Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: Fresenius Kabi Deutschland GmbH, Else-Kroener-Strasse 1, 61352 Bad Homburg v.d.Hoehe, Germany
Tyenne, in combination with methotrexate (MTX), is indicated for:
In these patients, Tyenne can be given as monotherapy in case of intolerance to MTX or where continued treatment with MTX is inappropriate. Tocilizumab has been shown to reduce the rate of progression of joint damage as measured by Xray and to improve physical function when given in combination with methotrexate.
Tyenne is indicated for the treatment of coronavirus disease 2019 (COVID-19) in adults who are receiving systemic corticosteroids and require supplemental oxygen or mechanical ventilation.
Tyenne is indicated for the treatment of active systemic juvenile idiopathic arthritis (sJIA) in patients 2 years of age and older, who have responded inadequately to previous therapy with NSAIDs and systemic corticosteroids. Tyenne can be given as monotherapy (in case of intolerance to MTX or where treatment with MTX is inappropriate) or in combination with MTX.
Tyenne in combination with methotrexate (MTX) is indicated for the treatment of juvenile idiopathic polyarthritis (pJIA; rheumatoid factor positive or negative and extended oligoarthritis) in patients 2 years of age and older, who have responded inadequately to previous therapy with MTX. Tyenne can be given as monotherapy in case of intolerance to MTX or where continued treatment with MTX is inappropriate.
Tyenne is indicated for the treatment of chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome (CRS) in adults and paediatric patients 2 years of age and older.
Treatment should be initiated by healthcare professionals experienced in the diagnosis and treatment of RA, COVID-19, sJIA, pJIA or CRS.
All patients treated with Tyenne should be given the Patient Alert Card.
The recommended posology is 8 mg/kg body weight (BW), given once every four weeks.
For individuals whose body weight is more than 100 kg, doses exceeding 800 mg per infusion are not recommended (see section 5.2).
Doses above 1.2 g have not been evaluated in clinical studies (see section 5.1).
Dose adjustments due to laboratory abnormalities (see section 4.4).
| Laboratory Value | Action |
|---|---|
| >1 to 3 x Upper Limit of Normal (ULN) | Modify the dose of the concomitant MTX if appropriate For persistent increases in this range, reduce Tyenne dose to 4 mg/kg or interrupt Tyenne until alanine aminotransferase (ALT) or aspartate aminotransferase (AST) have normalized Restart with 4 mg/kg or 8 mg/kg, as clinically appropriate |
| >3 to 5 x ULN (confirmed by repeat testing, see section 4.4). | Interrupt Tyenne dosing until <3 x ULN and follow recommendations above for >1 to 3 x ULN For persistent increases >3 x ULN, discontinue Tyenne |
| >5 x ULN | Discontinue Tyenne |
In patients not previously treated with tocilizumab, initiation is not recommended in patients with an absolute neutrophil count (ANC) below 2 × 109/L.
| Laboratory Value (cells x 109/L) | Action |
|---|---|
| ANC >1 | Maintain dose |
| ANC 0.5 to 1 | Interrupt Tyenne dosing When ANC increases >1 × 109/L resume Tyenne at 4 mg/kg and increase to 8 mg/kg as clinically appropriate |
| ANC <0.5 | Discontinue Tyenne |
| Laboratory Value (cells x 103/μL) | Action |
|---|---|
| 50 to 100 | Interrupt Tyenne dosing When platelet count >100 × 103/μL resume Tyenne at 4 mg/kg and increase to 8 mg/kg as clinically appropriate |
| <50 | Discontinue Tyenne |
The recommended posology for treatment of COVID-19 is a single 60-minute intravenous infusion of 8 mg/kg in patients who are receiving systemic corticosteroids and require supplemental oxygen or mechanical ventilation, see section 5.1. If clinical signs or symptoms worsen or do not improve after the first dose, one additional infusion of Tyenne 8 mg/kg may be administered. The interval between the two infusions should be at least 8 hours.
For individuals whose body weight is more than 100 kg, doses exceeding 800 mg per infusion are not recommended (see section 5.2).
Administration of Tyenne is not recommended in patients with COVID-19 who have any of the following laboratory abnormalities:
| Laboratory test type | Laboratory value | Action |
|---|---|---|
| Liver enzyme | >10x ULN | Administration of Tyenne is not recommended |
| Absolute neutrophil count | <1 × 109/L | |
| Platelet count | <50 × 103/μL |
The recommended posology for treatment of CRS given as a 60-minute intravenous infusion is 8 mg/kg in patients weighing greater than or equal to 30 kg or 12 mg/kg in patients weighing less than 30 kg. Tyenne can be given 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.
Patients with severe or life-threatening CRS frequently have cytopenias or elevated ALT or AST due to the underlying malignancy, preceding lymphodepleting chemotherapy or the CRS.
sJIA Patients:
The recommended posology in patients above 2 years of age is 8 mg/kg once every 2 weeks in patients weighing greater than or equal to 30 kg or 12 mg/kg once every 2 weeks in patients weighing less than 30 kg. The dose should be calculated based on the patient’s body weight at each administration. A change in dose should only be based on a consistent change in the patient’s body weight over time.
The safety and efficacy of intravenous tocilizumab in children below 2 years of age has not been established.
Dose interruptions of tocilizumab for the following laboratory abnormalities are recommended in sJIA patients in the tables below. If appropriate, the dose of concomitant MTX and/or other medicines should be modified or dosing stopped and tocilizumab dosing interrupted until the clinical situation has been evaluated. As there are many co-morbid conditions that may affect laboratory values in sJIA, the decision to discontinue Tyenne for a laboratory abnormality should be based upon the medical assessment of the individual patient.
| Laboratory Value | Action |
|---|---|
| >1 to 3 x ULN | Modify the dose of the concomitant MTX if appropriate. For persistent increases in this range, interrupt Tyenne until ALT/AST have normalized. |
| >3 x ULN to 5x ULN | Modify the dose of the concomitant MTX if appropriate. Interrupt Tyenne dosing until < 3x ULN and follow recommendations above for >1 to 3x ULN. |
| >5x ULN | Discontinue Tyenne. The decision to discontinue Tyenne in sJIA for a laboratory abnormality should be based on the medical assessment of the individual patient. |
| Laboratory Value (cells x 109/L) | Action |
|---|---|
| ANC >1 | Maintain dose |
| ANC 0.5 to 1 | Interrupt Tyenne dosing When ANC increases to >1 × 109/L resume Tyenne |
| ANC <0.5 | Discontinue Tyenne The decision to discontinue Tyenne in sJIA for a laboratory abnormality should be based on the medical assessment of the individual patient. |
| Laboratory Value (cells x 103/µL) | Action |
|---|---|
| 50 to 100 | Modify the dose of the concomitant MTX if appropriate Interrupt Tyenne dosing When platelet count is >100 × 103/μL resume Tyenne |
| <50 | Discontinue Tyenne. The decision to discontinue Tyenne in sJIA for a laboratory abnormality should be based on the medical assessment of the individual patient. |
There are insufficient clinical data to assess the impact of a tocilizumab dose reduction in sJIA patients who have experienced laboratory abnormalities.
Available data suggest that clinical improvement is observed within 6 weeks of initiation of treatment with tocilizumab. Continued therapy should be carefully reconsidered in a patient exhibiting no improvement within this timeframe.
pJIA Patients:
The recommended posology in patients above 2 years of age is 8 mg/kg once every 4 weeks in patients weighing greater than or equal to 30 kg or 10 mg/kg once every 4 weeks in patients weighing less than 30 kg. The dose should be calculated based on the patient’s body weight at each administration. A change in dose should only be based on a consistent change in the patient’s body weight over time.
The safety and efficacy of intravenous tocilizumab in children below 2 years of age has not been established.
Dose interruptions of tocilizumab for the following laboratory abnormalities are recommended in pJIA patients in the tables below. If appropriate, the dose of concomitant MTX and/or other medicines should be modified or dosing stopped and tocilizumab dosing interrupted until the clinical situation has been evaluated. As there are many co-morbid conditions that may affect laboratory values in pJIA, the decision to discontinue Tyenne for a laboratory abnormality should be based upon the medical assessment of the individual patient.
| Laboratory Value | Action |
|---|---|
| >1 to 3 x ULN | Modify the dose of the concomitant MTX if appropriate For persistent increases in this range, interrupt Tyenne until ALT/AST have normalized. |
| >3 x ULN to 5x ULN | Modify the dose of the concomitant MTX if appropriate Interrupt Tyenne dosing until <3x ULN and follow recommendations above for >1 to 3x ULN |
| >5x ULN | Discontinue Tyenne. The decision to discontinue Tyenne in pJIA for a laboratory abnormality should be based on the medical assessment of the individual patient. |
| Laboratory Value (cells x 109/L) | Action |
|---|---|
| ANC >1 | Maintain dose |
| ANC 0.5 to 1 | Interrupt Tyenne dosing When ANC increases to >1 × 109/L resume Tyenne |
| ANC <0.5 | Discontinue Tyenne The decision to discontinue Tyenne in pJIA for a laboratory abnormality should be based on the medical assessment of the individual patient. |
| Laboratory Value (cells x 103/μL) | Action |
|---|---|
| 50 to 100 | Modify the dose of the concomitant MTX if appropriate Interrupt Tyenne dosing When platelet count is >100 × 103/μL resume Tyenne |
| <50 | Discontinue Tyenne. The decision to discontinue Tyenne in pJIA for a laboratory abnormality should be based on the medical assessment of the individual patient. |
Reduction of tocilizumab dose due to laboratory abnormalities has not been studied in pJIA patients.
Available data suggest that clinical improvement is observed within 12 weeks of initiation of treatment with tocilizumab. Continued therapy should be carefully reconsidered in a patient exhibiting no improvement within this timeframe.
No dose adjustment is required in elderly patients >65 years of age.
No dose adjustment is required in patients with mild renal impairment. Tocilizumab has not been studied in patients with moderate to severe renal impairment (see section 5.2). Renal function should be monitored closely in these patients.
Tocilizumab has not been studied in patients with hepatic impairment. Therefore, no dose recommendations can be made.
After dilution, Tyenne for RA, sJIA, pJIA, CRS and COVID-19 patients should be administered as an intravenous infusion over 1 hour.
RA, sJIA, pJIA, CRS and COVID-19 Patients ≥30 kg Tyenne should be diluted to a final volume of 100 mL with sterile, non-pyrogenic sodium chloride 9 mg/mL (0.9%) or 4.5 mg/mL (0.45%) solution for injection using aseptic technique.
For instructions on dilution of the medicinal product before administration, see section 6.6.
sJIA, pJIA and CRS Patients <30 kg Tyenne should be diluted to a final volume of 50 mL with sterile, non-pyrogenic sodium chloride 9 mg/mL (0.9%) or 4.5 mg/mL (0.45%) solution for injection using aseptic technique.
For instructions on dilution of the medicinal product before administration, see section 6.6.
If signs and symptoms of an infusion related reaction occur, slow or stop the infusion and administer appropriate medicine/supportive care immediately, see section 4.4.
There are limited data available on overdose with tocilizumab. One case of accidental overdose was reported in which a patient with multiple myeloma received a single dose of 40 mg/kg. No adverse reactions were observed.
No serious adverse reactions were observed in healthy volunteers who received a single dose of tocilizumab up to 28 mg/kg, although dose limiting neutropenia was observed.
No case of an overdose in the paediatric population has been observed.
Unopened vial:
3 years.
The vial may be stored at temperatures up to a maximum of 25°C for a single period of up to 4 weeks. The vial must be protected from light and discarded if not used within the 4 week period.
Diluted medicinal product:
Chemical and physical in-use stability has been demonstrated for 24 hours up to 30ºC in sodium chloride 9 mg/mL (0.9%) or 4.5 mg/mL (0.45%) solution for injection.
From a microbiological point of view, the prepared solution for infusion should be used immediately. If not used immediately, in use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2–8°C and up to 8 hours at 30°C, unless dilution has taken place in controlled and validated aseptic conditions.
Store vials in a refrigerator (2°C–8°C). Do not freeze.
Keep the vial(s) in the outer carton in order to protect from light.
For storage conditions of the diluted medicinal product see section 6.3.
Tyenne is supplied in a vial (type I glass) with a stopper (bromobutyl rubber) containing 4 mL, 10 mL or 20 mL concentrate. Each pack contains 1 vial and multipacks contain 4 (4 packs of 1) vials.
Not all pack sizes may be marketed.
Parenteral medicinal products should be inspected visually for particulate matter or discolouration prior to administration. Only solutions which are clear and colourless to pale yellow and practically free of visible particles should be diluted.
Withdraw a volume of sterile, non-pyrogenic sodium chloride 9 mg/mL (0.9%) or 4.5 mg/mL (0.45%) solution for injection from a 100 mL infusion bag, equal to the volume of Tyenne concentrate required for the patients dose, under aseptic conditions. The required amount of Tyenne concentrate (0.4 mL/kg) should be withdrawn from the vial and placed in the 100 mL infusion bag. This should be a final volume of 100 mL. To mix the solution, gently invert the infusion bag to avoid foaming.
sJIA, pJIA and CRS Patients ≥30 kg:
Withdraw a volume of sterile, non-pyrogenic sodium chloride 9 mg/mL (0.9%) or 4.5 mg/mL (0.45%) solution for injection from a 100 mL infusion bag, equal to the volume of Tyenne concentrate required for the patients dose, under aseptic conditions. The required amount of Tyenne concentrate (0.4 mL/kg) should be withdrawn from the vial and placed in the 100 mL infusion bag. This should be a final volume of 100 mL. To mix the solution, gently invert the infusion bag to avoid foaming.
sJIA and CRS Patients <30 kg:
Withdraw a volume of sterile, non-pyrogenic sodium chloride 9 mg/mL (0.9%) or 4.5 mg/mL (0.45%) solution for injection from a 50 mL infusion bag, equal to the volume of Tyenne concentrate required for the patients dose, under aseptic conditions. The required amount of Tyenne concentrate (0.6 mL/kg) should be withdrawn from the vial and placed in the 50 mL infusion bag. This should be a final volume of 50 mL. To mix the solution, gently invert the infusion bag to avoid foaming.
pJIA Patients <30 kg:
Withdraw a volume of sterile, non-pyrogenic sodium chloride 9 mg/mL (0.9%) or 4.5 mg/mL (0.45%) solution for injection from a 50 mL infusion bag, equal to the volume of Tyenne concentrate required for the patients dose, under aseptic conditions. The required amount of Tyenne concentrate (0.5 mL/kg) should be withdrawn from the vial and placed in the 50 mL infusion bag. This should be a final volume of 50 mL. To mix the solution, gently invert the infusion bag to avoid foaming.
Tyenne is for single-use only.
Any unused product or waste material should be disposed of in accordance with local requirements.
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