IBudesonide kunye neFomoterol Aerosol

IBudesonide kunye neFomoterol Aerosol

Igama lesiqhelo: budesonide kunye nefomoterol fumarate dihydrate
Ifomu yesisindo: iaerosol
Udidi lweziyobisi: Indibaniselwano yeBronchodilator

By Uhlaziyo lweMedia; Ukuhlaziywa ngu-Varixcare.cz. Igqityelwe ukuhlaziywa ngoJuni 21, 2021.



Kweli Phepha
Yandisa

Iimpawu kunye nokusetyenziswa kweBudesonide kunye neFomoterol Aerosol

Unyango lwe-Asthma

IBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION I-AEROSOL ibonakalisiwe kunyango lwe-asthma kwizigulana ezineminyaka emi-6 nangaphezulu.



I-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION i-adrenergic agonist (LABA).

Imida ebalulekileyo yosetyenziso:



i-metformin eyandisiweyo yokukhutshwa kwedosi
I-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION I-AEROSOL ayiboniswanga ukukhululeka kwe-bronchospasm.

Ulondolozo lonyango lweZifo eziNgapheliyo zePulmonary

IBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL 160 / 4.5 ibonakalisiwe kunyango lokugcinwa kokuthintelwa komoya kwizigulana ezinesifo esinganyangekiyo semiphunga (COPD) kubandakanya i-bronchitis engapheliyo kunye / okanye i-emphysema. I-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL 160 / 4.5 ikwabonakalisiwe ukunciphisa ukwanda kwe-COPD. I-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL 160 / 4.5 kuphela kwamandla aboniswe kunyango lweCOPD.

Imida ebalulekileyo yosetyenziso:

I-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION I-AEROSOL ayiboniswanga ukukhululeka kwe-bronchospasm.

I-Budesonide kunye neFomoterol Aerosol Isikali kunye noLawulo

Ulwazi loLawulo

I-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION I-AOSOSOL kufuneka ilawulwe njenge-2 inhalations kabini yonke imihla (kusasa nangokuhlwa, malunga neeyure ezili-12 ngokwahlukana), yonke imihla ngendlela yomlomo kuphela. Emva kokuphefumla, isiguli kufuneka sihlambe umlomo ngamanzi ngaphandle kokuginya.



Inkulumbuso ye-BUDESONIDE kunye ne-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL ngaphambi kokuyisebenzisa okokuqala ngokukhupha izitshizi zovavanyo ezimbini emoyeni kude nobuso, ushukume kakuhle imizuzwana emi-5 ngaphambi kokutshiza. Kwiimeko apho i-inhaler ingasetyenziswanga ngaphezulu kweentsuku ezisi-7 okanye xa ilahliwe, yibhale kwakhona i-inhaler ngokugungquza kakuhle phambi kwesitshizi ngasinye kwaye ukhulule izitshizi zovavanyo ezimbini emoyeni kude nobuso.

Ukulawulwa rhoqo okanye inani eliphezulu le-inhalation (ngaphezulu kwe-2 inhalations kabini yonke imihla) yamandla amiselweyo e-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL ayikhuthazwanga njengoko ezinye izigulana kunokwenzeka ukuba zifumane iziphumo ezibi ngamanani aphezulu e-formoterol. Izigulana ezisebenzisa iBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL akufuneki zisebenzise i-LABA eyongezelelweyo nangasiphi na isizathu[Bona Izilumkiso kunye nokuLumkisa (5.3 , 5.12 )].

Isifo sombefu

Ukuba iimpawu zesifo sombefu ziyavela kwisithuba esiphakathi kwamayeza, i-inhaled, ibeta emfutshane esebenzayo2-umlinganisi kufuneka athathwe ukuze afumane uncedo kwangoko.

Abantu abadala kunye nabagulayo abakwishumi elivisayo iminyaka eli-12 yobudala nangaphezulu

Kwizigulana ezineminyaka eyi-12 ubudala nangaphezulu, idosi yi-2 inhalations ye-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL 80 / 4.5 okanye iBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL 160 / 4.5 kabini yonke imihla.

Iidosi zokuqala ezicetyiswayo ze-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION INHALATION AEROSOL kwizigulana ezineminyaka eli-12 ubudala nangaphezulu zisekwe kubukhali besifuba okanye inqanaba lolawulo lweempawu zesifo sombefu, kunye nomngcipheko wokonyuka kwe-corticosteroids yangoku.

Elona dosi liphezulu licetyiswayo kwizigulana zabantu abadala nakwishumi elivisayo elineminyaka eli-12 nangaphezulu liBUDESONIDE KUNYE NEFOMOTOLI FUMARATE DIHYDRATE INHALATION AEROSOL 160 / 4.5, inhalations ezimbini kabini yonke imihla.

Ukuphuculwa kolawulo lwesifuba kulandela ukurhogola kwe-BUDESONIDE KANYE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inokwenzeka kwisithuba semizuzu eli-15 uqalile unyango, nangona ubuninzi bezibonelelo bungafezekiswa kwiiveki ezi-2 okanye ngaphezulu emva konyango lokuqala. Isigulana ngasinye siya kufumana ixesha eliguqukayo ukuqala kunye nenqanaba lokukhululeka kwempawu.

Kwizigulana ezingaphenduli ngokwaneleyo kwidosi yokuqala emva kweeveki ezi-1-2 zonyango kunye ne-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL 80 / 4.5, endaweni ye-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL 160 / 4.5 inokubonelela ngolawulo lwesifuba.

Ukuba idosi yerejimeni esebenzayo ye-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL iyasilela ukubonelela ngolawulo olululo lwe-asthma, irejimeni yonyango kufuneka iphinde ivavanywe kwaye yongezwe iindlela zokonyango, (umzekelo, ukubuyisela amandla asezantsi eBUDESONIDE NE-FORMOTEROL FUMARATE Ngamandla aphezulu, ukongeza i-corticosteroid eyongeziweyo, okanye ukuqala i-corticosteroids yomlomo) kufuneka kuthathelwe ingqalelo.

Izigulana zabantwana ezineminyaka eyi-6 ukuya ngaphantsi kwe-12 iminyaka

Kwizigulana ezineminyaka engaphantsi kwe-12 ubudala, idosi yi-2 inhalations ye-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL 80 / 4.5 kabini yonke imihla.

Isifo esingapheliyo sePulmonary Disease

Kwizigulana ezine-COPD idosi ekhuthazwayo yi-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL 160 / 4.5, inhalation ezimbini kabini yonke imihla.

Ukuba ukuphefumla okufutshane kwenzeka phakathi kweedosi, i-inhaled, ibeta emfutshane esebenzayo2-umlinganisi kufuneka athathwe ukuze afumane uncedo kwangoko.

Iifom zedosi kunye namandla

I-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION I-AEROSOL iyafumaneka njenge-ineredr-inhaler yedosi equkethe indibaniselwano ye-budesonide (80 okanye 160 mcg) kunye ne-formoterol (4.5 mcg) njenge-inhalation aerosol kula mandla mabini alandelayo: 80 / 4.5 no-160 / 4.5. Amandla emilinganiselo nganye aqukethe ii-120 actuations nganye / ibhokisi. Amandla onke e-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION I-AEROSOL inikezelwa ngeplastikhi ebomvu yeplastikhi enesiciko sothuli esingwevu.

Ukungqinelana

Ukusetyenziswa kwe-budesonide kunye ne-formoterol fumarate dihydrate kuyangqinelana kwezi meko zilandelayo:

Unyango olusisiseko lwesimo se-asthmaticus okanye ezinye iziqendu ezibukhali zesifuba okanye i-COPD apho kufuneka khona amanyathelo abalulekileyo.
Hypersensitivity nakweyiphi na incindi kwiBUDESONIDE NAKWI-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL.

Izilumkiso kunye nokuQapha

Iziganeko ezinxulumene ne-Asthma enzulu-iZibhedlele, iiNtsholongwane kunye nokuFa

Ukusetyenziswa kwe-LABA njenge-monotherapy (ngaphandle kwe-ICS) yesifo sombefu kunxulunyaniswa nomngcipheko owandayo wokufa okunxulumene nesifuba [jongaI-Salmeterol Multicenter Isilingo soPhando lwe-Asthma (SMART)]. Idatha efumanekayo evela kuvavanyo lweklinikhi olulawulwayo ikwacebisa ukuba ukusetyenziswa kwe-LABA njenge-monotherapy kunyusa umngcipheko wokulaliswa esibhedlele okunxulumene nesifuba kwizigulana zabantwana nakwishumi elivisayo. Ezi ziphumo zithathwa njengeziphumo zeklasi ye-LABA. Xa i-LABA isetyenziselwa indibaniselwano yedosi emiselweyo kunye ne-ICS, idatha evela kuvavanyo olukhulu lweklinikhi ayibonisi ukonyuka okubonakalayo kumngcipheko weziganeko ezinxulumene nesifuba (esibhedlele, intubations, ukufa) xa kuthelekiswa ne-ICS yodwa (jongaIziganeko ezinxulumene ne-Asthma ne-ICS / LABA).

Iziganeko ezinxulumene ne-Asthma ne-ICS / LABA

Iine ezine ezinkulu, iiveki ezingama-26, ezingahleliwe, ezingaboniyo, ezilawulwa ngokukuko kuvavanyo lokhuselo lweklinikhi lwenziwa ukuvavanya umngcipheko weziganeko ezinxulumene nesifuba xa i-LABA yayisetyenziselwa ukudibanisa idosi esisigxina kunye ne-ICS xa kuthelekiswa ne-ICS kuphela kwizigulana ezinesifuba. Izilingo ezintathu zibandakanya abaguli abadala kunye nabakwishumi elivisayo abaneminyaka eyi-12 iminyaka: kuvavanyo olunye kuthelekiswa i-budesonide / formoterol (budesonide kunye nefomoterol fumarate dihydrate) ukuya kwi-budesonide[Bona Izifundo zeKlinikhi (14.1) ]; Ityala elinye lafanisa i-fluticasone propionate / salmeterol inhalation powder ukuya kwi-fluticasone propionate powder inhalation powder; kwaye ityala elinye lafanisa i-mometasone furoate / formoterol kunye ne-mometasone furoate. Ityala lesine libandakanya izigulana zabantwana i-4 ukuya kwi-11 yeminyaka ubudala kwaye ithelekisa i-fluticasone propionate / salmeterol inhalation powder kunye ne-fluticasone propionate powder inhalation powder. Indawo yokugqibela yokhuseleko kuzo zone izilingo yayizizinto ezinxulumene nesifuba (ukulaliswa esibhedlele, intubation kunye nokufa). Ikomiti yokugweba engaboniyo igqibe ukuba ngaba iziganeko zinxulumene ne-asthma.

Izilingo ezintathu zabantu abadala kunye nolutsha zenzelwe ukukhusela umngcipheko we-2.0, kwaye ulingo lwabantwana luyilelwe ukuthintela umngcipheko we-2.7. Uvavanyo ngalunye lomntu luhlangabeze injongo yalo echaziweyo kwaye lubonakalise ukungaphantsi kwe-ICS / LABA kwi-ICS kuphela. Uhlalutyo lwe-meta lwezilingo ezintathu zabantu abadala kunye nolutsha alukhange lubonakalise ukwanda okukhulu kumngcipheko wesiganeko esinxulumene nesifuba kunye ne-ICS / LABA indibaniselwano yedosi emiselweyo xa kuthelekiswa ne-ICS yodwa (1 Table). Ezi zilingo zazingenzelwanga ukuthintela wonke umngcipheko weziganeko ezinxulumene nesifuba kunye ne-ICS / LABA xa kuthelekiswa ne-ICS.

Itheyibhile yoku-1.
*
Izigulana ezingahleliwe ezithathe ubuncinci idosi e-1 yeziyobisi. Unyango olucwangcisiweyo olusetyenziselwa uhlalutyo.
& ikrele;
Uqikelelo kusetyenziswa imodeli ye-Cox yomlinganiso weengozi zexesha ukuya kumnyhadala wokuqala kunye neengozi ezisisiseko ezihanjiswe luvavanyo ngalunye lwe-3.
& Dagger;
Inani lezigulana ezithe zenzeka kwisithuba seenyanga ezi-6 emva kokusetyenziswa kokuqala kwesiyobisi okanye kwiintsuku ezisi-7 emva komhla wokugqibela weziyobisi, nokuba ungowuphi na umhla. Izigulana zinokuba nesiganeko esinye okanye nangaphezulu, kodwa kuphela sisiganeko sokuqala esabalelwa uhlalutyo. Ikomiti eyodwa, eyimfama, ezimeleyo yokugweba ichonge ukuba ingaba imicimbi inxulumene nesifuba na.

ICS / LABA

(N = 17,537) *

ICS

(N = 17,552) *

I-ICS / LABA vs ICS

Umyinge weengozi (95% CI) & ikrele;

Umnyhadala obalulekileyo onxulumene nesifuba & Dagger;

116

105

1.10 (0.85, 1.44)

Ukufa okunxulumene nesifuba

2

0

Intubation enxulumene nesifuba (endotracheal)

1

2

Isibhedlele esinxulumene nesifuba (stay ukuhlala iiyure ezingama-24)

115

105

ICS = Inhaled Corticosteroid, LABA = I-Beta2-adrenergic Agonist ende

Ulingo lokhuseleko lwabantwana lubandakanya abaguli abangama-6208 abagulayo abaneminyaka emi-4 ukuya kweli-11 ubudala abafumene i-ICS / LABA (i-fluticasone propionate / salmeterol inhalation powder) okanye i-ICS (i-fluticasone propionate powder inhalation powder). Kolu vavanyo, izigulana ezingama-27/3107 (0.9%) ezenzelwe i-ICS / LABA kunye ne-21/3101 (0.7%) yezigulana ezenzelwe i-ICS yafumana isiganeko esihambelana nesifuba. Akukho bantu babulawa sisifuba okanye intubation. I-ICS / LABA ayibonisanga mngcipheko ukwanda kakhulu kwesiganeko esinxulumene nesifuba xa kuthelekiswa ne-ICS esekwe kumda wengozi ocaciswe kwangaphambili (2.7), ngomlinganiso weengozi wexesha ukuya kumnyhadala wokuqala we-1.29 (95% CI: 0.73 , 2.27).

I-Salmeterol Multicenter Isilingo soPhando lwe-Asthma (SMART)

Iveki engama-28, i-placebo elawulwa yi-placebo yase-US ethelekisa ukhuseleko lwe-salmeterol kunye ne-placebo, nganye yongezwa kunyango lwe-asthma yesiqhelo, ibonise ukonyuka kokufa okuhambelana nesifuba kwizigulana ezifumana i-salmeterol (13 / 13,176 kwizigulana eziphathwe nge-salmeterol vs. / 13,179 kwizigulana eziphathwe nge-placebo; umngcipheko xa kuthelekiswa: 4.37 [95% CI 1.25, 15.34]). Ukusetyenziswa kwemvelaphi ye-ICS bekungafuneki kwi-SMART. Umngcipheko okhulayo wokufa okunxulumene nesifuba uthathwa njengempembelelo yeklasi ye-LABA monotherapy.

Izifundo zeFomoterol Monotherapy

Izifundo zonyango kunye nefomoterol esetyenziswe njenge-monotherapy iphakamise imeko ephezulu yokuqaqamba kwesifuba kwizigulana ezifumene ifomoterol kunaleyo ifumene i-placebo. Ubungakanani bezi zifundo bezingonelanga ukubala ngokuthe ngqo umahluko ekunyukeni kwesifuba phakathi kwamaqela onyango.

Ukudodobala kwezifo kunye neZiqendu eziBalulekileyo

I-Budesonide kunye ne-formoterol fumarate dihydrate akufuneki iqaliswe kwizigulana ngexesha lokuwohloka ngokukhawuleza okanye iziqendu ezinokubusongela ubomi be-asthma okanye i-COPD. I-Budesonide kunye ne-formoterol fumarate dihydrate khange ifundwe kwizigulana ezinesifo sombefu okanye i-COPD ewohlokayo. Ukuqaliswa kwe-budesonide kunye ne-formoterol fumarate dihydrate kolu seto akufanelekanga.

Ukonyusa ukusetyenziswa kwe-inhaled, ibeta emfutshane esebenza kancinci2-i -agonists luphawu lokuwohloka kwesifuba. Kule meko, isigulana sifuna ukuphononongwa kwangoko ngokuvavanywa kwakhona kwerejimeni yonyango, sinika ingqwalaselo eyodwa kwisidingo esinokubakho sokutshintsha amandla akhoyo e-budesonide kunye ne-formoterol fumarate dihydrate ngamandla aphezulu, yokongeza i-corticosteroid eyongezwe ngaphakathi, okanye ukuqala inkqubo ye-corticosteroids . Izigulana akufuneki zisebenzise ngaphezulu kwe-2 inhalations kabini yonke imihla (kusasa nangokuhlwa) zebudesonide kunye nefomoterol fumarate dihydrate.

I-Budesonide kunye ne-formoterol fumarate dihydrate akufuneki isetyenziselwe ukukhululeka kweempawu ezibi, okt njengonyango lokuhlangula kunyango lweziqendu ze-bronchospasm. I-beta e-inhaled, esebenza ngokufutshane2-i -agonist, hayi i-budesonide kunye ne-formoterol fumarate dihydrate, kufuneka isetyenziselwe ukunciphisa iimpawu ezibi njengokuphefumla kancinci.

Xa uqala unyango nge-budesonide kunye ne-formoterol fumarate dihydrate, abaguli abathathe ngomlomo okanye baphefumla, i-beta esebenza kancinci.2-abaphikisi rhoqo (umzekelo, amaxesha ama-4 ngemini) kufuneka bayalelwe ukuba bayeke ukusebenzisa rhoqo la machiza.

Ukusetyenziswa gwenxa kweBudesonide kunye neFomoterolum Fumarate Dihydrate kunye nokuSebenzisa kunye neBeta2-Agonists ezisebenza ixesha elide

Njengokuba kunjalo nezinye iziyobisi ezihogelweyo eziqukethe i-beta2I-adrenergic agents, i-budesonide kunye ne-formoterol fumarate dihydrate akufuneki isetyenziswe rhoqo kunokucetyiswa, ngeedosi eziphezulu kunokuba kucetyisiwe, okanye ngokudibeneyo namanye amayeza aqukethe i-LABA, njengokudlula. Iziphumo ezibalulekileyo zeklinikhi kunye nokufa kuye kwaxelwa kunxulunyaniswa nokusetyenziswa gwenxa kweziyobisi ze-inflamed. Izigulana ezisebenzisa i-budesonide kunye ne-formoterol fumarate dihydrate akufuneki zisebenzise enye i-LABA (umz.

Iziphumo zaseKhaya

Kwizifundo zeklinikhi, ukukhula kosulelo lwasekhaya lomlomo kunye nepharynx ngeICandida albicansyenzekile kwizigulana eziphathwe nge-budesonide kunye nefomoterol fumarate dihydrate. Xa olu sulelo lukhula, kufuneka lunyangwe ngendlela efanelekileyo yendawo okanye yenkqubo (okt, i-antifungal yomlomo) unyango ngelixa unyango nge-budesonide kunye ne-formoterol fumarate dihydrate iqhubeka, kodwa ngamanye amaxesha unyango nge-budesonide kunye ne-formoterol fumarate dihydrate inokufuna ukuphazanyiswa. Cebisa isigulana ukuba sihlambe umlomo waso ngamanzi ngaphandle kokuginya ukulandela ukuhogela ukunceda ukunciphisa umngcipheko we-oropharyngeal candidiasis.

I-Pneumonia kunye nezinye izifo ezosulelekileyo zokuphefumla

Oogqirha kufuneka bahlale beqaphele ukukhula kwe-pneumonia kwizigulana ezine-COPD njengeempawu zeklinikhi yenyumoniya kunye nokukhula okuxhaphakileyo okuqhubekayo. Usulelo olusemazantsi okuphefumla, kubandakanya inyumoniya, kuye kwaxelwa kulandela ukurhoxa kwe-corticosteroids.

Kwisifundo somsebenzi wemiphunga seenyanga ezili-6 sezigulana ezili-1704 ezineCOPD, kwabakho imeko ephezulu yosulelo lwemiphunga ngaphandle kwenyumoniya (umz. (7.6%) kunaleyo ifumana i-budesonide kunye ne-formoterol fumarate dihydrate 80 / 4.5 (3.2%), formotero1 4.5 mcg (4.6%) okanye placebo (3.3%). I-pneumonia ayenzekanga ngeziganeko ezinkulu kwi-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5 iqela (1.1%) xa kuthelekiswa ne-placebo (1.3%). Kwisifundo somsebenzi wemiphunga seenyanga ezili-12 kwizigulana ze-1964 ezine-COPD, kwabakho neziganeko eziphezulu zosulelo lwemiphunga ngaphandle kwenyumoniya kwizigulana ezifumana i-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5 (8.1%) kunaleyo ifumana i-budesonide kunye ne-formoterol fumarate dihydrate 80 / 4.5 (6.9%), formoterol 4.5 mcg (7.1%) okanye placebo (6.2%). Ngokufana nesifundo seenyanga ezi-6, inyumoniya ayenzekanga ngeziganeko ezinkulu kwi-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5 iqela (4.0%) xa kuthelekiswa ne-placebo (5.0%).

Uxinzelelo lwe-Immunosuppression

Izigulana ezikumachiza acinezela amajoni omzimba zisengozini yosulelo kunabantu abasempilweni. I-chicken pox kunye nemasisi, umzekelo, inokuba nekhosi ebaluleke ngakumbi okanye ebulalayo kubantwana okanye kubantu abadala abasebenzisa i-corticosteroids. Kubantwana abanjalo okanye abantu abadala abangakhange babe nezi zifo okanye bagonywe ngokufanelekileyo, kufuneka kuthathelwe ingqalelo ethile ukunqanda ukubekwa emngciphekweni. Ukuba idosi, indlela, kunye nexesha lolawulo lwe-corticosteroid luchaphazela njani umngcipheko wokuba nosulelo olusasazwayo alwaziwa. Igalelo lesifo esisisiseko kunye / okanye unyango lwe-corticosteroid lwangaphambili emngciphekweni alwaziwa. Ukuba iveziwe, unyango kunye ne-varicella zoster immune globulin (VZIG) okanye i-pooled intravenous immunoglobulin (IVIG), ngokufanelekileyo, inokubonakaliswa. Ukuba ibonakaliswe kwimasisi, iprophylaxis ene-immunoglobulin edibeneyo ye-intramuscular (IG) inokuboniswa (jonga iipakeji ezifanelekileyo zokufaka i-VZIG epheleleyo kunye ne-IG emisela ulwazi). Ukuba i-pox pox iyakhula, unyango ngee-antiviral agents lunokuqwalaselwa. Ukuphendula komzimba kwiyeza lokugonya i-varicella kwavavanywa kwizigulana zabantwana abanesifo sombefu kwiinyanga ezili-12 ukuya kwiminyaka esi-8 ngokumiswa kwe-inhalation inhalation.

Ilebhile evulekileyo, engacwangciswanga kuvavanyo lweklinikhi luvavanye ukuphendula kwamagciwane kwi-varicella vaccine kwizigulana ezingama-243 zesifuba iinyanga ezili-12 ukuya kwiminyaka esi-8 ubudala abanyangwa ngokumiswa kwe-inhalation ukumiswa kwe-0.25 mg ukuya kwi-1 mg yonke imihla (n = 151) okanye unyango lwe-ascma ye-noncorticosteroid (n = 92) (okt, beta2-abaphikisi, i-leukotriene receptor antagonists, cromones). Ipesenti yezigulana eziphuhlisa i-seroprotective antibody titer ye>I-5.0 (ixabiso le-gpELISA) ekuphenduleni kugonyo lwalufana nezigulana ezanyangelwa ukumiswa kwe-inhalation ukumiswa kwe-budesonide (85%), xa kuthelekiswa nezigulana ezanyangwa ngonyango lwe-ascma ye-noncorticosteroid (90%). Akukho sigulana siphathwe nge-budesonide inhalation ukunqunyanyiswa esivelise isifo senkukhu ngenxa yokugonywa.

I-inhalled corticosteroids kufuneka isetyenziswe ngononophelo, ukuba kunjalo, kwizigulana ezinesifo sephepha esisebenzayo okanye esidlulayo sephepha lokuphefumla; ukunganyangwa kwenkqubo yfungal, ibhaktiriya, intsholongwane, okanye usulelo lweparasitic; okanye ioyile herpes simplex.

Ukuhambisa abaguli ukusuka kunyango lweCorticosteroid Therapy

Unonophelo olukhethekileyo luyafuneka kwizigulana ezigqithiselwe ukusuka kwi-corticosteroids esebenzayo ukuya kwi-corticosteroids ngenxa yokufa ngenxa yokunqongophala kwe-adrenal kwenzekile kwizigulana ezinesifuba ngexesha nasemva kokudluliselwa ukusuka kwi-corticosteroids yenkqubo ukuya kwi-corticosteroids encinci ye-inhaled. Emva kokurhoxa kwinkqubo yecorticosteroids, kufuneka iinyanga ezininzi ukubuyisela ukusebenza kwehypothalamic-pituitary-adrenal (HPA).

Izigulana ebezigcinwe ngaphambili kwi-20 mg okanye nangaphezulu ngosuku lwe-prednisone (okanye elilinganayo) zinokuba sesichengeni, ngakumbi xa inkqubo yazo ye-corticosteroids iphantse yarhoxiswa ngokupheleleyo. Ngeli xesha lokucinezelwa kwe-HPA, abaguli banokubonisa ukungoneli kwe-adrenal xa bevezwa kukuqaqanjelwa, utyando, okanye usulelo (ngakumbi isisu) okanye ezinye iimeko ezinxulumene nelahleko enkulu ye-electrolyte. Nangona i-budesonide kunye ne-formoterol fumarate dihydrate inokubonelela ngolawulo lweempawu zesifo sombefu kwezi ziqendu, kwiidosi ezikhuthazwayo zibonelela ngexabiso elingaphantsi kwesiqhelo somzimba se-glucocorticoid ngokwenkqubo kwaye ayiboneleli ngomsebenzi we-mineralocorticoid oyimfuneko ekujonganeni nezi meko zikaxakeka.

Ngexesha loxinzelelo, uhlaselo olubi lwe-asthma okanye ukwanda kakhulu kwe-COPD, abaguli abaye bakhutshwa kwi-systemic corticosteroids kufuneka bayalelwe ukuba baphinde baqale ngomlomo i-corticosteroids (ngeedosi ezinkulu) kwangoko kwaye banxibelelane noogqirha babo ukuze baqhubeke nemfundo. Aba baguli kufuneka bafundiswe ukuba baphathe ikhadi lesilumkiso elibonisa ukuba banokufuna ukongezwa kwenkqubo yecorticosteroids ngexesha loxinzelelo, uhlaselo lwesifuba, okanye ukonyuka okukhulu kweCOPD.

Izigulana ezifuna i-corticosteroids yomlomo kufuneka zilunyulwe kancinci ukusuka ekusebenziseni kwenkqubo ye-corticosteroid emva kokudlulisela kwi-budesonide kunye ne-formoterol fumarate dihydrate. Ukuncitshiswa kweprednisone kunokufezekiswa ngokunciphisa idosi yemihla ngemihla ye-prednisone nge-2.5 mg qho ngeveki ngexesha lonyango nge-budesonide kunye ne-formoterol fumarate dihydrate. Umsebenzi wemiphunga (kuthetha ukunyanzeliswa kwevolumu yokuphelelwa lixesha kwimizuzwana eyi-1 [FEV1] okanye intsasa yokuphuma kokuphuma kokuphuma [PEF]), ukusetyenziswa kwe-beta-agonist, kunye ne-asthma okanye iimpawu zeCOPD kufuneka zijongwe ngononophelo ngexesha lokurhoxiswa kwe-corticosteroids yomlomo. Ukongeza, abaguli kufuneka bajongwe kwiimpawu kunye neempawu zokungoneliseki kwe-adrenal, njengokukhathala, ukungakhathali, ubuthathaka, isicaphucaphu kunye nokugabha, kunye ne-hypotension.

Ukuhanjiswa kwezigulana ukusuka kunyango lwe-corticosteroid yenkqubo ukuya kwi-inhaled corticosteroids okanye kwi-budesonide kunye ne-formoterol fumarate dihydrate inokukhupha iimeko ebezicinezelwe ngaphambili yinkqubo ye-corticosteroid yonyango (umzekelo, i-rhinitis, i-conjunctivitis, i-eczema, i-arthritis, iimeko ze-eosinophilic). Abanye abaguli banokuba neempawu zenkqubo yokurhoxa kwecorticosteroid esebenzayo (umzekelo, ukudibana kunye / okanye iintlungu zemisipha, iswekile, uxinzelelo) ngaphandle kokugcinwa okanye nokuphuculwa komsebenzi wokuphefumla.

Hypercorticism kunye noxinzelelo lweAdrenal

I-Budesonide, icandelo le-budesonide kunye ne-formoterol fumarate dihydrate, iya kuhlala inceda ukulawula iimpawu ze-asthma kunye ne-COPD ngokucinezelwa kancinci komsebenzi we-HPA kunonyango olulinganayo lonyango lwe-prednisone. Kuba i-budesonide ingena kwi-circulation kwaye inokuthi isebenze ngokwenkqubo kwiidosi eziphezulu, iziphumo eziluncedo ze-budesonide kunye ne-formoterol fumarate dihydrate ekunciphiseni ukungasebenzi kakuhle kwe-HPA kunokulindelwa kuphela xa iidosi ezinconywayo zingagqithiswanga kwaye izigulana ezizodwa zibalwa zedosi ephantsi esebenzayo.

Ngenxa yokubakho kokufakwa ngaphakathi kwe-corticosteroids, izigulana eziphathwe nge-budesonide kunye ne-formoterol fumarate dihydrate kufuneka ziqwalaselwe ngononophelo nakuphi na ubungqina benkqubo ye-corticosteroid. Unonophelo olukhethekileyo kufuneka lwenziwe ekuqwalaseleni abaguli emva kokusebenza okanye ngexesha loxinzelelo kubungqina bokungoneliseki kwempendulo ye-adrenal.

Kungenzeka ukuba inkqubo ye-corticosteroid enje nge-hypercorticism kunye noxinzelelo lwe-adrenal (kubandakanya ingxaki ye-adrenal) inokuvela kwinani elincinci lezigulana, ngakumbi xa i-budesonide ilawulwa ngaphezulu kuneedosi ezinconyelweyo ixesha elide. Ukuba iziphumo ezinjalo ziyenzeka, idosi ye-budesonide kunye ne-formoterol fumarate dihydrate kufuneka incitshiswe kancinci, ngokungqinelana neenkqubo ezamkelweyo zokunciphisa inkqubo yecorticosteroids kunye nolawulo lweempawu zesifuba.

Ukusebenzisana kweziyobisi kunye neCytochrome eStrong P450 3A4 Inhibitors

Isilumkiso kufuneka sisetyenziswe xa kuthathelwa ingqalelo ulawulo lwe-budesonide kunye ne-formoterol fumarate dihydrate kunye ne-ketoconazole, kunye nezinye i-CYP3A4 inhibitors ezomeleleyo (umz., Ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, Ukuvezwa kwenkqubo kwi-budesonide kunokwenzeka[Bona Ukusebenzisana kweziyobisi (7.1) kwaye Ikhemesti yezonyango (12.3) ].

IParadoxical Bronchospasm kunye neMpawu zoMoya eziPhezulu

Njengakwamanye amayeza afunxwayo, i-budesonide kunye ne-formoterol fumarate dihydrate zinokuvelisa i-bronchospasm ephikisayo, enokubusongela ubomi. Ukuba i-bronchospasm ephikisayo yenzeka ngokulandela idosi kunye ne-budesonide kunye ne-formoterol fumarate dihydrate, kufuneka inyangwe kwangoko nge-inhaled, bronchodilator emiselweyo, IBUDESONIDE NE-FORMOTEROL.

Ukuphendula ngokukhawuleza kweHypersensitivity

Ukuphendula kwangoko kwe-hypersensitivity kunokwenzeka emva kolawulo lwe-budesonide kunye ne-formoterol fumarate dihydrate, njengoko kubonisiwe ngamatyala e-urticaria, angioedema, rash, kunye ne-bronchospasm.

Iziphumo zenkqubo ye-Cardiovascular kunye ne-Central Nervous System

Ukunyusa i-beta-adrenergic stimuli kunxulunyaniswa nokubanjwa, i-angina, uxinzelelo lwegazi okanye i-hypotension, i-tachycardia enamaxabiso ukuya kuthi ga kwi-200 beats / min, arrhythmias, luvalo, intloko ebuhlungu, ukungcangcazela, ukubetha, isicaphucaphu, isiyezi, ukudinwa, ukuqaqanjelwa, kunye nokungalali[Bona Ukugqithisa (10 GS amanqaku). ]. Ke ngoko, i-budesonide kunye ne-formoterol fumarate dihydrate, njengazo zonke iimveliso ezinama-sympathomimetic amines, kufuneka isetyenziswe ngononophelo kwizigulana ezinesifo sentliziyo, ngakumbi ukungoneli kwemithambo yegazi, i-arrhythmias yentliziyo, kunye noxinzelelo lwegazi.

IFomoterolol, eyinxalenye ye-budesonide kunye ne-formoterol fumarate dihydrate, inokuvelisa isiphumo sentliziyo kwizigulana ezithile njengoko kulinganiswa ngenqanaba lokubetha, uxinzelelo lwegazi, kunye / okanye iimpawu. Nangona ezo zinto zinqabileyo emva kolawulo lwefomoterol kwiidosi ezinconyelwayo, ukuba ziyenzeka, ichiza linokufuna ukuba liyekwe. Ukongeza, ii-beta-agonists ziye zaxelwa ukuba zivelise utshintsho lwe-ECG, njengokucaba kwamaza e-T, ukwandiswa kwexesha le-QTc, kunye noxinzelelo lwecandelo le-ST. Ukubaluleka kweklinikhi kwezi zinto zifunyanisiweyo akungaziwa. Ukufa kuye kwaxelwa kunxulunyaniswa nokusetyenziswa gwenxa kweziyobisi ze-inhalled sympathomimetic.

Ukuncitshiswa koxinano lwamaminerali eBone

Ukuncipha kokuxinana kwethambo (i-BMD) kuye kwaqwalaselwa nolawulo lwexesha elide lweemveliso eziqukethe i-corticosteroids enganyangekiyo. Ukubaluleka kweklinikhi kotshintsho oluncinci kwi-BMD ngokubhekisele kwiziphumo zexesha elide njengokuqhekeka aziwa. Izigulana ezinomngcipheko omkhulu wokunciphisa umxholo wamaminerali amathambo, njengokunyanzelwa ixesha elide, imbali yosapho ye-osteoporosis, imeko ye-postmenopausal, ukusetyenziswa kwecuba, ukukhula, ukutya okungondlekiyo, okanye ukusetyenziswa gwenxa kweziyobisi ezinokunciphisa ithambo (umz., I-anticonvulsants, i-corticosteroids yomlomo ) kufuneka zibekwe esweni kwaye ziphathwe ngemigangatho emiselweyo yokhathalelo. Kuba abaguli abane-COPD bahlala benemingcipheko emininzi yokunciphisa i-BMD, uvavanyo lwe-BMD luyacetyiswa ngaphambi kokuqalisa i-budesonide kunye ne-formoterol fumarate dihydrate kwaye emva kwexesha emva koko. Ukuba ukuncitshiswa okubonakalayo kwi-BMD kubonwa kwaye i-budesonide kunye ne-formoterol fumarate dihydrate isathathelwa ingqalelo ibalulekile kwezonyango kunyango lwe-COPD yesigulana, ukusetyenziswa kwamayeza ukunyanga okanye ukuthintela i-osteoporosis kufuneka kuthathelwe ingqalelo ngamandla.

Iziphumo zonyango kunye ne-budesonide kunye ne-formoterol fumarate dihydrate i-160 / 4.5, i-budesonide kunye ne-formoterol fumarate dihydrate 80 / 4.5, i-formoterol 4.5 mcg, okanye i-placebo kwi-BMD yavavanywa kwiseti yezigulana ezingama-326 (abantu ababhinqileyo nabesilisa abaneminyaka engama-41 ukuya kuma-88 ubudala) I-COPD kwisifundo somsebenzi wemiphunga seenyanga ezili-12. Uvavanyo lwe-BMD lwengingqi ye-hip kunye ne-lumbar spine yenziwa kwisiseko kunye neeveki ezingama-52 kusetyenziswa amandla amabini e-x-ray absorptiometry (DEXA). Kuthetha ukuba utshintsho kwi-BMD ukusuka kwisiseko ukuya esiphelweni sonyango lwaluncinci (kuthetha utshintsho olususela -0.01 - 0.01 g / cm2). Iziphumo ze-ANCOVA zomqolo opheleleyo kunye ne-hip BMD iyonke esekwe esiphelweni sexesha lokunyanga ibonakalise ukuba zonke iiyometri ze-LS zithetha umlinganiso weqela lokunyanga ngamacala amabini asondele kwi-1, ebonisa ukuba iyonke, i-BMD ye-hip iyonke kunye nemimandla yomqolo iyonke ye-12 -ixesha lexesha lenyanga lalizinzile kulo lonke ixesha lonyango.

Iziphumo ekukhuleni

I-corticosteroids ekhutshwe ngomlomo inokubangela ukunciphisa ukukhula kwesantya xa kulawulwa kwizigulana zabantwana. Ukujonga ukukhula kwezigulana zabantwana ezifumana i-budesonide kunye ne-formoterol fumarate dihydrate rhoqo (umzekelo, nge-stadiometry). Ukunciphisa iziphumo zenkqubo ye-corticosteroids yomlomo, kubandakanya i-budesonide kunye ne-formoterol fumarate dihydrate, titrate idosi yesigulana ngasinye ukuya kumlinganiselo ophantsi olawula ngempumelelo iimpawu zakhe[Bona Isisombululo kunye noLawulo (2.2) kwaye Sebenzisa kubantu abathile (8.4) ].

I-Glaucoma kunye neCataract

I-Glaucoma, ukunyuka koxinzelelo lwe-intraocular, kunye ne-cataract kuye kwaxelwa kwizigulana ezinesifuba kunye ne-COPD kulandela ukulawulwa kwexesha elide kwe-corticosteroids, kunye ne-budesonide, icandelo le-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL. Ke ngoko, ukubek'esweni ngokusondeleyo kufanelekile kwizigulana ezinotshintsho kumbono okanye ngembali yokunyuka koxinzelelo lwe-intraocular, glaucoma, kunye / okanye i-cataract.

Iziphumo zonyango kunye ne-budesonide kunye ne-formoterol fumarate dihydrate i-160 / 4.5, i-budesonide kunye ne-formoterol fumarate dihydrate 80 / 4.5, i-formoterol i-4.5 mcg, okanye i-placebo kuphuhliso lwe-cataract okanye i-glaucoma yavavanywa kwiseti yezigulana ezingama-461 ezine-COPD kwimiphunga yeenyanga ezili-12. Umsebenzi wokufunda. Uviwo lwe-Ophthalmic lwenziwa kwisiseko, iiveki ezingama-24 kunye neeveki ezingama-52. Kwakukho izifundo ze-26 (i-6%) ngokunyuka kwamanqaku angaphantsi kwe-subcapsular ukusuka kwisiseko ukuya kwixabiso eliphezulu (> 0.7) ngexesha lonyango olungenamsebenzi. Utshintsho kumanqaku angaphantsi kwe-subcapsular of> 0.7 ukusuka kwisiseko kunyango oluphezulu lwenzekile kwizigulana ze-11 (9.0%) kwi-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5 iqela, izigulana ezi-4 (3.8%) kwi-budesonide kunye ne-formoterol fumarate dihydrate 80 / 4.5 iqela Izigulana ezi-5 (4.2%) kwiqela le-formoterol, kunye nezigulane ezi-6 (5.2%) kwiqela le-placebo.

Iimeko ze-Eosinophilic kunye neChurg-Strauss Syndrome

Kwiimeko ezinqabileyo, abaguli abakwi-inhaled corticosteroids banokubonisa iimeko ze-systemic eosinophilic. Abanye babaguli baneempawu zeklinikhi ze-vasculitis ehambelana neChurg-Strauss syndrome, imeko ehlala inyangwa yinkqubo ye-corticosteroid yonyango. Ezi ziganeko zihlala zihlala, kodwa kungekho rhoqo, zidibene nokunciphisa kunye / okanye ukurhoxiswa kwonyango lomlomo we-corticosteroid emva kokungeniswa kwe-corticosteroids enganyangekiyo. Oogqirha kufuneka bazilumkele i-eosinophilia, i-vasculitic rash, ukwanda kweempawu zamapulmoni, iingxaki zentliziyo, kunye / okanye i-neuropathy ebonisa kwizigulana zabo. Ubudlelwane obusisiseko phakathi kwe-budesonide kunye nezi meko zisezantsi azimiselwanga.

Imiqathango yokuHlala

I-Budesonide kunye ne-formoterol fumarate dihydrate, njengawo onke amayeza anee-sympathomimetic amines, kufuneka zisetyenziswe ngononophelo kwizigulana ezinengxaki yokuxhuzula okanye i-thyrotoxicosis nakwabo baphendula ngokungaqhelekanga kwii-amine zovelwano. Imilinganiselo ye-beta ehambelana nayo2-adrenoceptor agonist albuterol, xa ilawulwa ngaphakathi, kuye kwaxelwa ukuba mandundu wesifo seswekile kunye ne ketoacidosis.

IHypokalemia kunye neHyperglycemia

I-Beta-adrenergic agonist amayeza anokuvelisa i-hypokalemia ebalulekileyo kwezinye izigulana, ngokunokwenzeka ngokunyanzelwa kwe-intracellular shunting, enakho ukuvelisa iziphumo ezibi zentliziyo[Bona Ikhemesti yezonyango (12.2) ].Ukwehla kwe-potassium ye-serum kuhlala kudlulile, kungafuneki ukuba kongezwe. Utshintsho olubonakalayo lwezonyango kwiglucose yegazi kunye / okanye i-potassium ye-serum yabonwa rhoqo ngexesha lezifundo zeklinikhi kunye ne-budesonide kunye ne-formoterol fumarate dihydrate kwiidosi ezinconyelwayo.

Iziphumo ezingalunganga

Ukusetyenziswa kweLABA kunokubangela oku kulandelayo:

Iziganeko ezinxulumene nesifuba-esibhedlele, izibhedlele, ukufa[Bona Izilumkiso kunye nokuLumkisa (5.1) ].
Iziphumo zentliziyo kunye ne-central system[Bona Izilumkiso kunye noKhuseleko (5.12) ].

Inkqubo ye-corticosteroid yenkqubo kunye ne-inhaled inokubangela oku kulandelayo:

UCandidaalbicansusulelo[Bona Izilumkiso kunye nokuQapha (5.4) ]
I-pneumonia okanye izifo ezisezantsi zokuphefumla kwizigulana ezine-COPD[Bona Izilumkiso kunye nokuQapha (5.5) ]
Uxinzelelo lwe-Immunosuppression[Bona Izilumkiso kunye nokuQapha (5.6) ]
Hypercorticism kunye noxinzelelo lwe-adrenal[Bona Izilumkiso kunye noKhuseleko (5.8) ]
Iziphumo zokukhula kwizigulana zabantwana[Bona Izilumkiso kunye noKhuseleko (5.14) ]
I-Glaucoma kunye ne-cataract[Bona Izilumkiso kunye noKhuseleko (5.15) ]

Kuba ulingo lweklinikhi luqhutywa phantsi kweemeko ezahluka-hlukeneyo, amaqondo okusabela okungalunganga aqwalaselweyo kuvavanyo lweklinikhi yeyeza alinakuthelekiswa ngokuthe ngqo namaxabiso kuvavanyo lweklinikhi lelinye ichiza kwaye ayinakho ukubonakalisa amaxabiso abonwe ngokwenza.

Amava ovavanyo lweKlinikhi kwi-Asthma

Abantu abadala kunye nabagulayo abakwishumi elivisayo iminyaka eli-12 yobudala nangaphezulu

Idatha yokhuseleko ngokubanzi kubantu abadala nakwishumi elivisayo isekwe kwiimvavanyo zeklinikhi ezilawulwa ngokukuko kunye ne-placebo apho izigulana ezingama-3393 ezineminyaka eli-12 nangaphezulu (ama-2052 abantu ababhinqileyo kunye nabesilisa abayi-1341) abanesifo sombefu sobukrakra obahlukeneyo baphathwa nge-budesonide kunye ne-formoterol fumarate dihydrate 80 /4.5 okanye i-160 / 4.5 ithathe i-inhalation ezi-2 kanye okanye kabini imihla ngemihla iiveki ezili-12 ukuya kwezi-52. Kwezi zilingo, abaguli abakwi-budesonide kunye ne-formoterol fumarate dihydrate babeneminyaka yobudala engama-38 kwaye uninzi lwabo lwaluseCaucasian (82%).

Izehlo zeziganeko ezichaseneyo eziqhelekileyo kwiTheyibhile 2 engezantsi isekwe kwidatha edityanisiweyo evela kwi-12 yeveki, i-blind-blind, i-placebo-elawulwa kwizifundo zeklinikhi apho izigulana ezingama-401 zabantu abadala kunye nabakwishumi elivisayo (abesilisa abali-148 nabasetyhini abangama-253) iminyaka eyi-12 nangaphezulu inyangwe nge-2 inhalations ye-budesonide kunye ne-formoterol fumarate dihydrate 80 / 4.5 okanye i-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5 kabini yonke imihla. Iqela le-budesonide kunye ne-formoterol fumarate dihydrate liqulunqwe ikakhulu zizigulana zaseCaucasian (84%) ezineminyaka yobudala engama-38, kwaye iipesenti zithetha kwangaphambili nge-FEV1kwisiseko se-76 kunye ne-68 sama-80 / 4.5 mcg kunye namaqela onyango angama-160 / 4.5 mcg, ngokwahlukeneyo. Ulawulo lweengalo zokuthelekisa zibandakanya i-2 inhalations ye-budesonide HFA yedosi ye-inhaler (MDI) 80 okanye i-160 mcg, i-formoterol eyomileyo ye-inhaler (DPI) i-4.5 mcg, okanye i-placebo (MDI kunye ne-DPI) kabini yonke imihla. Itheyibhile 2 ibandakanya zonke iziganeko ezibi ezenzekileyo kwisehlo se>I-3% kuyo nayiphi na enye i-budesonide kunye ne-formoterol fumarate dihydrate group kwaye ixhaphake kakhulu kuneqela le-placebo elinedosi ephindwe kabini-yemihla ngemihla. Ekuqwalaseleni ezi datha, ukwanda kwexesha lokuvezwa kwesigulana kwi-budesonide kunye ne-formoterol fumarate dihydrate yezigulana kufuneka zithathelwe ingqalelo, njengoko iimeko zingalungelelaniswanga kukungalingani kwexesha lokunyanga.

Itheyibhile 2Ukuvela okungalunganga okwenzeka kwimeko ye-% 3% kwaye ixhaphake kakhulu kune-placebo kumaqela eBudesonide naseFomoterolum Fumarate Dihydrate amaqela: idatha edityanisiweyo evela kwiiveki ezintathu ze-12, iimfama ezimbini, iimfama ezilawulwa yi-placebo ezilawulwa zizifo ze-asthma kwizigulana ezineminyaka eyi-12 nangaphezulu
Unyango * IBudesonide kunye neFomoterol Fumarate Dihydrate IBudesonide Ifomoterolol Iplacebo
Isiganeko esibi 80 / 4.5
N = 277
%
160 / 4.5
N = 124
%
80 mcg
N = 121
%
160 mcg
N = 109
%
4.5 mcg
N = 237
%
N = 400
%
*
Zonke iindlela zonyango zenziwa njenge-2 inhalations kabini yonke imihla.

Nasopharyngitis

10.5

9.7

14.0

11.0

10.1

9.0

Intloko ebuhlungu

6.5

11.3

11.6

12.8

8.9

6.5

Usulelo oluphezulu lokuphefumula

7.6

10.5

8.3

9.2

7.6

7.8

Intlungu ye-Pharyngolaryngeal

6.1

8.9

5.0

7.3

3.0

4.8

Isinusitis

5.8

4.8

5.8

2.8

6.3

4.8

Umkhuhlane

3.2

2.4

6.6

0.9

3.0

1.3

Umqolo obuhlungu

3.2

1.6

2.5

5.5

2.1

0.8

Ukuxinana kwempumlo

2.5

3.2

2.5

3.7

1.3

1.0

Ukuphazamiseka esiswini

1.1

6.5

2.5

4.6

1.3

1.8

Ukuhlanza

1.4

3.2

0.8

2.8

1.7

1.0

I-Candidiasis yomlomo

1.4

3.2

0

0

0

0.8

Umndilili weXesha lokuBonakalisa (iintsuku)

77.7

73.8

77.0

71.4

62.4

55.9

Ukhuseleko lwexesha elide-uvavanyo lwe-asthma lwezonyango kwizigulana ezineminyaka eli-12 nangaphezulu

Izifundo zokhuselo lwexesha elide kwizigulana ezikwishumi elivisayo kunye nabantu abadala abaneminyaka eyi-12 ubudala nangaphezulu, baphathwa ukuya kuthi ga kunyaka omnye kwiidosi ukuya kuthi ga kwi-1280/36 mcg / ngosuku (640/18 mcg kabini yonke imihla), abonakalisanga lutshintsho lubalulekileyo lwezonyango kwimeko okanye iintlobo ezintsha zeziganeko ezichasayo ezivela emva kwexesha elide lonyango. Kwangokunjalo, akukho phatheni ibalulekileyo okanye engalindelekanga yokungaqhelekanga eye yaqwalaselwa ukuya kuthi ga kunyaka we-1 kumanyathelo okhuseleko kubandakanya i-chemistry, ihemmatology, i-ECG, iliso leHolter, kunye novavanyo lwe-HPA-axis.

Izigulana zabantwana 6 ukuya kuthi ga ngaphantsi kweminyaka eyi-12 yobudala

Idatha yokhuseleko kwizigulana zabantwana abaneminyaka eyi-6 ukuya kuthi ga ngaphantsi kweminyaka eyi-12 isekwe kwilingo le-1 leeveki ezili-12 zonyango. Izigulana (i-79 yabasetyhini kunye ne-105 yamadoda) abafumana i-inhalled corticosteroid ekungeneni kwetyala babengenangqondo kwi-budesonide kunye ne-formoterol fumarate dihydrate 80 / 4.5 (n = 92) okanye i-budesonide pMDI 80 mcg (n = 92), 2 inhalations kabini yonke imihla. Iprofayile yokhuselo ngokubanzi yezi zigulana yayifana naleyo yaqwalaselwa kwizigulana ezineminyaka eli-12 ubudala nangaphezulu abafumana i-budesonide kunye ne-formoterol fumarate dihydrate 80 / 4.5 kabini yonke imihla kwizifundo zoyilo olufanayo. Iziphumo eziqhelekileyo ezichaseneyo ezenzeke kwizigulana ezanyangwa nge-budesonide kunye ne-formoterol fumarate dihydrate 80 / 4.5 ene-frequency ye-≧ 3% kwaye rhoqo rhoqo kunabaguli abaphathwa kuphela nge-budesonide pMDI 80 mcg ibandakanya usulelo lwephepha lokuphefumla eliphezulu, i-pharyngitis, intloko ebuhlungu kunye ne-rhinitis.

Amava ovavanyo lweklinikhi kwizifo ezingapheliyo zokuthintela isifo sePulmonary

Idatha yokhuseleko echazwe apha ngezantsi ibonisa ukubonakaliswa kwe-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5 kwizigulana ze-1783. I-Budesonide kunye ne-formoterol fumarate dihydrate i-160 / 4.5 yafundwa kwizifundo zomsebenzi wemiphunga ezilawulwa yi-placebo (iinyanga ezi-6 ne-12 ubude), kunye nezifundo ezibini ezilawulwa ngokukuko (6 kunye neenyanga ezili-12 ubude) kwizigulana ezine-COPD.

Izehlo zeziganeko ezichaseneyo eziqhelekileyo kwiTheyibhile 3 engezantsi isekwe kwidatha edityanisiweyo evela kwizifundo ezibini ezingaboniyo, ezilawulwa yi-placebo ezilawulwa yimiphunga (6 kunye neenyanga ezili-12 ubude) apho izigulana ezingama-771 zabantu abadala zeCOPD (abesilisa abangama-496 nabasetyhini abangama-275) 40 Iminyaka yobudala nangaphezulu yanyangwa nge-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5, inhalation ezimbini kabini yonke imihla. Kwezi zigulana ezingama-651 zanyangwa iinyanga ezi-6 zaze ezingama-366 zanyangwa iinyanga ezili-12. I-budesonide kunye ne-formoterol fumarate dihydrate yeqela lalinabantu abaninzi baseCaucasian (93%) abaguli abaneminyaka yobudala engama-63, kunye neepesenti ezichaziweyo ezixela kwangaphambili nge-FEV1kwisiseko se-33%. Ulawulo lweengalo zokuthelekisa zibandakanya i-2 inhalations ye-budesonide HFA (MDI) 160 mcg, formoterol (DPI) 4.5 mcg okanye placebo (MDI kunye ne-DPI) kabini yonke imihla. Itheyibhile 3 ibandakanya zonke iziganeko ezichaseneyo ezenzeke kwizehlo ze-% 3% kwi-budesonide kunye ne-formoterol fumarate dihydrate group kwaye ngakumbi kuneqela le-placebo. Ekuqwalaseleni le datha, ukwanda kwexesha lokuvezwa kwesigulana kwi-budesonide kunye ne-formoterol fumarate dihydrate kufuneka ithathelwe ingqalelo, njengoko iimeko zingalungelelaniswanga kukungalingani kwexesha lokunyanga.

Itheyibhile 3Ukuvela okungalunganga okwenzeka kwimeko ye ≧ 3% kwaye ixhaphake kakhulu kune-placebo kwiqela leBudesonide kunye neFomoterolol Fumarate Dihydrate iqela: idatha edityanisiweyo evela kwizilingo ezimbini ze-COPD ezilawulwa ziimfama
*
Zonke iindlela zonyango zenziwa njenge-2 inhalations kabini yonke imihla.

Unyango *

IBudesonide kunye neFomoterol Fumarate Dihydrate

IBudesonide

Ifomoterolol

Iplacebo

Isiganeko esibi

160 / 4.5

N = 771

%

160 mcg

N = 275

%

4.5 mcg

N = 779

%

N = 781

%

Nasopharyngitis

7.3

3.3

5.8

4.9

I-candidiasis yomlomo

6.0

4.4

1.2

1.8

IBronchitis

5.4

4.7

4.5

3.5

Isinusitis

3.5

1.5

3.1

1.8

Ukusuleleka kwintsholongwane yentsholongwane

3.5

1.8

3.6

2.7

Umndilili weXesha lokuBonakalisa (iintsuku)

255.2

157.1

240.3

223.7

Usulelo lwemiphunga ngaphandle kwenyumoniya (ubukhulu becala i-bronchitis) lwenzeke kwipesenti enkulu yezifundo ezanyangwa nge-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5 xa kuthelekiswa ne-placebo (7.9% vs. 5.1% ngokwahlukeneyo). Kwakungekho iipateni zibalulekileyo zeklinikhi okanye ezingalindelekanga zokuchaphazeleka okuqwalaselweyo ukuya kuthi ga kunyaka we-1 kwikhemistri, ihematology, i-ECG, i-ECG (iHolter) yokujonga, i-HPA-axis, uxinano lweemaminerali zamathambo kunye novavanyo lwe-ophthalmology.

Iziphumo zokhuselo ezivela kwizifundo ezibini ezingaboniyo, ezilawulwa ngokukuko (6 kunye neenyanga ezili-12 ubude) apho izigulana ezili-1012 zabantu abadala ze-COPD (abesilisa abangama-616 nabasetyhini abangama-396) abaneminyaka engama-40 ubudala nangaphezulu baphathwa nge-budesonide kunye ne-formoterol fumarate dihydrate I-160 / 4.5, i-inhalation ezimbini eziphindwe kabini imihla ngemihla zazingqinelana nezifundo zomsebenzi wemiphunga.

Amava entengiso

Iziphumo ezichaseneyo zilandelayo zichongiwe ngexesha lokuvunywa kokusetyenziswa kwe-budesonide kunye ne-formoterol fumarate dihydrate. Ngenxa yokuba ezi mpendulo zichazwa ngokuzithandela ukusuka kubungakanani besayizi engaqinisekanga, akusoloko kunokwenzeka ukuba uqikelele ngokuthembekileyo ukuhamba kwabo rhoqo okanye ukuseka ubudlelwane obunobangela wokuvezwa kweziyobisi. Ezinye zeempendulo ezigwenxa zisenokuba ziye zabonwa kwizifundo zeklinikhi kunye ne-budesonide kunye ne-formoterol fumarate dihydrate.

Ukuphazamiseka kwentliziyo:i-angina pectoris, i-tachycardia, i-atrial kunye ne-ventricular tachyarrhythmias, i-atrial fibrillation, i-extrasystoles, i-palpitations

Iingxaki ze-Endocrine:I-hypercorticism, ukukhula kwe-velocity ukunciphisa kwizigulana zabantwana

Ukuphazamiseka kwamehlo:cataract, glaucoma, ukunyuka koxinzelelo lwe-intraocular

Iingxaki zesisu:i-oropharyngeal candidiasis, isicaphucaphu

Ukuphazamiseka kwenkqubo yomzimba:Ukuphendula ngokukhawuleza kunye nokulibaziseka kwe-hypersensitivity, njengempendulo ye-anaphylactic, angioedema, bronchospasm, urticaria, exanthema, dermatitis, pruritus

Ukuphazamiseka kwemetabolism kunye nesondlo:hyperglycemia, hypokalemia

Imisipha, izihlunu ezihlangeneyo, kunye nokuphazamiseka kwethambo:izihlunu zemithambo

Ukuphazamiseka kwenkqubo:ukungcangcazela, isiyezi

Ukuphazamiseka kwengqondo:Ukuphazamiseka kwindlela yokuziphatha, ukuphazamiseka kokulala, uvalo, ukuphazamiseka, uxinzelelo, ukungazinzi

Ukuphefumla, isifo se-thoracic, kunye nokuphazamiseka kwangaphakathi:i-dysphonia, ukukhwehlela, ukucaphuka komqala

Ulusu kunye nokuphazamiseka kwezicubu ezincinci:ukutyumka ulusu

Ukuphazamiseka kwemithambo:hypotension, uxinzelelo lwegazi

Ukusebenzisana kweziyobisi

Kwizifundo zeklinikhi, ukulawulwa ngokufanayo kwe-budesonide kunye ne-formoterol fumarate dihydrate kunye nezinye iziyobisi, ezinje nge-beta emfutshane esebenza2-i -agonists, i-intranasal corticosteroids, kunye ne-antihistamines / i-decongestants khange ibangele ukonyuka kwamaxesha okusabela okungalunganga. Akukho zifundo zokunxibelelana ngokusesikweni neziyobisi ezenziweyo nge-budesonide kunye nefomoterol fumarate dihydrate.

Inhibitors yeCytochrome P4503A4

Eyona ndlela iphambili yemetabolism ye-corticosteroids, kubandakanya i-budesonide, icandelo le-budesonide kunye ne-formoterol fumarate dihydrate, ihamba nge-cytochrome P450 (CYP) isoenzyme 3A4 (CYP3A4). Emva kolawulo lomlomo lwe-ketoconazole, inhibitor eyomeleleyo ye-CYP3A4, kuthetha ukuba uxinzelelo lweplasma lwe-budesonide elawulwa ngomlomo inyuke. Ulawulo oluhambelanayo lwe-CYP3A4 lunokuthintela imetabolism, kunye nokwandisa ukubonakaliswa kwenkqubo, kwi-budesonide. Isilumkiso kufuneka sisetyenziswe xa kuthathelwa ingqalelo ulawulo lwe-budesonide kunye ne-formoterol fumarate dihydrate ene-ketoconazole yexesha elide kunye nezinye i-CYP3A4 inhibitors ezomeleleyo (umz.[Bona Izilumkiso kunye nokuQapha (5.9) ].

I-Monoamine Oxidase Inhibitors kunye neTricyclic Antidepressants

I-Budesonide kunye ne-formoterol fumarate dihydrate kufuneka zenziwe ngononophelo kwizigulana ezinyangwa nge-monoamine oxidase inhibitors okanye i-tricyclic antidepressants, okanye kwiiveki ezi-2 zokuyekiswa kwezi arhente, kuba isenzo se-formoterol, icandelo le-budesonide kunye ne-formoterol fumarate dihydrate, kwi-vascular Inkqubo inokubakho kwezi arhente. Kwezilingo zeklinikhi kunye ne-budesonide kunye ne-formoterol fumarate dihydrate, inani eliqingqiweyo le-COPD kunye nezigulana zesifuba zifumene i-tricyclic antidepressants, kwaye, ke ngoko, akukho zigqibo zibalulekileyo zeklinikhi ezinokwenziwa.

I-Beta-Adrenergic Receptor yokuVimba iiarhente

I-Beta-blockers (kubandakanya i-eye eye) ayinako kuphela ukubamba isiphumo se-beta-agonists, njenge-formoterol, icandelo le-budesonide kunye ne-formoterol fumarate dihydrate, kodwa inokuvelisa i-bronchospasm eqatha kwizigulana ezinesifuba. Ke ngoko, izigulana ezinesifuba akufuneki ziphathwe nge-beta-blockers. Nangona kunjalo, phantsi kweemeko ezithile, akunakubakho ezinye iindlela ezamkelekileyo zokusetyenziswa kwe-beta-adrenergic blocking agents kwizigulana ezinesifuba. Kule meko, i-beta-blockers ye-cardioselective inokuqwalaselwa, nangona kufuneka ilawulwe ngononophelo.

Womchamo

Utshintsho lwe-ECG kunye / okanye i-hypokalemia enokuthi ibangelwe kukulawulwa kwe-non-potassium-sparing diuretics (enje nge-loop okanye i-thiazide diuretics) inokuba mandundu ngakumbi yi-beta-agonists, ngakumbi xa idosi ekhuthazwayo ye-beta-agonist idlulisiwe. Nangona ukubaluleka kweklinikhi kwezi ziphumo kungaziwa, isilumkiso siyacetyiswa kulawulo lwe-budesonide kunye ne-formoterol fumarate dihydrate kunye ne-non-potassium-sparing diuretics.

UKUSETYENZISWA KWABANTU ABAKHETHEKILEYO

Ukukhulelwa

Isishwankathelo somngcipheko

Akukho zifundo zaneleyo nezilawulwa kakuhle ze-budesonide kunye ne-formoterol fumarate dihydrate okanye elinye lezinto zalo, i-formoterol fumarate, kubafazi abakhulelweyo; nangona kunjalo izifundo ziyafumaneka kwelinye icandelo le-budesonide. Kwizifundo zokuvelisa izilwanyana, i-budesonide kunye ne-formoterol fumarate dihydrate, elawulwa yindlela yokuphefumla, yayiyi-teratogenic, i-embryocidal, kunye nokuncipha kobunzima bomntwana kwiigundane ezingaphantsi kwesona sininzi sokucetyiswa kwansuku zonke somntu (MRHDID) kwi-mcg / m2isiseko. I-Budesonide iyodwa, ilawulwa yindlela engaphantsi, yayiyi-teratogenic, i-embryocidal, kunye nokunciphisa ubunzima bomntwana kwiigundane kunye nemivundla engaphantsi kwe-MRHDID, kodwa ezi ziphumo azibonwanga kwiigundane ezazifumana iidosi ezi-inhaled ukuya kuthi ga kumaxesha e-4 i-MRHDID. Izifundo ezenziwa ngabasetyhini abakhulelweyo azibonisanga ukuba i-inhaled budesonide iyodwa inyusa umngcipheko wokungaqhelekanga xa kulawulwa ngexesha lokukhulelwa. Amava nge-corticosteroids yomlomo iphakamisa ukuba iintonga zithambekele ngakumbi kwiziphumo ze-teratogenic ezivela kukuvezwa kwe-corticosteroid kunabantu. IFomoterolol fumarate iyodwa, ilawulwa yindlela yomlomo, yayine-teratogenic kwiigundane kunye nemivundla kwi-1600 kunye nama-65,000 amaxesha e-MRHDID, ngokwahlukeneyo. IFomoterol fumarate nayo yayiyimbumba, ukonyuka kokuphulukana nokuzalwa komntwana ngexesha lokuzalwa nangexesha lokuncancisa, kunye nokwehla kobunzima bomntwana kwiigundane amaxesha ali-110 kwi-MRHDID. Ezi ziphumo zibi ngokubanzi zenzeka ngokuphindaphindiweyo kwi-MRHDID xa i-formoterol fumarate yayilawulwa yindlela yomlomo yokufumana ukubonakaliswa okuphezulu kwenkqubo. Akukho teratogenic, embryocidal, okanye iziphumo zophuhliso eziye zabonwa kwiigundane ezifumene iidosi ze-inhalation ukuya kuthi ga kuma-375 amaxesha e-MRHDID.

Umngcipheko oqikelelweyo wangemva kweziphene zokuzalwa kunye nokuphuphuma kwesisu sabantu ababonisiweyo asaziwa. Kubantu base-US ngokubanzi, umngcipheko wokuqikelelwa kwemvelaphi yeziphene zokuzalwa kunye nokuphuphuma kwesisu kukhulelwa okwamkelweyo kwezonyango yi-2% ukuya kwi-4% kunye ne-15% ukuya kuma-20% ngokwahlukeneyo.

Ukuqwalaselwa kweKlinikhi

Umama okhulelweyo onesifo kunye / okanye umbungu / umngcipheko womntwana

Kwabasetyhini abanesifo sombefu esingalawulekiyo okanye esilawulwa ngokuphakathi, kukho umngcipheko okhulayo weziphumo ezibi zangaphambi kokubeleka ezinje nge-preeclampsia kunina kunye nokukhula kwangaphambili, ubunzima bokuzalwa okuphantsi, kunye nokuncinci kwiminyaka yobudala bokukhulelwa. Abafazi abakhulelweyo abanesifuba kufuneka babekwe esweni kwaye amayeza ahlengahlengiswe njengoko kufuneka ukugcina ulawulo lwesifuba.

Umsebenzi okanye ukuhanjiswa

Akukho zifundo zoluntu zilawulwa kakuhle eziphande ngeziphumo ze-budesonide kunye ne-formoterol fumarate dihydrate ngexesha lomsebenzi kunye nokuhanjiswa. Ngenxa yokuphazamiseka kwe-beta-agonist kukuthintelwa kwesibeleko, ukusetyenziswa kwe-budesonide kunye ne-formoterol fumarate dihydrate ngexesha lomsebenzi kufuneka kuthintelwe kwabo baguli apho izibonelelo ngokucacileyo zingaphezulu komngcipheko.

Idatha

Idatha yaBantu

Izifundo zabasetyhini abakhulelweyo azibonisanga ukuba i-inhaled budesonide inyusa umngcipheko wokungaqhelekanga xa kulawulwa ngexesha lokukhulelwa. Iziphumo ezivela kubuninzi babahlali be-cohort epidemiological isifundo esihlaziya idatha evela kubhaliso abathathu baseSweden abagubungela malunga ne-99% yokukhulelwa ukusuka kwi-1995-1997 (okt, iRegistry yokuzalwa kweZonyango yaseSweden; iRegistry ye-Congenital Malformations; iRegistry Cardiology Registry) ayibonisi mngcipheko ukhulayo yokukhubazeka kokuzalwa ngokusetyenziswa kwe-inhaled budesonide ngexesha lokukhulelwa kwasekuqaleni. Ukukhubazeka okuzelweyo kwafundwa ngo-2014 kwiintsana ezizalwe ngoomama bexela ukusetyenziswa kwe-inhalled budesonide yesifo sombefu ekukhulelweni kwasekuqaleni (ngesiqhelo iiveki ezingama-10-12 emva kwexesha lokugqibela lokuya exesheni), ixesha apho uninzi lwezinto ezingalunganga zisenzeka. Izinga lokungazaliseki kokuzalwa okungafaniyo lalifana ngokuthelekiswa nenqanaba labemi ngokubanzi (3.8% vs. 3.5% ngokwahlukeneyo). Ukongeza, emva kokubhencwa kwi-inhaled budesonide, inani leentsana ezizalwe zinamacwecwe orofacial lalifana nenani elilindelweyo kubemi abaqhelekileyo (abantwana aba-4 ngokuchasene ne-3.3, ngokwahlukeneyo).

Ezi datha zinye zisetyenzisiwe kwisifundo sesibini ukuzisa itotali kwiintsana ezingama-2534 ezinoomama ababonakaliswe kwi-inhaled budesonide. Kolu phononongo, inqanaba lokungazalwa ngokuzalwa phakathi kweentsana ezinoomama abachaphazeleke kwi-inhaled budesonide ngexesha lokukhulelwa kwasekuqaleni kwakungahlukanga kwinqanaba labo bonke abantwana abasandul 'ukuzalwa ngexesha elifanayo (3.6%).

Idatha yezilwanyana

IBudesonide kunye neFomoterol Fumarate Dihydrate

Kwisifundo sokukhula komntwana esibelekweni kwiigundane ezikhulelweyo ezichongiweyo ngexesha le-organogenesis ukusuka kwiintsuku zokumitha nge-6-16, i-budesonide kunye ne-formoterol fumarate dihydrate evelise i-hernia ye-umbilical kwi-fetus kwiidosi ezingaphantsi kwe-MRHDID (kwi-mcg / m2Isiseko kwiidosi zoomama abakhulelweyo ze-12 / 0.66 mcg / kg / ngosuku nangaphezulu). Ubunzima bomntwana obuseluswini bancitshiswa malunga namaxesha ama-5 kunye nama-3 e-MRHDID, ngokwahlukeneyo (kwisiseko se-AUC kwidosi yoomama ye-80 / 4.4 mcg / kg (budesonide / formoterol)). Akukho ziphumo ze-teratogenic okanye ze-embryocidal zafunyanwa kwiidosi ezingaphantsi kwe-MRHDID (kwi-mcg / m2isiseko kwidosi yoomama ebhalwe ngaphakathi ye-2.5 / 0.14 mcg / kg / ngosuku).

IBudesonide

Kwisifundo sokuchuma kunye nokuzala kwakhona, iigundane ezingamadoda zazifakwe kwi-9 yeeveki kunye nabasetyhini kwiiveki ezi-2 ngaphambi kokubhangiswa kunye nangalo lonke ixesha lokudibana. Abafazi babedosiwe kude kulunyulwe inzala yabo. I-Budesonide ibangele ukwehla kokusebenza kokubeleka kokubeleka kunye nokusebenza kwentsana ngexesha lokuzalwa nangexesha lokuncancisa, kunye nokwehla kokufumana ubunzima bomzimba koomama, kwiidosi ezingaphantsi kwe-MRHDID (kwi-mcg / m2Isiseko kumayeza angaphantsi koomama angama-20 mcg / kg / ngosuku nangaphezulu). Akukho ziphumo ziye zaqwalaselwa kwidosi engaphantsi kwe-MRHDID (kwi-mcg / m2ngesiseko kwidosi engaphantsi koomama ye-5 mcg / kg / ngosuku).

Kwisifundo sophuhliso lwembungu esibelekweni kwimivundla ekhulelweyo efakwe ngexesha le-organogenesis ukusuka kwiintsuku zokumitha nge-6-18, i-budesonide ivelise ukulahleka komntwana, ukunciphisa ubunzima bomntwana, kunye nokungaqhelekanga kwamathambo kwiidosi ezingaphantsi kwe-MRHDID (kwi-mcg / m2ngesiseko kwidosi engaphantsi koomama ye-25 mcg / kg / ngosuku). Kwisifundo sokukhula komntwana esibelekweni kwiigundane ezikhulelweyo ezichongiweyo ngexesha le-organogenesis ukusuka kwiintsuku zokumitha nge-6 ukuya kwi-15, i-budesonide ivelise iimpembelelo ezifanayo zomntwana kumthamo malunga namaxesha asibhozo i-MRHDID (kwi-mcg / m2ngesiseko kwidosi engaphantsi koomama engaphantsi kwama-500 mcg / kg / ngosuku). Kwesinye isifundo sokukhula kombungu esibelekweni kwiigundane ezikhulelweyo, akukho ziphumo ze-teratogenic okanye ze-embryocidal zabonwa ngeedosi ukuya kuthi ga kumaxesha ama-4 e-MRHDID (kwi-mcg / m2ngesiseko kumthamo we-inhalation womama ukuya kuthi ga kwi-250 mcg / kg / ngosuku).

Kwisifundo sophuhliso lwasemva kwexesha kunye nasemva kokubeleka, iigundane ezikhutshiwe ukusuka kumhla wokukhulelwa we-15 ukuya kusuku lwasemva kokubeleka lwe-21, i-budesonide ayinampembelelo kuhambiso, kodwa ibinempembelelo ekukhuleni nasekuphuhlisweni kwembewu. Ukusinda kwenzalo kuncitshisiwe kwaye ukusinda kwenzalo kunciphisile ubunzima bomzimba ekuzalweni kwaye ngexesha lokuncancisa ngeedosi ezingaphantsi kwe-MRHDID nangaphezulu (kwi-mcg / m2Isiseko kumayeza angaphantsi koomama angama-20 mcg / kg / ngosuku nangaphezulu). Ezi zinto zifunyanisiweyo zenzeka kubukho botyhefu boomama.

Ifomoterolol

Kwisifundo sokuzala kunye nokuzala, iigundane ezingamadoda zachithwa ngomlomo iiveki ezili-9 kunye nabasetyhini kwiiveki ezi-2 ngaphambi kokubhangiswa kunye nexesha lokukhwelana. Abafazi babedosiwe ukuya kuthi ga kumhla wokukhulelwa kwe-19 okanye ukuya kuthi ga ekulunyulweni kwabantwana babo. Amadoda ayedanjiswa ukuya kuthi ga kwiiveki ezingama-25. I-hernia ye-umbilical yaqwalaselwa kwi-rat fetus kwiidosi zomlomo ngamaxesha angama-1600 nangaphezulu kune-MRHDID (kwi-mcg / m2ngesiseko kumthamo womlomo woomama we-3000 mcg / kg / ngosuku nangaphezulu). I-Brachygnathia yaqwalaselwa kwimveku engekazalwa kwidosi ngamaxesha angama-8000 i-MRHDID (kwi-mcg / m2ngesiseko kwidosi yomlomo yomama ye-15,000 mcg / kg / ngosuku). Ukukhulelwa kwandisiwe kwidosi eyi-8000 yamaxesha e-MRHDID (kwi-mcg / m2ngesiseko kwidosi yomlomo yomama ye-15,000 mcg / kg / ngosuku). Ukufa komntwana okhulayo kunye nokufa komntwana kwenzeka ngeedosi malunga namaxesha angama-1600 i-MRHDID nangaphezulu (kwi-mcg / m2ngesiseko kumthamo womlomo we-3000 mcg / kg / ngosuku nangaphezulu) ngexesha lokukhulelwa.

Kwisifundo sokukhula komntwana esibelekweni kwiigundane ezikhulelweyo ezichongiweyo ngexesha le-organogenesis ukusuka kwiintsuku zokumitha nge-6 ukuya kwe-15, akukho teratogenic, embryocidal okanye iziphumo zophuhliso zabonwa ngeedosi ukuya kuthi ga kuma-375 amaxesha e-MRHDID (kwi-mcg / m2Isiseko sedosi yokuhogelana koomama ukuya kuthi ga kwi-690 mcg / kg / ngosuku).

Kwisifundo sophuhliso lwembungu esibelekweni kwimivundla ekhulelweyo efakwe ngexesha le-organogenesis ukusuka kwiintsuku zokumitha nge-6-18, ii-cyst subcapsular cysts esibindini zabonwa kwimveku ngethamo lama-65,000 amaxesha e-MRHDID (kwi-mcg / m2ngesiseko sedosi yomlomo yomama ye-60,000 mcg / kg / ngosuku). Akukho ziphumo ze-teratogenic ziye zajongwa kwiidosi ukuya kuthi ga kuma-3800 amaxesha e-MRHDID (kwi-mcg / m2isiseko kumayeza omlomo womama ukuya kuthi ga kwi-3500 mcg / kg / ngosuku).

Kwisifundo sangaphambi nasemva kokuphuhliswa, iigundane zabasetyhini abakhulelweyo bafumana i-formoterol kumthamo womlomo we-0, 210, 840, kunye ne-3400 mcg / kg / ngosuku ukusukela kumhla wokumitha u-6 ukuya kwixesha lokuncancisa. Ukusinda kwabafundi kuncitshisiwe ukusuka ekuzalweni ukuya kusuku lwasemva kokubeleka 26 ngeedosi ezili-110 amaxesha e-MRHDID nangaphezulu (kwi-mcg / m2isiseko kumthamo womlomo woomama we-210 mcg / kg / ngosuku nangaphezulu), nangona kwakungekho bungqina bobudlelwane bempendulo yedosi. Kwakungekho ziphumo zinxulumene nonyango ekukhuleni komzimba, ukusebenza, kunye nokuziphatha kwamantshontsho.

Lactation

Isishwankathelo somngcipheko

Akukho datha ifumanekayo kwiziphumo ze-budesonide kunye ne-formoterol fumarate dihydrate, budesonide okanye formoterol fumarate kumntwana oncancisiweyo okanye kwimveliso yobisi. I-Budesonide, njengezinye i-corticosteroids ezi-inhaled, ikhoyo kubisi lomntu[bona idatha]. Akukho datha ifumanekayo kubukho be-formoterol fumarate kubisi lomntu. IFomoterolol fumarate ikho kubisi lwempuku[bona idatha]. Izibonelelo zophuhliso kunye nezempilo zokuncancisa kufuneka ziqwalaselwe kunye neemfuno zikamama zeklinikhi ze-budesonide kunye ne-formoterol fumarate dihydrate kunye naziphi na iziphumo ezinokubakho kusana olusancancisayo olusuka kwi-budesonide kunye ne-formoterol fumarate dihydrate okanye kwimeko engaphantsi yomama.

Idatha

Idatha yabantu ene-budesonide ehanjiswa nge-inhaler eyomileyo yomgubo ibonisa ukuba idosi yomlomo yemihla ngemihla ye-budesonide efumaneka kubisi lwebele elusaneni imalunga ne-0.3% ukuya kwi-1% yedosi ekhutshwe ngumama[Bona Ikhemesti yezonyango (12.3) ]. Kwi-budesonide kunye ne-formoterol fumarate dihydrate, idosi ye-budesonide efumaneka kusana kubisi lwebele, njengepesenti yedosi yoomama, kulindeleke ukuba ifane.

Kwisifundo sokuzala kunye nokuzala kwakhona kwiigundane, amanqanaba e-plasma ye-formoterol alinganiswa kumantshontsho ngosuku lwasemva kokubeleka lwe-15[Bona Sebenzisa kubantu abathile (8.1) ]. Kwaqikelelwa ukuba ubuninzi beplasma efunyanwa ngabantwana kwizilwanyana zoomama, kwelona thamo liphezulu le-15 mg / kg, emva kokonga kwaba yi-4.4% (0.24 nmol / L yenkunkuma vs 5.5 nmol / L kumama) .

Ukusetyenziswa kwabantwana

Ukhuseleko kunye nokusebenza kwe-budesonide kunye ne-formoterol fumarate dihydrate kwizigulana ze-asthma ezineminyaka eli-12 ubudala nangaphezulu sele zimiselwe kwizifundo ukuya kwiinyanga ezili-12. Kwezi veki zimbini zili-12, iimfama ezibini ezingaboniyo, ezilawulwa yi-placebo ezilawulwa yi-US kwizigulana ezingama-25 ukuya kwezili-17 ubudala ziye zaphathwa nge-budesonide kunye ne-formoterol fumarate dihydrate kabini yonke imihla[Bona Izifundo zeKlinikhi (14.1) ]. Iziphumo zokusebenza kweli qela leminyaka zazifana nezo zibonwe kwizigulana ezineminyaka eli-18 nangaphezulu. Kwakungekho mahluko ubonakalayo kuhlobo okanye ukuphindaphindeka kweziganeko ezimbi ezichazwe kweli qela leminyaka xa kuthelekiswa nezigulana ezineminyaka eli-18 ubudala nangaphezulu.

Ukhuseleko kunye nokusebenza kwe-budesonide kunye ne-formoterol fumarate dihydrate i-80 / 4.5 kwizigulana ze-asthma i-6 ukuya ngaphantsi kwe-12 yeminyaka ubudala sele zimiselwe kwizifundo ezinokufikelela kwiiveki ezili-12 [jonga Izifundo zeKlinikhi (14.1) ]. Iprofayile yokhuseleko kwezi zigulana ibingqinelana naleyo ibonwa kwizigulana ezineminyaka eli-12 ubudala nangaphezulu ezifumana i-budesonide kunye ne-formoterol fumarate dihydrate [jonga Iziphumo ezingalunganga (6.1) ].

Ukhuseleko kunye nokusebenza kwe-budesonide kunye ne-formoterol fumarate dihydrate kwizigulana ze-asthma ezingaphantsi kweminyaka emi-6 ubudala azikasekwa.

Izifundo zeklinikhi ezilawulwayo zibonise ukuba i-corticosteroids yomlomo e-inhaled kubandakanya i-budesonide, icandelo le-budesonide kunye ne-formoterol fumarate dihydrate, inokubangela ukunciphisa ukukhula kwesantya kwizigulana zabantwana. Esi siphumo siqwalaselwe ngokungabikho kobungqina belebhu yokucinezelwa kwe-HPA-axis, iphakamisa ukuba ukukhula kwesantya sisalathiso esibuthathaka senkqubo ye-corticosteroid yokuvezwa kwezigulana zabantwana kuneemvavanyo eziqhelekileyo ezisetyenziswayo zomsebenzi we-HPA-axis. Iziphumo zexesha elide zokuncitshiswa kwesantya sokukhula okunxulunyaniswa ne-corticosteroids yomlomo, kubandakanya nefuthe kubude bokugqibela abaziwa. Amandla okukhula okubambekayo kulandela ukuyeka unyango kunye ne-corticosteroids yomlomo engafundiswanga ngokwaneleyo.

Kuphononongo lwabantwana abanesifo sombeya abaneminyaka emi-5 ukuya kweli-12 ubudala, abo baphathwa nge-budesonide DPI 200 mcg kabini yonke imihla (n = 311) babenokwehla nge-1.1 isentimitha ekukhuleni xa kuthelekiswa nalabo bafumana i-placebo (n = 418) ekupheleni konyaka omnye ; Umahluko phakathi kwala maqela mabini onyango awuzange unyuke ngaphezulu kweminyaka emithathu yonyango olongezelelekileyo. Ukuphela kweminyaka emi-4, abantwana baphathwa nge-budesonide DPI kwaye abantwana baphathwa nge-placebo babenezantya ezifanayo zokukhula. Izigqibo ezithathwe kolu phononongo zinokudideka kukusetyenziswa ngokungalinganiyo kwe-corticosteroids kumaqela onyango kunye nokufakwa kwedatha kwizigulana ezifumana ukufikisa ngexesha lokufunda.

Ukukhula kwezigulana ezingabantwana abafumana i-corticosteroids yomlomo, kubandakanya i-budesonide kunye ne-formoterol fumarate dihydrate, kufuneka kubekwe esweni. Ukuba umntwana okanye umntwana ofikisayo nakweyiphi na i-corticosteroid ibonakala enexinzelelo lokukhula, kungenzeka ukuba unomdla ngakumbi kwesi siphumo kufuneka kuthathelwe ingqalelo. Iziphumo ezinokubakho zokukhula kunyango lwexesha elide kufuneka zilinganiswe kuthelekiswa nezibonelelo zonyango ezifunyenweyo. Ukunciphisa iziphumo zenkqubo ye-corticosteroids yomlomo, kubandakanya i-budesonide kunye ne-formoterol fumarate dihydrate, isiguli ngasinye kufuneka sinikezelwe kumandla asezantsi alawula isifuba sakhe[Bona Isisombululo kunye noLawulo (2) ].

Ukusetyenziswa kweGeriatric

Kwitotali yenani lezigulana ze-asthma ezanyangwa nge-budesonide kunye ne-formoterol fumarate dihydrate kabini ngemini kwizifundo zeeveki ezili-12 kunye nesifundo se-postmarketing yeeveki ezingama-26, i-791 yayineminyaka engama-65 ubudala okanye ngaphezulu, kubo i-141 yayineminyaka engama-75 ubudala okanye ngaphezulu.

Kwizifundo zeCOPD zeenyanga ezi-6 ukuya kwezi-12 ubude, izigulana ezingama-810 ziphathwe nge-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5, inhalations ezimbini kabini ngosuku zazineminyaka engama-65 ubudala nangaphezulu kwaye kwezi, izigulana ezili-177 zazineminyaka engama-75 ubudala nangaphezulu. Akukho mahluko ukhuseleko okanye ukusebenza okuqwalaselweyo phakathi kwezi zigulana kunye nezigulana ezisencinci, kunye namanye amava ezonyango axeliweyo awakhange abone umahluko kwiimpendulo phakathi kwabantu abadala kunye nezigulana ezisencinci.

Njengazo zonke iimveliso eziqukethe i-beta2-abaphikisi, isilumkiso esikhethekileyo kufuneka sijongwe xa kusetyenziswa i-budesonide kunye ne-formoterol fumarate dihydrate kwizigulana ezinesifo esine-cardiovascular disease esichaphazeleka kakubi yi-beta2-abaphikisi.

Ngokusekwe kwidatha ekhoyo ye-budesonide kunye ne-formoterol fumarate dihydrate okanye izinto zayo ezisebenzayo, akukho lungelelwaniso lwedosi ye-budesonide kunye ne-formoterol fumarate dihydrate kwizigulana ze-geriatric.

Ukonakala kweHepatic

Izifundo ezisesikweni ze-pharmacokinetic zisebenzisa i-budesonide kunye ne-formoterol fumarate dihydrate khange ziqhutywa kwizigulana ezinokukhubazeka kwe-hepatic. Nangona kunjalo, kuba zombini i-budesonide kunye ne-formoterol fumarate zisuswe ikakhulu yi-hepatic metabolism, ukungasebenzi kakuhle kwesibindi kunokukhokelela ekufumaneni i-budesonide kunye ne-formoterol fumarate kwi-plasma. Ke ngoko, abaguli abanesifo se-hepatic kufuneka bajongwe ngononophelo.

Ukuphazamiseka kwentliziyo

Izifundo ezisesikweni ze-pharmacokinetic zisebenzisa i-budesonide kunye ne-formoterol fumarate dihydrate khange iqhutywe kwizigulana ezinokukhubazeka kwezintso.

Ukugqithisa

I-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL

IBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL iqulethe zombini i-budesonide kunye ne-formoterol; Ke ngoko, umngcipheko onxulunyaniswa nomthamo ongaphaya kwento nganye echazwe apha ngezantsi isebenza kwiBUDESONIDE NAKWI-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL. Kwizifundo ze-pharmacokinetic, idosi enye ye-960/54 mcg (i-12 actuations ye-budesonide kunye ne-formoterol fumarate dihydrate 80 / 4.5) kunye ne-1280/36 mcg (i-8 actuations ye-160 / 4.5), yenziwa kwizigulana ezine-COPD. Itotali ye-1920/54 mcg (i-12 actuations ye-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5) yenziwa njengedosi enye kuzo zombini izifundo ezisempilweni kunye nezigulana ezinesifuba. Kwisifundo sexesha elide esilawulwa ngokusebenzayo sokhuseleko kwizigulana ezinesifo se-asthma nakwiminyaka eyi-12 ubudala nangaphezulu, i-budesonide kunye ne-formoterol fumarate dihydrate i-160 / 4.5 yenziwa ukuya kuthi ga kwiinyanga ezili-12 kwiidosi ukuya kuthi ga kabini eyona idosi iphakanyisiweyo yemihla ngemihla. Akukho ziphumo zibalulekileyo zeklinikhi ziqwalaselweyo kwezi zifundo.

IBudesonide

Ubungakanani beziphumo ezinobungozi emva kokugqithisa kwe-budesonide ziphantsi. Ukuba isetyenziswe kwiidosi ezigqithileyo ixesha elide, inkqubo yecorticosteroid enje ngehypercorticism inokwenzeka[Bona Izilumkiso kunye nokuQapha (5) ]. I-Budesonide amaxesha amahlanu elona thamo liphezulu licetyiswayo (i-3200 mcg mihla le) elawulwa ebantwini iiveki ezi-6 ibangele ukuncitshiswa okukhulu (iipesenti ezingama-27) kwimpendulo ye-plasma cortisol kwi-6-yure infusion ye-ACTH xa kuthelekiswa ne-placebo (+ 1%). Iziphumo ezihambelanayo ze-10 mg prednisone mihla le yayikukuncitshiswa kwe-35% kwimpendulo ye-cortisol ye-plasma kwi-ACTH.

Ifomoterolol

Ukugqithisa kwefomoterol kunokukhokelela ekubaxeni kweziphumo eziqhelekileyo kwi-beta2-i -agonists: ukuxhuzula, i-angina, uxinzelelo lwegazi, i-hypotension, i-tachycardia, i-atrial kunye ne-ventricular tachyarrhythmias, uloyiko, intloko ebuhlungu, ukungcangcazela, ukubetha, izihlunu, isicaphucaphu, isiyezi, ukuphazamiseka kokulala, i-metabolic acidosis, hyperglycemia, hypokalemia. Njengawo onke amayeza ovelwano, ukubanjwa kwentliziyo kunye nokufa kunokunxulunyaniswa nokuphathwa gadalala kwefomoterol. Akukho mpembelelo zibalulekileyo zeklinikhi zabonwa xa ifomoterolin yayisiwa kwizigulana ezindala ezine-bronchoconstriction ebukhali kwithamo le-90 mcg / ngosuku ngaphezulu kweeyure ezingama-3 okanye kwi-asthmatics ezinzileyo kathathu ngemini kwiqondo elipheleleyo le-54 mcg / ngosuku iintsuku ezi-3.

Unyango lwe-formoterol overdosage lubandakanya ukuyeka iyeza kunye neziko elifanelekileyo leempawu kunye / okanye unyango oluxhasayo. Ukusetyenziswa ngobuchule kwe-beta-receptor blocker ye-cardioselective kunokuqwalaselwa, kukhunjulwa ukuba amayeza anjalo anokuvelisa i-bronchospasm. Kukho ubungqina obaneleyo bokuchonga ukuba i-dialysis iluncedo kwi-overoterosos yefomoterol. Ukubeka iliso kwintliziyo kucetyiswa kwiimeko zokugqithisa.

Inkcazo yeBudesonide kunye neFomoterol yeAerosol

IBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL 80 / 4.5 kunye neBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL 160 / 4.5 nganye iqulethe imicroised budesonide kunye nefomoterol fumoterate fumarate dihydrate yomlomo kuphela.

Nganye i-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL 80 / 4.5 kunye ne-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL 160 / 4.5 ibhokisana eyenziwe njenge-hydrofluoroalkane (HFA 227; 1,1,1,2,3,3,opropro-3 -3 Uxinzelelo lwe-inhaler yedosi eneemitha ezi-120[Bona Iifom zedosi kunye namandla (3) kwaye Unikezo / ugcino kunye nokusingathwa (16) ]. Emva kokuphamba, i-actuation yeemitha nganye eyi-91 / 5.1 mcg okanye i-181 / 5.1 mcg kwivelufa kwaye ihambise i-80 / 4.5 mcg, okanye i-160 / 4.5 mcg (i-budesonide micronized / formoterol fumarate dihydrate micronized) evela kwi-actuator. Inani elichanekileyo leziyobisi elethwe emiphungeni linokuxhomekeka kwizigulana, ezinje ngokulungelelaniswa kokuqhutywa kwesixhobo kunye nenkuthazo ngenkqubo yokuhambisa. I-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL ikwanayo ne-povidone K25 USP njengearhente yokurhoxisa kunye ne-polyethylene glycol 1000 NF njengesithambisi.

I-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION I-AEROSOL kufuneka iphakanyiswe ngaphambi kokuba isetyenziswe okokuqala ngokukhupha izitshizi zovavanyo ezimbini emoyeni kude nobuso, ishukuma kakuhle imizuzwana emi-5 ngaphambi kokutshiza. Kwiimeko apho i-inhaler ingasetyenziswanga ngaphezulu kweentsuku ezisi-7 okanye xa ilahliwe, qalisa ukubuyisa inhaler kwakhona ngokushukuma kakuhle imizuzwana emi-5 phambi kokutshiza ngakunye kunye nokukhupha izitshizi zovavanyo ezimbini emoyeni kude nobuso.

Elinye icandelo elisebenzayo le-BUDESONIDE Kunye ne-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL yi-budesonide, i-corticosteroid etyunjwe ngemichiza njenge (RS) -11β, 16cy, 17,21-Tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal kunye butyraldehyde. I-Budesonide ibonelelwa njengomxube weepimers ezimbini (22R kunye ne-22S). Ifomula yobungqina beBudesonide yiC25H3. 4OKANYE6kunye nobunzima bayo beemolekyuli ngu-430.5. Ifomula yayo yile:

I-Budesonide imhlophe emhlophe ingabi mhlophe, ayinambitheki, ayinamphunga ingenakunyibilika emanzini nakwi-heptane, inyibilika kancinci kwi-ethanol, kwaye inyibilike ngokukhululekileyo kwi-chloroform. Ukwahlulahlulahlulahlula kwaso phakathi ko-octanol namanzi kwi-pH 7.4 ngu-1.6 x 103.

Elinye icandelo elisebenzayo le-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION I-AEROSOL yifomoterol fumarate dihydrate, ibeta ekhethiweyo2-i -agonist echongiweyo ngokwemichiza njenge (R *, R *) - (±) -N- [2-hydroxy-5- [1-hydroxy-2 - [[2- (4-methoxyphenyl) -1-methylethyl] amino] ethyl ] phenyl] formamide, (E) -2-butendioate (2: 1), dihydrate. Ifomula yobungqina befomoterol nguC42H56U-N4OKANYE14kunye nobunzima bayo beemolekyuli ngu-840.9. Ifomula yayo yile:

IFomoterolol fumarate dihydrate yimpuphu enyibilikayo emanzini. I-octanol-water partition coefficient kwi-pH 7.4 ngu-2.6. I-pKa ye-formoterol fumarate dihydrate kwi-25 ° C yi-7.9 yeqela le-phenolic kunye ne-9.2 yeqela le-amino.

I-Budesonide kunye neFomoterol Aerosol-kwiklinikhi ye-Pharmacology

Indlela yokuSebenza

I-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL

IBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL iqulethe zombini i-budesonide kunye ne-formoterol; Ke ngoko, iindlela zokusebenza ezichazwe apha ngezantsi zezinto ezizezinye zisebenza kwiBUDESONIDE NAKWI-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL. La machiza amele iindidi ezimbini zamayeza (i-corticosteroid eyenziweyo kunye ne-beta ekhethiweyo esebenza ixesha elide2-adrenoceptor agonist) ezineziphumo ezahlukeneyo kuklinikhi, komzimba, kunye nokuvuvukala kwe-COPD kunye nesifuba.

IBudesonide

I-Budesonide yi-anti-inflammatory corticosteroid ebonisa umsebenzi onamandla we-glucocorticoid kunye nomsebenzi ongenamandla we-mineralocorticoid. Kumgangathoi-In vitrokunye neemodeli zezilwanyana, i-budesonide ine-200 ephindwe kabini yokuhlangana kwe-glucocorticoid receptor kunye ne-1000-fold fold top anti-inflammatory potency kune-cortisol (rat croton oyile indlebe edema assay). Njengomlinganiselo wenkqubo yenkqubo, i-budesonide ingamaxesha angama-40 anamandla ngakumbi kune-cortisol xa ilawulwa ngendlela engaphantsi kunye namaxesha angama-25 anamandla ngakumbi xa ilawulwa ngomlomo kulingo lwe-rat thymus.

Kwizifundo ezinxulumene ne-glucocorticoid receptor, uhlobo lwe-22R lwe-budesonide lwaluphindwe kabini lusebenza njenge-22S epimer.I-In vitroIzifundo zibonise ukuba ezi ndlela zimbini zebudesonide aziphazamisani.

Ukuvuvukala yinto ebalulekileyo kwi-pathogenesis yeCOPD kunye ne-asthma. Iicorticosteroids zinoluhlu olubanzi lwezinto ezithintelayo ngokuchasene neentlobo ezininzi zeseli (umz. ukudumba. Ezi ntshukumo zichasene nokuvuvukala kwee-corticosteroids zinokuba negalelo ekusebenzeni kwazo kwi-COPD nakwi-asthma.

Izifundo kwizigulana ezinesifo sombefu zibonise umlinganiso olungileyo phakathi kwento echasene nokuvuvukala kunye neenkqubo zenkqubo ye-corticosteroid kuluhlu olubanzi lweedosi zebudesonide. Oku kucaciswa ngokudityaniswa kwempembelelo ephezulu yokulwa nokudumba, ukuqala kokudodobala kokuqala kokuthotywa kweziyobisi ngomlomo (85% -95%), kunye namandla asezantsi eemetabolites.

Ifomoterolol

IFomoterolol fumarate kukukhetha okukhethiweyo okuthatha ixesha elide2-adrenergic agonist (beta2-agonist) ukuqala ngokukhawuleza kwentshukumo. Inhaled formoterol fumarate isebenza ekuhlaleni kwimiphunga njenge-bronchodilator.I-In vitroIzifundo zibonise ukuba i-formoterol inemisebenzi engaphezulu kwama-200 yomsebenzi omkhulu we-agonist kwi-beta2-wamkeli kune-beta1abamkeli. Inkqubo ye-i-In vitroukubopha ukukhetha kwi-beta2Ngaphezulu kwe-beta1-adrenoceptors iphezulu kwifomoterol kune-albuterol (amaxesha ama-5), ngelixa i-salmeterol ine-beta ephezulu (kathathu)2Ukhetho lokukhetha ngaphezulu kwefomoterol.

Nangona i-beta2-i-Receptors zezona zibalulekileyo ze-adrenergic receptors kwimisipha egudileyo kunye ne-beta1-i -receptors zezona zibalulekileyo entliziyweni, kukwakhona ne-beta2-iizamkeli entliziyweni yomntu ezibandakanya i-10% ukuya kwi-50% ye-beta-adrenergic receptors iyonke. Umsebenzi ochanekileyo wezi receptors awusekwanga, kodwa baphakamisa ukuba kunokwenzeka ukuba nokuba kukhethwe i-beta2-i -agonists zinokuba nefuthe lentliziyo.

Iziphumo ze-pharmacologic ze-beta2-adrenoceptor agonist drug, kubandakanya i-formoterol, ubuncinci kwinxalenye ebangelwa kukukhuthaza i-intracellular adenyl cyclase, i-enzyme ebangela ukuguqulwa kwe-adenosine triphosphate (ATP) ibe yi-cyclic-3 ', 5'-adenosine monophosphate (cyclic AMP). Ukunyusa amanqanaba e-AMP ejikelezayo kubangela ukuphumla kwemisipha egudileyo kunye nokuthintela ukukhutshwa kwabalamli be-hypersensitivity kwangoko kwiiseli, ngakumbi kwiiseli zemasti.

I-In vitroUvavanyo lubonisa ukuba i-formoterol sisithintelo sokukhululwa kwabalamli be-mast cell, njenge-histamine kunye ne-leukotrienes, ukusuka kumphunga womntu. I-formoterol ikwathintela i-albamine ye-plasma eyenziweyo kwi-albin extravasation kwii-guinea pigs ezingafakwanga i-anesthetised pigs kwaye inqanda i-eosinophil influx kwizinja ezinempendulo yomoya. Ukufaneleka kwezii-In vitrokunye nokufunyanwa kwezilwanyana ebantwini akwaziwa.

Pharmacodynamics

Isifo sombefu

Iziphumo zentliziyo:Kwisifundo sedosi yokuwela ngaphezulu yokubandakanya abaguli abangama-201 abane-asthma eqhubekayo, unyango lwedosi enye ye-4.5, 9, kunye ne-18 mcg ye-formoterol ngokudibeneyo ne-320 mcg ye-budesonide ehanjiswa nge-BUDESONIDE Kunye ne-FORMOTEROL 320 mcg iyodwa. I-Dose-iyalele ukuphuculwa kwi-FEV1zaboniswa xa kuthelekiswa nebudesonide. Ii-ECGs kunye neesampulu zegazi zeswekile kunye nepotassium zafunyanwa emva kwethamo. Kwi-budesonide kunye ne-formoterol fumarate dihydrate, ukunyuka okuncinci kwi-serum glucose kunye nokuhla kwe-serum potassium (+0.44 mmol / L kunye -0.18 mmol / L kwelona dosi liphezulu, ngokulandelanayo) kwajongwa ngokwanda kwamanani e-formoterol, xa kuthelekiswa ne-budesonide. Kwii-ECGs, i-budesonide kunye ne-formoterol fumarate dihydrate ivelise ukunyuka okuncinci okuhambelana nethamo (malunga ne-3 bpm kwelona dose liphezulu), kunye namakhefu e-QTc (3-6 msec) xa kuthelekiswa ne-budesonide kuphela. Akukho sihloko sasine-QT okanye ixabiso le-QTc ≧ 500 msec.

E-United States, iiveki ezintlanu ezili-12, izifundo ezilawulwa ngokukuko kunye ne-placebo kunye neenyanga ezi-6 ezifundwayo ezilawulwa ngokukuko kuvavanywa abaguli abangama-2976 abaneminyaka emi-6 nangaphezulu abanesifuba. Inkqubo ye-pharmacodynamic ye-formoterol (intliziyo / ukubetha kwenqanaba, uxinzelelo lwegazi, ixesha le-QTc, i-potassium, kunye ne-glucose) zazifana nezigulana ezanyangwa nge-budesonide kunye ne-formoterol fumarate dihydrate, xa kuthelekiswa nezigulana ezanyangwa nge-formoterol eyomileyo yokuphefumla i-4.5 mcg, 2 inhalations kabini yonke imihla . Akukho sigulana sinexabiso le-QT okanye le-QTc ≧ 500 msec ngexesha lonyango.

Kwizifundo ezithathu ezilawulwa yi-placebo kulutsha nakubantu abadala abane-asthma, abaneminyaka eyi-12 ubudala nangaphezulu, abaguli abali-1232 (abaguli abangama-553 abakwi-budesonide kunye ne-formoterol fumarate dihydrate group) kuvavanyo oluqhubekayo lweeyure ezingama-24 ze-electrocardiographic. Ngokubanzi, kwakungekho mahluko ubalulekileyo kwimeko ye-ectopy ye-ventricular okanye ye-supraventricular ectopy kwaye akukho bungqina bokwanda komngcipheko wedysrhythmia ebalulekileyo kwi-budesonide kunye ne-formoterol fumarate dihydrate group xa kuthelekiswa ne-placebo.

Iziphumo ze-HPA-axis:Ngokubanzi, akukho ziphumo zibalulekileyo zeklinikhi kwi-HPA-axis, njengoko kulinganiswa ngeyure ye-24 ye-urinary cortisol, yaqwalaselwa kwi-budesonide kunye ne-formoterol fumarate dihydrate ephathwe ngabantu abadala okanye abafikisayo kwizigulana ukuya kwi-640/18 mcg / ngosuku xa kuthelekiswa nebudesonide.

Isifo esingapheliyo sePulmonary Disease

Iziphumo zentliziyo:Kwizifundo ezibini zomsebenzi wamaphaphu weCOPD, iinyanga ezi-6 kunye neenyanga ezili-12 ubude kubandakanya nezigulana ezingama-3668 zeCOPD, akukho mahluko ubalulekileyo eklinikhi obonwe kwinqanaba le-pulse, uxinzelelo lwegazi, i-potassium, kunye neswekile phakathi kwe-budesonide kunye ne-formoterol fumarate dihydrate, izinto ezizodwa ze-BUDESONIDE NE-FORMOTEROL I-FUMARATE DIHYDRATE INHALATION AEROSOL, kunye ne-placebo[Bona Izifundo zeKlinikhi (14.2) ].

Ii-ECGs ezirekhodwe kutyelelo lweklinikhi oluninzi kunyango kwizifundo zombini azibonisanga mahluko ubalulekileyo eklinikhi wenqanaba lentliziyo, isithuba se-PR, ubude be-QRS, inqanaba lentliziyo, imiqondiso ye-ischemia yentliziyo okanye ii-arrhythmias phakathi kwe-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5 i-monoproducts kunye ne-placebo, konke ilawulwa njenge-2 inhalations kabini yonke imihla. Ngokusekwe kwii-ECGs, izigulana ezi-6 ziphathwe nge-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5, 6 yezigulana ziphathwe nge-formoterol 4.5 mcg, kunye nezigulana ze-6 kwiqela le-placebo ezinamava e-fibrillation ye-atrial okanye ye-flutter ebengekho kwisiseko. Kwakungekho matyala e-tachycardia engafakwanga i-ventricular kwi-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5, formoterol 4.5 mcg, okanye amaqela e-placebo.

Kwisifundo seenyanga ezili-12, izigulana ezingama-520 ziye zavavanywa kuvavanyo oluqhubekayo lweeyure ezingama-24 ze-ECG (Holter) ngaphambi kwethamo lokuqala nasemva kweenyanga ezili-1 kunye ne-4 kunyango. Akukho mahluko ubalulekileyo eklinikhi kwii-ventricular okanye supraventricular arrhythmias, ventricular okanye supraventricular ectopic beats, okanye izinga lentliziyo labonwa phakathi kwamaqela anyangwa nge-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5, formoterol okanye i-placebo ethathwe njenge-2 inhalations kabini yonke imihla. Ngokusekwe kuhlolo lwe-ECG (Holter), isiguli esinye kwi-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5, akukho zigulana zikwifomoterol 4.5 mcg, kwaye abaguli abathathu kwiqela le-placebo bafumana i-atrill fibrillation okanye i-flutter ebengekho kwisiseko.

Iziphumo ze-HPA-axis:Amashumi amabini anesine iiyure ze-urinary cortisol zaqokelelwa kwi-subset edityanisiweyo (n = 616) yezigulana ezivela kwizifundo ezibini zomsebenzi wemiphunga weCOPD. Idatha ibonise malunga nama-30% asezantsi athetha iiyure ezingama-24 zokuchama ngaphandle kwamaxabiso e-cortisol alandelayo emva kolawulo olungapheliyo (> iinyanga ezi-6) zebudesonide kunye nefomoterol fumarate dihydrate, enxulumene ne-placebo. I-Budesonide kunye ne-formoterol fumarate dihydrate ibonakalise ukubonakaliswa koxinzelelo lwe-cortisol xa kuthelekiswa ne-budesonide 160 mcg iyodwa okanye ulawulo lwe-budesonide 160 mcg kunye ne-formoterol 4.5 mcg. Kwizigulana ezanyangwa nge-budesonide kunye ne-formoterol fumarate dihydrate, okanye i-placebo ukuya kuthi ga kwiinyanga ezili-12, ipesenti yezigulana ezisuke kwinto yesiqhelo zaya ezantsi kule milinganiselo ngokubanzi zazithelekiswa.

Ezinye iiMveliso zeBudesonide

Ukuqinisekisa ukuba ukufunxwa kwenkqubo ayisiyonto ibalulekileyo ekusebenzeni kweklinikhi kwe-inhaled budesonide, isifundo sonyango kwizigulana ezinesifuba senziwa ngokuthelekisa i-400 mcg budesonide elawulwa nge-inhaler ene-metered dose inhaler kunye ne-tube spacer ukuya kwi-1400 mcg ye-oral budesonide kunye ne-placebo . Isifundo sibonakalise ukusebenza kwe-inhaled budesonide kodwa hayi ngomlomo kufakwe i-budesonide, ngaphandle kwamanqanaba enkqubo afanayo. Ke ngoko, isiphumo sonyango lweedosi eziqhelekileyo ze-budesonide yomlomo ekhutshwe ngomlomo zichazwa ikakhulu kukusebenza ngokuthe ngqo kwendlela yokuphefumla.

I-inhaled budesonide ibonakalisiwe ukunciphisa ukubuyela kwindlela yomoya kwiimodeli ezahlukeneyo zomceli mngeni, kubandakanya i-histamine, i-methacholine, isodiyam metabisulfite, kunye ne-adenosine monophosphate kwizigulana ezinomoya womoya. Ukubaluleka kweklinikhi kwezi modeli akuqinisekanga.

Ukunyanga kwangaphambili nge-inhaled budesonide, i-1600 mcg mihla le (i-800 mcg kabini yonke imihla) kwiiveki ezi-2 kunciphise ukusabela okukhoyo (ukuqala kwesigaba sokuqala) kunye nokulibaziseka (ukusabela emva kwexesha) kwehle kwi-FEV1ukulandela umceli mngeni we-allergen.

Iziphumo zenkqubo ye-inhaled corticosteroids zinxulumene nokuchazwa kwenkqubo kwiziyobisi ezinjalo. Izifundo ze-Pharmacokinetic zibonise ukuba kubantu abadala nakubantwana abane-asthma ukubonakaliswa kwenkqubo kwi-budesonide kusezantsi nge-budesonide kunye ne-formoterol fumarate dihydrate, xa kuthelekiswa ne-inhaled budesonide elawulwa kwidosi efanayo ehanjisiweyo nge-inhaler eyomileyo yomgubo.[Bona Ikhemesti yezonyango (12.3) ]. Ke ngoko, iziphumo zenkqubo (i-HPA-axis kunye nokukhula) kwe-budesonide ehanjiswa kwi-budesonide kunye ne-formoterol fumarate dihydrate, kuya kulindeleka ukuba ingabi ngaphezulu kwento exeliweyo nge-inhaled budesonide xa ilawulwa ngeedosi ngokuthelekiswa nge-powder eyomileyo inhaler[Bona Sebenzisa kubantu abathile (8.4) ].

Iziphumo ze-HPA-axis:Iziphumo ze-inhaled budesonide elawulwa nge-inhaler eyomileyo ye-inhaler kwi-HPA-axis yafundwa kubantu abadala be-905 nakwizigulana zabantwana ezingama-404 ezine-asthma. Kwizigulana ezininzi, ukukwazi ukonyusa imveliso yecortisol ekuphenduleni kuxinzelelo, njengoko kuvavanywa kuvavanyo lwe-cosyntropin (ACTH), yahlala inyanisekile kunyango lwe-budesonide kwiidosi ezinconyelwayo. Kwizigulana zabantu abadala ezanyangwa nge-100, 200, 400, okanye i-800 mcg kabini yonke imihla kwiiveki ezili-12, iipesenti ezi-4, iipesenti ezi-2, ii-6%, kunye ne-13% ngokwahlukeneyo, zazinempendulo yecortisol evuselelekileyo engaqhelekanga (incopho yecortisol<14.5 mcg/dL assessed by liquid chromatography following short-cosyntropin test) as compared to 8% of patients treated with placebo. Similar results were obtained in pediatric patients. In another study in adults, doses of 400, 800, and 1600 mcg of inhaled budesonide twice daily for 6 weeks were examined; 1600 mcg twice daily (twice the maximum recommended dose) resulted in a 27% reduction in stimulated cortisol (6-hour ACTH infusion) while 10-mg prednisone resulted in a 35% reduction. In this study, no patient on budesonide at doses of 400 and 800 mcg twice daily met the criterion for an abnormal stimulated-cortisol response (peak cortisol <14.5 mcg/dL assessed by liquid chromatography) following ACTH infusion. An open-label, long-term follow-up of 1133 patients for up to 52 weeks confirmed the minimal effect on the HPA-axis (both basal- and stimulated-plasma cortisol) of budesonide when administered at recommended doses. In patients who had previously been oral-steroid-dependent, use of budesonide in recommended doses was associated with higher stimulated-cortisol response compared to baseline following 1 year of therapy.

Ezinye iimveliso zeFomoterol

Ngelixa ifuthe le-pharmacodynamic lihamba ngokukhuthaza ii-beta-adrenergic receptors, ukwenziwa okugqithileyo kwezi receptors zihlala zikhokelela ekungcangcazelweni kwemisipha kunye necramp, ukuqaqanjelwa sisisu, i-tachycardia, ukwehla kwi-potassium yeplasma, kunye nokunyuka kwe-glucose yegazi. Ifomolol ye-inhaled, njengenye i-beta2-Iziyobisi zeadonergic agonist, zinokuvelisa iziphumo ezinxulumene nedosi senhliziyo kunye nefuthe kwiglucose yegazi kunye / okanye kwi-serum potassium[Bona Izilumkiso kunye nokuQapha (5) ]. Kwi-budesonide kunye ne-formoterol fumarate dihydrate, ezi ziphumo zichaziwe kwi I-Clinical Pharmacology, i-Pharmacodynamics, i-BUDESONIDE kunye ne-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL (12.2) icandelo.

Ukusetyenziswa kweziyobisi ze-LABA kunokubangela ukunyamezelana nemiphumo ye-bronchoprotective kunye ne-bronchodilatory.

Ukuphindaphinda ukungaphenduli kwesibindi emva kokuyeka unyango lwe-beta-agonist engapheliyo.

Pharmacokinetics

I-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL

Ukufunxa

IBudesonide
Izifundo ezisempilweni:I-budesonide ekhutshwe ngomlomo ifakwa ngokukhawuleza kwimiphunga kwaye incopho yokufikelela kufikelelwa ngaphakathi kwemizuzu engama-20. Emva kolawulo lomlomo lwe-budesonide incopho ye-plasma yoxinaniso yafezekiswa malunga ne-1 ukuya kwiiyure ezi-2 kwaye ukufumaneka kwenkqubo ngokupheleleyo kwaba yi-6% -13% ngenxa yokupasa kokuqala kwemetabolism. Ngokwahlukileyo, uninzi lwe-budesonide ehanjiswe kwimiphunga yayixutywe ngokwenkqubo. Kwizifundo ezisempilweni, i-34% yedosi ebekiweyo yafakwa kwimiphunga (njengoko kuvavanywa indlela yoxinaniso lweplasma kunye nokusebenzisa inhaler yomgubo owomileyo we-budesonide) kunye nokufumaneka kwenkqubo eyi-39% yedosi yemitha.

Ukulandela ukulawulwa kwe-budesonide kunye ne-formoterol fumarate dihydrate i-160 / 4.5, inhalation ezimbini okanye ezine kabini yonke imihla kwiintsuku ezi-5 kwizifundo ezisempilweni, uxinzelelo lweplasma lwe-budesonide ngokubanzi lonyuka ngokulingana nedosi. Isalathiso seqela elifumene i-2 inhalations kabini yonke imihla yayiyi-1.32 ye-budesonide.

Izigulana ezinesifo sombefu:Kwisifundo sedosi enye, ngaphezulu kweedosi ezicetyiswayo ze-budesonide kunye ne-formoterol fumarate dihydrate (i-12 inhalations ye-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5) zanikezelwa kwizigulana ezinesifo sombefu esimodareyithayo. Incopho ye-budesonide ye-plasma yoxinzelelo lwe-4.5 nmol / L yenzeke kwimizuzu engama-20 emva kwedosi. Olu phononongo lubonakalise ukuba ukubonakaliswa kwenkqubo iyonke kwi-budesonide ukusuka kwi-budesonide kunye ne-formoterol fumarate dihydrate yayimalunga ne-30% isezantsi kune-inhaled budesonide nge-powder eyomileyo inhaler (DPI) kwithamo elifanayo lokuhambisa. Ukulandela ukulawulwa kwe-budesonide kunye ne-formoterol fumarate dihydrate, isiqingatha sobomi secandelo le-budesonide yayiziiyure ze-4.7.

Kwisifundo sedosi esiphindayo, elona thamo liphezulu licetyiswayo le-budesonide kunye ne-formoterol fumarate dihydrate (160 / 4.5, inhalations ezimbini kabini imihla ngemihla) zanikezelwa kwizigulana ezinesifo sombefu esifanelekileyo kunye nezifundo ezisempilweni kwiveki e-1. Incopho ye-budesonide plasma ye-1.2 nmol / L yenzeke kwimizuzu engama-21 kwizigulana ezinesifo sombefu. Incopho ye-budesonide ye-plasma yoxinaniso yayiyi-27% isezantsi kwizigulana zesifuba xa kuthelekiswa naleyo kwizifundo ezisempilweni. Nangona kunjalo, ukubonakaliswa kwe-budesonide iyonke kuthelekiswa naleyo kwizigulana zesifuba.

Ukuphakama kwesimo seplasma esisigxina se-budesonide elawulwa yi-DPI kubantu abadala abane-asthma avareji ye-0.6 kunye ne-1.6 nmol / L kumthamo we-180 mcg kunye ne-360 mcg kabini yonke imihla, ngokulandelelana. Kwizigulana ezinesifuba, i-budesonide ibonise ukonyuka komgama kwi-AUC kunye no-Cubuninzingedosi eyandayo emva kokubethwa okungatshatanga nokuphindaphindwayo kwe-inhaled budesonide.

Izigulana zeCOPD:Kwisifundo sedosi enye, i-12 inhalations ye-budesonide kunye ne-formoterol fumarate dihydrate 80 / 4.5 (iyonke idosi 960/54 mcg) zanikezelwa kwizigulana ezine-COPD. Kuthetha ukuba i-budesonide incopho ye-plasma yoxinzelelo lwe-3.3 nmol / L yenzeke kwimizuzu engama-30 emva kwedosi. Ukuvezwa kwenkqubo yeBudesonide kwakuthelekiswa phakathi kwe-budesonide kunye ne-formoterol fumarate dihydrate pMDI kunye nolawulo lwe-budesonide ngokusebenzisa i-ineredr yedosi ye-metered kunye ne-formoterol nge-inhaler eyomileyo ye-powder (budesonide 960 mcg kunye nefomoterol 54 mcg). Kwisifundo esifanayo, iqela elinelebhile evulekileyo yezigulana zesifo sombefu ezifumene idosi efanayo ephezulu ye-budesonide kunye ne-formoterol fumarate dihydrate. Kwi-budesonide, abaguli beCOPD babonisa i-12% enkulu ye-AUC kunye ne-10% esezantsi Cubuninzixa kuthelekiswa nezigulana zesifuba.

Kwinyanga ye-6 ebalulekileyo yokusebenza kwemiphunga kufundo lweklinikhi, idatha yozinzo lwe-pharmacokinetic ye-budesonide yafunyanwa kwiseti yezigulana ze-COPD ezineengalo zonyango lwe-budesonide kunye ne-formoterol fumarate dihydrate pMDI 160 / 4.5, budesonide kunye ne-formoterol fumarate dihydrate pMDI 80 / 4.5, I-budesonide 160 mcg, i-budesonide 160 mcg kunye ne-formoterol 4.5 mcg inikwe kunye, zonke zilawulwa njenge-inhalation ezi-2 kabini yonke imihla. Ukuvezwa kwenkqubo yeBudesonide (AUC kunye noCubuninzi) inyuke ngokulinganayo ngeedosi ukusuka kwi-80 mcg ukuya kwi-160 mcg kwaye yayiqhelekile phakathi kwamaqela amathathu onyango afumana idosi efanayo ye-budesonide (budesonide kunye nefomoterol fumarate dihydrate pMDI 160 / 4.5, budesonide 160 mcg, budesonide 160 mcg kunye nefomoterol 4.5 mcg elawulwa ngokudibeneyo ).

Ifomoterolol

I-inoterator formoterol ifunxwa ngokukhawuleza; Ukuqaqanjelwa kweplasma kufikelelwa kwisampulu yexesha lokuqala, ngaphakathi kwemizuzu emi-5 ukuya kweli-10 emva kwedosi. Njengakwiimveliso ezininzi zamachiza okuphefumla ngomlomo, kunokwenzeka ukuba uninzi lwefomoterol ekhuselweyo iginyiwe kwaye emva koko ifunxwe kwiphecana lesisu.

Izifundo ezisempilweni:Ukulandela ukulawulwa kwe-budesonide kunye ne-formoterol fumarate dihydrate (160 / 4.5, inhalation ezimbini okanye ezine kabini yonke imihla) kwiintsuku ezi-5 kwizifundo ezisempilweni, uxinzelelo lweplasma lwefomoterol ngokubanzi lonyuka ngokulingana nedosi. Isalathiso seqela elifumene i-2 inhalations kabini yonke imihla yayiyi-1.77 ye-formoterol.

Izigulana zesifo sombefu:Kwisifundo sedosi enye, ngaphezulu kweedosi ezicetyiswayo ze-budesonide kunye ne-formoterol fumarate dihydrate (i-12 inhalations ye-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5) zanikezelwa kwizigulana ezinesifo sombefu esimodareyithayo. Incopho yeplasma yoxinaniso lwefomoterol ye-136 pmol yenzeke kwimizuzu eyi-10 emva kwedosi. Phantse i-8% yedosi ehanjisiweyo yefomoterol yafunyanwa kumchamo njengechiza elingatshintshanga.

Kwisifundo sedosi esiphindayo, elona thamo liphezulu licetyiswayo le-budesonide kunye ne-formoterol fumarate dihydrate (160 / 4.5, inhalations ezimbini kabini imihla ngemihla) zanikezelwa kwizigulana ezinesifo sombefu esifanelekileyo kunye nezifundo ezisempilweni kwiveki e-1. I-Peak formoterol ye-plasma yoxinzelelo lwe-28 pmol / L yenzeke kwimizuzu ye-10 kwizigulana zesifuba. I-Peak formoterol ye-plasma yoxinaniso yayimalunga ne-42% esezantsi kwizigulana zesifuba xa kuthelekiswa naleyo kwizifundo ezisempilweni. Nangona kunjalo, ukubonakaliswa kwe-formoterol iyonke kuthelekiswa noko kwenzeka kwizigulana zesifuba.

Izigulana zeCOPD:Ukulandela ulawulo lwedosi enye ye-12 inhalations ye-budesonide kunye ne-formoterol fumarate dihydrate 80 / 4.5, kuthetha ukuba ifreyim formoterol yoxinaniso lweplasma ye-167 pmol / L yafezekiswa ngokukhawuleza kwimizuzu eli-15 emva kwedosi. Ukuvezwa kweFomoterol kwakumkhulu kancinci (~ 16-18%) ukusuka kwi-budesonide kunye ne-formoterol fumarate dihydrate pMDI xa kuthelekiswa nokulawulwa kwe-budesonide nge-ineredr yedosi ye-metered kunye ne-formoterol ngokusebenzisa i-inhaler eyomileyo yomgubo (idosi epheleleyo ye-budesonide 960 mcg kunye ne-formoterol 54 mcg). Kwisifundo esifanayo, iqela leelebhile evulekileyo yezigulana zesifo sombefu ezifumene idosi efanayo ye-budesonide kunye ne-formoterol fumarate dihydrate. Izigulana zeCOPD zibonise i-12-15% enkulu ye-AUC kunye neCubuninziyefomoterol xa kuthelekiswa nezigulana zesifuba.

Kwinyanga ye-6 ebalulekileyo yokusebenza kwemiphunga kufundo lweklinikhi, idatha yozinzo lwe-pharmacokinetic ye-formoterol yafunyanwa kwiseti yezigulana ze-COPD ezineengalo zonyango lwe-budesonide kunye ne-formoterol fumarate dihydrate pMDI 160 / 4.5, budesonide kunye ne-formoterol fumarate dihydrate pMDI 80 / 4.5, i-formoterol i-4.5 mcg, i-budesonide 160 mcg kunye ne-formoterol 4.5 mcg inikwe kunye, zonke zilawulwa njenge-inhalation ezi-2 kabini yonke imihla. Ukuvezwa kwenkqubo ye-formoterol njengoko kungqinwa yi-AUC, yayimalunga ne-30% kunye ne-16% ephezulu ukusuka kwi-budesonide kunye ne-formoterol fumarate dihydrate pMDI xa kuthelekiswa nefomoterol yodwa ingalo yonyango kunye nolawulo lwezinto ezizodwa zebudesonide kunye nefomoterol yonyango lwengalo, ngokulandelelana.

Ukuhanjiswa
IBudesonide:Umthamo wokuhanjiswa kwe-budesonide wawumalunga ne-3 L / kg. Kwakungu-85% -90% ebotshelelwe kwiiproteni zeplasma. Ukubopha kweeproteni bekuhlala kuluhlu loxinzelelo (i-1-100 nmol / L) iphunyezwe, kwaye igqithile, kucetyiswa iidosi ezamkelweyo. I-Budesonide ibonakalise encinci okanye ayibopheleli kwi-corticosteroid yokubopha i-globulin. I-Budesonide ikhawuleze ilinganiswe neeseli ezibomvu zegazi ngendlela yoxinaniso ezimeleyo kunye nomyinge weplasma wegazi omalunga ne-0.8.

IFomoterolol:Ngaphezulu koxinzelelo lwe-10-500 nmol / L, iproteni yeplasma ebopha i-RR kunye ne-SS enantiomers zefomoterol yayiyi-46% kunye ne-58% ngokwahlukeneyo. Ukugxininiswa kwefomoterol esetyenziselwa ukuvavanya ukubopha kweeproteni kweplasma kwakuphezulu kunoko kufunyenwe kwiplasma kulandela ukuphefumla idosi enye ye-54 mcg.

Imetabolism
IBudesonide: In vitroIzifundo ezibonisa ukuba ii-homogenates zesibindi somntu zibonise ukuba i-budesonide yayihamba ngokukhawuleza kwaye ibanzi kakhulu. Zimbini i-metabolites eziphambili ezenziwa nge-cytochrome P450 (CYP) isoenzyme 3A4 (CYP3A4) ekhutshwe nge-biotransformation ibekelwe bucala kwaye ichongwe njenge-16cy-hydroxyprednisolone kunye ne-6ß-hydroxybudesonide. Umsebenzi wecorticosteroid nganye yezi zinto zimbini zeemetabolites yayingaphantsi kwe-1% yento eyakhiweyo yomzali. Akukho mahluko ubulunga phakathi kwe-i-In vitrokwayekwi vivoIipatheni ze-metabolic zafunyanwa. Ukungasebenzi kakuhle kokungasebenzi kakuhle kwaqwalaselwa kwimiphunga yomntu kunye nokulungiselela kwe-serum.

IFomoterolol:I-metabolism ephambili ye-formoterol yi-glucuronidation ethe ngqo kunye ne-O-demethylation elandelwa kukudibana kwimetabolites engasebenziyo. Iindlela zesekethe metabolic zibandakanya i-deformylation kunye ne-sulfate conjugation. I-CYP2D6 kunye ne-CYP2C zichongiwe njengezinoxanduva ikakhulu kwi-O-demethylation.

Ukupheliswa
IBudesonide:I-Budesonide yayikhutshiwe kumchamo kunye nelindle ngohlobo lweemetabolites. Phantse iipesenti ezingama-60 zedosi efakwe emithanjeni efunyenwe kumchamo.

Akukho budesonide ingaguqukanga eyafunyanwa kumchamo. Ifom ye-22R ye-budesonide yayikhethwe ngokukhethekileyo sisibindi ngenkqubo ye-1.4 L / min ngokuchasene ne-1.0 L / min kwifom ye-22S. Isiphelo sobomi, iiyure ezi-2 ukuya kwezi-3, zazifana kuzo zombini iipimers kwaye zazizimeleyo ngethamo.

IFomoterolol:Ukukhutshwa kwefomoterol kwafundwa kwizifundo ezine ezisempilweni kulandela ukulawulwa ngaxeshanye kwefomoterol yereyibhile ngeendlela zomlomo kunye ne-IV. Kolo phononongo, iipesenti ezingama-62 ze-formololol ebhalwe i-radiolabeled yachithwa kumchamo ngelixa i-24% yasuswa kwilindle.

Abemi abakhethekileyo

Geriatric

I-pharmacokinetics ye-budesonide kunye ne-formoterol fumarate dihydrate kwizigulana ze-geriatric azifundiswanga ngokukodwa.

Babantwana

Ukujongwa kweplasma ye-budesonide kwakulinganiswa emva kolawulo lwe-inhalations ezine ze-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5 kwisifundo sedosi enye kwizigulana zabantwana abanesifuba, i-6 ukuya ngaphantsi kweminyaka eyi-12 ubudala. Ukuphakama kwe-budesonide ye-1.4 nmol / L yenzeke kwimizuzu engama-20 emva kwethamo. Olu phononongo lukwabonakalise ukuba ukubonakaliswa kwenkqubo iyonke kwi-budesonide ukusuka kwi-budesonide kunye ne-formoterol fumarate dihydrate yayimalunga ne-30% isezantsi kune-inhaled budesonide ngokusebenzisa i-inhaler eyomileyo yomgubo eyavavanywa kwidosi efanayo ehanjisiweyo. C idosi eqhelekileyoubuninzikunye ne-AUC0-infI-budesonide elandela inhalation yethamo elinye kubantwana aba-6 ukuya kuthi ga ngaphantsi kweminyaka eyi-12 ubudala babephantsi ngokwamanani kunokuba kubonwa kubantu abadala.

Ukulandela inhalation ezi-2 ze-budesonide kunye ne-formoterol fumarate dihydrate ye-160 / 4.5 yonyango kabini yonke imihla, i-formoterol Cubuninzikunye ne-AUC0-6imeko engagungqiyo kubantwana abaneminyaka emi-6 ukuya kwengaphantsi kwe-12 ubudala ithelekiswa naleyo yabonwa kubantu abadala.

Isini / ugqatso

Izifundo ezithile zokuvavanya iimpembelelo zesini kunye nohlanga kwi-pharmacokinetics ye-budesonide kunye ne-formoterol fumarate dihydrate khange zenziwe. Uhlalutyo lwabantu lwe-PK lwe-budesonide kunye ne-formoterol fumarate dihydrate yedatha ibonisa ukuba isini asichaphazeli i-pharmacokinetics ye-budesonide kunye ne-formoterol. Akukho zigqibo zinokutsalwa kwisiphumo sobuhlanga ngenxa yenani eliphantsi labangengabo abantu baseCaucasus abavavanyelwe iPK.

Oomama Abongikazi

Ubume be-budesonide xa ihanjiswa nge-inhalation evela kwi-inhaler eyomileyo ye-inhaler kumthamo we-200 okanye i-400 mcg kabini yonke imihla ubuncinci iinyanga ezi-3 yafundwa kwabafazi abasibhozo abancancisayo abanesifuba kwiinyanga ezi-1 ukuya kwezi-6 emva kokubeleka. Ukuchazwa kwenkqubo kwi-budesonide kula mabhinqa kubonakala ngathi kuthelekiswa nalawo angafuniyo ukuncancisa abafazi abanesifuba esivela kwezinye izifundo. Ubisi lwebele olufunyenwe ngaphezulu kweeyure ezisibhozo zedosi yedosi ityhile ukuba ubuninzi be-budesonide ye-400 kunye ne-800 mcg iyonke yemithamo yemihla ngemihla yayiyi-0.39 kunye ne-0.78 nmol / L, ngokwahlukeneyo, kwaye yenzeka ngaphakathi kwemizuzu engama-45 emva kwedosi. Idosi eqikelelweyo yomlomo yemihla ngemihla ye-budesonide ukusuka kubisi lwebele ukuya elusaneni imalunga ne-0.007 kunye ne-0.014 mcg / kg / ngosuku kwiirejimeni zedosi ezimbini ezisetyenziswe kolu phononongo, elimele malunga ne-0.3% ukuya kwi-1% yedosi ekhutshwe ngumama. Amanqanaba eBudesonide kwiisampulu zeplasma ezifunyenwe kwiintsana ezintlanu malunga nemizuzu engama-90 emva kokuncancisa (kwaye malunga nemizuzu eli-140 emva kolawulo lweziyobisi kunina) zazingaphantsi kwamanqanaba anokulinganiswa (<0.02 nmol/L in four infants and <0.04 nmol/L in one infant) [Bona Sebenzisa kwiindawo ezithile (8.2) ].

I-renal okanye i-Hepatic insufficiency

Akukho datha ngokubhekisele kusetyenziso oluthile lwe-budesonide kunye ne-formoterol fumarate dihydrate kwizigulana ezinokukhubazeka kwe-hepatic okanye i-renal. Ukunciphisa ukusebenza kwesibindi kunokuchaphazela ukususwa kwe-corticosteroids. I-Budesonide pharmacokinetics yachaphazeleka kukusebenza kwesibindi ngokungqinelanayo njengoko kungqinwa kukufumaneka kwenkqubo ephindiweyo emva kokungena ngomlomo. I-intravenous budesonide pharmacokinetics, nangona kunjalo, yayifana kwizigulana ze-cirrhotic nakwizifundo ezisempilweni. Idatha ethile ene-formoterol ayifumaneki, kodwa ngenxa yokuba i-formoterol ngokuyintloko ishenxiswa nge-hepatic metabolism, ukwanda kokuvezwa kunokulindeleka kwizigulana ezinesifo esibi.

Ukusebenzisana kweziyobisi

Uvavanyo olwenziwe ngethamo elinye lwenziwa ukuthelekisa i-pharmacokinetics ye-inhalations ezisibhozo zoku kulandelayo: i-budesonide, i-formoterol, kunye ne-budesonide kunye ne-formoterol elawulwa ngaxeshanye. Iziphumo zophononongo zibonise ukuba abukho ubungqina bokunxibelelana kwe-pharmacokinetic phakathi kwezinto ezimbini zebudesonide kunye nefomoterol fumarate dihydrate.

Izithintelo zeCytochrome P450 Enzymes

KetoconazoleI-Ketoconazole, inhibitor eyomeleleyo ye-cytochrome P450 (CYP) isoenzyme 3A4 (CYP3A4), eyona nto ibalulekileyo ye-enzyme ye-corticosteroids, inyusa amanqanaba e-plasma ye-budesonide yomlomo.

CimetidineKwidosi ekucetyiswa ukuba yenziwe, i-cimetidine, isithinteli esingachananga se-CYP enzymes, yayinefuthe elincinci kodwa elingabalulekanga kwezonyango kwi-pharmacokinetics ye-budesonide yomlomo.

Izifundo ezithile zokunxibelelana neziyobisi kunye nefomoterol khange zenziwe.

Unclinical Toxicology

ICarcinogenesis, iMutagenesis, ukungasebenzi kakuhle kokuchuma

IBudesonide

Izifundo zexesha elide zenziwa kwiigundane kunye neempuku kusetyenziswa ulawulo lomlomo ukuvavanya amandla e-carcinogenic e-budesonide.

Kwisifundo seminyaka emi-2 kwiigundane zeSprague-Dawley, i-budesonide ibangele ukonyuka okubonakalayo kweziganeko ze-gliomas kwiigundane ezingamadoda kwidosi yomlomo ye-50 mcg / kg (phantse ilingana ne-MRHDID kubantu abadala nasebantwaneni kwi-mcg / m2isiseko). Akukho tumorigenicity yabonwa kwiigundane ezingamadoda nabasetyhini kwiidosi ezichaziweyo zomlomo ukuya kuthi ga kwi-25 kunye ne-50 mcg / kg (malunga nokulingana ne-MRHDID kubantu abadala nasebantwaneni kwi-mcg / m2isiseko). Kwizifundo ezibini ezongezelelweyo ze-2-nyaka kwi-male Fischer kunye ne-Sprague-Dawley rats, i-budesonide ayibanga gliomas kwidosi yomlomo ye-50 mcg / kg (phantse ilingana ne-MRHDID kubantu abadala nakubantwana kwi-mcg / m2isiseko). Nangona kunjalo, kwiigundane zesilisa iSprague-Dawley, i-budesonide ibangele ukonyuka okubonakalayo kwizigulo zamathumba e-hepatocellular kwidosi yomlomo ye-50 mcg / kg (phantse ilingana ne-MRHDID kubantu abadala nasebantwaneni kwi-mcg / m2isiseko). Isalathiso esifanayo se-corticosteroids (i-prednisolone kunye ne-triamcinolone acetonide) kwezi zifundo zibini zibonise iziphumo ezifanayo.

Kwisifundo seeveki ezingama-91 kwiimpuku, i-budesonide ayibanga nonyango olunxulumene nonyango kwiidosi zomlomo ukuya kuthi ga kwi-200 mcg / kg (malunga namaxesha ama-2 e-MRHDID kubantu abadala nakubantwana kwi-mcg / m2isiseko).

I-Budesonide yayingeyiyo i-mutagenic okanye i-clastogenic kwiinkqubo zovavanyo ezahlukeneyo ezintandathu: ii-AmesSalmonella/ Uvavanyo lweplate microsome, uvavanyo lwempuku micronucleus, uvavanyo lwempuku ye-lymphoma, uvavanyo lwe-chromosome aberration kwii-lymphocyte zabantu, uvavanyo olunxibelelene nolwabelana ngesondoDrosophila melanogaster, kunye nohlalutyo lokulungiswa kwe-DNA kwinkcubeko ye-hepatocyte.

Ukuchuma kunye nokusebenza kokuzala kwakungachaphazeleki kwiigundane kwiidosi ezingaphantsi ukuya kuthi ga kwi-80 mcg / kg (malunga nokulingana ne-MRHDID kwi-mcg / m2isiseko). Nangona kunjalo, ibangele ukwehla kokusebenza kokubeleka kokubeleka kunye nokusebenza kwentsana ngexesha lokuzalwa kunye nexesha lokuncancisa, kunye nokwehla kokufumana ubunzima bomzimba koomama, kwiidosi ezingaphantsi kwe-20 mcg / kg nangaphezulu (ngaphantsi kwe-MRHDID kwi-mcg / m2isiseko). Akukho ziphumo zichongiweyo kwi-5 mcg / kg (ngaphantsi kwe-MRHDID kwi-mcg / m2isiseko).

Ifomoterolol

Izifundo zexesha elide zaqhutywa kwiimpuku kusetyenziswa ulawulo lomlomo kunye neempuku zisebenzisa ukuphefumla ukuvavanya amandla e-carcinogenic e-formoterol fumarate.

Kwisifundo se-carcinogenicity seenyanga ezingama-24 kwiimpuku ze-CD-1, i-formoterol kumthamo womlomo we-100 mcg / kg nangaphezulu (malunga nama-30 nama-15 amaxesha e-MRHDID kubantu abadala nasebantwaneni, ngokwahlukeneyo, kwi-mcg / m2Isiseko) kubangele ukonyuka okunxulumene nedosi kwisehlo se-leiomyomas yesibeleko.

Kwisifundo se-24-seenyanga se-carcinogenicity in Sprague-Dawley rats, ukwanda kweziganeko ze-mesovarian leiomyoma kunye ne-uterine leiomyosarcoma kwajongwa kwi-inhaled dose ye-130 mcg / kg (malunga nama-70 nama-35 amaxesha e-MRHDID kubantu abadala nasebantwaneni, ngokulandelelana, kwi mcg / m2isiseko). Akukho tumors yabonwa kwi-22 mcg / kg (malunga nama-12 kunye nama-6 amaxesha e-MRHDID kubantu abadala nasebantwaneni, ngokwahlukeneyo, kwi-mcg / m2isiseko).

Amanye amachiza e-beta-agonist abonakalise ngokufanayo ukwanda kwe-leiomyomas yecandelo lesini kwiintonga zabasetyhini. Ukuhambelana kwezi zinto zifunyanisiweyo kusetyenziso lomntu akwaziwa.

IFomoterolol yayingeyiyo i-mutagenic okanye i-clastogenic kwii-AmesSalmonella/ Uvavanyo lweplate microsome, uvavanyo lwempuku ye-lymphoma, uvavanyo lwe-chromosome aberration kwi-lymphocyte yabantu, kunye novavanyo lwe-rat micronucleus.

Ukuncitshiswa kokuchuma kunye / okanye ukusebenza kokuzala kuchongiwe kwiigundane ezingamadoda eziphathwe ngefomoterol kwidosi yomlomo ye-15,000 mcg / kg (malunga namaxesha angama-2200 amaxesha e-MRHDID kwisiseko se-AUC). Akukho siphumo sibonwe kwi-3000 mcg / kg (malunga namaxesha ayi-1600 iMRHDID kwi-mcg / m2isiseko). Kwisifundo esahlukileyo kunye neempuku zamadoda eziphathwe ngedosi yomlomo ye-15,000 mcg / kg (malunga nama-8000 amaxesha e-MRHDID kwi-mcg / m2base), bekukho iziphumo ze-testicular tubular atrophy kunye ne-spermatic debris kwii-testes nakwi-oligospermia kwii-epididymides. Akukho siphumo sokuzala safunyanwa kwiigundane zabasetyhini kwiidosi ukuya kuthi ga kwi-15,000 mcg / kg (malunga namaxesha ayi-1100 ama-MRHDID kwisiseko se-AUC).

I-Toxicology yezilwanyana kunye / okanye i-Pharmacology

Ngaphambi konyango:Izifundo kwizilwanyana zaselebhu (i-minipigs, iimpuku, kunye nezinja) zibonise ukwenzeka kwe-arrhythmias yentliziyo kunye nokufa ngesiquphe (ngobungqina be-histologic ye-myocardial necrosis) xa i-beta-agonists kunye ne-methylxanthines zilawulwa ngaxeshanye. Ukubaluleka kweklinikhi kwezi zinto zifunyanisiweyo akungaziwa.

Izifundo zonyango

Isifo sombefu

Izigulana ezinesifuba seminyaka eli-12 ubudala nangaphezulu

Kwizifundo ezibini zeklinikhi ngokuthelekisa i-budesonide kunye ne-formoterol fumarate dihydrate kunye nezinto zomntu ngamnye, ukuphuculwa kweendawo zokuphela kokusebenza kakhulu zazinkulu nge-budesonide kunye ne-formoterol fumarate dihydrate kunokusetyenziswa kwe-budesonide okanye i-formoterol yodwa. Ukongeza, olunye uphando lweklinikhi lubonise iziphumo ezifanayo phakathi kwe-budesonide kunye ne-formoterol fumarate dihydrate kunye nokusetyenziswa ngaxeshanye kwe-budesonide kunye ne-formoterol kumayeza ahambelanayo kwii-inhalers ezahlukeneyo.

Ukhuseleko kunye nokusebenza kwe-budesonide kunye ne-formoterol fumarate dihydrate kubonisiwe kwizifundo ezimbini zeklinikhi ezilawulwa ngokungekho mthethweni, ezingaboniyo, ezilawulwa yi-placebo ezibandakanya izigulana ezili-1076 ezineminyaka eli-12 ubudala nangaphezulu. I-budesonide elungisiweyo kunye ne-formoterol fumarate dihydrate yedosi ye-160/9 mcg, kunye ne-320/9 mcg kabini yonke imihla (idosi nganye elawulwa njenge-2 inhalations ye-80 / 4.5 kunye ne-160 / 4.5 mcg yamandla, ngokwahlukeneyo) ngokuthelekiswa ne-monocomponents (budesonide kunye nefomoterol ) kunye ne-placebo ukubonelela ngolwazi malunga nomthamo ofanelekileyo wokugubungela uluhlu lobukhali besifuba.

Isifundo soku-1: Ufundisiso lweklinikhi kunye neBudesonide kunye neFomoterol Fumarate Dihydrate 160 / 4.5

Olu phononongo lweeveki ezili-12 luvavanye abaguli abangama-596 abaneminyaka eli-12 ubudala nangaphezulu ngokuthelekisa i-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5, indibaniselwano yasimahla ye-budesonide 160 mcg kunye nefomoterol 4.5 mcg kwii-inhalers ezahlukileyo, budesonide 160 mcg, formoterol 4.5 mcg, kunye ne-placebo ; nganye ilawulwa njenge-inhalations ezi-2 kabini ngemini. Uphononongo lubandakanya ixesha lokubaleka-leveki ezi-2 kunye ne-budesonide 80 mcg, 2 inhalations kabini yonke imihla. Uninzi lwezigulana zine-asthma emodareyithayo kwaye bezisebenzisa ukumodareyitha ukuya kwiidosi eziphezulu ze-inhalled corticosteroids ngaphambi kokungena kufundo. Ukwenza i-Randomization kwahlulwahlulwa lonyango lwangaphambili lwe-corticosteroid ye-inhaled (i-71.6% kwimodareyitha- kunye ne-28.4% kwidosi ephezulu ye-corticosteroid ye-inhaled). Iipesenti ezichaziweyo ezixelwe kwangaphambili nge-FEV1kwisiseko sasiyi-68.1% kwaye sasifana kumaqela onyango. Amanqaku okuphela kokusebenza okuphucukileyo ayili-12 leeyure-avareji yethamo lwasemva kwedosi ye-FEV1ngeveki yesi-2, kunye nedosi yangaphambi kwethamo i-FEV1I-avareji ngaphezulu kwesifundo. Uphononongo lukwafuna ukuba izigulana ezonelise imeko echazwe kwangaphambili yesifo sombefu ukuba irhoxiswe. Iikhrayitheriya ezichasayo zesifuba-mbumbulu yayikukuncipha okubalulekileyo kwezonyango kwi-FEV1okanye i-PEF, ukwanda kokuhlangulwa kwe-albuterol, ukuvuka ebusuku ngenxa yesifuba, ungenelelo olungxamisekileyo okanye ukulaliswa esibhedlele ngenxa yesifuba, okanye imfuneko yonyango lwesifuba esingavumelekanga ngumgaqo. Ukuchongwa kwexesha lokuvuka ebusuku ngenxa yesifuba, izigulana zavunyelwa ukuba zihlale kwisifundo ngokokubona komphenyi ukuba akukho nanye yeendlela zokuba mandundu kwesifuba ezifezekisiweyo. Ipesenteji yezigulana ezirhoxayo ngenxa okanye yokuhlangabezana neekhrayitheriya ezichaziweyo zokuba mandundu kwesifo sombefu ibonakalisiwe kwiTheyibhile 4.

Itheyibhile 4 Inani kunye nepesenti yezigulana ezirhoxayo ngenxa yokuhlangabezana okanye ezichazwe kwiikhrayitheriya ezichazwe kwangaphambili zokuba mandundu kwesifuba (iSifundo 1)
*
Ezi khrayitheriya zavavanywa yonke imihla ngaphandle kwexesha lokutyelelwa kweklinikhi, ngaphandle kwe-FEV1, eyavavanywa kutyelelo ngalunye lweklinikhi.
& ikrele;
Iikhrayitheriya zomntu ngamnye zibonisiwe kwizigulana ezihlangabezana nawo nawuphi na umsitho wesifuba esichazwe kwangaphambili, nokuba imeko ithathe njani.
& Dagger;
Ukuchongwa kwexesha lokuvuka ebusuku ngenxa yesifuba, izigulana zavunyelwa ukuba zihlale kwisifundo ngokokubona komphenyi ukuba akukho nanye kwezi ndlela zafikelelwayo.

IBudesonide kunye neFomoterol Fumarate Dihydrate

160 / 4.5

n = 124

IBudesonide

I-160 mcg kunye neFomoterolol

4.5 mcg

n = 115

IBudesonide

160 mcg

n = 109

Ifomoterolol

4.5 mcg

n = 123

Iplacebo

n = 125

Izigulana zirhoxisiwe ngenxa yesiganeko sombefu esichazwe kwangaphambili *

I-13 (10.5)

13 (11.3)

Umanqaku 22 (20.2)

44 (35.8)

62 (49.6)

Izigulana ezinesiganeko sombefu esichazwe kwangaphambili * , & ikrele;

37 (29.8)

Umanqaku 24 (20.9)

Amanqaku angama-48 (44.0)

68 (55.3)

84 (67.2)

Ukuncipha kwi-FEV1

Umanqaku 4 (3.2)

Isi-8 (7.0)

Isixhenxe (6.4)

Ishumi elinesihlanu (12.2)

Ishumi elinanye (11.2)

Ukusetyenziswa kwamayeza okuhlangula

2 (1.6)

0

3 (2.8)

3 (2.4)

Isixhenxe (5.6)

Ukuncipha kwi-AM PEF

2 (1.6)

Isihlanu (4.3)

Isihlanu (4.6)

Umanqaku 17 (13.8)

Ishumi elinesihlanu (12.0)

Ukuvuka ebusuku & Dagger;

24 (19.4)

I-11 (9.6)

29 (26.6)

Amanqaku angama-32 (26.0)

49 (39.2)

Ukunyuka kwezonyango

Isixhenxe (5.6)

Isithandathu (5.2)

Isihlanu (4.6)

Umanqaku 17 (13.8)

Ishumi elinesithandathu (12.8)

Kuthetha ukutshintsha kwepesenti ukusuka kwisiseko kwi-FEV1Ukulinganiswa kwangoko ngaphambi kwedosi (idosi yaphambi) ngaphezulu kweeveki ezili-12 kubonisiwe kumzobo 1. Ngenxa yokuba olu phononongo lusebenzise iindlela ezichaziweyo zokurhoxa kwesifo sombefu, esibangele ukuba izinga lokurhoxa kumaqela onyango, i-FEV yangaphambi kwethamo1iziphumo kutyelelo lokugqibela olukhoyo lokugqibela (unyango, i-EOT) zikwanikezelwa. Izigulana ezifumana i-budesonide kunye ne-formoterol fumarate dihydrate i-160 / 4.5 ibinokuphucuka okubaluleke kakhulu ukusuka kwisiseko sokuqala kwethamo le-FEV1Ekupheleni konyango (0.19 L, 9.4%), xa kuthelekiswa ne-budesonide 160 mcg (0.10 L, 4.9%), formoterol 4.5 mcg (-0.12 L, -4.8%), kunye ne-placebo (-0.17 L, -6.9%) .

Umzobo 1 Kuthetha ukutshintsha kwepesenti ukusuka kwisiseko kwi-pre-dose FEV1Ngaphezulu kweeveki ezili-12 (Isifundo 1)

Iziphumo ze-budesonide kunye ne-formoterol fumarate dihydrate i-160 / 4.5 i-inhalation ezimbini kabini imihla ngemihla kwizinto ezikhethiweyo zendlela yokusebenza yesibini, kubandakanya kusasa nangokuhlwa i-PEF, ukusetyenziswa kwe-albuterol yokuhlangula, kunye neempawu zesifuba ngaphezulu kweeyure ezingama-24 kwisikali se-0-3 sibonisiwe kwiTheyibhile 5.

Itheyibhile 5 Amaxabiso athethwayo okhethiweyo okhethiweyo wokusebenza ngempumelelo (Isifundo 1)
Ukusebenza kuyahluka IBudesonide kunye neFomoterol Fumarate Dihydrate
160 / 4.5
(n * = 124)
IBudesonide
160 mcg kunye
Ifomoterol 4.5 mcg
(n * = 115)
IBudesonide
160 mcg
(n * = 109)
Ifomoterolol
4.5 mcg
(n * = 123)
Iplacebo
(n * = 125)
*
Inani lezigulana (n) lahluka kancinane ngenxa yenani lezigulana ekukho idatha kuzo zonke izinto eziguquguqukayo. Iziphumo ezibonisiweyo zisekwe kwidatha yokugqibela efumanekayo kuguqulelo ngalunye.

I-AM PEF (L / min) Isiseko

341

338

342

339

355

Utshintsho olusisiseko

35

28

9

-9

-18

PM PEF (L / min) Isiseko

351

348

357

354

369

Utshintsho olusisiseko

3. 4

26

7

-7

-18

Ukusetyenziswa kohlangulo lweAlbuterol

Isiseko

2.1

2.3

2.7

.5

2.4

Utshintsho olusisiseko

-1.0

-1.5

-0.8

-0.3

0.8

Umndilili wenqaku leempawu / ngosuku (isikali se-0-3)

Isiseko

0.99

1.03

1.04

1.04

1.08

Utshintsho olusisiseko

-0.28

-0.32

-0.14

-0.05

0.10

Impembelelo yesifo se-asthma kumgangatho wobomi obunxulumene nezempilo wavavanywa ngokusetyenziswa kweMigangatho ye-Asthma esemgangathweni yeMibuzo yoBomi (i-AQLQ (S)) (esekwe kwinqanaba lamanqaku ayi-7 apho i-1 = ukuphazamiseka okuphezulu kunye ne-7 = hayi ukukhubazeka). Izigulana ezifumana i-budesonide kunye ne-formoterol fumarate dihydrate i-160 / 4.5 ibinokuphuculwa okubonakalayo ekliniki kumgangatho wobomi othile, njengoko kuchaziwe ngumahluko ophakathi kwamaqela onyango lwe- 0.70 [95% CI 0.47, 0.93], xa kuthelekiswa ne-placebo).

Isifundo 2: Ufundisiso lweklinikhi kunye neBudesonide kunye neFomoterol Fumarate Dihydrate 80 / 4.5

Olu phononongo lweeveki ezili-12 lwalufana noyilo kwiSifundo 1, kwaye lubandakanya abaguli abangama-480 abaneminyaka eli-12 ubudala nangaphezulu. Olu phononongo luthelekise i-budesonide kunye ne-formoterol fumarate dihydrate 80 / 4.5, budesonide 80 mcg, formoterol 4.5 mcg, kunye ne-placebo; nganye ilawulwa njenge-inhalations ezi-2 kabini ngemini. Uphononongo lubandakanya ixesha lokuqhutywa kwe-placebo yeeveki ezi-2. Uninzi lwezigulana zazinesifo sombefu esimnene ukuya kumodareyitha kwaye zazisebenzisa amathamo asezantsi ukuya kumodareyitha e-inhaled corticosteroids ngaphambi kokufunda. Iipesenti ezichaziweyo ezixelwe kwangaphambili nge-FEV1kwisiseko sasiyi-71.3% kwaye sasifana kumaqela onyango. Ukusebenza ngokuguquguqukayo kunye neendawo zokugqibela zazifana nezo zikwisifundo 1.

Ipesenteji yezigulana ezirhoxayo ngenxa okanye yokuhlangabezana neekhrayitheriya ezichaziweyo zokuba mandundu kwesifo sombefu ibonakalisiwe kwiTheyibhile 6. Indlela yovavanyo kunye neendlela ezisetyenziswayo zazifana naleyo kwiSifundo 1.

Itheyibhile 6 Inani kunye nepesenti yezigulana ezirhoxayo ngenxa yokuhlangana okanye yokuhlangabezana neekhrayitheriya ezichaziweyo zokuba mandundu kwesifuba (Study 2)
*
Ezi khrayitheriya zavavanywa yonke imihla ngaphandle kwexesha lokutyelelwa kweklinikhi, ngaphandle kwe-FEV1, eyavavanywa kutyelelo ngalunye lweklinikhi.
& ikrele;
Iikhrayitheriya zomntu ngamnye zibonisiwe kwizigulana ezihlangabezana nawo nawuphi na umsitho wesifuba esichazwe kwangaphambili, nokuba imeko ithathe njani.
& Dagger;
Ukuchongwa kwexesha lokuvuka ebusuku ngenxa yesifuba, izigulana zavunyelwa ukuba zihlale kwisifundo ngokokubona komphenyi ukuba akukho nanye kwezi ndlela zafikelelwayo.

IBudesonide kunye neFomoterol Fumarate Dihydrate

80 / 4.5

(n = 123)

IBudesonide

80 mcg

(n = 121)

Ifomoterolol

4.5 mcg

(n = 114)

Iplacebo

(n = 122)

Izigulana zirhoxisiwe ngenxa yesiganeko sombefu esichazwe kwangaphambili *

Umanqaku 9 (7.3)

Isi-8 (6.6)

21 (18.4)

40 (32.8)

Izigulana ezinesiganeko sombefu esichazwe kwangaphambili * , & ikrele;

Izimvo eziyi-23 (18.7)

26 (21.5)

Amanqaku angama-48 (42.1)

I-69 (56.6)

Ukuncipha kwi-FEV1

3 (2.4)

Isi-3 (2.5)

I-11 (9.6)

Umanqaku 9 (7.4)

Ukusetyenziswa kwamayeza okuhlangula

1 (0.8)

Isi-3 (2.5)

1 (0.9)

Isi-3 (2.5)

Ukuncipha kwi-AM PEF

3 (2.4)

1 (0.8)

Isi-8 (7.0)

Ishumi elinanye (11.5)

Ukuvuka ebusuku & Dagger;

Umanqaku 17 (13.8)

Amashumi amabini (16.5)

31 (27.2)

Ngama-52 (42.6)

Ukunyuka kwezonyango

1 (0.8)

Isi-3 (2.5)

Isihlanu (4.4)

Amashumi amabini (16.4)

Kuthetha utshintsho lweepesenti ukusuka kwisiseko kwi-FEV yangaphambi kwethamo1ngaphezulu kweeveki ezili-12 zibonisiwe kuMzobo 2.

Umzobo 2 uthetha ukutshintsha kwepesenti ukusuka kwisiseko kwi-pre-dose FEV1Ngaphezulu kweeveki ezili-12 (Isifundo 2)

Iziphumo zokusebenza kwezinye iindawo zokuphela kwesibini, kubandakanya umgangatho wobomi, zazifana nezo zibonwe kwiSifundo 1.

Ukuseta kunye nexesha lokuSebenza kunye nokuqhubela phambili koPhuculo kuLawulo lwe-Asthma

Ukuqala kwesenzo kunye nokuqhubela phambili kokuphuculwa kolawulo lwesifuba kwavavanywa kwizifundo ezibini ezibalulekileyo zeklinikhi. Ixesha eliphakathi ukuqala konyango olubalulekileyo lwe-bronchodilation (> 15% yokuphuculwa kwe-FEV1) yabonwa kwisithuba semizuzu eli-15. Ukuphuculwa okuphezulu kwi-FEV1yenzekile ngaphakathi kweeyure ze-3, kwaye ukuphuculwa okubalulekileyo kwezonyango kwagcinwa ngaphezulu kweeyure ezili-12. Amanani 3 no-4 abonisa utshintsho lweepesenti ukusuka kwisiseko kwi-post-dose FEV1ngaphezulu kweeyure ezili-12 ngosuku lokhetho kunye nosuku lokugqibela lonyango lweSifundo 1.

Ukuncitshiswa kweempawu zesifuba kunye nokusetyenziswa kokuhlangulwa kwe-albuterol, kunye nokuphuculwa kwentsasa nangorhatya lwe-PEF, kwenzeka ngaphakathi kosuku lwe-1 lwedosi yokuqala ye-budesonide kunye ne-formoterol fumarate dihydrate; Ukuphuculwa kwezi zinto zixabisekileyo kwagcinwa ngaphezulu kweeveki ezili-12 zonyango.

Ukulandela idosi yokuqala ye-budesonide kunye nefomoterol fumarate dihydrate, FEV1iphuculwe ngokuphawulekayo ngexesha leeveki zokuqala ze-2 zonyango, yaqhubeka ibonisa ukuphucula kwiVeki ye-6 yokuvavanywa, kwaye yagcinwa ngeVeki ye-12 kwizifundo zombini.

Akukho kuncitshiswa kwisiphumo seyure ye-12 ye-bronchodilator esibonwe kunye ne-budesonide kunye ne-formoterol fumarate dihydrate 80 / 4.5 okanye i-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5, njengoko kuvavanyiwe yi-FEV1, emva kweeveki ezili-12 zonyango okanye kutyelelo lokugqibela olukhoyo.

FEV1Idatha evela kuFundo lwe-1 yokuvavanya i-budesonide kunye ne-formoterol fumarate dihydrate i-160 / 4.5 ibonakalisiwe kwi-3 kunye ne-4.

Umzobo 3 uthetha ukutshintsha kwepesenti ukusuka kwisiseko kwi-FEV1Ngomhla woLungiso (iSifundo 1)

Umzobo 4 uthetha ukutshintsha kwepesenti ukusuka kwisiseko kwi-FEV1Ekupheleni Konyango (Isifundo 1)

Izigulana ezine-asthma 6 ukuya ngaphantsi kweminyaka eyi-12 ubudala

Inkqubo yeklinikhi yokuxhasa ukusebenza kwe-budesonide kunye ne-formoterol fumarate dihydrate i-80 / 4.5 kubantwana abaneminyaka engaphantsi kwe-12 ubudala ibandakanya oku kulandelayo: 1) isifundo se-budesonide idiploma yokuqinisekisa, Ukusebenza ngokukuko kunye nokufunda kokhuseleko kwe-budesonide kunye ne-formoterol fumarate dihydrate yemveliso yokudibanisa.

Ukukhethwa kwe-budesonide 80 mcg kuxhaswe yiveki ye-6, engacwangciswanga, engaboniyo, elawulwa nge-placebo kwizigulana ezingama-304 zabantwana (152 budesonide, 152 placebo) 6 ukuya ngaphantsi kweminyaka eli-12 ubudala yesifuba. Iziphumo zabonisa ukuba i-budesonide 80 mcg (i-2 inhalations kabini yonke imihla) ibonelele ngokuphucuka okukhulu ngokuthelekiswa ne-placebo kwindawo yokugqibela yenguqu ukusuka kwisiseko ukuya kunyango lwe-avareji kwinyanga yangaphambi kwethamo le-PEF kunye nendawo yokugqibela yesiphelo yotshintsho kwidosi yangaphambi kusasa FEV1. Ukukhethwa kwethamo le-formoterol kuxhaswa kukungalawuleki, idosi enye, elawulwa yi-placebo, elawulwa ngokusebenzayo (Foradil Aerolizer 12 mcg), 5-indlela yokuwela ngaphaya kokufunda apho iidosi ze-2.25, 4.5 kunye ne-9 mcg formoterol zazilawulwa ngokudibeneyo ne-budesonide kwizigulana ezingama-54 zabantwana ezi-6 ukuya ngaphantsi kweminyaka eyi-12 ubudala ene-asthma. Iziphumo zabonisa impendulo yedosi ye-formoterol xa kuthelekiswa ne-placebo yesiphelo se-FEV1I-avareji yeeyure ezili-12 zedosi yasemva kwexesha kunye neqela le-9 mcg libonise iziphumo ezifanayo ngokuthelekiswa nolawulo olusebenzayo.

Isifundo sokusebenza ngokukuko sasiyiveki ye-12, engenamsebenzi, engaboni kabini, yokufunda okuninzi apho i-budesonide kunye ne-formoterol fumarate dihydrate i-80 / 4.5 yayithelekiswa ne-budesonide pMDI 80 mcg, nganye ilawulwa njenge-inhalation ezi-2 kabini yonke imihla, kwizigulana ze-184 zabantwana engaphantsi kweminyaka eli-12 ubudala ene-diagnostic yeklinikhi ebhaliweyo. Ekungeneni kwetyala, abantwana babenemfuno yoluhlu lweedosi eziphakathi zemihla ngemihla zokungenisa unyango lwe-corticosteroid okanye indibaniselwano enganyangekiyo yonyango lwe-corticosteroid kunye nonyango lwe-LABA, kwaye babonakalise iimpawu ngaphandle konyango olunedosi ephantsi ye-inhaled corticosteroid ngexesha le-2 ukuya kwi-4 yeveki yexesha lokubaleka . Umahluko ophambili wokusebenza ngempumelelo yayilutshintsho ukusuka kwisiseko ukuya kwiVeki ye-12 kwiklinikhi yokulinganisa i-1-iyure yethamo emva kwedosi ye-FEV1. Kwizigulana ezifumana i-budesonide kunye ne-formoterol fumarate dihydrate 80 / 4.5, kwabakho utshintsho olubalulekileyo ngokweenkcukacha-manani xa kuthelekiswa ne-budesonide kwiyure-1 yedosi yedosi ye-FEV1ephucule nge-0.28 L ukusuka kwisiseko ukuya kwiVeki ye-12, xa kuthelekiswa ne-0.17 L yabo bafumana i-budesonide 80 mcg (umahluko ophakathi kwe-0.12 L; 95% CI: 0.03, 0.20) (jonga Umzobo 5).

Umzobo 5 Utshintsho olususela kwisiseko kwiklinikhi-ilinganiswe ngeyure e-1 yethamo ledosi ye-FEV1ngaphezulu kweeveki ezili-12 (ukuSebenza ngokuFunda noKhuseleko kwizigulana ezinesi-6 ukuya ngaphantsi kweminyaka eli-12 ubudala).

Kwangokunjalo, ukuphuculwa kwaqwalaselwa kutshintsho ukusuka kwisiseko ukuya kwiVeki ye-12 yeyure ye-1 yeeyure zeklinikhi emva kwethamo (umahluko ophakathi kwe-25.5 L / min; 95% CI: 10.9, 40.0). Iziphumo ze-Bronchodilatory zabonakala kuvavanyo lokuqala kwimizuzu ye-15 ngosuku lwe-1 kwaye zigcinwa kwiVeki ye-12. Iklinikhi yethamo i-FEV1 yayiyi-0.10 L (95% CI: 0.02, 0.18). Akukho mahluko phakathi kwe-budesonide kunye ne-formoterol fumarate dihydrate kunye ne-budesonide yaqatshelwa ekuvuseleleni ebusuku, ukuhlangula ukusebenzisa i-albuterol, okanye amanqaku emibuzo yemibuzo nge-Asthma ye-Asthma ye-Life Questionnaire (PAQLQ). Umyinge wezigulana ubuncinci zokuphuculwa kwamanqaku e-0.5 ukusuka kwisiseko ukuya kwiVeki ye-12 kwi-PAQLQ yayiyi-42% kwi-budesonide kunye ne-formoterol fumarate dihydrate 80 / 4.5 kunye ne-46% kwi-budesonide 80 mcg.

Ukhuseleko lweNtengiso kunye noFundo ngokuSebenza

Iqela elingacwangciswanga, elingaboniyo kabini, elilinganayo-iqela, isifundo sokhuseleko xa kuthelekiswa i-budesonide kunye ne-formoterol fumarate dihydrate kunye ne-budesonide, nganye ilawulwa njenge-2 inhalations kabini yonke imihla ngaphezulu kweeveki ezingama-26 (NCT01444430). Injongo ephambili yokhuseleko yayikukuvavanya ukuba ngaba ukongezwa kwefomoterol kunyango lwe-budesonide (i-budesonide kunye ne-formoterol fumarate dihydrate) yayingeyonto iphantsi kune-budesonide ngokubhekisele kumngcipheko weziganeko ezinxulumene nesifuba (ukulaliswa esibhedlele okunxulumene ne-asthma, i-endotracheal intubation, kunye nokufa ). Uphononongo lwaluyilelwe ukukhupha umda wengozi echazwe kwangaphambili yeziganeko ezinzulu ezinxulumene nesifuba se-2.0. Ikomiti yokugweba engaboniyo igqibe ukuba ngaba iziganeko zinxulumene ne-asthma.

Olu phononongo lubhalise abaguli abaneminyaka eli-12 ubudala nangaphezulu, abanesifo se-asthma okungenani unyaka omnye, kwaye ubuncinci be-asthma exacerbation efuna unyango nge-systemic corticosteroids okanye isibhedlele esihambelana nesifuba kunyaka ophelileyo. Izigulana zabethelelwa kwelinye lamanqanaba amabini edosi ye-budesonide kunye ne-formoterol fumarate dihydrate okanye i-budesonide esekwe kuvavanyo lolawulo lwe-asthma kunye nonyango lwe-asthma oluqhubekayo. Izigulana ezinembali ye-asthma esongela ubomi azifakwanga. Uphononongo lubandakanya izigulana ze-11,693 [5846 ezifumana i-budesonide kunye ne-formoterol fumarate dihydrate (80 / 4.5 okanye 160 / 4.5) kunye ne-5847 efumana i-budesonide (80 okanye i-160 mcg)], abaneminyaka yobudala engama-44, kwaye i-66% yabo yayingamabhinqa kunye ne-69 % ibingabantu baseCaucasus.

I-Budesonide kunye ne-formoterol fumarate dihydrate yayingeyonto iphantsi kwi-budesonide ngokwexesha ukuya kwiziganeko zokuqala ezinxulumene nesifuba ngokubhekisele kumda ochaziweyo wangaphambili, kunye nomyinge weengozi we-1.07 [95% CI: 0.70, 1.65] (Itheyibhile 7 ).

Itheyibhile 7 Iziganeko ezinxulumene ne-Asthma (Ukhuseleko emva kokuThengisa kunye nokuSebenza ngokukuko)
*
N = lilonke inani lezigulana
& ikrele;
n = inani lezigulana ezinomsitho
& Dagger;
Umyinge weengozi wexesha ukuya kumnyhadala wokuqala wawusekwe kwimodeli yokwahlulahlulwa kwe-Cox engalinganiyo yonyango kunye ne-covariates yonyango (i-budesonide kunye ne-formoterol fumarate dihydrate vs. Ukuba uqikelelo oluphezulu lwe-95% ye-CI yomngcipheko ubukhona<2.0, then non-inferiority was concluded.
§
Ukulaliswa esibhedlele okunxulumene nesifuba, i-endotracheal intubation, okanye ukufa okwenzeke kwiinyanga ezi-6 emva kokusetyenziswa kokuqala kwesiyobisi okanye kwiintsuku ezisi-7 emva komhla wokugqibela weziyobisi, nangawuphi na umhla owawusemva koko. Izigulana zinokuba nesiganeko esinye okanye nangaphezulu, kodwa kuphela sisiganeko sokuqala esabalelwa uhlalutyo. Ikomiti eyodwa, eyimfama, ezimeleyo yokugweba ichonge ukuba ingaba imicimbi inxulumene nesifuba na.

IBudesonide kunye neFomoterol Fumarate Dihydrate

(N * = 5846)

n & ikrele; (%)

IBudesonide (N * = 5847)

n & ikrele; (%)

IBudesonide kunye neFomoterolum Fumarate Dihydrate vs.Budesonide Hazard ratio (95% CI) & Dagger;

Umnyhadala obalulekileyo onxulumene nesifuba §

Isi-43 (0.7)

40 (0.7)

I-1.07 (0.70, 1.65)

Ukufa okunxulumene nesifuba

2 (<0.1)

0

I-asthma enxulumene ne-endotracheal intubation

1 (<0.1)

0

Isibhedlele esinxulumene nesifuba

42 (0.7)

40 (0.7)

Isiphelo sokusebenza esisisiseko sokwanda kwesifo sombefu, esichazwa njengokwehla kwesifo sombefu esikhokelele ekusetyenzisweni kwenkqubo ye-corticosteroids ubuncinci iintsuku ezi-3, okanye ukulaliswa esibhedlele, okanye kwigumbi likaxakeka elindwendwela igumbi elifuna inkqubo yecorticosteroids. Umyinge weengozi oqikelelweyo wexesha ukuya kwinqanaba lokuqala lokukhula kwesifuba kwi-budesonide kunye ne-formoterol fumarate dihydrate xa kuthelekiswa ne-budesonide yayingu-0.84 [95% CI: 0.75, 0.94]. Esi siphumo siqhutywa ikakhulu kukuncitshiswa kwenkqubo yokusetyenziswa kwecorticosteroid.

Isifo esingapheliyo sePulmonary Disease

Umsebenzi wemiphunga

Ukusebenza kwe-budesonide kunye ne-formoterol fumarate dihydrate i-80 / 4.5 kunye ne-budesonide kunye ne-formoterol fumarate dihydrate i-160 / 4.5 kunyango lokugcinwa kokuthintelwa kokuhamba komoya kwizigulana ze-COPD kuvavanywe kwizifundo zamazwe aphesheya ezilawulwa ngokungekho mthethweni, ezingaboniyo kabini, ezenziwa ngaphezulu kweenyanga ezi-6. (Isifundo 1) kunye neenyanga ezili-12 (Isifundo 2), zizonke izigulana ezingama-3668 (amadoda angama-2416 kunye nabasetyhini abangama-1252). Uninzi lwezigulana (iipesenti ezingama-93) zazingabantu baseCaucasus. Zonke izigulana zacelwa ukuba ubuncinci zineminyaka engama-40 ubudala, zine-FEV1Ngaphantsi okanye ulingane nama-50% axeliweyo, ukufumanisa isifo kwiCOPD eneempawu zeminyaka emi-2 ubuncinci, kunye nembali yokutshaya ubuncinci iminyaka eli-10 yokupakisha, ngaphambi kokungena kulingo. Intsingiselo ye-prebronchodilator FEV1kwisiseko sezigulana ezibhalise kwisifundo kwakuqikelelwe i-34%. Amashumi amane anesibhozo eepesenti abaguli ababhalisiweyo babekwi-inhalled i-corticosteroids kwaye i-52.7% yezigulana zikwi-bronchodilators ye-anticholinergic emfutshane ngexesha lokubaleka. Kwi-randomization, i-corticosteroids enganyangekiweyo yapheliswa, kwaye i-ipratropium bromide yavunyelwa kwidosi ezinzileyo kwabo baguli babephathwa ngaphambili nge-anticholinergic bronchodilators. Izinto ezisisiseko zokusebenza ngokusempumeleleni kwezi zifundo zombini yayilutshintsho olususela kwisiseko sedosi yangaphambi kunye nedosi yasemva kwexesha ye-FEV1Ngexesha lonyango. Iziphumo zozibini zezifundo 1 kunye no-2 zichaziwe apha ngezantsi.

Isifundo 1

Le yayiyinyanga ye-6, isifundo esilawulwa yi-placebo sezigulana ze-1704 zeCOPD (kuthetha ukuba% yaxela kwangaphambili nge-FEV1kwisiseko esisukela kwi-33.5% -34.7%) eqhutywa ukubonisa ukusebenza kunye nokhuseleko lwe-budesonide kunye ne-formoterol fumarate dihydrate kunyango lokuthintela ukuhamba komoya kwi-COPD. Izigulana zazingeniswa kwelinye lala maqela onyango alandelayo: i-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5 (n = 277), budesonide kunye ne-formoterol fumarate dihydrate 80 / 4.5 (n = 281), budesonide 160 mcg + formoterol 4.5 mcg (n = 287), budesonide 160 mcg (n = 275), formoterol 4.5 mcg (n = 284), okanye placebo (n = 300). Izigulana ezifumana i-budesonide kunye ne-formoterol fumarate dihydrate i-160 / 4.5, i-inhalations ezimbini kabini imihla ngemihla, ibinokuphucuka okubaluleke kakhulu ukusuka kwisiseko kwi-pre-dose FEV1I-avareji ngaphezulu kwexesha lokunyanga [0.08 L, 10.7%] xa kuthelekiswa nefomoterol 4.5 mcg [0.04 L, 6.9%] kunye ne-placebo [0.01 L, 2.2%] (jonga umfanekiso 6). Izigulana ezifumana i-budesonide kunye ne-formoterol fumarate dihydrate 80 / 4.5, inhalations ezimbini kabini imihla ngemihla, khange zibenokuphucuka okukhulu ukusuka kwisiseko kwi-pre-dose FEV1I-avareji yexesha lokunyanga ngokuthelekiswa nefomoterol 4.5 mcg.

Umzobo 6 uthetha ukutshintsha kwepesenti ukusuka kwisiseko kwi-pre-dose FEV1ngaphezulu kweenyanga ezi-6 (Isifundo 1)

Izigulana ezifumana i-budesonide kunye ne-formoterol fumarate dihydrate i-160 / 4.5, i-inhalations ezimbini kabini imihla ngemihla, ibinokuphucuka okubaluleke kakhulu ukusuka kwisiseko se-1-iyure yethamo le-FEV1I-avareji ngaphezulu kwexesha lokunyanga [0.20 L, 22.6%], xa kuthelekiswa ne-budesonide 160 mcg [0.03 L, 4.9%] kunye ne-placebo [0.03 L, 4.1%] (jonga Umzobo 7).

Umzobo 7 uthetha ukutshintsha kwepesenti ukusuka kwisiseko kwi-1-iyure yethamo le-FEV1Ngaphezulu kweenyanga ezi-6 (Isifundo 1)

Isifundo 2

Le nto yayiyi-12-inyanga, isifundo esilawulwa yi-placebo se-COPD yezigulane ze-1964 (kuthetha ukuba% ixela i-FEV1kwisiseko esisukela kwi-33.7% -35.5%) eqhutywa ukubonisa ukusebenza kunye nokhuseleko lwe-budesonide kunye ne-formoterol fumarate dihydrate kunyango lokuthintela ukuhamba komoya kwi-COPD. Izigulana zazingeniswa kwelinye lala maqela onyango alandelayo: i-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5 (n = 494), budesonide kunye ne-formoterol fumarate dihydrate 80 / 4.5 (n = 494), formoterol 4.5 mcg (n = 495), okanye indawo (n = 481). Izigulana ezifumana i-budesonide kunye ne-formoterol fumarate dihydrate i-160 / 4.5, i-inhalations ezimbini kabini imihla ngemihla, zinokuphucuka okukhulu ukusuka kwisiseko kwi-pre-dose FEV1I-avareji ngaphezulu kwexesha lokunyanga [0.10 L, 10.8%] xa kuthelekiswa nefomoterol 4.5 mcg [0.06 L, 7.2%] kunye ne-placebo [0.01 L, 2.8%]. Izigulana ezifumana i-budesonide kunye ne-formoterol fumarate dihydrate 80 / 4.5, inhalations ezimbini kabini imihla ngemihla, khange zibenokuphucuka okukhulu ukusuka kwisiseko kwi-pre-dose FEV1I-avareji yexesha lokunyanga ngokuthelekiswa nefomoterol. Izigulana ezifumana i-budesonide kunye ne-formoterol fumarate dihydrate i-160 / 4.5, i-inhalations ezimbini kabini imihla ngemihla, ikwanokuphucuka okubalulekileyo ukusuka kwisiseko kwi-1-yure yethamo le-FEV1I-avareji ngaphezulu kwexesha lokunyanga [0.21 L, 24.0%] xa kuthelekiswa ne-placebo [0.02 L, 5.2%].

Uthotho lwe-FEV1Amanyathelo ngaphezulu kweeyure ze-12 afunyenwe kwiseti yezigulana kwiSifundo 1 (n = 99) kunye noFundo 2 (n = 121). Ixesha eliphakathi ukuqala kwe-bronchodilation, echazwe njenge-FEV1ukwanda kwe-15% okanye ngaphezulu ukusuka kwisiseko, kwenzeka kwimizuzu emi-5 emva kwethamo. Ukuphuculwa okuphezulu (kubalwa njengotshintsho oluphakathi ukusuka kwisiseko kwindawo nganye yexesha) kwi-FEV1yenzeke malunga neeyure ezi-2 zedosi yasemva kwethamo.

Kuzo zombini iZifundo 1 kunye ne-2, ukuphuculwa kokuphela kokuphela kokuphuma kokuphuma kokuphefumla kunye nokuncitshiswa kokusetyenziswa kwamayeza okusindisa kwakuxhasa ukusebenza kwe-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5.

Ukunyuka

Izifundo ze-3 kunye ne-4 zazenzelwe ngokukodwa ukuvavanya isiphumo se-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5 kukonyuka kwe-COPD.

Isifundo 3

Le yayiyinyanga ye-6, isifundo solawulo esisebenzayo esenziwe ukuvavanya isiphumo se-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5 xa kuthelekiswa nefomoterolol 4.5 mcg, nganye ilawulwa njenge-2 inhalations kabini yonke imihla, kwinqanaba lokumodareyitha kunye nokuqina kwe-COPD. Ukunyuka kweCOPD kwachazwa njengokuwohloka kweempawu ezi-2 okanye ezingaphezulu (i-dyspnea, ivolumu yesikhohlela, umbala wesikhohlela / ubushushu) okanye ukonakala kwaso nasiphi na isibonakaliso esi-1 esikhulu kunye nobuncinci beempawu ezincinci: umqala obuhlungu, umkhuhlane (ukuphuma kwempumlo kunye / okanye Ukuxinana ngeempumlo), umkhuhlane ngaphandle kwesizathu, ukukhohlela okwandileyo okanye ukunyuka kwamavili ubuncinci iintsuku ezi-2 zilandelelana. Ukunyanzelwa kwe-COPD kwathathelwa ingqalelo yobukrelekrele obuphakathi ukuba unyango lweempawu zenkqubo ye-corticosteroids (≧ iintsuku ezi-3) kunye / okanye ii-antibiotics zazifuneka, kwaye zazithathwa njengezinzima xa kufuneka isibhedlele. Uphononongo olwenziwe ngokulandelelana kwezifundo ezili-1219 ukuya kwi-budesonide kunye ne-formoterol fumarate dihydrate i-160 / 4.5 (606) kunye ne-formoterol 4.5 mcg (613) apho i-57% yayingamadoda kwaye i-92% yayiyi-Caucasian. Babeneminyaka engama-64 ubudala kunye nembali yokutshaya yeminyaka engama-39, kunye ne-46% echongwe njengabantu abatshayayo ngoku. Ekubalekeni, kuthetha ukuba i-post-bronchodilator% yaxela kwangaphambili i-FEV eqhelekileyo1yayiyi-48.7% (uluhlu: 16.0% ukuya kwi-78.1%), kwaye abaguli babenembali ubuncinci bokukhula kweCOPD kunyaka ophelileyo baphathwa ngenkqubo ye-corticosteroids kunye / okanye esibhedlele. Zonke izifundo zaphathwa nge-budesonide kunye ne-formoterol fumarate dihydrate i-160 / 4.5, inhalations ezimbini kabini yonke imihla ngexesha le-4-yeveki yokubaleka ngaphambi kokunikwa unyango lwetyala.

Isifundo 4

Le yayiyinyanga ye-12, isifundo solawulo esisebenzayo esabandakanya izifundo ze-811 eziphathwe nge-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5 okanye i-formoterol 4.5 mcg, nganye ilawulwa njenge-2 inhalations kabini yonke imihla. Uphononongo lwenziwe ukuvavanya ukunciphisa kwe-COPD kwizigulana ezine-COPD. Ukunyanzelwa kweCOPD kwachazwa njengokuwohloka kweCOPD efuna ikhosi ye-steroids yomlomo kunyango kunye / okanye esibhedlele. Olu phononongo lucwangcise izifundo ezingama-407 ukuya kwi-budesonide kunye ne-formoterol fumarate dihydrate i-160 / 4.5 kunye ne-404 ukuya kwi-formoterol 4.5 mcg apho i-61% yayingamadoda kwaye i-83% yayiyi-Caucasian. Babeneminyaka engama-63 ubudala kunye nembali yokutshaya yeminyaka engama-45, kunye nama-36% abonwa njengabantu abatshayayo ngoku. Ekubalekeni, kuthetha ukuba i-post-bronchodilator% yaxela kwangaphambili i-FEV eqhelekileyo1yayiyi-37.8% (uluhlu: 11.75% ukuya kuma-76.50%), kunye nembali ubuncinci bokukhula kweCOPD kunyaka ophelileyo waphathwa ngenkqubo ye-corticosteroids kunye / okanye i-antibiotics.

Kwisifundo 3, izifundo eziphathwe nge-budesonide kunye ne-formoterol fumarate dihydrate i-160 / 4.5, inhalations ezimbini kabini imihla ngemihla zazinomgangatho ophantsi kakhulu wokuqina / okomeleleyo we-COPD xa kuthelekiswa nefomoterol 4.5 mcg ngonciphiso lwe-26% (95% CI: 9% Iipesenti ezingama-39. Kwisifundo 4, izinga eliphantsi kakhulu lokunyuka konyaka liye labonwa nakwizifundo eziphathwe nge-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5 xa kuthelekiswa ne-formoterol 4.5 mcg ngokuncitshiswa kwe-35% (95% CI: 20%, 47%) (Itheyibhile 8).

Itheyibhile 8 UkuThintelwa kweZifo eziNgapheliyo zeSifo seMiphunga
n Uqikelelo lweRhafu yoNyaka Umyinge wenqanaba iBudesonide kunye neFomoterolum Fumarate Dihydrate 160 / 4.5 vs. IFomoterol 4.5 mcg

Unyango

Qikelela

95% CI

Isifundo 3

IBudesonide kunye neFomoterol Fumarate Dihydrate 160 / 4.5

606

0.94

0.74

0.61, 0.91

Ifomoterol 4.5 mcg

613

1.27

Isifundo 4

IBudesonide kunye neFomoterol Fumarate Dihydrate 160 / 4.5

404

0.68

0.65

0.53, 0.80

Ifomoterol 4.5 mcg

403

1.05

n - Inani lezigulana ezibandakanyiweyo kuseto lokusebenza ngempumelelo.

Umgangatho wobomi obunxulumene nempilo walinganiswa kusetyenziswa iphepha lemibuzo eliphefumlelweyo laseSt.

Kwisifundo 3, amaqondo abaphenduli be-SGRQ kwiinyanga ezi-6 (ezichazwe njengophuculo lwamanqaku e-4 okanye nangaphezulu njengombundu) yayiyi-40% kunye ne-33% ye-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5 kunye ne-formoterol 4.5 mcg, ngokulandelelana, nge Umyinge we-1.5 (95% CI: 1.0, 2.0) ye-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5 vs. formoterol 4.5 mcg. Kwisifundo 4, iqondo lokuphendula kwiinyanga ezili-12 yayiyi-50% kunye ne-49% ye-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5 kunye ne-formoterol 4.5 mcg, ngokwahlukeneyo, kunye nomyinge we-1.0 (95% CI: 0.8, 1,4) I-budesonide kunye ne-formoterol fumarate dihydrate 160 / 4.5 vs. formoterol 4.5 mcg.

Unikezo / ugcino kunye nokusingathwa

IBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION I-AEROSOL iyafumaneka ngamandla amabini kwaye inikwa ngokobungakanani beepakethe ezilandelayo:

Iifom zedosi kunye namandla

Ubungakanani bePakethe

I-NDC

I-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL

80 / 4.5

Inhalations ezili-120

0310-7372-20

I-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL

160 / 4.5

Inhalations ezili-120

0310-7370-20

Amandla onke anikezelwa njengesixhobo se-aluminium esicinezelekileyo kunye nesixhobo sokubala esiqhotyoshelweyo, umzimba obomvu weplastikhi enomlomo omhlophe, kunye nesiciko sothuli esimnyama. Ikhonkco nganye ye-inhalation eyi-120 ine-net yokugcwalisa ubunzima be-10.2 yeegram. Ibhokisi nganye yentsimbi ipakishwe kwifoyile engaphezulu kwesingxobo se-desiccant kwaye ibekwe ebhokisini. Ibhokisi nganye iqulethe ibhokisi enye kunye nephetshana loLwazi lweMonde.

Ibhokisi ye-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL kufuneka isetyenziswe kuphela kwi-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL actuator, kunye ne-BUDESONIDE ne-FORMOTEROL FUMARATE FUMARATE DIHYDRATE.

Inani elichanekileyo lamayeza kwi-inhalation nganye ayinakuqinisekiswa emva kokuba inani elinelebhileyo le-inhalation evela kwi-canister sele lisetyenzisiwe, nangona i-inhaler isenokungaziva ingenanto ngokupheleleyo kwaye ingaqhubeka nokusebenza. I-inhaler kufuneka ilahlwe xa inani elinelebhile le-inhalation lisetyenzisiwe okanye kwiinyanga ezi-3 emva kokususwa kwisingxobo se-foil. Ungaze utywilisele ibhokisi emanzini ukumisela isixa esisele kwisitya (uvavanyo lokudada).

Gcina kubushushu begumbi elilawulwayo ama-20 ° C ukuya kuma-25 ° C (68 ° F ukuya kuma-77 ° F) [jonga iUSP]. Gcina inhaler ngomlomo phantsi.

Ukufumana iziphumo ezilungileyo, i-canister kufuneka ibe kwiqondo lokushisa ngaphambi kokusebenzisa. Shake kakuhle imizuzwana emi-5 ngaphambi kokuyisebenzisa.

Gcina kude nokufikelela kwabantwana. Kuphephe ukutshiza emehlweni.

OKUQULATHIWEYO PHANTSI KWENGCINEZELELO.

Musa ukugqobhoza okanye ukutshisa. Musa ukugcina kufutshane nobushushu okanye idangatye elivulekileyo. Ukuchazwa kumaqondo obushushu angaphezu kwe-120ºF kunokubangela uqhushumbo. Ungaze uphose isikhongozeli emlilweni okanye kwisitovu.

Ulwazi ngeNgcebiso ngezigulana

Cebisa isigulana ukuba sifunde iilebheli ezivunyiweyo ze-FDA (Ulwazi loMonde kunye neMiyalelo yokuSebenzisa).

Iziganeko ezinxulumene ne-Asthma:Yazisa abaguli abane-asthma ukuba i-LABA xa isetyenziselwa yodwa yonyusa umngcipheko wokulaliswa esibhedlele okanye isifo esihlobene nesifuba. Idatha efumanekayo ibonisa ukuba xa i-ICS kunye ne-LABA zisetyenziswa kunye, ezinjenge-budesonide kunye ne-formoterol fumarate dihydrate, akukho lonyuko lubalulekileyo lomngcipheko wezi ziganeko.

Ayisiyo yeempawu eziQatha:Yazisa abaguli ukuba i-budesonide kunye ne-formoterol fumarate dihydrate ayenzelwanga ukuba inciphise iimpawu ezibi ze-asthma okanye i-COPD kwaye amathamo ongezelelweyo akufuneki asetyenziselwe loo njongo. Ukucebisa abaguli ukuba baphathe iimpawu ezibi kunye ne-beta e-inhaled, emfutshane2-i -agonist efana nealbuterol. Nika abaguli amayeza anjalo kwaye ufundise isigulana ngendlela ekufuneka sisetyenziswe ngayo.

Yalela abaguli ukuba bafune unyango ngokukhawuleza ukuba bafumana oku kulandelayo:

Ukuncipha kokusebenza kwe-inhaled, ibeta emfutshane esebenza kancinci2-abaphikisi
Isidingo sokuphefumla okungaphezulu kunesiqhelo se-inhaled, beta emfutshane2-abaphikisi
Ukwehla okubonakalayo kokusebenza kwemiphunga njengoko kuchaziwe ngugqirha

Xelela abaguli ukuba mabangayeki unyango nge-budesonide kunye ne-formoterol fumarate dihydrate ngaphandle kokhokelo lukagqirha / lomboneleli kuba iimpawu zinokuphinda zibuye emva kokuyeka.

Sukusebenzisa iBeta eyongezelelweyo esebenza ixesha elide2-Agonists:Yalela abaguli ukuba bangasebenzisi enye i-LABA yesifuba kunye neCOPD.

Iziphumo zasekhaya:Yazisa abaguli ukuba usulelo lwasekhaya kunyeICandida albicansKwenzeka emlonyeni nakwipharynx kwezinye izigulana. Ukuba i-oropharyngeal candidiasis iyakhula, kufuneka inyangwe ngendlela efanelekileyo yasekhaya okanye yenkqubo (okt. ukongamela kwezonyango. Ukucoca umlomo ngamanzi ngaphandle kokuginya emva kokuphefumla kuyacetyiswa ukunciphisa umngcipheko we-thrush.

Ukukrala kwemiphunga:Izigulana ezineCOPD zinomngcipheko ophezulu wenyumoniya; uyalele ukuba banxibelelane nomboneleli wabo wezempilo ukuba ngaba bakhula neempawu zenyumoniya.

Uxinzelelo lwe-immune:Lumkisa abaguli abakwiidosi ze-corticosteroids zokuzikhusela kwisifo se-chicken pox okanye imasisi kwaye, ukuba sichaziweyo, qhagamshelana nogqirha wabo ngaphandle kokulibazisa. Yazisa abaguli malunga nokuba mandundu kwesifo sephepha esikhoyo, ukungunda, ibhaktiriya, intsholongwane, okanye isifo sosasazo, okanye ioyile i-herpes simplex.

Hypercorticism kunye noxinzelelo lweAdrenal:Cebisa abaguli ukuba i-budesonide kunye ne-formoterol fumarate dihydrate inokubangela ukuba inkqubo ye-corticosteroid ye-hypercorticism kunye noxinzelelo lwe-adrenal. Ukongeza, yazisa abaguli ukuba ukusweleka ngenxa yokusilela kwe-adrenal kwenzeke ngexesha nasemva kokudluliselwa kwenkqubo yecorticosteroids. Izigulana kufuneka zitshintshe kancinci ukusuka kwinkqubo yecorticosteroids ukuba idlulisela kwi-budesonide kunye nefomoterol fumarate dihydrate.

Ukuncitshiswa koxinano lwamaminerali eBone:Ukucebisa abaguli abasemngciphekweni owandisiweyo wokunciphisa i-BMD ukuba ukusetyenziswa kwe-corticosteroids kunokubangela umngcipheko owongezelelweyo.

Ukwanda kweVelocity yokuKhula:Yazisa abaguli abafakela i-corticosteroids ngomlomo, icandelo le-budesonide kunye ne-formoterol fumarate dihydrate, kunokubangela ukunciphisa ukukhula kwesantya xa kufakwa kwizigulana zabantwana. Oogqirha kufuneka balandele ngokusondeleyo ukukhula kwabantwana nakwishumi elivisayo abathatha ii-corticosteroids ngayo nayiphi na indlela.

Iziphumo zeOcular:Ukusetyenziswa kwexesha elide kwe-corticosteroids enganyangekiyo kunokwandisa umngcipheko weengxaki zamehlo (cataract okanye glaucoma); Cinga ngokuhlolwa kwamehlo rhoqo.

Umngcipheko ohambelana nonyango lweBeta-Agonist:Yazisa abaguli ngeziphumo ezibi ezinxulumene ne-beta2-agonists, ezinje ngee-palpitations, iintlungu zesifuba, ukubetha kwentliziyo ngokukhawuleza, ukungcangcazela, okanye ukoyika.

© AstraZeneca 2019

Yenzelwe i: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850

Ngu: AstraZeneca Dunkerque Production, Dunkerque, France

Imveliso yaseFrance

Ulwazi loMonde

IBUDESONIDE (i-bue-DES-oh-nide) Kunye neFOMOTEROL (ye-MOH-teh-rol)
(budesonide 80 mcg kunye nefomoterol fumarate dihydrate 4.5 mcg)

IBUDESONIDE (i-bue-DES-oh-nide) Kunye neFOMOTEROL (ye-MOH-teh-rol)
(budesonide 160 mcg kunye nefomoterol fumarate dihydrate 4.5 mcg)

Yintoni iBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL?

I-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION I-AEROSOL idibanisa iyeza le-corticosteroid (ICS), ibudesonide kunye ne-beta esebenza ixesha elide2-adrenergic agonist (LABA) yeyeza, formoterol.

Ukungenisa i-corticosteroids kunceda ukunciphisa ukuvuvukala kwimiphunga. Ukudumba emiphungeni kungakhokelela kwiingxaki zokuphefumla.
Amayeza e-LABA asetyenziswa kubantu abanesifo esinganyangekiyo semiphunga (COPD) kunye nesifuba. Amayeza e-LABA anceda izihlunu ezijikeleze i-airways kwimiphunga yakho ukuba ihlale ikhululekile ukunqanda iimpawu ezinjengokuvutha, ukukhohlela, ukuqina kwesifuba kunye nokuphefumla okufutshane. Ezi mpawu zinokwenzeka xa izihlunu ezijikeleze iindlela zomoya ziqina. Oku kwenza ukuba kubenzima ukuphefumla. Kwiimeko ezinzima, ukuvutha kungayeka ukuphefumla kwaye kunokukhokelela ekufeni ukuba awunyangwa kwangoko.

IBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION I-AEROSOL ayisetyenziselwa ukunciphisa iingxaki zokuphefumla ngesiquphekwaye ayizukutshintsha indawo yokuphefumla inhaler.

IBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION I-AEROSOL isetyenziselwa isifuba kunye neCOPD ngolu hlobo lulandelayo:

Isifuba:I-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION I-AEROSOL isetyenziselwa ukulawula iimpawu zesifuba, kunye nokuthintela iimpawu ezinjengokubethwa ngumoya kwabantu abadala kunye nabantwana abaneminyaka emi-6 nangaphezulu.
I-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION I-AEROSOL iqulethe i-formoterol. Amayeza e-LABA afana ne-formoterol xa esetyenziselwa uwodwa anyusa umngcipheko wokufa kunye nokulaliswa esibhedlele ngenxa yeengxaki zesifuba. I-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL ine-ICS kunye ne-LABA. Xa i-ICS kunye ne-LABA zisetyenziswa kunye, Akukho bungozi bonyukayo bokulaliswa esibhedlele kunye nokufa ngenxa yeengxaki zesifuba. I-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION I-AEROSOL ayiyiyo eyabantu abadala kunye nabantwana abane-asthma abalawulwa kakuhle ngamayeza okulawula i-asthma, njengeqondo eliphantsi ukuya kweliphakathi le-ICS. I-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION I-AEROSOL yeyabantu abadala kunye nabantwana abanesifuba abafuna i-ICS kunye neyeza le-LABA.
Ayaziwa ukuba iBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION I-AEROSOL ikhuselekile kwaye iyasebenza kubantwana abangaphantsi kweminyaka emi-6 ubudala abane-asthma.
ICOPD: I-COPD sisifo sexesha elide (esingapheliyo) semiphunga esibandakanya i-bronchitis engapheliyo, i-emphysema, okanye zombini. I-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL 160 / 4.5 mcg isetyenziswe ixesha elide, njenge-2 inhalations 2 amaxesha ngosuku, ukuphucula iimpawu ze-COPD zokuphefumla okungcono kunye nokunciphisa inani le-flare-ups (ukwanda kweempawu zakho zeCOPD iintsuku ezininzi).

Sukusebenzisa i-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL:

ukunyanga iimpawu ezinzima zesifuba okanye i-COPD.
Ukuba uxabisa kuso nasiphi na isithako esiseBUDESONIDE NASE FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL. Jonga ukuphela kweli phetshana loluhlu lwezithako kwiBUDESONIDE NAKWI-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL.

Ngaphambi kokuba usebenzise iBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL, xelela umboneleli wakho wezempilo malunga nazo zonke iimeko zonyango, kubandakanya ukuba:

uneengxaki zentliziyo.
ukuba noxinzelelo lwegazi oluphezulu.
ukuxhuzula.
uneengxaki ze-thyroid.
unesifo seswekile.
uneengxaki zesibindi.
unesifo samathambo.
unengxaki yamajoni omzimba.
Unengxaki yamehlo njengokunyuka koxinzelelo kwiso, i-glaucoma, okanye i-cataract.
azidibani namayeza.
Unalo naluphi na uhlobo lwentsholongwane, ibhaktiriya, ukungunda, okanye usulelo lwesinambuzane.
badla ngokufumana irhashalala okanye imasisi.
ukhulelwe okanye ucwangcise ukukhulelwa. Ayaziwa ukuba i-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL ingalwenzakalisa usana lwakho olungekazalwa.
bayancancisa. I-Budesonide, esinye sezithako ezisebenzayo kwi-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL, idlulela kubisi lwebele. Wena kunye nomboneleli wakho wezempilo kufuneka uthathe isigqibo sokuba uza kuyithatha na iBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL ngelixa uncancisa.

Xelela umboneleli wakho wezempilo malunga nawo onke amayeza owathathayo kubandakanya amayeza kunye namayeza angaphaya ekhawuntareni, iivithamini, kunye nezongezo zemifuno. I-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL kunye namanye amayeza anokusebenzisana. Oku kunokubangela iziphumo ebezingalindelekanga ezimandundu. Ngokukodwa xelela umboneleli wakho wezononophelo lwempilo ukuba uthatha amayeza okubulala ukungunda okanye ngokuchasene ne-HIV.

Wazi onke amayeza owasebenzisayo. Gcina uluhlu kwaye ubonise umboneleli wakho wezempilo kunye nekhemistri ngalo lonke ixesha ufumana iyeza elitsha.

Ndingayisebenzisa njani iBUDESONIDE KUNYE NEFOMOTOLI YOKUFUMANEKA KWE-FUMARATE DIHYDRATE INHALATION AEROSOL?

Jonga imiyalelo yenyathelo ngenyathelo yokusebenzisa iBUDESONIDE Kunye neFOMOTOLI YOKUFUMANEKA KWI-FUMARATE DIHYDRATE INHALATION AEROSOL ekupheleni kweli phetshana leNgcaciso yoMguli.Sukusebenzisa i-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL ngaphandle kokuba umboneleli wakho wezempilo ukufundisile kwaye uqonda yonke into. Buza umboneleli wakho wezempilo okanye usokhemesti ukuba unayo nayiphi na imibuzo.

Sebenzisa i-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL ngokuchanekileyo njengoko kumiselwe.Sukuyisebenzisa rhoqo iBUDESONIDE KUNYE NEFOMOTOLI YOKUFUMANEKA KWE-FUMARATE DIHYDRATE INHALATION AEROSOL rhoqo kunokuba kumiselwe.IBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL iza ngamandla ama-2. Umboneleli wakho wezempilo umisele amandla alungele wena. Qaphela umohluko phakathi kwe-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL kunye namanye amayeza akho atshisayo, kubandakanya umohluko ekusetyenzisweni okumiselweyo nakwimbonakalo yomzimba.
Abantwana kufuneka basebenzise iBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL ngoncedo lomntu omdala, njengoko kuyalelwe ngumboneleli wezempilo womntwana.
I-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION I-AOSOSOL kufuneka ithathwe yonke imihla njenge-2 ekhukhumezayo kusasa kunye ne-2 ngokuhlwa ngokumalunga neeyure ezili-12 ngaphandle.
Ukuba uphosa idosi ye-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL, kuya kufuneka uthathe idosi elandelayo ngexesha elifanayo nesiqhelo.
Hlamba umlomo wakho ngamanzi uze uwachithe amanzi emva kwedosi nganye (ukukhukhumala kabini) kweBUDESONIDE NAKWE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL. Musa ukuwaginya amanzi. Oku kuya kunceda ukunciphisa ithuba lokufumana usulelo lwefungus (thrush) emlonyeni nasemqaleni.
Ukuba uthatha kakhulu i-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL, tsalela umnikezeli wakho wezempilo okanye uye kwigumbi likaxakeka elikufutshane esibhedlele kwangoko ukuba unempawu ezingaqhelekanga, ezinje ngokuncipha komoya, iintlungu zesifuba, ukonyuka kwentliziyo, okanye ukuzithemba .
Musa ukutshiza i-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL emehlweni akho. Ukuba ngempazamo ufumana iBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL emehlweni akho, hlamba amehlo akho ngamanzi, kwaye ukuba bomvu okanye ukucaphuka kuyaqhubeka, nxibelelana nomboneleli wakho wezempilo.
Sukutshintsha okanye uyeke nawaphi na amayeza asetyenziselwa ukulawula okanye ukunyanga iingxaki zakho zokuphefumla. Umboneleli wakho wezempilo uya kuwatshintsha amayeza akho xa kufuneka njalo.
Ngelixa usebenzisa i-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL amaxesha ama-2 ngosuku, musa ukusebenzisa amanye amayeza ane-LABA nangasiphi na isizathu. Buza umboneleli wakho wezempilo okanye usokhemisti ukuba ngaba amanye amayeza akho ngamayeza e-LABA.
IBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL ayizinciphisi iimpawu ngesiquphe. Soloko unamayeza okuhlangula inhaler kunye nawe ukunyanga iimpawu zequbuliso. Ukuba awunayo i-inhaler yokuhlangula, tsalela umnikezeli wakho wezempilo ukuba abekelwe yona.
Shayela umboneleli wakho wezempilo okanye ufumane unyango ngokukhawuleza ukuba:
iingxaki zakho zokuphefumla ziya zisiba mbi ngeBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL.
Kuya kufuneka usebenzise i-inhaler yakho yokuhlangula amayeza rhoqo kunesiqhelo.
iyeza lakho lokusindisa inhaler alisebenzi kuwe xa ususa iimpawu.
iziphumo zokuphakama kwemitha yakho ziyancipha. Umboneleli wakho wezempilo uya kukuxelela amanani afanelekileyo kuwe.
Iimpawu zakho aziphucuki emva kokusebenzisa iBUDESONIDE KUNYE NEFOMOTOLO YOKUFUMANEKA KWE-FUMARATE DIHYDRATE INHALATION AEROSOL rhoqo kwiveki e-1.

Zithini iziphumo ebezingalindelekanga ezinokubakho zeBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL?

I-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION I-AEROSOL inokubangela iziphumo ebezingalindelekanga ezibi, kubandakanya:

Sebenzisa kakhulu amayeza e-LABA kunokubangela:
iintlungu zesifuba
ukubetha kwentliziyo okukhawulezayo nokungaqhelekanga
ukungcangcazela
ukwanda koxinzelelo lwegazi
intloko ebuhlungu
uvalo
Usulelo lomngundo emlonyeni wakho okanye emqaleni (thrush). Hlamba umlomo wakho ngamanzi ngaphandle kokuginya emva kokusebenzisa iBUDESONIDE NE-FORMOTEROL.
I-pneumonia kunye nezinye izifo ezisezantsi zokuphefumla.Abantu abaneCOPD banethuba eliphezulu lokufumana inyumoniya kunye nolunye usulelo lwemiphunga. I-inhalled corticosteroids inokunyusa ithuba lokufumana inyumoniya. Fowunela umboneleli wakho wezempilo ukuba ubona naziphi na kwezi mpawu:
ukwanda kwemveliso yencindi (isikhohlela)
ifiva
ukwanda ukhohlokhohlo
utshintsho kumbala we-mucus
Ukugodola
ukwanda kweengxaki zokuphefumla
Iziphumo zomzimba kunye nethuba eliphezulu losulelo.Xelela umboneleli wakho wezempilo malunga nayiphi na imiqondiso yosulelo enje:
ifiva
iintlungu zomzimba
ndiziva ndidiniwe
ukugabha
intlungu
Ukugodola
isicaphucaphu
Ukungabikho kwe-adrenal.Ukungabikho kwe-adrenal yimeko apho i-adrenal gland ayenzi ngokwaneleyo i-hormone ye-steroid. Oku kunokwenzeka xa uyeka ukuthatha amayeza e-corticosteroid ngomlomo kwaye uqalise ukungenisa iyeza le-corticosteroid.
Ukonyusa isangqa emva kokuthatha iBUDESONIDE Kunye neFOMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL.Soloko une-inhaler yokuhlangula kunye nawe ukuze unyange ukubhuda ngesiquphe.
Iziphumo ezinobuzaza ezibangelwa kukungqubana komzimba, urhashalala, ukudumba kobuso, umlomo nolwimi kunye neengxaki zokuphefumla.Fowunela umboneleli wakho wezempilo okanye ufumane unyango olukhawulezileyo ukuba ufumana naziphi na iimpawu zokungaziphathi kakuhle.
Ukuxinana kwamaminerali amathambo asezantsi.Oku kunokwenzeka kubantu abanethuba eliphezulu lokuxinana kwamathambo (osteoporosis). Umboneleli wakho wezempilo kufuneka akuqwalasele oku ngexesha lonyango nge-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL.
Ukukhula kancinci kubantwana.Ukukhula komntwana kufuneka kuhlolwe rhoqo ngelixa kusetyenziswa iBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL.
Iingxaki zamehlo kubandakanya i-glaucoma kunye ne-cataract.Kuya kufuneka ube novavanyo lwamehlo rhoqo ngelixa usebenzisa i-BUDESONIDE Kunye ne-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL.
Ukudumba kwemithambo yegazi yakho. Oku kunokwenzeka kubantu abane-asthma. Xelela umboneleli wakho wezempilo kwangoko ukuba unayo:
imvakalelo yezikhonkwane kunye neenaliti okanye ukuba ndindisholo kweengalo zakho okanye imilenze
irhashalala
umkhuhlane njengeempawu
iintlungu kunye nokudumba kwesono
Ukuhla kumanqanaba egazi potassium (hypokalemia).
Ukwanda kwinqanaba leswekile yegazi (hyperglycemia).

Iziphumo eziqhelekileyo zeBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL zibandakanya:

Abantu abane-asthma:
ukucaphuka komqala
usulelo lwephepha lokuphefumla
ukudumba kwenwebu yangaphakathi ye sinus (sinusitis)
umqolo obuhlungu
isisu esibuhlungu
itrush emlonyeni nasemqaleni. Hlamba umlomo wakho ngamanzi ngaphandle kokuginya emva kokusetyenziswa ukunceda ukuthintela i-thrush
intloko ebuhlungu
intlungu yomqala
umkhuhlane
ukuxinana kwempumlo
ukugabha

Abantu abaneCOPD:

ukucaphuka komqala.
itrush emlonyeni nasemqaleni. Hlamba umlomo wakho ngamanzi ngaphandle kokuginya emva kokusetyenziswa ukunceda ukuthintela i-thrush.
usulelo kunye nokudumba inwebu yangaphakathi yetyhubhu inyumoniya (bronchitis).
ukudumba inwebu yangaphakathi kwi sinuses (sinusitis).
usulelo lwephepha lokuphefumla.

Xelela umboneleli wakho wezempilo malunga nayiphi na into echaphazelekayo ekukhathazayo okanye engapheliyo.

Ayizizo zonke iziphumo ebezingalindelekanga ezinokubakho ze-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL.

Shayela ugqirha wakho malunga neengcebiso. Unokuxela iziphumo ebezingalindelekanga kwi-FDA ngo-1-800-FDA-1088.

Unokuxela iziphumo ebezingalindelekanga kwi-AstraZeneca ngo-1-800-236-9933.

Ndingayigcina njani iBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL?

Gcina i-BUDESONIDE NE-FORMOTEROL.
Gcina i-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL ngomlomo phantsi.
Imixholo ye-BUDESONIDE kunye ne-FORMOTEROL FUMARATE DIHYDRATE INHALATION I-AEROSOL canister iphantsi koxinzelelo. Musa ukugqobhoza okanye ukuphosa ibhokisana emlilweni okanye kwisitovu. Sukuyisebenzisa okanye uyigcine kufutshane nobushushu okanye ilangatye elivulekileyo. Ukugcinwa ngaphezulu kwe-120ºF kunokubangela ukuba i-canister iqhume.
Yilahle kude iBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL xa ikhawuntara ifika kwi-zero (0) okanye kwiinyanga ezi-3 emva kokuba uthathe iBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL ngaphandle kwesikhwama sayo, nokuba yeyiphi eza kuqala.
Gcina iBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL kunye nawo onke amayeza kude nabantwana.

Ulwazi ngokubanzi malunga nokusetyenziswa okukhuselekileyo nokusebenzayo kweBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL.

Amayeza ngamanye amaxesha amiselwe ezinye iinjongo ngaphandle kwezo zidweliswe kwiphepha elineenkcukacha ngezigulana. Sukusebenzisa i-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL ngemeko engamiselwanga yona. Musa ukunika iBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL kwabanye abantu, nokuba baneempawu ezifanayo nezakho. Inokubenzakalisa.

Unokucela ulwazi kumboneleli wakho wezempilo okanye usokhemesti malunga ne-BUDESONIDE NE-FORMOTEROL.

Zithini izithako kwiBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL?

Izinto ezisebenzayo: i-micronised budesonide kunye ne-micronized formoterol fumarate dihydrate
Izinto ezingasebenziyo: i-hydrofluroalkane (HFA 227), i-povidone K25 USP, kunye ne-polyethylene glycol 1000 NF

Yenzelwe i: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850

Ngu: AstraZeneca Dunkerque Production, Dunkerque, France Imveliso yaseFrance

Ngolwazi oluthe kratya, tsalela umnxeba 1-800-236-9933.

Ukuhlaziywa: Julayi 2019

Imiyalelo yokusebenzisa

IBUDESONIDE (bue-DES-oh-nide) KUNYE NEFOMOTEROL (ye-MOH-teh-rol)
INDLELA YOKUTSHINTSHA UMSEBENZI

(budesonide 80 mcg kunye nefomoterol fumarate dihydrate 4.5 mcg)

IBUDESONIDE (bue-DES-oh-nide) KUNYE NEFOMOTEROL (ye-MOH-teh-rol)
INDLELA YOKUTSHINTSHA UMSEBENZI

(budesonide 160 mcg kunye nefomoterol fumarate dihydrate 4.5 mcg)

Indawo ethe tye

Ungayisebenzisa njani iBUDESONIDE Kunye neFOMOTEROL

Landela le miyalelo ingezantsi xa usebenzisa i-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL. Uya kuphefumlela ngaphakathi (ukusezela) iyeza. Ukuba unemibuzo, buza ugqirha wakho okanye usokhemesti.

Ukulungiselela i-BUDESONIDE kunye ne-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler yokusetyenziswa

1.
Thatha i-BUDESONIDE kunye ne-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL ngaphandle kwesikhwama sokukhusela umswakama ngaphambi kokuba usisebenzise okokuqala kwaye usilahle kude. Bhala umhla ovula ngawo ipokotho.
2.
Ikhawuntari incanyathiselwe phezulu kwisitya sentsimbi. Ikhawuntari iya kubala phantsi ngalo lonke ixesha ukhupha ukukhukhumala kweBUDESONIDE KUNYE NEFOMOTOLO YOKUFUMANEKA KWE-FUMARATE DIHYDRATE INHALATION AEROSOL. Utolo lukhomba kwinani le-inhalations (ukukhukhumala) elisele kwi-canister. Ikhawuntari iyayeka ukubala ngo-zero (0).
3.
Sebenzisa i-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION I-AEROSOL canister kuphela ebomvu ebomvu ye-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler enikwe imveliso. Iinxalenye zeBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION I-AEROSOL inhaler akufuneki isetyenziswe ngamalungu kuyo nayiphi na enye imveliso yokuphefumla.
Zine.
Shake i-BUDESONIDE kunye ne-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler kakuhle kwimizuzwana emi-5 phambi kokusetyenziswa ngakunye. Susa isiciko somlomo ngokucinezela ngobunono kumacala omabini, emva koko ukhuphe (jonga umfanekiso 2). Jonga into oyithethayo ngaphambi kokuyisebenzisa.
1.
Ukuncoma i-BUDESONIDE kunye ne-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler
Ngaphambi kokuba usebenzise iBUDESONIDE KUNYE NEFOMOTOLI YOKUFUMANEKA KWE-FUMARATE DIHYDRATE INHALATION AEROSOL okokuqala, kuya kufuneka uyiqale. Ukuqala kweBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL, yibambe kwindawo emi kuyo. Jonga uMzobo 1. Shake i-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler kakuhle kwimizuzwana emi-5. Bamba i-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler ejonge kude kuwe kwaye ucofe ezantsi ngokuqinileyo nangokugqibeleleyo kumphezulu wekhawuntari kwi-BUDESONIDE NE-FORMOTEROL. Emva koko yigungqise kwakhona imizuzwana emi-5 kwaye ukhulule uvavanyo lwesibini lokutshiza. I-BUDESONIDE kunye ne-FORMOTEROL FUMARATE DIHYDRATE INHALATION I-AEROSOL inhaler ngoku iyanconywa kwaye ilungele ukusetyenziswa. Emva kokuba uyincomile i-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler okokuqala, ikhawuntara iya kufunda i-120.

Ukuba awusebenzisi i-BUDESONIDE kunye ne-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler ngaphezulu kweentsuku ezisi-7 okanye ukuba uyayilahla, kuya kufuneka uphinde uphinde

Iindlela zokubamba i-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler yokusetyenziswa

OKANYE

Sebenzisa i-BUDESONIDE kunye ne-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler

1.
Shake i-BUDESONIDE kunye ne-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler kakuhle kwimizuzwana emi-5. Susa isiciko somlomo. Jonga into ethetha ngomlomo kwizinto zangaphandle.
2.
Phefumlela ngaphandle ngokupheleleyo. Bamba i-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler ukuya emlonyeni wakho. Beka umlomo omhlophe ngokupheleleyo emlonyeni wakho kwaye uvale imilebe yakho macala onke. Qinisekisa ukuba i-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION I-AEROSOL inhaler ithe tye kwaye ukuvulwa komlomo kukhombe ngasemva komqala wakho (jonga umfanekiso 5).
1.
Phefumlela ngaphakathi (rhalela ngaphakathi) nzulu kwaye ucothe ngomlomo wakho. Cinezela ezantsi ngokuqinileyo nangokugqibeleleyo kumphezulu wekhawuntara kwi-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler ukukhupha iyeza (jonga ii-3 kunye ne-4).
2.
Qhubeka uphefumle ngaphakathi (inhale) kwaye ubambe umphefumlo wakho malunga nemizuzwana eli-10, okanye ixesha elide ukhululekile. Phambi kokuba uphefumle ngaphandle (khupha umoya) khupha umnwe wakho phezulu kwekhawuntari. Gcina i-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler nkqo kwaye ususe emlonyeni wakho.
3.
Shake i-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler kwakhona kwimizuzwana emi-5 kwaye uphinde amanyathelo ama-7 ukuya kwele-9.

Emva kokusebenzisa i-BUDESONIDE kunye ne-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler

1.
Emva kokusetyenziswa, vala isiciko somlomo ngokutyhala kude kube kunqakraza endaweni.
2.
Emva kokuba ugqibile ukuthatha iBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL (2 ukukhukhumeza), hlamba umlomo ngamanzi. Khafula amanzi. Ungayiginyi.

Ukufunda ikhawuntari

Utolo kwikhawuntara ephezulu ye-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler ikhomba kwinani le-inhalations (ukukhukhumala) elishiye kwi-inhaler yakho.

I-COUNTER

Ikhawuntari iya kubala phantsi ngalo lonke ixesha ukhupha umsi weyeza (nokuba uyayithanda i-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler okanye xa usela iyeza).
Xa utolo kwikhawuntara lusondela kuma-20, uya kuqaphela ukuqala kwendawo etyheli ikwazise ukuba lixesha lokuba ubize umnikezeli wakho wezempilo ukuze azalise kwakhona.

I-COUNTER

Kubalulekile ukuba ubeke ingqalelo kwinani le-inhalation (ukukhukhumeza) elishiye kwi-BUDESONIDE kunye ne-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler ngokufunda ikhawuntara. Yilahle iBUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL xa ikhawuntara ibonisa i-zero (0) okanye iinyanga ezi-3 emva kokuba uthathe i-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler ephuma kwi-foil poch yayo, nokuba yeyiphi eza kuqala. I-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION I-AEROSOL inhaler isenokungaziva ingenanto kwaye ingaqhubeka nokusebenza, kodwa awuyi kufumana isixa esifanelekileyo samayeza ukuba uyaqhubeka nokuyisebenzisa. Sebenzisa i-BUDESONIDE entsha ne-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler kwaye ulandele imiyalelo ye-priming (jonga u-5 apha ngasentla).

Uyicoca njani i-BUDESONIDE kunye ne-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler

Coca umlomo omhlophe we-BUDESONIDE kunye ne-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler yonke imihla esi-7. Ukucoca umlomo:

Susa isiciko somlomo esingwevu
Sula ngaphakathi nangaphandle komlomo omhlophe ovula ngelaphu elicocekileyo nelomileyo
Guqula isiciko somlomo
Musa ukubeka i-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler emanzini
Sukuzama ukwahlula eyakhoI-BUDESONIDE NE-FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOLinhaler

Yenzelwe i: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850

Ngu: AstraZeneca Dunkerque Production, Dunkerque, France

Imveliso yaseFrance

Olu lwazi lweMonde kunye neMiyalelo yokuSebenzisa ivunyiwe yiU.S.Ukutya kunye noLawulo lweziyobisi.

© AstraZeneca 2019

Ukuhlaziywa: Julayi 2019

IPHEPHA / ILEBILE YOKUBONISA IPhaneli-80 / 4.5

I-NDC 0310-7372-20

Gcina ithe tye

IBudesonide kunye neFomoterol

Fumarate Dihydrate

Ukuphefumla iAerosol 80 / 4.5

budesonide 80 mcg / formoterol fumarate dihydrate 4.5 mcg

INDLELA YOKUTSHINTSHA UMSEBENZI

Inhalations ezili-120

Ukuphefumla ngomlomo kuphela

Rx kuphela

Yenzelwe:

I-AstraZeneca LP, iWilmington, DE 19850

Ngu: AstraZeneca Dunkerque Production

IDunkirk, eFrance

Imveliso yaseFrance

© AstraZeneca 2019

IPHEPHA / ILEBILE YOKUBONISA IPhaneli-160 / 4.5

I-NDC 0310-7370-20

Gcina ithe tye

IBudesonide kunye neFomoterol

Fumarate Dihydrate

Ukuphefumla iAerosol 160 / 4.5

budesonide 160 mcg / formoterol fumarate dihydrate 4.5 mcg

INDLELA YOKUTSHINTSHA UMSEBENZI

Inhalations ezili-120

Ukuphefumla ngomlomo kuphela

Rx kuphela

Yenzelwe:

I-AstraZeneca LP, iWilmington, DE 19850

Ngu: AstraZeneca Dunkerque Production

IDunkirk, eFrance

Imveliso yaseFrance

© AstraZeneca 2019

IBUDESONIDE Kunye neFOMOTOLI FUMARATE DIHYDRATE
i-budesonide kunye ne-formoterol fumarate dihydrate aerosol
Ulwazi lweMveliso
Uhlobo lweMveliso INKCAZELO YABANTU ILELAYIBHILE YEZIYOBISI Ikhowudi yento (Umthombo) I-NDC: 0310-7370
Umgaqo woLawulo UKUPHUMULA (UKUTSHWA) Ishedyuli ye-DEA
Isithako esisebenzayo / Umoya oSebenzayo
Igama lezithako Isiseko soMandla Amandla
IBUDESONIDE (IBUDESONIDE) IBUDESONIDE I-160 ug
I-FORMOTEROL FUMARATE (FORMOTEROL) I-FORMOTEROL FUMARATE ANHYDROUS 4.5 ug
Izithako ezingasebenziyo
Igama lezithako Amandla
IPOLYETHYLENE GLYCOL 1000
I-POVIDONE K25
APAFLURANE
Ukupakisha
# Ikhowudi yento Inkcazo yephakheji
1 I-NDC: 0310-7370-20 1 YOKUTHENGA 1 ibhokisi
1 ICANISTER KWIPHEPHA eli-1
1 I-120 AEROSOL kwi-1 CanISTER
Ulwazi lweNtengiso
Udidi lokuThengisa Inombolo yesicelo okanye iMonograph Citation Umhla wokuQalisa ukuThengisa Umhla Wokuphela Wentengiso
I-NDA igunyazisile igeneric I-NDA021929 03/01/2020
IBUDESONIDE Kunye neFOMOTOLI FUMARATE DIHYDRATE
i-budesonide kunye ne-formoterol fumarate dihydrate aerosol
Ulwazi lweMveliso
Uhlobo lweMveliso INKCAZELO YABANTU ILELAYIBHILE YEZIYOBISI Ikhowudi yento (Umthombo) I-NDC: 0310-7372
Umgaqo woLawulo UKUPHUMULA (UKUTSHWA) Ishedyuli ye-DEA
Isithako esisebenzayo / Umoya oSebenzayo
Igama lezithako Isiseko soMandla Amandla
IBUDESONIDE (IBUDESONIDE) IBUDESONIDE I-80 ug
I-FORMOTEROL FUMARATE (FORMOTEROL) I-FORMOTEROL FUMARATE ANHYDROUS 4.5 ug
Izithako ezingasebenziyo
Igama lezithako Amandla
I-POVIDONE K25
IPOLYETHYLENE GLYCOL 1000
APAFLURANE
Ukupakisha
# Ikhowudi yento Inkcazo yephakheji
1 I-NDC: 0310-7372-20 1 YOKUTHENGA 1 ibhokisi
1 ICANISTER KWIPHEPHA eli-1
1 I-120 AEROSOL kwi-1 CanISTER
Ulwazi lweNtengiso
Udidi lokuThengisa Inombolo yesicelo okanye iMonograph Citation Umhla wokuQalisa ukuThengisa Umhla Wokuphela Wentengiso
I-NDA igunyazisile igeneric I-NDA021929 03/01/2020
Umlebheli -I-AstraZeneca Pharmaceuticals LP (054743190)
Umbhalisi -I-AstraZeneca PLC (230790719)
I-AstraZeneca Pharmaceuticals LP

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