Tocimab

Tocimab 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)

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Tocimab 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)

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

• 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)

COVID-19

: Emergency use of Tocimab for the treatment of coronavirus disease 2019 in hospitalized adults and pediatric patients (2 years of age and older) who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)

Interruption of dosing may be needed for management of dose-related laboratory abnormalities including elevated liver enzymes, neutropenia, and thrombocytopenia.

Rheumatoid Arthritis

: Tocilizumab may be used as monotherapy or concomitantly with methotrexate or other non-biologic DMARDs as an intravenous infusion.

Recommended Intravenous Dosage Regimen

The recommended dosage of Tocilizumab for adult patients given as a 60-minute single intravenous drip infusion is 4 mg per kg of body weight every 4 weeks followed by an increase to 8 mg per kg of body weight every 4 weeks based on clinical response.

Reduction of dose from 8 mg per kg of body weight to 4 mg per kg of body weight is recommended for management of certain dose-related laboratory changes including elevated liver enzymes, neutropenia, and thrombocytopenia

Doses exceeding 800 mg per infusion are not recommended in RA patients

Polyarticular Juvenile Idiopathic Arthritis

: Tocilizumab may be used as an intravenous infusion or as a

subcutaneous injection alone or in combination with methotrexate. Do not change dose based solely on a single body weight measurement, as weight may fluctuate.

Recommended Intravenous Dosage Regimen: The recommended dosage of Tocilizumab for PJIA patients given once every 4 weeks as a 60-minute single intravenous drip infusion is:

• Patients less than 30 kg weight: 10 mg per kg of body weight
• Patients at or above 30 kg weight: 8 mg per kg of body weight
• Systemic Juvenile Idiopathic Arthritis

: Tocilizumab may be used as an intravenous infusion or as a subcutaneous injection alone or in combination with methotrexate. Do not change a dose based solely on a single body weight measurement, as weight may fluctuate.

Recommended Intravenous Dosage Regimen: The recommended dose of Tocilizumab for SJIA patients given

once every 2 weeks as a 60-minute single intravenous drip infusion is

• Patients less than 30 kg weight: 12 mg per kg of body weight
• Patients at or above 30 kg weight: 8 mg per kg of body weight
• Coronavirus Disease 2019
• : The recommended dosage of Tocilizumab is a single 60-minute

intravenous infusion as follows

Patients less than 30 kg weight: 12 mg per kg of body weight

Patients at or above 30 kg weight: 8 mg per kg of body weight

If clinical signs or symptoms worsen or do not improve after the first dose, one additional infusion of Tocilizumab may be administered at least 8 hours after the initial infusion. Maximum dosage in COVID-19 patients is 800 mg per infusion.

Cytokine Release Syndrome

: Use only the intravenous route for treatment of CRS. The recommended dose of Tocilizumab for treatment of CRS given as a 60-minute intravenous infusion is:

Recommended Intravenous CRS Dosage

Patients less than 30 kg weight: 12 mg per kg of body weight Alone or in combination with corticosteroids.

Patients at or above 30 kg weight: 8 mg per kg of body weight Alone or in combination with corticosteroids.

If no clinical improvement in the signs and symptoms of CRS occurs after the first dose, up to 3 additional doses of Tocilizumab may be administered. The interval between consecutive doses should be at least 8 hours. Doses exceeding 800 mg per infusion are not recommended in CRS patients.

Giant Cell Arteritis

The recommended dosage of Tocilizumab for adult patients given as a 60-minute single intravenous drip infusion is 6 mg per kg of body weight every 4 weeks in combination with a tapering course of glucocorticoids.

Tocilizumab can be used alone following discontinuation of glucocorticoids

Doses exceeding 600 mg per infusion are not recommended in GCA patients

Systemic Sclerosis-Associated Interstitial Lung Disease

The recommended dose of Tocilizumab for adult patients with SSc-ILD is 162 mg given once every week as a subcutaneous injection.

Intravenous administration is not approved for SSc-ILD

Administration of Intravenous Formulation

For adults with RA, GCA, CRS, PJIA and SJIA patients at or above 30 kg, dilute to 100 mL in 0.9% or 0.45% Sodium Chloride Injection, USP for intravenous infusion using aseptic technique

For PJIA, SJIA and CRS patients less than 30 kg, dilute to 50 mL in 0.9% or 0.45% Sodium Chloride Injection, USP for intravenous infusion using aseptic technique

Administer as a single intravenous drip infusion over 1 hour; do not administer as bolus or push.

Tocilizumab is a recombinant humanized anti-human interleukin 6 (IL-6) receptor monoclonal antibody of the

immunoglobulin IgG1K (gamma 1, kappa) subclass. Tocilizumab binds to both soluble and membrane-bound IL-6 receptors, 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-cells 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.

Most common adverse reactions [incidence of at least 5%): upper respiratory tract infections, nasopharyngitis, headache, hypertension, increased ALT, injection site reactions. Most common adverse reactions in COVID-19 (incidence >3%) are constipation, anxiety, diarrhea, insomnia, hypertension and nausea.

Tocilizumab is contraindicated in patients with known hypersensitivity to Tocilizumab.

Serious Infections

: Do not administer Tocimab during an active infection, including localized infections. If a serious infection develops, interrupt Tocimab until the infection is controlled

Tuberculosis

: Evaluate patients for tuberculosis risk factors and test for latent infection prior to initiating Tocimab

• Gastrointestinal Perforatio
• n: Use with caution in patients who may be at increased risk
• Hepatotoxicity

: Monitor patients for signs and symptoms of hepatic injury. Modify or discontinue Tocimab 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 Tocimab

Avoid using Tocimab with biological DMARDs.

It is recommended that Tocimab not be initiated in patients with an absolute neutrophil count (ANC) below 2000 per mm3 , platelet count below 100,000 per mm3 , or who have ALT or AST above 1.5 times the upper limit of normal (ULN)

Pediatric Use

: The safety and effectiveness of Tocimab in pediatric patients with conditions other than PJIA, SJIA or CRS have not been established. The safety and effectiveness in pediatric patients below the age of 2 have not been established in PJIA, SJIA, or CRS. Tocimab is not authorized or approved for emergency use for the treatment of COVID-19 in pediatric patients less than 2 years of age

Geriatric Use

: As there is a higher incidence of infections in the elderly population in general, caution should be used when treating the elderly

Hepatic Impairment

: The safety and efficacy of Tocimab have not been studied in patients with hepatic impairment, including patients with positive HBV and HCV serology

Renal Impairment

: No dose adjustment is required in patients with mild or moderate renal impairment. Tocimab has not been studied in patients with severe renal impairment

Based on animal data, may cause fetal harm. In case of COVID-19, Tocilizumab should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus. Discontinue drug or nursing taking into consideration importance of drug to mother. Breastfeeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.

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.

Exercise caution when coadministering Tocimab with CYP3A4 substrate drugs where decrease in effectiveness is undesirable, e.g., oral contraceptives, lovastatin, atorvastatin, etc. The effect of Tocimab on CYP450 enzyme activity may persist for several weeks after stopping therapy.

Store at a temperature of 2°C to 8°C in a dry place. Do not freeze.