Sarclisa

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ANNEX I  
 

SUMMARY OF PRODUCT CHARACTERISTICS  
 
 
 
 
 
 



 

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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
SARCLISA 20mg/mL concentrate for solution for infusion. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
 One ml of concentrate for solution for infusion contains 20 mg of isatuximab. 
 
Each vial contains 100 mg of isatuximab in 5 mL of concentrate (100 mg/5mL). 
Each vial contains 500 mg of  isatuximab in 25 mL of concentrate (500 mg/25mL). 
 
Isatuximab is an immunoglobulin G1 (IgG1) monoclonal antibody (mAb) produced from a 
mammalian cell line (Chinese Hamster Ovary, CHO). 
 
For the full list of excipients, see section 6.1.  
 
 
3. PHARMACEUTICAL FORM 
 
Concentrate for solution for infusion. 
Colourless to slightly yellow solution, essentially free of visible particulates. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications  
 
SARCLISA is indicated, in combination with pomalidomide and dexamethasone, for the treatment of 
adult patients with relapsed and refractory multiple myeloma (MM) who have received at least two 
prior therapies including lenalidomide and a proteasome inhibitor (PI) and have demonstrated disease 
progression on the last therapy. 
 
4.2 Posology and method of administration  
 
SARCLISA should be administered by a healthcare professional, in an environment where 
resuscitation facilities are available. 
 
Premedication 
Premedication should be used prior to SARCLISA infusion with the following medicinal products to 
reduce the risk and severity of infusion reactions: 

 • Dexamethasone 40 mg oral or intravenous (or 20 mg oral or intravenous for patients ≥75 years 
of age). 

• Acetaminophen 650 mg to 1000 mg oral (or equivalent). 

• H2 antagonists (ranitidine 50 mg intravenous or equivalent [e.g., cimetidine]), or oral proton 
pump inhibitors (e.g., omeprazole, esomeprazole). 

• Diphenhydramine 25 mg to 50 mg intravenous or oral (or equivalent [e.g., cetirizine, 
promethazine, dexchlorpheniramine]). The intravenous route is preferred for at least the first 4 
infusions. 



 

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The above recommended dose of dexamethasone (oral or intravenous) corresponds to the total dose to 
be administered only once before the infusion, as part of the premedication and the backbone 
treatment, before isatuximab and pomalidomide administration. 
 
The recommended premedication agents should be administered 15-60 minutes prior to starting a 
SARCLISA infusion. Patients who do not experience an infusion reaction upon their first 4 
administrations of SARCLISA may have their need for subsequent premedication reconsidered. 
 
Management of neutropenia 
The use of colony-stimulating factors (e.g. G-CSF) should be considered to mitigate the risk of 
neutropenia. In the event of grade 4 neutropenia, SARCLISA administration should be delayed until 
neutrophil count improves to at least 1.0 x 109/L (see section 4.4). 
 
Posology 

The recommended dose of SARCLISA is 10 mg/kg body weight administered as an intravenous 
infusion in combination with pomalidomide and dexamethasone (isatuximab regimen), according to 
the schedule in the Table 1: 

Table 1: SARCLISA dosing schedule in combination with pomalidomide and dexamethasone 
 

Cycles Dosing schedule 

Cycle 1  Days 1, 8, 15 and 22 (weekly) 

Cycle 2 and beyond  Days 1, 15 (every 2 weeks) 

 
Each treatment cycle consists of a 28-day period. Treatment is repeated until disease progression or 
unacceptable toxicity. 

For other medicinal products that are administered with SARCLISA, refer to the respective current 
summary of product characteristics. 

The administration schedule must be carefully followed. If a planned dose of SARCLISA is missed, 
administer the dose as soon as possible and adjust the treatment schedule accordingly, maintaining the 
treatment interval. 

Dose adjustments 
No dose reduction of SARCLISA is recommended. 
 
Administration adjustments should be made if patients experience infusion reactions (see “Method of 
administration” below). 
 
For other medicinal products that are administered with SARCLISA, the respective current summary 
of product characteristics should be considered. 
 
Special populations 
 
Elderly 
Based on population pharmacokinetic analysis, no dose adjustment is recommended in elderly 
patients. 
 
Patients with renal impairment 
Based on population pharmacokinetic analysis and on clinical safety, no dose adjustment is 
recommended in patients with mild to severe renal impairment (see section 5.2). 
 
Patients with hepatic impairment 
Based on population pharmacokinetic analysis, no dose adjustment is recommended in patients with 



 

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mild hepatic impairment. Data in patients with moderate and severe hepatic impairment are limited 
(see section 5.2), but there is no evidence to suggest that dose adjustment is required in these patients. 
 
Paediatric population 
The safety and efficacy of SARCLISA in children below 18 years of age have not been established. 
No data are available. 
 
Method of administration 
SARCLISA is for intravenous use. For instructions on dilution of the medicinal product before 
administration, see section 6.6. 
 
Infusion rates 
Following dilution, the SARCLISA infusion should be administered intravenously at the infusion rate 
presented in the Table 2 below (see section 5.1). Incremental escalation of the infusion rate should be 
considered only in the absence of infusion reactions (see section 4.8). 

 

Table 2: Infusion rates of SARCLISA administration 
 

 Dilution 
volume 

Initial rate 
 

Absence of 
infusion 
reaction 

Rate increment Maximum 
rate 

First infusion 250 mL 25 mL/ hour For 60 minutes 25 mL/hour every 
30 minutes 

150 mL/ hour

Second 
infusion 

250 mL 50 mL/ hour For 30 minutes 50 mL/ hour for 
30 minutes then 
increase by 100 
mL/ hr every 30 
minutes 

200 mL/ hour

Subsequent 
infusions 

250 mL 200 mL/ hour   200 mL/ hour

 
Administration adjustments should be made if patients experience infusion reactions (see section 4.4) 

 In patients who experience Grade 2 (moderate) infusion reactions, a temporary interruption in 
the infusion should be considered and additional symptomatic medicinal products can be 
administered. After improvement to grade ≤1 (mild), SARCLISA infusion may be resumed at 
half of the initial infusion rate under close monitoring and supportive care, as needed. If 
symptoms do not recur after 30 minutes, the infusion rate may be increased to the initial rate, 
and then increased incrementally, as shown in Table 2. 

 If symptoms do not resolve rapidly or do not improve to Grade ≤1 after interruption of 
SARCLISA infusion, recur after initial improvement with appropriate medicinal products, or 
require hospitalization or are life-threatening (Grade ≥3), treatment with SARCLISA should 
be permanently discontinued and additional supportive therapy should be administered, as 
needed. 

 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of its excipients listed in section 6.1. 

 
4.4 Special warnings and precautions for use 
 
Traceability 
In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
  



 

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Infusion reactions 
Infusion reactions, mostly mild or moderate, have been observed in 38.2% of patients treated with 
SARCLISA (see section 4.8). All infusion reactions started during the first SARCLISA infusion and 
resolved on the same day in 98% of the infusions. The most common symptoms of an infusion 
reaction included dyspnoea, cough, chills and nausea. The most common severe signs and symptoms 
included hypertension and dyspnoea (see section 4.8). 
 
To decrease the risk and severity of infusion reactions, patients should be pre-medicated prior to 
SARCLISA infusion with acetaminophen, H2 antagonists or proton pump inhibitors, diphenhydramine 
or equivalent; dexamethasone is to be used as both premedication and anti-myeloma treatment (see 
section 4.2). Vital signs should be frequently monitored during the entire SARCLISA infusion. When 
required, interrupt SARCLISA infusion and provide appropriate medical and supportive measures (see 
section 4.2). In case symptoms do not improve after interruption of SARCLISA infusion, recur after 
initial improvement with appropriate medicinal products, require hospitalization or are life-
threatening, permanently discontinue SARCLISA and institute appropriate management. 
 
Neutropenia 
Grade 3-4 neutropenia reported as laboratory abnormalities (84.9%) and neutropenic complications 
(30.3%) have been observed in patients treated with SARCLISA (see section 4.8).  
Complete blood cell counts should be monitored periodically during treatment. Patients with 
neutropenia should be monitored for signs of infection. No dose reductions of SARCLISA are 
recommended. SARCLISA dose delays and the use of colony-stimulating factors (e.g. G-CSF) should 
be considered to mitigate the risk of neutropenia (see section 4.2). 
 
Infection 
A higher incidence of infections including grade ≥ 3 infections, mainly pneumonia, upper respiratory 
tract infection and bronchitis, occurred with SARCLISA (see section 4.8). Patients receiving 
SARCLISA should be closely monitored for signs of infection and appropriate standard therapy 
instituted. Antibiotics, antifungal and antiviral prophylaxis can be considered during treatment. 
 
Second primary malignancies 
In ICARIA-MM study, second primary malignancies (SPMs) were reported in 6 patients (3.9%) 
treated with SARCLISA and in 1 patient (0.7%) treated with pomalidomide and dexamethasone, and 
included skin squamous cell carcinoma in 4 patients treated with SARCLISA and in 1 patient treated 
with pomalidomide and dexamethasone (see section 4.8). Patients continued treatment after resection 
of the skin squamous cell carcinoma. The overall incidence of SPMs in all the SARCLISA-exposed 
patients is 3%. Physicians should carefully evaluate patients before and during treatment as per IMWG 
guidelines for occurrence of SPM and initiate treatment as indicated. 
 
Interference with serological testing (indirect antiglobulin test) 
Isatuximab binds to CD38 on red blood cells (RBCs) and may result in a false positive indirect 
antiglobulin test (indirect Coombs test). To avoid potential problems with RBC transfusion, patients 
being treated with SARCLISA should have blood type and screen tests performed prior to the first 
infusion. Phenotyping may be considered prior to starting SARCLISA treatment as per local practice. 
If treatment with SARCLISA has already started, the blood bank should be informed. Patients should 
be monitored for theoretical risk of haemolysis. If an emergency transfusion is required, 
non- cross- matched ABO/Rh-compatible RBCs can be given as per local blood bank practices (see 
section 4.5). There is currently no available information with regards to how long the interference with 
the indirect Coombs test may persist after the last infusion of SARCLISA. Based on the half-life of 
isatuximab, it is anticipated that isatuximab mediated positive indirect Coombs test may persist for 
approximately 6 months after the last infusion. 
 
Interference with determination of complete response 
Isatuximab is an IgG kappa monoclonal antibody that could be detected on both serum protein 
electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of 
endogenous M-protein (see section 4.5). This interference can impact the accuracy of the 
determination of complete response in some patients with IgG kappa myeloma protein. Twenty-two 



 

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patients in the isatuximab regimen arm who met Very Good Partial Response (VGPR) criteria with 
only residual immunofixation-positivity were tested for interference. Serum samples from these 
patients were tested by mass spectrometry to separate isatuximab signal from the myeloma M-protein 
signal. (see section 4.5). 
 
Elderly 
Data are limited in the elderly population ≥ 85 years old (see section 4.2). 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Isatuximab has no impact on the pharmacokinetics of pomalidomide and vice versa. 
 
Interference with serological testing 
Because CD38 protein is expressed on the surface of red blood cells, isatuximab, an anti-CD38 
antibody, may interfere with blood bank serologic tests with potential false positive reactions in 
indirect antiglobulin tests (indirect Coombs tests), antibody detection (screening) tests, antibody 
identification panels, and antihuman globulin (AHG) crossmatches in patients treated with isatuximab 
(see section 4.4). The interference mitigation methods include treating reagent RBCs with 
dithiothreitol (DTT) to disrupt isatuximab binding or other locally validated methods. Since the Kell 
Blood group system is also sensitive to DTT treatment, Kell-negative units should be supplied after 
ruling out or identifying alloantibodies using DTT-treated RBCs. 
 
Interference with Serum Protein Electrophoresis and Immunofixation Tests 
Isatuximab may be detected by serum protein electrophoresis (SPE) and immunofixation (IFE) assays 
used for the monitoring of M-protein, and could interfere with accurate response classification based 
on International Myeloma Working Group (IMWG) criteria (see section 4.4). 

4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential/Contraception 
Women of childbearing potential treated with isatuximab should use effective contraception during 
treatment and for 5 months after cessation of treatment. 
 
Pregnancy 
There are no available data on  isatuximab use in pregnant women. Animal reproduction toxicity 
studies have not been conducted with  isatuximab. Immunoglobulin G1 monoclonal antibodies are 
known to cross the placenta after the first trimester of pregnancy. The use of isatuximab in pregnant 
women is not recommended.  
 
Breast-feeding 
It is unknown whether isatuximab is excreted in human milk. Human IgGs are known to be excreted in 
breast milk during the first few days after birth, which is decreasing to low concentrations soon 
afterwards; however, a risk to the breast-fed child cannot be excluded during this short period just 
after birth. For this specific period, a decision must be made whether to discontinue breast-feeding or 
to discontinue/abstain from isatuximab therapy taking into account the benefit of breast-feeding for the 
child and the benefit of therapy for the woman. Afterwards, isatuximab  could be used during breast-
feeding if clinically needed. 
 
Fertility 
No human and animal data are available to determine potential effects of isatuximab on fertility in 
males and females (see section 5.3). 
 
For other medicinal products that are administered with isatuximab, refer to the respective current 
summary of product characteristics. 
 



 

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4.7 Effects on ability to drive and use machines 
 

SARCLISA has no or negligible influence on the ability to drive and use machines. 

 
4.8 Undesirable effects 
 
Summary of the safety profile 
The most frequent adverse reactions (>20%) are neutropenia (46.7%), infusion reactions (38.2%), 
pneumonia (30.9%), upper respiratory tract infection (28.3%), diarrhoea (25.7%) and bronchitis 
(23.7%). 
 
The most frequent serious adverse reactions are pneumonia (9.9%) and febrile neutropenia (6.6%). 
 
Tabulated list of adverse reactions 
Adverse  reactions are described using the NCI Common Toxicity Criteria, the COSTART and the 
MedDRA terms. Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10); 
uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known 
(cannot be estimated from available data). 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.  
The adverse reactions were selected based on an incidence of ≥ 5% (all grades) or ≥ 2% (grades ≥3) of 
patients treated with isatuximab regimen group and based on the incidence rate being ≥ 5% greater in 
the isatuximab regimen group compared to the comparator regimen (pomalidomide and low-dose 
dexamethasone) group. The terms atrial fibrillation and skin squamous cell carcinoma were added 
because of their clinical relevance. 
 
  



 

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Table 3a: Adverse reactions reported in patients with multiple myeloma treated with isatuximab 
in combination with pomalidomide and low-dose dexamethasone (ICARIA-MM study) 
 
System Organ Class 

Preferred Term  
Adverse reaction Frequency Incidence (%) 

(N=152) 
Any Grade Grade ≥3 

Infections and 
infestations 

Pneumoniab Very common 47 (30.9) 40 (26.3) 

Upper respiratory tract 
infection* 

Very common 
43 (28.3) 5 (3.3) 

Bronchitis* Very common 36 (23.7) 5 (3.3)        

Neoplasms benign, 
malignant and 
unspecified (incl cysts 
and polyps) 

Skin squamous cell 
carcinoma 

Common 

4 (2.6) 2 (1.3) 

Blood and lymphatic 
system disorders 

Neutropeniac Very common 71 (46.7) 70 (46.1) 

Febrile neutropenia Very common 18 (11.8) 18 (11.8) 

Metabolism and 
nutrition disorders 

Decreased appetite* Common   15 (9.9) 2 (1.3) 

Cardiac disorders Atrial fibrillation Common 7 (4.6) 3 (2.0) 

Respiratory, thoracic 
and mediastinal 
disorders 

Dyspnoea* Very common 
23 (15.1) 6 (3.9) 

Gastrointestinal 
disorders 

Diarrhoea* Very common 39 (25.7) 3 (2.0) 

Nausea* Very common 23 (15.1) 0 

Vomiting* Very common 18 (11.8) 2 (1.3) 

Investigations Weight decreased* Common 10 (6.6) 0 

Injury, poisoning 
and procedural 
complications 

Infusion reaction 
 

Very common 58 (38.2) 4 (2.6) 

a Only TEAEs are reported in the Table 3. The haematology laboratory values are reported in the Table 4.  
b The term pneumonia is a grouping of the following terms: atypical pneumonia, bronchopulmonary 
aspergillosis, pneumonia, pneumonia haemophilus, pneumonia influenzal, pneumonia pneumococcal, pneumonia 
streptococcal, pneumonia viral, candida pneumonia, pneumonia bacterial, haemophilus infection, lung infection, 
pneumonia fungal and pneumocystis jirovecii pneumonia. 
c Haematology laboratory values were recorded as TEAEs only if they led to treatment discontinuation and/or 
dose modification and/or fulfilled a serious criterion and/or were defined as an AESI. 
* No grade 4                                                                                                                                                                                            
 
Description of selected adverse reactions 
 
Infusion reactions 
In ICARIA-MM, infusion reactions were reported in 58 patients (38.2%) treated with SARCLISA. All 
patients who experienced infusion reactions, experienced them during the 1st infusion of SARCLISA, 
with 3 patients (2.0%) also having infusion reactions at their 2nd infusion, and 2 patients (1.3%) at 
their 4th infusion.  Grade 1 infusion reactions were reported in 3.9%, Grade 2 in 31.6%, Grade 3 in 
1.3%, and Grade 4 in 1.3% of the patients. All infusion reactions were reversible and resolved the 



 

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same day in 98% of the infusions. Signs and symptoms of Grade 3 or higher infusion reactions 
included dyspnoea, hypertension and bronchospasm. 
The incidence of infusion interruptions because of infusion reactions was 28.9%.  The median time to 
infusion interruption was 55 minutes. 
Discontinuations from treatment due to infusion reaction were reported in 2.6% of patients in 
isatuximab regimen group. 
 
Infections 
In ICARIA-MM, the incidence of Grade 3 or higher infections was 42.8%.  Pneumonia was the most 
commonly reported severe infection with Grade 3 reported in 21.7% of patients in isatuximab regimen 
group compared to 16.1% in comparator regimen (pomalidomide and low-dose dexamethasone) group, 
and Grade 4 in 3.3% of patients in isatuximab regimen group compared to 2.7% in comparator regimen 
group. Discontinuations from treatment due to infection were reported in 2.6% of patients in isatuximab 
regimen group compared to 5.4% in comparator regimen group. Fatal infections were reported in 3.3% 
of patients in isatuximab regimen group and 4.0% in comparator regimen group. 
 
Haematology laboratory values 
 
Table 4: Haematology laboratory abnormalities in patients receiving isatuximab combined with 
pomalidomide and low-dose dexamethasone–versus pomalidomide and low-dose dexamethasone 
(ICARIA-MM) 
 
Laboratory 
parameter 

SARCLISA + Pomalidomide + low-
dose Dexamethasone 
n(%) 
(N=152) 

Pomalidomide + low-dose 
Dexamethasone 
n(%) 
(N=147) 

 All grades Grade 3 Grade 4 All grades Grade 3 Grade 4 
Anemia 151 (99.3) 48 (31.6) 0 145 (98.6) 41 (27.9) 0 
Neutropenia 146 (96.1) 37 (24.3) 92 (60.5) 137 (93.2) 57 (38.8) 46 (31.3) 
Lymphopenia 140 (92.1) 64 (42.1) 19 (12.5) 137 (93.2) 52 (35.4) 12 (8.2) 
Thrombocytopenia 127 (83.6) 22 (14.5) 25 (16.4) 118 (80.3) 14 (9.5) 22 (15.0) 
The denominator used for the percentage calculation is the number of patients with at least 1 
evaluation of the laboratory test during the considered observation period. 
 
Immunogenicity 
Across 6 clinical studies in multiple myeloma (MM) with isatuximab single agent and combination 
therapies including ICARIA-MM (N=564), the incidence of treatment emergent ADAs was 2.3%. No 
effect of ADAs was observed on pharmacokinetics, safety or efficacy of isatuximab. 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Signs and symptoms 
There has been no experience of overdosage in clinical studies. Doses of intravenous isatuximab up to 
20 mg/kg have been administered in clinical studies. 
 
Management 
There is no known specific antidote for SARCLISA overdose. In the event of overdose, monitor the 
patients for signs or symptoms of adverse reactions and take all appropriate measures immediately. 
 
 



 

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5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antineoplastic agents, monoclonal antibodies, ATC code: L01XC38. 
 
Mechanism of action 
Isatuximab is an IgG1-derived monoclonal antibody that binds to a specific extracellular epitope of 
CD38 receptor. CD38 is a transmembrane glycoprotein that is highly expressed on multiple myeloma 
cells. 

In vitro, isatuximab acts through IgG Fc-dependent mechanisms including: antibody dependent cell 
mediated cytotoxicity (ADCC), antibody dependent cellular phagocytosis (ADCP), and complement 
dependent cytotoxicity (CDC). Furthermore, isatuximab can also trigger tumor cell death by induction 
of apoptosis via an Fc-independent mechanism. 

In vitro, isatuximab blocks the enzymatic activity of CD38 which catalyzes the synthesis and 
hydrolysis of cyclic ADP-ribose (cADPR), a calcium mobilizing agent. Isatuximab inhibits the 
cADPR production from extracellular nicotinamide adenine dinucleotide (NAD) in multiple myeloma 
cells. 
 
In vitro, isatuximab can activate NK cells in the absence of CD38 positive target tumour cells. 
In vivo, a decrease in absolute counts of total CD16+ and CD56+ NK cells, CD19+ B-cells, CD4+ T-
cells and TREG (CD3+, CD4+, CD25+, CD127-) was observed in peripheral blood of patients treated 
with isatuximab monotherapy. 
 
In multiple myeloma patients, SARCLISA monotherapy induced clonal expansion of the T-cell 
receptor repertoire indicating an adaptive immune response. 
 
The combination of isatuximab and pomalidomide in vitro enhances cell lysis of CD38 expressing 
multiple myeloma cells by effector cells (ADCC), and by direct tumour cell killing compared to that 
of isatuximab alone.  In vivo animal experiments using a human multiple myeloma xenograft model in 
mice demonstrated that the combination of isatuximab and pomalidomide results in enhanced 
antitumour activity compared to the activity of isatuximab or pomalidomide alone. 
 
Clinical efficacy and safety 
ICARIA-MM (EFC14335) 
 
The efficacy and safety of SARCLISA in combination with pomalidomide and low-dose 
dexamethasone were evaluated in ICARIA-MM (EFC14335), a multicenter, multinational, 
randomised, open-label, 2-arm, phase III study in patients with relapsed and refractory multiple 
myeloma. Patients had received at least two prior therapies including lenalidomide and a proteasome 
inhibitor with disease progression on or within 60 days after the end of the previous therapy. Patients 
with primary refractory disease were excluded. 
 
A total of 307 patients were randomised in a 1:1 ratio to receive either SARCLISA in combination 
with pomalidomide and low-dose dexamethasone (isatuximab regimen, 154 patients) or pomalidomide 
and low-dose dexamethasone (comparator regimen, 153 patients). Treatment was administered in both 
groups in 28-day cycles until disease progression or unacceptable toxicity. SARCLISA 10 mg/kg was 
administered as an I.V. infusion weekly in the first cycle and every two weeks thereafter. 
Pomalidomide 4 mg was taken orally once daily from day 1 to day 21 of each 28-day cycle. Low-dose 
dexamethasone (oral/intravenous) 40 mg (20 mg for patients ≥75 years of age) was given on days 1, 8, 
15 and 22 for each 28-day cycle. 
 
Overall, demographic and disease characteristics at baseline were similar between the two treatment 
groups, with some minor imbalances. The median patient age was 67 years (range 36-86), 19.9% of 
patients were ≥75 years. ECOG PS was 0 in 35.7% of patients in the isatuximab arm and 45.1% in the 
comparator arm, 1 in 53.9% in the isatuximab arm and 44.4% in the comparator arm, and 2 in 10.4% 



 

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in the isatuximab arm and 10.5% in the comparator arm, 10.4% of patients in the isatuximab arm 
versus 10.5% in the comparator arm entered the study with a history of COPD or asthma, and 38.6% 
versus 33.3% of patients with renal impairment (creatinine clearance <60 mL/min/1.73 m²) were 
included in the isatuximab arm  versus the comparator arm , respectively. The International Staging 
System (ISS) stage at study entry was I in 37.5% (41.6% in the isatuximab arm and 33.3% in the 
comparator arm), II in 35.5% (34.4% in the isatuximab arm and 36.6% in the comparator arm) and III 
in 25.1% (22.1% in the isatuximab arm and 28.1% in the comparator arm) of patients. Overall, 19.5% 
of patients (15.6% in the isatuximab arm and 23.5% in the comparator arm) had high-risk 
chromosomal abnormalities at study entry; del(17p), t(4;14) and  t(14;16) were present in 12.1% 
(9.1% in the isatuximab arm and 15.0% in the comparator arm), 8.5%  (7.8% in the isatuximab arm 
and 9.2% in the comparator arm) and 1.6%  (0.6% in the isatuximab arm and 2.6% in the comparator 
arm) of patients, respectively. 
 
The median number of prior lines of therapy was 3 (range 2-11). All patients received a prior 
proteasome inhibitor, all patients received prior lenalidomide, and 56.4% of patients received prior 
stem cell transplantation. The majority of patients (92.5%) were refractory to lenalidomide, 75.9% 
to a proteasome inhibitor, and 72.6% to both an immunomodulatory and a proteasome inhibitor, and 
59% of patients were refractory to lenalidomide at last line of therapy. 
 
The median duration of treatment was 41.0 weeks for the isatuximab regimen group compared to 24.0 
weeks for the comparator regimen group. 
 
Progression free survival (PFS) was the primary efficacy endpoint of ICARIA-MM. The improvement 
in PFS represented a 40.4% reduction in the risk of disease progression or death in patients treated 
with the isatuximab regimen. 
 
Efficacy results are presented in the table 5 and Kaplan-Meier curves for PFS and OS are provided in 
Figures 1 and 2: 
 
  



 

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Table 5: Efficacy of SARCLISA in combination with pomalidomide and low-dose 
dexamethasone versus pomalidomide and low-dose dexamethasone in the treatment of multiple 
myeloma (intent-to-treat analysis) 
 

Endpoint SARCLISA + 
pomalidomide + low-dose 

dexamethasone 
N =154 

Pomalidomide + low-dose 
dexamethasone 

N = 153 

Progression-Free Survivala b   

Median (months) 
[95% CI] 

11.53 
[8.936-13.897] 

6.47 
[4.468-8.279] 

Hazard ratioc [95% CI] 0.596 [0.436-0.814] 

p-value (stratified log-rank test)c 0.0010 

Overall Response Rated 
Responders 
(sCR+CR+VGPR+PR) n(%) 
[95% CI]e 

 
 

93 (60.4) 
[0.5220-0.6817] 

 
 

54 (35.3) 
[0.2775-0.4342] 

Odds ratio vs comparator [95% 
exact CI] 

2.795 [1.715-4.562] 

p-value (stratified Cochran-
Mantel-Haenszel)c 

<0.0001 

Stringent Complete Response 
(sCR) + Complete Response 
(CR) n(%) 

7 (4.5) 3 (2.0) 

Very Good Partial Response 
(VGPR) n(%) 

42 (27.3) 10 (6.5) 

Partial Response (PR) n(%) 44 (28.6) 41 (26.8) 

VGPR or better n(%) 
[95% CI]e 

49 (31.8) 
[0.2455-0.3980] 

13 (8.5) 
[0.0460-0.1409] 

Odds ratio vs comparator [95% 
exact CI] 

5.026 [2.514-10.586] 

p-value (stratified Cochran-Mantel 
Haenszel)c 

<0.0001 

Duration of Responsef *  
Median in months [95% CI]g 

 
 

13.27 [10.612-NR]  

 
 

11.07 [8.542-NR] 
a PFS results were assessed by an Independent Response Committee based on central laboratory data for M-
protein and central radiologic imaging review using the International Myeloma Working Group (IMWG) 
criteria.  
b Patients without progressive disease or death before the analysis cut-off or the date of initiation of further anti-
myeloma treatment were censored at the date of the last valid disease assessment not showing disease 
progression performed prior to initiation of a further anti-myeloma treatment (if any) or the analysis cut-off date, 
whichever came first. 
c Stratified on age (<75 years versus >75 years) and number of previous lines of therapy (2 or 3 versus >3) 
according to IRT.  
d sCR, CR, VGPR and PR were evaluated by the IRC using the IMWG response criteria.  
e Estimated using Clopper-Pearson method. 



 

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f The duration of response was determined for patients who achieved a response of ≥PR (93 patients in the 
isatuximab arm and 54 patients in the comparator arm). Kaplan-Meier estimates of duration of response. 
g CI for Kaplan-Meier estimates are calculated with log-log transformation of survival function and methods of 
Brookmeyer and Crowle. 
*Cut-off date of 11-Oct-2018. Median follow-up time=11.60 months. HR<1 favors isatuximab regimen arm. 
NR: not reached 
 
In patients with high-risk cytogenetics (central laboratory assessment), median PFS was 7.49 (95% CI: 
2.628 to NC) in the isatuximab regimen group and 3.745 (95% CI: 2.793 to 7.885) in the comparator 
regimen group (HR=0.655; 95% CI: 0.334 to 1.283). PFS improvements in the isatuximab regimen 
group were also observed in patients >75 years (HR=0.479; 95% CI: 0.242 to 0.946), with ISS stage 
III at study entry (HR=0.635; 95% CI: 0.363 to 1.110), with baseline creatinine clearance < 60 
ml/min/1.73 m² (HR=0.502; 95% CI: 0.297 to 0.847), with > 3 prior lines of therapy (HR=0.590; 95% 
CI: 0.356 to 0.977), in patients refractory to prior therapy with lenalidomide (HR=0.593; 95% CI: 
0.431 to 0.816) or proteasome inhibitor (HR=0.578; 95% CI: 0.405 to 0.824) and in those refractory to 
lenalidomide at the last line before to the study entry (HR= 0.601; 95%CI: 0.436 to 0.828).  
Insufficient data is available to conclude on the efficacy of isatuximab regimen in patients previously 
treated with daratumumab (1 patient in the isatuximab arm and no patient in the comparator arm). 
 
The median time to first response in responders was 35 days in the isatuximab group versus 58 days in 
the comparator group. With a median duration of follow-up of 11.56 months in the isatuximab group 
and 11.73 months in the comparator group, median overall survival was not reached for either 
treatment group. The hazard ratio for OS was 0.687 (95% CI: 0.461-1.023, p-value=0.0631). 
 
Figure 1: Kaplan-Meier Curves of PFS – ITT population – ICARIA-MM (assessment by the 
IRC)  

 
  



 

14 

Figure 2: Kaplan-Meier Curves of OS – ITT population – ICARIA-MM 

 

 
Cutoff date = 11 October 2018 

 
In the ICARIA-MM (EFC14335) study, a weight-based volume was used for isatuximab infusion. The 
fixed volume infusion method as described in section 4.2 was evaluated in study TCD14079 Part B 
and pharmacokinetics simulations confirmed minimal differences between the pharmacokinetics 
following injection applying a volume based on patient weight and a fixed volume of 250 mL (see 
section 5.2). In study TCD14079 part B, there were no new safety signals or differences in efficacy as 
compared to the ICARIA-MM study. 
 
Paediatric population 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
SARCLISA in one or more subsets of the paediatric population in the treatment of malignant 
neoplasms of the haematopoietic and lymphoid tissue. See section 4.2 for information on paediatric 
use. 
 
5.2 Pharmacokinetic properties 
 
The pharmacokinetics of isatuximab were assessed in 476 patients with multiple myeloma treated with 
isatuximab intravenous infusion as a single agent or in combination with pomalidomide and 
dexamethasone, at doses ranging from 1 to 20 mg/kg, administered either once weekly; every 2 weeks; 
or every 2 weeks for 8 weeks followed by every 4 weeks; or every week for 4 weeks followed by 
every 2 weeks. 
 
Isatuximab displays nonlinear pharmacokinetics with target-mediated drug disposition due to its 
binding to CD38 receptor. 
Isatuximab exposure (area under the plasma concentration-time curve over the dosing interval AUC) 
increases in a greater than dose proportional manner from 1 to 20 mg/kg following every 2 weeks 
schedule, while no deviation to the dose proportionality is observed between 5 and 20 mg/kg 
following every week for 4 weeks followed by every 2 weeks schedule. This is due to the high 
contribution of nonlinear target-mediated clearance to the total clearance at doses below 5 mg/kg, 
which becomes negligible at higher doses. After isatuximab 10 mg/kg administration every week for 4 
weeks followed by every 2 weeks, the median time to reach steady state was 8 weeks with a 3.1-fold 
accumulation. The mean (CV%) predicted maximum plasma concentration Cmax and AUC at steady 



 

15 

state were 351 µg/mL (36.0%) and 72,600 µg.h/mL (51.7%), respectively. Although the change from 
a weight-based volume administration method for isatuximab infusion to the fixed volume infusion 
method resulted in changes in the tmax, the change had a limited impact on pharmacokinetics exposure 
with comparable simulated Cmax at steady state (283 µg/mL vs 284 µg/mL) and Ctrough at 4 
weeks (119 µg/mL vs 119 µg/mL) for a patient with median weight (76 kg). Also for other patient 
weight groups, Cmax and Ctrough were comparable. 
 
The pharmacokinetics of isatuximab and pomalidomide were not influenced by their 
co-administration. 
 
Distribution 
The estimated total volume of distribution of isatuximab is 8.75 L. 
 
Metabolism 
As a large protein, isatuximab is expected to be metabolized by non-saturable proteolytic catabolism 
processes. 
 
Elimination 
Isatuximab is eliminated by two parallel pathways, a nonlinear target-mediated pathway 
predominating at low concentrations, and a nonspecific linear pathway predominating at higher 
concentrations. In the therapeutic plasma concentrations range, the linear pathway is predominant and 
decreases over time by 50% to a steady state value of 9.55 mL/h (0.229 L/day). This is associated with 
a terminal half-life of 28 days. 
 
Specific populations 
 
Age  
The population pharmacokinetic analyses of 476 patients aged 36 to 85 years showed comparable 
exposure to isatuximab in patients <75 years old (n=406) versus ≥ 75 years old (n=70). 
 
Gender 
The population pharmacokinetic analysis with 207 female (43.5%) and 269 male (56.5%) patients 
showed no clinically meaningful effect of gender on isatuximab pharmacokinetics. 
 
Race 
The population pharmacokinetic analysis with 377 Caucasian (79%), 25 Asian (5%), 18 Black (4%), 
and 33 other race (7%) patients showed no clinically meaningful effect of race on isatuximab 
pharmacokinetics. 
 
Weight 
Isatuximab exposure (AUC) at steady state decreased with increasing body weight. 
 
Hepatic Impairment 
No formal studies of isatuximab in patients with hepatic impairment have been conducted. Out of the 
476 patients of the population pharmacokinetic analyses, 65 patients presented with mild hepatic 
impairment [total bilirubin 1 to 1.5 times upper limit of normal (ULN) or aspartate amino transferase 
(AST) > ULN] and 1 patient had moderate hepatic impairment (total bilirubin> 1.5 to 3 times ULN 
and any AST). Mild hepatic impairment had no clinically meaningful effect on the pharmacokinetics 
of isatuximab. The effect of moderate (total bilirubin >1.5 times to 3 times ULN and any AST) and 
severe hepatic impairment (total bilirubin >3 times ULN and any AST) on isatuximab 
pharmacokinetics is unknown. However, since isatuximab is a monoclonal antibody, it is not expected 
to be cleared via hepatic-enzyme mediated metabolism and as such, variation in hepatic function is not 
expected to affect the elimination of isatuximab (see section 4.2). 
 
Renal Impairment 
No formal studies of isatuximab in patients with renal impairment have been conducted. The 
population pharmacokinetic analyses on 476 patients included 192 patients with mild renal impairment 



 

16 

(60 mL/min/1.73 m2 ≤ estimated glomerular filtration rate (e-GFR) <90 mL/min/1.73 m2), 163 patients 
with moderate renal impairment (30 mL/min/1.73 m2≤ e-GFR < 60 mL/min/1.73 m2) and 12 patients 
with severe renal impairment (e-GFR <30 mL/min/1.73 m2). Analyses suggested no clinically 
meaningful effect of mild to severe renal impairment on isatuximab pharmacokinetics compared to 
normal renal function. 
 
Paediatric population 
Isatuximab was not evaluated in patients under 18 years of age. 
 
5.3 Preclinical safety data  
 
Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dose 
toxicity, albeit the species selected is not pharmacologically responsive and therefore the relevance for 
humans is not known. Genotoxicity, carcinogenic potential and toxicity to reproduction and 
development studies have not been performed. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sucrose 
Histidine hydrochloride monohydrate 
Histidine  
Polysorbate 80   
Water for injections 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
6.3 Shelf life 
 
Unopened Vial 
3 years 
 
After dilution 
Chemical and physical in-use stability of SARCLISA infusion solution has been demonstrated for 48 
hours at 2°C - 8°C, followed by 8 hours (including the infusion time) at room temperature.  
From a microbiological point of view, the product should be used immediately. If not used 
immediately, in-use storage times and conditions prior use are the responsibility of the user and would 
normally not be longer than 24 hours at 2°C to 8°C, unless dilution has taken place in controlled and 
validated aseptic conditions. 
No protection from light is required for storage in the infusion bag. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Store in the original package in order to protect from light. 
 
For storage conditions after dilution of the medicinal product, see section 6.3. 
 



 

17 

6.5 Nature and contents of container 
 
5 ml concentrate containing 100 mg of isatuximab in a 6 mL type I colourless clear glass vial closed 
with ETFE (copolymer of ethylene and tetrafluoroethylene)-coated bromobutyl stopper. The vials are 
crimped with an aluminium seal with a grey flip-off button. The fill volume has been established to 
ensure removal of 5 mL (i.e. 5.4 mL). Pack size of one or three vials. 
  
25 ml concentrate containing 500 mg of isatuximab in a 30 mL type I colourless clear glass vial closed 
with ETFE (copolymer of ethylene and tetrafluoroethylene)-coated bromobutyl stopper. The vials are 
crimped with an aluminium seal with a blue flip-off button. The fill volume has been established to 
ensure removal of 25 mL (i.e. 26 mL). Pack size of one vial. 

 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 

 
Preparation for the intravenous administration 
The preparation of the infusion solution must be done under aseptic conditions. 
 

 The dose (mg) of SARCLISA concentrate should be calculated based on patient weight 
(measured prior to each cycle to have the administered dose adjusted accordingly, see section 
4.2). More than one vial may be necessary to obtain the required dose for the patient. 

 Vials of SARCLISA concentrate should be visually inspected before dilution to ensure they do 
not contain any particles and are not discolored. 

 Do not shake vials. 
 The volume of diluent equal to the required volume of SARCLISA concentrate should be 

removed from a 250 mL sodium chloride 9 mg/mL (0.9%) solution for injection or glucose 
5% solution diluent bag. 

 The appropriate volume of SARCLISA concentrate should be withdrawn and diluted in the 
250 mL infusion bag with sodium chloride 9 mg/mL (0.9%) solution for injection or glucose 
5% solution. 

 The infusion bag must be made of polyolefins (PO), polyethylene (PE), polypropylene (PP), 
polyvinyl chloride (PVC) with di (2-ethylhexyl) phthalate (DEHP) or ethyl vinyl acetate 
(EVA). 

 Gently homogenize the diluted solution by inverting the bag. Do not shake. 
 
Administration 

 The infusion solution must be administered by intravenous infusion using an intravenous 
tubing infusion set (in PE, PVC with or without DEHP, polybudadiene (PBD) or polyurethane 
(PU)) with an in-line filter (polyethersulfone (PES), polysulfone or nylon).   

 The infusion solution should be administered for a period of time that will depend on the 
infusion rate (see section 4.2). 

 No protection from light is required for the prepared infusion bag in a standard artificial light 
environment. 

 Do not infuse SARCLISA solution concomitantly in the same intravenous line with other 
agents. 
 

Disposal 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
  



 

18 

7. MARKETING AUTHORISATION HOLDER 
 
sanofi-aventis groupe 
54 rue La Boétie 
75008 Paris 
France 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/20/1435/001 
EU/1/20/1435/002 
EU/1/20/1435/003 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 
  



 

19 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE 
SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR 
BATCH RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 
 
 



 

20 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer of the biological active substance 
 
Sanofi Chimie, 
9, quai Jules Guesde, BP35 
94403 Vitry-sur-Seine cedex, France 
 
Name and address of the manufacturer responsible for batch release 
 
Sanofi-Aventis Deutschland GmbH 
Industriepark Hoechst Brueningstrasse 50 
65926 Frankfurt am Main 
Germany 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
  
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
 Periodic safety update reports (PSURs) 
 
The requirements for submission of PSURs periodic safety update reports for this medicinal 
product are set out in the list of Union reference dates (EURD list) provided for under Article 
107c(7) of Directive 2001/83/EC and any subsequent updates published on the European 
medicines web-portal. 
 
The marketing authorisation holder (MAH) shall submit the first PSUR for this product within 
6 months following authorisation. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
 Risk management plan (RMP) 

 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance 
activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the 
marketing authorisation and any agreed subsequent updates of the RMP. 
 
An updated RMP should be submitted: 

 At the request of the European Medicines Agency; 
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
An updated RMP shall be submitted by {CHMP agreed deadline}. 
  



 

21 

 Additional risk minimisation measures 

The Healthcare professionals (HCPs) and blood bank educational material includes the 
following elements: 

 The Summary of Product Characteristics 
 The HCPs and Blood Banks brochure 
 Patient Alert Card 

 
The HCPs and Blood Banks brochure will contain the following key information: 
 
Relevant information of the safety concern “Interference with indirect antiglobulin test (indirect 
Coombs test)”: 
 

• Isatuximab bound to red blood cells (RBCs) may mask the detection of antibodies to minor 
antigens in the patient’s serum 

• The determination of a patient’s ABO and Rh blood type are not impacted 
 
Details on how to minimize the safety concern addressed by the additional risk minimization measures 
through appropriate measures: 
 

• All patients should be blood typed and screened prior to start treatment with isatuximab. 
Phenotyping may be considered prior to starting isatuximab treatment as per local practice. 

• There is currently no available information with regards to how long the interference with the 
indirect Coombs test may persist after the last infusion of isatuximab. Based on the half-life of 
isatuximab, isatuximab mediated positive indirect Coombs test may persist for approximately 
6 months after the last isatuximab infusion therefore the HCP should advise the patient to 
carry the Patient Alert Card until 6 months after the treatment has ended. 

• The interference mitigation methods include treating reagent RBCs with dithiothreitol (DTT) 
to disrupt isatuximab binding or other locally validated methods. Since the Kell Blood group 
system is also sensitive to DTT treatment, Kell-negative units should be supplied after ruling 
out or identifying alloantibodies using DTT-treated RBCs.  

• In case of urgent need for transfusion, non-cross matched ABO/Rh compatible RBC units can 
be administered as per local bank practices. 

• In the event of a planned transfusion, the HCPs should notify blood transfusion centres about 
the risk of interference with indirect antiglobulin tests. 

• Emphasize the need to consult the Summary of Product Characteristics (SmPC). 
• Instruct the HCP regarding the need to give the Patient Alert Card to the patients and to advise 

them to consult the Package Leaflet (PL). 
 
Patient Alert Card 
 
The Patient Alert Card will contain the following brief and concise information regarding the risk of 
“Interference with indirect antiglobulin test (indirect Coombs test)” both for patients and HCPs 
consulted by the patient: 
 

 A warning message for HCPs treating the patient at any time, including in conditions of 
emergency, that the patient is using SARCLISA (isatuximab), and that this treatment is 
associated with the Important Identified Risk of Interference with indirect antiglobulin test 
(Indirect Coombs test), which may persist for approximately 6 months after the last isatuximab 
infusion 

 A clear reference that the patient should continue to carry this card until 6 months after the 
treatment has ended. 

 Contact details of the prescriber and the patient. 
 
  



 

22 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



 

23 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



 

24 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT  
 
SARCLISA 20 mg/mL concentrate for solution for infusion 
isatuximab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial contains 100 mg of isatuximab in 5 mL of concentrate. 
Each vial contains 500 mg of isatuximab in 25 mL of concentrate. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: sucrose, histidine hydrochloride monohydrate, histidine, polysorbate 80, water for 
injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS  
 
Concentrate for solution for infusion 
1 vial, 100 mg/ 5mL 
3 vials, 100 mg/5 mL 
1 vial, 500 mg/25 mL 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intravenous use 
For single-use only 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Do not shake. 
 
 
8. EXPIRY DATE 
 
EXP: 
 
 



 

25 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Store in the original package in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
sanofi-aventis groupe 
54 rue La Boétie 
75008 Paris 
France 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/20/1435/001  
EU/1/20/1435/002  
EU/1/20/1435/003  
 
 
13. BATCH NUMBER  
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



 

26 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION  
 
SARCLISA 20 mg/ mL concentrate for solution for infusion 
isatuximab  
Intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE  
 
EXP: 
 
 
4. BATCH NUMBER 
 
Lot: 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
100 mg/5 mL  
500 mg/25 mL 
 
 
6. OTHER  
 
  



 

27 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
  



 

28 

Package leaflet: Information for the patient 
 

Sarclisa 20mg/ mL concentrate for solution for infusion 
isatuximab 

 
This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
 Keep this leaflet. You may need to read it again.  
 If you have any further questions, ask your doctor, pharmacist,  or nurse. 
 If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 

effects not listed in this leaflet. See section 4. 

 
What is in this leaflet 
 
1. What Sarclisa is and what it is used for  
2. What you need to know before you are given Sarclisa 
3. How Sarclisa is used 
4. Possible side effects 
5. How to store Sarclisa 
6. Contents of the pack and other information 
 
 
1. What Sarclisa is and what it is used for 
 
What Sarclisa is 
Sarclisa is a cancer medicine that contains the active substance isatuximab. It belongs to a group of 
medicines called “monoclonal antibodies”.  
Monoclonal antibodies, such as Sarclisa, are proteins that have been designed to recognise and attach 
themselves to a target substance. In the case of Sarclisa, the target is a substance called CD38 that is 
found on cells of multiple myeloma, a cancer of the bone marrow. By attaching to multiple myeloma 
cells, the medicine helps your immune system (the natural defences of your body) identify and destroy 
them. 
 
What is Sarclisa used for 
Sarclisa is used to treat multiple myeloma in patients who have had at least 2 treatments for multiple 
myeloma before. 
It is used together with two other medicines called pomalidomide and dexamethasone. 
 
If you have any questions on how Sarclisa works or about your treatment with Sarclisa, ask your 
doctor. 
 
2. What you need to know before you use Sarclisa 
 
You must not be given Sarclisa if: 
 you are allergic to isatuximab or any of the other ingredients of this medicine (listed in section 6). 

Warnings and precautions  
Talk to your doctor or nurse before using Sarclisa and follow all instructions carefully. 
 
Infusion reactions 
Tell your doctor or nurse immediately if you have signs of infusion reactions during or after the 
infusion of Sarclisa - see in section 4 for the list of signs of ‘Infusion reactions’. 



 

29 

 Before starting a Sarclisa infusion, you may be given medicines to reduce infusion reactions (see 
section 3). 

 Infusion reactions can happen during the Sarclisa infusion or after the infusion. These reactions 
are reversible. The hospital staff will monitor you closely during treatment. 

If you get an infusion reaction, your doctor or nurse may give you additional medicines to treat your 
symptoms and prevent complications, or temporarily stop, slow down, or completely stop the Sarclisa 
infusion. 
 
Fever and low number of white blood cells 
Tell your doctor or nurse immediately if you develop fever, as it may be a sign of infection. Sarclisa 
can lower the number of white blood cells - which are important for fighting infections.  
 
Blood transfusion 
If you need a blood transfusion, you will have a blood test first to match your blood type. 
  
Tell the person doing the blood test that you are being treated with Sarclisa, as it can affect the results 
of this blood test. 
 
Children and adolescents 
Sarclisa is not recommended for use in children and adolescents aged under 18 years. This is because 
this medicine has not been tested in this age group. 
 
Other medicines and Sarclisa 
Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other 
medicines. This includes medicines you can get without a prescription, and herbal medicines. 
 
 Sarclisa is used with other medicines when treating multiple myeloma. For information on these 
medicines, see their package leaflets. 
 
Pregnancy 
Ask your doctor, pharmacist or nurse for advice before using Sarclisa.  
Use of Sarclisais not recommended during pregnancy. If you are pregnant or planning to become 
pregnant, talk to your doctor about using Sarclisa. 
 
For information on pregnancy and other medicines that are taken with Sarclisa, please look at the 
package leaflet for these other medicines. 
 
Breast-feeding  
Ask your doctor, pharmacist or nurse for advice before using Sarclisa. 
 This is because Sarclisa may pass into breast milk.  It is not known how it could affect the baby. 
 You and your doctor will decide if the benefit of breastfeeding is greater than the risk to your 

baby. 

Contraception 
Women who are using Sarclisa and are able to become pregnant must use an effective method of 
contraception. Talk to your doctor about the method of contraception that you must use during this 
time. Use contraception during treatment - and for 5 months after the last dose of Sarclisa. 
 
Driving and using machines  
Sarclisa is unlikely to affect your ability to drive or use machines.  However, Isatuximab is used with 
other medicines that may affect your ability to drive or use machines. Please look at the package 
leaflet from the other medicines you take with isatuximab.  
 
 
  



 

30 

3. How Sarclisa is used 
 
How much Sarclisa is given 
The amount of Sarclisa you will be given is based on how much you weigh. The recommended dose is 
10 mg of Sarclisa per kilogram of your body weight. 
 
How Sarclisa is given  
Your doctor or nurse will give you Sarclisa as a drip into a vein (intravenous infusion). 
 
How often Sarclisa is given  
Sarclisa is used in treatment cycles of 28 days (4 weeks) . It is used with two other medicines called 
pomalidomide and dexamethasone.  
 In cycle 1: Sarclisa is given once a week on days 1, 8, 15 and 22 
 In cycle 2 and beyond: Sarclisa is given every 2 weeks - on days 1 and 15 
Your doctor will continue to treat you with Sarclisa as long as you benefit from it and the side effects 
are acceptable. 
 
Medicines given before Sarclisa 
You will be given the following medicines before infusion of Sarclisa . This is to help reduce your 
chances of getting infusion reactions: 
 medicines to reduce allergic reactions (anti-histamine) 
 medicines to reduce inflammation (corticosteroids) 
 medicine to reduce pain and fever 
 
If you miss a dose of Sarclisa  
It is very important that you go to all your appointments to make sure you receive your treatment at the 
right time for it to work properly. If you miss any appointments, call your doctor or nurse as soon as 
possible to reschedule the appointment. 
 
Your doctor or nurse will decide how your treatment should be continued. 
 
If you are given more Sarclisa than you should 
Sarclisa will be given to you by your doctor or nurse. If you are accidentally given too much (an 
overdose), your doctor will treat and monitor your side effects. 
 
If you stop using Sarclisa  
Do not stop your treatment with Sarclisa unless you have discussed that with your doctor. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Your doctor will discuss the side effects of Sarclisa with you and will explain the possible risks and 
benefits of your treatment with Sarclisa. 
 
The hospital staff will monitor your condition closely during treatment. Tell them immediately if you 
notice any of the effects below. 

 
Infusion reactions - Very common (may affect more than 1 in 10 people): 
Tell your doctor or nurse immediately if you feel unwell during or after the infusion of 
Sarclisa. 
 
The most common severe signs of infusion reaction include: 

 high blood pressure (hypertension) 



 

31 

 feeling short of breath 
 
The most common signs of infusion reaction include: 

 feeling short of breath 
 cough 
 chills 
 nausea 

 
You may also have other side effects during the infusion. Your doctor or nurse may decide to 
temporarily stop, slow down, or completely stop the Sarclisa infusion. They may also give you 
additional medicines to treat your symptoms and prevent complications. 
 

Other side effects 
Talk to your doctor, pharmacist or nurse immediately if you have any of the side effects listed below: 
 
Very common (may affect more than 1 in 10 people): 

 lower number of red blood cells (anaemia)  
 lower number of some white blood cells (neutrophils or lymphocytes) which are important in 

fighting infection 
 lower number of blood platelets (thrombocytopenia) - tell your doctor or nurse if you have any 

unusual bruising or bleeding. 
 infection of the lungs (pneumonia) 
 infection of the airways (such as nose, sinuses or throat) 
 diarrhoea 
 bronchitis 
 feeling short of breath 
 nausea 
 fever with a severe decrease in some white blood cells (febrile neutropenia) (see section 2 for 

further details) 
 vomiting 

 
Common (may affect up to1 in 10 people): 

 decreased appetite 
 weight loss 

 
If any of the above apply to you, or you are not sure, talk to your doctor, pharmacist or nurse 
immediately. 
 
Reporting of side effects  
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects, you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Sarclisa 
 
Sarclisa will be stored at the hospital or clinic. 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and the vial after ”EXP”. 
The expiry date refers to the last day of that month. 
 
Store in a refrigerator (2 °C-8 °C). Do not freeze. 



 

32 

Store in the original package in order to protect from light. 
 
Medicines should not be disposed of via wastewater. Your doctor,  pharmacist or nurse will throw 
away any medicines that are no longer being used. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Sarclisa contains 
 The active substance of Sarclisa is isatuximab. 
 One mL of concentrate contains 20 mg of isatuximab. 
 Each vial of concentrate contains either 100 mg of isatuximab in 5 mL of concentrate or 500 mg of 

isatuximab in 25 mL of concentrate. 
 The other ingredients (excipients) are sucrose, histidine hydrochloride monohydrate, histidine, 

polysorbate 80, and water for injections. 
 
What Sarclisa looks like and contents of the pack 
Sarclisa is a concentrate for solution for infusion. It is a colourless to slightly yellow liquid, essentially 
free of visible particles. Sarclisa is supplied as a carton pack containing 1 or 3 glass vials. 
 
Marketing Authorisation Holder 
sanofi-aventis groupe 
54 rue La Boétie 
75008 Paris 
France 
 
Manufacturer  
Sanofi-Aventis Deutschland GmbH 
Industriepark Hoechst Brueningstrasse 50 
65926 Frankfurt am Main 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Sanofi Belgium 
Tél/Tel: +32 (0)2 710 54 00 

Lietuva 
UAB «SANOFI-AVENTIS LIETUVA» 
Tel: +370 5 2755224 

България 
SANOFI BULGARIA EOOD 
Тел.: +359 (0)2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium  
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt. 
Tel.: +36 1 505 0050 

Danmark 
Sanofi A/S 
Tlf: +45 45 16 70 00 
 

Malta 
Sanofi S.r.l. 
Tel: +39 02 39394275 

Sanofi-Aventis Deutschland GmbH 
Tel.: 0800 04 36 996 
Tel. aus dem Ausland: +49 69 305 70 13 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 20 245 4000 

Eesti Norge 



 

33 

sanofi-aventis Estonia OÜ 
Tel: +372 627 34 88 
 

sanofi-aventis Norge AS 
Tlf: +47 67 10 71 00 

Ελλάδα 
sanofi-aventis AEBE 
Τηλ: +30 210 900 16 00 
 

Österreich 
sanofi-aventis GmbH 
Tel: +43 1 80 185 – 0 

España 
sanofi-aventis, S.A. 
Tel: +34 93 485 94 00 
 

Polska 
sanofi-aventis Sp. z o.o. 
Tel.: +48 22 280 00 00 

France 
sanofi-aventis France 
Tél: 0 800 222 555 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi - Produtos Farmacêuticos, Lda. 
Tel: +351 21 35 89 400 

Hrvatska 
sanofi-aventis Croatia d.o.o. 
Tel: +385 1 600 34 00 
 
Ireland 
sanofi-aventis Ireland Ltd.  T/A SANOFI 
Tel: +353 (0) 1 403 56 00 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 
 
Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 

Ísland 
Vistor hf. 
Sími: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 

Italia 
Sanofi S.r.l. 
Tel: 800.536 389 
 

Suomi/Finland 
Sanofi Oy 
Puh/Tel: +358 (0) 201 200 300 

Κύπρος 
sanofi-aventis Cyprus Ltd. 
Τηλ: +357 22 871600 
 

Sverige 
Sanofi AB 
Tel: +46 (0)8 634 50 00 

Latvija 
sanofi-aventis Latvia SIA 
Tel: +371 67 33 24 51 

United Kingdom 
Sanofi 
Tel: +44 (0) 845 372 7101 

 
This leaflet was last revised in .  
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments.  
 
This leaflet is available in all EU/EEA languages on the European Medicines Agency website.  
 
------------------------------------------------------------------------------------------------------------------------ 
 
The following information is intended for healthcare professionals only: 
 



 

34 

SARCLISA vials are for single-use only. The infusion solution must be prepared under aseptic 
conditions, and administered by a healthcare professional in an environment where resuscitation 
facilities are available. 

 Preparation and administration of SARCLISA 
 

 Calculate the dose (mg) of required SARCLISA concentrate, and determine the number of 
vials needed for the 10 mg/kg dose, based on the patient weight. More than one vial may be 
needed. 

 Visually check the SARCLISA concentrate before dilution to ensure it does not contain any 
particles and is not discoloured. 

 Remove the volume of diluent equal to the required volume of SARCLISA concentrate from a 
250 mL of sodium chloride 9 mg/mL (0.9%) solution for injection or glucose 5% solution 
diluent bag.  

 Withdraw the appropriate volume of SARCLISA concentrate and dilute it in the 250 mL 
infusion bag with sodium chloride 9 mg/mL (0.9%) solution for injection or glucose 5% 
solution.   
The infusion bag must be made of polyolefins (PO), polyethylene (PE), polypropylene (PP), 
polyvinyl chloride (PVC) with di (2-ethylhexyl) phthalate (DEHP) or ethyl vinyl acetate 
(EVA). 

 Gently invert the bag to homogenize the diluted solution. Do not shake. 
 Administer the infusion solution intravenously using an intravenous tubing infusion set (in PE, 

PVC with or without DEHP, polybudadiene (PBD) or polyurethane (PU)) with an in-line filter 
(polyethersulfone (PES), polysulfone or nylon). 

 Administer the infusion solution for a period of time that will depend on the infusion rate (see 
EU-SmPC section 4.2). 

 Use the prepared SARCLISA infusion solution immediately. If not used immediately, in-use 
storage times and conditions prior use are the responsibility of the user and should normally 
not be longer than 24 hours at 2°C - 8°C, unless dilution has taken place in controlled and 
validated aseptic conditions. 

 No protection from light is required for the prepared infusion bag in a standard artificial light 
environment. 

 Do not infuse SARCLISA solution concomitantly in the same intravenous line with other 
agents. 

 Discard all unused portions of solution. All materials that have been utilised for dilution and 
administration should be disposed of according to standard procedures. 

 
 


	ANNEX ISUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE ANDMANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETINGAUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE ANDEFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET