Isatuximab-irfc (Monograph)

Brand name: Sarclisa
Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Sep 10, 2025. Written by ASHP.

Introduction

Antineoplastic agent; a chimeric anti-CD38 monoclonal antibody.

Uses for Isatuximab-irfc

Multiple Myeloma

Used in combination with pomalidomide and dexamethasone for the treatment of multiple myeloma in adults who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor (designated an orphan drug by FDA for use in multiple myeloma).

Used in combination with carfilzomib and dexamethasone for the treatment of relapsed or refractory multiple myeloma in adults who have received 1 to 3 prior lines of therapy.

Used in combination with bortezomib, lenalidomide, and dexamethasone for the treatment of newly diagnosed multiple myeloma in adults who are not eligible for autologous stem cell transplant (ASCT).

Isatuximab-irfc Dosage and Administration

General

Pretreatment Screening

Because false positive indirect antiglobulin tests (indirect Coombs’ test) may occur during therapy with isatuximab, perform blood typing and screening prior to the first isatuximab infusion.

Patient Monitoring

Monitor vital signs frequently during isatuximab infusion.
Monitor patients for signs and symptoms of infection prior to and during treatment with isatuximab.
Monitor CBCs periodically during treatment.
Monitor patients for development of second primary malignancies.

Premedication and Prophylaxis

Administer the following premedications 15–60 minutes prior to each infusion to minimize the risk of infusion-related effects:
When administered in combination with isatuximab-irfc and pomalidomide: Dexamethasone 40 mg orally or IV (or 20 mg orally or IV for patients ≥75 years of age).
When administered in combination with isatuximab-irfc and carfilzomib: Dexamethasone 20 mg (IV on the days of isatuximab-irfc 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 isatuximab-irfc, bortezomib, and lenalidomide: Dexamethasone 20 mg (IV on the days of isatuximab-irfc infusions, orally on the other days).
In all patients, administer acetaminophen 650 mg to 1000 mg orally (or equivalent).
In all patients, administer an H₂ antagonist.
In all patients, administer diphenhydramine 25 mg to 50 mg orally or IV (or equivalent). The IV route is preferred for at least the first 4 infusions.
In all patients, initiate antibacterial and antiviral prophylaxis (e.g., herpes zoster prophylaxis) if needed based on standard guidelines.

Dispensing and Administration Precautions

Administer only in settings where emergency equipment and appropriate medical support is available to manage infusion-related reactions.

Administration

IV Administration

Administer by IV infusion using a polyurethane (PU), polybutadiene (PBD), polyvinyl chloride (PVC), or polyethylene (PE) infusion set equipped with a nylon, polysulfone, or polyethersulfone (PES) 0.22-µm inline filter.

Do not infuse simultaneously through the same IV line with any other drug.

If a dose is missed, administer dose as soon as possible. Adjust administration schedule to maintain appropriate treatment interval between doses.

Dilution

Must be diluted prior to IV infusion.

Remove the volume of diluent equal to the total required volume of injection concentrate from a 250-mL bag of 0.9% sodium chloride injection or 5% dextrose injection. Add the required volume of injection concentrate to the diluent in the polyolefin, polypropylene, ethyl vinyl acetate, PVC with di-(2-ethylhexyl) phthalate (DEHP), or PE infusion bag. Gently invert bag to mix solution; do not shake.

Discard any unused portions of the injection concentrate or diluted solution.

Rate of Administration

An incremental escalation of the infusion rate may be considered in the absence of infusion-related reactions. (See Table 1.)

Table 1. Recommended Incremental Escalation of Isatuximab-irfc Infusion Rate.1
Infusion	Initial Infusion Rate	Incremental Escalation of Infusion Rate
First	25 mL/hour	If infusion-related reactions do not occur after 60 minutes, increase infusion rate in increments of 25 mL/hour every 30 minutes to maximum rate of 150 mL/hour
Second	50 mL/hour	If infusion-related reactions do not occur after 30 minutes, continue current infusion rate (50 mL/hour) for 30 minutes then increase in increments of 100 mL/hour to maximum rate of 200 mL/hour
Subsequent	200 mL/hour	Do not exceed maximum rate of 200 mL/hour

For grade 2 or 3 infusion-related reactions, interrupt the infusion until the reaction has improved to grade 0 or 1. Upon resumption, reduce the rate by 50%; if the reaction does not recur following resumption at a reduced rate after 30 minutes, increase infusion rate to initial rate, followed by an incremental escalation of the infusion rate (see Table 1).

For grade 2 or 3 infusion-related reactions that do not improve following interruption of the infusion, persist or worsen despite appropriate symptomatic and supportive therapy, or require hospitalization, permanently discontinue therapy.

For grade 4 infusion-related reactions, permanently discontinue therapy.

Dosage

Calculate dosage based on actual body weight prior to each dose.

Consult the respective manufacturers' labeling or published protocols for information on the dosage, method of administration, and administration sequence of other antineoplastic agents used in combination regimens.

Adults

Multiple Myeloma (Combination with Pomalidomide and Dexamethasone)

IV

Cycle 1: 10 mg/kg on days 1, 8, 15, and 22 during cycle 1. Subsequent cycles: 10 mg/kg on days 1 and 15.

Repeat treatment cycles every 28 days.

Continue therapy until disease progression or unacceptable toxicity occurs.

Multiple Myeloma (Combination with Carfilzomib and Dexamethasone)

IV

Cycle 1: 10 mg/kg on days 1, 8, 15, and 22 during cycle 1. Subsequent cycles: 10 mg/kg on days 1 and 15.

Repeat treatment cycles every 28 days.

Continue therapy until disease progression or unacceptable toxicity occurs.

On the days where both isatuximab and carfilzomib are administered, administer dexamethasone first, followed by isatuximab and then carfilzomib.

Multiple Myeloma (Combination with Bortezomib, Lenalidomide, and Dexamethasone)

IV

Cycle 1 (42-day cycle): 10 mg/kg on days 1, 8, 15, 22, and 29.

Cycles 2 to 4 (42-day cycles): 10 mg/kg on days 1, 15, and 29.

Cycles 5 to 17 (28-day cycles): 10 mg/kg on days 1 and 15.

Cycles 18 and beyond (28-day cycles): 10 mg/kg on day 1 of each cycle.

Continue therapy until disease progression or unacceptable toxicity occurs.

Dosage Modification for Toxicity

No dosage reductions are recommended for adverse effects.

Hematologic Effects

For grade 4 neutropenia, interrupt treatment until neutrophil count recovers to ≥1000/mm³.

Infusion-related Effects

For grade 2 or greater infusion-related reactions, reduce infusion rate or permanently discontinue therapy depending on severity of reaction, and provide appropriate symptomatic and supportive therapy.

For grade 4 infusion-related reactions, permanently discontinue therapy.

Special Populations

Hepatic Impairment

Mild hepatic impairment (total bilirubin concentrations exceeding the ULN, but ≤1.5 times the ULN, or AST concentrations exceeding the ULN): No dosage adjustment required.

Renal Impairment

Mild to severe renal impairment (estimated glomerular filtration rate [eGFR] <90 mL/minute per 1.73 m²): No dosage adjustment required.

Geriatric Patients

No specific dosage recommendations.

Cautions for Isatuximab-irfc

Contraindications

Severe hypersensitivity to isatuximab or any ingredient in the formulation.

Warnings/Precautions

Combination Therapy

When used in combination with pomalidomide, carfilzomib, bortezomib, lenalidomide or dexamethasone, consider cautions, precautions, and contraindications for these drugs in addition to those for isatuximab.

Infusion-related Effects

Severe infusion-related reactions (e.g., angioedema, bronchospasm, cardiac arrest, dyspnea, swelling, hypertension, hypotension), including life-threatening anaphylaxis, reported in patients receiving isatuximab-containing regimens; generally occurred during the first infusion.

Administer premedication with dexamethasone, acetaminophen, a histamine H₂-antagonist, and diphenhydramine prior to each infusion.

Monitor vital signs frequently during infusions of the drug. Temporary interruption followed by a reduction in infusion rate or permanent discontinuance of therapy may be necessary depending on severity of infusion-related reaction; institute appropriate treatment and supportive care as clinically indicated.

Infections

Severe, life-threatening, or fatal infections may occur. In clinical trials, the most common type of serious infection was pneumonia.

Monitor patients for signs and symptoms of infection during therapy and administer appropriate treatment. Administer prophylactic antimicrobials.

Hematologic Effects

Neutropenia reported in patients receiving isatuximab-containing regimens.

Monitor CBCs periodically during treatment. If neutropenia develops, monitor for signs or symptoms of infection. Temporary interruption of therapy may be necessary.

Consider antibacterial and antiviral prophylaxis. Use of growth factors may be used to treat neutropenia as clinically indicated.

Development of Second Primary Malignancy

Second primary malignancies reported in patients receiving isatuximab-containing regimens.

Monitor patients for development of second primary malignancies.

Interference with Laboratory Testing

Indirect Antiglobulin Test

False positive indirect antiglobulin (Coombs’) test results reported. Positive indirect antiglobulin tests following discontinuance of an anti-CD38 monoclonal antibody may persist for up to 9 months following last infusion. Determination of ABO and Rh blood type not affected.

Isatuximab may also interfere with antibody detection tests, antibody identification panels, and antihuman globulin crossmatches.

If blood typing and screening did not occur prior to initiation of isatuximab therapy, inform blood bank to use dithiothreitol-treated RBCs for blood typing and screening. Do not assume a positive indirect antiglobulin test result in a patient receiving isatuximab is a false-positive since RBC alloantibodies may be present. If immediate transfusion is required because of emergency, transfuse non-cross-matched ABO/RhD blood type-compatible RBCs according to local protocols.

Interference with Serum Protein Electrophoresis and Immunofixation Tests

Isatuximab may interfere with serum protein electrophoresis (SPEP) and immunofixation electrophoresis (IFE) assays resulting in misinterpretation of tumor response in patients with IgG kappa myeloma protein.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm in humans based on mechanism of action; IgG₁ monoclonal antibodies cross the placenta. Effects on the fetus may include decreased bone mineral density and CD38-positive immune cell depletion. Defer administration of live vaccines to neonates and infants exposed to isatuximab in utero until a hematology evaluation is completed.

Females of reproductive potential should be advised to use effective contraceptive methods while receiving isatuximab and for at least 5 months after the last dose. Combination of isatuximab with pomalidomide or lenalidomide is contraindicated in pregnancy because pomalidomide or lenalidomide may cause birth defects and fetal death.

Immunogenicity

Potential for immunogenicity. Presence of anti-isatuximab antibodies does not appear to have a clinically meaningful effect on pharmacokinetics, safety, or efficacy of isatuximab.

Specific Populations

Pregnancy

May cause fetal harm.

The combination of isatuximab with pomalidomide or lenalidomide is contraindicated in pregnant women because pomalidomide or lenalidomide may cause birth defects and fetal death. Refer to the pomalidomide or lenalidomide prescribing information on use during pregnancy. Pomalidomide and lenalidomide are only available through a REMS program.

Lactation

Not known whether isatuximab is distributed into human milk; however, human IgG is distributed into milk.

Effects of drug on nursing infants or human milk production unknown.

Discontinue breast-feeding when isatuximab is used in combination with pomalidomide or lenalidomide and dexamethasone. Refer to the prescribing information for pomalidomide or lenalidomide for additional information.

Females and Males of Reproductive Potential

Avoid pregnancy during isatuximab therapy.

When isatuximab is used in combination with pomalidomide or lenalidomide, refer to the prescribing information for these drugs for pregnancy testing requirements prior to initiating therapy in females of reproductive potential.

Females of reproductive potential should be advised to use effective contraceptive methods while receiving isatuximab and for at least 5 months after the last dose.

Refer to the pomalidomide or lenalidomide labeling for contraception requirements prior to initiating treatment in both females of reproductive potential and in male patients.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

No overall differences in safety or efficacy relative to younger patients; however, possibility of increased sensitivity in some older individuals cannot be ruled out.

Hepatic Impairment

Systemic exposure not altered by mild hepatic impairment.

Not studied in patients with moderate or severe hepatic impairment.

Renal Impairment

Systemic exposure not altered by renal impairment.

Common Adverse Effects

Most common adverse reactions (≥20%) in patients receiving isatuximab-irfc in combination with pomalidomide and dexamethasone: upper respiratory tract infection, infusion-related reactions, pneumonia, diarrhea. Most common hematology laboratory abnormalities (≥80%) in these patients are decreased hemoglobin, decreased neutrophils, decreased lymphocytes, decreased platelets.

Most common adverse reactions (≥20%) in patients receiving isatuximab-irfc in combination with carfilzomib and dexamethasone: upper respiratory tract infection, infusion-related reactions, fatigue, hypertension, diarrhea, pneumonia, dyspnea, insomnia, bronchitis, cough, back pain. Most common hematology laboratory abnormalities (≥80%) in these patients are decreased hemoglobin, decreased lymphocytes, decreased platelets.

Most common adverse reactions (≥20%) in patients receiving isatuximab-irfc In combination with bortezomib, lenalidomide and dexamethasone: upper respiratory tract infections, diarrhea, fatigue, peripheral sensory neuropathy, pneumonia, musculoskeletal pain, cataract, constipation, peripheral edema, rash, infusion-related reaction, insomnia, COVID-19.

Most common hematologic laboratory abnormalities (≥80%) in patients receiving isatuximab-irfc In combination with bortezomib, lenalidomide and dexamethasone: decreased hemoglobin, decreased leukocytes, decreased lymphocytes, decreased platelets, decreased neutrophils.

Drug Interactions

No formal drug interaction studies.

Pharmacokinetics of isatuximab not expected to be affected by drugs affecting CYP isoenzymes or transport systems.

Isatuximab-irfc Pharmacokinetics

Absorption

Bioavailability

Systemic exposure increases in a dose-proportional manner over a dosage range of 5–20 mg/kg every week for 4 weeks, followed by every 2 weeks.

Steady-state concentrations are achieved within a median of 18 weeks, with 3.1-fold accumulation.

Special Populations

Mild hepatic impairment: No clinically important effect on systemic exposure to isatuximab.

Moderate or severe hepatic impairment: Not studied.

Renal impairment: No clinically important effect on systemic exposure to isatuximab.

Age (36–85 years) and sex do not appear to substantially affect pharmacokinetics of isatuximab.

Distribution

Extent

Human IgG crosses placenta and distributes into milk. Not known whether isatuximab is distributed into human milk.

Elimination

Metabolism

Expected to degrade into small peptides via catabolic pathways.

Clearance decreases with increasing dosage and repeated administration.

≥99% elimination of drug expected in approximately 2 months after last dose.

Stability

Storage

Parenteral

Injection Concentrate

2–8ºC in original carton to protect from light. Do not freeze or shake.

Diluted infusion solution: Administer immediately or store at 2–8ºC for up to 48 hours, followed by up to 8 hours at room temperature (including infusion time).

Actions

IgG₁ immunoglobulin produced from mammalian (Chinese hamster ovary) cells.
Binds to CD38, a transmembrane glycoprotein expressed on the surface of hematopoietic and tumor cells, including multiple myeloma cells.
Induces apoptosis of tumor cells and activates immune effector mechanisms (i.e., antibody-dependent cell-mediated cytotoxicity [ADCC], antibody-dependent cellular phagocytosis [ADCP], complement-dependent cytotoxicity [CDC]).
Suppresses CD38-positive T-regulatory cells and, in the absence of CD38-positive tumor cells, activation of natural killer (NK) cells.

Advice to Patients

Advise patients to read the manufacturer's patient labeling (Patient Information).
Risk of infusion-related reactions. Advise patients to immediately report any signs or symptoms of such reactions (e.g., shortness of breath; wheezing or difficulty breathing; swelling of the face, mouth, throat, or tongue; throat tightness; palpitations; dizziness, lightheadedness, or fainting; headache; cough; rash or itching; nausea; rhinitis or nasal congestion; chills).
Inform patients about the risk of developing infections during isatuximab treatment, and to immediately report any fever or symptoms of infection to their healthcare provider.
Inform patients of the risk of developing second primary malignancies during treatment with isatuximab-irfc.
Inform patients about the risk of cardiac failure during treatment with isatuximab when given with carfilzomib and dexamethasone, and the importance of immediately reporting any difficulty breathing, cough, or leg swelling to their healthcare provider.
Risk of laboratory test interference. Advise patients to inform clinicians and transfusion center personnel that they are receiving isatuximab-irfc in case a RBC transfusion is planned. Advise patients that isatuximab may affect the results of blood tests to match their blood type for approximately 6 months after their last infusion.
Risk of fetal harm. Advise pregnant women and females of reproductive potential of the potential hazard to a fetus and to use effective contraception during isatuximab treatment and for at least 5 months after the last dose of the drug.
Advise patients that pomalidomide or lenalidomide has the potential to cause fetal harm and 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.
Advise patients to inform clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Advise women to inform clinicians if they are breast-feeding or plan to breast-feed.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Isatuximab-irfc is available only through specialty pharmacies and distributors. Contact the manufacturer for additional information.