Posology : מינונים

4.2     Posology and method of administration

Treatment should be initiated by healthcare professionals experienced in the diagnosis and treatment of RA, COVID-19, sJIA, pJIA or CRS.

Posology
RA Patients

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).

Dose adjustments due to laboratory abnormalities (see section 4.4).

•       Liver enzyme abnormalities
Laboratory Value                                        Action

> 1 to 3 x Upper Modify the dose of the concomitant MTX if appropriate.
Limit of Normal
(ULN)            For persistent increases in this range, reduce Actemra dose to 4 mg/kg or interrupt Actemra 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      Interrupt Actemra dosing until < 3 x ULN and follow recommendations above for > 1 to 3 x ULN.
(confirmed       by repeat testing, see For persistent increases > 3 x ULN, discontinue Actemra.
section 4.4).

> 5 x ULN           Discontinue Actemra.


•       Low absolute neutrophil count (ANC)
In patients not previously treated with Actemra, initiation is not recommended in patients with an absolute neutrophil count (ANC) below 2 x 109/L.


Laboratory Value                                         Action
(cells x 109/ l )

ANC > 1                Maintain dose.

ANC 0.5 to 1           Interrupt Actemra dosing.
When ANC increases > 1 x 109/ l resume Actemra at 4 mg/kg and increase to 8 mg/kg as clinically appropriate.

ANC < 0.5              Discontinue Actemra.


•          Low platelet count
Laboratory Value                                         Action
(cells x 103/ μL)

50 to 100              Interrupt Actemra dosing

When platelet count > 100 x 103/μl resume Actemra at 4 mg/kg and increase to 8 mg/kg as clinically appropriate.

< 50                   Discontinue Actemra.

COVID-19 Patients

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 Actemra 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 Actemra 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 Actemra is Absolute neutrophil count                   < 1 x 109 /L            not recommended Platelet count                             < 50 x 103 /μL

Cytokine Release Syndrome (CRS) (adults and paediatrics)
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. Actemra 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 Actemra 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.


Special populations

Paediatric patients
 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 Actemra 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 Actemra until ALT/AST have normalized.

> 3 x ULN to 5x Modify the dose of the concomitant MTX if appropriate.
ULN
Interrupt Actemra dosing until < 3x ULN and follow recommendations above for >1 to 3x ULN.

> 5x ULN              Discontinue Actemra.

The decision to discontinue Actemra in sJIA for a laboratory abnormality should be based on the medical assessment of the individual patient.


•     Low absolute neutrophil count (ANC)

Laboratory Value                                       Action
(cells x 109/ l )
ANC > 1               Maintain dose.

ANC 0.5 to 1          Interrupt Actemra dosing.

When ANC increases to > 1 x 109/ l resume Actemra
ANC < 0.5             Discontinue Actemra

The decision to discontinue Actemra in sJIA for a laboratory abnormality should be based on the medical assessment of the individual patient.


•     Low platelet count

Laboratory Value                                        Action
(cells x 103/l)

50 to 100              Modify the dose of the concomitant MTX if appropriate.
Interrupt Actemra dosing.

When platelet count is > 100 x 103/l resume Actemra

< 50                   Discontinue Actemra.
The decision to discontinue Actemra 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 Actemra. 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 Actemra 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 Actemra until ALT/AST have normalized.

> 3 x ULN to 5x ULN      Modify the dose of the concomitant MTX if appropriate.

Interrupt Actemra dosing until < 3x ULN and follow recommendations above for >1 to 3x ULN.
> 5x ULN                 Discontinue Actemra.

The decision to discontinue Actemra in pJIA for a laboratory abnormality should be based on the medical assessment of the individual patient.


•      Low absolute neutrophil count (ANC)
Laboratory Value                                       Action
(cells x 109/ l )

ANC > 1                  Maintain dose.
ANC 0.5 to 1             Interrupt Actemra dosing

When ANC increases to > 1 x 109/ l resume Actemra

ANC < 0.5                Discontinue Actemra
The decision to discontinue Actemra in pJIA for a laboratory abnormality should be based on the medical assessment of the individual patient.


•     Low platelet count

Laboratory Value                                       Action
(cells x 103/l)
50 to 100              Modify the dose of the concomitant MTX if appropriate.

Interrupt Actemra dosing.

When platelet count is > 100 x 103/l resume Actemra
< 50                   Discontinue Actemra.

The decision to discontinue Actemra 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 Actemra. Continued therapy should be carefully reconsidered in a patient exhibiting no improvement within this timeframe.


Elderly
No dose adjustment is required in elderly patients >65 years of age.
Renal impairment
No dose adjustment is required in patients with mild renal impairment. Actemra 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.

Hepatic impairment
Actemra has not been studied in patients with hepatic impairment. Therefore, no dose recommendations can be made.

Method of administration
After dilution, Actemra 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
Actemra 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
Actemra 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.

If signs and symptoms of an infusion related reaction occur, slow or stop the infusion and administer appropriate medication/ supportive care immediately, see section 4.4.