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Isatuximab: Drug information

Isatuximab: Drug information
(For additional information see "Isatuximab: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Sarclisa
Brand Names: Canada
  • Sarclisa
Pharmacologic Category
  • Antineoplastic Agent, Anti-CD38;
  • Antineoplastic Agent, Monoclonal Antibody
Dosing: Adult

Note: Dosing is based on actual body weight (measure weight and adjust dose at the beginning of each cycle). Premedications are required prior to infusion. Initiate antiviral prophylaxis to prevent herpes zoster reactivation according to clinical and institutional guidelines. Consider antibiotic prophylaxis during isatuximab treatment. Administer in a facility with immediate access to emergency equipment and support to manage infusion reactions. Refer to the Dexamethasone, Carfilzomib, and Pomalidomide monographs for dosing information.

Multiple myeloma

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 [Attal 2019] or in combination with carfilzomib and dexamethasone [Moreau 2021]).

Cycle 2 and beyond: IV: 10 mg/kg on days 1 and 15 of a 28-day cycle (in combination with pomalidomide and dexamethasone [Attal 2019] or in combination with carfilzomib and dexamethasone [Moreau 2021]), 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.

Premedications: Administer 15 to 60 minutes prior to initiating isatuximab infusion to reduce the risk of infusion reaction:

- Dexamethasone: Dose corresponds to the dose used as part of the backbone combination treatment; administer only once on days isatuximab is administered.

Isatuximab, pomalidomide, and dexamethasone regimen: 40 mg IV or oral (20 mg IV or oral in patients ≥75 years of age).

Isatuximab, carfilzomib, and dexamethasone regimen: 20 mg IV on the days isatuximab and/or carfilzomib are administered. Refer to protocol for further information.

- Acetaminophen 650 mg to 1 g oral (or equivalent).

- An H2 antagonist.

- Diphenhydramine 25 to 50 mg IV or oral (or equivalent); for at least the first 4 infusions, the IV route is preferred.

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: Hepatic Impairment: Adult

No dosage adjustment is necessary.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Adjustment for Toxicity: Adult

No isatuximab dose reduction is recommended.

Hematologic toxicity, grade 4 neutropenia: Delay isatuximab treatment until neutrophil count recovers to ≥1,000/mm3 and provide supportive care with growth factors (according to institutional guidelines).

Infusion reactions: Grade 2 or higher: Interrupt infusion and provide appropriate medical management.

Grade 2 or 3 reaction: If 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.

Permanently discontinue (and provide appropriate medical management) for grade 2 or 3 symptoms that do not improve (to ≤ grade 1) after infusion interruption, if symptoms persist or worsen despite appropriate medications, if hospitalization is required, if anaphylactic reactions occur, or if grade 4 reaction (life-threatening) occurs.

Second primary malignancy (skin cancers): Withhold treatment for excision of skin cancer; patients with skin cancer were able to continue isatuximab treatment after resection.

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

No

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, 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 (relapsed or refractory):

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

Treatment of relapsed or refractory multiple myeloma (in combination with carfilzomib and dexamethasone) 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:

This medication is in a class the Institute for Safe Medication Practices includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Adverse Reactions (Significant): Considerations
Bone marrow suppression

Isatuximab (in combination with carfilzomib or pomalidomide and dexamethasone) commonly causes neutropenia (including grades 3 and 4 neutropenia), febrile neutropenia, and neutropenic infection. The most frequently occurring neutropenic infections during clinical trials included upper respiratory tract infections, pneumonia, and urinary tract infections. In one trial, median duration of grade ≥3 neutropenia was 9 days (Ref). May require treatment interruption. Anemia, lymphocytopenia, and thrombocytopenia have also commonly 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).

Infusion reaction

Infusion-related reactions are commonly observed with isatuximab (in combination with carfilzomib or pomalidomide and dexamethasone); most often characterized by cough, dyspnea, nasal congestion, and nausea. Patients who develop severe symptoms often experience bronchospasm, dyspnea, and hypertension. Angioedema, swelling, and hypotension may also occur; anaphylaxis has been reported rarely. 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, 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 55 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) 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)

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), 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), febrile neutropenia (1% to 12%; grade 3: 11%; grade 4: 1%) (table 4), lymphocytopenia (92% to 94%; grade 3: 42% to 52%; grade 4: 13% to 17% (table 5)), neutropenia (55% to 96%; grade 3: 18% to 24%; grade 4: 2% to 61%) (table 6), thrombocytopenia (84% to 94%; grade 3: 14% to 19%; grade 4: 11% to 16%) (table 7)

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

All grades: 1%

N/A

177

N/A

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 severe infusion-related reaction)

Infection: Infection (grades 3/4: 38% to 43%), neutropenic infection (2% to 25%)

Nervous system: Fatigue (42%)

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

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 (serious: 4%)

Dermatologic: Malignant neoplasm of skin (4%) (table 12)

Isatuximab: Adverse Reaction: Malignant Neoplasm of Skin

Drug (Isatuximab+ Pomalidomide or Carfilzomib + Dexamethasone)

Comparator

4%

2%

Hematologic & oncologic: Malignant solid tumor (2%) (table 13), second primary malignant neoplasm (4% to 7%)

Isatuximab: Adverse Reaction: Malignant Solid Tumor

Drug (Isatuximab+ Pomalidomide or Carfilzomib + Dexamethasone)

Comparator

2%

2%

Immunologic: Antibody development (2%)

Infection: Herpes zoster infection (2% to 5%)

<1%: Hypersensitivity: Anaphylaxis

Frequency not defined:

Cardiovascular: Hypotension

Hypersensitivity: Angioedema, cytokine release syndrome

Respiratory: Bronchospasm, nasal congestion

Miscellaneous: Swelling

Contraindications

Severe hypersensitivity to isatuximab or any component of the formulation.

Warnings/Precautions

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.

Other warnings/precautions:

• Test interference: Isatuximab binds to CD38 on RBCs, which may result in a false-positive indirect antiglobulin test (indirect Coombs test), antibody detection (screening) tests, antibody identification panels, and antihuman globulin crossmatches in patients treated with isatuximab. In clinical trials, the indirect antiglobulin test was positive during isatuximab treatment in approximately two-thirds of tested patients. In patients with a positive indirect antiglobulin test, blood transfusions were administered without evidence of hemolysis. ABO/RhD typing was not affected by isatuximab treatment. Conduct blood type and screening prior to the first isatuximab infusion; consider phenotyping prior to initiating treatment. If isatuximab treatment has already been initiated, inform the blood bank that the patient is receiving isatuximab and isatuximab interference with blood compatibility testing can be resolved using dithiothreitol-treated RBCs. If an emergency transfusion is required, non–cross-matched ABO/RhD-compatible RBCs can be given per local blood bank practices. Isatuximab is an IgG kappa monoclonal antibody that may be incidentally detected by serum protein electrophoresis and immunofixation assays used for endogenous M-protein monitoring and may interfere with the accuracy of determining complete response in some patients with IgG kappa myeloma protein.

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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

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

Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

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

Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. 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 (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy

COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy

COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect 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 enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: May enhance the immunosuppressive effect 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 enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 enhance the immunosuppressive effect 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

Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy

Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy

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

Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to 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 enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect 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

Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy

Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect 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 combination

Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination

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

Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification

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

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

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 pomalidomide; also refer to the Pomalidomide monograph 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 monoclonal antibody (IgG1). Placental transfer of human IgG is dependent upon the IgG subclass, maternal serum concentrations, birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (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 pomalidomide; pomalidomide is contraindicated for use during pregnancy. Refer to the pomalidomide monograph for additional information.

Breastfeeding Considerations

It is not known if isatuximab is present in breast milk. However, isatuximab is a monoclonal antibody (IgG1) and 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 pomalidomide; refer to the pomalidomide monograph 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 patients with neutropenia for signs of infection; 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

Distribution: Vd: 8.13 L.

Metabolism: Metabolized into small peptides by catabolic pathways.

Pharmacokinetics: Additional Considerations

Body weight: Isatuximab clearance increases with increasing body weight.

Pricing: US

Solution (Sarclisa Intravenous)

100 mg/5 mL (per mL): $172.09

500 mg/25 mL (per mL): $172.09

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.

Brand Names: International
  • Sarclisa (AT, AU, CZ, DK, EE, FR, HR, HU, LT, LV, NL, NO, PT)


For country code abbreviations (show table)
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  9. Moreau P, Dimopoulos MA, Mikhael J, et al; IKEMA study group. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial. Lancet. 2021;397(10292):2361-2371. doi:10.1016/S0140-6736(21)00592-4 [PubMed 34097854]
  10. Palmeira P, Quinello C, Silveira-Lessa AL, Zago CA, Carneiro-Sampaio M. IgG placental transfer in healthy and pathological pregnancies. Clin DevImmunol. 2012;2012:985646. doi:10.1155/2012/985646 [PubMed 22235228]
  11. Pentsuk N, van der Laan JW. An interspecies comparison of placental antibody transfer: new insights into developmental toxicity testing of monoclonal antibodies. Birth Defects Res B Dev Reprod Toxicol. 2009;86(4):328-344. doi:10.1002/bdrb.20201 [PubMed 19626656]
  12. Sarclisa (isatuximab) biologics license application (BLA) multi-disciplinary review and evaluation. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/761113Orig1s000MultidisciplineR.pdf. Published April 30, 2019. Accessed November 13, 2020.
  13. Sarclisa (isatuximab) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis US LLC; July 2022.
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