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). ... Read moreTocilizumab 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): Adults and pediatric patients 2 years of age and older with chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome.

Drugs used for Rheumatoid Arthritis

Tocilizumab is a recombinant humanized anti-human interleukin 6 (IL 6) receptor monoclonal antibody of the immunoglobulin (Ig) IgG1 subclass. Tocilizumab binds specifically to both soluble and membrane-bound IL 6 receptors (sIL 6R and mIL 6R), and has been shown to inhibit sIL 6R and mIL 6R-mediated signaling. Interleukin-6 is a multi-functional cytokine, produced by a variety of cell types involved in local paracrine function as well as regulation of systemic physiological and pathological processes eg, induction of immunoglobulin secretion, T-cell activation, induction of hepatic acute phase proteins and stimulation of haematopoiesis. Interleukin-6 has been implicated in the pathogenesis of diseases including inflammatory diseases, osteoporosis and neoplasia. The possibility exists for tocilizumab to affect host defences against infections and malignancies. The role of IL-6 receptor inhibition in the development of malignancies is not known.

General (IV or SC Injection): Substitution by any other biological medicinal product requires the consent of the prescribing physician. For adult patients with RA, tocilizumab may be administered as an IV infusion or a SC injection. For patients with pJIA and sJIA, tocilizumab is administered as an IV infusion. Tocilizumab IV formulation should be diluted by a healthcare professional with sterile 0.9% w/v sodium chloride solution using aseptic technique (see Caution for Usage). Tocilizumab is recommended for IV infusion over 1 hr.Tocilizumab SC formulation is administered with a single-use PFS+NSD or pre-filled pen. The 1st injection should be performed under the supervision of a qualified healthcare professional. The recommended injection sites (abdomen, thigh and upper arm) should be rotated and injections should never be given into moles, scars or areas where the skin is tender, bruised, red, hard or not intact.SC Injection: Adults: Rheumatoid Arthritis (RA): Recommended Dose: 162 mg given once every week as a SC injection. Tocilizumab can be used alone or in combination with MTX and/or other DMARDs. Patients transitioning from tocilizumab IV therapy to SC administration should administer the 1st SC dose at the time of the next scheduled IV dose under the supervision of a qualified healthcare professional. Tocilizumab SC formulation is not intended for IV administration.  Assess suitability of patient for SC home use and instruct patients to inform a healthcare professional if they experience symptoms of allergic reaction before administering the next dose. Patients should seek immediate medical attention if developing symptoms of serious allergic reactions

Interactions with CYP450 Substrates: Cytochrome P450s in the liver are down-regulated by infection and inflammation stimuli including cytokines such as IL-6. Inhibition of IL-6 signaling in RA patients treated with tocilizumab may restore CYP450 activities to higher levels than those in the absence of tocilizumab leading to increased metabolism of drugs that are CYP450 substrates. In vitro studies showed that tocilizumab has the potential to affect expression of multiple CYP enzymes including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. Its effect on CYP2C8 or transporters is unknown. In vivo studies with omeprazole, metabolized by CYP2C19 and CYP3A4, and simvastatin, metabolized by CYP3A4, showed up to a 28% and 57% decrease in exposure one week following a single dose of tocilizumab, respectively. The effect of tocilizumab on CYP enzymes may be clinically relevant for CYP450 substrates with narrow therapeutic index, where the dose is individually adjusted. Upon initiation or discontinuation of tocilizumab, in patients being treated with these types of medicinal products, perform therapeutic monitoring of effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) and the individual dose of the medicinal product adjusted as needed. Exercise caution when coadministering tocilizumab with CYP3A4 substrate drugs where decrease in effectiveness is undesirable, e.g., oral contraceptives, lovastatin, atorvastatin, etc. The effect of tocilizumab on CYP450 enzyme activity may persist for several weeks after stopping therapy

Hypersensitivity to tocilizumab or to any of the excipients.

Most common adverse reactions (incidence of at least 5%): upper respiratory tract infections, nasopharyngitis, headache, hypertension, increased ALT, injection site reactions.

Pregnancy Category- C. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risksLactation: Unknown whether distributed in breast milk, do not breast feed

Serious Infections- do not administer tocilizumab during an active infection, including localized infections. If a serious infection develops, interrupt tocilizumab 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 tocilizumab if abnormal liver tests persist or worsen or if clinical signs and symptoms of liver disease develop. Laboratory monitoring- recommended due to potential consequences of treatment-related changes in neutrophils, platelets, lipids, and liver function tests. Hypersensitivity reactions, including anaphylaxis and death have occurred. Live vaccines- Avoid use with tocilizumab.

There are limited data available on overdoses with tocilizumab. One case of accidental overdose was reported with intravenous tocilizumab in which a patient with multiple myeloma received a dose of 40 mg per kg. No adverse drug reactions were observed. No serious adverse drug reactions were observed in healthy volunteers who received single doses of up to 28 mg per kg, although all 5 patients at the highest dose of 28 mg per kg developed dose-limiting neutropenia. In case of an overdose, it is recommended that the patient be monitored for signs and symptoms of adverse reactions. Patients who develop adverse reactions should receive appropriate symptomatic treatment.

Tocilizumab must be refrigerated at 2ºC to 8ºC. Do not freeze. Protect the vials, syringes, and autoinjectors from light by storage in the original package until time of use, and keep syringes and autoinjectors dry.

Drugs used for Rheumatoid Arthritis

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.

Based on animal data, may cause fetal harm. Discontinue drug or nursing taking into consideration importance of drug to mother.