Overview
11 DESCRIPTION Tocilizumab-aazg is a recombinant humanized anti-human interleukin 6 (IL-6) receptor monoclonal antibody of the immunoglobulin IgG1κ (gamma 1, kappa) subclass with a typical H 2 L 2 polypeptide structure. Each light chain and heavy chain consists of 214 and 448 amino acids (excluding the C-terminal lysine), respectively.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Tocilizumab products bind to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R), and have 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.
Indications
- 1 INDICATIONS AND USAGE TYENNE® (tocilizumab-aazg) is an interleukin-6 (IL-6) receptor antagonist indicated for treatment of: Rheumatoid Arthritis (RA) ( 1.1 ) • 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) ( 1.2 ) • Adult patients with giant cell arteritis. Polyarticular Juvenile Idiopathic Arthritis (PJIA) ( 1.3 ) • Patients 2 years of age and older with active polyarticular juvenile idiopathic arthritis.
Common Doses
- 800 mg
- 600 mg
- 4 mg
- 8 mg
Dosage
2 DOSAGE AND ADMINISTRATION For RA, pJIA and sJIA, TYENNE may be used alone or in combination with methotrexate; and in RA, other non-biologic DMARDs may be used. ( 2 ) General Administration and Dosing Information ( 2.1 ) • RA, GCA, PJIA and SJIA – It is recommended that TYENNE not be initiated in patients with an absolute neutrophil count (ANC) below 2,000 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) ( 5.3 , 5.4 ).
Black Box Warning
WARNING: RISK OF SERIOUS INFECTIONS Patients treated with tocilizumab products including TYENNE are at increased risk for developing serious infections that may lead to hospitalization or death [see Warnings and Precautions ( 5.1 ), Adverse Reactions ( 6.1 )] . Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. If a serious infection develops, interrupt TYENNE until the infection is controlled. Reported infections include: • Active tuberculosis, which may present with pulmonary or extrapulmonary disease.
Contraindications
- 4 CONTRAINDICATIONS TYENNE is contraindicated in patients with known hypersensitivity to tocilizumab products [see Warnings and Precautions ( 5.6 )]. Known hypersensitivity to tocilizumab products. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in labeling: • Serious Infections [see Warnings and Precautions ( 5.1 )] • Gastrointestinal Perforations [see Warnings and Precautions ( 5.2 )] • Laboratory Parameters [see Warnings and Precautions ( 5.4 )] • Immunosuppression [see Warnings and Precautions ( 5.5 )] • Hypersensitivity Reactions, Including Anaphylaxis [see Warnings and Precautions ( 5.6 )] • Demyelinating Disorders [see Warnings and Precautions ( 5.7 )] • Active Hepatic Disease and Hepatic Impairment [see Warnings and Precautions ( 5.
Interactions
- 7 DRUG INTERACTIONS 7.1 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 tocilizumab with 10-25 mg MTX once weekly had no clinically significant effect on MTX exposure. Tocilizumab products have not been studied in combination with biological DMARDs such as TNF antagonists [see Dosage and Administration ( 2.2 )] .