Tocilizumab

ACTEMRA ® (tocilizumab) is an interleukin-6 (IL-6) receptor antagonist indicated for treatment of: Rheumatoid Arthritis (RA). Adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more Disease-Modifying Anti-Rheumatic Drugs (DMARDs). Giant Cell Arteritis (GCA). Adult patients with giant cell arteritis. Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD). Slowing the rate of decline in pulmonary function in adult patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) Polyarticular Juvenile Idiopathic Arthritis (PJIA). Patients 2 years of age and older with active polyarticular juvenile idiopathic arthritis. Systemic Juvenile Idiopathic Arthritis (SJIA). Patients 2 years of age and older with active systemic juvenile idiopathic arthritis. Cytokine Release Syndrome (CRS).

Tocilizumab binds to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R), and has been shown to inhibit IL-6-mediated signaling through these receptors. IL-6 is a pleiotropic pro-inflammatory cytokine produced by a variety of cell types including T- and B-cells, lymphocytes, monocytes and fibroblasts. IL-6 has been shown to be involved in diverse physiological processes such as T-cell activation, induction of immunoglobulin secretion, initiation of hepatic acute phase protein synthesis, and stimulation of hematopoietic precursor cell proliferation and differentiation. IL-6 is also produced by synovial and endothelial cells leading to local production of IL-6 in joints affected by inflammatory processes such as rheumatoid arthritis.

For RA, pJIA and sJIA, ACTEMRA may be used alone or in combination with methotrexate: and in RA, other non-biologic DMARDs may be used. General Administration and Dosing Information. RA, GCA, SSc-ILD, PJIA and SJIA – It is recommended that ACTEMRA not be initiated in patients with an absolute neutrophil count (ANC) below 2000 per mm 3, platelet count below 100,000 per mm 3, or ALT or AST above 1.5 times the upper limit of normal (ULN). COVID-19 – It is recommended that ACTEMRA not be initiated in patients with an absolute neutrophil count (ANC) below 1000 per mm 3, platelet count below 50,000 mm 3, or ALT or AST above 10 times ULN. In RA, CRS or COVID-19 patients, ACTEMRA doses exceeding 800 mg per infusion are not recommended. In GCA patients, ACTEMRA doses exceeding 600 mg per infusion are not recommended. Rheumatoid Arthritis.

ACTEMRA is contraindicated in patients with known hypersensitivity to ACTEMRA. Known hypersensitivity to ACTEMRA.

Boxed warning (risk of serious infections): Patients treated with ACTEMRA are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. If a serious infection develops, interrupt ACTEMRA until the infection is controlled. Serious Infections – do not administer ACTEMRA during an active infection, including localized infections. If a serious infection develops, interrupt ACTEMRA until the infection is controlled. Gastrointestinal (GI) perforation—use with caution in patients who may be at increased risk. Hepatotoxicity- Monitor patients for signs and symptoms of hepatic injury. Modify or discontinue ACTEMRA if abnormal liver tests persist or worsen or if clinical signs and symptoms of liver disease develop.

The following serious adverse reactions are described elsewhere in labeling: Serious Infections Gastrointestinal Perforations Laboratory Parameters Immunosuppression Hypersensitivity Reactions, Including Anaphylaxis Demyelinating Disorders Active Hepatic Disease and Hepatic Impairment Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not predict the rates observed in a broader patient population in clinical practice. Most common adverse reactions (incidence of at least 5%): upper respiratory tract infections, nasopharyngitis, headache, hypertension, increased ALT, injection site reactions.

Concomitant Drugs for Treatment of Adult Indications In RA patients, population pharmacokinetic analyses did not detect any effect of methotrexate (MTX), non-steroidal anti-inflammatory drugs or corticosteroids on tocilizumab clearance. Concomitant administration of a single intravenous dose of 10 mg/kg ACTEMRA with 10-25 mg MTX once weekly had no clinically significant effect on MTX exposure. ACTEMRA has not been studied in combination with biological DMARDs such as TNF antagonists. In GCA patients, no effect of concomitant corticosteroid on tocilizumab exposure was observed.

ACTEMRA must be refrigerated at 36°F to 46°F (2ºC to 8ºC). Do not freeze. Once removed from the refrigerator, the prefilled syringe and autoinjector can be stored up to 2 weeks at or below 86°F (30°C). Protect the vials, syringes, and autoinjectors from light by storage in the original package until time of use, and keep syringes and autoinjectors dry.