qanastek/EMEA-V3 huggingface dataset:
137 sweats, weakness, numbness of the hands or feet, heartburn, blurred vision, mouth ulceration, joint swelling and joint pain, decreased weight, dry mouth, dry skin, dry eye, decreased skin sensitivity, increased skin sensitivity, hot flushes, chills.
Dawn jaffettwaw bejn 1 sa 10 f’ kull 100 persuna Anoressija, sturdament, nuqqas ta ’ rqad, konġunktivite, żieda fid- dmugħ, tibdil fit- togħma, tinfaraġ, uġigħ jew nefħa fl- addome, nefħa b’ gass fl- istonku jew l- imsaren, stitikezza, ħakk, jiħfieflek jew jaqalek xagħrek b’ mod mhux tas- soltu, tgħereq ħafna matul il- lejl, tħossok bla saħħa, tnemnim ta ’ l - idejn jew tas- saqajn, żieda fil- piż, ħruq ta ’ stonku, vista mċajpra, ulċeri fil- ħalq, nefħa fil- ġogi u uġigħ fil- ġogi, tnaqqis fil- piż, ħalq xott, għajnejn xotti, tnaqqis tas- sensittività tal- ġilda, żieda tas- sensittività tal- ġilda, fwawar ta ’ sħana, dehxiet.
If any of the side effects gets serious or if you notice any other side effects not listed in this leaflet, please inform your doctor or pharmacist.
Jekk xi wieħed mill- effetti sekondarji jiggrava jew jekk tinnota xi effetti sekondarji li mhumiex imsemmijin f’ dan il- fuljett, jekk jogħġbok, għid lit- tabib jew lill- ispiżjar tiegħek.
What Glivec looks like and contents of the pack Glivec 400 mg film-coated tablets are very dark yellow to brownish-orange oval tablets with “ NVR” on one side and “ SL” on the other side.
Id- Dehra ta ’ Glivec u l- kontentuti tal- pakkett Pilloli miksija b’ rita Glivec ta ’ l- 400 mg huma pilloli ovali sofor skuri ħafna jagħtu fil- kannella - oranġjo b ’ “ NVR ” fuq naħa waħda u b ’ “ SL ” fuq l- oħra.
They are supplied in packs containing 10, 30 or 90 tablets, but these may not all be available in your country.
Jiġu f’ pakketti ta ’ 10, 30 jew 90 pillola, iżda jista ’ jkun li mhux il- pakketti kollha jkunu disponibbli f’ pajjiżek.
België/ Belgique/ Belgien Novartis Pharma N. V.
145 België/ Belgique/ Belgien Novartis Pharma N. V.
139 Lietuva Novartis Pharma Services Inc.
146 Lietuva Novartis Pharma Services Inc.
140
147
If you need more information about your medical condition or your treatment, read the Package Leaflet (also part of the EPAR) or contact your doctor or pharmacist.
Jekk inti teħtieġ aktar informazzjoni dwar il- kondizzjoni medika tiegħek jew it- trattament tiegħek, aqra l- Fuljett ta ’ Tagħrif (ukoll parti mill- EPAR) ikkuntattja lit- tabib jew lill- ispiżjar tiegħek.
What is Glubrava?
X’ inhu l- Glubrava?
Glubrava is a medicine that is available as white, oblong tablets containing two active substances, pioglitazone (15 mg) and metformin hydrochloride (850 mg).
Glubrava hija mediċina li hija disponibbli bħala pilloli bojod, tawwalin li fihom iż- żewġ sustanxi, pioglitazone (15 mg) u metformin hydrochloride (850 mg).
This medicine is the same as Competact, which is already authorised in the European Union (EU).
Din il- mediċina hija l- istess bħal Competact, li hija diġà awtorizzata fl- Unjoni Europea (UE).
The company that makes Competact has agreed that its scientific data can be used for Glubrava.
Il - kumpanija li tagħmel Competact qablet li l- informazzjoni xjentifika tagħha tista ’ tintuża għal Glubrava.
What is Glubrava used for?
Għal xiex huwa wżat il- Glubrava?
Glubrava is used in patients (particularly those who are overweight) who have non insulin-dependent diabetes (type 2 diabetes).
Il- Glubrava jintuża f’ pazjenti (b’ mod partikolari dawk li huma ħoxnin ħafna) li għandhom dijabete li ma tiddependix mill- insulina (dijabete tip 2).
Glubrava is used in patients who are not satisfactorily controlled on metformin (an anti-diabetes medicine) used on its own and at the maximum possible dose.
Glubrava jintuża f’ pazjenti li mhumiex ikkontrollati biżżejjed b’ metformin (mediċina anti dijabetika) meta wżat waħdu u bid- doża massima possibbli.
How is Glubrava used?
Kif jiġu wżat il- Glubrava?
The usual dose of Glubrava is one tablet taken twice a day.
Glubrava hija pillola waħda li tiġi meħuda darbtejn kuljum.
Patients changing from metformin only to Glubrava may need to introduce pioglitazone slowly until a dose of 30 mg per day is reached.
Pazjenti li jibdlu minn metformin biss għal Glubrava jistgħu jeħtieġu li jibdew il- pioglitazone bil- mod sakemm tintlaħaq id- doża ta ’ 30 mg kuljum.
It is possible to change to Glubrava directly from metformin if appropriate.
Huwa possibbli li ssir bidla minn Glubrava direttament għal metformin jekk ikun xieraq.
Taking Glubrava with or just after food may reduce any stomach problems caused by metformin.
Meta wieħed jieħu Glubrava ma ’ l- ikel jew eżatt wara jistgħu jitnaqqsu problemi bl- istonku kkawżati minn metformin.
Elderly patients should have their kidney function monitored regularly.
Pazjenti anzjani għandu jkollhom il- funzjoni tal- kliewi mmonitorja b’ mod regolari.
How does Glubrava work?
Kif jaħdem il- Glubrava?
Type 2 diabetes is a disease in which the pancreas does not make enough insulin to control the level of glucose in the blood.
Id- dijabete tat- Tip 2 hija marda li fiha, il- frixa ma tagħmilx biżżejjed insulina sabiex tikkontrolla l - livell ta ’ glukożju fid- demm.
Glubrava contains two active substances, which each have a different mode of action.
Glubrava fih żewġ sustanzi attivi, li jaħdmu b’ mod ta ’ azzjoni differenti kull waħda.
Pioglitazone makes cells (fat, muscle and liver) more sensitive to insulin, which means that the body makes better use of the insulin it produces.
Pioglitazone jagħmel iċ- ċelloli (ix- xaħam, il- muskoli u l- fwied) iktar sensittivi għall - insulina, li jfisser li l- ġisem jagħmel użu aħjar mill- insulina li jipproduċi.
Metformin works mainly by inhibiting glucose production and reducing its absorption in the gut.
Metformin jaħdem l- iktar billi jwaqqaf il- produzzjoni tal- glukożju u jnaqqas l- assorbiment tiegħu fl- intestini.
As a result of the action of both active substances, the blood glucose is reduced and this helps to control type 2 diabetes.
B’ riżultat ta ’ l - azzjoni taż- żewġ sustanzi attivi, jitnaqqas il- glukożju fid- demm u dan jgħin biex tiġi kkontrollata d - dijabete tat- tip 2.
How has Glubrava been studied?
Kif ġie studjat il- Glubrava?
Pioglitazone on its own has been approved by the EU under the name Actos, and can be used with metformin in type 2 diabetes patients who are not satisfactorily controlled on metformin alone.
Pioglitazone waħdu ġie approvat mill- UE taħt l- isem Actos, biex jintuża ma ’ metformin f’ pazjenti b’ dijabete tat- tip 2 li mhumiex ikkontrollati b’ mod soddisfaċenti b’ metformin waħdu.
Three studies of Actos used with metformin as separate tablets were used to support the use of Glubrava in the same indication.
It- tliet studji ta ’
They measured the level in the blood of a substance (HbA1c), which gives an indication of how well the blood glucose is controlled.
L- istudji kejlu l- livell fid- demm ta ’ sustanza (HbA1c).
What benefit has Glubrava shown during the studies?
X’ inhu l- benefiċċju tal- Glubrava matul l- istudji?
In all studies, adding pioglitazone 30 mg to metformin gave an improvement in the control of blood glucose, with levels of HbA1c which were further decreased by 0.64 to 0.89% compared to the levels on metformin alone.
Fl- istudji kollha, jżidu l- pioglitazone 30 mg ma ’ metformin ta titjib fil- kontroll taz- zokkor fid- demm, b’ livelli ta ’ HbA1c li ġew imnaqqsa b’ mod ulterjuri minn 0. 64% għal 0. 89% kumparat mal- livelli fuq metformin biss.
What is the risk associated with Glubrava?
X’ inhu r- riskju assoċjat ma ’ Glubrava?
The most common side effects of Glubrava (seen in between 1 and 10 patients in 100) are anaemia (low red blood cells), visual disturbance, weight increase, arthralgia (joint pain), headache, haematuria (blood in the urine) and erectile dysfunction (problems getting an erection).
L- effetti sekondarji l- aktar komuni ta ’ Glubrava (misjuba f’ bejn pazjent u 10 pazjenti f’ 100) huma anemija (rata ta ’ ċelloli ħomor fid- demm baxxa), disturbi tal- vista, żjieda fil- piż, artralġja (uġiegħ fil - ġogi), uġiegħ ta ’ ras, haematurja (demm fl- awrina) u nuqqas ta ’ ffunzjonar ta ’ l- erezzjoni (problemi sabiex wieħed ikollu erezzjoni).
For the full list of all side effects reported with Glubrava, see the Package Leaflet.
Għal- lista sħiħa ta 'l- effetti sekondarji rrappurtati ma' Glubrava, ara l - Fuljett ta 'Tagħrif.
Glubrava should not be used in people who may be hypersensitive (allergic) to pioglitazone, metformin or any of the other ingredients, and in patients who have heart failure, or problems with their liver or their kidneys.
Glubrava m’ għandhiex tintuża f’ persuni li jistgħu ikunu ipersensittivi (allerġiċi) għal pioglitazone, metformin jew kwalunkwe ingredjenti oħra msemmija, u f’ pazjenti li għandhom insuffiċjenza tal- qalb, jew problemi bil- fwied jew bil- kliewi.
Glubrava should not be used in patients who have a disease that causes lack of oxygen to the tissues such as a recent heart attack or shock.
Glubrava m’ għandux jintuża f’ pazjenti li għandhom marda li tikkawża nuqqas ta ’ ossiġenru fit- tessuti bħal attakk tal- qalb reċenti jew xokk.
Glubrava should not be used where there is alcohol intoxication, diabetic ketoacidosis (high levels of ketones), conditions that may affect the kidneys, and during breast-feeding.
Glubrava m’ għandux jintuża fejn hemm każ ta ’ intossikazzjoni alkoħolika, dijabete ketoacidosis (livell għoli ta ’ ketones), kondizzjonijiet li jistgħu jaffettwaw il- kliewi u matul it- treddiegħ.
Why has Glubrava been approved?
Kif ġie approvat il- Glubrava?
The Committee for Medicinal products for Human Use (CHMP) concluded that the effectiveness of pioglitazone and metformin in type 2 diabetes had been shown, and that Glubrava simplifies treatment and improves compliance when a combination of the active substances is required.
Il- Kumitat għal Prodotti Mediċinali għall- Użu mill- Bniedem (CHMP) ikkonkluda li l- effettività ta ’ pioglitazone u metformin f’ dijabete ta ’ tip 2 ġie muri, u li Kumitat għal Prodotti Mediċinali għall- Użu mill- Bniedem (CHMP) tissimplifika it- trattament u ttejjeb il- konformità meta tkun meħtieġa kumbinazzjoni tas- sustanzi attivi.
They decided that Glubrava’ s benefits are greater than its risks for the treatment of type 2 diabetes.
Huma ddeċidew li l- benefiċċji ta ’ Glubrava huma akbar mir- riskji tiegħu għat- trattament tad- dijabete tip 2.
They recommended that Glubrava be given marketing authorisation.
Huma rrakkommandaw li l- Glubrava jiġi mogħti awtorizazzjoni għat- tqegħid fuq is- suq.
Other information about Glubrava:
Informazzjoni oħra dwar il- Glubrava:
The European Commission granted a marketing authorisation valid throughout the EU for Glubrava to Takeda Global Research and Development Centre (Europe) Ltd on 11 December 2007.
Il- Kummissjoni Ewropea tat awtorizzazzjoni għat- tqegħid fis- suq valida fl- Unjoni Ewropea kollha lil Glubrava lil Takeda Global Research and Development Centre (Europe) Ltd fil- 11 ta ’ Diċembru 2007.
The full EPAR for Glubrava is available here.
L- EPAR sħiħ dwar Glubrava jista ’ jinstab hawnhekk.
This summary was last updated in 03-2008.
Dan is- sommarju ġie aġġornat l- aħħar fl- 03- 2008.
EU Number EU/ 1/ 07/ 421/ 001 EU/ 1/ 07/ 421/ 002 EU/ 1/ 07/ 421/ 003 EU/ 1/ 07/ 421/ 004 EU/ 1/ 07/ 421/ 005 EU/ 1/ 07/ 421/ 006 EU/ 1/ 07/ 421/ 007 EU/ 1/ 07/ 421/ 008 EU/ 1/ 07/ 421/ 009
Numru ta ’ l- EU EU/ 1/ 07/ 421/ 001 EU/ 1/ 07/ 421/ 002 EU/ 1/ 07/ 421/ 003 EU/ 1/ 07/ 421/ 004 EU/ 1/ 07/ 421/ 005 EU/ 1/ 07/ 421/ 006 EU/ 1/ 07/ 421/ 007 EU/ 1/ 07/ 421/ 008 EU/ 1/ 07/ 421/ 009
Invented name Glubrava Glubrava Glubrava Glubrava Glubrava Glubrava Glubrava Glubrava Glubrava
Isem Glubrava Glubrava Glubrava Glubrava Glubrava Glubrava Glubrava Glubrava Glubrava
Strength 15 mg/ 850 mg 15 mg/ 850 mg 15 mg/ 850 mg 15 mg/ 850 mg 15 mg/ 850 mg 15 mg/ 850 mg 15 mg/ 850 mg 15 mg/ 850 mg 15 mg/ 850 mg
Qawwa 15 mg/ 850 mg 15 mg/ 850 mg 15 mg/ 850 mg 15 mg/ 850 mg 15 mg/ 850 mg 15 mg/ 850 mg 15 mg/ 850 mg 15 mg/ 850 mg 15 mg/ 850 mg
Pharmaceutical Form Film-coated Tablet Film-coated Tablet Film-coated Tablet Film-coated Tablet Film-coated Tablet Film-coated Tablet Film-coated Tablet Film-coated Tablet Film-coated Tablet
Pillola miksija b’ rita.
Packaging blister (alu/ alu) blister (alu/ alu) blister (alu/ alu) blister (alu/ alu) blister (alu/ alu) blister (alu/ alu) blister (alu/ alu) blister (alu/ alu) blister (alu/ alu)
Il- pakkett Folja (alu/ alu) Folja (alu/ alu) Folja (alu/ alu) Folja (alu/ alu) Folja (alu/ alu) Folja (alu/ alu) Folja (alu/ alu) Folja (alu/ alu) Folja (alu/ alu)
Package size 14 28 30 50 56 60 90 98 180
Daqs tal- pakkett 14 28 30 50 56 60 90 98 180
Glubrava 15 mg/ 850 mg film-coated tablets.
Glubrava 15 mg/ 850 mg pilloli miksija b’ rita.
Each tablet contains 15 mg of pioglitazone (as hydrochloride) and 850 mg of metformin hydrochloride.
Kull pillola fiha 15 mg ta ’ pioglitazone (bħala hydrochloride) u 850 mg metformin hydrochloride.
Glubrava is indicated in the treatment of type 2 diabetes mellitus patients, particularly overweight patients, who are unable to achieve sufficient glycaemic control at their maximally tolerated dose of oral metformin alone.
Glubrava huwa ndikat fil- kura ta ’ pazjenti b’ dijabete mellitus tat- tip 2 speċjalment pażjenti b’ piż żejjed, li ma laħqux kontroll gliċemiku suffiċjenti fl- ogħla doża ttollerata ta ’ metformin mill- ħalq waħdu.
Dosage in adults The usual dose of Glubrava is 30 mg/ day pioglitazone plus 1700 mg/ day of metformin hydrochloride (this dosage is achievable with one tablet of Glubrava 15 mg/ 850 mg, taken twice a day).
Dożaġġ fl- adulti Id- doża tas- soltu ta ’ Glubrava hija ta ’ pioglitazone 30 mg/ kuljum flimkien ma ’ metformin hydrochloride 1700 mg/ kuljum (dan id- dożaġġ jintlaħaq minn pillola waħda ta ’ Glubrava 15 mg/ 850 mg, darbtejn kuljum).
Dose titration with pioglitazone (added to the optimal dose of metformin) should be considered before the patient is switched to Glubrava.
Titrazzjoni tad- doża b’ pioglitazone (miżjud mad- doża ottimali ta ’ metformin) għandha tiġi kkunsidrata qabel ma l- pazjent jinqaleb fuq Glubrava.
When clinically appropriate, direct change from metformin monotherapy to Glubrava may be considered.
Fejn klinikament xieraq, jista ’ jiġi kkunsidrat tibdil dirett minn monoterapija b’ metformin għal Glubrava.
Taking Glubrava with, or just after food, may reduce gastrointestinal symptoms associated with metformin.
Jekk Glubrava jittieħed ma ’ l- ikel jew eżatt wara l- ikel, is- sintomi gastro- intestinali assoċjati ma ’ metformin jistgħu jitnaqqsu.
Elderly As metformin is excreted via the kidney, and elderly patients have a tendency to decreased renal function, elderly patients taking Glubrava should have their renal function monitored regularly (see sections 4.3 and 4.4).
Anzjani Minħabba li metformin jitneħħa mill- kliewi, u pazjenti anzjani għandhom tendenza ta ’ funzjoni renali mnaqqsa, pazjenti anzjani li qed jieħdu Glubrava għandu jkollhom il- funzjoni renali tagħhom sorveljat b’ mod regolari (ara sezzjonijiet 4. 3 u 4. 4).
Patients with renal impairment Glubrava should not be used in patients with renal failure or renal dysfunction (creatinine clearance < 60 ml/ min)(see sections 4.3 and 4.4).
Pazjenti b’ indeboliment renali Glubrava m’ għandux jintuża f’ pazjenti b’ insuffiċjenza renali jew disfunzjoni renali (tneħħijja ta ’ krejatinina < 60 ml/ min) (ara sezzjonijiet 4. 3 u 4. 4).
Patients with hepatic impairment Glubrava should not be used in patients with hepatic impairment (see sections 4.3 and 4.4).
Pazjenti b’ indeboliment epatiku Glubrava m’ għandux jintuża f’ pazjenti b’ indeboliment epatiku (ara sezzjonijiet 4. 3 u 4. 4).
2 Children and adolescents There are no data available on the use of pioglitazone in patients under 18 years of age and therefore the use of Glubrava in this age group is not recommended.
2 Tfal u adolexxenti M’ hemmx tagħrif disponibbli dwar l- użu ta ’ pioglitazone f’ pazjenti taħt l- età ta ’ 18- il sena, u għalhekk l- użu tiegħu mhux rakkomandat f’ dan il- grupp ta ’ età.
Glubrava is contraindicated in patients with:
Glubrava huwa kontra- indikat f’ pazjenti b ’:
- Renal failure or renal dysfunction (creatinine clearance < 60 ml/ min) (see section 4.4).
- Insuffiċjenza renali jew disfunzjoni renali (tneħħijja ta ’ krejatinina < 60 ml/ min)
- Intravascular administration of iodinated contrast agents (see section 4.4)
- Għoti intravaskulari ta ’ aġenti ta ’ kuntrast ijodinati (ara sezzjoni 4. 4)
Lactic acidosis Lactic acidosis is a very rare, but serious, metabolic complication that can occur due to metformin accumulation.
Aċidożi lattika Aċidożi lattika hija kumplikazzjoni metabolika rari ħafna, iżda serja li tista ’ sseħħ minħabba akkumulazzjoni ta ’ metformin.
Diagnosi Lactic acidosis is characterised by acidotic dyspnoea, abdominal pain and hypothermia followed by coma.
Dijanjosi Aċidożi lattika hija karatterizzata minn qtugħ ta ’ nifs aċidotiku, uġigħ addominali u ipotermija segwita minn koma.
Diagnostic laboratory findings are decreased blood pH, plasma lactate levels above 5mmol/ l, and an increased anion gap and lactate/ pyruvate ratio.
Sejbiet dijanjostiċi tal- laboratorju huma pH tad- demm imnaqqas, livelli fil- plażma ta ’ lactate ogħla minn 5mmol/ l, u żieda fl- enajin gap u fil- proporzjon lactate/ pyruvate.
If metabolic acidosis is suspected, treatment with the medicinal product should be discontinued and the patient hospitalised immediately (see section 4.9).
Jekk ikun hemm suspett ta ’ aċidożi metabolika, kura bil- prodott mediċinali għandha titwaqqaf u l- pazjent jiddaħħal l- isptar immedjatament (ara sezzjoni 4. 9).
Renal Function As metformin is excreted by the kidney, serum creatinine concentrations should be determined regularly:
Funzjoni renali Minħabba li metformin jitneħħa mill- kliewi, il- konċentrazzjonijiet ta ’ krejatinina fis- serum għandhom jiġu determinati regolarment:
- at least two to four times a year in patients with serum creatinine levels at the upper limits of
- ta ’ l- inqas darbtejn sa erba ’ darbiet fis- sena f’ pazjenti b’ livelli ta ’ krejatinina fis- serum fl- ogħla
Decreased renal function in elderly patients is frequent and asymptomatic.
Funzjoni renali mnaqqsa f’ pazjenti anzjani hija frekwenti u bla sintomi.
3 Fluid retention and cardiac failure Pioglitazone can cause fluid retention, which may exacerbate or precipitate heart failure.
3 Żamma ta ’ fluwidu u insuffiċjenza kardijaka Pioglitazone jista ’ jikkawża żamma ta ’ fluwidu, li tista ’ tiggrava jew twassal għall- insuffiċjenza tal - qalb.
When treating patients who have at least one risk factor for development of congestive heart failure (e. g. prior myocardial infarction or symptomatic coronary artery disease), physicians should start with the lowest available dose and increase the dose gradually.
Meta jiġu kkurati pazjenti li għandhom ta ’ l- inqas fattur ta ’ riskju wieħed għall- iżvilupp ta ’ insuffiċjenza tal- qalb konġestiva (e. ż. infart mijokardijaku minn qabel jew marda sintomatika ta ’ l - arterji koronarji), it- tobba għandhom jibdew bl- inqas doża disponibbli ta ’ pioglitazone u jżidu d- doża bil- mod.
There have been cases of cardiac failure reported from the market when pioglitazone was used in combination with insulin or in patients with a history of cardiac failure.
Kien hemm każijiet ta ’ insufficjenza kardijaka rrappurtati mis- suq meta pioglitazone intuża flimkien ma ’ insulina jew f’ pazjenti b’ passat ta ’ insufficjenza kardijaka.
Since insulin and pioglitazone are associated with fluid retention, concomitant administration of insulin and Glubrava may increase the risk of oedema.
Minħabba li insulina u pioglitazone huma assoċjati ma ’ żamma ta ’ fluwidu, l - għoti ta ’ insulina u Glubrava flimkien tista ’ żżid ir- riskju ta ’ edima.
Glubrava should be discontinued if any deterioration in cardiac status occurs.
Glubrava għandu jitwaqqaf jekk iseħħ xi deterjorament fl- istat kardijaku.
Caution should be exercised in patients over 75 years because of the limited experience in this patient group.
Għandha tittieħed attenzjoni f’ pazjenti akbar minn 75 sena minħabba l- esperjenza limitata f’ dan il - grupp ta ’ pazjenti.
Monitoring of Liver Function There have been rare reports of hepatocellular dysfunction during post-marketing experience with pioglitazone (see section 4.8).
Sorveljanza tal- funzjoni tal- fwied Kien hemm rapporti rari ta ’ disfunzjoni epatoċellolari waqt l- esperjenza ta ’ wara li pioglitazone tqiegħed fis- suq (ara sezzjoni 4. 8).
It is recommended, therefore, that patients treated with Glubrava undergo periodic monitoring of liver enzymes.
Għalhekk, huwa rakkomandat li, pazjenti kkurati b’ Glubrava jkollhom l- enżimi tal- fwied immonitorjati perjodikament.
Liver enzymes should be checked prior to the initiation of therapy with Glubrava in all patients.
L- enżimi tal- fwied għandhom jiġu ċċekkjati qabel ma tinbeda terapija b’ Glubrava f’ kull pazjent.
Therapy with Glubrava should not be initiated in patients with increased baseline liver enzyme levels (ALT > 2.5 X upper limit of normal) or with any other evidence of liver disease.
Terapija b’ Glubrava m’ għandiex tinbeda f’ pazjenti b’ livelli ta ’ l- enżimi tal- fwied fil- linja bażika miżjuda (ALT > 2. 5 X l- ogħla limitu tan- normal) jew b’ xi evidenza oħra ta ’ mard tal- fwied.
Following initiation of therapy with Glubrava, it is recommended that liver enzymes be monitored periodically according to clinical judgement.
Wara l- bidu ta ’ terapija b’ Glubrava, huwa rakkomandat li l- enżimi tal- fwied ikunu mmonitorjati perjodikament ibbażat fuq ġudizzju kliniku.
If ALT levels are increased to 3 X upper limit of normal during Glubrava therapy, liver enzyme levels should be reassessed as soon as possible.
Jekk il- livelli ta ’ ALT jiżdiedu sa 3 X l- ogħla limitu tan - normal waqt it- terapija b’ Glubrava, il- livelli ta ’ l- enżimi tal- fwied għandhom jerġgħu jiġu ċċekkjati mill- aktar fis possibli.
If ALT levels remain > 3 X the upper limit of normal, therapy should be discontinued.
Jekk il- livelli ta ’ ALT jibqgħu > 3 X l- ogħla limitu 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 jissuġġerixxu disfunzjoni epatika, li jistgħu jinkludu tqaligħ bla raguni, rimettar, uġigħ addominali, għejja, anoressija u/ jew awrina skura, l- enżimi tal- fwied għandhom jiġu ċċekkjati.
The decision whether to continue the patient on therapy with Glubrava should be guided by clinical judgement pending laboratory evaluations.
Id- deċiżjoni dwar jekk il- pazjent għandux jitkompla bit- terapija b’ Glubrava għandha tiġi ggwidata minn ġudiżżju kliniku sakemm isiru l- valutazzjonijiet tal - laboratorju.
Weight Gain In clinical trials with pioglitazone there was evidence of dose related weight gain, which may be due to fat accumulation and in some cases associated with fluid retention.
Żieda fil- piż Fi provi kliniċi b’ pioglitazone kien hemm evidenza ta ’ żieda fil- piż relatata mad- doża, li tista ’ tkun minħabba akkumulazzjoni ta ’ xaħam u f’ xi każijiet assoċjata ma ’ żamma ta ’ fluwidu.
Haematology There was a small reduction in mean haemoglobin (4% relative reduction) and haematocrit (4.1% relative reduction) during therapy with pioglitazone, consistent with haemodilution.
Ematoloġija Kien hemm tnaqqis żgħir fil- medja ta ’ emoglobina (tnaqqis relattiv ta ’ 4%) u ematokrit (tnaqqis relattiv ta ’ 4. 1%) waqt terapija b’ pioglitazone, konsistenti ma ’ emodiluzzjoni.
Similar changes were seen in metformin (haemoglobin 3 - 4% and haematocrit 3.6 – 4.1% relative reductions) treated patients in comparative controlled trials with pioglitazone.
Tibdiliet simili dehru fi provi kkontrollati komparattivi b’ pioglitazone f’ pazjenti kkurati b’ metformin (tnaqqis relattiv fl - emoglobina ta ’ 3- 4% u fl- ematokrita ta ’ 3. 6- 4. 1%).
Eye disorders Post-marketing reports of new-onset or worsening diabetic macular oedema with decreased visual acuity have been reported with thiazolidinediones, including pioglitazone.
Ħafna minn dawn il -
Many of these patients reported concurrent peripheral oedema.
4 pazjenti rrappurtaw edima periferali fl- istess ħin.
It is unclear whether or not there is a direct association between pioglitazone and macular oedema but prescribers should be alert to the possibility of macular oedema if patients report disturbances in visual acuity; an appropriate ophthalmological referral should be considered.
Mhux ċar jekk hemmx assoċjazzjoni diretta bejn pioglitazone u l- edima makulari iżda t- tobba għandhom joqgħodu attenti għall- possibilità ta ’ edima makulari jekk il- pazjenti jirrappurtaw disturbi fl- akutezza viżwali; għandha tiġi kkunsidrata referenza oftalmoloġika xierqa.
4 Surgery As Glubrava contains metformin hydrochloride, the treatment should be discontinued 48 hours before elective surgery with general anaesthesia and should not be usually resumed earlier than 48 hours afterwards.
Kirurġija Minħabba li Glubrava fih metformin hydrochloride, il- kura għandha titwaqqaf 48 siegħa qabel kirurġija mhux obligatorja b’ anesteżija ġenerali u normalment m’ għandhiex terġa ’ tinbeda qabel 48 siegħa wara.
Administration of iodinated contrast agent The intravascular administration of iodinated contrast agents in radiological studies can lead to renal failure.
L- għoti ta ’ aġent ta ’ kuntrast jodinat L- għoti intravaskulari ta ’ aġenti ta ’ kuntrast jodinati fi studji radjuloġiċi tista ’ twassal għall - insuffiċjenza renali.
Therefore, due to the metformin active substance, Glubrava should be discontinued prior to, or at the time of the test and not reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal (see section 4.5).
Għalhekk, minħabba s- sustanza attiva metformin, Glubrava għandu jitwaqqaf qabel, jew fil- ħin tat- test u m’ għandux jerġa ’ jinbeda qabel 48 siegħa wara u biss wara li l- funzjoni renali tkun ġiet evalwata mill- ġdid u nstabet li hija normali (ara sezzjoni 4. 5).
Polycystic ovarian syndrome As a consequence of enhancing insulin action, pioglitazone treatment in patients with polycystic ovarian syndrome may result in resumption of ovulation.
Sindromu tal- ovarji poliċistiċi Minħabba li ssaħħaħ l- azzjoni ta ’ l- insulina, il- kura b’ pioglitazone f’ pazjenti bis- sindromu tal- ovarji poliċistiċi tista ’ twassal għal bidu mill- ġdid tal- ovulazzjoni.
Others An increased incidence in bone fractures in women was seen in a pooled analysis of adverse event reports of bone fracture from randomised, controlled, double blind clinical trials in over 8100 pioglitazone and 7400 comparator treated patients, on treatment for up to 3.5 years.
Oħrajn Kienet osservata żieda fl- inċidenza ta ’ fratturi fl- għadam fin- nisa f’ analiżi globali ta ’ rapporti ta ’ avvennimenti avversi ta ’ fratturi fl- għadam miksuba minn provi kliniċi randomised, ikkontrollati u double blind b’ aktar minn 8100 pazjent ikkurat b’ pioglitazone u 7400 pazjent ikkurat bi prodott ta ’ paragun, fuq kura sa 3. 5 snin.
In the 3.5 year cardiovascular risk PROactive study, 44/ 870 (5.1%; 1.0 fractures per 100 patient years) of pioglitazone-treated female patients experienced fractures compared to 23/ 905 (2.5%; 0.5 fractures per 100 patient years) of female patients treated with comparator.
Fl- istudju PROactive dwar ir- riskju kardjovaskulari li dam 3. 5 snin, 44/ 870 (5. 1%; 1. 0 fratturi kull 100 sena ta ’ pazjent) tal- pazjenti nisa kkurati b’ pioglitazone kellhom esperjenza ta ’ fratturi meta mqabbel ma ’ 23/ 905 (2. 5%; 0. 5 fratturi kull 100 sena ta ’ pazjent) tal- pazjenti nisa kkurati bi prodott ta ’ paragun.
No increase in fracture rates was observed in men treated with pioglitazone (1.7%) versus comparator (2.1%).
Ma kinietx osservata żieda fir- rata ta ’ fratturi f’ irġiel ikkurati b’ pioglitazone (1. 7%) meta mqabbla ma ’ prodott ta ’ paragun (2. 1%).
Pioglitazone should be used with caution during concomitant administration of cytochrome P450 2C8 inhibitors (e. g. gemfibrozil) or inducers (e. g. rifampicin).
Pioglitazone għandu jintuża b’ attenzjoni waqt l- għoti fl- istess ħin ta ’ inibituri (e. ż. gemfibrozil) jew indutturi (e. ż. rifampicin) taċ- ċitokromju P450 2C8.
Pioglitazone dose adjustment within the recommended posology or changes in diabetic treatment should be considered (see section 4.5).
Għandhom jiġu kkunsidrati aġġustament fid- doża ta ’ pioglitazone fil- firxa ta ’ pożoloġija rakkomandata jew bidliet fil- kura dijabetika (ara sezzjoni 4. 5).
There have been no formal interaction studies for Glubrava.
Ma sarux studji formali dwar l- interazzjonijiet ma ’ Glubrava.
The following statements reflect the information available on the individual active substances (pioglitazone and metformin).
Id- dikjarazzjonijiet li ġejjin jirriflettu l - informazzjoni disponibbli dwar is- sustanzi attivi individwali (pioglitazone u metformin).
Interaction studies have shown that pioglitazone has no relevant effect on either the pharmacokinetics or pharmacodynamics of digoxin, warfarin, phenprocoumon and metformin.
5 Studji dwar l- interazzjoni mal- prodott urew li pioglitazone m’ għandu l- ebda effett rilevanti la fuq il - farmakokinetika u l- anqas fuq il- farmakodinamika ta ’ digoxin, warfarin, phenprocoumon u metformin.
In vitro studies have shown no inhibition of any subtype of cytochrome P450.
Studji in vitro wrew li m’ hemm l- ebda induzzjoni ta ’ l- ebda sottotip ta ’ ċitokromju P450.
5 Co-administration of pioglitazone with gemfibrozil (an inhibitor of cytochrome P450 2C8) is reported to result in a 3-fold increase in AUC of pioglitazone.
Huwa rrappurtat li l- għoti ta ’ pioglitazone flimkien ma ’ gemfibrozil (inibitur taċ- ċitokromju P450 2C8) twassal għall- żieda ta ’ 3 darbiet fl- AUC ta ’ pioglitazone.
Co-administration of pioglitazone with rifampicin (an inducer of cytochrome P450 2C8) is reported to result in a 54% decrease in AUC of pioglitazone.
Huwa rrappurtat li l- għoti ta ’ pioglitazone flimkien ma ’ rifampicin (induttur taċ- ċitokromju P450 2C8) twassal għal tnaqqis ta ’ 54% fl- AUC ta ’ pioglitazone.
There is increased risk of lactic acidosis in acute alcohol intoxication (particularly in the case of fasting, malnutrition or hepatic insufficiency) due to the metformin active substance of Glubrava (see section 4.4).
Minħabba s- sustanza attiva metformin f’ Glubrava, hemm riskju akbar ta ’ aċidożi lattika f’ intossikazzjoni akuta bl- alkoħol (speċjament f’ każ ta ’ sawm, malnutrizzjoni jew insuffiċjenza epatika) (ara sezzjoni 4. 4).
Intravascular administration of iodinated contrast agents in radiological studies may lead to renal failure, resulting in metformin accumulation and risk of lactic acidosis.
L- għoti intravaskulari ta ’ aġenti ta ’ kuntrast jodinati fi studji radjuloġiċi tista ’ twassal għall - insuffiċjenza renali, li tirriżulta f’ akkumulazzjoni ta ’ metformin u riskju ta ’ aċidożi lattika.
Cationic drugs that are eliminated by renal tubular secretion (e. g. cimetidine) may interact with metformin by competing for common renal tubular transport systems.
Mediċini katijoniċi li huma eliminati permezz ta ’ sekrezzjoni tubolari renali (e. ż. cimetidine) jistgħu jinteraġixxu ma ’ metformin billi jikkompetu għal sistemi komuni ta ’ trasport tubolari renali.
Therefore, close monitoring of glycaemic control, dose adjustment within the recommended posology and changes in diabetic treatment should be considered when cationic drugs that are eliminated by renal tubular secretion are co-administered.
Għalhekk, sorveljanza mill- qrib tal- kontroll gliċemiku, aġġustament tad- doża fil- firxa ta ’ pożoloġija rakkomandata u bidliet fil- kura dijabetika għandhom jiġu kkunsidrati meta mediċini katijoniċi li jiġu eliminati permezz ta ’ sekrezzjoni tubolari renali jingħataw fl- istess ħin.
The patient should be informed and more frequent blood glucose monitoring performed, especially at the beginning of treatment.
Il- pazjent għandu jiġi nfurmat u għandha ssir sorveljanza aktar ta ’ spiss tal- glukożju fid- demm, speċjalment fil- bidu tal- kura.
ACE-inhibitors may decrease the blood glucose levels.
Inibituri- ACE jistgħu jnaqqsu l- livelli ta ’ glucose fid- demm.
For Glubrava no preclinical or clinical data on exposed pregnancies or lactation are available.
Għal Glubrava m’ hemmx tagħrif preklinku jew kliniku dwar l- użu waqt it- tqala jew treddigħ.
Risk related to pioglitazone There are no adequate human data from the use of pioglitazone in pregnant women.
Riskju relatat ma ’ pioglitazone M ’ hemmx tagħrif biżżejjed dwar l- użu ta ’ pioglitazone waqt it- tqala.
Risk related to metformin Animal studies have not revealed teratogenic effects.
Riskju relatat ma ’ metformin Studji fuq bhejjem ma wrewx effetti teratoġeniċi.
However, Glubrava should not be used during pregnancy and in women of child-bearing age not using contraceptive measures.
6 Madankollu, Glubrava m’ għandux jintuża waqt it- tqala u f’ nisa li jistgħu joħorgu tqal li mhux qed jużaw miżuri kontracettivi.
If a patient wishes to become pregnant or if a pregnancy occurs, treatment with Glubrava should be discontinued.
Jekk pazjenta tixtieq toħroġ tqila jew jekk tinqabad tqila, kura b ’ Glubrava għandha titwaqqaf.
Both pioglitazone and metformin have been shown to be present in the milk of lactating rats.
Intwera li kemm pioglitazone kif ukoll metformin huma preżenti fil- ħalib ta ’ firien li qed ireddgħu.
Glubrava must therefore not be used in women who are breast-feeding (see section 4.3).
Għalhekk Glubrava m’ għandux jingħata lill- nisa li qed ireddgħu (ara sezzjoni 4. 3).
6 4.7 Effects on ability to drive and use machines
4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
There have been no therapeutic clinical trials conducted with Glubrava tablets however bioequivalence of Glubrava with co-administered pioglitazone and metformin has been demonstrated (see section 5.2).
Ma saru l- ebda provi kliniċi terapewtiċi b’ pilloli Glubrava, iżda ġiet dimostrata l- bijoekwivalenza ta ’ Glubrava ma ’ pioglitazone u metformin mogħtija flimkien (ara sezzjoni 5. 2).
Frequencies are defined as: common (> 1/ 100 ,< 1/10); uncommon (> 1/1000 ,< 1/100); rare (> 1/ 10000 ,< 1/1000); very rare (< 1/10000); isolated reports; not known (cannot be estimated from the available data).
Il- frekwenzi huma definiti bħala: komuni (> 1/ 100), < 1/ 10; mhux komuni (> 1/ 1000), (< 1/ 100); rari (> 1/ 10000, < 1/ 1000); rari ħafna (< 1/ 10000); rapporti iżolati; mhux magħruf (ma tistax tittieħed stima mid- data disponibbli).
Gastrointestinal disorders Uncommon:
Disturbi gastro- intestinali Mhux komuni: gass
Metabolism and nutrition disorders Common:
Disturbi fil- metaboliżmu u n- nutrizzjoni Komuni:
Musculoskeletal system and connective tissue disorders Common:
Disturbi muskolu- skeletrali u tat- tessut konnettiv Komuni:
Renal and urinary Common:
Disturbi fil- kliewi u fis- sistema urinarja Komuni:
disorders haematuria
ematurja
Reproductive system and breast disorders Common:
Disturbi fis- sistema riproduttiva u fis- sider Komuni:
In active comparator controlled trials mean weight increase with pioglitazone given as monotherapy was 2 – 3 kg over one year.
7 Fi provi attivi kkontrollati ta ’ paragun, iż- żieda medja fil- piż bi pioglitazone mogħti bħala monoterapija kienet ta ’ 2- 3 kg fuq medda ta ’ sena.
Visual disturbance has been reported mainly early in treatment and is related to changes in blood glucose due to temporary alteration in the turgidity and refractive index of the lens as seen with other hypoglycaemic agents.
Disturbi viżwali ġew irrappurtati l- aktar fil- bidu tal- kura u huma relatati ma ’ bidliet fiż- żokkor fid - demm minħabba alterazzjoni temporanja fit- turġidità u fl- indiċi refrattiv tal- lenti kif osservat b’ aġenti ipogliċemiċi oħra.
7 In clinical trials with pioglitazone the incidence of elevations of ALT greater than three times the upper limit of normal was equal to placebo but less than that seen in metformin or sulphonylurea comparator groups.
Fi provi kliniċi b’ pioglitazone l- inċidenża ta ’ elevazzjonijiet ta ’ ALT aktar minn tlett darbiet l- ogħla limitu tan- normal kienet daqs il- plaċebo iżda inqas minn dik li dehret fil- gruppi ta ’ paragun b’ metformin jew b’ sulphonylurea.
In controlled clinical trials the incidence of reports of heart failure with pioglitazone treatment was the same as in placebo, metformin and sulphonylurea treatment groups, but was increased when used in combination therapy with insulin.
Fi provi kliniċi kkontrollati, l- inċidenza ta ’ rapporti ta ’ insuffiċjenza tal- qalb b’ kura b’ pioglitazone kienet l- istess bħall- gruppi ta ’ kura bil- plaċebo, metformin u sulphonylurea, iżda kienet miżjuda meta wżata f’ terapija kombinata ma ’ insulina.
Heart failure has been reported rarely with marketing use of pioglitazone, but more frequently when pioglitazone was used in combination with insulin or in patients with a history of cardiac failure.
Insuffiċjenza tal- qalb kienet irrappurtata b’ mod rari bl- użu ta ’ pioglitazone wara t- tqegħid fis- suq, iżda b’ mod aktar frekwenti meta pioglitazone intuża flimkien ma ’ insulina jew f’ pazjenti b’ passat ta ’ insuffiċjenza kardijaka.
Eye disorders Macular oedema:
Disturbi fl- għajnejn Edima makulari:
not known
mhux magħruf
Metabolism and nutrition disorders Very rare:
Disturbi fil- metaboliżmu u n- nutrizzjoni Rari ħafna:
Consideration of such aetiology is recommended if a patient presents with megaloplastic anaemia.
Jekk pazjent ikollu anemija megaloplastika, huwa rakkomandat li din l- etjoloġija tiġi kkunsidrata.
Gastrointestinal disorders Very common:
Distrubi gastro- intestinali Komuni ħafna:
Gastrointestinal disorders such as nausea, vomiting, diarrhoea, abdominal pain and loss of appetite.
Disturbi gastro- intestinali bħal tqalligħ, remettar, dijarea, uġigħ addominali u nuqqas ta ’ aptit.
These undesirable effects occur most frequently during initiation of therapy and resolve spontaneously in most cases.
Dawn l- effetti mhux mixtieqa isseħħu l- aktar waqt il- bidu tat - terapija u f’ ħafna każijiet ifiequ spontanjament.
Hepatobiliary disorders Isolated reports:
Disturbi fil- fwied u fil- marrara Rapporti iżolati:
Liver function tests abnormalities or hepatitis resolving upon metformin discontinuation.
Anormalitajiet fit- testijiet tal- funzjoni tal- fwied jew epatite li tfieq mal - waqfien ta ’ metformin.
Skin and subcutaneous tissue disorders Very rare:
Disturbi fil- ġilda u fit- tessut ta ’ taħt il- ġilda Rari ħafna:
A higher rate of
Twettqet analiżi ta ’ tagħrif miġbur ta ’ rapporti ta ’ avvennimenti avversi ta ’ fratturi fl- għadam minn provi kliniċi randomised, ikkontrollati b’ paragun, u double blind b’ aktar minn 8100 pazjent fil- gruppi kkurati b’ pioglitazone u 7400 pazjent fil- gruppi kkurrati bi prodott ta ’ paragun li damu sa 3. 5 snin.
8 fractures was observed in women taking pioglitazone (2.6%) versus comparator (1.7%).
Kienet osservata rata akbar ta ’ fratturi fl- għadam f’ nisa li kienu qed jieħdu pioglitazone (2. 6%) meta mqabbla mal- paragun (1. 7%).
No data are available with regard to overdose of Glubrava.
L- ebda każ ta ’ doża eċċessiva ma ġie rrappurtat b’ Glubrava.
Patients have taken pioglitazone at higher than the recommended highest dose of 45 mg daily.
Pazjenti ħadu pioglitazone f’ doża aktar mill- ogħla doża rakkomandata ta ’ 45 mg kuljum.
Glubrava combines two antihyperglycaemic agents with complementary mechanisms of action to improve glycaemic control in patients with type 2 diabetes: pioglitazone, a member of the thiazolidinedione class and metformin hydrochloride, a member of the biguanide class.
Glubrava jikkombina żewġ aġenti anti- ipergliċemiċi b’ mekkaniżmi t’ azzjoni li jikkumplimentaw lil xulxin biex itejbu l- kontroll gliċemiku f’ pazjenti b’ dijabete tat- tip 2: pioglitazone, membru tal- klassi thiazolidinedione u metformin hydrochloride, membru tal- klassi biguanide.
Thiazolidinediones act primarily by reducing insulin resistance and biguanides act primarily by decreasing endogenous hepatic glucose production.
Thiazolidinediones jaħdmu primarjament billi jnaqqsu r- reżistenza għall- insulina u biguanides jaħdmu primarjament billi jnaqqsu l- produzzjoni endoġena epatika ta ’ glucose.
Pioglitazone appears to act via activation of specific nuclear receptors (peroxisome proliferator activated receptor gamma) leading to increased insulin sensitivity of liver, fat and skeletal muscle cells in animals.
Pioglitazone jidher li jaħdem permezz ta ’ attivazzjoni ta ’ riċetturi nuklejari speċifiċi (prolifirator ta ’ peroxisome ta ’ riċettur gamma attivat) li jwassal għal żieda fis- sensittività għall- insulina f’ ċelloli tal- fwied, xaħam u tal- muskoli skeletrali fl- annimali.
The improved glycaemic control is associated with a reduction in both fasting and postprandial plasma insulin concentrations.
Il- kontroll gliċemiku mtejjeb huwa assoċjat ma ’ tnaqqis fil- konċentrazzjonijiet tal- insulina fil- plażma kemm waqt is- sawm kif ukoll wara l- ikel.
A clinical trial of pioglitazone vs. gliclazide as monotherapy was extended to two years in order to assess time to treatment failure (defined as appearance of HbA1c ≥ 8.0% after the first six months of therapy).
Analiżi Kaplan- Meier wriet ħin iqsar
Kaplan-Meier analysis showed shorter time to treatment failure in patients treated with gliclazide, compared with pioglitazone.
9 għall- falliment tal- kura f’ pazjenti kkurati b’ gliclazide, meta mqabbel ma ’ pioglitazone.
In a two-year study of combination therapy comparing pioglitazone with gliclazide when added to metformin, glycaemic control measured as mean change from baseline in HbA1c was similar between treatment groups after one year.
Fi studju ta ’ sentejn b’ terapija kombinata li qabbel pioglitazone ma ’ gliclazide meta miżjuda ma ’ metformin, il- kontroll gliċemiku mkejjel bħala it- tibdil medju mill- linja bażi ta ’ HbA1c kien simili bejn il- gruppi ta ’ kura wara l- ewwel sena.
Patients receiving
Fi prova kkontrollata bil- plaċebo, pazjenti b’ kontroll gliċemiku inadegwat minkejja perjodu ta ’ tliet xhur ta ’ ottimazzjoni bl- insulina kienu randomised għal pioglitazone jew plaċebo għal 12- il xahar.
9 pioglitazone had a mean reduction in HbA1c of 0.45% compared with those continuing on insulin alone, and a reduction of insulin dose in the pioglitazone treated group.
Pazjenti li kienu qed jirċievu pioglitazone kellhom tnaqqis medju f’ HbA1c ta ’ 0. 45% meta mqabbel ma dawk li komplew b’ insulina waħedha, u tnaqqis fid- doża ta ’ l- insulina fil- grupp ikkurat b’ pioglitazone.
In one year clinical trials, pioglitazone consistently gave a statistically significant reduction in the albumin/ creatinine ratio compared to baseline.
Fi provi kliniċi ta ’ sena, pioglitazone b’ mod konsistenti wassal għal tnaqqis statistikament sinifikanti fil- proporzjon ta ’ albumin/ krejatinina meta mqabbel mal- linja bażi.
In most clinical trials, reduced total plasma triglycerides and free fatty acids, and increased HDL-cholesterol levels were observed as compared to placebo, with small, but not clinically significant increases in LDL-cholesterol levels.
Fil- biċċa l- kbira tal- provi kliniċi, kienu osservati tnaqqis fit- triġliċeridi totali fil- plażma u fil- fatty acids ħielsa, u żieda fil- livelli ta ’ HDL- kolesterol meta mqabbel mal- plaċebo, b’ żiediet żgħar, iżda mhux ta ’ rilevanza klinika fil- livelli ta ’ LDL- kolesterol.
Pioglitazone did not cause statistically significant increases in LDL-cholesterol levels compared with placebo, whilst reductions where observed with metformin and gliclazide.
Pioglitazone ma wassalx għall - żieda statistikament sinifikanti fil- livell ta ’ LDL- kolesterol meta mqabbel mal- plaċebo, filwaqt li tnaqqis kien osservat b’ metformin u gliclazide.
In a 20-week study, as well as reducing fasting triglycerides, pioglitazone reduced postprandial hypertriglyceridaemia through an effect on both absorbed and hepatically synthesised triglycerides.
Fi studju ta ’ 20 ġimgħa, minbarra li naqqas it - triġliċeridi waqt is- sawm, pioglitazone naqqas l- ipertrigliċeridemija wara l- ikel permezz ta ’ effett kemm fuq it- trigliċeridi assorbiti kif ukoll fuq dawk prodotti mill- fwied.
To be eligible patients had to have had one or more of the following: myocardial infarction, stroke, percutaneous cardiac intervention or coronary artery bypass graft, acute coronary syndrome, coronary artery disease, or peripheral arterial obstructive disease.
Biex ikunu eliġibbli, il- pazjenti kellhom ikollhom wieħed jew aktar minn dawn li ġejjin: infart mijokardijaku, puplesijja, intervent kardijaku perkutanju jew bypass graft tal- arterja koronarja, sindrome koronarju akut, marda ta ’ l- arterji koronarji, jew marda ostruttiva ta ’ l- arterji periferali.
Although the study failed regarding its primary endpoint, which was a composite of all-cause mortality, non-fatal myocardial infarction, stroke, acute coronary syndrome, major leg amputation, coronary revascularisation and leg revascularisation, the results suggest that there are no long-term cardiovascular concerns regarding use of pioglitazone.
Għalkemm l- istudju falla rigward il- mira primarja tiegħu, li kienet komposta minn mortalità mill - kawżi kollha, infart mijokardijaku mhux fatali, puplesija, sindrome koronarju akut, amputazzjoni maġġuri tas- sieq, vaskularizazzjoni koronarja mill- ġdid u vaskularizazzjoni tas- sieq mill- ġdid, ir - riżultati jissuġġerixxu li ma hemm l- ebda riskji kardjovakulari fit- tul bl- użu ta ’ pioglitazone.
However, the incidence of oedema, weight gain and heart failure were increased.
Iżda, l - inċidenza ta ’ edima, żieda fil- piż u insuffiċjenza tal- qalb kienu miżjuda.
It does not stimulate insulin secretion and therefore does not produce hypoglycaemia.
Huwa ma jistimolax is- sekrezzjoni ta ’ l- insulina u għalhekk ma jipproduċix ipogliċemija.
Metformin may act via three mechanisms:
Metformin jista ’ jaħdem permezz ta ’ tliet mekkaniżmi:
- by delaying intestinal glucose absorption.
- billi jittardja l- assorbiment intestinali ta ’ glucose.
10 Metformin stimulates intracellular glycogen synthesis by acting on glycogen synthase.
Metformin jistimola s- sintesi intraċellolari ta ’ glycogen billi jaħdem fuq glycogen synthase.
group (29.8 events/ 1,000 patient-years) versus diet alone (43.3 events/ 1,000 patient-years), p=0.0023, and versus the combined sulphonylurea and insulin monotherapy groups (40.1 events/ 1,000 patient-years), p=0.0034
b’ metformin (29. 8 avveniment/ 1, 000 pazjent- snin) kontra l- grupp b’ dieta biss (43. 3 avveniment/ 1, 000 pazjent- snin), p=0. 0023, u kontra l- gruppi ta ’ monoterapija b’ sulphonylurea u b’ insulina kombinati (40. 1 avveniment/ 1, 000 pazjent- snin), p=0. 0034
- a significant reduction of the absolute risk of any diabetes-related mortality: metformin 7.5
- tnaqqis sinifikanti fir- riskju assolut ta ’ kull mortalità relatata ma ’ dijabete: metformin
events/ 1,000 patient-years, diet alone 12.7 events/ 1,000 patient-years, p=0.017
7. 5 episodji/ 1, 000 pazjent- snin, dieta biss 12. 7 avvenimenti/ 1, 000 pazjent- snin, p=0. 017
Bioequivalence studies in healthy volunteers have shown Glubrava to be bioequivalent to the administration of pioglitazone and metformin given as separate tablets.
Studji ta ’ bijoekwivalenza f’ voluntiera b’ saħħithom urew li Glubrava huwa bijoekwivalenti għall - għoti ta ’ pioglitazone u metformin mogħtija bħala pilloli separati.
Food had no effect on the AUC and Cmax of pioglitazone when Glubrava was administered to healthy volunteers.
L- ikel ma kellu l- ebda effett fuq l- AUC u Cmax ta ’ pioglitazone meta Glubrava ngħata lil voluntiera b’ saħħithom.
The following statements reflect the pharmacokinetic properties of the individual active substances of Glubrava.
Id- dikjarazzjonijiet li ġejjin jirriflettu l- proprjetajiet farmakokinetiċi tas- sustanzi attivi individwali f’ Glubrava.
Pioglitazone
11 Pioglitazone
Absorption Following oral administration, pioglitazone is rapidly absorbed, and peak plasma concentrations of unchanged pioglitazone are usually achieved 2 hours after administration.
Assorbiment Wara għoti mill- ħalq, pioglitazone jiġi assorbit malajr, u l- ogħla konċentrazzjonijiet fil- plażma ta ’ pioglitazone mhux mibdul normalment jintlaħqu sagħtejn wara l- għoti.
Proportional increases of the plasma concentration were observed for doses from 2 – 60 mg.
Żieda proporzjonali fil - konċentrazzjoni fil- plażma kienet osservata f’ dozi minn 2- 60 mg.
Distribution The estimated volume of distribution in humans is 0.25 l/ kg.
Distribuzzjoni Il- volum stmat ta ’ distribuzzjoni fil- bnedmin huwa ta ’ 0. 25 l/ kg.