SARCLISA CONCENTRATE FOR SOLUTION FOR INFUSION 20MG/ML

INFUSION, SOLUTION CONCENTRATE

**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 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). _Prevention of infection_ Antibacterial and antiviral prophylaxis (such as herpes zoster prophylaxis) can be considered during treatment (see section 4.4 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). 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:  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 package insert – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_. 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 package insert 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 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). _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 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_), 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 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_. Infusion rates Following dilution, the SARCLISA infusion should be administered intravenously at the infusion rate presented in Table 2 below (see section 5.1 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). Incremental escalation of the infusion rate should be considered only in the absence of infusion reactions (see section 4.8 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_).  Administration adjustments should be made if patients experience infusion reactions (see section 4.4 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_) - In patients necessitating an intervention (Grade 2, moderate infusion reactions), a temporary interruption in the infusion should be considered and additional symptomatic medicinal products can be administered. After symptom improvement to grade ≤1 (mild), SARCLISA infusion may be resumed at half 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.