ear), and vomiting (13%, 0.74 events per patient-year).
In open-label clinical studies of children with JIA, adverse events reported in those aged 2 to 4 years were similar to adverse events reported in older children.
In post-marketing experience, the following additional serious adverse events have been reported in pediatric patients: abscess with bacteremia, optic neuritis, pancytopenia, seizures, tuberculous arthritis, urinary tract infection (see WARNINGS), coagulopathy, cutaneous vasculitis, and transaminase elevations. The frequency of these events and their causal relationship to ENBREL® therapy are unknown.
Patients with Heart Failure
Two randomized placebo-controlled studies have been performed in patients with CHF. In one study, patients received either ENBREL® 25 mg twice weekly, 25 mg three times weekly, or placebo. In a second study, patients received either ENBREL® 25 mg once weekly, 25 mg twice weekly, or placebo. Results of the first study suggested higher mortality in patients treated with ENBREL® at either schedule compared to placebo. Results of the second study did not corroborate these observations. Analyses did not identify specific factors associated with increased risk of adverse outcomes in heart failure patients treated with ENBREL® (see PRECAUTIONS: Patients with Heart Failure).
Adverse Reaction Information from Spontaneous Reports
Adverse events have been reported during post-approval use of ENBREL®. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to ENBREL® exposure.
Additional adverse events are listed by body system below:
Body as a whole: angioedema, fatigue, fever, flu syndrome, generalized pain, weight gain
Cardiovascular: chest pain, vasodilation (flushing), new-onset congestive heart failure (see PRECAUTIONS: Patients with Heart Failure)
Digestive: altered sense of taste, anorexia, diarrhea, dry mouth, intestinal perforation
Hematologic/Lymphatic: adenopathy, anemia, aplastic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia (see WARNINGS)
Hepatobiliary: autoimmune hepatitis
Musculoskeletal: joint pain, lupus-like syndrome with manifestations including rash consistent with subacute or discoid lupus
Nervous: paresthesias, stroke, seizures and central nervous system events suggestive of multiple sclerosis or isolated demyelinating conditions such as transverse myelitis or optic neuritis (see WARNINGS)
Ocular: dry eyes, ocular inflammation
Respiratory: dyspnea, interstitial lung disease, pulmonary disease, worsening of prior lung disorder
Skin: cutaneous vasculitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, pruritus, subcutaneous nodules, urticaria, new or worsening psoriasis (all sub-types including pustular and palmoplantar)
OVERDOSAGE
The maximum tolerated dose of ENBREL® has not been established in humans. Toxicology studies have been performed in monkeys at doses up to 30 times the human dose with no evidence of dose-limiting toxicities. No dose-limiting toxicities have been observed during clinical trials of ENBREL®. Single IV doses up to 60 mg/m2 have been administered to healthy volunteers in an endotoxemia study without evidence of dose-limiting toxicities.
DOSAGE AND ADMINISTRATION
General
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