b'B:8.5"T:7.5"S:7"SARCLISARx OnlyGently homogenize the diluted solution by inverting the bag. Do not shake.(isatuximab-irfc) injection, for intravenous use 2.5 Administration Administer the infusion solution by intravenous infusion using an intravenous tubingBrief Summary of Prescribing Information infusionset(inPE,PVCwithorwithoutDEHP,polybutadiene[PBD],orpolyurethane[PU])with a 0.22 micron in-line lter (polyethersulfone [PES], polysulfone, or nylon).1 INDICATIONS AND USAGEThe infusion solution should be administered for a period of time that will depend on theSARCLISA is indicated: infusionrate(seeTable2).UsepreparedSARCLISAinfusionsolutionwithin48hourswhen incombinationwithpomalidomideanddexamethasone,forthetreatmentofadultpatients storedrefrigeratedat2Cto8C,followedby8hours(includingtheinfusiontime)atroomwithmultiplemyelomawhohavereceivedatleast2priortherapiesincludinglenalidomide temperature.and a proteasome inhibitor.DonotadministerSARCLISAinfusionsolutionconcomitantlyinthesameintravenousline incombinationwithcarlzomibanddexamethasone,forthetreatmentofadultpatientswith with other agents.relapsed 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-2 DOSAGE AND ADMINISTRATION ethasone rst, followed by SARCLISA infusion, then followed by carlzomib infusion.2.1 Recommended Dosage Infusion Rates Administer pre-infusion medications [see Dosage and Administration (2.2)]. Followingdilution,administertheSARCLISAinfusionsolutionintravenouslyattheinfusionrates SARCLISAshouldbeadministeredbyahealthcareprofessional,withimmediateaccessto presented in Table 2. Incremental escalation of the infusion rate should be considered only inemergency equipment and appropriate medical support to manage infusion-related reac- the absence of infusion-related reactions [see Warnings and Precautions (5.1) and Adversetions if they occur [see Warnings and Precautions (5.1)]. Reactions (6.1)].The recommended dose of SARCLISA is 10 mg/kg actual body weight administered as anintravenous infusion in combination with pomalidomide and dexamethasone or in combination Table 2: Infusion Rates of SARCLISAAdministrationwithcarlzomibanddexamethasone,accordingtothescheduleinTable1[seeClinicalStudies Dilution Initial Absence of Rate Maximum(14) in the full prescribing information]. Volume Rate Infusion- Increment RateTable 1: SARCLISA Dosing Schedule in Combination with Pomalidomide and RelatedDexamethasone or in Combination with Carlzomib and Dexamethasone ReactionCycle Dosing schedule First 250 mL 25 mL/ For 60 25 mL/hour 150 mL/infusion hour minutes every 30 hourCycle 1 Days 1, 8, 15, and 22 (weekly) minutesCycle 2 and beyond Days 1, 15 (every 2 weeks) Second 250 mL 50 mL/ For 30 50 mL/hour 200 mL/infusion hour minutes for 30 hourminutes thenEach treatment cycle consists of a 28-day period. Treatment is repeated until disease increase byprogression or unacceptable toxicity. 100 mL/hourSARCLISA is used in combination with pomalidomide and dexamethasone or in combinationwith 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 hourmanufacturers prescribing information.Missed SARCLISA Doses 4 CONTRAINDICATIONSIfaplanneddoseofSARCLISAismissed,administerthedoseassoonaspossibleandadjust SARCLISAiscontraindicatedinpatientswithseverehypersensitivitytoisatuximab-irfcortoanythe treatment schedule accordingly, maintaining the treatment interval. of its excipients [see Warnings and Precautions (5.1)].2.2 Recommended Premedications and Antiviral Prophylaxis 5 WARNINGS AND PRECAUTIONS 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 Reactionsseverity of infusion-related reactions [see Warnings and Precautions (5.1)]: Serious infusion-related reactions including life-threatening anaphylactic reactions have oc- WhenadministeredincombinationwithSARCLISAandpomalidomide:Dexamethasone40 curred with SARCLISA treatment. Severe signs and symptoms included cardiac arrest,mgorallyorintravenously(or20mgorallyorintravenouslyforpatients 75yearsofage). hypertension, hypotension, bronchospasm, dyspnea, angioedema, and swelling.WhenadministeredincombinationwithSARCLISAandcarlzomib:Dexamethasone20mg Based on ICARIA-MM, infusion-related reactions occurred in 38% of patients treated with(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)]. Allcycle 2 and beyond, and orally on day 23 in all cycles). infusion-relatedreactionsstartedduringtherstSARCLISAinfusionandresolvedonthesame Acetaminophen 650 mg to 1,000 mg orally (or equivalent). day in 98% of the cases.In IKEMA, infusion-related reactions occurred in 46% of patients treated with SARCLISA, H2 antagonists carlzomib, and dexamethasone (Isa-Kd). In the Isa-Kd arm, the infusion-related reactions Diphenhydramine25mgto50mgorallyorintravenously(orequivalent).Theintravenous occurredontheinfusiondayin99%ofepisodes.InpatientstreatedwithIsa-Kd,95%ofthoseroute is preferred for at least the rst 4 infusions. experiencing an infusion-related reaction experienced it during the rst cycle of treatment.AllTheaboverecommendeddoseofdexamethasone(orallyorintravenously)correspondstothe infusion-relatedreactionsresolved:withinthesamedayin74%ofepisodes,andthedayafterdosetobeadministeredbeforeinfusionaspartofthepremedicationandpartofthebackbone in 24% of episodes [see Adverse Reactions (6.1)].treatment. Administer dexamethasone before SARCLISA and pomalidomide and before Themostcommonsymptoms(5%)ofaninfusion-relatedreactioninICARIA-MMandIKEMASARCLISA and carlzomib administration. (N=329) included dyspnea, cough, nasal congestion, and nausea. Anaphylactic reactionsAdminister the recommended premedication agents 15 to 60 minutes prior to starting a occurred in less than 1% of patients.SARCLISA infusion. To decrease the risk and severity of infusion-related reactions, premedicate patients prior toProphylaxis for Herpes Zoster Reactivation SARCLISAinfusionwithacetaminophen,H2antagonists,diphenhydramine,orequivalent,andInitiateantiviralprophylaxistopreventherpeszosterreactivationbasedonstandardguidelines dexamethasone [see Dosage and Administration (2.2)].[see Adverse Reactions (6.1)]. Monitor vital signs frequently during the entire SARCLISAinfusion. For patients with grade 22.3 Dose Modications reactions, interrupt SARCLISA infusion and provide appropriate medical management. ForNo dose reduction of SARCLISA is recommended. Dose delay may be required to allow patientswithgrade2orgrade3reactions,ifsymptomsimprovetograde 1,restartSARCLISArecovery 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(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 themanufacturers prescribing information. initial rate, and then increased incrementally, as shown in Table 2 [see Dosage and Adminis-2.4 Preparation tration (2.5)]. In case symptoms do not improve to grade 1 after interruption of SARCLISAPrepare the solution for infusion using aseptic technique as follows: infusion, persist or worsen despite appropriate medications, or require hospitalization, perma-Calculatethedose(mg)ofrequiredSARCLISAbasedonactualpatientweight(measuredprior nentlydiscontinueSARCLISAandinstituteappropriatemanagement.Permanentlydiscontinueto each cycle to have the administered dose adjusted accordingly) [see Dosage and Admin- SARCLISA if an anaphylactic reaction or life-threatening (grade 4) infusion-related reactionistration (2.1)]. More than one SARCLISAvial may be necessary to obtain the required dose occurs and institute appropriate management.for the patient. 5.2 NeutropeniaSARCLISA may cause neutropenia. 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 34ation prior to administration, whenever solution and container permit. neutropeniaoccurredin85%ofpatients.Neutropeniccomplicationsoccurredin30%ofpatients, Remove the volume of diluent from the 250 mL Sodium Chloride Injection, USP, or 5% includingfebrileneutropenia(12%)andneutropenicinfections(25%),denedasinfectionwithDextrose Injection, USP diluent bag that is equal to the required volume of SARCLISA concurrentgrade 3neutropenia.Themostfrequentneutropenicinfectionsincludedinfectionsinjection. of the upper respiratory tract (10%), lower respiratory tract (9%), and urinary tract (3%) [see WithdrawthenecessaryvolumeofSARCLISAinjectionfromthevialanddilutebyadding Adverse Reactions (6.1)].totheinfusionbagof0.9%SodiumChlorideInjection,USPor5%DextroseInjection,USP. In patients treated with Isa-Kd, neutropenia occurred in 55% of patients, with grade 34 Theinfusionbagmustbemadeofpolyolens(PO),polyethylene(PE),polypropylene(PP), neutropeniain19%ofpatients(grade3in18%andgrade4in1.7%).Neutropeniccomplicationspolyvinyl 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(EVA). (1.7%) [see Adverse Reactions (6.1)].12049085_SAR_US_Branded_2_Page_Journal Ad_A_M4FR.indd 2 1/5/24 4:14 PMPREPARED BY 12049085-vc12049124 US Branded 2-Page Journal Ad (A-size) Label Update M4FRJob 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-Page Client: NOVARTIS Journal Ad Label Update - MAT-US-2307253-v2.0Product: US SarclisaClient Code: MAT-US-2307253-v2.0-12/2023 Additional InformationWF Issue # 10351122 At Release, rename to: "12049085 Sarclisa US Releasing as: PDFx1A Branded 2-Page Journal Ad Label Update - MAT-Final Size: 7.5" x 10.5" US-2307253-v2.0"Finishing: TrimGutter: -Inks Additional Comments for SizingColors: 4C & BWBlack NoneTeamProducer: Anna VolkovaAD: Melissa PettyAE: Ian Grabowich Scale: 1"= 1"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" hDigital Artist: M. 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