Isatuximab: Drug information

For additional information see "Isatuximab: Patient drug information"

For abbreviations, symbols, and age group definitions show table

Brand Names: US

Sarclisa

Brand Names: Canada

Sarclisa

Pharmacologic Category

Antineoplastic Agent, Anti-CD38;
Antineoplastic Agent, Monoclonal Antibody

Dosing: Adult

Dosage guidance:

Safety: Premedications are required prior to infusion to reduce the risk and severity of infusion reactions. Administer in a facility with immediate access to emergency equipment and support to manage infusion reactions.

Dosing: Dosing is based on actual body weight (measure weight and adjust dose at the beginning of each cycle).

Clinical considerations: Initiate antibacterial and antiviral prophylaxis (eg, for herpes zoster prophylaxis) if needed based on clinical and institutional guidelines. Conduct blood type and screening prior to the first isatuximab infusion; consider phenotyping prior to initiating treatment.

Multiple myeloma, newly diagnosed

Multiple myeloma, newly diagnosed (ineligible for hematopoietic cell transplantation):

Isa-VRd regimen:

Cycle 1 (induction): IV: 10 mg/kg on days 1, 8, 15, 22, and 29 of a 42-day cycle (in combination with bortezomib, lenalidomide, and dexamethasone (Ref)).

Cycles 2 to 4 (induction): IV: 10 mg/kg on days 1, 15, and 29 of a 42-day cycle (in combination with bortezomib, lenalidomide, and dexamethasone (Ref)).

Cycles 5 to 17 (continuous phase): IV: 10 mg/kg on days 1 and 15 of a 28-day cycle (in combination with lenalidomide and dexamethasone (Ref)).

Cycle 18 and beyond (continuous phase): IV: 10 mg/kg on day 1 of a 28-day cycle (in combination with lenalidomide and dexamethasone); continue until disease progression or unacceptable toxicity (Ref).

Multiple myeloma, relapsed or refractory

Multiple myeloma, relapsed or refractory:

Cycle 1: IV: 10 mg/kg on days 1, 8, 15, and 22 of a 28-day cycle (in combination with pomalidomide and dexamethasone (Ref) or in combination with carfilzomib and dexamethasone (Ref)).

Cycle 2 and beyond: IV: 10 mg/kg on days 1 and 15 of a 28-day cycle (in combination with pomalidomide and dexamethasone (Ref) or in combination with carfilzomib and dexamethasone (Ref)), continue until disease progression or unacceptable toxicity.

Missed dose: If a planned isatuximab dose is missed, administer the dose as soon as possible and then adjust the treatment schedule accordingly, maintaining the treatment interval.

Premedication:

**Isatuximab Premedications**
Premedication class	Premedication and dose	Administration route (for the premedication)	Dosing window (prior to isatuximab)
^a Dexamethasone dose corresponds to the dose used as part of the backbone combination treatment; administer only once on days isatuximab is administered. ^b Administer dexamethasone prior to isatuximab and pomalidomide, prior to isatuximab and carfilzomib, and prior to isatuximab, bortezomib, and lenalidomide on pertinent treatment days.
Antipyretic (administer for all isatuximab doses)	Acetaminophen (650 mg to 1 g) or equivalent	Oral	15 to 60 minutes
Antihistamine (administer for all isatuximab doses; IV route preferred for at least the first 4 doses)	Diphenhydramine (25 to 50 mg) or equivalent	IV or oral	15 to 60 minutes
H₂ antagonist (administer for all isatuximab doses)	Per institutional standard		15 to 60 minutes
Glucocorticoid (in combination with isatuximab and pomalidomide)	Dexamethasone 40 mg (or 20 mg in patients ≥75 years of age)^a	Oral or IV	15 to 60 minutes^b
Glucocorticoid (in combination with isatuximab and carfilzomib)	Dexamethasone 20 mg^a	IV on days of isatuximab and/or carfilzomib infusions (cycle 1: days 1, 2, 8, 9, 15, 16, and 22; cycles 2 and beyond: days 1, 2, 8, 9, 15, and 16); oral on days where isatuximab and/or carfilzomib are not administered (cycle 1: day 23; cycle 2 and beyond: days 22 and 23)	15 to 60 minutes^b
Glucocorticoid (in combination with isatuximab, bortezomib, and lenalidomide)	Dexamethasone 20 mg^a	IV on days of isatuximab infusion; oral on other treatment days	15 to 60 minutes^b

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

No dosage adjustment is necessary.

Dosing: Liver Impairment: Adult

No dosage adjustment is necessary.

Dosing: Obesity: Adult

American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m² : The dosing in the FDA-approved prescribing information should be followed in all patients, regardless of obesity status. If a patient with a BMI ≥30 kg/m²experiences high-grade toxicity from systemic anticancer therapy, the same dosage modification recommendations should be followed for all patients, regardless of obesity status (Ref).

Dosing: Adjustment for Toxicity: Adult

Note: No isatuximab dose reduction is recommended. Other concomitant anticancer therapies may also require dosage modification.

Isatuximab Recommended Dosage Adjustments for Adverse Reactions
Adverse reaction	Severity	Isatuximab dosage modification
Hematologic toxicity
Neutropenia	Grade 4	Delay isatuximab until neutrophil count recovers to ≥1,000/mm³ and provide supportive care with growth factors (according to institutional guidelines).
Nonhematologic toxicity
Infection	Any	Treat appropriately.
Infusion reaction	Grade 2 or 3 reaction	Interrupt isatuximab infusion and provide appropriate medical management. Symptoms improve to grade 1 or lower after infusion interruption: Restart isatuximab infusion at half of the initial infusion rate with close monitoring (and with supportive care as needed); if symptoms do not recur after 30 minutes, may increase the infusion rate to the initial rate, and then increase incrementally. Symptoms do not* improve to grade 1 or lower after infusion interruption, persist or worsen despite medical management, or hospitalization required*: Permanently discontinue isatuximab.
Infusion reaction	Grade 4 (life-threatening) or anaphylactic reaction	Interrupt isatuximab infusion and provide appropriate medical management. Permanently discontinue isatuximab.
Second primary malignancy (skin cancers)	Any	Most patients with non-melanoma skin cancer were able to continue isatuximab treatment after resection of the skin cancer.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions (Significant): Considerations

Bone marrow suppression

Isatuximab (in combination with carfilzomib or pomalidomide and dexamethasone) may cause neutropenia (including grades 3 and 4 neutropenia), febrile neutropenia, and neutropenic infection. In one trial, median duration of grade ≥3 neutropenia was 9 days (Ref). May require treatment interruption. Anemia, lymphocytopenia, and thrombocytopenia have also been reported.

Mechanism: Non-dose-related (Ref); impact of concurrent drugs must be considered.

Onset: Intermediate; in one trial, median time to onset of first grade ≥3 neutropenia was 22 days (Ref).

Infection

Isatuximab (in combination with carfilzomib or pomalidomide and dexamethasone) has been reported to cause infections, including opportunistic infections and serious infections. In clinical trials, the most commonly occurring serious infection was pneumonia.

Infusion reaction

Infusion-related reactions may be observed with isatuximab (in combination with carfilzomib or pomalidomide and dexamethasone). Reported severe symptoms include angioedema, cardiac arrest, bronchospasm, dyspnea, hypertension, hypotension, and swelling; anaphylaxis and anaphylactic shock have also been reported (Ref). During clinical trials, most infusion reactions resolved on the same day either spontaneously or with treatment (Ref). Infusion reactions may result in treatment interruption, infusion rate adjustment, and/or discontinuation.

Mechanism: Non-dose-related (Ref).

Onset: Rapid; most reactions occurred during the first infusion (Ref). The median time to infusion interruption due to infusion-related reactions was 61 minutes (range: 4 to 240 minutes) minutes in clinical trials.

Risk factors:

• Faster rate of infusion

Second primary malignancies

Second primary malignant neoplasms (SPM) have been reported with isatuximab (in combination with carfilzomib or pomalidomide and dexamethasone) during and after discontinuation of therapy and include malignant neoplasm of the skin and malignant solid tumor.

Mechanism: Time-related. Exact mechanism is not established; impact of disease process and concurrent medications must be considered.

Onset: Delayed; in clinical trials, the median interval from first dose to diagnosis of SPM was ~7 months (Ref).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. As reported in combination with carfilzomib or pomalidomide plus dexamethasone.

>10%:

Cardiovascular: Hypertension (37%) (table 1)Hypertension

**Isatuximab: Adverse Reaction: Hypertension**
Drug (Isatuximab + Carfilzomib + Dexamethasone)	Comparator (Carfilzomib + Dexamethasone)	Number of Patients (Isatuximab + Carfilzomib + Dexamethasone)	Number of Patients (Carfilzomib + Dexamethasone)
37%	32%	177	122

Gastrointestinal: Diarrhea (26% to 36%; grade 3: 2% to 3%), nausea (15%) (table 2)Nausea, vomiting (12% to 15%; grade 3: 1%)

**Isatuximab: Adverse Reaction: Nausea**
Drug (Isatuximab + Pomalidomide + Dexamethasone)	Comparator (Pomalidomide + Dexamethasone)	Number of Patients (Isatuximab + Pomalidomide + Dexamethasone)	Number of Patients (Pomalidomide + Dexamethasone)
15%	9%	152	149

Hematologic & oncologic: Anemia (99%; grade 3: 22% to 32%) (table 3)Anemia, febrile neutropenia (12%; grades 3/4: 1% to 11%) (table 4)Febrile Neutropenia, lymphocytopenia (92% to 94%; grades 3/4: 13% to 52%) (table 5)Lymphocytopenia, neutropenia (55% to 96%; grades 3/4: 2% to 61%) (table 6)Neutropenia, positive indirect Coombs’ test (false positive: 63% to 68%), thrombocytopenia (84% to 94%; grades 3/4: 11% to 19%) (table 7)Thrombocytopenia

**Isatuximab: Adverse Reaction: Anemia**
Drug (Isatuximab + Pomalidomide or Carfilzomib + Dexamethasone)	Comparator (Pomalidomide + Dexamethasone)	Comparator (Carfilzomib + Dexamethasone)	Number of Patients (Isatuximab + Pomalidomide or Carfilzomib + Dexamethasone)	Number of Patients (Comparator)
All grades: 99%	97%	N/A	152	149
All grades: 99%	N/A	99%	177	122
Grade 3: 32%	28%	N/A	152	149
Grade 3: 22%	N/A	20%	177	122

**Isatuximab: Adverse Reaction: Febrile Neutropenia**
Drug (Isatuximab + Pomalidomide + Dexamethasone)	Comparator (Pomalidomide + Dexamethasone)	Number of Patients (Isatuximab + Pomalidomide + Dexamethasone)	Number of Patients (Pomalidomide + Dexamethasone)
All grades: 12%	2%	152	149
Grade 3: 11%	1%	152	149
Grade 4: 1%	0.7%	152	149

**Isatuximab: Adverse Reaction: Lymphocytopenia**
Drug (Isatuximab + Pomalidomide or Carfilzomib + Dexamethasone)	Comparator (Pomalidomide + Dexamethasone)	Comparator (Carfilzomib + Dexamethasone)	Number of Patients (Isatuximab + Pomalidomide or Carfilzomib + Dexamethasone)	Number of Patients (Comparator)
All grades: 94%	N/A	95%	177	122
All grades: 92%	92%	N/A	152	149
Grade 3: 52%	N/A	43%	177	122
Grade 3: 42%	35%	N/A	152	149
Grade 4: 17%	N/A	14%	177	122
Grade 4: 13%	8%	N/A	152	149

**Isatuximab: Adverse Reaction: Neutropenia**
Drug (Isatuximab + Pomalidomide or Carfilzomib + Dexamethasone)	Comparator (Pomalidomide + Dexamethasone)	Comparator (Carfilzomib + Dexamethasone)	Number of Patients (Isatuximab + Pomalidomide or Carfilzomib + Dexamethasone)	Number of Patients (Comparator)
All grades: 96%	92%	N/A	152	149
Grade 4: 61%	31%	N/A	152	149
All grades: 55%	N/A	43%	177	122
Grade 3: 24%	38%	N/A	152	149
Grade 3: 18%	N/A	7%	177	122
Grade 4: 2%	N/A	0.8%	177	122

**Isatuximab: Adverse Reaction: Thrombocytopenia**
Drug (Isatuximab + Pomalidomide or Carfilzomib + Dexamethasone)	Comparator (Pomalidomide + Dexamethasone)	Comparator (Carfilzomib + Dexamethasone)	Number of Patients (Isatuximab + Pomalidomide or Carfilzomib + Dexamethasone)	Number of Patients (Comparator)
All grades: 94%	N/A	88%	177	122
All grades: 84%	79%	N/A	152	149
Grade 3: 19%	N/A	16%	177	122
Grade 4: 16%	15%	N/A	152	149
Grade 3: 14%	9%	N/A	152	149
Grade 4: 11%	N/A	8%	177	122

Hypersensitivity: Infusion-related reaction (38% to 46%; including cytokine release syndrome)

Nervous system: Fatigue (42%)

Respiratory: Bronchitis (24%), cough (23% (table 8)Cough), dyspnea (17% to 29%) (table 9)Dyspnea, pneumonia (31% to 36%) (table 10)Pneumonia, upper respiratory tract infection (57% to 67%) (table 11)Upper Respiratory Tract Infection

**Isatuximab: Adverse Reaction: Cough**
Drug (Isatuximab + Carfilzomib + Dexamethasone)	Comparator (Carfilzomib + Dexamethasone)	Number of Patients (Isatuximab + Carfilzomib + Dexamethasone)	Number of Patients (Carfilzomib + Dexamethasone)
23%	15%	177	122

**Isatuximab: Adverse Reaction: Dyspnea**
Drug (Isatuximab + Pomalidomide or Carfilzomib + Dexamethasone)	Comparator (Pomalidomide + Dexamethasone)	Comparator (Carfilzomib + Dexamethasone)	Number of Patients (Isatuximab + Pomalidomide or Carfilzomib + Dexamethasone)	Number of Patients (Comparator)
29%	N/A	24%	177	122
17%	12%	N/A	152	149

**Isatuximab: Adverse Reaction: Pneumonia**
Drug (Isatuximab + Pomalidomide or Carfilzomib + Dexamethasone)	Comparator (Pomalidomide + Dexamethasone)	Comparator (Carfilzomib + Dexamethasone)	Number of Patients (Isatuximab + Pomalidomide or Carfilzomib + Dexamethasone)	Number of Patients (Comparator)
36%	N/A	30%	177	122
31%	23%	N/A	152	149

**Isatuximab: Adverse Reaction: Upper Respiratory Tract Infection**
Drug (Isatuximab + Pomalidomide or Carfilzomib + Dexamethasone)	Comparator (Pomalidomide + Dexamethasone)	Comparator (Carfilzomib + Dexamethasone)	Number of Patients (Isatuximab + Pomalidomide or Carfilzomib + Dexamethasone)	Number of Patients (Comparator)
67%	N/A	57%	177	122
57%	42%	N/A	152	149

1% to 10%:

Cardiovascular: Heart failure (7%)

Hematologic & oncologic: Second primary malignant neoplasm (7% to 10%; including malignant neoplasm of skin, malignant solid tumor)

Immunologic: Antibody development (<2%)

<1%: Hypersensitivity: Anaphylaxis

Frequency not defined:

Hypersensitivity: Angioedema

Infection: Infection (including opportunistic infection, serious infection), neutropenic infection

Postmarketing: Hypersensitivity: Anaphylactic shock (Torres Górriz 2024)

Contraindications

Severe hypersensitivity to isatuximab or any component of the formulation.

Warnings/Precautions

Special populations:

• Older adults: Adverse reactions (including neutropenia) and adverse reactions leading to dose modifications occurred at a higher frequency in patients ≥75 years of age compared to patients <75 years of age receiving isatuximab (in combination with bortezomib, lenalidomide, and dexamethasone) for treatment of newly diagnosed multiple myeloma.

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous [preservative free]:

Sarclisa: isatuximab-irfc 20 mg/mL (5 mL, 25 mL) [contains polysorbate 80]

Generic Equivalent Available: US

Pricing: US

Solution (Sarclisa Intravenous)

100 mg/5 mL (per mL): $202.31

500 mg/25 mL (per mL): $202.31

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Sarclisa: 100 mg/5 mL (5 mL); 500 mg/25 mL (25 mL) [contains polysorbate 80]

Prescribing and Access Restrictions

Available through authorized specialty distributors and specialty pharmacies. Information regarding distribution is available from the manufacturer at SanofiCareAssist.com/hcp/Sarclisa or at 1-833-930-2273.

Administration: Adult

IV: Administer as an IV infusion using an IV tubing infusion set made of polyethylene, polyvinyl chloride (PVC) with or without di-2-ethylhexyl phthalate (DEHP), polybutadiene, or polyurethane with a 0.22 micron in-line polyethersulfone (PES), polysulfone, or nylon filter. Infusion duration depends on the rate of infusion. Do not infuse with other medications via the same IV line.

When used in combination with carfilzomib and dexamethasone, on the days when both isatuximab and carfilzomib are administered, administer dexamethasone first, followed by isatuximab, and then carfilzomib.

Infusion rate (based on a 250 mL infusion bag volume; escalate infusion rate only in the absence of infusion reactions):

First infusion: Initiate at 25 mL/hour for 60 minutes; if tolerated, increase rate by 25 mL/hour every 30 minutes to a maximum rate of 150 mL/hour.

Second infusion: Initiate at 50 mL/hour for 30 minutes; if tolerated, increase rate by 50 mL/hour for 30 minutes, then increase rate by 100 mL/hour to a maximum rate of 200 mL/hour.

Subsequent infusions: Initiate at 200 mL/hour; maximum rate: 200 mL/hour.

Use: Labeled Indications

Multiple myeloma, newly diagnosed:

Treatment (in combination with bortezomib, lenalidomide, and dexamethasone) of newly diagnosed multiple myeloma in adults who are not eligible for autologous hematopoietic cell transplant.

Multiple myeloma, relapsed or refractory:

Treatment (in combination with pomalidomide and dexamethasone) of multiple myeloma in adults who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor.

Treatment (in combination with carfilzomib and dexamethasone) of relapsed or refractory multiple myeloma in adults who have received 1 to 3 prior lines of therapy.

Medication Safety Issues

Sound-alike/look-alike issues:

Isatuximab may be confused with daratumumab, dinutuximab, elotuzumab, ipilimumab, ixabepilone, ixazomib, loncastuximab tesirine, margetuximab, siltuximab.

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor

Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid

Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor

Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor

Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid

BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of BCG Products. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor

Brivudine: May increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid

Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid

Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor

Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid

Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid

CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor

Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Miscellaneous Oncologic Agents) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor

COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor

Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Denosumab: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification

Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid

Efgartigimod Alfa: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor

Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid

Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid

Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid

Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor

Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification

Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider Therapy Modification

Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor

Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Mumps- Rubella- or Varicella-Containing Live Vaccines may increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid

Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid

Nipocalimab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor

Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor

Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor

Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor

Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor

Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid

Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification

Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor

Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification

Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid

Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification

Rozanolixizumab: May decrease therapeutic effects of Fc Receptor-Binding Agents. Risk C: Monitor

Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid

Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification

Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor

Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid

Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid

Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid

Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid

Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor

Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid

Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification

Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Zoster Vaccine (Live/Attenuated): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid

Reproductive Considerations

Evaluate pregnancy status prior to use in patients who could become pregnant. Patients who could become pregnant should use effective contraception during therapy and for 5 months after the last isatuximab dose.

Isatuximab is used in combination with lenalidomide or pomalidomide; also refer to the lenalidomide and pomalidomide monographs for additional information related to use in patients who could become pregnant and patients with partners who could become pregnant.

Pregnancy Considerations

Isatuximab is a chimeric monoclonal antibody (IgG1). Human IgG crosses the placenta. Fetal exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and GA, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Clements 2020; Palmeira 2012; Pentsuk 2009).

Based on the mechanism of action, in utero exposure to isatuximab may cause fetal harm, including depletion of fetal CD38-positive immune cells and decreased bone density.

Isatuximab is used in combination with lenalidomide or pomalidomide. Refer to the lenalidomide and pomalidomide monographs for additional information.

Breastfeeding Considerations

It is not known if isatuximab is present in breast milk.

Isatuximab is a chimeric monoclonal antibody (IgG1); maternal IgG is known to be present in breast milk.

Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer. Isatuximab is used in combination with lenalidomide or pomalidomide; refer to the lenalidomide and pomalidomide monographs for additional information.

Monitoring Parameters

Conduct blood type and screening prior to the first isatuximab infusion; consider phenotyping prior to starting isatuximab treatment. Monitor CBC periodically during treatment. Evaluate pregnancy status prior to use in patients who could become pregnant. Monitor vital signs frequently during entire infusion; monitor for signs/symptoms of infusion reaction. Monitor for signs of infection (including in patients with neutropenia) prior to and during treatment; monitor for the development of second primary malignancies.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Mechanism of Action

Isatuximab is an IgG1-derived monoclonal antibody directed against CD38. CD38 is expressed on the surface of hematopoietic and tumor cells, including multiple myeloma cells. Isatuximab has antitumor activity via antibody-dependent, cell-mediated cytotoxicity; complement-dependent cytotoxicity; and antibody-dependent cellular phagocytosis and directly inhibits activity of CD38 ectoenzymes (Attal 2019). Isatuximab can activate natural killer cells in the absence of CD38-positive target tumor cells and suppresses CD38-positive T-regulatory cells. The combination of isatuximab plus pomalidomide enhanced antibody-dependent, cell-mediated cytotoxicity activity and direct tumor cell killing compared to isatuximab alone (in vitro) and enhanced antitumor activity compared to isatuximab or pomalidomide activities alone in animal models.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: V_d: 8.13 L.

Metabolism: Metabolized into small peptides by catabolic pathways.

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Body weight: Isatuximab clearance increases with increasing body weight.

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AE) United Arab Emirates: Sarclisa;
(AR) Argentina: Sarclisa;
(AT) Austria: Sarclisa;
(BE) Belgium: Sarclisa;
(BG) Bulgaria: Sarclisa;
(BR) Brazil: Sarclisa;
(CH) Switzerland: Sarclisa;
(CZ) Czech Republic: Sarclisa;
(DE) Germany: Sarclisa;
(ES) Spain: Sarclisa;
(FI) Finland: Sarclisa;
(FR) France: Sarclisa;
(GB) United Kingdom: Sarclisa;
(HK) Hong Kong: Sarclisa;
(IT) Italy: Sarclisa;
(JP) Japan: Sarclisa;
(KW) Kuwait: Sarclisa;
(LT) Lithuania: Sarclisa;
(MX) Mexico: Sarclisa;
(NL) Netherlands: Sarclisa;
(NO) Norway: Sarclisa;
(PL) Poland: Sarclisa;
(PR) Puerto Rico: Sarclisa;
(PT) Portugal: Sarclisa;
(QA) Qatar: Sarclisa;
(RO) Romania: Sarclisa;
(RU) Russian Federation: Sarclisa;
(SE) Sweden: Sarclisa;
(SK) Slovakia: Sarclisa;
(TR) Turkey: Sarclisa;
(TW) Taiwan: Sarclisa

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Topic 127258 Version 130.0

خرید پکیج

Isatuximab: Drug information