Budesonide thiab Formoterol Aerosol

Lub npe dav: budesonide thiab formoterol fumarate dihydrate
Dosage form: aerosol
Chav kawm tshuaj: Kev sib xyaw ua ke ntawm bronchodilator



Ntawm nplooj ntawv no
Nthuav

Cov lus qhia thiab kev siv rau Budesonide thiab Formoterol Aerosol

Kev kho mob hawb pob

BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL yog qhia rau kev kho mob hawb pob hauv cov neeg mob hnub nyoog 6 xyoo thiab laus dua.



BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL yuav tsum tau siv rau cov neeg mob uas tsis tau tswj kom txaus ntawm cov tshuaj tiv thaiv kab mob hawb pob mus ntev xws li inhaled corticosteroid (ICS) lossis nws tus kab mob warrants pib kho nrog ob qho tib si nqus tau corticosteroid beet2 thiab ntev-activ. adrenergic agonist (LABA).

Cov kev txwv tseem ceeb ntawm kev siv:



BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL tsis yog qhia rau kev kho mob bronchospasm.

Kho Kev Kho Mob Mob Hlwb Obstructive Pulmonary Disease

BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL 160/4.5 yog qhia rau kev saib xyuas kev kho mob ntawm cov hlab ntsws hauv cov neeg mob uas muaj kab mob ntsws ntev (COPD) nrog rau cov mob ntsws ntev thiab / lossis emphysema. BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL 160/4.5 kuj tau qhia kom txo qis exacerbations ntawm COPD. BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL 160/4.5 yog tib lub zog qhia rau kev kho mob COPD.

Cov kev txwv tseem ceeb ntawm kev siv:

BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL tsis yog qhia rau kev kho mob bronchospasm.

Budesonide thiab Formoterol Aerosol Dosage thiab Administration

Cov ntaub ntawv tswj hwm

BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL yuav tsum tau muab raws li 2 inhalations ob zaug ib hnub twg (sab sawv ntxov thiab yav tsaus ntuj, kwv yees li 12 teev sib nrug), txhua hnub los ntawm kev nqus qhov ncauj nkaus xwb. Tom qab nqus tau, tus neeg mob yuav tsum yaug lub qhov ncauj nrog dej yam tsis tau nqos.



Prime BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL ua ntej siv thawj zaug los ntawm kev tso ob lub tshuaj tsuag rau hauv huab cua kom deb ntawm lub ntsej muag, co zoo rau 5 vib nas this ua ntej txhua cov tshuaj tsuag. Nyob rau hauv cov rooj plaub uas tsis tau siv lub tshuab nqus tsev ntau tshaj 7 hnub los yog thaum nws tau poob lawm, thawj lub tshuab nqus pa rov qab los ntawm kev co zoo ua ntej txhua yam tshuaj tsuag thiab tso ob lub tshuaj tsuag rau hauv huab cua kom deb ntawm lub ntsej muag.

hloov los ntawm wellbutrin sr rau xl

Kev tswj hwm ntau zaus lossis ntau dua ntawm kev nqus pa (ntau dua 2 inhalations ob zaug hauv ib hnub) ntawm lub zog ntawm BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL tsis pom zoo vim qee cov neeg mob yuav muaj kev cuam tshuam ntau dua nrog cov koob tshuaj ntau dua ntawm formoterol. Cov neeg mob uas siv BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL yuav tsum tsis txhob siv LABA ntxiv rau ib qho laj thawj twg[saib Ceeb toom thiab ceev faj (5.3 , 5.12 )].

Mob hawb pob

Yog tias cov tsos mob hawb pob tshwm sim nyob rau hauv lub sij hawm ntawm koob tshuaj, ib qho inhaled, short-acting betaob- agonist yuav tsum tau noj kom sai sai.

Cov neeg laus thiab cov hluas muaj hnub nyoog 12 xyoos thiab laus dua

Rau cov neeg mob hnub nyoog 12 xyoos thiab laus dua, qhov ntau npaum yog 2 inhalations ntawm BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL 80/4.5 los yog BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL. 16 hnub ob zaug.

Cov lus pom zoo pib noj rau BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL rau cov neeg mob hnub nyoog 12 xyoos thiab laus dua yog ua raws li cov neeg mob mob hawb pob lossis theem tswj cov tsos mob hawb pob, thiab muaj feem yuav ua rau muaj kev phom sij ntawm cov tshuaj corticosteroids uas tau nqus tam sim no.

Qhov siab tshaj plaws pom zoo noj rau cov neeg laus thiab cov tub ntxhais hluas hnub nyoog 12 xyoos thiab laus dua yog BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL 160/4.5, ob qhov nqus tau ob zaug ib hnub.

Kev txhim kho hauv kev tswj kev mob ntsws asthma tom qab nqus tau cov kev tswj hwm ntawm BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL tuaj yeem tshwm sim hauv 15 feeb ntawm kev pib kho, txawm tias qhov txiaj ntsig siab tshaj plaws yuav tsis ua tiav rau 2 lub lis piam lossis ntev dua tom qab pib kho. Cov neeg mob ib leeg yuav muaj lub sijhawm hloov pauv mus rau qhov pib thiab qib ntawm cov tsos mob nyem.

Rau cov neeg mob uas tsis teb txaus rau qhov pib koob tshuaj tom qab 1-2 lub lis piam ntawm kev kho mob nrog BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL 80/4.5, hloov nrog BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION 4.5.

Yog tias yav dhau los siv tau zoo ntawm BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL tsis tuaj yeem muab kev tswj hwm kev mob hawb pob, cov kev kho mob yuav tsum tau rov ntsuam xyuas thiab ntxiv cov kev xaiv kho mob, (xws li, hloov lub zog qis ntawm BUDESONERATIONHYDTEROLE Nrog lub zog siab dua, ntxiv cov nqus tau pa corticosteroid ntxiv, lossis pib qhov ncauj corticosteroids) yuav tsum tau txiav txim siab.

Cov menyuam yaus hnub nyoog qis dua 6 txog 12 xyoos

Rau cov neeg mob hnub nyoog 6 mus rau tsawg dua 12 xyoos, qhov ntau npaum yog 2 inhalations ntawm BUDESONIDE thiab FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL 80/4.5 ob zaug ib hnub.

Chronic Obstructive Pulmonary Disease

Rau cov neeg mob uas muaj COPD cov koob tshuaj pom zoo yog BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL 160/4.5, ob qhov nqus tau ob zaug ib hnub.

Yog hais tias ua tsis taus pa luv tshwm sim nyob rau hauv lub sij hawm ntawm koob tshuaj, ib tug inhaled, short-acting betaob- agonist yuav tsum tau noj kom sai sai.

Daim ntawv siv tshuaj thiab muaj zog

BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL yog muaj nyob rau hauv ib tug metered-dose inhaler uas muaj ib tug ua ke ntawm budesonide (80 los yog 160 mcg) thiab formoterol (4.5 mcg) raws li ib tug inhalation aerosol nyob rau hauv ob lub zog nram qab no: 40.5 / .41 / 40. Txhua qhov koob tshuaj muaj zog muaj 120 actuations per / canister. Txhua lub zog ntawm BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL yog muab nrog lub tshuab hluav taws xob liab nrog lub hau grey plua plav.

Contraindications

Kev siv budesonide thiab formoterol fumarate dihydrate yog contraindicated nyob rau hauv cov nram qab no tej yam kev mob:

Kev kho mob tseem ceeb ntawm cov xwm txheej asthmaticus lossis lwm yam mob hnyav ntawm mob hawb pob lossis COPD qhov yuav tsum tau ntsuas hnyav.
Hypersensitivity rau ib qho ntawm cov khoom xyaw hauv BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL.

Ceeb toom thiab ceev faj

Mob hawb pob-Raws li xwm txheej – tsev kho mob, intubations thiab tuag

Kev siv LABA raws li kev kho mob monotherapy (tsis muaj ICS) rau kev mob ntsws asthma yog txuam nrog kev pheej hmoo ntawm kev mob ntsws asthma ntxiv [saibSalmeterol Multicenter Asthma Research Trial (SMART)]. Muaj cov ntaub ntawv los ntawm kev tswj xyuas kev sim tshuaj ntsuam xyuas kuj qhia tias kev siv LABA raws li kev kho mob monotherapy ua rau muaj kev pheej hmoo ntawm kev mob hawb pob hauv tsev kho mob hauv cov menyuam yaus thiab cov hluas. Cov kev tshawb pom no suav hais tias yog cov txiaj ntsig ntawm LABA. Thaum LABA tau siv rau hauv kev sib xyaw ua ke nrog ICS, cov ntaub ntawv los ntawm kev sim tshuaj loj tsis qhia qhov kev pheej hmoo ntawm kev mob hawb pob loj heev (kev kho mob, intubations, tuag) piv rau ICS ib leeg (saibMob hawb pob ntsig txog cov xwm txheej nrog ICS/LABA).

Mob hawb pob ntsig txog cov xwm txheej nrog ICS/LABA

Plaub qhov loj, 26-lub lim tiam, randomized, dig muag, active-tswj chaw soj ntsuam kev nyab xeeb kev sim tau ua los soj ntsuam cov kev pheej hmoo ntawm mob hawb pob mob hnyav tshwm sim thaum LABA tau siv nyob rau hauv tas li koob tshuaj ua ke nrog ICS piv rau ICS ib leeg rau cov neeg mob hawb pob. Peb qhov kev sim suav nrog cov neeg laus thiab cov tub ntxhais hluas hnub nyoog ≧12 xyoo: ib qho kev sim piv rau budesonide / formoterol (budesonide thiab formoterol fumarate dihydrate) rau budesonide[saib Kev Tshawb Fawb Txog Kev Kho Mob (14.1) ]; ib qho kev sim piv rau fluticasone propionate / salmeterol inhalation hmoov rau fluticasone propionate inhalation hmoov; thiab ib qho kev sim piv rau mometasone furoate / formoterol rau mometasone furoate. Qhov kev sim thib plaub suav nrog cov neeg mob menyuam yaus hnub nyoog 4 txog 11 xyoos thiab piv rau fluticasone propionate / salmeterol inhalation hmoov rau fluticasone propionate inhalation hmoov. Lub hauv paus kev nyab xeeb kawg rau tag nrho plaub qhov kev sim yog mob hawb pob mob hnyav (kev kho mob, intubations thiab tuag). Pawg neeg saib xyuas qhov muag tsis pom kev txiav txim siab seb cov xwm txheej puas muaj mob hawb pob.

Peb qhov kev sim siab rau cov neeg laus thiab cov tub ntxhais hluas tau tsim los txiav txim siab qhov kev pheej hmoo ntawm 2.0, thiab kev sim menyuam yaus tau tsim los txiav txim qhov kev pheej hmoo ntawm 2.7. Txhua qhov kev sim ua tau raws li nws lub hom phiaj tau teev tseg ua ntej thiab pom tias tsis muaj qhov tsis zoo ntawm ICS / LABA rau ICS ib leeg. Ib qho kev ntsuam xyuas meta ntawm peb qhov kev sim rau cov neeg laus thiab cov tub ntxhais hluas tsis tau qhia tias muaj kev pheej hmoo ntawm kev mob hawb pob loj heev nrog ICS / LABA tsau-dose ua ke piv nrog ICS ib leeg (Table 1). Cov kev sim no tsis tau tsim los txiav txim tawm txhua qhov kev pheej hmoo rau cov xwm txheej mob hawb pob loj nrog ICS / LABA piv nrog ICS.

Table 1. Meta-analyses of Asthma-Related Events in Patients with Asthma Hnub nyoog 12 xyoos thiab laus dua
*
Randomized cov neeg mob uas tau noj tsawg kawg yog 1 koob tshuaj ntawm kev kawm tshuaj. Kev npaj kho mob siv rau kev tshuaj xyuas.
Kwv yees siv Cox proportional txaus ntshai qauv ntawm lub sij hawm rau thawj qhov kev tshwm sim nrog lub hauv paus kev phom sij stratified los ntawm txhua qhov ntawm 3 qhov kev sim.
Tus naj npawb ntawm cov neeg mob uas muaj xwm txheej tshwm sim nyob rau hauv 6 lub hlis tom qab thawj zaug siv tshuaj los yog 7 hnub tom qab hnub kawg ntawm kev tshawb fawb tshuaj, seb hnub twg yog tom qab. Cov neeg mob tuaj yeem muaj ib lossis ntau qhov xwm txheej, tab sis tsuas yog thawj qhov kev tshwm sim raug suav rau kev tshuaj xyuas. Ib pawg neeg saib xyuas qhov muag tsis pom kev, txiav txim siab seb cov xwm txheej puas muaj mob hawb pob.

ICS/LAB

(Nov = 17,537) *

ICS

(Nov = 17,552) *

ICS/LABA vs ICS

Kev puas tsuaj piv (95% CI)

Kev mob hawb pob mob hnyav

116

105

1.10 (0.85, 1.44)

Asthma-related tuag

ob

0

Asthma-related intubation (endotracheal)

ib

ob

Kev mus pw hauv tsev kho mob hawb pob (≧ nyob 24-teev)

115

105

ICS = Inhaled Corticosteroid, LABA = Long-acting Beta2-adrenergic Agonist

Kev sim tshuaj xyuas kev nyab xeeb rau menyuam yaus suav nrog 6208 tus neeg mob menyuam yaus hnub nyoog 4 txog 11 xyoos uas tau txais ICS / LABA (fluticasone propionate / salmeterol inhalation hmoov) lossis ICS (fluticasone propionate inhalation hmoov). Hauv qhov kev sim no, 27/3107 (0.9%) cov neeg mob randomized rau ICS/LABA thiab 21/3101 (0.7%) cov neeg mob randomized rau ICS tau ntsib teeb meem mob hawb pob. Tsis muaj kev tuag los yog mob ntsws asthma. ICS/LABA tsis tau qhia txog qhov muaj kev pheej hmoo ntau ntxiv ntawm qhov tshwm sim mob hawb pob hnyav piv rau ICS raws li qhov kev pheej hmoo tshwj xeeb ua ntej (2.7), nrog kwv yees qhov phom sij ntawm lub sijhawm rau thawj qhov tshwm sim ntawm 1.29 (95% CI: 0.73). , 2.27 ib.).

Salmeterol Multicenter Asthma Research Trial (SMART)

Kev sim 28-lub lim tiam, placebo-tswj US kev sim uas piv kev nyab xeeb ntawm salmeterol nrog cov placebo, txhua qhov ntxiv rau kev kho mob hawb pob, pom tias muaj kev nce ntxiv hauv cov neeg mob hawb pob uas tau txais salmeterol (13/13,176 hauv cov neeg mob kho nrog salmeterol vs 3. /13,179 nyob rau hauv cov neeg mob kho nrog cov placebo; tus txheeb ze txaus ntshai: 4.37 [95% CI 1.25, 15.34]). Kev siv keeb kwm yav dhau ICS tsis tas yuav tsum muaj hauv SMART. Qhov kev pheej hmoo ntau ntxiv ntawm kev tuag los ntawm kev mob hawb pob yog suav tias yog cov txiaj ntsig ntawm LABA monotherapy.

Formoterol Monotherapy Studies

Cov kev tshawb fawb soj ntsuam nrog formoterol siv los ua monotherapy qhia tias muaj qhov tshwm sim ntau dua ntawm kev mob ntsws asthma exacerbation hauv cov neeg mob uas tau txais formoterol dua li cov neeg tau txais cov placebo. Qhov ntau thiab tsawg ntawm cov kev tshawb fawb no tsis tsim nyog los ntsuas qhov sib txawv ntawm kev mob ntsws asthma hnyav ntawm pab pawg kho mob.

Deterioration ntawm Kab Mob thiab Kab Mob Sib Kis

Budesonide thiab formoterol fumarate dihydrate yuav tsum tsis txhob pib rau hauv cov neeg mob thaum lub sij hawm deterioration sai heev los yog tej zaum yuav ua rau lub neej muaj teeb meem ntawm mob hawb pob lossis COPD. Budesonide thiab formoterol fumarate dihydrate tsis tau kawm hauv cov neeg mob uas mob hawb pob lossis COPD. Kev pib ntawm budesonide thiab formoterol fumarate dihydrate hauv qhov chaw no tsis tsim nyog.

Ntxiv rau kev siv inhaled, luv-acting betaob- agonists yog ib tug cim ntawm deteriorating asthma. Hauv qhov xwm txheej no, tus neeg mob yuav tsum tau rov ntsuam xyuas tam sim nrog kev tshuaj ntsuam xyuas kev kho mob, muab kev txiav txim siab tshwj xeeb rau qhov xav tau los hloov lub zog tam sim no ntawm budesonide thiab formoterol fumarate dihydrate nrog lub zog siab dua, ntxiv cov nqus tau pa corticosteroid ntxiv, lossis pib cov kab mob corticosteroids. . Cov neeg mob yuav tsum tsis txhob siv ntau tshaj 2 inhalations ob zaug ib hnub twg (thaum sawv ntxov thiab yav tsaus ntuj) ntawm budesonide thiab formoterol fumarate dihydrate.

Budesonide thiab formoterol fumarate dihydrate yuav tsum tsis txhob siv rau kev kho mob ntawm cov tsos mob, piv txwv li, raws li kev cawm dim rau kev kho mob ntawm cov mob bronchospasm. Ib qho inhaled, luv-acting betaob-agonist, tsis yog budesonide thiab formoterol fumarate dihydrate, yuav tsum tau siv los txo cov tsos mob xws li ua tsis taus pa.

Thaum pib kho nrog budesonide thiab formoterol fumarate dihydrate, cov neeg mob uas tau noj qhov ncauj los yog nqus tau, luv-acting beta.ob-agonists tsis tu ncua (piv txwv li, 4 zaug hauv ib hnub) yuav tsum tau qhia kom tsis txhob siv cov tshuaj no li niaj zaus.

Kev siv ntau dhau ntawm Budesonide thiab Formoterol Fumarate Dihydrate thiab siv nrog lwm cov Beta2-Agonists ntev

Raws li nrog rau lwm cov tshuaj inhaled muaj betaob-adrenergic agents, budesonide thiab formoterol fumarate dihydrate yuav tsum tsis txhob siv ntau zaus tshaj li kev pom zoo, ntawm cov koob tshuaj ntau dua li kev pom zoo, lossis ua ke nrog lwm cov tshuaj uas muaj LABA, vim tias kev siv tshuaj ntau dhau yuav ua rau. Clinically tseem ceeb ntawm cov hlab plawv thiab cov neeg tuag tau raug tshaj tawm nyob rau hauv koom nrog kev siv ntau dhau ntawm cov tshuaj inhaled sympathomimetic. Cov neeg mob uas siv budesonide thiab formoterol fumarate dihydrate yuav tsum tsis txhob siv ib qho ntxiv LABA (xws li salmeterol, formoterol fumarate, arformoterol tartrate) rau ib qho laj thawj, suav nrog kev tiv thaiv kev tawm dag zog ntawm lub ntsws (EIB) lossis kev kho mob hawb pob lossis COPD.

Cov teebmeem hauv zos

Nyob rau hauv kev tshawb fawb soj ntsuam, kev loj hlob ntawm localized kab mob ntawm lub qhov ncauj thiab pharynx nrogCov kab mob Candida albicanstau tshwm sim hauv cov neeg mob kho nrog budesonide thiab formoterol fumarate dihydrate. Thaum muaj tus kab mob zoo li no tshwm sim, nws yuav tsum tau kho nrog kev kho mob hauv zos lossis cov kab ke (piv txwv li, qhov ncauj tshuaj tiv thaiv kab mob) thaum kho nrog budesonide thiab formoterol fumarate dihydrate txuas ntxiv, tab sis qee zaum kev kho nrog budesonide thiab formoterol fumarate dihydrate yuav tsum tau cuam tshuam. Qhia tus neeg mob kom yaug nws lub qhov ncauj nrog dej yam tsis tau nqos tom qab nqus tau los pab txo qis kev pheej hmoo ntawm oropharyngeal candidiasis.

Pneumonia thiab lwm yam kab mob ua pa qis

Cov kws kho mob yuav tsum tau ceev faj txog qhov muaj peev xwm ntawm kev mob ntsws ntsws hauv cov neeg mob COPD raws li qhov chaw kho mob ntawm mob ntsws thiab exacerbations nquag sib tshooj. Cov kab mob ua pa qis, suav nrog mob ntsws, tau raug tshaj tawm tom qab nqus tau cov tshuaj corticosteroids.

Hauv 6 lub hlis kev ua haujlwm ntawm lub ntsws ntawm 1704 tus neeg mob nrog COPD, muaj qhov tshwm sim ntau dua ntawm kev mob ntsws ntsws uas tsis yog mob ntsws (xws li, mob ntsws, kab mob ua pa qis, thiab lwm yam) hauv cov neeg mob tau txais budesonide thiab formoterol fumarate dihydrate 160/4.5. (7.6%) dua li ntawm cov neeg tau txais budesonide thiab formoterol fumarate dihydrate 80/4.5 (3.2%), formotero1 4.5 mcg (4.6%) lossis placebo (3.3%). Pneumonia tsis tshwm sim nrog qhov tshwm sim ntau dua hauv budesonide thiab formoterol fumarate dihydrate 160/4.5 pawg (1.1%) piv nrog cov placebo (1.3%). Hauv 12 lub hlis kev ua haujlwm ntawm lub ntsws ntawm 1964 cov neeg mob nrog COPD, kuj tseem muaj qhov tshwm sim ntau dua ntawm kev mob ntsws ntsws uas tsis yog mob ntsws hauv cov neeg mob uas tau txais budesonide thiab formoterol fumarate dihydrate 160/4.5 (8.1%) dua li ntawm cov tau txais budesonide thiab formoterol fumarate dihydrate. 80/4.5 (6.9%), formoterol 4.5 mcg (7.1%) lossis placebo (6.2%). Zoo ib yam li txoj kev tshawb fawb 6 lub hlis, mob ntsws tsis tshwm sim nrog qhov tshwm sim ntau dua hauv budesonide thiab formoterol fumarate dihydrate 160/4.5 pawg (4.0%) piv nrog cov placebo (5.0%).

Kev tiv thaiv kab mob

Cov neeg mob uas noj tshuaj uas txwv tsis pub lub cev tiv thaiv kab mob kis tau yooj yim dua li cov neeg noj qab haus huv. Piv txwv li, qaib pox thiab qhua pias, tuaj yeem muaj qhov hnyav dua lossis ua rau tuag taus rau cov menyuam yaus lossis cov neeg laus uas siv corticosteroids. Hauv cov menyuam yaus lossis cov neeg laus uas tsis tau muaj cov kab mob no lossis tau txhaj tshuaj kom raug, yuav tsum tau saib xyuas tshwj xeeb kom tsis txhob kis tau. Yuav ua li cas koob tshuaj, txoj kev, thiab lub sij hawm ntawm kev tswj hwm corticosteroid cuam tshuam qhov kev pheej hmoo ntawm kev tsim kab mob sib kis tsis paub. Kev koom tes ntawm tus kab mob hauv qab thiab / lossis kev kho corticosteroid ua ntej rau qhov kev pheej hmoo kuj tsis paub. Yog tias kis tau, kev kho mob nrog varicella zoster immune globulin (VZIG) lossis cov tshuaj txhaj tshuaj tiv thaiv kab mob (IVIG), raws li qhov tsim nyog, yuav raug qhia. Yog tias raug mob qhua pias, prophylaxis nrog pooled intramuscular immunoglobulin (IG) tej zaum yuav raug qhia (saib cov pob khoom sib txuas kom tiav VZIG thiab IG cov ntaub ntawv sau npe). Yog tias mob pox tshwm sim, kev kho mob nrog tshuaj tua kab mob yuav raug txiav txim siab. Lub cev tiv thaiv kab mob rau cov tshuaj tiv thaiv kab mob varicella tau soj ntsuam hauv cov neeg mob uas muaj mob hawb pob hnub nyoog 12 hli txog 8 xyoo nrog budesonide inhalation suspension.

Ib daim ntawv qhib, tsis yog kev soj ntsuam kuaj mob tau tshuaj xyuas lub cev tiv thaiv kab mob rau cov tshuaj tiv thaiv kab mob varicella hauv 243 tus neeg mob hawb pob 12 hlis txog 8 xyoo uas tau kho nrog budesonide inhalation suspension 0.25 mg rau 1 mg txhua hnub (n = 151) lossis noncorticosteroidn kho mob hawb pob. = 92) (ie, betaob- agonists, leukotriene receptor antagonists, cromones). Qhov feem pua ​​​​ntawm cov neeg mob tsim ib qho seroprotective antibody titer ntawm>5.0 (gpELISA tus nqi) hauv cov lus teb rau kev txhaj tshuaj tiv thaiv zoo ib yam hauv cov neeg mob kho nrog budesonide inhalation suspension (85%), piv rau cov neeg mob kho nrog noncorticosteroid asthma therapy (90%). Tsis muaj tus neeg mob kho nrog budesonide inhalation suspension tsim qaib pox los ntawm kev txhaj tshuaj.

Inhaled corticosteroids yuav tsum tau siv nrog ceev faj, yog hais tias tag nrho, nyob rau hauv cov neeg mob uas muaj active los yog quiescent tuberculosis kab mob ntawm tus kab mob ua pa; tsis kho cov kab mob fungal, kab mob, kab mob, lossis kab mob parasitic; los yog ocular herpes simplex.

Hloov Cov Neeg Mob Los Ntawm Kev Kho Mob Corticosteroid

Kev saib xyuas tshwj xeeb yog xav tau rau cov neeg mob uas tau hloov pauv los ntawm cov kab mob corticosteroids mus rau nqus tau cov tshuaj corticosteroids vim tias kev tuag ntawm adrenal tsis txaus tau tshwm sim rau cov neeg mob hawb pob thaum lub sij hawm thiab tom qab hloov los ntawm cov kab mob corticosteroids mus rau qhov tsis muaj qhov nqus corticosteroids. Tom qab tshem tawm ntawm cov kab mob corticosteroids, ntau lub hlis yuav tsum tau rov qab ua haujlwm ntawm hypothalamic-pituitary-adrenal (HPA).

Cov neeg mob uas tau khaws cia yav dhau los ntawm 20 mg lossis ntau dua hauv ib hnub ntawm prednisone (lossis nws qhov sib npaug) yuav raug cuam tshuam tshaj plaws, tshwj xeeb tshaj yog thaum lawv cov kab mob corticosteroids tau yuav luag tag nrho. Thaum lub sij hawm no ntawm HPA suppression, cov neeg mob yuav pom cov tsos mob thiab cov tsos mob ntawm adrenal insufficiency thaum raug mob, phais, los yog kis kab mob (tshwj xeeb tshaj yog gastroenteritis) los yog lwm yam mob uas txuam nrog heev electrolyte poob. Txawm hais tias budesonide thiab formoterol fumarate dihydrate tuaj yeem muab kev tswj hwm ntawm cov tsos mob hawb pob thaum lub sijhawm no, hauv cov koob tshuaj pom zoo nws muab tsawg dua li ib txwm siv lub cev ntawm glucocorticoid system thiab tsis muab cov haujlwm mineralocorticoid uas tsim nyog rau kev daws cov xwm txheej no.

Thaum lub sij hawm muaj kev ntxhov siab, mob hawb pob lossis mob COPD hnyav heev, cov neeg mob uas tau raug tshem tawm ntawm cov kab mob corticosteroids yuav tsum tau qhia kom rov pib kho qhov ncauj corticosteroids (hauv koob tshuaj loj) tam sim ntawd thiab tiv tauj lawv cov kws kho mob rau kev qhia ntxiv. Cov neeg mob no kuj yuav tsum tau qhia kom nqa daim ntawv ceeb toom qhia tias lawv yuav xav tau cov tshuaj corticosteroids ntxiv thaum lub sijhawm muaj kev ntxhov siab, mob hawb pob hnyav, lossis mob COPD hnyav heev.

Cov neeg mob uas xav tau qhov ncauj corticosteroids yuav tsum tau maj mam maj mam los ntawm kev siv corticosteroid tom qab hloov mus rau budesonide thiab formoterol fumarate dihydrate. Kev txo qis Prednisone tuaj yeem ua tiav los ntawm kev txo cov koob tshuaj prednisone txhua hnub los ntawm 2.5 mg rau ib lub lim tiam thaum kho nrog budesonide thiab formoterol fumarate dihydrate. Lub ntsws muaj nuj nqi (txhais tau tias yuam kom lub ntim ntim hauv 1 thib ob [FEVib] lossis thaum sawv ntxov ncov tas sij hawm ntws [PEF]), kev siv beta-agonist, thiab cov tsos mob hawb pob lossis COPD yuav tsum tau ua tib zoo saib xyuas thaum tshem tawm ntawm qhov ncauj corticosteroids. Tsis tas li ntawd, cov neeg mob yuav tsum tau soj ntsuam cov tsos mob thiab cov tsos mob ntawm adrenal insufficiency, xws li qaug zog, lassitude, tsis muaj zog, xeev siab thiab ntuav, thiab hypotension.

Kev hloov ntawm cov neeg mob los ntawm kev kho mob corticosteroid rau nqus tau corticosteroids lossis budesonide thiab formoterol fumarate dihydrate tuaj yeem tshem tawm cov xwm txheej yav dhau los los ntawm kev kho mob corticosteroid (xws li, rhinitis, conjunctivitis, eczema, mob caj dab, eosinophilic mob). Qee tus neeg mob yuav ntsib cov tsos mob ntawm kev ua haujlwm ntawm kev tshem tawm corticosteroid (piv txwv li, kev sib koom tes thiab / lossis mob leeg, lassitude, kev nyuaj siab) txawm tias kev saib xyuas lossis kev txhim kho ntawm kev ua pa.

Hypercorticism thiab Adrenal Suppression

Budesonide, ib feem ntawm budesonide thiab formoterol fumarate dihydrate, feem ntau yuav pab tswj kev mob hawb pob thiab COPD cov tsos mob nrog tsawg dua kev ua haujlwm ntawm HPA dua li kev kho qhov ncauj sib npaug ntawm qhov ncauj ntawm prednisone. Txij li thaum budesonide tau nqus mus rau hauv cov hlab ntsha thiab tuaj yeem ua haujlwm ua haujlwm ntawm cov koob tshuaj ntau dua, cov txiaj ntsig zoo ntawm budesonide thiab formoterol fumarate dihydrate hauv kev txo qis HPA tsis ua haujlwm tuaj yeem xav tau tsuas yog thaum cov koob tshuaj pom zoo tsis pub tshaj thiab tus neeg mob tau titrated rau qhov qis tshaj koob tshuaj.

Vim tias muaj peev xwm nqus tau cov tshuaj corticosteroids hauv lub cev, cov neeg mob kho nrog budesonide thiab formoterol fumarate dihydrate yuav tsum tau ua tib zoo saib xyuas txhua yam pov thawj ntawm cov teebmeem corticosteroid. Kev saib xyuas tshwj xeeb yuav tsum tau ua nyob rau hauv kev soj ntsuam cov neeg mob tom qab phais lossis thaum lub sijhawm muaj kev ntxhov siab rau cov pov thawj ntawm cov lus teb tsis txaus adrenal.

Nws muaj peev xwm hais tias cov teebmeem ntawm corticosteroid xws li hypercorticism thiab adrenal tsub zuj zuj (nrog rau cov teebmeem ntawm adrenal) tuaj yeem tshwm sim hauv cov neeg mob tsawg, tshwj xeeb tshaj yog thaum noj budesonide ntau dua li cov koob tshuaj pom zoo rau lub sijhawm ntev. Yog tias cov teebmeem tshwm sim, qhov ntau npaum li cas ntawm budesonide thiab formoterol fumarate dihydrate yuav tsum tau txo qis, ua raws li cov txheej txheem lees paub los txo cov kab mob corticosteroids thiab tswj cov tsos mob hawb pob.

Kev Sib Tham Tshuaj Nrog Muaj Zog Cytochrome P450 3A4 Inhibitors

Kev ceev faj yuav tsum tau siv thaum xav txog kev sib koom ua ke ntawm budesonide thiab formoterol fumarate dihydrate nrog ketoconazole, thiab lwm yam kev paub muaj zog CYP3A4 inhibitors (xws li, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saliavir cuam tshuam rau saliavir). Cov kab mob raug rau budesonide tuaj yeem tshwm sim[saib Kev Sib Tham Txog Tshuaj (7.1) thiab Clinical Pharmacology (12.3) ].

Paradoxical Bronchospasm thiab Upper Airway Symptoms

Raws li nrog rau lwm cov tshuaj uas nqus tau pa, budesonide thiab formoterol fumarate dihydrate tuaj yeem tsim cov kab mob paradoxical bronchospasm, uas yuav ua rau muaj kev hem thawj rau lub neej. Yog hais tias paradoxical bronchospasm tshwm sim tom qab noj nrog budesonide thiab formoterol fumarate dihydrate, nws yuav tsum tau kho tam sim ntawd nrog ib tug inhaled, short-acting bronchodilator, BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL yuav tsum tau txiav tam sim ntawd.

Tam sim Hypersensitivity Reactions

Cov tshuaj tiv thaiv kev ntxhov siab tam sim ntawd tuaj yeem tshwm sim tom qab kev tswj hwm ntawm budesonide thiab formoterol fumarate dihydrate, raws li pom los ntawm cov mob urticaria, angioedema, pob liab liab, thiab bronchospasm.

Mob plawv thiab Central Nervous System cuam tshuam

Beta-adrenergic stimulation ntau dhau tau cuam tshuam nrog qaug dab peg, angina, kub siab lossis hypotension, tachycardia nrog tus nqi txog li 200 tus neeg ntaus / min, arrhythmias, nervousness, taub hau, tshee, tshee, xeev siab, kiv taub hau, qaug zog, malaise, thiab insomnia.[saib Kev noj ntau dhau (10) ]. Yog li ntawd, budesonide thiab formoterol fumarate dihydrate, zoo li tag nrho cov khoom uas muaj sympathomimetic amines, yuav tsum tau siv nrog ceev faj rau cov neeg mob uas muaj mob plawv, tshwj xeeb tshaj yog coronary insufficiency, plawv arrhythmias, thiab kub siab.

Formoterol, ib feem ntawm budesonide thiab formoterol fumarate dihydrate, tuaj yeem tsim cov txiaj ntsig tseem ceeb ntawm cov hlab plawv hauv qee cov neeg mob raws li ntsuas los ntawm pulse rate, ntshav siab, thiab / lossis cov tsos mob. Txawm hais tias cov teebmeem no tsis tshua muaj tshwm sim tom qab kev tswj hwm ntawm formoterol ntawm cov koob tshuaj pom zoo, yog tias lawv tshwm sim, cov tshuaj yuav tsum tau txiav tawm. Tsis tas li ntawd, beta-agonists tau tshaj tawm los tsim ECG hloov pauv, xws li flattening ntawm T yoj, ncua sij hawm ntawm QTc ntu, thiab ST ntu kev nyuaj siab. Lub chaw kho mob tseem ceeb ntawm cov kev tshawb pom no tsis paub. Cov neeg tuag tau raug tshaj tawm nyob rau hauv koom nrog kev siv ntau dhau ntawm cov tshuaj inhaled sympathomimetic.

Txo cov pob txha Mineral ntom

Kev txo qis hauv pob txha pob txha pob txha ntom ntom (BMD) tau pom nrog kev tswj hwm mus ntev ntawm cov khoom uas nqus tau corticosteroids. Qhov tseem ceeb ntawm kev kho mob ntawm cov kev hloov me me hauv BMD hais txog qhov tshwm sim mus sij hawm ntev xws li kev puas tsuaj yog tsis paub. Cov neeg mob uas muaj feem cuam tshuam loj rau cov pob txha tsis zoo, xws li kev ncua ntev, tsev neeg keeb kwm ntawm osteoporosis, postmenopausal status, haus luam yeeb, hnub nyoog siab, noj zaub mov tsis zoo, los yog siv cov tshuaj uas tuaj yeem txo cov pob txha loj (xws li, tshuaj tiv thaiv kab mob, qhov ncauj corticosteroids. ) yuav tsum tau saib xyuas thiab kho nrog cov qauv tsim kho. Txij li cov neeg mob COPD feem ntau muaj ntau yam kev pheej hmoo rau txo BMD, kev ntsuam xyuas ntawm BMD tau pom zoo ua ntej pib pib budesonide thiab formoterol fumarate dihydrate thiab ib ntus tom qab ntawd. Yog tias qhov txo qis hauv BMD tau pom thiab budesonide thiab formoterol fumarate dihydrate tseem suav tias yog kev kho mob tseem ceeb rau tus neeg mob txoj kev kho COPD, kev siv tshuaj los kho lossis tiv thaiv kev mob pob txha yuav tsum tau txiav txim siab.

Cov teebmeem ntawm kev kho mob nrog budesonide thiab formoterol fumarate dihydrate 160/4.5, budesonide thiab formoterol fumarate dihydrate 80/4.5, formoterol 4.5 mcg, los yog placebo ntawm BMD tau soj ntsuam nyob rau hauv ib pawg ntawm 326 cov neeg mob (poj niam thiab txiv neej hnub nyoog 41 txog 88 xyoo) COPD nyob rau hauv 12-lub hlis kev ua haujlwm ntawm lub ntsws. BMD kev ntsuam xyuas ntawm thaj tsam ntawm lub duav thiab lub lumbar qaum teb tau ua nyob rau hauv lub hauv paus thiab 52 lub lis piam siv dual zog x-ray absorptiometry (DEXA) scans. Kev hloov pauv hauv BMD los ntawm qhov pib mus rau qhov kawg ntawm kev kho mob me me (txhais tau tias kev hloov pauv ntawm -0.01 - 0.01 g / cm3)ob). ANCOVA cov txiaj ntsig rau tag nrho cov txha nraub qaum thiab tag nrho lub duav BMD raws li qhov kawg ntawm lub sijhawm kho mob tau pom tias tag nrho cov geometric LS Mean ratios rau cov kev sib piv ntawm cov pab pawg kho mob sib piv tau ze rau 1, qhia tias tag nrho, BMD rau tag nrho lub duav thiab tag nrho cov txha nraub qaum rau 12. -lub hlis lub sij hawm taw tes tau ruaj khov nyob rau tag nrho lub sij hawm kho.

Qhov cuam tshuam rau kev loj hlob

Qhov ncauj nqus corticosteroids tuaj yeem ua rau txo qis hauv kev loj hlob sai thaum muab rau cov neeg mob menyuam yaus. Saib xyuas kev loj hlob ntawm cov neeg mob menyuam yaus uas tau txais budesonide thiab formoterol fumarate dihydrate niaj hnub (piv txwv li, ntawm stadiometry). Txhawm rau txo qis cov teebmeem ntawm qhov ncauj qhov nqus corticosteroids, suav nrog budesonide thiab formoterol fumarate dihydrate, titrate txhua tus neeg mob cov koob tshuaj rau qhov qis tshaj plaws uas tswj tau nws cov tsos mob.[saib Dosage thiab Administration (2.2) thiab Siv hauv Cov Pej Xeem Tshwj Xeeb (8.4) ].

Glaucoma thiab Cataracts

Glaucoma, nce intraocular siab, thiab cataracts tau tshaj tawm rau cov neeg mob hawb pob thiab COPD tom qab kev tswj hwm lub sijhawm ntev ntawm kev nqus cov tshuaj corticosteroids, suav nrog budesonide, ib feem ntawm BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL. Yog li ntawd, kev soj ntsuam ze yog lav rau cov neeg mob uas muaj kev hloov hauv lub zeem muag lossis nrog keeb kwm ntawm kev kub siab intraocular, glaucoma, thiab / lossis cataracts.

Cov teebmeem ntawm kev kho mob nrog budesonide thiab formoterol fumarate dihydrate 160/4.5, budesonide thiab formoterol fumarate dihydrate 80/4.5, formoterol 4.5 mcg, los yog placebo ntawm kev loj hlob ntawm cataracts los yog glaucoma tau soj ntsuam nyob rau hauv ib tug subset ntawm 461 mob ntsws nrog COPD nyob rau hauv lub COPD. kev kawm ua haujlwm. Kev kuaj pom qhov muag tau ua nyob rau hauv lub hauv paus, 24 lub lis piam, thiab 52 lub lis piam. Muaj 26 cov ntsiab lus (6%) nrog qhov nce hauv cov qhab nia tom qab subcapsular los ntawm lub hauv paus mus rau tus nqi siab tshaj (> 0.7) thaum lub sijhawm kho mob randomized. Cov kev hloov pauv hauv cov qhab nia tom qab subcapsular ntawm> 0.7 los ntawm lub hauv paus rau kev kho mob siab tshaj plaws tshwm sim hauv 11 tus neeg mob (9.0%) hauv budesonide thiab formoterol fumarate dihydrate 160/4.5 pawg, 4 cov neeg mob (3.8%) hauv budesonide thiab formoterol fumarate dihydrate 80/4.5 pawg. , 5 tus neeg mob (4.2%) hauv pawg formoterol, thiab 6 tus neeg mob (5.2%) hauv pawg placebo.

Eosinophilic Conditions thiab Churg-Strauss Syndrome

Muaj tsawg zaus, cov neeg mob ntawm qhov nqus tau corticosteroids tuaj yeem tshwm sim nrog cov kab mob eosinophilic. Qee cov neeg mob no muaj cov tsos mob ntawm vasculitis zoo ib yam nrog Churg-Strauss syndrome, ib qho mob uas feem ntau kho nrog kev kho mob corticosteroid. Cov xwm txheej no feem ntau, tab sis tsis tas li, tau cuam tshuam nrog kev txo qis thiab / lossis tshem tawm ntawm qhov ncauj corticosteroid kho tom qab kev qhia txog kev nqus corticosteroids. Cov kws kho mob yuav tsum tau ceeb toom rau eosinophilia, vasculitic ua pob liab vog, cov tsos mob ntawm lub ntsws, mob plawv, thiab / lossis neuropathy tshwm sim hauv lawv cov neeg mob. Kev sib raug zoo ntawm budesonide thiab cov xwm txheej hauv qab no tsis tau tsim.

Coexisting Conditions

Budesonide thiab formoterol fumarate dihydrate, zoo li tag nrho cov tshuaj uas muaj sympathomimetic amines, yuav tsum tau siv nrog ceev faj rau cov neeg mob convulsive disorders los yog thyrotoxicosis thiab nyob rau hauv cov neeg uas txawv txawv teb rau sympathomimetic amines. Cov koob tshuaj uas cuam tshuam nrog betaob-adrenoceptor agonist albuterol, thaum noj tshuaj intravenously, tau tshaj tawm tias ua rau mob ntshav qab zib mellitus thiab ketoacidosis ntau ntxiv.

Hypokalemia thiab Hyperglycemia

Cov tshuaj beta-adrenergic agonist tuaj yeem tsim cov tshuaj hypokalemia tseem ceeb hauv qee cov neeg mob, tuaj yeem dhau los ntawm intracellular shunting, uas muaj peev xwm ua rau muaj kev cuam tshuam rau cov hlab plawv.[saib Clinical Pharmacology (12.2) ].Kev txo qis hauv cov poov tshuaj hauv cov ntshav feem ntau yog ncua sijhawm, tsis tas yuav tsum tau ntxiv. Cov kev hloov pauv tseem ceeb hauv cov ntshav qabzib thiab / lossis cov poov tshuaj hauv cov ntshav tau pom ntau zaus thaum cov kev tshawb fawb soj ntsuam nrog budesonide thiab formoterol fumarate dihydrate ntawm cov koob tshuaj pom zoo.

Kev Phem Tsis Zoo

Kev siv LABA tuaj yeem ua rau cov hauv qab no:

Cov xwm txheej hnyav mob hawb pob - pw hauv tsev kho mob, intubations, tuag[saib Ceeb toom thiab ceev faj (5.1) ].
Cov teebmeem ntawm lub plawv thiab lub paj hlwb[saib Ceeb toom thiab ceev faj (5.12) ].

Kev siv lub cev thiab nqus tau corticosteroid tuaj yeem ua rau cov hauv qab no:

Candidaalbicanskab mob[saib Ceeb toom thiab ceev faj (5.4) ]
Mob ntsws los yog kab mob ua pa qis hauv cov neeg mob COPD[saib Ceeb toom thiab ceev faj (5.5) ]
Kev tiv thaiv kab mob[saib Ceeb toom thiab ceev faj (5.6) ]
Hypercorticism thiab adrenal suppression[saib Ceeb toom thiab ceev faj (5.8) ]
Kev loj hlob tshwm sim hauv cov neeg mob me[saib Ceeb toom thiab ceev faj (5.14) ]
Glaucoma thiab cataracts[saib Ceeb toom thiab ceev faj (5.15) ]

Vim tias kev sim tshuaj tau ua nyob rau hauv ntau yam sib txawv, cov tshuaj tiv thaiv tsis zoo uas tau pom nyob rau hauv kev sim tshuaj ntawm cov tshuaj tsis tuaj yeem ncaj qha piv rau cov nqi hauv kev sim tshuaj ntawm lwm cov tshuaj thiab tej zaum yuav tsis cuam tshuam txog cov nqi kev coj ua.

Clinical Trials Experience in Asthma

Cov neeg laus thiab cov hluas muaj hnub nyoog 12 xyoos thiab laus dua

Cov ntaub ntawv kev nyab xeeb tag nrho hauv cov neeg laus thiab cov tub ntxhais hluas yog ua raws li 10 qhov kev ua haujlwm- thiab cov tshuaj placebo-tswj tshuaj nyob rau hauv uas 3393 cov neeg mob hnub nyoog 12 xyoo thiab laus dua (2052 poj niam thiab 1341 txiv neej) nrog mob hawb pob ntawm qhov sib txawv hnyav tau kho nrog budesonide thiab formoterol fumarate dihydrate. /4.5 lossis 160/4.5 noj 2 inhalations ib zaug lossis ob zaug ib hnub rau 12 txog 52 lub lis piam. Hauv cov kev sim no, cov neeg mob ntawm budesonide thiab formoterol fumarate dihydrate muaj hnub nyoog nruab nrab ntawm 38 xyoo thiab feem ntau Caucasian (82%).

Qhov tshwm sim ntawm cov xwm txheej tsis zoo nyob rau hauv Table 2 hauv qab no yog ua raws li cov ntaub ntawv sib sau los ntawm peb 12 lub lis piam, ob qhov muag tsis pom kev, cov tshuaj placebo tswj cov kev tshawb fawb uas 401 cov neeg laus thiab cov hluas (148 cov txiv neej thiab 253 poj niam) hnub nyoog 12 xyoo thiab laus dua. kho nrog 2 inhalations ntawm budesonide thiab formoterol fumarate dihydrate 80/4.5 los yog budesonide thiab formoterol fumarate dihydrate 160/4.5 ob zaug ib hnub twg. Cov pab pawg budesonide thiab formoterol fumarate dihydrate yog tsim los ntawm feem ntau Caucasian (84%) cov neeg mob uas muaj hnub nyoog nruab nrab ntawm 38 xyoo, thiab ib feem pua ​​​​ntawm cov kwv yees FEVibnyob rau hauv lub hauv paus ntawm 76 thiab 68 rau 80/4.5 mcg thiab 160/4.5 mcg pab pawg kho mob, feem. Tswj caj npab rau kev sib piv suav nrog 2 inhalations ntawm budesonide HFA metered dose inhaler (MDI) 80 lossis 160 mcg, formoterol qhuav hmoov inhaler (DPI) 4.5 mcg, lossis placebo (MDI thiab DPI) ob zaug ib hnub. Table 2 suav nrog tag nrho cov xwm txheej tsis zoo uas tshwm sim ntawm qhov xwm txheej>3% nyob rau hauv ib qho budesonide thiab formoterol fumarate dihydrate pawg thiab feem ntau ntau dua li hauv pawg placebo nrog kev noj ob zaug ib hnub. Hauv kev xav txog cov ntaub ntawv no, qhov nruab nrab ntev ntawm cov neeg mob raug rau budesonide thiab formoterol fumarate dihydrate cov neeg mob yuav tsum raug coj mus rau hauv tus account, vim tias qhov xwm txheej tsis raug kho rau qhov tsis sib xws ntawm lub sijhawm kho.

Table 2 Cov kev phiv tshwm sim tshwm sim ntawm qhov tshwm sim ntawm ≧ 3% thiab feem ntau ntau dua li cov placebo hauv Budesonide thiab Formoterol Fumarate Dihydrate pawg: cov ntaub ntawv sib sau los ntawm peb 12 lub lis piam, ob-dig muag, tshuaj placebo-tswj tshuaj mob hawb pob hauv cov neeg mob 12 xyoo thiab laus dua.
Kev kho mob * Budesonide thiab Formoterol Fumarate Dihydrate Budesonide Formoterol Cov tshuaj placebo
Kev tshwm sim tsis zoo 80/4.5
NPE = 277
%
160/4.5
NPE = 124
%
80mcg ua
NPE = 121
%
160 mcg
NPE = 109
%
4.5mcg ua
NPE = 237
%
NPV = 400
%
*
Tag nrho cov kev kho mob tau muab raws li 2 inhalations ob zaug ib hnub twg.

Nasopharyngitis

10.5

9.7 ib

14.0 Nws

11.0 Nws

10.1

9.0 ib

Mob taub hau

6.5

11.3

11.6

12.8 ib

8.9 ib

6.5

Upper respiratory tract infection

7.6

10.5

8.3

9.2 ib

7.6

7.8 ib

Mob pharyngolaryngeal

6.1

8.9 ib

5.0

7.3

3.0

4.8

Sinusitis

5.8

4.8

5.8

2.8

6.3

4.8

Mob khaub thuas

3.2

2.4

6.6

0.9 ua

3.0

1.3

Mob nraub qaum

3.2

1.6

2.5

5.5

2.1

0.8 ua

Nasal congestion

2.5

3.2

2.5

3.7

1.3

1.0

Mob plab

1.1

6.5

2.5

4.6

1.3

1.8

ntuav

1.4

3.2

0.8 ua

2.8

1.7

1.0

Qhov ncauj Candidiasis

1.4

3.2

0

0

0

0.8 ua

Lub Sijhawm Nruab Nrab ntawm Kev Tshaj Tawm (hnub)

77.7 ib

73.8 ua

77.0 ua

71.4 ib

62.4 ib

55.9 ua

Kev nyab xeeb mus ntev - kev sim tshuaj kho mob hawb pob hauv cov neeg mob 12 xyoo thiab laus dua

Kev tshawb fawb txog kev nyab xeeb mus sij hawm ntev hauv cov tub ntxhais hluas thiab cov neeg laus cov neeg mob hnub nyoog 12 xyoos thiab laus dua, kho txog li 1 xyoos ntawm koob tshuaj txog 1280/36 mcg / hnub (640/18 mcg ob zaug ib hnub), qhia tias tsis muaj kev hloov pauv tseem ceeb hauv qhov xwm txheej. los yog hom tshiab ntawm cov xwm txheej tsis zoo tshwm sim tom qab lub sij hawm ntev ntawm kev kho mob. Ib yam li ntawd, tsis muaj cov qauv tseem ceeb lossis tsis xav txog ntawm qhov txawv txav tau raug soj ntsuam txog li 1 xyoos hauv kev ntsuas kev nyab xeeb suav nrog chemistry, hematology, ECG, Holter saib, thiab kev ntsuas HPA-axis.

Cov neeg mob menyuam yaus hnub nyoog qis dua 6 txog 12 xyoos

Cov ntaub ntawv kev nyab xeeb rau cov neeg mob menyuam yaus hnub nyoog qis dua 6 txog 12 xyoos yog ua raws li 1 sim ntawm 12 lub lis piam kho mob. Cov neeg mob (79 tus poj niam thiab 105 txiv neej) tau txais kev nqus corticosteroid ntawm kev sim nkag tau randomized rau budesonide thiab formoterol fumarate dihydrate 80/4.5 (n = 92) lossis budesonide pMDI 80 mcg (n = 92), 2 inhalations ob zaug ib hnub. Tag nrho cov ntaub ntawv kev nyab xeeb ntawm cov neeg mob no zoo ib yam li cov neeg mob hnub nyoog 12 xyoos thiab laus dua uas tau txais budesonide thiab formoterol fumarate dihydrate 80/4.5 ob zaug ib hnub hauv kev tshawb fawb ntawm cov qauv zoo sib xws. Cov kev phiv tshwm sim uas tshwm sim hauv cov neeg mob kho nrog budesonide thiab formoterol fumarate dihydrate 80/4.5 nrog zaus ntawm ≧3% thiab ntau zaus tshaj li cov neeg mob kho nrog budesonide pMDI 80 mcg suav nrog cov kab mob ua pa sab saud, pharyngitis, mob taub hau, thiab rhinitis.

Clinical Trials Experience in Chronic Obstructive Pulmonary Disease

Cov ntaub ntawv kev nyab xeeb tau piav qhia hauv qab no qhia txog kev raug budesonide thiab formoterol fumarate dihydrate 160/4.5 hauv 1783 tus neeg mob. Budesonide thiab formoterol fumarate dihydrate 160/4.5 tau kawm nyob rau hauv ob txoj kev tshawb fawb placebo-tswj lub ntsws ua haujlwm (6 thiab 12 lub hlis nyob rau lub sijhawm), thiab ob txoj kev tshawb fawb tswj kev ua kom hnyav (6 thiab 12 lub hlis hauv lub sijhawm) hauv cov neeg mob COPD.

Qhov tshwm sim ntawm cov xwm txheej tsis zoo hauv Table 3 hauv qab no yog ua raws li cov ntaub ntawv sib sau los ntawm ob qhov muag tsis pom kev, cov tshuaj placebo tswj lub ntsws ua haujlwm hauv kev tshawb fawb soj ntsuam (6 thiab 12 lub hlis nyob rau lub sijhawm) uas 771 tus neeg laus COPD (496 txiv neej thiab 275 poj niam) 40 hnub nyoog thiab laus dua tau kho nrog budesonide thiab formoterol fumarate dihydrate 160/4.5, ob inhalations ob zaug ib hnub twg. Ntawm cov neeg mob no 651 tau kho rau 6 lub hlis thiab 366 tau kho rau 12 lub hlis. Cov pab pawg budesonide thiab formoterol fumarate dihydrate yog tsim los ntawm feem ntau Caucasian (93%) cov neeg mob uas muaj hnub nyoog nruab nrab ntawm 63 xyoo, thiab ib feem pua ​​​​ntawm cov kwv yees FEVibntawm lub hauv paus ntawm 33%. Tswj caj npab rau kev sib piv suav nrog 2 inhalations ntawm budesonide HFA (MDI) 160 mcg, formoterol (DPI) 4.5 mcg lossis placebo (MDI thiab DPI) ob zaug ib hnub. Table 3 suav nrog tag nrho cov xwm txheej tsis zoo uas tshwm sim ntawm qhov tshwm sim ntawm ≧3% hauv pawg budesonide thiab formoterol fumarate dihydrate thiab feem ntau ntau dua li hauv pawg placebo. Hauv kev xav txog cov ntaub ntawv no, qhov nruab nrab ntev ntawm cov neeg mob raug rau budesonide thiab formoterol fumarate dihydrate yuav tsum raug coj mus rau hauv tus account, vim tias qhov xwm txheej tsis raug kho rau qhov tsis sib xws ntawm lub sijhawm kho.

Table 3 Cov kev phiv tshwm sim tshwm sim ntawm qhov tshwm sim ntawm ≧ 3% thiab ntau dua li cov placebo hauv Budesonide thiab Formoterol Fumarate Dihydrate pawg: cov ntaub ntawv sib sau los ntawm ob qhov muag tsis pom kev, cov placebo-tswj kev kuaj mob COPD
*
Tag nrho cov kev kho mob tau muab raws li 2 inhalations ob zaug ib hnub twg.

Kev kho mob *

Budesonide thiab Formoterol Fumarate Dihydrate

Budesonide

Formoterol

Cov tshuaj placebo

Kev tshwm sim tsis zoo

160/4.5

NPE = 771

%

160 mcg

NPE = 275

%

4.5mcg ua

NPE = 779

%

NPE = 781

%

Nasopharyngitis

7.3

3.3

5.8

4.9

Qhov ncauj candidiasis

6.0

4.4

1.2

1.8

Mob ntsws

5.4

4.7

4.5

3.5

Sinusitis

3.5

1.5

3.1

1.8

Upper pa ib ntsuj av tau kab mob viral

3.5

1.8

3.6

2.7

Lub Sijhawm Nruab Nrab ntawm Kev Tshaj Tawm (hnub)

255.2 ib

157.1 ib

240.3 ib

223.7 ib

Cov kab mob ntsws uas tsis yog mob ntsws (feem ntau yog mob ntsws) tshwm sim hauv feem pua ​​​​ntawm cov neeg mob kho nrog budesonide thiab formoterol fumarate dihydrate 160/4.5 piv nrog cov placebo (7.9% vs. 5.1%, feem). Muaj tsis muaj cov qauv kev xav tsis txog ntawm kev hloov pauv txog li 1 xyoos, tshuaj xyuas (hpa-axis, cov pob txha ntxhia, cov pob txha ntxhia, cov pob txha ntxhia thiab cov kev ntsuas ophthalmology.

Cov kev tshawb pom kev nyab xeeb los ntawm ob qhov kev tshawb fawb ob qhov muag tsis pom kev, tswj kev ua haujlwm hnyav (6 thiab 12 lub hlis hauv lub sijhawm) uas 1012 tus neeg laus COPD (616 tus txiv neej thiab 396 tus poj niam) 40 xyoo thiab laus dua tau kho nrog budesonide thiab formoterol fumarate dihydrate. 160/4.5, ob qhov nqus tau ob zaug ib hnub tau ua raws li kev tshawb fawb ntawm lub ntsws.

Postmarketing Experience

Cov kev cuam tshuam tsis zoo hauv qab no tau raug txheeb xyuas thaum pom zoo siv budesonide thiab formoterol fumarate dihydrate. Vim tias cov tshuaj tiv thaiv no tau lees paub los ntawm cov pej xeem tsis paub meej qhov loj, nws tsis yog ib txwm ua tau kom ntseeg tau tias lawv cov zaus los yog tsim kom muaj kev sib raug zoo rau kev siv tshuaj. Qee qhov kev cuam tshuam tsis zoo no kuj tseem tau pom hauv kev tshawb fawb soj ntsuam nrog budesonide thiab formoterol fumarate dihydrate.

Mob plawv:angina pectoris, tachycardia, atrial thiab ventricular tachyarrhythmias, atrial fibrillation, extrasystoles, palpitations

Cov kab mob endocrine:hypercorticism, kev loj hlob nrawm txo hauv cov neeg mob menyuam yaus

Qhov muag tsis pom kev:cataract, glaucoma, nce intraocular siab

Mob plab hnyuv:oropharyngeal candidiasis, xeev siab

Cov kab mob tiv thaiv kab mob:Cov tshuaj tiv thaiv tam sim thiab qeeb qeeb, xws li cov tshuaj tiv thaiv anaphylactic, angioedema, bronchospasm, urticaria, exanthema, dermatitis, pruritus

Metabolic thiab noj zaub mov tsis zoo:hyperglycemia, hypokalemia

Musculoskeletal, connective cov ntaub so ntswg, thiab pob txha mob:mob leeg

Cov tsos mob ntawm lub paj hlwb:tshee, kiv taub hau

Psychiatric Disorders:kev coj tus cwj pwm cuam tshuam, pw tsaug zog cuam tshuam, nervousness, agitation, kev nyuaj siab, nyob tsis tswm

Ua pa, thoracic, thiab mediastinal mob:dysphonia, hnoos, caj pas khaus

Cov kab mob ntawm daim tawv nqaij thiab cov nqaij mos subcutaneous:tawv nqaij tawv

Cov kab mob vascular:hypotension, ntshav siab

Kev Sib Tham Tshuaj

Hauv kev tshawb fawb soj ntsuam, kev tswj hwm ib txhij ntawm budesonide thiab formoterol fumarate dihydrate thiab lwm yam tshuaj, xws li luv luv-acting beta.ob-agonists, intranasal corticosteroids, thiab antihistamines / decongestants tsis ua rau muaj kev cuam tshuam ntau zaus. Tsis muaj kev tshawb fawb txog kev sib raug zoo ntawm cov tshuaj tau ua nrog budesonide thiab formoterol fumarate dihydrate.

Inhibitors ntawm Cytochrome P4503A4

Txoj hauv kev tseem ceeb ntawm cov metabolism ntawm corticosteroids, suav nrog budesonide, ib feem ntawm budesonide thiab formoterol fumarate dihydrate, yog ntawm cytochrome P450 (CYP) isoenzyme 3A4 (CYP3A4). Tom qab kev tswj hwm qhov ncauj ntawm ketoconazole, muaj zog inhibitor ntawm CYP3A4, qhov nruab nrab plasma concentration ntawm qhov ncauj tswj hwm budesonide nce. Concomitant kev tswj hwm ntawm CYP3A4 tuaj yeem cuam tshuam cov metabolism ntawm, thiab ua rau kom muaj kev cuam tshuam rau, budesonide. Kev ceev faj yuav tsum tau siv thaum xav txog kev sib koom ua ke ntawm budesonide thiab formoterol fumarate dihydrate nrog ketoconazole mus sij hawm ntev thiab lwm yam muaj zog CYP3A4 inhibitors (piv txwv li, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saliteavir, liteavir.[saib Ceeb toom thiab ceev faj (5.9) ].

Monoamine Oxidase Inhibitors thiab Tricyclic Antidepressants

Budesonide thiab formoterol fumarate dihydrate yuav tsum tau noj nrog ceev faj rau cov neeg mob uas tau kho nrog monoamine oxidase inhibitors los yog tricyclic antidepressants, los yog nyob rau hauv 2 lub lis piam ntawm discontinuation ntawm cov neeg ua hauj, vim hais tias qhov kev txiav txim ntawm formoterol, ib feem ntawm budesonide thiab formoterol fumarate dihydrate, nyob rau hauv lub vascular. Cov kab ke no tuaj yeem muaj zog los ntawm cov neeg ua haujlwm no. Hauv kev sim tshuaj nrog budesonide thiab formoterol fumarate dihydrate, tsawg tus neeg mob COPD thiab mob ntsws asthma tau txais tricyclic antidepressants, thiab, yog li ntawd, tsis muaj cov ntsiab lus tseem ceeb hauv kev kho mob ntawm cov xwm txheej tsis zoo tuaj yeem ua.

Beta-Adrenergic Receptor Blocking Agents

Beta-blockers (nrog rau qhov muag tee) yuav tsis tsuas thaiv cov pulmonary nyhuv ntawm beta-agonists, xws li formoterol, ib feem ntawm budesonide thiab formoterol fumarate dihydrate, tab sis tej zaum yuav ua rau mob hnyav bronchospasm rau cov neeg mob hawb pob. Yog li, cov neeg mob hawb pob yuav tsum tsis txhob raug kho nrog beta-blockers. Txawm li cas los xij, nyob rau qee qhov xwm txheej, tej zaum yuav tsis muaj lwm txoj hauv kev rau kev siv beta-adrenergic thaiv cov neeg ua haujlwm hauv cov neeg mob hawb pob. Hauv qhov chaw no, cardioselective beta-blockers tuaj yeem raug txiav txim siab, txawm hais tias lawv yuav tsum tau tswj hwm nrog ceev faj.

Diuretics

ECG hloov pauv thiab / lossis hypokalemia uas tuaj yeem tshwm sim los ntawm kev tswj hwm ntawm cov tshuaj uas tsis yog-potassium-sparing diuretics (xws li lub voj lossis thiazide diuretics) tuaj yeem ua rau mob hnyav los ntawm beta-agonists, tshwj xeeb tshaj yog thaum cov koob tshuaj pom zoo ntawm beta-agonist ntau dhau. Txawm hais tias qhov tseem ceeb ntawm kev kho mob ntawm cov teebmeem no tsis paub, kev ceev faj yog qhia nyob rau hauv kev sib koom tes ntawm budesonide thiab formoterol fumarate dihydrate nrog tsis-potassium-sparing diuretics.

Siv rau hauv cov neeg tshwj xeeb

Kev xeeb tub

Risk Summary

Tsis muaj kev tshawb fawb txaus thiab tswj tau zoo ntawm budesonide thiab formoterol fumarate dihydrate los yog ib qho ntawm nws cov khoom xyaw, formoterol fumarate, hauv cov poj niam cev xeeb tub; Txawm li cas los xij cov kev tshawb fawb muaj nyob rau lwm cov tshuaj budesonide. Hauv kev tshawb fawb tsiaj txhu, budesonide thiab formoterol fumarate dihydrate, tswj hwm los ntawm txoj kev nqus pa, yog teratogenic, embryocidal, thiab txo qhov hnyav ntawm tus menyuam hauv nas tsawg dua li qhov siab tshaj plaws tau pom zoo tib neeg niaj hnub nqus tshuaj (MRHDID) ntawm ib mcg / m.obhauv paus. Budesonide ib leeg, tswj hwm los ntawm txoj kev subcutaneous, yog teratogenic, embryocidal, thiab txo qis hauv plab hauv cov nas thiab luav tsawg dua li MRHDID, tab sis cov teebmeem no tsis tau pom hauv cov nas uas tau txais cov tshuaj nqus mus txog 4 zaug ntawm MRHDID. Kev tshawb fawb ntawm cov poj niam cev xeeb tub tsis tau pom tias nqus tau budesonide ib leeg ua rau muaj kev pheej hmoo ntawm kev txawv txav thaum siv thaum cev xeeb tub. Kev paub nrog qhov ncauj corticosteroids qhia tias nas muaj ntau dua rau cov teebmeem teratogenic los ntawm kev raug corticosteroid ntau dua li tib neeg. Formoterol fumarate ib leeg, tswj hwm los ntawm qhov ncauj, yog teratogenic hauv nas thiab luav ntawm 1600 thiab 65,000 npaug ntawm MRHDID, raws li. Formoterol fumarate kuj yog embryocidal, nce pup poob thaum yug thiab thaum lactation, thiab txo tus menyuam qhov hnyav hauv nas ntawm 110 npaug ntawm MRHDID. Cov kev tsis zoo no feem ntau tshwm sim ntawm ntau qhov ntau ntawm MRHDID thaum formoterol fumarate tau tswj hwm los ntawm qhov ncauj txoj hauv kev kom ua tiav cov kab mob siab. Tsis muaj teratogenic, embryocidal, lossis kev loj hlob cuam tshuam tau pom hauv cov nas uas tau txais cov tshuaj nqus nqus mus txog 375 npaug ntawm MRHDID.

Kev kwv yees keeb kwm yav dhau los ntawm kev yug me nyuam loj thiab nchuav menyuam ntawm cov neeg uas tau qhia tsis paub. Hauv Teb Chaws Asmeskas cov pej xeem, kwv yees keeb kwm kev pheej hmoo ntawm kev yug me nyuam loj thiab nchuav menyuam hauv kev kuaj mob pom zoo yog 2% mus rau 4% thiab 15% mus rau 20%, feem.

Kev txiav txim siab kho mob

Kab Mob-Associated Maternal and/lossis Embryo/Fetal risk

Hauv cov poj niam uas muaj mob hawb pob tsis zoo lossis tsis muaj kev tswj hwm tus mob hawb pob, muaj kev pheej hmoo ntau ntxiv ntawm ntau qhov tshwm sim tsis zoo xws li preeclampsia hauv leej niam thiab yug ntxov ntxov, qhov hnyav yug me me, thiab me me rau lub hnub nyoog gestational hauv cov menyuam mos. Cov poj niam cev xeeb tub uas muaj mob hawb pob yuav tsum tau saib xyuas zoo thiab kho tshuaj raws li qhov tsim nyog los tswj kev mob hawb pob zoo.

Kev Ua Haujlwm lossis Kev Xa Khoom

Tsis muaj kev tswj xyuas tib neeg zoo uas tau tshawb xyuas qhov cuam tshuam ntawm budesonide thiab formoterol fumarate dihydrate thaum lub sijhawm ua haujlwm thiab xa khoom. Vim tias muaj peev xwm ua rau beta-agonist cuam tshuam nrog uterine contractility, kev siv budesonide thiab formoterol fumarate dihydrate thaum lub sij hawm ua hauj lwm yuav tsum txwv rau cov neeg mob uas cov txiaj ntsig tau pom tseeb dua qhov kev pheej hmoo.

Cov ntaub ntawv

Tib neeg cov ntaub ntawv

Kev tshawb fawb ntawm cov poj niam cev xeeb tub tsis tau pom tias nqus tau budesonide ua rau muaj kev pheej hmoo ntawm kev txawv txav thaum siv thaum cev xeeb tub. Cov txiaj ntsig tau los ntawm cov pej xeem loj-raws li kev tshawb fawb txog kev sib kis kab mob tshuaj xyuas cov ntaub ntawv los ntawm peb qhov kev sau npe Swedish uas suav txog kwv yees li 99% ntawm cev xeeb tub los ntawm 1995-1997 (piv txwv li, Swedish Medical Birth Registry; Registry of Congenital Malformations; Child Cardiology tsis muaj kev pheej hmoo ntxiv) rau congenital malformations los ntawm kev siv inhaled budesonide thaum ntxov cev xeeb tub. Congenital malformations tau kawm nyob rau hauv 2014 cov me nyuam yug los rau cov niam qhia txog kev siv cov nqus tau pa budesonide rau mob hawb pob thaum ntxov cev xeeb tub (feem ntau 10-12 lub lis piam tom qab lub caij nyoog poj niam kawg), lub sij hawm uas feem ntau loj malformations tshwm sim. Tus nqi ntawm cov ntaub ntawv sau tseg tsis zoo yog qhov zoo sib xws rau cov pej xeem sawv daws (3.8% vs. 3.5%, feem). Tsis tas li ntawd, tom qab kis tau rau qhov nqus tau budesonide, tus naj npawb ntawm cov me nyuam yug los nrog orofacial clefts zoo ib yam li cov neeg xav tau nyob rau hauv ib txwm pej xeem (4 cov me nyuam vs. 3.3, feem).

Cov ntaub ntawv tib yam no tau siv nyob rau hauv ib txoj kev tshawb fawb thib ob uas coj tag nrho rau 2534 tus menyuam mos uas nws niam tau txais kev nqus budesonide. Nyob rau hauv txoj kev tshawb no, tus nqi ntawm congenital malformations ntawm cov me nyuam mos uas nws niam tau raug rau nqus tau pa budesonide thaum ntxov cev xeeb tub tsis txawv ntawm tus nqi rau tag nrho cov me nyuam mos nyob rau hauv tib lub sij hawm (3.6%).

Cov ntaub ntawv tsiaj

Budesonide thiab Formoterol Fumarate Dihydrate

Hauv kev tshawb fawb txog kev loj hlob ntawm embryo-fetal hauv cov nas cev xeeb tub tau txhaj tshuaj thaum lub sijhawm organogenesis los ntawm gestation hnub 6-16, budesonide thiab formoterol fumarate dihydrate tsim lub plab hernia hauv fetuses ntawm koob tshuaj tsawg dua MRHDID (ntawm ib mcg / m.obnyob rau hauv cov koob tshuaj ntawm leej niam nqus pa ntawm 12/0.66 mcg / kg / hnub thiab siab dua). Qhov hnyav ntawm tus menyuam hauv plab tau txo qis ntawm kwv yees li 5 thiab 3 npaug ntawm MRHDID, raws li txoj cai (raws li AUC raws li tus menyuam nqus pa ntawm 80/4.4 mcg / kg (budesonide / formoterol)). Tsis muaj cov teebmeem teratogenic lossis embryocidal tau kuaj pom ntawm koob tshuaj tsawg dua li MRHDID (ntawm ib mcg / mobhauv paus ntawm tus niam qhov nqus nqus ntawm 2.5 / 0.14 mcg / kg / hnub).

Budesonide

Hauv kev tshawb fawb txog kev xeeb tub thiab kev yug me nyuam, txiv neej nas tau txhaj tshuaj subcutaneously rau 9 lub lis piam thiab cov poj niam rau 2 lub lis piam ua ntej ua khub thiab thoob plaws lub sijhawm mating. Cov poj niam tau txhaj tshuaj mus txog thaum lawv cov xeeb ntxwv. Budesonide ua rau txo qis hauv kev muaj peev xwm ua ntej yug menyuam thiab kev muaj peev xwm ntawm cov menyuam thaum yug los thiab thaum lub sijhawm lactation, nrog rau kev txo qis hauv niam lub cev hnyav nce, ntawm koob tshuaj tsawg dua MRHDID (ntawm ib mcg / m.obhauv paus ntawm niam txiv subcutaneous koob tshuaj ntawm 20 mcg / kg / hnub thiab siab dua). Tsis muaj cov teebmeem zoo li no tau sau tseg ntawm koob tshuaj tsawg dua MRHDID (ntawm mcg / mobnyob rau hauv cov koob tshuaj ntawm leej niam subcutaneous ntawm 5 mcg / kg / hnub).

Nyob rau hauv ib txoj kev tshawb fawb embryo-fetal hauv cev xeeb tub luav noj thaum lub sij hawm organogenesis los ntawm gestation hnub 6-18, budesonide ua rau fetal poob, poob fetal hnyav, thiab skeletal abnormalities ntawm koob tshuaj tsawg tshaj li MRHDID (ntawm ib mcg / m.obnyob rau hauv cov koob tshuaj ntawm leej niam subcutaneous ntawm 25 mcg / kg / hnub). Hauv kev tshawb fawb txog kev loj hlob ntawm embryo-fetal nyob rau hauv cov nas cev xeeb tub koob tshuaj thaum lub sij hawm organogenesis los ntawm gestation hnub 6-15, budesonide ua rau muaj kev cuam tshuam fetal zoo sib xws ntawm koob tshuaj kwv yees li 8 npaug ntawm MRHDID (ntawm ib mcg / m.obnyob rau hauv cov koob tshuaj ntawm leej niam subcutaneous ntawm 500 mcg / kg / hnub). Hauv lwm txoj kev tshawb fawb embryo-fetal hauv cov nas cev xeeb tub, tsis muaj qhov cuam tshuam teratogenic lossis embryocidal tshwm sim ntawm koob tshuaj txog 4 zaug ntawm MRHDID (ntawm ib mcg / m.obhauv paus ntawm kev nqus pa ntawm leej niam mus txog 250 mcg / kg / hnub).

Hauv kev tshawb fawb txog kev loj hlob ntawm peri-thiab tom qab yug me nyuam, nas tau txhaj tshuaj txij hnub xeeb tub 15 txog hnub tom qab yug me nyuam 21, budesonide tsis muaj kev cuam tshuam rau kev yug menyuam, tab sis tau muaj kev cuam tshuam rau kev loj hlob thiab kev loj hlob ntawm cov xeeb ntxwv. Cov menyuam muaj sia nyob tau txo qis thiab cov menyuam muaj sia nyob tau txo qis lub cev qhov hnyav thaum yug thiab thaum lactation ntawm koob tshuaj tsawg dua MRHDID thiab siab dua (ntawm ib mcg / mobhauv paus ntawm niam txiv subcutaneous koob tshuaj ntawm 20 mcg / kg / hnub thiab siab dua). Cov kev tshawb pom no tau tshwm sim nyob rau hauv lub xub ntiag ntawm niam txiv toxicity.

Formoterol

Hauv kev tshawb fawb txog kev xeeb tub thiab kev yug me nyuam, txiv neej nas tau noj tshuaj noj rau 9 lub lis piam thiab cov poj niam rau 2 lub lis piam ua ntej ua khub thiab thoob plaws lub sijhawm mating. Cov poj niam tau txhaj tshuaj mus txog hnub yug 19 lossis txog rau thaum lawv cov xeeb ntxwv. Cov txiv neej tau txhaj tshuaj mus txog 25 lub lis piam. Umbilical hernia tau pom nyob rau hauv nas fetuses ntawm qhov ncauj koob tshuaj 1600 zaug thiab ntau dua MRHDID (ntawm ib mcg / mobhauv paus ntawm niam txiv qhov ncauj koob tshuaj ntawm 3000 mcg / kg / hnub thiab siab dua). Brachygnatia tau pom nyob rau hauv nas fetuses ntawm koob tshuaj 8000 npaug ntawm MRHDID (ntawm ib mcg / mobraws li kev noj tshuaj ntawm leej niam qhov ncauj ntawm 15,000 mcg / kg / hnub). Kev xeeb tub tau ntev ntawm koob tshuaj 8000 npaug ntawm MRHDID (ntawm mcg / mobraws li kev noj tshuaj ntawm leej niam qhov ncauj ntawm 15,000 mcg / kg / hnub). Fetal thiab menyuam tuag tshwm sim ntawm koob tshuaj kwv yees li 1600 npaug ntawm MRHDID thiab siab dua (ntawm mcg / mobhauv paus ntawm qhov ncauj koob tshuaj ntawm 3000 mcg / kg / hnub thiab siab dua) thaum cev xeeb tub.

Hauv kev tshawb fawb txog kev loj hlob ntawm embryo-fetal hauv cov nas cev xeeb tub tau txhaj tshuaj thaum lub sijhawm organogenesis txij hnub xeeb tub 6-15, tsis muaj teratogenic, embryocidal lossis kev loj hlob cuam tshuam tau pom ntawm koob tshuaj txog 375 npaug ntawm MRHDID (ntawm ib mcg / m.obhauv paus nrog rau leej niam nqus tau cov koob tshuaj txog li 690 mcg/kg/hnub).

Hauv kev tshawb fawb txog kev loj hlob ntawm embryo-fetal nyob rau hauv cev xeeb tub luav noj thaum lub sij hawm organogenesis los ntawm gestation hnub 6-18, subcapsular cysts ntawm daim siab tau pom nyob rau hauv lub fetuses ntawm ib koob tshuaj 65,000 lub sij hawm MRHDID (ntawm ib mcg / m.obraws li niam txiv qhov ncauj koob tshuaj ntawm 60,000 mcg/kg/hnub). Tsis muaj cov teebmeem teratogenic tau pom ntawm koob tshuaj txog li 3800 npaug ntawm MRHDID (ntawm mcg / mobraws li niam txiv qhov ncauj koob tshuaj txog li 3500 mcg/kg/hnub).

Hauv kev tshawb fawb ua ntej thiab tom qab yug me nyuam, cov poj niam cev xeeb tub nas tau txais cov tshuaj formoterol ntawm qhov ncauj ntawm 0, 210, 840, thiab 3400 mcg / kg / hnub txij li hnub yug hnub 6 mus txog rau lub sijhawm lactation. Pup ciaj sia taus raug txo txij thaum yug mus txog hnub tom qab yug menyuam 26 ntawm koob tshuaj 110 npaug ntawm MRHDID thiab siab dua (ntawm mcg / mobhauv paus ntawm niam txiv qhov ncauj koob tshuaj ntawm 210 mcg / kg / hnub thiab siab dua), txawm hais tias tsis muaj pov thawj ntawm kev sib raug zoo ntawm koob tshuaj. Tsis muaj kev kho mob cuam tshuam rau lub cev, kev ua haujlwm, thiab kev coj tus cwj pwm ntawm cov menyuam nas.

lactation

Risk Summary

Tsis muaj cov ntaub ntawv muaj nyob rau ntawm cov teebmeem ntawm budesonide thiab formoterol fumarate dihydrate, budesonide los yog formoterol fumarate ntawm tus menyuam noj mis los yog ntawm cov kua mis. Budesonide, zoo li lwm yam corticosteroids inhaled, muaj nyob rau hauv tib neeg cov kua mis[saib cov ntaub ntawv]. Tsis muaj cov ntaub ntawv muaj nyob ntawm qhov muaj ntawm formoterol fumarate hauv tib neeg cov kua mis. Formoterol fumarate muaj nyob rau hauv cov kua mis nyuj[saib cov ntaub ntawv]. Cov txiaj ntsig kev loj hlob thiab kev noj qab haus huv ntawm kev pub niam mis yuav tsum tau txiav txim siab nrog rau leej niam qhov kev xav tau ntawm budesonide thiab formoterol fumarate dihydrate thiab tej zaum yuav muaj kev cuam tshuam rau tus menyuam mos noj mis los ntawm budesonide thiab formoterol fumarate dihydrate los yog los ntawm tus menyuam hauv plab.

Cov ntaub ntawv

Tib neeg cov ntaub ntawv nrog budesonide xa los ntawm qhuav hmoov inhaler qhia tias tag nrho cov koob tshuaj ntawm qhov ncauj txhua hnub ntawm budesonide muaj nyob rau hauv cov kua mis rau tus me nyuam yog kwv yees li 0.3% mus rau 1% ntawm cov koob tshuaj uas nqus los ntawm leej niam.[saib Tshuaj Kho Mob (12.3) ]. Rau budesonide thiab formoterol fumarate dihydrate, koob tshuaj budesonide muaj rau tus menyuam mos hauv cov kua mis, raws li feem pua ​​​​ntawm cov koob tshuaj niam txiv, yuav tsum xav tias yuav zoo ib yam.

Hauv kev tshawb fawb txog kev xeeb tub thiab kev yug me nyuam hauv cov nas, plasma qib ntawm formoterol tau ntsuas hauv cov menyuam yaus hnub tom qab yug menyuam 15.[saib Siv hauv Cov Pej Xeem Tshwj Xeeb (8.1) ]. Nws tau kwv yees tias qhov siab tshaj plaws plasma concentration uas cov menyuam tau txais los ntawm leej niam cov tsiaj, ntawm qhov siab tshaj plaws ntawm 15 mg / kg, tom qab kev laus yog 4.4% (0.24 nmol / L rau lub litter vs. 5.5 nmol / L rau leej niam). .

Kev siv menyuam yaus

Kev nyab xeeb thiab kev ua tau zoo ntawm budesonide thiab formoterol fumarate dihydrate hauv cov neeg mob hawb pob muaj hnub nyoog 12 xyoos thiab laus dua tau tsim hauv kev tshawb fawb txog li 12 lub hlis. Hauv ob lub lis piam 12, ob-dig muag, placebo-tswj US pivotal kev tshawb fawb 25 cov neeg mob hnub nyoog 12 txog 17 xyoo tau kho nrog budesonide thiab formoterol fumarate dihydrate ob zaug ib hnub.[saib Kev Tshawb Fawb Txog Kev Kho Mob (14.1) ]. Cov txiaj ntsig tau txais txiaj ntsig hauv pawg hnub nyoog no zoo ib yam li cov uas tau pom hauv cov neeg mob 18 xyoo thiab laus dua. Tsis muaj qhov sib txawv pom tseeb hauv hom lossis zaus ntawm cov xwm txheej tsis zoo tau tshaj tawm hauv pawg hnub nyoog no piv rau cov neeg mob hnub nyoog 18 xyoo thiab laus dua.

Kev nyab xeeb thiab kev ua tau zoo ntawm budesonide thiab formoterol fumarate dihydrate 80/4.5 hauv cov neeg mob hawb pob 6 txog 12 xyoos tau tsim nyob rau hauv kev tshawb fawb txog li 12 lub lis piam [saib Kev Tshawb Fawb Txog Kev Kho Mob (14.1) ]. Cov ntaub ntawv kev nyab xeeb hauv cov neeg mob no tau ua raws li qhov pom hauv cov neeg mob hnub nyoog 12 xyoos thiab laus dua uas tau txais budesonide thiab formoterol fumarate dihydrate [saib Kev Tsis Pom Zoo (6.1) ].

Kev nyab xeeb thiab kev ua tau zoo ntawm budesonide thiab formoterol fumarate dihydrate nyob rau hauv cov neeg mob hawb pob qis dua 6 xyoo tsis tau tsim.

Cov kev tshawb fawb soj ntsuam tau pom tias qhov ncauj nqus corticosteroids suav nrog budesonide, ib feem ntawm budesonide thiab formoterol fumarate dihydrate, yuav ua rau txo qis kev loj hlob tshaj tawm hauv cov neeg mob menyuam yaus. Cov txiaj ntsig no tau pom thaum tsis muaj cov pov thawj hauv chaw kuaj mob ntawm HPA-axis suppression, qhia tias qhov kev loj hlob sai yog qhov qhia tau ntau dua ntawm cov kab mob corticosteroid raug rau cov neeg mob ntau dua li qee qhov kev sim siv HPA-axis muaj nuj nqi. Cov txiaj ntsig ntev ntawm qhov kev txo qis hauv kev loj hlob nrawm cuam tshuam nrog qhov ncauj nqus corticosteroids, suav nrog qhov cuam tshuam ntawm qhov siab kawg tsis paub. Lub peev xwm rau kev loj hlob sai tom qab txiav kev kho mob nrog qhov ncauj nqus corticosteroids tsis tau kawm txaus.

Hauv kev tshawb fawb ntawm cov menyuam yaus mob hawb pob hnub nyoog 5 txog 12 xyoos, cov neeg kho nrog budesonide DPI 200 mcg ob zaug ib hnub (n = 311) tau txo qis kev loj hlob ntawm 1.1 centimeter piv nrog cov placebo (n = 418) thaum kawg ntawm ib xyoos. ; qhov sib txawv ntawm ob pab pawg kho mob no tsis tau nce ntxiv rau peb xyoos ntawm kev kho mob ntxiv. Thaum kawg ntawm 4 xyoos, cov menyuam yaus kho nrog budesonide DPI thiab cov menyuam yaus kho nrog cov placebo muaj qhov loj hlob zoo sib xws. Cov lus xaus uas tau txais los ntawm txoj kev tshawb no yuav ua rau muaj kev tsis sib haum xeeb ntawm kev siv corticosteroids hauv pawg kho mob thiab suav nrog cov ntaub ntawv los ntawm cov neeg mob uas muaj hnub nyoog laus thaum lub sijhawm kawm.

Kev loj hlob ntawm cov menyuam yaus uas tau txais qhov ncauj nqus corticosteroids, suav nrog budesonide thiab formoterol fumarate dihydrate, yuav tsum tau saib xyuas. Yog hais tias ib tug me nyuam los yog cov tub ntxhais hluas ntawm ib qho corticosteroid zoo li muaj kev loj hlob inhibition, qhov ua tau tias nws yog qhov tshwj xeeb tshaj yog rau cov nyhuv no. Cov txiaj ntsig loj hlob ntawm kev kho mob ntev yuav tsum tau hnyav rau cov txiaj ntsig kho mob tau txais. Txhawm rau txo qis cov teebmeem ntawm qhov ncauj qhov nqus corticosteroids, suav nrog budesonide thiab formoterol fumarate dihydrate, txhua tus neeg mob yuav tsum tau titrated rau lub zog qis tshaj plaws uas tswj hwm nws tus mob hawb pob.[saib Dosage thiab Administration (2) ].

Kev siv Geriatric

Ntawm tag nrho cov neeg mob hawb pob tau kho nrog budesonide thiab formoterol fumarate dihydrate ob zaug ib hnub nyob rau hauv ob txoj kev tshawb fawb 12-lub lim tiam thiab 26-lub lim tiam kev tshawb fawb tom khw, 791 muaj hnub nyoog 65 xyoo lossis laus dua, ntawm 141 hnub nyoog 75 xyoo lossis laus dua.

Hauv kev tshawb fawb COPD ntawm 6 mus rau 12 lub hlis ntev, 810 cov neeg mob kho nrog budesonide thiab formoterol fumarate dihydrate 160/4.5, ob qhov nqus tau ob zaug ib hnub yog 65 xyoo thiab siab dua thiab ntawm cov, 177 cov neeg mob muaj hnub nyoog 75 xyoo thiab laus dua. Tsis muaj qhov sib txawv ntawm kev nyab xeeb lossis kev ua tau zoo ntawm cov neeg mob no thiab cov neeg mob yau, thiab lwm yam kev paub txog kev kho mob tsis tau txheeb xyuas qhov sib txawv ntawm cov lus teb ntawm cov neeg laus thiab cov neeg hluas.

Raws li nrog rau lwm yam khoom uas muaj betaob-agonists, yuav tsum tau ceev faj tshwj xeeb thaum siv budesonide thiab formoterol fumarate dihydrate hauv cov neeg mob laus uas muaj kab mob plawv uas tuaj yeem cuam tshuam los ntawm beta.ob- agonists.

Raws li cov ntaub ntawv muaj nyob rau budesonide thiab formoterol fumarate dihydrate los yog nws cov khoom nquag, tsis muaj kev hloov kho ntawm cov tshuaj budesonide thiab formoterol fumarate dihydrate hauv cov neeg mob geriatric.

Hepatic Impairment

Kev tshawb fawb tshuaj pharmacokinetic siv budesonide thiab formoterol fumarate dihydrate tsis tau ua rau cov neeg mob uas muaj lub siab tsis zoo. Txawm li cas los xij, txij li ob qho tib si budesonide thiab formoterol fumarate feem ntau tshem tawm los ntawm cov kab mob siab metabolism, kev ua haujlwm tsis zoo ntawm daim siab tuaj yeem ua rau tsub zuj zuj ntawm budesonide thiab formoterol fumarate hauv plasma. Yog li ntawd, cov neeg mob uas muaj kab mob siab yuav tsum tau saib xyuas kom zoo.

Lub raum Impairment

Kev tshawb fawb tshuaj pharmacokinetic siv budesonide thiab formoterol fumarate dihydrate tsis tau ua rau cov neeg mob lub raum tsis zoo.

Kev noj ntau dhau

BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL

BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL muaj ob qho tib si budesonide thiab formoterol; Yog li ntawd, cov kev pheej hmoo cuam tshuam nrog kev noj ntau dhau rau cov tib neeg cov khoom tau piav qhia hauv qab no siv rau BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL. Hauv kev tshawb fawb pharmacokinetic, ib koob tshuaj ntawm 960/54 mcg (12 actuations ntawm budesonide thiab formoterol fumarate dihydrate 80/4.5) thiab 1280/36 mcg (8 actuations ntawm 160/4.5), tau muab rau cov neeg mob COPD. Tag nrho ntawm 1920/54 mcg (12 actuations ntawm budesonide thiab formoterol fumarate dihydrate 160/4.5) tau muab coj los ua ib koob tshuaj rau cov neeg noj qab haus huv thiab cov neeg mob hawb pob. Hauv kev tshawb fawb txog kev tswj xyuas kev nyab xeeb mus ntev hauv cov tub ntxhais hluas thiab cov neeg laus mob hawb pob muaj hnub nyoog 12 xyoos thiab laus dua, budesonide thiab formoterol fumarate dihydrate 160/4.5 tau muab rau 12 lub hlis ntawm koob tshuaj txog li ob zaug qhov siab tshaj plaws tau pom zoo noj txhua hnub. Tsis muaj qhov tshwm sim tsis zoo tshwm sim nyob rau hauv ib qho ntawm cov kev tshawb fawb no.

Budesonide

Lub peev xwm ua rau mob hnyav tom qab noj ntau dhau ntawm budesonide yog tsawg. Yog tias siv cov koob tshuaj ntau dhau rau lub sijhawm ntev, cov teebmeem corticosteroid xws li hypercorticism tuaj yeem tshwm sim.[saib Ceeb toom thiab ceev faj (5) ]. Budesonide ntawm tsib zaug ntawm qhov siab tshaj plaws pom zoo koob tshuaj (3200 mcg txhua hnub) muab rau tib neeg rau 6 lub lis piam ua rau txo qis (27%) hauv cov ntshav cortisol cov lus teb rau 6-teev kev txhaj tshuaj ntawm ACTH piv nrog cov placebo (+1%). Cov txiaj ntsig zoo sib xws ntawm 10 mg prednisone txhua hnub yog 35% txo qis hauv cov ntshav cortisol cov lus teb rau ACTH.

Formoterol

Kev noj tshuaj ntau dhau ntawm formoterol yuav ua rau muaj kev cuam tshuam loj heev rau betaob- agonists: qaug dab peg, angina, kub siab, hypotension, tachycardia, atrial thiab ventricular tachyarrhythmias, nervousness, taub hau, tshee, palpitations, nqaij cramps, xeev siab, kiv taub hau, pw tsaug zog cuam tshuam, metabolic acidosis, hyperglycemia, hypokalemia. Raws li nrog rau tag nrho cov tshuaj sympathomimetic, lub plawv nres thiab txawm tuag yuav cuam tshuam nrog kev tsim txom ntawm formoterol. Tsis muaj qhov cuam tshuam loj heev hauv kev kho mob tau pom thaum formoterol raug xa mus rau cov neeg laus uas muaj mob bronchoconstriction ntawm ib koob ntawm 90 mcg / hnub dhau 3 teev lossis kom muaj mob hawb pob 3 zaug hauv ib hnub ntawm tag nrho cov koob tshuaj 54 mcg / hnub rau 3 hnub.

Kev kho mob ntawm formoterol overdosage muaj kev txiav tawm ntawm cov tshuaj ua ke nrog lub chaw haujlwm ntawm cov tsos mob thiab / lossis kev txhawb nqa. Kev txiav txim siab siv cardioselective beta-receptor blocker yuav raug txiav txim siab, ua rau lub siab xav tias cov tshuaj no tuaj yeem ua rau bronchospasm. Muaj pov thawj tsis txaus los txiav txim siab seb kev lim ntshav puas muaj txiaj ntsig zoo rau kev noj ntau dhau ntawm formoterol. Kev soj ntsuam plawv yog pom zoo nyob rau hauv cov ntaub ntawv ntawm overdosage.

Budesonide thiab Formoterol Aerosol Nqe lus piav qhia

BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL 80/4.5 thiab BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL 160/4.5 txhua tus muaj micronized budesonide thiab micronized hauv formation hydroterol fumarate nkaus xwb.

Txhua BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL 80/4.5 thiab BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL 160/4.5 canister yog formulated raws li ib tug hydrofluoroalkane 321, 3 propane, HFA, 2-propylene, fluoroalkane 2, 3-propylene, HFA, 3-propylene, fluoroalkane, 3-propylene, fluoroalkane. Pressurized metered koob tshuaj inhaler muaj 120 actuations[saib Dosage Forms thiab Strength (3) thiab Yuav Siv Li Cas / Khaws thiab Ua Haujlwm (16) ]. Tom qab priming, txhua actuation meters 91/5.1 mcg los yog 181/5.1 mcg los ntawm lub valve thiab xa 80/4.5 mcg, los yog 160/4.5 mcg (budesonide micronized / formoterol fumarate dihydrate micronized) los ntawm tus actuator. Tus nqi tiag tiag ntawm cov tshuaj xa mus rau lub ntsws tuaj yeem nyob ntawm tus neeg mob yam xwm txheej, xws li kev sib koom tes ntawm kev ua haujlwm ntawm cov cuab yeej thiab kev tshoov siab los ntawm kev xa khoom. BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL kuj muaj povidone K25 USP ua tus neeg sawv cev ncua thiab polyethylene glycol 1000 NF ua cov roj nplua nyeem.

BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL yuav tsum tau primed ua ntej siv thawj zaug los ntawm kev tso ob yam tshuaj tsuag rau saum huab cua kom deb ntawm lub ntsej muag, co zoo rau 5 vib nas this ua ntej txhua yam tshuaj tsuag. Nyob rau hauv rooj plaub uas tsis tau siv lub tshuab nqus tsev ntau tshaj 7 hnub lossis thaum nws tau poob lawm, rov ua dua lub tshuab nqus pa los ntawm kev co zoo rau 5 vib nas this ua ntej txhua cov tshuaj tsuag thiab tso ob lub tshuaj tsuag rau hauv huab cua kom deb ntawm lub ntsej muag.

Ib qho tseem ceeb ntawm BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL yog budesonide, ib qho tshuaj corticosteroid uas raug xaiv raws li (RS)-11β, 16α, 17,21-Tetrahydroxypregna-1,4-diene-3,71-dione cyclone nrog butyraldehyde. Budesonide yog muab raws li kev sib xyaw ntawm ob epimers (22R thiab 22S). Cov mis empirical ntawm budesonide yog C25H3. 4LUB6thiab nws qhov hnyav molecular yog 430.5. Nws cov qauv qauv yog:

Budesonide yog cov hmoov dawb dawb rau dawb, tsis qab, tsis muaj ntxhiab hmoov uas siv tau hauv dej thiab hauv heptane, sparingly soluble hauv ethanol, thiab dawb do soluble hauv chloroform. Nws qhov sib faib coefficient ntawm octanol thiab dej ntawm pH 7.4 yog 1.6 x 103.

Lwm yam tseem ceeb ntawm BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL yog formoterol fumarate dihydrate, xaiv beta.ob-agonist tsim tshuaj raws li (R*,R*)-(±)-N-[2-hydroxy-5-[1-hydroxy-2-[[2-(4-methoxyphenyl)-1-methylethyl]amino]ethyl phenyl]formamide, (E)-2-butendioate (2: 1), dihydrate. Cov mis mos ntawm formoterol yog C42H56N4LUB14thiab nws qhov hnyav molecular yog 840.9. Nws cov qauv qauv yog:

Formoterol fumarate dihydrate yog cov hmoov uas yog me ntsis soluble hauv dej. Nws octanol-dej faib coefficient ntawm pH 7.4 yog 2.6. Cov pKa ntawm formoterol fumarate dihydrate ntawm 25 ° C yog 7.9 rau phenolic pawg thiab 9.2 rau cov amino pawg.

Budesonide thiab Formoterol Aerosol - Clinical Pharmacology

Mechanism ntawm Action

BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL

BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL muaj ob qho tib si budesonide thiab formoterol; Yog li ntawd, cov txheej txheem ntawm kev txiav txim tau piav qhia hauv qab no rau tus kheej cov khoom siv rau BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL. Cov tshuaj no sawv cev rau ob chav kawm ntawm cov tshuaj (ib qho hluavtaws corticosteroid thiab kev ua yeeb yam ntev beta.ob-adrenoceptor agonist) uas muaj kev cuam tshuam sib txawv ntawm kev kho mob, lub cev nqaij daim tawv, thiab kev mob tshwm sim ntawm COPD thiab mob hawb pob.

Budesonide

Budesonide yog ib qho tshuaj tiv thaiv kab mob corticosteroid uas nthuav tawm cov haujlwm muaj zog glucocorticoid thiab tsis muaj zog mineralocorticoid kev ua haujlwm. Hauv tus qauvhauv vitrothiab cov qauv tsiaj, budesonide muaj kwv yees li 200-fold ntau dua affinity rau cov glucocorticoid receptor thiab 1000-fold ntau dua cov tshuaj tiv thaiv kab mob uas muaj zog tshaj li cortisol (rat croton oil ear edema assay). Raws li kev ntsuas ntawm kev ua haujlwm hauv lub cev, budesonide yog 40 npaug ntau dua li cortisol thaum muab tshuaj subcutaneously thiab 25 npaug ntau lub zog thaum siv qhov ncauj hauv cov nas thymus involution assay.

Hauv kev tshawb fawb glucocorticoid receptor affinity, 22R daim ntawv ntawm budesonide yog ob zaug ua haujlwm zoo li 22S epimer.Hauv vitroCov kev tshawb fawb qhia tias ob hom budesonide tsis cuam tshuam.

Kev mob ntsws yog ib qho tseem ceeb hauv cov kab mob COPD thiab mob hawb pob. Corticosteroids muaj ntau yam inhibitory kev ua ub no tawm tsam ntau hom cell (xws li mast cells, eosinophils, neutrophils, macrophages, thiab lymphocytes) thiab cov neeg nruab nrab (xws li, histamine, eicosanoids, leukotrienes, thiab cytokines) koom nrog kev ua xua thiab tsis ua xua-media. mob. Cov tshuaj tiv thaiv kab mob no ntawm corticosteroids tuaj yeem ua rau lawv cov txiaj ntsig zoo hauv COPD thiab mob hawb pob.

Cov kev tshawb fawb hauv cov neeg mob hawb pob tau pom qhov sib piv zoo ntawm cov tshuaj tiv thaiv kab mob thiab cov kab mob corticosteroid cuam tshuam ntau ntawm cov koob tshuaj budesonide. Qhov no tau piav qhia los ntawm kev sib xyaw ua ke ntawm cov tshuaj tiv thaiv kab mob hauv zos uas muaj zog heev, ua ntej dhau los ntawm hepatic degradation ntawm qhov ncauj absorbed yeeb tshuaj (85% -95%), thiab tsawg potency ntawm tsim metabolites.

Formoterol

Formoterol fumarate yog ib qho kev xaiv ntev ntev betaob-adrenergic agonist (betaob-agonist) nrog kev pib sai sai. Inhaled formoterol fumarate ua haujlwm hauv zos hauv lub ntsws ua bronchodilator.Hauv vitroCov kev tshawb fawb tau pom tias formoterol muaj ntau dua 200-fold ntau dua agonist kev ua ntawm betaob- receptors tshaj ntawm betaib- receptors. Covhauv vitrokhi selectivity rau betaob- dhau betaib-adrenoceptors siab dua rau formoterol dua li albuterol (5 zaug), thaum salmeterol muaj ntau dua (3 zaug) betaob-selectivity piv dua formoterol.

Txawm hais tias betaob- receptors yog qhov tseem ceeb tshaj plaws adrenergic receptors hauv bronchial du nqaij thiab betaib- receptors yog cov receptors tseem ceeb hauv lub plawv, kuj tseem muaj betaob-receptors nyob rau hauv tib neeg lub plawv muaj 10% mus rau 50% ntawm tag nrho cov beta-adrenergic receptors. Lub luag haujlwm meej ntawm cov receptors no tsis tau tsim, tab sis lawv tsa qhov muaj peev xwm txawm tias xaiv beta heev.ob-agonists tuaj yeem ua rau mob plawv.

Cov tshuaj pharmacological ntawm betaob-adrenoceptor agonist cov tshuaj, suav nrog cov formoterol, tsawg kawg yog ib feem ntawm kev txhawb nqa ntawm intracellular adenyl cyclase, lub enzyme uas ua rau kev hloov pauv ntawm adenosine triphosphate (ATP) rau cyclic-3', 5'-adenosine monophosphate (cyclic AMP). Kev nce qib cyclic AMP ua rau kom muaj kev so ntawm cov leeg nqaij bronchial thiab inhibition ntawm kev tso tawm ntawm cov neeg nruab nrab ntawm cov hlwb tam sim ntawd, tshwj xeeb tshaj yog los ntawm cov hlwb mast.

Hauv vitrocov kev ntsuam xyuas qhia tau hais tias formoterol yog ib qho inhibitor ntawm kev tso tawm ntawm mast cell mediators, xws li histamine thiab leukotrienes, los ntawm tib neeg lub ntsws. Formoterol tseem inhibits histamine-induced plasma albumin extravasation nyob rau hauv anesthetized guinea npua thiab inhibits allergen-induced eosinophil influx nyob rau hauv cov dev nrog rau txoj kev ua pa hyper-responsiveness. Qhov tseeb ntawm cov nohauv vitrothiab kev tshawb nrhiav tsiaj rau tib neeg tsis paub.

Pharmacodynamics

Mob hawb pob

Cov teebmeem ntawm lub plawv:Hauv kev tshawb fawb ib zaug ib zaug nrog rau 201 cov neeg mob uas muaj mob hawb pob, kev kho ib zaug ntawm 4.5, 9, thiab 18 mcg ntawm formoterol ua ke nrog 320 mcg ntawm budesonide xa los ntawm BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE DIHYDRATE INHYDRATE. 320mcg ib. Kev txhim kho koob txhaj tshuaj hauv FEVibtau pom thaum piv nrog budesonide. ECGs thiab ntshav kuaj ntshav qabzib thiab potassium tau txais tom qab koob tshuaj. Rau budesonide thiab formoterol fumarate dihydrate, me me txhais tau tias nce hauv cov piam thaj hauv cov ntshav thiab txo qis hauv cov poov tshuaj hauv cov ntshav (+ 0.44 mmol / L thiab -0.18 mmol / L ntawm koob tshuaj ntau tshaj, raws li) tau pom nrog nce koob tshuaj formoterol, piv rau budesonide. Hauv ECGs, budesonide thiab formoterol fumarate dihydrate tsim cov tshuaj me me ntsig txog qhov nce hauv lub plawv dhia (kwv yees li 3 bpm ntawm koob tshuaj ntau tshaj), thiab QTc ntu (3-6 msec) piv rau budesonide ib leeg. Tsis muaj cov ntsiab lus muaj QT lossis QTc tus nqi ≧500 msec.

Hauv Tebchaws Meskas, tsib 12-lub lim tiam, cov kev tshawb fawb-thiab cov tshuaj placebo-tswj thiab ib qho 6-hli kev tswj xyuas kev tshawb fawb tau soj ntsuam 2976 tus neeg mob hnub nyoog 6 xyoo thiab laus dua nrog mob hawb pob. Cov teebmeem pharmacodynamic ntawm formoterol (lub plawv / mem tes, ntshav siab, QTc ntu, potassium, thiab qabzib) zoo ib yam hauv cov neeg mob kho nrog budesonide thiab formoterol fumarate dihydrate, piv nrog cov neeg mob kho nrog formoterol qhuav inhalation hmoov 4.5 mcg, 2 inhalations ob zaug ib hnub. . Tsis muaj tus neeg mob muaj QT lossis QTc tus nqi ≧500 msec thaum kho.

Hauv peb txoj kev tshawb fawb tswj cov placebo hauv cov tub ntxhais hluas thiab cov neeg laus uas muaj mob hawb pob, hnub nyoog 12 xyoo thiab laus dua, tag nrho ntawm 1232 tus neeg mob (553 tus neeg mob hauv budesonide thiab formoterol fumarate dihydrate pawg) tau soj ntsuam tas li 24-teev electrocardiographic xyuas. Zuag qhia tag nrho, tsis muaj qhov sib txawv tseem ceeb hauv qhov tshwm sim ntawm ventricular lossis supraventricular ectopy thiab tsis muaj pov thawj ntawm kev pheej hmoo siab rau kev kho mob tseem ceeb dysrhythmia hauv budesonide thiab formoterol fumarate dihydrate pawg piv rau cov placebo.

Cov teebmeem ntawm HPA-axis:Zuag qhia tag nrho, tsis muaj qhov cuam tshuam tseem ceeb ntawm HPA-axis, raws li ntsuas los ntawm 24-teev urinary cortisol, tau soj ntsuam rau budesonide thiab formoterol fumarate dihydrate kho cov neeg laus lossis cov hluas ntawm koob tshuaj txog 640/18 mcg / hnub piv rau budesonide.

Chronic Obstructive Pulmonary Disease

Cov teebmeem ntawm lub plawv:Hauv ob txoj kev tshawb fawb COPD lub ntsws ua haujlwm, 6 lub hlis thiab 12 lub hlis nyob rau lub sijhawm suav nrog 3668 tus neeg mob COPD, tsis muaj qhov sib txawv tseem ceeb hauv kev kho mob hauv cov mem tes, ntshav siab, potassium, thiab qabzib ntawm budesonide thiab formoterol fumarate dihydrate, tus kheej cov khoom ntawm BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL, thiab cov placebo[saib Kev Kawm Kho Mob (14.2) ].

ECGs tau sau tseg ntawm ntau lub tsev kho mob mus ntsib kev kho mob hauv ob txoj kev tshawb fawb pom tias tsis muaj qhov sib txawv tseem ceeb ntawm lub plawv dhia, PR lub sijhawm, QRS lub sijhawm, lub plawv dhia, cov tsos mob ntawm lub plawv ischemia lossis arrhythmias ntawm budesonide thiab formoterol fumarate dihydrate 160/4.5 cov monoproducts thiab placebo, tag nrho. muab raws li 2 inhalations ob zaug ib hnub twg. Raws li ECGs, 6 cov neeg mob kho nrog budesonide thiab formoterol fumarate dihydrate 160/4.5, 6 cov neeg mob kho nrog formoterol 4.5 mcg, thiab 6 cov neeg mob hauv pawg placebo tau ntsib atrial fibrillation lossis flutter uas tsis muaj nyob rau hauv lub hauv paus. Tsis muaj cov neeg mob uas tsis muaj kev cuam tshuam ventricular tachycardia hauv budesonide thiab formoterol fumarate dihydrate 160/4.5, formoterol 4.5 mcg, lossis placebo pawg.

Hauv kev tshawb fawb 12 lub hlis, 520 tus neeg mob tau soj ntsuam tas li 24-teev ECG (Holter) kev tshuaj xyuas ua ntej thawj koob tshuaj thiab tom qab kwv yees li 1 thiab 4 lub hlis ntawm kev kho mob. Tsis muaj qhov sib txawv tseem ceeb hauv ventricular lossis supraventricular arrhythmias, ventricular lossis supraventricular ectopic beats, lossis lub plawv dhia tau pom ntawm cov pab pawg kho nrog budesonide thiab formoterol fumarate dihydrate 160/4.5, formoterol lossis placebo noj li 2 inhalations ob zaug ib hnub. Raws li kev soj ntsuam ECG (Holter), ib tus neeg mob ntawm budesonide thiab formoterol fumarate dihydrate 160/4.5, tsis muaj cov neeg mob ntawm formoterol 4.5 mcg, thiab peb tus neeg mob hauv pawg placebo tau ntsib atrial fibrillation lossis flutter uas tsis muaj nyob rau hauv lub hauv paus.

Cov teebmeem ntawm HPA-axis:Nees nkaum plaub teev kev ntsuas cortisol urinary cortisol tau sau rau hauv ib pawg sib koom ua ke (n = 616) ntawm cov neeg mob los ntawm ob txoj kev tshawb fawb txog COPD lub ntsws. Cov ntaub ntawv qhia txog kwv yees li 30% qis dua txhais tau tias 24-teev tso zis dawb cortisol qhov tseem ceeb tom qab kev tswj hwm mob ntev (> 6 lub hlis) ntawm budesonide thiab formoterol fumarate dihydrate, txheeb ze rau cov placebo. Budesonide thiab formoterol fumarate dihydrate tau tshwm sim los ua pov thawj piv rau cortisol suppression rau budesonide 160 mcg ib leeg los yog kev koom tes ntawm budesonide 160 mcg thiab formoterol 4.5 mcg. Rau cov neeg mob kho nrog budesonide thiab formoterol fumarate dihydrate, los yog cov placebo txog li 12 lub hlis, feem pua ​​​​ntawm cov neeg mob uas hloov ntawm ib txwm mus rau qis rau qhov ntsuas no feem ntau sib piv.

Lwm cov khoom siv Budesonide

Txhawm rau kom paub meej tias qhov kev nqus dej tsis yog qhov tseem ceeb hauv kev kho mob ntawm qhov nqus tau budesonide, kev tshawb fawb soj ntsuam hauv cov neeg mob hawb pob tau ua piv txwv 400 mcg budesonide tswj hwm los ntawm kev siv tshuaj tua kab mob siab nrog lub raj spacer rau 1400 mcg ntawm qhov ncauj qhov ncauj. . Txoj kev tshawb no tau pom qhov ua tau zoo ntawm kev nqus tau budesonide tab sis tsis yog qhov ncauj noj budesonide, txawm hais tias muaj kev sib piv ntawm cov kab ke. Yog li, cov txiaj ntsig kho mob ntawm cov tshuaj ib txwm siv ntawm qhov ncauj nqus budesonide tau piav qhia ntau los ntawm nws qhov kev txiav txim ncaj qha rau ntawm txoj hlab pa.

Inhaled budesonide tau pom tias yuav txo qis kev ua pa ntawm txoj hlab ntsws mus rau ntau yam kev sib tw qauv, suav nrog histamine, methacholine, sodium metabisulfite, thiab adenosine monophosphate hauv cov neeg mob uas muaj cov pa ua pa. Qhov kev soj ntsuam qhov tseeb ntawm cov qauv no tsis paub meej.

Pretreatment nrog inhaled budesonide, 1600 mcg ib hnub twg (800 mcg ob zaug ib hnub) rau 2 lub lis piam txo qhov mob (thaum ntxov cov tshuaj tiv thaiv) thiab qeeb (late-theem cov tshuaj tiv thaiv) txo qis hauv FEV.ibtom qab nqus tau cov tshuaj allergen.

Cov teebmeem ntawm qhov nqus tau corticosteroids cuam tshuam rau lub cev raug rau cov tshuaj no. Cov kev tshawb fawb Pharmacokinetic tau pom tias nyob rau hauv cov neeg laus thiab cov menyuam yaus uas muaj mob hawb pob qhov kev raug mob rau budesonide yog qis dua nrog budesonide thiab formoterol fumarate dihydrate, piv nrog rau cov nqus tau pa budesonide tau siv tib lub sijhawm xa los ntawm kev nqus cov hmoov qhuav.[saib Tshuaj Kho Mob (12.3) ]. Yog li ntawd, cov teebmeem ntawm lub cev (HPA-axis thiab kev loj hlob) ntawm budesonide xa los ntawm budesonide thiab formoterol fumarate dihydrate, yuav tsum tsis muaj ntau tshaj li qhov tau tshaj tawm rau cov nqus tau pa budesonide thaum noj cov tshuaj sib piv ntawm cov hmoov qhuav inhaler.[saib Siv hauv Cov Pej Xeem Tshwj Xeeb (8.4) ].

Cov teebmeem ntawm HPA-axis:Cov teebmeem ntawm qhov nqus tau budesonide tau siv los ntawm kev nqus cov hmoov qhuav ntawm HPA-axis tau kawm hauv 905 tus neeg laus thiab 404 tus neeg mob mob hawb pob. Rau cov neeg mob feem ntau, muaj peev xwm nce cortisol ntau lawm hauv kev teb rau kev ntxhov siab, raws li kev soj ntsuam los ntawm cosyntropin (ACTH) stimulation test, tseem nyob twj ywm nrog kev kho mob budesonide ntawm koob tshuaj pom zoo. Rau cov neeg laus cov neeg mob kho nrog 100, 200, 400, los yog 800 mcg ob zaug ib hnub twg rau 12 lub lis piam, 4%, 2%, 6%, thiab 13%, feem, muaj qhov txawv txav cortisol teb (peak cortisol<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.

Lwm cov khoom Formoterol

Thaum cov tshuaj pharmacodynamic cuam tshuam los ntawm kev txhawb nqa ntawm beta-adrenergic receptors, kev ua haujlwm ntau dhau ntawm cov receptors feem ntau ua rau cov leeg pob txha tremor thiab cramps, insomnia, tachycardia, txo qis hauv plasma potassium, thiab nce hauv ntshav qabzib. Inhaled formoterol, zoo li lwm yam betaob-adrenergic agonist cov tshuaj, tuaj yeem tsim cov tshuaj tiv thaiv kab mob plawv thiab cuam tshuam rau cov ntshav qabzib thiab / lossis cov ntshav liab.[saib Ceeb toom thiab ceev faj (5) ]. Rau budesonide thiab formoterol fumarate dihydrate, cov teebmeem no tau piav qhia nyob rau hauv Clinical Pharmacology, Pharmacodynamics, BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INhalation AEROSOL (12.2) ntu.

Kev siv cov tshuaj LABA tuaj yeem ua rau muaj kev ua siab ntev rau bronchoprotective thiab bronchodilatory teebmeem.

Rebound bronchial hyperresponsiveness tom qab tso tseg ntawm kev kho mob ntev ntev ntawm beta-agonist tsis tau pom.

Pharmacokinetics

BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL

Kev nqus

Budesonide
Cov ntsiab lus noj qab haus huv:Qhov ncauj nqus tau budesonide yog nqus tau sai hauv lub ntsws thiab qhov siab tshaj plaws yog feem ntau mus txog hauv 20 feeb. Tom qab kev tswj hwm ntawm qhov ncauj ntawm budesonide ncov plasma concentration tau ua tiav nyob rau hauv li 1 mus rau 2 teev thiab qhov muaj peev xwm ua tau zoo yog 6% -13% vim muaj cov metabolism hauv thawj zaug. Nyob rau hauv sib piv, feem ntau ntawm cov budesonide xa mus rau lub ntsws yog systemically absorbed. Hauv cov neeg noj qab haus huv, 34% ntawm cov tshuaj ntsuas tau muab tso rau hauv lub ntsws (raws li kev soj ntsuam los ntawm plasma concentration method thiab siv budesonide-muaj cov hmoov qhuav inhaler) nrog rau qhov muaj peev xwm ntawm 39% ntawm cov tshuaj metered.

Tom qab kev tswj hwm ntawm budesonide thiab formoterol fumarate dihydrate 160/4.5, ob lossis plaub qhov nqus tau ob zaug ib hnub rau 5 hnub hauv cov neeg noj qab haus huv, cov ntshav plasma concentration ntawm budesonide feem ntau nce hauv kev faib ua feem rau koob tshuaj. Qhov sib xyaw ua ke rau cov pab pawg uas tau txais 2 inhalations ob zaug ib hnub yog 1.32 rau budesonide.

Cov neeg mob hawb pob:Hauv kev tshawb fawb ib zaug, ntau dua li cov koob tshuaj pom zoo ntawm budesonide thiab formoterol fumarate dihydrate (12 inhalations ntawm budesonide thiab formoterol fumarate dihydrate 160/4.5) tau muab rau cov neeg mob uas muaj mob hawb pob. Peak budesonide plasma concentration ntawm 4.5 nmol / L tshwm sim ntawm 20 feeb tom qab noj. Txoj kev tshawb no pom tau hais tias tag nrho cov kab mob raug rau budesonide los ntawm budesonide thiab formoterol fumarate dihydrate yog kwv yees li 30% qis dua los ntawm kev nqus tau budesonide los ntawm cov hmoov qhuav inhaler (DPI) ntawm tib qhov xa tawm. Tom qab kev tswj hwm ntawm budesonide thiab formoterol fumarate dihydrate, ib nrab-lub neej ntawm budesonide tivthaiv yog 4.7 teev.

Hauv kev tshawb fawb txog koob tshuaj dua, qhov siab tshaj plaws tau pom zoo koob tshuaj budesonide thiab formoterol fumarate dihydrate (160/4.5, ob qhov nqus tau ob zaug ib hnub) tau muab rau cov neeg mob uas muaj mob hawb pob thiab noj qab nyob zoo rau 1 lub lis piam. Peak budesonide plasma concentration ntawm 1.2 nmol / L tshwm sim ntawm 21 feeb hauv cov neeg mob hawb pob. Peak budesonide plasma concentration yog 27% qis dua hauv cov neeg mob hawb pob piv rau cov neeg noj qab haus huv. Txawm li cas los xij, tag nrho cov kev raug mob ntawm budesonide tau muab piv rau cov neeg mob hawb pob.

Peak steady-state plasma concentrations ntawm budesonide tswj los ntawm DPI rau cov neeg laus uas muaj mob hawb pob nruab nrab ntawm 0.6 thiab 1.6 nmol / L ntawm koob tshuaj 180 mcg thiab 360 mcg ob zaug ib hnub, feem. Hauv cov neeg mob hawb pob, budesonide pom qhov nce hauv AUC thiab CmaxNrog rau kev siv tshuaj ntau ntxiv tom qab ob qho tib si ib zaug thiab rov ua dua ntawm qhov nqus tau budesonide.

Cov neeg mob COPD:Hauv kev tshawb fawb ib zaug, 12 inhalations ntawm budesonide thiab formoterol fumarate dihydrate 80/4.5 (tag nrho koob tshuaj 960/54 mcg) tau muab rau cov neeg mob COPD. Lub ntsiab lus ntawm budesonide ncov plasma concentration ntawm 3.3 nmol / L tshwm sim ntawm 30 feeb tom qab noj. Budesonide systemic exposure yog sib piv ntawm budesonide thiab formoterol fumarate dihydrate pMDI thiab coadministration ntawm budesonide los ntawm ib tug metered-dose inhaler thiab formoterol ntawm qhuav hmoov inhaler (budesonide 960 mcg thiab formoterol 54 mcg). Nyob rau hauv tib txoj kev tshawb no, ib pab pawg neeg qhib cov neeg mob hawb pob kuj tau txais tib koob tshuaj ntau dua ntawm budesonide thiab formoterol fumarate dihydrate. Rau budesonide, cov neeg mob COPD nthuav tawm 12% ntau dua AUC thiab 10% qis Cmaxpiv rau cov neeg mob hawb pob.

Hauv 6-lub hlis pivotal ntsws ua haujlwm hauv kev tshawb fawb soj ntsuam, cov ntaub ntawv nyob rau hauv lub xeev pharmacokinetic ntawm budesonide tau txais nyob rau hauv ib pawg ntawm COPD cov neeg mob nrog kev kho caj npab ntawm budesonide thiab formoterol fumarate dihydrate pMDI 160/4.5, budesonide thiab formoterol fumarate dihydrate p.MDI, 80. budesonide 160 mcg, budesonide 160 mcg thiab formoterol 4.5 mcg muab ua ke, txhua tus tswj hwm li 2 inhalations ob zaug ib hnub. Budesonide systemic raug (AUC thiab Cmax) nce proportionally nrog koob tshuaj los ntawm 80 mcg mus rau 160 mcg thiab feem ntau zoo sib xws ntawm 3 pawg kho mob tau txais tib koob tshuaj budesonide (budesonide thiab formoterol fumarate dihydrate pMDI 160/4.5, budesonide 160 mcg, budesonide 150 mcgistered formotecister 4. ).

Formoterol

Inhaled formoterol yog absorbed sai heev; Qhov siab tshaj plaws ntawm cov ntshav plasma feem ntau mus txog ntawm thawj lub sijhawm kuaj ntshav plasma, hauv 5-10 feeb tom qab noj. Raws li nrog ntau cov khoom siv tshuaj rau kev nqus ntawm qhov ncauj, nws yuav zoo li tias feem ntau ntawm cov nqus tau pa formoterol xa tau nqos thiab tom qab ntawd nqus los ntawm txoj hnyuv.

Cov ntsiab lus noj qab haus huv:Ua raws li kev tswj hwm ntawm budesonide thiab formoterol fumarate dihydrate (160/4.5, ob lossis plaub qhov nqus tau ob zaug ib hnub) rau 5 hnub hauv cov neeg noj qab haus huv, cov ntshav plasma concentration ntawm formoterol feem ntau nce nyob rau hauv feem ntawm cov tshuaj. Qhov sib xyaw ua ke rau cov pab pawg uas tau txais 2 inhalations ob zaug ib hnub yog 1.77 rau formoterol.

Cov neeg mob hawb pob:Hauv kev tshawb fawb ib zaug, ntau dua li cov koob tshuaj pom zoo ntawm budesonide thiab formoterol fumarate dihydrate (12 inhalations ntawm budesonide thiab formoterol fumarate dihydrate 160/4.5) tau muab rau cov neeg mob uas muaj mob hawb pob. Peak plasma concentration rau formoterol ntawm 136 pmol tshwm sim ntawm 10 feeb tom qab noj. Kwv yees li 8% ntawm cov tshuaj xa tawm ntawm cov tshuaj formoterol tau zoo nyob hauv cov zis raws li cov tshuaj tsis hloov pauv.

Hauv kev tshawb fawb txog koob tshuaj dua, qhov siab tshaj plaws tau pom zoo koob tshuaj budesonide thiab formoterol fumarate dihydrate (160/4.5, ob qhov nqus tau ob zaug ib hnub) tau muab rau cov neeg mob uas muaj mob hawb pob thiab noj qab nyob zoo rau 1 lub lis piam. Peak formoterol plasma concentration ntawm 28 pmol / L tshwm sim ntawm 10 feeb hauv cov neeg mob hawb pob. Peak formoterol plasma concentration yog kwv yees li 42% qis dua hauv cov neeg mob hawb pob piv rau cov neeg noj qab haus huv. Txawm li cas los xij, tag nrho cov kev raug mob ntawm formoterol tau muab piv rau cov neeg mob hawb pob.

Cov neeg mob COPD:Tom qab noj ib zaug ib zaug ntawm 12 inhalations ntawm budesonide thiab formoterol fumarate dihydrate 80/4.5, txhais tau tias ncov formoterol plasma concentration ntawm 167 pmol / L tau ua tiav sai ntawm 15 feeb tom qab noj. Formoterol raug me ntsis ntau dua (~ 16-18%) los ntawm budesonide thiab formoterol fumarate dihydrate pMDI piv rau coadministration budesonide los ntawm ib tug metered-dose inhaler thiab formoterol ntawm ib tug qhuav hmoov inhaler (tag nrho cov koob tshuaj budesonide 960 mcg thiab formoterol 54). Hauv tib txoj kev tshawb fawb, ib pawg qhib daim ntawv lo ntawm cov neeg mob ntsws asthma nruab nrab tau txais tib koob tshuaj budesonide thiab formoterol fumarate dihydrate. Cov neeg mob COPD tau nthuav tawm 12-15% ntau dua AUC thiab Cmaxforformoterol piv rau cov neeg mob hawb pob.

Nyob rau hauv 6-hli pivotal lub ntsws ua haujlwm kev tshawb fawb soj ntsuam, cov ntaub ntawv nyob rau hauv lub xeev pharmacokinetic ntawm formoterol tau txais nyob rau hauv ib tug subset ntawm COPD cov neeg mob nrog kev kho mob caj npab ntawm budesonide thiab formoterol fumarate dihydrate pMDI 160/4.5, budesonide thiab formoterol fumarate dihydrate pMDI, 80/4. formoterol 4.5 mcg, budesonide 160 mcg thiab formoterol 4.5 mcg muab ua ke, txhua tus tswj hwm li 2 inhalations ob zaug ib hnub. Lub cev raug ntawm formoterol raws li pov thawj los ntawm AUC, yog kwv yees li 30% thiab 16% siab dua los ntawm budesonide thiab formoterol fumarate dihydrate pMDI piv rau formoterol ib leeg kho caj npab thiab coadministration ntawm tus kheej cov khoom ntawm budesonide thiab formoterol kho caj npab, feem.

Kev faib tawm
Budesonide:Qhov ntim ntawm kev faib tawm ntawm budesonide yog kwv yees li 3 L / kg. Nws yog 85% -90% khi rau plasma proteins. Protein binding yog tas mus li ntawm qhov ntau ntawm cov concentration (1-100 nmol / L) ua tiav nrog, thiab tshaj, pom zoo kom nqus tau cov koob tshuaj. Budesonide pom me ntsis los yog tsis muaj khi rau corticosteroid binding globulin. Budesonide sib npaug sai nrog cov qe ntshav liab nyob rau hauv ib qho kev xav ywj pheej nrog cov ntshav plasma piv txog li 0.8.

Formoterol:Tshaj li cov concentration ntau ntawm 10-500 nmol / L, plasma protein khi rau RR thiab SS enantiomers ntawm formoterol yog 46% thiab 58%, feem. Qhov siab ntawm formoterol siv los ntsuas cov ntshav plasma protein khi tau siab dua li cov ua tiav hauv cov ntshav tom qab nqus tau ntawm ib koob tshuaj 54 mcg.

Metabolism
Budesonide: Hauv vitroCov kev tshawb fawb nrog tib neeg lub siab homogenates tau pom tias budesonide tau sai thiab nthuav dav metabolized. Ob qhov loj metabolites tsim los ntawm cytochrome P450 (CYP) isoenzyme 3A4 (CYP3A4) catalyzed biotransformation tau raug cais thiab txheeb xyuas tias yog 16α-hydroxyprednisolone thiab 6ß-hydroxybudesonide. Cov kev ua corticosteroid ntawm txhua ntawm ob lub metabolites yog tsawg dua 1% ntawm cov niam txiv compound. Tsis muaj qhov sib txawv ntawm qhov zoohauv vitrothiabnyobkuaj pom cov qauv metabolic. Kev tsis pom zoo metabolic tau pom nyob rau hauv tib neeg lub ntsws thiab kev npaj cov ntshav.

Formoterol:Thawj cov metabolism hauv formoterol yog los ntawm glucuronidation ncaj qha thiab los ntawm O-demethylation ua raws li kev sib txuas rau cov metabolites tsis ua haujlwm. Ob txoj hauv kev metabolic suav nrog deformylation thiab sulfate conjugation. CYP2D6 thiab CYP2C tau pom tias yog lub luag haujlwm tseem ceeb rau O-demethylation.

Kev tshem tawm
Budesonide:Budesonide tau tawm hauv cov zis thiab quav hauv daim ntawv ntawm metabolites. Kwv yees li 60% ntawm cov koob tshuaj radiolabeled tso rau hauv cov hlab ntsha tau zoo nyob hauv cov zis.

Tsis muaj kev hloov pauv budesonide hauv cov zis. Daim ntawv 22R ntawm budesonide tau zoo dua los ntawm lub siab nrog kev tshem tawm ntawm 1.4 L / min vs. 1.0 L / min rau daim ntawv 22S. Lub davhlau ya nyob twg ib nrab-lub neej, 2 mus rau 3 teev, yog tib yam rau ob qho tib si epimers thiab yog ywj siab ntawm koob.

Formoterol:Cov excretion ntawm formoterol tau kawm nyob rau hauv plaub yam kev noj qab haus huv tom qab ib txhij tswj hwm ntawm radiolabeled formoterol ntawm lub qhov ncauj thiab IV txoj kev. Hauv txoj kev tshawb no, 62% ntawm radiolabeled formoterol tau tawm hauv cov zis thaum 24% raug tshem tawm hauv cov quav.

Cov pejxeem tshwj xeeb

Cov neeg laus

Cov tshuaj pharmacokinetics ntawm budesonide thiab formoterol fumarate dihydrate hauv cov neeg mob laus tsis tau kawm tshwj xeeb.

Cov menyuam yaus

Plasma concentrations ntawm budesonide tau ntsuas tom qab kev tswj hwm ntawm plaub qhov nqus ntawm budesonide thiab formoterol fumarate dihydrate 160/4.5 hauv kev tshawb fawb ib zaug hauv cov neeg mob hawb pob, 6 mus rau tsawg dua 12 xyoo. Peak budesonide concentrations ntawm 1.4 nmol / L tshwm sim ntawm 20 feeb tom qab koob tshuaj. Txoj kev tshawb no kuj pom tau hais tias tag nrho cov kab mob raug rau budesonide los ntawm budesonide thiab formoterol fumarate dihydrate yog kwv yees li 30% qis dua los ntawm nqus tau pa budesonide los ntawm cov hmoov qhuav inhaler uas kuj tau soj ntsuam ntawm tib cov tshuaj xa. Dose-normalized Cmaxthiab AUC0-inf ibntawm budesonide tom qab txhaj tshuaj ib zaug hauv cov menyuam yaus hnub nyoog 6 txog 12 xyoos tau qis dua qhov pom hauv cov neeg laus.

Tom qab 2 inhalations ntawm budesonide thiab formoterol fumarate dihydrate 160/4.5 ob zaug kev kho mob txhua hnub, formoterol Cmaxthiab AUC0-6nyob rau hauv lub xeev khov kho nyob rau hauv cov me nyuam 6 mus rau tsawg dua 12 xyoo ntawm lub hnub nyoog yog piv rau cov uas pom nyob rau hauv cov neeg laus.

Poj niam los txiv neej / haiv neeg

Cov kev tshawb fawb tshwj xeeb los tshuaj xyuas qhov cuam tshuam ntawm poj niam txiv neej thiab haiv neeg ntawm cov tshuaj pharmacokinetics ntawm budesonide thiab formoterol fumarate dihydrate tsis tau ua. PK tsom xam ntawm budesonide thiab formoterol fumarate dihydrate cov ntaub ntawv qhia tias poj niam txiv neej tsis cuam tshuam rau pharmacokinetics ntawm budesonide thiab formoterol. Tsis muaj kev txiav txim siab tuaj yeem cuam tshuam txog kev cuam tshuam ntawm haiv neeg vim muaj pes tsawg tus neeg tsis yog neeg Caucasians raug ntsuas rau PK.

Niam laus

Kev tso tawm ntawm budesonide thaum xa los ntawm kev nqus tau los ntawm kev nqus cov hmoov qhuav ntawm koob tshuaj 200 lossis 400 mcg ob zaug ib hnub rau tsawg kawg 3 lub hlis tau kawm hauv yim tus poj niam lactating mob hawb pob los ntawm 1 txog 6 lub hlis tom qab yug menyuam. Kev raug mob rau budesonide hauv cov poj niam no zoo li piv rau cov poj niam uas tsis yog lactating nrog mob hawb pob los ntawm lwm cov kev tshawb fawb. Cov mis nyuj uas tau txais ntau tshaj li yim teev tom qab koob tshuaj tau qhia tias qhov siab tshaj plaws ntawm budesonide rau 400 thiab 800 mcg tag nrho cov koob tshuaj txhua hnub yog 0.39 thiab 0.78 nmol / L, raws li, thiab tshwm sim hauv 45 feeb tom qab noj. Qhov kwv yees qhov ncauj txhua hnub koob tshuaj budesonide los ntawm niam mis rau tus menyuam mos yog kwv yees li 0.007 thiab 0.014 mcg / kg / hnub rau ob koob tshuaj uas siv hauv txoj kev tshawb no, uas sawv cev kwv yees li 0.3% mus rau 1% ntawm cov koob txhaj tshuaj los ntawm leej niam. Budesonide qib hauv cov plasma cov qauv tau txais los ntawm tsib tus menyuam mos ntawm li 90 feeb tom qab pub niam mis (thiab li 140 feeb tom qab noj tshuaj rau leej niam) yog qis dua qib (<0.02 nmol/L in four infants and <0.04 nmol/L in one infant) [saib Siv hauv Cov Pej Xeem Tshwj Xeeb (8.2) ].

Lub raum lossis Hepatic Insufficiency

Tsis muaj cov ntaub ntawv hais txog kev siv tshwj xeeb ntawm budesonide thiab formoterol fumarate dihydrate hauv cov neeg mob uas muaj kab mob siab lossis lub raum tsis zoo. Txo lub siab ua haujlwm yuav cuam tshuam rau kev tshem tawm corticosteroids. Budesonide pharmacokinetics tau cuam tshuam los ntawm kev cuam tshuam lub siab ua haujlwm raws li kev pom zoo los ntawm kev muaj ob npaug tom qab noj qhov ncauj. Cov tshuaj budesonide cov tshuaj pharmacokinetics yog, txawm li cas los xij, zoo ib yam hauv cov neeg mob cirrhotic thiab cov neeg noj qab haus huv. Cov ntaub ntawv tshwj xeeb nrog formoterol tsis muaj, tab sis vim tias formoterol feem ntau raug tshem tawm los ntawm cov metabolism hauv siab, qhov tshwm sim tuaj yeem tshwm sim hauv cov neeg mob uas muaj lub siab tsis zoo.

Tshuaj-Drug Interactions

Ib txoj kev tshawb fawb ib zaug ib zaug tau ua los sib piv cov tshuaj pharmacokinetics ntawm yim inhalations ntawm cov hauv qab no: budesonide, formoterol, thiab budesonide ntxiv rau cov tshuaj formoterol ua ke. Cov txiaj ntsig ntawm txoj kev tshawb fawb tau qhia tias tsis muaj pov thawj ntawm kev sib cuam tshuam ntawm pharmacokinetic ntawm ob lub ntsiab lus ntawm budesonide thiab formoterol fumarate dihydrate.

Inhibitors ntawm Cytochrome P450 Enzymes

Ketoconazole: Ketoconazole, muaj zog inhibitor ntawm cytochrome P450 (CYP) isoenzyme 3A4 (CYP3A4), lub ntsiab metabolic enzyme rau corticosteroids, nce ntshav plasma qib ntawm qhov ncauj noj budesonide.

Cimetidine: Ntawm cov koob tshuaj pom zoo, cimetidine, uas tsis yog tshwj xeeb inhibitor ntawm CYP enzymes, muaj qhov cuam tshuam me ntsis tab sis kev kho mob tsis zoo rau cov tshuaj pharmacokinetics ntawm qhov ncauj budesonide.

Kev tshawb fawb tshwj xeeb-tshuaj yeeb tshuaj nrog cov tshuaj formoterol tsis tau ua.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Budesonide

Cov kev tshawb fawb mus sij hawm ntev tau ua nyob rau hauv nas thiab nas siv qhov ncauj tswj hwm los ntsuas qhov muaj peev xwm carcinogenic ntawm budesonide.

Hauv kev tshawb fawb 2 xyoo hauv Sprague-Dawley nas, budesonide ua rau muaj qhov tshwm sim ntawm gliomas hauv cov txiv neej nas ntawm qhov ncauj ntawm 50 mcg / kg (kwv yees sib npaug rau MRHDID hauv cov neeg laus thiab menyuam yaus ntawm ib mcg / m.obhauv paus). Tsis muaj qog nqaij hlav hauv cov txiv neej thiab poj niam nas ntawm cov koob tshuaj ntawm qhov ncauj txog li 25 thiab 50 mcg / kg (kwv yees sib npaug rau MRHDID hauv cov neeg laus thiab menyuam yaus ntawm mcg / mobhauv paus). Hauv ob qhov kev tshawb fawb 2-xyoo ntxiv hauv txiv neej Fischer thiab Sprague-Dawley nas, budesonide ua rau tsis muaj gliomas ntawm qhov ncauj ntawm 50 mcg / kg (kwv yees sib npaug rau MRHDID hauv cov neeg laus thiab menyuam yaus ntawm mcg / m.obhauv paus). Txawm li cas los xij, hauv cov txiv neej Sprague-Dawley nas, budesonide ua rau muaj qhov tshwm sim ntawm cov qog hepatocellular ntawm qhov ncauj ntawm 50 mcg / kg (kwv yees sib npaug rau MRHDID hauv cov neeg laus thiab menyuam yaus ntawm mcg / m.obhauv paus). Cov ntaub ntawv sib xyaw corticosteroids (prednisolone thiab triamcinolone acetonide) hauv ob qhov kev tshawb fawb no tau pom qhov kev tshawb pom zoo sib xws.

Hauv kev kawm 91-lub lim tiam hauv cov nas, budesonide ua rau tsis muaj kev kho mob carcinogenicity ntawm qhov ncauj txog 200 mcg / kg (kwv yees li 2 npaug ntawm MRHDID hauv cov neeg laus thiab cov menyuam yaus ntawm mcg / m.obhauv paus).

Budesonide tsis yog mutagenic los yog clastogenic nyob rau hauv rau ntau yam kev xeem systems: AmesSalmonella/microsome plate test, nas micronucleus test, nas lymphoma test, chromosome aberration test in human lymphocytes, sex-linked recessive lethal test nyob rau hauvDrosophila melanogaster, thiab DNA kho kev tsom xam hauv nas hepatocyte kab lis kev cai.

Fertility thiab kev ua me nyuam tsis muaj kev cuam tshuam rau cov nas ntawm cov tshuaj subcutaneous txog 80 mcg / kg (kwv yees sib npaug ntawm MRHDID ntawm ib mcg / mobhauv paus). Txawm li cas los xij, nws ua rau txo qis hauv kev muaj peev xwm ua ntej yug menyuam thiab kev muaj peev xwm ntawm cov menyuam yaus thaum yug los thiab thaum lub sijhawm lactation, nrog rau kev txo qis hauv niam lub cev hnyav nce, ntawm cov koob tshuaj subcutaneous ntawm 20 mcg / kg thiab siab dua (tsawg dua MRHDID ntawm mcg / mobhauv paus). Tsis muaj cov teebmeem zoo li no tau sau tseg ntawm 5 mcg / kg (tsawg dua li MRHDID ntawm mcg / mobhauv paus).

Formoterol

Kev tshawb fawb mus sij hawm ntev tau ua nyob rau hauv cov nas uas siv qhov ncauj tswj hwm thiab nas siv inhalation thawj coj los soj ntsuam cov carcinogenic peev xwm ntawm formoterol fumarate.

Hauv kev kawm 24-hli carcinogenicity hauv CD-1 nas, formoterol ntawm qhov ncauj koob tshuaj ntawm 100 mcg / kg thiab siab dua (kwv yees li 30 thiab 15 npaug ntawm MRHDID rau cov neeg laus thiab menyuam yaus, raws li, ntawm mcg / m.obhauv paus) ua rau muaj kev nce ntxiv ntawm qhov tshwm sim ntawm uterine leiomyomas.

Hauv kev tshawb fawb 24-hli carcinogenicity hauv Sprague-Dawley nas, qhov tshwm sim ntawm mesovarian leiomyoma thiab uterine leiomyosarcoma tau pom ntawm qhov nqus tau ntawm 130 mcg / kg (kwv yees li 70 thiab 35 npaug ntawm MRHDID hauv cov neeg laus thiab menyuam yaus, feem ntau, mcg/mobhauv paus). Tsis muaj cov qog pom ntawm 22 mcg / kg (kwv yees li 12 thiab 6 npaug ntawm MRHDID hauv cov neeg laus thiab menyuam yaus, feem, ntawm ib mcg / mobhauv paus).

Lwm cov tshuaj beta-agonist tau pom zoo sib xws hauv leiomyomas ntawm qhov chaw mos hauv cov poj niam nas. Qhov cuam tshuam ntawm cov kev tshawb pom no rau tib neeg siv tsis paub.

Formoterol tsis yog mutagenic lossis clastogenic hauv AmesSalmonella/ microsome plate test, nas lymphoma test, chromosome aberration test in human lymphocytes, thiab nas micronucleus test.

Kev txo qis ntawm kev muaj menyuam thiab / lossis kev ua menyuam yaus tau pom nyob rau hauv cov txiv neej nas kho nrog formoterol ntawm qhov ncauj ntawm 15,000 mcg / kg (kwv yees li 2200 npaug ntawm MRHDID ntawm AUC hauv paus). Tsis muaj cov nyhuv zoo li no tau pom ntawm 3000 mcg / kg (kwv yees li 1600 npaug ntawm MRHDID ntawm mcg / mobhauv paus). Hauv ib qho kev tshawb fawb cais nrog cov txiv neej nas kho nrog qhov ncauj koob tshuaj ntawm 15,000 mcg / kg (kwv yees li 8000 npaug ntawm MRHDID ntawm ib mcg / mobHauv paus), muaj kev tshawb pom ntawm testicular tubular atrophy thiab spermatic khib nyiab nyob rau hauv cov noob qes thiab oligospermia hauv epididymides. Tsis muaj kev cuam tshuam rau kev xeeb tub hauv poj niam nas ntawm koob tshuaj txog 15,000 mcg / kg (kwv yees li 1100 npaug ntawm MRHDID ntawm AUC hauv paus).

Tsiaj Toxicology thiab/los yog Pharmacology

Preclinical:Cov kev tshawb fawb hauv cov tsiaj txhu (minipigs, nas, thiab dev) tau pom qhov tshwm sim ntawm lub plawv arrhythmias thiab kev tuag tam sim ntawd (nrog cov pov thawj histologic ntawm myocardial necrosis) thaum beta-agonists thiab methylxanthines tau noj ib txhij. Lub chaw kho mob tseem ceeb ntawm cov kev tshawb pom no tsis paub.

Kev tshawb fawb soj ntsuam

Mob hawb pob

Cov neeg mob hawb pob muaj hnub nyoog 12 xyoos thiab laus dua

Hauv ob txoj kev tshawb fawb soj ntsuam sib piv budesonide thiab formoterol fumarate dihydrate nrog rau tus kheej cov khoom, kev txhim kho nyob rau hauv feem ntau cov ntsiab lus kawg tau zoo dua nrog budesonide thiab formoterol fumarate dihydrate dua nrog kev siv budesonide los yog formoterol ib leeg. Tsis tas li ntawd, ib qho kev tshawb fawb soj ntsuam tau pom cov txiaj ntsig zoo sib xws ntawm budesonide thiab formoterol fumarate dihydrate thiab kev siv tib lub sijhawm ntawm budesonide thiab formoterol ntawm cov koob tshuaj sib txuas los ntawm cov tshuaj inhalers.

Kev nyab xeeb thiab kev ua tau zoo ntawm budesonide thiab formoterol fumarate dihydrate tau pom nyob rau hauv ob qho tib si randomized, ob-dig muag, placebo-tswj US kev tshawb fawb soj ntsuam nrog rau 1076 cov neeg mob 12 xyoo thiab laus dua. Tsau budesonide thiab formoterol fumarate dihydrate ntau npaum li cas ntawm 160/9 mcg, thiab 320/9 mcg ob zaug ib hnub (txhua koob tshuaj raws li 2 inhalations ntawm 80/4.5 thiab 160/4.5 mcg zog, raws li) tau muab piv nrog cov monocomponents (ib qho tshuaj monocomponents). ) thiab cov placebo los muab cov ntaub ntawv hais txog kev noj tshuaj kom tsim nyog los npog ntau yam kev mob ntsws asthma.

Kawm 1: Kev Tshawb Fawb Kev Tshawb Fawb nrog Budesonide thiab Formoterol Fumarate Dihydrate 160/4.5

Txoj kev tshawb no 12-lub lim tiam tau soj ntsuam 596 tus neeg mob hnub nyoog 12 xyoos thiab laus dua los ntawm kev sib piv budesonide thiab formoterol fumarate dihydrate 160/4.5, kev sib xyaw dawb ntawm budesonide 160 mcg ntxiv rau formoterol 4.5 mcg hauv cov inhalers cais, budesonide 150 mcg, thiab budesonide 4. ; txhua tus muab raws li 2 inhalations ob zaug ib hnub twg. Txoj kev tshawb no suav nrog 2 lub lis piam ua haujlwm nrog budesonide 80 mcg, 2 inhalations ob zaug ib hnub. Cov neeg mob feem ntau muaj mob hawb pob mus rau mob hawb pob thiab tau siv cov tshuaj corticosteroids tsawg mus rau siab ua ntej nkag mus kawm. Randomization tau stratified los ntawm yav dhau los inhaled corticosteroid kho (71.6% ntawm nruab nrab- thiab 28.4% ntawm high-dose inhaled corticosteroid). Tus nqi nruab nrab kwv yees FEVibnyob rau hauv lub hauv paus yog 68.1% thiab zoo sib xws nyob rau hauv pab pawg kho mob. Cov ntsiab lus tseem ceeb ntawm kev ua tau zoo yog 12-teev-nruab nrab tom qab koob tshuaj FEVibntawm lub lim tiam 2, thiab pre-dose FEVibnruab nrab ntawm qhov kev kawm. Txoj kev tshawb no tseem xav kom cov neeg mob uas txaus siab rau qhov kev ntsuas ua ntej kev mob ntsws asthma-mob hnyav dua. Cov txheej txheem kho mob hawb pob-mob hawb pob ua ntej yog qhov tseem ceeb hauv kev kho mob txo qis hauv FEViblos yog PEF, nce kev siv cawm albuterol, pw tsaug zog thaum hmo ntuj vim mob hawb pob, kev cuam tshuam thaum muaj xwm txheej ceev lossis mus pw hauv tsev kho mob vim mob hawb pob, lossis kev xav tau rau kev siv tshuaj kho mob hawb pob tsis tso cai los ntawm txoj cai. Rau cov txheej txheem ntawm kev pw tsaug zog thaum hmo ntuj vim mob hawb pob, cov neeg mob tau tso cai nyob hauv txoj kev tshawb fawb ntawm qhov kev txiav txim siab ntawm tus neeg soj ntsuam yog tias tsis muaj lwm yam kev mob hawb pob-mob hnyav dua. Qhov feem pua ​​​​ntawm cov neeg mob tshem tawm vim lossis ua tau raws li cov txheej txheem ua ntej rau kev mob hawb pob yog qhia hauv Table 4.

Table 4 Tus naj npawb thiab feem pua ​​​​ntawm cov neeg mob tshem tawm vim los yog ua tau raws li cov txheej txheem ua ntej rau kev mob hawb pob (Study 1)
*
Cov qauv no tau raug soj ntsuam txhua hnub tsis hais txog lub sijhawm mus ntsib kws kho mob, tshwj tsis yog FEV.ib, uas tau soj ntsuam ntawm txhua qhov chaw kuaj mob.
Cov txheej txheem ntawm tus kheej raug qhia rau cov neeg mob ntsib ib qho kev tshwm sim mob hawb pob ua ntej, tsis hais txog kev tshem tawm.
Rau cov txheej txheem ntawm kev pw tsaug zog thaum hmo ntuj vim mob hawb pob, cov neeg mob tau tso cai nyob hauv txoj kev tshawb fawb ntawm qhov kev txiav txim siab ntawm tus neeg tshawb xyuas yog tias tsis muaj lwm yam kev ua tau zoo.

Budesonide thiab Formoterol Fumarate Dihydrate

160/4.5

n = 124

Budesonide

160 mcg plus Formoterol

4.5mcg ua

n = 115

Budesonide

160 mcg

n = 109

Formoterol

4.5mcg ua

n = 123

Cov tshuaj placebo

n = 125

Cov neeg mob tshem tawm vim qhov tshwm sim ua mob hawb pob ua ntej *

13 (10.5) Nws.

13 (11.3) Nws.

22 (20.2) thiab

44 (35.8) thiab

62 (49.6) thiab

Cov neeg mob uas muaj mob hawb pob ua ntej * ,

37 (29.8 hli)

24 (20.9) Nws.

48 (44.0)

68 (55.3)

84 (67.2) thiab

Txo hauv FEVib

4 (3.2)

8 (7.0)

7 (6.4) thiab

15 (12.2) Nws.

14 (11.2) thiab

Kev siv tshuaj cawm siav

2 (1.6)

0

3 (2.8)

3 (2.4)

7 (5.6)

Txo hauv AM PEF

2 (1.6)

5 (4.3)

5 (4.6)

17 (13.8) Nws.

15 (12.0) Nws.

Hmo ntuj awakenings

24 (19.4 hli.)

11 (9.6) thiab

29 (26.6) Nws.

32 (26.0) Nws.

49 (39.2) thiab

Clinical exacerbation

7 (5.6)

6 (5.2)

5 (4.6)

17 (13.8) Nws.

16 (12.8) Nws.

Qhov feem pua ​​​​tau hloov pauv los ntawm qhov pib hauv FEVibntsuas tam sim ua ntej txhaj tshuaj (pre-dose) tshaj 12 lub lis piam yog pom nyob rau hauv daim duab 1. Vim tias txoj kev tshawb no tau siv cov txheej txheem tshem tawm ua ntej rau kev mob hawb pob, uas ua rau muaj qhov sib txawv ntawm kev tshem tawm hauv pawg kho mob, pre-dose FEV.ibCov txiaj ntsig ntawm kev mus ntsib zaum kawg (kawg kho, EOT) kuj tau muab. Cov neeg mob tau txais budesonide thiab formoterol fumarate dihydrate 160/4.5 tau txais txiaj ntsig zoo dua los ntawm cov hauv paus hauv paus hauv koob tshuaj FEV.ibThaum kawg ntawm kev kho mob (0.19 L, 9.4%), piv nrog budesonide 160 mcg (0.10 L, 4.9%), formoterol 4.5 mcg (-0.12 L, -4.8%), thiab placebo (-0.17 L, -6.9%) .

Daim duab 1 txhais tau tias qhov feem pua ​​​​ntawm Kev Hloov Pauv Los Ntawm Lub hauv paus hauv Pre-dose FEVibTshaj 12 lub lis piam (Study 1)

Cov nyhuv ntawm budesonide thiab formoterol fumarate dihydrate 160/4.5 ob qhov nqus tau ob zaug ib hnub ntawm kev xaiv cov txiaj ntsig zoo sib xws, suav nrog thaum sawv ntxov thiab yav tsaus ntuj PEF, albuterol cawm siv, thiab cov tsos mob hawb pob tshaj 24 teev ntawm 0-3 teev yog qhia hauv Table 5.

Table 5 Qhov tseem ceeb ntawm qhov tseem ceeb rau kev xaiv cov kev ua tau zoo sib xws (Study 1)
Kev ua tau zoo Variable Budesonide thiab Formoterol Fumarate Dihydrate
160/4.5
(n * = 124)
Budesonide
160 mcg plus
Formoterol 4.5 mcg
(n * = 115)
Budesonide
160 mcg
(n * = 109)
Formoterol
4.5mcg ua
(n * = 123)
Cov tshuaj placebo
(n * = 125)
*
Tus naj npawb ntawm cov neeg mob (n) txawv me ntsis vim cov neeg mob cov ntaub ntawv muaj nyob rau txhua qhov sib txawv. Cov txiaj ntsig tau pom yog nyob ntawm cov ntaub ntawv muaj nyob kawg rau txhua qhov sib txawv.

AM PEB (L/min) Baseline

341

338

342 ib

339 ib

355

Hloov los ntawm Baseline

35

28

9

-9

-18

PM PEB (L / min) Baseline

351

348

357 ib

354 ib

ib 369

Hloov los ntawm Baseline

3. 4

26

7

-7

-18

Kev siv Albuterol cawm

Lub hauv paus

2.1

23

2.7

.5

2.4

Hloov los ntawm Baseline

-1.0

-1.5

-0.8

-0.3

0.8 ua

Tus qhab nia nruab nrab / hnub (0–3 teev)

Lub hauv paus

0.99 ib

1.03 ib

1.04 ib

1.04 ib

1.08 Nws

Hloov los ntawm Baseline

-0.28

-0.32 Nws

-0.14

-0.05 Nws

0.10

Qhov kev cuam tshuam ntawm kev mob hawb pob rau cov neeg mob kev noj qab haus huv ntawm lub neej tau raug soj ntsuam los ntawm kev siv tus qauv Asthma Quality of Life Questionnaire (AQLQ(S)) (raws li 7-point scale qhov twg 1 = qhov siab tshaj plaws tsis zoo thiab 7 = tsis muaj. kev puas tsuaj). Cov neeg mob tau txais budesonide thiab formoterol fumarate dihydrate 160/4.5 tau kho lub ntsiab lus txhim kho hauv tag nrho cov mob hawb pob tshwj xeeb ntawm lub neej, raws li tau hais los ntawm qhov sib txawv nruab nrab ntawm pab pawg kho mob ntawm> 0.5 cov ntsiab lus hauv kev hloov pauv los ntawm lub hauv paus hauv tag nrho cov qhab nia AQLQ (qhov sib txawv hauv AQLQ tus qhab nia ntawm 0.70 [95% CI 0.47, 0.93], piv rau cov placebo).

Kawm 2: Kev Tshawb Fawb Kev Tshawb Fawb nrog Budesonide thiab Formoterol Fumarate Dihydrate 80/4.5

Txoj kev tshawb no 12 lub lis piam tau zoo ib yam hauv kev tsim rau Kev Kawm 1, thiab suav nrog 480 tus neeg mob hnub nyoog 12 xyoos thiab laus dua. Txoj kev tshawb no piv rau budesonide thiab formoterol fumarate dihydrate 80/4.5, budesonide 80 mcg, formoterol 4.5 mcg, thiab placebo; txhua tus muab raws li 2 inhalations ob zaug ib hnub twg. Txoj kev tshawb no suav nrog 2 lub lis piam cov placebo khiav-hauv lub sijhawm. Cov neeg mob feem ntau muaj mob hawb pob me mus rau nruab nrab thiab tau siv cov tshuaj tsawg mus rau nruab nrab ntawm qhov nqus tau corticosteroids ua ntej nkag mus kawm. Tus nqi nruab nrab kwv yees FEVibnyob rau hauv lub hauv paus yog 71.3% thiab zoo sib xws nyob rau hauv pab pawg kho mob. Cov kev hloov pauv tau zoo thiab cov ntsiab lus kawg tau zoo ib yam rau cov hauv Kev Kawm 1.

Qhov feem pua ​​​​ntawm cov neeg mob tshem tawm vim los yog ua tau raws li cov txheej txheem ua ntej rau kev mob hawb pob mob hawb pob yog qhia hauv Table 6. Cov txheej txheem ntawm kev soj ntsuam thiab cov qauv siv tau zoo ib yam li hauv Kev Kawm 1.

Table 6 Tus naj npawb thiab feem pua ​​​​ntawm cov neeg mob tshem tawm vim los yog ua tau raws li cov txheej txheem ua ntej rau kev mob hawb pob (Study 2)
*
Cov qauv no tau raug soj ntsuam txhua hnub tsis hais txog lub sijhawm mus ntsib kws kho mob, tshwj tsis yog FEV.ib, uas tau soj ntsuam ntawm txhua qhov chaw kuaj mob.
Cov txheej txheem ntawm tus kheej raug qhia rau cov neeg mob ntsib ib qho kev tshwm sim mob hawb pob ua ntej, tsis hais txog kev tshem tawm.
Rau cov txheej txheem ntawm kev pw tsaug zog thaum hmo ntuj vim mob hawb pob, cov neeg mob tau tso cai nyob hauv txoj kev tshawb fawb ntawm qhov kev txiav txim siab ntawm tus neeg tshawb xyuas yog tias tsis muaj lwm yam kev ua tau zoo.

Budesonide thiab Formoterol Fumarate Dihydrate

80/4.5

(n = 123)

Budesonide

80mcg ua

(n = 121)

Formoterol

4.5mcg ua

(n = 114)

Cov tshuaj placebo

(n = 122)

Cov neeg mob tshem tawm vim qhov tshwm sim ua mob hawb pob ua ntej *

9 (7.3) thiab

8 (6.6)

21 (18.4 hli.)

40 (32.8 hli.)

Cov neeg mob uas muaj mob hawb pob ua ntej * ,

23 (18.7) Nws.

26 (21.5) Nws.

48 (42.1)

69 (56.6)

Txo hauv FEVib

3 (2.4)

3 (2.5)

11 (9.6) thiab

9 (7.4) thiab

Kev siv tshuaj cawm siav

1 (0.8)

3 (2.5)

1 (0.9)

3 (2.5)

Txo hauv AM PEF

3 (2.4)

1 (0.8)

8 (7.0)

14 (11.5) Nws.

Hmo ntuj tsaug zog

17 (13.8) Nws.

20 (16.5) Nws.

31 (27.2) thiab

52 (42.6) thiab

Clinical exacerbation

1 (0.8)

3 (2.5)

5 (4.4)

20 (16.4) thiab

Qhov feem pua ​​​​ntawm cov txiaj ntsig hloov pauv los ntawm cov kab hauv qab hauv cov koob tshuaj ua ntej FEVibtshaj 12 lub lis piam yog tso tawm nyob rau hauv daim duab 2.

Daim duab 2 txhais tau tias qhov feem pua ​​​​ntawm Kev Hloov Pauv Los Ntawm Lub hauv paus hauv Pre-dose FEVibTshaj 12 lub lis piam (Study 2)

Cov txiaj ntsig ua tau zoo rau lwm cov ntsiab lus thib ob, suav nrog kev ua neej zoo, zoo ib yam li cov tau pom hauv Kev Kawm 1.

Pib thiab Lub Sijhawm Ua Haujlwm thiab Kev Txhim Kho ntawm Kev Txhim Kho Hauv Kev Tiv Thaiv Kab Mob hawb pob

Qhov pib ntawm kev nqis tes ua thiab kev nce qib ntawm kev txhim kho hauv kev tswj kev mob ntsws asthma tau raug soj ntsuam hauv ob qhov kev tshawb fawb tseem ceeb. Lub sijhawm nruab nrab ntawm qhov pib ntawm kev kho mob tseem ceeb bronchodilation (> 15% kev txhim kho hauv FEVib) tau pom hauv 15 feeb. Kev txhim kho siab tshaj plaws hauv FEVibtshwm sim nyob rau hauv 3 teev, thiab kev kho mob tseem ceeb txhim kho tau khaws cia ntau tshaj 12 teev. Daim duab 3 thiab 4 qhia qhov feem pua ​​​​ntawm kev hloov pauv los ntawm cov hauv paus hauv qab koob tshuaj FEVibtshaj 12 teev nyob rau hnub ntawm randomization thiab hnub kawg ntawm kev kho mob rau Kev Kawm 1.

Kev txo qis hauv cov tsos mob hawb pob thiab hauv kev siv albuterol cawm, nrog rau kev txhim kho thaum sawv ntxov thiab yav tsaus ntuj PEF, tshwm sim hauv 1 hnub ntawm thawj koob tshuaj budesonide thiab formoterol fumarate dihydrate; Kev txhim kho hauv cov kev hloov pauv no tau khaws cia hauv 12 lub lis piam ntawm kev kho.

Tom qab thawj koob tshuaj budesonide thiab formoterol fumarate dihydrate, FEVibtxhim kho tau zoo heev thaum thawj 2 lub lis piam ntawm kev kho mob, txuas ntxiv qhia kev txhim kho ntawm Lub Limtiam 6 kev ntsuam xyuas, thiab tau tswj xyuas los ntawm Lub Limtiam 12 rau ob qho kev tshawb fawb.

Tsis muaj qhov txo qis hauv 12-teev bronchodilator nyhuv tau pom nrog budesonide thiab formoterol fumarate dihydrate 80/4.5 los yog budesonide thiab formoterol fumarate dihydrate 160/4.5, raws li kev soj ntsuam los ntawm FEVib, tom qab 12 lub lis piam ntawm kev kho mob los yog thaum kawg tuaj ntsib.

FEVibCov ntaub ntawv los ntawm Kev Kawm 1 kev ntsuas budesonide thiab formoterol fumarate dihydrate 160/4.5 yog tso tawm nyob rau hauv daim duab 3 thiab 4.

Daim duab 3 Qhov Kev Hloov Pauv Hloov Los Ntawm Lub hauv paus hauv FEVibHnub ntawm Randomization (Study 1)

Daim duab 4 Lub ntsiab lus feem pua ​​​​ntawm Kev Hloov Pauv Los Ntawm Lub hauv paus hauv FEVibThaum kawg ntawm Kev Kho Mob (Study 1)

Cov neeg mob hawb pob 6 mus rau tsawg dua 12 xyoos

Qhov kev pab cuam kho mob los txhawb kev ua tau zoo ntawm budesonide thiab formoterol fumarate dihydrate 80/4.5 hauv cov menyuam yaus hnub nyoog qis dua 12 xyoos suav nrog cov hauv qab no: 1) kev tshawb fawb txog koob tshuaj budesonide, 2) kev tshawb nrhiav tshuaj formoterol, thiab 3) ib qho Kev ua tau zoo thiab kev nyab xeeb kev kawm ntawm budesonide thiab formoterol fumarate dihydrate ua ke cov khoom.

Kev xaiv ntawm budesonide 80 mcg tau txais kev txhawb nqa los ntawm 6-lub lim tiam, randomized, ob qhov muag tsis pom kev, kev tshuaj placebo-tswj hauv 304 cov neeg mob (152 budesonide, 152 placebo) 6 mus rau tsawg dua 12 xyoo nrog mob hawb pob. Cov txiaj ntsig tau pom tias budesonide 80 mcg (2 inhalations ob zaug hauv ib hnub) tau muab cov txiaj ntsig kev txhim kho ntau dua piv rau cov placebo rau thawj qhov kawg ntawm kev hloov pauv los ntawm lub hauv paus mus rau lub sijhawm kho mob nruab nrab hauv kev noj tshuaj ua ntej thaum sawv ntxov PEF thiab qhov tseem ceeb thib ob qhov kawg ntawm kev hloov pauv hauv koob tshuaj ua ntej. sawv ntxov FEVib. Kev xaiv ntawm cov koob tshuaj formoterol tau txais kev txhawb nqa los ntawm ib qho randomized, ib koob tshuaj, placebo-tswj, active-tswj (Foradil Aerolizer 12 mcg), 5-txoj kev hla kev kawm uas koob tshuaj 2.25, 4.5 thiab 9 mcg formoterol tau tswj hwm hauv ua ke nrog budesonide hauv 54 cov neeg mob me nyuam yaus hnub nyoog 6 txog 12 xyoos nrog mob hawb pob. Cov txiaj ntsig tau pom cov lus teb koob tshuaj ntawm formoterol piv rau cov placebo rau thawj qhov kawg ntawm FEVibqhov nruab nrab tshaj li 12 teev tom qab koob tshuaj thiab 9 mcg pawg tau pom cov txiaj ntsig zoo sib xws piv rau kev tswj hwm.

Txoj kev tshawb fawb pom zoo yog 12 lub lis piam, randomized, ob qhov muag tsis pom kev, ntau qhov chaw kawm nyob rau hauv uas budesonide thiab formoterol fumarate dihydrate 80/4.5 tau muab piv nrog budesonide pMDI 80 mcg, txhua tus tswj hwm li 2 inhalations ob zaug ib hnub, hauv 1864 rau cov neeg mob me. muaj hnub nyoog qis dua 12 xyoos nrog cov ntaub ntawv kho mob ntawm kev mob ntsws asthma. Thaum nkag mus sim, cov menyuam yaus muaj qhov yuav tsum tau muaj rau txhua hnub nruab nrab koob tshuaj nqus tau corticosteroid kho lossis kho ua ke ntawm kev nqus tau corticosteroid thiab LABA txoj kev kho, thiab pom cov tsos mob txawm tias kev kho mob nrog cov tshuaj nqus tau qis corticosteroid thaum lub sijhawm 2 mus rau 4 lub lis piam khiav. . Thawj qhov kev ua tau zoo sib txawv tau hloov pauv los ntawm lub hauv paus mus rau Lub Limtiam 12 hauv chaw kho mob ntsuas 1-teev tom qab koob tshuaj FEVib. Hauv cov neeg mob uas tau txais budesonide thiab formoterol fumarate dihydrate 80/4.5, muaj qhov hloov pauv tseem ceeb piv rau budesonide hauv 1-teev tom qab koob tshuaj FEV.ibuas txhim kho los ntawm 0.28 L los ntawm lub hauv paus mus rau Lub Limtiam 12, piv nrog 0.17 L rau cov neeg tau txais budesonide 80 mcg (txhais tau qhov sib txawv 0.12 L; 95% CI: 0.03, 0.20) (saib daim duab 5).

Daim duab 5 Hloov Los Ntawm Lub Hauv Paus Hauv Tsev Kho Mob-Measured 1-teev Tom Qab FEVibTshaj li 12 lub lis piam (Kev Tshawb Fawb Txog Kev Ua Haujlwm thiab Kev Nyab Xeeb hauv Cov Neeg Mob 6 mus rau qis dua 12 xyoos).

Ib yam li ntawd, kev txhim kho tau pom nyob rau hauv kev hloov pauv ntawm lub hauv paus mus rau Lub Limtiam 12 rau 1-teev tom qab noj tshuaj hauv tsev kho mob PEF (txhais tau qhov sib txawv 25.5 L / min; 95% CI: 10.9, 40.0). Cov teebmeem ntawm bronchodilatory tau tshwm sim los ntawm thawj qhov kev ntsuam xyuas ntawm 15 feeb ntawm hnub 1 thiab tau khaws cia ntawm Lub Limtiam 12. Qhov kwv yees qhov txawv nruab nrab ntawm budesonide thiab formoterol fumarate dihydrate 80/4.5 thiab budesonide nrog rau kev hloov ntawm lub hauv paus mus rau Lub Limtiam 12 hauv 15 feeb tom qab- koob tshuaj FEV1 yog 0.10 L (95% CI: 0.02, 0.18). Tsis muaj qhov sib txawv ntawm budesonide thiab formoterol fumarate dihydrate thiab budesonide tau sau tseg thaum hmo ntuj awakenings, cawm albuterol siv, los yog Pediatric Asthma Quality Questionnaire (PAQLQ) cov qhab nia. Qhov feem pua ​​​​ntawm cov neeg mob uas muaj tsawg kawg yog 0.5 cov ntsiab lus kev txhim kho los ntawm lub hauv paus rau Lub Limtiam 12 hauv PAQLQ yog 42% ntawm budesonide thiab formoterol fumarate dihydrate 80/4.5 thiab 46% ntawm budesonide 80 mcg.

Postmarketing Kev Nyab Xeeb thiab Kev Tshawb Fawb Txog Kev Ua Haujlwm

Ib qho randomized, ob-dig muag, sib luag-pab pawg, kev tshawb fawb txog kev nyab xeeb piv rau budesonide thiab formoterol fumarate dihydrate nrog budesonide, txhua tus tswj hwm li 2 inhalations ob zaug ib hnub dhau 26 lub lis piam (NCT01444430). Lub hom phiaj tseem ceeb ntawm kev nyab xeeb yog los soj ntsuam seb qhov sib ntxiv ntawm formoterol rau budesonide txoj kev kho (budesonide thiab formoterol fumarate dihydrate) tsis yog qis dua rau budesonide raws li qhov kev pheej hmoo ntawm mob hawb pob mob hnyav (mob mob hawb pob, mob ntsws asthma, endotracheal intubation, thiab tuag. ). Txoj kev tshawb no tau tsim los txiav txim qhov kev pheej hmoo ua ntej ntawm cov xwm txheej mob hawb pob loj ntawm 2.0. Pawg neeg saib xyuas qhov muag tsis pom kev txiav txim siab seb cov xwm txheej puas muaj mob hawb pob.

Txoj kev tshawb no tau tso npe rau cov neeg mob uas muaj hnub nyoog 12 xyoos thiab laus dua, muaj kev kuaj mob ntsws asthma tsawg kawg yog 1 xyoos, thiab muaj tsawg kawg yog 1 mob hawb pob exacerbation xav tau kev kho mob nrog cov kab mob corticosteroids lossis kev mob ntsws asthma hauv tsev kho mob xyoo dhau los. Cov neeg mob tau stratified rau ib qho ntawm ob koob tshuaj budesonide thiab formoterol fumarate dihydrate los yog budesonide raws li kev soj ntsuam ntawm kev tswj kev mob ntsws asthma thiab kev kho mob hawb pob tsis tu ncua. Cov neeg mob uas muaj keeb kwm ntawm kev ua rau mob hawb pob raug tshem tawm. Txoj kev tshawb no suav nrog 11,693 tus neeg mob [5846 tau txais budesonide thiab formoterol fumarate dihydrate (80/4.5 lossis 160/4.5) thiab 5847 tau txais budesonide (80 lossis 160 mcg)], uas nws lub hnub nyoog nruab nrab yog 44 xyoo, thiab ntawm 66% yog poj niam thiab 69. % yog Caucasian.

Budesonide thiab formoterol fumarate dihydrate tsis yog qhov qis dua rau budesonide raws li lub sijhawm rau thawj qhov xwm txheej mob hawb pob raws li qhov kev pheej hmoo ua ntej, nrog kev kwv yees qhov phom sij ntawm 1.07 [95% CI: 0.70, 1.65] (Table 7 ).

Table 7 Cov Txheej Txheem Tseem Ceeb Tshaj Plaws (Postmarketing Safety and Efficacy study)
*
N = tag nrho cov neeg mob
n = tus naj npawb ntawm cov neeg mob nrog qhov xwm txheej
Qhov phom sij piv rau lub sijhawm rau thawj qhov kev tshwm sim yog raws li tus qauv tsis-stratified Cox proportional txaus ntshai qauv nrog covariates ntawm kev kho mob (budesonide thiab formoterol fumarate dihydrate vs. budesonide) thiab nqus tau corticosteroid koob tshuaj (160 mcg vs. 80 mcg), raws li randomized. Yog tias qhov tshwm sim saum toj 95% CI kwv yees rau tus txheeb ze pheej hmoo yog<2.0, then non-inferiority was concluded.
§
Kev mus pw hauv tsev kho mob hawb pob, endotracheal intubation, lossis kev tuag uas tshwm sim hauv 6 lub hlis tom qab siv tshuaj thawj zaug lossis 7 hnub tom qab hnub kawg ntawm kev kawm tshuaj, txawm tias hnub twg tom qab. Cov neeg mob tuaj yeem muaj ib lossis ntau qhov xwm txheej, tab sis tsuas yog thawj qhov kev tshwm sim raug suav rau kev tshuaj xyuas. Ib pawg neeg saib xyuas qhov muag tsis pom kev, txiav txim siab seb cov xwm txheej puas muaj mob hawb pob.

Budesonide thiab Formoterol Fumarate Dihydrate

(N * = 5846)

n (%)

Budesonide (N * = 5847)

n (%)

Budesonide thiab Formoterol Fumarate Dihydrate vs. Budesonide Hazard ratio (95% CI)

Kev mob hawb pob mob hnyav §

43 (0.7 hli)

40 (0.7 hli)

1.07 (0.70, 1.65)

Asthma-related tuag

ob (<0.1)

0

Asthma-related endotracheal intubation

ib (<0.1)

0

Kev kho mob hawb pob

42 (0.7 hli)

40 (0.7 hli)

Thawj qhov kev ua tau zoo kawg nkaus yog mob hawb pob, txhais tau tias yog kev mob ntsws asthma uas ua rau siv cov tshuaj corticosteroids tsawg kawg 3 hnub, lossis mus pw hauv tsev kho mob, lossis chav kho mob xwm txheej ceev uas yuav tsum tau siv cov tshuaj corticosteroids. Qhov kwv yees qhov phom sij rau lub sijhawm rau thawj tus mob hawb pob exacerbation tus nqi rau budesonide thiab formoterol fumarate dihydrate txheeb ze rau budesonide yog 0.84 [95% CI: 0.75, 0.94]. Qhov txiaj ntsig no feem ntau yog tsav los ntawm kev txo qis hauv kev siv cov tshuaj corticosteroid.

Chronic Obstructive Pulmonary Disease

Lub ntsws ua haujlwm

Kev ua tau zoo ntawm budesonide thiab formoterol fumarate dihydrate 80/4.5 thiab budesonide thiab formoterol fumarate dihydrate 160/4.5 hauv kev kho mob ntawm cov hlab ntsha hauv cov neeg mob COPD tau soj ntsuam nyob rau hauv ob qho tib si randomized, ob-dig muag, placebo-tswj cov kev tshawb fawb thoob ntiaj teb 6 lub hlis. (Study 1) thiab 12 lub hlis (Study 2), nyob rau hauv tag nrho ntawm 3668 tus neeg mob (2416 txiv neej thiab 1252 poj niam). Feem ntau ntawm cov neeg mob (93%) yog Caucasian. Txhua tus neeg mob yuav tsum muaj hnub nyoog tsawg kawg yog 40 xyoo, nrog FEVibtsawg dua lossis sib npaug li 50% kwv yees, kev kuaj mob ntawm COPD nrog cov tsos mob tsawg kawg 2 xyoos, thiab keeb kwm haus luam yeeb tsawg kawg yog 10 xyoo, ua ntej nkag mus rau qhov kev sim. Qhov nruab nrab prebronchodilator FEVibnyob rau hauv lub hauv paus ntawm cov neeg mob cuv npe kawm nyob rau hauv txoj kev tshawb no yog 34% kwv yees. Plaub caug-yim feem pua ​​​​ntawm cov neeg mob tau tso npe tau txais kev nqus corticosteroids thiab 52.7% ntawm cov neeg mob tau ua haujlwm luv luv anticholinergic bronchodilators thaum lub sijhawm khiav. Ntawm randomization, inhaled corticosteroids raug txiav tawm, thiab ipratropium bromide tau tso cai nyob rau hauv ib qho chaw ruaj khov rau cov neeg mob yav tas los kho nrog luv-acting anticholinergic bronchodilators. Cov kev ua tau zoo ntawm kev sib koom ua ke hauv ob txoj kev tshawb fawb yog qhov kev hloov pauv los ntawm cov hauv paus hauv qhov nruab nrab koob tshuaj ua ntej thiab 1-teev tom qab koob tshuaj FEVibdhau lub sijhawm kho. Cov txiaj ntsig ntawm ob qho kev tshawb fawb 1 thiab 2 tau piav qhia hauv qab no.

Kawm 1

Qhov no yog 6-hli, kev tshuaj placebo-tswj ntawm 1704 cov neeg mob COPD (txhais tau tias % kwv yees FEVibntawm lub hauv paus pib txij li 33.5% -34.7%) tau ua los ua kom pom qhov ua tau zoo thiab kev nyab xeeb ntawm budesonide thiab formoterol fumarate dihydrate hauv kev kho mob ntawm airflow obstruction hauv COPD. Cov neeg mob tau randomized rau ib qho ntawm cov kev kho mob hauv qab no: budesonide thiab formoterol fumarate dihydrate 160/4.5 (n = 277), budesonide thiab formoterol fumarate dihydrate 80/4.5 (n = 281), budesonide 160 mcg + formoterol 4.5 mcg ( 287), budesonide 160 mcg (n = 275), formoterol 4.5 mcg (n = 284), lossis placebo (n = 300). Cov neeg mob tau txais budesonide thiab formoterol fumarate dihydrate 160/4.5, ob qhov nqus tau ob zaug ib hnub, tau txais txiaj ntsig zoo dua los ntawm cov hauv paus hauv paus hauv kev noj tshuaj ua ntej FEV.ibqhov nruab nrab ntawm lub sijhawm kho [0.08 L, 10.7%] piv nrog formoterol 4.5 mcg [0.04 L, 6.9%] thiab placebo [0.01 L, 2.2%] (saib daim duab 6). Cov neeg mob tau txais budesonide thiab formoterol fumarate dihydrate 80/4.5, ob qhov nqus tau ob zaug ib hnub, tsis muaj kev txhim kho ntau dua los ntawm cov hauv paus hauv paus hauv koob tshuaj FEV ua ntej.ibQhov nruab nrab ntawm lub sijhawm kho mob piv nrog cov tshuaj formoterol 4.5 mcg.

Daim duab 6 txhais tau tias feem pua ​​​​ntawm Kev Hloov Pauv Los Ntawm Lub hauv paus hauv Pre-dose FEVibTshaj 6 Lub Hlis (Study 1)

Cov neeg mob tau txais budesonide thiab formoterol fumarate dihydrate 160/4.5, ob qhov nqus tau ob zaug ib hnub, tau txais txiaj ntsig zoo dua los ntawm cov hauv paus hauv 1-teev tom qab koob tshuaj FEV.ibnruab nrab ntawm lub sijhawm kho [0.20 L, 22.6%], piv nrog budesonide 160 mcg [0.03 L, 4.9%] thiab placebo [0.03 L, 4.1%] (saib daim duab 7).

Daim duab 7 Lub ntsiab lus feem pua ​​​​ntawm Kev Hloov Pauv Los Ntawm Lub Hauv Paus hauv 1-teev Tom Qab FEVibTshaj 6 lub hlis (Study 1)

Kawm 2

Qhov no yog 12-hli, kev tshuaj placebo-tswj ntawm 1964 cov neeg mob COPD (txhais tau tias % kwv yees FEVibntawm lub hauv paus pib txij li 33.7% -35.5%) tau ua los ua kom pom qhov ua tau zoo thiab kev nyab xeeb ntawm budesonide thiab formoterol fumarate dihydrate hauv kev kho mob ntawm airflow obstruction hauv COPD. Cov neeg mob tau randomized rau ib qho ntawm cov kev kho mob hauv qab no: budesonide thiab formoterol fumarate dihydrate 160/4.5 (n = 494), budesonide thiab formoterol fumarate dihydrate 80/4.5 (n = 494), formoterol 4.5 mcg (n = 495), los yog cov placebo (n=481). Cov neeg mob tau txais budesonide thiab formoterol fumarate dihydrate 160/4.5, ob qhov nqus tau ob zaug ib hnub, tau txais kev txhim kho ntau dua los ntawm cov hauv paus ntsiab lus ntawm kev noj tshuaj ua ntej FEV.ibQhov nruab nrab ntawm lub sijhawm kho [0.10 L, 10.8%] piv nrog formoterol 4.5 mcg [0.06 L, 7.2%] thiab placebo [0.01 L, 2.8%]. Cov neeg mob tau txais budesonide thiab formoterol fumarate dihydrate 80/4.5, ob qhov nqus tau ob zaug ib hnub, tsis muaj kev txhim kho loj dua los ntawm cov hauv paus hauv paus hauv qhov txhais tau tias ua ntej koob FEV.ibnruab nrab ntawm lub sijhawm kho mob piv rau formoterol. Cov neeg mob tau txais budesonide thiab formoterol fumarate dihydrate 160/4.5, ob qhov nqus tau ob zaug ib hnub, kuj tseem muaj txiaj ntsig zoo dua los ntawm cov hauv paus hauv 1-teev tom qab koob tshuaj FEV.ibQhov nruab nrab ntawm lub sijhawm kho [0.21 L, 24.0%] piv nrog cov placebo [0.02 L, 5.2%].

FEV seriesibKev ntsuas ntau tshaj 12 teev tau txais nyob rau hauv ib pawg ntawm cov neeg mob hauv Kev Kawm 1 (n=99) thiab Kawm 2 (n=121). Lub sijhawm nruab nrab ntawm qhov pib ntawm bronchodilation, txhais tau tias yog FEVibnce ntawm 15% lossis ntau dua los ntawm qhov pib, tshwm sim ntawm 5 feeb tom qab noj tshuaj. Kev txhim kho siab tshaj plaws (xws li qhov nruab nrab hloov pauv ntawm qhov pib ntawm txhua lub sijhawm) hauv FEVibtshwm sim ntawm kwv yees li 2 teev tom qab noj tshuaj.

Hauv ob qho tib si Kev Kawm 1 thiab 2, kev txhim kho nyob rau hauv cov ntsiab lus thib ob ntawm thaum sawv ntxov thiab yav tsaus ntuj ncov tas mus li thiab txo qis hauv kev siv tshuaj cawm siav tau txhawb nqa kev ua tau zoo ntawm budesonide thiab formoterol fumarate dihydrate 160/4.5.

Exacerbations

Cov kev tshawb fawb 3 thiab 4 tau tsim los ntsuas qhov cuam tshuam ntawm budesonide thiab formoterol fumarate dihydrate 160/4.5 ntawm COPD exacerbations.

Kawm 3

Qhov no yog 6-hli, kev tswj hwm kev ua haujlwm tau ua los ntsuas cov txiaj ntsig ntawm budesonide thiab formoterol fumarate dihydrate 160/4.5 piv rau formoterol 4.5 mcg, txhua tus tswj hwm li 2 inhalations ob zaug ib hnub, ntawm tus nqi nruab nrab thiab hnyav COPD exacerbations. COPD exacerbations tau txhais tias yog qhov ua rau mob hnyav ntawm 2 lossis ntau dua cov tsos mob loj (dyspnea, hnoos qeev ntim, hnoos qeev xim / purulence) lossis ua rau muaj 1 tus tsos mob loj ua ke nrog yam tsawg kawg 1 ntawm cov tsos mob me: mob caj pas, mob khaub thuas (qhov ntswg tawm thiab / lossis qhov ntswg congestion), kub taub hau yam tsis muaj lwm yam ua rau, hnoos ntau ntxiv los yog hawb pob ntxiv rau tsawg kawg 2 hnub sib law liag. COPD exacerbations raug txiav txim siab ntawm qhov mob hnyav yog tias kho cov tsos mob nrog cov kab mob corticosteroids (≧3 hnub) thiab / lossis cov tshuaj tua kab mob, thiab raug txiav txim siab hnyav yog tias yuav tsum tau mus pw hauv tsev kho mob. Txoj kev tshawb no randomized 1219 kev kawm rau budesonide thiab formoterol fumarate dihydrate 160/4.5 (606) thiab formoterol 4.5 mcg (613) uas 57% yog txiv neej thiab 92% yog Caucasian. Lawv muaj hnub nyoog nruab nrab ntawm 64 xyoo thiab keeb kwm haus luam yeeb nruab nrab ntawm 39 pob xyoo, nrog 46% txheeb xyuas tias yog cov neeg haus luam yeeb tam sim no. Thaum khiav hauv, qhov nruab nrab tom qab bronchodilator % kwv yees li qub FEVibyog 48.7% (ntau npaum li cas: 16.0% txog 78.1%), thiab cov neeg mob muaj keeb kwm tsawg kawg yog 1 COPD exacerbation nyob rau xyoo dhau los tau kho nrog cov kab mob corticosteroids thiab / lossis pw hauv tsev kho mob. Txhua qhov kev kawm tau raug kho nrog budesonide thiab formoterol fumarate dihydrate 160/4.5, ob qhov nqus tau ob zaug ib hnub nyob rau hauv 4-lub lim tiam khiav-hauv lub sijhawm ua ntej tau muab kev sim kho.

Kawm 4

Qhov no yog 12-hli, active-tswj txoj kev kawm uas suav nrog 811 cov kev kawm kho nrog budesonide thiab formoterol fumarate dihydrate 160/4.5 los yog formoterol 4.5 mcg, txhua tus tswj raws li 2 inhalations ob zaug ib hnub twg. Txoj kev tshawb no tau ua los ntsuas rau COPD exacerbation txo qis hauv cov neeg mob COPD. COPD exacerbations tau txhais tias ua rau COPD zuj zus ntxiv uas yuav tsum tau muaj kev kho qhov ncauj steroids rau kev kho mob thiab / lossis pw hauv tsev kho mob. Txoj kev tshawb no randomized 407 cov ntsiab lus rau budesonide thiab formoterol fumarate dihydrate 160/4.5 thiab 404 rau formoterol 4.5 mcg ntawm 61% yog txiv neej thiab 83% yog Caucasian. Lawv muaj hnub nyoog nruab nrab ntawm 63 xyoo thiab keeb kwm haus luam yeeb nruab nrab ntawm 45 xyoo pob, nrog 36% pom tias yog cov neeg haus luam yeeb tam sim no. Thaum khiav hauv, qhov nruab nrab tom qab bronchodilator % kwv yees li qub FEVibyog 37.8% (ntau npaum li cas: 11.75% txog 76.50%), thiab keeb kwm ntawm tsawg kawg yog 1 COPD exacerbation xyoo dhau los tau kho nrog cov kab mob corticosteroids thiab / lossis tshuaj tua kab mob.

Hauv Txoj Kev Kawm 3, cov kev kho mob nrog budesonide thiab formoterol fumarate dihydrate 160/4.5, ob qhov nqus tau ob zaug ib hnub tau qis dua ib xyoos ib zaug ntawm kev mob COPD exacerbations piv nrog formoterol 4.5 mcg nrog qhov txo qis ntawm 26% (95% CI: 9%. , 39%). Hauv Kev Kawm 4, qhov txo qis txhua xyoo ntawm exacerbations kuj tau pom nyob rau hauv cov kev kho mob nrog budesonide thiab formoterol fumarate dihydrate 160/4.5 piv nrog formoterol 4.5 mcg nrog qhov txo qis ntawm 35% (95% CI: 20%, 47%) (Table 8).

Table 8 Chronic Obstructive Pulmonary Disease Exacerbations
n Kev kwv yees tus nqi txhua xyoo Tus nqi piv Budesonide thiab Formoterol Fumarate Dihydrate 160/4.5 vs Formoterol 4.5 mcg

Kev kho mob

Kwv yees

95% CI

Kawm 3

Budesonide thiab Formoterol Fumarate Dihydrate 160/4.5

606

0.94 ib

0.74 ib

0.61, 0.91 Nws

Formoterol 4.5 mcg

613

1.27

Kawm 4

Budesonide thiab Formoterol Fumarate Dihydrate 160/4.5

404

0.68 ib

0.65 ib

0.53, 0.80 Nws

Formoterol 4.5 mcg

403

1.05 Nws

n - Tus naj npawb ntawm cov neeg mob suav nrog hauv kev tshuaj xyuas kev ua tau zoo.

Kev noj qab haus huv ntsig txog lub neej raug ntsuas los ntawm St. George's Respiratory Questionnaire (SGRQ) hauv ob qho tib si COPD exacerbation soj ntsuam kev tshawb fawb.

Hauv Kev Kawm 3, SGRQ cov neeg teb cov nqi ntawm 6-hli (txhais tias yog kev txhim kho hauv cov qhab nia ntawm 4 lossis ntau dua raws li qhov pib) yog 40% thiab 33% rau budesonide thiab formoterol fumarate dihydrate 160/4.5 thiab formoterol 4.5 mcg, raws li, qhov sib txawv ntawm 1.5 (95% CI: 1.0, 2.0) rau budesonide thiab formoterol fumarate dihydrate 160/4.5 vs. formoterol 4.5 mcg. Hauv Kev Kawm 4, cov neeg teb cov lus teb ntawm 12-hli yog 50% thiab 49% rau budesonide thiab formoterol fumarate dihydrate 160/4.5 thiab formoterol 4.5 mcg, raws li, nrog rau qhov sib txawv ntawm 1.0 (95% CI: 0.8, 1,4). rau budesonide thiab formoterol fumarate dihydrate 160/4.5 vs. formoterol 4.5 mcg.

Yuav Ua Li Cas Muab / Cia thiab tuav

BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL muaj nyob rau hauv ob lub zog thiab tau muab rau hauv cov pob loj hauv qab no:

Daim ntawv siv tshuaj thiab muaj zog

Pob Loj

NDC

BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL

80/4.5

120 Inhalations

0310-7372-20

BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL

160/4.5

120 Inhalations

0310-7370-20 ib

Txhua lub zog yog muab los ua ib lub tshuab nqus tsev siab nrog cov khoom siv suav nrog, lub cev xim liab lub cev nrog lub qhov ncauj dawb, thiab txuas nrog cov plua plav grey. Txhua 120 lub tshuab nqus pa muaj qhov hnyav ntawm 10.2 grams. Txhua lub kaus poom tau ntim rau hauv ib lub hnab ntawv ci nrog cov hnab ntim desiccant thiab muab tso rau hauv ib lub thawv. Txhua lub thawv muaj ib lub kaus poom thiab ib daim ntawv qhia txog Tus Neeg Mob.

BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL canister yuav tsum tsuas yog siv nrog BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL actuator, thiab cov tshuaj BUDESONIDE THIAB FORMOTEROL FUMARATE yuav tsum tsis txhob siv lwm yam tshuaj.

Qhov tseeb ntawm cov tshuaj nyob rau hauv txhua qhov inhalation tsis tuaj yeem ua kom ntseeg tau tom qab siv cov ntawv sau npe ntawm cov nqus nqus pa los ntawm lub kaus poom, txawm tias lub tshuab nqus pa yuav tsis hnov ​​​​tsw kiag li thiab tuaj yeem ua haujlwm ntxiv. Lub tshuab nqus tsev yuav tsum muab pov tseg thaum cov ntawv sau npe ntawm cov nqus nqus tau siv los yog hauv 3 lub hlis tom qab tshem tawm ntawm lub hnab ntawv. Tsis txhob muab tso rau hauv lub lauj kaub rau hauv dej kom txiav txim siab txog qhov seem hauv lub kaus poom (float test).

Khaws ntawm qhov chaw tswj qhov kub ntawm 20 ° C txog 25 ° C (68 ° F txog 77 ° F) [saib USP]. Khaws lub inhaler nrog lub qhov ncauj cia.

Txhawm rau kom tau txais txiaj ntsig zoo tshaj plaws, lub kaus mom yuav tsum nyob hauv chav sov ua ntej siv. Co zoo rau 5 vib nas this ua ntej siv.

Khaws kom deb ntawm cov menyuam yaus. Tsis txhob tsuag rau qhov muag.

COV TSEV KAWM NTAWV.

Tsis txhob thas lossis incinerate. Tsis txhob cia ze rau qhov kub thiab qhov hluav taws kub. Qhov kub thiab txias tshaj 120ºF tuaj yeem ua rau tawg. Tsis txhob muab lub thawv pov tseg rau hauv hluav taws lossis qhov cub.

Cov Ntaub Ntawv Qhia Txog Tus Neeg Mob

Qhia tus neeg mob kom nyeem cov ntawv pom zoo los ntawm FDA rau tus neeg mob (Cov Ntaub Ntawv Tus Neeg Mob thiab Cov Lus Qhia rau Kev Siv).

Mob hawb pob ntsig txog cov xwm txheej:Qhia rau cov neeg mob hawb pob tias LABA thaum siv ib leeg ua rau muaj kev pheej hmoo ntawm kev mob hawb pob lossis mob hawb pob. Muaj cov ntaub ntawv qhia tias thaum ICS thiab LABA siv ua ke, xws li nrog budesonide thiab formoterol fumarate dihydrate, tsis muaj qhov pheej hmoo ntawm cov xwm txheej no.

Tsis yog rau cov tsos mob hnyav:Qhia rau cov neeg mob tias budesonide thiab formoterol fumarate dihydrate tsis yog los txo cov tsos mob ntawm tus mob hawb pob lossis COPD thiab cov koob tshuaj ntxiv yuav tsum tsis txhob siv rau lub hom phiaj ntawd. Qhia rau cov neeg mob kom kho cov tsos mob hnyav nrog qhov nqus tau, ua kom luv luv betaob- agonist xws li albuterol. Muab cov tshuaj no rau cov neeg mob thiab qhia tus neeg mob txog seb nws yuav tsum siv li cas.

Qhia cov neeg mob mus nrhiav kev kho mob tam sim yog tias lawv ntsib ib qho hauv qab no:

Txo qhov ua tau zoo ntawm inhaled, luv-acting betaob- agonists
Xav tau kev nqus pa ntau dua li niaj zaus ntawm nqus tau pa, luv-acting betaob- agonists
Qhov txo qis hauv lub ntsws ua haujlwm raws li tus kws kho mob tau hais tseg

Qhia rau cov neeg mob tias lawv yuav tsum tsis txhob tso tseg kev kho mob nrog budesonide thiab formoterol fumarate dihydrate yam tsis muaj kws kho mob / tus kws kho mob qhia vim tias cov tsos mob yuav rov zoo dua tom qab txiav tawm.

Tsis txhob siv Ntxiv Long-Acting Betaob-Agonists:Qhia cov neeg mob tsis txhob siv lwm yam LABA rau mob hawb pob thiab COPD.

Cov teebmeem hauv zos:Qhia rau cov neeg mob uas muaj kab mob hauv zos nrogCov kab mob Candida albicanstshwm sim hauv qhov ncauj thiab pharynx hauv qee cov neeg mob. Yog hais tias oropharyngeal candidiasis tshwm sim, nws yuav tsum tau kho nrog kev kho mob hauv zos los yog cov kab mob (piv txwv li, qhov ncauj) kev kho cov kab mob fungal thaum tseem txuas ntxiv kho nrog budesonide thiab formoterol fumarate dihydrate, tab sis qee zaum kev kho nrog budesonide thiab formoterol fumarate dihydrate yuav tsum tau cuam tshuam ib ntus. kev saib xyuas kev kho mob. Kev yaug lub qhov ncauj nrog dej yam tsis tau nqos tom qab nqus tau yog qhia kom txo tau txoj kev pheej hmoo ntawm thrush.

Mob ntsws o:Cov neeg mob uas muaj COPD muaj kev pheej hmoo siab ntsws ntsws; qhia kom lawv tiv tauj lawv tus kws kho mob yog tias lawv muaj cov tsos mob ntawm mob ntsws.

Immunosuppression:Ceeb toom rau cov neeg mob uas tau txhaj tshuaj tiv thaiv kab mob corticosteroids kom tsis txhob kis tus kab mob qhua pias lossis qhua pias thiab, yog tias kis tau, mus ntsib lawv tus kws kho mob yam tsis tau ncua. Qhia rau cov neeg mob txog qhov muaj peev xwm ua rau cov kab mob uas twb muaj lawm, cov kab mob fungal, kab mob, kab mob, los yog kab mob cab, los yog ocular herpes simplex.

Hypercorticism thiab Adrenal Suppression:Qhia rau cov neeg mob tias budesonide thiab formoterol fumarate dihydrate tuaj yeem ua rau cov kab mob corticosteroid cuam tshuam ntawm hypercorticism thiab adrenal suppression. Tsis tas li ntawd, qhia rau cov neeg mob tias kev tuag vim yog qhov tsis txaus ntawm adrenal tau tshwm sim thaum thiab tom qab hloov los ntawm cov kab mob corticosteroids. Cov neeg mob yuav tsum tau qeeb qeeb los ntawm cov kab mob corticosteroids yog hloov mus rau budesonide thiab formoterol fumarate dihydrate.

Txo hauv Pob Txha Mineral Density:Qhia rau cov neeg mob uas muaj kev pheej hmoo ntau ntxiv rau BMD txo qis tias kev siv corticosteroids yuav ua rau muaj kev pheej hmoo ntxiv.

Txo kev loj hlob ceev:Qhia rau cov neeg mob tias qhov ncauj nqus corticosteroids, ib feem ntawm budesonide thiab formoterol fumarate dihydrate, yuav ua rau txo qis kev loj hlob tshaj tawm thaum muab rau cov neeg mob menyuam yaus. Cov kws kho mob yuav tsum ua tib zoo ua raws li kev loj hlob ntawm cov menyuam yaus thiab cov tub ntxhais hluas noj corticosteroids los ntawm txhua txoj kev.

Cov teebmeem ntawm Ocular:Kev siv ntev ntev ntawm kev nqus corticosteroids tuaj yeem ua rau muaj kev pheej hmoo ntawm qee qhov muag teeb meem (cataracts lossis glaucoma); xav txog kev kuaj qhov muag tsis tu ncua.

Risks Associated Nrog Beta-Agonist Therapy:Qhia rau cov neeg mob txog cov kev phiv cuam tshuam nrog beta2-agonists, xws li palpitations, mob hauv siab, plawv dhia ceev, tshee, lossis ntxhov siab.

© AstraZeneca 2019

Chaw tsim tshuaj paus: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850

Los ntawm: AstraZeneca Dunkerque Production, Dunkirk, Fabkis

Cov khoom ntawm Fabkis

Cov Ntaub Ntawv Tus Neeg Mob

BUDESONIDE (bue-DES-oh-nide) THIAB FORMOTEROL (for-MOH-teh-rol) FUMARATE DIHYDRATE IN HALATION AEROSOL
(budesonide 80 mcg thiab formoterol fumarate dihydrate 4.5 mcg)

BUDESONIDE (bue-DES-oh-nide) THIAB FORMOTEROL (for-MOH-teh-rol) FUMARATE DIHYDRATE IN HALATION AEROSOL
(budesonide 160 mcg thiab formoterol fumarate dihydrate 4.5 mcg)

BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL yog dab tsi?

BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL ua ke cov tshuaj inhaled corticosteroid (ICS), budesonide thiab beta ua haujlwm ntev.ob-adrenergic agonist (LABA), tshuaj formoterol.

Inhaled corticosteroids pab txo qhov mob hauv lub ntsws. Kev mob hauv lub ntsws tuaj yeem ua rau muaj teeb meem ua pa.
Cov tshuaj LABA yog siv rau cov neeg uas muaj kab mob obstructive pulmonary (COPD) thiab mob hawb pob. LABA cov tshuaj pab cov leeg nqaij ib ncig ntawm cov hlab ntsws hauv koj lub ntsws kom nyob twj ywm kom tsis txhob muaj cov tsos mob xws li hawb pob, hnoos, mob hauv siab, thiab ua tsis taus pa. Cov tsos mob no tuaj yeem tshwm sim thaum cov leeg nqaij ib ncig ntawm cov hlab cua nruj. Qhov no ua rau nws ua tsis taus pa. Hauv cov xwm txheej hnyav, hawb pob tuaj yeem nres koj ua pa thiab tuaj yeem ua rau tuag yog tias tsis kho tam sim ntawd.

BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL tsis yog siv los daws teeb meem ua pa saithiab yuav tsis hloov lub nqus nqus pa.

BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL yog siv rau kev mob ntsws asthma thiab COPD raws li hauv qab no:

Mob hawb pob:BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL yog siv los tswj cov tsos mob ntawm mob hawb pob, thiab tiv thaiv cov tsos mob xws li hawb pob hauv cov neeg laus thiab cov menyuam hnub nyoog 6 thiab laus dua.
BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL muaj cov formoterol. LABA cov tshuaj xws li formoterol thaum siv ib leeg ua rau muaj kev pheej hmoo ntawm kev tuag thiab mus pw hauv tsev kho mob los ntawm teeb meem hawb pob. BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL muaj ICS thiab LABA. Thaum ICS thiab LABA siv ua ke, tsis muaj kev pheej hmoo ntau ntxiv hauv tsev kho mob thiab tuag los ntawm teeb meem mob hawb pob. BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL tsis yog rau cov neeg laus thiab cov menyuam yaus uas muaj mob hawb pob uas tswj tau zoo nrog cov tshuaj tiv thaiv kab mob hawb pob, xws li cov tshuaj qis rau nruab nrab ntawm ICS. BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL yog rau cov neeg laus thiab menyuam yaus uas muaj mob hawb pob uas xav tau ob qho tshuaj ICS thiab LABA.
Nws tsis paub yog tias BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL muaj kev nyab xeeb thiab siv tau rau cov menyuam yaus hnub nyoog qis dua 6 xyoo uas muaj mob hawb pob.
COPD: COPD yog kab mob ntsws ntev (ntev) uas muaj xws li mob ntsws ntsws, mob ntsws, lossis ob qho tib si. BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL 160/4.5 mcg yog siv mus sij hawm ntev, raws li 2 inhalations 2 zaug hauv ib hnub, txhawm rau txhim kho cov tsos mob ntawm COPD kom ua pa zoo dua thiab txo tus naj npawb ntawm flare-ups (qhov ua rau koj cov tsos mob COPD zuj zus rau ob peb hnub).

Tsis txhob siv BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL:

los kho cov tsos mob hnyav heev ntawm hawb pob lossis COPD.
Yog tias koj ua xua rau ib qho ntawm cov khoom xyaw hauv BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL. Saib qhov kawg ntawm daim ntawv no rau cov npe ntawm cov khoom xyaw hauv BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL.

Ua ntej koj siv BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL, qhia koj tus kws kho mob txog tag nrho koj cov mob, suav nrog yog tias koj:

muaj teeb meem plawv.
muaj ntshav siab.
muaj qaug dab peg.
muaj teeb meem thyroid.
muaj ntshav qab zib.
muaj teeb meem daim siab.
muaj osteoporosis.
muaj teeb meem tiv thaiv kab mob.
muaj teeb meem qhov muag xws li nce siab hauv qhov muag, glaucoma, lossis cataracts.
tsis haum rau tej yam tshuaj.
muaj tej yam kab mob, kab mob, fungal, los yog kab mob parasitic.
raug kab mob pox los yog qhua pias.
cev xeeb tub los yog npaj yuav xeeb tub. Nws tsis paub yog tias BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL tuaj yeem ua mob rau koj tus menyuam hauv plab.
pub niam mis. Budesonide, ib qho ntawm cov khoom xyaw nquag hauv BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL, nkag mus rau hauv cov kua mis. Koj thiab koj tus kws kho mob yuav tsum txiav txim siab seb koj puas yuav noj BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL thaum pub niam mis.

Qhia rau koj tus kws kho mob txog txhua yam tshuaj uas koj noj nrog rau cov tshuaj noj thiab tshuaj tom khw muag khoom, cov vitamins, thiab tshuaj ntsuab tshuaj ntsuab. BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL thiab lwm yam tshuaj yuav cuam tshuam rau ib leeg. Qhov no yuav ua rau muaj kev phiv loj heev. Tshwj xeeb tshaj yog qhia rau koj tus kws kho mob yog tias koj noj tshuaj tua kab mob lossis tshuaj tiv thaiv kab mob HIV.

Paub tag nrho cov tshuaj koj noj. Khaws ib daim ntawv teev npe thiab qhia rau koj tus kws kho mob thiab kws muag tshuaj txhua zaus koj tau txais cov tshuaj tshiab.

Kuv yuav siv BUDESONIDE thiab FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL li cas?

Saib cov lus qhia ua ntu zus rau kev siv BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL tom kawg ntawm Daim Ntawv Qhia Tus Neeg Mob no.Tsis txhob siv BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL tshwj tsis yog koj tus kws kho mob tau qhia koj thiab koj nkag siab txhua yam. Nug koj tus kws kho mob lossis tus kws muag tshuaj yog tias koj muaj lus nug.

Siv BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL raws nraim li tau sau tseg.Tsis txhob siv BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL ntau dua li qhov tau sau tseg.BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL los ntawm 2 lub zog. Koj tus kws kho mob tau sau lub zog uas zoo tshaj rau koj. Nco ntsoov qhov sib txawv ntawm BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL thiab koj lwm cov tshuaj uas nqus tau, suav nrog qhov sib txawv ntawm kev siv tshuaj thiab lub cev zoo li qub.
Cov menyuam yaus yuav tsum siv BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL nrog cov neeg laus pab, raws li tus menyuam tus kws kho mob qhia.
BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL yuav tsum tau noj txhua hnub raws li 2 puffs thaum sawv ntxov thiab 2 puffs nyob rau yav tsaus ntuj txog 12 teev sib nrug.
Yog tias koj tsis nco qab koob tshuaj BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL, koj yuav tsum noj koj cov koob tshuaj ntxiv rau tib lub sijhawm koj ib txwm ua.
Yaug koj lub qhov ncauj nrog dej thiab nchuav dej tawm tom qab txhua koob tshuaj (2 puffs) ntawm BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL. Tsis txhob nqos dej. Qhov no yuav pab txo qis txoj hauv kev kis tus kab mob fungal (thrush) hauv qhov ncauj thiab caj pas.
Yog tias koj noj ntau dhau BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL, hu rau koj tus kws kho mob lossis mus rau lub tsev kho mob xwm txheej ceev tam sim ntawd yog tias koj muaj cov tsos mob txawv txawv, xws li ua tsis taus pa, mob hauv siab, nce plawv dhia, lossis tshee. .
Tsis txhob tsuag BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INhalation AEROSOL hauv koj ob lub qhov muag. Yog tias koj tau txais BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL hauv koj lub qhov muag, yaug koj ob lub qhov muag nrog dej, thiab yog tias liab lossis khaus tshwm sim, nrog koj tus kws kho mob tham.
Tsis txhob hloov lossis tso tseg cov tshuaj uas siv los tswj lossis kho koj cov teebmeem ua pa. Koj tus kws kho mob yuav hloov koj cov tshuaj raws li xav tau.
Thaum koj siv BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL 2 zaug hauv ib hnub, tsis txhob siv lwm cov tshuaj uas muaj LABA vim li cas. Nug koj tus kws kho mob lossis tus kws muag tshuaj seb koj cov tshuaj twg yog cov tshuaj LABA.
BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL tsis txo cov tsos mob tshwm sim. Ib txwm muaj cov tshuaj cawm siav nrog koj los kho cov tsos mob tshwm sim. Yog tias koj tsis muaj lub tshuab nqus pa, hu rau koj tus kws kho mob kom muaj ib qho tshuaj rau koj.
Hu rau koj tus kws kho mob lossis mus ntsib kev kho mob tam sim yog tias:
koj cov teeb meem ua pa phem zuj zus tuaj nrog BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL.
koj yuav tsum siv koj cov tshuaj cawm siav ntau dua li niaj zaus.
koj cov tshuaj nqus pa cawm siav tsis ua haujlwm zoo rau koj ntawm kev txo cov tsos mob.
koj qhov siab tshaj plaws flow meter tau txo qis. Koj tus kws kho mob yuav qhia koj cov lej uas tsim nyog rau koj.
koj cov tsos mob tsis zoo tom qab siv BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL tsis tu ncua rau 1 lub lis piam.

Dab tsi yog qhov tshwm sim ntawm BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL yog dab tsi?

BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL tuaj yeem ua rau muaj kev phiv loj heev, suav nrog:

Kev siv cov tshuaj LABA ntau dhau tuaj yeem ua rau:
mob hauv siab
lub plawv dhia ceev thiab tsis xwm yeem
tshee
nce ntshav siab
mob taub hau
ntxhov siab
Kab mob fungal hauv koj lub qhov ncauj lossis caj pas (thrush). Yaug koj lub qhov ncauj nrog dej yam tsis tau nqos tom qab siv BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL los pab txo koj txoj kev kis tus kab mob.
Pneumonia thiab lwm yam kab mob ua pa hauv qab.Cov neeg uas muaj COPD muaj feem ntau dua ntawm kev mob ntsws thiab lwm yam mob ntsws. Inhaled corticosteroids tuaj yeem ua rau muaj mob ntsws. Hu rau koj tus kws kho mob yog tias koj pom ib qho ntawm cov tsos mob no:
nce mucus (sputum) ntau lawm
ua npaws
nce hnoos
hloov hauv mucus xim
txias
ua tsis taus pa ntxiv
Kev tiv thaiv kab mob cuam tshuam thiab muaj feem ntau dua rau kev kis kab mob.Qhia rau koj tus kws kho mob txog cov tsos mob ntawm tus kab mob xws li:
ua npaws
mob lub cev
xav nkees
ntuav
mob
txias
xeev siab
Adrenal tsis txaus.Adrenal insufficiency yog ib yam mob uas cov qog adrenal tsis tsim cov tshuaj steroid txaus. Qhov no tuaj yeem tshwm sim thaum koj tsis noj tshuaj corticosteroid hauv qhov ncauj thiab pib nqus cov tshuaj corticosteroid.
Ua kom hawb pob muaj cai tom qab noj BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INhalation AEROSOL.Ib txwm muaj lub tshuab nqus pa cawm siav nrog koj los kho mob hawb pob.
Kev ua xua hnyav xws li pob khaus, khaus khaus, o ntawm lub ntsej muag, qhov ncauj, thiab tus nplaig, thiab ua pa.Hu rau koj tus kws kho mob lossis tau txais kev kho mob xwm txheej ceev yog tias koj tau txais cov tsos mob ntawm kev tsis haum tshuaj loj.
Txo cov pob txha ntxhia pob txha.Qhov no tuaj yeem tshwm sim rau cov neeg uas muaj feem ntau rau cov pob txha pob txha tsawg (osteoporosis). Koj tus kws kho mob yuav tsum kuaj xyuas koj rau qhov no thaum kho nrog BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL.
Kev loj hlob qeeb hauv cov menyuam yaus.Tus me nyuam txoj kev loj hlob yuav tsum tau kuaj xyuas tsis tu ncua thaum siv BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL.
Teeb meem qhov muag nrog rau glaucoma thiab cataracts.Koj yuav tsum tau kuaj qhov muag tsis tu ncua thaum siv BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL.
o ntawm koj cov hlab ntsha. Qhov no tuaj yeem tshwm sim hauv cov neeg mob hawb pob. Qhia rau koj tus kws kho mob tam sim yog tias koj muaj:
kev xav ntawm tus pins thiab koob lossis loog ntawm koj txhais tes lossis ob txhais ceg
ua pob liab liab
mob khaub thuas zoo li cov tsos mob
mob thiab o ntawm sinuses
Txo cov poov tshuaj hauv cov ntshav (hypokalemia).
Ua kom cov ntshav qab zib ntau ntxiv (hyperglycemia).

Cov kev mob tshwm sim feem ntau ntawm BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL suav nrog:

Cov neeg mob hawb pob:
caj pas khaus
kab mob ua pa sab sauv
o ntawm mucous daim nyias nyias ntawm sinuses (sinusitis)
mob nraub qaum
plab tsis xis nyob
thrush nyob rau hauv lub qhov ncauj thiab caj pas. Yaug koj lub qhov ncauj nrog dej yam tsis tau nqos tom qab siv los pab tiv thaiv thrush
mob taub hau
mob caj pas
mob khaub thuas
qhov ntswg congestion
ntuav

Cov neeg uas muaj COPD:

mob caj pas.
thrush nyob rau hauv lub qhov ncauj thiab caj pas. Yaug koj lub qhov ncauj nrog dej yam tsis tau nqos tom qab siv los pab tiv thaiv thrush.
kab mob thiab o ntawm mucous daim nyias nyias ntawm lub bronchial hlab (bronchitis).
o ntawm cov mucous daim nyias nyias nyob rau hauv lub sinuses (sinusitis).
kab mob ua pa sab sauv.

Qhia rau koj tus kws kho mob txog cov kev mob tshwm sim uas cuam tshuam rau koj lossis qhov ntawd tsis ploj mus.

Cov no tsis yog tag nrho cov kev mob tshwm sim ntawm BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL.

Hu rau koj tus kws kho mob kom paub cov lus qhia txog kev mob tshwm sim. Koj tuaj yeem tshaj tawm cov kev mob tshwm sim rau FDA ntawm 1-800-FDA-1088.

Koj tseem tuaj yeem tshaj tawm cov kev mob tshwm sim rau AstraZeneca ntawm 1-800-236-9933.

Kuv yuav khaws BUDESONIDE thiab FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL li cas?

Khaws BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL ntawm chav tsev kub ntawm 68 ° F txog 77 ° F (20 ° C txog 25 ° C).
Khaws BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL nrog lub qhov ncauj.
Cov ntsiab lus ntawm koj BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL canister yog nyob rau hauv siab. Tsis txhob thas lossis pov lub kaus poom rau hauv qhov hluav taws kub lossis qhov cub. Tsis txhob siv los yog khaws cia ze ntawm qhov kub thiab qhov hluav taws kub. Cia siab tshaj 120ºF tuaj yeem ua rau lub kaus mom tawg.
Pov tseg BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL thaum lub txee nce mus txog xoom (0) lossis 3 lub hlis tom qab koj noj BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL tawm ntawm nws lub hnab ntawv ci, qhov twg los ua ntej.
Khaws BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL thiab txhua yam tshuaj kom deb ntawm menyuam yaus.

Cov ntaub ntawv dav dav txog kev nyab xeeb thiab siv tau zoo ntawm BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL.

Cov tshuaj qee zaum raug muab rau cov hom phiaj uas tsis yog cov teev nyob rau hauv Daim Ntawv Qhia Txog Tus Neeg Mob. Tsis txhob siv BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL rau ib qho xwm txheej uas nws tsis tau sau tseg. Tsis txhob muab BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL rau lwm tus neeg, txawm tias lawv muaj cov tsos mob zoo li koj muaj. Nws yuav ua mob rau lawv.

Koj tuaj yeem nug koj tus kws kho mob lossis tus kws muag tshuaj rau cov ntaub ntawv hais txog BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL uas sau rau cov kws kho mob.

Dab tsi yog cov khoom xyaw hauv BUDESONIDE thiab FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL?

Cov khoom xyaw nquag: micronized budesonide thiab micronized formoterol fumarate dihydrate
Cov khoom xyaw uas tsis muaj zog: hydrofluroalkane (HFA 227), povidone K25 USP, thiab polyethylene glycol 1000 NF

Chaw tsim tshuaj paus: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850

Los ntawm: AstraZeneca Dunkerque Production, Dunkerque, Fabkis Cov khoom ntawm Fabkis

Yog xav paub ntxiv, hu rau 1-800-236-9933.

Kho tshiab: Lub Xya hli ntuj 2019

Cov lus qhia rau kev siv

BUDESONIDE (bue-DES-oh-nide) THIAB FORMOTEROL (for-MOH-teh-rol) FUMARATE DIHYDRATE
INHALATION AEROSOL

(budesonide 80 mcg thiab formoterol fumarate dihydrate 4.5 mcg)

BUDESONIDE (bue-DES-oh-nide) THIAB FORMOTEROL (for-MOH-teh-rol) FUMARATE DIHYDRATE
INHALATION AEROSOL

(budesonide 160 mcg thiab formoterol fumarate dihydrate 4.5 mcg)

Upright txoj hauj lwm

Yuav Siv BUDESONIDE thiab FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL li cas

Ua raws li cov lus qhia hauv qab no rau kev siv BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL. Koj yuav ua pa-in (inhale) cov tshuaj. Yog tias koj muaj lus nug, nug koj tus kws kho mob lossis tus kws muag tshuaj.

Npaj koj BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler rau kev siv

ib.
Nqa koj cov BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL tawm ntawm lub hnab ntim dej noo tiv thaiv ua ntej koj siv thawj zaug thiab muab cov ntawv pov tseg pov tseg. Sau hnub uas koj qhib lub hnab ntawv rau ntawm lub thawv.
ob.
Ib lub txee yog txuas nrog rau sab saum toj ntawm cov hlau canister. Lub txee yuav suav rov qab txhua zaus koj tso ib lub puff ntawm BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INhalation AEROSOL. Tus xub taw qhia rau tus naj npawb ntawm inhalations (puffs) sab laug hauv lub kaus poom. Lub txee yuav nres suav ntawm xoom (0).
3.
Siv BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL canister nkaus xwb nrog cov liab BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL inhaler nkag nrog cov khoom. Qhov chaw ntawm BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler yuav tsum tsis txhob siv nrog cov khoom los ntawm lwm yam khoom nqus pa.
Plaub.
Caw koj cov BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL inhaler zoo rau 5 vib nas this ua ntej siv. Tshem lub qhov ncauj npog los ntawm nyem maj mam ntawm ob sab, ces rub tawm (saib daim duab 2). Tshawb xyuas lub qhov ncauj rau cov khoom txawv teb chaws ua ntej siv.
ib.
Priming koj BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL inhaler
Ua ntej koj siv BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL thawj zaug, koj yuav tsum tau ua thawj zaug. Txhawm rau thawj BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL, tuav nws hauv txoj haujlwm ncaj. Saib daim duab 1. Co lub BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL nqus tau zoo rau 5 vib nas this. Tuav koj BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL inhaler tig ntsej muag ntawm koj thiab nias kom ruaj khov thiab tag nrho rau saum lub txee ntawm BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL tshuaj tsuag. Tom qab ntawd co nws dua rau 5 vib nas this thiab tso cov tshuaj tsuag thib ob. Koj BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL inhaler yog tam sim no primed thiab npaj siv. Tom qab koj tau primed lub BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL inhaler thawj zaug, lub txee yuav nyeem 120.

Yog tias koj tsis siv koj cov BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL inhaler rau ntau tshaj 7 hnub lossis yog tias koj tso nws, koj yuav tsum tau rov ua dua.

Txoj hauv kev los tuav lub BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler siv

LOSSIS

Siv koj lub BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL inhaler

ib.
Caw koj BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL inhaler zoo rau 5 vib nas this. Tshem lub qhov ncauj npog. Tshawb xyuas lub qhov ncauj rau cov khoom txawv teb chaws.
ob.
Ua pa tawm tag nrho (exhale). Tuav lub BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL inhaler mus rau koj lub qhov ncauj. Muab lub qhov ncauj dawb tso rau hauv koj lub qhov ncauj thiab kaw koj daim di ncauj ib ncig ntawm nws. Xyuas kom tseeb tias BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL inhaler yog ncaj thiab tias qhov qhib ntawm lub qhov ncauj yog taw rau sab nraub qaum ntawm koj caj pas (saib daim duab 5).
ib.
Ua pa (inhale) tob thiab maj mam los ntawm koj lub qhov ncauj. Nias kom ruaj khov thiab tag nrho rau saum lub txee ntawm BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler kom tso cov tshuaj (saib daim duab 3 thiab 4).
ob.
Txuas ntxiv ua pa (inhales) thiab tuav koj cov pa li 10 vib nas this, lossis ntev npaum li nws xis nyob. Ua ntej koj ua pa tawm (exhale), tso koj tus ntiv tes los ntawm sab saum toj ntawm lub txee. Khaws BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL inhaler ncaj nraim thiab tshem tawm ntawm koj lub qhov ncauj.
3.
Co lub BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL inhaler dua rau 5 vib nas this thiab rov ua cov kauj ruam 7 mus rau 9.

Tom qab siv koj cov BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL inhaler

ib.
Tom qab siv, kaw lub qhov ncauj npog los ntawm thawb kom txog thaum nws nyem rau hauv qhov chaw.
ob.
Tom qab koj ua tiav kev noj BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL (2 puffs), yaug koj lub qhov ncauj nrog dej. Ncaim dej. Tsis txhob nqos.

Nyeem lub txee

Lub xub nyob rau ntawm lub txee rau saum lub BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL inhaler taw qhia rau cov naj npawb ntawm inhalations (puffs) sab laug hauv koj lub tshuab nqus pa.

COUNTER

Lub txee yuav suav rov qab txhua zaus koj tso cov tshuaj puff (txawm tias thaum priming koj BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler lossis thaum noj cov tshuaj).
Thaum xub thawj ntawm lub txee nce mus txog 20, koj yuav pom qhov pib ntawm thaj tsam daj qhia rau koj paub tias nws yog lub sijhawm hu rau koj tus kws kho mob kom rov ua dua.

COUNTER

Nws yog ib qho tseem ceeb uas koj yuav tsum xyuam xim rau tus naj npawb ntawm inhalations (puffs) tshuav nyob rau hauv koj BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler los ntawm kev nyeem cov txee. Muab pov tseg BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL thaum lub txee qhia xoom (0) lossis 3 lub hlis tom qab koj nqa koj BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL inhaler tawm ntawm nws lub hnab ntawv thawj zaug. Koj lub BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOL inhaler yuav tsis hnov ​​​​qab thiab nws yuav ua haujlwm ntxiv, tab sis koj yuav tsis tau txais cov tshuaj zoo yog tias koj pheej siv nws. Siv BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler tshiab thiab ua raws li cov lus qhia rau priming (saib cov lus qhia 5 saum toj no).

Yuav ua li cas ntxuav koj BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler

Ntxuav lub qhov ncauj dawb ntawm koj lub BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler txhua 7 hnub. Los ntxuav lub qhov ncauj:

Tshem tawm lub qhov ncauj qhov ncauj grey
So sab hauv thiab sab nraud ntawm lub qhov ncauj dawb qhib nrog ib daim ntaub huv, qhuav
Hloov lub qhov ncauj npog
Tsis txhob muab BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE INHALATION AEROSOL inhaler rau hauv dej
Tsis txhob sim sib cais kojBUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE IN HALATION AEROSOLnqus tau pa

Chaw tsim tshuaj paus: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850

Los ntawm: AstraZeneca Dunkerque Production, Dunkirk, Fabkis

Cov khoom ntawm Fabkis

Cov Ntaub Ntawv Tus Neeg Mob thiab Cov Lus Qhia rau Kev Siv no tau pom zoo los ntawm US Food and Drug Administration.

© AstraZeneca 2019

Kho tshiab: Lub Xya hli ntuj 2019

PACKAGE/LABEL DISPLAY PANEL – 80/4.5

NDC 0310-7372-20

Khaws Upright

Budesonide thiab Formoterol

Fumarate Dihydrate

Inhalation Aerosol 80/4.5

budesonide 80 mcg / formoterol fumarate dihydrate 4.5 mcg

INHALATION AEROSOL

120 inhalations

Rau qhov ncauj Inhalation nkaus xwb

Rx xwb

Manufactured rau:

AstraZeneca LP, Wilmington, DE 19850

Los ntawm: AstraZeneca Dunkerque Production

Dunkirk, Fabkis

Cov khoom ntawm Fabkis

© AstraZeneca 2019

PACKAGE/LABEL DISPLAY PANEL – 160/4.5

NDC 0310-7370-20

Khaws Upright

Budesonide thiab Formoterol

Fumarate Dihydrate

Inhalation Aerosol 160/4.5

budesonide 160 mcg / formoterol fumarate dihydrate 4.5 mcg

INHALATION AEROSOL

120 inhalations

Rau qhov ncauj Inhalation nkaus xwb

Rx xwb

Manufactured rau:

AstraZeneca LP, Wilmington, DE 19850

Los ntawm: AstraZeneca Dunkerque Production

Dunkirk, Fabkis

Cov khoom ntawm Fabkis

© AstraZeneca 2019

BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE
budesonide thiab formoterol fumarate dihydrate aerosol
Cov ntaub ntawv khoom
Yam khoom HUMAN PRESCRIPTION DRUG LABEL Yam khoom Code (Source) NDC: 0310-7370
Txoj kev tswj hwm Ua pa (INHALATION) DEA Teem caij
Cov khoom xyaw nquag / Active Moiety
Cov khoom xyaw npe Lub hauv paus muaj zog Lub zog
BUDESONIDE (BUDESONIDE) BUDESONIDE 160 ua
FORMOTEROL FUMARATE (FORMOTEROL) FORMOTEROL FUMARATE ANHYDROUS 4.5 ua
Cov khoom xyaw uas tsis muaj zog
Cov khoom xyaw npe Lub zog
POLYETHYLENE GLYCOL 1000
POVIDONE K25
APAFLURANE
Ntim
# Yam khoom Code Pob piav qhia
ib NDC: 0310-7370-20 1 POUCH hauv 1 CARTON
ib 1 CANISTER hauv 1 POUCH
ib 120 AEROSOL hauv 1 CANISTER
Cov ntaub ntawv lag luam
Kev lag luam qeb Daim ntawv thov Number los yog Monograph Citation Hnub pib ua lag luam Hnub Kawg Ua Lag Luam
NDA tso cai generic NDA021929 03/01/2020
BUDESONIDE THIAB FORMOTEROL FUMARATE DIHYDRATE
budesonide thiab formoterol fumarate dihydrate aerosol
Cov ntaub ntawv khoom
Yam khoom HUMAN PRESCRIPTION DRUG LABEL Yam khoom Code (Source) NDC: 0310-7372
Txoj kev tswj hwm Ua pa (INHALATION) DEA Teem caij
Cov khoom xyaw nquag / Active Moiety
Cov khoom xyaw npe Lub hauv paus muaj zog Lub zog
BUDESONIDE (BUDESONIDE) BUDESONIDE 8 0ug
FORMOTEROL FUMARATE (FORMOTEROL) FORMOTEROL FUMARATE ANHYDROUS 4.5 ua
Cov khoom xyaw uas tsis muaj zog
Cov khoom xyaw npe Lub zog
POVIDONE K25
POLYETHYLENE GLYCOL 1000
APAFLURANE
Ntim
# Yam khoom Code Pob piav qhia
ib NDC: 0310-7372-20 1 POUCH hauv 1 CARTON
ib 1 CANISTER hauv 1 POUCH
ib 120 AEROSOL hauv 1 CANISTER
Cov ntaub ntawv lag luam
Kev lag luam qeb Daim ntawv thov Number los yog Monograph Citation Hnub pib ua lag luam Hnub Kawg Ua Lag Luam
NDA tso cai generic NDA 021929 03/01/2020
Labeler -AstraZeneca Pharmaceuticals LP (054743190)
Tus neeg sau npe -AstraZeneca PLC (230790719)
AstraZeneca Pharmaceuticals LP