No

Antirheumatic, Disease Modifying

Reduction in signs and symptoms of moderately to severely active rheumatoid arthritis in patients who have had an inadequate response to one or more disease-modifying antirheumatic drugs (DMARDs).

B

Developmental toxicity studies performed in animals have revealed no evidence of harm to the fetus. There are no studies in pregnant women; this drug should be used during pregnancy only if clearly needed.

Etanercept should not be administered to patients with any active infection including chronic or local ones. Do not administer to patients with known hypersensitivity to etanercept or any of its components.

Etanercept may affect defenses against infections and malignancies. Safety and efficacy in patients with immunosuppression or chronic infections have not been evaluated. Discontinue administration if patient develops a serious infection. Do not start drug administration in patients with an active infection.

Allergic reactions may occur (<0.5%), but anaphylaxis has not been observed. If an anaphylactic reaction or other serious allergic reaction occurs, administration of etanercept should be discontinued immediately and appropriate therapy initiated.

Patients should be brought up to date with all immunizations before initiating therapy. No data are available concerning the effects of etanercept on vaccination. Live vaccines should not be given concurrently. No data are available concerning secondary transmission of live vaccines in patients receiving etanercept. Patients with a significant exposure to varicella virus should temporarily discontinue etanercept. Treatment with varicella zoster immune globulin should be considered.

Events reported include those >3% with incidence higher than placebo

Central nervous system: Headache (17%)

Local: Injection site reaction (37%)

Respiratory: Respiratory tract infection (38%), upper respiratory tract infection (29%), rhinitis (12%)

Miscellaneous: Infection (35%), positive ANA (11%), positive anti-double stranded DNA antibodies (15% by RIA, 3% by Crithidia lucilae assay)

>3% to 10%:

Central nervous system: Dizziness (7%)

Dermatologic: Rash (5%)

Gastrointestinal: Abdominal pain (5%), dyspepsia (4%)

Neuromuscular and skeletal: Weakness (5%)

Respiratory: Pharyngitis (7%), respiratory disorder (5%), sinusitis (3%)

<3%: Malignancies, serious infection, heart failure, myocardial infarction, myocardial ischemia, cerebral ischemia, hypertension, hypotension, cholecystitis, pancreatitis, gastrointestinal hemorrhage, bursitis, depression, dyspnea

Pediatric patients (JRA): The percentages of patients reporting abdominal pain (17%) and vomiting (14.5%) was higher than in adult RA. Two patients developed varicella infection associated with aseptic meningitis which resolved without complications (see Warnings/Precautions).

No dose-limiting toxicities have been observed during clinical trials. Single I.V. doses up to 60 mg/m² have been administered to healthy volunteers in an endotoxemia study without evidence of dose-limiting toxicities.

Specific drug interaction studies have not been conducted with etanercept

The dose tray containing etanercept (sterile powder) must be refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze. Reconstituted solutions of etanercept should be administered as soon as possible after reconstitution. If not administered immediately after reconstitution, etanercept may be stored in the vial at 2°C to 8°C (36°F to 46°F) for up to 6 hours.

Etanercept is a recombinant DNA-derived protein composed of tumor necrosis factor receptor (TNFR) linked to the Fc portion of human IgG1. Etanercept binds tumor necrosis factor (TNF) and blocks its interaction with cell surface receptors. TNF plays an important role in the inflammatory processes of rheumatoid arthritis (RA) and the resulting joint pathology.

Onset of effect: Within 2-3 weeks

Metabolism: Children: Clearance: 45.9 mL/hour/m²; Adults: Clearance: 89 mL/hour (52 mL/hour/m²)

Half-life: 115 hours (98-300 hours)

Time to peak: 72 hours (48-96 hours)

S.C.:

Adult: 25 mg given twice weekly; if the physician determines that it is appropriate, patients may self-inject after proper training in injection technique

Elderly: Although greater sensitivity of some elderly patients cannot be ruled out, no overall differences in safety or effectiveness were observed

Dizziness is common; may cause depression

None noted

No information available to require special precautions

No effects or complications reported

If self-injecting, follow instructions for injection and disposal of needles exactly. If redness, swelling, or irritation appears at the injection site, contact prescriber. Do not have any vaccinations while using this medication without consulting prescriber first. You may experience headache or dizziness (use caution when driving or engaging in tasks requiring alertness until response to drug is known). If stomach pain or cramping, unusual bleeding or bruising, blood in vomitus, stool, or urine occurs, stop taking medication and contact prescriber. Report skin rash, unusual muscle or bone weakness, or signs of respiratory flu or other infection (eg, chills, fever, sore throat, easy bruising or bleeding, mouth sores, unhealed sores). Breast-feeding precautions: Consult prescriber if breast-feeding.

Powder for injection: 25 mg

Breedveld F, "New Tumor Necrosis Factor-Alpha Biologic Therapies for Rheumatoid Arthritis," Eur Cytokine Netw, 1998, 9(3):233-8.

Data on file, Immunex Corporation.

Feldmann M, Brennan FM, and Maini RN, "Role of Cytokines in Rheumatoid Arthritis," Annu Rev Immunol, 1996, 14:397-440.

Felson DT, Anderson JJ, Boers M, et al, "American College of Rheumatology. Preliminary Definition of Improvement in Rheumatoid Arthritis," Arthritis Rheum, 1995, 38(6):727-35.

Fisher CJ Jr, Agosti JM, Opal SM, et al, "Treatment of Septic Shock With the Tumor Necrosis Factor Receptor:Fc Fusion Protein. The Soluble TNF Receptor Sepsis Study Group," N Engl J Med, 1996, 334(26):1697-702.

Giannini EH, Ruperto N, Ravelli A, et al, "Preliminary Definition of Improvement in Juvenile Arthritis," Arthritis Rheum, 1997, 40(7):1202-9.

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(3):141-7.

"New Drugs for Rheumatoid Arthritis," Med Lett Drugs Ther, 1998, 40(1040):110-2.

Ramey DR, Fries JF, and Singh G, "The Health Assessment Questionnaire 1995 - Status and Review," Spilker B, ed, Quality of Life and Pharmacoeconomics in Clinical Trials, 2nd ed, Philadelphia, PA: Lippincott-Raven, 1996.

Saxne T, Palladino MA Jr, Heinegard D, et al, "Detection of Tumor Necrosis Factor Alpha but Not Tumor Necrosis Factor Beta in Rheumatoid Arthritis Synovial Fluid and Serum," Arthritis Rheum, 1988, 31(8):1041-5.

Smith CA, Farrah T, and Goodwin RG, "The TNF Receptor Superfamily of Cellular and Viral Proteins: Activation, Costimulation, and Death," Cell, 1994, 76(6):959-62.

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(4):253-9.

Wooley PH, Dutcher J, Widmer MB, et al, "Influence of a Recombinant Human Soluble Tumor Necrosis Factor Receptor FC Fusion Protein on Type II Collagen-Induced Arthritis in Mice," J Immunol, 1993, 151(11):6602-7.