KPATKA XAPAKTEPHCTIKA litactipitvsera. 65.00% ' coumee BCLEM Hep S78 7 14 -te- 2002 L MME HA JIEKAPCTBEHHA IPOAYKT Waaiep 20 mg/ml wikexunonen pasrsop Idafer 20 mg/m! solution for injection 2. KAYECTBEH H KOJMYECTBEH ChCTAB Beaxa awnyza Haadep or 5 ml cranpxa 100 mg xkes30 toa bopMara Ha KeneseH saxapar (xeneseH xnuRpoKcHsaxaposent KOMILIEKE (iron hydroxide sucrose complex), Koevo cporacrerea Ha 20 mg, 2ke930 Ha ml. ) net fora Viaadep coepxa 0 7 mg Harpuit ua ml, KouTo ca exeHpaseuHi wa 0,4% or npertoppastrennit MaxcuManeH HeBeH npHem oT 2 g HaTpuii 3a BkapacteH. 3a memHna crvctK Ha NoMoMUNTe BeMlecTBa BIDKTe TO'Ka 6.1 3. JIEKAPCTBEHA ®OPMA Weoxextmorten pastsop. Haaibep ¢ TeMHoKaisB, Henpospasen BoneH pasTROp. 4. KJIMHMUHM AHH 41 Tepauestwsae noxasamus Uinadep ¢ noxasaus 3a nosesmte na aenesent xed: ¢ Koraro ¢ name xnmunea ya oT Oyp90 NaanaHe Ha eH30. © Tip naunerrm, komo we Toxlepupar nepoparen >xene3eH mpMeM HAM He crassa HanHAMeHMATA, © Kéneto xeneanite nposykr 34 nepopanuo MpHsOKCHNE ne ca eqbexTUBHI (ANP. NH AKCTHBHO ekamamuresHo 3aGoaaBane Ha Yepaara). Haadep rps6sa na ce npraara camo KoraTo NoKa3aHHeTO Ce NOTBELPANABA OT CROTBETHHTE WacneaBaHHA. 42° Josmposxa w 1a mpHToxenwe Tipocaenspaitre sxwmarestio nanmeHtifte 3a mpHsHaur H CHAMMTTOMH 1a peaKiVHH 1a CepEXYYBCTBMTeAHOCT no BpeMe Ha H c:tes| BEKO MpuuToxesINe Ha inadep. ‘Hinadep rps6na ga ce npunara camo npH HenocpexcTReHo HanHune Ha Nepconan, O6y4eH 4a OUCHABA 1 oBNAKaBa aHAhMIAKTIUNM PeakUMH H TKIHM FbIMOKHOCTH 2a OCHTYPABAKE Ha PeAHAMALLA. Tlaumenrst spa6pa 4a Gone HaGmosanan 3a HeXxeTaHM peaktMN B MPONBAKEHHE Ha Hall-MaTKO 30 nimtyrn exen neaxo nprioxenne Ha Haadep (axe pases 4.4). josuponxa Kymynarupuara nosa Hinatep rpaGsa na Obie Msuvcslena MMMBHAYAAHO 3a BCEKHK My ‘psGna na ce npesstrasa,Vownenspane Ha aozata: OGuara kymyaaruena to3a Maadep exensaneHTHa Ha OOUNE IKeTeIeH nedynUT (me) ce oNpeseA 3aBHCHMOCT OT HHBOTO Ha XeMornoGuna (Hb) H oT TenecHoTo Terso (TT). JJosata Maadep tpx6wa 2a Gore waMnCHeHa MNAMBHAYAIHO 5a NCEKH NANINeHT chopes TOTAMHNA westeseH AedNUTT No cAcaHATA ‘opmysia na Ganzoni, tanpimep: 6m Keaesen aedunwer [mg] = TT [kg] x (Keaano muse wa Hb —axruseeko uano na Hb) [g/dl] x 2,4* + narpynano xes0 [mg] TT mon 35 kg: 2Kenano nso na Hb = 13 g/dl w narpynawo wesia30 = 15 mg/kg TT TT35kgmnoseve: —2Kenaso nnso wa Hb = 15 g/dl u Hatpynano xxeaa30 = 500 mg @axrop 2,4 = 0,0034 (cbarbprkanHe Ha xken30 B Hb = 0,34%) x 0,07 (oGeM KpbB = 7% or TT) x 1000 (npeepeutane or [g] 8 [mg]) x 10 ‘Otters ui: at (omy = Sumer axenesen aedbuurr [me 20 mg xxeas30/ml OGmoro KonHYecTBO Haadep HeoGXoAMMO 3a NpHAOKeHHE (8 ml) cMloped TeeCHOTO Ter10, ‘baxtnveckoTo HitBo Ha Hb Ht xkeaaHOTO HHBO Ha Hb*: Ske 15 15 15, 10kg 3 3 25 2 zl 15 kg. 5 45 35 3 20 kg 65 55 5 4 25 kg 8 7 6 55 30kg 95 85, 75 65 35 kg. 125 15 10 9 40 kg 13.5 12 im 95 45 kg 15 13 1s 10 50 kg, 16 14 12 105 55 kg 17 15 13 i 60 kg 18 16 135 115 65 kg. 19 16,5 14,5 12 70 kg 20 175 15 125 75 kp 21 18, 16 1B 80 kg 22,5 195 16,5 135 85 kg 235 20,5 17 4 90 kg 24, 21,5 18 14s * TT non 35 kg: 2Kesano Huo Ha Hb = 13 g/dl TT 35 kgunoneve: — Kes1ano nupo na Hb = 15 g/dl 3a na mpeo6pasysare Hb (mM) 8 Hb (g/dl) ywnoxxere 110 1,6, B eayuai, ve oGmara HeoGxonuMa jo%a HAABHIIaBA MaKCHMAIHATa NlOSBOZTeHA EAMMHNHA 2038, _ Torawa npHTOKeHHETO TpABBA Ja ce pases.fovucnnsane 3a. amos loagsane na 2ce1430 npu xy unodepwane Aosara Hnaibep Heo6xommwa sa KoMMeHicHpae HenocTHTa Ha MeIAIO MORE MA.Co HIHHICAM € Tomomtra wa enemeure bopmystH: Bcxyuati ve ¢ ussecmuo xonuvecmaomo uzzyGena xpee: Tipunaranero Ha 200 mg wenx30 (10 ml Uinadep) rpxGea na ce wspasu 8 ysenmuenne Ha Hb, npHOnwautenHo exsHRaieHTHo Ha | eaMHHua xp (400 ml npet Hb = 15 g/dl Hb). Kounvectao xens30 3a psacraxonssaxe [mg] = Bpoit waryGenu xpoonn eammnn x 200 mg wm HeoGxoanmo xonmyecrao Haadep [ml] = Bpolt nsryGenu xpspae eswmnmuya x 10 mt B cayyaii ve Hyporo Ha Hb ¢ no-HneKo oT eaaHOTO: Dopmynara jlonycka, We He € HEOBXOAHMO ‘BEACTAHOBABAHe Ha MaTpyTAHOTO 2¢s1590. 2Kena0 2a sactawopaane [mg] = TT fxg] x 2,4 (xenan Hb — daxrwecks Hb) [e/a] Tipimep: 3a TT = 60 kg W nawaaxsane Ka Hb = 1 gid] —> = 150 mg xexa30 3a ppscranonazane 7,5 ml neoGxoaum Haadep 3a MaxciamiaTa NperlopENHrena caMIHa H ceAMMTaHA nOsA BHDKTe ,HopMavttia HOSpoBKa” Ht »Makenmani mpenopssntrentin exHOKpaTHH H CeAMMuEH 03H”, Hopuasna dosuposxa: Bospacmuu ‘5-10 ml Haaipep (100-200 mg xexx30) | 20 3 msTH ceaMaTHo. 3a Bpemero Ha npraarane u cboTHouIeHMeTO Ha paspexctare BrbkTe Ham Ha npHnOxeHHe”. Teduampuvna nonynayua Hanne ¢ eronaM oGem saHKH TpH nea no Bpeme Fa NpoyBAHNE. AKO KIMHHYHOTO CHeTOAHIHE FO maucKBa, npenopoiTenio e aa ne ce Hasenuasa 0,15 ml Hnadep (3 mg we%30) na kg renecHo refuo He noseve oF rpi m-Tn cemMIFIO. 3a Bpemero ha npwiiarane x choTHonIehHeTO Ha paspexctave nitxTe ,HaNnll Ha npHoacHe” Me win wc Bospacmnu Karo winkekusia, MaxciMamiara TomepHpana 03a Ha Jett, NpHOKeHA He HoReYe OT 3 ITBTH CeAMHHO: © 10 ml Hnagep (200 mg xxens20), neokexrupavo sal-wanko sa 10 MunyTH, Karo undysns, waxcmasiaTa TonepHpava 03a Ha jeH, NpHAOKeHA He HOBEIC OT BEMMTEIK ceAMIFIEO: © Hanmer saa 70 kg tenecuo Tero: 500 mg xe830 (25 ml Hiaaiep) Hali-maako 3a 3% aca, © Tlauyterri rerno 70 kg TenccHo Terno H no-wanko: 7 mg xenm30/kg TesIeeHO Ter0 Hail- Mako 3a 3 ¥4 Hace, Bpeneto 32 uuchysusta AaneHo k Havin Ha MpitoxcHHic” tpa6Ra sla ce criaaBa CTPHKTHO, OPH AKO TANENTST He NONY4aHa MaKcHMaNHATA TONePHpala ENMMWHIA 2038. Hasta npunoxenue 7 Hasuu na npanoxenne Zaihi 7 Hinadep TpsGea 2a ce npwuiara camo rio wHTpapeHoseH mbt. ToBa Moxke a cTAHe pes mB in ie uucby3us, GaBHO HiDKeKTHpAHe WIM MIPSKO FEB BEMOIHATA JMHMS Ha AHANW3ATOpA.Hurpapenosia kamkona uny3ns Haadep tpa6na a ce paspexza B ctepwsien 0,9% m/V pastnop Ha naTpes xaopua (NaCl). Paspexmanero tps6pa na crasa erlocpescTBeHO Mpe ast HNY3UsTa H pAsTBOPLT TpaGwa ja ce ‘npwara kako enensa: Maxcumazen o6em aa Fora Haadep Tosa Haaep Paspemmane Ha Muaamasno ppeme 3a (mg xexs10) ‘ml Hinadep) etepaaten 0,9% m/V nysus pasrsop a NaCl 100 mg Sm 100 ml 15 wanyTa 200 mg. 10 mi 200 mi 30 soy 300 mg 15 mi 300 mi 15 aaca 400 mg 20 mil 400 mi 25 4aca ‘500 mg 25 ml 500 mi 3,5 waca To nprsmin ceppsanu cbc craGwinocrra, pasTBopH paspeseH AO no-HHiCKa KOHMeHTpaLuHa Ha 2KeNA20 He ca ROMYCTHNH, Humpasenos10 unacexmupane Vaabep moxe aa Gunte npuioxen Sasto miTpasewosHo npu exopoct 1 ml Nepaspesteu pasTHop 1 Mamnyra 1 Ges 2a ce HansAuranaT 10 ml (200 mg xen0) Ha MIEKCKUAS. Huscexmupane ava eenomama sunua na duansamop Higaep more 1a Gere mpstoxen no ppeMe tia XeMOzHANHsa AMPeKTHO BEB neHOSHATA THN Ha ‘AMaLLHBATOPA IIpH CBULHTE YCNOBHA KAKTO 38 HIFTpABeHOaNo HHEKEKTHPAHE. 43° Mporasonoxasa Ynotpe6ara Ha Haadep ¢ npoTuBonoxasana pu cmeAHHTe CbCTOAHHA: © Cepsxayacramreniocr Kom axnusHoTo pemiectso, xem Huaibep Ha KoM Hoe OT MlOMOMLEDITE pemecrea, HsGpoenn # roux 6.1; © Hisnectat cepuosii peakusi Ha expbXayBCTBHTesIHOCT KOM APYTH MpOHYRTH Ha 26193070 38 naperrrepaaiio MpHioxsene; © Avent, xosro He e nprsiiena oT HenOcTHT Ha wens30; © Flaunt 2a nperonapnane c xcensv0 HTH HacreACTReHM HAPYINeHHX MIpH YoROABAHE Ha KENIOTO. 4.4 Cnensaaun mperynpexnenus s npermasia Mepka upm yuotpe6a Tlapenrrepantio npwnaranyre npenaparn na xenm0TO Morar Ja MpemHsBHKaT PeaKUHH WA CRPEXNYBCTOHTERHOCT, BKIMOMHTEAHO CepHOSHH H TIOTeHURATHO daranH anadynaxrHsun/aniaHtaxTONAH peakiqu. PeaxtiNh Ha capEX4yBCTBHTe-HOCT ca CLOOUIARaHH H en naperrrepasiio MpHarast KOMMIEKCH Ha xeNSOTO B NOSK, KOHTO MpEAH TOBA He ca IpesWRNKBANI CROHTHS, AKMONMTEAHO AenmAKa 3axaposa. CEoSulaEaH ca Cy" Ha cEpwxsyRcraMeAHOCT, KoHTTO NporpecupaT 0 cmapoMa Ha Kounis (ocrep anepraen cnaswM Ha opoHapuite aptepa, Koitro Mome sla ZoBEAe 20 MHOKApLeN HApapxT, BH. TOHKA 4.8). B HRKOAKO [MpoyspanHs, MpOBeAeHH MpH MALHCHTH ¢ AHAMHe3a 30 peaKLA Wa CEPLXTYBCTBHTENHOCT KbM > KONEIEH ACKCTPAH MIN KEeICH FMOKOHAT e AoKAsAHO, He Matep ce MoHaca AoGpe. 3a uaRECTHH CepwosHit PeaxuIMM Ha cupExNTyBCTBTEAHOCT KEM AAPYTH NPOAYKTH Ha 2esse20TO 34 TapeHTe pnnoxenne mike ToxKa 4.3. Pucker of peakWHH! Ha CBPBXYYBCTBMTCHINOCT ¢ NOBHLNEH MPH MALWEHTH C HOBECTHH uIC7O NeKapeTBCHH ANeprH, BICHOYHTEIHO NaNveHTH c avaMHesa 3a Teka ACTMA, eX} atonwena aneprus.Vista u nownien pHek oF peakuMit tia CBpEXSYBCTBHTeTHOCT KM NapeHTEpaH KOMIITEKCH Ht 2xeXH}0TO MH MALeHTH ¢ HMyHHH HAH BEGMAAHTeAH saGosABAHNA (HAM. cHcTeMeH sync epktematoaye, peamarouseH aprpi). Handep tpa6sa 2a ce npuara camo npu HeriocpeacraeHo HasIMNMe Ha nepcowan O6y'eH sta oNeHARA W onmaziaBa aviadiTaKTHTMAH peaKUK H TEsLHH BEAMOKHOCTH 34 OCHTYpaBAHe Ha peanMMalNis. Bcext auweHt TpaGea fa ce HA6MOAABA 3a HeMeNAHH peaKtOAM Haii-ManKo 30 MHHYTH ciIeM BomKA uoxexamns ¢ Harpep. ipa sssuuxeane Ha peakuin Ha copBxYySCTaHTEMHOCT HH MPHSHAL HA HenloHOCHMOCT MIO EpeMe Ha IpHATaHeTO eYeHHeTO TpAGBA ja Ce MpeycTastonH HesaGaBHo. Heo6xosmmo e namraneTo Ha ycaoBHs sa cepslewo-Ces1opoOHa peaHMMalbis 4 cpencTBa sa ‘OBnaIABANE Ha OCTpH anapWraKTHNHH/anApHIAKTOMNK PEAKIM, BRMOGHTENHO HEDKEKTIMOHEN pasTeop Ha anpenazm 1:1000. Jlomsmmurentio eveHe ¢ aITTHXHCTaMMHH H/iIM KOPTHKOCTEpOMLIH ‘TpaOba 2a Ge npHaara no uenecKoGpasHocr. Tipu nauneura ¢ tepHoapo6na aucdytkipsa xena30 3a NaperrrepamHo npHomenMe TpAGRA 1a ce pwsara eaMHicTeeHo Che BKHMaTemMHA OUCHKA Ha CboTHOMTeHHETO Nomsa/pHeK. TIpwctararieTo Wa 2ke7a30 3a NlapeHTTepatKo MpHuiOmeHHe TPsGea xa ce HAORTRA NH NANHEHTH ¢ MepHOApOGKA aAMcd>yHIKUMa, KoraTO NpeTOBapsaHeTo ¢ 2eNsI0 € dpakrop 3a NpewumHTanyas. TipenopEYBa ce BHHMaTeNHO HaSMOAeRHE Ha CTaTYca Ha weNASOTO 3A fa Ce HSBeTHE MPeTOBAPBAHC ¢ 22:1830. 2Kenmo 3a napeHTepanHo npwtoweHHe TpAGEA fa ce npHlara npesAsKuBO B cays Ha OCTpA HAM xponwana uudexuns. [penopiypa ce nprioxennero via Maacep a ce mpeycTaHoBH mpi nalqAeHTH © Gaxtepxesna. ip nayyentH ¢ xpornuita nebexnv TpaGEa sa ce HSBLPUIH OUeHKa OA3A/PHCK. Tlapaneniosnoro usrwaaHe TpaGea 2a ce HaGarBa, THit KATO HsTHHaKeTO Ha Haadep Ha MACTOTO Ha MIDKEKTMpAHE MOE a TORERE 10 GONKA, SBIMATEHHE H KadaBO OUBETABANE Ma KOAATA. 45 Bsanmozelicrnne c apyra rekapersenm upoaykTH # apyra oput saanmonelicn Kaxro pH pcwvi napenrrepantiu npoayirn c xeas30 ce mpeniopsssa Haabep sia He ce npwiara ‘enHOBpeMeHHO c JipyrH Mepopamnn MpoAyKTH ¢ 2keI830, Tsll xavO abCOpGIUERTA Ha 2ETBOTO 5a nepopanto npwioxeHue Moxe ja Gene Haaren. 4.6 Depranurer, Gpemennocr a Kopmene Bpemennocr Tlanesar iui mma orpawiienn gant (2a waxona Ha 11o-ManKo ot 300 cnysas Ha 6pewettHocT) oT ynotpeGara va xces1a3ha 2axaposa upH GpemeHHH eK 8 MypaHtA TpMMecTHp. HeronemusT Oe ‘natn (2a Haxonta oT 300 10 1000 exry4ax Ha Gpemensocr) oT ynotpedara na Hnabep mpi Gpewennit 2KCHH BED BTOPHA H TpeTHA TPHMECTEP He AABa OCHOBAHK 9a Tpepora GTHOCKO GesoMIAcHOCTTA Ha Malika HM HopoponeHoTo. HeoSxoaHMa ¢ BHUMaTemHa npeMenKa Ha ceoTHOMIeHHeTO noma/pHeK npeAH yrlorpeba Mo BPEME Ha Gpeeniocr, karo Haabep He tps6pa Aa ce mpwnara no Bpeme Ha GpemettiocT, OCBEH AKO He € xarreropHano HeoGxonHM0 (Bx. TONKA 4.4). 2Kenssoxednusrrna anewHs pes MspRHA TpHMECTEp Ka GpeMenHocTTa MOxe B MHIOrO CHAK Ja ce exyBa ¢ 2kes30 34 repopanuo npistoxenme. Hevernero ¢ Haadep tpaGna za ce Orpavsn 20 BTOpHA H TPETHA TPHMECTED AKO ce NPeLeHH, Ye NONSATA NpeDHIIABA NlOTEHUHAMINNK PACK KAKTO 2a atixara, Taxa Wa geryca. Crea npwuioxxerne wa naperrtepasi AenAOCKABPAILM JeKAPCTBCHH TIPOAYKTH MORE 1a BESHEKHE eranna Gpanixapaus. Tx o6nKNOBeHO e NpeXoAHA Me NOcTeAHIA OT PeAKINA Ha cepmxsyacrawtenioct np maiixara, TLiomet rps6sa Ja ce mpocreAaua BiIIMATeNHO NO BpeMe Ha MirrpageHosHo MpMnOxKeHMe ua NaperTepasTHH KENAOCEALPHANU TeKAPCTHENK MPOMYET GpemenHn xenH, TIpoyspannara Bspxy KHROTHA He HOKAQBAT NpeKK WIM HeripeKH spent ederTH HO Ory pempoayxrupHara ToRcHuMocT (mK. TONKA 5.3).pmcne Hima neqocrartna unibopMaulna 3a CKCKPeMH Ha XKENA30TO B KEPMATa MpH HOBCKA Cea, HirrpapeoaHioTo MpHoxeHHe Ha we.taSta Saxaposa, B eano kavienano mpoydsane 10 32papi Matin xepwasnar ¢ xeueseH emu nomysasaT 100 mg xene3s0 Non HopMara Ha wesIesHa 3aXaposa. ‘Yerupn AHH cxea AeveHMeTo CHIIKPRAHHETO Ha KETO B KEPMATA He € YBEANNEHO M HANA HUKAKEE [pasniixa ¢ koHrponnara rpyna (n = 5). He Moxe Aa Ce WSKMOWH PHCK $a HOBOPONEHNTE/KYPMANIETATA ‘pH excnosnurta Ha xes1830 nomyseHO or Haadep apes MalisiHoTO Mako, CAeROBATEAHO TpAGHA a ‘ce HOBHPNH MpeueHKa Ha ChOTHOWEHHETO Nos3a/pHEK. TipeaMHHaMiTe AAHHH He NloKasBaT NpeKH WI HeNpeKH BpeAHH edbekTH 3a KEPMaKTO. ITpH -AKTHpaulH TUrEXORe TpeTMpanu c 7Fe-Genssaria wesNsHa 38xapoza Ce HAGMOABA HUCKA CeKPELIA HA 2xE2930 B MAKOTO M TpaHohep Ha 2KeN30 B TloKOReMHeTO, Hama ReposTHOCT HeMeTaGonNsupaa -xeANSHa SAXBPO3A a NpeMHNE B MAHINNHOTO MARKO. Seprunmser He ce naGmoxasar espexry wa reveuHeTo ¢ xens3tsa saxapoca BuPKY GepTHLATeTa, NOB LENHETO Ha swdyrocpane M panHoTo eMGpHoHanHo passiTTHe IPH TuTEXoBe. 4.7 Egexa sepxy enocoSnoerra 38 modupane « paGora ¢ Mamunn Manko nepoatno ¢ Haatep a okaspa amine B»pxy criocoSniocTra 3a modupanie wan pabora c Manmutta, Ho axo BESHMKNaT CHMITTOMH KETO BHEHE Ha CBAT, OBLPKANOCT HH HYBCTRO 3a 2aMauHIOCT ‘eney mpasioxenne Ha Haadep, sacernanire nainesTa He TpaGea na wopupar wu na paGorst ManIMIH AOKATO OTILYMAT CHMMTTOMHTE. 48 Hexenann sexapernenn peaxnan Hall-uecto ceoGumananara nexestana xeKapcTeetia peaks pH KaMKHIHH npoy'Bania c Maaep & ACreYSHA, KOSTO BEGHHKBA ¢ HecTOTa 4,5 cHGveTaa Ha 100 yaacruMun. Halt-snaHHMuTe cepHodHH HexesaH TeKapeTBeHH peakuMH cBEpsBant ¢ Haadep ca peakiytite Ha CEPBXYYBCTBATEHOCT, KOMTO BBSHHKRAT ¢ HecTOTa 0,25 eROUTHUK Ha 100 yHaCTHIRIN B KEGEL RSTITBANHS. Hemenarmre xexapcreci peak cooGmienn cre mproxenueTo Ha Mnadep mp 4064 yuacraMtn 1B RTHRIPSHE HOMITBAHH, a Taka CBUIO H CbOGMeEHHTe OT NocTMapKeTHHIToRATa yIOTpEGA ca pencrapenm B raGamuiara no-A0ay. (Cucremo- Meera [Hevecrm [Peake T opranea xac | 1/100, < 1/10) 1/1000, < 1/100) /@ 1/10 000, < 1/1000) Pee [Hapymenus ma | CeppxsypersHrennoc ‘Avaianaxronant smyanara ir wm peaxiunn, cucrema aurmocnen Hapymenus na |[fnereysna FaasoGonwe, enene |Cwnxon, Tlonioxeno 1860 meponara Ha cet, napectesis, |comnionestHoc |1a ctsHanne, jenerema, xumoecresit Ir cucToanne 1a | OGbpKaHocT, arya wa jexaanne, Tpewoatioct, TpeMop. Cepacamn Tlasrorranoon mapymenns(Cactemo- Wecra Hesecrn Peawn (C nemseen opranen «ase | 2 1/100, < 1/10) © 1/1000, < 1/100) |@1/10000, | secrora” /< 1/1000) Cerone Xunorouns, Basiepaanane, bacOwr Timpreynaropent Bapymem xnnepronns oname, tposGodac6ur_| Pecnuparopan, Tacs Bponxocnasem rpeaam Mequacranaat apymenns. Hapynienus ua Xpomarypax 6xGpenmre a BuxcounnTe aerate Crowamno- _ |Taene Tlospoiqane, xopennia Goaxa, qwapas, samex Hapymenus na Tipyparyc, opus Vpraxapua, Komara lepirrent noskoanata Mycxyamn crass, myexyano MaaarHs, aprpastr Hs, /cxeaetuara Goaxa B xpaiirasunrre, leacrema (Goaka B rp6a ‘epeqmmurenmat [Peaxtua na macroto a|Crynenu tpennn, — |F'peana Gomxa, |Cryaera nor, weoxexrupane/andysis |actens, yaopa, | xxnepxnsposa, | epaartonoxcHiHe 2 mepudeper oToK, mmpexcna , Gueaoer, Gonna Tpuonon0640 saonasaHe, sero wasa.t0 Mowe a papupa Jor naKonKo aca |n0 nawomo 00 Ffoemuena ananm — |Tosmmena faxumiorpachepass, | xpusna xakrar noswunena acnaprar | xexngporeviasa anunorpanedbepasa, HosHunena ranca- rxyrant |Tpaxcdepasa, oBHiueH cepymer | Gepurun tee 1) Chotrannn coo6urests or noctMapKerMHropata ynotpeGa 2) Hali-wecro nokuameaHi ca: Ha MACTOTO Ha MEEXeKTHPane/MHIDY3HA: GOAKA, CKCTABASAUMA, BRITANCHHe, PEAKS, MpOMANA Ha LIBETA, XEMATOM, CBPGEK. CroSuranane Ha nogosypaiin HexKcaHM peaKuAl CroSuasanero nia nogosmpani HexxenaHn peaKuNM cneM paspemiauane 32 ynloTpeGa Ha 2c mponyxr e Baxto. Topa NoSBONAEA Ja NpOLIDKH Ha6MIOACHMETO Ha CROTHOLIEHHETO deKapcraenus npomykt. OT MenMUMHCKHTe CneuWaINCTH ce WHCKRA 1a CHOOMLABAT nojowpana Hesxenata peaKuns “pes:Vamonmrentia arenuus no nexapersara, ya ffaan Cpyen” Ne 8, 1303 Cops, ‘rea: +35928903417,, yeBcaitr: www.bdaby. 49° Tipenosupane Tipexosmpanero Moxe Ja plu npetosapsane c HeNA0, KoeTO MoXke ja ce MposBH Nox GopMara ua xemocieposa. Fpexosupanero TpaGea a ce eKyRa KAKTO MPetIeHH 3a HEOGKONHMO JeKYBAMIUT JTekap © 2es1830 XenaTHpamlo cpeacTBO WAM cTlopea CTaNNApTHATa MEMMUHHCKA MpaRTHKA. 5. @APMAKONOTH4HH CBOHCTBA 5.1 Dapmaxonmamusun cpoticrea ‘Papwaxorepanesrima rpyna: AMTH-aHeMMMeH Mperiapar, wesA30, napeHtrepaneH npenapar, ATC ox: BO3AC Mexanizes Ha nelicrsne 2Keassuara saxaposa, akTusHara cecraaka Ha Maaep © ckcTapeHa oT MHOToRMpeHa CopLesHHa OT 2kenesen (II) xatapoxcna oGrpagena c TomaM 6poll HeKOBATEHTHO CaRpsAHH MOEKY:IM 3aXaP032, Kontuiexcet na cpemtho worexysmHo Terno (Mw) npGznsirenno 43 kDa, Muoroaapenara kensaHa ‘cwplieBina Ha CTpYKTYpa, oTOGNa Ha TasH Ha CBpUEHHHATA Ha GuSHOTOTHUHELA HATPY BAI HENIIO potenn — depitut, Koanaekcbr © mpeanasnaveH a npes0cTaBa 1lo KOHTpOAHpAH HAYHK YCBOAMO 2keaa30 3a TpAHCHOpTUTe H HATPYNBAMNH NpoTeUTIA B TsLOTO (HaNp. CboTRETHO TpaHcipepuH H ‘depurun). Cates KirtpaneHosHo MpHLiOKeHMe MHOTOsApeHaTa ‘KeIHsHA CHPLEBKHA OT KOMILIERCA ce HOEMA TMpeaMHo oT peTHky.10-eHnoTesHETa CHCTeMA B HepHA ApOG, calesKaTa H KOCTHHA MO3tK. Karo BTOpa CTBMIKA HeAAIOTO ce HSTIONSBa 3a CHFTeS Ha Hb, MHOTOGUH M ApyTH akessTI0-CHAEpHRALLHE HOMME HTH Ce HATPYMIBA NpeAWMHO B HepHHR APOE nod dopmara Ha hepurHe. Kanan Hedbponocua Baeucumo om duarusa xponuno Ge6perno saborseane ‘Tipoysparie LU98001 ¢ npocneKrHBHo, oTKPHTO MIpoy'¥BaHe ¢ EAHO paMo 3a VACHE ABAHE Ha euxacnocrta 4 6exonacHoctra wa Vaadep npr rannerty Ha XeMonnanesa ¢ akenasone>HLNTHA axemus (Hb xonnenrpauns > 8 u < 11,0 g/dl, TSAT < 20%, u cepymen epurin < 300 wg/l), Koro: ca nomysasann THuEPO tepanuis. O60 77 naumenra [44 (57%) wresKe; cpessia suapact 62,5 (awanason: 24-85 ronuni)] ca ytacreamn B poysBaHeTo 1 ca moaysapari 100 mg xeN%30 NO? opmara Ha Maadep, npiiarato pes AHAMNAHATA IKE & HIpOABIDKeHHe Ha MaxcHMym 10 ceasica B pamxarre tia 3 10 4 ceaMMUM. Cpentia oOme 2038 OT 983,1 + 105,63 mg xenAs0 HOA opMaTa Ha Haadep e mpwioxera 8 pamxnre Ha cpeano 9,8 + 1,06 ceanca #a ynamH3a. Hb > 11 g/dl e nocruruar nip 39/45 (87%; 95% JIM 76,5, 96,9) or noxnexamure Ha ouenKa nauneHTH. Ilono6un pesy/TaTH ce ‘uaSmoanat npH Monynausara ,.c Hameperte 3a nedeHHe” (ITT) 60/77 (78%; 95% fIM 68,5, 87.3). Maxcrmannoto rlosiiuere 1a cepyuiilis epiruy oT 83,6 + 11,69 ug/l 20 360,3 * 36,81 wgiL(n= 41) ce HaGmozana npHt sapspurbane Ha neNenneTo c Maahep. Maxcumanioto nosuiiesHe (nacummane c Tpanceepun) or 17,1 # 1,5% go 27,6 + 2,7% (n= 41) ce HaGmonasa nipocaegapane Ha 5-rara ceaMHua..Hesasucumo om duawsa xponuito 6e6pewo sabornsane Tipoysmane 1 VEN03027 ¢ orkpuo, paroMHsupaHo MpoyaBane 32 cpasHenne Ha Haadep 4 Nepopaten -xene2eH cynhar pH BEspacTHM nauHeHtTH © OvOperta HemOCTETE OCT Ht xenssonednurTna anemua (Hb < 11,0 g/dl, cepymen hepuTun < 300 yg/l, mTSAT < 25%) ¢ wis Gea THUEPO repanus, Maunesmure ca pantounesnpann Ha 1000 mg 2xen%20 nog opmara Ha Hxacpep (500 mg unpysna B npoxsmxcHHe Ha 3,5 10 4 aca » unre 0 u 14 winn 200 mg winKeKLIN, NpHOMeHH 8 MpombNKeHHE Ha 2 no 5 maENyTH B S pasnusH cryyas oT [lex O ao Jew 14) Han xenesen cynpat 325 mg (6S mg xenm.0), 3 msTH AAeBHO B MpoABIDKeHHE Ha 56 AHH. O60 9 aIIMeHTH Ca BKIMONEHH BEB BesKa Tpyiia 3a neNenne. CTATHCTHECKH HATHM HO-TOnaM AAA manweTh » rpynara wa Huabep (35/79; 44,3%) b cpapenve ¢ rpynara Ha sKens30 3a Nepopanio pnnoxenue (23/82; 28,0%) mma yaenuuenue 1a Hb > 1,0 g/dl no Bpene Ha mpoyssaHeTo (p= 0,034), Kawmursen orrosop (ae;bummapan karo yuenuienne Ha Hb > 1,0 g/dl w ysemeenne Ha copyuna depirim > 160 pg/l) ¢ HaGmogapan no-vecro np naumeHTH, nexyBanh ¢ Haabep (31/79; 39,296) 8 cpannerme ¢ xenss0 sa nepopanHo npwnoxenwe (1/82; 1,2%); p< 0,001. Eqwo panomusupato, xourponmpano npoysnarte cpantinsa Hutathep ¢ axenas0 3a nepopasto MpHaomeHHe MPH 91 nauHeHTH CE saGorBaNeTo ApAsHAMO ReGen0 HepBO Hc aneMsta (HD < 11,5 g/dl). Tauermire ca pariaomustipas 3a nonywasar nepopaHtt Ta6xeTKH C 2830 200 mg, ‘ana smeTH aHeRHO (n = 46) wan Hinadbep (n= 45), npHaralt Karo enHOKparKa i.v. 11032 oT 200 mg, 2KENAIO BEAHEK CEnMUEHO HIM Mpes CesLMNA B HPOALDKEHHE Ha 20 cemMMUN, YeTempHEceT Ht TPHME Trauwexr # spynata Ha Mnadep savepuipar mpoymavero B cpantene c 35 naunenTH w rpyrtara Ha 2xenx30 34 nepopantio npwaoxene (p = 0,0009). B xpaa Ha nevenneTo 66% oT nauncirHre # rpynara va Haabep muar nosmitetme wa Hb > 2,0 gidl s cpashenne c 47% w rpynara Ha xen%30 28 tlepopasno pusoxesne (p = 0,07). B rpymara 1a xeaas0 sa nepopasiuo npatoxenwe 41% nanyenH WaT aHeMHA B Kpas Ha Npoy4panieTo B cpasnenue ¢ 16% B rpynara Ha Maadep (p = 0,007). Yerapuaccer 4 aba npouetira ot nayveirrire B rpynata ssa Maadep zocTurat cboa pedepeuten Hb (15 g/dl mpi Mbrete 4 13 g/dl mpi Xennrre) & cpannenve ¢ 22% B rpynata Wa Xes1x0 3a Nepopamio pHOACHE (p= 0,04). Caedpoduren nepuod EqMo mpocriecruBio, parzoMmrsupaHo, KONTPOsIHpaHO HIMHTRAKE MpH 43 2xeHN CHE CHEMPORT axeamorepuurrua abiemns (Hb <9 gill u cepynen depurun < 15 yg/l na 24-48 aca exer paxanero) cpanriasa 2 x 200 mg xxeuuK30 nloa hopmara Ha Hxabep, mpraarano p Jan 2 4 (n= 22), © 200 mg xenmo 3a nepopanko npHtoxeHHe oa hopMara Ha weNeseH cy-naT, AABAHO HRA MT suheBHo B npomemDxeHMe a 6 cenumnut (n = 21). 3HatHTenHO To-BACOKE HBA Ha Hb ce naGmonabar B Tpynara Ha Handep » cpasenve ¢ rpymara Ha xeng30 sa nepopao upauiowene # pnt 5 x14 ( <0,01). Cpeanoro nosurenne Ha Hb oT wsxomHoto HiBo B [eH 5 ¢ 2,5 p/dl 8 rpynara na Haarep 10,7 gidl w rpynra wa xesi820 32 nepopanto npunoxeune. Jo [leu 40 uaMa aHasinMa pasmitia 8 Hnpara va Hb Mexuly rpyninre 2a newertve, Hiaa 3HasHMo MOBMIUCHHE Ha CepyMUIEA (epHTHE B rpynara Ha Hiaabep 10 Jlex 5, a cepyanuar dpepmrun ocrasa sHawnTenno no-BHCOK B rpyriara ia Hinadep 8 cpaprictine c rpynara Ha *ke1n30 3a Nepopaimio npwiorkeHie pes ULIOTO Npoy'wAHe (@< 0,01 s Dian 5 w 14 p < 0,05 5 Jen 40). Bpemennocm B eano panaomusnpato, orkpirro mpoydeane 90 KeHH B TpeTHa TPHMECTbp Ha OpeMeHHOCTIA xxenmoaedpuuirria anewna (Hb 8 0 10,5 g/dl w cepyMen epi < 13 w9/l) ca pape Toaysasar Haadep (n = 45) Han epopaten momMatozen KoMntext (n = 45). was ‘ ouucsenara o6iia 04a xes1m0 non opwara sa Haadep © mprunarana » uposayiaasye rn -Makcinwaria eamunsia s103a 200 mg KATO UNby3Ha M MaKCHMasIHA ZHCBHE 03a 408 pug seainkS. Fpynara wa 2ces10 2a nepopanvo npiioxennte nomysasa 100 mg xexx30 nox @ppwara va TaGaeret howroimwan =! > NCFpynara Ha Hinadep B cpasietie ¢ rpynara wa mena30 3a Nepopanio mpmsloxkeHne # new 28 M mpi pexsianeTo (P < 0,01). Tipn paxkaaneto Gpoxr Ha naumerTKHTe AOCTHTHAAIH wenaHOTO HitBO 11a Hb € 43 (95,6%) m 28 (62,2%), cborseTHo B rpynara Ha Mjadep #8 rpynara Ha 2ena20 3a Mepopastio Apaaoxenue (p< 0,001). Crofivocrue Ha cepymuina dbepirTHH ce yReMNMawAT SHANHMO ¢ BPEMeTO HB apete rpynin — na Hutadep (p< 0,05) # wa xens30 3a nepopanHo npuioxeHue (p < 0,05). 5.2 Mapmakoxaneruuna csoiicrna Paanpenenenue ‘Gepoxunerikara wa xeasuata saxaposa, Geassauia c pazwoaktunen “Fe 4 "Fe e ouenena np 6 auWeHTH ¢ aneMua H xponmna GyOpeua HexocTareMHOcT. TTpes rrspante 6-8 waca “Fe ce noma 8 ‘NepHLt apo6, exteakava 1 KoCTHA Mo3BK. TloeMaHieTo Ha panMoakTMBHOCTTa oT GoraTaTa Ha Maxposarnt cxeska ce cMstTa sa npeteTARHTesIHO 3a NOCMANETO Ha 2KEAAIOTO OT PETHKY.IO- ennoremara cucreMa, Crea aurpaseHoaio uipKeKrinpane Ha 3apapH OGpoBOmUM € eAMHNa 100 mg 1038 H.e30 KATO 2xensotta saxaposa MaKCHMAZTIMTe OSU CEpyMHH KOMUEHTpallAH Ha 2keAs30 ce NoerAraT 10 MUNHyTH ‘cen mioxexupasieTo Mm waar cpema xouNenTpaLuss 538 umol/l. OGewest Ha paanpeneneHse ta EHTTpaHA KOMMapTUNeHT OTToBaps Ha obeMa rxiaawa (MpHGMNSHTERHO 3 sHTpA). Buotpanchopmauna Tipx mikexrupane saxapozata 10 ronaMa cTeneH ce AMCOURMpa H MHOTORMpeHaTa *eNASHA. Chplleshiia Ce NOEMA FABKO OT PeTHKYNO-eHAOTeAHATA CHCTEMA Ha WepHUS APOG, cACSKATA H KOCTHHA mosox. YeTHpH CeAMHIH CHET MPHIOKEHETO YeROmBAHeTO Ha KEEIOTO OT MEPREHHTE KPBBHH ater papupa oT 59 10 97%. Emnanupane Konmuiekeer na xessanata saxaposa sa cpeavio MoseKysino Tero (Mw) npuGasurenno 43 kDa, KoeTo € JOcTaTB'HO TonAMO 3a 2a npexOTEpATH GESpeutio eaMMANMpane. BuopeHoTo ennMnHMpae ‘Ha 2keIS20TO RESHHKEAMO Npes MEpBHTe 4 vaca Chea wiIKKeKTApaNeTO Ha Osa Hulaep oT 100 mg, 2xensEI0 cKoTRETETRA Ha No-wanxo oF 5% or norara. Cnen 24 vaca OGiuaTa CepyMia KORUEHTpAns Ha 2Ke20TO € HAMaTeHa 10 HHBOTO pes MpHoxcHHETO. BEOpesHOTO eAIMMMMEMpANE Ha FaxApOdATA e ‘oKono 75% oF npHuiomenara 2038. 5.3 Mpexenmmen Aawan 98 Gesonaesocr Hexmmeanuire aan ne noKaspat ocoGen prick 3a xopa Ha Gasara Ha KOHBeHIMOHAAHHTS Mpoyeariua sa TOKcHYHOCT MPH MHOFOKpATHO NpiinaraNte, FHOTOKCHYHOCT, penpORYKTHRHA ‘TOKCHYHOCT H TOKCHYHOCT 3a passHTHeTO. 6. @APMAUEBTHYHH JAHHH 6.1 Cuncex aa womoumare nemecToa Bona sa uroxexsyt Harpues xwapoxen (sa kopexux wa pH) 6.2 Hecunmectumocrs: ‘Toon aekapersen mpoaykr te TpaGka a ce cMecBa C APYTH NeKapeTReHH MPONYKTH C HSK ‘eMecna ¢ APYTH pasTHOpHs WI TeKapCTReHH MpoAYicTH. He ca MSBCCTHH CHBMECTHIN onaxonkH ocveH Tesi OF creKsto, nommeTHAeH H PVC.63 Cpox na roquoct q Hany 3a 3 roman (Cpox na rognoct caea mppo oTBapsne Ha OnaKopKaTa (Or markpoOwonornana regia TOuKa NPOAYKTET TpAGeA a ce HanOM3Ba HesaBaBHo. ee 6. crepwren 2 Xwanueckara w busuecka craGwitoct No EpeMe Ha ynoTpe6a e AeMOHCTpHpana 4a 24 aca Mp 25°C. Ho ot muxpoSuonorwuna txeaHia TONKA MponyKTsT TpAGRA Ja ce HsTIO:SBa HesaGARHO Cale asTeapane, Axo He ce HanlonaBa RezHATa, BpeMeTO 3a CBXPAHEHHE Mo BpeMe Ha ynOoTpeGa H YenonwaTa npezin ynorpeba ca orrosopHocT wa NoTpeGHTeNd H OBuYAliHO ca He NoReue oF 24 aca imp 2 0 8°C. 64 Cnenmasnm yrasat su HA CLXpaNenMe Dla ne ce cexpannsa wan 25°C. [la ne ce sampass Tia ce cexpansna 8 opurinania onaKoeKa. 3a yononusra Ha cexpattenne cxtex paspexaane HM 1tspBo OTBApaHe Ha NeKAPeTBEHNA MpONYKT swxre TouKa 6.3. 65 Bax w ceanpxanue ma onaxopxaTa S ml pasreop # equa amnyaa (creKa0 Tam I) B onakoBKH 10 5. Axunyau ot 5 ml (100 mg xez2830) no 5 8 onaKopKa. 6.6 Cheunasum mpennasnn mepint npa woxeepasue u paGora HeoSxoqumo e npes ynorpeda annymre ja Ghat sHAMaTEIKO NpoBepeH 3a HAMHAHE 1 cenumenti u nospemu. Hsrionspalire cago ove3M, KONTO ChAbpxaT XOMOTeHEH pasTBop 6e3 ceAHMCHT. Haaacep ne paGpa fa ce emecna c apyrit xekapeTseHH IpoAyKTH c HBKIONeHHe Ha crepHuteHt 0,9% m/V pastsop Ha HaTpHeB Xnopin sa paspensane. 3a YkasaHHa 9a paspeskiaHeTO Ha NpOAY KT pean Npwtoxcune wKTe TouKA 4.2. Pasteoper TpaGea na ¢ Ha BHM Kaban # GucTBp. Beaka awnyna Haabep ¢ npeanasnavesa camo 3a enHoKpaTua ynoTpeGa. Hevsnonseannsr sekapeTaeH MpolykT KH oTTa,KBMHOTe MaTepHanH OT Hero Tpx6Ra ja Ce WIXBUPART B CHOTBETETBHNE c MECTHHTE HSHCKBANIR 7. HPHTEXATEJHA PA3PEWEHHETO 3A YNOTPEBA Vifor France 100-101 Terrasse Boieldiew Tour Franklin La Défense 8 92042 Paris La Défense Cedex pars rem: +33 (0) 1 41 06 5890 dhaxe:+ 33 (0) 1 41 06 58998 HOMEP(A) HA PA3PELIEHHETO 3A YIIOTPEBA Perncrpauwouen No 20020040 9. {ATA HA ITBPBO PA3PELIEHHE 3A YIIOTPEBA Zara va spyo paspemazane: 23.05.1996 r. Tara wa nocaeaio noquosasane: 29.02.2012 r. 10. JATAHA AKTYAJIM3MPAHE HA TEKCTA 12/2021