qanastek/EMEA-V3 huggingface dataset:
Increased monitoring of the patient is recommended if AVANDAMET is used in combination particularly with insulin but also with a sulphonylurea.
Aktar monitoraġġ tal- pazjent huwa rrakkomandat b’ mod speċjali jekk AVANDAMET jintuża flimkien ma ’ l- insulina iżda anke ma sulphonylurea.
Heart failure was also reported more frequently in patients with a history of heart failure; oedema and heart failure was also reported more frequently in elderly patients and in patients with mild or moderate renal failure.
L- insuffiċjenza tal- qalb kienet ukoll iżjed frekwenti f’ pazjenti b’ passat ta ’ insuffiċjenza tal- qalb; edema u insuffiċjenza tal- qalb kienu wkoll irrapurtati aktar spiss f’ pazjenti anzjani u f’ pazjenti b’ falliment tal- kliewi ħafif jew moderat.
Caution should be exercised in patients over 75 years because of the limited experience in this patient group.
Għandu jkun hemm kawtela f’ pazjenti ta ’ aktar minn 75 sena minħabba l- esperjenza limitata f’ dan il- grupp ta 'pazjenti.
Since NSAIDs, insulin and rosiglitazone are all associated with fluid retention, concomitant administration may increase the risk of oedema.
Billi l- NSAIDs, l- insulina u r- rosiglitazone huma assoċjati mar- ritenzjoni tal- fluwidu, it- teħid flimkien ta’ dawn, jista ’ jżid ir- riskju ta ’ edema.
There are limited clinical trial data in patients with ischaemic heart disease and/ or peripheral arterial disease.
4 b’ mard iskemiku tal- qalb u/ jew mard ta ’ l- arterji ta ’ l- idejn u s- saqajn.
4 Acute Coronary Syndrome (ACS) Patients experiencing an ACS have not been studied in rosiglitazone controlled clinical trials.
Sindromu Koronarju Akut (ACS) Pazjenti li esperjenzaw ACS ma ġewx studjati fi studji kliniċi kkontrollati b’ rosiglitazone.
Monitoring of liver function There have been rare reports of hepatocellular dysfunction during post-marketing experience with rosiglitazone (see section 4.8).
Monitoraġġ tal- funzjoni tal- fwied Fl- esperjenza b’ rosiglitazone wara t- tqegħid fis- suq, kien hemm rapporti rari ta ’ ħsara fil- funzjoni taċ - ċelloli tal- fwied (ara sezzjoni 4. 8).
There is limited experience with rosiglitazone in patients with elevated liver enzymes (ALT > 2.5 times the upper limit of normal).
Teżisti esperjenza limitata ta ’ rosiglitazone f’ pazjenti b’ livell għoli ta ’ enzimi tal- fwied (ALT > 2. 5 darba l- limitu ta ’ fuq tan- normal).
Therefore, liver enzymes should be checked prior to the initiation of therapy with AVANDAMET in all patients and periodically thereafter based on clinical judgement.
Għalhekk, enzimi tal- fwied għandhom jiġu eżaminati qabel ma tinbeda l- kura b’ AVANDAMET fil- pazjenti kollha u perjodikament wara fuq bażi ta ’ ġudizzju kliniku.
Therapy with AVANDAMET should not be initiated in patients with increased baseline liver enzyme levels (ALT > 2.5 times the upper limit of normal) or with any other evidence of liver disease.
M ’ għandiex tinbeda kura b’ AVANDAMET f’ pazjenti b’ livell għoli ta ’ dawn l- enżimi (ALT > 2. 5 darba l- limitu ta ’ fuq tan- normal) jew b’ xi evidenza oħra ta ’ mard tal- fwied.
If ALT levels are increased to > 3 times the upper limit of normal during AVANDAMET therapy, liver enzyme levels should be reassessed as soon as possible.
Jekk il- livelli ta ’ l- ALT jogħlew sa > 3 darbiet l- limitu ta ’ fuq tan - normal waqt il- kura b’ AVANDAMET, il- livelli ta ’ l- enżimi tal- fwied għandhom jerġgħu jkunu eżaminati mill- aktar fis possibli.
If ALT levels remain > 3 times the upper limit of normal, therapy should be discontinued.
Jekk il- livelli tal- ALT jibqgħu > 3 darbiet l- limitu ta ’ fuq tan- normal, il- kura għandha titwaqqaf.
The decision whether to continue the patient on therapy with AVANDAMET should be guided by clinical judgement pending laboratory evaluations.
Jekk xi pazjent jiżviluppa sintomi li jissuġġerixxu problemi fil- fwied, bħal dardir mingħajr raġuni, rimettar, uġigħ ta ’ żaqq, għejja, nuqqas t ’ aptit, u/ jew urina skura, l- enżimi tal - fwied għandhom ikunu eżaminati. Wieħed għandu joqgħod fuq il- ġudizzju kliniku sabiex jiddeċidi jekk il- kura b’ AVANDAMET għandhiex titkompla sakemm jaslu r- riżultati tal- laboratorju.
If jaundice is observed, therapy should be discontinued.
Jekk toħroġ is- suffejra, il- kura għandha titwaqqaf.
Eye disorders Post-marketing reports of new-onset or worsening diabetic macular oedema with decreased visual acuity have been reported with thiazolidinediones, including rosiglitazone.
Mard ta ’ l- għajnejn Kien hemm rapporti ta ’ wara t- tqegħid fis- suq ta ’ bidu ta ’ edema makulari tad- dijabete b’ tnaqqis fl - akutezza fil- vista jew li din tmur għall- agħar wara li jittieħdu t- thiazolidinediones, inkluż ir - rosiglitazone.
It is unclear whether or not there is a direct association between rosiglitazone and macular oedema but prescribers should be alert to the possibility of macular oedema if patients report disturbances in visual acuity and appropriate ophthalmologic referral should be considered.
Mhux ċar jekk hemmx assoċjazzjoni diretta bejn ir- rosiglitazone u l- edema makulari imma min jippreskrivi dan il - prodott għandu jkun avżat bil- possibiltà ta ’ edema makulari jekk pażjent jirrapporta disturbi fl - akutezza tal- vista u għandu jikkunsidra jibgħat lil- pazjent għall- parir xieraq ta ’ speċjalista ta ’ l - għajnejn.
Weight gain In clinical trials with rosiglitazone there was evidence of dose-related weight gain, which was greater when used in combination with insulin.
Żjieda fil- piż Fi studji kliniċi b’ rosiglitazone kien hemm evidenza ta ’ żjieda fil- piż relatat mad- doża, li kien akbar meta kien użat flimkien ma ’ insulina.
Therefore weight should be closely monitored, given that it may be attributable to fluid retention, which may be associated with cardiac failure.
Għalhekk wieħed għandu jżomm għajnejh fuq il- piż, billi dan jista ’ jkun minħabba ritenzjoni ta ’ fluwidu, li jista ’ jkun assoċjat ma ’ insuffiċjenza tal- qalb.
Anaemia Rosiglitazone treatment is associated with a dose-related reduction of haemoglobin levels.
Anemija Waqt il- kura b’ rosiglitazone jista ’ jkun hemm tnaqqis fil- livell ta ’ l- emoglobina relatat mad- doża.
In patients with low haemoglobin levels before initiating therapy, there is an increased risk of anaemia during treatment with AVANDAMET.
F’ dawk il- pazjenti li jkollhom livell baxx ta ’ emoglobina qabel jibdew il- kura, hemm riskju akbar ta ’ anemija waqt li jkunu qed jieħdu AVANDAMET.
Hypoglycaemia Patients receiving AVANDAMET in combination with a sulphonylurea or insulin may be at risk for dose-related hypoglycaemia.
Ipogliċemija Pazjenti li qed jirċievu AVANDAMET flimkien ma sulphonylurea jew insulina jista ’ jkollhom ir - riskju ta ’ ipogliċemija relatata mad- doża.
Increased monitoring of the patient and a reduction in the dose of the concomitant agent may be necessary.
Jista ’ jkun meħtieġ aktar monitoraġġ tal- pazjent u tnaqqis fid- doża tat- trattament konkomitanti.
Surgery As AVANDAMET contains metformin hydrochloride, the treatment should be discontinued 48 hours before elective surgery with general anaesthesia and should not usually be resumed earlier than 48 hours afterwards.
Kirurġija Billi AVANDAMET fih metformin hydrochloride, il- kura għandha titwaqqaf 48 siegħa qabel operazzjoni bil- loppju ġenerali, u ġeneralment m’ għandux jerġa ’ jinbeda qabel igħaddu 48 siegħa.
Administration of iodinated contrast agent The intravascular administration of iodinated contrast agents in radiological studies can lead to renal failure.
Amministrazzjoni ta ’ kimiċi ta ’ kuntrast li fihom Iodine L- amministazzjoni intravaskolari ta ’ kimiċi ta ’ kuntrast li fihom iodine fi studji radjoloġiċi jista ’ jwassal għall- falliment tal- kliewi.
Therefore, due to the metformin active substance, AVANDAMET should be discontinued prior to, or at the time of the test and not reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal (see section 4.5).
5 AVANDAMET għandu jitwaqqaf qabel jew waqt li jsir l- eżami u ma jerġax jinbeda qabel igħaddu 48 siegħa, u jerġa jingħata biss jekk it- testijiet tal- kliewi juru li qed jaħdmu sew (ara sezzjoni 4. 5)
5 Bone disorders In a long-term study an increased incidence of bone fractures (foot, hand and arm) was observed in female patients taking rosiglitazone as monotherapy (see section 4.8).
Mard ta ’ l- għadam Fi studju fit- tul ġiet osservata inċidenza akbar ta ’ ksur fl- għadam (fis- saqajn, fl- idejn u fid- dirgħajn) f’ pazjenti nisa li jkunu qed jieħdu rosiglitazone bħala monoterapija (ara sezzjoni 4. 8).
Other precautions Premenopausal women have received rosiglitazone during clinical studies.
Prekawzjonijiet oħra Nisa li għadhom mhux fil- menopawsa ħadu rosiglitazone waqt studji kliniċi.
Although hormonal imbalance has been seen in preclinical studies (see section 5.3), no significant undesirable effects associated with menstrual disorders have been observed.
Għalkemm studji pri - kliniċi wrew xi żbilanċ ormonali (ara sezzjoni 5. 3), l- ebda effett negattiv sinifikanti fuq il - mestruwazzjoni ma ġie osservat.
As a consequence of improving insulin sensitivity, resumption of ovulation may occur in patients who are anovulatory due to insulin resistance.
Minħabba li jtejjeb is- sensittività għall- insulina, dawk in- nisa li ma jovulawx minħabba reżistenza għall- insulina jistgħu jerġgħu jibdew jovulaw.
Patients should be aware of the risk of pregnancy (see section 4.6).
Il- pazjenti għandhom ikunu informati dwar ir- riskju ta ’ tqala (ara sezzjoni 4. 6).
AVANDAMET should be used with caution during concomitant administration of CYP2C8 inhibitors (e. g. gemfibrozil) or inducers (e. g. rifampicin), due to the effect on rosiglitazone pharmacokinetics (see section 4.5).
AVANDAMET għandu jintuża b’ attenzjoni waqt li jkun jittieħed flimkien ma ’ impedituri CYP2C8 (e. ż. gemfibrozil) jew inducers (e. ż. rifampicin) minħabba l- effett fuq il- farmakokinetika tar - rosiglitazone (ara sezzjoni 4. 5).
Furthermore, AVANDAMET should be used with caution during concomitant administration of cationic medicinal products that are eliminated by renal tubular secretion (e. g. cimetidine) due to the effect on metformin pharmacokinetics (see section 4.5).
Barra minn hekk, AVANDAMET għandu jintuża b’ attenzjoni meta jingħata flimkien ma ’ prodotti mediċinali katajoniċi li jiġu eliminati permezz ta ’ sekrezzjoni tubulari renali (e. ż. cimetidine) minħabba l- effett fuq il- farmakokinetika tal- metformin (ara sezzjoni 4. 5).
Glycaemic control should be monitored closely.
Għandu jkun hemm monitoraġġ mill- qrib tal- kontroll gliċemiku.
AVANDAMET dose adjustment within the recommended posology or changes in diabetic treatment should be considered.
L- aġġustament tad- doża ta ’ AVANDAMET skond il- pożoloġija rakkomandata jew tibdil fit- trattament dijabetiku għandu jiġi kkunsidrat..
All patients should continue their diet with regular distribution of carbohydrate intake during the day.
Il- pazjenti kollha għandhom ikomplu d- dieta bit- tqassim regolari tal- karboidrati matul il- jum.
Overweight patients should continue their energy-restricted diet.
Pazjenti b’ piż żejjed għandhom ikomplu bid- dieta nieqsa mill- enerġija.
The usual laboratory tests for diabetes monitoring should be performed regularly.
It- testijiet tal- laboratorju għall- kontroll tad- dijabete li jsiru normalment għandhom jiġu magħmula regolarment.
AVANDAMET tablets contain lactose and therefore should not be administered to patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
AVANDAMET fih il- lattożju u għalhekk m’ għandux jingħata lil pazjenti bi problemi rari ereditarji ta ’ intolleranza għall- galttożju, in- nuqqas ta ’ Lapp lactase jew meta l- ġisem ma jassorbix sew il- glukożju/ galattożju.
There have been no formal interaction studies for AVANDAMET, however the concomitant use of the active substances in patients in clinical studies and in widespread clinical use has not resulted in any unexpected interactions.
Għadhom ma sarux studji formali dwar prodotti li ma jaqblux ma ’ AVANDAMET, izda l- użu simultanju ta ’ sustanzi attivi f’ pazjenti fi studji kliniċi u f’ użu kliniku mifrux ma rriżulta f’ ebda interazzjoni mhux mistennija.
The following statements reflect the information available on the individual active substances (rosiglitazone and metformin).
L- istqarrijiet segwenti jirriflettu l- informazzjoni disponibbli dwar is - sustanzi attivi individwali (rosiglitazone u metformin).
Avoid consumption of alcohol and medicinal products containing alcohol.
Għandu jiġi evitat il- konsum ta ’ l- alkoħol u prodotti mediċinali li fihom l- alkoħol.
Cationic medicinal products that are eliminated by renal tubular secretion (e. g. cimetidine) may interact with metformin by competing for common renal tubular transport systems.
Prodotti mediċinali katajoniċi li jiġu eliminati permezz ta’ sekrezzjoni tubulari renali (e. ż. cimetidine) jistgħu ma jaqblux ma metformin billi jikkompetu għall- istess sistema ta ’ trasport tubulari 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 sar f’ seba ’ voluntiera normali u f’ saħħithom wera li cimetidine amministrat f’ doża ta ’ 400mg darbtejn kuljum, żied l- esponiment sistemiku 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 medicinal products that are eliminated by renal tubular secretion are co-administered (see section 4.4).
Għalhekk għandu jkun hemm monitoraġġ b’ attenzjoni tal- kontroll ġliċemiku, aġġustament tad- doża skond il - pożoloġija rakkomandata u bdil fit- trattament tad- dijabete għandu jiġi kkunsidrat meta prodotti
In vitro studies demonstrate that rosiglitazone is predominantly metabolised by CYP2C8, with CYP2C9 as only a minor pathway.
Studji in vitro juru li rosiglitazone huwa l- iktar metabolizzat permezz ta ’ CYP2C8, b’ CYP2C9 iservi biss bħala mogħdija żgħira.
Co-administration of rosiglitazone with gemfibrozil (an inhibitor of CYP2C8) resulted in a twofold increase in rosiglitazone plasma concentrations.
L- għoti flimkien ta ’ rosiglitazone ma ’ gemfibrozil (impeditur ta ’ CYP2C8) irriżulta f’ żjieda doppja ta ’ konċentrazzjonijiet ta ’ rosiglitazone fil- plażma.
Since there is a potential for an increase in the risk of dose-related adverse reactions, a decrease in rosiglitazone dose may be needed.
Billi jeżisti l- potenzjal ta ’ żjieda ta ’ riskju ta ’ reazzjonijiet avversi li għandhom x’ jaqsmu mad- doża, jista ’ jkun meħtieġ tnaqqis fid- doża ta ’ rosiglitazone.
6 Co-administration of rosiglitazone with rifampicin (an inducer of CYP2C8) resulted in a 66% decrease in rosiglitazone plasma concentrations.
L- għoti flimkien ta ’ rosiglitazone ma ’ rifampiċin (inducer ta ’ CYP2C8) irriżulta fi tnaqqis ta ’ 66% fil - konċentrazzjonijiet ta ’ rosiglitazone fil- plażma.
It cannot be excluded that other inducers (e. g. phenytoin, carbamazepine, phenobarbital, St John’ s wort) may also affect rosiglitazone exposure.
Ma jistax jiġi eskluż li inducers oħra (e. ż. phenytoin, carbamazepine, phenobarbital, St John’ s wort) jistgħu wkoll ikollhom effett fuq l- esponiment għal rosiglitazone.
The rosiglitazone dose may need to be increased.
Jista ’ jkun li d- doża ta ’ rosiglitazone ikollha tiżdied.
Close monitoring of glycaemic control should be considered (see section 4.4).
Għandu jiġi kkunsidrat il - monitoraġġ b’ attenzjoni tal- kontroll gliċemiku (ara sezzjoni 4. 4).
Concomitant administration of rosiglitazone with the oral antihyperglycaemic agents glibenclamide and acarbose did not result in any clinically relevant pharmacokinetic interactions.
Meta rozoglitazone ġie mogħti flimkien ma ’ l- aġenti anti- ipergliċemiċi orali glibenclamide u acarbose ma ’ rriżultax li kien hemm xi interazzjonijiet farmakokinetiċi klinikament relevanti.
No clinically relevant interactions with digoxin, the CYP2C9 substrate warfarin, the CYP3A4 substrates nifedipine, ethinylestradiol or norethindrone were observed after co-administration with rosiglitazone.
Meta rosiglitazone ingħata flimkien ma ’ digoxin, is- sustrat CYP2C9 warfarin, is- sustrati CYP3A4 nifedipine, ethinylestradiol jew noretindrone ma ġewx osservati l- ebda interazzjonijiet klinikament relevanti.
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.
Meta kimiċi ta ’ kuntrast li fihom iodine jiġu amministrati fis- sistema vaskulari, dan jista ’ jwassal għal kollass fil- kliewi, li jirriżulta f’ akkumolu ta ’ metformin u riskju ta ’ aċidu lattiku. L- amministrazzjoni ta ’ metformin għandha titwaqqaf qabel jew meta jsir it- test u m’ għandiex terġa ’ tibda sa ’ 48 siegħa wara u tingħata biss wara li jerġa ’ jiġi evalwat u żgurat li l- kliewi qed jiffunzjonaw normalment.
Combination requiring precautions for use Glucocorticoids (given by systemic and local routes) beta-2-agonists, and diuretics have intrinsic hyperglycaemic activity.
Glukokortikojdi (mogħtija permezz ta ’ rotot sistemiċi u lokali) beta- 2- agonists, u djuretiċi fihom attività ipergliċemika intrinsika.
The patient should be informed and more frequent blood glucose monitoring performed, especially at the beginning of treatment.
Il- pazjent għandu jkun mgħarraf u jsir monitoraġġ iktar spiss tal - glukożju fid- 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 ikun hemm bżonn, id- dużaġġ tal- prodott mediċinali anti- ipergliċemiku għandu jiġi aġġustat waqt it- terapija mal- prodott mediċinali l- ieħor u meta dan ma jitkompliex.
ACE-inhibitors may decrease the blood glucose levels.
Inibituri- ACE jistgħu jnaqqsu l- livelli tal- glukożju fid- demm.
If necessary, the dosage of the antihyperglycaemic medicinal product should be adjusted during therapy with the other medicinal product and on its discontinuation.
Jekk ikun hemm bżonn, id- dużaġġ tal - prodott mediċinali anti- ipergliċemiku għandu jiġi aġġustat waqt it- terapija mal- prodott mediċinali l - ieħor u meta dan ma jitkompliex.
For AVANDAMET no preclinical or clinical data on exposed pregnancies or lactation are available.
M’ hemm l- ebda tagħrif pri- kliniku jew kliniku disponibbli dwar l- effetti ta ’ AVANDAMET fuq tqala u treddigħ.
Rosiglitazone has been reported to cross the human placenta and to be detectable in foetal tissues.
Ġie rrappurtat li rosiglitazone jgħaddi mill- plaċenta umana u kien hemm traċċi tiegħu fit- tessuti tal - fetu.
There are no adequate data from the use of rosiglitazone in pregnant women.
M’ hemmx tagħrif adegwat mill- użu ta ’ rosiglitazone f’ nisa tqal.
Studies in animals have shown reproductive toxicity (see section 5.3).
Studji fuq annimali wrew tossiċità fuq is- sistema riproduttiva (ara sezzjoni 5. 3).
The potential risk for humans is unknown.
Ir- riskju potenzjali fuq il- bniedem mhux magħruf.
Therefore, AVANDAMET should not be used during pregnancy.
Għalhekk, AVANDAMET m’ għandux jintuża waqt it- tqala.
If a patient wishes to become pregnant or if pregnancy occurs, treatment with AVANDAMET should be discontinued unless the expected benefit to the mother outweighs the potential risk to the foetus.
Jekk pazjenta tixtieq tinqabad tqila jew jekk isseħħ tqala, il- kura b’ AVANDAMET m’ għandiex titkompla sakemm il- benefiċċju mistenni għall- omm ma jkunx ikbar mir- riskju potenzjali għall- fetu.
Both rosiglitazone and metformin have been detected in the milk of experimental animals.
Kemm rosiglitazone kif ukoll metformin instabu fil- ħalib ta ’ l- annimali taħt esperiment.
It is not known whether breast-feeding will lead to exposure of the infant to the medicinal product.
Mhux magħruf jekk it- treddigħ iwassalx biex it- tarbija tkun esposta għall- prodott mediċinali.
AVANDAMET must therefore not be used in women who are breast-feeding (see section 4.3).
(ara sezzjoni 4. 3)
AVANDAMET has no or negligible influence on the ability to drive and use machines.
AVANDAMET m’ għandu l- ebda jew ftit li xejn effet fuq il- ħila ta ’ sewqan u l- użu ta ’ magni.
Adverse reactions are presented below for each of the component parts of AVANDAMET.
Reazzjonijiet mhux mixtieqa għal kull komponent ta’ AVANDAMET huma ppreżentati hawn taħt.
An adverse reaction is only presented for the fixed dose combination if it has not been seen in one of the component parts of AVANDAMET or if it occurred at a higher frequency than that listed for a component part.
Reazzjoni mhux mixtieqa għad- doża fissa kombinata hija ppreżentata biss jekk din ma ’ tfaċċatx f’ wieħed mill- komponenti ta ’ AVANDAMET jew jekk ġrat b’ frekwenza ogħla minn dik indikata f’ komponent minnhom.
7 Adverse reactions for each treatment regimen are presented below by system organ class and absolute frequency.
Reazzjonijiet mhux mixtieqa għal kull terapija huma elenkati hawn taħt skond il- klassi tas- sistemi u l - organi u l- frekwenza assoluta.
For dose-related adverse reactions the frequency category reflects the higher dose of rosiglitazone.
Għar- reazzjonijiet sekondarji relatati mad- doża l- kategorija ta ’ frekwenza tirrifletti l- ogħla doża tar- rosiglitazone.
Frequency categories do not account for other factors including varying study duration, pre-existing conditions and baseline patient characteristics.
Il- kategoriji ta ’ frekwenza ma jirriflettux fatturi oħra inkluż it- tul ta ’ żmien varjabbli ta ’ l- istudju, kundizzjonijiet li kienu hemm qabel u karatteristiċi ta ’ linja bażi tal- pazjent.
Adverse reaction frequency categories assigned based on clinical trial experience may not reflect the frequency of adverse events occurring during normal clinical practice.
Il- kategoriji ta ’ frekwenza ta ’ reazzjonijiet mhux mixtieqa assenjati fuq bażi ta ’ esperjenza minn provi kliniċi mhux neċessarjament jirriflettu l- frekwenza ta ’ effetti mhux mixtieqa li jseħħu fil- prattika klinika.
Frequencies are defined as: very common (≥ 1/ 10), common (≥ 1/ 100 to < 1/ 10), uncommon (≥ 1/ 1,000 to < 1/ 100), rare (≥ 1/ 10,000 to < 1/ 1000) and very rare (< 1/ 10,000 including isolated reports).
Il- frekwenzi huma definiti bħala: komuni ħafna (≥1/ 10), komuni (≥1/ 100 sa < 1/ 10), mhux komuni (≥1/ 1, 000 sa < 1/ 100), rari (≥1/ 10, 000, < 1/ 1000) u rari ħafna (< 1/ 10000 inkluż rapporti iżolati)..
Data from double-blind studies confirm that the safety profile of concomitant rosiglitazone and metformin is similar to that of the combined adverse reaction profile for the two medicinal products.
Tagħrif minn studji double- blind jikkonferma li l- profil ta ’ sigurta` ta ’ rosiglitazone u metformin flimkien jixbaħ il- profil kkombinat tar- reazzjonijiet mhux mixtieqa għaż- żewġ prodotti mediċinali.
Data with AVANDAMET is also consistent with this combined adverse reaction profile.
Tagħrif b’ AVANDAMET huwa wkoll konsistenti ma ’ dan il- profil kkombinat ta ’ reazzjonijiet mhux mixtieqa.
Clinical trial data (addition of insulin to established AVANDAMET therapy) In a single study (n=322) where insulin was added to patients established on AVANDAMET, no new adverse events were observed in excess of those already defined for either AVANDAMET or rosiglitazone combination therapies.
Tagħrif minn provi kliniċi (żjieda ta’ l- insulina ma ’ trattamet stabbilit b’ AVANDAMET) Fi studju wieħed (n=322) fejn żdieded l- insulina lill- pazjenti stabbiliti b’ AVANDAMET, l- ebda reazzjonijiet mhux mixtieqa ma ġew innutati aktar minn dawk li diġà ġew definiti għal AVANDAMET jew trattament ikkombinat b’ rosiglitazone.
However, the risk of both fluid related adverse events and hypoglycaemia are increased when AVANDAMET is used in combination with insulin.
Madanakollu, ir- riskji sekondarji ta ’ retenzjoni tal- fluwidu kif ukoll l- ipogliċemija jiżdiedu meta AVANDAMET jintuża flimkien ma ’ l - insulina.
Clinical trial data Adverse reactions for each treatment regimen are presented below by system organ class and absolute frequency.
Tagħrif minn provi kliniċi Reazzjonijiet mhux mixtieqa għal kull terapija huma elenkati hawn taħt skond il- klassi tas- sistemi u l - organi u l- frekwenza assoluta.
For dose-related adverse reactions the frequency category reflects the higher dose of rosiglitazone.
Għar- reazzjonijiet mhux mixtieqa relatati mad- doża l- kategorija ta ’ frekwenza tirrifletti l- ogħla doża tar- rosiglitazone.
Table 1 lists adverse reactions identified from an integrated clinical trial population of over 5,000 rosiglitazone-treated patients.
It- tabella 1 telenka reazzjonijiet mhux mixtieqa identifikati fi prova klinika f’ grupp integrat ta ’ aktar minn 5, 000 pazjent li kienu fuq trattament b’ rosiglitazone.
Within each system organ class, adverse reactions are presented in the table by decreasing frequency for the rosiglitazone monotherapy treatment regimen.
F’ kull klassi tas- sistemi u l- organi, effetti mhux mixtieqa għal monoterapija b’ rosiglitazone huma ppreżentati fit- tabella f’ ordni ta ’ tnaqqis fil - frekwenza.
Frequency of adverse reaction by treatment regimen Rosiglitazone Rosiglitazone with Rosiglitazone with monotherapy metformin metformin and sulphonylurea
Frekwenza ta ’ reazzjonijiet mhux mixtieqa skond it- terapija Monoterapija Rosiglitazone ma ’ Rosiglitazone ma ’ b’ rosiglitazone metformin metformin u sulphonylurea
Blood and the lymphatic system disorders anaemia granulocytopaenia
Mard tad- demm u tas- sistema
Metabolism and nutrition disorders hypercholesterolaemia1 hypertriglyceridaemia
Mard marbut mal- metaboliżmu u n- nutrizzjoni iperkolesterolemija 1 ipertrigliċeridemija
hyperlipaemia weight increase increased appetite
iperlipemija żjieda fil- piż żjieda fl- aptit
hypoglycaemia
ipogliċemja
Nervous system disorders dizziness* headache*
Mard tas- sistema nervuża sturdament * uġigħ ta ’ ras *
cardiac failure2
insuffiċjenza tal- qalb 2
cardiac ischaemia3*
iskemja kardijaka3 *
Gastrointestinal disorders constipation
Mard gastro- intestinali stitikezza
Musculoskeletal and connective tissue disorders bone fractures4 myalgia*
Mard muskolu- skelettrali u tal- connective tissue ksur ta ’ l- għadam4 Uġigħ fil- muskoli *
General disorders and administration site conditions oedema
Mard ġenerali u kondizzjonijiet ta ’ mnejn jingħata edema
*The frequency category for the background incidence of these events, as taken from placebo group data from clinical trials, is'common '.
* Il- kategorija ta ’ frekwenza għall- isfond ta ’ l- inċidenza ta ’ dawn l- effetti, kif meħud mit- tagħrif mill - grupp plaċebo fi provi kliniċi, hija ‘ komuni ’.
1 Hypercholesterolaemia was reported in up to 5.3% of patients treated with rosiglitazone (monotherapy, dual or triple oral therapy).
1 Iperkolesterolemija ġiet irrappurtata sa f’ 5. 3% ta’ pazjenti fuq terapija ta ’ rosiglitazone (monoterapija u terapija orali doppja jew trippla).
The elevated total cholesterol levels were associated with an increase in both LDLc and HDLc, but the ratio of total cholesterol:
Il- livell sħiħ elevat tal- kolesterol kien assoċjat ma ’ żjieda kemm fl - LDLc kif ukoll fil- HDLc, iżda l- proporzjon tal- kolesterol sħiħ:
HDLc was unchanged or improved in long term studies.
HDLc ma nbidilx jew tjieb fis- studji fit- tul.
2 An increased incidence of heart failure has been observed when rosiglitazone was added to treatment regimens with a sulphonylurea (either as dual or triple therapy), and appeared higher with 8 mg rosiglitazone compared to 4 mg rosiglitazone (total daily dose).
2 Inċidenza ikbar ta ’ insuffiċjenza tal- qalb ġiet osservata meta rosiglitazone ġie miżjud ma ’ terapiji b’ sulphonylurea (b’ terapija doppja jew trippla), u deher li kienet ogħla b’ 8 mg rosiglitazone meta mqabbla ma 4 mg rosiglitazone (doża sħiħa ta ’ kuljum).
The incidence of heart failure on triple oral therapy was 1.4% in the main double blind study, compared to 0.4% for metformin plus sulphonylurea dual therapy.
L- inċidenza ta ’ insuffiċjenza tal- qalb f’ terapija orali trippla kienet ta ’ 1. 4% fl- istudju double blind prinċipali, meta mqabbla ma ’ 0. 4% għal terapija doppja b’ metformin u sulphonylurea.
The incidence of heart failure in combination with insulin (rosiglitazone added to established insulin therapy) was 2.4%, compared to insulin alone, 1.1%.
L- inċidenza ta ’ insuffiċjenza tal- qalb f’ kombinazzjoni ma ’ l- insulina (rosiglitazone miżjud ma ’ terapija b’ insulina stabbilita) kienet ta ’ 2. 4%, meta mqabbla ma ’ insulina waħedha, 1. 1%.
In a placebo-controlled one-year trial in patients with congestive heart failure NYHA class I-II, worsening or possible worsening of heart failure occurred in 6.4% of patients treated with rosiglitazone, compared with 3.5% on placebo.
9 Fi prova ta ’ sena kkontrollata bi plaċebo, f’ pazjenti b’ waqfien tal- qalb konġestiva NYHA klassi I- II, kien hemm deterjorament jew deterjorament possibbli ta ’ insuffiċjenza tal- qalb f’ 6. 4% tal- pazjenti trattati b’ rosiglitazone, meta mqabbla ma ’ 3. 5% bi plaċebo.
9 3 In a retrospective analysis of data from 42 pooled short-term clinical studies, the overall incidence of events typically associated with cardiac ischaemia was higher for rosiglitazone containing regimens, 1.99% versus combined active and placebo comparators, 1.51% [Hazard ratio 1.31 (95% confidence interval 1.01 - 1.70)].
3 F’ analiżi retrospettiva ta ’ tagħrif minn 42 studji kliniċi fuq tul ta ’ żmien qasir, miġbura flimkien, l - inċidenza ġenerali ta ’ każi assoċjati tipikament ma ’ iskemija kardijaka kienet ogħla fil- każ ta ’ terapija li jkun fiha rosiglitazone, 1. 99% kontra komparaturi attivi kombinati jew plaċebo, 1. 51% [Hazard ratio 1. 31 (95% confidence interval 1. 01 – 1. 70)].
In a large observational study where patients were well-matched at baseline, the incidence of the composite endpoint myocardial infarction and coronary revascularization was 17.46 events per 1000 person years for rosiglitazone containing regimens and 17.57 events per 1000 person years for other anti-diabetic agents [Hazard ratio 0.93 (95% confidence interval 0.80 - 1.10)].
Fi studju estensiv ta ’ osservazzjoni li fih pazjenti kienu magħżulin tajjeb f’ linja ta ’ bażi, l- inċidenza ta ’ infart mijokardijaku endpoint b’ mod kompost u rivaskularizzazzjoni koronarja kienet ta ’ 17. 46 każi għal kull 1000 sena ħajja ta ’ persuna b’ terapija li fiha rosiglitazone u 17. 57 każi għal kull 1000 sena ħajja ta ’ persuna fil- każ ta ’ aġenti oħra anti- dijabetiċi [Hazard ratio 0. 93 (95% confidence interval 0. 80 – 1. 10)].
In their entirety, the available data on the risk of myocardial ischaemia are inconclusive.
Ma ’ tulhom kollha, l- informazzjoni disponibbli fuq ir- riskju ta ’ iskemja mijokardijaka m’ hijiex konklussiva.
4 In a long-term randomised (4 to 6 year) monotherapy study in recently diagnosed patients with type 2 diabetes mellitus, an increased incidence of bone fractures was noted after the first year of treatment in female patients taking rosiglitazone (9.3%, 2.7 patients per 100 patient years) vs metformin (5.1%, 1.5 patients per 100 patient years) or glyburide/ glibenclamide (3.5%, 1.3 patients per 100 patient years).
4 Fi studju randomised fit- tul (4 sa 6 snin) b’ monoterapija fuq pazjenti li jkun għadu kemm instab li jbatu bid- dijabete mellitus tip 2, ġiet innotata inċidenza akbar ta ’ ksur fl- għadam wara l- ewwel sena ta ’ trattament f’ pazjenti nisa li jkunu jieħdu rosiglitazone (9. 3%, 2. 7 pazjenti kull 100 sena ta ’ pazjenti) vs metformin (5. 1%, 1. 5 pazjenti kull 100 sena ta ’ pazjenti) jew glyburide/ glibenclamide (3. 5%, 1. 3 pazjenti kull 100 sena ta ’ pazjenti).
In double-blind clinical trials with rosiglitazone the incidence of elevations of ALT greater than three times the upper limit of normal was equal to placebo (0.2%) and less than that of the active comparators (0.5% metformin/ sulphonylureas).
Fi provi kliniċi double blind b’ rosiglitazone, l- inċidenza ta ’ żidiet fl- ALT aktar minn tlett darbiet ta ’ l - ogħla limitu tan- normal kienet daqs tal- placebo (0. 2%) u anqas minn dik tal- komparaturi attivi (0. 5% meformin/ sulphonylureas).
The incidence of all adverse events relating to liver and biliary systems was < 1.5% in any treatment group and similar to placebo.
L- inċidenza tal- effetti kollha mhux mixtieqa li għandhom x’ jaqsmu mas - sistemi tal- fwied u tal- marrara kienet ta ’ < 1. 5% fi kwalunkwe grupp ta ’ trattament u jixbaħ lil dak bi plaċebo.
Post-marketing data In addition to the adverse reactions identified from clinical trial data, the adverse reactions presented in Table 2 have been identified in post approval use of rosiglitazone.
Tagħrif ta ’ wara t- tqegħid fis- suq Min barra r- reazzjonijiet mhux mixtieqa identifikati mit- tagħrif minn provi kliniċi, reazzjonijiet mhux mixtieqa ppreżentati f’ Tabella 2, ġew identifikati waqt l- użu ta ’ wara l- awtorizzazzjoni tar - rosiglitazone
anaphylactic reaction
reazzjoni anafilattika
congestive heart failure/ pulmonary oedema
insuffiċjenza tal- qalb konġestiva / edema pulmonari
hepatic dysfunction, primarily evidenced by elevated hepatic enzymes5
indeboliment tal- funzjoni tal- fwied, indikat primarjament minn għoli fl- enzimi tal- fwied 5
Skin and subcutaneous tissue disorders (see Immune system disorders)
Mard tal- ġilda u tat- tessuti ta ’ taħt il- ġilda (ara Mard tas- sistema immuni) 5
angioedema skin reactions (e. g. urticaria, pruritis, rash) 5
anġjodema reazzjonijiet fil- ġilda (eż. urtikarja, ħakk, raxx)
Rare cases of elevated liver enzymes and hepatocellular dysfunction have been reported.
Każi rari ta ’ żjieda fl- enżimi tal- fwied u ħsara fil- funzjoni taċ- ċelloli tal- fwied kienu rappurtati.
In very rare cases, a fatal outcome has been reported.
F’ każi rari ħafna kienu rrappurtati ukoll mwiet.
Clinical Trial Data and Post-marketing data
Tagħrif minn Provi Kliniċi u Tagħrif ta ’ Wara t- Tqegħid fis- Suq
Table 3.
It- Tabella 3 tippreżenta ir- reazzjonijiet mhux mixtieqa skond il- kategoriji tal- klassi tas- sistemi u l - organi u l- frekwenza.
The frequency of metformin adverse reactions identified from clinical trial and post- marketing data
Il- frekwenza ta ’ reazzjonijiet mhux mixtieqa ta ’ metformin identifikati minn provi kliniċi u tagħrif wara t- tqegħid fis- suq
gastrointestinal symptoms6
sintomi gastro- intestinali6
Metabolism and nutrition disorders lactic acidosis vitamin B12 deficiency7
Mard marbut mal- metaboliżmu u n- nutrizzjoni aċidożi lattika defiċjenza tal- vitamina B12 7
metallic taste
togħma ta ’ metall
Hepatobiliary disorders liver function disorders Hepatitis
Mard tal- fwied u tal- marrara mard tal- funzjoni tal- fwied epatite
Skin and subcutaneous disorders
Mard tal- ġilda u tat- tessuti ta’ taħt il- ġilda
urticaria erythema pruritis 6
urtikarja ħmura ħakk 6
Very rare Very rare Very rare
Rari ħafna Rari ħafna Rari ħafna
Gastrointestinal symptoms such as nausea, vomiting, diarrhoea, abdominal pain and loss of appetite occur most frequently during initiation of therapy and resolve spontaneously in most cases.
Sintomi gastro- intestinali bħal dardir, rimettar, dijarrea, uġigħ ta ’ żaqq u nuqqas ta ’ aptit iseħħu l- iktar frekwenti matul il- bidu tat- terapija u jieqfu waħidhom fil- biċċa l- kbira tal- każi.
7 Long-term treatment with metformin has been associated with a decrease in vitamin B12 absorption which may very rarely result in clinically significant vitamin B12 deficiency (e. g. megaloblastic anaemia).
7 Trattament fit- tul b’ metformin ġie assoċjat ma ’ tnaqqis fl- assorbiment tal- vitamina B12 li f’ każi rari ħafna jirriżulta f’ effett kliniku sinifikanti ta ’ defiċjenza tal- vitamina B12 (e. ż. anemija megaloblastika)
No data are available with regard to overdose of AVANDAMET.
Ma hemm l- ebda tagħrif dwar doża eċċessiva ta ’ AVANDAMET.
Limited data are available with regard to overdose of rosiglitazone in humans.
Jeżisti tagħrif limitat dwar doża eċċessiva ta ’ rosiglitazone fil- bniediem.
In clinical studies in volunteers rosiglitazone has been administered at single oral doses of up to 20 mg and was well tolerated.
Fi studji kliniċi fuq voluntiera, rosiglitazone ġie amministrat f’ dożi orali individwali sa ’ 20mg u kien ittollerat tajjeb.
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 qawwija ta ’ metformin (jew riskji koeżistenti ta ’ aċidożi lattika) tista ’ twassal għal aċidożi lattika li hija emerġenza medika u li trid tiġi ttrattata fi sptar.
In the event of an overdose, it is recommended that appropriate supportive treatment is initiated as dictated by the patient's clinical status.
F’ każ ta ’ doża eċċessiva, huwa rrakkomandat li tinbeda kura xierqa ta ’ sosteniment, skond l- istat kliniku tal- pazjent.
The most effective method to remove lactate and metformin is haemodialysis, however rosiglitazone is highly protein bound and is not cleared by haemodialysis.
Madankollu rosiglitazone għandu bażi qawwija ta ’ proteini u ma ’ jitneħħiex permezz ta ’ dijaliżi tad- demm.
Pharmacotherapeutic group:
Kategorija:
Combinations of oral blood glucose lowering medicinal products, ATC code:
Prodotti mediċinali orali kkombinati li jnaqqsu l- livell ta ’ zokkor fid- demm, kodiċi ATC:
AVANDAMET combines two antihyperglycaemic agents with complimentary mechanisms of action to improve glycaemic control in patients with type 2 diabetes: rosiglitazone maleate, a member of the thiazolidinedione class and metformin hydrochloride, a member of the biguanide class.
AVANDAMET jikkombina żewġ aġenti anti- ipergliċemiċi permezz ta ’ mekkaniżmu ta ’ azzjoni kumplimentari biex itejjeb il- kontrol tal- glukożju fid- demm f’ pazjenti b’ dijabete tip 2: rosiglitazone maleate, membru tal- klassi thiazolidinedione, u metformin hydrochloride, membru tal- klassi
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 l - biguanides jaħdmu primarjament billi jnaqqsu l- produzzjoni endoġena ta ’ glukożju fil- fwied.
Rosiglitazone Rosiglitazone is a selective agonist at the PPARγ (peroxisome proliferator activated receptor gamma) nuclear receptor and is a member of the thiazolidinedione class of antihyperglycaemic agents.
Rosiglitazone Rosiglitazone huwa agonist selettiv fir- receptor nuklejari PPARγ (peroxisome proliferator activated receptor gamma) u huwa membru tal- klassi ta ’ aġenti anti- ipergliċemiċi thiazolidinedione.
It reduces glycaemia by reducing insulin resistance at adipose tissue, skeletal muscle and liver.
Huwa jnaqqas il- glukożju fid- demm billi jnaqqas ir- reżistenza għall- insulina fit- tessut xaħmi (adipose), fil - muskolu skeletali u fil- fwied.
The antihyperglycaemic activity of rosiglitazone has been demonstrated in a number of animal models of type 2 diabetes.
L- attività anti- ipergliċemika ta ’ rosiglitazone ġiet murija f’ numru ta ’ mudelli ta ’ annimali b’ dijabete tat- tip 2.
In addition, rosiglitazone preserved ß-cell function as shown by increased pancreatic islet mass and insulin content and prevented the development of overt hyperglycaemia in animal models of type 2 diabetes.
Barra minn hekk, rosiglitazone ippreserva l- funzjoni taċ- cellula β kif muri miż- żjieda fil - massa ta ’ ċelloli (islets) fil- frixa u l- kontenut ta ’ l- insulina u evita l- iżvilupp ta ’ ipergliċemija f’ mudelli ta ’ annimali b’ dijabete ta ’ tip 2.
Rosiglitazone did not stimulate pancreatic insulin secretion or induce hypoglycaemia in rats and mice.
Rosiglitazone la stimola tnixxija ta ’ l- insulina mill- frixa u lanqas induċa ipogliċemija fil- firien u l- ġrieden.
The major metabolite (a para-hydroxy-sulphate) with high affinity to the soluble human PPARγ, exhibited relatively high potency in a glucose tolerance assay in obese mice.
Il- prodott ewlieni tal- metaboliżmu (sustanza tat- tip para - hydroxy- sulphate) b’ affinità għolja għas- sustanza umana PPARγ solubbli, wera qawwa relattivament għolja f’ analiżi dwar it- tolleranza għall- glukożju fi ġrieden smien.
The clinical relevance of this observation has not been fully elucidated.
Ir- relevanza klinika ta ’ din l - osservazzjoni għadha ma ’ ġietx iċċarata għal kollox.
In clinical trials, the glucose lowering effects observed with rosiglitazone are gradual in onset with near maximal reductions in fasting plasma glucose (FPG) evident following approximately 8 weeks of therapy.
Fi provi kliniċi, l- effetti ta ’ tnaqqis fil- glukożju osservati b’ rosiglitazone huma gradwali fil- bidu b’ evidenza ta ’ riduzzjoni kważi massima fil- livell ta’ glukożju fil- plażma meta l- pazjent ikun sajjem (FPG), wara bejn wieħed u ieħor tmien ġimgħat ta ’ terapija.
The improved glycaemic control is associated with reductions in both fasting and post- prandial glucose.
It- titjib fil- kontroll gliċemiku huwa assoċċjat mat- tnaqqis fil- livell ta’ glukożju meta l- pazjent ikun sajjem kif ukoll fil- livell wara l- ikel.
Rosiglitazone was associated with increases in weight.
Rosiglitazone ġie assoċjat ma ’ żjieda fil- piż.
In mechanistic studies, the weight increase was predominantly shown to be due to increased subcutaneous fat with decreased visceral and intra-hepatic fat.
Fi studji mekkanistiċi, iż- żjieda fil- piż kienet murija fil - biċċa l- kbira tal- każi bħala kawża ta ’ żjieda fix- xaħam taħt il- ġilda bi tnaqqis fix- xaħam fil- vixxri u mad- dawra tal- fwied.
Consistent with the mechanism of action, rosiglitazone in combination with metformin reduced insulin resistance and improved pancreatic ß-cell function.
Konsistenti mal- mekkaniżmu t’ azzjoni, rosiglitazone flimkien ma ’ metformin naqqas ir- reżistenza għall- insulina u tejjeb il- funzjoni taċ- ċellula β fil- frixa.
Improved glycaemic control was also associated with significant decreases in free fatty acids.
It- titjib fil- kontroll gliċemiku kien ukoll assoċjat ma ’ tnaqqis sinifikanti ta ’ free fatty acids.
As a consequence of different but complementary mechanisms of action, combination therapy of rosiglitazone with metformin resulted in additive effects on glycaemic control in type 2 diabetic patients.
B’ konsegwenza tal- mekkaniżmi ta ’ azzjoni differenti iżda kumplimentari, terapija b’ rosiglitazone u metformin irriżultat f’ effetti additivi fuq il - kontroll gliċemiku f’ pazjenti dijabetiċi ta ’ tip 2.
In studies with a maximal duration of three years, rosiglitazone given once or twice daily in dual oral therapy with metformin produced a sustained improvement in glycaemic control (FPG and HbA1c).
Fi studji b’ tul massimu ta ’ tlett snin, rosiglitazone mogħti darba jew darbtejn kuljum f’ terapija orali doppja ma ’ metformin wassal għal titjib sostnut fil- kontroll gliċemiku (FPG u HbA1c).
A more pronounced glucose-lowering effect was observed in obese patients.
Effett iktar inċiżiv ta ’ tnaqqis fil- glukożju ġie osservat f’ pazjenti smien.
An outcome study has not been completed with rosiglitazone, therefore the long-term benefits associated with improved glycaemic control of rosiglitazone have not been demonstrated.
Studju finali għadu ma ġiex konkluż fuq rosiglitazone u għalhekk il- benefiċċji fuq medda twila assoċjati ma ’ titjib fil- kontroll gliċemiku ta ’ rosiglitazone għadhom ma ġewx murija.
At 18 months, in an ongoing long term comparator study, rosiglitazone in dual oral therapy with metformin was non-inferior to the combination of sulphonylurea plus metformin for lowering HbA1c.
Wara 18- il xahar, fi studju kontinwu fit- tul b’ komparaturi, rosiglitazone f’ terapija orali doppja ma ’ metformin ma kienx inferjuri għal kombinazzjoni ta ’ sulphonylurea u metformin biex inaqqas l - HbA1c.
An active controlled clinical trial (rosiglitazone up to 8 mg daily or metformin up to 2,000 mg daily) of 24 weeks duration was performed in 197 children (10-17 years of age) with type 2 diabetes.
Prova klinika kkontrollata attiva (rosiglitazone sa 8mg kuljum jew metformin sa 2, 000mg kuljum) li dam 24 ġimgħa sar fuq 197 tifel u tifla (eta ’ bejn 10 u 17- il sena) b’ dijabete tat- tip 2.
Improvement in HbA1c from baseline achieved statistical significance only in the metformin group.
Titjib fl- HbA1c mill- linja bażi kiseb statistika sinifikanti biss fil- grupp tal- metformin.
Rosiglitazone failed to demonstrate non-inferiority to metformin.
Rosiglitazone ma weriex li m’ huwiex inferjuri għall- metformin.
Following rosiglitazone treatment, there were no new safety concerns noted in children compared to adult patients with type 2 diabetes mellitus.
Wara trattament b’ rosiglitazone, ma ġew innutati l- ebda problemi ta ’ sigurtà fit- tfal meta mqabbla ma’ pazjenti adulti b’ dijabete mellitus tat- tip 2.
No long-term efficacy and safety data are available in paediatric patients.
Ma hemmx tagħrif dwar effikaċija u sigurtà f’ pazjenti pedjatriċi.
12 There are no studies completed assessing long-term cardiovascular outcome in patients receiving rosiglitazone in combination with metformin.
M’ hemmx studji konklużi li jkejlu r- riżultati kardjovaskulari fuq medda twila f’ pazjenti li jieħdu rosiglitazone flimkien ma ’ metformin
Metformin Metformin is a biguanide with antihyperglycaemic effects, lowering both basal and postprandial plasma glucose.
Metformin Metformin huwa biguanide b’ effetti anti- ipergliċemiċi, li jbaxxu kemm il- livell bażi u l- livell ta ’ wara l- ikel tal- glukożju fil- plażma.
It does not stimulate insulin secretion and therefore does not produce hypoglycaemia.
Ma jistimulax tnixxija ta ’ l- insulina u għalhekk ma jikkawzax ipogliċemija.
Metformin may act via three mechanisms:
13 Metformin jista ’ jaġixxi permezz ta ’ tlett mekkaniżmi:
- by reduction of hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis,
- permezz ta ’ tnaqqis fil- produzzjoni tal- glukożju fil- fwied billi jżomm lura glukoneoġenesi u
- in muscle, by modestly increasing insulin sensitivity, improving peripheral glucose uptake and
- fil- muskolu, billi jżid ftit is- sensitività għall- insulina u b’ hekk itejjeb l- assorbiment u l- użu
utilisation,
periferali tal- glukożju.
- by delaying intestinal glucose absorption.
- billi jittardja l- assorbiment intestinali tal- glukożju.
Metformin increases the transport capacity of specific types of membrane glucose transporters (GLUT-1 and GLUT-4).
Metformin jistimola s- sinteżi tal- glajkoġen intraċellulari billi jaġixxi fuq glycogen synthase Metformin iżid il- kapaċità ta ’ trasport ta ’ tipi speċifiċi ta ’ membrane glucose transporters (GLUT- 1 u GLUT- 4)
In humans, independently of its action on glycaemia, metformin has favourable effects on lipid metabolism.
Fil- bniedem, indipendentement mill- azzjoni tiegħu fuq il- gliċemija, metformin għandu effetti favorevoli fuq il- metaboliżmu lipidu.
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 kontrollati fuq żmien medju jew twil: metformin inaqqas il- kolesterol totali, LDLc u livelli ta ’ trigliċeridi.
The prospective randomised (UKPDS) study has established the long-term benefit of intensive blood glucose control in type 2 diabetes.
L- istudju każwali prospettiv (UKPDS) stabbilixxa l- benefiċċji fuq medda twila ta ’ kontroll fuq il - glukożju fid- demm f’ każi ta ’ dijabete ta ’ tip 2.
Analysis of the results for overweight patients treated with metformin after failure of diet alone showed:
Analiżi tar- riżultati għal pazjenti b’ piż eċċessiv ikkurati b’ metformin wara li falliet id- dieta waħidha wrew:
- a significant reduction of the absolute risk of any diabetes-related complication in the metformin
- tnaqqis sinifikanti fir- riskju assolut ta ’ kumplikazzjoni relatata mad- dijabete fil- grupp ta ’
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
metformin (29. 8 każi/ 1, 000 snin ta ’ kura (patient- years)) imqabbel ma ’ dieta waħidha (43. 3 każi/ 1, 000 snin ta ’ kura), p=0. 0023, u mqabbel ma ’ gruppi ta ’ monoterapija kkombinata bis - sulphonylurea u l- insulina (40. 1 każi/ 1, 000 snin ta ’ kura), p=0. 0034
- a significant reduction of the absolute risk of diabetes-related mortality: metformin
- tnaqqis sinifikanti tar- riskju assolut ta ’ mwiet relatati mad- dijabete: metformin 7. 5 każi/ 1, 000