qanastek/EMEA-V3 huggingface dataset:
Each tablet contains 15 mg of pioglitazone (as hydrochloride) and 850 mg of metformin hydrochloride.
Kull pillola fiha 15 mg ta ’ pioglitazone (bħala hydrochloride) u 650 mg metformin hydrochloride.
For a full list of excipients, see section 6.1.
Għallista kompleta ta ’ sustanzi mhux attivi, ara sezzjoni 6. 1.
Film-coated tablet
Pillola miksija b’ rita.
The tablets are white to off-white, oblong, film-coated, embossed ‘ 15 / 850’ on one face and ‘ 4833M’ on the other.
Il- pilloli huma bojod għal abjad maħmuġ, oblung, miksija b’ rita mmarkati b ’ ‘ 15/ 850 ’ fuq naħa u ‘ 4833M ’ fuq l- oħra.
Competact is indicated in the treatment of type 2 diabetes mellitus patients, particularly overweight patients, who are unable to achieve sufficient glycaemic control at their maximally tolerated dose of oral metformin alone.
Competact huwa ndikat fil- kura ta ’ pazjenti b’ dijabete mellitus tat- tip 2 speċjalment pażjenti b’ piż żejjed, li ma laħqux kontroll gliċemiku suffiċjenti fl- għola doża ttollerata ta ’ metformin mill- ħalq waħdu.
Dosage in adults:
Dożaġġ fl- adulti:
The usual dose of Competact is 30 mg/ day pioglitazone plus 1700 mg/ day of metformin hydrochloride (this dosage is achievable with one tablet of Competact 15 mg/ 850 mg, taken twice a day).
Id- doża tas- soltu ta ’ Competacthija ta ’ pioglitazone 30 mg/ kuljum flimkien ma ’ metformin hydrochloride 1700 mg/ kuljum (dan id- dożaġġ jintlaħaq minn pillola waħda ta ’ Competact 15 mg/ 850 mg, darbtejn kuljum).
Dose titration with pioglitazone (added to the optimal dose of metformin) should be considered before the patient is switched to Competact.
Titrazzjoni tad- doża b’ pioglitazone (miżjud mad- doża ottimali ta ’ metformin) għandha tiġi kkunsidrata qabel ma l- pazjent jinqaleb fuq Competact.
When clinically appropriate, direct change from metformin monotherapy to Competact may be considered.
Fejn klinikament xieraq, jista ’ jiġi kkunsidrat tibdil dirett minn monoterapija b’ metformin għal Competact.
Taking Competact with, or just after food, may reduce gastrointestinal symptoms associated with metformin.
Jekk Competact jittieħed ma ’ l- ikel jew eżatt wara l- ikel, is- sintomi gastro- intestinali assoċjati ma ’ metformin jistgħu jitnaqqsu.
As metformin is excreted via the kidney, and elderly patients have a tendency to decreased renal function, elderly patients taking Competact should have their renal function monitored regularly (see sections 4.3 and 4.4).
Minħabba li metformin jitneħħa mill- kliewi, u pazjenti anzjani għandhom tendenza ta ’ funzjoni renali mnaqqsa, pazjenti anzjani li qed jieħdu Competact għandu jkollhom il- funzjoni renali tagħhom sorveljat b’ mod regolari (ara sezzjonijiet 4. 3 u 4. 4).
Competact should not be used in patients with renal failure or renal dysfunction (creatinine clearance < 60 ml/ min)(see sections 4.3 and 4.4).
Competact m’ għandux jintuża f’ pazjenti b’ indeboliment epatiku (ara sezzjonijiet 4. 3 u 4. 4).
2 Patients with hepatic impairment:
2 Tfal u adolexxenti:
There are no data available on the use of pioglitazone in patients under 18 years of age and therefore the use of Competact in this age group is not recommended.
M’ hemmx tagħrif disponibbli dwar l- użu ta ’ pioglitazone f’ pazjenti taħt l- eta ’ ta ’ 18- il sena, u għalhekk l- użu tiegħu mhux rakkomandat f’ dan il- grupp ta ’ eta ’.
Competact is contraindicated in patients with:
Competact huwa kontra- indikat f’ pazjenti b ’:
- Hypersensitivity to the active substances or to any of the excipients
- Sensittività eċċessiva għas- sustanza attiva jew għal xi sustanzi mhux attivi
- Cardiac failure or history of cardiac failure (NYHA stages I to IV)
- Insuffiċjenza kardijaka jew passat ta ’ insuffiċjenza kardijaka (NYHA stadju I sa IV)
- Acute or chronic disease which may cause tissue hypoxia such as cardiac or respiratory failure,
- Mard akut jew kroniku li jista ’ jikkawża ipoksja fit- tessut bħal insufficjenza kardijaka jew
recent myocardial infarction, shock
respiratorja, infart mijokardiku riċenti, xokk
- Hepatic impairment
- Indeboliment epatiku
- Acute alcohol intoxication, alcoholism
- Intossikazzjoni akuta ta ’ alkoħol, alkoħoliżmu
- Diabetic ketoacidosis or diabetic pre-coma
- Ketoaċidożi dijabetika jew pre- koma dijabetika
- Renal failure or renal dysfunction (creatinine clearance < 60 ml/ min) (see section 4.4).
- Insuffiċjenza renali jew disfunzjoni renali (tneħħijja ta ’ krejatinina < 60 ml/ min) (ara sezzjoni
- Acute conditions with the potential to alter renal function such as:
- Kundizzjonijiet akuti b’ potenzjal li jbiddlu l- funzjoni renali bħal:
- Dehydration
- Deidratazzjoni
- Severe infection
- Infezzjoni severa
- Shock
- Xokk
- Intravascular administration of iodinated contrast agents (see section 4.4)
- Għotja intravaskulari ta ’ aġenti ta ’ kuntrast ijodinati (ara sezzjoni 4. 4)
- Lactation
- Treddigħ
There is no clinical experience of pioglitazone in triple combination with other oral antidiabetic agents.
M’ hemmx esperjenza klinika ta ’ pioglitazone f’ taħlita trippla ma ’ aġenti anti- dijabetiċi mill- ħalq oħra.
Lactic acidosis:
Aċidożi lattika:
Lactic acidosis is a very rare, but serious, metabolic complication that can occur due to metformin accumulation.
Aċidożi lattika hija kumplikazzjoni metabolika rari ħafna, iżda serja li tista ’ sseħħ minħabba akkumulazzjoni ta ’ metformin.
Reported cases of lactic acidosis in patients on metformin have occurred primarily in diabetic patients with significant renal failure.
Każijiet irrappurtati ta ’ aċidożi lattika f’ pazjenti fuq metformin seħħew l- aktar f’ pazjenti dijabetiċi b’ insuffiċjenza renali sinifikanti.
The incidence of lactic acidosis can and should be reduced by assessing also other associated risk factors such as poorly controlled diabetes, ketosis, prolonged fasting, excessive alcohol intake, hepatic insufficiency and any condition associated with hypoxia.
L- inċidenza ta ’ aċidożi lattika tista ’ u għandha tiġi mnaqqsa ukoll permezz ta ’ analiżi ta ’ fatturi ta ’ riskju oħra bħal dijabete mhux ikkontrollata tajjeb, ketożi, sawm imtawwal, teħid eċċessiv ta ’ alkoħol, insuffiċjenza epatika u kull kundizzjoni assoċjata ma ’ ipoksja.
Diagnosis:
Dijanjosi:
Lactic acidosis is characterised by acidotic dyspnoea, abdominal pain and hypothermia followed by coma.
Aċidożi lattika hija karatterizzata minn qtugħ ta ’ nifs aċidotiku, uġigħ addominali u ipotermija segwita minn koma.
Diagnostic laboratory findings are decreased blood pH, plasma lactate levels above 5mmol/ l, and an increased anion gap and lactate/ pyruvate ratio.
Sejbiet dijanjostiċi tal- laboratorju huma pH tad- demm imnaqqas, livelli fil- plażma ta ’ lactate għola minn 5mmol/ l, u żieda fl- anion gap u fil- proporzjon lactate/ pyruvate.
If metabolic acidosis is suspected, treatment with the medicinal product should be discontinued and the patient hospitalised immediately (see section 4.9).
Jekk ikun hemm suspett ta ’ aċidożi metabolika, kura bil- prodott mediċinali għandha titwaqqaf u l- pazjent jiddaħħal l - isptar immedjatament (ara sezzjoni 4. 9).
Renal Function:
Fuzjoni renali:
As metformin is excreted by the kidney, serum creatinine concentrations should be determined regularly:
Minħabba li metformin jitneħħa mill- kliewi, il- konċentrazzjonijiet ta ’ krejatinina fis- serum għandhom jiġu determinati regolarment:
- at least once a year in patients with normal renal function
- ta ’ l- inqas darba fis- sena f’ pazjenti b’ funzjoni renali normali
- at least two to four times a year in patients with serum creatinine levels at the upper limits of
- ta ’ l- inqas darbtejn sa erba ’ darbiet fis- sena f’ pazjenti b’ livelli ta ’ krejatinina fis- serum fl- għola
normal and in elderly subjects
limiti tan- normal u f’ soġġetti anzjani
3 Decreased renal function in elderly patients is frequent and asymptomatic.
Funzjoni renali mnaqqsa f’ pazjenti anzjani hija frekwenti u bla sintomi.
Special caution should be exercised in situations where renal function may become impaired, for example when initiating antihypertensive therapy or diuretic therapy and when starting treatment with a NSAID.
Għandha tittieħed kawtela speċjali f’ sitwazzjonijiet fejn il- funzjoni renali tista ’ tkun imnaqqsa, per eżempju meta tinbeda terapija anti- ipertensiva jew terapija dijuretika u meta tinbeda kura b’ NSAID.
Fluid retention and cardiac failure:
Żamma ta ’ fluwidu u insuffiċjenza kardijaka:
When treating patients who have at least one risk factor for development of congestive heart failure (e. g. prior myocardial infarction or symptomatic coronary artery disease), physicians should start with the lowest available dose and increase the dose gradually.
Meta jiġu kkurati pazjenti li għandhom ta ’ l- inqas fattur ta ’ riskju wieħed għall- iżvilupp ta ’ insuffiċjenza tal- qalb konġestiva (e. ż. infart mijokardijaku minn qabel jew marda sintomatika ta ’ l -
Patients should be observed for signs and symptoms of heart failure, weight gain or oedema particularly those with reduced cardiac reserve.
Il- pazjenti għandhom jiġu osservati għal sinjali u sintomi ta ’ insufficjenza tal- qalb, żieda fil - piż jew edima, speċjalment dawk b’ riserva kardijaka mnaqqsa.
There have been cases of cardiac failure reported from the market when pioglitazone was used in combination with insulin. or patients with a history of cardiac failure.
Kien hemm każijiet ta ’ insufficjenza kardijaka rrappurtati mis- suq meta pioglitazone intuża flimkien ma ’ insulina jew f’ pazjenti b’ passat ta ’ insufficjenza kardijaka.
Since insulin and pioglitazone are associated with fluid retention, concomitant administration of insulin and Competact may increase the risk of oedema.
Minħabba li insulina u pioglitazone huma assoċjati ma ’ żamma ta ’ fluwidu, l - għotja ta NSAIDs u Competact flimkien tista ’ żżid ir- riskju ta ’ edima.
Competact should be discontinued if any deterioration in cardiac status occurs.
Competact għandu jitwaqqaf jekk iseħħ xi deterjorament fl- istat kardijaku.
A cardiovascular outcome study of pioglitazone has been performed in patients under 75 years with type 2 diabetes mellitus and pre-existing major macrovascular disease.
Twettaq studju dwar l- effett kardjovaskulari ta ’ pioglitazone f’ pazjenti taħt 75 sena b’ dijabete mellitus tat- tip 2 u b’ marda makrovaskulari maġġuri eżistenti minn qabel.
Pioglitazone or placebo was added to existing antidiabetic and cardiovascular therapy for up to 3.5 years.
Pioglitazone jew plaċebo kienu miżjuda mat- terapija antidijabetika u kardjovaskulari eżistenti sa 3. 5 snin.
This study showed an increase in reports of heart failure, however this did not lead to an increase in mortality in this study.
Dan l- istudju wera żieda fir- rapporti ta ’ insuffiċjenza tal- qalb, iżda dan ma wassalx għall- żieda fil- mortalità f’ dan l- istudju.
Caution should be exercised in patients over 75 years because of the limited experience in this patient group.
Għandha tittieħed attenzjoni f’ pazjenti li għandhom aktar minn 75 sena minħabba l- esperjenza limitata f’ dan il- grupp ta ’ pazjenti.
Monitoring of Liver Function:
Sorveljanza tal- funzjoni tal- fwied:
There have been rare reports of hepatocellular dysfunction during post-marketing experience with pioglitazone (see section 4.8).
Kien hemm rapporti rari ta ’ disfunzjoni epatoċellolari waqt l- esperjenza ta ’ wara li pioglitazone ġie mqiegħed fis- suq (ara sezzjoni 4. 8).
It is recommended, therefore, that patients treated with Competact undergo periodic monitoring of liver enzymes.
Għalhekk, huwa rakkomandat li, pazjenti kkurati b’ Pioglitazone Competact jkollhom l- enżimi tal- fwied immonitorjati perjodikament.
Liver enzymes should be checked prior to the initiation of therapy with Competact in all patients.
L- enżimi tal- fwied għandhom jiġu ċċekkjati qabel ma tinbeda terapija Competact f’ kull pazjent.
Therapy with Competact should not be initiated in patients with increased baseline liver enzyme levels (ALT > 2.5 X upper limit of normal) or with any other evidence of liver disease.
Terapija Competact m’ għandiex tinbeda f’ pazjenti b’ livelli ta ’ l- enżimi tal- fwied fil- linja bażika miżjuda (ALT > 2. 5 X l- għola limitu tan- normal) jew b’ xi evidenza oħra ta ’ mard tal- fwied.
Following initiation of therapy with Competact, it is recommended that liver enzymes be monitored periodically according to clinical judgement.
Wara l- bidu ta ’ terapija Competact, huwa rakkomandat li l- enżimi tal- fwied ikunu immonitorjati perjodikament ibbażat fuq ġudizzju kliniku.
If ALT levels are increased to 3 X upper limit of normal during Competact therapy, liver enzyme levels should be reassessed as soon as possible.
Jekk il- livelli ta ’ ALT jiżdiedu sa 3 X l- għola limitu tan - normal waqt it- terapija Competact, il- livelli ta ’ l- enżimi tal- fwied għandhom jerġu jiġu ċċekkjati mill - aktar fis possibli.
If any patient develops symptoms suggesting hepatic dysfunction, which may include unexplained nausea, vomiting, abdominal pain, fatigue, anorexia and/ or dark urine, liver enzymes should be checked.
Jekk xi pazjent jiżviluppa sintomi li jissuġġerixxu disfunzjoni epatika, li jistgħu jinkludu tqallih mhux spjegat, rimettar, uġigħ addominali, għejja, anoressija u/ jew awrina skura, l- enżimi tal - fwied għandhom jiġu ċċekkjati.
The decision whether to continue the patient on therapy with Competact should be guided by clinical judgement pending laboratory evaluations.
Id- deċiżjoni dwar jekk il- pazjent għandux jitkompla bit- terapija Competact għandha tiġi ggwidata minn ġudiżżju kliniku sakemm isiru l- valutazzjonijiet tal - laboratorju.
If jaundice is observed, drug therapy should be discontinued.
Jekk tkun osservata suffejra, it- terapija bil- mediċina għandha titwaqqaf.
Weight Gain:
Żieda fil- piż:
In clinical trials with pioglitazone there was evidence of dose related weight gain, which may be due to fat accumulation and in some cases associated with fluid retention.
Fi provi kliniċi b’ pioglitazone kien hemm evidenza ta ’ żieda fil- piż relatata mad- doża, li tista ’ tkun minħabba akkumulazzjoni ta ’ xaħam u f’ xi każijiet assoċjata ma ’ żamma ta ’ fluwidu.
Haematology:
Ematoloġija:
Similar changes were seen in metformin (haemoglobin 3 - 4% and haematocrit 3.6 – 4.1% relative reductions) treated patients in comparative controlled trials with pioglitazone.
Tibdiliet simili dehru fi provi kkontrollati komparattivi b’ pioglitazone f’ pazjenti kkurati b’ metformin (tnaqqis relattiv fl - emoglobina ta ’ 3 - 4% u fl- ematokrita ta ’ 3. 6 – 4. 1%).
Hypoglycaemia Patients receiving pioglitazone in dual oral therapy with a sulphonylurea may be at risk for dose- related hypoglycaemia, and a reduction in the dose of the sulphonylurea may be necessary.
Ipogliċemija Pazjenti li qed jirċievu pioglitazone f’ terapija orali doppja ma ’ sulphonylurea jista jkunu f’ riskju ta ’ ipogliċemija relatat mad- doża, u jista ’ jkun meħtieġ tnaqqis fid- doża tas- sulphonylurea.
4 Eye disorders:
4 Kirurġija:
As Competact contains metformin hydrochloride, the treatment should be discontinued 48 hours before elective surgery with general anaesthesia and should not be usually resumed earlier than 48 hours afterwards.
Minħabba li Competact fih metformin hydrochloride, il- kura għandha titwaqqaf 48 siegħa qabel kirurġija mhux obligatorja b’ anesteżija ġenerali u normalment m’ għandhiex terġgħa tinbeda qabel 48 siegħa wara.
Administration of iodinated contrast agent:
L- għotja ta ’ aġent ta ’ kuntrast jodinat:
The intravascular administration of iodinated contrast agents in radiological studies can lead to renal failure.
L- għotja intravaskulari ta ’ aġenti ta ’ kuntrast jodinati fi studji radjuloġiċi tista ’ twassal għall - insuffiċjenza renali.
Therefore, due to the metformin active substance, Competact should be discontinued prior to, or at the time of the test and not reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal (see section 4.5).
Għalhekk, minħabba s- sustanza attiva metformin, Competact għandu jitwaqqaf qabel, jew fil- ħin tat- test u m’ għandux jerġa ’ jinbeda qabel 48 siegħa wara u biss wara li l- funzjoni renali tkun ġiet evalwata mill- ġdid u nstabet li hija normali (ara sezzjoni 4. 5).
Polycystic ovarian syndrome:
Sindromu tal- ovarji poliċistiċi:
As a consequence of enhancing insulin action, pioglitazone treatment in patients with polycystic ovarian syndrome may result in resumption of ovulation.
Minħabba li ssaħħaħ l- azzjoni ta ’ l- insulina, il- kura b’ pioglitazone f’ pazjenti bis- sindromu tal- ovarji poliċistiċi tista ’ twassal għal bidu mill- ġdid tal- ovulazzjoni.
These patients may be at risk of pregnancy.
Dawn il- pazjenti jistghu ikunu f’ riskju ta ’ tqala.
Patients should be aware of the risk of pregnancy and if a patient wishes to become pregnant or if pregnancy occurs, the treatment should be discontinued (see section 4.6).
Il- pazjenti għandhom ikunu konxji tar- riskju ta ’ tqala u jekk il- pazjenta tixtieq toħroġ tqila jew jekk ikun hemm tqala, il- kura għandha titwaqqaf (ara sezzjoni 4. 6).
Others:
Oħrajn:
Fractures were observed in 2.6% of women taking pioglitazone compared to 1.7% of women treated with a comparator.
Fratturi kienu osservati f ’ 2. 6% ta ’ nisa li kienu qed jieħdu pioglitazone meta mqabbel ma ’ 1. 7% tan - nisa kkurati bi prodott paragun.
The fracture incidence calculated was 1.9 fractures per 100 patient years in women treated with pioglitazone and 1.1 fractures per 100 patient years in women treated with a comparator.
L- inċidenza ta ’ fratturi kkalkulata kienet ta ’ 1. 9 fratturi kull 100 sena ta ’ pazjent f’ nisa kkurati b’ pioglitazone u 1. 1 fratturi kull 100 sena ta ’ pazjent f’ nisa kkurati bi prodott ta ’ paragun.
Glycaemic control should be monitored
Il- kontroll gliċemiku għandu jiġi sorveljat mill - viċin.
There have been no formal interaction studies for Competact.
Ma sarux studji formali dwar l- effett ta ’ mediċini jew ta ’ affarijiet oħra fuq l- effett farmaċewtiku ta ’ - Competact.
The following statements reflect the information available on the individual active substances (pioglitazone and metformin).
Id- dikjarazzjonijiet li ġejjin jirriflettu l- informazzjoni disponibbli dwar is- sustanzi attivi individwali (pioglitazone u metformin).
Interaction studies have shown that pioglitazone has no relevant effect on either the pharmacokinetics or pharmacodynamics of digoxin, warfarin, phenprocoumon and metformin.
Studji dwar l- effett ta ’ mediċini jew ta ’ affarijiet oħra fuq l- effett farmaċewtiku tal- prodott urew li pioglitazone m’ għandu l- ebda effett rilevanti la fuq il- farmakokinetika u l- anqas fuq il - farmakodinamika ta ’ digoxin, warfarin, phenprocoumon u metformin.
In vitro studies have shown no inhibition of any subtype of cytochrome P450.
Mhumiex mistennija
Interactions with substances metabolised by these enzymes, e. g. oral contraceptives, cyclosporin, calcium channel blockers, and HMGCoA reductase inhibitors are not to be expected.
5 interazzjonijiet ma ’ sustanzi metabolizzati minn dawn l- enżimi, e. ż. kontraċettivi mill- ħalq, cyclosporin, imblokkaturi tal- kanali tal- kalċju, u inibituri ta ’ HMGCoA reductase.
Co-administration of pioglitazone with gemfibrozil (an inhibitor of cytochrome P450 2C8) is reported to result in a 3-fold increase in AUC of pioglitazone.
Huwa rrappurtat li l- għotja ta ’ pioglitazone flimkien ma ’ gemfibrozil (inibitur taċ- ċitokromju P450 2C8) twassal għall- żieda ta ’ 3 darbiet fl- AUC ta ’ pioglitazone.
Since there is a potential for an increase in dose- related adverse events, a decrease in the dose of pioglitazone may be needed when gemfibrozil is concomitantly administered.
Minħabba li hemm potenzjal ta ’ żieda fl- effetti avversi relatati mad- doża, jista ’ jkun hemm bżonn ta ’ tnaqqis fid- doża ta ’ pioglitazone meta gemfibrozil jingħata fl- istess ħin.
Close monitoring of glycaemic control should be considered (see section 4.4).
Moniteraġġ mill- viċin tal- kontroll gliċemiku għandha tiġi kkunsidrata (ara sezzjoni 4. 4).
Co-administration of pioglitazone with rifampicin (an inducer of cytochrome P450 2C8) is reported to result in a 54% decrease in AUC of pioglitazone.
Huwa rrappurtat li l- għotja ta ’ pioglitazone flimkien ma ’ rifampicin (induttur taċ- ċitokromju P450 2C8) twassal għal tnaqqis ta ’ 54% fl- AUC ta ’ pioglitazone.
Close monitoring of glycaemic control should be considered (see section 4.4).
Sorveljanza mill - viċin tal- kontroll gliċemiku għandha tiġi kkunsidrata (ara sezzjoni 4. 4).
There is increased risk of lactic acidosis in acute alcohol intoxication (particularly in the case of fasting, malnutrition or hepatic insufficiency) due to the metformin active substance of Competact (see section 4.4).
Minħabba s- sustanza attiva metformin f ’ Competact, hemm riskju akbar ta ’ aċidożi lattika f’ intossikazzjoni akuta bl- alkoħol (speċjament f’ każ ta ’ sawm, malnutrizzjoni jew insuffiċjenza epatika) (ara sezzjoni 4. 4).
Avoid consumption of alcohol and medicinal products containing alcohol.
Evita l- konsum ta ’ alkoħol u prodotti mediċinali li fihom l- alkoħol.
Intravascular administration of iodinated contrast agents in radiological studies may lead to renal failure, resulting in metformin accumulation and risk of lactic acidosis.
L- għotja intravaskulari ta ’ aġenti ta ’ kuntrast jodinati fi studji radjuloġiċi tista ’ twassal għall - insuffiċjenza renali, li tirriżulta f’ akkumulazzjoni ta ’ metformin u riskju ta ’ aċidożi lattika.
Metformin should be discontinued prior to, or at the time of the test and not reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal.
Metformin għandu jitwaqqaf qabel, jew fil- ħin tat- test u m’ għandux jinbeda qabel 48 siegħa wara u biss wara li l - funzjoni renali tkun ġiet evalwata mill- ġdid u nstabet li hija normali.
Cationic drugs that are eliminated by renal tubular secretion (e. g. cimetidine) may interact with metformin by competing for common renal tubular transport systems.
Mediċini katijoniċi li huma eliminati permezz ta ’ tneħħijja tubolari renali (e. ż. cimetidine) jistgħu jinteraġixxu ma ’ metformin billi jikkompetu għal sistemi komuni ta ’ trasport tubolari renali.
A study conducted in seven normal healthy volunteers showed that cimetidine, administered as 400 mg twice daily, increased metformin systemic exposure (AUC) by 50% and Cmax by 81%.
Studju li twettaq f’ seba ’ voluntiera normali u b’ saħħithom wera li cimetidine, mogħti bħala 400 mg darbtejn kuljum, żied l- espożizzjoni sistemika ta ’ metformin (AUC) b’ 50% u Cmax b’ 81%.
Therefore, close monitoring of glycaemic control, dose adjustment within the recommended posology and changes in diabetic treatment should be considered when cationic drugs that are eliminated by renal tubular secretion are co-administered.
Għalhekk, sorveljanza mill- qrib tal- kontroll gliċemiku, aġġustament tad- doża fil- firxa ta ’ dożaġġ rakkomandata u bidliet fil- kura dijabetika għandhom jiġu kkunsidrati meta mediċini katijoniċi li jiġu eliminati permezz ta ’ tneħħijja tubolari renali jingħataw fl- istess ħin.
Combinations requiring precautions for use Glucocorticoids (given by systemic and local routes), beta-2-agonists, and diuretics have intrinsic hyperglycaemic activity.
Taħlitiet li jinħtieġu prekawzjonijiet għall- użu Glukokortikojdi (mogħtija permezz ta ’ rotta sistemika u lokali), agonisti- beta- 2, u dijuretiċi għandhom attività ipergliċemika intrinsika.
The patient should be informed and more frequent blood glucose monitoring performed, especially at the beginning of treatment.
Il- pazjent għandu jiġi nfurmat u għandha ssir sorveljanza aktar ta ’ spiss tal- glucose fi- demm, speċjalment fil- bidu tal- kura.
If necessary, the dosage of the antihyperglycaemic medicinal product should be adjusted during therapy with the other medicinal product and on its discontinuation.
Jekk hemm bżonn, id- dożaġġ tal- prodott mediċinali anti- ipergliċemiku għandu jiġi aġġustat waqt it- terapija bil- prodott mediċinali l- ieħor u meta jitwaqqaf.
ACE-inhibitors may decrease the blood glucose levels.
Inibituri- ACE jistgħu jnaqqsu il- livelli ta ’ glucose fid- demm.
6 Risk related to pioglitazone:
4. 6 Tqala u Treddigħ
There are no adequate human data from the use of pioglitazone in pregnant women.
M ’ hemmx tagħrif biżżejjed dwar l- użu ta ’ pioglitazone waqt it- tqala.
Animal studies have not shown teratogenic effects but have shown foetotoxicity related to the pharmacologic action (see section 5.3).
Studji fuq bhejjem ma wrewx effetti teratoġeniċi iżda wrew tossiċità lill- fetu relatata ma ’ l- azzjoni farmakologika (ara sezzjoni 5. 3).
Risk related to metformin:
Riskju relatat ma ’ metformin:
Animal studies have not revealed teratogenic effects.
Studji fuq bhejjem ma wrewx effetti teratoġeniċi.
Small clinical trials have not revealed metformin to have malformative effects.
Provi kliniċi żgħar ma wrewx li metformin għandu effetti malformattivi.
However, Competact should not be used during pregnancy and in women of child-bearing age not using contraceptive measures.
Madankollu, Competact m’ għandux jintuża waqt it- tqala u f’ nisa li jistgħu joħorgu tqal li mhux qed jużaw miżuri kontracettivi.
If a patient wishes to become pregnant or if a pregnancy occurs, treatment with Competact should be discontinued.
Jekk pazjenta tixtieq toħroġ tqila jew jekk isseħħ tqala, kura b ’ Competact għandha titwaqqaf.
Both pioglitazone and metformin have been shown to be present in the milk of lactating rats.
6 Intwera li kemm pioglitazone kif ukoll metformin huma preżenti fil- ħalib ta ’ firien li qed ireddgħu.
It is not known whether breast-feeding will lead to exposure of the infant to the medicinal product.
Mhux magħruf jekk treddigħ iwassalx għal espożizzjoni tat- tarbija għall- prodott mediċinali.
Competact must therefore not be used in women who are breast-feeding (see section 4.3).
Għalhekk Competact m’ għandux jingħata lill- nisa li qed ireddgħu (ara sezzjoni 4. 3).
There have been no therapeutic clinical trials conducted with Competact tablets however bioequivalence of Competact with co-administered pioglitazone and metformin has been demonstrated (see section 5.2).
Ma saru l- ebda provi kliniċi terapewtiċi b’ pilloli Competact, iżda ġiet dimostrata l- bijoekwivalenza ta ’ Competact ma ’ pioglitazone u metformin mogħtija flimkien (ara sezzjoni 5. 2).
Adverse reactions reported in excess (> 0.5%) of placebo and as more than an isolated case in patients receiving pioglitazone in combination with metformin in double-blind studies are listed below as MedDRA preferred term by system organ class and absolute frequency.
Reazzjonijiet avversi rrappurtati aktar (> 0. 5%) milli fil- plaċebo u f’ aktar minn każ iżolat f’ pazjenti li qed jirċievu pioglitazone flimkien ma ’ metformin fi studji double- blind huma mniżżla hawn taħt bis - sistema ta ’ terminu ppreferut MedDRA permeżż tas- sistema tal- klassifika tal- organi u frekwenza assoluta.
Frequencies are defined as: common (> 1/ 100 ,< 1/10); uncommon (> 1/1000 ,< 1/100); rare (> 1/ 10000 ,< 1/1000); very rare (< 1/10000); isolated reports; not known (cannot be estimated from the available data).
Il- frekwenzi huma definiti bħala: komuni > 1/ 100, < 1/ 10; mhux komuni > 1/ 1000, < 1/ 100; rari > 1/ 10000, < 1/ 1000; rari ħafna < 1/ 10000; rapporti iżolati; mhux magħruf (ma tistax tittieħed stima mid- data disponibbli).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
F’ kull sezzjoni ta ’ frekwenza, l- effetti l- aktar serji huma mniżżla l- ewwel, segwiti minn dawk anqas serji.
PIOGLITAZONE IN COMBINATION THERAPY WITH METFORMIN
PIOGLITAZONE F’ TERAPIJA KOMBINATA MA ’ METFORMIN
Blood and lymphatic system disorders
Disturbi tad- demm u tas- sistema limfatika Komuni:
Eye disorders
Disturbi f l- għajnejn Komuni:
Gastrointestinal disorders
Disturbi gastro- intestinali Mhux komuni: gass
Metabolism and nutrition disorders
Disturbi fil- metaboliżmu u n- nutrizzjoni Komuni:
Musculoskeletal system and connective tissue disorders
Disturbi muskolu- skeletrali u tal- connective tissue Komuni:
Nervous system disorders
Disturbi fis- sistema nervuża Komuni:
headache
uġigħ ta ’ ras
Renal and urinary disorders
Disturbi fil- kliewi u fis- sistema urinarja Komuni:
Common:
ematurja
Reproductive system
Disturbi fis- sistema riproduttiva u fis- sider Komuni:
In active comparator controlled trials oedema was reported in 6.3% of patients treated with metformin and pioglitazone, whereas the addition of sulphonylurea to metformin treatment resulted in oedema in 2.2% of patients.
Fi provi attivi kkontrollati ta ’ paragun, edima kienet irrappurtata f’ 6. 3% tal- pazjenti kkurati b’ metformin u pioglitazone, filwaqt li ż- żieda ta ’ sulphonylurea ma ’ kura b’ metformin wasslet għall - edima f’ 2. 2% tal- pazjenti.
The reports of oedema were generally mild to moderate and usually did not require discontinuation of treatment.
Ir- rapporti ta ’ edima ġeneralment kienu ħfief għal moderati u normalment ma kienux jinħtieġu l- waqfien tal- kura.
In combination trials pioglitazone added to metformin resulted in mean weight increase over one year of 1.5 kg.
Fi provi ta ’ taħlita, pioglitazone miżjud ma ’ metformin wassal għall- żieda medja fil- piż fuq medda ta ’ sena ta ’ 1. 5 kg.
Visual disturbance has been reported mainly early in treatment and is related to changes in blood glucose due to temporary alteration in the turgidity and refractive index of the lens as seen with other hypoglycaemic agents.
7 Disturbi viżwali ġew irrappurtati l- aktar fil- bidu tal- kura u huma relatati ma ’ bidliet fiż- żokkor fid - demm minħabba alterazzjoni temporanja fit- turġidità u fl- indiċi refrattiv tal- lenti kif osservat b’ aġenti ipogliċemiċi oħra.
In clinical trials with pioglitazone the incidence of elevations of ALT greater than three times the upper limit of normal was equal to placebo but less than that seen in metformin or sulphonylurea comparator groups.
Fi provi kliniċi b’ pioglitazone l- inċidenża ta ’ elevazzjonijiet ta ’ ALT aktar minn tlett darbiet l- għola limitu tan- normal kienet daqs il- plaċebo iżda inqas minn dik li dehret fil- gruppi ta ’ paragun b’ metformin jew b’ sulphonylurea.
Mean levels of liver enzymes decreased with treatment with pioglitazone.
Livelli medji tal- enżimi tal- fwied naqsu b’ kura b’ pioglitazone.
In controlled clinical trials the incidence of reports of heart failure with pioglitazone treatment was the same as in placebo, metformin and sulphonylurea treatment groups, but was increased when used in combination therapy with insulin.
Fi provi kliniċi kkontrollati, l- inċidenza ta ’ rapporti ta ’ insuffiċjenza tal- qalb b’ kura b’ pioglitazone kienet l- istess bħall- gruppi ta ’ kura bil- plaċebo, metformin u sulphonylurea, iżda kienet miżjuda meta wżata f’ terapija kombinata ma’ linsulina.
In an outcome study of patients with pre-existing major macrovascular disease, the incidence of serious heart failure was 1.6% higher with pioglitazone than with placebo, when added to therapy that included insulin.
Fi studju dwar l- effett ta ’ pazjenti b’ marda makrovaskulari eżistenti minn qabel, l- inċidenza ta ’ insuffiċjenza tal- qalb serja kienet 1. 6% ogħla b’ pioglitazone milli bil- plaċebo, meta miżjud ma ’ terapija li kienet tinkludi l- insulina.
However, this did not lead to an increase in mortality in this study.
Iżda, dan ma wassalx għal żieda fil - mortalità f’ dan l- istudju.
Heart failure has been reported rarely with marketing use of pioglitazone, but more frequently when pioglitazone was used in combination with insulin or in patients with a history of cardiac failure.
Insuffiċjenza tal- qalb kienet irrappurtata b’ mod rari bl- użu ta ’ pioglitazone wara t- tqegħid fis- suq, iżda b’ mod aktar frekwenti meta pioglitazone intuża flimkien ma ’ l- insulina jew f’ pazjenti b’ passat ta ’ insuffiċjenza kardijaka.
Additional information on the individual active substances of the fixed dose combination
Tagħrif ieħor dwar is- sustanzi attivi individwali tat- taħlita ta ’ doża fissa
In double blind placebo controlled clinical trials with pioglitazone upper respiratory tract infection and hypoaesthesia were common; sinusitis and insomnia were uncommon.
Fi provi kliniċi double blind ikkontrollati bil- plaċebo, infezzjonijiet fil- passaġġ respiratorju ta ’ fuq u ipoesteżija kienu komuni; sinusite u insomnija ma kienux komuni.
POST-MARKETING DATA
TAGĦRIF TA ’ WARA T- TQEGĦID FIS- SUQ
Eye disorders
Disturbi fl- għajnejn Edima makulari: mhux magħruf
Metabolism and nutrition disorders:
Disturbi fil- metaboliżmu u n- nutrizzjoni:
Decrease of vitamin B12 absorption with decrease of serum levels during long-term use of metformin.
Tnaqqis fl- assorbiment ta ’ vitamina B12 bi tnaqqis tal- livelli fis- serum waqt użu fit- tul ta ’ metformin.
Consideration of such aetiology is recommended if a patient presents with megaloplastic anaemia.
Jekk pazjent ikollu anemija megaloplastika, huwa rakkomandat li kundizzjoni bħal din tiġi kkunsidrata.
Lactic acidosis (see 4.4 Special warnings and precautions for use).
Aċidożi lattika (ara 4. 4 Twissijiet speċjali u prekawzjonijiet għall- użu).
Taste disturbance
Disturbi fit- togħma
Gastrointestinal disorders:
Distrubi gastro- intestinali:
Gastrointestinal disorders such as nausea, vomiting, diarrhoea, abdominal pain and loss of appetite.
Disturbi gastro- intestinali bħal tqallih, remettar, dijarrea, uġigħ addominali u nuqqas ta ’ aptit.
These undesirable effects occur most frequently during initiation of therapy and resolve spontaneously in most cases.
Dawn l- effetti mhux mixtieqa isseħħu l- aktar waqt il- bidu tat- terapija u f’ ħafna każijiet ifiequ spontanjament.
Isolated reports:
Rapporti iżolati:
Liver function tests abnormalities or hepatitis resolving upon metformin discontinuation.
Anormalitajiet fit- testijiet tal- funzjoni tal- fwied jew epatite li tfieq mal- waqfien ta ’ metformin.
Skin and subcutaneous tissue disorders:
Disturbi fil- ġilda u fit- tessut ta ’ taħt il- ġilda:
Skin reactions such as erythema, pruritis, urticaria.
Reazzjonijiet fil- ġilda bħal eritema, ħakk u urtikarja.
A pooled analysis was conducted of adverse event reports of bone fractures from randomised, comparator controlled, double blind clinical trials in over 8100 patients in the pioglitazone-treated groups and 7400 in the comparator-treated groups of up to 3.5 years duration.
8 Twettqet analiżi ta ’ tagħrif miġbur ta ’ rapporti ta ’ avvennimenti avversi ta ’ fratturi fl- għadam minn provi kliniċi randomised, ikkontrollati b’ paragun, u double blind b’ aktar minn 8100 pazjent fil- gruppi kkurati b’ pioglitazone u 7400 pazjent fil- gruppi kkurrati bi prodott paragun li damu sa 3. 5 snin.
No data are available with regard to overdose of Competact.
L- ebda każ ta ’ doża eċċessiva ma ġie rrappurtat Competact.
A large overdose of metformin (or coexisting risks of lactic acidosis) may lead to lactic acidosis which is a medical emergency and must be treated in hospital.
Doża eċċessiva għolja ta ’ metformin (jew riskji diġà eżistenti ta ’ aċidożi lattika) tista ’ twassal għal aċidożi lattika li hija emerġenza medika u għandha tiġi kkurata fl- isptar.
The most effective method to remove lactate and metformin is haemodialysis.
L- aktar metodu effettiv biex tneħħi lactate u metformin hija bl- emodijalisi.
Combinations of oral blood glucose lowering drugs, ATC code:
Taħlitiet ta ’ mediċini orali li jbaxxu ż- żokkor fid- demm; kodiċi ATC:
Competact combines two antihyperglycaemic agents with complementary mechanisms of action to improve glycaemic control in patients with type 2 diabetes: pioglitazone, a member of the thiazolidinedione class and metformin hydrochloride, a member of the biguanide class.
Competact jikkombina żewġ aġenti anti- ipergliċemiċi b’ mekkaniżmi t’ azzjoni li jikkumplimentaw lil xulxin biex itejbu l- kontroll gliċemiku f’ pazjenti b’ dijabete tat- tip 2: pioglitazone, membru tal- klassi thiazolidinedione u metformin hydrochloride, membru tal- klassi biguanide.
Thiazolidinediones act primarily by reducing insulin resistance and biguanides act primarily by decreasing endogenous hepatic glucose production..
Thiazolidinediones jaħdmu primarjament billi jnaqqsu r- reżistenza għall- insulina u biguanides jaħdmu primarjament billi jnaqqsu l- produzzjoni endoġena epatika ta ’ glucose.
Treatment with pioglitazone has been shown to reduce hepatic glucose output and to increase peripheral glucose disposal in the case of insulin resistance.
Kura b’ pioglitazone intweriet li tnaqqas il- produzzjoni ta ’ glucose mill- fwied u żżid it- tneħħijja periferali ta ’ glucose f’ każ ta ’ reżistenza għall- insulina.
The improved glycaemic control is associated with a reduction in both fasting and postprandial plasma insulin concentrations.
Il - kontroll gliċemiku mtejjeb huwa assoċjat ma ’ tnaqqis fil- konċentrazzjonijiet tal- insulina fil- plażma kemm waqt is- sawm kif ukoll wara l- ikel.
A clinical trial of pioglitazone vs. gliclazide as monotherapy was extended to two years in order to assess time to treatment failure (defined as appearance of HbA1c ≥ 8.0% after the first six months of therapy).
Prova klinika ta ’ pioglitazone vs. gliclazide bħala monoterapija ġiet estiża għal sentejn sabiex jiġi studjat il- ħin sal- falliment tal- kura (definit bħala d - dehra ta ’ HbA1c ≥ 8. 0% wara l- ewwel sitt xhur ta ’ terapija).
In a two-year study of combination therapy comparing pioglitazone with gliclazide when added to metformin, glycaemic control measured as mean change from baseline in HbA1c was similar between treatment groups after one year.
Fi studju ta ’ sentejn b’ terapija kombinata li qabbel pioglitazone ma ’ gliclazide meta miżjuda ma ’ metformin, il- kontroll gliċemiku mkejjel bħala it- tibdil medju mill- linja bażika ta ’ HbA1c kien simili bejn il- gruppi ta ’ kura wara l -
In a placebo controlled trial, patients with inadequate glycaemic control despite a three month insulin optimisation period were randomised to pioglitazone or placebo for 12 months.
Fi prova kkontrollata bil- plaċebo, pazjenti b’ kontroll gliċemiku inadegwat minkejja perjodu ta ’ tliet xhur ta ’ ottimazzjoni bl- insulina kienu randomised għal pioglitazone jew plaċebo għal 12- il xahar.
Patients receiving pioglitazone had a mean reduction in HbA1c of 0.45% compared with those continuing on insulin alone, and a reduction of insulin dose in the pioglitazone treated group.
Pazjenti li kienu qed jirċievu pioglitazone kellhom tnaqqis medju f’ HbA1c ta ’ 0. 45% meta mqabbel ma dawk li komplew b’ insulina waħedha, u tnaqqis fid- doża ta ’ l- insulina fil- grupp ikkurat b’ pioglitazone.
In one year clinical trials, pioglitazone consistently gave a statistically significant reduction in the albumin/ creatinine ratio compared to baseline.
Fi provi kliniċi ta ’ sena, pioglitazone b’ mod konsistenti wassal għal tnaqqis statistikament sinifikanti fil- proporzjon ta ’ albumin/ krejatinina meta mqabbel mal- linja bażika.
Similar changes in body fat distribution on pioglitazone have been accompanied by an improvement in insulin sensitivity.
Tibdiliet simili fid- distribuzzjoni tax- xaħam fil- ġisem b’ pioglitazone saru flimkien ma ’ titjib fis - sensitività għall- insulina.
In most clinical trials, reduced total plasma triglycerides and free fatty acids, and increased HDL- cholesterol levels were observed as compared to placebo, with small, but not clinically significant increases in LDL-cholesterol levels.
Fil- biċċa l- kbira tal- provi kliniċi, kienu osservati tnaqqis fit- triġliċeridi totali fil- plażma u fil- fatty acids ħielsa, u żieda fil- livelli ta ’ HDL- kolesterol meta mqabbel mal- plaċebo, b’ żiediet żgħar, iżda mhux ta ’ rilevanza klinika fil- livelli ta ’ LDL- kolesterol.
In clinical trials of up to two years duration, pioglitazone reduced total plasma triglycerides and free fatty acids, and increased HDL-cholesterol levels, compared with placebo, metformin or gliclazide.
Fi provi kliniċi li damu sa sentejn, pioglitazone naqqas it- triġliċeridi totali fil- plażma u l- fatty acids ħielsa, u żied l- livelli ta ’ HDL kolesterol, meta mqabbel mal- plaċebo, metformin jew gliclazide.
Pioglitazone did not cause statistically significant increases in LDL- cholesterol levels compared with placebo, whilst reductions where observed with metformin and gliclazide.
Pioglitazone ma wassalx għall - żieda statistikament sinifikanti fil- livell ta ’ LDL cholesterol meta mqabbel mal- plaċebo, filwaqt li tnaqqis kien osservat b’ metformin u gliclazide.
In a 20-week study, as well as reducing fasting triglycerides, pioglitazone reduced postprandial hypertriglyceridaemia through an effect on both absorbed and hepatically synthesised
Fi studju ta ’ 20 ġimgħa, minbarra li naqqas it - triġliċeridi waqt is- sawm, pioglitazone naqqas l- ipertrigliċeridemija wara l- ikel permezz ta ’ effett kemm fuq it- trigliċeridi assorbiti kif ukoll fuq dawk prodotti mill- fwied.
These effects were independent of pioglitazone’ s effects on glycaemia and were statistically significantly different to glibenclamide.
Dawn l- effetti kienu indipendenti mill- effetti ta ’ pioglitazone fuq il- gliċemija u kienu differenti b’ mod statistikament sinifikanti minn dawk ta ’ glibenclamide.
In PROactive, a cardiovascular outcome study, 5238 patients with type 2 diabetes mellitus and pre- existing major macrovascular disease were randomised to pioglitazone or placebo in addition to existing antidiabetic and cardiovascular therapy, for up to 3.5 years.
Fi PROactive, studju dwar l- effett kardjovaskulari, 5238 pazjent b’ dijabete mellitus tat- tip 2 u b’ marda makrovaskulari maġġuri eżistenti minn qabel kienu randomised għal pioglitazone jew plaċebo flimkien ma ’ terapija antidijabetika u kardjovaskulari eżistenti, sa 3. 5 snin.
The study population had an average age of 62 years; the average duration of diabetes was 9.5 years.
Il- popolazzjoni ta ’ studju kellha età medja ta ’ 62 sena; it- tul medju ta ’ dijabete kien 9. 5 sena.
Approximately one third of patients were receiving insulin in combination with metformin and/ or a sulphonylurea.
Madwar terz tal- pazjenti kienu qed jirċievu insulina flimkien ma ’ metformin u/ jew sulphonylurea.
To be eligibile patients had to have had one or more of the following: myocardial infarction, stroke, percutaneous cardiac intervention or coronary artery bypass graft, acute coronary syndrome, coronary artery disease, or peripheral arterial obstructive disease.
Biex ikunu eliġibbli, pazjenti kellu jkollhom wieħed jew aktar minn dawn li ġejjin: infart mijokardijaku, puplesijja, intervent kardijaku perkutanju jew bypass graft tal- arterja koronarja, sindrome koronarju akut, marda ta ’ l- arterji koronarji, jew marda ostruttiva ta ’ l- arterji periferali.
Almost half of the patients had a previous myocardial infarction and approximately 20% had had a stroke.
Kważi nofs il- pazjenti kellhom infart mijokardijaku minn qabel u madwar 20% kellhom puplesija minn qabel.
Approximately half of the study population had at least two of the cardiovascular history entry criteria.
Madwar nofs il- popolazzjoni ta ’ l- istudju kellhom minn ta ’ l- inqas żewġ kriterji ta ’ dħul ta ’ passat kardjovaskulari.
Almost all subjects (95%) were receiving cardiovascular medications (beta blockers, ACE inhibitors, angiotensin II antagonists, calcium channel blockers, nitrates, diuretics, aspirin, statins, fibrates).
Kważi l - individwi kollha (95%) kienu qed jirċievu medikazzjonijiet kardjovaskulari (imblokkaturi tar- riċetturi beta, inibituri ACE, antagonisti ta ’ angiotensin II, imblokkaturi tal- kanali tal- kalċju, nitrati, dijuretiċi, aspirina, statins, fibrates).
Although the study failed regarding its primary endpoint, which was a composite of all-cause mortality, non-fatal myocardial infarction, stroke, acute coronary syndrome, major leg amputation, coronary revascularisation and leg revascularisation, the results suggest that there are no long-term cardiovascular concerns regarding use of pioglitazone.
Għalkemm l- istudju falla rigward il- mira primarja tiegħu, li kienet komposta minn mortalità tal- kawżi kollha, infart mijokardijaku mhux fatali, puplesija, sindrome koronarju akut, amputazzjoni maġġuri tas- sieq, vaskularizazzjoni koronarja mill- ġdid u vaskularizazzjoni tas- sieq mill- ġdid, ir- riżultati jissuġġerixxu li ma hemm l- ebda riskji kardjovakulari fit- tul dwar l- użu ta ’ pioglitazone.
However, the incidence of oedema, weight gain and heart failure were increased.
Iżda, l - inċidenza ta ’ edima, żieda fil- piż u insuffiċjenza tal- qalb kienet miżjuda.
No increase in mortality from heart failure was observed.
Ma kienet osservata l- ebda żieda fil- mortalità kkawżata minn insuffiċjenza tal- qalb.
Metformin is a biguanide with antihyperglycaemic effects, lowering both basal and postprandial plasma glucose.
Metformin huwa biguanide b’ effetti anti- ipergliċemiċi, li jnaqqas kemm il- glucose basali fil- plażma kif ukoll dak ta ’ wara l- ikel.
It does not stimulate insulin secretion and therefore does not produce hypoglycaemia.
Huwa ma jistimolax it- tnixxija ta ’ l- insulina u għalhekk ma jipproduċix ipogliċemija.
Metformin may act via three mechanisms:
10 Metformin jista ’ jaħdem permezz ta ’ tliet mekkaniżmi:
- by reduction of hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis
- billi jnaqqas il- produzzjoni ta ’ glucose epatiku billi jinibixxi glukoneoġenesi u glikoġenolisi
- in muscle, by modestly increasing insulin sensitivity, improving peripheral glucose uptake and
- fil- muskolu, billi jżid bi ftit is- sensittività għall- insulina, itejjeb il- ġbir u l- utilizzazzjoni
utilisation
periferika ta ’ glucose
- by delaying intestinal glucose absorption.
- billi jittardja l- assorbiment ta ’ glucose mill- musrana.
Metformin stimulates intracellular glycogen synthesis by acting on glycogen synthase.
Metformin jistimola s- sintesi intraċellolari ta ’ glycogen billi jaħdem fuq glycogen synthase.
Metformin increases the transport capacity of specific types of membrane glucose transporters (GLUT-1 and GLUT-4).
Metformin iżid il- kapaċità ta ’ trasport ta ’ tipi speċifiċi ta ’ trasportaturi tal- membrana ta ’ glucose (GLUT- 1 u GLUT- 4).
In humans, independently of its action on glycaemia, metformin has favourable effects on lipid metabolism.
Fil- bnedmin, indipendentement mill- azzjoni tiegħu fuq il- gliċemija, metformin għandu effetti favorevoli fuq il- metaboliżmu tal- lipidi.
This has been shown at therapeutic doses in controlled, medium-term or long-term clinical studies: metformin reduces total cholesterol, LDLc and triglyceride levels.
Dan intwera f’ dożi terapewtiċi fi studji kliniċi kkontrollati ta ’ tul ta ’ żmien medju jew twil: metformin naqqas il- livelli ta ’ kolesterol totali, LDLc u triglyceride.
The prospective randomised (UKPDS) study has established the long-term benefit of intensive blood glucose control in type 2 diabetes.
L- istudju prospettiv randomised (UKPDS) stabbilixxa il- benefiċċju fit- tul ta ’ kontroll intensiv ta ’ glucose fid- demm f’ dijabete tat- tip 2.
Analysis of the results for overweight patients treated with metformin after failure of diet alone showed:
Analiżi tar- riżultati f’ pazjenti b’ piż żejjed kkurati b ’ metformin wara falliment ta ’ dieta waħedha wera:
- a significant reduction of the absolute risk of any diabetes-related complication in the metformin
- tnaqqis sinifikanti tar- riskju assolut ta ’ kull kumplikazzjoni relatata ma ’ dijabete fil- grupp
group (29.8 events/ 1,000 patient-years) 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
b’ metformin (29. 8 episodju/ 1, 000 pazjent- snin) kontra l- grupp b’ dieta biss (43. 3 episodju/ 1, 000 pazjent- snin), p=0. 0023, u kontra l- gruppi ta ’ monoterapija b’ sulphonylurea u b’ insulina kombinati (40. 1 episodju/ 1, 000 pazjent- snin), p=0. 0034
- a significant reduction of the absolute risk of any diabetes-related mortality: metformin 7.5
- tnaqqis sinifikanti fir- riskju assolut ta ’ kull mortalità relatata ma ’ dijabete: metformin 7. 5
events/ 1,000 patient-years, diet alone 12.7 events/ 1,000 patient-years, p=0.017
episodji/ 1, 000 pazjent- snin, dieta biss 12. 7 episodji/ 1, 000 pazjent- snin, p=0. 017
- a significant reduction of the absolute risk of overall mortality: metformin 13.5 events/ 1,000
- tnaqqis sinifikanti fir- riskju assolut ta ’ mortalità globali: metformin 13. 5 episodji/ 1, 000 pazjent -