Posology : מינונים

4.2      Posology and method of administration

SARCLISA should be administered by a healthcare professional, in an environment where resuscitation facilities are available.

Premedication
Premedication should be used prior to SARCLISA infusion with the following medicinal products to reduce the risk and severity of infusion reactions:
• Dexamethasone 40 mg oral or intravenous (or 20 mg oral or intravenous for patients ≥75 years of age) when administered in combination with isatuximab and pomalidomide, Dexamethasone 20 mg (intravenous on the days of isatuximab and/or carfilzomib infusions, and oral on the other days): when administered in combination with isatuximab and carfilzomib.
• Acetaminophen 650 mg to 1000 mg oral (or equivalent).
• Diphenhydramine 25 mg to 50 mg intravenous or oral (or equivalent [e.g., cetirizine, promethazine, dexchlorpheniramine]). The intravenous route is preferred for at least the first 4 infusions.


The above recommended dose of dexamethasone (oral or intravenous) corresponds to the total dose to be administered only once before the infusion, as part of the premedication and the backbone treatment, before isatuximab and pomalidomide and before isatuximab and carfilzomib administration.

The recommended premedication agents should be administered 15-60 minutes prior to starting a SARCLISA infusion. Patients who do not experience an infusion reaction upon their first 4 administrations of SARCLISA may have their need for subsequent premedication reconsidered.

Management of neutropenia
The use of colony-stimulating factors (e.g. G-CSF) should be considered to mitigate the risk of neutropenia. In the event of grade 4 neutropenia, SARCLISA administration should be delayed until neutrophil count improves to at least 1.0 x 109/L (see section 4.4).

Prevention of infection
Antibacterial and antiviral prophylaxis (such as herpes zoster prophylaxis) can be considered during treatment (see section 4.4).

Posology
The recommended dose of SARCLISA is 10 mg/kg body weight administered as an intravenous infusion in combination with pomalidomide and dexamethasone (Isa-Pd) , or in combination with carfilzomib and dexamethasone (Isa-Kd), according to the schedule in Table 1: Table 1: SARCLISA dosing schedule in combination with pomalidomide and dexamethasone or in combination with carfilzomib and dexamethasone

Cycles                             Dosing schedule

Cycle 1                                             Days 1, 8, 15 and 22 (weekly) 
Cycle 2 and beyond                                  Days 1, 15 (every 2 weeks) 
Each treatment cycle consists of a 28-day period. Treatment is repeated until disease progression or unacceptable toxicity.
For other medicinal products that are administered with SARCLISA, see section 5.1 and the respective current summary of product characteristics.
The administration schedule must be carefully followed. If a planned dose of SARCLISA is missed, administer the dose as soon as possible and adjust the treatment schedule accordingly, maintaining the treatment interval.
Dose adjustments
No dose reduction of SARCLISA is recommended.

Administration adjustments should be made if patients experience infusion reactions (see “Method of administration” below).

For other medicinal products that are administered with SARCLISA, the respective current summary of product characteristics should be considered.

Special populations

Elderly
Based on population pharmacokinetic analysis, no dose adjustment is recommended in elderly patients.



Patients with renal impairment
Based on population pharmacokinetic analysis and on clinical safety, no dose adjustment is recommended in patients with mild to severe renal impairment (see section 5.2).

Patients with hepatic impairment
Based on population pharmacokinetic analysis, no dose adjustment is recommended in patients with mild hepatic impairment. Data in patients with moderate and severe hepatic impairment are limited (see section 5.2), but there is no evidence to suggest that dose adjustment is required in these patients.

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

Method of administration
SARCLISA is for intravenous use. For instructions on dilution of the medicinal product before administration, see section 6.6.

Infusion rates
Following dilution, the SARCLISA infusion should be administered intravenously at the infusion rate presented in Table 2 below (see section 5.1). Incremental escalation of the infusion rate should be considered only in the absence of infusion reactions (see section 4.8).

Table 2: Infusion rates of SARCLISA administration

Dilution   Initial rate   Absence of          Rate increment          Maximum volume                    infusion                                    rate reaction
First infusion        250 mL     25 mL/ hour    For 60 minutes      25 mL/hour every        150 mL/ hour 30 minutes
Second                           50 mL/ hour                        50 mL/ hour for         200 mL/ hour infusion                                                            30 minutes then 250 mL                    For 30 minutes      increase by 100 mL/ hour

Subsequent            250 mL     200 mL/ hour                                               200 mL/ hour infusions

Administration adjustments should be made if patients experience infusion reactions (see section 4.4) • In patients necessitating an intervention (Grade 2, moderate infusion reactions), a temporary interruption inthe infusion should be considered and additional symptomatic medicinal products can be administered. After symptom improvement to grade ≤1 (mild), SARCLISA infusion may be resumed athalf of the initial infusion rate under close monitoring and supportive care, as needed. If symptoms do not recur after 30 minutes, the infusion rate may be increased to the initial rate, and then increased incrementally, as shown in Table 2.
• If symptoms do not resolve rapidly or do not improve to Grade ≤1 after interruption of SARCLISA infusion, persist or worsen despite appropriate medicinal products, or require hospitalization or are life-threatening , treatment with SARCLISA should be permanently discontinued and additional supportive therapy should be administered, as needed.