Class: Disease-modifying Antirheumatic Agents
VA Class: MS190
Chemical Name: 1-235-Tumor necrosis factor receptor (human) fusion protein with 236-467-immunoglobulin G1 (human γ1-chain Fc fragment), dimer
Molecular Formula: C2224H3472N618O701S36 (monomer)
CAS Number: 185243-69-0
Brands: Enbrel
Special Alerts:
[Posted 09/07/2011] ISSUE: FDA notified healthcare professionals that the Boxed Warning for the entire class of Tumor Necrosis Factor-alpha (TNF) blockers has been updated to include the risk of infection from two bacterial pathogens, Legionella and Listeria. In addition, the Boxed Warning and Warnings and Precautions sections of the labels for all of the TNF blockers have been revised so that they contain consistent information about the risk for serious infections and the associated disease-causing pathogens.
Patients treated with TNF blockers are at increased risk for developing serious infections involving multiple organ systems and sites that may lead to hospitalization or death due to bacterial, mycobacterial, fungal, viral, parasitic, and other opportunistic pathogens.
BACKGROUND: The class of TNF blockers are used to treat Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, and/or juvenile idiopathic arthritis.
RECOMMENDATION: The risks and the benefits of TNF blockers should be considered prior to initiating therapy in patients with chronic or recurrent infection and patients with underlying conditions that may predispose them to infection. See the Drug Safety Communication for a listing of recommendations for healthcare professionals and patients, as well as a data summary. For more information visit the FDA website at: and .
[Posted 04/14/2011] ISSUE: FDA continues to receive reports of a rare cancer of white blood cells (known as Hepatosplenic T-Cell Lymphoma or HSTCL, primarily in adolescents and young adults being treated for Crohn’s disease and ulcerative colitis with medicines known as tumor necrosis factors (TNF) blockers, as well as with azathioprine, and/or mercaptopurine. TNF blockers include infliximab (Remicade), etancercept (Enbrel), adalimumab (Humira), certolizumab pegol (Cimzia) and golimumab (Simponi).
BACKGROUND: HSTCL is an aggressive (fast-growing) cancer and is usually fatal. The majority of cases reported were in patients being treated for Crohn’s disease or ulcerative colitis, but also included a patient being treated for psoriasis and two patients being treated for rheumatoid arthritis. FDA is now updating the number of reported cases of HSTCL.
Although most reported cases of HSTCL occurred in patients treated with a combination of medicines known to suppress the immune system, including the TNF blockers, azathioprine, and/or mercaptopurine, there have been cases reported in patients receiving azathioprine or mercaptopurine alone.
Educate patients and caregivers about the signs and symptoms of malignancies such as HSTCL so that they are aware of and can seek evaluation and treatment of any signs or symptoms. These may include splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, and weight loss.
Monitor for the emergence of malignancies when a patient has been treated with TNF blockers, azathioprine, and/or mercaptopurine.
Know that people with rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, psoriatic arthritis and plaque psoriasis may be more likely to develop lymphoma than the general U.S. population. Therefore, it may be difficult to measure the added risk of TNF blockers, azathioprine, and/or meracaptopurine.
Read the Drug Safety Communications for other specific recommendations for Healthcare Professionals and Patients and the Data Summary for additional information. For more information visit the FDA website at: and .
REMS:
FDA approved a REMS for etanercept to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
- Serious Infections
Serious, sometimes fatal infections including tuberculosis (frequently disseminated or extrapulmonary), bacterial and viral infections, invasive fungal infections (may be disseminated), and other opportunistic infections reported.1 (See Infectious Complications under Cautions.)
Carefully consider risks and benefits prior to initiating etanercept therapy in patients with chronic or recurring infections.1
Evaluate patients for latent tuberculosis infection prior to and periodically during etanercept therapy; if indicated, initiate appropriate antimycobacterial regimen prior to initiating etanercept therapy.1
Closely monitor patients for infection, including active tuberculosis in those with a negative tuberculin skin test, during and after treatment.1 Discontinue etanercept if serious infection or sepsis occurs.1 Consider empiric antifungal therapy if serious systemic illness occurs in a patient at risk for invasive fungal infections.1
Introduction
Biologic response modifier and disease-modifying antirheumatic drug (DMARD); a recombinant DNA-derived human immunoglobulin G1 (IgG1) monoclonal antibody specific for human tumor necrosis factor (TNF; TNF-α).1 2 3 4 5 6 8 9 32 33
Uses for Etanercept
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Rheumatoid Arthritis in Adults
Used to manage the signs and symptoms of rheumatoid arthritis, to induce a major clinical response, to improve physical function, and to inhibit progression of structural damage associated with the disease in adults with moderate to severe active rheumatoid arthritis.1 2 3 4 5 6 7 8 15 17 32 33 34 70 111 112 117
Can be initiated in combination with methotrexate or alone.1
Juvenile Arthritis
Management of the signs and symptoms of moderate to severe active polyarticular course juvenile idiopathic arthritis in children.1 29 33 54 77 78 84
Psoriatic Arthritis
Used to manage the signs and symptoms of active arthritis, to improve physical function, and to inhibit progression of structural damage associated with the disease in patients with psoriatic arthritis.1 72 76 118
Can be used in combination with methotrexate in patients who have not responded adequately to therapy with methotrexate alone.1 72 76
Ankylosing Spondylitis
Management of the signs and symptoms of active ankylosing spondylitis.1 121
Psoriasis
Management of moderate to severe chronic plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.1 108 109 119
Wegener’s Granulomatosis
Has been investigated for the management of Wegener’s granulomatosis†34 59 (designated an orphan drug by FDA for this use).57 Use with standard immunosuppressive agents has been associated with an increased incidence of solid malignant tumors without added clinical benefit.103 110 122 Use to induce or maintain remission currently is not justified.103 110 122 Use in patients with Wegener’s granulomatosis† receiving immunosuppressive therapy is not recommended.1 (See Malignancies and Lymphoproliferative Disorders under Cautions and see Specific Drugs and Laboratory Tests under Interactions.)
Etanercept Dosage and Administration
General
Concomitant Therapy
Methotrexate, glucocorticoids, salicylates, NSAIAs, and analgesics may be continued in adults with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.1 7
Glucocorticoids, NSAIAs, and analgesics may be continued in pediatric patients with juvenile idiopathic arthritis.1
REMS Program
FDA has approved a Risk Evaluation and Mitigation Strategy (REMS) for etanercept.130
The program consists of a medication guide that must be provided to patients (see Advice to Patients) and a communication plan targeting selected groups of clinicians.130 The communication plan is not intended to continue throughout the lifetime of the product.130
The goals are to inform patients about the serious risks associated with the drug and to inform clinicians about invasive fungal infections associated with use of TNF blocking agents (see Warnings/Precautions under Cautions).130
Administration
Sub-Q Administration
Adults and children receiving 50-mg dose: Administer dose as a single injection or as 2 injections given on the same day or 3–4 days apart.1 133
Administer sub-Q injections into the thighs, abdomen, or upper arm.132 133 134 Rotate injection sites.132 133 134 Do not inject into areas where skin is tender, bruised, red, or hard or into scars or stretch marks; whenever possible, avoid injecting drug into psoriatic lesions.132 133 134
Development of local reactions at the injection site does not preclude continued therapy.64
Allow etanercept prefilled syringe and prefilled auto-injector to reach room temperature (about 15–30 minutes) prior to administration.1 Do not remove the needle cover until the prefilled syringe or prefilled auto-injector has reached room temperature.1 132 Solution may contain a small amount of visible, white, proteinaceous particulates; do not administer if discolored or cloudy, or if foreign particulate matter is present.1
Intended for use under the guidance and supervision of a clinician, but may be self-administered if the clinician determines that the patient and/or their caregiver is competent to prepare and safely administer the drug.1 55 The initial self-administered dose should be made under the supervision of a healthcare professional.1
Reconstitution (25-mg Multiple-dose Vial)
Reconstitute lyophilized powder by adding 1 mL of bacteriostatic water for injection (containing 0.9% benzyl alcohol) provided by the manufacturer to a 25-mg vial to provide a solution containing 25 mg/mL.1
During reconstitution, very slowly add the diluent to the vial and gently swirl the contents to minimize foaming during dissolution; some foaming will occur.1
May use vial adapter supplied by manufacturer to facilitate reconstitution and withdrawal of dose if only one dose will be withdrawn from the vial.1
Avoid shaking and excessive or vigorous agitation of the vial to avoid excessive foaming.1
The final volume in the vial will be about 1 mL.134
Dissolution usually takes less than 10 minutes.1
Do not filter solutions during preparation or administration.1
Do not mix contents of one vial with, or transfer contents of one vial into, contents of another vial.1 Do not mix with other drugs.1
Preparation Considerations
50-mg dose given as a single injection: Preferred preparations are the 50-mg prefilled syringe or prefilled auto-injector.1 132 133
50-mg dose given as 2 injections: Appropriate preparation is the 25-mg vial or prefilled syringe.1 133 134
Do not use 25-mg prefilled syringe in children weighing <31 kg.133 Do not use 50-mg prefilled syringe or auto-injector in children weighing <63 kg.132 133
Dosage
Pediatric Patients
Juvenile Arthritis
Sub-Q
Children 2–17 years of age: 0.8 mg/kg (maximum 50 mg) per week.1
Adults
Rheumatoid Arthritis
Sub-Q
50 mg weekly.1
Psoriatic Arthritis
Sub-Q
50 mg weekly.1
Ankylosing Spondylitis
Sub-Q
50 mg weekly.1
Psoriasis
Sub-Q
Initially, 50 mg twice weekly for 3 months.1 Initial dosages of 25 mg once or twice weekly also have been effective; proportion of responders related to etanercept dosage.1
Maintenance dosage: 50 mg once weekly.1
Prescribing Limits
Pediatric Patients
Juvenile Arthritis
Sub-Q
Maximum 50 mg weekly.1
Adults
Rheumatoid Arthritis
Sub-Q
Maximum 50 mg weekly.1
Psoriatic Arthritis
Sub-Q
Maximum 50 mg weekly.1
Ankylosing Spondylitis
Sub-Q
Maximum 50 mg weekly.1
Special Populations
Renal Impairment
Limited data indicate that dosage adjustment is not necessary in patients with renal failure.123
Cautions for Etanercept
Contraindications
Warnings/Precautions
Warnings
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Infectious Complications
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Serious, sometimes fatal infections (including bacterial, mycobacterial, invasive fungal, viral, and other opportunistic infections) reported with etanercept or other TNF blocking agents,1 27 129 particularly in patients receiving concomitant therapy with other immunosuppressive agents (e.g., methotrexate, corticosteroids).1 The most common opportunistic infections include tuberculosis, histoplasmosis, aspergillosis, candidiasis, coccidioidomycosis, listeriosis, and pneumocystosis.1 Infections frequently are disseminated.1
Do not initiate etanercept in patients with active infections, including clinically important localized infections.1 16 36 48 Consider potential risks and benefits of the drug prior to initiating therapy in patients with a history of chronic or recurring infections, patients with underlying conditions that may predispose them to infections, and patients who have been exposed to tuberculosis or who have resided or traveled in regions where tuberculosis or mycoses such as histoplasmosis, coccidioidomycosis, and blastomycosis are endemic.1
Closely monitor patients during and after etanercept therapy for signs or symptoms of infection (e.g., fever, malaise, weight loss, sweats, cough, dyspnea, pulmonary infiltrates, serious systemic illness including shock).1 129
If new infection occurs during therapy, perform thorough diagnostic evaluation (appropriate for immunocompromised patient), initiate appropriate anti-infective therapy, and closely monitor patient.1 129 Discontinue etanercept if serious infection or sepsis develops.1 16 36 48 129
Evaluate all patients for active or latent tuberculosis and for risk factors for tuberculosis prior to and periodically during therapy.1 When indicated, initiate appropriate antimycobacterial regimen for treatment of latent tuberculosis infection prior to etanercept therapy.1 Also consider antimycobacterial therapy prior to etanercept therapy for individuals with a history of latent or active tuberculosis in whom an adequate course of antimycobacterial treatment cannot be confirmed and for individuals with a negative tuberculin skin test who have risk factors for tuberculosis.1 Consultation with a tuberculosis specialist is recommended when deciding whether to initiate antimycobacterial therapy.1
Reactivation of latent tuberculosis reported in patients receiving etanercept, although data suggest that risk is lower with etanercept than with TNF-blocking monoclonal antibodies.1
Monitor all patients, including those with negative tuberculin skin tests, for active tuberculosis.1 Strongly consider tuberculosis in patients who develop new infections while receiving etanercept, especially if they previously have traveled to countries where tuberculosis is highly prevalent or have been in close contact with an individual with active tuberculosis.1
Invasive fungal infections often not recognized in patients receiving TNF blocking agents; this has led to delays in appropriate treatment.129
Consider empiric antifungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.1 129 Whenever feasible, consult specialist in fungal infections when making decisions regarding initiation and duration of antifungal therapy.1 129
When deciding whether to reinitiate TNF blocking agent therapy following resolution of an invasive fungal infection, reevaluate risks and benefits, particularly in patients who reside in regions where mycoses are endemic.129 Whenever feasible, consult specialist in fungal infections.129
Increased incidence of serious infection and neutropenia observed with concomitant use of etanercept and anakinra (a human interleukin-1 receptor antagonist).1 (See Specific Drugs and Laboratory Tests under Interactions.)
Increased incidence of infection and serious infection reported with concomitant use of a TNF blocking agent and abatacept.1 127 (See Specific Drugs and Laboratory Tests under Interactions.)
Malignancies and Lymphoproliferative Disorders
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Lymphoma and other malignancies (some fatal) reported during postmarketing surveillance in children and adolescents receiving TNF blocking agents, particularly in those receiving other immunosuppressive agents (e.g., azathioprine, methotrexate) concomitantly.1 128 Malignancies included lymphomas (about 50% of the cases) (e.g., Hodgkin’s disease, non-Hodgkin’s lymphoma) and various other malignancies (e.g., leukemia, melanoma, solid organ cancers), including rare malignancies usually associated with immunosuppression and malignancies not usually observed in children and adolescents (e.g., leiomyosarcoma, hepatic malignancies, renal cell carcinoma).1 128 Median time to occurrence was 30 months (range: 1–84 months) after the initial TNF blocking agent dose.1 FDA has concluded that there is an increased risk of malignancy with TNF blocking agents in children and adolescents; however, the strength of the association is not fully characterized.128
In controlled studies, lymphoma was reported more frequently in patients receiving etanercept or other TNF blocking agents than in control patients.1 99 Patients with rheumatoid arthritis, especially those with highly active disease, may be at increased risk of lymphoma.1
Acute and chronic leukemias (some fatal) reported during postmarketing surveillance of TNF blocking agents in adults and pediatric patients, particularly in those receiving other immunosuppressive agents concomitantly.1 128 Leukemia (most commonly acute myeloid leukemia, chronic lymphocytic leukemia, and chronic myeloid leukemia) generally occurred during first 2 years of therapy.128 FDA has concluded that there is a possible association between TNF blocking agents and development of leukemia; interpretation of findings is complicated because patients with rheumatoid arthritis may be at increased risk for leukemia independent of any treatment with TNF blocking agents.1 128
Nonmelanoma skin cancer reported in patients receiving TNF blocking agents, including etanercept.1 Consider periodic dermatologic examinations in all patients at increased risk.1
For malignancies other than lymphoma and nonmelanoma skin cancer, no differences in exposure-adjusted occurrence rates observed between etanercept-treated patients and control patients.1
Solid noncutaneous malignant tumors reported in patients with Wegener’s granulomatosis receiving etanercept and cyclophosphamide; malignancies not reported in control patients receiving standard immunosuppressive therapy (corticosteroids plus cyclophosphamide or methotrexate) for Wegener’s granulomatosis.1 122 (See Specific Drugs and Laboratory Tests under Interactions.)
Role of TNF blocking agents in development of malignancies not fully determined.1 128
Some immune related diseases (e.g., Crohn’s disease) have been shown to increase risk of cancer independent of treatment with TNF blocking agents, while for others (e.g., juvenile idiopathic arthritis) it is unknown whether there is an increased risk of cancer.128
Consider possibility of and monitor for occurrence of malignancies during and following treatment with TNF blocking agents.128
Sensitivity Reactions
Hypersensitivity Reactions
Possible allergic reactions.1 If serious allergic reaction or anaphylaxis occurs, immediately discontinue etanercept and initiate appropriate therapy.1
Latex Sensitivity
The needle covers of prefilled syringes and prefilled auto-injectors contain dry natural rubber (latex); individuals sensitive to latex should not handle the needle covers.1 124 125 126
Other Warnings and Precautions
Nervous System Effects
New onset or exacerbation of CNS demyelinating disorders (some presenting with mental status changes and some associated with permanent disability) and peripheral nervous system demyelinating disorders reported rarely with etanercept or other TNF blocking agents.1 TNF blockers associated with increased disease activity in patients with multiple sclerosis.71 73 74
Multiple sclerosis,1 88 transverse myelitis,1 optic neuritis,1 Guillain-Barré syndrome,1 peripheral demyelinating neuropathies,1 and new onset or exacerbation of seizure disorders1 reported in patients receiving etanercept.1
Exercise caution when considering etanercept therapy in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders.1 73 74
Cardiovascular Effects
Worsening CHF (with and without identifiable precipitating factors) and, rarely, new-onset CHF (including in patients without known cardiovascular disease) reported, sometimes in patients <50 years of age.1 Use with caution and monitor carefully in patients with heart failure.1
One study evaluating etanercept for treatment of CHF suggested higher mortality rate in etanercept-treated patients versus placebo recipients.1
Hematologic Effects
Possible pancytopenia including aplastic anemia, sometimes with fatal outcome.1 Use with caution in patients with a history of substantial hematologic abnormalities.1 Consider discontinuance in patients with confirmed hematologic abnormalities.1
Hepatitis B Virus (HBV) Reactivation
Reactivation of HBV infection reported in patients who are chronic carriers of the virus (i.e., hepatitis B surface antigen-positive [HBsAg-positive]).1 Death reported in a few individuals.1 Use of multiple immunosuppressive agents may contribute to HBV reactivation.1
Screen at-risk patients prior to initiation of therapy.1 Evaluate and monitor HBV carriers before, during, and for up to several months after therapy.1 Safety and efficacy of antiviral therapy for prevention of HBV reactivation not established.1 Discontinue etanercept and initiate appropriate treatment (e.g., antiviral therapy) if HBV reactivation occurs.1 Not known whether etanercept can be readministered once control of a reactivated HBV infection is achieved; caution advised in this situation.1
Immunization
Patients may receive inactivated vaccines.1 Avoid live vaccines (e.g., measles virus vaccine live, mumps virus vaccine live, rubella virus vaccine live, poliovirus vaccine live oral, typhoid vaccine live oral, varicella virus vaccine live, yellow fever vaccine).1 (See Interactions.)
Immunologic Reactions and Antibody Formation
Possible formation of autoimmune antibodies.1 15 32 33 Lupus-like syndrome or autoimmune hepatitis reported rarely;1 87 may resolve upon discontinuance of the drug.1 If manifestations suggestive of lupus-like syndrome or autoimmune hepatitis develop, discontinue etanercept and carefully evaluate patient.1 36 48 56
Nonneutralizing antibodies to etanercept may develop.1 Long-term immunogenicity remains to be determined.1
Psoriasis
New-onset psoriasis, including pustular and palmoplantar psoriasis, reported with TNF blocking agents, including etanercept.1 128 Onset observed weeks to years following initiation of drug.128 Some patients required hospitalization.128 Most patients experienced improvement following discontinuance of the TNF blocking agent.128 FDA has concluded that there is a possible association between use of TNF blocking agents and development of psoriasis.128
Exacerbation of existing psoriasis also reported.1
Consider possibility of and monitor for manifestations (e.g., new rash) of new or worsening psoriasis, particularly pustular and palmoplantar psoriasis.128
Patients with Alcoholic Hepatitis
Use in patients with moderate to severe alcoholic hepatitis associated with higher mortality rate following 6 months of use; use with caution in such patients.1
Patients with Diabetes Mellitus
Hypoglycemia reported following initiation of etanercept therapy in diabetic patients receiving antidiabetic agents.1 Some patients required reduction in dosage of the antidiabetic agent.1
Specific Populations
Pregnancy
Category B.1
Pregnancy registry at 877-311-8972.1
Lactation
Not known whether etanercept is distributed into milk or is absorbed systemically following ingestion.1 Discontinue nursing or the drug.1
Pediatric Use
Used for treatment of polyarticular course juvenile idiopathic arthritis in children ≥2 years of age.1 Not studied in children <2 years of age with juvenile idiopathic arthritis.1 Safety and efficacy not established in children with plaque psoriasis.1
Review vaccination status of the child and administer all age-appropriate vaccines, if possible, prior to initiation of therapy.1 82
Varicella infection associated with aseptic meningitis reported.1 If a varicella-susceptible child has a clinically important exposure to varicella while receiving etanercept, discontinue the drug temporarily and consider use of varicella-zoster immune globulin.1
Types of infections generally are mild and consistent with those commonly reported in the general pediatric population,1 but serious infections have occurred.135
Frequencies and types of adverse effects reported in pediatric patients similar to those in adults.1 Adverse effects reported in children 2–4 years of age similar to those reported in older children.1
Malignancies, some fatal, reported in children and adolescents who received TNF blocking agents.1 128 (See Malignancies and Lymphoproliferative Disorders under Cautions.)
Geriatric Use
No substantial differences in safety or efficacy relative to younger adults;1 34 61 however, insufficient experience in geriatric patients with psoriasis to determine whether they respond differently than younger adults.1
Possible increased incidence of infections in geriatric patients; use with caution.1
Common Adverse Effects
Injection site reactions, infections (including respiratory tract and other infections).1
Interactions for Etanercept
Administered concomitantly with methotrexate, glucocorticoids, salicylates, NSAIAs, and/or analgesics in clinical studies.1
Vaccines
Patients may receive inactivated vaccines.1
Avoid live vaccines.1 No data available on secondary transmission of infection by live vaccines in etanercept-treated patients.1
Specific Drugs and Laboratory Tests
Drug or Test
|
Interaction
|
Comments
|
|---|
Abatacept
|
Increased incidence of infection and serious infection, without additional clinical benefit, reported with abatacept and TNF blocking agents in rheumatoid arthritis1 127
|
Concomitant use not recommended1 127
|
Anakinra
|
Increased incidence of serious infections and increased risk of neutropenia, without additional clinical benefit, reported in rheumatoid arthritis1
|
Concomitant use not recommended1
|
Cyclophosphamide
|
Concomitant use associated with increased incidence of solid malignant tumors without additional clinical benefit1 122
|
Concomitant use not recommended1
|
Methotrexate
|
Pharmacokinetic interaction unlikely1
Concomitant use not associated with additive toxicity7
|
|
Pneumococcal polysaccharide vaccine
|
B-cell immune response adequate in etanercept-treated psoriatic arthritis patients, although titers moderately lower and twofold increases less common than in controls1
|
Clinical importance of observed differences not known1
|
Sulfasalazine
|
Decrease in neutrophil counts reported1
|
Clinical importance unknown1
|
Test for troponin
|
False-positive troponin determinations using murine monoclonal antibody-based assay (i.e., AxSym Troponin, Abbott)65
|
Use of reformulated AxSym Troponin I assay containing goat protein67 may eliminate interference65
|
Etanercept Pharmacokinetics
Absorption
Bioavailability
Bioavailability following sub-Q administration is approximately 60%.31 Peak plasma concentrations achieved within 69 hours.1
Distribution
Extent
Not known whether etanercept crosses the placenta.1
Not known whether etanercept is distributed into milk.1
Elimination
Half-life
68 hours in healthy adults;40 102 hours in adults with rheumatoid arthritis.1
Stability
Storage
Parenteral
Powder for Injection
2–8°C.1 Do not freeze.1
Store reconstituted solutions at 2–8°C;34 134 do not freeze.34 Discard reconstituted solutions after 14 days.1
Prefilled Syringe and Prefilled Auto-injector
2–8°C.1 Do not freeze.1 Store in original carton until time of administration.1 Do not shake.1
Actions
Potent antagonist of TNF biologic activity.1 2 3 4 5 6 7 8 9 32 33
High binding affinity for TNF and lymphotoxin-α (TNF-β);1 2 3 4 5 6 8 9 13 33 35 37 each molecule can bind to 2 TNF molecules.33 Prevents the binding of TNF to cell surface TNF receptors, thereby blocking the biologic activity of TNF.1 2 3 4 5 6 7 8 9 33 37
Produced by recombinant DNA technology in a mammalian cell expression system.1
Advice to Patients
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
A copy of the manufacturer’s patient information (medication guide) for etanercept must be provided to all patients with each prescription of the drug.1 128 (See REMS Program under Dosage and Administration.) Importance of advising patients about potential benefits and risks of etanercept.1 128 Importance of patients reading the medication guide prior to initiation of therapy and each time the prescription is refilled.136
If the patient or caregiver is to administer etanercept, provide careful instructions regarding proper dosage and administration of etanercept, including proper aseptic technique, and proper disposal of needles and syringes.1
Importance of advising patients to seek immediate medical attention if signs and symptoms suggestive of blood dyscrasias (e.g., persistent fever, bruising, bleeding, pallor) or infection (e.g., fever, chills, flu-like symptoms, cough, burning or pain on urination) develop.1 136
Risk of lymphoma, leukemia, or other malignancies with TNF blocking agents.1 128 Importance of informing patients and families about the increased risk of cancer development in children and adolescents, taking into account the clinical utility of TNF blocking agents, the benefits and risks of other immunosuppressive drugs, and the risks associated with untreated disease.128 Importance of promptly informing clinicians if signs and symptoms of cancer occur (e.g., unexplained weight loss; fatigue; swollen lymph nodes in the neck, underarm, or groin; easy bruising or bleeding).128
Risk of new or worsening neurologic conditions (e.g., demyelinating disorders).1 Importance of informing clinician if signs or symptoms of such conditions (e.g., numbness, tingling, changes in vision, weakness in arms and legs) occur.1 136
Risk of new or worsening heart failure.1 Importance of informing clinician if signs or symptoms of heart failure (e.g., shortness of breath, swelling of the feet or lower legs) occur.1 136
Risk of autoimmune disorders (e.g., lupus-like syndrome, autoimmune hepatitis).1 Importance of informing clinician if signs or symptoms of lupus-like syndrome (e.g., rash on face and arms) or autoimmune hepatitis (e.g., fatigue, jaundice, poor appetite, vomiting, right-sided abdominal pain) occur.1 136
Risk of new-onset psoriasis or worsening of existing psoriasis.1 128 Importance of informing clinicians of any manifestations of new or worsening psoriasis (e.g., new rash).128 136
Importance of alerting clinician if allergy to latex exists.1
Importance of promptly contacting a clinician if manifestations of an allergic reaction (e.g., rash, facial swelling, difficulty breathing) occur.136
Importance of taking the drug as prescribed and of not altering or discontinuing therapy without first consulting with a clinician.128
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any other illnesses (e.g., concomitant or recurrent infections, history of tuberculosis, history of HBV infection).1 129
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Etanercept
Routes
|
Dosage Forms
|
Strengths
|
Brand Names
|
Manufacturer
|
|---|
Parenteral
|
For injection, for subcutaneous use
|
25 mg
|
Enbrel (with prefilled syringe containing 1 mL bacteriostatic water for injection [with benzyl alcohol 0.9%] diluent, plunger, vial adapter, and alcohol swabs)
|
Amgen, (also promoted by Pfizer)
|
|
Injection, for subcutaneous use
|
25 mg/0.5 mL
|
Enbrel |
