ray (refer to local recommendations). Prescribers should be aware of false-negative tuberculin skin test results, particularly in those patients with severe illness or immunocompromise. Treatment with etanercept is contraindicated in patients with confirmed active tuberculosis infection. Latent tuberculosis infection must be prevented before starting treatment with etanercept. Some patients who tested negative for latent tuberculosis infection before treatment developed active tuberculosis infection after taking etanercept. Physicians should monitor patients for signs and symptoms of active tuberculosis infection while taking etanercept, including those who test negative for latent infection. Applicable local treatment guidelines should be consulted. If a patient is diagnosed with latent tuberculosis, anti-tuberculosis treatment must be initiated according to local recommendations before starting etanercept. In this setting, the benefit/risk balance of treatment with etanercept should be carefully considered. People with rheumatoid arthritis are more likely to develop tuberculosis infection. u2003 Patients should be informed that they should seek medical guidance if they develop signs/symptoms of tuberculosis (e.g., persistent cough, weight loss, low-grade fever) during or after treatment with etanercept.

Hepatitis B virus activation: Hepatitis B virus (HBV) activation has been reported in chronic hepatitis B virus carriers treated with TNF inhibitors, including etanercept. Patients at risk for HBV infection must be evaluated for prior HBV infection before initiating anti-TNF therapy. The causal relationship between etanercept and HBV activation is unclear. Patients who have been diagnosed as HBV carriers should use etanercept with caution. If HBV carriers are treated with etanercept, they should be monitored for signs and symptoms of reactivation of HBV infection and appropriate treatment should be instituted if necessary.

Hepatitis C exacerbations: Hepatitis C exacerbations have been reported in patients treated with etanercept, but the causal relationship between etanercept and hepatitis C exacerbations has not been established.

Hypoglycemia in Diabetic Patients: Hypoglycemia has been reported in patients treated with etanercept after taking antidiabetic medications, and some of these patients had to reduce their antidiabetic medications.

Combined therapy with etanercept and anakinra: Combination therapy with etanercept and anakinra is associated with an increased risk of serious infections and neutropenia compared with etanercept alone. This combination therapy has not been shown to increase clinical efficacy. Therefore, the combined use of etanercept and anakinra is not recommended.

Storage:

This product should be stored in a refrigerator at 2°C – 8°C before use. Do not freeze.

This product should be used immediately after dissolving. Proven chemical and physical stability 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 the vial should be stored at 2°C – Store in refrigerator at 8°C for up to 6 hours. If not used within 6 hours, the solution should be discarded. Refrigerated solutions should be allowed to reach room temperature before injection.

Mechanism of action:

Most joint pathology in rheumatoid arthritis and ankylosing spondylitis is mediated by pro-inflammatory molecules, which are linked to a network controlled by tumor necrosis factor (TNF). TNF is a cytokine that plays a leading role in the inflammatory response of rheumatoid arthritis. Elevated TNF levels can also be found in the serum and synovial tissue of patients with ankylosing spondylitis. Etanercept is a competitive inhibitor of TNF receptors on the cell surface and can inhibit the biological activity of TNF, thereby blocking TNF-mediated cellular responses. Etanercept may also be involved in regulating biological responses controlled by other downstream molecules (such as cytokines, adhesion molecules or proteases) induced or regulated by TNF.

Safety and efficacy:

To evaluate the efficacy and safety of etanercept 50 mg once a week in the treatment of active ankylosing spondylitis (AS). 29 patients with ankylosing spondylitis were selected and given 50 mg, once/week, subcutaneous injection treatment. The incidence of low back pain, waist morning stiffness time, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) were evaluated and analyzed at weeks 0, 2, 4, 6, 8, 10 and 12 as required. Changes in adverse reactions were observed for an average of 6 months. Results: Compared with the time of enrollment, the incidence of low back pain in patients after 3 months of treatment was significantly reduced (P0.05 or P0.01), the time of morning stiffness in the waist was significantly shortened (P0.05), and the BASDAI score dropped from (7.1±1.6) before treatment to (4.2±1.8) ) (P=0.001), the BASFI score dropped from (7.8±1.4) before treatment to (3.8±1.2) (P=0.001), ESR and CRP were significantly reduced (P0.05), and the symptom improvement was mainly pain at the tendon insertion point, followed by morning stiffness. The BASDAI score of this group of patients improved during the follow-up period (P=0.04), and 1 patient developed injection site reaction. Conclusion: This study confirms that etanercept can alleviate the condition of most patients with ankylosing spondylitis and has minor side effects. 50 mg once a week for the treatment of active AS. It has the characteristics of easy use, rapid onset, significant efficacy, and good tolerance. The long-term effect remains to be further observed.