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Etanercept

Pronunciation

Pronunciation: ee-TAN-er-sept
Class: Immunomodulator

Trade Names

Enbrel
- Injection, solution 25 mg
- Injection, solution 50 mg
- Injection, lyophilized powder for solution 25 mg

Pharmacology

Binds specifically to tumor necrosis factor (TNF), blocking its interaction with cell surface TNF receptors and modulating biological responses induced or regulated by TNF.

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Pharmacokinetics

Absorption

C max is approximately 1.1 mcg/mL and T max is approximately 69 h (single 25 mg dose). C max increases 2- to 7-fold, while AUC increases approximately 4-fold with repeated dosing.

Elimination

The half-life is approximately 102 h. Cl is approximately 160 mL/h.

Special Populations

Renal Function Impairment

No studies conducted.

Hepatic Function Impairment

No studies conducted.

Elderly

Pharmacokinetic parameters are not different.

Children

Cl is slightly reduced in patients 4 to 8 y of age.

Gender

Pharmacokinetic parameters are not different.

Indications and Usage

Reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in moderately to severely active rheumatoid arthritis (RA); reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in children 2 y and older; reducing signs and symptoms in patients with active ankylosing spondylitis; treatment of adults 18 y and older with chronic, moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy; reducing signs and symptoms, inhibiting the progression of structural damage of active arthritis, and improving physical function in patients with psoriatic arthritis.

Unlabeled Uses

Crohn disease; graft versus host disease; hidradenitis suppurativa; idiopathic thrombocytopenic purpura; nephrotic syndrome; pyoderma gangrenosum.

Contraindications

Sepsis.

Dosage and Administration

Ankylosing Spondylitis, Psoriatic Arthritis, Rheumatoid Arthritis
Adults

Subcutaneous 50 mg/wk (max, 50 mg/wk in RA).

Juvenile Idiopathic Arthritis
Children 2 y and older 63 kg or more

Subcutaneous 50 mg/wk.

62 kg or less

Subcutaneous 0.8 mg/kg/wk.

Plaque Psoriasis
Adults

Subcutaneous 50 mg 2 times/wk for 3 mo followed by reduction to a maintenance dosage of 50 mg/wk. Starting dosages of 25 or 50 mg/wk were also shown to be efficacious.

General Advice

  • For subcutaneous use only.
  • Do not administer if particulate matter, cloudiness, or discoloration is noted. There may be small white particles of protein in the solution; this is not unusual for proteinaceous solutions.
  • Allow prefilled syringe or SureClick autoinjector to reach room temperature (approximately 15 to 30 min) before administering. Do not remove the needle shield while allowing the prefilled syringe to reach room temperature. Do not shake.
  • Reconstitute powder using only supplied diluent (sterile bacteriostatic water for injection). Follow manufacturer's instructions.
  • Use vial adapter if reconstituted solution will be administered as a single dose. If the vial will be used for multiple doses, use a 25-gauge needle for reconstituting and withdrawing etanercept.
  • To prevent excessive foaming, inject diluent very slowly into medication vial and swirl gently to dissolve. Do not shake or vigorously agitate medication vial. Complete dissolution may take up to 10 min.
  • Do not filter reconstituted solution. Do not mix contents with or transfer to another vial of etanercept. Do not add other medications to etanercept or reconstitute with other diluents.
  • In adults, methotrexate, glucocorticoids, salicylates, NSAIDs, and analgesics may be continued during treatment with etanercept. In juvenile idiopathic arthritis patients, glucocorticoids, NSAIDs, or analgesics may be continued during treatment with etanercept.

Storage/Stability

Refrigerate between 36° and 46°F. Do not freeze. Keep prefilled syringes and autoinjectors in the original carton to protect from light until time of use. Use reconstituted solution immediately or refrigerate between 36° and 46°F for up to 14 days. Discard the solution if it is not used within 14 days.

Drug Interactions

Abatacept

Concurrent use resulted in an increased incidence of serious adverse events, including infection, without demonstrating increased clinical benefit. Concurrent therapy is not recommended.

Anakinra

A 7% rate of serious infections was observed during coadministration, which was higher than observed with etanercept alone. Concurrent therapy is not recommended.

Cyclophosphamide

Risk of noncutaneous solid malignancies may be increased. Concurrent use is not recommended.

Immunosuppressive agents (eg, corticosteroids)

Use of etanercept in patients with Wegener granulomatosis who are receiving immunosuppressive agents is not recommended.

Sulfasalazine

Concomitant use caused a mild decrease in mean neutrophil counts. The clinical importance of this observation is unknown.

Tocilizumab

Coadministration with tocilizumab may increase the risk of serious infection. Avoid concurrent use.

Vaccines, live

The effectiveness of live vaccines may be reduced. Do not give live vaccines concurrently with etanercept.

Adverse Reactions

Cardiovascular

CHF (postmarketing).

CNS

Convulsions, demyelination, multiple sclerosis, paresthesias, transverse myelitis (postmarketing).

Dermatologic

Rash (13%); pruritus (5%); urticaria (2%); cutaneous lupus erythematosus, cutaneous vasculitis, erythema multiforme, new or worsening psoriasis, melanoma and nonmelanoma skin cancer, Merkel cell carcinoma, Stevens-Johnson syndrome, subcutaneous nodules, TEN (postmarketing).

EENT

Optic neuritis, uveitis (postmarketing).

GI

Diarrhea (16%); inflammatory bowel disease (postmarketing).

Hematologic-Lymphatic

Anemia, aplastic anemia, leukopenia, lymphadenopathy, neutropenia, pancytopenia, thrombocytopenia (postmarketing).

Hepatic

Autoimmune hepatitis, transaminase elevations (postmarketing).

Hypersensitivity

Hypersensitivity (1%).

Local

Injection-site reactions (43%).

Respiratory

Upper respiratory tract infections (65%); non-upper respiratory tract infections (54%); interstitial lung disease, pneumonia (postmarketing).

Miscellaneous

Infections, including bacteria, fungal, and viral (81%); positive anti–double-stranded DNA antibodies (15%); antinuclear antibodies (11%); pyrexia (2%); angioedema, chest pain, lupus-like syndrome, macrophage activation syndrome, opportunistic infections (including atypical mycobacterial infection, herpes zoster, aspergillosis, and Pneumocystis jiroveci ), protozoal infections, systemic vasculitis (postmarketing).

Precautions

Warnings

Patients treated with etanercept are at an increased risk of developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants, such as methotrexate or corticosteroids.

Discontinue etanercept if a patient develops a serious infection or sepsis. Reported infections include active tuberculosis (TB), including reactivation of latent TB; invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis; bacterial, viral, and other infections caused by opportunistic pathogens, including Legionella and Listeria .

Carefully consider the risks and benefits of treatment with etanercept prior to initiating therapy in patients with chronic or recurrent infections. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with etanercept, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

Lymphoma and other malignancies (including leukemia and skin cancer), some fatal, have been reported in children and adolescent patients treated with TNF blockers, including etanercept.


Monitor

Closely monitor patients for the development of signs and symptoms of infection during and after treatment with etanercept, including the development of TB in patients who tested negative for latent TB infection prior to initiating therapy. Closely monitor a patient who develops a new infection during treatment and have the patient undergo a prompt and complete diagnostic workup appropriate for an immunocompromised patient. Evaluate patients for TB risk factors and test for latent infection prior to initiating etanercept and periodically during therapy. Closely monitor patients who are carriers of hepatitis B virus (HBV) and require treatment with etanercept for clinical and laboratory signs of active HBV infection throughout therapy and for several months following termination of therapy. Consider periodic skin examinations for all patients at increased risk for skin cancer. Monitor all patients for exacerbation or new-onset of CHF.


Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy not established in children younger than 2 y with juvenile idiopathic arthritis. Safety and efficacy in children with plaque psoriasis have not been established.

Elderly

Because there is a higher incidence of infection in elderly patients, use with caution.

Hypersensitivity

Allergic reactions, including anaphylaxis, may occur.

Hepatic Function

Use with caution in patients with moderate to severe alcoholic hepatitis.

Special Risk Patients

Exercise caution when considering the use of etanercept in patients who have been exposed to TB, with a history of opportunistic infection, who have resided or traveled in areas of endemic TB or endemic mycoses, or with underlying conditions, such as advanced or poorly controlled diabetes, that may predispose them to infections.

Autoimmunity

Formation of autoantibodies and, rarely, development of lupus-like syndrome or autoimmune hepatitis may occur.

Benzyl alcohol

The diluent preservative contains benzyl alcohol, which has been associated with fatal gasping syndrome in premature infants.

CNS effects

Agents that inhibit TNF have been associated with rare cases of 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. Transverse myelitis, optic neuritis, multiple sclerosis, Guillian-Barré syndrome, other peripheral demyelinating neuropathies, and new onset or exacerbation of seizure disorders have been observed.

Heart failure

Worsening of CHF, with and without identifiable precipitating factors, and new-onset CHF, including CHF in patients without known preexisting CV disease, have been reported.

Hematologic

Rare and sometimes fatal cases of pancytopenia, including aplastic anemia, have been reported.

Hepatitis B reactivation

Etanercept has been associated with rare cases of reactivation of HBV, which may be fatal, in chronic carriers of the virus.

Hypoglycemia

May occur.

Immunizations

Do not coadminister with live virus vaccines. If possible, ensure that patients with juvenile idiopathic arthritis are up to date with all immunizations in agreement with current guidelines prior to initiating therapy. Temporarily discontinue therapy in patients with significant exposure to varicella virus and consider prophylactic treatment with varicella zoster immune globulin.

Latex allergy

The needle cover of the prefilled syringe and SureClick autoinjector contain natural rubber (latex).

Wegener granulomatosis

The use of etanercept in patients with Wegener granulomatosis receiving immunosuppressive agents is not recommended; coadministration in these patients was associated with a higher incidence of noncutaneous solid malignancies and no improvement in clinical outcomes.

Overdosage

Symptoms

Single IV doses of up to 60 mg/m 2 have been administered without evidence of dose-limiting toxicities.

Patient Information

  • Advise patient, family, or caregiver to read the Medication Guide before starting therapy and with each refill.
  • Instruct patients to seek medical evaluation immediately if they develop symptoms of a severe allergic reaction.
  • Inform patients that etanercept may lower the ability of their immune system to fight infections. Advise patients of the importance of contacting their health care provider if they develop any symptoms of infection, TB, or reactivation of HBV infection.
  • Advise patients to report any signs of new or worsening medical conditions, such as CNS demyelinating disorders, heart failure, or autoimmune disorders, such as lupus-like syndrome or autoimmune hepatitis.
  • Counsel patients about the risk of lymphoma and other malignancies while receiving etanercept.
  • Advise patients to report any symptoms suggestive of a pancytopenia, such as bruising, bleeding, persistent fever, or pallor.
  • If patient or caregiver will be administering at home, ensure the patient or caregiver understands how to store, prepare, and administer the dose, and how to dispose of used equipment and supplies. The first injection should be performed under the supervision of a qualified health provider.
  • Warn patients not to receive live vaccines while undergoing etanercept therapy.
  • Advise latex-sensitive patients that the needle cover on the prefilled syringe and the SureClick autoinjector contains dry natural rubber (latex).

Copyright © 2009 Wolters Kluwer Health.

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