qanastek/EMEA-V3 huggingface dataset:
Rosiglitazone and glimepiride are both highly protein bound and would not be expected to be cleared by haemodialysis.
Rosiglitazone u glimepiride it- tnejn kemm huma mimlijin proteini u ma jitneħħewx malajr b’ emodijalisi.
Combinations of oral blood glucose lowering drugs, ATC code:
Kombinazzjonijiet ta ’ mediċini li jittieħdu mill- ħalq u li jnaqqsu l - glukosju fid- demm, Kodiċi ATC:
AVAGLIM combines two antidiabetic 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 glimepiride, a member of the sulphonylurea class.
Rosiglitazone maleate, membru tal- kategorija thiazolidinedione u glimepiride, membru tal- kategorija sulphonylurea.
Thiazolidinediones act primarily by reducing insulin resistance and sulphonylureas act primarily by stimulating release of insulin from functioning pancreatic β -cells.
Thiazolidinediones jaġixxu primarjament billi jnaqqsu r- reżistenza għall- insulina u sulphonylureas billi jistimulaw ir- rilaxx ta ’ l- insulina minn ċelluli β tal- pankreas li jkunu jiffunzjonaw.
A study comparing AVAGLIM to monotherapy rosiglitazone or glimepiride demonstrated incremental benefit in control of glycaemia of the fixed-dose combination over monotherapy.
Studju li jqabbel AVAGLIM ma ’ monoterapija b’ rosiglitazone jew glimepiride wera benefiċċju akbar fil- kontroll ta ’ gliċemija tal- kombinazzjoni b’ doża fissa fuq monoterapija.
No new safety findings were observed.
Ma ġewx osservati xi sejbiet ġodda ta ’ sigurta`.
The clinical trial program in support of this fixed dose combination only compared rosiglitazone and glimepiride to glimepiride monotherapy and not to monotherapy with other sulphonylureas.
Il- programm ta ’ prova klinika b’ appoġġ għal din il- kombinazzjoni ta ’ doża fissa qabbel biss rosiglitazone u glimepiride ma ’ monoterapija bi glimepiride u mhux ma monoterapija ma sulphonylureas oħra.
Rosiglitazone Rosiglitazone is a selective agonist at the PPARγ (peroxisome proliferator activated receptor gamma) nuclear receptor and is a member of the thiazolidinedione class of antihyperglycaemic agents.
Rosiglitazone Rosiglitazone huwa agonist selettiv fir- riċettur nukleari PPARγ (peroxisome proliferator activated receptor gamma) u hu membru tal- kategorija ta ’ thiazolidinedione ta ’ aġenti anti- ipergliċemiċi.
It reduces glycaemia by reducing insulin resistance at adipose tissue, skeletal muscle and liver.
Hu jnaqqas il- gliċemija billi jnaqqas ir- reżistenza għall- insulina fit- tessut xaħmi, fil- muskolu skeletriku u fil- fwied.
The antihyperglycaemic activity of rosiglitazone has been demonstrated in a number of animal models of type 2 diabetes.
L- attivita` anti- ipergliċemika ta ’ rosiglitazone intweriet f’ numru ta ’ mudelli ta ’ annimali b’ dijabete tat - tip 2.
In addition, rosiglitazone preserved ß-cell function as shown by increased pancreatic islet mass and insulin content and prevented the development of overt hyperglycaemia in animal models of type 2 diabetes.
Barra dan, rosiglitazone żamm il- funzjoni taċ- ċelluli ß kif deher b’ żjieda fil- massa islet pankreatika u kontenut ta ’ insulina u pprevjena l- iżvilupp ta ’ ipergliċemija mhux moħbija f’ mudelli ta ’ annimali bid- dijabete ta ’ tip 2.
Rosiglitazone did not stimulate pancreatic insulin secretion or induce hypoglycaemia in rats and mice.
Rosiglitazone ma stimulax it- tnixxija ta ’ insulina fil- pankreas u lanqas ma kkawża ipogliċemija f’ firien jew ġrieden.
The major metabolite (a para-hydroxy-sulphate) with high affinity to the soluble human PPARγ, exhibited relatively high potency in a glucose tolerance assay in obese mice.
Il- metabolit prinċipali (sulfat para- hydroxy) b’ xebħ kbir mal- PPARγ uman li jinħall, wera potenza relattivament għolja f’ analiżi ta ’ tolleranza ta ’ glukosju fi ġrieden ħoxnin.
The clinical relevance of this observation has not been fully elucidated.
Ir- relevanza klinika ta’ din l- osservazzjoni għadha ma ġietx iċċarata biżżejjed.
In clinical trials, the glucose lowering effects observed with rosiglitazone are gradual in onset with near maximal reductions in fasting plasma glucose (FPG) evident following approximately 8 weeks of therapy.
Fi provi kliniċi, l- effetti li jnaqqsu l- glukosju osservati b’ rosiglitazone jibdew bil- mod waqt li kważi t - tnaqqis massimu fil- glukosju bi plażma fis- sawm (FPG) kienu evidenti wara bejn wieħed u ieħor 8 ġimgħat ta ’ terapija.
The improved glycaemic control is associated with reductions in both fasting and post- prandial glucose.
Il- kontroll gliċemiku aħjar hu assoċjat ma ’ tnaqqis ta ’ glukosju kemm waqt sawm u kemm wara l- ikel.
12 Rosiglitazone was associated with increases in weight.
13 Rosiglitazone kien assoċjat ma ’ żjidiet fil- piż.
In mechanistic studies, the weight increase was predominantly shown to be due to increased subcutaneous fat with decreased visceral and intra-hepatic fat.
Fi studji mekkanistiċi, iż- żjieda fil- piż deher li kienet prinċipalment dovuta għal żjieda fix- xaħam ta ’ taħt il- ġilda flimkien ma ’ tnaqqis ta ’ xaħam vixxerali u intra- epatiku.
Consistent with the mechanism of action, rosiglitazone reduced insulin resistance and improved pancreatic ß-cell function.
Waqt li konsistenti fil- mekkaniżmu ta ’ azzjoni, rosiglitazone naqqas ir- reżistenza għall- insulina u tejjeb il- funzjoni biċ- ċellula ß fil- pankreas.
Improved glycaemic control was also associated with significant decreases in free fatty acids.
Titjib ta ’ kontroll gliċemiku ġie wkoll assoċjat ma ’ tnaqqis sostanzjali ta ’ aċidi xaħmin liberi.
As a consequence of different but complementary mechanisms of action, dual oral therapy of rosiglitazone with a sulphonylurea or metformin resulted in additive effects on glycaemic control in type 2 diabetic patients.
Konsegwenza ta ’ mekkaniżmi differenti imma kumplementari ta ’ azzjoni, terapija doppja mill- ħalq b’ rosiglitazone b’ sulphonylurea jew metformin irriżultat f’ effetti addittivi fil- kontroll gliċemiku f’ pazjenti b’ dijabete ta ’ tip 2.
In studies with a maximal duration of three years, rosiglitazone given once or twice daily produced a sustained improvement in glycaemic control (FPG and HbA1c).
Fi studji li jieħdu massimu ta ’ tliet snin, rosiglitazone mogħti darba jew darbtejn kuljum ipproduċa titjib kontinwu fil- kontroll gliċemiku (FPG u HbA1c).
A more pronounced glucose-lowering effect was observed in obese patients.
Effett ieħor aktar ċar ta ’ nuqqas ta ’ glukosju ġie osservat f’ pazjenti ħoxnin ħafna.
An outcome study has not been completed with rosiglitazone, therefore the long-term benefits associated with improved glycaemic control have not been demonstrated.
Studju dwar ir- riżultati finali għad ma ġiex mitmum dwar rosiglizatone, għalhekk il- benefiċċji fit- tul assoċjati ma ’ kontroll gliċemiku aħjar għad ma dehrux.
At 18 months, in an ongoing long term comparator study, rosiglitazone in dual oral therapy with metformin or a sulphonylurea was non-inferior to the combination of sulphonylurea plus metformin for lowering HbA1c.
Wara 18- il xahar, fi studju kontinwu fit- tul b’ komparaturi, rosiglitazone b’ terapija doppja orali ma ’ metformin jew xi sulphonylurea ma kienx inferjuri għal kombinazzjoni ta ’ sulphonylurea u metformin biex inaqqas l- HbA1c.
There are no studies completed assessing long-term cardiovascular outcome in patients receiving rosiglitazone.
Ma hemmx studji kompletati li jivvalutaw ir- riżultat kardjovaskulari fit- tul f’ pazjenti li jieħdu rosiglitazone.
Glimepiride Glimepiride is an orally active hypoglycaemic substance belonging to the sulphonylurea group.
Glimepiride Glimepiride hi sustanza ipogliċemika attiva li tittieħed mill- ħalq u li tagħmel mall- grupp ta ’ sulphonylureas.
It may be used in non-insulin dependent diabetes mellitus.
Tista ’ tintuża għal dijabete mellitus li ma tkunx dipendenti fuq insulina.
Glimepiride acts mainly by stimulating the release of insulin from the beta cells of the pancreas.
Glimepiride taġixxi prinċipalment billi tistimula r- rilaxx ta ’ insulina miċ- ċelluli beta tal- pankreas.
As with other sulphonylureas, this effect is based on an improvement in responsiveness of pancreatic beta cells to the physiological glucose stimulus.
Bħal fil- każ ta ’ sulphonylureas oħra, dan l- effett hu bażat fuq titjib fir- rispons taċ- ċelluli beta tal- pankreas għall - istimolu għal glukosju fisjoloġiku.
In addition, glimepiride seems to have pronounced extrapancreatic effects, also postulated for other sulphonylureas.
Barra dan, glimepiride jidher li għandu effetti ċari extra - pankreatiċi, li japplika wkoll għal sulphonylureas oħra.
Sulphonylureas regulate insulin secretion by closing the ATP-dependent potassium channels in the beta cell membrane.
Sulphonylureas jirregolaw it- tnixxija ta ’ insulina billi jagħlqu l- kanali dipendenti fuq ATP ta ’ potassju fil- membrana taċ- ċelluli beta.
Closure of the potassium channels leads to depolarisation of the beta cell and results by opening of the calcium channels – to an increased influx of calcium into the cell.
L- għeluq tal- kanali tal- potassju jwassal għal depolarizzazzjoni taċ - ċelluli beta u jirriżulta bil- ftuħ tal- kanali tal- kalċju – f’ influss miżjud ta ’ kalċju għal ġoċ- ċellula.
This leads to a release of insulin by exocytosis.
Dan iwassal għal rilaxx ta ’ insulina permezz ta ’ eżoċitosi.
Glimepiride binds with a high exchange rate to a beta cell membrane protein which is associated with the ATP-sensitive potassium channel but which differs from the usual sulphonylurea binding site.
Glimepiride teħel b’ rata ta ’ bdil mgħaġġel ma ’ proteina ta ’ membrana ta ’ ċellula beta li hi assoċjata mal- kanal tal- potassju sensittiv għal ATP iżda li tiddifferixxi mis- sit normali li fih jeħlu s - sulphonylureas.
Extrapancreatic effects include an improvement in insulin sensitivity of peripheral tissue and a reduction in hepatic uptake of insulin.
Effetti extra- pankreatiċi jinkludu titjib fis- sensittivita` għall- insulina ta ’ tessuti periferali u tnaqqis ta ’ insulina li tgħaddi fil- fwied.
Glimepiride very rapidly increases the number of active glucose transport molecules in the plasma membranes of muscle and fat cells, resulting in stimulation of glucose uptake.
Glimepiride iżid malajr ħafna n- numru ta ’ molekuli attivi għat- trasport ta ’ glukosju fil- membrani tal - plażma fiċ- ċelluli tal- muskoli u x- xaħam, u dan jirriżulta fi stimulazzjoni ta ’ kif jgħaddi l- glukosju.
Glimepiride increases the activity of glycosyl-phosphatidylinositol-specific phospholipase C, which may be associated with drug-induced lipogenesis and glycogenesis in isolated fat and muscle cells.
Glimepiride iżid l- attivita` tal - glycosyl- phosphatidylinositol- specific phospholipase C, li jista ’ jiġi assoċjat ma ’ lipoġenesi u glikoġenesi kaġunati minn mediċini f’ ċelluli iżolati tax- xaħam u l- muskoli.
Glimepiride inhibits the hepatic glucose production by increasing the intracellular concentration of fructose-2,6 bisphosphate, which in turn inhibits gluconeogenesis.
Glimepiride jimpedixxi l- produzzjoni ta ’ glukosju fil- fwied billi jżid il- konċentrazzjoni intra- ċellulari ta ’ fructose- 2- 6 biphosphate, li min- naħa tiegħu jimpedixxi l- glukoneoġenesi.
The minimum effective oral dose is approximately 0.6 mg.
Id- doża minima effettiva li tittieħed mill- ħalq hi bejn wieħed u ieħor 0. 6 mg.
The effect of glimepiride is dose- dependent and reproducible.
L- effett ta ’ glimepiride jiddependi mid- doża u jista ’ jkun riprodott.
The physiological response to acute physical exercise, a reduction in insulin secretion, is maintained during treatment with glimepiride.
Ir- rispons fisjoloġiku għal eżerċizzju fiżiku akut, tnaqqis mit- tnixxija ta ’ l- insulina, jinżamm waqt trattament bi glimepiride.
There was no significant difference in the effect regardless of whether the drug was taken 30 minutes before or immediately before a meal.
Ma kien hemm ebda differenza sostanzjali fl- effett kemm jekk il- mediċina tkun ittieħdet 30 minuta qabel l- ikel u kemm jekk tkun ittieħdet immedjatament wara l- ikel.
In diabetic patients, good metabolic control over 24 hours can be achieved with a single daily dose.
F’ pazjenti dijabetiċi, kontroll metaboliku tajjeb jista ’ jinkiseb b’ doża waħda kuljum.
Although the hydroxy metabolite of glimepiride caused a small but significant reduction in serum glucose, it accounts for only a minor part of the total drug effect.
Għalkemm il- metabolit hydroxy ta ’ glimepiride ikkawża tnaqqis żgħir iżda sinifikanti ta ’ glukosju fis- serum, dan hu biss parti żgħira mill - effett totali tal- mediċina.
Single oral doses of glimepiride in 14 healthy adult subjects had no clinically significant effect on the steady-state pharmacokinetics of rosiglitazone.
Dożi singoli orali ta ’ glimepiride f’ 14- il suġġett adulti u f’ saħħithom ma kellhom ebda effett sinifikanti kliniku fuq il- farmakokinetiċi steady- state ta ’ rosiglitazone.
No clinically significant reductions in glimepiride AUC and Cmax were observed after repeat doses of rosiglitazone for eight days in healthy adult subjects.
Ebda tnaqqis sinifikanti kliniku ta ’ AUC u Cmax ma ġie osservat wara dożi ripetuti ta ’ rosiglitazone għal tmint ijiem f’ suġġetti adulti f’ saħħithom.
In a bioequivalence study under fasted conditions, the AUC and Cmax of rosiglitazone and the AUC of glimepiride following a single dose of a 4 mg/ 4 mg combination tablet were bioequivalent to concomitant administration of rosiglitazone 4 mg and glimepiride 4 mg.
Fi studju ta ’ bijoekwivalenza f’ kondizzjonijiet ta ’ sawm, l- AUC u Cmax ta ’ rosiglitazone u l- AUC ta ’ glimepiride wara doża waħda ta ’ pillola 4 mg/ 4 mg kombinata kienu bijoekwivalenti għal teħid konkomitanti ta ’ rosiglitazone 4 mg u glimepiride 4 mg.
In the fed state, the rate and extent of absorption of the rosiglitazone-glimepiride 4 mg/ 4 mg combination were equivalent to concomitant administration of 4 mg rosiglitazone and 4 mg glimepiride.
Fuq stonku mimli, ir- rata u l- firxa ta ’ assorbiment tal- kombinazzjoni rosiglitazone- glimepiride 4 mg/ 4 mg kienu ekwivalenti għat- teħid konkomitanti ta ’ 4 mg rosiglitazone u 4 mg glimepiride.
Administration of the 4 mg/ 4 mg combination with food led to an increase in glimepiride exposure compared to that observed on administration in the fasted state.
L - għoti tal- kombinazzjoni 4 mg/ 4 mg ma ’ l- ikel wassal għal żjieda fl- esponiment ta ’ glimepiride meta mqabbel ma ’ dak osservat fl- għoti fi stat sajjem.
Glimepiride AUC0-t, AUC0-inf and Cmax were increased by 30%, 19% and 55% respectively, on average.
L- AUC0- t, AUC0- inf u Cmax ta ’ glimepiride żdiedu bi 30%, 19% u 55% rispettivament, bħala medja.
For rosiglitazone, Cmax values were decreased by approximately 32% with food.
Fil- kas ta ’ rosiglitazone, il- valuri Cmax naqsu bejn wieħed u ieħor bi 32% ma ’ l- ikel.
The AUC and Cmax of glimepiride increased in a dose-proportional manner following administration of rosiglitazone-glimepiride 4 mg/ 1 mg, 4 mg/ 2 mg, and 4 mg/ 4 mg.
L- AUC u Cmax ta ’ glimepiride żdiedu b’ mod proporzjonat skond id- dożi wara t- teħid ta ’ rosiglitazone - glimepiride 4 mg/ 1 mg, 4 mg/ 2 mg, u 4 mg/ 4 mg.
The following statements reflect the pharmacokinetic properties of the individual components of AVAGLIM.
Il- konklużjonijiet mniżżlin hawn taħt jirriflettu l- effetti farmakokinetiċi tal- komponenti individwali ta ’ AVAGLIM.
Rosiglitazone Absorption Absolute bioavailability of rosiglitazone following both a 4 and an 8 mg oral dose is approximately 99%.
Rosiglitazone Assorbiment Il - bijodisponibilta` assoluta ta ’ rosiglitazone wara dożi orali ta ’ 4 u anke 8 mg hi bejn wieħed u ieħor ta ’ 99%.
Plasma concentrations are approximately dose proportional over the therapeutic dose range.
Il- konċentrazzjonijiet tal- plażma huma bejn wieħed u ieħor fi proporzjon skond il- firxa 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 fasted state.
It- teħid ta ’ rosiglitazone ma ’ l- ikel ma rriżulta f’ ebda bidla fl- esponiment ġenerali (AUC), għalkemm ġew osservati tnaqqis żgħir fis - Cmax (bejn wieħed u ieħor 20- 28%) u dewmien fit - tmax (bejn wieħed u ieħor 1. 75 s) meta mqabbla ma ’ teħid ta ’ dożi 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 mhumiex klinikament sinifikanti u għalhekk mhux meħtieġ li rosiglitazone jingħata f’ xi ħin partikolari minħabba l- ikel.
The absorption of rosiglitazone is not affected by increases in gastric pH.
L- assorbiment ta ’ rosiglitazone mhuwiex affettwat minn żjidiet 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 bejn wieħed uieħor 14 1 f’ voluntieri f’ saħħithom.
Plasma protein binding of rosiglitazone is high (approximately 99.8%) and is not influenced by concentration or age.
It- twaħħil tal- proteini tal- plażma ta ’ rosiglitazone hu għoli (bejn wieħed u ieħor 99. 8%) u mhuwiex influwenzat minn konċentrazzjoni jew minn eta`.
The protein binding of the major metabolite (a para-hydroxy-sulphate) is very high (> 99.99%).
It- twaħħil tal- proteini tal - metabolit prinċipali (sulfat para- hydroxy) hu għoli ħafna (99. 99%).
Metabolism Metabolism of rosiglitazone is extensive with no parent compound being excreted unchanged.
Metaboliżmu Il- metaboliżmu ta ’ rosiglitazone hu estensiv u mingħajr ebda ġenitur kompost ma jiġi ppurgat bla jinbidel.
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- demetilazzjoni u idrosilazzjoni, segwiti konjugazzjoni ma ’ sulfat u aċidu glukuroniku.
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- kontribuzzjoni tal- metabolit ewlieni (sulfat para - idrosija) għall- attivita` ġenerali anti- ipergliċemika ta ’ rosiglitazone me ġietx iċċarata għal kollox fil - bniedem u ma jistax jiġi eskluż li l- metabolit jista ’ jikkontribwixxi għall- attivita`.
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 m’ għandux iqajjem dubji dwar sigurta` dwar popolazzjonijiet fil- mira jew speċjali għaliex indeboliment tal- fwied hu kontra- indikat u l- istudji kliniċi tal- fażi III inkludew numru konsiderevoli ta ’ pazjenti anzjani u pazjenti b’ indeboliment ħafif sa moderat tal- kliewi.
In vitro studies demonstrate that rosiglitazone is predominantly metabolised by CYP2C8, with a minor contribution by CYP2C9.
15 Studji in vitro juru li rosiglitazone hu prinċipalment metabolizzat b’ CYP2C8, b’ kontribuzzjoni żgħira ta ’ CYP2C9.
14 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.
Billi m’ hemmx inibizzjoni in vitro sinifikanti ta ’ CYP1A2, 2A6, 2C19, 2D6, 2E1, 3A jew 4A ma ’ rosiglitazone, hemm probabbilta` żgħira ta ’ interazzjonijiet sinifikanti bażati fuq metaboliżmu ma ’ sustanzi metabolizzati b’ dawn l- enzimi 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.
Studju in vivo dwar interazzjoni ma ’ warfarin indika li rosiglitazone ma joħloqx interazzjoni ma ’ substrati CYP2C9 in vivo.
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 Tneħħija ta ’ plażma totali ta ’ rosiglitazone hi madwar 3 l/ s u l- half- life ta ’ eliminazzjoni terminali ta ’ rosiglitazone hi bejn wieħed u ieħor 3- 4 s.
There is no evidence for unexpected accumulation of rosiglitazone after once or twice daily dosing.
Ma hemm ebda evidenza għal xi akkumulazzjoni mhux mistennija ta ’ rosiglitazone wara dożi ta ’ 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.
Ir- rotta ewlenija ta ’ eliminazzjoni mill- ġisem hi l- awrina li permezz tagħha titneħħa bejn wieħed u ieħor żewġ terzi tad - doża, waqt li eliminazzjoni minn purgar hi bejn wieħed u ieħor 25% tad- doża.
No intact active substance is excreted in urine or faeces.
Ebda sustanza attiva intatta ma tiġi eliminata fl- awrina jew fil- purgar.
The terminal half-life for radioactivity was about 130 h indicating that elimination of metabolites is very slow.
Il- half- life terminali ta ’ radjoattivita` kienet madwar 130 s li indikat li l- eliminazzjoni tal- metaboliti kienet baxxa 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.
Akkumulazzjoni ta ’ metaboliti fil - plażma hi mistennija wara dożi ripetuti, speċjalment dik tal- metabolita ewlenija (para- hydroxy - sulphate) li dwaru tkun antiċipata akkumulazzjoni ta ’ tmien darbiet aktar.
Glimepiride Absorption After oral administration, glimepiride is completely (100%) absorbed from the gastrointestinal tract.
Glimepiride Assorbiment Wara li jittieħed mill- ħalq, glimepiride jiġi assorbit kompletament mill- apparat gastrointestinali.
Studies with single oral doses in normal subjects and with multiple oral doses in patients with type 2 diabetes mellitus have shown significant absorption of glimepiride within 1 h after administration and Cmax at approximately 2.5 h.
Studji b’ dożi singoli orali f’ suġġetti normali u b’ dożi orali multipli fuq pazjenti bid- dijabete mellitus tat - tip 2 urew assorbiment sinifikanti ta ’ glimepiride siegħa wara li jittieħdu u Cmax bejn wieħed u ieħor wara 2. 5 sigħat.
There is a linear relationship between dose and both Cmax and AUC.
Hemm relazzjoni lineari kemm bejn id- doża u kemm Cmax u l - AUC.
Distribution After intravenous dosing in normal subjects, the volume of distribution was 8.8 l (113 ml/ kg), and the total body clearance was 47.8 ml/ min.
Distribuzzjoni Wara dożi fil- vini fuq suġġetti normali, il- volum ta ’ distribuzzjoni kien 8. 81 (113 ml/ mg), u t- tneħħija totali mill- ġisem kienet 47. 8 ml/ min.
Protein binding was greater than 99.5%.
L- irbit tal- proteini kien aktar minn 99. 5%.
Metabolism Glimepiride is completely metabolised by oxidative biotransformation after either an intravenous or oral dose.
Metaboliżmu Glimepiride jiġi metabolizzat kompletament b’ bijotrasformazzjoni ossidattiva wara doża ġol- vina jew mill- ħalq.
The major metabolites are the cyclohexyl hydroxy methyl derivative (M1) and the carboxyl derivative (M2).
Il- metaboli ewlenin huma d- derivattiva cyclohexyl hydroxy methyl (M1) u d- derivattiva carboxyl (M2).
CYP2C9 has been shown to be involved in the biotransformation of glimepiride to M1.
CYP2C9 deher li kien involut fil- bijotrasformazzjoni ta ’ glimepiride għal M1.
M1 is further metabolised to M2 by one or several cytosolic enzymes.
M1 jiġi wkoll metabolizzat għal M2 b’ enzima ċitosolika waħda jew aktar.
M1, but not M2, possesses about 1/ 3 of the pharmacological activity as compared to its parent in an animal model.
M1, iżda mhux M2, tippossied kważi 1/ 3 ta ’ l- attivita` farmakoloġika meta mqabbla mal- ġenitur tagħha f’ annimal mudell.
The clinical significance of the glucose-lowering effect of M1 is unclear.
Is- sinifikat kliniku ta ’ l- effett ta ’ tnaqqis ta ’ glukosju ta ’ M1 mhuwiex ċar.
Elimination The elimination half-life of glimepiride is approximately 5 to 8 h.
Eliminazzjoni L- eliminazzjoni tal- half- life ta ’ glimepiride hi bejn wieħed u ieħor minn 5 sa 8 sigħat.
When 14C-glimepiride was given orally, approximately 60% of the total radioactivity was recovered in the urine in seven days and M1 (predominant) and M2 accounted for 80 to 90% of that recovered in the urine.
Meta 14C - glimepiride ingħata mill- ħalq, kważi 60% tar- radjoattivita` totali ġiet irkuprata mill- awrina f’ sebat ijiem u M1( predominanti) u M2 kienu jiffurmaw minn 80 sa 90% ta ’ dak irkuprat mill- awrina.
Approximately 40% of the total radioactivity was recovered in faeces and M1 and M2 (predominant) accounted for about 70% of that recovered in faeces.
Kważi 40% tar- radjoattivita` totali ġie rkuprat mill- purgar u M1 u M2 (predominanti) kienu jiffurmaw kważi 70% ta ’ dak irkuprat mill- purgar.
No parent drug was recovered from urine or faeces.
Ma ġiet irkuprata ebda mediċina ġenitur mill- awrina jew il- purgar.
After intravenous dosing in patients, no significant biliary excretion of glimepiride or its M1 metabolite was observed.
Wara dożi mill- vini f’ pazjenti, ebda tnixxija biljari sinifikanti ta ’ glimepiride jew tal- metabolit M1 tiegħu ma kienet osservata.
Special populations Gender:
Popolazzjonijiet speċjali Ġeneru:
In the pooled population pharmacokinetic analysis, there were no marked differences in the pharmacokinetics of rosiglitazone or glimepiride between males and females.
Minn ġabra ta ’ analiżi farmakokinetika tal- popolazzjoni, ma kien hemm ebda differenzi notevoli fil- farmakokinetiċi ta ’ rosiglitazone jew glimepiride bejn nisa u rġiel.
In the pooled population pharmacokinetic analysis, age was not found to influence the pharmacokinetics of rosiglitazone or glimepiride to any significant extent.
Minn ġabra ta ’ analiżi farmakokinetika tal- popolazzjoni, instab li l- eta` ma nfluwenzatx il - farmakokinetiċi ta ’ rosiglitazone jew glimepiride b’ xi mod sinifikanti.
Hepatic impairment:
16 Ħsara fil- fwied:
Following rosiglitazone treatment in cirrhotic patients with moderate (Child- Pugh B) hepatic impairment, unbound Cmax and AUC were 2- and 3-fold higher than in normal subjects.
Wara trattament b’ rosiglitazone fuq pazjenti ċirrotiċi bi ħsara moderata (Child- Pugh B) fil- fwied, unbound Cmax u AUC kienu 2 u 3 darbiet aktar minn dawk f’ suġġetti normali.
The inter-subject variability was large, with a 7-fold difference in unbound AUC between patients.
Il - varjabilita` bejn is- suġġetti kienet kbira, b’ differenza ta ’ 7 darbiet aktar f’ dik li hi unbound AUC bejn il- pazjenti.
No adequate pharmacokinetic studies of glimepiride have been conducted in subjects with functional hepatic impairment.
Ma twettqu ebda studji farmakokinetiċi adegwati bi glimepiride fuq suġġetti bi ħsara fil - funzjonament tal- fwied.
Therefore AVAGLIM should not be used in patients with hepatic impairment (see section 4.3)
Għalhekk AVAGLIM m’ għandux jintuża fuq pazjenti bi ħsara fil- fwied (ara sezzjoni 4. 3).
15 Renal insufficiency:
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 ebda differenzi kliniċi fil- farmakokinetiċi ta ’ rosiglitazone f’ pazjenti b’ indeboliment fil- kliewi jew fl- aħħar stadju tal- mard tal- kliewi jew dijalisi kronika.
There are no data from the use of glimepiride in patients on renal dialysis (see section 4.3).
M’ hemm ebda tagħrif dwar l- użu ta ’ glimepiride f’ pazjenti fuq dijalisi tal- kliewi (ara sezzjoni 4. 3).
A multiple-dose titration study with glimepiride conducted in 16 patients with type 2 diabetes mellitus with renal impairment using doses ranging from 1 to 8 mg daily for three months showed that all patients with a creatinine clearance less than 22 ml/ min had adequate control of their glucose levels with a dosage regimen of only 1 mg daily (see section 4.2 and 4.4).
Studju ta ’ titrazzjoni b’ ħafna dożi ta ’ glimepiride li twettqu fuq 16- il pazjent bid- dijabete mellitus ta ’ tip 2 b’ indeboliment tal- kliewi bl- użu ta ’ dożi li jvarjaw minn 1 sa 8 mg kuljum għal tliet xhur urew li l- pazjenti kollha bi tneħħija ta ’ kreatinina li tkun inqas minn 22 ml/ min kellhom kontroll adegwat tal - livelli tal- glukosju tagħhom b’ sistema ta ’ dożi ta ’ 1 mg biss kuljum (ara sezzjoni 4. 2 u 4. 4).
No animal studies have been conducted with the combined products in AVAGLIM.
Ma saru ebda studji fuq annimali bil- prodotti kombinati f’ AVAGLIM.
The following data are findings in studies performed with rosiglitazone or glimepiride individually.
It- tagħrif li ġej juri s- sejbiet fi studji li twettqu b’ rosiglitazone jew glimepiride individwalment.
Rosiglitazone Undesirable effects observed in animal studies with possible relevance to clinical use were as follows:
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 flimkien ma ’ tnaqqis fil- parametri taċ- ċelloli ħomor u żieda fil- piż tal- qalb.
Increases in liver weight, plasma ALT (dog only) and fat tissue were also observed.
Żjidiet fil- piż tal- fwied, plażma ALT (klieb biss) u tessut xaħmi kienu wkoll osservati.
Similar effects have been seen with other thiazolidinediones.
Effetti simili ġew osservati wkoll b’ thiazolidinediones.
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- għoti ta ’ rosiglitazone lil firien bejn in- nofs u l - aħħar tal- ġestazzjoni kien assoċjat 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 s- sintesi ta ’ l- estradjol 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 ta ’ 200 darba iktar mid- doża farmakoloġikament attiva żiedet il- multipliċità ta ’ tumur fil - kolon.
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, rosiglitazone għen fid- distinzjoni u r - revoka ta ’ tibdil mutaġeniku fiċ- ċelloli karċinoġeniċi 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 ’ annimali li jgerrmu.
Glimepiride Preclinical effects were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use or were caused by the pharmacodynamic effect (hypoglycaemia) of the substance.
Glimepiride Effetti pre- kliniċi ġew osservati biss f’ esponimenti meqjusa li jeċċedu suffiċjentement l- ogħla esponiment uman u indikaw rilevanza minima għal użu kliniku jew kienu kawżati mill- effett farmakokinetiku (ipogliċemija) tas- sustanza.
This was based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenicity, and fertility.
Dan kien bażat fuq studji konvenzjonali ta ’ sigurta` farmakoloġika, tossiċita` minn dożi ripetuti, ġenotossiċita`, karċinoġeneċita`, u fertilita`.
Studies on embryofoetal development and pre-and postnatal development revealed eye malformations, skeletal anomalies, abortions, and an increased foetal death rate.
Studji dwar l- iżvilupp embrijofetali u żviluppi ta ’ qabel u wara t- twelid urew formazzjoni difettuża fl- għajnejn, anomaliji skeletriċi, aborti, u żjieda ta ’ mwiet tal- fetu.
Reproduction toxicology findings may be related to the pharmacodynamic action of glimepiride.
Sejbiet dwar tossikoloġija riproduttiva jistgħu ikunu relatati ma ’ l- azzjoni farmakodinamika ta ’ glimepiride.
Glimepiride is excreted into the milk of lactating rats.
Glimepiride jitneħħa għal gol- ħalib ta ’ firien li jkunu jreddgħu.
6.
Dożi għolja mogħtija lil firien nisa jikkawżaw ipogliċemija fi ġrieden żgħar li jkunu jerdgħu (ara sezzjoni 4. 6)
4/ 4 Tablet core:
4/ 4 Il- qalba tal- pillola:
Sodium starch glycolate Type A Hypromellose (E464) Microcrystalline cellulose (E460) Lactose monohydrate Magnesium stearate.
Sodium starch glycolate Type A Hypromellose (E464) Microcrystalline cellulose (E460) Lactose monohydrate Magnesium stearate.
16 Film coat:
Ir- rita tal- kisja:
Hypromellose (E464) Titanium dioxide (E171) Macrogol 400 Iron oxide black (E172) Iron oxide red (E172).
Hypromellose (E464) Titanium dioxide (E171) Macrogol 400 Ossidu iswed tal- ħadid (E172) Ossidu aħmar tal- ħadid (E172).
This medicinal product does not require any special storage conditions.
Dan il- prodott mediċinali ma jitlobx xi kondizzjonijiet speċjali għall- ħażna tiegħu
Opaque blisters (PVC/ PVDC/ aluminium).
Pakketti ta ’ folji blister opaki (PVC/ PVDC aluminju).
Packs of 14, 28, 56, 84 or 112 tablets.
Pakketti ta ’ 14, 28, 56, 84 jew 112- il pillola.
Not all pack sizes may be marketed.
Mhux il- pakketti tad- daqsijiet kollha jkunu għall- skop kummerċjali.
Any unused product should be disposed of in accordance with local requirements.
Kull prodott li ma jkunx intuża għandu 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, Ir- Renju Unit..
27 June 2006
27 ta ’ Ġunju 2006
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- website ta ’ l- Aġenzija Ewropea dwar il- mediċini (EMEA) http: // www. emea. europa. eu /. >
AVAGLIM 8 mg/ 4 mg film-coated tablets.
AVAGLIM 8mg/ 4mg pilloli miksijin b’ rita
Each tablet contains rosiglitazone maleate corresponding to 8 mg rosiglitazone and 4 mg glimepiride.
Kull pillola fiha rosiglitazone maleate li jikkorrispondi għal 8mg rosiglitazone u 4 mg glimepiride
- contains lactose (approximately 235 mg)
- fih lattosju (bejn wieħed u ieħor 235 mg)
Red, biconvex, rounded triangular tablet with “ gsk” debossed on one side and “ 8/ 4” on the other side
Pillola ħamra, bi- konvessa, triangolari u magħmula fit- tond li għandha minqux “ gsk ” fuq naħa waħda u “ 8/ 4 ” fuq in- naħa l- oħra.
AVAGLIM is indicated in the treatment of type 2 diabetes mellitus patients who are unable to achieve sufficient glycaemic control on optimal dosage of sulphonylurea monotherapy, and for whom metformin is inappropriate because of contraindication or intolerance.
AVAGLIM hu indikat biss fit- trattament ta ’ pazjenti bid- dijabete mellitus tip 2 li ma jistgħux jiksbu kontroll gliċemiku biżżejjed bl- aħjar dożaġġ ta ’ monoterapija b’ sulphonylurea, u li għalihom metformin mhux adattat minħabba kontraindikazzjoni jew nuqqas ta ’ tolleranza.
Concomitant administration should be considered before the patient is switched to AVAGLIM.
Għandu jiġi kkunsidrat it- teħid konkomitanti meta pazjent tinbdielu t- terapija b’ AVAGLIM.
The starting dose is 4 mg/ day rosiglitazone plus 4 mg/ day glimepiride (given as one tablet AVAGLIM 4 mg/ 4 mg).
Id- doża tal- bidu hi 4 mg/ kuljum rosiglitazone u 4 mg/ kuljum glimepiride (mogħtija bħala pillola AVAGLIM waħda ta ’ 4 mg/ 4 mg).
AVAGLIM may be used to substitute concomitant sulphonylurea and rosiglitazone in established dual oral therapy providing the patient has achieved at least half-maximum dose of sulphonylurea.
AVAGLIM jista ’ jintuża minflok sulphonylurea u rosiglitazone flimkien f’ terapija orali doppja u stabbilita basta li l- pazjent ikun kiseb għall- inqas id- doża ta ’ nofs massimu tas - sulphonylurea.
The dose of the rosiglitazone component can be increased after 8 weeks if required.
20 Id- doża tal- komponent tar - rosiglitazone tista ’ tiżdied wara 8 ġimgħat jekk ikun meħtieġ.
The maximum recommended daily dose is 8 mg rosiglitazone/ 4 mg glimepiride (given as one AVAGLIM tablet 8 mg/ 4 mg, once daily).
Id- doża massima rakkomandata għal kuljum hi 8 mg rosiglitazone/ 4 mg glimepiride (mogħtija bħala pillola waħda AVAGLIM 8 mg/ 4mg, darba kuljum.).
An increase in the rosiglitazone component to 8 mg/ day should be undertaken
Żjieda fil- komponent ta ’ rosiglitazone għal 8 mg/ 4 mg trid tiġi kkunsidrata b’ attenzjoni wara evalwazzjoni klinika xierqa li tistabbilixxi r- riskju li pazjent jista ’ jiżviluppa effetti mhux mixtieqa relatati maż- żamma ta ’ fluwidi (ara sezzjoni 4. 4 u 4. 8).
18 cautiously following appropriate clinical evaluation to assess the patient’ s risk of developing adverse reactions relating to fluid retention (see 4.4 and 4.8).
Jekk jitfaċċaw sintomi ipogliċemiċi, il- pazjent għandu jerġa ’ lura għal terapija konkomitanti u jaġġusta kif jixraq id- doża ta ’ glimepiride.
If hypoglycaemic symptoms occur, the patient should revert to concomitant therapy and adjust the glimepiride dose as appropriate.
Anzjani Minħabba l- possibilta` ta ’ tnaqqis fil- funzjonament tal- kliewi fil- bidu u fil- kontinwazzjoni ta ’ terapija b’ AVAGLIM f’ pazjenti anzjani għandhom jibqgħu taħt sorveljanza medika b’ attenzjoni kbira minħabba żjieda fis- suxxettibilta` għal ipogliċemija (ara sezzjoni 4. 4).
Elderly Due to the potential for decreased renal function the initiation and maintenance of therapy with AVAGLIM in elderly patients should be under close medical supervision due to an increased susceptibility to hypoglycaemia (see section 4.4).
Pazjenti b’ indeboliment tal- kliewi Indeboliment ħafif jew moderat tal- kliewi (tneħħija ta ’ kreatinina ta ’ 30 sa 80 ml/ min):
Patients with renal impairment Mild or moderate renal impairment (creatinine clearance 30 to 80 ml/ min): -Patients changing to AVAGLIM from sulphonylurea therapies other than glimepiride may be at an increased risk of hypoglycaemia (see section 4.4).
glimepiride jista ’ jiżdidilhom ir- riskju ta ’ ipogliċemija (ara sezzjoni 4. 4).
The following statements refer to AVAGLIM or the two individual active substances (rosiglitazone and glimepiride).
Il- punti li ġejjin jirreferixxu għal AVAGLIM jew għaż- żewġ sustanzi individwali u attivi (rosiglitazone u glimepiride)
It is advised that patients established on rosiglitazone and chlorpropamide concomitant therapy should not switch to AVAGLIM as chlorpropamide has a long half-life which may increase the risk of hypoglycaemia.
Pazjenti stabbiliti fuq terapija ta ’ rosiglitazone u chlorpropamide flimkien m’ għandhomx jaqilbu għal AVAGLIM għax chlorpropamide għandu half- life fit- tul li tista ’ żżid ir - riskju ta ’ ipogliċemija.
If risk factors for hypoglycaemia are present (including renal insufficiency, low body weight, malnourishment, co-administration with certain other medicinal products (see section 4.5) or if the patient’ s life-style changes) it may be necessary to revert to concomitant therapy and down titrate the glimepiride dose.
21 sezzjoni 4. 5) jew jekk jinbidel l- istil tal- ħajja tal- pazjent) jista ’ jkun hemm bżonn li wieħed jerga ’ jdur għal terapija konkomitanti u b’ doża ta ’ glimepiride li tiżdied jew titnaqqas ftit ftit.
19 Fluid retention and cardiac failure Thiazolidinediones can cause fluid retention which may exacerbate or precipitate signs or symptoms of congestive heart failure.
Retenzjoni ta ’ fluwidu u insuffiċjenza tal- qalb Thiazolidinediones jistgħu jikkawżaw retenzjoni ta ’ fluwidu li tista ’ tħarrax jew tipprovoka sinjali jew sintomi ta ’ insuffiċjenza tal- qalb konġestiva.
Rosiglitazone can cause dose-dependent fluid retention.
Rosiglitazone jista ’ jikkawża retenzjoni ta ’ fluwidu li tiddependi mid- doża.
All patients, particularly those receiving concurrent insulin 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 jieħdu wkoll kura b’ insulina, dawk f’ riskju ta ’ insuffiċjenza tal- qalb u dawk b’ riżerva kardijaka 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 waqfien tal- qalb.
Heart failure was also reported more frequently in patients with a history of heart failure; oedema and heart failure was also reported more frequently in elderly patients and in patients with mild or moderate renal failure.
Waqfien tal- qalb ġie wkoll rappurtat aktar ta ’ spiss f’ pazjenti bi storja ta ’ waqfien tal- qalb; edema u insuffiċjena tal- qalb kienet irrapurtata ukoll aktar spiss f’ pazjenti anzjani u f’ pazjenti b’ insuffiċjenza ħafifa jew moderata tal- kliewi.
Caution should be exercised in patients over 75 years because of the limited experience in this patient group.
Għandha jkun hemm kawtela f’ pazjenti ta ’ aktar minn 75 sena minħabba n- nuqqas ta ’ esperjenza f’ dan il- grupp ta ’ pazjenti.
Therefore, liver enzymes should be checked prior to the initiation of therapy with AVAGLIM in all patients and periodically thereafter based on clinical judgement.
Għalhekk, enzimi fil- fwied għandhom jiġu ċċekkjati qabel tinbeda terapija b’ AVAGLIM fil- pazjenti kollha u perjodikament wara bażati fuq ġudizzju kliniku.
If ALT levels are increased to > 3X upper limit of normal during rosiglitazone therapy, liver enzyme levels should be reassessed as soon as possible.
Jekk il- livelli ALT jiżdiedu għal > 3X tal- limitu għoli tan- normal waqt terapija b’ rosiglitazone, il- livelli ta ’ enzimi tal- fwied għandhom jerġgħu jiġu eżaminati mill- ġdid kemm jista ’ jkun malajr.
If ALT levels remain > 3X the upper limit of normal, therapy should be discontinued.
Jekk il- livelli ALT jibqgħu > 3X tal- limitu ta ’ fuq tan- normal, it- terapija għandha titwaqqaf.
If any patient develops symptoms suggesting hepatic dysfunction, which may include unexplained nausea, vomiting, abdominal pain, fatigue, anorexia and/ or dark urine, liver enzymes should be checked.
Jekk xi pazjent jiżviluppa sintomi li jindikaw funzjonament ħażin tal- fwied, li jinkludu dardir bla ma tkun taf għaliex, remettar, uġigħ addominali, għeja, anoreksja u/ jew awrina skura, għandhom jiġu ċċekkjati l- enzimi tal- fwied.
The decision whether to continue the patient on therapy with AVAGLIM should be guided by clinical judgement pending laboratory evaluations.
Id- deċiżjoni dwar jekk il- pazjent għandux jitħalla fuq terapija b’ AVAGLIM għandha ssir b’ ġudizzju kliniku sakemm isiru l- valutazzjonijiet tal- laboratorju.
Eye disorders Post-marketing reports of new-onset or worsening diabetic macular oedema with decreased visual acuity have been reported with thiazolidinediones, including rosiglitazone.
22 Kien hemm rapporti ta ’ wara t- tqegħid fis- suq ta ’ bidu ta ’ edema makulari tad- dijabete b’ tnaqqis fl - akutezza fil- vista jew li din tmur għall- agħar wara li jittieħdu t - thiazolidinediones, incluż ir - rosiglitazone.
As a consequence of improving insulin sensitivity, resumption of ovulation may occur in patients who are anovulatory due to insulin resistance.
B’ riżultat ta ’ titjib ta ’ sensittivita` għalll- insulina, tista ’ terġa tibda l - ovulazzjoni f’ pazjenti li huma anovulatorji minħabba reżistenza għall- insulina.
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 provi kliniċi b’ rosiglitazone kien hemm sinjali ta ’ żjieda fil- piż li għandha x’ taqsam mad- dożi, li kienet akbar meta intuża flimkien ma ’ insulina.
Therefore weight should be closely monitored, given that it may be attributable to fluid retention, which may be associated with cardiac failure.
Għalhekk il- piż għandu jkun osservat mill- viċin, billi jista ’ jkun minħabba ritenzjoni ta ’ fluwidu, li jista 'jkun assoċjat ma ’ insuffiċjenza tal- qalb.
Administration with other medicinal products Rosiglitazone should be used with caution during concomitant administration of CYP2C8 inhibitors (e. g. gemfibrozil) or inducers (e. g. rifampicin).
Teħid flimkien ma ’ prodotti mediċinali oħra Rosiglitazone għandu jintuża b’ attenzjoni waqt li jkun jittieħed flimkien ma ’ impedituri CYP2C8 (e. g. gemfibrozil) jew inducers (e. g. rifampicin).
AVAGLIM dose adjustment within the recommended posology or changes in diabetic treatment should be considered.
L- aġġustament tad- doża ta ’ AVAGLIM skond il - pożoloġija rakkomandata jew tibdil fit- trattament dijabetiku għandu jiġi kkunsidrat.
Lactose intolerance AVAGLIM 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.
Intolleranza ta ’ lattosju Il- pilloli AVAGLIM fihom il- lattosju u għalhekk m’ għandhomx jingħataw lil pazjenti bi problemi rari u ereditarji ta ’ intolleranza galattosja, ta ’ defiċjenza Lapp lactase jew ta ’ assorbiment ħażin ta ’ glukosju- galattosju.
4.5 Interaction with other medicinal products and other forms of interaction
23 4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
21 Rosiglitazone In vitro studies demonstrate that rosiglitazone is predominantly metabolised by CYP2C8, with CYP2C9 as only a minor pathway.
Rosiglitazone Studji in vitro juru li rosiglitazone jimmetabolizza prinċipalment b’ CYP2C8, waqt li CYP2C9 ikun sempliċement passaġġ żgħir.
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. g. phenytoin, carbamazepine, phenobarbital, St John’ s wort) jistgħu ukoll ikollhom effett fuq l - esponiment għal rosiglitazone.
Concomitant administration of rosiglitazone with the oral anti-diabetic agents metformin, glimepiride, glibenclamide and acarbose did not result in any clinically relevant pharmacokinetic interactions.
It- teħid flimkien ta ’ rosiglitazone ma ’ l- aġenti anti- dijabetiċi mill- ħalq metformin, glimepiride, glibenclamide u acarbose ma rriżulta f’ ebda interazzjoni farmakokinetika rilevanti klinika.
No clinically relevant interactions with digoxin, the CYP2C9 substrate warfarin, the CYP3A4 substrates nifedipine, ethinylestradiol or norethindrone were observed after co-administration with rosiglitazone.
Ma ġew osservati ebda interazzjonijiet kliniċi rilevanti ma ’ digoxin, mas- substrat CYP2C9 warfarin, mas- substrati CYP3A4 nifedipine, ethinylestradiol jew norethindrone wara li ttieħdu flimkien ma ’ rosiglitazone.
Glimepiride If glimepiride is taken simultaneously with certain other medicines, both undesired increases and decreases in the hypoglycaemic action of glimepiride can occur.
Glimepiride Jekk glimepiride jittieħed fl- istess ħin ma ’ ċerti mediċini oħra, jistgħu jirriżultaw żjidiet u tnaqqis mhux mixtieqa fl- azzjoni ipogliċemika ta ’ glimepiride.
For this reason, other medicines should only be taken with the knowledge (or at the prescription) of the doctor.
Għaldaqstant, mediċini oħra għandhom jittieħdu biss meta t- tabib ikun jaf bihom (jew bir- riċetta).