Posology : מינונים

4.2   Posology and method of administration

Tocilizumab SC formulation is administered with a single-use PFS+NSD. Treatment should be initiated by healthcare professionals experienced in the diagnosis and treatment of RA, sJIA, pJIA and / or GCA. The first injection should be performed under the supervision of a qualified health care professional. A patient or parent/guardian can self-inject Actemra only if the physician determines that it is appropriate and the patient or parent/guardian agrees to medical follow-up as necessary and has been trained in proper injection technique.

Patients who transition from tocilizumab IV therapy to SC administration should administer the first SC dose at the time of the next scheduled IV dose under the supervision of a qualified health care professional.

Suitability of the patient or parent/guardian for subcutaneous home use should be assessed and patients or parent/guardian instructed to inform a healthcare professional before administering the next dose if they experience symptoms of an allergic reaction. Patients should seek immediate medical attention if developing symptoms of serious allergic reactions (see section 4.4).

Posology

RA
The recommended posology is subcutaneous 162 mg once every week.
Limited information is available regarding switching patients from Actemra intravenous formulation to Actemra subcutaneous fixed dose formulation. The once every week dosing interval should be followed.

Patients transitioning from intravenous to subcutaneous formulation should administer their first subcutaneous dose instead of the next scheduled intravenous dose under the supervision of a qualified healthcare professional.

GCA
The recommended posology is subcutaneous 162 mg once every week in combination with a tapering course of glucocorticoids. Actemra can be used alone following discontinuation of glucocorticoids.
Actemra monotherapy should not be used for the treatment of acute relapses (see 4.4).

Based upon the chronic nature of GCA, treatment beyond 52 weeks should be guided by disease activity, physician discretion, and patient choice.


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

•          Liver enzyme abnormalities
Laboratory Value                                         Action

> 1 to 3 x Upper Dose modify concomitant DMARDs (RA) or immunomodulatory agents Limit of Normal (GCA) if appropriate.
(ULN)
For persistent increases in this range, reduce Actemra dose frequency to every other week injection or interrupt Actemra until alanine aminotransferase (ALT) or aspartate aminotransferase (AST) have normalised.

Restart with weekly or every other week injection, 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.

For persistent increases > 3 x ULN (confirmed by repeat testing, see 4.4.), discontinue Actemra.

> 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 dosing every other week and increase to every week injection, 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 dosing every other week and increase to every week injection as clinically appropriate.

< 50                 Discontinue Actemra.

RA and GCA
Missed dose
If a patient misses a subcutaneous weekly injection of Actemra within 7 days of the scheduled dose, he/she should be instructed to take the missed dose on the next scheduled day. If a patient misses a subcutaneous once every other week injection of Actemra within 7 days of the scheduled dose, he/she should be instructed to take the missed dose immediately and the next dose on the next scheduled day.

Special populations

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.

Paediatric patients
The safety and efficacy of Actemra subcutaneous formulation in children from birth to less than 1 year have not been established. No data are available.

A change in dose should only be based on a consistent change in the patient’s body weight over time.
Actemra can be used alone or in combination with MTX.
 sJIA Patients
The recommended posology in patients above 1 year of age is subcutaneous 162 mg once every week in patients weighing greater than or equal to 30 kg or subcutaneous 162 mg once every 2 weeks in patients weighing less than 30 kg.
Patients must have a minimum body weight of 10 kg when receiving Actemra subcutaneously.
 pJIA Patients:
The recommended posology in patients above 2 years of age is subcutaneous 162 mg once every 2 weeks in patients weighing greater than or equal to 30 kg or subcutaneous 162 mg once every 3 weeks in patients weighing less than 30 kg.

Dose adjustments due to laboratory abnormalities (sJIA and pJIA)

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 sJIA or 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 sJIA or 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 sJIA or 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 sJIA or pJIA for a laboratory abnormality should be based on the medical assessment of the individual patient.

Reduction of tocilizumab dosing frequency due to laboratory abnormalities has not been studied in sJIA or pJIA patients.

The safety and efficacy of Actemra subcutaneous formulation in children with conditions other than sJIA or pJIA have not been established.

Available data with the IV formulation 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.

Missed dose
If a sJIA patient misses a subcutaneous weekly injection of Actemra within 7 days of the scheduled dose, he/she should be instructed to take the missed dose on the next scheduled day. If a patient misses a subcutaneous once every 2 week injection of Actemra within 7 days of the scheduled dose, he/she should be instructed to take the missed dose immediately and the next dose on the next scheduled day.

If a pJIA patient misses a subcutaneous injection of Actemra within 7 days of the scheduled dose, he/she should take the missed dose as soon as they remember and take the next dose at the regular scheduled time. If a patient misses a subcutaneous injection of Actemra by more than 7 days of the scheduled dose or is unsure when to inject Actemra, call the doctor or pharmacist.

Method of administration
Actemra is for subcutaneous use. After proper training in injection technique, patients may self-inject with Actemra if their physician determines that it is appropriate. The total content (0.9 mL) of the pre- filled syringe should be administered as a subcutaneous injection. The recommended injection sites (abdomen, thigh and upper arm) should be rotated and injections should never be given into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact.

The pre-filled syringe should not be shaken.

Comprehensive instructions for the administration of Actemra in a pre-filled syringe are given in the package leaflet, see section 6.6.