Etanercept

GENERIC AVAILABLE: No

The most common side effects are:

• mild to moderate itching,
• pain,
• swelling and redness at the site of injection,
• headache,
• dizziness,
• nasal and throat.

TNF alpha has an important role in the responses of the immune system to infections. Thus, blocking the action of TNF alpha with etanercept may worsen or increase the occurrence of infections such as tuberculosis, bacterial sepsis, invasive fungal infections (such as histoplasmosis), and other opportunistic infections (infections that occur primarily in patients with suppressed immune systems). Patients with serious infections should not receive etanercept, and etanercept should be discontinued if a patient develops a serious infection. Etanercept should be used with caution in patients prone to infection, such as those with advanced or poorly controlled diabetes. Children should receive their recommended immunizations before treatment with etanercept.

Some reported associated conditions may or may not be related to etanercept.

Other important side effects include:

• cancer,
• multiple sclerosis,
• myelitis, and
• optic neuritis.

For this reason, etanercept is not recommended for persons with preexisting disease of the central nervous system (brain and/or spinal cord) or for those with multiple sclerosis, myelitis, or optic neuritis. Additionally, rare cases of seriously low blood counts (pancytopenia) have been reported in patients using etanercept. New cases or worsening of congestive heart failure may occur.

Etanercept, a tumor necrosis factor (TNF) blocker, is a dimeric fusion protein consisting of the extracellular ligand-binding portion of the human 75 kilodalton (p75) tumor necrosis factor receptor (TNFR) linked to the Fc portion of human IgG1. The Fc component of etanercept contains the CH2 domain, the CH3 domain and hinge region, but not the CH1 domain of IgG1. Etanercept is produced by recombinant DNA technology in a Chinese hamster ovary (CHO) mammalian cell expression system. It consists of 934 amino acids and has an apparent molecular weight of approximately 150 kilodaltons.

Enbrel (etanercept) Injection in the single-dose prefilled syringe and the single-dose prefilled SureClick autoinjector is clear and colorless, sterile, preservative-free solution, and is formulated at pH 6.3 ± 0.2.

Enbrel (etanercept) for Injection is supplied in a multiple-dose vial as a sterile, white, preservative-free, lyophilized powder. Reconstitution with 1 mL of the supplied Sterile Bacteriostatic Water for Injection, USP (containing 0.9% benzyl alcohol) yields a multiple-dose, clear, and colorless solution 1 mL containing 25 mg of Enbrel, with a pH of 7.4 ± 0.3.

Enbrel (etanercept) Injection in the Enbrel Mini single-dose prefilled cartridge for use with the AutoTouch reusable autoinjector is clear and colorless, sterile, preservative-free solution, and is formulated at pH 6.3 ± 0.2.

Table 5: Contents of Enbrel

Etanercept is part of the drug class:

• Tumor necrosis factor alpha

You should not use this medication if you are allergic to etanercept, or if you have a severe infection such as sepsis (infection of the blood).

Some people using etanercept have developed a rare fast-growing type of lymphoma (cancer). This condition affects the liver, spleen, and bone marrow, and it can be fatal. This has occurred mainly in teenagers and young adults using etanercept or similar medicines to treat Crohn's disease or ulcerative colitis. However, people with autoimmune disorders (including psoriasis) may have a higher risk of lymphoma. Talk to your doctor about your individual risk.

Before using etanercept, tell your doctor if you have ever had tuberculosis, if anyone in your household has tuberculosis, or if you have recently traveled to an area where tuberculosis is common.

To make sure you can safely use etanercept, tell your doctor if you have any of these other conditions:

• a weak immune system, or any type of infection including a skin infection or open sores;
• diabetes;
• congestive heart failure;
• a nerve disorder such as multiple sclerosis, myelitis, or optic neuritis;
• epilepsy or other seizure disorder;
• asthma or other breathing disorder;
• if you have ever had hepatitis B;
• if you are allergic to latex rubber; or
• if you are scheduled to receive any vaccines, or if you have recently been vaccinated with BCG (Bacille Calmette-Guerin).

FDA pregnancy category B. Etanercept is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether etanercept passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Children using this medication should be current on all childhood immunizations before starting treatment with etanercept.

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 with or without methotrexate.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.)

Inflammatory Bowel Disease

Not effective in the treatment of inflammatory bowel disease†.1

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

(et a NER sept)

Patients treated with etanercept are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients treated with etanercept 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 the following:

Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Test patients for latent TB before etanercept use and during therapy. Initiate treatment for latent infection prior to etanercept use.

Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric antifungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.

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 long-term 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, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor (TNF) blockers, including etanercept.

Applies to etanercept: subcutaneous kit, subcutaneous solution

Respiratory

Very common (10% or more): Non-upper respiratory infection (38%), upper respiratory infection (29%), rhinitis (12%)
Common (1% to 10%): Pharyngitis, cough, respiratory disorder, sinusitis
Uncommon (0.1% to 1%): Interstitial lung disease (including pneumonitis and pulmonary fibrosis)[Ref]

Immunologic

Very common (10% or more): Infections (including upper respiratory tract infections, bronchitis, cystitis, skin infections)
Uncommon (0.1% to 1%): Serious infections (including pneumonia, cellulitis, septic arthritis, sepsis, parasitic infection)
Rare (less than 0.1%): Tuberculosis, opportunistic infections (including invasive fungal, protozoal, bacterial, atypical mycobacterial, viral infections, Legionella), subacute cutaneous lupus erythematosus, discoid lupus erythematosus, lupus-like syndrome
Frequency not reported: Listeria, hepatitis B reactivation
Postmarketing reports: Macrophage activation syndrome, systemic vasculitis, sarcoidosis[Ref]

Nervous system

Very common (10% or more): Headache (17%)
Common (1% to 10%): Dizziness
Rare (less than 0.1%): Seizures, CNS demyelinating events suggestive of multiple sclerosis or localized demyelinating conditions, such as optic neuritis and transverse myelitis
Very rare (less than 0.01%): Peripheral demyelinating events (including Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, demyelinating polyneuropathy, multifocal motor neuropathy)
Postmarketing reports: Paresthesias[Ref]

Gastrointestinal

Common (1% to 10%): Abdominal pain, dyspepsia, diarrhea, nausea, vomiting, mouth ulcers, altered sense of taste, esophagitis, gastritis
Uncommon (0.1% to 1%): Dry mouth
Rare (less than 0.1%): Anorexia
Frequency not reported: Intestinal perforation
Postmarketing reports: Inflammatory bowel disease (IBD)[Ref]

Cardiovascular

Rare (less than 0.1%): Worsening of congestive heart failure
Postmarketing reports: Chest pain[Ref]

Dermatologic

Common (1% to 10%): Pruritus, rash
Uncommon (0.1% to 1%): Angioedema, urticaria, rash, psoriasiform rash, psoriasis (including new onset or worsening and pustular, primarily palms and soles)
Rare (less than 0.1%): Cutaneous vasculitis (including leukocytoclastic vasculitis), Stevens-Johnson syndrome, erythema multiforme
Very rare (less than 0.01%): Toxic epidermal necrolysis
Postmarketing reports: Angioedema[Ref]

Local

Very common (10% or more): Injection site reactions (including bleeding, bruising, erythema, itching, pain, swelling)[Ref]

Hematologic

Uncommon (0.1% to 1%): Thrombocytopenia
Rare (less than 0.1%): Anemia, leukopenia, neutropenia, pancytopenia
Very rare (less than 0.01%): Aplastic anemia
Postmarketing reports: Lymphadenopathy[Ref]

Ocular

Uncommon (0.1% to 1%): Uveitis, scleritis
Rare (less than 0.1%): Inflammation, dry eyes[Ref]

Hypersensitivity

Common (1% to 10%): Allergic reactions, autoantibody formation
Uncommon (0.1% to 1%): Systemic vasculitis (including anti-neutrophilic cytoplasmic antibody positive vasculitis)
Rare (less than 0.1%): Serious allergic/anaphylactic reactions (including angioedema, bronchospasm), sarcoidosis
Frequency not reported: Macrophage activation syndrome, worsening of symptoms of dermatomyositis[Ref]

Oncologic

Uncommon (0.1% to 1%): Non-melanoma skin cancers
Rare (less than 0.1%): Lymphoma, melanoma
Frequency not reported: Leukemia, Merkel cell carcinoma, leukemia[Ref]

Hepatic

Rare (less than 0.1%): Elevated liver enzymes, autoimmune hepatitis
Postmarketing reports: Hepatitis B reactivation[Ref]

Genitourinary

Frequency not reported: Urinary tract infection[Ref]

Renal

Renal side effects including pyelonephritis have been reported. At least one case of necrotizing crescentic glomerulonephritis has been reported, in addition to a case of proliferative lupus nephritis.

Other

Common (1% to 10%): Fever, asthenia[Ref]

General

The most commonly reported adverse reactions are injection site reactions (such as pain, swelling, itching, reddening and bleeding at the puncture site), infections (such as upper respiratory infections, bronchitis, bladder infections and skin infections), allergic reactions, development of autoantibodies, itching, and fever.[Ref]

Some side effects of etanercept may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Using etanercept may increase your risk of developing certain types of cancer, including a rare type of lymphoma. Ask your doctor about your specific risk.

Etanercept can weaken your immune system. Serious and sometimes fatal infections may occur. Call your doctor right away if you have signs of infection such as: fever, chills, cough, sweating, body aches, skin sores or redness, diarrhea, burning when you urinate, or feeling very tired or short of breath.

Avoid being near people who are sick or have infections. Call your doctor for preventive treatment if you are exposed to chicken pox.

Do not receive a "live" vaccine while using etanercept. The vaccine may not work as well during this time, and may not fully protect you from disease. Live vaccines include measles, mumps, rubella (MMR), polio, rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Serious and sometimes fatal infections may occur. Call your doctor right away if you have signs of infection such as: fever, chills, cough, sweating, body aches, skin sores or redness, diarrhea, weight loss, burning when you urinate, coughing up blood, or feeling very tired or short of breath.

Also call your doctor at once if you have:

• blood problems--fever, pale skin, easy bruising or bleeding;

• liver problems--upper stomach pain, vomiting, tiredness, loss of appetite, jaundice (yellowing of the skin or eyes);

• lupus-like syndrome--joint pain or swelling, chest discomfort, feeling short of breath, skin rash on your cheeks or arms (worsens in sunlight);

• nerve problems--numbness or tingling, problems with vision, or weak feeling in your arms or legs;

• new or worsening psoriasis--skin redness or scaly patches, raised bumps filled with pus;

• signs of heart failure--shortness of breath with swelling of your ankles or feet, rapid weight gain;

• signs of lymphoma--fever, night sweats, weight loss, stomach pain or swelling, chest pain, cough, trouble breathing, swollen glands (in your neck, armpits, or groin); or

• signs of tuberculosis--fever, cough, night sweats, loss of appetite, weight loss, feeling constantly tired.

Common side effects may include:

• pain, swelling, itching, or redness where the medicine was injected;

• headache; or

• cold symptoms such as stuffy nose, sneezing, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.