Enbrel

[etanercept]

The impact of long-term treatment with ENBRELŪ on the development of autoimmune diseases is unknown. Rare adverse event reports have described patients with rheumatoid factor positiveand/or erosive RA who have developed additional autoantibodies in conjunction with rash and other features suggesting a lupus-like syndrome.

Other Adverse Reactions

Table 10 summarizes events reported in at least 3% of all patients with higher incidence in patients treated with ENBRELŪ compared to controls in placebo-controlled RA trials (including thecombination methotrexate trial) and relevant events from Study III. In placebo-controlled plaque psoriasis trials, the percentages of patients reporting injection site reactions were lower in the placebo dose group (6.4%) than in the ENBRELŪ dose groups (15.5%) in Studies I and II.Otherwise, the percentages of patients reporting adverse events in the 50 mg twice a week dose group were similar to those observed in the 25 mg twice a week dose group or placebo group.

Text Continues Below

---

In psoriasis Study I, there were no serious adverse events of worsening psoriasis following withdrawal of study drug. However, adverse events of worsening psoriasis including three serious adverse events were observed during the course of the clinical trials. Urticaria and non-infectious hepatitis were observed in a small number of patients and angioedema was observed in one patient inclinical studies. Urticaria and angioedema have also been reported in spontaneous post-marketing reports. Adverse events in psoriatic arthritis, ankylosing spondylitis, and plaque psoriasis trials were similar to those reported in RA clinical trials.

In controlled trials of RA and psoriatic arthritis, rates of serious adverse events were seen at afrequency of approximately 5% among ENBRELŪ- and control-treated patients. In controlled trials of plaque psoriasis, rates of serious adverse events were seen at a frequency of < 1.5% among ENBRELŪ- and placebo-treated patients in the first 3 months of treatment. Among patients with RA in placebo-controlled, active-controlled, and open-label trials of ENBRELŪ, malignancies (seeWARNINGS: Malignancies, ADVERSE REACTIONS: Malignancies) and infections (seeADVERSE REACTIONS: Infections) were the most common serious adverse events observed.

Other infrequent serious adverse events observed in RA, psoriatic arthritis, ankylosing spondylitis, or plaque psoriasis clinical trials are listed by body system below:

Cardiovascular:
heart failure, myocardial infarction, myocardial ischemia, hypertension, hypotension, deep vein thrombosis, thrombophlebitis

Digestive:
cholecystitis, pancreatitis, gastrointestinal hemorrhage, appendicitis

Hematologic/Lymphatic:
lymphadenopathy

Musculoskeletal:
bursitis, polymyositis

Nervous:
cerebral ischemia, depression, multiple sclerosis (see WARNINGS: Neurologic Events)

Respiratory:
dyspnea, pulmonary embolism, sarcoidosis

Skin:
worsening psoriasis

Urogenital:
membranous glomerulonephropathy, kidney calculus

In a randomized controlled trial in which 51 patients with RA received ENBRELŪ 50 mg twiceweekly and 25 patients received ENBRELŪ 25 mg twice weekly, the following serious adverseevents were observed in the 50 mg twice weekly arm: gastrointestinal bleeding, normal pressure hydrocephalus, seizure, and stroke. No serious adverse events were observed in the 25 mg arm.

Adverse Reactions in Patients with JRA

In general, the adverse events in pediatric patients were similar in frequency and type as those seen in adult patients (see WARNINGS and other sections under ADVERSE REACTIONS).Differences from adults and other special considerations are discussed in the following paragraphs. Severe adverse reactions reported in 69 JRA patients ages 4 to 17 years included varicella (see alsoPRECAUTIONS: Immunizations), gastroenteritis, depression/personality disorder, cutaneousulcer, esophagitis/gastritis, group A streptococcal septic shock, Type 1 diabetes mellitus, and soft tissue and post-operative wound infection.

Forty-three of 69 (62%) children with JRA experienced an infection while receiving ENBRELŪduring three months of study (part 1 open-label), and the frequency and severity of infections wassimilar in 58 patients completing 12 months of open-label extension therapy. The types ofinfections reported in JRA patients were generally mild and consistent with those commonly seenin outpatient pediatric populations. Two JRA patients developed varicella infection and signs andsymptoms of aseptic meningitis which resolved without sequelae.

The following adverse events were reported more commonly in 69 JRA patients receiving 3months of ENBRELŪ compared to the 349 adult RA patients in placebo-controlled trials. These included headache (19% of patients, 1.7 events per patient-year), nausea (9%, 1.0 events perpatient-year), abdominal pain (19%, 0.74 events per patient-year), and vomiting (13%, 0.74 eventsper patient-year).

In post-marketing experience, the following additional serious adverse events have been reported inpediatric 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 ENBRELŪtherapy are unknown.

Patients with Heart Failure

Two randomized placebo-controlled studies have been performed in patients with CHF. In one study, patients received either ENBRELŪ 25 mg twice weekly, 25 mg three times weekly, orplacebo. In a second study, patients received either ENBRELŪ 25 mg once weekly, 25 mg twiceweekly, or placebo. Results of the first study suggested higher mortality in patients treated withENBRELŪ 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 ofadverse outcomes in heart failure patients treated with ENBRELŪ (see PRECAUTIONS: Patientswith Heart Failure).

Adverse Reaction Information from Spontaneous Reports

Adverse events have been reported during post-approval use of ENBRELŪ. Because these eventsare reported voluntarily from a population of uncertain size, it is not always possible to reliablyestimate their frequency or establish a causal relationship to ENBRELŪ 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)

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, pruritis, subcutaneous nodules, urticaria

Drug Interactions

Specific drug interaction studies have not been conducted with ENBRELŪ. However, it was observed that the pharmacokinetics of ENBRELŪ was unaltered by concomitant methotrexate in rheumatoid arthritis patients. In a study in which patients with active RA were treated for up to 24 weeks with concurrent ENBRELŪ and anakinra therapy, a 7% rate of serious infections was observed, which was higher than that observed with ENBRELŪ alone (0%) (see also WARNINGS). Two percent of patients treated concurrently with ENBRELŪ and anakinra developed neutropenia (ANC < 1 x 109/L).

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long-term animal studies have not been conducted to evaluate the carcinogenic potential ofENBRELŪ or its effect on fertility. Mutagenesis studies were conducted in vitro and in vivo, and no evidence of mutagenic activity was observed.

Pregnancy (Category B)

Developmental toxicity studies have been performed in rats and rabbits at doses ranging from 60-to 100-fold higher than the human dose and have revealed no evidence of harm to the fetus due to ENBRELŪ. There are, however, no studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

It is not known whether ENBRELŪ is excreted in human milk or absorbed systemically after ingestion. Because many drugs and immunoglobulins are excreted in human milk, and because ofthe potential for serious adverse reactions in nursing infants from ENBRELŪ, a decision should bemade whether to discontinue nursing or to discontinue the drug.

Geriatric Use

A total of 480 RA patients and 89 plaque psoriasis patients ages 65 years or older have been studied in clinical trials. No overall differences in safety or effectiveness were observed between these patients and younger patients. Because there is a higher incidence of infections in the elderly population in general, caution should be used in treating the elderly.

Pediatric Use

ENBRELŪ is indicated for treatment of polyarticular-course juvenile rheumatoid arthritis inpatients who have had an inadequate response to one or more DMARDs. For issues relevant to pediatric patients, in addition to other sections of the label, see also WARNINGS;PRECAUTIONS: Immunizations; and ADVERSE REACTIONS: Adverse Reactions in Patients with JRA. ENBRELŪ has not been studied in children < 4 years of age.
The safety and efficacy of ENBRELŪ in pediatric patients with plaque psoriasis have not been studied.

Page:  << Prev | 1 | 2 | 3 | 4 | 5