Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: Roche Registration GmbH, Emil-Barell-Strasse 1, 79639, Grenzach-Wyhlen, Germany
RoActemra, in combination with methotrexate (MTX), is indicated for:
In these patients, RoActemra can be given as monotherapy in case of intolerance to MTX or where continued treatment with MTX is inappropriate. RoActemra has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function when given in combination with methotrexate.
RoActemra 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. RoActemra can be given as monotherapy (in case of intolerance to MTX or where treatment with MTX is inappropriate) or in combination with MTX.
RoActemra 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.
RoActemra can be given as monotherapy in case of intolerance to MTX or where continued treatment with MTX is inappropriate.
RoActemra 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, sJIA, pJIA or CRS. All patients treated with RoActemra should be given the Patient Alert Card.
The recommended posology is 8 mg/kg body weight, 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).
Liver enzyme abnormalities:
| 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 RoActemra dose to 4 mg/kg or interrupt RoActemra until alanine aminotransferase (ALT) or aspartate aminotransferase (AST) have normalised. 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 RoActemra dosing until < 3 x ULN and follow recommendations above for >1 to 3 x ULN. For persistent increases > 3 x ULN, discontinue RoActemra |
| >5 x ULN | Discontinue RoActemra. |
Low absolute neutrophil count (ANC):
In patients not previously treated with RoActemra, 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 RoActemra dosing. hen ANC increases >1 × 109/l resume RoActemra at 4 mg/kg and increase to 8 mg/kg as clinically appropriate |
| ANC <0.5 | Discontinue RoActemra |
Low platelet count:
| Laboratory Value (cells x 103/μL) | Action |
|---|---|
| 50 to 100 | Interrupt RoActemra dosing. When platelet count >100 × 103/μ resume RoActemra at 4 mg/kg and increase to 8 mg/kg as clinically appropriate |
| <50 | Discontinue RoActemra |
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. RoActemra 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 RoActemra 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.
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 RoActemra 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 medications 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 tocilizumab for a laboratory abnormality should be based upon the medical assessment of the individual patient.
Liver enzyme abnormalities:
| Laboratory Value | Action |
|---|---|
| >1 to 3 x ULN | Modify the dose of the concomitant MTX if appropriate. For persistent increases in this range, interrupt RoActemra until ALT/AST have normalized. |
| >3 x ULN to 5 x ULN | Modify the dose of the concomitant MTX if appropriate. Interrupt RoActemra dosing until <3x ULN and follow recommendations above for >1 to 3 x ULN |
| >5 x ULN | Discontinue RoActemra. The decision to discontinue RoActemra in sJIA for a laboratory abnormality should be based on the medical assessment of the individual patient. |
Low absolute neutrophil count (ANC):
| Laboratory Value (cells x 109/l) | Action |
|---|---|
| ANC >1 | Maintain dose |
| ANC 0.5 to 1 | Interrupt RoActemra dosing. When ANC increases to >1 × 109/l resume RoActemra |
| ANC <0.5 | Discontinue RoActemra. The decision to discontinue RoActemra in sJIA for a laboratory abnormality should be based on the medical assessment of the individual patient. |
Low platelet count:
| Laboratory Value (cells x 103/µl) | Action |
|---|---|
| 50 to 100 | Modify the dose of the concomitant MTX if appropriate. Interrupt RoActemra dosing. When platelet count is >100 × 103/µl resume RoActemra |
| <50 | Discontinue RoActemra. The decision to discontinue RoActemra in sJIA 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 sJIA patients.
Available data suggest that clinical improvement is observed within 6 weeks of initiation of treatment with RoActemra. Continued therapy should be carefully reconsidered in a patient exhibiting no improvement within this timeframe.
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 RoActemra 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 medications 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 effect laboratory values in pJIA, the decision to discontinue tocilizumab for a laboratory abnormality should be based upon the medical assessment of the individual patient.
Liver enzyme abnormalities:
| Laboratory Value | Action |
|---|---|
| >1 to 3 x ULN | Modify the dose of the concomitant MTX if appropriate. For persistent increases in this range, interrupt RoActemra until ALT/AST have normalized. |
| >3 x ULN to 5x ULN | Modify the dose of the concomitant MTX if appropriate. Interrupt RoActemra dosing until <3x ULN and follow recommendations above for >1 to 3x ULN |
| >5 x ULN | Discontinue RoActemra. The decision to discontinue RoActemra in pJIA for a laboratory abnormality should be based on the medical assessment of the individual patient. |
Low absolute neutrophil count (ANC):
| Laboratory Value (cells x 109/l) | Action |
|---|---|
| ANC >1 | Maintain dose |
| ANC 0.5 to 1 | Interrupt RoActemra dosing. When ANC increases to >1 × 109/l resume RoActemra |
| ANC <0.5 | Discontinue RoActemra. The decision to discontinue RoActemra in pJIA for a laboratory abnormality should be based on the medical assessment of the individual patient. |
Low platelet count:
| Laboratory Value (cells x 103/µl) | Action |
|---|---|
| 50 to 100 | Modify the dose of the concomitant MTX if appropriate. Interrupt RoActemra dosing. When platelet count is >100 × 103/µl resume RoActemra |
| <50 | Discontinue RoActemra. The decision to discontinue RoActemra 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 RoActemra. 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. RoActemra 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.
RoActemra has not been studied in patients with hepatic impairment. Therefore, no dose recommendations can be made.
After dilution, RoActemra for RA, sJIA, pJIA, and CRS patients should be administered as an intravenous infusion over 1 hour.
RA, sJIA, pJIA and CRS Patients ≥30 kg RoActemra should be diluted to a final volume of 100 mL with sterile, non-pyrogenic sodium chloride 9 mg/mL (0.9%) 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 RoActemra should be diluted to a final volume of 50 mL with sterile, non-pyrogenic sodium chloride 9 mg/mL (0.9%) solution for injection using aseptic technique.
For instructions on dilution of the medicinal product before administration, see section 6.6.
There are limited data available on overdose with RoActemra. 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 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: 30 months.
Diluted product: After dilution, the prepared solution for infusion is physically and chemically stable in sodium chloride 9 mg/mL (0.9%) solution for injection at 30oC for 24 hours.
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°C–8°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.
RoActemra is supplied in a vial (type I glass) with a stopper (butyl rubber) containing 4 mL, 10 mL or 20 mL concentrate. Pack sizes of 1 and 4 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 to opalescent, colourless to pale yellow and free of visible particles should be diluted.
Withdraw a volume of sterile, non-pyrogenic sodium chloride 9 mg/mL (0.9%) solution for injection from a 100 mL infusion bag, equal to the volume of RoActemra concentrate required for the patients dose, under aseptic conditions. The required amount of RoActemra 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.
Withdraw a volume of sterile, non-pyrogenic sodium chloride 9 mg/mL (0.9%) solution for injection from a 100 mL infusion bag, equal to the volume of RoActemra concentrate required for the patients dose, under aseptic conditions. The required amount of RoActemra 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.
Withdraw a volume of sterile, non-pyrogenic sodium chloride 9 mg/mL (0.9%) solution for injection from a 50 mL infusion bag, equal to the volume of RoActemra concentrate required for the patients dose, under aseptic conditions. The required amount of RoActemra 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.
Withdraw a volume of sterile, non-pyrogenic sodium chloride 9 mg/mL (0.9%) solution for injection from a 50 mL infusion bag, equal to the volume of RoActemra concentrate required for the patients dose, under aseptic conditions. The required amount of RoActemra 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. RoActemra is for single-use only. Any unused product or waste material should be disposed of in accordance with local requirements.
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