Important Safety Information
Indications

INDICATIONS

  • TYENNE is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more Disease-Modifying Anti-Rheumatic Drugs (DMARDs).

  • TYENNE is indicated for the treatment of giant cell arteritis (GCA) in adult patients.

  • TYENNE is indicated for the treatment of active polyarticular juvenile idiopathic arthritis (PJIA) in patients 2 years of age and older.

  • TYENNE is indicated for the treatment of active systemic juvenile idiopathic arthritis (SJIA) in patients 2 years of age and older.

  • TYENNE is indicated for the treatment of chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome in adults and pediatric patients 2 years of age and older.

  • TYENNE is indicated for the treatment of coronavirus disease 2019 (COVID-19) in hospitalized adult patients who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

IMPORTANT SAFETY INFORMATION

RISK OF SERIOUS INFECTIONS:

Patients treated with TYENNE are at increased risk for developing serious infections that may lead to hospitalization or death, including tuberculosis (TB), bacterial, invasive fungal, viral, or other opportunistic infections. 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. Patients, except those with COVID-19, should be tested for latent tuberculosis before TYENNE use and during therapy (except patients with COVID-19). Treatment for latent infection should be initiated prior to TYENNE use.
  • Invasive fungal infections, including candidiasis, aspergillosis, and pneumocystis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.
  • Bacterial, viral and other infections due to opportunistic pathogens.

The risks and benefits of treatment with TYENNE should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection.

Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with TYENNE, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.

CONTRAINDICATIONS

Known hypersensitivity to Tocilizumab products.

WARNINGS AND PRECAUTIONS

COVID-19

Monitor for signs and symptoms of new infections during and after treatment with TYENNE in patients with COVID-19. Limited information is available regarding the use of TYENNE in patients with COVID-19 and concomitant serious active infections. The risks and benefits of treatment with TYENNE in patients with COVID-19 and other concurrent infections should be considered.

Gastrointestinal Perforations

Events of gastrointestinal (GI) perforation have been reported in clinical trials, primarily as complications of diverticulitis in RA patients. Use TYENNE with caution in patients who may be at increased risk for GI perforation. Promptly evaluate patients presenting with new-onset abdominal symptoms for early identification of GI perforation.

Hepatotoxicity

Serious cases of hepatic injury have been observed in patients taking intravenous or subcutaneous Tocilizumab. Some of these cases have resulted in liver transplant or death. Time to onset for cases ranged from months to years after treatment initiation. Most cases presented with marked elevations of transaminases (> 5 times ULN), and some cases presented with signs or symptoms of liver dysfunction and only mildly elevated transaminases.

Treatment with Tocilizumab was associated with a higher incidence of transaminase elevations; increased frequency and magnitude of these elevations were observed when Tocilizumab was used in combination with potentially hepatotoxic drugs (e.g., methotrexate).

It is not recommended to initiate TYENNE treatment in RA, GCA, PJIA, and SJIA patients with elevated transaminases ALT or AST greater than 1.5x ULN. In patients who develop elevated ALT or AST greater than 5x ULN discontinue TYENNE.

Patients who are hospitalized with COVID-19 may have elevated AST or ALT levels. Multiorgan failure with involvement of the liver is recognized as a complication of severe COVID- 19. The decision to administer TYENNE should balance the potential risks of acute treatment with TYENNE against the potential benefit of treating COVID-19. It is not recommended to initiate TYENNE treatment in COVID-19 patients with elevated ALT or AST above 10x ULN. Monitor ALT and AST during treatment.

Measure liver tests promptly in patients who report symptoms that may indicate liver injury. If the patient is found to have abnormal liver tests, TYENNE treatment should be interrupted. TYENNE should only be restarted in patients with another explanation for the liver test abnormalities after normalization of the liver tests.

Laboratory Parameters

Laboratory monitoring is recommended due to potential consequences of treatment-related laboratory abnormalities in neutrophils, platelets, lipids, and liver function tests. Dosage modifications may be required.

Neutropenia: Treatment with Tocilizumab was associated with a higher incidence of neutropenia. It is not recommended to initiate TYENNE treatment in RA, GCA, PJIA, and SJIA patients with a low neutrophil count i.e., absolute neutrophil count (ANC) less than 2000 per mm3. In patients who develop an ANC less than 500 per mm3 treatment is not recommended.

It is not recommended to initiate TYENNE treatment in COVID-19 patients with an ANC less than 1000 per mm3. Neutrophils should be monitored.

Thrombocytopenia: Treatment with Tocilizumab was associated with a reduction in platelet counts. It is not recommended to initiate TYENNE in RA, GCA, PJIA, and SJIA patients with a platelet count below 100,000 per mm3. In patients who develop a platelet count less than 50000 per mm3, treatment is not recommended.

It is not recommended to initiate TYENNE treatment in COVID-19 patients with a platelet count less than 50000 per mm3. Platelets should be monitored.

Elevated Liver Enzymes: It is not recommended to initiate TYENNE treatment in patients with elevated transaminases ALT or AST >1.5x ULN. In patients who develop elevated ALT or AST >5x ULN, treatment is not recommended.

Lipid Abnormalities: Treatment with Tocilizumab was associated with increases in lipid parameters such as total cholesterol, triglycerides, LDL cholesterols, and/or HDL cholesterol.

Immunosuppression

The impact of treatment with Tocilizumab on the development of malignancies is not known, but malignancies were observed in clinical studies with Tocilizumab. TYENNE is an immunosuppressant, and treatment with immunosuppressants may result in an increased risk of malignancies.

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis, have been reported in association with Tocilizumab and anaphylactic events with a fatal outcome have been reported with intravenous infusion of Tocilizumab. Additionally, serious cutaneous reactions, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), have been reported in patients with autoinflammatory conditions treated with Tocilizumab products. TYENNE for intravenous use should only be infused by a healthcare professional with appropriate medical support to manage anaphylaxis. For TYENNE subcutaneous injection, advise patients to seek immediate medical attention if they experience any symptoms of a hypersensitivity reaction. If anaphylaxis or other hypersensitivity reaction occurs, stop administration of TYENNE immediately and discontinue TYENNE permanently. Do not administer TYENNE to patients with known hypersensitivity to TYENNE.

Demyelinating Disorders

The impact of treatment with Tocilizumab on demyelinating disorders is not known, but multiple sclerosis and chronic inflammatory demyelinating polyneuropathy were reported rarely in clinical studies. Monitor patients for signs and symptoms of demyelinating disorders. Prescribers should exercise caution in considering the use of TYENNE in patients with preexisting or recent-onset demyelinating disorders.

Active Hepatic Disease and Hepatic Impairment

Treatment with TYENNE is not recommended in patients with active hepatic disease or hepatic impairment.

Vaccinations

Avoid use of live vaccines concurrently with TYENNE. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving TYENNE or on the effectiveness of vaccination in patients receiving TYENNE. Patients should be brought up to date on all recommended vaccinations prior to initiation of TYENNE therapy, if possible.

ADVERSE REACTIONS

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

DRUG INTERACTIONS

In GCA patients, no effect of concomitant corticosteroid on Tocilizumab exposure was observed.

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 TYENNE may restore CYP450 activities to higher levels than those in the absence of TYENNE leading to increased metabolism of drugs that are CYP450 substrates.

Exercise caution when co-administering TYENNE with CYP3A4 substrate drugs where decrease in effectiveness is undesirable, e.g., oral contraceptives, lovastatin, atorvastatin, etc.

USE IN PREGNANCY

The limited available data with Tocilizumab products in pregnant women are not sufficient to determine whether there is a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Fresenius Kabi at (800) 551-7176.

INDICATIONS

TYENNE is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more Disease-Modifying Anti-Rheumatic Drugs (DMARDs).

TYENNE is indicated for the treatment of giant cell arteritis (GCA) in adult patients.

TYENNE is indicated for the treatment of active polyarticular juvenile idiopathic arthritis (PJIA) in patients 2 years of age and older.

TYENNE is indicated for the treatment of active systemic juvenile idiopathic arthritis (SJIA) in patients 2 years of age and older.

TYENNE is indicated for the treatment of chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome in adults and pediatric patients 2 years of age and older.

TYENNE is indicated for the treatment of coronavirus disease 2019 (COVID-19) in hospitalized adult patients who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

Please see additional Important Safety information in Prescribing Information, including BOXED WARNING.

TYENNE® (tocilizumab-aazg)
IV Dosing Calculator

For IV dosing, easily determine a patient’s correct dose of TYENNE using the Dosing Calculator below.*

Please enter valid patient weight
Please select a dosage amount

In RA, doses exceeding 800 mg per infusion are not recommended.

For Rheumatoid Arthritis:

  • Can be used in combination with DMARDs or as monotherapy
  • Recommended starting dosage is 4 mg/kg every 4 weeks followed by an increase to 8 mg/kg every 4 weeks based on clinical response

Complete the form to
view dosing information.

Weight would exceed recommended maximum dose (800 mg).
Please view the dosing chart below or see the Full Prescribing Information.

No results available for weights lower than 11.3 kg. Please view the dosing chart below
or see the Full Prescribing Information.

IV Dosing Information

- mg/- mL

Vial Recommendations

-

80 mg

4 mL

-

200 mg

10 mL

-

400 mg

20 mL

Unused dose: - mg

Vial recommendations are calculated to minimize product wastage.

Please enter valid patient weight

Recommended dosage: 6 mg/kg

In GCA, doses exceeding 600 mg per infusion are not recommended.

For Giant Cell Arteritis:

  • Recommended dosage is 6 mg/kg every 4 weeks in combination with a tapering course of glucocorticoids. TYENNE can be used alone following discontinuation of glucocorticoids

Complete the form to
view dosing information.

Weight would exceed recommended maximum dose (600 mg).
Please view the dosing chart below or see the Full Prescribing Information.

No results available for weights lower than 11.3 kg. Please view the dosing chart below
or see the Full Prescribing Information.

IV Dosing Information

- mg/- mL

Vial Recommendations

-

80 mg

4 mL

-

200 mg

10 mL

-

400 mg

20 mL

Unused dose: - mg

Vial recommendations are calculated to minimize product wastage.

Please enter valid patient weight

Patients <30 kg: 10 mg/kg

Patients ≥30 kg: 8 mg/kg

For Polyarticular Juvenile Idiopathic Arthritis:

  • Recommended dosing every 4 weeks

Complete the form to
view dosing information.

No results found for weight greater than 100 kg. See full Prescribing Information.

No results available for weights lower than 6.8 kg. Please view the dosing chart below
or see the Full Prescribing Information.

IV Dosing Information

- mg/- mL

Vial Recommendations

-

80 mg

4 mL

-

200 mg

10 mL

-

400 mg

20 mL

Unused dose: - mg

Vial recommendations are calculated to minimize product wastage.

Please enter valid patient weight

Patients <30 kg: 12 mg/kg

Patients ≥30 kg: 8 mg/kg

For Systemic Juvenile Idiopathic Arthritis:

  • Recommended dosing every 2 weeks

Complete the form to
view dosing information.

No results found for weight greater than 100 kg. See full Prescribing Information.

No results available for weights lower than 6.8 kg. Please view the dosing chart below
or see the Full Prescribing Information.

IV Dosing Information

- mg/- mL

Vial Recommendations

-

80 mg

4 mL

-

200 mg

10 mL

-

400 mg

20 mL

Unused dose: - mg

Vial recommendations are calculated to minimize product wastage.

*By using this resource, you agree to the following: This Dosing Calculator is being provided “AS IS” and is intended for use only by qualified health care providers. All calculations should be confirmed before use. Fresenius Kabi makes no claims as to the accuracy of the information contained herein. The information being provided is not a substitute for clinical judgment. Neither Fresenius Kabi, nor any other party involved in the preparation or publication of this site, shall be liable to you or others for any decisions made or actions taken by you or others in reliance on this information. 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. 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. The Dosing Calculator should not replace professional judgment or clinical experience. For additional dosing information, please refer to the Full Prescribing Information. The Dosing Calculator is not a substitute for medical examination.

A print version of the Dosing Calculator is available.



DMARD, disease-modifying antirheumatic drug; GCA, giant cell arteritis; IV, intravenous; PJIA, polyarticular juvenile idiopathic arthritis; RA, rheumatoid arthritis; SJIA, systemic juvenile idiopathic arthritis.

Learn more about TYENNE

INDICATIONS

  • TYENNE is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more Disease-Modifying Anti-Rheumatic Drugs (DMARDs).

  • TYENNE is indicated for the treatment of giant cell arteritis (GCA) in adult patients.

  • TYENNE is indicated for the treatment of active polyarticular juvenile idiopathic arthritis (PJIA) in patients 2 years of age and older.

  • TYENNE is indicated for the treatment of active systemic juvenile idiopathic arthritis (SJIA) in patients 2 years of age and older.

  • TYENNE is indicated for the treatment of chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome in adults and pediatric patients 2 years of age and older.

  • TYENNE is indicated for the treatment of coronavirus disease 2019 (COVID-19) in hospitalized adult patients who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

IMPORTANT SAFETY INFORMATION

RISK OF SERIOUS INFECTIONS:

Patients treated with TYENNE are at increased risk for developing serious infections that may lead to hospitalization or death, including tuberculosis (TB), bacterial, invasive fungal, viral, or other opportunistic infections. 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. Patients, except those with COVID-19, should be tested for latent tuberculosis before TYENNE use and during therapy (except patients with COVID-19). Treatment for latent infection should be initiated prior to TYENNE use.
  • Invasive fungal infections, including candidiasis, aspergillosis, and pneumocystis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.
  • Bacterial, viral and other infections due to opportunistic pathogens.

The risks and benefits of treatment with TYENNE should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection.

Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with TYENNE, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.

CONTRAINDICATIONS

Known hypersensitivity to Tocilizumab products.

WARNINGS AND PRECAUTIONS

COVID-19

Monitor for signs and symptoms of new infections during and after treatment with TYENNE in patients with COVID-19. Limited information is available regarding the use of TYENNE in patients with COVID-19 and concomitant serious active infections. The risks and benefits of treatment with TYENNE in patients with COVID-19 and other concurrent infections should be considered.

Gastrointestinal Perforations

Events of gastrointestinal (GI) perforation have been reported in clinical trials, primarily as complications of diverticulitis in RA patients. Use TYENNE with caution in patients who may be at increased risk for GI perforation. Promptly evaluate patients presenting with new-onset abdominal symptoms for early identification of GI perforation.

Hepatotoxicity

Serious cases of hepatic injury have been observed in patients taking intravenous or subcutaneous Tocilizumab. Some of these cases have resulted in liver transplant or death. Time to onset for cases ranged from months to years after treatment initiation. Most cases presented with marked elevations of transaminases (> 5 times ULN), and some cases presented with signs or symptoms of liver dysfunction and only mildly elevated transaminases.

Treatment with Tocilizumab was associated with a higher incidence of transaminase elevations; increased frequency and magnitude of these elevations were observed when Tocilizumab was used in combination with potentially hepatotoxic drugs (e.g., methotrexate).

It is not recommended to initiate TYENNE treatment in RA, GCA, PJIA, and SJIA patients with elevated transaminases ALT or AST greater than 1.5x ULN. In patients who develop elevated ALT or AST greater than 5x ULN discontinue TYENNE.

Patients who are hospitalized with COVID-19 may have elevated AST or ALT levels. Multiorgan failure with involvement of the liver is recognized as a complication of severe COVID- 19. The decision to administer TYENNE should balance the potential risks of acute treatment with TYENNE against the potential benefit of treating COVID-19. It is not recommended to initiate TYENNE treatment in COVID-19 patients with elevated ALT or AST above 10x ULN. Monitor ALT and AST during treatment.

Measure liver tests promptly in patients who report symptoms that may indicate liver injury. If the patient is found to have abnormal liver tests, TYENNE treatment should be interrupted. TYENNE should only be restarted in patients with another explanation for the liver test abnormalities after normalization of the liver tests.

Laboratory Parameters

Laboratory monitoring is recommended due to potential consequences of treatment-related laboratory abnormalities in neutrophils, platelets, lipids, and liver function tests. Dosage modifications may be required.

Neutropenia: Treatment with Tocilizumab was associated with a higher incidence of neutropenia. It is not recommended to initiate TYENNE treatment in RA, GCA, PJIA, and SJIA patients with a low neutrophil count i.e., absolute neutrophil count (ANC) less than 2000 per mm3. In patients who develop an ANC less than 500 per mm3 treatment is not recommended.

It is not recommended to initiate TYENNE treatment in COVID-19 patients with an ANC less than 1000 per mm3. Neutrophils should be monitored.

Thrombocytopenia: Treatment with Tocilizumab was associated with a reduction in platelet counts. It is not recommended to initiate TYENNE in RA, GCA, PJIA, and SJIA patients with a platelet count below 100,000 per mm3. In patients who develop a platelet count less than 50000 per mm3, treatment is not recommended.

It is not recommended to initiate TYENNE treatment in COVID-19 patients with a platelet count less than 50000 per mm3. Platelets should be monitored.

Elevated Liver Enzymes: It is not recommended to initiate TYENNE treatment in patients with elevated transaminases ALT or AST >1.5x ULN. In patients who develop elevated ALT or AST >5x ULN, treatment is not recommended.

Lipid Abnormalities: Treatment with Tocilizumab was associated with increases in lipid parameters such as total cholesterol, triglycerides, LDL cholesterols, and/or HDL cholesterol.

Immunosuppression

The impact of treatment with Tocilizumab on the development of malignancies is not known, but malignancies were observed in clinical studies with Tocilizumab. TYENNE is an immunosuppressant, and treatment with immunosuppressants may result in an increased risk of malignancies.

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis, have been reported in association with Tocilizumab and anaphylactic events with a fatal outcome have been reported with intravenous infusion of Tocilizumab. Additionally, serious cutaneous reactions, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), have been reported in patients with autoinflammatory conditions treated with Tocilizumab products. TYENNE for intravenous use should only be infused by a healthcare professional with appropriate medical support to manage anaphylaxis. For TYENNE subcutaneous injection, advise patients to seek immediate medical attention if they experience any symptoms of a hypersensitivity reaction. If anaphylaxis or other hypersensitivity reaction occurs, stop administration of TYENNE immediately and discontinue TYENNE permanently. Do not administer TYENNE to patients with known hypersensitivity to TYENNE.

Demyelinating Disorders

The impact of treatment with Tocilizumab on demyelinating disorders is not known, but multiple sclerosis and chronic inflammatory demyelinating polyneuropathy were reported rarely in clinical studies. Monitor patients for signs and symptoms of demyelinating disorders. Prescribers should exercise caution in considering the use of TYENNE in patients with preexisting or recent-onset demyelinating disorders.

Active Hepatic Disease and Hepatic Impairment

Treatment with TYENNE is not recommended in patients with active hepatic disease or hepatic impairment.

Vaccinations

Avoid use of live vaccines concurrently with TYENNE. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving TYENNE or on the effectiveness of vaccination in patients receiving TYENNE. Patients should be brought up to date on all recommended vaccinations prior to initiation of TYENNE therapy, if possible.

ADVERSE REACTIONS

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

DRUG INTERACTIONS

In GCA patients, no effect of concomitant corticosteroid on Tocilizumab exposure was observed.

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 TYENNE may restore CYP450 activities to higher levels than those in the absence of TYENNE leading to increased metabolism of drugs that are CYP450 substrates.

Exercise caution when co-administering TYENNE with CYP3A4 substrate drugs where decrease in effectiveness is undesirable, e.g., oral contraceptives, lovastatin, atorvastatin, etc.

USE IN PREGNANCY

The limited available data with Tocilizumab products in pregnant women are not sufficient to determine whether there is a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Fresenius Kabi at (800) 551-7176.

INDICATIONS

TYENNE is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more Disease-Modifying Anti-Rheumatic Drugs (DMARDs).

TYENNE is indicated for the treatment of giant cell arteritis (GCA) in adult patients.

TYENNE is indicated for the treatment of active polyarticular juvenile idiopathic arthritis (PJIA) in patients 2 years of age and older.

TYENNE is indicated for the treatment of active systemic juvenile idiopathic arthritis (SJIA) in patients 2 years of age and older.

TYENNE is indicated for the treatment of chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome in adults and pediatric patients 2 years of age and older.

TYENNE is indicated for the treatment of coronavirus disease 2019 (COVID-19) in hospitalized adult patients who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

Please see additional Important Safety information in Prescribing Information, including BOXED WARNING.

Important Safety Information
Indications

INDICATIONS

  • TYENNE is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more Disease-Modifying Anti-Rheumatic Drugs (DMARDs).

  • TYENNE is indicated for the treatment of giant cell arteritis (GCA) in adult patients.

  • TYENNE is indicated for the treatment of active polyarticular juvenile idiopathic arthritis (PJIA) in patients 2 years of age and older.

  • TYENNE is indicated for the treatment of active systemic juvenile idiopathic arthritis (SJIA) in patients 2 years of age and older.

  • TYENNE is indicated for the treatment of chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome in adults and pediatric patients 2 years of age and older.

  • TYENNE is indicated for the treatment of coronavirus disease 2019 (COVID-19) in hospitalized adult patients who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

IMPORTANT SAFETY INFORMATION

RISK OF SERIOUS INFECTIONS:

Patients treated with TYENNE are at increased risk for developing serious infections that may lead to hospitalization or death, including tuberculosis (TB), bacterial, invasive fungal, viral, or other opportunistic infections. 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. Patients, except those with COVID-19, should be tested for latent tuberculosis before TYENNE use and during therapy (except patients with COVID-19). Treatment for latent infection should be initiated prior to TYENNE use.
  • Invasive fungal infections, including candidiasis, aspergillosis, and pneumocystis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.
  • Bacterial, viral and other infections due to opportunistic pathogens.

The risks and benefits of treatment with TYENNE should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection.

Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with TYENNE, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.

CONTRAINDICATIONS

Known hypersensitivity to Tocilizumab products.

WARNINGS AND PRECAUTIONS

COVID-19

Monitor for signs and symptoms of new infections during and after treatment with TYENNE in patients with COVID-19. Limited information is available regarding the use of TYENNE in patients with COVID-19 and concomitant serious active infections. The risks and benefits of treatment with TYENNE in patients with COVID-19 and other concurrent infections should be considered.

Gastrointestinal Perforations

Events of gastrointestinal (GI) perforation have been reported in clinical trials, primarily as complications of diverticulitis in RA patients. Use TYENNE with caution in patients who may be at increased risk for GI perforation. Promptly evaluate patients presenting with new-onset abdominal symptoms for early identification of GI perforation.

Hepatotoxicity

Serious cases of hepatic injury have been observed in patients taking intravenous or subcutaneous Tocilizumab. Some of these cases have resulted in liver transplant or death. Time to onset for cases ranged from months to years after treatment initiation. Most cases presented with marked elevations of transaminases (> 5 times ULN), and some cases presented with signs or symptoms of liver dysfunction and only mildly elevated transaminases.

Treatment with Tocilizumab was associated with a higher incidence of transaminase elevations; increased frequency and magnitude of these elevations were observed when Tocilizumab was used in combination with potentially hepatotoxic drugs (e.g., methotrexate).

It is not recommended to initiate TYENNE treatment in RA, GCA, PJIA, and SJIA patients with elevated transaminases ALT or AST greater than 1.5x ULN. In patients who develop elevated ALT or AST greater than 5x ULN discontinue TYENNE.

Patients who are hospitalized with COVID-19 may have elevated AST or ALT levels. Multiorgan failure with involvement of the liver is recognized as a complication of severe COVID- 19. The decision to administer TYENNE should balance the potential risks of acute treatment with TYENNE against the potential benefit of treating COVID-19. It is not recommended to initiate TYENNE treatment in COVID-19 patients with elevated ALT or AST above 10x ULN. Monitor ALT and AST during treatment.

Measure liver tests promptly in patients who report symptoms that may indicate liver injury. If the patient is found to have abnormal liver tests, TYENNE treatment should be interrupted. TYENNE should only be restarted in patients with another explanation for the liver test abnormalities after normalization of the liver tests.

Laboratory Parameters

Laboratory monitoring is recommended due to potential consequences of treatment-related laboratory abnormalities in neutrophils, platelets, lipids, and liver function tests. Dosage modifications may be required.

Neutropenia: Treatment with Tocilizumab was associated with a higher incidence of neutropenia. It is not recommended to initiate TYENNE treatment in RA, GCA, PJIA, and SJIA patients with a low neutrophil count i.e., absolute neutrophil count (ANC) less than 2000 per mm3. In patients who develop an ANC less than 500 per mm3 treatment is not recommended.

It is not recommended to initiate TYENNE treatment in COVID-19 patients with an ANC less than 1000 per mm3. Neutrophils should be monitored.

Thrombocytopenia: Treatment with Tocilizumab was associated with a reduction in platelet counts. It is not recommended to initiate TYENNE in RA, GCA, PJIA, and SJIA patients with a platelet count below 100,000 per mm3. In patients who develop a platelet count less than 50000 per mm3, treatment is not recommended.

It is not recommended to initiate TYENNE treatment in COVID-19 patients with a platelet count less than 50000 per mm3. Platelets should be monitored.

Elevated Liver Enzymes: It is not recommended to initiate TYENNE treatment in patients with elevated transaminases ALT or AST >1.5x ULN. In patients who develop elevated ALT or AST >5x ULN, treatment is not recommended.

Lipid Abnormalities: Treatment with Tocilizumab was associated with increases in lipid parameters such as total cholesterol, triglycerides, LDL cholesterols, and/or HDL cholesterol.

Immunosuppression

The impact of treatment with Tocilizumab on the development of malignancies is not known, but malignancies were observed in clinical studies with Tocilizumab. TYENNE is an immunosuppressant, and treatment with immunosuppressants may result in an increased risk of malignancies.

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis, have been reported in association with Tocilizumab and anaphylactic events with a fatal outcome have been reported with intravenous infusion of Tocilizumab. Additionally, serious cutaneous reactions, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), have been reported in patients with autoinflammatory conditions treated with Tocilizumab products. TYENNE for intravenous use should only be infused by a healthcare professional with appropriate medical support to manage anaphylaxis. For TYENNE subcutaneous injection, advise patients to seek immediate medical attention if they experience any symptoms of a hypersensitivity reaction. If anaphylaxis or other hypersensitivity reaction occurs, stop administration of TYENNE immediately and discontinue TYENNE permanently. Do not administer TYENNE to patients with known hypersensitivity to TYENNE.

Demyelinating Disorders

The impact of treatment with Tocilizumab on demyelinating disorders is not known, but multiple sclerosis and chronic inflammatory demyelinating polyneuropathy were reported rarely in clinical studies. Monitor patients for signs and symptoms of demyelinating disorders. Prescribers should exercise caution in considering the use of TYENNE in patients with preexisting or recent-onset demyelinating disorders.

Active Hepatic Disease and Hepatic Impairment

Treatment with TYENNE is not recommended in patients with active hepatic disease or hepatic impairment.

Vaccinations

Avoid use of live vaccines concurrently with TYENNE. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving TYENNE or on the effectiveness of vaccination in patients receiving TYENNE. Patients should be brought up to date on all recommended vaccinations prior to initiation of TYENNE therapy, if possible.

ADVERSE REACTIONS

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

DRUG INTERACTIONS

In GCA patients, no effect of concomitant corticosteroid on Tocilizumab exposure was observed.

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 TYENNE may restore CYP450 activities to higher levels than those in the absence of TYENNE leading to increased metabolism of drugs that are CYP450 substrates.

Exercise caution when co-administering TYENNE with CYP3A4 substrate drugs where decrease in effectiveness is undesirable, e.g., oral contraceptives, lovastatin, atorvastatin, etc.

USE IN PREGNANCY

The limited available data with Tocilizumab products in pregnant women are not sufficient to determine whether there is a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Fresenius Kabi at (800) 551-7176.

INDICATIONS

TYENNE is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more Disease-Modifying Anti-Rheumatic Drugs (DMARDs).

TYENNE is indicated for the treatment of giant cell arteritis (GCA) in adult patients.

TYENNE is indicated for the treatment of active polyarticular juvenile idiopathic arthritis (PJIA) in patients 2 years of age and older.

TYENNE is indicated for the treatment of active systemic juvenile idiopathic arthritis (SJIA) in patients 2 years of age and older.

TYENNE is indicated for the treatment of chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome in adults and pediatric patients 2 years of age and older.

TYENNE is indicated for the treatment of coronavirus disease 2019 (COVID-19) in hospitalized adult patients who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

Please see additional Important Safety information in Prescribing Information, including BOXED WARNING.