qanastek/EMEA-V3 huggingface dataset:
Hepatic impairment Galvus should not be used in patients with hepatic impairment, including patients with pre-treatment ALT or AST > 3x ULN.
Indeboliment tal- fwied Galvus mgħandux jintuża f’ pazjenti b’ indeboliment tal- fwied, inklużi pazjenti li jkollhom ALT jew AST qabel il- kura ta > 3 darbiet l- ULN.
Liver enzyme monitoring Rare cases of hepatic dysfunction (including hepatitis) have been reported.
Monitoraġġ ta ’ l- enzimi tal- fwied Każijiet rari ta ’ funzjoni mhux normali tal- fwied (inkluża l- epatite) kienu rrappurtati.
In these cases, the patients were generally asymptomatic without clinical sequelae and liver function test results returned to normal after discontinuation of treatment.
F’ dawn il - każijiet. il- pazjenti b’ mod ġenerali ma kellhomx konsegwenzi kliniċi u r- riżultati tat- testijiet tal - funzjoni tal- fwied reġgħu lura għan- normal wara li twaqfet il- kura.
Liver function tests should be performed prior to the initiation of treatment with Galvus in order to know the patient’ s baseline value.
It- testijiet tal- funzjoni tal- fwied għandhom isiru qabel ma tinbeda l- kura b’ Galvus sabiex ikun magħruf il- valur tal- linja bażi tal - pazjent.
Liver function should be monitored during treatment with Galvus at three-month intervals during the first year and periodically thereafter.
Il- funzjoni tal- fwied għandha tiġi monitorata waqt il- kura b’ Galvus f’ intervalli ta ’ tlett xhur fl- ewwel sena u darba kulltant minn hemm ’ l quddiem.
Patients who develop increased transaminase levels should be monitored with a second liver function evaluation to confirm the finding and be followed thereafter with frequent liver function tests until the abnormality(ies) return(s) to normal.
Pazjenti li jiżviluppaw żiediet fil- livelli ta ’ transaminases għandhom jiġu monitorati b’ evalwazzjoni oħra tal- funzjoni tal- fwied sabiex tiġi kkonfermata s- sejba u jibqgħu jiġu segwiti minn hemm ‘ l quddiem b’ testijiet tal- funzjoni tal- fwied frekwenti sakemm l- anormalità( jiet) jiġi( u) lura għan- normal.
Should an increase in AST or ALT of 3x ULN or greater persist, withdrawal of Galvus therapy is recommended.
Jekk żieda fl- AST jew ALT ta ’ 3 darbiet il- ULN jew aktar jippersisti, huwa rakkomandat li t- terapija b’ Galvus titwaqqaf.
Patients who develop jaundice or other signs suggestive of liver dysfunction should discontinue Galvus.
Pazjenti li jiżviluppaw is- suffejra jew sinjali li jindikaw funzjoni anormali tal- fwied għandhom iwaqqfu Galvus.
Following withdrawal of treatment with Galvus and LFT normalisation, treatment with Galvus should not be reinitiated.
Wara t- twaqqif tal- kura b’ Galvus u LFT ikun ġie lura għan- normal, il- kura b’ Galvus mgħandhiex terġa tinbeda.
3 Cardiac failure Experience with vildagliptin therapy in patients with congestive heart failure of New York Heart Association (NYHA) functional class I-II is limited and therefore vildagliptin should be used cautiously in these patients.
3 Insuffiċejnza kardijaka L- esperjenza b’ terapija ta ’ vildagliptin f’ pazjenti b’ insuffiċjenza tal- qalb konġestiva ta ’ klassi funzjonali ta ’ l- Assoċjazzjoni Tal- Qalb ta ’ New York (NYHA) I- II hija limitata u għalhekk vildagliptin għandu jintuża b’ attenzjoni f’ dawn il- pazjenti.
There is no experience of vildagliptin use in clinical trials in patients with NYHA functional class III-IV and therefore use is not recommended in these patients.
M’ hemmx esperjenza bl- użu ta ’ vildagliptin fi provi kliniċi f’ pazjenti bi klassi funzjonali NYHA III- IV u għalhekk l- użu mhux rakkomandat f’ dawn il- pazjenti.
Skin disorders Skin lesions, including blistering and ulceration have been reported in extremities of monkeys in non- clinical toxicology studies (see section 5.3).
Disturbi fil- ġilda Feriti fil- ġilda, inklużi bżieżaq u ulċeri kienu irrappurtati fit- truf ta ’ xadini fi studji tossikoloġi mhux kliniċi (ara sezzjoni 5. 3).
Although skin lesions were not observed at an increased incidence in clinical trials, there was limited experience in patients with diabetic skin complications.
Għalkemm feriti fil- ġilda ma dehrux aktar spissi waqt provi kliniċi, kien hemm esperjenza limitata b’ pazjenti li kellhom komplikazzjonijiet tal- ġilda minħabba d- dijabete.
Therefore, in keeping with routine care of the diabetic patient, monitoring for skin disorders, such as blistering or ulceration, is recommended.
Għalhekk, waqt il- kura ta ’ pazjenti dijabetiċi, monitoraġġ ta ’ disturbi fil- ġilda, bħall bżieżaq jew ulċeri, huwa rakkomandat.
Excipients The tablets contain lactose.
Sustanzi mhux attivi Il- pilloli fihom lactose.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Pazjenti b’ mard ereditarju rari ta ’ intolleranza għal galactose, defiċjenza ta ’ Lapp lactase jew malassorbiment ta ’ glucose- galactose m’ għandhomx jieħdu din il- mediċina.
Vildagliptin has a low potential for interactions with co-administered medicinal products.
Vildagliptin għandu potenzjali baxx għal interazzjonijiet meta jingħata flimkien ma ’ prodotti mediċinali.
Since vildagliptin is not a cytochrome P (CYP) 450 enzyme substrate and does not inhibit or induce CYP 450 enzymes, it is not likely to interact with active substances that are substrates, inhibitors or inducers of these enzymes.
Peress li vildagliptin mhuwiex sottostrat ta ’ l- enzima cytochrome P (CYP) 450 u la jinibixxi u l- anqas jinduċi l- enzimi CYP 450, x’ aktarx li ma tinteraġġixxix ma ’ sustanzi attivi li huma sottostrati, inibituri jew indutturi ta ’ dawn l- enzimi.
Combination with pioglitazone, metformin and glyburide Results from studies conducted with these oral antidiabetics have shown no clinically relevant pharmacokinetic interactions.
Kombinazzjoni ma ’ pioglitazone, metformin u glyburide Riżultati minn studji li saru b’ dawn l- antidijabetiċi orali ma wrew l- ebda interazzjonijiet farmakokinetiċi.
Digoxin (Pgp substrate), warfarin (CYP2C9 substrate) Clinical studies performed with healthy subjects have shown no clinically relevant pharmacokinetic interactions.
Digoxin (sottostrat Pgp), warfarin (sottostrat CYP2C9) Provi kliniċi li saru b’ individwi b’ saħħithom ma wrew l- ebda interazzjonijiet farmakonikentiċi.
However, this has not been established in the target population.
Madankollu, dan ma ġiex stabbilit fil- popolazzjoni milquta.
Combination with amlodipine, ramipril, valsartan or simvastatin Drug-drug interaction studies in healthy subjects were conducted with amlodipine, ramipril, valsartan and simvastatin.
Kombinazzjoni ma ’ amlodopine, ramipril, valsartan jew simvastatin Studji ta ’ interazzjonijiet bejn il- mediċini f’ individwi b’ saħħithom saru b’ amlodipine, ramipril, valsartan u simvastatin.
In these studies, no clinically relevant pharmacokinetic interactions were observed after co-administration with vildagliptin.
F’ dawn l- istudji, ma dehrux interazzjonijiet farmakokinetiċi li kienu klinikament relevanti wara li ngħataw ma ’ vildagliptin.
As with other oral antidiabetic medicinal products the hypoglycaemic effect of vildagliptin may be reduced by certain active substances, including thiazides, corticosteroids, thyroid products and sympathomimetics.
Bħal prodotti mediċinali antidijabetiċi orali oħrajn l- effett ipogliċemiku ta ’ vildagliptin jista ’ jitnaqqas b’ ċerti sustanzi attivi, inklużi thiazides, kortikosterojdi, prodotti tat- tirojde u simpatomimetiċi.
There are no adequate data from the use of vildagliptin in pregnant women.
M’ hemmx tagħrif biżżejjed dwar l- użu ta ’ vildagliptin waqt it- tqala.
Studies in animals have shown reproductive toxicity at high doses (see section 5.3).
Studji fuq bhejjem urew ħsara fuq is- sistema riproduttiva b’ dożi għoljin (ara sezzjoni 5. 3).
Due to lack of human data, Galvus should not be used during pregnancy.
Minħabba nuqqas ta ’ dejta fil- bniedem, Galvus m’ għandux jintuża waqt it- tqala.
It is not known whether vildagliptin is excreted in human breast milk.
Mhux magħruf jekk Galvus joħroġx mal- ħalib tal- mara.
Animal studies have shown excretion of vildagliptin in milk.
Studji fl- annimali wrew li vildagliptin jitneħħa fil- ħalib.
Galvus should not be used during lactation.
Galvus m’ għandux jintuża waqt it- treddigħ.
Patients who experience dizziness as an undesirable effect should avoid driving vehicles or using machines.
Pazjenti li jaqbadhom sturdament bħala effett mhux mixtieq għandhom jevitaw li jsuqu karozzi jew jħaddmu magni.
Safety data were obtained from a total of 3,784 patients exposed to vildagliptin at a daily dose of 50 mg (once daily) or 100 mg (50 mg twice daily or 100 mg once daily) in controlled trials of at least 12 weeks duration.
Tagħrif dwar is- sigurtà inkiseb minn 3, 784 pazjent espost għal vildagliptin b’ doża ta ’ 50 mg kuljum (darba kuljum) jew 100 mg (50 mg darbtejn kuljum jew 100 mg darba kuljum) fi provi kliniċi kontrollati li damu mill- anqas 12- il ġimgħa.
Of these patients, 2,264 patients received vildagliptin as monotherapy and 1,520 patients received vildagliptin in combination with another medicinal product.
Minn dawn, 2, 264 pazjent rċievew vildagliptin waħdu u 1, 520 pazjent rċievew vildagliptin f’ kombinazzjoni ma ’ prodott mediċinali ieħor.
2,682 patients were treated with vildagliptin 100 mg daily (either 50 mg twice daily or 100 mg once daily) and 1,102 patients were treated with vildagliptin 50 mg once daily.
2, 682 pazjent kienu kkurati b’ vildagliptin 100 mg kuljum (50 mg darbtejn kuljum jew 100 mg darba kuljum) u 1, 102 pazjent kienu kkurati b’ vildagliptin 50 mg darba kuljum.
The majority of adverse reactions in these trials were mild and transient, not requiring treatment discontinuations.
Il- parti l- kbira tar- reazzjonijiet avversi f’ dawn il- provi kienu ħfief u momentanji, mingħajr ma kienu jeħtieġu twaqqif tal- kura.
No association was found between adverse reactions and age, ethnicity, duration of exposure or daily dose.
Ma nstabitx assoċjazzjoni bejn ir- reazzjonijiet avversi u l- età, razza, tul ta ’ l - esponiment jew doża ta ’ kuljum.
Rare cases of hepatic dysfunction (including hepatitis) have been reported.
Każijiet rari ta ’ funzjoni mhux normali tal- fwied (inkluża l- epatite) kienu rrappurtati.
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.
Rare cases of angioedema have been reported on vildagliptin at a similar rate to controls.
Każijiet rari ta ’ anġjoedema kienu rrappurtati b’ vildagliptin b’ rati simili għall- dawk bil- kontroll.
A greater proportion of cases were reported when vildagliptin was administered in combination with an angiotensin converting enzyme inhibitor (ACE-Inhibitor).
Proporzjon akbar ta ’ każijiet kienu rrappurtati meta vildagliptin ingħata flimkien ma ’ inibitur ta ’ l - enzima li tikkonverti l- angiotensin (inibitur- ACE).
The majority of events were mild in severity and resolved with ongoing vildagliptin treatment.
Il- parti l- kbira tal- każijiet kienu ħfief fil- qawwa u għaddew bit- tkomplija tal- kura b’ vildagliptin.
Adverse reactions reported in patients who received Galvus in double-blind studies as monotherapy and add-on therapies are listed below for each indication by system organ class and absolute frequency.
Reazzjonijiet avversi rrappurtati f’ pazjenti li rċievew Galvus fi studji double blind bħala monoterapija u terapiji miżjuda huma elenkati hawn taħt għall- kull indikazzjoni bil- klassi ta ’ l- organi tas- sistema u frekwenza assoluta.
Frequencies are defined as very common (≥ 1/ 10), common (≥ 1/ 100, < 1/ 10), uncommon (≥ 1/ 1,000, < 1/ 100), rare (≥ 1/ 10,000 to < 1/ 1,000), very rare (< 1/ 10,000), not known (cannot be estimated from the available data).
Il- frekwenzi huma definiti komuni ħafna (≥1/ 10), komuni (≥1/ 100, < 1/ 10) jew mhux komuni (≥1/ 1, 000, < 1/ 100), rari (≥1/ 10, 000 sa < 1/ 1, 000), rari ħafna (< 1/ 10, 000), mhux magħruf (ma jistax jiġi stmat mid- dejta disponibbli).
Combination with metformin In controlled clinical trials with the combination of vildagliptin 100 mg daily + metformin, no withdrawal due to adverse reactions was reported in either the vildagliptin 100 mg daily + metformin or the placebo + metformin treatment groups.
Meta jittieħed flimkien ma ’ metformin Fi provi kliniċi bil- kontrol meta vildagliptin 100 mg kuljum ingħata flimkien ma ’ metformin, l- ebda twaqqif minħabba reazzjonijiet avversi ma kien irrappurtat kemm fil- gruppi ta ’ kura b’ vildagliptin 100 mg kuljum flimkien ma ’ metformin jew fil grupp tal- plaċebo flimkien ma ’ metformin.
In clinical trials, the incidence of hypoglycaemia was common in patients receiving vildagliptin 100 mg daily in combination with metformin (1%) and uncommon in patients receiving placebo + metformin (0.4%).
Fi studji kliniċi, l- inċidenza ta ’ l- ipogliċemija kienet komuni f’ pazjenti li kienu qed jirċievu vildagliptin 100 mg kuljum f’ kombinazzjoni ma ’ metformin (1%) u mhux komuni f’ pazjenti li kienu qed jirċievu plaċebo + metformin (0. 4%).
No severe hypoglycaemic events were reported in the vildagliptin arms.
Ma kienx hemm każijiet ta ’ ipogliċemija severa rrappurtati fil- friegħi ta ’ 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, l- 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).
Adverse reactions reported in patients who received Galvus 100 mg daily in combination with metformin in double-blind studies (N=208)
5 Tabella 1 Reazzjonijiet avversi rrappurtati f’ pazjenti li rċievew Galvus 100 mg kuljum ma ’ metformin fi studji double- blind (N=208)
Tremor Headache Dizziness Fatigue
Tregħid Uġigħ ta ’ ras Strudament Għeja
Combination with a sulphonylurea In controlled clinical trials with the combination of vildagliptin 50 mg + a sulphonylurea, the overall incidence of withdrawals due to adverse reactions was 0.6% in the vildagliptin 50 mg + sulphonylurea vs 0% in the placebo + sulphonylurea treatment group.
Meta jittieħed flimkien ma ’ sulphonylurea Fi provi kliniċi bil- kontroll meta vildagliptin 50 mg ingħata ma ’ sulphonylurea, l- inċidenza globali tat - twaqqif minħabba reazzjonijiet avversi kienet 0. 6% fil- grupp ta ’ kura b’ vildagliptin 50 mg ma ’ sulphonylurea kontra 0% fil- grupp bil- plaċebo ma ’ sulphonylurea.
In clinical trials, the incidence of hypoglycaemia when vildagliptin 50 mg once daily was added to glimepiride was 1.2% versus 0.6% for placebo + glimepiride.
Fi provi kliniċi, l- inċdenza ta ’ ipoglċemija meta vildagliptin 50 mg ingħata darba kuljum flimkien ma ’ glimepiride kienet ta ’ 1. 2% kontra 0. 6% għall- plaċebo flimkien ma ’ glimepiride.
No severe hypoglycaemic events were reported in the vildagliptin arms.
L- ebda każijiet ta ’ ipogliċemija severa ma kienu rrappurtati fil- friegħi b’ vildagliptin.
In clinical trials, weight did not change from baseline when vildagliptin 50 mg daily was added to glimepiride (-0.1 kg and -0.4 kg for vildagliptin and placebo, respectively).
Fi provi kliniċi, il- piż ma nbidilx mill- linja bażi meta vildagliptin 50 mg kien miżjud ma ’ glimepiride (- 0. 1 kg u - 0. 4 kg għal vildagliptin u plaċebo, rispettivament).
Adverse reactions reported in patients who received Galvus 50 mg in combination with a sulphonylurea in double-blind studies (N=170)
Tabella 2 Reazzjonijiet avversi rrappurtati f’ pazjenti li rċievew Galvus 100 mg kuljum ma ’ sulphonylurea fi studji double- blind (N=170)
Nasopharyngitis
Nażofarinġite
Common Common Common Common
Komuni Komuni Komuni Komuni
Tremor Headache Dizziness Asthenia
Tregħid Uġigħ ta ’ ras Strudament Astenja
Combination with a thiazolidinedione In controlled clinical trials with the combination of vildagliptin 100 mg daily+ a thiazolidinedione, no withdrawal due to adverse reactions was reported in either the vildagliptin 100 mg daily + thiazolidinedione or the placebo + thiazolidinedione treatment groups.
Meta jittieħed flimkien ma ’ thiazolidinedione Fi provi kliniċi bil- kontroll meta vildagliptin 100 mg kuljum ingħata ma ’ thiazolidinedione, ma kien irrappurtat l- ebda każ ta ’ twaqqif minħabba reazzjonijiet avversi kemm fil- grupp ta ’ kura b’ vildagiptin 100 mg kuljum flimkien ma ’ thiazolidinedione jew fil- plaċebo flimkien ma ’ thiazolidinedione.
In clinical trials, the incidence of hypoglycaemia was uncommon in patients receiving vildagliptin + pioglitazone (0.6%) but common in patients receiving placebo + pioglitazone (1.9%).
Fi provi kliniċi, l- inċidenza ta ’ ipogliċemija ma kienitx komuni f’ pazjenti li kienu qed jirċievu vildagliptin flimkien ma ’ pioglitazone (0. 6%) iżda komuni f’ pazjenti li kienu qed jirċievu plaċebo flimkien ma ’ pioglitazone (1. 9%).
No severe hypoglycaemic events were reported in the vildagliptin arms.
Ma kienu rrappurtati l- ebda każijiet ta ’ ipogliċemija severa fil - friegħi b’ vildagliptin.
In the pioglitazone add-on study, the absolute weight increases with placebo, Galvus 100 mg daily were 1.4 and 2.7 kg, respectively.
Fl- istudju biż- żieda ta ’ pioglitazone, il- piż assolut jiżdied bil- plaċebo u b’ Galvus 100 mg kuljum kienu 1. 4 u 2. 7 kg rispettivament.
The incidence of peripheral oedema when vildagliptin 100 mg daily was added to a maximum dose of background pioglitazone (45 mg once daily) was 7.0%, compared to 2.5% for background pioglitazone alone.
L- inċidenza ta ’ edema periferali meta kien miżjud vildagliptin 100 mg kuljum ma ’ doża massima ta ’ pioglitazone fl- isfond (45 mg darba kuljum) kienet 7. 0%, imqabbla ma ’ 2. 5% għall- pioglitazone fl - isfond waħdu.
Adverse reactions reported in patients who received Galvus 100 mg daily in combination with a thiazolidinedione in double-blind studies (N=158)
6 Tabella 3 Reazzjonijiet avversi rrappurtati f’ pazjenti li rċievew Galvus 100 mg flimkien ma ’ thiazolidinedione fi studji double- blind (N=158)
Uncommon Uncommon
Mhux komuni Mhux komuni
Headache Asthenia
Uġigħ ta ’ ras Astenja
Weight increase Hypoglycaemia
Żieda fil- piż Ipogliċemija
In addition, in controlled monotherapy trials with vildagliptin the overall incidence of withdrawals 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%).
Minbarra hekk, fi provi kontrollati b’ monoterapija b’ vildagliptin, l- inċidenza globali ta ’ dawk li kellhom iwaqqfuh minħabba reazzjonijiet avversi ma kienitx akbar għal pazjenti ikkurati 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 kontrollati b’ monoterapija għat- tqabbil, l- ipogliċemija kienet mhux komuni, irrappurtata f’ 0. 4% (7 minn 1, 855) tal- pazjenti ikkurati b’ vildagliptin 100 mg kuljum imqabbla ma ’ 0. 2% (2 minn 1, 082) tal- pazjenti ikkurati fil- gruppi bi plaċebo jew mediċina attiva għat- tqabbil, mingħajr ma ġew rappurtati każijiet serji sew severi.
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).
Fi 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).
Adverse reactions reported in patients who received Galvus 100 mg daily as monotherapy in double-blind studies (N=1,855)
Tabella 4 Reazzjonijiet avversi rrappurtati f’ pazjenti li rċievew Galvus 100 mg kuljum bħala monoterapija fi studji double- blind (N=1, 855)
Musculoskeletal and connective tissue disorders
Disturbi muskolu- skeltrali u tal- connective tissue
Upper respiratory tract infection Nasopharyngitis
Infezzjoni respiratorja fin- naħa ta ’ fuq Nażofarinġite
Information regarding overdose with vildagliptin is limited.
Informazzjoni dwar doża eċċessiva b’ vildagliptin hija limitata.
Information on the likely symptoms of overdose was taken from a rising dose tolerability study in healthy subjects given Galvus for 10 days.
L- informazzjoni dwar x’ aktarx li jkunu s- sintomi ta ’ doża eċċessiva inkisbu minn studju dwar it - tolleranza għal doża ta ’ Galvus miżjuda mogħtija lill- individwi b’ saħħithom 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 ta ’ parasteżija ħafifa u mumentanja, deni, edema u żiediet mumentanji fil- livelli ta ’ lipase.
At 600 mg, one subject experienced oedema of the feet and hands, and increases in creatine phosphokinase (CPK), aspartate aminotransferase (AST), C-reactive protein (CRP) and myoglobin levels.
B’ 600 mg, individwu wieħed kellu edema tas- saqajn u l- idejn, u żiediet tal- krejatinina phosphokinase (CPK), aspartate amintotransferase (AST), proteina reattiva- C (CRP) u livelli ta ’ mijoglobina.
Three other subjects experienced oedema of the feet, with paraesthesia in two cases.
Tlett individwi oħra kellhom edema f’ saqajhom, bi parasteżija f’ żewġ każijiet.
All symptoms and laboratory abnormalities resolved without treatment after discontinuation of the study medicinal product.
Is- sintomi kollha u l- anormalitajiet tal- laboratorju għaddew mingħajr kura wara li l- prodott mediċinali li kien qed jiġi studjat twaqqaf.
7 Management In the event of an overdose, supportive management is recommended.
7 Maniġġar F’ każ ta ’ doża eċċessiva, huwa rakkomandat maniġġar ta ’ support.
Vildagliptin cannot be removed by haemodialysis.
Vildagliptin ma jistax jitneħħa b’ emodijalisi.
However, the major hydrolysis metabolite (LAY 151) can be removed by haemodialysis.
Madankollu, il- metabolu ta ’ l- idroliżi ewlieni (LAY 151) jista ’ jitneħħa b’ emodijalisi.
Dipeptidyl peptidase 4 (DPP-4) inhibitors, ATC code:
Impedituri dipeptidyl peptidase (DPP- 4), Kodiċi ATC:
Vildagliptin, a member of the islet enhancer class, is a potent and selective DPP-4 inhibitor.
Vildagliptin, membru tal- klassi islet enhancer, huwa inibitur qawwi u silettiv DPP- 4.
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 (glucagon-like peptide 1) and GIP (glucose-dependent insulinotropic polypeptide).
L- għotja ta ’ vildagliptin twassal għal impediment mgħaġġel u komplet ta ’ l- attività DPP- 4, li twassal għal livelli endoġeni ogħla ta ’ waqt is- sawm u wara l- ikel ta ’ ormoni inkretin GLP- 1 (peptidu 1 li jixbah il- glukagon) u GIP (polypeptidu insulinotropiku dipendenti fuq glucose).
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.
Bis- saħħa taż- żieda li jġib fil- livelli endoġeni ta ’ dawn l- ormoni inkretin, vildagliptin itejjeb is - sensittività taċ- ċelluli beta għal glucose, li jwassal għal sekrezzjoni aħjar ta ’ l- insulina dipendenti 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 bid- dijabete tat- tip 2 tejbet b’ mod sinifikanti l- markaturi tal- funzjoni taċ- ċelluli beta inkuż HOMA- β (Evalwar- β tal- Mudell ta ’ Omejostażi), proporzjon tal- pro- insulina ma ’ l- insulina u l- kejl ta ’ kemm juru rispons iċ- ċelluli beta mit- test tat - tolleranza li jieħu ħafna kampjuni.
In non-diabetic (normal glycaemic) individuals, vildagliptin does not stimulate insulin secretion or reduce glucose levels.
F’ individwi mhux dijabetiċi (gliċemija normali), vildagliptin ma jikkawżax stimulazzjoni tas- sekrezzjoni ta ’ l- insulina jew inaqqas il- livelli ta ’ glucose.
By increasing endogenous GLP-1 levels, vildagliptin also enhances the sensitivity of alpha cells to glucose, resulting in more glucose-appropriate glucagon secretion.
Bis- saħħa taż- żieda li jġib fil- livelli endoġeni GLP- 1, vildagliptin itejjeb ukoll is- sensittività taċ- ċelluli alfa għal glucose, li jwassal għal sekrezzjoni ta ’ glukagon aktar xierqa għal 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 fiż- żieda tal- proporzjon insulina/ glukagon waqt ipergliċemija minħabba ż- żiediet fil- livelli ta ’ ormoni inkretin iwassal għal tnaqqis fil- produzzjoni epatika ta ’ glucose waqt is- sawm u wara l- ikel, li jwassal 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 għandhom żiediet fil- livelli ta ’ GLP- 1 li jittardja t- tbattil ta ’ l- istonku ma jidhirx waqt il- kura b’ vildagliptin.
A total of 5,759 patients with type 2 diabetes participated in 13 double-blind placebo- or active- controlled clinical trials of at least 12-weeks’ treatment duration.
Total ta ’ 5, 759 pazjent b’ dijabete tat- tip 2 ħadu sehem fi 13- il prova klinika double- blind kontrollati bi plaċebo jew attivi b’ kura li damet mill- anqas 12- il ġimgħa.
In these studies, vildagliptin was administered to 3,784 patients at daily doses of 50 mg once daily (N=1,102), 50 mg twice daily (N=2,027) or 100 mg once daily (N=655).
F’ dawn l- istudji, vildagliptin ingħata lil 3, 784 pazjent kuljum b’ dożi ta ’ 50 mg darba kuljum (N=1, 102), 50 mg darbtejn kuljum (N=2, 027) jew 100 mg darba kuljum (N=655).
The number of male and female patients receiving vildagliptin 50 mg once daily or 100 mg daily was 2,069 and 1,715, respectively.
In- numru ta ’ pazjenti maskili u femminili li kienu qed jirċievu vildagliptin 50 mg darba kuljum jew 100 mg kuljum kien 2, 069 u 1, 715, rispettivament.
The number of patients receiving vildagliptin 50 mg once daily or 100 mg daily who were ≥ 65 years of age was 664 and 121 of the patients were ≥ 75 years of age.
In- numru ta ’ pazjenti li kienu qed jirċievu vildagliptin 50 mg darba kuljum jew 100 mg kuljum li kellhom ≥ 65 sena kien 664 u 121 tal- pazjenti kellhom ≥ 75 sena.
In these trials, vildagliptin was administered as monotherapy in drug-naïve patients with type 2 diabetes or in combination in patients not adequately controlled by other antidiabetic medicinal products.
F’ dawn il- provi, vildagliptin ingħata bħala monoterapija f’ pazjenti naive għall- mediċina b’ dijabete tat- tip 2 jew f’ kombinazzjoni f’ pazjenti li ma kienux kontrollati b’ mod xieraq bi prodotti mediċinali kontra d- dijabete oħrajn.
Overall, vildagliptin improved glycaemic control when given as monotherapy or when used in combination with metformin, a sulphonylurea, and a thiazolidinedione, as measured by clinically relevant reductions in HbA1c from baseline at study endpoint (see Table 5).
B’ mod ġenerali, vildagliptin tejjeb il- kontroll gliċemiku meta ngħata bħala monoterapija jew meta ntuża f’ kombinazzjoni ma ’ metformin, sulphonylurea u thiazolidinedione kif imkejjel minn tnaqqis klinikament rilevanti fl- HbA1c mill- linja bażi fl- endpoint ta ’ l- istudju (ara Tabella 5).
In clinical trials, the magnitude of HbA1c reductions with vildagliptin was greater in patients with higher baseline HbA1c.
Fi provi kliniċi, il- grad ta ’ tnaqqis fl- HbA1c b’ vildagliptin kien akbar fil- pazjenti li kellhom HbA1c ogħla fil- linja bażi.
In a 52-week double-blind controlled trial, vildagliptin (50 mg twice daily) reduced baseline HbA1c by -1% compared to -1.6% for metformin (titrated to 2 g/ day) statistical non-inferiority was not achieved.
Fi prova double- blind kontrollata li damet 52- ġimgħa, vildagliptin (50 mg darbtejn kuljum) naqqas l - HbA1c mill- linja bażi b ’ - 1% meta mqabbel ma ’ - 1. 6% għal metformin (miżjud għal 2 g/ jum) ma nstabx li ma kienx inferjuri b’ mod statistiku.
8 Patients treated with vildagliptin reported significantly lower incidences of gastrointestinal adverse reactions versus those treated with metformin.
Pazjenti kkurati b’ vildagliptin irrappurtaw effetti avversi gastro - intestinali b’ inċidenza aktar baxxa b’ mod sinifikanti kontra dawk ikkurati b’ metformin.
In a 24-week double-blind controlled trial, vildagliptin (50 mg twice daily) was compared to rosiglitazone (8 mg once daily).
8 Fi prova double- blind kontrollata li damet 24- ġimgħa, vildagliptin (50 mg darbtejn kuljum) kien imqabbel ma ’ rosiglitazone (8 mg darba kuljum).
Mean reductions were -1.20% with vildagliptin and -1.48% with rosiglitazone in patients with mean baseline HbA1c of 8.7%.
Il- medji tat- tnaqqis kienu - 1. 20% b’ vildagliptin u - 1. 48% b’ rosiglitazone f’ pazjenti bil- linja bażi ta ’ HbA1c ta ’ 8. 7%.
Patients receiving rosiglitazone experienced a mean increase in weight (+1.6 kg) while those receiving vildagliptin experienced no weight gain (-0.3 kg).
Pazjenti li kienu qed jirċievu rosiglitazone kellhom żieda fil- piż (+1. 6 kg) fil- waqt li dawk li kienu qed jirċievu vildagliptin ma kellhomx żieda fil- piż (- 0. 3 kg).
4.1% respectively).
L- inċidenza ta ’ edema periferali kienet aktar baxxa fil- grupp b’ vildagliptin milli fil- grupp b’ rosiglitazone (2. 1% kontra 4. 1% rispettivament).
Key efficacy results of vildagliptin in placebo-controlled monotherapy trials and in add-on combination therapy trials (primary efficacy ITT population)
Riżultati importanti dwar l- effikaċja ta ’ vildagliptin fi provi b’ monoterapija kontrollati bi plaċebo u fi provi b’ terapija ta ’ kombinazzjoni miżjuda (l- effikaċja ewlenija tal- popolazzjoni ITT)
Monotherapy placebo
Studji kontrollati b’ monoterapija
Mean
Medja ta ’
Mean change
Il- medja tal -
Placebo-
ta ’ plaċebo
controlled studies
HbA1c fil -
baseline
bidla mill- linja
from baseline in
bil- plaċebo mill -
corrected mean
linja
HbA1c (%)
bażi (%)
HbA1c (%) at week 24
bażi fl- HbA1c (%) ma ’ ġimgħa 24
change in HbA1c (%) at week 24 (95%CI)
medja tal- bidla fl - HbA1c (%) ma ’ ġimgħa 24 (95% CI)
Study 2301:
Studju 2301:
Vildagliptin 50 mg twice daily (N=90)
Vildagliptin 50 mg darbtejn kuljum (N=90)
-0.8
- 0. 8
-0.5* (-0.8, -0.1)
- 0. 5 * (- 0. 8, - 0. 1)
Study 2384:
Studju 2384:
Vildagliptin 50 mg twice daily (N=79)
Vildagliptin 50 mg darbtejn kuljum (N=79)
-0.7* (-1.1, -0.4)
- 0. 7 * (- 1. 1, - 0. 4)
* p < 0.05 for comparison versus placebo Add-on / Combination studies Vildagliptin 50 mg twice daily + metformin (N=143)
* p < 0. 05 għat- tqabbil kontra plaċebo Studji miżjuda/ Kombinazzjoni Vildagliptin 50 mg darbtejn kuljum + metformin (N=143)
-0.9
- 0. 9
-1.1* (-1.4, -0.8)
- 1. 1 * (- 1. 4, - 0. 8)
Vildagliptin 50 mg daily + glimepiride (N=132)
Vildagliptin 50 mg kuljum + glimepiride (N=132)
-0.6* (-0.9, -0.4)
- 0. 6 * (- 0. 9, - 0. 4)
Vildagliptin 50 mg twice daily + pioglitazone (N=136)
Vildagliptin 50 mg darbtejn kuljum + pioglitazone (N=136)
-1.0
- 1. 0
-0.7* (-0.9, -0.4)
- 0. 7 * (- 0. 9, - 0. 4)
* p < 0.05 for comparison versus placebo + comparator
* p < 0. 05 għat- tqabbil kontra plaċebo + kumparatur
Absorption Following oral administration in the fasting state, vildagliptin is rapidly absorbed, with peak plasma concentrations observed at 1.7 hours.
Assorbiment Wara li jittieħed mill- ħalq fi stat ta ’ sawm, vildagliptin jiġi assorbit malajr bl- ogħla konċentrazzjonijiet fil- plażma jidhru mal- 1. 7 sigħat.
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 biex jintlaħaq l- ogħla konċentrazzjoni fil - plażma għal 2. 5 sigħat, iżda ma jibdilx l- esponiment globali (AUC).
Administration of vildagliptin with food resulted in a decreased Cmax (19%).
L- għotja ta ’ vildagliptin ma ’ l - ikel wasslet għal tnaqqis fis- Cmax (19%).
However, the magnitude of change is not clinically significant, so that Galvus can be given with or without food.
Madankollu, id- daqs tal- bidla mhiex klinikament sinfikanti, b’ hekk Galvus jista ’ jingħata ma ’ l- ikel jew mingħajr ikel.
Distribution The plasma protein binding of vildagliptin is low (9.3%) and vildagliptin distributes equally between plasma and red blood cells.
Distribuzzjoni Vildagliptin jeħel ftit (9. 3%) mal- proteini tal- plażma 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.
Biotransformation Metabolism is the major elimination pathway for vildagliptin in humans, accounting for 69% of the dose.
Biotrasformazzjoni Il- metaboliżmu huwa l- mezz ewlieni ta ’ l- eliminazzjoni ta ’ vildagliptin fil- bniedem, li jgħodd għal 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 maġġuri (LAY 151) huwa inattiv mill- lat farmakoloġiku u huwa l- prodott ta ’ l- isdroliżi tal- parti cyano, li tgħodd għal 57% tad- doża, segwit bil- prodott ta ’ l- idroliżi ta ’ l- amide (4% tad- doża).
In vitro data in human kidney microsomes suggest that the kidney may be one of the major organs contributing to the hydrolysis of vildagliptin to its major inactive metabolite, LAY151.
Dejta in vitro fil- mikrosomi tal- kilwa tal- bniedem jindikaw li il- kilwa tista ’ tkun wieħed mill- organi ewlenin li jikkontribwixxu għall- idroliżi ta ’ vildagliptin fil- metabolu ewlieni tiegħu, LAY151.
DPP-4 contributes partially to the hydrolysis of vildagliptin based on an in vivo study using DPP-4 deficient rats.
DPP- 4 jieħu sehem b’ mod parzjali fl- idroliżi ta ’ vildagliptin skond studji in vivo bl - użu ta ’ firien li għandhom deffiċjenza ta ’ DPP- 4.
Vildagliptin is not metabolised by CYP 450 enzymes to any quantifiable extent.
Vildagliptin mhux metabolizzat b’ enzimi cytochrome P450 f’ ammont li jista ’ jiġi kwantifikat.
Accordingly, the metabolic clearance of vildagliptin is not anticipated to be affected by co-medications that are CYP 9 450 inhibitors and/ or inducers.
9 ta ’ CYP 450.
In vitro studies demonstrated that vildagliptin does not inhibit/ induce CYP 450 enzymes.
Studji in vitro wrew li vildagliptin ma jikkawżax l- impediment/ induzzjoni ta ’ 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 ma jeffettwax it- tneħħija metabolika ta ’ medikazzjonijiet li jiġu 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 is recovered in the faeces.
Eliminazzjoni Wara li [14C] vildagliptin jittieħed mill- ħalq, madwar 85% tad- doża kienet eskretata fl- awrina u 15% tad- doża kienet irkuprata 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 għal 23% tad- doża wara li jittieħed mill- ħalq.
After intravenous administration to healthy subjects, the total plasma and renal clearances of vildagliptin are 41 and 13 l/ h, respectively.
Wara li jingħata minn ġol- vina f’ individwi b’ saħħithom, it- tneħħija totali tal- plażma u renali ta ’ vildagliptin 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 li jingħata minn ġol- vina hija madwar sagħtejn.
The elimination half- life after oral administration is approximately 3 hours.
Il- half- life ta ’ l - eliminazzjoni wara li jittieħed mill- ħalq hija madwar 3 sigħat.
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.
Linearità / nuqqas ta linearità Is- Cmax ta ’ vildagliptin u l- erja taħt il- kurvi tal- konċentrazzjonijiet fil- plażma kontra l- ħin (AUC) żdiedet b’ mod kważi proporzjonali mad- doża fil- medda tad- doża terapewtika.
Characteristics in patients Gender 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).
Karatteristiċi fil- pazjenti Sess Ma dehrux differenzi ta ’ rilevanza klinika fil- farmakokinetika ta ’ vildagliptin bejn individwi b’ saħħithom maskili u femminili f’ medda wiesa ’ ta ’ etajiet u indiċi tal- massa tal- ġisem (BMI).
DPP-4 inhibition by vildagliptin is not affected by gender.
L - inibizzjoni ta ’ DPP- 4 minn vildagliptin mhiex effettwata mis- sess.
Age 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).
Età F’ individwi anzjani (≥ 70 sena) b’ saħħithom, l- esponiment globali ta ’ vildagliptin (100 mg darba kuljum) żdied b’ 32%, b’ żieda ta ’ 18% ta ’ l- ogħla konċentrazzjoni fil- plażma meta mqabbel ma ’ individwi żgħażagħ (18- 40 sena) b’ saħħithom.
These changes are, however, not considered to be clinically relevant.
Dawn il- bidliet, madankollu, mhux meqjusa li huma klinikament rilevanti.
DPP-4 inhibition by vildagliptin is not affected by age.
L- inibizzjoni ta ’ DPP- 4 minn vildagliptin mhux effettwat mill- età.
Hepatic impairment The effect of impaired hepatic function on the pharmacokinetics of vildagliptin was studied in patients with mild, moderate and severe hepatic impairment based on the Child-Pugh scores (ranging from 6 for mild to 12 for severe) in comparison with healthy subjects.
Indeboliment tal- fwied L- effett ta ’ indeboliment fil- funzjoni epatika fuq il- farmakokinetika ta ’ vildagliptin kienet studjata f’ pazjenti b’ indeboliment tal- fwied ħafif, moderat u sever skond il- punteġġi Child- Pugh (minn 6 għal ħafif sa 12 għal sever) imqabbla ma ’ individwi b’ saħħithom.
The exposure to vildagliptin after a single dose in patients with mild and moderate hepatic impairment was decreased (20% and 8%, respectively), while the exposure to vildagliptin for patients with severe impairment was increased by 22%.
L- esponiment għal vildagliptin wara doża waħda f’ pazjenti b’ indeboliment ħafif u moderat kien imnaqqas (20% u 8%, rispettivament), fil- waqt li l- esponiment għal vildagliptin f’ pazjenti b’ indeboliment tal- fwied sever kien miżjud b’ 22%.
The maximum change (increase or decrease) in the exposure to vildagliptin is ~30%, which is not considered to be clinically relevant.
Il- bidla massima (żieda jew tnaqqis) fl- esponiment għal vildagliptin hija ~30% li mhix meqjusa klinikament rilevanti.
There was no correlation between the severity of the hepatic disease and changes in the exposure to vildagliptin.
Ma kienx hemm korrelazzjoni bejn is- severità tal- mard tal- fwied u l- bidliet fl- esponiment għal vildagliptin.
Renal impairment 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.
Indeboliment renali F’ individwi b’ indeboliment renali ħafif, moderat jew sever, l- esponiment sistemiku għal vildagliptin kien miżjud (Cmax 8- 66%; AUC 32- 134%) u t- tneħħija totali mill- ġisem tnaqqset meta mqabbla ma ’ individwi b’ funzjoni renali normali.
Ethnic group Limited data suggest that race does not have any major influence on vildagliptin pharmacokinetics.
Grupp etniku Dejta limitata tindika li r- razza m’ għandiex teffettwa l- farmakokinetika ta ’ 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).
Il- konduzzjoni ta ’ l- impulsi fil- qalb dehru ttardjati fi klieb b’ doża mingħajr effett ta ’ 15 mg/ kg (7 - darbiet l- esponiment fil- bniedem ibbażat fuq is- Cmax).
Accumulation of foamy alveolar macrophages in the lung was observed in rats and mice.
L- akkumulu ta ’ makrofaġi alveolari li jgħamlu r- rawgħa fil- pulmun deher fil- firien u fil- 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- darba l- esponiment fil- bniedem).
Gastrointestinal symptoms, particularly soft faeces, mucoid faeces, diarrhoea and, at higher doses, faecal blood were observed in dogs.
10 Sintomi gastro- intestinali, l- aktar ippurgar artab, ippurgar bi żlieġa, dijarea u, b’ dożi ogħla, demm fl - ippurgar dehru fi klieb.
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 għal 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 l- ewwel żvilupp ta ’ l- embriju fil- firien wera li mhemmx tixkil fil- fertilità, ħila ta ’ riproduzzjoni jew l- ewwel żvilupp ta ’ l- embriju minn vildagliptin.
Embryo-foetal toxicity was evaluated in rats and rabbits.
It- tossiċità fuq l- embriju u l- fetu kienet evalwata fil- firien u fil- 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).
Inċidenza akbar ta ’ kustilji mbewqa dehret fil- firien b’ mod assoċjat ma ’ tnaqqis fil- parametri tal- piż tal- ġisem ta ’ l- omm, b’ doża mingħajr effett ta ’ 75 mg/ kg (10 - darbiet 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- għadam li jindikaw ittardjar fl- iżvilupp dehru biss fil- preżenza ta ’ tossiċità severa għall- 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 ’ 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 ma ’ tossiċità fl- omm b’ ≥ 150 mg/ kg u kienu jinkludu tnaqqis mumentanju fil- piż tal- ġisem u tnaqqis fl- attività motorjali 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).
Studju dwar il- kanċeroġeniċità li dam sentejn sar fuq firien b’ dożi orali 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 dehrietx żieda fl- inċidenza ta ’ tumuri li kienu ġejjin minn vildagliptin.
Another two-year carcinogenicity study was conducted in mice at oral doses up to 1,000 mg/ kg.
Studju ieħor dwar il- kanċeroġeniċità sar fi ġrieden b’ dożi orali sa ’ 1, 000 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.
Dehret żieda fl- inċidenza ta ’ adenokarċenomi tal- mammarji u haemangiosarcomas 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- ġrieden mhiex meqjusa li tirrappreżenta riskju sinifikanti għal bnedmin ibbażat minn- nuqqas ta ’ ġenotossiċità ta ’ vildagliptin u l- metabolu ewlieni, il- fatt li t- tumuri seħħew fi speċi waħda biss u l- proporzjonijiet għoljin ta ’ l- esponimenti sistemiċi li bihom dehru t- tumuri.
In a 13-week toxicology study in cynomolgus monkeys, skin lesions have been recorded at doses ≥ 5 mg/ kg/ day.
Fi studju tossikioloġiku li dam 13- il ġimgħa fuq xadini cynomolgus, leżjonijiet fil- ġilda kienu reġistrati b’ dożi ta’ ≥ 5 mg/ kg/ jum.
These were consistently located on the extremities (hands, feet, ears and tail).
Dawn seħħew b’ modkonsistenti fl- estremitajiet (l- idejn, saqajn, widnejn u d- demb).
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 daqs l- esponiment AUC fil- bniedem bid- doża ta ’ 100 mg), dehru biss bżieżaq.
They were reversible despite continued treatment and were not associated with histopathological abnormalities.
Fiequ minkejja li tkompliet il- kura 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 tfarfar, ġilda li titqaxxar, skorċa u selħiet fid- demb bil- bidliet istopatoloġici korrelatati kienu nnutati b’ dożi ta ’ ≥ 20 mg/ kg/ jum (madwar 3 darbiet l- esponiment AUC fil- bniedem bid- doża ta ’ 100 mg).
Necrotic lesions of the tail were observed at ≥ 80 mg/ kg/ day.
Leżjonijiet nekrotiċi tad- demb 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.
Leżjonijiet fil- ġilda ma kienux riversibbli fix- xadini kkurati b’ 160 mg/ kg/ jum waqt perijodu ta ’ rkupru ta ’ 4 gimgħat.
Lactose, anhydrous Cellulose, microcrystalline Sodium starch glycolate (type A) Magnesium stearate
Lactose, anhydrous Cellulose, microcrystalline Sodium starch glycolate (type A) Magnesium stearate
6.4 Special precautions for storage
Ma jgħoddx f’ dan il- każ.
6.5 Nature and contents of container
11 6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
Aluminium/ Aluminium (PA/ Al/ PVC/ /Al) blister Available in packs containing 7, 14, 28, 30, 56, 60, 90, 112, 180 or 336 tablets and in multipacks containing 336 (3x112) tablets.
Aluminium/ Aluminium (PA/ Al/ PVC // Al) folja Jiġi f’ pakketti li jkun fihom 7, 14, 28, 30, 56, 60, 90, 112, 180 jew 336 pillola u f’ pakketti b’ hafna li jkollhom 336 (3x112) pilloli.
Novartis Pharma GmbH Roonstrasse 25 D-90429 Nürnberg Germany
Novartis Pharma GmbH Roonstrasse 25 D- 90429 Nürnberg Il- Ġermanja
Pharmacovigilance system The MAH must ensure that the system of pharmacovigilance, as described in version 3.0 (17 June 2008) presented in Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning before and whilst the product is on the market.
Sistema ta ’ farmakoviġilianza L- MAH għandu jaċċerta ruħu li is- sistema ta ’ farmakoviġilanza, kif deskritta fil- verżjoni 3. 0 (17 ta ’ Ġunju 2008) preżentata f’ Modulu 1. 8. 1 ta ’ l- Applikazzjoni għall- Awtorizzazzjoni għat- Tqegħid fis - Suq, tkun f’ lokha u taħdem qabel u waqt li l- prodott ikun fis- suq.