Posology : מינונים

4.2   Posology and method of administration
Treatment should be initiated and supervised by healthcare professionals experienced in the diagnosis and treatment of rheumatoid arthritis and polymyalgia rheumatica.

Posology
Rheumatoid Arthritis
The recommended dose of sarilumab is 200 mg once every 2 weeks administered as a subcutaneous injection.

Reduction of dose from 200 mg once every 2 weeks to 150 mg once every 2 weeks is recommended for management of neutropenia, thrombocytopenia, and liver enzyme elevations.

Polymyalgia Rheumatica
Initiate treatment with Kevzara in patients who had at least one episode of unequivocal PMR flare while attempting to taper prednisone at a dose that is ≥7.5 mg/day or equivalent The recommended dosage of KEVZARA is 200 mg once every two weeks given as a subcutaneous injection, in combination with a tapering course of systemic corticosteroids. KEVZARA can be used as monotherapy following discontinuation of corticosteroids.

Discontinue KEVZARA if the patient develops neutropenia (using ANC results obtained at the end of the dosing interval), thrombocytopenia, or liver enzyme abnormalities.

Dose modification:
Treatment with sarilumab should be withheld in patients who develop a serious infection or an opportunistic infection until the infection is controlled [see Special warnings and precautions for use (4.4)].

Initiating treatment with sarilumab is not recommended in patients with a low neutrophil count, i.e.
absolute neutrophil count (ANC) less than 2 x 109/L.

Initiating treatment with sarilumab is not recommended in patients with a platelet count below 150 x 103/µL.

Table 1: Dosage Modifications due to Neutropenia, Thrombocytopenia, or Elevated Liver Enzymes in Patients with Rheumatoid Arthritis (see sections 4.4 and 4.8):



Low Absolute Neutrophil Count (see section 5.1)
Lab Value (cells x 109/L) Recommendation
ANC greater than 1         Current dose of sarilumab should be maintained.
ANC 0.5-1                 Treatment with sarilumab should be withheld until >1 x 109/L.
sarilumab can then be resumed at 150 mg every 2 weeks and increased to 200 mg every 2 weeks as clinically appropriate.
ANC less than 0.5         Treatment with sarilumab should be discontinued.

Low Platelet Count
Lab Value (cells x            Recommendation
103/µL)
50 to 100                     Treatment with sarilumab should be withheld until >100 x 103/µL.
sarilumab can then be resumed at 150 mg every 2 weeks and increased to 200 mg every 2 weeks as clinically appropriate.
Less than 50                  If confirmed by repeat testing, treatment with sarilumab should be discontinued.

Liver Enzyme Abnormalities
Lab Value                Recommendation
ALT > 1 to 3 x Upper     Clinically appropriate dose modification of concomitant DMARDs Limit of Normal (ULN)    should be considered.
ALT > 3 to 5 x ULN       Treatment with sarilumab should be withheld until < 3 x ULN.
sarilumab can then be resumed at 150 mg every 2 weeks and increased to 200 mg every 2 weeks as clinically appropriate.
ALT > 5 x ULN            Treatment with sarilumab should be discontinued.


Dosage Modifications for Patients with Polymyalgia Rheumatica
•     Laboratory Abnormalities: Discontinue KEVZARA in patients with PMR who develop the following laboratory abnormalities [see Special warnings and precautions for use (4.4)]: o     neutropenia (ANC below 1,000 per mm3 at the end of the dosing interval) o     thrombocytopenia (platelet count below 100,000 per mm3) o     ALT elevations 3 times above the ULN

Dosage modifications have not been studied in patients with PMR with these conditions. For treatment initiation criteria, refer to the dosage recommendations for PMR [see Posology and method of administration (4.2)].

Missed dose
If a dose of sarilumab is missed and it has been 3 days or less since the missed dose, the next dose should be administered as soon as possible. The subsequent dose should be administered at the regularly scheduled time. If it has been 4 days or more since the missed dose, the subsequent dose should be administered at the next regularly scheduled time, the dose should not be doubled.

Special populations
Renal impairment
No dose adjustment is required in patients with mild to moderate renal impairment. Sarilumab has not been studied in patients with severe renal impairment (see section 5.2).

Hepatic impairment
The safety and efficacy of sarilumab have not been studied in patients with hepatic impairment, including patients with positive hepatitis B virus (HBV) or hepatitis C virus (HCV) serology (see section 4.4).

Elderly
No dose adjustment is required in patients over 65 years of age (see section 4.4).

Paediatric population
The safety and efficacy of sarilumab in children up to 18 years of age have not been established. No data are available.

Method of administration
Subcutaneous use.

The total content (1.14 ml) of the pre-filled syringe/pre-filled pen should be administered as a subcutaneous injection. Injection sites (abdomen, thigh and upper arm) should be rotated with each injection. sarilumab should not be injected into skin that is tender, damaged, or has bruises or scars.

A patient may self-inject sarilumab or the patient's caregiver may administer sarilumab if their healthcare professional determines that it is appropriate. Proper training should be provided to patients and/or caregivers on the preparation and administration of sarilumab prior to use.

Comprehensive instructions for administration of this medicinal product are given in the package leaflet.