Questions about Rheumatoid Arthritis? Get answers from our expert.

Generic Name: Etanercept
Class: Disease-modifying Antirheumatic Drugs
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

Warning(s)

  • Serious Infections
  • Increased risk of serious infections involving various organ systems and sites that may require hospitalization or result in death; tuberculosis (frequently disseminated or extrapulmonary), invasive fungal infections (may be disseminated), bacterial (e.g., legionellosis, listeriosis) and viral infections, and other opportunistic infections reported.1 27 129 137 (See Infectious Complications under Cautions.)

  • Carefully consider risks and benefits prior to initiating etanercept therapy in patients with chronic or recurring infections.1 137

  • Evaluate patients for latent tuberculosis infection prior to and periodically during etanercept therapy; if indicated, initiate appropriate antimycobacterial regimen prior to initiating etanercept therapy.1 137

  • Closely monitor patients for infection, including active tuberculosis in those with a negative tuberculin skin test, during and after treatment.1 129 137 Discontinue etanercept if serious infection or sepsis occurs.1 129 Consider empiric antifungal therapy if serious systemic illness occurs in a patient at risk for invasive fungal infections.1 129 137

  • Malignancy
  • Lymphoma and other malignancies (some fatal) reported in children and adolescents receiving TNF blocking agents.1 128 138 (See Malignancies and Lymphoproliferative Disorders under Cautions.)

REMS:

FDA approved a REMS for etanercept to ensure that the benefits outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().

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 Enbrel

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

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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 granulomatosis34 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.)

Inflammatory Bowel Disease

Not effective in the treatment of inflammatory bowel disease.1

Enbrel 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

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 Enbrel

Contraindications

  • Sepsis.1

Warnings/Precautions

Warnings

Infectious Complications

Increased risk of serious infections involving various organ systems and sites that may require hospitalization or result in death.1 137 Opportunistic infections caused by bacterial, mycobacterial, invasive fungal, viral, parasitic, or other opportunistic organisms (e.g., aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis, tuberculosis) reported, particularly in patients receiving concomitant therapy with immunosuppressive agents (e.g., methotrexate, corticosteroids).1 27 129 137 Infections frequently are disseminated.1 (See Boxed Warning.)

Increased incidence of serious infections observed with concomitant use of a TNF blocking agent and anakinra or abatacept.1 127 140 (See Specific Drugs and Laboratory Tests under Interactions.)

Patients >65 years of age, with comorbid conditions, and/or receiving concomitant therapy with immunosuppressive agents (e.g., corticosteroids, methotrexate) may be at increased risk of infection.1 137

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, recurring, or opportunistic 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.1 137

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).1 129 137

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.1 137 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

Failure to recognize invasive fungal infections 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.1 129 137 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

Malignancies and Lymphoproliferative Disorders

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

Hepatosplenic T-cell lymphoma (a rare, aggressive, usually fatal T-cell lymphoma) reported mainly in adolescents and young adults with Crohn’s disease or ulcerative colitis receiving TNF blocking agents and/or thiopurine analogs (mercaptopurine or azathioprine).138 Most of the patients received a combination of immunosuppressive agents, including TNF blocking agents and thiopurine analogs.138

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 Crohn’s disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, or plaque psoriasis, especially those with highly active disease, may be at increased risk of lymphoma;1 138 may be difficult to measure added risk of TNF-blocking agents, azathioprine, and/or mercaptopurine.138

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

Melanoma and nonmelanoma skin cancer reported in patients receiving TNF blocking agents, including etanercept.1 Merkel cell carcinoma reported infrequently in patients who received 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.)

In controlled studies of other TNF blocking agents in adults at increased risk of malignancies (e.g., patients with COPD and a history of heavy smoking), a greater proportion of malignancies occurred in patients receiving the TNF blocking agent compared with control patients.142

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.128 138

Carefully consider risks and benefits of TNF blocking agents, especially in adolescents and young adults and especially in the treatment of Crohn’s disease or ulcerative colitis;138 etanercept is not effective in the management of inflammatory bowel disease.1

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

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

Sensitivity Reactions

Possible allergic reactions.1 If serious allergic reaction or anaphylaxis occurs, immediately discontinue etanercept and initiate appropriate therapy.1

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

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, and exacerbation of existing psoriasis reported with TNF blocking agents, including etanercept.1 128 Most patients experienced improvement following discontinuance of the TNF blocking agent.128

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.)

Inflammatory bowel disease reported rarely in patients with juvenile idiopathic arthritis receiving etanercept; the drug is not effective in the management of inflammatory bowel disease.1

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 Enbrel

Administered concomitantly with methotrexate, glucocorticoids, salicylates, NSAIAs, and/or analgesics in clinical studies.1

Biologic Antirheumatic Agents

Use caution when switching from one biologic DMARD to another, since overlapping biologic activity may further increase the risk of infection.142

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

Use caution when switching from one biologic DMARD to another, since overlapping biologic activity may further increase risk of infection142

Anakinra

Increased incidence of serious infections and neutropenia, without additional clinical benefit, reported in rheumatoid arthritis1 140

Concomitant use not recommended1

Use caution when switching from one biologic DMARD to another, since overlapping biologic activity may further increase risk of infection142

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

Rituximab

Increased risk of serious infection reported in patients who received rituximab and subsequently received a TNF blocking agent142

Use caution when switching from one biologic DMARD to another, since overlapping biologic activity may further increase risk of infection142

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

Tocilizumab

Concomitant use not studied; possibility of increased immunosuppression and increased risk of infection139

Avoid concomitant use139

Use caution when switching from one biologic DMARD to another, since overlapping biologic activity may further increase risk of infection142

Enbrel 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

  • A copy of the manufacturer’s patient information (medication guide) for etanercept should be provided to all patients with each prescription of the drug.1 128 Importance of advising patients about potential benefits and risks of etanercept.1 128 137 138 Importance of patients reading the medication guide prior to initiation of therapy and each time the prescription is refilled.128 136 137 138

  • 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

  • Increased susceptibility to infection.1 136 137 Importance of seeking immediate medical attention if signs and symptoms suggestive of infection (e.g., fever, chills, flu-like symptoms, cough, burning or pain on urination) develop.1 136

  • Risk of lymphoma, including hepatosplenic T-cell lymphoma, leukemia, or other malignancies with TNF blocking agents.1 128 138 Importance of informing patients and caregivers about the increased risk of cancer development in children, adolescents, and young adults, taking into account the clinical utility of TNF blocking agents, the relative risks and benefits of these and other immunosuppressive drugs, and the risks associated with untreated disease.1 128 138 Importance of promptly informing clinicians if signs and symptoms of malignancies (e.g., unexplained weight loss; fatigue; abdominal pain; persistent fever; night sweats; easy bruising or bleeding; swollen lymph nodes in the neck, underarm, or groin; easy bruising or bleeding; hepatomegaly or splenomegaly) occur.128 138

  • Importance of informing clinician of any new or worsening medical conditions (e.g., neurologic conditions [e.g., demyelinating disorders], heart failure, autoimmune disorders [e.g., lupus-like syndrome, autoimmune hepatitis], psoriasis, cytopenias).1 128 136

  • 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.128 138

  • 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 concomitant illnesses or any history of cancer, tuberculosis, HBV infection, or other chronic or recurring infections.1 129 137

  • 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 (available as disposable prefilled syringes)

Amgen, (also promoted by Pfizer)

50 mg/mL

Enbrel (available as disposable prefilled syringes and prefilled auto-injectors [SureClick)

Amgen, (also promoted by Pfizer)

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Enbrel 25MG Kit (AMGEN): 4/$979.01 or 8/$1,940.87

Enbrel 25MG/0.5ML Solution (AMGEN): 1/$260.99 or 2/$760.97

Enbrel 50MG/ML Solution (AMGEN): 4/$1,903.07 or 8/$3,760.97

Enbrel SureClick 50MG/ML Solution (AMGEN): 4/$2,030.98 or 12/$5,827.13

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions March 27, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Amgen/Pfizer. Enbrel (etanercept) prescribing information. Thousand Oaks, CA; 2011 Sep.

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3. Moreland LW, Baumgartner SW, Schiff MH et al. Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N Engl J Med. 1997; 337:141-7. [IDIS 388682] [PubMed 9219699]

4. Szekanecz Z, Koch AE, Kunkel SL et al. Cytokines in rheumatoid arthritis: potential targets for pharmacological intervention. Drugs Aging. 1998; 12:377-90. [PubMed 9606615]

5. Breedveld F. New tumor necrosis factor-alpha biologic therapies for rheumatoid arthritis. Eur Cytokine Netw. 1998; 9:233-8. [PubMed 9831171]

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7. Weinblatt ME, Kremer JM, Bankhurst AD et al. A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med. 1999; 340:253-9. [IDIS 417654] [PubMed 9920948]

8. O’Dell JR. Anticytokine therapy—a new era in the treatment of rheumatoid arthritis? N Engl J Med. 1999; 340:310-2. Editorial.

9. Mohler KM, Torrance DS, Smith CA et al. Soluble tumor necrosis factor (TNF) receptors are effective therapeutic agents in lethal endotoxemia and function simultaneously as both TNF carriers and TNF antagonists. J Immunol. 1993; 151:1548-61. [PubMed 8393046]

10. Roux-Lombard P, Punzi L, Hasler F et al. Soluble tumor necrosis factor receptors in human inflammatory synovial fluids. Arthritis Rheum. 1993; 36:485-9. [PubMed 8384452]

11. Cope AP, Aderka D, Doherty M et al. Increased levels of soluble tumor necrosis factor receptors in the sera and synovial fluid of patients with rheumatic diseases. Arthritis Rheum. 1992; 35:1160-9. [PubMed 1329774]

12. Beutler B, van Huffel C. Unraveling function in the TNF ligand and receptor families. Science. 1994; 264:667-8. [PubMed 8171316]

13. Nam MH, Reda D, Boujoukos AJ et al. Recombinant human dimeric tumor necrosis factor (TNF) receptor (TNFR:Fc): safety and pharmacokinetics in human volunteers. Clin Res. 1993; 41:249A.

14. Jacobs CA, Beckmann MP, Mohler K et al. Pharmacokinetic parameters and biodistribution of soluble cytokine receptors. Int Rev Exp Pathol. 1993; 34B:123-35.

15. Moreland LW, Schiff MH, Baumgartner SW et al. Etanercept therapy in rheumatoid arthritis: a randomized, controlled trial. Ann Intern Med. 1999; 130:478-86. [IDIS 421342] [PubMed 10075615]

16. Furst DE, Keystone E, Maini RN et al. Recapitulation of the round-table discussion—assessing the role of anti-tumor necrosis factor therapy in the treatment of rheumatoid arthritis. Rheumatology (Oxford). 1999; 38(Suppl 2):50-3. [PubMed 10646494]

17. Moreland LW, Baumgartner SW, Tindall EA et al. Longterm safety and efficacy of TNF receptor (P75) Fc fusion protein (TNFR:FC; Enbrel) in DMARD refractory rheumatoid arthritis (RA). Arthritis Rheum. 1998; 41(Suppl):S364.

18. Felson DT, Anderson JJ, Boers M et al. American College of Rheumatology preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum. 1995; 38:727-35. [PubMed 7779114]

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