qanastek/EMEA-V3 huggingface dataset:
This may constitute a risk in situations where these abilities are of special importance od
Pr
The safety of EXUBERA alone, or in combination with subcutaneous insulin or oral agents has been al
Is- sigurtà ta ’ EXUBERA waħidha, jew f’ kumbinazzjoni ma ’ insulina mogħtija taħt il- ġilda jew mediċini orali ġiet evalwata fi studji kliniċi b’ aktar minn 2, 700 pazjent b’ dijabete ta ’ tip 1 jew tip 2.
evaluated in clinical studies of more than 2700 patients with type 1 or type 2 diabetes, including more than 1975 adults exposed for greater than 6 months and more than 745 adults for greater than 2 years. in ic ed M
Fost dawn, aktar minn 1975 adult ġew esposti għal aktar minn 6 xhur u aktar minn 745 adult ġew esposti għal aktar minn sentejn.
7 The table below contains adverse reactions seen in controlled clinical studies including more than 1970 patients exposed to EXUBERA.
7 It- tabella hawn taħt fiha r- reazzjonijiet avversi li dehru fi provi kliniċi b’ kontrolli li jinkludu aktar minn 1970 pazjent esposti għal EXUBERA.
Common Common
Sistema tal - Ġisem
(1/ 10)
Komuni Ħafna (≥ 1/ 10)
(1/ 100, < 1/ 10)
Komuni (≥ 1/ 100, < 1/ 10)
(1/ 1000, < 1/ 100) Pharyngitis
Mhux Komuni (≥ 1/ 1000, < 1/ 100)
Metabolism and Nutritional Disorders
Infezzjonijiet u
Hypoglycaemia
Farinġite
ed
Infestazzjonijiet
Respiratory,
Disturbi fil -
Cough
Ipogliċemija
Dyspnoea
t metaboliżmu u n -
Epistaxis
za nutrizzjoni
Thoracic and Mediastinal
Disturbi
Productive Cough Throat Irritation
Sogħla
Bronchospasm Wheezing
Qtugħ ta ’ Nifs
Disorders
respiratorji,
Dry Throat
Sogħla Produttiva
Dysphonia
Bronkospażmu
Pharyngolaryngeal
toraċiċi u
ho Pain Tonsillar Disorder
Irritazzjoni tal- Gerżuma
Gastrointestinal Disorders
medjastinali
Dry Mouth
Gerżuma Xotta
ra
aw Farinġolarinġeali Disturbi Tonsillari
General
Disturbi gastro -
Chest Pain
Ħalq Xott
Disorders and Administration
x intestinali
Site Co
du
nditions n
Disturbi ġenerali u kondizzjonijiet
Note:
ta 'mnejn jingħata ’ g Nota:
In the overall clinical program, including uncontrolled extension studies, there were two lo reports of pleural effusion in which a treatment-related effect could not be excluded.
Fil- program kliniku totali, inkluż studji t’ estensjoni mingħajr kontrolli, kien hemm żewġ rapporti ta ’ tnixxija plewrali fejn effett relatat mat- trattament ma setax jiġi eskluż. im
Hypoglycaemia o tn
Ipogliċemija il
As with other insulins, hypoglycaemia was the most frequently observed undesirable effect in patients treated with EXUBERA. uc
Bħal b’ insulini oħra, l- ipogilċemija kienet l- aktar effett mhux mixtieq osservat b’ mod frekwenti f’ pazjenti ttrattati b’ EXUBERA. al in
Cough od
Sogħla iċ
The cough tended to occur within seconds to minutes after insulin inhalation and was predominantly mild in severity.
Is- sogħla kellha t- tendenza li tibda fi żmien sekondi sa minuti wara l- inalazzjoni ta ’ l- insulina u din kienet prinċipalment ħafifa fis- serjetà.
This cough decreased over time.
Din is- sogħla naqset maż- żmien.
One percent of patients discontinued EXUBERA pr
Wieħed fil- mija tal- pazjenti ed
treatment due to cough.
waqqfu t- trattament b’ EXUBERA minħabba s- sogħla. m
Dyspnoea al in
Qtugħ ta ’ Nifs t
The majority (> 95%) of dyspnoea was reported as mild to moderate.
Il- maġġoranza (> 95%) tal- qtugħ ta ’ nifs kien irrapportat bħala ħafif għal moderat.
In EXUBERA treated subjects 0.4% discontinued treatment due to dyspnoea. ic
b’ EXUBERA, 0. 4% waqqfu t- trattament minħabba l- qtugħ ta ’ nifs. od
Chest pain ed
Uġigħ fis- sider Pr
A range of different chest symptoms were reported as treatment-related adverse reactions and were M
Ġiet irrapportata firxa sħiħa ta ’ sintomi tas- sider differenti bħala reazzjonijiet avversi relatati mat - trattament u saret referenza għalihom bħala uġigħ fis- sider mhux speċifiku.
The majority (> 95%) of these events was reported as mild to moderate.
Il- maġġoranza (> 95%) ta ’ dawn ir- reazzjonijiet kienu rrapportati bħala ħfief għal moderati.
One subject in the EXUBERA and one in the comparator group discontinued treatment due to chest pain.
Pazjent wieħed fil- grupp ta ’ EXUBERA u wieħed fil- grupp ta ’ tqabbil waqqfu t- trattament minħabba uġigħ fis- sider.
Importantly, the incidence of all-causality adverse events related to coronary artery disease, such as angina pectoris or myocardial infarction was not increased with the use of EXUBERA.
Huwa importanti li jingħad li l- inċidenza tal- kawżi kollha ta ’ reazzjonijiet avversi relatati ma ’ mard ta ’ l - arterji koronarji, bħal anġina pektoris jew attakk tal- qalb ma żdiditx bl- użu ta ’ EXUBERA.
8 Other reactions
8 Tnaqqis fl- FEV1
Small treatment group differences in decline of FEV1 were observed in the EXUBERA group relative to comparator therapy.
Ġew osservati differenzi żgħar fit- tnaqqis ta ’ FEV1 fil- grupp ta ’ trattament, jiġifieri fil- grupp ta ’ EXUBERA meta mqabbel ma ’ terapija ta ’ tqabbil.
In clinical studies of up to two years duration, there was no accelerated decline beyond 3-6 months.
Fi studji kliniċi ta ’ inqas minn sentejn, ma kien hemm l- ebda tnaqqis aċċellerat wara 3- 6 xhur.
Discontinuation of EXUBERA therapy after 2 years resulted in resolution of treatment group differences within 6 weeks (see sections 4.4 and 5.1).
Twaqqif ta ’ terapija b’ EXUBERA wara sentejn irriżulta f’ riżoluzzjoni tad- differenzi fil- gruppi tat- trattament fi żmien 6 ġimgħat (ara sezzjonijiet 4. 4 u 5. 1).
A decline from baseline in FEV1 of > 15% occurred in 1.3% of EXUBERA-treated type 1 subjects
Kien hemm tnaqqis mil- linja bażi ta ’ referenza ta ’ FEV1 ta ’ > 15% f’ 1. 3% ta ’ pazjenti ta ’ tip 1 ittrattati
ed and in 5.0% of EXUBERA-treated type 2 subjects.
t b’ EXUBERA u f’ 5. 0% ta ’ pazjenti ta ’ tip 2 ittrattati b’ EXUBERA.
Insulin antibodies
za Antikorpi ta ’ l- Insulina
In clinical
riz Antikorpi ta ’ l- insulina jistgħu jiżviluppaw waqt trattament bl- insulini kollha inkluż EXUBERA.
ho trials, insulin antibodies developed more frequently and mean levels of insulin antibodies were higher in patients who switched their subcutaneous human insulin to EXUBERA compared to subjects who remained on subcutaneous human insulin.
Fi provi kliniċi, antikorpi ta ’ l- insulina żviluppaw b’ mod aktar frekwenti u l- livelli ta ’ antikorpi ta ’ l -
Insulin antibody levels were higher in patients with type 1
to insulina kienu ogħla f’ pazjenti li qalbu l- insulina umana tagħhom li tittieħed taħt il- ġilda għal
ut diabetes compared to type 2 diabetes and plateaued within 6-12 months of exposure in both groups.
Livelli ta ’ antikorpi ta ’ l- insulina kienu ogħla f’ pazjenti bid- dijabete tat- tip 1 meta mqabbla ma ’ dijabete tat - tip 2 u laħqu livell li baqa ’ ma nbidilx fi żmien 6- 12- il xahar ta ’ espożizzjoni fiż- żewġ gruppi.
ra No clinical significance of these antibodies has been identified.
Ma ġie identifikat l- ebda sinifikat kliniku ta ’ dawn l- antikorpi.
As with other insulins, generalised allergic reactions may occur very rarely.
x du Reazzjonijiet ta ’ Sensittività Eċċessiva ħa Bħal b’ insulini oħra, reazzjonijiet allerġiċi ġenerali jistgħu jseħħu b’ mod rari ħafna.
Such reactions to insulin or the excipients may, for example, be associated with generalised skin reactions, angio-oedema, bronchospasm, hypotension and shock and may be life-threatening (see section 4.4 Respiratory). lo
Reazzjonijiet bħal dawn għall- insulina jew is- sustanzi mhux attivi jistgħu, per eżempju, jkunu assoċjati ma ’ reazzjonijiet ġenerali tal- ġilda, anġjo- edema, bronkospażmi, pressjoni baxxa u xokk u jistgħu jkunu ta ’ theddida ’ g għall- ħajja (ara sezzjoni 4. 4 Respiratorji). im
Oedema and refraction abnormalities of the eye o tn
Edema u anormalitajiet fir- refrazzjoni ta ’ l- għajn il
Insulin therapy may cause sodium retention and oedema.
Terapija bl- insulina tista ’ tikkaġuna ritenzjoni ta ’ sodju u edema.
Refraction abnormalities of the eye may occur upon initiation of insulin therapy.
Anormalitajiet fir- refrazzjoni ta ’ l - għajn jistgħu jseħħu hekk kif tinbeda t- terapija bl- insulina.
These effects are usually transitory. uc
Dawn l- effetti huma ġeneralment al
4.9 Overdose od
temporanji. in
Hypoglycaemia may occur as a result of an excess of insulin relative to food intake, energy expenditure or both. pr
L- ipogliċemija tista ’ sseħħ bħala riżultat ta ’ eċċess ta ’ insulina meta mqabbel mat- teħid ta ’ l- ikel, ħela ed
Mild episodes of hypoglycaemia usually can be treated with oral carbohydrates.
Jistgħu jkunu m
Adjustments in drug dosage, meal patterns, or exercise may be needed. al
meħtieġa aġġustamenti fid- doża tal- mediċina, fil- mod kif jittieħed l- ikel jew fl- eżerċizzju. t
More severe episodes, with coma, seizure, or neurological impairment may be treated with in
Episodji aktar serji, b’ koma, aċċessjoni, jew indeboliment newroloġiku jistgħu jiġu ttrattati bi ot
intramuscular/ subcutaneous glucagon (0.5 to 1 mg) or concentrated intravenous glucose.
glukagon intramuskolari/ taħt il- ġilda (0. 5 sa 1 mg) jew glukosju ikkonċentrat mogħti ġol- vini.
Glucose ic
Jekk il - od
must also be given intravenously, if the patient does not respond to glucagon within 10 to 15 minutes. ed
Pr
M
Kif jerġa ’ jiġi f’ sensih huwa rrikmandat li l- pazjent jingħata karboidrat orali sabiex ma jirkadix.
Medicinal products used in diabetes, ATC code:
Prodotti mediċinali wżati fid- dijabete, Kodiċi ATC:
9 Mode of Action
Mod ta ’ kif jaħdem
Human insulin lowers blood glucose and promotes anabolic effects as well as decreasing catabolic effects, increases the transport of glucose into cells as well as the formation of glycogen in the muscles and the liver, and improves pyruvate utilisation.
L- insulina umana tbaxxi l- glukosju u tippromwovi effetti anaboliċi kif ukoll tnaqqas effetti kataboliċi, iżżid it- trasport ta ’ glukosju għal ġewwa ċ- ċelloli kif ukoll iżżid il- formazzjoni ta ’ glycogen fil -
It inhibits glycogenolysis and gluconeogenesis, increases lipogenesis in the liver and adipose tissue and inhibits lipolysis.
t za muskoli u l- fwied, u ttejjeb l- użu ta ’ pyruvate.
It also promotes the uptake of amino acids into cells and promotes protein synthesis and enhances the uptake of potassium into cells.
Hija timpedixxi glycogenolysis u gluconeogenesis, iżżid il- lipoġenesi fil- fwied u tessut adipożju u timpedixxi l- lipoliżi.
Inhaled human insulin, like fast-acting insulin analogues, has a more rapid onset of glucose lowering
riz ta ’ aċidi amminiċi għal ġewwa ċ- ċelloli u tippromwovi s- sintesi ta ’ proteini u żżid it- teħid ta ’ potassju għal ġoċ- ċelloli.
ed activity compared to subcutaneously administered soluble human insulin.
It- tul
Inhaled human insulin has a duration of glucose lowering activity comparable to subcutaneously administered fast-acting human insulin and longer than fast-acting insulin analogues (see Figure 1).
aw ta ’ żmien kemm iddum għaddejja l- attività li tbaxxi l- glukosju jista ’ jitqabbel ma ’ dak ta ’ l- insulina umana li taħdem malajr mogħtija taħt il- ġilda u huwa itwal minn analogi ta ’ l- insulina li jaħdmu malajr (ara Figura 1).
ris ho SC Lispro (18 U) Mean GIR (% of Maximum)
x du SC Lispro (18 U) Exubera (6mg) ħa GIR medja (% tal -
Exubera (6mg)
Insulina Umana li Massimu
ut) Fast-acting
Tahdem Malajr ’ g
ra Human Insulin (18 U)
(18 U) im il al
Time (min) o
Hin (min) in iċ
Mean Glucose Infusion Rate (GIR) Normalised to GIRmax for Each Subject Treatment Versus Time in Healthy Volunteers. uc
Rata ta ’ Infużjoni ta ’ Glukosju Medja (GIR) Normalizzata għal GIRmax għal Kull ed
When human insulin is inhaled, the onset of glucose lowering activity is within 10-20 minutes, the od
Meta l- insulina umana hija inalata, il- bidu ta ’ l- attività li tbaxxi l- glukosju jseħħ fi żmien 10- 20 m
maximum effect is exerted approximately 2 hours after inhalation.
minuta, l- effett massimu jseħħ madwar sagħtejn wara l- inalazzjoni.
The duration of action lasts approximately 6 hours. pr
L- azzjoni ddum għaddejja bejn wieħed u ieħor 6 sigħat. t ot
In subjects with type 1 or type 2 diabetes, inhaled human insulin has a faster onset of glucose lowering effect in the early hours after dosing when compared with subcutaneously administered fast- al
F’ suġġetti b’ dijabete ta ’ tip 1 jew 2, l- azzjoni b’ effett li jbaxxi l- glukosju ta ’ l- insulina inalata tibda aktar malajr fis- sigħat bikrin wara d- dożaġġ meta mqabbla ma ’ l- insulina umana li taħdem malajr od
acting human insulin. in
Pr
comparable to that of subcutaneously administered fast-acting human insulin in subjects with type 1 and 2 diabetes mellitus. ed
Il- varjiabilità ta ’ l- attività li tbaxxi l- glukosju ta ’ insulina umana inalata bejn is- suġġetti nfushom kienet ġeneralment komparabbli ma ’ dik ta ’ l- insulina umana li taħdem malajr mogħtija taħt il- ġilda f’ suġġetti b’ dijabete mellitus tip 1 u 2.
Use of inhaled human insulin is associated with an increase in frequency, and levels of insulin M
L- użu ta ’ insulina inalata huwa assoċjat ma ’ żieda fil- frekwenza, u livelli ta ’ antikorpi ta ’ l- insulina.
In a prospective exploratory 6 month study in subjects with type 1 diabetes, alterations in the glucose pharmacodynamics with inhaled human insulin were not observed.
Fi studju esploratorju prospettiv ta ’ 6 xhur f’ suġġetti b’ dijabete tip 1, ma ġewx osservati alterazzjonijiet fil- farmakodinamiċi b’ insulina inalata.
10 Type 1 Diabetes
10 Tagħrif fuq il- Provi Kliniċi
In clinical trials in type 1 diabetes, patients using a regimen of EXUBERA in combination with long- or intermediate-acting insulin had similar reductions in HbA1c compared with patients taking subcutaneous insulin alone.
Fi provi kliniċi f’ dijabete tip 1, pazjenti li jużaw reġimen ta ’ EXUBERA f’ kombinazzjoni ta ’ insulina li taħdem b’ mod intermedju jew fit- tul, kellhom tnaqqis simili fil- HbA1c meta mqabbel ma ’ pazjenti li qed jieħdu insulina taħt il- ġilda biss.
The percentage of patients who achieved a goal of HbA1c < 7.0% was comparable between the treatment groups.
Il- perċentwal ta ’ pazjenti li laħqu l- mira ta ’ HbA1c < 7. 0% kien
Fasting plasma glucose levels were significantly lower in patients treated with regimens including EXUBERA compared with those treated with subcutaneously administered fast-acting human insulin only regimens.
riz EXUBERA meta mqabbla ma ’ dawk ittrattati b’ reġimens b’ insulina umana li taħdem malajr mogħtija taħt il- ġilda biss.
ed Type 2 Diabetes
to Dijabete ta ’ Tip 2
ris Patients in a clinical trial for type 2 diabetes, who used a regimen of EXUBERA in combination with long- or intermediate-acting insulin, had similar changes in HbA1c compared with patients treated
aw Pazjenti fi prova klinika għad- dijabete ta ’ Tip 2, li użaw reġimen ta ’ EXUBERA f’ kombinazzjoni ma ’ insulina li taħdem b’ mod intermedju jew fit- tul kellhom tnaqqis simili fil- HbA1c meta mqabbla ma ’
ho with subcutaneous insulin alone.
x pazjenti li kienu qed jieħdu insulina taħt il- ġilda biss.
ut ra In clinical trials involving patients with type 2 diabetes not sufficiently controlled with oral agents alone, patients using a regimen of EXUBERA alone or in combination with oral agents, had greater improvements in HbA1c compared with patients treated with oral agents alone.
du Livelli sajmin ta ’ glukosju fil- plażżma kienu ferm aktar baxxi f’ pazjenti ttrattati b’ reġimens li jinkludu EXUBERA meta mqabbla ma ’ dawk ittrattati b’ reġimens b’ insulina umana li taħdem malajr mogħtija taħt il- ġilda biss. ħa Fi provi kliniċi li jinvolvu pazjenti b’ dijabete ta ’ tip 2 li mhumiex ikkontrollati biżżejjed b’ mediċini ’ g orali biss, pazjenti li użaw reġimen ta ’ EXUBERA biss jew flimkien ma ’ mediċini orali kellhom titjib akbar fil- HbA1c meta mqabbla ma ’ pazjenti ttrattati b’ mediċini orali biss.
In most of these
Fil- parti l- kbira ta ’ dawn l - im
ge studies the percentages of patients achieving HbA1c < 7.0% were higher for patients using a regimen including EXUBERA compared to patients on oral agents alone.
istudji, il- perċentwali ta ’ pazjenti li laħqu HbA1c < 7. 0% kienu ogħla għal pazjenti fuq reġimen li kien jinkludi EXUBERA meta mqabbla ma ’ pazjenti fuq mediċini orali biss.
Fasting plasma glucose was similar n to or lower in patients using a regimen including EXUBERA compared to patients treated with oral agents alone.
Livelli sajmin ta ’ glukosju kienu simili għal jew aktar baxxi f’ pazjenti li ħadu reġimen li kien jinkludi EXUBERA meta mqabbla il
In patients with type 2 diabetes sufficiently controlled with oral agents the glycaemic lo control was not further improved by inhaled insulin.
F’ pazjenti b’ dijabete tip 2 ikkontrollata biżżejjed al
FEV1 decline o tn
Tnaqqis fil- FEV1 in
Randomised, open label parallel group studies were conducted to examine FEV1 changes following initiation of EXUBERA therapy in type 1 and 2 subjects.
Kemm suġġetti ttrattati ed
Both EXUBERA and comparator treated subjects experienced declines in lung function over time during these trials (Figures 2 and 3).
b’ EXUBERA kif ukoll dawk ittrattati b’ mediċina ta ’ tqabbil, maż- żmien esperjenzaw tnaqqis fil - funzjoni tal- pulmun waqt dawn il- provi (Figuri 2 u 3).
Small uc
Differenzi żgħar fil- grupp ta ’ trattament (li jiffavorixxu l- mediċina ta ’ tqabbil) fil- bidla mil- linja ta ’ referenza bażi ta ’ 0. 034L f’ tip 1 u 0. 039L m
treatment group differences (favouring comparator) in change from baseline of 0.034L in type 1 and 0.039L in type 2 occurred after 2 years of therapy. od
f’ tip 2 seħħew wara sentejn ta ’ terapija. t
A decline from baseline in FEV1 of > 15% occurred in 1.3% of EXUBERA-treated and 1.0% of pr
Seħħ tnaqqis fil- FEV1 mil- linja bażi ta ’ > 15% f’ 1. 3% ta ’ suġġetti ta ’ tip 1 ittrattati b’ EXUBERA u ot
comparator-treated type 1 subjects and in 5.0% of EXUBERA-treated and 3.4% of comparator-treated type 2 subjects. al in ic ed M
f’ 1. 0% ta ’ dawk ittrattati b’ mediċina ta ’ tqabbil u f’ 5. 0% ta ’ suġġetti ta ’ tip 2 ittrattati b’ EXUBERA u fi 3. 4% ta ’ dawk ittrattati b’ mediċina ta ’ tqabbil. od Pr
0 .1 0 .0 5 0
0. 3
- 0 .0 5
INH
(Mean +/ - SD)
0. 2 5 Bidla minn Linja ta ’ bażi f’ FEV1 (L) K o m p a ra tur 0. 2 0. 1 5 0. 1 0. 0 5 0 (Medja + / - SD)
- 0 .1
- 0. 0 5
- 0 .1 5
- 0. 1
ed
t - 0. 1 5
ris
- 0. 4
- 0 .4
- 0. 4 5
- 0 .4 5
riz
Baseline
Linja ta ’ bażi
Visit (weeks)
aw Żjara (gimghat)
ut N=Number of Subjects at Baseline, week 12, week 24, week 36, week 48, week 60, week 72,
N=Numru ta ’ Suggetti fil- Linja Bażi, gimgha 12, gimgha 24, gimgha 36, gimgha 48, gimgha 60, gimgha 72, gimgha 84, gimgha 96, LOCF.
INH N= 236, 231, 233, 233, 235, 235, 226, 217, 208, 236.
x INH N= 236, 231, 233, 233, 235, 235, 226, 217, 208, 236.
Comparator N= 253, 238, 252, 248, 252, 249, 230, 224, 216, 253.
Komparatur N= 253, 238, 252, 248, 252, 249, 230, 224, 216, 253.
Figure 2.
du Figura 2.
nge from Baseline in FEV1 (L) in patients with type 1 diabetes mellitus.
Bidla Ossservata mil- Linja ta ’ Referenza Bażi fl- FEV1 (L) f’ pazjenti b’ dijabete mellitus tip ħa 1. ’ g im
o
INH Comparator Komparatur INH Washout INH Washout 0. 3 Bidla minn Linja Bażi ta ’ Referenza f’ FEV1 (L)
Comparator
0. 25 Change from Baseline in FEV1 (L)
0.3
il
INH Washout
0. 2 0. 15 0. 1 al
0.25 Change from Baseline in FEV1 (L)
0. 05 (Mean + / - SD)
0.2 0.15 0.1 0.05 (Mean +/ - SD)
0 (Medja + / - SD)
od
- 0. 05 in
0 -0.05 -0.1 -0.15 pr
- 0. 1 - 0. 15 iċ
-0.2 -0.25 -0.3 -0.35 al
- 0. 2 - 0. 25 - 0. 3 ed
-0.4 -0.45
- 0. 35 - 0. 4
-0.5
- 0. 45 - 0. 5
Comparative Phase
Fażi komparattiva Comparative Phase
Washout Phase
Fażi ta ’ washout Washout Phase
Visit (weeks) N=Number of Subjects at Baseline, week 52, week 104, week +6, week +12. ed
INH and INH washout N=158, 155, 143, 139, 123.
INH and INH washout N=158, 155, 143, 139, 123.
INH u INH washout N=158, 155, 143, 139, 123.
Comparator N=145, 143, 125, 129, 120.
Pr
M
Bidla Osservata mil- Linja ta ’ Referenza Bażi fl- FEV1 (L) f’ pazjenti b’ dijabete mellitus tip 1.
In Phase 2/ 3 trials, 9 out of 2498 subjects treated with EXUBERA were discontinued from trials due to a decline in pulmonary function whose end of study FEV1 showed a decline of ≥ 15% from baseline.
Fi provi ta ’ Fażi 2/ 3, 9 minn 2, 498 pazjent ittrattat b’ EXUBERA twaqqfu mill- provi minħabba tnaqqis fil- funzjoni pulmonari li l- FEV1 tagħha fl- aħħar ta ’ l- istudju wera tnaqqis ta ’ 15% mil- linja bażi ta ’ referenza.
These subjects experienced an average decrease in FEV1 of 21% (range 16%-33%) from baseline and were treated with EXUBERA for an average of 23 months.
Dawn is- suġġetti esperjenzaw tnaqqis medju fl- FEV1 ta ’ 21% (fuq medda ta ’ 16% - 33%) mil- linja ta ’ referenza bażi u kienu ttrattati b’ EXUBERA għal medja ta ’ 23 xahar.
6 of these discontinued subjects underwent follow-up pulmonary function testing.
Sitta minn dawn is - suġġetti li twaqqfu sarulhom testijiet ta ’ follow- up tal- funzjoni pulmonari.
No further information is available for the remaining 3 subjects who discontinued.
Minn dawn il- pazjenti, 5
12 FEV1 reversibility
12 urew titjib sinifikattiv fl- FEV1 wara t- twaqqif tat- terapija u suġġett wieħed ma naqasx aktar mill- valur ta ’ tmiem l- istudju.
In type 1 subjects, resolution of small treatment group differences (0.010L favouring comparator) occurred within 2 weeks of EXUBERA cessation following 12 weeks of therapy.
F’ suġġetti ta ’ tip 1, kien hemm riżoluzzjoni ta ’ differenzi żgħar fil- grupp ta ’ trattament (0. 010L jiffavorixxi l- mediċina ta ’ tqabbil) fi żmien ġimagħtejn mit - twaqqif ta ’ EXUBERA wara 12- il ġimgħa ta ’ terapija.
In type 2 subjects, resolution of small treatment group differences (0.039L favouring comparator) occurred within 6 weeks of EXUBERA cessation following 2 years of therapy (Figure 3).
F’ pazjenti ta ’ tip 2, seħħet riżoluzzjoni ta ’ differenzi żgħar fil- grupp ta ’ trattament (0. 039L jiffavorixxi l- mediċina ta ’ tqabbil) fi żmien 6 ġimgħat mit - twaqqif ta ’ EXUBERA wara sentejn ta ’
In a smaller group (n=36) of mixed type 1 and 2 subjects treated with EXUBERA for > 36 months, cessation of therapy resulted in a mean FEV1 increase of 0.036L over the subsequent 6 months.
Fi grupp iżgħar (n=36) ta ’ suġġetti tip 1 u 2 imħallta, ittrattati b’ EXUBERA għal >
5.2 Pharmacokinetic properties
riz 5. 2 Tagħrif farmakokinetiku
ed Absorption
Assorbiment
ris Inhaled human insulin is delivered by the pulmonary route.
to aw L- insulina inalata hija imwassla permezz tar- rotta pulmonari.
ho human insulin in healthy subjects and in subjects with type 1 or type 2 diabetes (see Figure 4).
L- insulina umana inalata hija assorbita malajr daqs analogi ta ’ l- insulina li jaħdmu malajr u aktar malajr minn insulina umana li taħdem malajr mogħtija taħt il- ġilda f’ suġġetti b’ saħħithom u f’ suġġetti bid- dijabete ta ’ tip 1 jew ta ’ tip 2 (ara Figura 4).
ut ra 80
x du ħa 80 Bidla minn Linja Bażi ta ’ Insulina Mingħajr Serum
ge 70 Change From Baseline Serum Free Insulin
’ g 70 Change From Baseline Serum Free Insulin
60 n Inha le d Ins ulin Concentration (uU/ ml)
60 Konċentrazzjoni (uU/ ml)
lo
Insulina mogħtija taħt il- ġilda
40 o
40 al
Fast-acting Human Insulin (12 IU) tn
Insulina Umana li taħdem malajr (12 30 in
20 uc
IU) 20 iċ
10 od
10 ed
0
m
e (m in)
T im e (m in) Ħin (min) t ot
Mean changes in serum free insulin concentrations (µU/ mL) after inhalation of 4mg of human insulin or subcutaneous injection of 12 IU fast-acting human insulin in obese subjects with type 2 diabetes. al in
Tibdil medju fil- konċentrazzjonijiet ħielsa ta ’ insulina fis- serum (µU/ mL) wara inalazzjoni ta ’ 4 mg ta ’ insulina umana jew injezzjoni taħt il- ġilda ta ’ 12 IU insulina umana li taħdem malajr od
The time to peak insulin concentration (Tmax) is generally half of that for subcutaneously administered fast-acting human insulin.
f’ suġġetti ħoxnin ħafna b’ dijabete tip 2.
Peak insulin concentration is reached generally by 45 minutes for inhaled ic
Il- ħin biex tintlaħaq il- konċentrazzjoni massima ta ’ l- insulina (Tmax) huwa ġeneralment nofs dak ta ’ Pr
human insulin.
insulina umana li taħdem malajr mogħtija taħt il- ġilda.
Intrasubject variability of time to peak insulin concentrations was less for inhaled human insulin than for subcutaneous fast-acting human insulin in subjects with type 1 or 2 diabetes. ed
Il- konċentrazzjoni massima ta ’ l- insulina ġeneralment tintlaħaq f’ 45 minuta għal insulina umana inalata.
In subjects with type 1 diabetes mellitus, inhaled human insulin had a comparable intrasubject M
Il- varjabilità fis- suġġetti tal- ħin biex tintlaħaq il- konċentrazzjoni massima ta ’ l- insulina kienet inqas għal insulina umana inalata milli għal insulina umana li taħdem malajr mogħtija taħt il- ġilda f’ pazjenti b’ dijabete ta ’ tip 1 jew 2.
variability of AUC to subcutaneously administered fast-acting human insulin.
F’ pazjenti bid- dijabete mellitus, l- insulina umana inalata kellha varjiabilità ta ’ l- AUC fis- suġġetti komparabbli għal insulina umana li taħdem malajr mogħtija taħt il- ġilda.
For Cmax, the intrasubject variability of inhaled insulin is greater than that of subcutaneously administered fast- acting human insulin.
Għas- Cmax il- varjiabilità ta ’ insulina inalata fis- suġġetti hija akbar minn dik ta ’ l- insulina umana li taħdem malajr mogħtija taħt il -
In obese subjects with type 2 diabetes, intrasubject variability was comparable to or less than that of subcutaneously administered fast-acting human insulin for Cmax and AUC.
F’ suġġetti ħoxnin b’ dijabete tat- tip 2, il- varjiabilità fis- suġġetti kienet komparabbli għal jew inqas minn dik ta ’ insulina umana li taħdem malajr mogħtija taħt il- ġilda għas - Cmax u l- AUC.
The relative bioavailability of EXUBERA compared to subcutaneous fast-acting human insulin is approximately 10%.
Il- bijodisponibilità relattiva ta ’ EXUBERA meta mqabbla ma ’ insulina umana li taħdem malajr mogħtija taħt il- ġilda hija madwar 10%.
Unlike subcutaneous insulin preparations, the bioavailability of EXUBERA is not influenced by Body Mass Index.
Il- bijodisponibilità ta ’ EXUBERA mhix influwenzata mill - Indiċi tal- Massa tal- Ġisem, mhux bħal preparazzjonijiet ta ’ insulina mogħtija taħt il- ġilda.
In a study in healthy subjects, systemic exposure (AUC and Cmax) of inhaled human insulin
Fi studju f’ pazjenti b’ saħħithom, l- espożizzjoni sistemika (AUC u Cmax) ta ’ insulina umana inalata żdiedet b’ mod bejn wieħed u ieħor proporzjonali għad- doża minn 1 mg għal 6 mg meta ngħataw
13 increased in an approximately dose proportional fashion from 1 mg to 6 mg when a maximum of two blisters from either strength or their combination was administered.
Fi studju fejn
In a study where the dosage form of three 1 mg blisters was compared with one 3 mg blister, Cmax and AUC of inhaling three 1 mg blisters were approximately 30% and 40% greater, respectively, than that of inhaling from one 3 mg blister, indicating that three 1 mg blisters are not interchangeable with one 3 mg blister (see sections 2, 4.2 and 4.4).
za il- forma tad- dożaġġ ta ’ tliet bżieżaq ta ’ 1 mg ġiet imqabbla ma ’ dik ta ’ bużżieqa waħda ta ’ 3 mg, is - Cmax u l- AUC ta ’ l- inalazzjoni ta ’ bużżieqa waħda ta ’ 3 mg kienu madwar 30% u 40% akbar,
An explanation for the differences in bioavailability appears to be the different energy to mass ratio between the 1 and 3 mg unit blisters
riz rispettivament, milli dawk ta ’ inalazzjoni ta ’ bużżieqa waħda ta ’ 3 mg, li tindika li 3 bżieżaq ta ’ 1 mg mhumiex skambjabbli ma ’ bużżieqa ta ’ 3 mg (ara sezzjoni 2, 4. 2 u 4. 4).
ed since with less powder in the blister the inhaler is more efficient in breaking up or de-agglomerating the powder leading to a larger proportion of smaller aerodynamic particle sizes for the 1 mg blister (see sections 2 and 4.4).
to Bijodisponibilità madwar 40% ogħla ta ’ tlett bżieżaq ta ’ doża waħda ta ’ 1 mg meta imqabbla ma ’ doża waħda ta ’ 3 mg kienet osservata f’ suġġetti b’ saħħithom.
ris Distribution
L- ispjegazzjoni għad- differenzi fil -
ho Following oral inhalation of a single dose of human insulin approximately 30% of the total blister content remains in the blister or device, 20% is deposited in the oropharynx, 10% in the conducting
aw bijodisponibilità jidher li hija l- proporzjon differenti ta ’ l- enerġija kontra l- massa bejn bużżieqa waħda ta ’ 1 mg u bużżieqa ta ’ 3 mg minħabba li b’ inqas trab fil- bużżieqa, l- inalatur huwa aktar effiċjenti fit - tkissir jew deagglomerazzjoni tat- trab li jwassal għal proporzjon akbar ta ’ partikuli erodinamiċi żgħar
ut airways and 40% reaches the deep lung.
x għall- bużżieqa ta ’ 1 mg (ara sezzjonijiet 2 u 4. 4).
ra Animal studies did not show that inhaled human insulin accumulates in the lung.
du Distribuzzjoni Wara inalazzjoni orali ta ’ doża waħda ta ’ insulina umana
Special Populations
ħa madwar 30% tal- kontenut totali tal- bużżieqa
Smoking
jibqa ’ fil- bużżieqa jew fl- inalatur, 20% huwa depożitat fl- orofarinġi, 10% fil- passaġġi li jwasslu l- arja ’ g u 40% jilħaq fil- fond tal- pulmun. im
lo
Studji fl- annimali ma wrewx li insulina inalata takkumula fil- pulmun.
n
Populazzjoniet Speċjali il al
ge
Tipjip in
Smoking greatly increases the rate and extent of absorption of inhaled human insulin (Cmax about 3 to 5 times and AUC about 2 to 3 times higher) and therefore could increase the risk of hypoglycaemia o
It- tipjip iżid bil- bosta r- rata u l- firxa ta ’ assorbiment ta ’ l- insulina umana inalata (is- Cmax huwa madwar 3 sa 5 drabi u l- AUC huwa madwar 2 jew 3 drabi ogħla) u għalhekk jista ’ jżid ir- riskju ta ’ iċ
(see sections 4.3 and 4.5). tn
ipogliċemija (ara sezzjonijiet 4. 3 u 4. 5). ed
When EXUBERA was administered to healthy volunteers following 2-hours of passive exposure to cigarette smoke in a controlled experimental setting, insulin AUC and Cmax were reduced by uc
Meta EXUBERA ngħatat lil voluntiera b’ saħħithom wara sagħtejn ta ’ espożizzjoni passiva għad - duħħan tas- sigaretti f’ sitwazzjoni esperimentali, l- AUC u s- Cmax ta ’ l- insulina tnaqqsu b’ madwar 17% m
approximately 17 and 30%, respectively (see section 4.5). od
u 30%, rispettivament (ara sezzjonijiet 4. 5). t
Respiratory Diseases (Underlying Lung Disease) pr
Mard Respiratorju (Mard tal- Pulmun Diġà Eżistenti) ot
In non-diabetic subjects with mild to moderate asthma, AUC and Cmax for inhaled human insulin in the absence of treatment with a bronchodilator was slightly less than in subjects without asthma. al
F’ suġġetti mhux dijabetiċi b’ ażżma ħafifa għal moderata, l- AUC u s- Cmax għal insulina inalata fin - od
In non-diabetic subjects with COPD, the absorption of inhaled human insulin appeared greater compared with that in subjects without COPD (see section 4.4). in ic
nuqqas ta ’ trattament kienu daqsxejn anqas minn dawk f’ suġġetti mingħajr ażżma.
Administration of fluticasone 30 minutes prior to EXUBERA did not affect the pharmacokinetics of EXUBERA in non-diabetic subjects with mild-moderate asthma (see section 4.5).
F’ suġġetti mhux dijabetiċi b’ COPD, l- assorbiment ta ’ insulina inalata deher ogħla meta mqabbel ma ’ dak f’ suġġetti mingħajr COPD (ara sezzjoni 4. 4).
Renal impairment
Għoti ta ’ salbutamol 30 minuta qabel EXUBERA f’ suġġetti mhux dijabetiċi b’ ażżma ħafifa- moderata wassal għal żieda fl- AUC u s- Cmax ta ’ l- insulina ta ’ madwar 25% u 51% meta mqabbla ma ’ meta EXUBERA ngħatat waħidha.
The effect of renal impairment on the absorption of inhaled human insulin has not been studied (see section 4.2).
Għoti ta ’ fluticasone 30 minuta qabel EXUBERA ma effettwax il- farmakokinetiċi ta ’ EXUBERA f’ suġġetti mhux dijabetiċi b’ ażżma ħafifa- moderata (ara sezzjoni 4. 5).
14 Hepatic impairment
14 Indeboliment tal- kliewi
The effect of hepatic impairment on the absorption of inhaled human insulin has not been studied (see section 4.2).
L- effett ta ’ indeboliment tal- fwied fuq l- assorbiment ta ’ insulina umana inalata ma ġiex studjat (ara sezzjoni 4. 2)
Gender
t za Sess
In subjects with diabetes and in subjects without diabetes, no apparent differences in absorption of inhaled human insulin were observed between men and women.
riz F’ pazjenti bid- dijabete u f’ pazjenti mingħajr dijabete, ma ġiet osservata l- ebda differenza evidenti fl - assorbiment ta ’ insulina inalata bejn l- irġiel u n- nisa.
ed Children and adolescents
to Tfal u adolexxenti
In children (6-11 years) and adolescents (12-17 years) with type 1 diabetes, inhaled human insulin
aw Fi tfal (6- 11- il sena) u adolexxenti (12- 17- il sena) b’ dijabete tip 1, l- insulina umana inalata kienet assorbita aktar malajr milli insulina li taħdem malajr.
ris was absorbed more rapidly than fast-acting human insulin.
Anzjani ħa F’ pazjenti akbar b’ dijabete ta ’ tip 2, l- insulina inalata kienet assorbita aktar malajr milli insulina ’ g umana li taħdem malajr mogħtija taħt il- ġilda.
Bioavailability of inhaled human insulin relative to subcutaneously administered fast-acting human insulin was comparable to that of adult
Il- bijodisponibilità ta ’ insulina umana inalata meta mqabbla ma ’ insulina umana li taħdem malajr mogħtija taħt il- ġilda kienet komparabbli ma ’ dik im
ho subjects with type 1 diabetes (see section 4.2).
f’ suġġetti adulti iżgħar b’ dijabete tip 2.
Elderly
5. 3 Tagħrif ta 'qabel l- użu kliniku dwar is- sigurtà tal- mediċina il
ut ra In older subjects with type 2 diabetes, inhaled human insulin was absorbed more rapidly than subcutaneously administered fast-acting human insulin.
Studji ta ’ tossiċità ta ’ l- inalazzjoni fil- firien u fix- xadini għal mhux aktar minn 6 xhur ma taw l- ebda al
5.3 Preclinical safety data n ge lo Inhalation toxicity studies in rats and monkeys for up to 6 months gave no evidence for a special risk to the respiratory tract due to insulin inhalation powder. o tn
evidenza għal riskju speċjali għall- passaġġi respiratorji minnħabba l- inalazzjoni ta ’ trab ta ’ l- insulina. in iċ
PHARMACEUTICAL PARTICULARS uc
TAGĦRIF FARMAĊEWTIKU ed
6.1 List of excipients od
6. 1 Lista ta ’ sustanzi mhux attivi m
Mannitol Glycine pr
Mannitol Glycine t
Sodium Citrate (as dihydrate) Sodium Hydroxide al
Sodium Citrate (bħala dihydrate) ot
6.2 Incompatibilities in
6. 2 Inkompatibilitajiet Pr
Not applicable. ic
Ma jgħoddx f’ dan il- każ.
6.3 Shelf life ed
6. 3 Żmien kemm idum tajjeb il- prodott mediċinali
M
Sentejn.
After first opening the foil overwrap:
Wara li tiftaħ il- qartas tal- bużżieqa:
3 months.
3 xhur.
6.4 Special precautions for storage
15 6. 4 Prekawzjonijiet speċjali għall- ħażna
Store below 30oC.
Aħżen f’ temperatura taħt 30oC.
Store in the original package in order to protect from moisture.
Aħżen fil- kontenitur oriġinali sabiex tilqa ’ mill- umdità.
After opening the foil overwrap:
Wara li tiftaħ il- qartas tal- bużżieqa:
Store below 25oC.
Aħżen f’ temperatura taħt 25oC.
Do not refrigerate or freeze the unit dose blisters.
Tpoġġix il- bużżieqa ta ’ doża waħda fil- friġġ jew fil- friża.
15 The inhaler and its components should be stored and used in a dry place.
L- inalatur u l- komponeneti tiegħu għandhom jinħażnu u jintużaw f’ post xott.
Do not refrigerate or freeze the insulin inhaler.
t za Tpoġġix l- inalatur ta ’ l- insulina fil- friġġ jew fil- friża.
6.5 Nature and contents of container
riz 6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
One blister card contains 6 perforated unit dose blisters (PVC/ Aluminium).
Bużżieqa waħda fiha 6 bżieżaq ipperforati (PVC/ Aluminju) ta ’ doża waħda.
Five blister cards are in a clear plastic (PET) thermoformed tray with a desiccant and covered with a clear plastic (PET) lid.
to bżieżaq jiġu fi trej tal- plastik ċar (PET) iffurmat bis- sħana flimkien ma ’ dessikant u miksi b’ għatu tal - plastik trasparenti (PET).
The tray is sealed in a foil laminate pouch with a desiccant.
It- trej huwa ssiġilat f’ pawċ laminat tal- fojl flimkien ma ’ dessikant.
ed Packaging sizes supplied:
aw Daqsijiet ta ’ pakketti fornuti:
ris • Cardboard box containing 30 x 1 PVC/ Aluminium perforated unit dose blisters (1 pouch)
x • Kaxxa tal- kartun fiha 30 x 1 bżieżaq ipperforati tal- PVC/ Aluminju ta ’ doża waħda (pawċ 1)
ho • Cardboard box containing 60 x 1 PVC/ Aluminium perforated unit dose blisters (2 pouches)
du • Kaxxa tal- kartun fiha 60 x 1 bżieżaq ipperforati tal- PVC/ Aluminju ta ’ doża waħda (2 pawċijiet) ħa • Kaxxa tal- kartun fiha 90 x 1 bżieżaq ipperforati tal- PVC/ Aluminju ta ’ doża waħda (3 pawċijiet) ’ g • Kaxxa tal- kartun fiha 180 x 1 bżieżaq ipperforati tal- PVC/ Aluminju ta ’ doża waħda (6 pawċijiet) im
ut • Cardboard box containing 90 x 1 PVC/ Aluminium perforated unit dose blisters (3 pouches)
• Kaxxa tal- kartun fiha 270 x 1 bżieżaq ipperforati tal- PVC/ Aluminju ta ’ doża waħda (9 pawċijiet)
ra • Cardboard box containing 180 x 1 PVC/ Aluminium perforated unit dose blisters (6 pouches)
Kaxxa tal- kartun fiha 60 x 1 bżieżaq ipperforati tal- PVC/ Aluminju ta ’ doża waħda (2 pawċijiet) u 2 Units ta ’ Rilaxx ta ’ l- Insulina (IRU) fuq ir- riħ al
• Cardboard box containing 270 x 1 PVC/ Aluminium perforated unit dose blisters (9 pouches)
• Kaxxa tal- kartun fiha 270 x 1 bżieżaq ipperforati tal- PVC/ Aluminju ta ’ doża waħda (9 pawċijiet) in
• ge Cardboard box containing 60 x 1 PVC/ Aluminium perforated unit dose blisters (2 pouches) and 2 spare Insulin Release Units (IRU) n lo • Cardboard box containing 270 x 1 PVC/ Aluminium perforated unit dose blisters (9 pouches) and 6 spare Insulin Release Units (IRU) o tn
• Kitt fih 90 x 1 bżieżaq ipperforati tal- PVC/ Aluminju b’ doża waħda (3 pawċijiet), inalatur ta ’ l - ed
• A kit containing 90 x 1 PVC/ Aluminium perforated unit dose blisters (3 pouches), 1 insulin inhaler, 1 spare chamber and 6 spare Insulin Release Units (IRU) uc
insulina, ċejmber fuq ir- riħ u 6 Units ta ’ Rilaxx ta ’ l- Insulina (IRU) fuq ir- riħ
Additional insulin inhaler, insulin release units and chamber packages are available. od
Jiġu wkoll inalatur ta ’ l- insulina, Units ta ’ Rilaxx ta ’ l- insulina u pakketti taċ- ċejmbers addizjonali. m
Not all pack sizes may be marketed. pr
Jista ’ jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għal skop kummerċjali. t ot
6.6 Special precautions for disposal and other handling
6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema u għal immaniġġar ieħor od
EXUBERA unit dose blisters must only be used with the insulin inhaler. al in
Pr
The insulin inhaler should be replaced annually. ic
L- inalatur ta ’ l- insulina għandu jinbidel kull sena.
The Insulin Release Unit (IRU) should be replaced once every 2 weeks. ed
Il- Unit ta ’ Rilaxx ta ’ l- Insulina (IRU) għandu jinbidel darba kull ġimagħtejn.
In this case, the Insulin M
Jekk l- inalatur ta ’ l- insulina jkun espost bi żvista għal kondizzjonijiet estremament umidi waqt l- użu, dan issoltu jirriżulta fi tnaqqis tad- doża ta ’ l- insulina mogħtija.
Release Unit (IRU) must be changed prior to the next inhalation (see section 4.4).
F’ dan il- każ, il- Unit ta ’ Rilaxx ta ’ l - Insulina (IRU) irid jiġi mibdul qabel l- inalazzjoni li jkun imiss (ara sezzjoni 4. 4).
Pfizer Limited Ramsgate Road, Sandwich, Kent, CT13, 9NJ United Kingdom
Pfizer Limited Ramsgate Road, Sandwich, Kent, CT13, 9NJ Ir- Renju Unit
ed EU/ 1/ 05/ 327/ 001 EU/ 1/ 05/ 327/ 002
t za EU/ 1/ 05/ 327/ 001 EU/ 1/ 05/ 327/ 002 EU/ 1/ 05/ 327/ 003
ris EU/ 1/ 05/ 327/ 003 EU/ 1/ 05/ 327/ 004
riz EU/ 1/ 05/ 327/ 004 EU/ 1/ 05/ 327/ 005
ut EU/ 1/ 05/ 327/ 008
aw EU/ 1/ 05/ 327/ 008
ra 9.
x 9.
DATE OF REVISION OF THE TEXT o tn uc od pr al in ic ed M
DATA TA ’ META ĠIET RIVEDUTA L- KITBA ’ g im il al in iċ ed m t ot od Pr
EXUBERA 3 mg inhalation powder pre-dispensed.
EXUBERA 3 mg trab għall- inalazzjoni magħmul għal- lest.
Each unit dose blister contains 3 mg insulin human.
Kull bużżieqa ta ’ doża waħda fiha 3 mg ta ’ insulina umana.
The starting and subsequent dosage (dose and timings) should be determined individually by the physician and adjusted according to the patient’ s individual response and requirements (e. g. diet, physical activity and life-style).
18 Id- dożaġġ tal- bidu u dak sussegwenti (doża u ħinijiet) għandhom jiġu stabbiliti mit- tabib u għandhom jiġu aġġustati skond ir- reazzjoni u l- ħtiġijiet individwali tal- pazjent (eż. dieta, attività fiżika u stil ta ’ ħajja).
18 Daily doses and timing of administration
Dożi ta ’ kuljum u ħinijiet ta ’ meta tingħata
The total daily dose should be divided into three pre-meal doses.
Id- doża totali ta ’ kuljum għandha tiġi
Approximate guidelines for initial, pre-meal EXUBERA doses, based on patient body weight, are indicated in Table 1:
t za mqassma fi tlett dożi ta ’ qabel l- ikel.
ed
Linji ta ’ gwida approssimattivi għal dożi inizjali ta ’ qabel l- ikel ta ’ EXUBERA, ibbażati fuq il- piż tal -
Initial Dose per Approximate
riz ġisem tal- pazjent, huma indikati f’ Tabella 1.
ris
IU
ho
x
ut
2 ħa
Approximate Guidelines for Initial, Pre-Meal EXUBERA Dose (based on patient
Linji ta ’ Gwida Approssimattivi għal Dożi Inizjali ta ’ Qabel l- Ikel ta ’ EXUBERA (fuq il- bażi tal- piż tal- ġisem tal- pazjent). im
A 1 mg blister of inhaled insulin is approximately equivalent to 3 IU of subcutaneously injected fast- n acting human insulin.
Bużżieqa ta ’ 1 mg ta ’ insulina inalata hija ekwivalenti għal madwar 3 IU insulina li taħdem malajr li tingħata taħt il- ġilda.
A 3 mg blister of inhaled insulin is approximately equivalent to 8 IU of lo subcutaneously injected fast-acting human insulin.
Bużżieqa ta ’ 3 mg ta ’ insulina inalata hija ekwivalenti għal madwar 8 IU insulina il
Table 1 above presents the approximate IU dose of fast-acting human insulin for initial, pre-meal EXUBERA doses in mg. o tn
Tabella 1 hawn fuq tippreżenta d- doża IU approssimattiva ta ’ insulina li taħdem malajr għal dożi inizjali ta ’ qabel l- ikel ta ’ EXUBERA f’ mg. al in
Therefore, EXUBERA should be used with caution in patients of low body weight.
Għaldaqstant, EXUBERA għandha tintuża b’ kawtela f’ pazjenti b’ piż tal- ġisem ħafif.
The use of EXUBERA in patients requiring dose titrations of less than 1 mg is not recommended (see section 4.4). uc
L- użu ta ’ EXUBERA f’ pazjenti li jeħtieġu titrazzjonijiet tad- doża ta ’ inqas minn 1 mg m’ huwiex irrikmandat iċ
Dose adjustment may be required based on the meal size and nutrient composition, time of day od
(ara sezzjoni 4. 4). ed
(higher insulin requirements in the morning), pre-meal blood glucose concentration, recent or anticipated exercise. pr
Jista ’ jkun hemm bżonn ta ’ aġġustament tad- doża u dan ikun jiddependi fuq id- daqs ta ’ l- ikla u l - kompożizzjoni nutrittiva, il- ħin tal- ġurnata (ħtiġijiet akbar ta ’ insulina filgħodu), il- konċentrazzjoni m
During intercurrent respiratory illness (e. g. bronchitis, upper respiratory tract infections) close monitoring of blood glucose concentrations and dose adjustment may be required on an individual al
tal- glukosju fid- demm ta ’ qabel l- ikel, l- eżerċizzju reċenti jew mistenni.
basis (see section 4.4). in
Waqt mard respiratorju interkurrenti (eż. bronkite, infezzjonijiet fil- passaġġi tal- parti ta ’ fuq tas - t ot
For further details on how to use the insulin inhaler refer to the instructions for use (IFU). ic
sistema respiratorja), tista ’ tkun meħtieġa sorveljanza mill- qrib tal- konċentrazzjonijiet tal- glukosju fid - demm kif ukoll aġġustament tad- doża fuq bażi individwali (ara sezzjoni 4. 4). od
In patients with hepatic or renal impairment insulin requirements may be diminished.
Għal aktar dettalji fuq kif tuża l- inalatur ta ’ l- insulina rreferi għall- istruzzjonijiet fuq l- użu (IFU).
Children and adolescents
Indeboliment tal- fwied u tal- kliewi
Long-term safety of inhaled human insulin has not been established in paediatric patients with diabetes and its use is therefore not recommended in patients under 18 years of age (see section 5.2).
F’ pazjenti b’ indeboliment tal- fwied jew tal- kliewi, jista ’ jkun hemm inqas ħtieġa għall- insulina.
Elderly
Tfal u adoloxxenti
Experience with inhaled insulin in patients
Is- sigurtà fuq tul ta ’ żmien ta ’ insulina umana ma ġietx stabbilita f’ pazjenti pedjatriċi bid- djabete u l - użu tagħha għaldaqstant mhuwiex irrikmandat f’ pazjenti taħt it- 18- il sena (ara sezzjoni 5. 2).
19 Congestive heart failure
19 Anzjani
Hypersensitivity to the active substance or to any of the excipients (see section 6.1).
riz Sensittività eċċessiva għas- sustanza attiva jew għal xi sustanzi mhux attivi (ara sezzjoni 6. 1).
ed Patients must not smoke during therapy with EXUBERA and must have stopped smoking at least 6 months prior to starting EXUBERA therapy.
to Il- pazjenti m’ għandhomx ipejpu waqt terapija b’ EXUBERA u għandhom ikunu waqfu t- tipjip
ris be discontinued immediately due to the increased risk of hypoglycaemia and an alternative treatment utilised (see section 5.2).
Jekk pazjent jibda jew jerġa ’ jibda jpejjep, EXUBERA għandha titwaqqaf minnufih minħabba riskju akbar ta ’ ipogliċemija u għandu jintuża trattament alternattiv (ara sezzjoni 5. 2).
ho Poorly controlled, unstable, or severe asthma.
x du Ażżma mhux ikkontrollata sewwa, instabbli jew qawwija.
ut Severe (GOLD stage III or IV) Chronic obstructive pulmonary disease (COPD).
Mard pulmonari kroniku u ostruttiv (COPD), qawwi (Stadji III jew IV GOLD). ħa 4. 4 Twissijiet speċjali u prekawzjonijiet għall- użu ’ g
ra 4.4 Special warnings and precautions for use
Pazjenti mibdija fuq EXUBERA għandhom jirċievu struzzjonijiet komprensivi fuq l- użu ta ’ l- inalatur im
ge Patients started on EXUBERA must receive comprehensive instructions in the use of the inhaler (see IFU).
tagħhom (ara IFU).
Patients should inhale the insulin powder from the mouthpiece in one slow and steady n inhalation.
Il- pazjenti għandhom jinalaw it- trab ta ’ l- insulina mill- parti li tidħol fil- ħalq f’ teħida ta ’ nifs waħda bil- mod u soda.
A consistent and standard inhalation technique should be employed to ensure both optimal and consistent drug lo delivery. o
Għandha tintuża teknika ta ’ ġbid tan- nifs konsistenti u standard il
Patients should avoid exposing the product to high moisture or relative humidity conditions e. g. a tn
Meta jieħdu d- doża tagħhom, il- pazjenti għandhom jevitaw li jesponu l- prodott għal kondizzjonijiet ta ’ in
steamy bathroom, when taking their dose.
umdità għolja u relattivament umidi eż. kamra tal- banju bil- fwar. iċ
If the insulin inhaler is inadvertently exposed to extremely moist conditions during use this usually uc
Jekk l- inalatur ta ’ l- insulina jkun involontarjament espost għal kondizzjonijiet estremament umidi ed
leads to a subsequent decreased the insulin dose delivered from the inhaler.
waqt l- użu, dan issoltu jirriżulta fi tnaqqis tad- doża ta ’ l- insulina mogħtija.
In this case, the Insulin Release Unit (IRU) must be changed prior to the next inhalation (see section 6.6). od
F’ dan il- każ, il- Unit ta ’ Rilaxx ta ’ l- Insulina (IRU) irid jinbidel qabel l- inalazzjoni li jkun imiss (ara sezzjoni 6. 6). m
Dosing pr
Dożaġġ t
Transferring a patient to another type or brand of insulin should be done under strict medical supervision as this may result in a change in dosage. al
Trasferiment ta ’ pazjent minn fuq tip jew ditta ta ’ insulina għal oħra għandu jsir taħt sorveljanza ot
Consecutive inhalation of three 1 mg unit dose blisters causes a significantly higher insulin exposure in
medika stretta għaliex dan jista ’ jirriżulta f’ bidla fid- dożaġġ. od
than inhalation of one 3 mg unit dose blister.
Inalazzjoni konsekuttiva ta ’ tliet bżieżaq ta ’ doża waħda ta ’ 1 mg jikkaġunaw espożizzjoni ogħla minn inalazzjoni waħda ta ’ doża waħda ta ’ 3 mg.
Therefore three 1 mg unit dose blisters should not be ic
Għaldaqstant, tliet bżieżaq ta ’ doża waħda ta ’ 1 mg Pr
substituted for one 3 mg unit dose blister (see sections 2, 4.2 and 5.2). ed
m’ għandhomx jiġu sostitwiti minn bużżieqa ta ’ doża waħda ta ’ 3 mg (ara sezzjonijiet 2, 4. 2 u 5. 2).
M
Jekk il- bużżieqa ta ’ 3 mg tkun temporanjament mhux disponibbli, żewġ bżieżaq ta ’ 1 mg għandhom jissostitwixxuha u l- glukosju fid- demm għandu jiġi sorveljat mill- qrib.
20 the insulin requirement.
20 Ipogliċemija
Symptoms of hypoglycaemia usually occur suddenly.
L- ipogliċemija, b’ mod ġenerali hi l- aktar effett frekwenti mhux mixtieq ta ’ terapija bl- insulina nkluż EXUBERA u ħafna mediċini ta ’ kontra d- dijabete oħra, li tista ’ sseħħ jekk id- doża ta ’ l- insulina tkun għolja wisq meta mqabbla mal- ħtieġa għall- insulina.
They may include cold sweats, cool pale skin, fatigue, nervousness or tremor, anxiousness, unusual tiredness or weakness, confusion, difficulty in concentration, drowsiness, excessive hunger, vision changes, headache, nausea and palpitation.
Attakki ipogliċemiċi qawwija, b’ mod speċjali jekk rikorrenti, jistgħu jwasslu għal ħsara newroloġika.
Severe hypoglycaemia may lead to unconsciousness and/ or convulsions and may result in temporary or permanent impairment of brain function or even death.
Episodji ipogliċemiċi fit- tul jew serji jistgħu jkunu ta ’ theddida għall- ħajja.
Hypoglycaemia can generally be corrected by immediate carbohydrate intake.
Sintomi ta ’ ipogliċemija ġeneralment iseħħu f’ daqqa.