SARCLISA Concentrate for solution for infusion Ref.[50841] Active ingredients: Isatuximab

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 × 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:

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:

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 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.

Signs and symptoms

There has been no experience of overdosage of isatuximab in clinical studies. Doses of intravenous isatuximab up to 20 mg/kg have been administered in clinical studies.

Management

There is no known specific antidote for SARCLISA overdose. In the event of overdose, monitor the patients for signs or symptoms of adverse reactions and take all appropriate measures immediately.

Unopened Vial:

3 years.

After dilution:

Chemical and physical in-use stability of SARCLISA infusion solution has been demonstrated for 48 hours at 2°C-8°C, followed by 8 hours (including the infusion time) at room temperature (15°C-25°C).

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.

No protection from light is required for storage in the infusion bag.

Store in a refrigerator (2°C-8°C).

Do not freeze.

Store in the original package in order to protect from light.

For storage conditions after dilution of the medicinal product, see section 6.3.

5 ml concentrate containing 100 mg of isatuximab in a 6 mL type I colourless clear glass vial closed with ETFE (copolymer of ethylene and tetrafluoroethylene)-coated bromobutyl stopper. The vials are crimped with an aluminium seal with a grey flip-off button. The fill volume has been established to ensure removal of 5 mL (i.e. 5.4 mL). Pack size of one or three vials.

25 ml concentrate containing 500 mg of isatuximab in a 30 mL type I colourless clear glass vial closed with ETFE (copolymer of ethylene and tetrafluoroethylene)-coated bromobutyl stopper. The vials are crimped with an aluminium seal with a blue flip-off button. The fill volume has been established to ensure removal of 25 mL (i.e. 26 mL). Pack size of one vial.

Not all pack sizes may be marketed.

Preparation for the intravenous administration:

The preparation of the infusion solution must be done under aseptic conditions.

• The dose (mg) of SARCLISA concentrate should be calculated based on patient weight (measured prior to each cycle to have the administered dose adjusted accordingly, see section 4.2). More than one vial may be necessary to obtain the required dose for the patient.
• Vials of SARCLISA concentrate should be visually inspected before dilution to ensure they do not contain any particles and are not discoloured.
• Do not shake vials.
• The volume of diluent equal to the required volume of SARCLISA concentrate should be removed from a 250 mL sodium chloride 9 mg/mL (0.9%) solution for injection or glucose 5% solution diluent bag.
• The appropriate volume of SARCLISA concentrate should be withdrawn from the SARCLISA vial and diluted in the 250 mL infusion bag with sodium chloride 9 mg/mL (0.9%) solution for injection or glucose 5% solution.
• The infusion bag must be made of polyolefins (PO), polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC) with di (2-ethylhexyl) phthalate (DEHP) or ethyl vinyl acetate (EVA).
• Gently homogenize the diluted solution by inverting the bag. Do not shake.

Administration:

• The infusion solution must be administered by intravenous infusion using an intravenous tubing infusion set (in PE, PVC with or without DEHP, polybutadiene (PBD) or polyurethane (PU)) with a 0.22 micron in-line filter (polyethersulfone (PES), polysulfone or nylon).
• The infusion solution should be administered for a period of time that will depend on the infusion rate (see section 4.2).
• No protection from light is required for the prepared infusion bag in a standard artificial light environment.
• Do not infuse SARCLISA solution concomitantly in the same intravenous line with other agents.

Disposal:

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.