Sarclisa must be administered under the supervision of a healthcare professional, and the administration site must be equipped with immediately available emergency equipment and medical support to manage potential infusion-related reactions.
1. Recommended Dosage
The recommended dosage of isatuximab is 10 mg/kg based on actual body weight, administered by intravenous infusion. The dosing schedule depends on the combination regimen, as follows:
In combination with pomalidomide and dexamethasone (Isa-Pd)
Cycle 1 (28‑day cycle): Administer on Days 1, 8, 15, and 22 (weekly).
Cycle 2 and thereafter (28‑day cycle): Administer on Days 1 and 15 (every two weeks).
In combination with carfilzomib and dexamethasone (Isa-Kd)
The dosing schedule is identical to the Isa‑Pd regimen described above.
Cycle 1 (28‑day cycle): Administer on Days 1, 8, 15, and 22 (weekly).
Cycle 2 and thereafter (28‑day cycle): Administer on Days 1 and 15 (every two weeks).
In combination with bortezomib, lenalidomide, and dexamethasone (Isa-VRd)
Cycle 1 (42‑day cycle): Administer on Days 1, 8, 15, 22, and 29.
Cycles 2 to 4 (42‑day cycle): Administer on Days 1, 15, and 29 (every two weeks).
Cycles 5 to 17 (28‑day cycle): Administer on Days 1 and 15 (every two weeks).
Cycle 18 and thereafter (28‑day cycle): Administer on Day 1 (every four weeks).
Treatment should continue until disease progression or unacceptable toxicity. For dosing information of other drugs in the combination, refer to the respective manufacturer’s prescribing information.
2. Management of Missed Doses
If a planned dose is missed, administer it as soon as possible and adjust the treatment schedule accordingly to maintain the dosing interval.
3. Recommended Premedication and Antimicrobial Prophylaxis
Premedication: To reduce the frequency and severity of infusion‑related reactions, the following medications should be given 15 to 60 minutes before each isatuximab infusion:
Dexamethasone: The dose varies depending on the combination regimen.
Isa-Pd regimen: 40 mg orally or intravenously (20 mg for patients aged ≥75 years).
Isa-Kd regimen: 20 mg intravenously on isatuximab and/or carfilzomib infusion days; orally on Day 22 of Cycle 2 and thereafter; and orally on Day 23 of all cycles.
Isa-VRd regimen: 20 mg intravenously on isatuximab infusion days, and 20 mg orally on other days.
Acetaminophen: 650 mg to 1,000 mg orally (or equivalent).
H2‑receptor antagonist: Standard dose.
Diphenhydramine: 25 mg to 50 mg orally or intravenously (or equivalent). For the first 4 infusions, intravenous administration is recommended.
Antimicrobial prophylaxis: Consider initiating antibacterial and antiviral prophylaxis (e.g., varicella‑zoster virus prophylaxis) according to standard guidelines.
4. Dose Adjustments
Dose reduction of isatuximab is not recommended. In case of hematologic toxicity, dose delay may be needed to allow recovery of blood cell counts.
5. Preparation
Calculate the total required dose (in mg) based on the patient’s body weight.
From a 250 mL infusion bag of 0.9% sodium chloride injection or 5% dextrose injection, withdraw a volume of diluent equal to the required volume of isatuximab intravenous injection.
Withdraw the required volume of isatuximab concentrate from the vial and add it to the infusion bag for dilution. Discard any unused portion remaining in the vial.
The infusion bag material must be polyolefin, polyethylene, polypropylene, PVC containing DEHP, or ethylene‑vinyl acetate.
Gently invert the infusion bag to mix the diluted solution. Do not shake.
6. Administration
Administer by intravenous infusion using an infusion line (material: PE, PVC with or without DEHP, polybutadiene, or polyurethane) equipped with a 0.22‑micron in‑line filter.
The infusion time depends on the infusion rate.
The prepared infusion solution may be stored under refrigeration for 48 hours, followed by up to 8 hours at room temperature.
Do not co‑administer other drugs through the same intravenous line.
On days when isatuximab and carfilzomib are given on the same day, the order of administration should be: dexamethasone first, then isatuximab, and finally carfilzomib.
7. Infusion Rates
The recommended infusion rates should be followed and adjusted based on the patient’s tolerability. Rate escalation should be considered only in the absence of infusion‑related reactions.
