Tocilizumab

Brand Names: Tofidence

Drug Class: Interleukin-6 Receptor Antagonist

Overview

11 DESCRIPTION Tocilizumab-bavi 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, respectively. The four polypeptide chains are linked intra- and inter-molecularly by disulfide bonds.

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 TOFIDENCE™ (tocilizumab-bavi) 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, TOFIDENCE 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 TOFIDENCE 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). ( 5.3 , 5.

Black Box Warning

WARNING: RISK OF SERIOUS INFECTIONS Patients treated with tocilizumab products including TOFIDENCE 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 TOFIDENCE until the infection is controlled. Reported infections include: Active tuberculosis, which may present with pulmonary or extrapulmonary disease.

Contraindications

  • 4 CONTRAINDICATIONS TOFIDENCE 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) ].