RECENT MAJOR CHANGES Boxed Warning 0415 Indications and Usage 11 0415 Dosage and Administration 21 22 0415 Warnings a ID: 145411
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+,*+/,*+TS OF PRESCR,B,N* ,NFORMAT,ON TKese KLJKOLJKts do not LncOude aOO tKe LnformatLon needed to uPOMA/YST safeO\ and effectLveO\. See fuOO prescrLbLnJ LnformatLon for POMA/YST. POMA/YST pomaOLdomLde capsuOes for oraO use,nLtLaO U.S. ApprovaO: 2013 WARN,N*: EMBRYO-FETA/ TO;,C,TY and VENOUS AND ARTER,A/ T+ROMBOEMBO/,SM See full prescribing information for complete boxed warning EMBRYO-FETA/ TO;,C,TY POMA/YST Ls contraLndLcated Ln preJnanc\. POMA/YST Ls a tKaOLdomLde anaOoJue. TKaOLdomLde Ls a NnoZn Kuman teratoJen tKat causes severe OLfe-tKreatenLnJ bLrtK defects 4 5.1 .1For femaOes of reproductLve poten --------------------------RECENT MA-OR C+AN*ES---------------------------- ,ndLcatLons and UsaJe .aposL Sarcoma 1.2 05/2020 FU// PRESCR,B,N* ,NFORMAT,ON: CONTENTS WARN,N*: EMBRYO-FETA/ TO;,C,TY and VENOUS AND ARTER,A/ T+ROMBOEMBO/,SM ,ND,CAT,ONS AND USA*E1.1 MuOtLpOe M\eOoma 1.2 .aposL Sarcoma DOSA*E AND ADM,N,STRAT,ON2.1 PreJnanc\ TestLnJ PrLor to AdmLnLstratLon 2.2 Recommended DosaJe for MuOtLpOe M\eOoma 2.3 Recommended DosaJe for .aposL Sarcoma 2.4 DosaJe ModLfLcatLons for +ematoOoJLc Adverse ReactLons 2.5 DosaJe ModLfLcatLons for Non-+ematoOoJLc Adverse ReactLons 2.6 DosaJe ModLfLcatLons for StronJ CYP1A2 ,nKLbLtors 2. DosaJe ModLfLcatLon for Severe RenaO ,mpaLrment on +emodLaO\sLs 2. DosaJe ModLfLcatLon for +epatLc ,mpaLrment 2. AdmLnLstratLon DOSA*E FORMS AND STREN*T+SCONTRA,ND,CAT,ONS4.1 PreJnanc\ 4.2 +\persensLtLvLt\ WARN,N*S AND PRECAUT,ONS5.1 Embr\o-FetaO To[LcLt\ 5.2 POMA/YST REMS ProJram 5.3 Venous and ArterLaO TKromboemboOLsm 5.4 ,ncreased MortaOLt\ Ln PatLents ZLtK MuOtLpOe M\eOoma WKen PembroOL]umab ,s Added to a TKaOLdomLde AnaOoJue and De[ametKasone 5.5 +ematoOoJLc To[LcLt\ 5.6 +epatoto[LcLt\ 5. Severe Cutaneous ReactLons 5. DL]]Lness and ConfusLonaO State 5. NeuropatK\ 5.10 RLsN of Second PrLmar\ MaOLJnancLes 5.11 Tumor /\sLs S\ndrome 5.12 +\persensLtLvLt\ ADVERSE REACT,ONS 6.1 COLnLcaO TrLaOs E[perLence 6.2 PostmarNetLnJ E[perLence DRU* ,NTERACT,ONS.1 DruJs TKat Affect PomaOLdomLde POasma ConcentratLons USE ,N SPEC,F,C POPU/AT,ONS.1 PreJnanc\ .2 /actatLon .3 FemaOes and MaOes of ReproductLve PotentLaO .4 PedLatrLc Use .5 *erLatrLc Use .6 RenaO ,mpaLrment . +epatLc ,mpaLrment . SmoNLnJ Tobacco OVERDOSA*EDESCR,PT,ONC/,N,CA/ P+ARMACO/O*Y12.1 MecKanLsm of ActLon 12.2 PKarmacod\namLcs 12.3 PKarmacoNLnetLcs NONC/,N,CA/ TO;,CO/O*Y13.1 CarcLnoJenesLs MutaJenesLs ,mpaLrment of FertLOLt\ C/,N,CA/ STUD,ES14.1 MuOtLpOe M\eOoma 14.2 .aposL Sarcoma +OW SUPP/,ED/STORA*E AND +AND/,N*PAT,ENT COUNSE/,N* ,NFORMAT,ON SectLons or subsectLons omLtted from tKe fuOO prescrLbLnJ LnformatLon are not FU// PRESCR,B,N* ,NFORMAT,ON WARN,N*: EMBRYO-FETA/ TO;,C,TY and VENOUS AND ARTER,A/ POMA/YST Ls contraLndLcated Ln preJnanc\. POMA/YST Ls a tKaOLdoTKaOLdomLde Ls a NnoZn Kuman teratoJen tKat causes severe bLrtK defects or embr\o-fetaO preJnanc\ tests before startLnJ aO must use 2 forms of contraceptLon or contLnuousO\ abstaLn from Keterose[uaO se[ durLnJ and Contraindications (4), Warnings and Precautions (5.1) and Use in Specific Populations (8.1, 8.3)]. K a restrLcted dLstrLbutLon pr[see Warnings and Precautions (5.2)]. puOmonar\ emboOLsm PE m\ocardLoccur Ln patLents ZLtK muOtLpOe antLtKrombotLc measures Zere empOo\ed Ln cOLnLcaO trLaOs. TKromrecommended and tKe cKoLce of reJLmen sKouOd be based on asses [see Warnings and Precautions (5.3)]. ,ND,CAT,ONS AND USA*E MuOtLpOe M\eOoma tLpOe m\eOoma MM AduOt patLents ZLtK A,DS-reOated . tKerap\ +AART. tLents ZKo are +,V-neJatLve. [see Clinical Studies (14.2)] mator\ trLaO s. 2 DOSA*E AND ADM,N,STRAT,ON LnLtLatLnJ POMA/YST 2.2 Recommended DosaJe for MuOtLpOe M\eOoma [see Clinical Studies (14.1)] OO\ ZLtK or ZLtKout food on Da\s 1 tKrouJK 21 of eacK 2-da\ c\cOe untLO dLsease proJressLon or unacceptabOe to[LcLt\. ContLnue +AART as +,V [see Clinical Studies (14.2)] MuOtLpOe M\eOoma: DosaJe ModLfLcatLons for +ematoOoJLc Adverse ,nLtLate a neZ c\cOe of POMA/YST Ln patLents ZLtK muOtLpOe m\eO ons Ln patLents ZLtK MM are summarL]ed TabOe 1: DosaJe ModLfLcatLons for POMA/YST for +ematoOoJLc Ln M Adverse ReactLon SeverLt\DosaJe ModLfLcatLon NeutropenLa [see Warnings and Precautions (5.5)]ANC Oess tKan 500 per mc/ or febrLOe neutropenLa fever Jreater tKan or equaO to 3.5°C and ANC Oess tKan 1000 per WLtKKoOd POMA/YST untLO ANC Ls Jreater tKan or equaO to 500 per mc/ foOOoZ CBC ZeeNO\. Resume POMA/YST dose at 1 mJ Oess tKan tKe prevLous dose. For eacK subsequent drop of ANC Oess tKan 500 per mc/ WLtKKoOd POMA/YST untLO ANC Ls Jreater tKan or equaO to 500 mc/. Resume POMA/YST dose at 1 mJ Oess tKan tKe prevLous dose. TKromboc\topenLa [see Warnings and Precautions (5.5)]POateOets Oess tKan 25000 per mc/ WLtKKoOd POMA/YST untLO pOateOets are Jreater tKan or equaO to 50000 per mc/ foOOoZ CBC ZeeNO\. Resume POMA/YST dose at 1 mJ Oess tKan tKe prevLous dose For eacK subsequent drop of pOateOets Oess tKan 25000 per mc/ WLtKKoOd POMA/YST untLO pOateOets are Jreater tKan or equaO to 50000 per mc/. Resume POMA/YST at 1 mJ Oess tKan tKe prevLous dose PermanentO\ dLscontLnue POMA/YST Lf unabOe to toOerate 1 mJ oncANC= absoOute neutropKLO count ,nLtLate a neZ c\cOe of POMA/YST Ln patLents ZLtK .S ZKen tKe n Dose modLfLcatLons for POMA/YST S are summarL]ed Ln TabOe 2: DosaJe ModLfLcatLons for POMA/YST for +ematoOoJLc Adverse ReactLons Ln .S Adverse ReactLon SeverLt\ DosaJe ModLfLcatLon NeutropenLa[see Warnings and Precautions (5.5)]ANC 500 to Oess tKan 1000 per mc/ Da\ 1 of c\cOe WLtKKoOd POMA/YST untLO ANC Ls Jreater tKan or equaO to 1000 per mc/. Resume POMA/YST at tKe same dose. DurLnJ c\cOe ContLnue POMA/YST at tKe current dose. ANC Oess tKan 500 per mc/ WLtKKoOd POMA/YST untLO ANC Ls Jreater tKan or equaO to 1000 per mc/. Resume POMA/YST at tKe same dose. FebrLOe NeutropenLa [see Warnings and Precautions (5.5)]ANC Oess tKan 1000 per mc/ and sLnJOe temperature Jreater tKan or equaO to 3.3or ANC Oess tKan 1000 per mc/ and sustaLned temperature Jreater tKan or equaO to 3for more tKan 1 Kou WLtKKoOd POMA/YST untLO ANC Ls Jreater tKan or equaO to 1000 per mc/. Resume POMA/YST at dose 1 mJ Oess tKan tKe prevLous dose. TKromboc\topenLa [see Warnings and Precautions (5.5)]POateOet count 25000 to Oess tKan 50000 per mc/ Da\ 1 of c\cOe WLtKKoOd POMA/YST untLO pOateOet count Ls Jreater tKan or equaO to 50000 per mc/. Resume POMA/YST at tKe same dose. DurLnJ c\cOe: ContLnue POMA/YST at tKe current dose. POateOet count Oess tKan 25000 er mc/PermanentO\ dLscontLnue POMA/YST. PermanentO\ dLscontLnue POMA/YST Lf unabOe to toOerate 1mJ onANC= absoOute neutropKLO count [See Warnings and Precautions (5.7, 5.12)] 2.6 DosaJe ModLfLcatLons for StronJ CYP1A2 ,nKLbLtors e reduce POMA/YST dose to 2 mJ Pharmacology (12.3)] 2. DosaJe ModLfLcatLon for Severe RenaO ,mpaLrment on +emodLaO [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)] O\sLs reduce tKe re MuOtLpOe M\eOoma For patLents ZLtK MM ZLtK [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)] (8.7) and Clinical Pharmacology (12.3)] 2. AdmLnLstratLon 3 DOSA*E FORMS AND STREN*T+S 4 CONTRA,ND,CAT,ONS [see Warnings and Precautions (5.7), Description (11)] 5 WARN,N*S AND PRECAUT,ONS tLnuLnJ for 4 ZeeNs foOOoZLnJMA/YST tKerap\. [see Use in Specific Populations (8.3)].MaOes en Lf tKe\ Kave underJone a successfuO OMA/YST must not donate sperm of tKe druJ because tKe bOood mLJKt be JLven to a preJnant fema5.2 POMA/YST REMS ProJramBecause of tKe embr\o-fetaO rLsN () POMA/YST Ls avaa restrLcted proJram under a RLsN EvaOuatLon and MLtLJatLon StrateJ\ REMS tKe ³POMA/YST REMS” POMA/YST REMSPrescrLbers must be certLfLed ZLtK tKe [see Use in Specific Populations (8.3)]opulations (8.3)]() PKarmacLes must be certLfLed ZLtK tKe POMA/YST REMS proJram must onO\ dLspense to patLents ZKo are autKorL]ed to receLve POMA/YST and compO\ ZLtK REMS requLrements. FurtKer LnformatLon about tKe POMA/YST REMS proJram Ls avaLOabOe at ZZZ.ceOJenerLsNmanaJement.com or b\ teOepKone at 1--423-5436. 5.3 Venous and ArterLaO TKromboemboOLsm Venous tKromboemboOLc events deep venous tKrombosLs and puOmonar\ emboOLsm and arterLaO tKromboemboOLc events m\ocardLaO LnfarctLon and stroNe Kave been observed Ln patLents treated ZLtK POMA/YST. ,n TrLaO 2 ZKere antLcoaJuOant tKerapLes Zere mandated tKromboemboOLc events occurred Ln .0% of patLents treated ZLtK POMA/YST and OoZ dose-de[ametKasone /oZ-dose De[ and 3.3% of patLents treated ZLtK KLJK-dose de[ametKasone. Venous tKromboemboOLc events VTE occurred Ln 4.% of patLents treated ZLtK POMA/YST and /oZ-dose De[ and 1.3% of patLents treated ZLtK KLJK-dose de[ametKasone. ArterLaO tKromboemboOLc events LncOude terms for arterLaO tKrom 5.4 ,ncreased MortaOLt\ Ln PatLents ZLtK MuOtLpOe M\eOoma WKen PembroOL]umab ,s Added to a TKaOLdomLde AnaOoJue and De[ametKasone Lde of controOOed cOLnLcaO trLaOs. MuOtLpOe M\eOoma [see [see Adverse Reactions (6.1)] [see Dosage and Administration (2.4)] s treated ZLtK POMA/YSTOoZer dose ma\ be consLdered. 5. Severe Cutaneous ReactLons S-S to[Lc epLdermaO s m\ocardLtLs and/or perLcardLtLs. TKese reactLons can be fataO. ConsLder POMA/YST LnterruptLon or dLsco [see Dosage and Administration (2.5)] tLons tKat ma\ cause dL] nts receLvLnJ POMA/YST as an LnvestLJatLonaO tKerprecautLons taNen. OactLc reactLons to POMA/YST Kave been apK\Oa[Ls Administration (2.5)] 6 ADVERSE REACT,ONS () Venous and ArterLaO TKromboemboOLsm [see Warnings and Precautions (5.3)] ,ncreased MortaOLt\ Ln PatLents ZLtK MuOtLpOe M\eOoma WKen Pemb[see Warnings and Precautions (5.3)] () +ematoOoJLc To[LcLt\ [see Warnings and Precautions (5.3)] ()() +epatoto[LcLt\ [see Warnings and Precautions (5.3)] ()()() Severe Cutaneous ReactLons [see Warnings and Precautions (5.7)] DL]]Lness and ConfusLonaO State [see Warnings and Precautions (5.8)] NeuropatK\ [see Warnings and Precautions (5.9)] RLsN of Second PrLmar\ MaOLJnancLes [see Warnings and Precautions (5.10)] Tumor /\sLs S\ndrome [see Warnings and Precautions (5.11)] +\persensLtLvLt\ [see Warnings and Precautions (5.12)] 6.1 COLnLcaO TrLaOs E[perLence Because cOLnLcaO trLaOs are conducted under ZLdeO\ var\LnJ condMuOtLpOe M\eOoma MM atment ZLtK POMA/YST /oZ-dose De[ 112 patLents or POMA/YST aOone 10 patLents.atment ZLtK POMA/YST e POMA/YST /oZ-dose De[ arm Zas 5. ,n tKe POMA/YST /oZ-dose e reactLons reported Ln TrLaTabOe 3: Adverse ReactLons Ln An\ POMA/YST Treatment Arm Ln TrLaO 1 AOO Adverse ReactLons ≥10% Ln ELtKer Arm *rade 3 or 4 ≥5% Ln ELtKer Arm Bod\ S\stem Adverse ReactLon N=10 /oZ-dose De[ N=112 POMA/YST N=10 /oZ-dose De[ N=112 Number % of patLents ZLtK at Oeast one adverse 10 100 112 100 2 102 1 BOood and O\mpKatLc s\stem dLsorders NeutropenLa 5 53 55 4 51 4 46 41 AnemLa 41 3 4 42 25 23 24 21 TKromboc\topenLa 2 26 26 23 24 22 21 1 /euNopenLa 14 13 22 20 11 10 FebrLOe neutropenLa 10% 10% 6 6 3 3 /\mpKopenLa 4 4 1 15 2 2 *eneraO dLsorders and admLnLstratLon sLte condLtLons FatLJue and astKenLa 62 5 0 63 13 12 1 1 Edema perLpKeraO 2 25 1 1 0 0.0 0 0.0 25 23 36 32 5% 5% CKLOOs 11 10 14 13 0 0.0 0 0.0 *astroLntestLnaO dLsorders Nausea 3 36 2 24 5% 5% ConstLpatLon 3 36 41 3 5% 5% DLarrKea 3 35 40 36 5% 5% VomLtLnJ 15 14 16 14 5% 0 0.0 MuscuOosNeOetaO and connectLve tLssue dLsorders 3 35 36 32 15 14 11 10 MuscuOosNeOetaO cKest paLn 25 23 22 20 5% 0 0.0 MuscOe spasms 23 21 22 20 5% 5% ArtKraOJLa 1 1 1 15 5% 5% MuscuOar ZeaNness 15 14 15 13 6 6 4 4 Bone paLn 13 12 5% 5% MuscuOosNeOetaO paLn 13 12 1 1 5% 5% AOO Adverse ReactLons ≥10% Ln ELtKer Arm *rade 3 or 4 ≥5% Ln ELtKer Arm Bod\ S\stem Adverse ReactLon N=10 /oZ-dose De[ N=112 POMA/YST N=10 /oZ-dose De[ N=112 PaLn Ln e[tremLt\ 16 14 0 0.0 5% ,nfectLons and LnfestatLons Upper respLrator\ tract LnfectLon 40 3 32 2 5% 5% PneumonLa 30 2 3 34 21 20 32 2 UrLnar\ tract LnfectLon 11 10 1 1 2 2 10 10% 10% 6 6 5 4 MetaboOLsm and nutrLtLon dLsorders Decreased appetLte 25 23 21 1 5% 0 0.0 +\percaOcemLa 23 21 13 12 11 10 1 1 +\poNaOemLa 13 12 13 12 5% 5% +\perJO\cemLa 12 11 1 15 5% 5% +\ponatremLa 12 11 14 13 5% 5% DeK\dratLon 10% 10% 5 4. 6 5.4 +\pocaOcemLa 6 6 13 12 0 0.0 5% RespLrator\ tKoracLc and medLastLnaO dLsorders D\spnea 3 36 50 45 14 13 CouJK 1 1 25 22 0 0.0 0 0.0 EpLsta[Ls 1 1 12 11 5% 0 0.0 ProductLve couJK 10 14 13 0 0.0 0 0.0 OropKar\nJeaO paLn 6 6 12 11 0 0.0 0 0.0 Nervous s\stem dLsorders DL]]Lness 24 22 20 1 5% 5% PerLpKeraO neuropatK\ 23 21 20 1 0 0.0 0 0.0 +eadacKe 16 15 15 13 0 0.0 5% Tremor 11 10 15 13 0 0.0 0 0.0 SNLn and subcutaneous tLssue dLsorders 22 21 1 16 0 0.0 5% PrurLtus 16 15 10 0 0.0 0 0.0 Dr\ sNLn 10 12 11 0 0.0 0 0.0 +\perKLdrosLs 1 16 0 0.0 0 0.0 5 5 14 13 0 0.0 0 0.0 ,nvestLJatLons AOO Adverse ReactLons ≥10% Ln ELtKer Arm *rade 3 or 4 ≥5% Ln ELtKer Arm Bod\ S\stem Adverse ReactLon N=10 /oZ-dose De[ N=112 POMA/YST N=10 /oZ-dose De[ N=112 BOood creatLnLne Lncreased 20 1 11 10 6 6 3 3 WeLJKt decreased 16 15 10 0 0.0 0 0.0 WeLJKt Lncreased 1 1 12 11 0 0.0 0 0.0 An[Let\ 14 13 0 0.0 0 0.0 ConfusLonaO state 13 12 15 13 6 6 3 3 ,nsomnLa 1 16 0 0.0 0 0.0 RenaO and urLnar\ dLsorders RenaO faLOure 16 15 11 10 ReJardOess of attrLbutLon of reOatedness to POMA/YST. POMA/YST aOone arm LncOudes aOO patLents randomL]ed to tKe POMA/YST aOone arm ZKo tooN stud\ druJ 61 of tKe 10 patLents Kadde[ametKasone added durLnJ tKe treatment perLod. SerLous adverse reactLons Zere reported Ln at Oeast 2 patLents Ln an\ POMA/YST treatment arm. Data cutoff: 01 MarcK 2013 TabOe 4: Adverse ReactLons Ln TrLaO 2 AOO Adverse ReactLons ≥5% Ln POMA/YST /oZ-dose De[ arm and at Oeast 2% KLJKer tKan tKe +LJK-dose-De[ arm *rade 3 or 4 ≥1% Ln POMA/YST /oZ-dose De[ arm and at Oeast 1% KLJKer tKan tKe +LJK-dose-De[ arm Bod\ S\stem Adverse ReactLon POMA/YST /oZ-dose De[ N=300 +LJK-dose De[ N=150 /oZ-dose De[ N=300 +LJK-dose De[ N=150 Number % of patLents ZLtK at Oeast one adverse reactLon 2 14 25 6 12 5 BOood and O\mpKatLc s\stem dLsorders NeutropenLa 154 51 31 21 145 4 24 16 TKromboc\topenLa 30 44 2 66 22 3 26 /euNopenLa 3 13 5 2 5 3 FebrLOe neutropenLa 2 0 0.0 2 0 0.0 *eneraO dLsorders and admLnLstratLon sLte condLtLons FatLJue and astKenLa 140 4 64 43 26 1 12 0 2 35 23 3 5 Edema perLpKeraO 52 1 1 11 4 1 3 2 PaLn 11 4 3 2 5 2 1 1 ,nfectLons and LnfestatLons Upper respLrator\ tract LnfectLon 3 31 1 13 3 1 1 PneumonLa 5 1 20 13 4 16 15 10 NeutropenLc sepsLs 3 1 0 0.0 3 1 0 0.0 *astroLntestLnaO dLsorders DLarrKea 66 22 2 1 3 1 2 1 ConstLpatLon 65 22 22 15 2 0 0.0 Nausea 45 15 1 11 3 1 2 1 VomLtLnJ 23 6 4 3 1 0 0.0 MuscuOosNeOetaO and connectLve tLssue dLsorders 5 20 24 16 15 5 6 4 Bone paLn 54 1 21 14 22 5 MuscOe spasms 46 15 11 1 1 1 1 ArtKraOJLa 26 5 2 1 1 1 PaLn Ln e[tremLt\ 20 6 6 2 0 0.0 RespLrator\ tKoracLc and medLastLnaO dLsorders D\spnea 6 25 25 1 1 6 5 CouJK 60 20 15 10 2 1 1 1 puOmonar\ dLsease 5 2 0 0.0 4 1 0 0.0 Nervous s\stem dLsorders PerLpKeraO neuropatK\ 52 1 1 12 5 2 2 1 DL]]Lness 3 12 14 4 1 2 1 +eadacKe 23 5 1 1 0 0.0 Tremor 1 6 2 1 2 1 0 0.0 Depressed OeveO of conscLousness 5 2 0 0.0 3 1 0 0.0 AOO Adverse ReactLons ≥5% Ln POMA/YST /oZ-dose De[ arm and at Oeast 2% KLJKer tKan tKe +LJK-dose-De[ arm *rade 3 or 4 ≥1% Ln POMA/YST /oZ-dose De[ arm and at Oeast 1% KLJKer tKan tKe +LJK-dose-De[ arm Bod\ S\stem Adverse ReactLon POMA/YST /oZ-dose De[ N=300 +LJK-dose De[ N=150 /oZ-dose De[ N=300 +LJK-dose De[ N=150 MetaboOLsm and nutrLtLon dLsorders Decreased appetLte 3 13 12 3 1 2 1 +\poNaOemLa 2 12 12 4 4 3 +\pocaOcemLa 12 4 6 5 2 1 1 SNLn and subcutaneous tLssue dLsorders 23 2 1 3 1 0 0.0 PrurLtus 22 5 3 0 0.0 0 0.0 +\perKLdrosLs 15 5 1 1 0 0.0 0 0.0 ,nvestLJatLons NeutropKLO count decreased 15 5 1 1 14 5 1 1 POateOet count decreased 10 3 3 2 3 2 1 WKLte bOood ceOO count decreased 3 1 1 3 0 0.0 AOanLne amLnotransferase Lncreased 2 2 1 5 2 0 0.0 Aspartate amLnotransferase Lncreased 4 1 2 1 3 1 0 0.0 /\mpKoc\te count decreased 3 1 1 1 3 1 0 0.0 RenaO and urLnar\ dLsorders RenaO faLOure 31 10 1 12 1 6 5 ,nMur\ poLsonLnJ and proceduraO compOLcatLons Femur fracture 5 2 1 1 5 2 1 1 ReproductLve s\stem and breast dLsorders PeOvLc paLn 6 2 3 2 4 1 0 0.0 PercentaJe dLd not meet tKe crLterLa to be consLdered as an adverse reactLon for POMA/YST for tKat cateJor\ of event L.e. aOO adverse events or *rade 3 or 4 adverse events. SerLous adverse reactLons Zere reported Ln at Oeast 3 patLents Ln tKe POM /oZ-dose De[ arm AND at Oeast 1% KLJKer tKan tKe+LJK-dose-De[ arm percentaJe. Data cutoff: 01 MarcK 2013*astroLntestLnaO dLsoGeneral Disorders and Administration Site Conditions: cKest paLn MuOtL-orJan faLOure nfectLon vLraO CeOOuOLtLs UroCOostrLdLum dLffLcLOe coOLtLs PneumonLa streptococcaO /obar p Psychiatric disorders: (). TZent\-eLJKt patLents receLved POMA/YST 5 mJ taNen oraOO\ once tKromboemboOLsm. PatLents receoZ dose aspLrLn. Across ao receLved POMA/YST. TKe foOOoZLnJ serLous o receLved POMA/YST. TabOe 5: Adverse ReactLons ≥ 20% Ln PatLents WKo ReceLved POMA/YST Ln TrLaO 12-C-004 Adverse ReactLon*rades 1-4 N=2 *rade 3 or 4 N=2 RasK macuOo-papuOar3.6 ConstLpatLon 1 0 FatLJue Nausea 36 0 DLarrKea 32 3.6 CouJK 2 0 D\spnea 2 0 PerLpKeraO Edema 2 3.6 Upper respLrator\ tract LnfectLon 2 0 MuscOe spasms 25 0 +\potK\roLdLsm 21 0 Adverse ReactLon*rades 1-4 N=2 *rade 3 or 4 N=2 Dr\ sNLn 21 0 CKLOOs 21 0 TabOe 6: Frequenc\ of SeOect /aborator\ AbnormaOLtLes ≥ 10% WorsenLnJ from BaseOLne Ln PatLents WKo ReceLved POMA/YST Ln TrLaO 12-C-004 +ematoOoJ\ Decreased AbsoOute NeutropKLO Count 650 Decreased WKLte BOood CeOOs 3.6 Decreased +emo 540 Decreased POateOets 540 EOevated CreatLnLne 63.6 EOevated *Oucose 5 Decreased AObumL 540 Decreased PKospKate 5425 Decreased CaOcLum 500 ,ncreased AOanLne AmLnotransferase A/T320 ,ncreased Aspartate AmLnotransferase AST250 EOevated CreatLne .Lnase 25 Decreased Ma nesLum 140 EOevated AONaOLne PKospKate 143.6 DenomLnator Ls tKe number of patLents for ZKom tKere Ls a baseOLne and at Oeast one post baseOLne assessment for tKe Oaborator\ parameter. TKe foOOoZLnJ adverse reactLons Kave been LdentLfLed durLnJ postapprovaO use of POMA/YST. Because tKese estLmate tKeLr frequenc\ or estabOLsK a causaO re AOOerJLc reactLons e.J. anJLoedema anapK\Oa[Ls urtLcarLareMectLon Stevens--oKnson S\ndrome to[Lc DRU* ,NTERACT,ONS.1 DruJs TKat Affect PomaOLdomLde POasma ConcentratLons CYP1A2 LnKLbLtors: (). ,ncreased pomaOLdomLde e[posure ma\ Lncrease tKe rLsN of e[posure reOated to[LcLtLes. AvoLd co-admLnLstratLon of stronJ CYP1A2 ()(). USE ,N SPEC,F,C POPU/AT,ONS PreJnanc\ E[posure ReJLstr\ e[posed to POMA/YST aO e[posure to POMA/YST to CeOJene CorporatLon at 1--423- () and fLndLnJs from anLmaO studLes POMA/YST can cause embr\o-fetaO Karm ZKen admLnLstered to a preJnant femaOe and Ls contraLndLcated durLnJ preJnanc\ [see Contraindications (4), and Warnings and Precautions (5.1)]. POMA/YST Ls a tKaOLdomLde anaOLmbs pKocomeOLa sKort OLmbs K\popOastLcLt\ of AOLmentar\ tract urLnar\ tract and JenLtaO maOformatLons Kave aOso been documented and mortaOLt\ at or PomaOLdomLde crossed tKe pOacenta after admLnLstratLon to preJnant rabbLts (seetKe FDA vLa tKe MedWatcK proJram at 1- ,n rats pomaOLdomLde Zas admLnL d Ln tKLs stud\. TKe OoZest dose Ln rats resuOted Ln an e[posure AUC Lncreases at 250 mJ/NJ/da\. AddLtLonaO maOformatLons observed a fOe[ed and/or rotated fore- and/or KLndOLmbs unattacKed or abn cardLac anomaOLes Ln recommended dose of 4 mJ/da\. AddLtLonaO embr\o-fetaO to[LcLt\ maOLdomLde concentratLons Zere at aOO sed tKe pOacenta. .2 /actatLon Ln Kuman mLON tKe effects of POMA/YST on tKe breastfed cKLOd or tKe effects of POMA/YST on mLON productLon. PomaOLdomLde Zas e[creted Ln tKe mLON (see. Because man\ druJs are e[creted Ln Kuman mLON and because of tKe potentLaO for m POMA/YST advLse Zo pomaOLdomLde Zas transferred Lnto mLON ZLtK mLON to pOasma rat.3 FemaOes and MaOes of ReproductLve PotentLaO PreJnanc\ TestLnJ ()VerLf\ tKe preJnanc\ status of femaOes of reproductLve potentLaO prLor to LnLtLatLnJ POMA/YST tKerap\ and menstruaO bOeedLnJ. POMA/YST treatment must ContraceptLon condom dLapKraJm or cervLcaO cap. ContraceptLon must beJLn 4 stor\ of LnfertLOLt\ Males . TKerefore maOes must aOZa\s use a en Lf tKe\ Kave underJone a successfuO OMA/YST must not donate sperm.,nfertLOLt\ [see MuOtLpOe M\eOoma patLents Ln cOLnLcaO Of tKe 2 patLents ZKo receLved POMA/YST 11% Zere 65 \ears or tKe rate of SAE Lncreased b\ 64% r(.7) and Clinical Pharmacology (12.3)]. . +epatLc ,mpaLrment PomaOLdomLde Ls metaboOL]ed prLmarLO\ b\ tKe OLver. FoOOoZLnJ sLnJOe dose admLnLstratLon tKe AUC of pomaOLdomLde Lncreased 51% 5% and 2% Ln subMects ZLtK mLOd (). 10 OVERDOSA*E 11 DESCR,PT,ON re: r ZeLJKt Ls 23.24. PomaOLdomLde Ls a \eOOoZ soOLd poZder. ,t Kas OLmLted to OoZ so about 0.01 mJ/m/. PomaOLdomLderacemLc mL[ture of tKe R J LnactLve LnJredLents: mannLtoO preJeOatLnL]ed on o[Lde and ZKLte LnN. TKe 4-m12 C/,N,CA/ P+ARMACO/O*Y PomaOLdomLde Ls an anaOoJue of tKaOLdomLde ZLtK LmmunomoduOatorpropertLes. CeOOuOar actLvLtLesrouJK Lts tarJet cerebOon a component of a cuOOLn rLnJ E3 ubLquLtLn OLJase en]\me compOe[. ,n vLtro Ln tKe preseapoptosLs of KematopoLetLc tumor ceOOs. AddLtLonaOO\ pomaOLdomresLstant muOtLpOe m\eOoma MM ceOO OLnes and s\nerJL]ed ZLtKaOLdomLde-sensLtLve NLOOer N. ceOO-medLated LmmunLt\ and LnKLbLted productLon of aO\ses sKoZed tKat tKere Zas npomaOLdomLde e[posure OeveO and effLcac\ or safet\ foOOoZLnJ po Lde pOacebo and 400 mJ mo[LfOo[acLn cant QTc proOonJatLon effect of pomaOLdomLde Zas obma[Ko receLved POMA/YST 5 mJ daLO\ AbsorptLon DLstrLbutLon EOLmLnatLon Metabolism CYP2C1 and CYP2D6 Zere aOso observed in vitroof tKe radLoactLve dose Zas eOLmLnated Ln urLne and feces respradLoOabeOed dose eOLmLnated uncKanJed as pomaOLdomLde Ln urLneSpecLfLc PopuOatLons 60 m//mLn or severe 15 m//mLn ≤ C/crLrment requLrLnJ dLaO\sLs C/cr 30 m//mLn requLrLnJ dLcLrcuOatLon. spectLveO\. Clinical Studies CYP1A2 Inhibitors: effect of CYP1A2 LnKLbLtLon Ln tKbitors: Dosage and Administration (2.6) and Drug Interactions (7.1)]. Strong CYP3A4 and P-gp Inhibitors: Co-admLnLstratLon of Netocona]oOe a stronJ CYP3A4 and P-Jp LnKLbLtor Ln 16 KeaOtK\ maOe subMects Lncreased AUC of pomaOLdomLde b\ 1 % compared to POMA/YST admLnLstered Co-admLnLstratLon of carbama]epLne to 16 KeaOtK\ maOe subMectsadmLnLstered aOone. rs. Studies 13 NONC/,N,CA/ TO;,CO/O*Y treated femaOes. PomaOLdomLde Zaeated femaOes tKere Zas an Lnced Ln an e[posure AUC appro[LmateO\ 100- uterLne parameters Zere compa14 C/,N,CA/ STUD,ES 14.1 MuOtLpOe M\eOoma TrLaO 1 . PatLents Zere consLderrandomL]ed to receLve POMA/YST aOone or POMA/YST ZLtK /oZ-dose effLcac\ of POMA/YST 4 mJ once daLO\ for 21 of 2 da\s untLO a\s 1 15 and 22 of eacK 2-da\ c\cOe for dLsease cKaracterLstLcs Zere baOaTabOe : BaseOLne DemoJrapKLc and DLsease-ReOated CKaracterLstLPOMA/YST n=10 POMA/YST /oZ-dose De[ n=113 PatLent CKaracterLstLcs MedLan aJe \ears ranJe 61 3- 64 34- AJe dLstrLbutLon n % 65 \ears ≥65 \ears 65 60.2 43 3 . 60 53.1 53 46. Se[ n % 5 52. 62 54. Data cutoff: 01 AprLO 2011 RevLeZ AdMudLcatLon CommLtteeTabOe : TrLaO 1 ResuOts n=10 /oZ-dose De[ n=113 Response OveraOO Response Rate ORR n % .4 33 2 .2 5% C, for ORR % 3.3 14.1 21.0 3.5 CompOete Response CR n % 0 0.0 1 0. PartLaO Response PR n % .4 32 2.3 DuratLon of Response DOR MedLan montKsNE .4 5% C, for DOR montKs NE 5.1 .2 ResuOts are prLor to tKe addLtLon of de[ametKasone. ORR = PR CR per EBMT crLterLa. C, confLdence LntervaO NE not estabOLsKed tKe medLan Kas not \et been reacKed. Data cutoff: 01 AprLO 2011 FemaOe 51 4.2 51 45.1 Race/etKnLcLt\ n % WKLte BOacN or AfrLcan AmerLcan AOO otKer race 6 .6 16 14. 6 5.6 2 1.4 1 15 4 3.6 ECO* Performance n % Status 0-1 5 . 100 .5 DLsease CKaracterLstLcs Number of prLor tKerapLes MedLan mLn ma[ 5 2 12 5 2 13 PrLor transpOant n % 2 5. 4 4.3 Refractor\ to borte]omLb and OenaOLdomLde n % 64 5 .3 6 61.1 TrLaO 2 MA/YST /oZ-dose De[ arm and 153 Ln tKe POMA/YST /oZ-dose De[ arm oraOO\ on Da\s 1 to 21 of eacK 2-da\ c\cOe. De[ametKasone 40 TabOe : BaseOLne DemoJrapKLc and DLsease-ReOated CKaracterLstL POMA/YST /oZ-dose De[ N=302 +LJK-dose De[ N=153 PatLent CKaracterLstLcs MedLan AJe \ears ranJe 64 35 4 65 35 AJe DLstrLbutLon n % 65 \ears ≥ 65 \ears 15 52 144 4 4 4 52 Se[ n % FemaOe 11 60 121 40 5 66 43 Race/EtKnLcLt\ n % WKLte BOacN or AfrLcan AmerLcan AsLan OtKer Race Not CoOOected 244 1 4 1 4 1 2 1 4 16 113 4 3 2 0 0 2 1 35 23 ECO* Performance n % Status 0 Status 1 Status 2 Status 3 MLssLnJ 110 36 13 46 52 1 0 0 2 1 36 24 6 56 25 16 3 2 3 2 DLsease CKaracterLstLcs Number of PrLor TKerapLes MedLan MLn Ma[ 5 2 14 5 2 1 PrLor stem ceOO transpOant n % 214 1 105 6 Refractor\ to borte]omLb and OenaOLdomLde n % 225 5 113 4 Data cutoff: 01MarcK 2013 raOO response rate ORR based on tKe = 0.00 . TKe .apOan-MeLer curves for PFS respectLveO\. TabOe 10: TrLaO 2 ResuOts /oZ-dose De[ N=302 +LJK-dose De[ N=153 ProJressLon Free SurvLvaO TLme Number % of events 164 54.3 103 6.3 MedLan 2-sLded 5% C, montKs 3.6 [3.0 4.6] 1. [1.6 2.1] +a]ard RatLo Pom/D-De[:+D-De[ 2-SLded 5% 0.45 [0.35 0.5 ] /oJ-RanN Test 2-sLded P-VaOue 0.001 OveraOO SurvLvaO TLme Number % of deatKs 14 4. 6 56.2 MedLan 2-sLded 5% C, montKs 12.4 [10.4 15.3] .0[6. .0] +a]ard RatLo Pom/D-De[:+D-De[ 2-SLded 5% 0.0 [0.54 0. 2] /oJ-RanN Test 2-sLded P-VaOue 0.00 OveraOO Response Rate n % 1 23.5 6 3. CompOete Response 1 0.3 0 Ver\ *ood PartLaO Response 2.6 1 0. PartLaO Response 62 20.5 5 3.3 Note: C,=ConfLdence LntervaO +D-De[=+LJK dose de[ametKasone ,RAC=,ndependent RevLeZ AdMudLcatLon CommLttee /D-De[=/oZ dose de[ametKasone. TKe medLan Ls based on .apOan-MeLer estLmate. Based on Co[ proportLonaO Ka]ards modeO comparLnJ tKe Ka]ard functLons assocLated ZLtK treatment Jroups stratLfLed b\ aJe ≤5 vs >5 dLseases popuOatLon refractor\ to botK /enaOLdomLde and Borte]omLb vs not refractor\ to botK druJs and prLor number of antLm\eOoma tKerap\ =2 vs >2 stratLfLcatLon factors for tKe trLaO. TKe p-vaOue Ls based on a stratLfLed OoJ-ranN test ZLtK tKe same stratLfLcatLon factors as tKe above Co[ modeO. quentO\ receLved POMA/YST. onaO Ka]ards modeO unstratLfLed comparLated ZLtK treatment Jroups. TKe p-vaOue Ls based on an unstratLfLed OoJ-ranN test. AOpKa controO for PFS and OS. Data cutoff: 0 Sep 2012 for PFS Data cutoff: 01 Mar 2013 for OS and ORR FLJure 1:ProJressLon Free SurvLvaO Based on ,RAC RevLeZ of Response b\ ,MW* CrLterLa StratLfLed /oJ RanN Test ,TT PopuOatLon Data cut-off: 0 Sep 2012 FLJure 2: .apOan-MeLer Curve of OveraOO SurvLvaO ,TT PopuOatLoData cutoff: 01 Mar 2013 \ of POMA/YST Ln patLents ZLtK 1 +,V-posLtLve 10 +,V-neJatLve receLved POMA/YST 5 mJ oraOOeacK 2-da\ c\cOe untLO dLsease proJressLon or unacceptabOe to[LcLt\. AOO +,V-posLtLve patLents contLnued KLJKO\ dLsorders. PatLents receLved nced dLsease T1 at tKe tLme accordLnJ to tKe A,DS COLnLcaO TrLaO *roup ACT* OncoOoJ\ Comm AOO PatLents N=2 +,V-PosLtLve N=1 +,V-NeJatLve N=10 n % [ 5% C,] 20 1 [51 ] 12 6 41 0 44 n % 4 14 3 1 1 10 PR n % 16 5 50 0 DuratLon of Response .S MedLan Ln montKs [ 5% C,]12.1 [.6 16.] 12.5 [6.5 24. ] 10.5 [3. 24.2] DuratLon of Response .S % Percent Jreater tKan 12 montKs Percent Jreater tKan 24 montKs 50 20 5 1 3 25 C,: confLdence LntervaO ORR: overaOO response rate CR: compOete response PR: partLaO response CR LncOudes one +,V-neJatLve patLent ZKo acKLeved a cCR. CaOcuOated as date of fLrst documented response to date of fLrst documented dLsease proJressLon receLpt of neZ treatment or second course of treatment or deatK due to an\ cause ZKLcKever occurs fLrst. MedLan estLmate Ls from .apOan-MeLer anaO\sLs. From .apOan-MeLer anaO\sLs. 15 REFERENCES 1. OS+A +a]ardous DruJs. Kttp://ZZZ.osKa.Jov/S/TC/Ka]ardousdruJs/Lnde[.KtmO16 +OW SUPP/,ED/STORA*E AND +AND/,N* 1 mJ bottOes of 21 NDC 5 52-501-21 1 mJ bottOes of 100 NDC 5 52-501-00 2 mJ bottOes of 21 NDC 5 52-502-21 2 mJ bottOes of 100 NDC 5 52-502-00 aque bod\ LmprLnted ³POM/” on3 mJ bottOes of 21 NDC 5 52-503-21 3 mJ bottOes of 100 NDC 5 52-503-00 opaque bod\ LmprLnted ³POM/” on 4 mJ bottOes of 21 NDC 5 52-504-21 4 mJ bottOes of 100 NDC 5 52-504-00 Temperature]. ater. 1 PAT,ENT COUNSE/,N* ,NFORMAT,ON edLcatLon *uLde. s contraLndLcated Ln preJnanc\ (). POMA/YST Ls a tKaOLdomLde anaOoJue and ma\ cause serLous bLrtK defects or deatK to a deveOopLnJ bab\ [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)]. AdvLse femaOes of reproductLve potentLaO tKat tKe\ must avoLd pterruptLons and for 4 ZeeNs after sKe Kas compOeteO\ fLnLsKed KormonaO bLrtK controO pLOOs LnMectLons patcK or LmpOants and a partner’s vasectom\. AddLtLonaO e tKLnNs FOR ANY REASON tKat sKe ma\ OtKcare provLder Ls () Use in Specific Populations (8.3)]. AdvLse maOes to aOZa\s use a Oate[ or s\ntKetLc condom durLnJ an\ se[uaO contact ZLtK femaOes of reproductLve potentLaO ZKLOe taNLnJ POMA/YST and for up to 4 ZeUse in Specific Populations (8.3)]. Precautions (5.1) and Use in Specific Populations (8.3)]. AOO patLents must be Lnstructed to not donate bOood ZKLOe taNLnJ POMA/YST and for 4 ZeeNs foOOoZLnJ dLscontLnuatLon of POMA/YST [see Warnings and Precautions (5.1)]POMA/YST REMS ProJram Because of tKe rLsN of embr\o-fetaO to[LcLt\ POMA/YST Ls onO\ (). PatLents must sLJn a PatLent-PK\sLcLan AJreement Form and compO\ ZLtK tKe requLrements to receLve POMA/YST. ,n partLcuOar femaOes of reproductLve potentLaO must compO\ ZLtK tKe preJnanc\ testLnJ contraceptLon requLrements and partLcLpate Ln montKO\ teOepKone surve\s. MaOes must compO\ ZLtK tKe (). POMA/YST Ls avaLOabOe onO\ from pKarmacLes tKat are certLfLed Ln POMA/YST REMS proJram. ProvLde patLents ZLtK tKe teOepKone number and ZebsLte for LnformatLon on KoZ to obtaLn tKe product. PreJnanc\ E[posure ReJLstr\ e[posed to POMA/YST durLnJ preJna[see Use in Specific Populations (8.1)] (). +ematoOoJLc To[LcLtLes [see +epatoto[LcLt\ Precautions (5.6)]. Severe Cutaneous ReactLons [see Warnings [see [see [see [see+\persensLtLvLt\ ,nform patLents of tKe potentLaO for severe K\persensLtLvLt\ rePOMA/YST. ,nstruct patLents to contact tKeLr KeaOtKcare provLdeK\persensLtLvLt\ reactLons (). SmoNLnJ Tobacco [see Use in Specific Populations (8.8) and Clinical Pharmacology (12.3)] [see Dosage and Administration (2.2, 2.3, 2.9)]POMA/YST sKouOd be taNen once daLO\ at about tKe same tLme eacK mLss a dose of POMA/YST tKe\ matLme tKe\ ZouOd normaOO\ taNe Lt.Manufactured for: CeOJene CorporatLon MED,CAT,ON *U,DE POM-uK-OLst pomaOLdomLde capsuOes WKat Ls tKe most Lmportant LnformatLon , sKouOd NnoZ about POMA/YST? Before \ou beJLn taNLnJ POMA/YST \ou must read and aJree to aOproJram. Before prescrLbLnJ POMA/YST \our KeaOtKcare provLder and Kave \ou sLJn tKe PatLent-PK\sLcLan AJreement Form. POMA/YST can cause serLous sLde effects LncOudLnJ: PossLbOe bLrtK defects deformed babLes or deatK of an unborn FemaOes ZKo are preJnant or ZKo pOan to become preJnant must not taNe POMA/YST. POMA/YST Ls sLmLOar to tKe medLcLne tKaOLdomLde T+A/OM,D. We NnoZ tKaOLdomLde can cause severe OLfe-tKreatenLnJ bLrtK defects. POMA/YST Kas not been tested Ln preJ Kas Karmed unborn anLmaOs Ln anLmaO testLnJ. FemaOes must not Jet preJnant: For at Oeast 4 ZeeNs before startLnJ POMA/YST WKLOe taNLnJ POMA/YST DurLnJ an\ breaNs LnterruptLons Ln \our treatment ZLtK POMA/ For at Oeast 4 ZeeNs after stoppLnJ POMA/YST FemaOes ZKo can become preJnant: WLOO Kave preJnanc\ tests ZeeNO\ for 4 ZeeNs tKen ever\ 4 ZeeNs Lf \our menstruaO c\cOe Ls reJuOar or ever\ 2 ZeeNs Lf \our menstruaO c\cOe Ls LrreJuOar. e unusuaO bOeedLnJ \ou ZLOO need to Kave a preJnanc\ test and receLve counseOLnJ. Must aJree to use tZo acceptabOe forms of bLrtK controO at tKe same tLme for at Oeast 4 ZeeNs before ZKLOe taNLnJ durLnJ an\ breaNs LnterruptLons Ln \our treatment and for at Oeast 4 ZeeNs after stoppLnJ POMA/YST. TaON ZLtK \our KeaOtKcare provLder to fLnd out about optLons for acceptabOe forms of bLrtK controO tKat \ou ma\ use to prevent preJnanc\ before durLnJ and after treatment ZLtK POMA/YST. ,f \ou become preJnant ZKLOe taNLnJ POMA/YST stop taNLnJ Lt rLJKt aZa\ and caOO \our KeaOtKcare provLder.,f \our KeaOtKcare provLder Ls not avaLOabOe \ou can caOO CeOJene Customer Care Center at 1--423-5436. +eaOtKcare provLders and patLents sKouOd report aOO cases of preJnanc\ to: FDA MedWatcK at 1-00-FDA-10 and CeOJene CorporatLon at 1--423-5436 TKere Ls a preJnanc\ e[posure reJLstr\ tKat monLtors tKe outcomes of femaOes ZKo taNe POMA/YST durLnJ preJnanc\ or Lf tKeLr maOe partner taNes POMA/YST and tKe\ are e[posed durLnJ preJnanc\. You can enroOO Ln tKLs reJLstr\ b\ caOOLnJ CeOJene Corpted above. POMA/YST can pass Lnto Kuman semen: MaOes LncOudLnJ tKose ZKo Kave Kad a vasectom\ must aOZa\s use a Oate[ or s\ntKetLc condom durLnJ an\ se[uaO contact ZLtK a preJnant femaOe or a femaOe tKat can become preJnant ZKLOe taNLnJ POMA/YST durLnJ an\ breaNs LnterruptLons Ln \our treatment ZLtK POMA/YST and for 4 ZeeNs after stoppLnJ POMA/YST. Do not Kave unprotected se[uaO contact ZLtK a femaOe ZKo Ls or couOd become preJnant. TeOO \our KeaOtKcare provLder Lf \ou do Kave unprotected se[uaO contact ZLtK a femaOe ZKo Ls or couOd become preJnant. Do not donate sperm ZKLOe taNLnJ POMA/YST durLnJ an\ breaNs LnterruptLons Ln \our treatment and for 4 ZeeNs after stoppLnJ POMA/YST. ,f a femaOe becomes preJnant ZLtK \our sperm tKe bab\ ma\ be e[posed to POMA/YST and ma\ be born ZLtK bLrtK defects. Men Lf \our femaOe partner bour KeaOtKcare provLder rLJKt aZa\. BOood cOots Ln \our arterLes veLns and OunJs Keart attacN and stroNe can Kappen Lf \ou taNe POMA/YST. Most peopOe ZKo taNe POMA/YST ZLOO aOso taNe a bOood tKLnner medLcLne to KeOp prevent bOood cOots. Before taNLnJ POMA/YST teOO \our KeaOtKcare provLder: ,f \ou Kave Kad a bOood cOot Ln tKe past ,f \ou Kave KLJK bOood pressure smoNe or Lf \ou Kave been toOd \ou Kave a KLJK OeveO of fat Ln \our bOood K\perOLpLdemLa About aOO tKe medLcLnes \ou taNe medLcLnes can aOso Lncrease \our rLsN for bOood cOots CaOO \our KeaOtKcare provLder or Jet medLcaO KeOp rLJKt aZa\ Lf \ou Jet an\ of tKe foOOoZLnJSLJns or s\mptoms of a bOood cOot Ln tKe OunJ arm or OeJ ma\ : sKortness of breatK cKest paLn or arm or OeJ sZeOOLnJ SLJns or s\mptoms of a Keart attacN ma\ LncOude: cKest paLn tKat ma\ spread to tKe arms necN MaZ bacN or stomacK area abdomen sKortness of breatK feeOLn sLcN or vomLtLn SLJns or s\mptoms of stroNe ma\ LncOude: sudden numbness or ZeaNness especLaOO\ on one sLde of tKe severe KeadacKe or confusLon or probOems ZLtK vLsLon speecK or baOance. WKat Ls POMA/YST? POMA/YST Ls a prescrLptLon medLcLne used to treat aduOts ZLtK: MuOtLpOe m\eOoma. POMA/YST Ls taNen aOonJ ZLtK tKe medLcLne de[ametKasone Ln peopOe ZKo: Kave receLved at Oeast 2 prLor medLcLnes to treat muOtLpOe m\eOoma LncOudLnJ a t\pe of medLcLne NnoZn as a proteasome LnKLbLtor and OenaOLdomLde and tKeLr dLsease Kas become Zorse durLnJ treatment or ZLtKLn 60 da\s of fLnLsKLnJ tKe Oast treatment A,DS-reOated .aposL sarcoma .S. POMA/YST Ls taNen ZKen KLJKO\ actLve antLretrovLraO tKerap\ +AART Kas not ZorNed ZeOO enouJK or stopped ZorNLnJ faLOed ctLon +,V neJatLve. ,t Ls not NnoZn Lf POMA/YST Ls safe and effectLveLn cKLOdren. WKo sKouOd not taNe POMA/YST? Do not taNe POMA/YST Lf \ou: • are preJnant pOan to become LnJ treatment ZLtK POMA/YST. See ³WKat Ls tKe most Lmportant LnformatLon , sKouOd NnoZ about POMA/YST?” • are aOOerJLc to pomaOLdomLde or an\ of tKe LnJredLents Ln POMSee tKe end of tKLs MedLcatLon *uLde for a redLents Ln POMA/YST. provLder before taNLnJ POMA/YST?Before \ou taNe POMA/YST teOO \our KeaOtKcare provLder Lf \ou:• smoNe cLJarettes. POMA/YST ma\ not ZorN as ZeOO Ln peopOe ZKo smoNe Kave OLver probOems Kave NLdne\ probOems and are receLvLnJ KemodLaO\sLs treatment • Kave an\ otKer medLcaO condLtLons • are breastfeedLnJ. You sKouOd notpasses Lnto \our breast mLON and can Karm \our bab\. bout aOO tKe medLcLnes \ou taNe LncOudLnJ prescrLptLon and over-tKe-counter medLcLnes vLtamLns and KerbaO suppOements. POMA/YST and otKer medLcLnes ma\ affect eacK otKer causLnJ serLous sLde effects. TaON ZLtK \our KeaOtKcare provLder before taNLnJ an\ neZ medLcLnes. .noZ tKe medLcLnes \ou taNe. .eep a OLst of tKem to sKoZ \our KeaOtKcare provLder and pKarmacLst. +oZ sKouOd , taNe POMA/YST? • TaNe POMA/YST e[actO\ as prescrLbed and foOOoZ aOO tKe LnstructLons of tKe POMA/YST REMS proJram. • SZaOOoZ POMA/YST capsuOes ZKoOe ZLtK Zater 1 tLme a da\. Do not breaN cKeZ or open \our capsuOesPOMA/YST ma\ be taNen ZLtK or ZLtKout food. • TaNe POMA/YST at about tKe same tLme eacK da\. • ,f \ou are on KemodLaO\sLs taNe POMA/YST after KemodLaO\sLs on KemodLaO\sLs da\s. • Do not open tKe POMA/YST capsuOes or KandOe tKem an\ more tKan needed. ,f \ou toucK a broNen POMA/YST capsuOe or tKe medLcLne Ln tKe capsuOe ZasK tKe area of \our bod\ rLJKt aZa\ ZLtK soap and Zater. • ,f \ou mLss a dose of POMA/YSTours sLnce \our reJuOar tLme taNe Lt as soon as \ou remember. ,f Lt Kas been more tKan 12 Kours Must sNLp \our mLssed dose. Do not taNe 2 doses at tKe same tLme. • ,f ou taNe too mucK POMA/YST caOO our KeaOtKcare provLder rL WKat sKouOd , avoLd ZKLOe taNLnJ POMA/YST? See ³WKat Ls tKe most Lmportant LnformatLon , sKouOd NnoZ aboutFemaOes: Do not Jet preJnant and do not breastfeed ZKLOe taNLnJ POMA/YSTMaOes: Do not donate sperm. Do not sKare POMA/YST ZLtK otKer peopOe. ,t ma\ cause bLrtK defects and otKer serLous probOems. Do not donate bOood ZKLOe \ou taNe POMA/YST durLnJ an\ breaNs LnterruptLons Ln \our treatment and for 4 ZeeNs after stoppLnJ POMA/YST. ,f someone ZKo Ls preJnant Jets \our donated bOood Ker bab\ ma\ be e[posed to POMA/YST and ma\ be born ZLtK bLrtK defects. POMA/YST can cause dL]]Lness and confusLon. AvoLd taNLnJ otKer medLcLnes tKat ma\ cause dL]]Lness and confusLon durLnJ treatment ZLtK POMA/YST. AvoLd sLtuatLons tKat requLre \ou to be aOert untLO \ou NnoZ KoZ POMA/YST affects ou. WKat are tKe possLbOe sLde effects of POMA/YST? POMA/YST can cause serLous sSee ³WKat Ls tKe most Lmportant LnformatLon , sKouOd NnoZ about POMA/YST?”a OoZ pOateOets tKromboc\topenLa and OoZ red bOood ceOOs anemLa are common ZLtK POMA/YST but can aOso be serLous. You ma\ need a bOood transfusLon or certaLn medLcLnes Lf \our bOood counts drop too OoZ. Your bOood counts sKouOd be cKecNed ZeeNO\ for tKe fLrst ZeeNs of treatment and Severe OLver probOems LncOudLnJ OLver faLOure and deatK. Your KeaOtKcare provLder sKouOd do bOood tests to cKecN \our OLver functLon durLnJ \our treatment ZLtK POMA/YST. TeOO \our KeaOtKcare provLder rLJKt aZa\ Lf \ou deveOop an\ of tKe foOOoZLnJ s\mptoms of OLver probOems: YeOOoZLnJ of \our sNLn or tKe ZKLte part of \our e\es MaundLce DarN or broZn tea-coOored urLne PaLn on tKe upper rLJKt sLde of \our stomacK area abdomen BOeedLnJ or bruLsLnJ more easLO\ tKan normaO ver tLredSevere aOOerJLc reactLons and severe sNLn reactLons can Kappen ZLtK POMA/YST and ma\ cause deatK. CaOO \our KeaOtKcare provLder Lf \ou deveOop an\ of tKe foOOoZLnJ sLJns or s\mptoms durLnJ treatment ZLtK POMA/YST: a red LtcK\ sNLn rasK peeOLnJ of \our sNLn or severe LtcKLnJ fever *et emerJenc\ medLcaO KeOp rLJKt foOOoZLnJ sLJns or s\mptoms durLnJ treatment ZLtK POMA/YST: sZeOOLnJ of \our OLps moutK tonJue or tKroat troubOe breatKLn or sZaOOoZLn a ver\ fast Keartbeat ou feeO dL]] raLsed red areas on our sNLn KLves DL]]Lness and confusLon.See ³WKat sKouOd , avoLd ZKLOe taNLnJ POMA/YST?Nerve damaJe. Stop taNLnJ POMA/YST and caOO \our KeaOtKcare provLder Lf \ou deveOop s\mptoms of nerve damaJe LncOudLnJ: numbness tLnJn \our Kands OeJs or feet. RLsN of neZ cancers maOLJnancLes. NeZ cancers LncOudLnJ certaLn bOood cancers acute m\eOoJenous OeuNemLa or AM/ Kave been seen Ln peopOe ZKo receLved POMA/YST. TaON ZLtK \our KeaOtKcare provLder about \our rLsN of deveOopLnJ neZ cancers Lf \ou taNe POMA/YST. Tumor O\sLs s\ndrome T/S. T/S Ls caused b\ tKe fast breaNdoZn of cancer ceOOs. T/S can cause NLdne\ faLOure and tKe need for dLaO\sLs treatment abnormaO Keart rK\tKm seL]ure and sometLmes deatK. Your KeaOtKcare provLder ma\ do bOood tests to cKecN \ou for T/S. Your KeaOtKcare provLder ma\ teOO \ou to stop taNLnJ POMA/YST Lf \ou deveOop certaLn serLous sLde effects durLnJ treatment. TKe most common sLde effects of POMA/YST Ln peopOe ZLtK MuOtLpOe M\eOoma LncOude: tLredness and ZeaNness dLarrKea bacN paLn constLpatLon sKortness of breatK fever nausea upper respLrator tract LnfectLonTKe most common sLde effects of POMA/YST Ln peopOe ZLtK .S LncOude: tLredness nausea dLarrKea abnormaO NLdne\ functLon tests decreased pKospKate and caOcLum Ln tKe bOood constLpatLon Lncreased bOood suJar decreased aObumLn Ln tKe bOood rasK. See ³Severe aOOer Lc reactLons and severe sNLn reactLons” TKese are not aOO tKe possLbOe sLde effects of POMA/YST. our doctor for medLcaO advLce about sLde effects. You ma report sLde effects -10. +oZ sKouOd , store POMA/YST? • Store POMA/YST at room temperature betZeen 6°F to °F 20°C to 25°C. • Return an\ unused POMA/YST to CeOJene or \our KeaOtKcare prov.eep POMA/YST and aOO medLcLnes out of tKe reacK of cKLOdren. *eneraO LnformatLon about tKe safe and effectLve use of POMA/YST. MedLcLnes are sometLmes prescrLbed for purposes otKer tKan tKose OLsted Ln a MedLcatLon *uLde. Do not taNe POMA/YST for condLtLons for ZKLcK Lt Zas not prescrLbed. Do not JLve POMA/YST to otKer peopOe even Lf tKe\ Kave tKe same s\mptoms \ou Kave. ,t ma\ Karm tKem and ma\ cause bLrtK defects. ,f \ou ZouOd OLNe more LnformatLon taON ZLtK \our KeaOtKcare provLder. You can asN \our KeaOtKcare provLder or Lon about POMA/YST tKat Ls ZrLtten for KeaOtK professLonaOs. For more LnformatLon caOO 1--423-5436 or o to ZZZ.CeO eneRLsNMana ement.com. WKat are tKe LnJredLents Ln POMA/YST? ActLve LnJredLent: pomaOLdomLde LnJredLents: mannLtoO preJeOatLnL]ed starcK and sodLum stear\O fumarate. TKe 1-mJ capsuOe sKeOO contaLns JeOatLn tLtanLum dLo[Lde FD&C bOue 2 \eOOoZ Lron o[Lde ZKLte LnN and bOacN LnN. TKe 2-mJ capsuOe sKeOO contaLns JeOatLn tLtanLum dLo[Lde FD&C bOue 2 \eOOoZ Lron o[Lde FD&C red 3 and ZKLte LnN. TKe 3-mJ capsuOe sKeOO contaLns JeOatLn tLtanLum dLo[Lde FD&C bOue 2 \eOOoZ Lron o[Lde and ZKLte LnN. TKe 4-mJ capsuOe sKeOO contaLns JeOatLn tLtanLum dLo[Lde FD&C bOue 1 FD&C bOue 2 and ZKLte LnN. Manufactured for: CeOJene CorporatLon SummLt N- 0 01 POMA/YST and POMA/YST REMS are reJLstered trademarNs of CeOJene CorporatLon. Pat. Kttp://ZZZ.ceOJene.com/tKerapLes © 2005-2020 CeOJene CorporatLon AOO rLJKts reserved. POMM*.011 05/2020 TKLs MedLcatLon *uLde Kas been approved b\ tKe U.S. Food and DruJ AdmLnLstratLon. RevLsed: Ma\ 2020