Standard Dose
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 ). • COVID-19 – It is recommended that TYENNE not be initiated in patients with an absolute neutrophil count (ANC) below 1,000 per mm 3 , platelet count below 50,000 mm 3 , or ALT or AST above 10 times ULN ( 5.3 , 5.4 ) . • In RA, CRS or COVID-19 patients, TYENNE doses exceeding 800 mg per infusion are not recommended. ( 2.2 , 2.9 , 12.3 ) • In GCA patients, TYENNE doses exceeding 600 mg per infusion are not recommended. ( 2.3 , 12.3 ) Rheumatoid Arthritis ( 2.2 ) Recommended Adult Intravenous Dosage: When used in combination with non-biologic DMARDs or as monotherapy the recommended starting dose is 4 mg per kg every 4 weeks followed by an increase to 8 mg per kg every 4 weeks based on clinical response. Recommended Adult Subcutaneous Dosage: Patients less than 100 kg weight 162 mg administered subcutaneously every other week, followed by an increase to every week based on clinical response Patients at or above 100 kg weight 162 mg administered subcutaneously every week Giant Cell Arteritis ( 2.3 ) Recommended Adult Intravenous Dosage: The recommended dose is 6 mg per kg every 4 weeks in combination with a tapering course of glucocorticoids. TYENNE can be used alone following discontinuation of glucocorticoids. Recommended Adult Subcutaneous Dosage: The recommended dose is 162 mg given once every week as a subcutaneous injection, in combination with a tapering course of glucocorticoids. A dose of 162 mg given once every other week as a subcutaneous injection, in combination with a tapering course of glucocorticoids, may be prescribed based on clinical considerations. TYENNE can be used alone following discontinuation of glucocorticoids. Polyarticular Juvenile Idiopathic Arthritis ( 2.4 ) Recommended Intravenous PJIA Dosage Every 4 Weeks Patients less than 30 kg weight 10 mg per kg Patients at or above 30 kg weight 8 mg per kg Recommended Subcutaneous PJIA Dosage Patients less than 30 kg weight 162 mg once every three weeks Patients at or above 30 kg weight 162 mg once every two weeks Systemic Juvenile Idiopathic Arthritis ( 2.5 ) Recommended Intravenous SJIA Dosage Every 2 Weeks Patients less than 30 kg weight 12 mg per kg Patients at or above 30 kg weight 8 mg per kg Recommended Subcutaneous SJIA Dosage Patients less than 30 kg weight 162 mg every two weeks Patients at or above 30 kg weight 162 mg every week Cytokine Release Syndrome ( 2.6 ) Recommended Intravenous CRS Dosage Patients less than 30 kg weight 12 mg per kg Patients at or above 30 kg weight 8 mg per kg Alone or in combination with corticosteroids . Coronavirus Disease 2019 ( 2.7 ) The recommended dosage of TYENNE for adult patients with COVID-19 is 8 mg per kg administered by a 60-minute intravenous infusion. Administration of Intravenous formulation ( 2.8 ) • For patients with RA, GCA, COVID-19, CRS, PJIA, 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. Administration of Subcutaneous formulation ( 2.9 ) • Follow the Instructions for Use for prefilled syringe and prefilled autoinjector Dose Modifications ( 2.10 ) Recommended for management of certain dose-related laboratory changes including elevated liver enzymes, neutropenia, and thrombocytopenia. 2.1 General Considerations for Administration Not Recommended for Concomitant Use with Biological DMARDs Tocilizumab products have not been studied in combination with biological DMARDs such as TNF antagonists, IL-1R antagonists, anti-CD20 monoclonal antibodies and selective co-stimulation modulators because of the possibility of increased immunosuppression and increased risk of infection. Avoid using TYENNE with biological DMARDs. Baseline Laboratory Evaluation Prior to Treatment Obtain and assess baseline complete blood count (CBC) and liver function tests prior to treatment. 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) [see Warnings and Precautions ( 5.3 , 5.4 )] . CRS – Patients with severe or life-threatening CRS frequently have cytopenias or elevated ALT or AST due to the lymphodepleting chemotherapy or the CRS. The decision to administer TYENNE should take into account the potential benefit of treating the CRS versus the risks of short-term treatment with TYENNE. COVID-19 – It is recommended that TYENNE not be initiated in patients with an absolute neutrophil count (ANC) below 1,000 per mm 3 , platelet count below 50,000 mm 3 , or ALT or AST above 10 times ULN [see Warnings and Precautions ( 5.3 , 5.4 )] . 2.2 Recommended Dosage for Rheumatoid Arthritis TYENNE may be used as monotherapy or concomitantly with methotrexate or other non-biologic DMARDs as an intravenous infusion or as a subcutaneous injection. Recommended Intravenous Dosage Regimen: The recommended dosage of TYENNE for adult patients given as a 60-minute single intravenous drip infusion is 4 mg per kg every 4 weeks followed by an increase to 8 mg per kg every 4 weeks based on clinical response. • Reduction of dose from 8 mg per kg to 4 mg per kg is recommended for management of certain dose-related laboratory changes including elevated liver enzymes, neutropenia, and thrombocytopenia [see Dosage and Administration ( 2.10 ), Warnings and Precautions ( 5.3 , 5.4 ), and Adverse Reactions ( 6.1 )] . • Doses exceeding 800 mg per infusion are not recommended in RA patients [see Clinical Pharmacology ( 12.3 )] . Recommended Subcutaneous Dosage Regimen: Patients less than 100 kg weight 162 mg administered subcutaneously every other week, followed by an increase to every week based on clinical response Patients at or above 100 kg weight 162 mg administered subcutaneously every week When transitioning from TYENNE intravenous therapy to subcutaneous administration administer the first subcutaneous dose instead of the next scheduled intravenous dose. Interruption of dose or reduction in frequency of administration of subcutaneous dose from every week to every other week dosing is recommended for management of certain dose-related laboratory changes including elevated liver enzymes, neutropenia, and thrombocytopenia [see Dosage and Administration ( 2.10 ), Warnings and Precautions ( 5.3 , 5.4 ), and Adverse Reactions ( 6.2 )]. 2.3 Recommended Dosage for Giant Cell Arteritis Recommended Intravenous Dosage Regimen: The recommended dosage of TYENNE for adult patients given as a 60-minute single intravenous drip infusion is 6 mg per kg every 4 weeks in combination with a tapering course of glucocorticoids. TYENNE can be used alone following discontinuation of glucocorticoids. • Interruption of dosing may be needed for management of dose-related laboratory abnormalities including elevated liver enzymes, neutropenia, and thrombocytopenia [see Dosage and Administration ( 2.10 )] . • Doses exceeding 600 mg per infusion are not recommended in GCA patients [see Clinical Pharmacology ( 12.3 )] . Recommended Subcutaneous Dosage Regimen: The recommended dose of TYENNE for adult patients with GCA is 162 mg given once every week as a subcutaneous injection in combination with a tapering course of glucocorticoids. A dose of 162 mg given once every other week as a subcutaneous injection in combination with a tapering course of glucocorticoids may be prescribed based on clinical considerations. TYENNE can be used alone following discontinuation of glucocorticoids. When transitioning from TYENNE intravenous therapy to subcutaneous administration, administer the first subcutaneous dose instead of the next scheduled intravenous dose. Interruption of dose or reduction in frequency of administration of subcutaneous dose from every week to every other week dosing may be needed for management of dose-related laboratory abnormalities including elevated liver enzymes, neutropenia, and thrombocytopenia [see Dosage and Administration ( 2.10 )]. 2.4 Recommended Dosage for Polyarticular Juvenile Idiopathic Arthritis TYENNE 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 visit body weight measurement, as weight may fluctuate. Recommended Intravenous Dosage Regimen: The recommended dosage of TYENNE for PJIA patients given once every 4 weeks as a 60-minute single intravenous drip infusion is: Recommended Intravenous PJIA Dosage Every 4 Weeks Patients less than 30 kg weight 10 mg per kg Patients at or above 30 kg weight 8 mg per kg Recommended Subcutaneous Dosage Regimen: Recommended Subcutaneous PJIA Dosage Patients less than 30 kg weight 162 mg once every 3 weeks Patients at or above 30 kg weight 162 mg once every 2 weeks When transitioning from TYENNE intravenous therapy to subcutaneous administration, administer the first subcutaneous dose instead of the next scheduled intravenous dose. Interruption of dosing may be needed for management of dose-related laboratory abnormalities including elevated liver enzymes, neutropenia, and thrombocytopenia [see Dosage and Administration ( 2.10 )]. 2.5 Recommended Dosage for Systemic Juvenile Idiopathic Arthritis TYENNE 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 visit body weight measurement, as weight may fluctuate. Recommended Intravenous Dosage Regimen: The recommended dose of TYENNE for SJIA patients given once every 2 weeks as a 60-minute single intravenous drip infusion is: Recommended Intravenous SJIA Dosage Every 2 Weeks Patients less than 30 kg weight 12 mg per kg Patients at or above 30 kg weight 8 mg per kg Recommended Subcutaneous Dosage Regimen: Recommended Subcutaneous SJIA Dosage Patients less than 30 kg weight 162 mg once every two weeks Patients at or above 30 kg weight 162 mg once every week When transitioning from TYENNE intravenous therapy to subcutaneous administration, administer the first subcutaneous dose when the next scheduled intravenous dose is due. Interruption of dosing may be needed for management of dose-related laboratory abnormalities including elevated liver enzymes, neutropenia, and thrombocytopenia [see Dosage and Administration ( 2.10 )] . 2.6 Recommended Dosage for Cytokine Release Syndrome (CRS) Use only the intravenous route for treatment of CRS. The recommended dose of TYENNE 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 Patients at or above 30 kg weight 8 mg per kg 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 TYENNE 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. • Subcutaneous administration is not approved for CRS. 2.7 Coronavirus Disease 2019 (COVID-19) Administer TYENNE by intravenous infusion only. The recommended dosage of TYENNE for treatment of adult patients with COVID-19 is 8 mg per kg administered as a single 60-minute intravenous infusion. If clinical signs or symptoms worsen or do not improve after the first dose, one additional infusion of TYENNE may be administered at least 8 hours after the initial infusion. • Doses exceeding 800 mg per infusion are not recommended in patients with COVID-19. • Subcutaneous administration is not approved for COVID-19. 2.8 Preparation and Administration Instructions for Intravenous Infusion TYENNE for intravenous infusion should be diluted by a healthcare professional using aseptic technique as follows: • Use a sterile needle and syringe to prepare TYENNE. • Patients less than 30 kg : use a 50 mL infusion bag or bottle of 0.9% or 0.45% Sodium Chloride Injection, USP, and then follow steps 1 and 2 below. • Patients at or above 30 kg weight : use a 100 mL infusion bag or bottle, and then follow steps 1 and 2 below. - Step 1. Withdraw a volume of 0.9% or 0.45% Sodium Chloride Injection, USP, equal to the volume of the TYENNE injection required for the patient's dose from the infusion bag or bottle [see Dosage and Administration ( 2.2 , 2.4 , 2.5 , 2.6 )] . For Intravenous Use: Volume of TYENNE Injection per kg of Body Weight Dosage Indication Volume of TYENNE injection per kg of body weight 4 mg/kg Adult RA 0.2 mL/kg 6 mg/kg Adult GCA 0.3 mL/kg 8 mg/kg Adult RA Adult COVID-19 SJIA, PJIA and CRS (greater than or equal to 30 kg of body weight) 0.4 mL/kg 10 mg/kg PJIA (less than 30 kg of body weight) 0.5 mL/kg 12 mg/kg SJIA and CRS (less than 30 kg of body weight) 0.6 mL/kg - Step 2. Withdraw the amount of TYENNE for intravenous infusion from the vial(s) and add slowly into the 0.9% or 0.45% Sodium Chloride Injection, USP infusion bag or bottle. To mix the solution, gently invert the bag to avoid foaming. • The prepared solution for infusion should be used immediately. If not used immediately, the diluted tocilizumab solutions may be refrigerated at 36°F to 46°F (2°C to 8°C) up to 24 hours, or stored at room temperature at or below 77°F (25°C) for up to 4 hours and should be protected from light. Administration of diluted TYENNE solution must be completed within this period of time. • TYENNE solutions do not contain preservatives; therefore, unused product remaining in the vials should not be used. • Allow the fully diluted TYENNE solution to reach room temperature prior to infusion. • The infusion should be administered over 60 minutes and must be administered with an infusion set. Do not administer as an intravenous push or bolus. • TYENNE should not be infused concomitantly in the same intravenous line with other drugs. No physical or biochemical compatibility studies have been conducted to evaluate the co-administration of TYENNE with other drugs. • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If particulates and discolorations are noted, the product should not be used. • Fully diluted TYENNE solutions are compatible with polypropylene, polyethylene and polyvinyl chloride infusion bags and bottles, and glass infusion bottles. 2.9 Preparation and Administration Instructions for Subcutaneous Injection • TYENNE for subcutaneous injection is not intended for intravenous drip infusion. • Assess suitability of patient for subcutaneous home use and instruct patients to inform a healthcare professional before administering the next dose if they experience any symptoms of allergic reaction. Patients should seek immediate medical attention if they develop symptoms of serious allergic reactions. TYENNE subcutaneous injection is intended for use under the guidance of a healthcare practitioner. After proper training in subcutaneous injection technique, a patient may self-inject TYENNE or the patient's caregiver may administer TYENNE if a healthcare practitioner determines that it is appropriate. PJIA and SJIA patients may self-inject with the TYENNE prefilled syringe or autoinjector, or the patient's caregiver may administer TYENNE if both the healthcare practitioner and the parent/legal guardian determine it is appropriate [see Use in Specific Populations ( 8.4 )] . Patients, or patient caregivers, should be instructed to follow the directions provided in the Instructions for Use (IFU) for additional details on medication administration. • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use TYENNE prefilled syringes (PFS) or prefilled autoinjectors exhibiting particulate matter, cloudiness, or discoloration. TYENNE for subcutaneous administration should be clear and colorless to pale yellow. Do not use if any part of the PFS or autoinjector appears to be damaged. • Patients using TYENNE for subcutaneous administration should be instructed to inject the full amount in the syringe (0.9 mL) or full amount in the autoinjector (0.9 mL), which provides 162 mg of TYENNE, according to the directions provided in the IFU. • Injection sites should be rotated with each injection and should never be given into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact. 2.10 Dosage Modifications due to Serious Infections or Laboratory Abnormalities Serious Infections Hold TYENNE treatment if a patient develops a serious infection until the infection is controlled. Laboratory Abnormalities Rheumatoid Arthritis and Giant Cell Arteritis Liver Enzyme Abnormalities [see Warnings and Precautions ( 5.3 , 5.4 )] Lab Value Recommendation for RA Recommendation for GCA Greater than 1 to 3x ULN Dose modify concomitant DMARDs if appropriate For persistent increases in this range: • For patients receiving intravenous TYENNE, reduce dose to 4 mg per kg or hold TYENNE until ALT or AST have normalized • For patients receiving subcutaneous TYENNE, reduce injection frequency to every other week or hold dosing until ALT or AST have normalized. Resume TYENNE at every other week and increase frequency to every week as clinically appropriate Dose modify immunomodulatory agents if appropriate For persistent increases in this range: • For patients receiving Intravenous TYENNE, hold TYENNE until ALT or AST have normalized • For patients receiving subcutaneous TYENNE, reduce injection frequency to every other week or hold dosing until ALT or AST have normalized. Resume TYENNE at every other week and increase frequency to every week as clinically appropriate Greater than 3 to 5x ULN (confirmed by repeat testing) Hold TYENNE dosing until less than 3x ULN and follow recommendations above for greater than 1 to 3x ULN For persistent increases greater than 3x ULN, discontinue TYENNE Hold TYENNE dosing until less than 3x ULN and follow recommendations above for greater than 1 to 3x ULN For persistent increases greater than 3x ULN, discontinue TYENNE Greater than 5x ULN Discontinue TYENNE Discontinue TYENNE Low Absolute Neutrophil Count (ANC) [see Warnings and Precautions ( 5.4 )] Lab Value (cells per mm 3 ) Recommendation for RA Recommendation for GCA ANC greater than 1,000 Maintain dose Maintain dose ANC 500 to 1,000 Hold TYENNE dosing When ANC greater than 1,000 cells per mm 3 : • For patients receiving intravenous TYENNE, resume TYENNE at 4 mg per kg and increase to 8 mg per kg as clinically appropriate • For patients receiving subcutaneous TYENNE, resume TYENNE at every other week and increase frequency to every week as clinically appropriate Hold TYENNE dosing When ANC greater than 1,000 cells per mm 3 : • For patients receiving intravenous TYENNE, resume TYENNE at 6 mg per kg • For patients receiving subcutaneous TYENNE, resume TYENNE at every other week and increase frequency to every week as clinically appropriate ANC less than 500 Discontinue TYENNE Discontinue TYENNE Low Platelet Count [see Warnings and Precautions ( 5.4 )] Lab Value (cells per mm 3 ) Recommendation for RA Recommendation for GCA 50,000 to 100,000 Hold TYENNE dosing When platelet count is greater than 100,000 cells per mm 3 : • For patients receiving intravenous TYENNE, resume TYENNE at 4 mg per kg and increase to 8 mg per kg as clinically appropriate • For patients receiving subcutaneous TYENNE, resume TYENNE at every other week and increase frequency to every week as clinically appropriate Hold TYENNE dosing When platelet count is greater than 100,000 cells per mm 3 : • For patients receiving intravenous TYENNE, resume TYENNE at 6 mg per kg • For patients receiving subcutaneous TYENNE, resume TYENNE at every other week and increase frequency to every week as clinically appropriate Less than 50,000 Discontinue TYENNE Discontinue TYENNE Polyarticular and Systemic Juvenile Idiopathic Arthritis Dose reduction of tocilizumab products has not been studied in the PJIA and SJIA populations. Dose interruptions of TYENNE are recommended for liver enzyme abnormalities, low neutrophil counts, and low platelet counts in patients with PJIA and SJIA at levels similar to what is outlined above for patients with RA and GCA. If appropriate, dose modify or stop concomitant methotrexate and/or other medications and hold TYENNE dosing until the clinical situation has been evaluated. In PJIA and SJIA the decision to discontinue TYENNE for a laboratory abnormality should be based upon the medical assessment of the individual patient.