etanercept (Enbrel, Erelzi, etanercept-szzs)

Dosing and uses of Enbrel, Erelzi (etanercept)

• Adult
• Pediatric

 

Adult dosage forms and strengths

injection solution, prefilled syringe

• 25mg/mL (Enbrel, Erelzi)
• 50mg/mL (Enbrel, Erelzi)

injection solution, prefilled autoinjector

• 50mg/mL (Enbrel, Erelzi)

injection powder for reconstitution

• 25mg/vial (Enbrel)

Biosimilars to EnbreL

• Erelzi (etanercept-szzs)

 

Ankylosing Spondylitis

Enbrel, Erelzi

Indicated for reducing signs and symptoms in patients with active ankylosing spondylitis

50 mg SC once weekly or 25 mg SC twice weekly; if twice weekly, doses should be given on same day or 3-4 days apart

Methotrexate, glucocorticoids, salicylates, NSAIDs, or analgesics may be continued during treatment

 

Adult Rheumatoid Arthritis

Enbrel, Erelzi

Indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis

50 mg SC once weekly

Methotrexate, glucocorticoids, salicylates, NSAIDs, or analgesics may be continued during treatment

 

Psoriatic Arthritis

Enbrel, Erelzi

Indicated for reducing signs and symptoms, inhibiting the progression of structural damage of active arthritis, and improving physical function in patients with psoriatic arthritis

50 mg SC once weekly

Methotrexate, glucocorticoids, salicylates, NSAIDs, or analgesics may be continued during treatment

 

Plaque Psoriasis

Enbrel, Erelzi

Indicated for adults (≥18 yr) with chronic moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy

Initial: 50 mg SC twice weekly for 3 months

Maintenance: 50 mg SC once weekly

 

Pediatric dosage forms and strengths

injection solution, prefilled syringe

• 25mg/mL (Enbrel, Erelzi)
• 50mg/mL (Enbrel, Erelzi)

injection solution, prefilled autoinjector

• 50mg/mL (Enbrel, Erelzi)

injection powder for reconstitution

• 25mg/vial (Enbrel)

Biosimilars to EnbreL

• Erelzi (etanercept-szzs)

 

Juvenile Rheumatoid Arthritis

Enbrel, Erelzi

Indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis (JIA) in patients aged ≥2 years

<2 years: Safety and efficacy not established

<63 kg: 0.8 mg/kg SC weekly; not to exceed 50 mg weekly

≥63 kg: 50 mg SC weekly

Glucocorticoids, NSAIDs, or analgesics may be continued during treatment

 

Enbrel, Erelzi (etanercept) adverse (side) effects

>10%

Non-upper respiratory tract infection (38%)

Injection-site reaction (37%)

Upper respiratory tract infection (29%)

Headache (17%)

Rhinitis (12%)

 

1-10%

Nausea (9%)

Dizziness (7%)

Pharyngitis (7%)

Abdominal pain (5%)

Vomiting (3%)

Hematologic disorders (thrombocytopenia, aplastic anemia, leukopenia)

 

Postmarketing Reports

Blood and lymphatic system disorders: Pancytopenia, anemia, leukopenia, neutropenia, thrombocytopenia, lymphadenopathy, aplastic anemia

Cardiac disorders: Congestive heart failure

Gastrointestinal disorders: Inflammatory bowel disease (IBd

General disorders: Angioedema, chest pain

Hepatobiliary disorders: Autoimmune hepatitis, elevated transaminases

Immune disorders: macrophage activation syndrome, systemic vasculitis

Musculoskeletal and connective tissue disorders: Lupus-like syndrome

Neoplasms benign, malignant, and unspecified: Melanoma and non-melanoma skin cancers, Merkel cell carcinoma

Nervous system disorders: Convulsions, multiple sclerosis, demyelination, optic neuritis, transverse myelitis, paresthesias

Ocular disorders: Uveitis, scleritis

Respiratory, thoracic and mediastinal disorders: Interstitial lung disease

Skin and subcutaneous tissue disorders: Cutaneous lupus erythematosus, cutaneous vasculitis (including leukocytoclastic vasculitis), erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, subcutaneous nodule, new or worsening psoriasis (all sub-types including pustular and palmoplantar)

Hepatosplenic T-cell lymphoma

• Rare postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL; an aggressive, rare, and usually fatal type of T-cell lymphoma) have been reported, primarily in adolescent and young adult patients with Crohn disease and ulcerative colitis treated with TNF blockers but also in 1 patient being treated for psoriasis and 2 patients being treated for rheumatoid arthritis
• Most reported cases with TNF blockers have occurred with concomitant treatment with azathioprine or 6-mercaptopurine (6-MP), though some cases have been reported with azathioprine or 6-MP alone
• HSTCL cases have been identified in FDA Adverse Event Reporting System (AERS) database, literature, and HSTCL Cancer Survivors Network: infliximab (20 cases), etanercept (1), adalimumab (2), infliximab/adalimumab (5), certolizumab (0), golimumab (0), azathioprine (12), 6-MP (3) 

 

Warnings

Black box warnings

Serious infection risk

• Increased risk of developing serious infections resulting in hospitalization or death; most patients were taking concomitant immunosuppressants (eg, methotrexate, corticosteroids)
• Patients older than 65 years may be at greater risk
• Discontinue if patient develops serious infection or sepsis
• Reported infections include the following:
• (1) Active tuberculosis (TB), including reactivation of latent TB (frequently present with disseminated or extrapulmonary disease); test for latent TB before use and during therapy; treat latent infection before use
• (2) Invasive fungal infections (eg, histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, pneumocystosis); may present with disseminated, rather than localized, disease; antigen/antibody testing for histoplasmosis may be negative in some patients with active infection; initiate empiric antifungal therapy if severe systemic illness develops
• (3) Infections caused by other bacterial (eg, Legionella, Listeria), mycobacterial (eg, Mycobacterium tuberculosis), and viral (eg, hepatitis B virus) opportunistic pathogens

Malignancy

• Lymphoma and other malignancies, some fatal, have been reported in children and adolescents treated with tumor necrosis factor (TNF) blockers
• Cases of acute and chronic leukemia have been reported in association with postmarketing TNF-blocker use in rheumatoid arthritis (RA) and other indications; patients with RA may be at higher (approximately 2-fold greater) risk for leukemia than general population
• Manufacturer required to report all malignancies to FDA for complete and consistent analysis

 

Contraindications

Active serious infections

Sepsis

Concurrent cyclophosphamide therapy or patients with Wegener granulomatosis receiving immunosuppressive therapy

Hypersensitivity

Concomitant use of live vaccines

 

Cautions

HBV-positive status, history of or susceptibility to recurring infections, history of blood dyscrasias

Consider empiric anti-fungal therapy for patients at risk for invasive fungal infections who develop a systemic severe illness while receiving therapy

Monitor closely for signs or symptoms of demyelinating disease (eg, confusion, numbness, vision changes)

Increased risk of lymphoma and TB; monitor for TB

Possibility of lupuslike symptoms or development of autoimmune hepatitis; discontinue if such symptoms develop

Consider discontinuing if hematologic disorders (eg, pancytopenia, leukopenia, thrombocytopenia, aplastic anemia) occur; consider stopping therapy

Diluent for multidose vial contains benzyl alcohol as preservative

Children should be up to date with immunizations before starting drug

Increased risk of lymphoma and other cancers reported in children and adolescents

Enhanced safety surveillance requirements to capture malignancy data; manufacturers required to report all malignancies to FDA for complete and consistent analysis

Occurrence of leukemia and new-onset psoriasis reported in patients treated with TNF blockers

Worsening or new onset congestive heart failure reported with TNF blockers; Exercise caution when using in patients who have heart failure; TNFalpha inhibitors should only be considered in patients with HF if there are no other reasonable treatment options, and then only consider in patients with compensated HF

 

Pregnancy and lactation

Pregnancy category: B

Lactation: Not known if drug excreted in breast milk; discontinue drug, or do not nurse

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Enbrel, Erelzi (etanercept)

Mechanism of action

Binds and inactivates TNF, thereby preventing synovial inflammation

 

Absorption

Bioavailability: 60%

Onset: 1-2 weeks

Peak plasma time (single 25-mg dose): 69 ± 34 hr

Peak plasma concentration (single 25-mg dose): 1.1 ± 0.6 mcg/mL

 

Distribution

Vd: 12 L

 

Elimination

Half-life: ~5 days

Clearance: 160 mL/hr (varies)

 

Administration

Preparation

For a more comfortable injection, leave prefilled syringe/autoinjector/reconstituted vial at room temperature for ~15-30 minutes before injecting

Do not remove the needle cover while allowing to reach room temperature

Reconstituting multi-use viaL

• Reconstituted vial powder with 1 mL of the supplied sterile bacteriostatic water for injection
• Dissolution generally takes <10 minutes
• Resulting concentration is 25 mg/mL
• Do not use if discolored or cloudy, or if particulate matter remains
• Withdraw the correct dose of reconstituted solution into the syringe, some foam or bubbles may remain in the vial
• Remove the syringe from the vial adapter or remove the 25-gauge needle from the syringe; attach a 27-gauge needle for SC injection
• The contents of one vial of etanercept solution should not be mixed with, or transferred into, the contents of another vial of etanercept
• No other medications should be added to solutions containing etanercept, and do not reconstitute with other diluents
• Do not filter reconstituted solution during preparation or administration

 

Injection Sites

Rotate injection sites

Clean injection site area with alcohol wipe and let skin dry Inject SC in top of thighs, abdomen (avoid 2-inch area around navel), or outer area of upper arm

Do not inject areas of skin that are tender, bruised, red, or hard

Avoid injecting area with scars or stretch marks

For psoriasis, avoid injecting directly into raised, thick, red, or scaly skin patch or lesion

 

Storage

Refrigerate at 36-46°F (2-8°C)

Do not shake

Store in the original carton to protect from light or physical damage

For convenience, storage of individual syringes, autoinjectors, or vials at room temperature for a maximum single period of 14 days is permissible, with protection from light and sources of heat

Once stored at room temperature, do not place back in the refrigerator

Discard if not used within 14 days at room temperature

Once a vial has been reconstituted, the solution must be used immediately or may be refrigerated for up to 14 days

Do not store in extreme heat or cold

Do not freeze