b'B:8.5" B:8.5"T:7.5" T:7.5"S:7" S:7"SARCLISARx OnlyGently homogenize the diluted solution by inverting the bag. Do not shake. Monitor complete blood cell counts periodically during treatment. Consider the use of antibac- SARCLISA (isatuximab-irfc) injection, for intravenous use 2.5 Administration terialandantiviralprophylaxisduringtreatment[seeDosageandAdministration(2.2)].Monitor (isatuximab-irfc) injection, for intravenous use Administer the infusion solution by intravenous infusion using an intravenous tubing patientswithneutropeniaforsignsofinfection.Incaseofgrade4neutropeniadelaySARCLISABrief Summary of Prescribing Information infusionset(inPE,PVCwithorwithoutDEHP,polybutadiene[PBD],orpolyurethane[PU]) dose until neutrophil count recovery to at least 110 9 /L, and provide supportive care with Table 3: Adverse Reactions (10%) in Patients Receiving SARCLISA,with a 0.22 micron in-line lter (polyethersulfone [PES], polysulfone, or nylon). growth factors, according to institutional guidelines. No dose reductions of SARCLISA are Pomalidomide, and Dexamethasone with a Difference Between Arms of 5%1 INDICATIONS AND USAGEThe infusion solution should be administered for a period of time that will depend on the recommended. Compared to Control Arm in ICARIA-MM TrialSARCLISA is indicated: infusionrate(seeTable2).UsepreparedSARCLISAinfusionsolutionwithin48hourswhen 5.3 Second Primary Malignancies Adverse SARCLISA + Pomalidomide + Pomalidomide + incombinationwithpomalidomideanddexamethasone,forthetreatmentofadultpatients storedrefrigeratedat2Cto8C,followedby8hours(includingtheinfusiontime)atroom TheincidenceofsecondprimarymalignanciesisincreasedinpatientstreatedwithSARCLISA- Reactions Dexamethasone (Isa-Pd) Dexamethasone (Pd)withmultiplemyelomawhohavereceivedatleast2priortherapiesincludinglenalidomide temperature. containing regimens. The overall incidence of second primary malignancies in all theand a proteasome inhibitor.DonotadministerSARCLISAinfusionsolutionconcomitantlyinthesameintravenousline SARCLISA-exposed patients was 4.1%. (N=152) (N=149) incombinationwithcarlzomibanddexamethasone,forthetreatmentofadultpatientswith with other agents. InICARIA-MM,atamedianfollow-uptimeof52months,secondprimarymalignanciesoccurred All Grade 3 Grade 4 All Grade 3 Grade 4relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy.On the days where both SARCLISAand carlzomib are administered, administer dexam- in 7% of patients in the Isa-Pd arm and in 2% of patients in the Pd arm. Grades (%) (%) Grades (%) (%)2 DOSAGE AND ADMINISTRATION ethasone rst, followed by SARCLISA infusion, then followed by carlzomib infusion. InongoingIKEMAstudy,atamedianfollow-uptimeof21months,secondprimarymalignancies (%) (%)2.1 Recommended Dosage Infusion Rates occurred in 7% of patients in the Isa-Kd arm and in 4.9% of patients in the Kd arm. Administer pre-infusion medications [see Dosage and Administration (2.2)]. Followingdilution,administertheSARCLISAinfusionsolutionintravenouslyattheinfusionrates The most common (1%) second primary malignancies in ICARIA-MM and IKEMA (N=329) General disorders and administration site conditions SARCLISAshouldbeadministeredbyahealthcareprofessional,withimmediateaccessto presented in Table 2. Incremental escalation of the infusion rate should be considered only inthe absence of infusion-related reactions [see Warnings and Precautions (5.1) and Adverse included skin cancers (5% with SARCLISA-containing regimens and 2.6% with comparative Infusion-relatedemergency equipment and appropriate medical support to manage infusion-related reac- Reactions (6.1)]. regimens)andsolidtumorsotherthanskincancer(3%withSARCLISA-containingregimensand reaction * 38 1.3 1.3 0 0 0tions if they occur [see Warnings and Precautions (5.1)]. 1.8% with comparative regimens). All patients with non-melanoma skin cancer continuedThe recommended dose of SARCLISA is 10 mg/kg actual body weight administered as an treatment after resection of the skin cancer. Infectionsintravenous infusion in combination with pomalidomide and dexamethasone or in combination Table 2: Infusion Rates of SARCLISAAdministrationwithcarlzomibanddexamethasone,accordingtothescheduleinTable1[seeClinicalStudies Monitor patients for the development of second primary malignancies. Upper respiratory(14) in the full prescribing information]. Dilution Initial Absence of Rate Maximum 5.4 Laboratory Test Interference tract infection57 9 0 42 3.4 0Volume Rate Infusion- Increment Rate Interference with Serological Testing (Indirect Antiglobulin Test)Table 1: SARCLISA Dosing Schedule in Combination with Pomalidomide and Related SARCLISAbindstoCD38onredbloodcells(RBCs)andmayresultinafalsepositiveindirect Pneumonia31 22 3.3 23 16 2.7Dexamethasone or in Combination with Carlzomib and Dexamethasone Reaction antiglobulintest(indirectCoombstest).TheindirectantiglobulintestwaspositiveduringIsa-Pd Blood and lymphatic system disordersFirst 250 mL 25 mL/ For 60 25 mL/hour 150 mL/ treatment in 68% of the tested patients, and during Isa-Kd treatment in 63% of patients. InCycle Dosing schedule infusion hour minutes every 30 hour patients with a positive indirect antiglobulin test, blood transfusions were administered without Febrile neutropenia 12 11 1.3 2 1.3 0.7Cycle 1 Days 1, 8, 15, and 22 (weekly) minutes evidence of hemolysis. ABO/RhD typing was not affected by SARCLISA treatment. Respiratory, thoracic and mediastinal disordersBeforetherstSARCLISAinfusion,conductbloodtypeandscreentestsonSARCLISA-treatedCycle 2 and beyond Days 1, 15 (every 2 weeks) Second 250 mL 50 mL/ For 30 50 mL/hour 200 mL/ patients. Consider phenotyping prior to starting SARCLISA treatment. If treatment with Dyspnea17 5 0 12 1.3 0infusion hour minutes for 30 hour SARCLISAhas already started, inform the blood bank that the patient is receiving SARCLISAminutes then andSARCLISAinterferencewithbloodcompatibilitytestingcanberesolvedusingdithiothreitol- Gastrointestinal disordersEach treatment cycle consists of a 28-day period. Treatment is repeated until disease increase by treatedRBCs.Ifanemergencytransfusionisrequired,noncross-matchedABO/RhD-compat-progression or unacceptable toxicity. 100 mL/hour ible RBCs can be given as per local blood bank practices [see Drug Interactions (7.1)]. Diarrhea 26 2 0 19 0.7 0SARCLISA is used in combination with pomalidomide and dexamethasone or in combination Interference with Serum Protein Electrophoresis and Immunoxation Tests Nausea 15 0 0 9 0 0with carlzomib and dexamethasone. For dosing instructions of combination agents adminis- Subsequent 250 mL 200 mL/ 200 mL/tered with SARCLISA, see Clinical Studies (14) in the full prescribing information and infusions hour hour SARCLISA is an IgG kappa monoclonal antibody that can be incidentally detected on both Vomiting 12 1.3 0 3.4 0 0manufacturers prescribing information. serum protein electrophoresis and immunoxation assays used for the clinical monitoring ofMissed SARCLISA Doses 4 CONTRAINDICATIONS endogenous M-protein. This interference can impact the accuracy of the determination of CTCAE version 4.03SARCLISAiscontraindicatedinpatientswithseverehypersensitivitytoisatuximab-irfcortoany complete response in some patients with IgG kappa myeloma protein [see Drug Interactions *Infusion-related reaction includes infusion-related reaction, cytokine release syndrome, andIfaplanneddoseofSARCLISAismissed,administerthedoseassoonaspossibleandadjust (7.1)].the treatment schedule accordingly, maintaining the treatment interval. of its excipients [see Warnings and Precautions (5.1)]. 5.5 Embryo-Fetal Toxicity drug hypersensitivity.2.2 Recommended Premedications and Antiviral Prophylaxis 5 WARNINGS AND PRECAUTIONS Based S:10" on T:10.5" the B:11.25" mechanism of action, SARCLISAcan cause fetal harm when administered to a Upper respiratory tract infection includes bronchiolitis, bronchitis, bronchitis viral, chronic S:10" T:10.5" B:11.25"Administer the following premedications prior to SARCLISA infusion to reduce the risk and 5.1 Infusion-Related Reactions pregnant woman. SARCLISA may cause fetal immune cell depletion and decreased bone sinusitis, fungal pharyngitis, inuenza-like illness, laryngitis, nasopharyngitis, parainuenzaeseverity of infusion-related reactions [see Warnings and Precautions (5.1)]: Serious infusion-related reactions including life-threatening anaphylactic reactions have oc- density.Advisepregnantwomenofthepotentialrisktoafetus.Advisefemaleswithreproductive virus infection, pharyngitis, respiratory tract infection, respiratory tract infection viral, rhinitis, WhenadministeredincombinationwithSARCLISAandpomalidomide:Dexamethasone40 curred with SARCLISA treatment. Severe signs and symptoms included cardiac arrest, potential to use an effective method of contraception during treatment with SARCLISAand for sinusitis, tracheitis, upper respiratory tract infection, and upper respiratory tract infectionmgorallyorintravenously(or20mgorallyorintravenouslyforpatients 75yearsofage). hypertension, hypotension, bronchospasm, dyspnea, angioedema, and swelling. 5 months after the last dose [see Use in Specic Populations (8.1, 8.3)]. The combination of bacterial.WhenadministeredincombinationwithSARCLISAandcarlzomib:Dexamethasone20mg Based on ICARIA-MM, infusion-related reactions occurred in 38% of patients treated with SARCLISA with pomalidomide is contraindicated in pregnant women because pomalidomide Pneumonia includes atypical pneumonia, bronchopulmonary aspergillosis, pneumonia, pneu-(intravenously on the days of SARCLISAand/or carlzomib infusions, orally on day 22 in SARCLISA, pomalidomide, and dexamethasone (Isa-Pd) [see Adverse Reactions (6.1)]. All may cause birth defects and death of the unborn child. Refer to the pomalidomide prescribing moniahaemophilus,pneumoniainuenzal,pneumoniapneumococcal,pneumoniastreptococ-cycle 2 and beyond, and orally on day 23 in all cycles). infusion-relatedreactionsstartedduringtherstSARCLISAinfusionandresolvedonthesame information on use during pregnancy. cal, pneumonia viral, candida pneumonia, pneumonia bacterial, haemophilus infection, lung Acetaminophen 650 mg to 1,000 mg orally (or equivalent). day in 98% of the cases. 6 ADVERSE REACTIONS infection, pneumonia fungal, and pneumocystis jirovecii pneumonia. H2 antagonists In IKEMA, infusion-related reactions occurred in 46% of patients treated with SARCLISA, ThefollowingclinicallysignicantadversereactionsfromSARCLISAarealsodescribedinother Dyspnea includes dyspnea, dyspnea exertional, and dyspnea at rest.carlzomib, and dexamethasone (Isa-Kd). In the Isa-Kd arm, the infusion-related reactions Diphenhydramine25mgto50mgorallyorintravenously(orequivalent).Theintravenous occurredontheinfusiondayin99%ofepisodes.InpatientstreatedwithIsa-Kd,95%ofthose sections of the labeling:route is preferred for at least the rst 4 infusions. experiencing an infusion-related reaction experienced it during the rst cycle of treatment.AllInfusion-Related Reactions [see Warnings and Precautions (5.1)] Table 4 summarizes the hematology laboratory abnormalities in ICARIA-MM.Theaboverecommendeddoseofdexamethasone(orallyorintravenously)correspondstothe infusion-relatedreactionsresolved:withinthesamedayin74%ofepisodes,andthedayafterNeutropenia [see Warnings and Precautions (5.2)] Table 4: Hematology Laboratory Abnormalities During the Treatment Period indosetobeadministeredbeforeinfusionaspartofthepremedicationandpartofthebackbone in 24% of episodes [see Adverse Reactions (6.1)].Second Primary Malignancies [see Warnings and Precautions (5.3)] Patients Receiving Isa-Pd versus Pd in ICARIA-MMtreatment. Administer dexamethasone before SARCLISA and pomalidomide and before Themostcommonsymptoms(5%)ofaninfusion-relatedreactioninICARIA-MMandIKEMA 6.1 Clinical Trials ExperienceSARCLISA and carlzomib administration. (N=329) included dyspnea, cough, nasal congestion, and nausea. Anaphylactic reactions Because clinical trials are conducted under widely varying conditions, adverse reaction rates Laboratory SARCLISA + Pomalidomide + Pomalidomide +Administer the recommended premedication agents 15 to 60 minutes prior to starting a occurred in less than 1% of patients. observedintheclinicaltrialsofadrugcannotbedirectlycomparedtoratesintheclinicaltrials Parameter Dexamethasone (Isa-Pd) Dexamethasone (Pd)SARCLISA infusion. To decrease the risk and severity of infusion-related reactions, premedicate patients prior to of another drug and may not reect the rates observed in practice.Prophylaxis for Herpes Zoster Reactivation SARCLISAinfusionwithacetaminophen,H2antagonists,diphenhydramine,orequivalent,and Multiple Myeloma (N=152) (N=149)Initiateantiviralprophylaxistopreventherpeszosterreactivationbasedonstandardguidelines dexamethasone [see Dosage and Administration (2.2)]. Combination treatment with pomalidomide and dexamethasone (Isa-Pd) All Grade 3 Grade 4 All Grade 3 Grade 4[see Adverse Reactions (6.1)]. Monitor vital signs frequently during the entire SARCLISAinfusion. For patients with grade 2 The safety of SARCLISAwas evaluated in ICARIA-MM, a randomized, open-label clinical trial Grades (%) (%) Grades (%) (%)2.3 Dose Modications reactions, interrupt SARCLISA infusion and provide appropriate medical management. For in patients with previously treated multiple myeloma. Patients received SARCLISA 10 mg/kg (%) (%)No dose reduction of SARCLISA is recommended. Dose delay may be required to allow patientswithgrade2orgrade3reactions,ifsymptomsimprovetograde 1,restartSARCLISA intravenously, weekly in the rst cycle and every two weeks thereafter, in combination withrecovery of blood counts in the event of hematological toxicity [see Warnings and Precautions infusion at half of the initial infusion rate, with supportive care as needed, and closely monitor pomalidomideanddexamethasone(Isa-Pd)(n=152)orpomalidomideanddexamethasone(Pd) Hemoglobin 99 32 0 97 28 0(5.2, 5.4)]. For information concerning drugs given in combination with SARCLISA, see patients. If symptoms do not recur after 30 minutes, the infusion rate may be increased to the (n=149) [see Clinical Studies (14) in the full prescribing information].Among patients receiving decreasedinitial rate, and then increased incrementally, as shown in Table 2 [see Dosage and Adminis-manufacturers prescribing information. tration (2.5)]. In case symptoms do not improve to grade 1 after interruption of SARCLISA Isa-Pd, 66% were exposed to SARCLISAfor 6 months or longer and 24% were exposed for Neutrophils 96 24 61 92 38 312.4 Preparation infusion, persist or worsen despite appropriate medications, or require hospitalization, perma- greater than 12 months or longer. decreasedPrepare the solution for infusion using aseptic technique as follows: nentlydiscontinueSARCLISAandinstituteappropriatemanagement.Permanentlydiscontinue Serious adverse reactions occurred in 62% of patients receiving Isa-Pd. Serious adverseCalculatethedose(mg)ofrequiredSARCLISAbasedonactualpatientweight(measuredprior SARCLISA if an anaphylactic reaction or life-threatening (grade 4) infusion-related reaction reactionsin 5%ofpatientswhoreceivedIsa-Pdincludedpneumonia(26%),upperrespiratory Lymphocytes 92 42 13 92 35 8to each cycle to have the administered dose adjusted accordingly) [see Dosage and Admin- occurs and institute appropriate management. tractinfections(7%),andfebrileneutropenia(7%).Fataladversereactionsoccurredin11%of decreasedistration (2.1)]. More than one SARCLISAvial may be necessary to obtain the required dose 5.2 Neutropenia patients(thosethatoccurredinmorethan1%ofpatientswerepneumoniaandotherinfections Platelets decreased 84 14 16 79 9 15for the patient. SARCLISA may cause neutropenia. [3%]). Parenteral drug products should be inspected visually for particulate matter and discolor- In patients treated with Isa-Pd, neutropenia occurred in 96% of patients and grade 34 Permanent treatment discontinuation due to an adverse reaction (grades 14) occurred in 7% The denominator used to calculate the percentages was based on the safety population.ation prior to administration, whenever solution and container permit. neutropeniaoccurredin85%ofpatients.Neutropeniccomplicationsoccurredin30%ofpatients, of patients who received Isa-Pd. The most frequent adverse reactions requiring permanent Remove the volume of diluent from the 250 mL Sodium Chloride Injection, USP, or 5% includingfebrileneutropenia(12%)andneutropenicinfections(25%),denedasinfectionwith discontinuation in patients who received Isa-Pd were infections (2.6%). SARCLISAalone was Combination treatment with carlzomib and dexamethasone (Isa-Kd)Dextrose Injection, USP diluent bag that is equal to the required volume of SARCLISA concurrentgrade 3neutropenia.Themostfrequentneutropenicinfectionsincludedinfections discontinued in 3% of patients due to infusion-related reactions. The safety of SARCLISA was evaluated in IKEMA, a randomized, open-label clinical trial ininjection. of the upper respiratory tract (10%), lower respiratory tract (9%), and urinary tract (3%) [see Dosage interruptions due to an adverse reaction occurred in 31% of patients who received patients with previously treated multiple myeloma. Patients received SARCLISA 10 mg/kg WithdrawthenecessaryvolumeofSARCLISAinjectionfromthevialanddilutebyadding Adverse Reactions (6.1)]. SARCLISA. The most frequent adverse reaction requiring dosage interruption was infusion- intravenously weekly in the rst cycle, and every two weeks thereafter, in combination withtotheinfusionbagof0.9%SodiumChlorideInjection,USPor5%DextroseInjection,USP. In patients treated with Isa-Kd, neutropenia occurred in 55% of patients, with grade 34 related reaction (28%). carlzomib and dexamethasone (Isa-Kd) (n=177) or carlzomib and dexamethasone (Kd) Theinfusionbagmustbemadeofpolyolens(PO),polyethylene(PE),polypropylene(PP), neutropeniain19%ofpatients(grade3in18%andgrade4in1.7%).Neutropeniccomplications The most common adverse reactions (20%) were upper respiratory tract infection, infusion- (n=122) [see Clinical Studies (14) in the full prescribing information].Among patients receivingpolyvinyl chloride (PVC) with di-(2-ethylhexyl) phthalate (DEHP) or ethyl vinyl acetate occurred in 2.8% of patients, including febrile neutropenia (1.1%) and neutropenic infections related reactions, pneumonia, and diarrhea. Isa-Kd, 68% were exposed to SARCLISAfor 12 months or longer and 51% were exposed for(EVA). (1.7%) [see Adverse Reactions (6.1)]. Table 3 summarizes the adverse reactions in ICARIA-MM. greater than 18 months.12049085_SAR_US_Branded_2_Page_Journal Ad_A_M4FR.indd 2 1/5/24 4:14 PM 12049085_SAR_US_Branded_2_Page_Journal Ad_A_M4FR.indd 3 1/5/24 4:14 PMPREPARED BY PREPARED BY12049085-vc12049124 US Branded 2-Page Journal Ad (A-size) Label Update M4FR 12049085-vc12049124 US Branded 2-Page Journal Ad (A-size) Label Update M4FRJob info Images FontsSpecial Instructions Job info Images FontsSpecial InstructionsDate: 1-5-2024 4:14 PM isa-bplr-sl-nov23.pdf (100%; 52KB) Arial Narrow (Regular) Rename f12049085 Sarclisa US Branded 2-PageDate: 1-5-2024 4:14 PM isa-bplr-sl-nov23.pdf (100%; 52KB) Arial Narrow (Regular) Rename f12049085 Sarclisa US Branded 2-Page Client: NOVARTIS Journal Ad Label Update - MAT-US-2307253-v2.0 Client: NOVARTIS Journal Ad Label Update - MAT-US-2307253-v2.0Product: US Sarclisa Product: US SarclisaClient Code: MAT-US-2307253-v2.0-12/2023 Additional Information Client Code: MAT-US-2307253-v2.0-12/2023 Additional InformationWF Issue # 10351122 At Release, rename to: "12049085 Sarclisa USWF Issue # 10351122 At Release, rename to: "12049085 Sarclisa US Releasing as: PDFx1A Branded 2-Page Journal Ad Label Update - MAT- Releasing as: PDFx1A Branded 2-Page Journal Ad Label Update - MAT-Final Size: 7.5" x 10.5" US-2307253-v2.0" Final Size: 7.5" x 10.5" US-2307253-v2.0"Finishing: Trim Finishing: TrimGutter: -Inks Additional Comments for Sizing Gutter: -Inks Additional Comments for SizingColors: 4C & BWBlack None Colors: 4C & BWBlack NoneTeam TeamProducer: Anna Volkova Producer: Anna VolkovaAD: Melissa Petty AD: Melissa PettyAE: Ian Grabowich Scale: 1" = 1" AE: Ian Grabowich Scale: 1" = 1"QC: LW Bleed 17" w x 11.25" h 17" w x 11.25" h QC: LW Bleed 17" w x 11.25" h 17" w x 11.25" hProduction: Heather Cave Trim/Flat 15" w x 10.5" h 15" w x 10.5" h Production: Heather Cave Trim/Flat 15" w x 10.5" h 15" w x 10.5" hDigital Artist: M. Tenga Live/Safety 14.5" w x 10" h 14.5" w x 10" hDigital Artist: M. Tenga Live/Safety 14.5" w x 10" h 14.5" w x 10" h Path: PrePress:Sanofi:Sanofi_Sarclisa_US_H:12049085:12049085_SAR_US_Branded_2_Page_Journal Ad_A_M4FR.indd Path: PrePress:Sanofi:Sanofi_Sarclisa_US_H:12049085:12049085_SAR_US_Branded_2_Page_Journal Ad_A_M4FR.inddPDFX1A _ PDFX1A _'