qanastek/EMEA-V3 huggingface dataset:
Rare cases of hepatic dysfunction (including hepatitis) have been reported with vildagliptin.
Każijiet rari ta ’ funzjoni mhux normali tal- fwied (inkluża l- epatite) kienu rrappurtati b’ vildagliptin.
In these cases, the patients were generally asymptomatic without clinical sequelae and liver function returned to normal after discontinuation of treatment.
F’ dawn il- każijiet, il- pazjenti kienu b’ mod ġenerali mingħajr sintomi u ma kellhomx konsegwenzi kliniċi u l- funzjoni tal- fwied marret lura għan- normal wara li twaqqfet il- kura.
In data from controlled monotherapy and add-on therapy trials of up to 24 weeks in duration, the incidence of ALT or AST elevations ≥ 3x ULN (classified as present on at least 2 consecutive measurements or at the final on-treatment visit) was 0.2%, 0.3% and 0.2% for vildagliptin 50 mg once daily, vildagliptin 50 mg twice daily and all comparators, respectively.
Minn dejta minn monoterapija kontrollata u provi add- on li damu sa 24 ġimgħa, l- inċidenza ta ’ żiediet fl- ALT jew AST kienet ≥ 3 darbiet ULN (klassifikata bħala preżenti f’ mill- anqas 2 kejliet wara xulxin jew fl- aħħar żjara fuq il- kura) kienu 0. 2%, 0. 3% u 0. 2% għal vildagliptin 50 mg kuljum, vildagliptin 50 mg darbtejn kuljum u l- kumparaturi kollha, rispettivament.
These elevations in transaminases were generally asymptomatic, non-progressive in nature and not associated with cholestasis or jaundice.
Dawn iż- żiediet fit- transaminases kienu ġeneralment mingħajr sintomi, ta ’ natura li ma javvanzawx u mhux assoċjati ma ’ kolestażi jew suffejra.
Rare cases of angioedema have been reported on vildagliptin at a similar rate to controls.
Każijiet rari ta ’ anġjoedema kienu rrappurtati fuq vildagliptin b’ rata simili għal dik tal- kontrolli.
A greater proportion of cases were reported when vildagliptin was administered in combination with an ACE inhibitor.
Proporzjon akbar ta ’ każijiet kienu rrappurtati meta vildagliptin ingħata flimkien ma ’ impeditur ACE.
The majority of events were mild in severity and resolved with ongoing vildagliptin treatment.
Il- maġġoranza tal- każijiet kienu ħfief fil- qawwa u għaddew meta tkompliet il- kura b’ vildagliptin.
Adverse reactions reported in patients who received vildagliptin in double-blind studies as add-on therapy to metformin (Table 1) and as monotherapy (Table 2) are listed below by system organ class and absolute frequency.
Reazzjonijiet avversi rrappurtati f’ pazjenti li rċevew vildagliptin fi studji double- blind bħala terapija li ġiet miżjuda ma ’ metformin (Tabella 1) u bħala monoterapija (Tabella 2) huma elenkati hawn taħt skond il- klassi tas- sistema ta ’ l- organi u frekwenza assoluta.
Adverse reactions listed in Table 3 are based on information available from the metformin Summary of Product Characteristics available in the EU.
Reazzjonijiet avversi elenkati f’ Tabella 3 huma bbażati fuq l- informazzjoni li hemm fis- Sommarju tal- Karatteristiċi tal- Prodott ta ’ metformin li hemm fl- EU.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Il- frekwenzi huma definiti bħala komuni ħafna (≥1/ 10); komuni (≥1/ 100, < 1/ 10); mhux komuni (≥1/ 1, 000, < 1/ 100); rari (≥1/ 10, 000, < 1/ 1, 000); rari ħafna (< 1/ 10, 000), mhux magħruf (ma tistax tittieħed stima mid- data disponibbli).
Adverse reactions reported in patients who received vildagliptin 100 mg daily as add-on therapy to metformin compared to placebo plus metformin in double-blind studies (N=208)
6 Tabella 1 Reazzjonijiet avversi rrappurtati f’ pazjenti li rċevew vildagliptin 100 mg kuljum bħala terapija li ġiet miżjuda ma ’ metformin meta mqabbla ma ’ plaċebo ma ’ metformin fi studji double- blind (N=208)
Common Common Common Uncommon
Komuni Komuni Komuni Mhux komuni
Tremor Headache Dizziness Fatigue
Tregħid Uġigħ ta ’ ras Sturdament Għeja
Gastrointestinal disorders
Disturbi Gastro- intestinali
Nausea
Dardir
In controlled clinical trials with the combination of vildagliptin 100 mg daily plus metformin, no withdrawal due to adverse reactions was reported in ei ther the vildagliptin 100 mg daily plus metformin or the placebo plus metformin treatment groups.
Fi provi kliniċi bil- kontroll bit- taħlita ta ’ vildagliptin 100 mg kuljum ma ’ metformin, l- ebda twaqqif minħabba reazzjonijiet avversi ma kien irrappurtat la fil- gruppi ta ’ trattament b’ vildagliptin 100 mg kuljum flimkien ma ’ metformin jew fil- grupp tal- plaċebo ma ’ metformin.
In clinical trials, the incidence of hypoglycaemia was common in patients receiving vildagliptin in combination with metformin (1%) and uncommon in patients receiving placebo + metformin (0.4%).
Fi provikliniċi, l- inċidenza ta ’ l- ipogliċemija kienet komuni f’ pazjenti li kienu qed jirċievu vildagliptin flimkien ma ’ metformin (1%) u mhux komuni f’ pazjenti li kienu qed jirċievu plaċebo flimkien ma ’ metformin (0. 4%).
No severe hypoglycaemic events were reported in the vildagliptin arms.
Ma kienux irrappurtati każijiet severi ta ’ ipogliċemija severa fil- friegħi fuq vildagliptin.
In clinical trials, weight did not change from baseline when vildagliptin 100 mg daily was added to metformin (+0.2 kg and -1.0 kg for vildagliptin and placebo, respectively).
Fi provi kliniċi, il- piż ma nbidilx mill- linja bażi meta vildagliptin 100 mg kuljum kien miżjud ma ’ metformin (+0. 2 kg u - 1. 0 kg għal vildagliptin u plaċebo, rispettivament).
Additional information on the individual active substances of the fixed combination
Informazzjoni oħra fuq is- sustanzi attivi individwali għall- kombinazzjoni fissa
Adverse reactions reported in patients who received vildagliptin 100 mg daily as monotherapy in double-blind studies (N=1855)
Tabella 2 Reazzjonijiet avversi rrappurtati f’ pazjenti li rċevew vildagliptin 100 mg kuljum bħala monoterapija fi studji double- blind (N=1855)
Common Uncommon
Komuni Mhux komuni
Dizziness Headache
Sturdament Uġigħ ta ’ ras
Constipation
Stitikezza
Very rare Very rare
Rari ħafna Rari ħafna
Upper respiratory tract infection Nasopharyngitis
Infezzjoni tal- passaġġ respiratorju fin- naħa ta ’ fuq Nażofarinġite
Oedema peripheral
Edema periferali
The overall incidence of withdrawals from controlled monotherapy trials due to adverse reactions was no greater for patients treated with vildagliptin at doses of 100 mg daily (0.3%) than for placebo (0.6%) or comparators (0.5%).
L- inċidenza globali tat- twaqqif mill- provi bil- kontroll b’ monoterapija minħabba r- reazzjonijiet avversi ma kienitx akbar għall- pazjenti kkurati b’ vildagliptin b’ dożi ta ’ 100 mg kuljum (0. 3%) milli għall - plaċebo (0. 6%) jew kumparaturi (0. 5%).
In comparative controlled monotherapy studies, hypoglycaemia was uncommon, reported in 0.4% (7 of 1,855) of patients treated with vildagliptin 100 mg daily compared to 0.2% (2 of 1,082) of patients in the groups treated with an active comparator or placebo, with no serious or severe events reported.
Fi studji għat- tqabbil bil- kontroll b’ monoterapija, ipogliċemija kienet irrappurtata rari f’ 0. 4% (7 minn 1, 855) tal- pazjenti kkurati b’ vildagliptin 100 mg kuljum mqabbla ma ’ 0. 2% (2 minn 1, 082) tal - pazjenti fil- gruppi ikkurati b’ kumparatur attiv jew plaċebo, mingħajr ma kienu rrappurtati każijiet serji jew severi.
7 In clinical trials, weight did not change from baseline when vildagliptin 100 mg daily was administered as monotherapy (-0.3 kg and -1.3 kg for vildagliptin and placebo, respectively).
7 Fil- provi kliniċi, il- piż ma nbidilx mill- linja bażi meta vildagliptin 100 mg kuljum ingħata bħala monoterapija (- 0. 3 kg u - 1. 3 kg għal vildagliptin u plaċebo, rispettivament).
Table 3
Tabella 3 Reazzjonijiet magħrufa għall- komponent metformin
Very Rare
Rari ħafna
Decrease of vitamin B12 absorption and lactic acidosis*
Tnaqqis ta ’ l- assorbiment tal- vitamina B12 u aċidożi lattika *
Metallic taste
Togħma ta ’ metall
Nausea, vomiting, diarrhoea, abdominal pain and loss of appetite
Dardir, rimettar, dijarea, uġigħ addominali u telf ta ’ l- aptit
Liver function test abnormalities or hepatitis**
Anormalitajiet tat- test tal- funzjoni tal- fwied jew epatite **
Skin reactions such as erythema, pruritus and urticaria
Reazzjonijiet tal- ġilda bħall- ħmura, ħakk u urtikarja
*A decrease in vitamin B12 absorption with decrease in serum levels has been very rarely observed in patients treated long-term with metformin.
* Tnaqqis fl- assorbiment ta ’ vitamina B12 flimkien ma ’ tnaqqis fil- livelli fis- serum deher rari ħafna f’ pazjenti li kienu kkurati għal żmien twil b’ metformin.
Consideration of such aetiology is recommended if a patient presents with megaloblastic anaemia. **Isolated cases of liver function test abnormalities or hepatitis resolving upon metformin discontinuation have been reported.
Din it- tip ta ’ etjoloġija għandha titqies jekk il - pazjent ikollu anemija megaloblastika. ** Każijiet iżolati ta ’ anormalitajiet fit- test tal- funzjoni tal- fwied jew epatite li għaddew meta twaqqaf metformin kienu rrappurtati.
Gastrointestinal undesirable effects occur most frequently during initiation of therapy and resolve spontaneously in most cases.
Effetti mhux mixtieqa gastro- intestinali iseħħu b’ mod l- aktar frekwenti meta tinbeda t- terapija u jgħaddu waħidhom fil- parti l- kbira tal- każijiet.
To prevent them, it is recommended that metformin be taken in 2 daily doses during or after meals.
Biex jiġu evitati, huwa rakkomandat li metformin jittieħed f’ 2 dożi kuljum waqt jew wara l- ikel.
A slow increase in the dose may also improve gastrointestinal tolerability.
It- tnaqqis bil- mod tad- doża jista ’ wkoll itejjeb it - tolerabilità gastrointestinali.
No data are available with regard to overdose of Eucreas.
M’ hemmx dejta dwar doża eċċessiva b’ Eucreas.
Vildagliptin Information regarding overdose with vildagliptin is limited.
Vildagliptin Informazzjoni dwar doża eċċessiva b’ vildagliptin hija limitata.
Information on the likely symptoms of overdose with vildagliptin was taken from a rising dose tolerability study in healthy subjects given vildagliptin for 10 days.
Informazzjoni dwar x’ aktarx li jkunu s- sintomi ta ’ doża eċċessiva b’ vildagliptin inkisbet minn studju b’ doża li tiġi miżjuda f’ individwi b’ saħħithom li ngħataw vildagliptin għal 10 ijiem.
At 400 mg, there were three cases of muscle pain, and individual cases of mild and transient paraesthesia, fever, oedema and a transient increase in lipase levels.
B’ 400 mg kien hemm tlett każijiet ta ’ uġigħ fil- muskoli, u każijiet individwali ħfief u mumentanji ta ’ parasteżija, deni, edema u żieda mumentanja tal- livelli tal- lipase.
At 600 mg, one subject experienced oedema of the feet and hands, and increases in creatine phosphokinase (CPK), AST, C-reactive protein (CRP) and myoglobin levels.Three other subjects experienced oedema of the feet, with paraesthesia in two cases.
Tlett individwi oħrajn kellhom edema tas- saqajn, kif ukoll parasteżija f’ żewġ każijiet.
All symptoms and laboratory abnormalities resolved without treatment after discontinuation of the study medicinal product.
Is - sintomi kollha u anormalitajiet tal- laboratorju għaddew mingħajr kura wara li twaqqaf il- prodott mediċinali li kien qed jiġi studjat.
Metformin A large overdose of metformin (or co-existing risk of lactic acidosis) may lead to lactic acidosis, which is a medical emergency and must be treated in hospital.
Metformin Doża eċċessiva ħafna ta ’ metformin (jew riskju fl- istess waqt ta ’ aċidożi lattika) tista ’ twassal għal aċidożi lattika, li hija emerġenża medika li għandha tiġi ikkurata fi sptar.
Management The most effective method of removing metformin is haemodialysis.
Immaniġġar L- aktar mod effettiv biex tneħħi metformin huwa l- emodijalisi.
However, vildagliptin cannot be removed by haemodialysis, although the major hydrolysis metabolite (LAY 151) can.
Madankollu, vildagliptin ma jistax jitneħħa bl- emodijalisi, għalkemm il- metabolu ewlieni tal- hydrolysis (LAY 151) jista ’.
Supportive management is recommended.
Immaniġġar ta ’ support huwa rakkomandat.
Combinations of oral blood glucose lowering drugs, ATC code:
Kombinazzjonijiet ta ’ mediċini li jbaxxu l- glucose fid- demm, Kodiċi ATC:
Eucreas combines two antihyperglycaemic agents with complimentary mechanisms of action to improve glycaemic control in patients with type 2 diabetes: vildagliptin, a member of the islet enhancer class, and metformin hydrochloride, a member of the biguanide class.
Eucreas jikkombina żewġ aġenti kontra l- ipergliċemija b’ mekkaniżmu ta ’ azzjoni kumplimentari sabiex jitjieb il- kontroll ta ’ pazjenti bid- dijabete tat- tip 2: vildagliptin, membru tal- klassi li jtejjeb l - islet, u metformin hydrochloride, membru tal- klassi biguanide.
Vildagliptin, a member of the islet enhancer class, is a potent and selective dipeptidyl-peptidase-4 (DPP-4) inhibitor.
Vildagliptin, membru tal- klassi li jtejjeb l- islet, huwa impeditur qawwi u silettiv ta ’ dipeptidyl - peptidase- 4 (DPP- 4).
Metformin acts primarily by decreasing endogenous hepatic glucose production.
Metformin jaħdem primarjament billi jnaqqas il- produzzjoni endoġena tal - glucose mill- fwied.
Vildagliptin added to patients whose glycaemic control was not satisfactory despite treatment with metformin monotherapy resulted after 6-month treatment in additional statistically significant mean reductions in HbA1c compared to placebo (between group differences of -0.7% to -1.1% for vildagliptin 50 mg and 100 mg, respectively).
Meta vildagliptin kien miżjud f’ pazjenti li l- kontroll gliċemiku tagħhom ma kienx sodisfaċenti minkejja kura b’ monoterpija ta ’ metformin irriżulta li wara 6 xhur ta ’ kura kien hemm żieda statistikament sinifikanti fil- medja ta ’ tnaqqis ta ’ HbA1c meta mqabbel mal- plaċebo (differenzi bejn il - gruppi ta ’ - 0. 7% sa ’ - 1. 1% għal vildagliptin 50 mg u 100 mg rispettivament).
The proportion of patients who achieved a decrease in HbA1c of ≥ 0.7% from baseline was statistically significantly higher in both vildagliptin plus metformin groups (46% and 60%, respectively) versus the metformin plus placebo group (20%).
Il- proporzjon ta ’ pazjenti li kisbu tnaqqis fl - HbA1c ta ’ ≥ 0. 7% mill- linja bażi kien ogħla statistikament sinifikanti kemm fil - gruppi ta ’ vildagliptin ma ’ metformin (46% u 60%, rispettivament) kontra l- grupp ta ’ metformin mal - plaċebo (20%).
Vildagliptin Vildagliptin acts primarily by inhibiting DPP-4, the enzyme responsible for the degradation of the incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide).
Vildagliptin Vildagliptin jaħdem l- aktar billi jinibixxi DPP- 4, l- enzima responsabbli għad- degradazzjoni ta ’ l - ormoni incretin GLP- 1 (peptajd- 1 li jixbah lil glucagon) u GIP (polipeptajd insulinotropiku li jiddependi fuq il- glucose).
The administration of vildagliptin results in a rapid and complete inhibition of DPP-4 activity resulting in increased fasting and postprandial endogenous levels of the incretin hormones GLP-1 and GIP.
L- għotja ta ’ vildagliptin twassal għall- impediment mgħaġġel u komplet ta ’ l- attività tad- DPP- 4 li twassal għal żieda fil- livelli endoġeni ta ’ waqt is- sawm u wara l- ikel ta ’ l- ormoni inkretin GLP- 1 u GIP.
By increasing the endogenous levels of these incretin hormones, vildagliptin enhances the sensitivity of beta cells to glucose, resulting in improved glucose-dependent insulin secretion.
Meta jżid il- livelli endoġeni ta ’ dawn l- ormoni inkretin, vildagliptin itejjeb is- sensittività taċ- ċelluli beta għall- glucose, li jwassal għal titjib fis- sekrezzjoni ta ’ l- insulina li tiddependi mill- glucose.
Treatment with vildagliptin 50-100 mg daily in patients with type 2 diabetes significantly improved markers of beta cell function including HOMA-β (Homeostasis Model Assessment–β), proinsulin to insulin ratio and measures of beta cell responsiveness from the frequently-sampled meal tolerance test.
Kura b’ vildagliptin 50- 100 mg kuljum f’ pazjenti b’ dijabete tat- tip 2 tejjeb b’ mod sinifikanti l- markaturi tal - funzjoni taċ- ċelluli beta inklużi HOMA- β (Stima tal- Mudell B’ Omeostażi- β), proporzjoni tal - proinsulina ma ’ l- insulina u kejl tar- risponsittività taċ- ċelluli beta mit- testijiet tat- tolleranza għall- ikel li jiġu kampjunati spissi.
In non-diabetic (normal glycaemic) individuals, vildagliptin does not stimulate insulin secretion or reduce glucose levels.
F’ individwi mhux dijabetiċi (gliċemija normali), vildagliptin ma jistimulax is- sekrezzjoni ta’ l- insulina jew inaqqas livelli tal- glucose.
By increasing endogenous GLP-1 levels, vildagliptin also enhances the sensitivity of alpha cells to glucose, resulting in more glucose-appropriate glucagon secretion.
Billi jżid il- livelli endoġeni tal- GLP- 1, vildagliptin iżid ukoll is- sensittività taċ- ċelluli alfa għall - glucose, u b’ hekk ikun hemm sekrezzjoni aktar xierqa tal- glucagon skond il- glucose.
The enhanced increase in the insulin/glucagon ratio during hyperglycaemia due to increased incretin hormone levels results in a decrease in fasting and postprandial hepatic glucose production, leading to reduced glycaemia.
It- titjib fil- proporzjon ta ’ l- insulina/ glucagon waqt l- ipergliċemija minħabba ż- żieda fil- livelli ta ’ l - ormoni inkretin tirriżulta f’ tnaqqis fil- produzzjoni ta ’ glucose waqt is- sawm u wara l- ikel, li twassal għal tnaqqis fil- gliċemija.
The known effect of increased GLP-1 levels delaying gastric emptying is not observed with vildagliptin treatment.
L- effett magħruf li jkollha ż- żieda fil- livelli ta ’ GLP- 1 li jittardja t- tbattil gastriku ma jidhirx bil- kura b’ vildagliptin.
Metformin Metformin is a biguanide with antihyperglycaemic effects, lowering both basal and postprandial plasma glucose.
Metformin Metformin huwa biguanide b’ effetti kontra l- ipergliċemija, jnaqqas kemm il- glucose fil- plasma basiku kif ukoll dak ta ’ wara l- ikel.
It does not stimulate insulin secretion and therefore does not produce hypoglycaemia or increased weight gain.
Ma jistimulax is- sekrezzjoni ta ’ l- insulina u għalhekk ma jikkawżax ipogliċemija jew żieda fil- piż.
Metformin may exert its glucose -lowering effect via three mechanisms:
9 Metformin jista ’ jeżerċita l- effett tiegħu li jnaqqas il- glucose permezz ta ’ tlett mekkaniżmi:
- by reduction of hepatic glucose production through inhibition of gluconeogenesis and
- billi jnaqqas il- produzzjoni tal- glucose mill- fwied billi jimpedixxi l- glukoneoġenesi u
glycogenolysis;
glyjkoġenoliżi;
- in muscle, by modestly increasing insulin sensitivity, improving peripheral glucose uptake and
- fil- muskoli, billi jżid b’ mod modest is- sensittività għall- insulina, u b’ hekk itejjeb ir- risorbiment
utilisation;
tal- glucose periferali u l- użu tiegħu;
- by delaying intestinal glucose absorption.
- billi jittardja l- assorbiment tal- glucose mill- imsaren.
Metformin stimulates intracellular glycogen synthesis by acting on glycogen synthase and increases the transport capacity of specific types of membrane glucose transporters (GLUT-1 and GLUT-4).
Metformin jistimula is- sintesi ta ’ glycogen fiċ- ċelluli billi jaħdem fuq glycogen synthase u jżid il- ħila ta ’ trasport ta ’ ċerti tipi ta ’ trasportaturi ta ’ glucose fil- membrana (GLUT- 1 u GLUT- 4).
In humans, independently of its action on glycaemia, metformin has favourable effects on lipid metabolism.
Fil- bniedem, b’ mod indipendenti mill- effett tiegħu fuq il- gliċemija, metformin għandu effetti tajbin fuq il- metaboliżmu tal- lipidi.
This has been shown at therapeutic doses in controlled, medium-term or long-term clinical studies: metformin reduces serum levels of total cholesterol, LDL cholesterol and triglycerides.
Dan intwera b’ dożi terapewtiċi fi studji kliniċi bil- kontroll fuq żmien medju jew twil: meformin inaqqas il- livelli fis- serum tal- kolesterol totali, kolesterol tat- tip LDL u livelli tat- trigliċeridi.
The prospective randomised UKPDS (UK Prospective Diabetes Study) study has established the long- term benefit of intensive blood glucose control in type 2 diabetes.
L- istudju prospettiv randomised UKPDS (Studju Prospettiv tad- Dijabete UK) stabilixxa l- benefiċċju fuq żmien twil tal- kontroll tal- glucose fid- demm fid- dijabete tat- tip 2.
Analysis of the results for overweight patients treated with metformin after failure of diet alone showed:
Analiżi tar- riżultati għall - pażjenti li għandhom piż eċċessiv li ġew ikkurati b’ metformin wara li d- dieta waħidha falliet uriet:
- a significant reduction in the absolute risk of any diabetes-related complication in the metformin
- tnaqqis sinifikanti fir- riskju assolut ta ’ kwalunkwe kumplikazzjoni relatata mad- dijabete fil -
group (29.8 events/1,000 patient -ye ars) versus diet alone (43.3 events/1,000 patient-years), p=0.0023, and versus the combined sulphonylurea and insulin monotherapy groups (40.1 events/1,000 patient-years), p=0.0034;
grupp fuq metformin (29. 8 każijiet/ 1, 000 sena tal- pazjent) kontra d- dieta waħidha (43. 3 każijiet/ 1, 000 sena tal- pazjent), p=0. 0023, u kontra l- gruppi b’ sulphonylurea kombinata u monoterapija bl- insulina (40. 1 każijiet/ 1, 000 sena tal- pazjent), p=0. 0034;
- a significant reduction in the absolute risk of diabetes-related mortality: metformin
- tnaqqis sinifikanti fir- riskju assolut ta ’ mortalità relatata mad- dijabete: metformin
7.5 events/1,000 patient -ye ars, diet alone 12.7 events/1,000 patient-years, p=0.017;
7. 5 każijiet/ 1, 000 sena tal- pazjent, dieta waħidha 12. 7 każijiet/ 1, 000 sena tal- pazjent, p=0. 017;
- a significant reduction in the absolute risk of overall mortality: metformin
- tnaqqis sinifikanti fir- riskju assolut ta ’ mortalità: metformin 13. 5 każijiet/ 1, 000 sena tal- pazjent
13.5 events/1,000 patient -ye ars 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);
kontra dieta waħidha 20. 6 każijiet/ 1, 000 sena tal- pazjent (p=0. 011), u kontra l- gruppi b’ sulphonylurea kombinata u monoterapija bl- insulina 18. 9 każijiet/ 1, 000 sena tal- pazjent (p=0. 021);
- a significant reduction in the absolute risk of myocardial infarction: metformin
- tnaqqis sinifikanti fir- riskju assolut ta ’ infart mijokardijaku: metformin 11- il każ/ 1, 000 sena tal -
11 events/1,000 patient-years, diet alone 18 events/1,000 patient-years (p=0.01).
pazjent, dieta waħidha 18- il każ/ 1, 000 sena tal- pazjent (p=0. 01).
Eucreas Absorption Bioequivalence has been demonstrated between Eucreas at three dose strengths (50 mg/500 mg, 50 mg/850 mg and 50 mg/1000 mg) versus free combination of vildagliptin and metformin hydrochloride tablets at the corresponding doses.
Eucreas Assorbiment Intweriet bioekwivalenza mejn Eucreas fi tlett qawwiet ta ’ dożi (50 mg/ 500 mg, 50 mg/ 850 mg u 50 mg/ 1000 mg), kontra kombinazzjoni ħielsa ta ’ pilloli ta ’ vildagliptin u metformin hydrochloride bid- dożi li jikkorrispondu għalihom.
Food does not affect the extent and rate of absorption of vildagliptin from Eucreas.
L- ikel ma jeffettwax il- grad u r- rata ta ’ assorbiment ta ’ vildagliptin minn Eucreas.
The rate and extent of absorption of metformin from Eucreas 50 mg/1000 mg were decreased when given with food as reflected by the decrease in Cmax by 26%, AUC by 7% and delayed Tmax (2.0 to 4.0 h).
Ir- rata u l- grad ta ’ assorbiment ta ’ metformin milEucreas 50 mg/ 1000 mg kienu mnaqqsa meta mogħtija ma ’ l- ikel bi tnaqqis fis- Cmax b’ 26%, AUC b’ 7% u Tmax ittardjat (2. 0 sa 4. 0 h).
The following statements reflect the pharmacokinetic properties of the individual active substances of Eucreas.
Id- dikjarazzjonijiet li ġejjin jirriflettu il- kwalitajiet farmakokinetiċi tas- sustanzi attivi f’ Eucreas.
Vildagliptin Absorption Following oral administration in the fasting state, vildagliptin is rapidly absorbed with peak plasma concentrations observed at 1.7 hours.
Vildagliptin Assorbiment Wara li jittieħed mill- ħalq fi stat ta ’ sawm, vildagliptin jiġi assorbit malajr bl- ogħla konċentrazzjonijiet fil- plażma jidhru wara 1. 7 siegħat.
Food slightly delays the time to peak plasma concentration to 2.5 hours, but does not alter the overall exposure (AUC).
L- ikel jittardja bi ftit il- ħin sabiex jintlaħqu l- ogħla konċentrazzjonijiet fil- plażma għal 2. 5 siegħat, iżda ma jibdilx l- esponiment globali (AUC).
Administration of vildagliptin with food resulted in a decreased Cmax (19%) compared to dosing in the fasting state.
L- għotja ta ’ vildagliptin ma ’ l- ikel irriżultat fi tnaqqis fis- Cmax (19%) meta mqabbel ma ’ dożi mogħtija fi stat sawmi.
However, the magnitude of change is not clinically significant, so that vildagliptin can be given with or without food.
Madankollu d- daqs tal- bidla mhuwiex klinikament sinifikanti, għalhekk vildagliptin jista ’ jingħata ma ’ l- ikel jew waħdu.
The absolute bioavailability is 85%.
Il- biodisponibilità assoluta hija 85%.
Distribution The plasma protein binding of vildagliptin is low (9.3%) and vildagliptin distributes equally between plasma and red blood cells.
10 Distribuzzjoni Vildagliptin jorbot b’ mod dgħajjef mal- proteini tal- plażma (9. 3%) u vildagliptin jinfirex b’ mod ugwali bejn il- plażma u ċ- ċelluli ħomor tad- demm.
The mean volume of distribution of vildagliptin at steady-state after intravenous administration (Vss) is 71 litres, suggesting extravascular distribution.
Il- medja tal- volum tad- distribuzzjoni ta ’ vildagliptin fi stat- fiss wara li jingħata minn ġol- vina (Vss) hija 71 litru, li jindika distribuzzjoni ekstravaskulari.
10 Biotransformation Metabolism is the major elimination pathway for vildagliptin in humans, accounting for 69% of the dose.
Biotrasformazzjoni Fil- bniedem il- metaboliżmu huwa l- mezz ewlieni li bih jitnehha vildagliptin, li jgħodd 69% tad- doża.
The major metabolite (LAY 151) is pharmacologically inactive and is the hydrolysis product of the cyano moiety, accounting for 57% of the dose, followed by the amide hydrolysis product (4% of dose).
Il- metabolu ewlieni (LAY 151) mhuwiex attiv mill- lat farmakoloġiku u huwa l- prodott ta ’ l- idroliżi tal- parti cyano, li tgħodd 57% tad- doża, segwita mill- prodott ta ’ l- isdroliżi ta ’ l- amide (4% tad- doża).
DPP-4 contributes partially to the hydrolysis of vildagliptin based on an in vivo study using DPP-4 deficient rats.
DPP- 4 jikkontribwixxi parzjalment għall- isdroliżi ta ’ vildagliptin ibbażat minn studju in vivo bl- użu ta ’ firien li ma kellhomx DPP- 4.
Vildagliptin is not metabolised by CYP 450 enzymes to any quantifiable extent, and accordingly the metabolic clearance of vildagliptin is not anticipated to be affected by co- medications that are CYP 450 inhibitors and/or inducers.
Vildagliptin ma jiġix metabolizzat mill- enzimi CYP 450 b’ ammont li jista ’ jiġi kwantifikat, u b’ hekk it- tneħħija metabolika ta ’ vildagliptin mhux mistennija li tiġi effettwata meta tingħata ma ’ mediċini oħrajn li huma impedituri u/ jew indutturi tas- CYP 450.
In vitro studies demonstrated that vildagliptin does not inhibit/induce CYP 450 enzymes.
Studji in vitro wrew li vildagliptin ma jimpedixxix/ jinduċix l- enzimi CYP 450.
Therefore, vildagliptin is not likely to affect metabolic clearance of co-medications metabolised by CYP 1A2, CYP 2C8, CYP 2C9, CYP 2C19, CYP 2D6, CYP 2E1 or CYP 3A4/5.
Għalhekk, vildagliptin x’ aktarx li ma jeffettwax it- tneħħija metabolika ta ’ dawn il- medikamenti li jingħataw flimkien li huma metabolizzati permezz ta ’ CYP 1A2, CYP 2C8, CYP 2C9, CYP 2C19, CYP 2D6, CYP 2E1 jew CYP 3A4/ 5.
Elimination Following oral administration of [14C] vildagliptin, approximately 85% of the dose was excreted into the urine and 15% of the dose was recovered in the faeces.
Eliminazzjoni Wara li ngħata vildagliptin [14C] mill- ħalq, madwar 85% tad- doża tneħħiet fl- awrina u 15% tad- doża instabet fl- ippurgar.
Renal excretion of the unchanged vildagliptin accounted for 23% of the dose after oral administration.
L- eskrezzjoni renali ta ’ vildagliptin mhux mibdul kienet tgħodd għall 23% tad - doża wara li ngħata mill- ħalq.
After intravenous administration to healthy subjects, the total plasma and renal clearances of vildagliptin are 41 and 13 l/h, respectively.
Wara l- għotja minn ġol- vina lill- individwi b’ saħħithom, it- tneħħija totali ta ’ vildagliptin mill- plażma u mill- kliewi huma 41 u 13 l/ h, rispettivament.
The mean elimination half-life after intravenous administration is approximately 2 hours.
Il- medja tal- half- life ta ’ l- eliminazzjoni wara l- għotja minn ġol- vina hija madwar 2 siegħat.
The elimination half-life after oral administration is approximately 3 hours.
Il- half- life ta ’ l- eliminazzjoni wara li jingħata mill- ħalq hija madwar 3 siegħat.
Linearity / non-linearity The Cmax for vildagliptin and the area under the plasma concentrations versus time curves (AUC) increased in an approximately dose proportional manner over the therapeutic dose range.
Linjarità / nuqqas ta ’ linjarità Is- Cmax għal vildagliptin u l- erja taħt il- kurva tal- konċentrazzjoni fil- plażma kontra l- ħin (AUC) żdiedu b’ mod li kien kważi proporzjonali mad- doża fuq il- medda terapewtika.
Characteristics in patients Gender:
Karatteristiċi fil- pazjenti Sess:
No clinically relevant differences in the pharmacokinetics of vildagliptin were observed between male and female healthy subjects within a wide range of age and body mass index (BMI).
Ma dehrux differenzi klinikament rilevanti bejn il- farmakokinetika ta ’ vildagliptin fl- irġiel u n - nisa b’ saħħithom f’ medda wiesa ’ ta ’ etajiet u indiċi tal- massa tal- ġisem (BMI).
DPP-4 inhibition by vildagliptin is not affected by gender.
L- impediment ta ’ DPP- 4 minn vildagliptin mhux effettwat miss- sess.
Age:
Età:
In healthy elderly subjects (≥ 70 years), the overall exposure of vildagliptin (100 mg once daily) was increased by 32%, with an 18% increase in peak plasma concentration as compared to young healthy subjects (18-40 years).
F’ individwi b’ saħħithom anzjani (≥ 70 sena), l- esponiment globali ta ’ vildagliptin (100 mg darba kuljum) żdied b’ 32%, b’ żieda ta ’ 18% fl- ogħla konċentrazzjoni fl- plażma meta mqabbla ma ’ individwi b’ saħħithom żgħażagħ (18- 40 sena).
These changes are not considered to be clinically relevant, however.
Madankollu, dawn il- bidliet mhumiex meqjusa klinikament rilevanti.
DPP-4 inhibition by vildagliptin is not affected by age.
L- impediment ta ’ DPP- 4 minn vildagliptin mhux effettwat mill- età.
In subjects with mild, moderate or severe hepatic impairment (Child-Pugh A-C) there were no clinically significant changes (maximum ~30%) in exposure to vildagliptin.
F’ individwi b’ indeboliment epatiku ħafif, moderat jew sever (Child- Pugh A- C) ma kienx hemm bidliet klinikament sinifikanti (massimu ~30%) fl- esponiment għal vildagliptin.
In subjects with mild, moderate, or severe renal impairment, systemic exposure to vildagliptin was increased (Cmax 8-66%; AUC 32-134%) and total body clearance was reduced compared to subjects with normal renal function.
F’ individwi b’ indeboliment renali ħafif, moderat, jew sever, l- esponiment sistemiku għal vildagliptin żdiedet (Cmax 8- 66%, AUC 32- 134%) u t- tneħħija totali mill- ġisem tnaqqset meta mqabbla ma ’ individwi b’ funzjoni renali normali.
Ethnic group:
Grupp etniku:
Limited data suggest that race does not have any major influence on vildagliptin pharmacokinetics.
Dejta limitata tindika li r- razza mgħandhiex influwenza maġġuri fuq il- farmakokinetika ta ’ vildagliptin.
Metformin Absorption After an oral dose of metformin, the maximum plasma concentration (Cmax) is achieved after about 2.5 h..
Metformin Assorbiment Wara doża metformin li tittieħed mill- ħalq, il- konċentrazzjoni massima fil- plażma (Cmax) tintlaħaq wara madwar 2. 5 h.
Absolute bioavailability of a 500 mg metformin tablet is approximately 50-60% in healthy subjects.
Il- biodisponibilità assoluta ta ’ pillola metformin ta ’ 500 mg hija madwar 50- 60% f’ individwi b’ saħħithom.
After an oral dose, the non-absorbed fraction recovered in faeces was 20-30%.
Wara doża li tittieħed mill- ħalq, il- frazzjoni li ma tiġix assorbita irkuprata mill- ippurgar kienet 20- 30%.
After oral administration, metformin absorption is saturable and incomplete.
11 Wara li jingħata mill- ħalq, l- assorbiment ta ’ metformin jiġi saturat u mhux komplet.
It is assumed that the pharmacokinetics of metformin absorption are non-linear.
Huwa assumat li l- farmakokinetika ta ’ l- assorbiment ta ’ metformin mhix linjari.
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.
Bid- dożi ta ’ metformin tas- soltu u skedi ta ’ dożaġġi, il- konċentrazzjonijiet fil- plażma fi stat- fiss jintlaħqu fi żmien 24- 48 h u huma b’ mod ġenerali anqas 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 bil- kontroll, l- ogħla livelli ta ’ metformin fil - plażma (Cmax) ma qabżux 4 µg/ ml, anki bl- ogħla dożi.
11 Food slightly delays and decreases the extent of the absorption of metformin.
L- ikel jittardja bi ftit u jnaqqas il- grad ta ’ assorbiment ta ’ metformin.
Following administration of a dose of 850 mg, the plasma peak concentration was 40% lower, AUC was decreased by 25% and time to peak plasma concentration was prolonged by 35 minutes.
Wara li tingħata doża ta ’ 850 mg, l- ogħla konċentrazzjoni fil- plażma kienet 40% aktar baxxa, AUC kien imnaqqas b’ 25% u l- ħin sabiex inkisbet l- ogħla konċentrazzjoni fil- plażma ittawlet b’ 35 minuta.
The clinical relevance of this decrease is unknown.
Ir- rilevanza klinika ta ’ dan it- tnaqqis mhux magħrufa.
Distribution Plasma protein binding is negligible.
Distribuzzjoni L- ammont li jorbot mal- proteini fil- plażma huwa ftit li xejn.
Metformin partitions into erythrocytes.
Metformin jinqasam fl- eritroċiti.
The mean volume of distribution (Vd) ranged between 63-276 litres.
Il- medja tal- volum tad- distribuzzjoni (Vd) kella medda ta ’ bejn 63- 276 litru.
Metabolism Metformin is excreted unchanged in the urine.
Metaboliżmu Metformin jitneħħa mingħajr ma jiġi mibdul fl- awrina.
Elimination Metformin is eliminated by renal excretion.
Eliminazzjoni Metformin jiġi eliminat permezz ta ’ tneħħija renali.
Renal clearance of metformin is > 400 ml/min, indicating that metformin is eliminated by glomerular filtration and tubular secretion.
It- tneħħija renali ta ’ metformin hija > 400 ml/ min, li jindika li metformin jiġi eliminat permezz ta ’ filtrazzjoni mill- glomeruli u skrezzjoni mit- tubi.
Following an oral dose, the apparent terminal elimination half-life is approximately 6.5 h.
Wara doża mill- ħalq, il- half- life ta ’ l- eliminazzjoni apparenti fl- aħħar tkun 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 l- funzjoni renali tkun indebolita, it- tneħħija renali titnaqqas b’ mod proporzonali ma ’ dak tal- krejatinina u għalhekk il- half- life ta ’ l- eliminazzjoni jitwal, u dan iwassal għal żieda fil- livelli ta ’ metformin fil - plażma.
Animal studies of up to 13-week duration have been conducted with the combined substances in Eucreas.
Studji f’ annimali li damu sa ’ 13- il ġimgħa saru bis- sustanzi kombinati f’ Eucreas.
No new toxicities associated with the combination were identified.
Ma nstabux tossiċitajiet ġodda assoċjati mal- kombinazzjoni.
The following data are findings from studies performed with vildagliptin or metformin individually.
Id- dejta li ġejja huma sejbiet li nkisbu minn studji li saru b’ vildagliptin jew metformin waħidhom.
Vildagliptin Intra-cardiac impulse conduction delays were observed in dogs with a no-effect dose of 15 mg/kg (7- fold human exposure based on Cmax).
Vildagliptin Ittardjar fil- konduzzjoni ta ’ impulsi fil- qalb dehru fi klieb b’ doża mingħajr effett ta ’ 15 mg/ kg (7- darbiet l- esponiment fil- bniedem ibbażat fuq Cmax).
Accumulation of foamy alveolar macrophages in the lung was observed in rats and mice.
Akkumulu ta ’ makrofaġi alvejolari fil- pulmun dehru fil- firien u ġrieden.
The no- effect dose in rats was 25 mg/kg (5-fold human exposure based on AUC) and in mice 750 mg/kg (142- fold human exposure).
Id- doża mingħajr effett fil - firien kienet 25 mg/ kg (5- darbiet l- esponiment fil- bniedem ibbażat fuq l- AUC) u fil- ġrieden 750 mg/ kg (142- darbiet l- esponiment fil- bniedem).
Gastrointestinal symptoms, particularly soft faeces, mucoid faeces, diarrhoea and, at higher doses, faecal blood were observed in dogs.
Sintomi gastro- intestinali, l- aktar ippurgar artab, ippurgar mukuż, dijarea u, b’ dożi ogħla, demm fl - ippurgar dehru fil- klieb.
A no-effect level was not established.
Livell mingħajr effett ma ġiex stabbilit.
Vildagliptin was not mutagenic in conventional in vitro and in vivo tests for genotoxicity.
Vildagliptin ma kienx mutaġeniku f’ testijiet konvenzjonali in vitro u in vivo għall- ġenotossiċità.
A fertility and early embryonic development study in rats revealed no evidence of impaired fertility, reproductive performance or early embryonic development due to vildagliptin.
Studju dwar il- fertilità u żvilupp bikri fil- firien ma wera l- ebda evidenza ta ’ tixkil fil- fertilità, ħila riproduttiva jew żvilupp bikri ta ’ l- embriju minnħabba vildagliptin.
Embryofoetal toxicity was evaluated in rats and rabbits.
Tossiċità fl- embriju u l- fetu kienet evalwata fil- firien u l- fniek.
An increased incidence of wavy ribs was observed in rats in association with reduced maternal body weight parameters, with a no-effect dose of 75 mg/kg (10-fold human exposure).
Żieda fl- inċidenza ta ’ kustilji imbewqa dehret fil- firien b’ assoċjazzjoni ma ’ tnaqqis fil- parametri tal- piż tal- ġisem ta ’ l- omm, b’ doża mingħajr effett ta ’ 75 mg/ kg (10- il darba l- esponiment fil- bniedem).
In rabbits, decreased foetal weight and skeletal variations indicative of developmental delays were noted only in the presence of severe maternal toxicity, with a no-effect dose of 50 mg/kg (9-fold human exposure).
Fil- fniek, tnaqqis fil- piż tal- fetu u bidliet fl- iskeletru li jindikaw ittardjar fl - iżvilupp dehru biss meta kien hemm tossiċità severa fl- omm, b’ doża mingħajr effett ta ’ 50 mg/ kg (9- darbiet l- esponiment fil- bniedem).
A pre- and postnatal development study was performed in rats.
Studju ta ’ l- iżvilupp qabel u wara t- twelid sar fil- firien.
Findings were only observed in association with maternal toxicity at ≥ 150 mg/kg and included a transient decrease in body weight and reduced motor activity in the F1 generation.
Is- sejbiet dehru biss b’ assoċjazzjoni ma ’ tossiċità fl- omm b’ ≥ 150 mg/ kg u kienu jinkludu tnaqqis mumentanju fil- piż tal- ġisem u tnaqqis fl- attività motriċi fil- ġenerazzjoni F1.
A two-year carcinogenicity study was conducted in rats at oral doses up to 900 mg/kg (approximately 200 times human exposure at the maximum recommended dose).
12 Studju dwar il- kanċeroġeniċità li dam sentejn sar fil- firien b’ dożi mill- ħalq sa ’ 900 mg/ kg (madwar 200 darba l- esponiment fil- bniedem bl- ogħla doża rakkomandata).
No increases in tumour incidence attributable to vildagliptin were observed.
Ma dehrux żiediet fl- inċidenzi ta ’ tumuri li ġejjin minn vildagliptin.
Another two-year carcinogenicity study was conducted in mice at oral doses up to 1000 mg/kg.
Studju ieħor dwar il- kanċeroġeniċità li dam sentejn sar fil- ġrieden b’ dożi mill- ħalq sa ’ 1000 mg/ kg.
An increased incidence of mammary adenocarcinomas and haemangiosarcomas was observed with a no-effect dose of 500 mg/kg (59-fold human exposure) and 100 mg/kg (16-fold human exposure), respectively.
Żieda fl- adenokanċeromi tal- mammarji u haemangiosrcomas dehru b’ doża mingħajr effett ta ’ 500 mg/ kg (59 darba l- esponiment fil- bniedem) u 100 mg/ kg (16- il darba l - esponiment fil- bniedem), rispettivament.
The increased incidence of these tumours in mice is considered not to represent a significant risk to humans based on the lack of genotoxicity of vildagliptin and its principal metabolite, the occurrence of tumours only in one species, and the high systemic exposure ratios at which tumours were observed.
Iż- żieda fl- inċidenza ta ’ dawn it- tumuri fil- ġriedem mhijiex meqjusa li tirrapreżenta riskju sinifikanti għall- bnedmin ibbażat minn- nuqqas ta ’ ġenotossiċità ta ’ vildagliptin u l- metabolu ewlieni tiegħu, id- dehra tat- tumuri fi speċi waħda biss, u il- proporzonijiet sistemiċi għoljin li bihom dehru dawn it- tumuri.
12 In a 13-week toxicology study in cynomolgus monkeys, skin lesions have been recorded at doses ≥ 5 mg/kg/day.
Fi studju tossikoloġiku ta ’ 13- il ġimgħa f’ xadini cynomolgus, feriti fil- ġilda kienu reġistrati b’ dożi ta ’ ≥ 5 mg/ kg/ jum.
These were consistently located on the extremities (hands, feet, ears and tail).
Dawn kienu lokalizzati b’ mod konsistenti fit- truf (idejn, saqajn, widnejn u denb).
At 5 mg/kg/day (approximately equivalent to human AUC exposure at the 100 mg dose), only blisters were observed.
B ’ 5 mg/ kg/ jum (kważi ekwivalenti għall- esponiment AUC fil- bniedem b’ doża ta ’ 100 mg), dehru biss nfatet.
They were reversible despite continued treatment and were not associated with histopathological abnormalities.
Dawn għaddew avolja l- kura kompliet u ma kienux assoċjati ma ’ anormalitajiet istopatoloġiċi.
Flaking skin, peeling skin, scabs and tail sores with correlating histopathological changes were noted at doses ≥ 20 mg/kg/day (approximately 3 times human AUC exposure at the 100 mg dose).
Ġilda li tinqala, ġilda li titqaxxar, qxur u selħiet fid- denb flimkien ma ’ bidliet istopatoloġiċi korrelatanti kienu nnutati b’ dożi ≥ 20 mg/ kg/ jum (madwar 3 darbiet l- esponiment ta ’ l- AUC fil - bniedem b’ doża ta ’ 100 mg).
Necrotic lesions of the tail were observed at ≥ 80 mg/kg/day.
Feriti nekrotiċi tad- denb dehru b’ ≥ 80 mg/ kg/ jum..
Skin lesions were not reversible in the monkeys treated at 160 mg/kg/day during a 4-week recovery period.
Il- feriti fil- ġilda ma għaddewx fix- xadini ikkurati b’ 160 mg/ kg/ jum waqt perijodu ta ’ rkupru li dam 4- ġimgħat.
Metformin Non-clinical data on metformin reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential and toxicity to reproduction.
Metformin Informazzjoni mhux klinika għal metformin ma turi l- ebda periklu speċjali għall- bnedmin ibbażata fuq studji konvenzjonali ta ’ sigurtà farmakoloġika, effett tossiku minn dożi ripetuti, ġenetossiċita, riskju kanċeroġeniku potenzjali u effett tossiku fuq is- sistema riproduttiva.
Hydroxypropylcellulose Magnesium stearate
Hydroxypropylcellulose Magnesium stearate
Film-coating:
Kisja tar- rita:
Hypromellose Titanium dioxide (E 171) Iron oxide, yellow (E 172) Macrogol 4000 Talc
Hypromellose Titanium dioxide (E 171) Iron oxide, yellow (E 172) Macrogol 4000 Talc
Store in the original package (blister) in order to protect from moisture.
Aħżen fil- pakkett oriġinali (folja) sabiex tilqa ’ mill- umdità.
6.5 Nature and contents of container
Aluminium/ Aluminium (PA/ Al/ PVC // Al) folja
Aluminium/Aluminium (PA/Al/PVC//Al) blister Available in packs containing 10, 30, 60, 120,180 or 360 film-coated tablets and in multi-packs containing 120 (2x60), 180 (3x60) or 360 (6x60) film-coated tablets.
13 Jiġi f’ pakketti li jkun fihom 10, 30, 60, 120, 180 jew 360 pillola miksija b’ rita u f’ pakketti b’ ħafna li fihom 120 (2x60), 180 (3x60) jew 360 (6x60) pilloli miksija b’ rita.
Not all pack sizes and tablet strengths may be marketed.
Jista ’ jkun li mhux il- pakketti tad- daqsijiet kollha u l- qawwiet kollha jkunu għall- skop kummerċjali.
Eucreas 50 mg/1000 mg film-coated tablets
Eucreas 50 mg/ 1000 mg pilloli miksijin b’ rita
Each film-coated tablet contains 50 mg of vildagliptin and 1000 mg of metformin hydrochloride (corresponding to 780 mg of metformin).
Kull pillola miksija b’ rita fiha 50 mg vildagliptin u 1000 mg metformin hydrochloride (li jissarraf f’ 780 mg ta ’ metformin).
Dark yellow, ovaloid film-coated tablet with bevelled edge, imprinted with “NVR” on one side and “FLO” on the other side.
Pillola miksija b’ rita safra skura, b’ għamla li tagħti fl- ovali b’ xifer imżerżaq, ittimbrata b ’ “ NVR ” fuq naħa waħda u “ FLO ” fuq in- naħa l- oħra.
Adults Based on the patient’s current dose of metformin, Eucreas may be initiated at either the 50 mg/850 mg or 50 mg/1000 mg tablet strength twice daily, one tablet in the morning and the other in the evening.
Adulti Ibbażat fuq id- doża ta ’ metformin li jkun qed jieħu l- pazjent, Eucreas jista ’ jinbeda b’ pillola ta ’ 50 mg/ 850 mg jew ta ’ 50 mg/ 1000 mg darbtejn kuljum, pillola waħda filgħodu u l- oħra filgħaxija.
Additional information on special populations Renal impairment Eucreas should not be used in patients with creatinine clearance < 60 ml/min (see sections 4.3, 4.4 and 5.2).
Informazzjoni oħra fuq popolazzjonijiet speċjali Indeboliment renali Eucreas m’ għandux jintuża f’ pazjenti bi tneħħija tal- krejatinina < 60 ml/ min (ara sezzjonijiet 4. 3, 4. 4 u 5. 2).
15 Elderly (≥ 65 years) As metformin is excreted via the kidney, and elderly patients have a tendency to decreased renal function, elderly patients taking Eucreas should have their renal function monitored regularly (see section 4.4).
15 Anzjani (≥ 65 sena) Peress illi metformin jitneħħa mill- kilwa, u pazjenti anzjani għandhom it- tendenza li jkollhom funzjoni renali mnaqsa, pazjenti anzjani li jkunu qed jieħdu Eucreas għandu jkollhom il- funzjoni renali immonitorata b’ mod regolari (ara sezzjoni 4. 4).
− Hypersensitivity to the active substances or to any of the excipients − Diabetic ketoacidosis or diabetic pre -coma − Renal failure or renal dysfunction defined as creatinine clearance < 60 ml/min (see section 4.4) − Acute conditions with the potential to alter renal function, such as:
− Sensittività eċċessiva għas- sustanzi attivi jew għal xi sustanzi mhux attivi. − Ketoaċidożi tad- dijabete jew pri- koma tad- dijabete. − Insuffiċjenza renali jew disfunzjoni renali definita bħala tneħħija tal- krejatinina < 60 ml/ min (ara sezzjoni 4. 4). − Kundizzjonijiet akuti li jistgħu jibdlu l- funzjoni renali, bħal:
Hepatic impairment Patients with hepatic impairment, including those with pre-treatment ALT or AST > 3x ULN, should not be treated with Eucreas (see sections 4.2, 4.3 and 4.8).
Indeboliment tal- fwied Pazjenti b’ indeboliment epatiku, inklużi pazjenti li jkollhom ALT jew AST qabel il- kura > 3 darbiet ULN, m’ għandhomx jiġu kkurati b’ Eucreas (ara sezzjonijiet 4. 2, 4. 3 u 4. 8).
4.5 Interaction with other medicinal products and other forms of interaction
17 4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarjiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
17 Vildagliptin Vildagliptin has a low potential for interactions with co-administered medicinal products.
Vildagliptin Vildagliptin għandu potenzjal baxx għal l- effetti mhux mixtieqa meta jingħata flimkien ma ’ prodotti mediċinali.
Drug-drug interaction studies with digoxin (P-glycoprotein substrate) and warfarin (CYP2C9 substrate) in healthy subjects have shown no clinically relevant pharmacokinetic interactions after co- administration with vildagliptin.
Studji kliniċi ta ’ interazzjoni bejn il- mediċini li saru b’ digoxin (sottostrat ta ’ glikoproteina- P) u warfarin (sottostrat ta ’ CYP2C9) f’ individwi b’ saħħithom ma wrew l- ebda interazzjonijiet farmakokinetiċi klinikament rilevanti wara li ngħataw flimkien ma ’ vildagliptin.
Angiotensin converting enzyme (ACE) inhibitors may decrease the blood glucose levels.
18 Impedituri ta ’ angiotensin converting enzyme (ACE) jistgħu jnaqqsu l- livelli tal- glucose fid- demm.
Adverse reactions reported in patients who received vildagliptin 100 mg daily as add-on therapy to metformin compared to placebo plus metformin in double-blind studies (N=208)
19 Tabella 1 Reazzjonijiet avversi rrappurtati f’ pazjenti li rċevew vildagliptin 100 mg kuljum bħala terapija li ġiet miżjuda ma ’ metformin meta mqabbla ma ’ plaċebo ma ’ metformin fi studji double- blind (N=208)
In controlled clinical trials with the combination of vildagliptin 100 mg daily plus metformin, no withdrawal due to adverse reactions was reported in either the vildagliptin 100 mg daily plus metformin or the placebo plus metformin treatment groups.
Fi provi kliniċi bil- kontroll bit- taħlita ta ’ vildagliptin 100 mg kuljum ma ’ metformin, l- ebda twaqqif minħabba reazzjonijiet avversi ma kien irrappurtat la fil- gruppi ta ’ trattament b’ vildagliptin 100 mg kuljum flimkien ma ’ metformin jew fil- grupp tal- plaċebo ma ’ metformin.