Important Safety Information
Indications

INDICATIONS

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

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

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

IMPORTANT SAFETY INFORMATION

RISK OF SERIOUS INFECTIONS:

Patients treated with TYENNE® (tocilizumab-aazg) 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 should be tested for latent tuberculosis before TYENNE use and during therapy. 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.

CONTRAINDICATION

TYENNE is contraindicated in patients with known hypersensitivity to tocilizumab products.

WARNINGS AND PRECAUTIONS

Gastrointestinal Perforations

Events of gastrointestinal (GI) perforation have been reported in clinical trials, primarily as complications of diverticulitis in patients treated with tocilizumab. 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 products. 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.

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 products 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.

Thrombocytopenia: Treatment with tocilizumab products 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 50,000 per mm3, treatment is not recommended.

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 products 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 products 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 products and anaphylactic events with a fatal outcome have been reported with intravenous infusion of 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 tocilizumab products.

Demyelinating Disorders

The impact of treatment with tocilizumab products 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 REACTIONS

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

Exercise caution when coadministering 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 and miscarriage.

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.

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

Home Safety & Evidence

Meeting and exceeding the FDA’s requirements for biosimilarity

TYENNE® (tocilizumab-aazg) is approved by the US Food & Drug Administration (FDA) based on its proven similarity to Actemra® (tocilizumab) in1-5:

  • Pharmacokinetic (PK) & Pharmacodynamic (PD) Profiles
  • Efficacy
  • Safety & Immunogenicity

No clinically meaningful differences to Actemra2-5

An FDA-approved tocilizumab biosimilar, TYENNE met and exceeded FDA requirements for biosimilar approval based on the totality of evidence.1-5

A table that outlines the steps for Biosimilar development, and how TYENNE met each step A table that outlines the steps for Biosimilar development, and how TYENNE met each step

Comparable safety analysis in a phase III study

A safety analysis set compared adverse events in patients with moderate-to-severe rheumatoid arthritis between those treated with TYENNE and those treated with Actemra.5

Table depicting comparable safety via adverse events in both TYENNE and Actemra Table depicting comparable safety via adverse events in both TYENNE and Actemra

AE, Adverse Event; SAE, Serious Adverse Event; AESI, Adverse Events of Special Interest.

Line graph indicating the TYENNE Zubrzycka-Sienkiewicz study Line graph indicating the TYENNE Zubrzycka-Sienkiewicz study

TYENNE efficacy: equivalent to Actemraa

Analysis of DAS28-ESR changes throughout the 52-week efficacy assessment revealed similar decreases, seen as early as week 2, with both TYENNE and EU-approved tocilizumab.5

Line graph indicating equivalent efficacy between TYENNE and Actemra Line graph indicating equivalent efficacy between TYENNE and Actemra

Change from baseline over 52 weeks in DAS28-ESR in patients with moderate-to-severe rheumatoid arthritis initially randomized to TYENNE or EU-approved tocilizumab and in those rerandomized from EU-approved tocilizumab to TYENNE at week 24, ITT analysis set.5

DAS28-ESR, Disease Activity Score-28 Joint erythrocyte sedimentation rate; EU, European Union; ITT, intention to treat.

aActemra is represented by EU-approved tocilizumab in the study.

Line graph indicating the TYENNE Zubrzycka-Sienkiewicz study Line graph indicating the TYENNE Zubrzycka-Sienkiewicz study

Comparable PK profiles for both devices

Study results showed the pharmacokinetic profiles of TYENNE autoinjector and TYENNE pre-filled syringe were comparable.4

Line graph indicating comparable PK profiles between TYENNE autoinjector and TYENNE pre-filled syringe Line graph indicating comparable PK profiles between TYENNE autoinjector and TYENNE pre-filled syringe

h, hours; SD, standard deviation.

Line graph indicating the TYENNE Tomaszewska-Kiecana M study Line graph indicating the TYENNE Tomaszewska-Kiecana M study

aOn day 1, subjects were randomly assigned to one of the two treatment sequences (PFS → AI or AI → PFS) as well as to one of three injection sites (lower abdomen, upper thigh, or outer area of the upper arm).

bTocilizumab was administered on day 1 of each period (day 43 of period 1 corresponded to day 1 of period 2).

cIn period 2, subjects were crossed over to the opposite treatment to that given in period 1.

Note: pharmacokinetics, safety, and tolerability were evaluated up to 42 days postdose in each period.

AI, auto-injector; PFS, pre-filled syringe.

A proven similar PK profile3

In a double-blind, single-center, two-arm, parallel-group study of 128 healthy volunteers randomized to receive a single IV dosage of either tocilizumab product, TYENNE’s safety, tolerability, and immunogenicity of IV administration was compared to Actemra’s. The results showed a similar pharmacokinetic (PK) profile between the two.3

Proven similar pharmacokinetic (PK) profile between TYENNE® and Actemra® (tocilizumab)3

A line graph outlining a proven similar pharmacokinetic (PK) profile between TYENNE and Actemra A line graph outlining a proven similar pharmacokinetic (PK) profile between TYENNE and Actemra
Line graph indicating the TYENNE Zubrzycka-Sienkiewicz 2024 study Line graph indicating the TYENNE Zubrzycka-Sienkiewicz 2024 study

Safety and tolerability highly similar to Actemra3

In a study of two groups of healthy males and non-pregnant, non-breastfeeding females aged 18-55 years, while similar rates of adverse events (AEs) were reported in both groups, no AEs leading to study discontinuation were reported for either of the treatments. Changes in local tolerability, laboratory values, vital signs, and ECGs were similar between TYENNE and its reference product.3

A table showing adverse event (AE) data for TYENNE, resulting in safety and tolerability highly similar to Actemra A table showing adverse event (AE) data for TYENNE, resulting in safety and tolerability highly similar to Actemra

No clinically significant differences between treatment groups were noted.

aImmunogenicity was measured as a secondary endpoint. Secondary safety endpoints, standardized according to regulatory requirements, included treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and predefined adverse events of special interest (AESIs), which included hypersensitivity reactions events (NCI-CTCAE Grade ≥ 3) reported as serious and serious infections. Infusion site reactions (ISRs), vital signs, clinical laboratory values including hematology, chemistry, and urinalysis, and 12-lead electrocardiogram (ECG) were also considered.

Line graph indicating the TYENNE Zubrzycka-Sienkiewicz 2024 study Line graph indicating the TYENNE Zubrzycka-Sienkiewicz 2024 study
An orange, multi-faceted gemstone

A seamless treatment experience

Transitioning or initiating a patient to a biosimilar should be simple. TYENNE offers safety and tolerability highly similar to Actemra—as well as the same administration options as Actemra—in order to put all the benefits of a multifaceted, FDA-approved tocilizumab biosimilar in your hands.1,2

Why prescribe TYENNE?

Familiarity for your patients switching from Actemra

TYENNE offers the same subcutaneous options as well as the same dosing forms and strengths as IV Actemra.1 That means patients transitioning from Actemra can keep the same route of administration they’re familiar with. Learn more about dosing and explore our Dosing Calculator.

View Dosing Calculator

Connect with your Immunology Sales Specialist

Fresenius Kabi offers every prescriber a connection to a regionally based Immunology Sales Specialist (ISS). Your ISS can answer questions and provide support as you begin transitioning and treating your patients. Ready for an introduction?

Meet your specialist

INDICATIONS

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

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

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

IMPORTANT SAFETY INFORMATION

RISK OF SERIOUS INFECTIONS:

Patients treated with TYENNE® (tocilizumab-aazg) 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 should be tested for latent tuberculosis before TYENNE use and during therapy. 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.

CONTRAINDICATION

TYENNE is contraindicated in patients with known hypersensitivity to tocilizumab products.

WARNINGS AND PRECAUTIONS

Gastrointestinal Perforations

Events of gastrointestinal (GI) perforation have been reported in clinical trials, primarily as complications of diverticulitis in patients treated with tocilizumab. 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 products. 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.

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 products 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.

Thrombocytopenia: Treatment with tocilizumab products 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 50,000 per mm3, treatment is not recommended.

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 products 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 products 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 products and anaphylactic events with a fatal outcome have been reported with intravenous infusion of 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 tocilizumab products.

Demyelinating Disorders

The impact of treatment with tocilizumab products 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 REACTIONS

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

Exercise caution when coadministering 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 and miscarriage.

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.

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

Important Safety Information
Indications

INDICATIONS

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

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

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

IMPORTANT SAFETY INFORMATION

RISK OF SERIOUS INFECTIONS:

Patients treated with TYENNE® (tocilizumab-aazg) 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 should be tested for latent tuberculosis before TYENNE use and during therapy. 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.

CONTRAINDICATION

TYENNE is contraindicated in patients with known hypersensitivity to tocilizumab products.

WARNINGS AND PRECAUTIONS

Gastrointestinal Perforations

Events of gastrointestinal (GI) perforation have been reported in clinical trials, primarily as complications of diverticulitis in patients treated with tocilizumab. 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 products. 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.

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 products 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.

Thrombocytopenia: Treatment with tocilizumab products 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 50,000 per mm3, treatment is not recommended.

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 products 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 products 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 products and anaphylactic events with a fatal outcome have been reported with intravenous infusion of 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 tocilizumab products.

Demyelinating Disorders

The impact of treatment with tocilizumab products 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 REACTIONS

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

Exercise caution when coadministering 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 and miscarriage.

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.

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

References:

  1. TYENNE. Package insert. Fresenius Kabi USA, LLC; 2024.
  2. Schwabe C, Illes A, Ullmann M, et al. Pharmacokinetics and pharmacodynamics of a proposed tocilizumab biosimilar MSB11456 versus both the US-licensed and EU-approved products: a randomized, double-blind trial. Expert Rev Clin Immunol. 2022;18(5):533-543.
  3. Tomaszewska-Kiecana M, Ullmann M, Petit-Frere C, et al. Pharmacokinetics of a proposed tocilizumab biosimilar (MSB11456) versus US-licensed tocilizumab: results of a randomized, double-blind, single-intravenous dose study in healthy adults. Expert Rev Clin Immunol. 2023;19(4):439-446. doi:10.1080/1744666X.2023.2174104
  4. Tomaszewska-Kiecana M, Dryja A, Ullmann M, et al. Pharmacokinetics and tolerability of prefilled syringe and auto-injector presentations of MSB11456: results of a randomized, single-dose study in healthy adults. Expert Rev Clin Immunol. 2023;19(4):447-455.
  5. Zubrzycka-Sienkiewicz A, Klama K, Ullmann M, et al. Comparison of the efficacy and safety of a proposed biosimilar MSB11456 with tocilizumab reference product in subjects with moderate-to-severe rheumatoid arthritis: results of a randomised double-blind study. RMD Open. 2024;10:e003596. doi:10.1136/rmdopen-2023-003596