qanastek/EMEA-V3 huggingface dataset:
7.5 events/ 1,000 patient-years, diet alone 12.7 events/ 1,000 patient-years, p=0.017
snin ta ’ kura, dieta waħidha 12. 7 każi/ 1, 000 snin ta ’ kura, p=0. 017
- a significant reduction of the absolute risk of overall mortality: metformin 13.5 events/ 1,000
- tnaqqis sinifikanti fir- riskju assolut ta ’ mwiet in generali: metformin 13. 5 każi/ 1, 000 snin ta ’
patient-years versus diet alone 20.6 events/ 1,000 patient-years (p=0.011), and versus the combined sulphonylurea and insulin monotherapy groups 18.9 events/ 1,000 patient-years (p=0.021)
kura komparat ma ’ dieta waħidha 20. 6 każi/ 1, 000 snin ta ’ kura (p=0. 011) u kkomparat ma ’ gruppi ta ’ monoterapija b’ sulphonylurea u insulina kkombinati 18. 9 każi/ 1, 000 snin ta ’ kura (p=0. 021)
- a significant reduction in the absolute risk of myocardial infarction: metformin 11 events/ 1,000
- tnaqqis sinifikanti fir- riskju assolut ta ’ infart mijokardjali: metformin 11- il każ/ 1, 000 snin ta ’
patient-years, diet alone 18 events/ 1,000 patient-years (p=0.01).
kura, dieta waħidha 18- il każ/ 1, 000 snin ta ’ kura (p=0. 01).
AVANDAMET Absorption No statistically significant difference was observed between the absorption characteristics of rosiglitazone and metformin from the AVANDAMET tablet and those obtained from rosiglitazone maleate and metformin hydrochloride tablets, respectively.
AVANDAMET Assorbiment L- ebda differenza statistikament sinifikanti ma ġiet osservata bejn il- karatteristiċi ta ’ assorbiment ta ’ rosiglitazone u metformin mill- pillola AVANDAMET u dawk miġbura minn pilloli ta ’ rosiglitazone maleate u metformin hydrochloride, rispettivament.
Food had no effect on the AUC of rosiglitazone or metformin when AVANDAMET was administered to healthy volunteers.
L- ikel ma kellu l- ebda effett fuq l- AUC ta ’ rosiglitazone jew metformin meta AVANDAMET ġie amministrat lil voluntiera b’ saħħithom.
In the fed state, Cmax was lower (22% rosiglitazone and 15% metformin) and tmax delayed (by approximately 1.5 h rosiglitazone and 0.5 h metformin).
Wara l- ikel, Cmax kien iktar baxx (22% rosiglitazone u 15% metformin) u tmax ittardjat (b’ madwar 1. 5 h rosiglitazone u 0. 5 h metformin).
This food-effect is not considered clinically significant.
Dan l- effett ta ’ l- ikel mhux ikkunsidrat klinikament sinifikanti.
The following statements reflect the pharmacokinetic properties of the individual active substances of AVANDAMET.
L- istqarrijiet segwenti jirriflettu l- karatteristiċi farmakokinetiċi tas- sustanzi attivi individwali ta ’ AVANDAMET.
13 Absolute bioavailability of rosiglitazone following both a 4 and an 8 mg oral dose is approximately 99%.
Rosiglitazone Assorbiment Biodisponibilità assoluta ta ’ rosiglitazone wara doża orali kemm ta ’ 4 mg kif ukoll ta ’ 8 mg hija ta ’ madwar 99%.
Rosiglitazone plasma concentrations peak at around 1 h after dosing.
Konċentrazzjonijiet fil- plażma ta ’ rosiglitazone jilħqu l- ogħla livell madwar siegħa wara li tittieħed id- doża.
Plasma concentrations are approximately dose proportional over the therapeutic dose range.
Konċentrazzjonijiet fil- plażma huma bejn wieħed u ieħor proporzjonali mad- doża tul l- iskala kollha ta ’ dożi terapewtiċi.
Administration of rosiglitazone with food resulted in no change in overall exposure (AUC), although a small decrease in Cmax (approximately 20-28%) and a delay in tmax (approximately 1.75 h) were observed compared to dosing in the fasting state.
L- ogħti ta ’ rosiglitazone ma ’ l- ikel ma rriżulta fl- ebda bidla fl- esponiment globali (AUC), għalkemm tnaqqis żgħir fis- Cmax (madwar 20- 28%) u ttardjar fit- tmax (madwar 1. 75 h) ġew osservati meta imqabbla ma ’ l- ogħti ta ’ doża fi stat ta ’ sawm.
These small changes are not clinically significant and, therefore, it is not necessary to administer rosiglitazone at any particular time in relation to meals.
Dawn il- bidliet żgħar m’ humiex klinikament sinifikanti
Distribution The volume of distribution of rosiglitazone is approximately 14 l in healthy volunteers.
14 u għalhekk mhux neċessarju li rosiglitazone jiġi mogħti f’ xi ħin partikolari in relazzjoni ma ’ l- ikel.
Plasma protein binding of rosiglitazone is high (approximately 99.8%) and is not influenced by concentration or age.
L- irbit ta ’ rosiglitazone mal- proteini fil- plażma huwa għoli (madwar 99. 8%) u mhux affetwat mill - konċentrazzjoni jew l- eta ’.
The protein binding of the major metabolite (a para-hydroxy-sulphate) is very high (> 99.99%).
L- irbit mal- proteini tal- prodott ewlieni tal- metaboliżmu (para- hydroxy - sulphate) huwa għoli ħafna (> 99. 99%).
Metabolism Metabolism of rosiglitazone is extensive with no parent compound being excreted unchanged.
Metaboliżmu Il- metaboliżmu ta ’ rosiglitazone huwa estensiv mingħajr l- ebda parti minnu ma tiġi mneħħija intatta.
The major routes of metabolism are N-demethylation and hydroxylation, followed by conjugation with sulphate and glucuronic acid.
Ir- rotot ewlenin ta ’ metaboliżmu huma N- demethylation u hydroxylation, segwiti permezz ta ’ konjugazzjoni bis- sulphate u glucuronic acid.
The contribution of the major metabolite (a para-hydroxy-sulphate) to the overall antihyperglycaemic activity of rosiglitazone has not been fully elucidated in man and it cannot be ruled out that the metabolite may contribute to the activity.
Il- kontribut tal- prodott ewlieni tal- metaboliżmu (para - hydroxy- sulphate) fuq l- attività anti- ipergliċemika ġenerali ta ’ rosiglitazone għadu ma ġiex iċċarat għal kollox fil- bniedem u wieħed ma jistax jeskludi li l- prodott tal- metaboliżmu jista ’ jikkontribwixxi għal din l- attività.
However, this raises no safety concern regarding target or special populations as hepatic impairment is contraindicated and the phase III clinical studies included a considerable number of elderly patients and patients with mild to moderate renal impairment.
Madankollu, dan ma jqanqal l- ebda tħassib dwar is- sigurtà fil- konfront ta ’ popolazzjonijiet milquta jew speċjali għax ħsara fil- fwied hija kontra- indikata u studji kliniċi f’ fażi III inkludew numru konsiderevoli ta ’ pazjenti anzjani u pazjenti bi ħsara fil- fwied ta ’ natura żgħira jew moderata.
In vitro studies demonstrate that rosiglitazone is predominantly metabolised by CYP2C8, with a minor contribution by CYP2C9.
Studji in vitro juru li rosiglitazone huwa fil- biċċa l- kbir metaboliżżat minn CYP2C8, b’ kontribut żgħir minn CYP2C9.
Since there is no significant in vitro inhibition of CYP1A2, 2A6, 2C19, 2D6, 2E1, 3A or 4A with rosiglitazone, there is a low probability of significant metabolism-based interactions with substances metabolised by these P450 enzymes.
Peress li m’ hemmx inibizzjoni in vitro sinifikanti ta ’ CYP1A2, 2A6, 2CI9, 2D6, 3A jew 4A ma ’ rosiglitazone, hemm probabbiltà żgħira ta ’ interazzjonijiet bażati fuq il- metaboliżmu ma ’ sustanzi metabolizzati minn dawn l- enżimi P450.
Rosiglitazone showed moderate inhibition of CYP2C8 (IC50 18 µM) and low inhibition of CYP2C9 (IC50 50 µM) in vitro (see section 4.5).
Rosiglitazone wera inibizzjoni moderata ta ’ CYP2C8 (IC50 18 μM) u inibizzjoni baxxa ta ’ CYP2C9 (IC50 50 μM) in vitro (ara sezzjoni 4. 5).
An in vivo interaction study with warfarin indicated that rosiglitazone does not interact with CYP2C9 substrates in vivo.
Meta ntuża warfarin fi studju ta ’ interazzjoni in vitro, ġie ndikat li rosiglitazone ma jgħamilx interazzjoni ma ’ sustrati in vivo ta ’ CYP2C9.
Elimination Total plasma clearance of rosiglitazone is around 3 l/ h and the terminal elimination half-life of rosiglitazone is approximately 3-4 h.
Eliminazzjoni L- eliminazzjoni totali tal- plażma minn rosiglitazone hija madwar 3 1/ h u l- half- life għall - eliminazzjoni terminali ta ’ rosiglitazone hi madwar 3- 4 h.
There is no evidence for unexpected accumulation of rosiglitazone after once or twice daily dosing.
M’ hemm l- ebda evidenza ta ’ akkumolu mhux mistenni ta ’ rosiglitazone wara l- għoti ta ’ doża darba jew darbtejn kuljum.
The major route of excretion is the urine with approximately two-thirds of the dose being eliminated by this route, whereas faecal elimination accounts for approximately 25% of dose.
Sadattant, eliminazzjoni ma ’ l- ippurgar tkopri madwar 25% tad- doża.
No intact active substance is excreted in urine or faeces.
L- ebda sustanza attiva intatta m’ hi mneħħija fl- awrina jew fl- ippurgar.
The terminal half-life for radioactivity was about 130 h indicating that elimination of metabolites is very slow.
Il- half- life terminali għar- radjuattività kienet madwar 130 h u dan jindika li l- eliminazzjoni tal- metaboli issir bil- mod ħafna.
Accumulation of the metabolites in plasma is expected upon repeated dosing, especially that of the major metabolite (a para-hydroxy-sulphate) for which an 8-fold accumulation is anticipated.
L- akkumolu ta ’ metaboli fil- plażma jkun mistenni meta d- doża tiġi ripetuta, partikolarment dak tal- prodott tal- metaboliżmu ewlieni (para - hydroxy- sulphate) li għalih huwa antiċipat akkumolu ta ’ tmien darbiet iktar.
Special populations Gender:
Popolazzjonijiet speċjali Sess:
In the pooled population pharmacokinetic analysis, there were no marked differences in the pharmacokinetics of rosiglitazone between males and females.
Minn ġabra ta ’ analiżi tal- farmakokinetika tal- popolazzjoni, ma kienx hemm differenza partikolari fil- proċessi farmakokinetiċi ta ’ rosiglitazone bejn l- irġiel u n- nisa.
In the pooled population pharmacokinetic analysis, age was not found to influence the pharmacokinetics of rosiglitazone to any significant extent.
Minn ġabra ta ’ analiżi tal- farmakokinetika tal- popolazzjoni, l- età ma nstabitx li taffetwa l - proċessi farmakokinetiċi ta ’ rosiglitazone b’ xi mod sinifikanti.
Population pharmacokinetic analysis including 96 paediatric patients aged 10 to 18 years and weighing 35 to 178 kg suggested similar mean CL/ F in children and adults.
Analiżi farmakokinetika ta’ popolazzjoni li kienet tinkludi 96 pazjent pedjatriku li l- eta ’ tagħhom kienet bejn l- 10 u t- 18- il sena u li kienu jiżnu bejn il- 35 u l- 178 kg implikat medja tixtiebaħ ta ’ CL/ F bejn it- tfal u l- adulti.
Individual CL/ F in the paediatric population was in the same range as individual adult data.
CL/ F dehret li donnha kienet indipendenti mill- eta ’ iżda żdiedet mal- piż fil- popolazzjoni pedjatrika.
In cirrhotic patients with moderate (Child-Pugh B) hepatic impairment, unbound Cmax and AUC were 2- and 3-fold higher than in normal subjects.
Indeboliment tal- fwied: f’ pazjenti morda b’ ċirrożi b’ indeboliment moderat (Child- Pugh B) tal- fwied, unbound Cmax u AUC kienu darbtejn u 3 darbiet ogħla minn f’ suġġetti normali.
The inter-subject variability was large, with a 7-fold difference in unbound AUC between patients.
Il- varjabilità bejn is - suġġetti kienet kbira b’ differenza ta ’ 7 darbiet f’ unbound AUC bejn pazjenti.
Renal insufficiency:
15 Insuffiċjenza tal- kliewi:
There are no clinically significant differences in the pharmacokinetics of rosiglitazone in patients with renal impairment or end stage renal disease on chronic dialysis.
M’ hemm l- ebda differenzi klinikament sinifikanti fil- proċessi farmakokinetiċi ta ’ rosiglitazone f’ pazjenti b’ indeboliment tal- kliewi jew fl- aħħar stadju ta ’ mard tal- kliewi jew dijaliżi kronika.
Metformin Absorption After an oral dose of metformin, tmax is reached in 2.5 h.
Metformin Assorbiment Wara doża orali ta ’ metformin, tmax jintlaħaq f’ 2. 5h.
Absolute bioavailability of a 500 mg metformin tablet is approximately 50-60% in healthy subjects.
Biodisponibilità assoluta ta ’ pillola metformin tal- 500 mg hi ta ’ madwar 50- 60% f’ suġġetti b’ saħħithom.
After an oral dose, the non-absorbed fraction recovered in faeces was 20-30%.
Wara doża orali, il- parti mhux assorbita irkuprata mill- ippurgar kienet ta ’ 20- 30%.
After oral administration, metformin absorption is saturable and incomplete.
Wara li jittieħed mill- ħalq, l- assorbiment ta ’ metformin ikun għadu mhux komplet.
It is assumed that the pharmacokinetics of metformin absorption is non-linear.
Huwa presunt li l - proċess farmakokinetiku ta ’ assorbiment ta ’ metformin mhux lineari.
At the usual metformin doses and dosing schedules, steady state plasma concentrations are reached within 24-48 h and are generally less than 1 µg/ ml.
Fid- dożi u skemi ta ’ dużaġġ ta ’ metformin komuni, konċentrazzjonijiet fil- plażma ta ’ l- istat fiss jintlaħqu bejn 24- 48 siegħa wara u ġeneralment huma inqas minn 1 μg/ ml.
In controlled clinical trials, maximum metformin plasma levels (Cmax) did not exceed 4 µg/ ml, even at maximum doses.
Fi provi kliniċi kontrollati, livelli massimi fil- plażma ta ’ metformin (Cmax) ma qabżux l- 4 μg/ ml, anke b’ dożi massimi.
Food decreases the extent and slightly delays the absorption of metformin.
L- ikel inaqqas il- livell u jittardja xi ftit l- assorbiment ta ’ metformin.
Following administration of a dose of 850 mg, a 40% lower plasma peak concentration, a 25% decrease in AUC and a 35 min prolongation of time to peak plasma concentration was observed.
Wara li tingħata doża ta ’ 850 mg, ġiet osservata konċentrazzjoni massima fil- plażma 40% iktar baxxa, tnaqqis ta ’ 25% f’ AUC u titwil ta ’ 35 minuta biex il- konċentrazzjoni tal- plażma laħqet il- massimu.
The clinical relevance of this decrease is unknown.
Ir- relevanza klinika ta ’ dan it - tnaqqis mhix magħrufa.
Distribution Plasma protein binding is negligible.
Distribuzzjoni L- irbit mal- proteini tal- plażma (plażma Protein binding) huwa negliġibbli.
Metformin partitions into erythrocytes.
Metformin jinqasam f’ eritroċiti.
The blood peak is lower than the plasma peak and appears at approximately the same time.
Il- massimu tad- demm huwa iktar baxx minn dak tal- plażma u jidher f’ madwar l- istess ħin.
The red blood cells most likely represent a secondary compartment of distribution.
Probabbilment, iċ- ċelloli ħomor tad- demm jirrappreżentaw kompartiment sekondarju ta ’ distribuzzjoni.
The mean Vd ranged between 63 – 276 l.
Il- Vd medju varja bejn 63- 276 l.
Metabolism Metformin is excreted unchanged in the urine.
Metaboliżmu Metformin jitneħħa mingħajr ma jinbidel fl- awrina.
No metabolites have been identified in humans.
L- ebda metaboli ma ġew identifikati fil- bniedem.
Elimination Renal clearance of metformin is > 400 ml/ min, indicating that metformin is eliminated by glomerular filtration and tubular secretion.
Eliminazzjoni Il- clearance mill- kliewi ta ’ metformin hija > 400 ml/ min u jindika li metformin hu eliminat permezz ta ’ filtrazzjoni glomerulari u tisfija tubulari.
Following an oral dose, the apparent terminal elimination half-life is approximately 6.5 h.
Wara doża orali, il- half- life ta ’ eliminazzjoni terminali jidher li hija ta ’ madwar 6. 5 h.
When renal function is impaired, renal clearance is decreased in proportion to that of creatinine and thus the elimination half-life is prolonged, leading to increased levels of metformin in plasma.
Meta jkun hemm indeboliment fil- funzjoni tal- kliewi, il- clearance tal- kliewi tonqos in proporzjon ma ’ dik tal- krejatinina u għalhekk il- half- life ta ’ eliminazzjoni hija mtawla; dan iwassal għal żjieda fil- livelli ta ’ metformin fil- plażma.
No animal studies have been conducted with the combined products in AVANDAMET.
Ma saru ebda studji fuq annimali bil- prodotti kombinati ta ’ AVANDAMET.
The following data are findings in studies performed with rosiglitazone or metformin individually.
It- tagħrif segwenti ġie skopert fi studji li saru b’ rosiglitazone u metformin individwalment.
Rosiglitazone Undesirable effects observed in animal studies with possible relevance to clinical use were as follows:
Rosiglitazone Effetti mhux mixtieqa osservati fi studji fuq annimali b’ relevanza possibbli għal użu kliniku huma kif ġej:
An increase in plasma volume accompanied by decrease in red cell parameters and increase in heart weight.
Żjieda fil- volum ta ’ plażma akkumpanjat minn tnaqqis fil- parametri taċ- ċelloli ħomor u żjieda fil - piż tal- qalb.
In reproductive toxicity studies, administration of rosiglitazone to rats during mid-late gestation was associated with foetal death and retarded foetal development.
Fi studji dwar tossiċità fuq is- sistema riproduttiva, l- ogħti ta ’ rosiglitazone lill- firien bejn in- nofs u l - aħħar tal- ġestazzjoni kienet assoċjata mal- mewt tal- fetu u żvilupp ritardjat tal- fetu.
In addition, rosiglitazone inhibited ovarian oestradiol and progesterone synthesis and lowered plasma levels of these hormones resulting in effects on oestrus/ menstrual cycles and fertility (see section 4.4).
Barra minn hekk, rosiglitazone jostakola is- sintesi ta ’ l- oestradiol ta ’ l- ovarju u l- progesterone u baxxa l- livelli fil - plażma ta ’ dawn l- ormoni biex b’ hekk wassal għal effetti fuq iċ- ċikli oestrus/ menstruwali u fertilità (ara sezzjoni 4. 4).
In an animal model for familial adenomatous polyposis (FAP), treatment with rosiglitazone at 200 times the pharmacologically active dose increased tumour multiplicity in the colon.
F’ mudell ta ’ annimal ittestjat għal polipożi familjali adenomatuża (FAP), il- kura b’ rosiglitazone b’ doża 200 iktar mid- doża farmakoloġikament attiva żiedet il- multipliċità ta ’ tumur fil- kolon.
The relevance of this finding is unknown.
Ir - 16 relevanża ta ’ dan il- fatt mhix magħrufa.
However, rosiglitazone promoted differentiation and reversal of mutagenic
Madankollu, in vitro, rosiglitazone għen fid- distinzjoni u r - revoka ta ’ tibdil mutaġeniku fiċ- ċelloli kanċeroġeni tal- kolon uman.
In addition, rosiglitazone was not genotoxic in a battery of in vivo and in vitro genotoxicity studies and there was no evidence of colon tumours in lifetime studies of rosiglitazone in two rodent species.
Barra minn hekk, rosiglitazone ma kienx ġenotossiku f’ serje ta ’ studji dwar ġenotossiċità kemm in vivo kif ukoll in vitro u ma hemm l- ebda evidenza ta ’ tumuri fil- kolon li toħroġ minn studji fuq rosiglitazone li saru tul il- ħajja kollha ta ’ żewġ speċi ta ’ mammali gerriema (rodents).
Metformin Non-clinical data for metformin reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction.
Metformin Tagħrif mhux kliniku għal metformin ma jiżvela l- ebda periklu speċjali għall- bniedem ibbażat fuq studji konvenzjonali dwar farmakoloġija ta ’ sigurta ’, tossiċità f’ dożi ripetuti, ġenotossiċità, potenzjal kanċeroġenu u tossiċità ta ’ riproduzzjoni.
Sodium starch glycollate Hypromellose (E464) Microcrystalline cellulose (E460) Lactose monohydrate Povidone (E1201) Magnesium stearate.
Sodium starch glycollate Hypromellose (E464) Microcrystalline cellulose (E460) Lactose monohydrate Povidone (E1201) Magnesium stearate.
Film coat:
Rita tal- kisja:
Hypromellose (E464) Titanium dioxide (E171) Macrogol Iron oxide yellow (E172).
Hypromellose (E464) Titanium dioxide (E171) Macrogol Iron oxide yellow (E172).
Opaque blisters (PVC/ PVdC/ aluminium).
Folji blister opaki (PVC/ PVdC/ aluminju).
Packs of 28, 56, 112, 336 (3x112) and 360 tablets.
Pakki ta ’ 28, 56, 112, 336 (3x112) u 360 pillola.
Any unused product should be disposed of in accordance with local requirements.
Kull fdal tal- prodott li ma jkunx intuża għandu jintrema kif jitolbu l- liġijiet lokali.
MARKETING AUTHORISATION HOLDER
ID- DETENUR TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ
20 October 2003 Date of latest renewal:
20 t’ Ottubru 2003 Data ta ’ l- aħħar tiġdid:
20 October 2008
20 t’ Ottubru 2008
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu
Informazzjoni dettaljata dwar din il- mediċina tinsab fuq il- website ta ’ l- Aġenzija Ewropea dwar il - Mediċini (EMEA) http: www. emea. europa. eu
AVANDAMET 2 mg/ 500 mg film-coated tablets
AVANDAMET 2 mg/ 500 mg pilloli miksija b’ rita.
Each tablet contains 2 mg of rosiglitazone (as rosiglitazone maleate) and 500 mg of metformin hydrochloride (corresponding to metformin free base 390 mg).
Kull pillola fiha 2 mg rosiglitazone (bħala rosiglitazone maleate) u 500 mg metformin hydrochloride (jikkorrespondu għal bażi ta ’ 390 mg metformin liberu).
Each tablet contains lactose (approximately 11 mg)
Sustanzi mhux attivi, Kull pillola fiha lattosju (bejn wieħed u ieħor 11 mg)
Pale pink film-coated tablets marked "gsk" on one side and "2/ 500" on the other.
Pilloli roża ċari miksija b’ rita, bil- marka “ gsk ” fuq naħa waħda u “ 2/ 500 ” fuq in- naħa l- oħra.
metformin alone.
ta ’ metformin waħdu
4 mg/ day rosiglitazone with the dose of metformin substituting that already being taken.
d’ doża ta 4mg kuljum rosiglitazone bid- doża ta ’ metformin minflok dik li tkun qed tittieħed diġà.
An increase in the rosiglitazone component to 8 mg/ day should be undertaken cautiously following appropriate clinical evaluation to assess the patient's risk of developing adverse reactions relating to fluid retention (see sections 4.4 and 4.8).
Żjieda fil- komponent ta ’ rosiglitazone għal 8 mg kuljum trid tiġi magħmula b’ attenzjoni wara evalwazzjoni klinika xierqa li tistabbilixxi r- riskju li pazjent jista ’ jiżviluppa effetti mhux mixtieqa relatati ma ’ retenzjoni ta ’ fluwidu (ara sezzjonijiet 4. 4 u 4. 8).
Patients with renal impairment AVANDAMET should not be used in patients with renal failure or renal dysfunction e. g. serum creatinine levels > 135 μ mol/ l in males and > 110 μ mol/ l in females and/ or creatinine clearance < 70 ml/ min (see sections 4.3 and 4.4).
Pazjenti b’ funzjoni tal- kliewi baxxa AVANDAMET m’ għandux jintuża f’ pazjenti b’ insuffiċjenza tal- kliewi jew fejn il- kliewi ma jaħdmux sew eż. livelli seroloġiċi ta ’ krejatinina > 135µmol/ l fl- irġiel u > 110µmol/ l fin- nisa u/ jew clearance tal - krejatinina < 70 ml/ min (ara sezzjonijiet 4. 3 u 4. 4).
- hypersensitivity to rosiglitazone, metformin hydrochloride or to any of the excipients
− sensittività eċċessiva għal rosiglitazone, għal metformin hydrochloride jew għal xi sustanzi mhux attivi − insuffiċjenza tal- qalb jew passat ta ’ din il- kundizzjoni (stadji tan- New York Heart Association (NYHA) I sa IV) − Sindromu Koronarju Akut (anġina instabbli, NSTEMI u STEMI) (ara sezzjoni 4. 4) − mard akut jew kroniku li jista jikkawża nuqqas ta ’ ossiġnu fil- livell ċellolari bħal: − falliment tas- sistema tal- qalb jew respiratorja − infart tal- qalb reċenti − xokk − indeboliment tal- fwied − intossikazzjoni akuta bl- alkoħol, vizzju ta ’ xorb alkoħoliku eċċessiv (ara sezzjoni 4. 4) − stat dijabetiku ta ’ ketoaċidożi jew stat dijabetiku pre- koma − insuffiċjenza tal- kliewi jew il- kliewi ma jaħdmux sew eż. livelli seroloġiċi tal- krejatinina > 135 µmol/ l fl- irġiel > 110µmol/ l fin- nisa u/ jew tneħħija ta ’ kreatinina ta ’ < 70 ml/ min (ara sezzjoni. 4) − kundizzjonijiet akuti li jistgħu jibdlu l- funzjoni tal- kliewi bħal: − nuqqas ta ’ ilma fil- ġisem − infezzjoni qawwija − xokk − amministrazzjoni intravaskulari ta ’ kimiċi għall- kuntrast li fihom Iodine (ara sezzjoni 4. 4) − nisa li qed ireddgħu.
- acute conditions with the potential to alter renal function such as:
20 4. 4 Twissijiet speċjali u prekawzjonijiet speċjali għall- użu
The incidence of lactic acidosis can and should be reduced by also assessing other associated risk factors such as poorly controlled diabetes, ketosis,
L- inċidenza ta ’ aċidozi lattika tista ’ u għandha tkun imnaqqsa billi wieħed jikkunsidra wkoll fatturi oħra li jżidu r- riskju bħal dijabete mhux ikkontrollata sew, livell għoli ta ’ ketones, sawm fit- tul, xorb alkoħoliku eċċessiv, insuffiċjenza tal- fwied u kull kundizzjoni assoċjata man- nuqqas ta ’ ossiġnu.
All patients, particularly those receiving concurrent insulin but also sulphonylurea therapy, those at risk for heart failure, and those with reduced cardiac reserve, should be monitored for signs and symptoms of adverse reactions relating to fluid retention, including weight gain and heart failure.
Il- pazjenti kollha, speċjalment dawk li qed jieħdu t- trattament flimkien ma ’ l- insulina u sulphonylurea, dawk li għandhom riskju ta ’ insuffiċjenza tal- qalb u dawk b’ riżerva tal- qalb mnaqqsa, għandhom jiġu monitorjati għal xi sinjali jew sintomi ta ’ effetti mhux mixtieqa li għandhom x’ jaqsmu ma retenzjoni ta ’ fluwidu, inklużi żjieda fil- piż u insuffiċjenza tal- qalb.
AVANDAMET must be discontinued if any deterioration in cardiac status occurs.
AVANDAMET għandu jitwaqqaf fil- każ ta ’ xi deterjorament fl- istat kardijaku.
The decision to initiate AVANDAMET in combination with a sulphonylurea should include consideration of alternative therapies.
Qabel tittieħed id- deċiżjoni li jinbeda AVANDAMET flimkien ma sulphonylurea għandhom jiġu kkunsidrati terapiji alternativi.
Caution should be exercised in patients over 75 years because of the limited experience in this patient group.
Għandu jkun hemm kawtela f’ pazjenti ta ’ aktar minn 75 sena minħabba esperjenza limitata f’ dan il- grupp ta ’ pazjenti.
Insulin should only be added to established rosiglitazone therapy in exceptional cases and under close supervision.
21 L- insulina għandha tiżdied biss f’ kura stabbilita b’ rosiglitazone f’ każijiet speċjali u taħt osservazzjoni mill- viċin.
20 Acute Coronary Syndrome (ACS) Patients experiencing an ACS have not been studied in rosiglitazone controlled clinical trials.
Sindromu Koronarju Akut (ACS) Pazjenti li esperjenzaw ACS ma ġewx studjati fi studji kliniċi kkontrollati b’ rosiglitazone.
Weight gain In clinical trials with rosiglitazone there was evidence of dose-related weight gain, which was greater when used in combination with insulin.
Żjieda fil- piż Fi studji kliniċi b’ rosiglitazone kien hemm evidenza ta ’ żjieda fil- piż relatat mad- doża, li kienet akbar meta intuża flimkien ma ’ insulina.
Increased monitoring of the patient and a reduction in the dose of the concomitant agent may be necessary.
Kirurġija Billi AVANDAMET fih metformin hydrochloride, il- kura għandha titwaqqaf 48 siegħa qabel
Surgery As AVANDAMET contains metformin hydrochloride, the treatment should be discontinued 48 hours before elective surgery with general anaesthesia and should not usually be resumed earlier than 48 hours afterwards.
22 operazzjoni bil- loppju ġenerali, u ġeneralment m’ għandux jerġa ’ jinbeda qabel igħaddu 48 siegħa.
Therefore, due to the metformin active substance, AVANDAMET should be discontinued prior to, or at the time of the test and not reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal (see section 4.5).
Għalhekk, minħabba s- sustanza attiva metformin, AVANDAMET għandu jitwaqqaf qabel jew waqt li jsir l- eżami u ma jerġax jinbeda qabel igħaddu 48 siegħa, u jerġa jingħata biss jekk it- testijiet tal- kliewi juru li qed jaħdmu sew (ara sezzjoni 4. 5)
21 Bone disorders In a long-term study an increased incidence of bone fractures (foot, hand and arm) was observed in female patients taking rosiglitazone as monotherapy (see section 4.8).
Mard ta ’ l- għadam Fi studju fit- tul ġiet osservata inċidenza akbar ta ’ ksur fl- għadam (fis- saqajn, fl- idejn u fid- dirgħajn) f’ pazjenti nisa li jkunu qed jieħdu rosiglitazone bħala monoterapija (ara sezzjoni 4. 8).
AVANDAMET dose adjustment within the recommended posology or changes in diabetic treatment should be considered.
L- aġġustament tad- doża ta ’ AVANDAMET skond il- pożoloġija rakkomandata jew tibdil fit- trattament dijabetiku għandu jiġi kkunsidrat.
AVANDAMET tablets contain lactose and therefore should not be administered to patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
AVANDAMET fih il- lactose u għalhekk m’ għandux jingħata lil pazjenti bi problemi rari ereditarji ta ’ intolleranza għall- galattożju, defiċjenza Lapp lactase jew meta l- ġisem ma jassorbix sew il- glukożju/ galattożju.
Cationic medicinal products that are eliminated by renal tubular secretion (e. g. cimetidine) may interact with metformin by competing for common renal tubular transport systems.
23 Prodotti mediċinali katajoniċi li jiġu eliminati permezz ta’ sekrezzjoni tubulari renali (e. ż. cimetidine) jistagħu ma jaqblux ma metformin billi jikkompetu għall- istess sistema ta ’ trasport tubulari renali.
Therefore, close monitoring of glycaemic control, dose adjustment within the recommended posology and changes in diabetic treatment should be considered when cationic medicinal products that are eliminated by renal tubular secretion are co-administered (see section 4.4).
Għalhekk għandu jkun hemm monitoraġġ b’ attenzjoni tal- kontroll ġliċemiku, aġġustament tad- doża skond il - pożoloġija rakkomandata u bdil fit- trattament tad- dijabete għandu jiġi kkunsidrat meta prodotti mediċinali katajoniċi li jiġu eliminati permezz ta ’ sekrezzjoni tubulati renali jingħaw flimkien (ara sezzjoni 4. 4).
22 Co-administration of rosiglitazone with rifampicin (an inducer of CYP2C8) resulted in a 66% decrease in rosiglitazone plasma concentrations.
L- għoti flimkien ta ’ rosiglitazone ma ’ rifampiċin (inducer ta ’ CYP2C8) irriżulta fi tnaqqis ta ’ 66% fil- konċentrazzjonijiet ta ’ rosiglitazone fil- plażma.
It cannot be excluded that other inducers (e. g. phenytoin, carbamazepine, phenobarbital, St John’ s wort) may also affect rosiglitazone exposure.
Ma jistax jiġi eskluż li inducers oħra (e. ż. phenytoin, carbamazepine, phenobarbital, St John’ s wort) jistgħu wkoll ikollhom effett fuq l - esponiment għal rosiglitazone.
Therefore, AVANDAMET should not be used during pregnancy.
24 Għalhekk, AVANDAMET m’ għandux jintuża waqt it- tqala.
23 Adverse reactions for each treatment regimen are presented below by system organ class and absolute frequency.
Reazzjonijiet mhux mixtieqa għal kull terapija huma elenkati hawn taħt skond il- klassi tas- sistemi u l - organi u l- frekwenza assoluta.
Clinical trial data (addition of insulin to established AVANDAMET therapy) In a single study (n=322) where insulin was added to patients established on AVANDAMET, no new adverse events were observed in excess of those already defined for either AVANDAMET or rosiglitazone combination therapies.
Tagħrif minn provi kliniċi (żjieda ta’ l- insulina ma ’ trattamet stabbilit b’ AVANDAMET) Fi studju wieħed (n=322) fejn żdieded l- insulina lill- pazjenti stabbiliti b’ AVANDAMET, lebda reazzjonijiet mhux mixtieqa ma ġew innutati aktar minn dawk li diġà ġew definiti għal AVANDAMET jew trattament ikkombinat b’ rosiglitazone.
However, the risk of both fluid related adverse events and hypoglycaemia are increased when AVANDAMET is used in combination with insulin.
Madanakollu, ir- riskji mhux mixtieqa ta ’ retenzjoni tal- fluwidu kif ukoll l- ipogliċemija jiżdiedu meta AVANDAMET jintuża flimkien ma ’ l - insulina.
24 Table 1.
25 Tabella 1.
Frequency of adverse reaction by treatment regimen Rosiglitazone Rosiglitazone with Rosiglitazone with monotherapy metformin metformin and sulphonylurea
Frekwenza ta ’ reazzjonijiet avversi skond it- terapija Monoterapija Rosiglitazone ma ’ Rosiglitazone ma ’ b’ rosiglitazone metformin metformin u sulphonylurea
Blood and the lymphatic system disorders Anaemia granulocytopaenia
Mard tad- demm u tas- sistema
Hyperlipaemia weight increase increased appetite
iperlipemija żjieda fil- piż żjieda fl- aptit
Hypoglycaemia
ipogliċemja
Gastrointestinal disorders Constipation
Mard gastro- intestinali stitikezza
Musculoskeletal and connective tissue disorders bone fractures4 myalgia*
Mard muskolu- skelettrali u tal- connective tissue ksur ta ’ l- għadam4 uġigħ fil- muskoli *
General disorders and administration site conditions Oedema
Mard ġenerali u kondizzjonijiet ta ’ mnejn jingħata edema
In a placebo-controlled one-year trial in patients with congestive heart failure NYHA class I-II, worsening or possible worsening of heart failure occurred in 6.4% of patients treated with rosiglitazone, compared with 3.5% on placebo.
26 Fi prova ta ’ sena kkontrollata bi plaċebo, f’ pazjenti b’ waqfien tal- qalb konġestiva NYHA klassi I- II, kien hemm deterjorament jew deterjorament possibbli ta ’ insuffiċjenza tal- qalb f’ 6. 4% tal- pazjenti trattati b’ rosiglitazone, meta mqabbla ma ’ 3. 5% bi plaċebo.
25 3 In a retrospective analysis of data from 42 pooled short-term clinical studies, the overall incidence of events typically associated with cardiac ischaemia was higher for rosiglitazone containing regimens, 1.99% versus combined active and placebo comparators, 1.51% [Hazard ratio 1.31 (95% confidence interval 1.01 - 1.70)].
3 F’ analiżi retrospettiva ta ’ tagħrif minn 42 studji kliniċi fuq tul ta ’ żmien qasir, miġbura flimkien, l - inċidenza ġenerali ta ’ każi assoċjati tipikament ma ’ iskemija kardijaka kienet ogħla fil- każ ta ’ terapija li jkun fiha rosiglitazone, 1. 99% kontra komparaturi attivi kombinati u plaċebo, 1. 51% [Hazard ratio 1. 31 (95% confidence interval 1. 01 – 1. 70)].
Angioedema skin reactions (e. g. urticaria, pruritis, rash) 5
anġjodema reazzjonijiet fil- ġilda (eż. urtikarja, ħakk, raxx)
urticaria Erythema Pruritis 6
urtikarja ħmura ħakk 6
Gastrointestinal symptoms such as nausea, vomiting, diarrhoea, abdominal pain and loss of appetite occur most frequently during initiation of therapy and resolve spontaneously in most cases.
Sintomi gastrointestinali bħal dardir, rimettar, dijarrea, uġigħ ta ’ żaqq u nuqqas ta ’ aptit iseħħu l- iktar frekwenti matul il- bidu tat- terapija u jieqfu waħidhom fil- biċċa l- kbira tal- każi.
In clinical studies in volunteers rosiglitazone has been administered at single oral doses of up to 20 mg and was well tolerated.
Fi studji kliniċi fuq volontiera, rosiglitazone ġie amministrat f’ dożi orali individwali sa ’ 20mg u kien ittollerat tajjeb.
27 5.1 Pharmacodynamic properties
5. 1 Tagħrif farmakodinamiku
Combinations of oral blood glucose lowering medicinal products, ATC code:
Prodotti Mediċinali orali kkombinati li jnaqqsu l- livell ta ’ zokkor fid - demm, kodiċi ATC:
AVANDAMET combines two antihyperglycaemic agents with complimentary mechanisms of action to improve glycaemic control in patients with type 2 diabetes: rosiglitazone maleate, a member of the thiazolidinedione class and metformin hydrochloride, a member of the biguanide class.
AVANDAMET jikkombina żewġ aġenti anti- ipergliċemiċi permezz ta ’ mekkaniżmu ta ’ azzjoni kumplimentari biex itejjeb il- kontrol tal- glukożju fid- demm f’ pazjenti b’ dijabete tip 2: rosiglitazone
An active controlled clinical trial (rosiglitazone up to 8 mg daily or metformin up to 2,000 mg daily) of 24 weeks duration was performed in 197 children (10-17 years of age) with type 2 diabetes.
Prova klinika kkontrollata attiva (rosiglitazone sa 8mg kuljum jew metformin sa 2, 000mg kuljum) li dam 24 ġimgha sar fuq 197 tifel u tifla (eta ’ bejn 10 u 17- il sena) b’ dijabete tat- tip 2.
28 There are no studies completed assessing long-term cardiovascular outcome in patients receiving rosiglitazone in combination with metformin.
M’ hemmx studji konklużi li jkejlu r- riżultati kardjovaskulari fuq medda twila f’ pazjenti li jieħdu rosiglitazone flimkien ma ’ metformin.
29 Metformin Metformin is a biguanide with antihyperglycaemic effects, lowering both basal and postprandial plasma glucose.
30 Metformin Metformin huwa biguanide b’ effetti anti- ipergliċemiċi, li jbaxxu kemm il- livell bażi u l- livell ta ’ wara l- ikel tal- glukożju fil- plażma.
Metformin may act via three mechanisms:
Metformin jista ’ jaġixxi permezz ta ’ tlett mekkaniżmi:
- by reduction of hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis
- permezz ta ’ tnaqqis fil- produzzjoni tal- glukożju fil- fwied billi jżomm lura glukoneoġenesi u
utilisation
periferali tal- glukożju.
Metformin stimulates intracellular glycogen synthesis by acting on glycogen synthase.
Metformin jistimola s- sinteżi tal- glajkoġen intraċellulari billi jaġixxi fuq glycogen synthase
Metformin increases the transport capacity of specific types of membrane glucose transporters (GLUT-1 and GLUT-4).
Metformin iżid il- kapaċità ta ’ trasport ta ’ tipi speċifiċi ta ’ membrane glucose transporters (GLUT- 1 u GLUT- 4)
Rosiglitazone Absorption Absolute bioavailability of rosiglitazone following both a 4 and an 8 mg oral dose is approximately 99%.
31 Rosiglitazone Assorbiment Biodisponibilità assoluta ta ’ rosiglitazone wara doża orali kemm ta ’ 4 mg kif ukoll ta ’ 8 mg hija ta ’ madwar 99%.
Administration of rosiglitazone with food resulted in no change in overall exposure (AUC), although a small decrease in Cmax (approximately 20-28%) and a delay in tmax (approximately 1.75 h) were
L- ogħti ta ’ rosiglitazone ma ’ l- ikel ma rriżulta fl- ebda bidla fl- esponiment globali (AUC), għalkemm tnaqqis żgħir fis- Cmax (madwar 20- 28%) u ttardjar fit- tmax (madwar 1. 75 h) ġew osservati meta imqabbla ma ’ l- ogħti ta ’ doża fi stat ta ’ sawm.
These small changes are not clinically significant and, therefore, it is not necessary to administer rosiglitazone at any particular time in relation to meals.
Dawn il- bidliet żgħar m’ humiex klinikament sinifikanti u għalhekk mhux neċessarju li rosiglitazone jiġi mogħti f’ xi ħin partikolari in relazzjoni ma ’ l- ikel.
The absorption of rosiglitazone is not affected by increases in gastric pH.
L - assorbiment ta ’ rosiglitazone mhux affetwat minn żiediet fil- pH gastriku.
Distribution The volume of distribution of rosiglitazone is approximately 14 l in healthy volunteers.
Distribuzzjoni Il- volum ta ’ distribuzzjoni ta ’ rosiglitazone hu madwar 141 f’ volontiera b’ saħħithom.
Elderly:
32 Anzjani:
Rosiglitazone Undesirable effects observed in animal studies with possible relevance to clinical use were as follows:
33 Rosiglitazone Effetti mhux mixtieqa osservati fi studji fuq annimali b’ relevanza possibbli għal użu kliniku huma kif ġej:
The relevance of this finding is unknown.
Ir - relevanża ta ’ dan il- fatt mhix magħrufa.
However, rosiglitazone promoted differentiation and reversal of mutagenic changes in human colon cancer cells in vitro.
Madankollu, in vitro, rosiglitazone għen fid- distinzjoni u r - revoka ta ’ tibdil mutaġeniku fiċ- ċelloli kanċeroġeni tal- kolon uman.
32 Metformin Non-clinical data for metformin reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction.
Metformin Tagħrif mhux kliniku għal metformin ma jiżvela l- ebda periklu speċjali għall- bniedem ibbażat fuq studji konvenzjonali dwar farmakoloġija ta ’ sigurta ’, tossiċità f’ dożi ripetuti, ġenotossiċità, potenzjal kanċeroġenu u tossiċità ta ’ riproduzzjoni.
Hypromellose (E464) Titanium dioxide (E171) Macrogol Iron oxide red (E172).
Hypromellose (E464) Titanium dioxide (E171) Macrogol Iron oxide red (E172).
Any unused product should be disposed of in accordance with local requirements.
Kull fdal tal- prodott li ma jkunx intuża ghandu jintrema kif jitolbu l- liġijiet lokali.
SmithKline Beecham plc 980 Great West Road Brentford, Middlesex TW8 9GS United Kingdom
SmithKline Beecham plc 980 Great West Road Brentford, Middlesex TW8 9GS Renju Unit
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu
Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- websajt ta ’ l- Aġenzija Ewropea dwar il - Mediċini (EMEA) http: www. emea. europa. eu.
AVANDAMET 2 mg/ 1000 mg film-coated tablets
AVANDAMET 2 mg/ 1000 mg pilloli miksija b’ rita.
Each tablet contains 2 mg of rosiglitazone (as rosiglitazone maleate) and 1000 mg of metformin hydrochloride (corresponding to metformin free base 780 mg).
Kull pillola fiha 2 mg rosiglitazone (bħala rosiglitazone maleate) u 1000 mg metformin hydrochloride (jikkorrespondu għal bażi ta ’ 780 mg metformin liberu).
Yellow film-coated tablets marked "gsk" on one side and "2/ 1000" on the other.
Pilloli sofor miksija b’ rita, bil- marka “ gsk ” fuq naħa waħda u “ 2/ 1000 ” fuq in- naħa l- oħra.
For the different dosage regimens, AVANDAMET is available in appropriate strengths.
Għal regoli ta ’ trattament b’ dożi differenti, AVANDAMENT jinstab f’ dożi adattati.
35 Triple oral therapy (rosiglitazone, metformin and sulphonylurea) (see section 4.4)
36 Terapija orali trippla (rosiglitazone, metformin u sulphonylurea) (ara sezzjoni 4. 4)
- hypersensitivity to rosiglitazone, metformin hydrochloride or to any of the excipients
− sensittività eċċessiva għal rosiglitazone, għal metformin hydrochloride jew għal xi sustanzi mhux attivi − insuffiċjenza tal- qalb jew passat ta ’ din il- kundizzjoni (stadji tan- New York Heart Association (NYHA) I sa IV) − Sindromu Koronarju Akut (anġina instabbli, NSTEMI u STEMI (ara sezzjoni 4. 4) − mard akut jew kroniku li jista jikkawża nuqqas ta ’ ossiġnu fil- livell ċellolari bħal: − falliment tas- sistema tal- qalb jew respiratorja − infart tal- qalb reċenti − xokk − indeboliment tal- fwied − intossikazzjoni akuta bl- alkoħol, vizzju ta ’ xorb alkoħoliku eċċessiv (ara sezzjoni 4. 4) − stat dijabetiku ta ’ ketoaċidożi jew stat dijabetiku pre- koma − insuffiċjenza tal- kliewi jew il- kliewi ma jaħdmux sew eż. livelli seroloġiċi tal- krejatinina > 135 µmol/ l fl- irġiel > 110µmol/ l fin- nisa u/ jew tneħħija ta ’ kreatinina ta ’ < 70 ml/ min (ara sezzjoni. 4) − kundizzjonijiet akuti li jistgħu jibdlu l- funzjoni tal- kliewi bħal: − nuqqas ta ’ ilma fil- ġisem − infezzjoni qawwija − xokk − amministrazzjoni intravaskulari ta ’ kimiċi għall- kuntrast li fihom Iodine (ara sezzjoni 4. 4) − nisa li qed ireddgħu.
- acute conditions with the potential to alter renal function such as:
37 4. 4 Twissijiet speċjali u prekawzjonijiet speċjali għall- użu
Insulin should only be added to established rosiglitazone therapy in exceptional cases and under close supervision.
38 L- insulina għandha tiżdied biss f’ kura stabbilita b’ rosiglitazone f’ każijiet speċjali u taħt osservazzjoni mill- viċin.
37 Patients experiencing an ACS have not been studied in rosiglitazone controlled clinical trials.
Sindromu Koronarju Akut (ACS) Pazjenti li esperjenzaw ACS ma ġewx studjati fi studji kliniċi kkontrollati b’ rosiglitazone.
Weight gain In clinical trials with rosiglitazone there was evidence of dose-related weight gain, which was greater when used in combination with insulin.
Żjieda fil- piż Fi studji kliniċi b’ rosiglitazone kien hemm evidenza ta ’ żjieda fil- piż relatat mad- doża, li kienet akbar meta intuża flimkien ma 'insulina.
Surgery As AVANDAMET contains metformin hydrochloride, the treatment should be discontinued 48 hours before elective surgery with general anaesthesia and should not usually be resumed earlier than 48 hours afterwards.
39 operazzjoni bil- loppju ġenerali, u ġeneralment m’ għandux jerġa ’ jinbeda qabel igħaddu 48 siegħa.
This increased incidence was
Mard ta ’ l- għadam Fi studju fit- tul ġiet osservata inċidenza akbar ta ’ ksur fl- għadam (fis- saqajn, fl- idejn u fid- dirgħajn) f’ pazjenti nisa li jkunu qed jieħdu rosiglitazone bħala monoterapija (ara sezzjoni 4. 8).
38 noted after the first year of treatment and remained during the course of the study.
Din l- inċidenza akbar ġiet innotata wara l- ewwel sena tat- trattament u matul il- kumplament ta ’ l- istudju.
Cationic medicinal products that are eliminated by renal tubular secretion (e. g. cimetidine) may interact with metformin by competing for common renal tubular transport systems.
40 Prodotti mediċinali katajoniċi li jiġu eliminati permezz ta’ sekrezzjoni tubulari renali (e. ż. cimetidine) jistagħu ma jaqblux ma metformin billi jikkompetu għall- istess sistema ta ’ trasport tubulari renali.
Co-administration of rosiglitazone with rifampicin (an inducer of CYP2C8) resulted in a 66% decrease in rosiglitazone plasma concentrations.
L- għoti flimkien ta ’ rosiglitazone ma ’ rifampiċin (inducer ta ’ CYP2C8) irriżulta fi tnaqqis ta ’ 66% fil- konċentrazzjonijiet ta ’ rosiglitazone fil- plażma.
The
Ma jistax jiġi eskluż li inducers oħra (e. ż. phenytoin, carbamazepine, phenobarbital, St John’ s wort) jistgħu wkoll ikollhom effett fuq l - esponiment għal rosiglitazone.
39 rosiglitazone dose may need to be increased.
Jista ’ jkun li d- doża ta ’ rosiglitazone għandha tiżdied.
Rosiglitazone has been reported to cross the human placenta and to be detectable in foetal tissues.
Ġie rrappurtat li rosiglitazon jgħaddi mill- plaċenta umana u kien hemm traċċi tiegħu fit- tessuti tal- fetu.
Therefore, AVANDAMET should not be used during pregnancy.
41 Għalhekk, AVANDAMET m’ għandux jintuża waqt it- tqala.
Adverse reactions for each treatment regimen are presented below by system organ class and absolute frequency.
Reazzjonijiet mhux mixtieqa għal kull terapija huma elenkati hawn taħt skond il- klassi tas- sistemi u l - organi u l- frekwenza assoluta.
Adverse reaction frequency categories
Il- kategoriji ta ’ frekwenza ta ’ reazzjonijiet mhux mixtieqa assenjati fuq bażi ta ’ esperjenza minn provi kliniċi mhux neċessarjament jirriflettu l- frekwenza ta ’ effetti mhux mixtieqa li jseħħu fil- prattika klinika.
Frequencies are defined as: very common (≥ 1/ 10), common (≥ 1/ 100 to < 1/ 10), uncommon (≥ 1/ 1,000 to < 1/ 100), rare (≥ 1/ 10,000 to < 1/ 1000) and very rare (< 1/ 10,000 including isolated reports).
Il- frekwenzi huma definiti bħala: komuni ħafna (≥1/ 10), komuni (≥1/ 100 sa < 1/ 10), mhux komuni (≥1/ 1, 000 sa < 1/ 100), rari (≥1/ 10, 000 sa < 1/ 1000) u rari ħafna (< 1/ 10000 inkluż rapporti iżolati)..
41 Table 1.
42 Tabella 1.
The incidence of heart failure in combination with insulin (rosiglitazone added to established insulin therapy) was 2.4%, compared to insulin alone, 1.1%.
43 ma ’ l- insulina (rosiglitazone miżjud ma ’ terapija b’ insulina stabbilita) kienet ta ’ 2. 4%, meta mqabbla ma ’ insulina waħedha, 1. 1%.
42 In a placebo-controlled one-year trial in patients with congestive heart failure NYHA class I-II, worsening or possible worsening of heart failure occurred in 6.4% of patients treated with rosiglitazone, compared with 3.5% on placebo.
Fi prova ta ’ sena kkontrollata bi plaċebo, f’ pazjenti b’ waqfien tal- qalb konġestiva NYHA klassi I- II, kien hemm deterjorament jew deterjorament possibbli ta ’ insuffiċjenza tal- qalb f’ 6. 4% tal- pazjenti trattati b’ rosiglitazone, meta mqabbla ma ’ 3. 5% bi plaċebo.
3 In a retrospective analysis of data from 42 pooled short-term clinical studies, the overall incidence of events typically associated with cardiac ischaemia was higher for rosiglitazone containing regimens, 1.99% versus combined active and placebo comparators, 1.51% [Hazard ratio 1.31 (95% confidence interval 1.01 - 1.70)].
3 F’ analiżi retrospettiva ta ’ tagħrif minn 42 studji kliniċi fuq tul ta ’ żmien qasir, miġbura flimkien, l - inċidenza ġenerali ta ’ każi assoċjati tipikament ma ’ iskemija kardijaka kienet ogħla fil- każ ta ’ terapija li jkun fiha rosiglitazone, 1. 99% kontra komparaturi attivi kombinati u plaċebo, 1. 51% [Hazard ratio 1. 31 (95% confidence interval 1. 01 – 1. 70)].
This risk was increased when rosiglitazone was added to established insulin and in patients receiving nitrates for known ischaemic heart disease.
Dan ir- riskju żdied meta rosiglitazone ġie miżjud f’ pazjenti stabbiliti fuq insulina u f’ pazjenti li kienu qegħdin jieħdu nitrates minħabba mard iskemu tal- qalb magħruf.
Immune system disorders (see Skin and subcutaneous tissue disorders) anaphylactic reaction
Mard tas- sistema immuni (ara mard tal- ġilda u tat- tessuti ta ’ taħt il- ġilda)
Cardiac disorders congestive heart failure/ pulmonary oedema
Mard tal- qalb
Skin and subcutaneous tissue disorders (see Immune system disorders) angioedema skin reactions (e. g. urticaria, pruritis, rash) 5
Mard tal- ġilda u tat- tessuti ta ’ taħt il- ġilda (ara Mard tas- sistema immuni) 5
Table 3 presents adverse reactions by system organ class and by frequency category.
It- Tabella 3 tippreżenta ir- reazzjonijiet mhux mixtieqa skond il- kategoriji tal- klassi tas- sistemi u l - organi u l- frekwenza.
Frequency categories are based on information available from metformin Summary of Product Characteristics available in the EU.
Kategoriji tal- frekwenza huma bbażati fuq informazzjoni li hemm fis- Sommarju tal- Karatteristici tal- Prodott disponibbli fl- UE.
Hepatobiliary disorders liver function disorders hepatitis
Mard tal- fwied u tal- marrara mard tal- funzjoni tal- fwied epatite
AVANDAMET combines two antihyperglycaemic agents with complimentary mechanisms of action to improve glycaemic control in patients with type 2 diabetes: rosiglitazone maleate, a member of the
AVANDAMET jikkombina żewġ aġenti anti- ipergliċemiċi permezz ta ’ mekkaniżmu ta ’ azzjoni kumplimentari biex itejjeb il- kontrol tal- glukożju fid- demm f’ pazjenti b’ dijabete tip 2: rosiglitazone