Sarclisa

Q: Who makes Sarclisa?

Sarclisa is listed by 1 labeler in the FDA NDC directory, including Sanofi-Aventis U.S. LLC.

isatuximab · Injection, Solution, Concentrate · Intravenous

Prescription (Rx) CD38-directed Cytolytic Antibody

Uses

1 INDICATIONS AND USAGE SARCLISA is indicated: in combination with pomalidomide and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor. in combination with carfilzomib and dexamethasone, for the treatment of adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy. in combination with bortezomib, lenalidomide, and dexamethasone, for the treatment of adult patients with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant (ASCT). SARCLISA is a CD38-directed cytolytic antibody indicated: in combination with pomalidomide and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor. in combination with carfilzomib and dexamethasone, for the treatment of adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy. in combination with bortezomib, lenalidomide and dexamethasone, for the treatment of adult patients with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant (ASCT). ( 1 )

Dosage and administration

Premedicate with dexamethasone, acetaminophen, H2 antagonists, and diphenhydramine. ( 2.2 ) The recommended dosage of SARCLISA is 10 mg/kg as an intravenous infusion. See full prescribing information for SARCLISA schedules of administration and drugs used in combination. ( 2.1 ) 2.1 Recommended Dosage Administer pre-infusion medications [see Dosage and Administration (2.2) ] . SARCLISA should be administered by a healthcare professional, with immediate access to emergency equipment and appropriate medical support to manage infusion-related reactions if they occur [see Warnings and Precautions (5.1) ] . The recommended dose of SARCLISA is 10 mg/kg actual body weight administered as an intravenous infusion in combination with pomalidomide and dexamethasone or in combination with carfilzomib and dexamethasone, or in combination with bortezomib, lenalidomide, and dexamethasone. SARCLISA dosing schedules are provided in Tables 1 and 2 [see Clinical Studies (14) ]. Table 1: SARCLISA Dosing Schedule in Combination with Pomalidomide and Dexamethasone or in Combination with Carfilzomib and Dexamethasone Cycles Dosing schedules Cycle 1 (28-day cycle) Days 1, 8, 15, and 22 (weekly) Cycle 2 and beyond (28-day cycles) Days 1, 15 (every 2 weeks) Table 2: SARCLISA Dosing Schedule in Combination with Bortezomib, Lenalidomide, and Dexamethasone Cycles Dosing schedules Cycle 1 (42-day cycle) Days 1, 8, 15, 22, and 29 Cycles 2 to 4 (42-day cycles) Days 1, 15, and 29 (every 2 weeks) Cycles 5 to 17 (28-day cycles) Days 1 and 15 (every 2 weeks) Cycles 18 and beyond (28-day cycles) Day 1 (every 4 weeks) Treatment is repeated until disease progression or unacceptable toxicity. SARCLISA is used in combination with pomalidomide and dexamethasone or in combination with carfilzomib and dexamethasone or in combination with bortezomib, lenalidomide, and dexamethasone. For dosing instructions of combination agents administered with SARCLISA, see Clinical Studies (14) and manufacturer's prescribing information. Missed SARCLISA Doses 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. 2.2 Recommended Premedications and Antimicrobial Prophylaxis Recommended Premedications Administer the following premedications prior to SARCLISA infusion to reduce the risk and severity of infusion-related reactions [see Warnings and Precautions (5.1) ] : When administered in combination with SARCLISA and pomalidomide: Dexamethasone 40 mg orally or intravenously (or 20 mg orally or intravenously for patients ≥75 years of age). When administered in combination with SARCLISA and carfilzomib: Dexamethasone 20 mg (intravenously on the days of SARCLISA and/or carfilzomib infusions, orally on day 22 in cycle 2 and beyond, and orally on day 23 in all cycles). When administered in combination with SARCLISA, bortezomib, and lenalidomide: Dexamethasone 20 mg (intravenously on the days of SARCLISA infusions, orally on the other days). Acetaminophen 650 mg to 1,000 mg orally (or equivalent). H2 antagonist Diphenhydramine 25 mg to 50 mg orally or intravenously (or equivalent). The intravenous route is preferred for at least the first 4 infusions. The above recommended dose of dexamethasone (orally or intravenously) corresponds to the dose to be administered before infusion as part of the premedication and part of the backbone treatment. Administer dexamethasone before SARCLISA and pomalidomide, before SARCLISA and carfilzomib, and before SARCLISA, bortezomib, and lenalidomide administration. Administer the recommended premedication agents 15 to 60 minutes prior to starting a SARCLISA infusion. Recommended Antimicrobial Prophylaxis Initiate antibacterial and antiviral prophylaxis (such as herpes zoster prophylaxis) if needed based on standard guidelines [see Warnings and Precautions (5.2) ] . 2.3 Dosage Modifications No dose reduction of SARCLISA is recommended. Dose delay may be required to allow recovery of blood counts in the event of hematological toxicity [see Warnings and Precautions (5.3 , 5.5) ] . For information concerning drugs given in combination with SARCLISA, see manufacturer's prescribing information. 2.4 Preparation Prepare the solution for infusion using aseptic technique as follows: Calculate the dose (mg) of required SARCLISA based on actual patient weight (measured prior to each cycle to have the administered dose adjusted accordingly) [see Dosage and Administration (2.1) ] . More than one SARCLISA vial may be necessary to obtain the required dose for the patient. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Remove the volume of diluent from the 250 mL Sodium Chloride Injection, or 5% Dextrose Injection, diluent bag that is equal to the required volume of SARCLISA injection. Withdraw the necessary volume of SARCLISA injection from the vial and dilute by adding to the infusion bag of 0.9% Sodium Chloride Injection, or 5% Dextrose Injection. Discard any unused portion left in the vial. 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. 2.5 Administration Administer the infusion solution 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 Table 3 ). Use prepared SARCLISA infusion solution within 48 hours when stored refrigerated at 2°C to 8°C, followed by 8 hours (including the infusion time) at room temperature.

Dosage forms and strengths

3 DOSAGE FORMS AND STRENGTHS SARCLISA is a clear to slightly opalescent, colorless to slightly yellow solution, essentially free of visible particulates available as: Injection: 100 mg/5 mL (20 mg/mL) in a single-dose vial Injection: 500 mg/25 mL (20 mg/mL) in a single-dose vial Injection: 100 mg/5 mL (20 mg/mL) solution in single-dose vial ( 3 ) 500 mg/25 mL (20 mg/mL) solution in single-dose vial ( 3 )

Contraindications

4 CONTRAINDICATIONS SARCLISA is contraindicated in patients with severe hypersensitivity to isatuximab-irfc or to any of its excipients [see Warnings and Precautions (5.1) ] . Patients with severe hypersensitivity to isatuximab-irfc or to any of its excipients. ( 4 )

Warnings and precautions

Infusion-Related Reactions : In case of grade ≥2, interrupt SARCLISA and manage medically. Permanently discontinue for grade 4 infusion-related reactions or anaphylactic reaction. ( 5.1 ) Infections : SARCLISA can cause serious and fatal infections. Monitor patients for signs and symptoms of infection and treat appropriately. ( 5.2 ) Neutropenia : Monitor complete blood cell counts periodically during treatment. Monitor patients with neutropenia for signs of infection. SARCLISA dose delays and the use of colony-stimulating factor may be required to allow improvement of neutrophil count. ( 5.3 ) Second Primary Malignancies (SPM) : Monitor patients for the development of second primary malignancies. ( 5.4 ) Laboratory Test Interference : Interference with Serological Testing (Indirect Antiglobulin Test): Type and screen patients prior to starting treatment. Inform blood banks that a patient has received SARCLISA. ( 5.5 , 7.1 ) Interference with Serum Protein Electrophoresis and Immunofixation Tests: SARCLISA may interfere with the assays used to monitor M-protein, which may impact the determination of complete response. ( 5.5 , 7.1 ) Embryo-Fetal Toxicity : Can cause fetal harm. ( 5.6 ) 5.1 Infusion-Related Reactions SARCLISA can cause severe and/or serious infusion-related reactions including anaphylactic reactions. These reactions can be life-threatening and fatal outcomes have been reported [see Adverse Reactions (6.2) ]. Severe signs and symptoms included cardiac arrest, hypertension, hypotension, bronchospasm, dyspnea, angioedema, and swelling. In clinical trials (ICARIA-MM, IKEMA, and IMROZ), in patients treated with SARCLISA (N=592), infusion-related reactions occurred in 206 patients (35%). Among these 206 patients, 92% experienced infusion-related reactions during the first infusion and 12% after the first cycle. The most common symptoms (≥5%) of an infusion-related reaction included dyspnea and cough. Grade 1 infusion-related reactions were reported in 6% of patients, grade 2 in 28%, and grade 3 or 4 in 1.2%. Anaphylactic reactions occurred in less than 1% of patients. The total incidence of SARCLISA infusion interruptions was less than 1% and the incidence of patients with at least one SARCLISA infusion interruption due to infusion-related reactions was 26%. The median time to first SARCLISA infusion interruption was 61 minutes (range 4 to 240 minutes). SARCLISA was discontinued in 1% of patients due to infusion-related reactions. To decrease the risk and severity of infusion-related reactions, premedicate patients prior to SARCLISA infusion with acetaminophen, H2 antagonists, diphenhydramine, or equivalent, and dexamethasone [see Dosage and Administration (2.2) ] . Monitor vital signs frequently during the entire SARCLISA infusion. For patients with grade ≥2 reactions, interrupt SARCLISA infusion and provide appropriate medical management. For patients with grade 2 or grade 3 reactions, if symptoms improve to grade ≤1, restart SARCLISA infusion at half of the initial infusion rate, with supportive care as needed, and closely monitor patients. 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 3 [see Dosage and Administration (2.5) ] . In case symptoms do not improve to grade ≤1 after interruption of SARCLISA infusion, persist or worsen despite appropriate medications, or require hospitalization, permanently discontinue SARCLISA and institute appropriate management. Permanently discontinue SARCLISA if an anaphylactic reaction or life-threatening (grade 4) infusion-related reaction occurs and institute appropriate management. 5.2 Infections SARCLISA can cause severe, life-threatening, or fatal infections. In patients who received SARCLISA at the recommended dose in ICARIA-MM, IKEMA, and IMROZ (N=592), serious infections, including opportunistic infections, occurred in 46% of patients, grade 3 or 4 infections occurred in 43%, and fatal infections occurred in 4.7%. The most common type of serious infection reported was pneumonia (32%). Monitor patients for signs and symptoms of infection prior to and during treatment with SARCLISA and treat appropriately. Administer prophylactic antimicrobials according to guidelines [see Dosage and Administration (2.2) ] . 5.3 Neutropenia SARCLISA can cause neutropenia. In clinical trials (ICARIA-MM, IKEMA, and IMROZ), in patients treated with SARCLISA (N=592), neutropenia based on laboratory values occurred in 81%, with grade 3 or 4 occurring in 52%. Neutropenic infections occurred in 12% of patients, with grade 3 or 4 in 4.9%, and febrile neutropenia in 4% [see Adverse Reactions (6.1) ] . Monitor complete blood cell counts periodically during treatment. If needed, use antibacterial and antiviral prophylaxis during treatment [see Dosage and Administration (2.2) ] . Monitor patients with neutropenia for signs of infection. In case of grade 4 neutropenia delay SARCLISA dose until neutrophil count recovery to at least 1 × 10 9 /L, and provide supportive care with growth factors, according to institutional guidelines. No dose reductions of SARCLISA are recommended. 5.4 Second Primary Malignancies The incidence of second primary malignancies, during treatment and post-treatment, is increased in patients treated with SARCLISA-containing regimens. In clinical trials (ICARIA-MM, IKEMA, and IMROZ), in patients treated with SARCLISA (N=592), second primary malignancies occurred in 71 patients (12%). In ICARIA-MM, at a median follow-up time of 52 months, second primary malignancies occurred in 7% of patients in the Isa-Pd arm and in 2% of patients in the Pd arm. In IKEMA study, at a median follow-up time of 57 months, second primary malignancies occurred in 10% of patients in the Isa-Kd arm and in 8% of patients in the Kd arm.

Side effects

The following clinically significant adverse reactions from SARCLISA are also described in other sections of the labeling: Infusion-Related Reactions [see Warnings and Precautions (5.1) ] Infections [see Warnings and Precautions (5.2) ] Neutropenia [see Warnings and Precautions (5.3) ] Second Primary Malignancies [see Warnings and Precautions (5.4) ] In combination with pomalidomide and dexamethasone : The most common adverse reactions (≥20%) are upper respiratory tract infection, infusion-related reactions, pneumonia, and diarrhea. The most common hematology laboratory abnormalities (≥80%) are decreased hemoglobin, decreased neutrophils, decreased lymphocytes, and decreased platelets. ( 6.1 ) In combination with carfilzomib and dexamethasone : The most common adverse reactions (≥20%) are upper respiratory tract infection, infusion-related reactions, fatigue, hypertension, diarrhea, pneumonia, dyspnea, insomnia, bronchitis, cough, and back pain. The most common hematology laboratory abnormalities (≥80%) are decreased hemoglobin, decreased lymphocytes, and decreased platelets. ( 6.1 ) In combination with bortezomib, lenalidomide and dexamethasone : The most common adverse reactions (≥20%) are upper respiratory tract infections, diarrhea, fatigue, peripheral sensory neuropathy, pneumonia, musculoskeletal pain, cataract, constipation, peripheral edema, rash, infusion-related reaction, insomnia, and COVID-19. The most common hematologic laboratory abnormalities (≥80%) are decreased hemoglobin, decreased leukocytes, decreased lymphocytes, decreased platelets, and decreased neutrophils. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact sanofi-aventis U.S. LLC at 1-800-633-1610 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Relapsed and/or Refractory Multiple Myeloma Combination treatment with pomalidomide and dexamethasone (Isa-Pd) The safety of SARCLISA was evaluated in ICARIA-MM, a randomized, open-label clinical trial in patients with previously treated multiple myeloma. Patients received SARCLISA 10 mg/kg intravenously, weekly in the first cycle and every two weeks thereafter, in combination with pomalidomide and dexamethasone (Isa-Pd) (n=152) or pomalidomide and dexamethasone (Pd) (n=149) [see Clinical Studies (14) ] . Among patients receiving Isa-Pd, 66% were exposed to SARCLISA for 6 months or longer and 24% were exposed for greater than 12 months or longer. Serious adverse reactions occurred in 62% of patients receiving Isa-Pd. Serious adverse reactions in >5% of patients who received Isa-Pd included pneumonia (26%), upper respiratory tract infections (7%), and febrile neutropenia (7%). Fatal adverse reactions occurred in 11% of patients (those that occurred in more than 1% of patients were pneumonia and other infections [3%]). Permanent treatment discontinuation due to an adverse reaction (grades 1–4) occurred in 7% of patients who received Isa-Pd. The most frequent adverse reactions requiring permanent discontinuation in patients who received Isa-Pd were infections (2.6%). SARCLISA alone was discontinued in 3% of patients due to infusion-related reactions. Dosage interruptions due to an adverse reaction occurred in 31% of patients who received SARCLISA. The most frequent adverse reaction requiring dosage interruption was infusion-related reaction (28%). The most common adverse reactions (≥20%) were upper respiratory tract infection, infusion-related reactions, pneumonia, and diarrhea. Table 4 summarizes the adverse reactions in ICARIA-MM. Table 4: Adverse Reactions (≥10%) in Patients Receiving SARCLISA, Pomalidomide, and Dexamethasone with a Difference Between Arms of ≥5% Compared to Control Arm in ICARIA-MM Trial Adverse Reactions SARCLISA + Pomalidomide + Dexamethasone (Isa-Pd) Pomalidomide + Dexamethasone (Pd) (N=152) (N=149) All Grades (%) Grade 3 (%) Grade 4 (%) All Grades (%) Grade 3 (%) Grade 4 (%) CTCAE version 4.03 General disorders and administration site conditions Infusion-related reaction Infusion-related reaction includes infusion-related reaction, cytokine release syndrome, and drug hypersensitivity. 38 1.3 1.3 0 0 0 Infections Upper respiratory tract infection Upper respiratory tract infection includes bronchiolitis, bronchitis, bronchitis viral, chronic sinusitis, fungal pharyngitis, influenza-like illness, laryngitis, nasopharyngitis, parainfluenzae virus infection, pharyngitis, respiratory tract infection, respiratory tract infection viral, rhinitis, sinusitis, tracheitis, upper respiratory tract infection, and upper respiratory tract infection bacterial. 57 9 0 42 3.4 0 Pneumonia Pneumonia includes atypical pneumonia, bronchopulmonary aspergillosis, pneumonia, pneumonia haemophilus, pneumonia influenzal, pneumonia pneumococcal, pneumonia streptococcal, pneumonia viral, candida pneumonia, pneumonia bacterial, haemophilus infection, lung infection, pneumonia fungal, and pneumocystis jirovecii pneumonia. 31 22 3.3 23 16 2.7 Blood and lymphatic system disorders Febrile neutropenia 12 11 1.3 2 1.3 0.7 Respiratory, thoracic and mediastinal disorders Dyspnea Dyspnea includes dyspnea, dyspnea exertional, and dyspnea at rest. 17 5 0 12 1.3 0 Gastrointestinal disorders Diarrhea 26 2 0 19 0.7 0 Nausea 15 0 0 9 0 0 Vomiting 12 1.3 0 3.4 0 0 Table 5 summarizes the hematology laboratory abnormalities in ICARIA-MM.

Drug interactions

7.1 Laboratory Test Interference Interference with Serological Testing SARCLISA, an anti-CD38 antibody, may interfere with blood bank serologic tests with false positive reactions in indirect antiglobulin tests (indirect Coombs tests), antibody detection (screening) tests, antibody identification panels, and antihuman globulin crossmatches in patients treated with SARCLISA [see Warnings and Precautions (5.5) ] . Interference with Serum Protein Electrophoresis and Immunofixation Tests SARCLISA may be incidentally detected by serum protein electrophoresis and immunofixation assays used for the monitoring of M-protein and may interfere with accurate response classification based on International Myeloma Working Group (IMWG) criteria [see Warnings and Precautions (5.5) ] . In patients with persistent very good partial response, where interference is suspected, consider using an FDA-cleared isatuximab-irfc-specific IFE assay to distinguish isatuximab from any remaining endogenous M protein in the patient's serum to facilitate determination of a complete response.

Use in specific populations

Lactation : Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary SARCLISA can cause fetal harm when administered to a pregnant woman. The assessment of isatuximab-irfc-associated risks is based on the mechanism of action and data from target antigen CD38 knockout animal models (see Data ). There are no available data on SARCLISA use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Animal reproduction toxicity studies have not been conducted with isatuximab-irfc. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, miscarriage, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The combination of SARCLISA and pomalidomide or lenalidomide is contraindicated in pregnant women because pomalidomide and lenalidomide may cause birth defects and death of the unborn child. Refer to the pomalidomide or lenalidomide prescribing information on use during pregnancy. Pomalidomide and lenalidomide are only available through a REMS program. Clinical Considerations Fetal/neonatal reactions Immunoglobulin G1 monoclonal antibodies are known to cross the placenta. Based on its mechanism of action, SARCLISA may cause depletion of fetal CD38-positive immune cells and decreased bone density. Defer administration of live vaccines to neonates and infants exposed to SARCLISA in utero until a hematology evaluation is completed. Data Animal data Mice that were genetically modified to eliminate all CD38 expression (CD38 knockout mice) had reduced bone density which recovered 5 months after birth. Data from studies using CD38 knockout animal models also suggest the involvement of CD38 in regulating humoral immune responses (mice), feto-maternal immune tolerance (mice), and early embryonic development (frogs). 8.2 Lactation Risk Summary There are no available data on the presence of isatuximab-irfc in human milk, milk production, or the effects on the breastfed child. Maternal immunoglobulin G is known to be present in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed infant to SARCLISA are unknown. Because of the potential for serious adverse reactions in the breastfed child from isatuximab-irfc administered in combination with pomalidomide or lenalidomide and dexamethasone, advise lactating women not to breastfeed during treatment with SARCLISA. Refer to pomalidomide or lenalidomide prescribing information for additional information. 8.3 Females and Males of Reproductive Potential SARCLISA can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] . Pregnancy Testing With the combination of SARCLISA with pomalidomide or lenalidomide, refer to the pomalidomide or lenalidomide labeling for pregnancy testing requirements prior to initiating treatment in females of reproductive potential. Contraception Females Advise female patients of reproductive potential to use effective contraception during treatment and for 5 months after the last dose of SARCLISA. Additionally, refer to the pomalidomide or lenalidomide labeling for contraception requirements prior to initiating treatment in females of reproductive potential. Males Refer to the pomalidomide or lenalidomide prescribing information. 8.4 Pediatric Use The safety and effectiveness of SARCLISA in pediatric patients have not been established. The safety and efficacy of SARCLISA in combination with chemotherapy were assessed, but not established, in an open-label study (ACT15378, ISAKIDS, NCT03860844) in 62 pediatric patients aged 1.4 years to < 17 years with relapsed or refractory T-acute lymphoblastic leukemia (T-ALL), B-acute lymphoblastic leukemia (B-ALL), or acute myeloid leukemia (AML). No new safety signals were observed in pediatric patients in this trial. Body weight adjusted clearance at steady state and volume of distribution of isatuximab in pediatric patients were within the range of values that were observed in adults. 8.5 Geriatric Use Of the total number of patients with relapsed or refractory multiple myeloma in clinical studies of SARCLISA, 56% (n=586) were 65 years of age and older, while 16% (n=163) were 75 years of age and older [see Clinical Studies (14) ] . No overall differences in safety or effectiveness were observed between patients 65 years of age and older compared to younger patients, and other reported clinical experience has not identified differences in responses between the adults 65 years of age and older and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Of the total number of SARCLISA-treated patients with newly diagnosed multiple myeloma in IMROZ, 72% (n=319) were less than 75 years of age and 28% (n=125) were 75 years of age and older. The clinical trial did not enroll patients over age 80 [see Clinical Studies (14) ] . Adverse reactions occurring at a higher frequency in the SARCLISA arm (≥5%) in patients 75 years of age and older included neutropenia. Adverse reactions leading to dose modifications in patients 75 years of age and older occurred at a higher frequency (≥5%) in the SARCLISA arm. The hazard ratio for overall survival (OS) in patients 75 years of age and older was 1.25 [95% CI: 0.68 to 2.3].

Pregnancy

8.1 Pregnancy Risk Summary SARCLISA can cause fetal harm when administered to a pregnant woman. The assessment of isatuximab-irfc-associated risks is based on the mechanism of action and data from target antigen CD38 knockout animal models (see Data ). There are no available data on SARCLISA use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Animal reproduction toxicity studies have not been conducted with isatuximab-irfc. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, miscarriage, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The combination of SARCLISA and pomalidomide or lenalidomide is contraindicated in pregnant women because pomalidomide and lenalidomide may cause birth defects and death of the unborn child. Refer to the pomalidomide or lenalidomide prescribing information on use during pregnancy. Pomalidomide and lenalidomide are only available through a REMS program. Clinical Considerations Fetal/neonatal reactions Immunoglobulin G1 monoclonal antibodies are known to cross the placenta. Based on its mechanism of action, SARCLISA may cause depletion of fetal CD38-positive immune cells and decreased bone density. Defer administration of live vaccines to neonates and infants exposed to SARCLISA in utero until a hematology evaluation is completed. Data Animal data Mice that were genetically modified to eliminate all CD38 expression (CD38 knockout mice) had reduced bone density which recovered 5 months after birth. Data from studies using CD38 knockout animal models also suggest the involvement of CD38 in regulating humoral immune responses (mice), feto-maternal immune tolerance (mice), and early embryonic development (frogs).

Pediatric use

8.4 Pediatric Use The safety and effectiveness of SARCLISA in pediatric patients have not been established. The safety and efficacy of SARCLISA in combination with chemotherapy were assessed, but not established, in an open-label study (ACT15378, ISAKIDS, NCT03860844) in 62 pediatric patients aged 1.4 years to < 17 years with relapsed or refractory T-acute lymphoblastic leukemia (T-ALL), B-acute lymphoblastic leukemia (B-ALL), or acute myeloid leukemia (AML). No new safety signals were observed in pediatric patients in this trial. Body weight adjusted clearance at steady state and volume of distribution of isatuximab in pediatric patients were within the range of values that were observed in adults.

Geriatric use

8.5 Geriatric Use Of the total number of patients with relapsed or refractory multiple myeloma in clinical studies of SARCLISA, 56% (n=586) were 65 years of age and older, while 16% (n=163) were 75 years of age and older [see Clinical Studies (14) ] . No overall differences in safety or effectiveness were observed between patients 65 years of age and older compared to younger patients, and other reported clinical experience has not identified differences in responses between the adults 65 years of age and older and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Of the total number of SARCLISA-treated patients with newly diagnosed multiple myeloma in IMROZ, 72% (n=319) were less than 75 years of age and 28% (n=125) were 75 years of age and older. The clinical trial did not enroll patients over age 80 [see Clinical Studies (14) ] . Adverse reactions occurring at a higher frequency in the SARCLISA arm (≥5%) in patients 75 years of age and older included neutropenia. Adverse reactions leading to dose modifications in patients 75 years of age and older occurred at a higher frequency (≥5%) in the SARCLISA arm. The hazard ratio for overall survival (OS) in patients 75 years of age and older was 1.25 [95% CI: 0.68 to 2.3].

Description

Isatuximab-irfc, a CD38-directed cytolytic antibody, is a chimeric immunoglobulin G1 (IgG1) monoclonal antibody (mAb). Isatuximab-irfc is produced from a mammalian cell line (Chinese hamster ovary, CHO) using a fed-batch production process. Isatuximab-irfc is composed of two identical immunoglobulin kappa light chains and two identical immunoglobulin gamma heavy chains and has an overall molecular weight of approximately 148 kDa. SARCLISA (isatuximab-irfc) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution, essentially free of visible particles in a single-dose vial for intravenous use. Each vial contains either 100 mg/5 mL or 500 mg/25 mL of isatuximab-irfc at a concentration of 20 mg/mL with a pH of 6.0. Each mL of solution contains 20 mg isatuximab-irfc, histidine (1.46 mg), histidine hydrochloride monohydrate (2.22 mg), polysorbate 80 (0.2 mg), sucrose (100 mg), and water for injection.

Mechanism of action

12.1 Mechanism of Action Isatuximab-irfc is an IgG1-derived monoclonal antibody that binds to CD38 expressed on the surface of hematopoietic and tumor cells, including multiple myeloma cells. Isatuximab-irfc induces apoptosis of tumor cells and activation of immune effector mechanisms including antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement dependent cytotoxicity (CDC). Isatuximab-irfc inhibits the ADP-ribosyl cyclase activity of CD38. Isatuximab-irfc can activate natural killer (NK) cells in the absence of CD38-positive target tumor cells and suppresses CD38-positive T-regulatory cells. The combination of isatuximab-irfc and pomalidomide enhanced ADCC activity and direct tumor cell killing compared to that of isatuximab-irfc alone in vitro , and enhanced antitumor activity compared to the activity of isatuximab-irfc or pomalidomide alone in a human multiple myeloma xenograft model.

How supplied

How Supplied SARCLISA (isatuximab-irfc) injection is a clear to slightly opalescent, colorless to slightly yellow solution, essentially free of visible particulates, supplied as follows: One 100 mg/5 mL (20 mg/mL) single-dose vial in a carton: NDC 0024-0654-01 One 500 mg/25 mL (20 mg/mL) single-dose vial in a carton: NDC 0024-0656-01 Storage Store in a refrigerator at 36°F to 46°F (2°C to 8°C) in the original carton to protect from light. Do not freeze. Do not shake. Handling and Disposal Discard unused portion of solution. All materials that have been utilized for dilution and administration should be disposed of according to standard procedures.

Storage

Storage Store in a refrigerator at 36°F to 46°F (2°C to 8°C) in the original carton to protect from light. Do not freeze. Do not shake. Handling and Disposal Discard unused portion of solution. All materials that have been utilized for dilution and administration should be disposed of according to standard procedures.

Patient information

Advise the patient to read the FDA-approved patient labeling (Patient Information). Infusion-Related Reaction Advise patients to seek immediate medical attention for any of the following signs and symptoms of infusion-related reactions: shortness of breath, wheezing or trouble breathing; swelling of the face, mouth, throat, or tongue; throat tightness; palpitations; dizziness, lightheadedness, or fainting; headache; cough; rash or itching; nausea; runny or stuffy nose; or chills [see Warnings and Precautions (5.1) ] . Infections Inform patients about the risk of developing infections during SARCLISA treatment, and to report immediately any fever or symptoms of infection to their healthcare provider [see Warnings and Precautions (5.2) ] . Neutropenia Inform patients about the risk of neutropenia and infection during SARCLISA treatment and the importance of reporting immediately any fever or symptoms of infection to their healthcare provider [see Warnings and Precautions (5.3) and Adverse Reactions (6.1) ] . Second Primary Malignancies Inform patients of the risk of developing second primary malignancies during treatment with SARCLISA when given with pomalidomide and dexamethasone or with carfilzomib and dexamethasone, or with bortezomib, lenalidomide, and dexamethasone [see Warnings and Precautions (5.4) ] . Cardiac Toxicities Inform patients about the risk of cardiac failure during treatment with SARCLISA when given with carfilzomib and dexamethasone, and the importance of reporting immediately any difficulty breathing, cough, or leg swelling to their healthcare provider [see Adverse Reactions (6.1) ] . Interference with Laboratory Tests Advise patients to inform healthcare providers and transfusion center personnel that they are treated with SARCLISA in case a red blood cell transfusion is planned. Advise patients that SARCLISA may affect the results of blood tests to match their blood type for approximately 6 months after their last infusion of SARCLISA [see Warnings and Precautions (5.5) and Drug Interactions (7.1) ] . Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 5 months after the last dose of SARCLISA [see Use in Specific Populations (8.1 , 8.3) ] . Advise patients that pomalidomide or lenalidomide have the potential to cause fetal harm and have specific requirements regarding contraception, pregnancy testing, blood and sperm donation, and transmission in sperm. Advise patients to report suspected or known pregnancies. Pomalidomide and lenalidomide are only available through a REMS program [see Use in Specific Populations (8.1 , 8.3) ] .

Label text from the FDA structured product label by Sanofi-Aventis U.S. LLC (revised Jul 7, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Isatuximab in 2 products

Sarclisa NDC products (2)

NDC	Strength & form	Labeler	Type
0024-0654	Isatuximab 100 mg/5mL Injection, Solution, Concentrate	Sanofi-Aventis U.S. LLC	BLA
0024-0656	Isatuximab 500 mg/25mL Injection, Solution, Concentrate	Sanofi-Aventis U.S. LLC	BLA

Frequently asked questions

What is Sarclisa used for?

What are the side effects of Sarclisa?

Who makes Sarclisa?

Sarclisa is listed by 1 labeler in the FDA NDC directory, including Sanofi-Aventis U.S. LLC.