ENBREL

DO NOT remove the needle cover while allowing the prefilled syringe or SureClick® autoinjector to reach room temperature. Prior to administration, visually inspect the solution for particulate matter and discolouration. There may be small white particles of protein in the solution.

This is not unusual for proteinaceous solutions. The solution should not be used if discoloured or cloudy, or if foreign particulate matter is present. 5 Missed Dose Patients who miss a dose of ENBREL should be advised to inject their dose as soon as they remember, then take the next dose at the regular(ly) scheduled time.

Among RA patients in placebo-controlled, active-controlled, and open-label trials of ENBREL, infections and malignancies were the most common serious adverse events observed. Other infrequent serious adverse events observed in RA, PsA, AS or PsO clinical trials are listed below by body system: Cardiovascular: cardiomyopathy, fainting, heart failure, hypertension, hypotension, myocardial infarction, myocardial ischemia, deep vein thrombosis, thrombophlebitis Digestive: cholecystitis, diarrhea, esophageal ulcer, gastrointestinal hemorrhage, pancreatitis, appendicitis ENBREL Product Monograph Page 18 of 85 General: impaired healing, asthenia Hematologic/Lymphatic: lymphadenopathy, myelodysplastic syndrome, necrotizing granulomatous lymphadenitis Hepatic: hepatic disorder, hepatic steatosis Musculoskeletal: bursitis, fistula, fracture nonunion, polymyositis Nervous: anxiety, cerebral ischemia, convulsion, depression, multiple sclerosis Respiratory: asthma, dyspnea, pulmonary embolism, sarcoidosis Skin: worsening psoriasis Urogenital: membranous glomerulonephropathy, kidney calculus In a randomized controlled trial in which 51 patients with RA received ENBREL 50 mg twice weekly and 25 patients received ENBREL 25 mg twice weekly, the following serious adverse events 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. In controlled trials, the proportion of patients who discontinued treatment due to adverse events was approximately 4% in both the ENBREL and placebo treatment groups. The vast majority of these patients were treated with the recommended dose of 25 mg SC twice weekly.

In adult PsO studies, ENBREL doses studied were 25 mg SC once or twice a week and 50 mg SC once or twice a week. In three randomized, placebo-controlled studies of adult patients with PsO, the safety profile for patients receiving 50 mg twice a week was similar to those receiving 25 mg once or twice weekly, and all were similar to placebo.

No cumulative toxicities were observed in long term studies in adult patients with PsO up to 144 weeks and AS up to 192 weeks. 26%) placebo-treated patients. 49). In the long-term open-label RA studies, the rate of death did not increase over time with increasing exposure to ENBREL.

08%) ENBREL-treated patients compared to 0 of 720 placebo-treated patients. 25). No deaths were reported in PsA, AS, or JIA studies. 2 Clinical Trial Adverse Reactions Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. ENBREL Product Monograph Page 19 of 85 Adverse reactions reported in at least 1% of all patients who received ENBREL in placebo- controlled RA trials (including the combination methotrexate trial) are outlined in Table 1 below.

Adverse reactions reported in JIA, adult PsA, AS, and adult PsO trials were similar to those reported in RA clinical trials. Table 1. Percent of Rheumatoid Arthritis Patients Reporting Adverse Reactions  1% by Body System and Preferred Term in Controlled Clinical […]

Prescribers are reminded of the risk of false negative tuberculin skin test results, especially in patients who are severely ill or immuno-compromised. If active tuberculosis is diagnosed, ENBREL therapy should not be initiated. If inactive (‘latent’) tuberculosis is diagnosed, treatment should be started with anti-tuberculosis therapy before the initiation of ENBREL.

In this situation, the benefit/risk balance of ENBREL therapy should be very carefully considered. Anti-tuberculosis therapy should also be considered prior to initiation of ENBREL in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection.

Consultation with a physician with expertise in the treatment of tuberculosis is recommended to aid in the decision whether initiating anti-tuberculosis therapy is appropriate for an individual patient. Patients should be monitored for the development of signs and symptoms of infection during and after treatment with ENBREL, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.

Tests for latent tuberculosis infection may be falsely negative while on therapy with ENBREL. Tuberculosis should be strongly considered in patients who develop a new infection during ENBREL treatment, especially in patients who have previously or recently traveled to countries with a high prevalence of tuberculosis, or who have had close contact with a person with active tuberculosis.

Histoplasmosis and other invasive fungal infections are not consistently recognized in patients taking TNF-blockers, including ENBREL. This has resulted in delays in appropriate treatment, sometimes resulting in death. For patients who reside or travel in regions where mycoses are endemic, invasive fungal infection should be suspected if they develop a serious systemic illness.

Appropriate empiric antifungal therapy may be initiated while a diagnostic workup is being performed. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. When feasible, the decision to administer empiric antifungal therapy in these patients should be made in consultation with a physician with expertise in the diagnosis and treatment of invasive ENBREL Product Monograph Page 10 of 85 fungal infections and taking into account both the risk for severe fungal infection and the risks of antifungal therapy.

ENBREL should be discontinued if a patient develops a serious infection or sepsis. A patient who develops a new infection during treatment with ENBREL should be closely monitored, undergo a prompt and complete diagnostic workup appropriate for an immunocompromised patient, and antimicrobial therapy should be initiated, as appropriate.

In post-marketing studies of patients with JIA, serious infections have been reported in approximately 3% of patients. 8%). General Parenteral administration of any biologic product should be attended by appropriate precautions in case an allergic or untoward reaction occurs.

Allergic reactions associated with administration of ENBREL during clinical trials have been reported in < 2% of patients. If any serious allergic or anaphylactic reaction occurs, administration of ENBREL should be discontinued immediately and appropriate therapy initiated.

Concurrent ENBREL and anakinra treatment Serious infections and neutropenia were seen in clinical studies with concurrent use of anakinra and ENBREL with no added clinical benefit compared to ENBREL alone. Because of the nature of the adverse events seen with combination of ENBREL and anakinra therapy, the combination of ENBREL and anakinra is not recommended (see DRUG INTERACTIONS).

Concurrent ENBREL and abatacept treatment In clinical studies, concurrent administration of […]