qanastek/EMEA-V3 huggingface dataset:
Therefore, based upon the safety profile of AVANDAMET, which requires a continuous evaluation, the CHMP concluded that the MAH should submit one additional renewal application in 5 years time.
Għalhekk, abbażi tal- profil tas- sigurtà ta ’ AVANDAMET, li jeħtieġ evalwazzjoni kontinwa, is- CHMP ikkonkluda li l- MAH għandu jissottometti applikazzjoni addizzjonali waħda ta ’ tiġdid ħames snin oħra.
What is Avandia?
X' inhi Avandia?
Avandia is a medicine containing the active substance rosiglitazone.
Avandia hija mediċina li fiha s- sustanza attiva rosiglitazone.
It is available as tablets (pink:
Hija disponibbli bħala pilloli (roża:
2 mg; orange:
2 mg), oranġjo:
4 mg; red-brown:
4 mg, jew ħomor fil- kannella:
What is Avandia used for?
Għal xiex tintuża Avandia?
Avandia is used in adult patients (particularly those who are overweight) who have type 2 diabetes (non-insulin-dependent diabetes).
Avandia tintuża f' pazjenti adulti (l- aktar jekk għandhom piż żejjed) li jbatu minn dijabete tat- tip 2 (mhux dipendenti mill- insulina).
Avandia may be used on its own in patients for whom metformin (an antidiabetes medicine) is not suitable.
Avandia tista 'tintuża waħedha f' pazjenti li għalihom il- metformina (mediċina kontra d- dijabete) ma tkunx adatta.
Avandia may also be used in combination with metformin (‘ dual therapy’) in type 2 diabetes patients who are not satisfactorily controlled on metformin alone, or with a sulphonylurea (another type of antidiabetes medicine) when metformin is not suitable.
Avandia tista 'tintuża wkoll flimkien mal- metformina (' terapija dupliċi ') f' pazjenti li jbatu mid- dijabete tat- tip 2 li ma jkunux jistgħu jiġu kkontrollati b' mod sodisfaċjenti meta tintuża biss il- metformina waħedha, jew ma' sulfonilurea (tip ieħor ta 'mediċina kontra d- dijabete) meta l- metformina ma tkunx adatta.
Avandia may also be used with both metformin and a sulphonylurea (‘ triple therapy’), in patients with insufficient control of their disease despite dual oral therapy.
Il- mediċina tista 'tinkiseb biss b' riċetta tat- tabib.
How is Avandia used?
Kif tintuża Avandia?
Avandia can be taken with or without food.
Avandia tista 'tingħata ma' l- ikel jew waħedha.
The recommended starting dose is 4 mg daily, given as a single dose, or in two 2 mg doses.
Id- doża inizjali rakkomandata hi ta '4 mg kuljum, mogħtija bħala doża waħda, jew f' żewġ dożi ta' 2 mg.
This dose may need to be increased to 8 mg daily after eight weeks if better blood sugar control is needed, given as a single dose, or in two 4 mg doses.
Din id- doża tista 'tiżdied għal 8 mg kuljum wara tmien ġimgħat jekk ikun meħtieġ kontroll aħjar taz- zokkor fid- demm u tista' tingħata f' daqqa jew maqsuma f' żewġ dożi ta '4 mg.
However, this should be done with caution in patients who are also taking a sulphonylurea, due to the risk of fluid retention.
Madankollu, dan għandu jsir b' kawtela fil- pazjenti li jkunu qed jieħdu wkoll sulfonilurea, minħabba r- riskju ta 'żamma tal- fluwidi.
How does Avandia work?
Kif taħdem Avandia?
Type 2 diabetes is a disease in which the pancreas does not make enough insulin to control the level of glucose (sugar) in the blood or when the body is unable to use insulin effectively.
Id- dijabete tat- tip 2 hi marda li fiha, il- frixa (pankreas) ma tipproduċix biżżejjed insulina biex tikkontrolla l- livell ta 'glukożju (zokkor) fid- demm jew meta l- ġisem ma jkunx kapaċi juża l- insulina b' mod effikaċi.
The active substance in Avandia, rosiglitazone, makes cells (fat, muscle and liver) more sensitive to insulin, which means that the body makes better use of the insulin it produces.
Rosiglitazone, is- sustanza attiva f' Avandia, tagħmel iċ- ċelloli (tax- xaħam, tal- muskoli u tal- fwied) iktar sensittivi għall- insulina, li jfisser li l- ġisem ikun jista 'jagħmel użu aħjar mill- insulina li jipproduċi.
As a consequence, the blood glucose is reduced and this helps to control type 2 diabetes.
Minħabba f' hekk il- glukożju fid- demm jitnaqqas u dan jgħin il- kontroll tad- dijabete tat - tip 2.
Treatment of type 2 diabetes with Avandia is in addition to diet and exercise.
It- trattament b' Avandia għad- dijabete tat- tieni tip għandu jsir flimkien mad- dieta u l- eżerċizzju.
Reproduction is authorised provided the source is acknowledged. using one other antidiabetes medicine (metformin or a sulphonylurea), or who were already using a combination of two antidiabetes medicines (metformin and a sulphonylurea).
Avandia, użata waħedha, tqabblet fi studju mal- plaċebo (trattament finta), mal- metformina jew mal - glibenbklamide (tip ta 'sulfonilurea).
The studies measured the level of a substance in the blood called glycosylated haemoglobin (HbA1c), which gives an indication of how well the blood glucose is controlled.
Dan il- livell jagħti indikazzjoni ta 'kemm hu kkontrollat tajjeb iz- zokkor fid- demm.
What benefit has Avandia shown during the studies?
X' inhu l- benefiċċju ta 'Avandia li ntwera f' dawn l- istudji?
Avandia given alone was more effective than placebo in reducing HbA1c.
Avandia mogħtija waħedha kienet ferm superjuri għall- plaċebo fit- tnaqqis ta 'l- HbA1c.
Combination with other antidiabetes medicines led to further decreases in the level of HbA1c, indicating that blood glucose levels had been further reduced.
Il - kombinazzjoni tagħha ma 'mediċini oħra ta' kontra d- dijabete wasslet għal iktar tnaqqis fil- livell ta 'l - HbA1c, li juri li l- livelli tal- glukożju fid- demm komplew jonqsu.
What is the risk associated with Avandia?
X' inhu r- riskju assoċjat ma 'Avandia?
The most common side effects with Avandia (seen in between 1 and 10 patients in 100) are anaemia (low red blood cell counts), hypercholesterolaemia (high blood cholesterol levels), hypertriglyceridaemia (high blood levels of triglycerides, a type of fat), hyperlipaemia (high blood levels of lipids, another type of fat), weight increase, increased appetite, cardiac ischaemia (reduced oxygen supply to the heart muscle), constipation, bone fractures (broken bones), hypoglycaemia (low blood glucose) and oedema (swelling).
L- iktar effetti sekondarji komuni ma 'Avandia (li dehru f' bejn pazjent wieħed u għaxra minn kull mija) huma l- anemija (ammonti baxxi ta' ċelloli ħomor fid- demm), iperkolesterolemija (livelli għolja ta 'kolesterol fid- demm), ipertrigliċeridemija (livelli għolja ta' trigliċeridi, tip ta 'xaħam, fid- demm), iperlipemija (livelli għolja ta' lipidi, tip ieħor ta 'xaħam fid- demm), żieda fil- piż, żieda fl- aptit, iskemija kardijaka (tnaqqis ta' ossiġenu għall- muskolu tal- qalb), stitikezza, ksur ta 'l- għadam, ipogliċemija (livell baxx ta' glukożju) u edema (nefħa).
For the full list of all side effects reported with Avandia, see the Package Leaflet.
Għal- lista sħiħa ta 'effetti sekondarji rrappurtati ma' Avandia, ara l- Fuljett ta 'Tagħrif.
Avandia should not be used in people who may be hypersensitive (allergic) to rosiglitazone or any of the other ingredients.
Avandia ma għandux jingħata lil persuni li aktarx huma ipersensittivi (allerġiċi) għal rosiglitazone jew għal xi sustanza oħra tagħha.
It should not be used in patients who have heart failure, problems with their liver, an ‘ acute coronary syndrome’ such as unstable angina (a severe type of chest pain that changes in intensity) or certain types of heart attack, or complications of diabetes (diabetic ketoacidosis or diabetic precoma).
Ma għandhiex tintuża f' pazjenti li jkollhom ħsara fil- qalb, problemi fil - fwied, 'sindromu koronarju akut' bħala anġina instabbli (tip gravi ta 'wġigħ fis- sider li l- intensità tiegħu tinbidel) jew ċerti tipi ta' attakk tal- qalb, jew kumplikazzjonijiet relatati mad- dijabete (ketoaċidożi djabetika jew prekoma djabetika).
The doses of Avandia may need to be adjusted when given with certain other medicines such as gemfibrozil or rifampicin.
Jista 'jkun meħtieġ li d- dożi ta' Avandia jiġu aġġustati meta din tingħata ma 'ċerti mediċini oħra bħal gemfibrozil jew rifampicin.
The full list is available in the Package Leaflet.
Il- lista sħiħa ta 'dawn il- mediċini tinsab fil- Fuljett ta' Tagħrif.
Why has Avandia been approved?
Għaliex ġiet approvata Avandia?
The Committee for Medicinal Products for Human Use (CHMP) decided that Avandia’ s benefits are greater than its risks for the treatment of type 2 diabetes mellitus.
Il- Kumitat għall- Prodotti Mediċinali għall- Użu mill- Bniedem (CHMP) iddeċieda li Avandia għandu iktar benefiċċji milli riskji fit- trattament tad- dijabete mellitu tat- tieni tip.
The Committee recommended that Avandia be given marketing authorisation.
Il- Kumitat irrakkomanda li Avandia jingħata l- awtorizzazzjoni għat- tqegħid fis- suq.
Other information about Avandia:
Tagħrif ieħor dwar Avandia:
The European Commission granted a marketing authorisation valid throughout the European Union for Avandia to SmithKline Beecham plc on 11 July 2000.
Il- Kummissjoni Ewropea tat awtorizzazzjoni għat- tqegħid fis- suq valida madwar l- Unjoni Ewropea kollha għal Avandia lil SmithKline Beecham plc fil- 11 ta 'Lulju 2000.
The marketing authorisation was renewed on 11 July 2005.
L- awtorizzazzjoni għat- tqegħid fis- suq ġiet imġedda fil- 11 ta 'Lulju 2005.
The full EPAR for Avandia can be found here.
L- EPAR sħiħ għal Avandia huwa disponibbli minn hawn.
SUMMARY OF PRODUCT CHARACTERISTICS
SOMMARJU TAL- KARATTERSITICI TAL- PRODOTT
AVANDIA 2 mg film-coated tablets.
AVANDIA 2 mg pilloli miksijin b’ rita.
Each tablet contains rosiglitazone maleate corresponding to 2 mg rosiglitazone.
Kull pillola fiha rosiglitazone maleate li jikkorrispondi għal 2 mg ta ’ rosiglitazone.
Excipient Contains lactose (approximately 108 mg).
Sustanza mhux attiva, Fih lattosju (bejn wieħed u ieħor 108 mg)
Pink film-coated tablets debossed with “ GSK” on one side and "2" on the other side.
Pilloli roża miksija b’ rita li għandhom il- marka “ GSK ” imħaffra fuq naħa waħda u “ 2 ” fuq in- naħa l - oħra.
Rosiglitazone is indicated in the treatment of type 2 diabetes mellitus:
Rosiglitazone hu indikat fit- trattament tad- dialbete mellitus tat- tip 2;,
as monotherapy – in patients (particularly overweight patients) inadequately controlled by diet and exercise for whom metformin is inappropriate because of contraindications or intolerance
bħala monotherapija – fil- pazjenti (b’ mod partikolari dawk li għandhom piż żejjed) li mhumiex ikkontrollati biżżejjed bid- dieta u bl- eżerċizzju u li għalihom il- metformin m’ huwiex adattat minħabba kontra - indikazzjoni jew intolleranza
as dual oral therapy in combination with – metformin, in patients (particularly overweight patients) with insufficient glycaemic control despite maximal tolerated dose of monotherapy with metformin – a sulphonylurea, only in patients who show intolerance to metformin or for whom metformin is contraindicated, with insufficient glycaemic control despite monotherapy with a sulphonylurea
bħala terapija orali doppja ma ’ – metformin, fil- pazjenti (b’ mod partikolari dawk li għandhom piż żejjed) li m’ għandhomx kontroll glikimiku suffiċjenti minkejja l- ogħla doża ttollerata ta ’ monoterapija b’ metformin – sulphonylurea, f’ dawk il- pazjenti biss li juru intolleranza għall metformin jew għall- dawk li għalihom il- metformin huwa kontra- indikat, u li m’ ghandhomx kontroll glikimiku suffiċjenti minkejja monoterapija b’ sulphonylurea
as triple oral therapy in combination with – metformin and a sulphonylurea, in patients (particularly overweight patients) with insufficient glycaemic control despite dual oral therapy (see section 4.4).
bħala terapija orali trippla flimkien ma ’ – metformin u sulphonylurea, fil- pazjenti (b’ mod partikolari dawk li għandhom piż żejjed) li m’ għandhomx kontroll glikimiku suffiċjenti minkejja terapija orali doppja (aera sezzjoni 4. 4).
Experience from clinical trials with rosiglitazone is currently limited to three years.
L- esperjenza mill- provi kliniċi b’ rosiglitazone bħalissa hi limitata għal tliet snin.
The long-term benefits of therapy with rosiglitazone have not been demonstrated (see section 5.1).
Il- benefiċċji fit- tul tat- terapija b’ rosiglitazone għadhom ma ntwerewx (ara s- sezzjoni 5. 1).
Rosiglitazone therapy is usually initiated at 4 mg/ day.
It- terapija b’ rosiglitazone ġeneralment tinbeda b’ 4 mg kuljum.
This dose can be increased to 8 mg/ day after eight weeks if greater glycaemic control is required.
Din id- doża tista ’ tiżdied għal 8 mg kuljum wara tmien ġimgħat jekk ikun meħtieġ aktar kontroll glikimiku.
In patients administered rosiglitazone in combination with a sulphonylurea, an increase in rosiglitazone to 8 mg/ day should be undertaken cautiously following appropriate clinical evaluation to assess the patient's risk of developing adverse reactions relating to fluid retention (see 4.4 and 4.8).
Fil- pazjenti li jingħataw rosiglitazone flimkien ma sulphonylurea, żjieda fid- doża ta ’ rosiglitazone għal 8mg kuljum għandha ssir b’ kawtela wara li ssir evalwazzjoni klinika xierqa li teżamina kemm il- pazjent għandu ir- riskju li jiżviluppa reazzjonijiet mhux mixtieqa li għandhom x’ jaqsmu mar- retenzjoni tal- fluwidu (ara sezzjoni 4. 4 u 4. 8).
Rosiglitazone may be given once or twice a day.
2 Rosiglitazone jista ’ jingħata darba jew darbtejn kuljum.
Rosiglitazone may be taken with or without food.
Rosiglitazone jista ’ jittieħed ma ’ l- ikel jew mhux ma ’ l- ikel.
2 Elderly (see section 4.4 Fluid retention and cardiac failure) No dose adjustment is required in the elderly.
Anzjani (ara sezzjoni 4. 4 Retenzjoni ta ’ fluwidu u insuffiċjenza tal- qalb) Ma huwa meħtieġ l- ebda aġġustament tad- doża għall- anzjani.
Patients with renal impairment (see section 4.4 Fluid retention and cardiac failure) No dose adjustment is required in patients with mild and moderate renal insufficiency.
Pazjenti b’ indeboliment renali (ara sezzjoni 4. 4 Retenzjoni ta ’ fluwidu u insuffiċjenza tal- qalb) Ma huwa meħtieġ l- l- ebda aġġustament tad- doża għall- pazjenti b’ insuffiċjenza renali ħafifa jew moderata.
Limited data are available in patients with severe renal insufficiency (creatinine clearance < 30 ml/ min) and therefore rosiglitazone should be used with caution in these patients.
It- tagħrif li jeżisti dwar pazjenti b’ insuffiċjenza renali qawwija (eliminazzjoni ta ’ kreatinina < 30 ml/ min) hija limitata u għalhekk rosiglitazone għandu jintuża bl- attenzjoni f’ dawn il- pazjenti.
Patients with hepatic impairment Rosiglitazone should not be used in patients with hepatic impairment.
Pazjenti b’ indeboliment tal- fwied Rosiglitazone m’ għandux jintuża fil- pazjenti bi ħsara epatika.
The available data do not support efficacy in the paediatric population and therefore such use is not recommended.
Tfal u adolexxenti Ma jeżisti l- l- ebda tagħrif dwar l- użu ta ’ rosiglitazone fil- pazjenti ta ’ taħt l- 10 snin, Għat- tfal ta ’ bejn l - 10 u s- 17- il sena, hemm tagħdrif limitat dwar rosiglitazone bħala monoterapija (ara sezzjonijiet 5. 1 u 5. 2). It- tagħrif disponibbli ma jsostnix l- effikaċja fil- popolazzjoni pedjatrika u għalhekk tali użu m’ huwiex rakkomandat
Use of rosiglitazone is contraindicated in patients with:
L- użu ta ’ rosiglitazone hu kontra- indikat fil- pazjenti li għandhom:
− known hypersensitivity to rosiglitazone or to any of the excipients
− sensittività eċċessiva magħrufa għar- rosiglitazone jew għal xi sustanzi mhux attivi tal- pillola, jew
− cardiac failure or history of cardiac failure (NYHA class I to IV)
insuffiċjenza tal- qalb jew storja ta ’ insuffiċjenza tal- qalb (NYHA klassijiet I sa IV)
− an Acute Coronary Syndrome (unstable angina, NSTEMI and STEMI) (see section 4.4)
− Sindromu Koronarju Akut (anġina instabbli, NSTEMI u STEMI) (ara sezzjoni 4. 4)
− hepatic impairment
− indeboliment epatiku,
- diabetic ketoacidosis or diabetic pre-coma.
− ketoaċidożi fid- dijabete jew stat ta ’ qabel koma fid- dijabete.
Rosiglitazone can cause dose-dependent fluid retention.
Retenzjoni ta ’ fluwidu u insuffiċjenza tal- qalb Thiazolidinediones jistgħu iwasslu għal retenzjoni ta ’ fluwidu u din tista ’ tħarrax jew tipprovoka sinjali jew sintomi ta ’ insuffiċjenza tal- qalb konġestiva Rosiglitazone jista ’ jikkawża retenzjoni ta ’ fluwidu li tiddependi mid- doża.
All patients, particularly those receiving concurrent insulin or sulphonylurea therapy, those at risk for heart failure, and those with reduced cardiac reserve, should be monitored for signs and symptoms of adverse reactions relating to fluid retention, including weight gain and heart failure.
Il- pazjenti kollha, speċjalment dawk li qed jieħdu t - trattament flimkien ma ’ l- insulina jew sulphonylurea, dawk li għandhom ir- riskju ta ’ insuffiċjenza tal - qalb u dawk b’ riżerva tal- qalb mnaqqsa, għandhom jiġu monitorjati għal xi sinjali jew sintomi ta ’ effetti sekondarji li għandhom x’ jaqsmu ma retenzjoni ta ’ fluwidu, inklużi żjieda fil- piż u insuffiċjenza tal- qalb.
Increased monitoring of the patient is recommended if rosiglitazone is used in combination with metformin and insulin.
Huwa rakkomandat li jiżdied il- monitoraġġ tal- pazjent jekk rosiglitazone jintuża flimkien ma ’ metformin u l- insulina.
Rosiglitazone should be discontinued if any deterioration in cardiac status occurs.
Rosiglitazone għandu jitwaqqaf fil- każ ta ’ xi deterjorament fl- istat kardijaku.
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.
Insuffiċjenza tal- qalb kienet irrapuratata ukoll b’ mod aktar frekwenti f’ pazjenti bi storja ta ’ insuffiċjenza tal- qalb; edima u insuffiċjenza tal- qalb kienu rrapurtati wkoll b’ mod aktar frekwenti fl - anzjani, u f’ pazjenti b’ indeboliment ħafif jew moderat tal- kliewi.
Caution should be exercised in patients over 75 years because of the limited experience in this patient group.
Billi l- NSAIDs u r -
Since NSAIDs and rosiglitazone are associated with fluid retention, concomitant administration may increase the risk of oedema.
3 rosiglitazone huma assoċjati mar- ritenzjoni tal- fluwidu, it- teħid flimkien ta’ dawn jista ’ jżid ir- riskju ta ’ edima.
Combination with insulin An increased incidence of cardiac failure has been observed in clinical trials when rosiglitazone is used in combination with insulin.
Għoti flimkien ma ’ l- insulina Inċidenza ogħla ta ’ insuffiċjenza tal- qalb ġiet osservata fi provi kliniċi meta rosiglitazone jintuża flimkien ma ’ l- insulina.
Insulin and rosiglitazone are both associated with fluid retention, concomitant administration may increase the risk of oedema and could increase the risk of ischaemic heart disease.
L- insulina u rosiglitazone huma t- tnejn assoċjati ma ’ retenzjoni ta ’ fluwidu, meta dawn jittieħdu flimkien hemm riskju ogħla ta ’ edima u riskju ogħla ta ’ mard iskemiku tal- qalb.
Insulin should only be added to established rosiglitazone therapy in exceptional cases and under close supervision.
L- insulina għandha tiġi miżjuda ma ’ terapija stabbilita b’ rosiglitazone f’ każijiet eċċezzjonali biss u waqt superviżjoni mill- qrib.
3 Myocardial Ischaemia The available data indicate that treatment with rosiglitazone may be associated with an increased risk of myocardial ischaemic events (see section 4.8).
Iskemja Mijokardijaka L- informazzjoni disponibbli turi li kura b’ rosiglitazone tista ’ tkun assoċjata ma ’ riskju akbar ta ’ eventi iskemiċi mijokardijaċi (ara sezzjoni 4. 8).
Therefore, as a precaution, the use of rosiglitazone is not recommended in these patients, particularly those with myocardial ischaemic symptoms.
Għalhekk, bħala prekawzjoni, l- użu ta ’ rosiglitazone m’ huwiex rakkomandat f’ dawn il- pazjenti, l- aktar dawk b’ sintomi ta ’ iskemja mijokardijaka.
In view of the potential for development of heart failure in these patients, rosiglitazone should therefore not be initiated in patients having an acute coronary event and it should be discontinued during the acute phase (see section 4.3).
Minħabba l- potenzjal ta ’ żvilupp ta ’ insuffiċjenza tal- qalb f’ dawn il- pazjenti, rosiglitazone m’ għandux jinbeda f’ pazjenti li kellhom event koronarju akut u għandu jitwaqqaf fil- fażi akuta (ara sezzjoni 4. 3).
Monitoring of liver function There have been rare reports of hepatocellular dysfunction during post-marketing experience (see section 4.8).
Monitoraġġ tal- funzjoni tal- fwied Kien hemm rapporti rari ta ’ funzjoni ħażina epatoċellulari waqt l- esperjenza ta ’ wara t- tqegħid fis- suq (ara s- sezzjoni 4. 8).
There is limited experience with rosiglitazone in patients with elevated liver enzymes (ALT > 2.5X upper limit of normal).
Teżisti esperjenza limitata b’ 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 rosiglitazone in all patients and periodically thereafter based on clinical judgement.
Għalhekk, enzimi tal- fwied għandhom jiġu eżaminati qabel ma tinbeda l- kura b’ AVANDIA fil- pazjenti kollha u perjodikament wara fuq bażi ta ’ ġudizzju kliniku.
Therapy with rosiglitazone should not be initiated in patients with increased baseline liver enzyme levels (ALT > 2.5X upper limit of normal) or with any other evidence of liver disease.
Terapija b’ rosiglitazone m’ għandhiex tinbeda f’ pazjenti b’ linja bażi ta ’ enżimi tal - fwied għolja (ALT > 2. 5 darba l- limitu ta ’ fuq tan- normal) jew b’ xi ħjiel ieħor ta ’ mard tal- fwied.
If ALT levels are increased to > 3X upper limit of normal during rosiglitazone therapy, liver enzyme levels should be reassessed as soon as possible.
Jekk il- livelli ta ’ l- ALT jiżdiedu għal > 3 darbiet il- limitu ta ’ fuq tan- normal waqt terapija b’ rosiglitazone, il- livelli ta ’ l- enzimi tal- fwied għandhom jiġu rivalutati mill- aktar fis possibbli.
If ALT levels remain > 3X the upper limit of normal, therapy should be discontinued.
Jekk il- livelli ta ’ l - ALT jibqgħu > 3 darbiet il- limitu ta ’ fuq tan- normal, it- terapija għandha titwaqqaf.
If any patient develops symptoms suggesting hepatic dysfunction, which may include unexplained nausea, vomiting, abdominal pain, fatigue, anorexia and/ or dark urine, liver enzymes should be checked.
Jekk xi pazjent jiżviluppa sintomi li jindikaw funzjoni ħażina epatika, li jistgħu jinkludu dardir bla spjegazzjoni, remettar, uġigħ ta ’ żaqq, għejja, anoreksja u/ jew awrina skura, l- enzimi tal- fwied għandhom jiġu ċċekkjati.
The decision whether to continue the patient on therapy with rosiglitazone should be guided by clinical judgement pending laboratory evaluations.
Id- deċiżjoni jekk il- pazjent ikomplix it- terapija b’ rosiglitazone għandha tkun iggwidata b’ ġudizzju kliniku skond valutazzjonijiet tal- laboratorju.
If jaundice is observed, drug therapy should be discontinued.
Jekk tiġi nnotata s- suffejra, din it- terapija 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 ’ edima makulari tad- dijabete b’ tnaqqis fl - akutezza fil- vista jew li din tmur għall- agħar wara li jittieħdu t- thiazolidinediones, inkluż ir - rosiglitazone.
Many of these patients reported concurrent peripheral oedema.
Ħafna minn dawn il- pazjenti rrappurtaw edima periferali fl- istess ħin.
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- edima makulari imma min jippreskrivi dan il - prodott għandu jkun avżat bil- possibiltà ta ’ edima 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 kienet akbar fil- każ ta 'użu flimkien ma ’ l- 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, minħabba li dan l- effett jista ’ jkun kawżat mir- retenzjoni ta ’ fluwidu, li tista ’ tkun assoċjata ma ’ l- insuffiċjenza tal- qalb.
Anaemia Rosiglitazone treatment is associated with a dose-related reduction of haemoglobin levels.
4 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 rosiglitazone.
F’ dawk il- pazjenti li jkollhom livell baxx ta ’ emoglobina qabel jibdew il- kura, hemm ir- riskju akbar ta ’ anemija waqt li jkunu qed jieħdu rosiglitazone
Hypoglycaemia Patients receiving rosiglitazone in combination therapy with a sulphonylurea or with insulin, may be at risk for dose-related hypoglycaemia.
Ipogliċemija Pazjenti li qed jirċievu rosiglitazone f’ terapija flimkien ma ’ sulphonylurea jew ma ’ l- 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 hemm bżonn ta ’ iżjed monitoraġġ tal - pazjent u ta ’ tnaqqis fid- doża tal- mediċina li qed tittieħed flimkien ma ’ rosiglitazone.
Triple oral therapy The use of rosiglitazone in triple oral therapy, in combination with metformin and a sulphonylurea, may be associated with increased risks for fluid retention and heart failure, as well as hypoglycaemia (see section 4.8).
Terapija orali trippla L- użu ta ’ rosiglitazone f’ terapija orali trippla, flimkien ma ’ metformin u sulphonylurea, jista ’ jkun assoċjat ma riskji ogħla ta ’ retenzjoni tal- fluwidu w insuffiċjenza tal- qalb, kif ukoll ipogliċemija (ara sezzjoni 4. 8).
Increased monitoring of the patient is recommended and adjustment of the dose of sulphonylurea may be necessary.
Monitoraġġ aktar ta ’ spiss tal- pazjent huwa rrakommandat u jista ’ jkun hemm bżonn ta ’ aġġustament tad- doża ta ’ sulphonylurea.
The decision to initiate triple oral therapy should include consideration of the alternative to switch the patient to insulin.
Id- deċiżjoni li tinbeda terapija orali trippla għandha tinkludi l- konsiderazzjoni li l- pazjent jaqleb fuq l- insulina.
4 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).
Others Premenopausal women have received rosiglitazone during clinical studies.
Oħrajn Nisa ta ’ qabel il- menopawsa rċevew 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 qabel l- użu kliniku wrew xi żbilanċi ormonali (ara s- sezzjoni 5. 3), ma ġew innotati l- ebda effetti mhux mixtieqa sinifikanti assoċjati ma ’ problemi mestruwali.
As a consequence of improving insulin sensitivity, resumption of ovulation may occur in patients who are anovulatory due to insulin resistance.
Bħala konsegwenza ta ’ titjib fis- sensittività għall - insulina, il- bidu mill- ġdid ta ’ l- ovulazzjoni jista ’ jseħħ fil- pazjenti fejn din kienet waqfet minħabba reżistenza għall- insulina.
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 jafu dwar ir- riskju ta ’ tqala u jekk pazjenta tixtieq tinqabad tqila jew jekk tinqabad tqila t- trattament għandu jitwaqqaf (ara s- sezzjoni 4. 6).
Rosiglitazone should be used with caution in patients with severe renal insufficiency (creatinine clearance < 30 ml/ min).
Rosiglitazone għandu jintuża b’ attenzjoni fil- pazjenti b’ insuffiċjenza renali qawwija (eliminazzjoni ta ’ kreatinina < 30 ml kull minuta).
Glycaemic control should be monitored closely.
Rosiglitazone għandu jintuża b’ attenzjoni waqt li jkun jittieħed flimkien ma ’ impedituri CYP2C8 (e. ż. gemfibrozil) jew inducers (e. ż. rifampicin) Għandu jkun hemm monitoraġġ mill- qrib tal- kontroll gliċemiku.
Rosiglitazone dose adjustment within the recommended posology or changes in diabetic treatment should be considered (see section 4.5).
L- aġġustament tad- doża ta ’ rosiglitazone skond il- pożoloġija rakkomandata jew tibdil fit - trattament dijabetiku għandu jiġi kkunsidrat.
AVANDIA 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.
Rosiglitazone 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.
In vitro studies demonstrate that rosiglitazone is predominantly metabolised by CYP2C8, with CYP2C9 as only a minor pathway.
Studji in vitro juru li rosiglitazone jiġi metabolizzat l- aktar mis- CYP2C8, is- CYP2C9 hija rotta minuri biss.
It cannot be excluded that other inducers (e. g. phenytoin, carbamazepine, phenobarbital, St John’ s wort) may also affect rosiglitazone exposure.
5 phenytoin, carbamazepine, phenobarbital, St John’ s wort) jistgħu wkoll ikollhom effett fuq l - esponiment għal rosiglitazone.
Clinically significant interactions with CYP2C9 substrates or inhibitors are not anticipated.
Mhux mistenni li jkun hemm effetti mhux mixtieqa klinikament rilevanti b’ sustrati tas- CYP2C9.
Concomitant administration with the oral anti-diabetic agents metformin, glibenclamide and acarbose did not result in any clinically relevant pharmacokinetic interactions with rosiglitazone.
Meta rosiglitazone ġie mogħti flimkien ma ’ l- aġenti anti- diabetiċi orali metformin, glibenclamide u acarbose ma ’ rriżultax li kien hemm xi interazzjonijiet farmakokinetiċi klinikament relevanti.
Moderate ingestion of alcohol with rosiglitazone has no effect on glycaemic control.
It- teħid moderat ta ’ l- alkoħol ma ’ rosiglitazone m’ għandux effett fuq il- kontroll tal- livell taz - zokkor fid - demm
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 ġew osservati l- ebda interazzjonijiet klinikament relevanti.
Studies in animals have
Ma hemmx biżżejjed tagħrif mill- użu ta ’ rosiglitazone f’ nisa tqal.
5 shown reproductive toxicity (see section 5.3).
Studji fuq bhejjem urew ħsara fuq is- sistema riproduttiva (ara s- sezzjoni 5. 3).
Rosiglitazone should not be used during pregnancy.
Rosiglitazone m’ għandux jintuża waqt tqala.
Rosiglitazone has been detected in the milk of experimental animals.
Rosiglitazone instab fil- ħalib tal- bhejjem taħt esperiment.
It is not known whether breast- feeding will lead to exposure of the infant to drug.
Mhux magħruf jekk it- treddigħ iwassalx biex it- tarbija tkun esposta għall- prodott mediċinali.
Rosiglitazone should therefore not be used in women who are breast-feeding.
Għalhekk rosiglitazone m’ għandux jintuża f’ nisa li qed ireddgħu.
AVANDIA has no or negligible influence on the ability to drive and use machines.
AVANDIA m’ għandu l- ebda effett jew ftit li xejn għandu effett fuq il- ħila biex issuq jew biex tħaddem magni.
Clinical trial data
Tagħrif minn provi kliniċi
Adverse reactions for each treatment regimen are presented below by system organ class and absolute frequency.
Reazzjonijiet mhux mixtieqa għal kull tip ta ’ 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 ta’ r- rosiglitazone.
Frequencies are defined as: very common ≥ 1/ 10; common ≥ 1/ 100, < 1/ 10; and uncommon ≥ 1/ 1000, < 1/ 100.
Il- frekwenzi huma definiti bħala: komuni ħafna ≥1/ 10; komuni ≥1/ 100; < 1/ 10; u mhux komuni ≥1/ 1, 000, < 1/ 100.
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 frequency grouping, adverse reactions are presented in order of decreasing seriousness.
F’ kull grupp ta ’ frekwenza, effetti mhux mixtieqa jidhru skond ordni ta ’ tnaqqis fis- serjeta` tal- każ.
The frequency of adverse reactions identified from clinical trial data
Frekwenza ta ’ reazzjonijiet mhux mixtieqa identifikati mit- tagħrif minn provi kliniċi
Frequency of adverse reaction by treatment regimen
Frekwenza ta ’ reazzjonijiet avversi skond it- tip ta ’ terapija
RSG + MET
RSG RSG + MET RSG + SU
Blood and the lymphatic system disorders anaemia leucopaenia thrombocytopaenia granulocytopaenia
Mard tad- demm u tas- sistema limfatika anemija lewkopenja tromboċitopenja granuloċitopenja
Common Common Common Common Common
Komuni Komuni Komuni
Metabolism and nutrition disorders hypercholesterolaemia1 hypertriglyceridaemia
Mard marbut mal- metaboliżmu u n- nutrizzjoni iperkolesterolemija1 ipertrigilċeridemija
Common Common Common
Komuni Komuni
Common Common Uncommon
Komuni Komuni
Nervous system disorders dizziness* headache*
Mard tas- sistema nervuża sturdament * Uġigħ ta ’ ras *
Cardiac disorders
Komuni
cardiac failure2
Mard tal- qalb
cardiac ischaemia3*
Iskemja kardijaka3 *
constipation
Mard gastro- intestinali stitikezza
Musculoskeletal and connective tissue disorders bone fractures 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 kundizzjonijijet ta ’ mnejn jingħata edima
Common Common Very common Very common
Komuni ħafna
RSG - Rosiglitazone monotherapy; RSG + MET - Rosiglitazone with metformin; RSG + SU - Rosiglitazone with sulphonylurea; RSG + MET + SU - Rosiglitazone with metformin and sulphonylurea
RSG – Monoterapija b’ rosiglitazone; RSG + MET - Rosiglitazone flimkien ma ’ metformin; RSG + SU
The elevated total cholesterol levels were associated with increase in both LDLc and HDLc, but the ratio of total cholesterol: HDLc was unchanged or improved in long term studies.
Il- livell sħiħ elevat tal- kolesterol kien assoċjat ma ’ żjieda kemm fl - LDLc kif ukoll fil- HDLc, iżda l- proporzjon tal- kolesterol sħiħ: HDLc ma nbidilx jew tjieb fis- studji fit - tul.
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 7 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 7 ma ’ l- insulina (rosiglitazone miżjud ma ’ terapija b’ insulina stabbilita) kienet ta ’ 2. 4%, meta mqabbla ma ’ insulina waħedha, 1. 1%.
Moreover in patients with congestive heart failure NYHA class I-II, a placebo-controlled one-year trial demonstrated worsening or possible worsening of heart failure in 6.4% of patients treated with rosiglitazone, compared with 3.5% on placebo.
Barra dan, 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.
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 u plaċebo flimkien, 1. 51% [Hazard ratio 1. 31 (95% confidence interval 1. 01 – 1. 70)].
Three large long-term prospective randomised controlled clinical trials (mean duration 41 months; 14,067 patients), comparing rosiglitazone to some other approved oral antidiabetic agents or placebo, have not confirmed or excluded this risk.
Tlett studji kliniċi kbar fuq tul ta ’ żmien twil, prospettivi, randomised u kontrollati (tul ta ’ żmien medja ta ’ 41 xahar; 14, 067 pazjenti), li qabblu rosiglitazone ma ’ xi aġenti orali anti- dijabetiċi approvati jew plaċebo, ma kkonfermawx jew eskludew dan ir- riskju.
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.
Frequencies are defined as: rare ≥ 1/ 10,000, < 1/ 1000 and very rare < 1/ 10,000 including isolated reports.
Il- frekwenzi huma definiti bħala rari > 1/ 10, 000, < 1/ 1000 u rari ħafna < 1/ 10, 000 inkluż rapporti iżolati.
The frequency of adverse reactions identified from post-marketing data
Il- frekwenza ta ’ reazzjonijiet mhux mixtieqa identifikati mit- tagħrif ta ’ wara t - tqegħid fis- suq
macular oedema
edima makulari
Cardiac disorders congestive heart failure/ pulmonary oedema
insuffiċjenza tal- qalb konġestiva / edima pulmonari
Skin and subcutaneous tissue disorders (see Immune system disorders) angioedema skin reactions (e. g. urticaria, pruritus, rash) 5
Mard tal- ġilda u tat- tessuti ta ’ taħt il- ġilda (ara Mard tas- sistema immuni) 5
In very rare cases a fatal outcome has been reported.
F’ każi rari ħafna kienu rrappurtati ukoll mwiet.
Limited data are available with regard to overdose in humans.
Jeżisti tagħrif limitat dwar doża eċċessiva ta ’ rosiglitazone fil- bniedem.
In the event of an overdose, it is recommended that appropriate supportive treatment should be 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.
Rosiglitazone is highly protein bound and is not cleared by haemodialysis.
Rosiglitazone jintrabat ħafna mal- proteini u ma ’ jitneħħiex permezz ta ’ dijaliżi tad - demm.
Pharmacotherapeutic group: oral blood glucose lowering drugs, thiazolidinediones, ATC code:
Kategorija farmakoterapewtika: mediċini orali li jbaxxu l- glukożju fid- demm, thiazolidinediones, Kodiċi ATC:
Rosiglitazone is a selective agonist at the PPARγ (peroxisomal proliferator activated receptor gamma) nuclear receptor and is a member of the thiazolidinedione class of anti-diabetic agents.
Rosiglitazone huwa agonist selettiv fir- receptor nuklejari PPARγ (peroxisome proliferator activated receptor gamma) u huwa membru tal- klassi ta ’ aġenti anti- diabetiċi 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.
Preclinical data The antihyperglycaemic activity of rosiglitazone has been demonstrated in a number of animal models of type 2 diabetes.
Tagħrif pre- kliniku 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- ċellula 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.
The major metabolite (para-hydroxy-sulphate) with high affinity to the soluble human PPARγ, exhibited relatively high potency in a glucose tolerance assay in obese mouse.
9 hydroxy- sulphate) b’ affinità għolja għas- sustanza umana PPARγ solubbli, wera qawwa relattivament għolja f’ analiżi dwar it- tolleranza għall- glukożju fi ġrieden smien.
9 Clinical trials data 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.
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.
Consistent with the mechanism of action, rosiglitazone 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.
As a consequence of different but complementary mechanisms of action, dual oral therapy of rosiglitazone with a sulphonylurea or metformin resulted in additive effects on glycaemic control in type 2 diabetic patients.
B’ konsegwenza tal- mekkaniżmi ta ’ azzjoni differenti iżda kumplimentari, terapija orali doppja b’ rosiglitazone flimkien ma’ sulphonylurea jew metformin irriżulta 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 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).
An outcome study has not been completed with rosiglitazone, therefore the long-term benefits associated with improved glycaemic control 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 or a sulphonylurea was non-inferior to the combination of sulphonylurea plus metformin for lowering HbA1c.
Wara 18- il xahar, fi studju kontinwu fit- tul b’ komparaturi, rosiglitazone f’ terapija orali doppja ma ’ metformin jew sulphonylurea ma kienx inferjuri għal kombinazzjoni ta ’ sulphonylurea u metformin biex inaqqas l- HbA1c.
There are no studies completed assessing long-term cardiovascular outcome in patients receiving rosiglitazone.
M’ hemmx studji konklużi li jkejlu r- riżultati kardjovaskulari fuq medda twila f’ pazjenti li jieħdu rosiglitazone flimkien ma ’ metformin.
Absorption Absolute bioavailability of rosiglitazone following both a 4 and an 8 mg oral dose is approximately 99%.
Assorbiment Il- bijodisponibilità assoluta ta ’ rosiglitazone wara doża orali ta ’ 4 kif ukoll ta ’ 8 mg hija madwar 99%.
Rosiglitazone plasma concentrations peak at around 1 hour after dosing.
Il- konċentrazzjonijiet ta ’ rosiglitazone fil- plażma jilħqu l- ogħla livell madwar siegħa wara li tingħata d- doża.
Administration of rosiglitazone with food resulted in no change in overall exposure (AUC), although a small decrease in Cmax (approximately 20% to 28%) and a delay in tmax (ca.1.75 h) were observed compared to dosing in the fasting state.
L- għoti ta ’ rosiglitazone ma ’ l- ikel ma rriżulta fl- ebda bidla fl- espożizzjoni totali (AUC), għalkemm tnaqqis żgħir fis- Cmax (madwar 20- 28%) u dewmien fit- tmax (ca. 1. 75 h) ġew innotati meta mqabbla ma ’ l- għoti tad- doża fi stat ta ’ sawm.
These small changes are not clinically significant and, therefore, it is not necessary to administer rosiglitazone at any particular time in relation to meals.
Dawn il- bidliet żgħar m’ humiex klinikament sinifikanti, u għalhekk m’ hemmx ħtieġa li tagħti rosiglitazone f’ xi ħin partikolari skond l- ikliet.
The absorption of rosiglitazone is not affected by increases in gastric pH.
L- assorbiment ta ’ rosiglitazone m’ huwiex affettwat b’ żidiet fil- pH ta ’ l- istonku.
Distribution The volume of distribution of rosiglitazone is approximately 14 litres in healthy volunteers.
Distribuzzjoni Il- volum tad- distribuzzjoni ta ’ rosiglitazone huwa madwar 14- il litru fil- voluntiera b’ saħħithom.
Plasma protein binding of rosiglitazone is high (approximately 99.8%) and is not influenced by concentration or age.
L - irbit ta ’ rosiglitazone mal- proteini tal- plażma huwa għoli (madwar 99. 8%) u mhuwiex influwenzat 10 mill- konċentrazzjoni jew mill- età.
The protein binding of the major metabolite (para-hydroxy-sulphate) is very high (> 99.99%).
L- irbit mal- proteini tal- metabolit prinċipali (sulfat para- idrossidu) hu għoli ħafna (> 99. 99%).
The contribution of the major metabolite (para-hydroxy-sulphate) to the
Ir- rotot ewlenin ta ’ metaboliżmu huma N- demethylation u hydroxylation, segwiti permezz ta ’ konjugazzjoni bis- sulphate u glucuronic acid.
10 overall anti-diabetic activity of rosiglitazone has not been fully elucidated in man and it cannot be ruled out that the metabolite may contribute to the activity.
Il- kontribut tal- prodott ewlieni tal- metaboliżmu (para - hydroxy- sulphate) fuq l- attività anti- ipergliċemika ġenerali ta ’ rosiglitazone għadu ma ġiex iċċarat għal kollox fil- bniedem u wieħed ma jistax jeskludi li l- prodott tal- metaboliżmu jista ’ jikkontribwixxi għal din l- attività.
Elimination Total plasma clearance of rosiglitazone is around 3 l/ h and the terminal elimination half-life of rosiglitazone is approximately 3 to 4 hours.
Eliminazzjoni L- eliminazzjoni totali tal- plażma minn rosiglitazone hija madwar 3 1/ h u l- half- life għall - eliminazzjoni terminali ta ’ rosiglitazone hi madwar 3- 4 h.
No intact drug is excreted in urine or faeces.
L- ebda sustanza attiva intatta m’ hi mneħħija fl- awrina jew fl- ippurgar.
The terminal half-life for radioactivity was about 130 hours indicating that elimination of metabolites is very slow.
Il- half- life terminali għar- radjuattività kienet madwar 130 h u dan jindika li l- eliminazzjoni tal- metaboli issir bil- mod ħafna.
Accumulation of the metabolites in plasma is expected upon repeated dosing, especially that of the major metabolite (para-hydroxy-sulphate) for which an 8-fold accumulation is anticipated.
L- akkumolu ta ’ metaboli fil- plażma jkun mistenni meta d- doża tiġi ripetuta, partikolarment dak tal- prodott tal- metaboliżmu ewlieni (para - hydroxy- sulphate) li għalih huwa antiċipat akkumolu ta ’ tmien darbiet iktar.