qanastek/EMEA-V3 huggingface dataset:
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- edema makulari, iżda it- tobba għandhom joqgħodu attenti għall- possibilità ta ’ edema makulari jekk il- pazjenti jirrappurtaw disturbi fl- akutezza viżiva; għandha tiġi kkunsidrata referenza oftalmoloġika xieraq.
The fracture incidence calculated was 1.9 fractures per 100 patient years in women treated with pioglitazone and 1.1 fractures per 100 patient years in women treated with a comparator.
4 L- inċidenza ta ’ fratturi kkalkulata kienet ta ’ 1. 9 fratturi kull 100 sena ta ’ pazjent f’ nisa kkurati b’ pioglitazone u 1. 1 fratturi kull 100 sena ta ’ pazjent f’ nisa kkurati bi prodott ta ’ paragun.
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
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 paragun.
As a consequence of enhancing insulin action, pioglitazone treatment in patients with polycystic ovarian syndrome may result in resumption of ovulation.
Bħala konsegwenza ta ’ azzjoni msaħħa ta ’ l- insluina, kura b’ pioglitazone f’ pazjenti bis- sindromu ta ’ ovarji poliċistiċi tista ’ twassal għall- bidu mill- ġdid tal- ovulazzjoni.
Patients should be aware of the risk of pregnancy and if a patient wishes to become pregnant or if pregnancy occurs, the treatment should be discontinued (see section 4.6).
Il- pazjenti għandhom ikunu konxji tar- riskju ta ’ tqala u jekk il- pazjenta tixtieq toħroġ tqila jew jekk it- tqala sseħħ, il- kura għandha titwaqqaf (ara sezzjoni 4. 6).
The tablets contain lactose monohydrate and therefore should not be administered to patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
Il- pilloli fihom lattosju monohydrate u għalhekk m’ għandhomx jingħataw lill- pazjenti bi problemi ereditarji rari ta ’ intolleranza għall- galaktosju, defiċjenza Lapp lactase jew assorbiment ħażin ta ’ glukosju- galaktosju.
There have been no formal interaction studies for Tandemact, however, the concomitant use of the active substances in patients in clinical use has not resulted in any unexpected interactions.
Għal Tandemact, ma sarux studji formali dwar l- effett ta ’ mediċini jew ta ’ affarijiet oħra fuq l- effett farmaċewtiku tal- prodott, iżda l- użu fl- istess ħin ta ’ sustanzi attivi f’ pazjenti waqt l- użu kliniku ma wasslux għall- effetti mhux mistennija.
The following statements reflect the information available on the individual active substances (pioglitazone and glimepiride).
Id- dikjarazzjonijiet li ġejjin jirriflettu l- informazzjoni disponibbli dwar is- sustanzi attivi individwali (pioglitazone u glimepiride).
Co-administration of pioglitazone with sulphonylureas does not appear to affect the pharmacokinetics of the sulphonylurea.
L- għotja ta ’ pioglitazone flimkien ma ’ sulphonylureas ma tidhirx li taffettwa il- farmakokinetika ta ’ sulphonylurea.
Studies in man suggest no induction of the main inducible cytochrome P450, 1A, 2C8/ 9 and 3A4.
Studji fil - bniedem jissuġġerixxu li m’ hemm l- ebda induzzjoni taċ- ċitokromju prinċipali induċibbli P450, 1A, 2C8/ 9 u 3A4.
Since there is a potential for an increase in dose- related adverse events, a decrease in the dose of pioglitazone may be needed when gemfibrozil is concomitantly administered.
Minħabba li hemm potenzjal ta ’ żieda fl- effetti avversi relatati mad- doża, jista ’ jkun hemm bżonn ta ’ tnaqqis fid- doża ta ’ pioglitazone meta gemfibrozil jingħata fl- sitess ħin.
Co-administration of pioglitazone with rifampicin (an inducer of cytochrome P450 2C8) is reported to result in a 54% decrease in AUC of pioglitazone.
Ħuwa rrappurtat li l- għotja ta ’ pioglitazone flimkien ma ’ rifampicin (induttur taċ- ċitokromju P450 2C8) twassal għal tnaqqis ta ’ 54% fl- AUC ta ’ pioglitazone.
If glimepiride is taken simultaneously with certain other medicinal products, both undesired increases and decreases in the hypoglycaemic action of glimepiride can occur.
Jekk glimepiride jittieħed fl- istess ħin ma ’ ċertu prodotti mediċinali oħra, jista ’ jkun hemm kemm żiediet kif ukoll tnaqqis mhux mixtieqa fl- azzjoni ipogliċemika ta ’ glimepiride.
For this reason, other medicinal products should only be taken with Tandemact with the knowledge (or at the prescription) of the doctor.
Minħabba f’ hekk, prodotti mediċinali oħra għandhom jittieħdu ma ’ Tandemact biss b’ kunsens (jew b’ riċetta) tat- tabib.
Based on the experience with glimepiride and with other sulphonylurea the following interactions have to be mentioned.
Ibbażat fuq l- esperjenza b’ glimepiride u b’ sulphonylurea oħra l- interazzjonijiet li ġejjin għandhom jissemmew.
Potentiation of the blood-glucose-lowering effect and, thus, in some instances hypoglycaemia may occur when one of the following active substances is taken, for example:
Żieda fl- effett li jbaxxi l- glukosju fid- demm u għalhekk, xi kultant, tista ’ sseħħ ipogliċemija meta jittieħed wieħed minn dawn is- sustanżi attivi li ġejjin, per eżempju:
5 phenylbutazone, azapropazon and oxyfenbutazone insulin and oral antidiabetic products metformin salicylates and p-amino-salicylic acid anabolic steroids and male sex hormones chloramphenicol coumarin anticoagulants fenfluramine fibrates ACE inhibitors fluoxetine allopurinol sympatholytics cyclo-, tro-and iphosphamides sulphinpyrazone certain long-acting sulphonamides tetracyclines MAO-inhibitors quinolone antibiotics probenecid miconazol pentoxyfylline (high dose parenteral) tritoqualine fluconazole
phenylbutazone, azapropazon u oxyfenbutazone insulina u prodotti anti- dijabetiċi orali metformin salicylates u p- amino- salicylic acid sterojdi anaboliċi u ormoni sesswali ta ’ l- irġiel chloramphenicol coumarin anticoagulants fenfluramine fibrates inibituri ACE fluoxetine allopurinol sympatholytics cyclo -, tro - u iphosphamides sulphinpyrazone ċertu sulphonamides li jaħdmu fit- tul tetracyclines inibituri MAO anti- bijotiċi quinolone probenecid miconazol pentoxyfylline (doża għolja mogħtija b’ mod parenterali) tritoqualine fluconazole
Weakening of the blood-glucose-lowering effect and, thus raised blood glucose levels may occur when one of the following active substances is taken, for example:
Tnaqqis fl- effett li jbaxxi l- glukosju fid- demm u għalhekk jista ’ jkun hemm żieda fil- livelli ta ’ glukosju fid- demm meta jittieħed wieħed minn dawn is- sustanzi attivi li ġejjin, per eżempju:
oestrogens and progestagens, saluretics, thiazide diuretics, thyroid stimulating agents, glucocorticoids, phenothiazine derivatives, chlorpromazine, adrenaline and sympathicomimetics, nicotinic acid (high dosages) and nicotinic acid derivatives, laxatives (long-term use), phenytoin, diazoxide, glucagon, barbiturates and rifampicin. acetozolamide
oestrogens u progestagens, saluretics, dijuretiċi thiazide, aġenti li jistimolaw it- tirojde, glukokortikojdi, derivati minn phenothiazine, chlorpromazine, adrenalina u sympathicomimetics, nicotinic acid (dożi għolja) u derivanti minn nicotinic acid, porog (użu fit- tul), phenytoin, diazoxide, glucagon, barbiturates u rifampicin. acetozolamide
H2 antagonists, betablockers, clonidine and reserpine may lead to either potentiation or weakening of the blood glucose lowering effect.
Antagonisti H2, imblukkaturi beta, clonidine u reserpine jistgħu jwasslu għal żieda jew għal tnaqqis fl - effett li jbaxxi l- glukosju fid- demm.
Under the influence of sympatholytic active substances such as betablockers, clonidine, guanethidine and reserpine, the signs of adrenergic counterregulation to hypoglycaemia may be reduced or absent.
6 Taħt l- influwenza ta ’ sustanzi attivi simpatolitiċi bħal imblukkaturi beta, clonidine, guanethidine u reserpine, is- sinjali ta ’ kontra- regolazzjoni adrinerġika għall- ipogliċemija jistgħu jkunu mnaqqsa jew assenti.
Alcohol intake may potentiate or weaken the hypoglycaemic action of glimepiride in an unpredictable fashion.
It- teħid ta ’ alkoħol jista ’ jsaħħaħ jew idgħajjef l- azzjoni ipogliċemika ta ’ glimepiride f’ mod mhux predikabbli.
Glimepiride may either potentiate or weaken the effects of coumarin derivatives.
Glimepiride jista ’ jsaħħaħ jew idgħajjef l- effetti ta ’ derivati ta ’ coumarin.
There are no adequate data from the use of pioglitazone and glimepiride in pregnant women.
M’ hemmx tgħarif biżżejjed dwar l- użu ta ’ pioglitazone u glimepiride waqt it- tqala.
Studies of pioglitazone in animals have shown reproductive toxicity (see section 5.3).
Studji fuq bhejjem urew ħsara fuq is- sistema riproduttiva (ara sezzjoni 5. 3).
Tandemact should not be used during pregnancy.
Tandemact m’ għandux jintuża waqt it- tqala.
6 Sulphonylurea-derivatives like glimepiride pass into the breast milk.
Derivati ta ’ sulphonylurea bħal glimepiride jgħaddu fil- ħalib tas- sider.
Pioglitazone has been shown to be present in the milk of lactating rats.
Pioglitazone intwera li huwa preżenti fil- ħalib ta ’ firien li qed ireddgħu.
It is not known whether pioglitazone is secreted in human milk.
Mhux magħruf jekk pioglitazone jitneħħix fil- ħalib uman.
Therefore, Tandemact must not be administered to breast-feeding women.
Għalhekk, Tandemact m’ għandux jingħata lill- nisa li qed ireddgħu.
The patient’ s ability to concentrate and react may be impaired as a result of hypoglycaemia or hyperglycaemia from glimepiride or, for example, as a result of visual impairment.
Il- ħila tal- pazjent biex jikkonċentra u jirreaġixxi tista ’ tkun imnaqqsa minħabba l- ipogliċemija jew ipergliċemija minn glimepiride jew, per eżmpju, bħala riżultat ta ’ indeboliment tal- vista.
This may constitute a risk in situations where these abilities are of special importance (e. g. driving a car or operating machines).
Din tista ’ tkun riskju f’ sitwazzjonijiet fejn dawn il- ħiliet huma ta ’ importanza speċjali (e. ż. sewqan ta ’ karozza jew tħaddim ta ’ magni).
Patients should be advised to take precautions to avoid hypoglycaemia whilst driving.
Il- pazjenti għandhom jiġu avżati biex jieħdu prekawzjonijiet sabiex jevitaw l- ipogliċemija waqt is - sewqan.
This is particularly important in those who have reduced or absent awareness of the warnings of hypoglycaemia or have frequent episodes of hypoglycaemia.
Dan huwa partikolarment importanti f’ dawk li għandhom sensazzjoni mnaqqsa jew nieqsa għat- twissijiet ta ’ ipogliċemija jew għandhom episodji frekwenti ta ’ ipogliċemija.
It should be considered whether it is advisable to drive or operate machines in these circumstances.
F’ dawn iċ - ċirkostanzi għandu jiġi kkunsidrat jekk huwiex xieraq li ssuq jew tħaddem magni.
No therapeutic clinical trials have been conducted with Tandemact.
Ma saru l- ebda provi kliniċi terpewtiċi b’ Tandemact.
However, bioequivalence of Tandemact with coadministered pioglitazone and glimepiride has been demonstrated (see section 5.2).
Iżda, ġiet dimostrata l- bijoekwivalenza ta ’ Tandemact ma ’ pioglitazone u glimeprimide mogħtija flimkien (ara sezzjoni 5. 2).
Adverse reactions reported in excess (> 0.5%) of placebo and as more than an isolated case in patients receiving pioglitazone in double-blind studies in combination with a sulphonylurea, including glimepiride, are listed below as MedDRA preferred term by system organ class and absolute frequency.
Reazzjonijiet avversi rrappurtati aktar (> 0. 5%) milli fil- plaċebo u f’ aktar minn każ iżolat f’ pazjenti li qed jirċievu pioglitazone flimkien ma ’ sulphonylurea, inluż glimeprimide fi studji double- blind huma mniżżla hawn taħt bis- sistema ta ’ terminu ppreferut MedDRA permeżż tas- sistema tal- klassifika tal - organi u frekwenza assoluta.
Frequencies are defined as: common > 1/ 100 ,< 1/10; uncommon > 1/1000 ,< 1/100; rare > 1/ 10000 ,< 1/1000; very rare < 1/10000; isolated reports: not known (cannot be estimated from the available data).
Il- frekwenzi huma definiti bħala: komuni > 1/ 100, < 1/ 10; mhux komuni > 1/ 1000, < 1/ 100; rari > 1/ 10000, < 1/ 1000; rari ħafna < 1/ 10000; rapporti iżolati: mhux magħruf (ma tistax tittieħed stima mid- data disponibbli).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
L- effetti li huma l- aktar serji għandhom jitniżżlu l - ewwel, segwiti minn dawk anqas serji.
General disorders and administration site conditions Uncommon:
7 Disturbi ġenerali u kondizzjonijiet ta 'mnejn jingħata Mhux komuni: għeja
7 Renal and urinary disorders Uncommon:
Disturbi fil- kliewi u fis- sistema urinarja Mhux komuni: glikosurja, proteina fl- awrina
Oedema was reported in 6 – 9% of patients treated with pioglitazone over one year in controlled clinical trials.
Edema kienet irrappurtata f’ 6 – 9% tal- pazjenti kkurati b’ pioglitazone fuq medda ta ’ sena fi provi kliniċi kkontrollati.
The oedema rates for comparator groups (sulphonylurea, metformin) were 2 – 5%.
Ir- rati ta ’ edema għall- gruppi ta ’ paragun (sulphonylurea, metformin) kienu ta ’ 2 – 5%.
The reports of oedema were generally mild to moderate and usually did not require discontinuation of treatment.
Ir- rapporti ta ’ edema ġeneralment kienu ħfief għal moderati u normalment ma kienux jinħtieġu l - waqfien tal- kura.
In combination trials pioglitazone added to a sulphonylurea resulted in a mean weight increase over one year of 2.8 kg.
Fi provi ta ’ taħlita, pioglitazone miżjud ma ’ sulphonylurea wassal għall - żieda medja fil- piż ta ’ 2. 8 kg fuq medda ta ’ sena.
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 klinċi b’ pioglitazone l- inċidenża ta ’ elevazzjonijiet ta ’ ALT aktar minn tlett darbiet l- għola limitu tan- normal kienet daqs il- plaċebo iżda inqas minn dik li deheret 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 klinċi kkontrollati l- inċidenza ta ’ rapporti ta ’ insuffiċjenza tal- qalb b’ kura ta ’ pioglitazone kienet l- istess bħall- gruppi ta ’ kura bil- plaċebo, metformin u sulphonylurea, iżda kienet miżjuda meta wżata f’ terapija kombinata ma ’ insulina.
In an outcome study of patients with pre-existing major macrovascular disease, the incidence of serious heart failure was 1.6% higher with pioglitazone than with placebo, when added to therapy that included in insulin.
Fi studju dwar l- effett ta ’ pazjenti b’ marda makrovaskulari eżistenti minn qabel, l- inċidenza ta ’ insuffiċjenza tal- qalb serja kienet 1. 6% ogħla b’ pioglitazone milli bil- plaċebo, meta miżjud ma ’ terapija li kienet tinkludi l- insulina.
Additional information on the individual active substances of the fixed dose combination
8 Tagħrif ieħor dwar is- sustanzi attivi individwali tat- taħlita ta ’ doża fissa
In double blind placebo controlled clinical trials with pioglitazone upper respiratory tract infection and hypoaesthesia were common; sinusitis and insomnia were uncommon.
Fi provi kliniċi double blind ikkontrollati bil- plaċebo, infezzjonijiet fil- passaġġ respiratorju ta ’ fuq u ipoesteżija kienu komuni; sinożite u insomnija ma kienux komuni.
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.
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.
Heart failure has been reported rarely with marketing use of pioglitazone.
Insuffiċjenza tal- qalb kienet irrappurtata b’ mod rari bl- użu ta ’ pioglitazone wara t- tqegħid fis- suq
POST MARKETING DATA
TAGĦRIF TA ’ WARA T- TQEGĦID FIS- SUQ
Eye disorders Macular oedema:
Disturbi fl- għajnejn Edema makulari:
Based on experience with glimepiride and with other sulphonylureas the following adverse reactions have to be mentioned.
Ibbażat fuq esperjenza b’ glimepiride u b’ sulphonylurea oħra l- effetti avversi li ġejjin għandhom jissemmew.
8 Immune system disorders Very rare:
Disturbi fis- sistema immuni Rari ħafna:
Allergic shock, allergic vasculitis
Xokk allerġiku, vaskulite allerġika
Blood and lymphatic system disorders Rare:
u tas- sistema limfatika
Changes in haematology
Tibdiliet fl- ematoloġija
Gastro-intestinal disorders Very rare:
Disturbi gastro- intestinali Rari ħafna:
Vomiting, diarrhoea, nausea, abdominal pressure, feeling of fullness in the stomach, abdominal pain
Remettar, dijarrea, tqalliħ, tagħfis addominali, tħoss l- istonku mimli, uġigħ addominali
Hepatitis, impairment of liver function (with cholestasis and jaundice)
Epatite, indeboliment tal- funzjoni epatika (b’ kolestasi u suffejra)
Skin and subcutaneous tissue disorders Very rare:
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda Rari ħafna:
Hypersensitivity to light
Sensittività eċċessiva għad- dawl
Very rare:
Investigazzjonijiet Rari ħafna:
Decrease in sodium serum concentrations
Tnaqqis fil- konċentrazzjonijiet tas- sodju fis- serum
In very rare cases mild hypersensivity reactions may develop into serious reactions with dyspnoea, fall in blood pressure and sometimes shock.
F’ każijiet rari ħafna reazzjonijiet ta ’ sensittività eċċessiva jistgħu jiżviluppaw f’ reazzjonijiet serji bi qtugħ ta ’ nifs, tnaqqis qawwi fil- pressjoni tad- demm u xi kultant xokk.
Hypersensitivity reactions of the skin may occur as itching, rash, and urticaria.
Reazzjonijiet ta ’ sensittività eċċessiva tal- ġilda jistgħu jseħħu bħala ħakk, raxx u urtikarja.
Cross allergenicity with sulphonylureas, sulphonamides or related substances is possible.
Allerġeniċità ma ’ sulphonylureas, sulphonamides jew sustanzi relatati hija possibbli.
Moderate to severe thrombocytopenia, leucopenia, erythrocytopenia, agranulocytopenia, agranulocytosis, haemolytic anemia and pancyto-penia may occur.
Tromboċitopenija, leukopenija, eritroċitopenija, agranuloċitopenija, agranuloċitosi, anemija emolitika u panċito- penija moderata għal severa jistgħu jseħħu.
These are in general reversible upon discontinuation of medication.
Ġeneralment dawn huma riversibbli mal - waqfien tal- medikazzjoni.
Gastro-intestinal complaints are very rare and seldom lead to discontinuation of therapy.
Problemi gastro- intestinali huma rari ħafna u rarament iwasslu għall- waqfien tat- terapija.
Elevation of liver enzymes may occur.
Jista ’ jkun hemm żieda fl- enżimi tal- fwied.
In very rare cases, impairment of liver function (e. g. with cholestasis and jaundice) may develop, as well as hepatitis which may progress to liver failure.
F’ każijiet rari ħafna, jista ’ jiżviluppa indeboliment tal - funżjoni tal- fwied (e. ż. b’ kolestasi u suffejra), kif ukoll epatite li tista ’ tiżviluppa f’ insuffiċjenza tal - fwied.
A pooled analysis was conducted of adverse event reports of bone fractures from randomised, comparator controlled, double blind clinical trials in over 8100 patients in the pioglitazone-treated groups and 7400 in the comparator-treated groups of up to 3.5 years duration.
9 Twettqet analiżi ta ’ tagħrif miġbur ta ’ rapporti ta ’ avvennimenti avversi ta ’ fratturi fl- għadam minn provi kliniċi randomised, ikkontrollati b’ paragun, u double blind b’ aktar minn 8100 pazjent fil- gruppi kkurati b’ pioglitazone u 7400 pazjent fil- gruppi kkurrati bi prodott paragun li damu sa 3. 5 snin.
After ingestion of an overdosage of glimepiride, hypoglycaemia may occur, lasting from 12 to 72 hours, and may recur after initial recovery.
Wara t- teħid ta ’ doża eċċessiva ta ’ glimepiride, tista sseħħ ipogliċemija, li ddum minn 12 sa 72 siegħa, u tista ’ terġa ’ sseħħ wara l- irkupru iniżjali.
Symptoms may not be present for up to 24 hours after ingestion.
Is- sintomi jistgħu ma jidrhux sa 24 siegħa wara t- teħid.
In general observation in hospital is recommended.
Ġeneralment, ossevazzjoni fi sptar hija rakkomandata.
Nausea, vomiting and epigastric pain may occur.
Jista ’ jkun hemm tqalliħ, remettar w uġigħ epigastriku.
The hypoglycaemia may in general be accompanied by neurological symptoms like restlessness, tremor, visual disturbances, coordination problems, sleepiness, coma and convulsions.
L- ipogliċemija tista ’ ħafna drabi tkun akkompanjata minn sintomi newroloġiċi bħal irrekwitezza, rogħda, disturbi fil- vista, problemi ta ’ koordinazzjoni, ngħas, koma u konvulżjonijiet.
9 Treatment of overdosage of Tandemact primarily consists of preventing absorption of glimepiride by inducing vomiting and then drinking water or lemonade with activated charcoal (adsorbent) and sodium-sulphate (laxative).
Kura ta ’ doża eċċessiva ta ’ Tandemact tikkonsisti primarjament minn impediment ta ’ l- assorbiment ta ’ glimepiride billi jiġi ndott ir- remettar u wara jinxtorob ilma jew luminata b’ faħam attivat (assorbent) u sodium- sulphate (lassattiv).
If large quantities have been ingested, gastric lavage is indicated, followed by activated charcoal and sodium-sulphate.
Jekk ittieħdu kwantitajiet kbar, tlaħliħ ta ’ l- istonku huwa ndikat, segwit minn faħam attivat u sodium- sulphate.
In case of (severe) overdosage hospitalization in an intensive care department is indicated.
F’ każ ta ’ doża eċċessiva (severa) huwa indikat li wieħed jiddaħħal l- isptar f’ dipartiment ta ’ kura intensiva.
Start the administration of glucose as soon as possible, if necessary by a bolus intravenous injection of 50 ml of a 50% solution, followed by an infusion of a 10% solution with strict monitoring of blood glucose.
Ibda l- għotja ta ’ glukosju mill- aktar fis possibbli, jekk hemm bżonn b’ injezzjoni bolus ġol- vina ta ’ 50 ml ta ’ soluzzjoni ta ’ 50%, segwita minn infużjoni ta ’ soluzzjoni ta ’ 10% b’ sorveljanza stretta ta ’ glukosju fid- demm.
Further treatment should be symptomatic.
Aktar kura għandha tkun sintomatika.
In particular when treating hypoglycaemia due to accidental intake of Tandemact in infants and young children, the dose of glucose given must be carefully controlled to avoid the possibility of producing dangerous hyperglycaemia.
Speċjalment meta qed tiġi kkurata l- ipogliċemija minħabba t- teħid bi żball ta ’ Tandemact fit- trabi u tfal żgħar, id- doża ta ’ glukosju li tingħata għandha tiġi kkontrollata sew biex tiġi evitata l- possibilità li tipproduċi ipergliċemija perikoluża.
Blood glucose should be closely monitored.
Il- glukosju fid- demm għandu jiġi sorveljat mill- viċin.
Combinations of oral blood glucose lowering drugs; ATC code:
Taħlitiet ta ’ mediċini mill- ħalq li jbaxxu ż- żokkor fid- demm; kodiċi ATC:
Tandemact 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 glimepiride, a member of the sulphonylurea class.
Tandemact jikkombina żewġ aġenti anti- ipergliċemiċi b’ mekkaniżmi ta ’ azzjoni li jikkumplimentaw lil xulxin biex itejbu l- kontroll gliċemiku f’ pazjenti b’ dijabete tat- tip 2: pioglitazone, membru tal - klassi thiazolidinedione u glimepiride, membru tal- klassi sulphonylurea.
Thiazolidinediones act primarily by reducing insulin resistance and sulphonylureas primarily by inducing insulin release from pancreatic beta cells.
Thiazolidinediones jaħdmu primarjament billi jnaqqsu r- reżistenza għal l- insulina u sulphonylureas jaħdmu primarjament billi jinduċu r- reħa ta ’ l- insulina miċ- ċelloli beta tal- frixa.
Pioglitazone
10 Pioglitazone
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 (peroxisome proliferator activated receptor gamma) li twassal għal żieda fis- sensittività għall- insulina tal- fwied, xaħam u ċelloli tal- muskoli skeletrali fl- annimali.
Treatment with pioglitazone has been shown to reduce hepatic glucose output and to increase peripheral glucose disposal in the case of insulin resistance.
Kura b’ pioglitazone intweriet li tnaqqas il- produzzjoni ta ’ glukosju mill- fwied u żżid it- tneħħijja periferali ta ’ glukosju f’ każ ta ’ reżistenza għall- insulina.
HOMA analysis shows that pioglitazone improves beta cell function as well as increasing insulin sensitivity.
Analiżi HOMA turi li pioglitazone itejjeb il- funzjoni taċ- ċellola beta kif ukoll iżid is- sensittività għall - insulina.
10 The effect of pioglitazone (45 mg monotherapy vs. placebo) was studied in a small 18-week trial in type 2 diabetics.
L- effett ta ’ pioglitazone (45 mg monoterapija vs. plaċebo) kien studjat fi prova żgħira ta ’ 18- il ġimgħa f’ pazjenti bid- dijabete tat- tip 2.
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, pazjenti kellu jkollhom wieħed jew aktar minn dawn li ġejjin: infart mijokardijaku, puplesijja, intervent kardijaku perkutanju jew bypass graft tal- arterja koronarja, sindrome koronarju akut, marda ta ’ l- arterji koronarji, jew marda ostruttiva ta ’ l- arterji periferali.
Almost half of the patients had a previous myocardial infarction and approximately 20% had had a stroke.
Kważi nofs il- pazjenti kellhom infart 11 mijokardijaku minn qabel u madwar 20% kellhom puplesija minn qabel.
Glimepiride acts mainly by stimulating insulin release from pancreatic beta cells.
Glimepiride jaħdem prinċipalment billi jistimola r- reħa ta ’ insulina minn ċelloli beta tal- frixa.
As with other sulphonylureas this effect is based on an increase of responsiveness of the pancreatic beta cells to the physiological glucose stimulus.
Bħal b’ sulphonylureas oħra, dan l- effett huwa bbażat fuq żieda fis- sensibilità ta ’ ċelloli beta tal- firxa għal l- stimolu fiżjoloġiku ta ’ glukosju.
In addition, glimepiride seems to have pronounced extrapancreatic effects also postulated for other sulphonylureas.
Barra minn hekk, glimepiride jidher li għandu effetti extrapankrejatiċi qawwija li jidrhu f’ sulphonylureas oħra.
Insulin release:
Reħa ta ’ insulina:
Sulphonylureas regulate insulin secretion by closing the ATP-sensitive potassium channel in the beta cell membrane.
Sulphonylureas jirregolaw ir- reħa ta ’ insulina billi jagħlqu l- kanali tal- potassju sensittivi għal ATP fil - membrana taċ- ċellola beta.
Closing the potassium channel induces depolarisation of the beta cell and results – by opening of calcium channels – in an increased influx of calcium into the cell.
L- għeluq tal- kanal tal- potassju jwassal għal depolarizzazzjoni taċ- ċellola beta u jirriżulta – billi jiftaħ il- kanali tal- kalċju – f’ żieda fid- dħul ta ’ kalċju fiċ- ċellola.
This leads to insulin release through exocytosis.
Dan iwassal għar- reħa ta ’ insulina permezz ta ’ exoċitożi.
Glimepiride binds with a high exchange rate to a beta cell membrane protein which is associated with the ATP-sensitive potassium channel but which is different from the usual sulphonylurea binding site.
Glimepiride jeħel b’ rata għolja ma ’ proteina tal - membrana taċ- ċellola beta li hija assoċjata mal- kanal tal- potassju sensittiv għal ATP iżda li hija differenti mis- sit ta ’ twaħħil tas- soltu ta ’ sulphonylurea.
Extrapancreatic activity:
Attività extrapankrejatika:
The extrapancreatic effects are for example an improvement of the sensitivity of the peripheral tissue for insulin and a decrease of the insulin uptake by the liver.
L- effetti extrapankrejatiċi huma per eżempju titjib fis- sensittività tat- tessuti periferali għall- insulina u tnaqqis fit- tneħħija ta ’ l- insulina mill- fwied.
The uptake of glucose from blood into peripheral muscle and fat tissues occurs via a special transport proteins, located in the cells membrane.
It- teħid ta ’ glukosju mid- demm għal ġol- muskoli periferali u t- tessuti tax- xaħam iseħħ permezz ta ’ proteini ta ’ trasport speċjali, li jinstabu fil- membrana taċ- ċelloli.
The transport of glucose in these tissues is the rate limiting step in the use of glucose.
It- trasport ta ’ glukosju f’ dawn it - tessuti huwa l- pass li jillimita r- rata fl- użu ta ’ glukosju.
Glimepiride increases very rapidly the number of active glucose transport molecules in the plasma membranes of muscle and fat cells, resulting in stimulated glucose uptake.
Glimepiride iżid malajr ħafna in- numru ta ’ molekoli attivi għat- trasport ta ’ glukosju fil- membrani tal- plażma ta ’ ċelloli tal- muskoli u tax- xaħam, u jirriżulta fi tneħħija stimolata ta ’ glukosju.
11 Glimepiride increases the activity of the glycosyl-phosphatidylinositol-specific phospholipase C which may be correlated with the induced lipogenesis and glycogenesis in isolated fat and muscle cells.
Glimepiride iżid l- attività ta ’ phospholipase C sepċifiku għal glycosyl- phosphatidylinositol li tista ’ tiġi kkorrelata mal- lipoġenesi u glikoġnesi indotta f’ ċellolli iżolati tax- xaħam u tal- muskoli.
Glimepiride inhibits the glucose production in the liver by increasing the intracellular concentration of fructose-2,6-bisphosphate, which in turn inhibits the gluconeogenesis.
Glimepiride jinibixxi l- produzzjoni ta ’ glukosju fil- fwied billi jżid il - konċentrazzjoni intraċellolari ta ’ fructose- 2, 6- bisphosphate, li wara huwa wholl jinibixxi l - glukoneoġenesi.
In healthy persons, the minimum effective oral dose is approximately 0.6 mg.
F’ persuni b’ saħħithom, id- doża orali minima effettiva hija ta ’ madwar 0. 6 mg.
The effect of glimepiride is dose-dependent and reproducible.
L- effett ta ’ glimepiride huwa dipendenti mid- doża u riprodottiv.
The physiological response to acute physical exercise, reduction of insulin secretion, is still present under glimepiride.
Ir- rispons fiżjoloġiku għall- eżerċizzju fiżiku akut, tnaqqis fir - reħa ta ’ l- insulina, xorta huwa preżenti b’ glimepiride.
There was no significant difference in effect regardless of whether glimepiride was given 30 minutes or immediately before a meal.
Meta glimepiride ingħata 30 minuta qabel ikla jew eżatt qabel, ma kienx hemm differenza sinifikanti fl- effett.
In diabetic patients, good metabolic control over 24 hours can be achieved with a single daily dose.
F’ pazjenti dijabetiċi, kontroll metaboliku tajjeb fuq medda ta ’ 24 siegħa jista ’ jintlaħaq b’ doża waħda kuljum.
Although the hydroxy metabolite of glimepiride caused a small but significant decrease in serum glucose in healthy persons, it accounts for only a minor part of the total effect.
Għalkemm il- metabolit hydroxy ta ’ glimepiride wassal għal tnaqqis żgħir iżda sinifikanti ta ’ glukosju fis- serum f’ persuni b’ saħħithom, huwa responsabli biss għall- parti minuri tal- effett totali.
Studies in human volunteers have shown Tandemact to be bioequivalent to the administration of pioglitazone and glimepiride given as separate tablets.
Studji ta ’ bijoekwivalenza f’ volontiera b’ saħħithom urew li Tandemact huwa bijoekwivalenti għal għotja ta ’ pioglitazone u glimepiride mogħtija bħala pilloli separati.
The following statements reflect the pharmacokinetic properties of the individual active substances of Tandemact
Id- dikjarazzjonijiet li ġejjin jirriflettu il- proprjetajiet farmakokinetiċi tas- sustanzi attivi individwali f’ Tandemact.
When activity, concentrations and protein binding are taken into account, pioglitazone and metabolite M-III contribute equally to efficacy.
Meta l- attività, konċentrazzjonijiet u twaħħil mal- proteini jittieħdu f’ konsiderazzjoni, pioglitazone u l- metabolita M- III jikkontribwew l- istess għall- effikaċja.
There is no induction of the main inducible P450 isoenzymes 1A, 2C8/ 9, and 3A4 in man.
Ma hemm l- ebda induzzjoni tal- isożimi prinċipali ta ’ P450 induċibbli 1A, 2C8/ 9, u 3A4 fil- bniedem.
Concomitant administration of pioglitazone with gemfibrozil (an inhibitor of cytochrome P450 2C8) or with rifampicin (an inducer of cytochrome P450 2C8) is reported to increase or decrease, respectively, the plasma concentration of pioglitazone (see section 4.5).
L- għotja ta ’ pioglitazone flimkien ma ’ gemfibrozil (inibitur taċ- ċitokromju P450 2C8) jew ma ’ rifampicin (induttur taċ- ċitokromju P450 2C8) hija rrappurtata li żżid jew tnaqqas, rispettivament, il - konċentrazzjoni ta ’ pioglitazone fil- plażma (ara sezzjoni 4. 5).
12 Elimination:
Eliminazzjoni:
Following oral administration of radiolabeled pioglitazone to man, recovered label was mainly in faeces (55%) and a lesser amount in urine (45%).
Wara għotja ta ’ pioglitazone radjutikketjat mill- ħalq lill- bniedem, it- tikkettjar miġbur kien l- aktar fil - feċi (55%) u f’ ammont inqas fl- awrina (45%).
Patients with renal impairment:
13 Pazjenti b’ indeboliment renali:
The bioavailability of glimepiride after oral administration is complete.
Il- bijodisponibilità ta ’ glimepiride wara għotja orali hija kompluta.
Food intake has no relevant influence on absorption, only absorption rate is slightly diminished.
It- teħid ta ’ l- ikel m’ għandu l- ebda nfluwenza rilevanti fuq l- assorbiment, ir- rata ta ’ l- assorbiment biss hija kemmxejn imnaqqsa.
Maximum serum concentrations (Cmax) are reached approximately 2.5 hours after oral intake (mean 0.3 µg/ ml during multiple dosing of 4 mg daily) and there is a linear relationship between dose and both Cmax and AUC (area under the time/ concentration curve).
Konċentrazzjonijiet massimi fis- serum (Cmax) jintlaħqu f’ madwar 2. 5 sigħat wara t- teħid orali (medja ta ’ 0. 3 µg/ ml waqt dożaġġ multiplu ta ’ 4 mg kuljum) u hemm relazzjoni linejari bejn id- doża u Cmax u id- doża l- AUC (erja taħt il- kurva ta ’ ħin/ konċentrazzjoni).
Glimepiride has a very low distribution volume (approximately 8.8 litres) which is roughly equal to the albumin distribution space, high protein binding (> 99%), and a low clearance (approximately 48 ml/ min).
Glimepiride għandu volum ta ’ distribuzzjoni żgħir ħafna (madwar 8. 8 litri) li huwa bejn wieħed u ieħor ugwali għal l- ispazju ta ’ distribuzzjoni ta ’ l- albumina, twaħħil għoli mal- proteini (> 99%), u tneħħijja baxxa (madwar 48 ml/ min).
In animals, glimepiride is excreted in milk.
Fil- bhejjem, glimepiride jitneħħa fil- ħalib.
Glimepiride is transferred to the placenta.
Glimepiride jiġi trasferit għal ġol- plaċenta.
Passage of the blood brain barrier is low.
Passaġġ tal - barriera ta ’ bejn id- demm u l- moħħ huwa baxx.
Biotransformation and elimination:
Bijotransformazzjoni u eliminazzjoni:
Mean dominant serum half-life, which is of relevance for the serum concentrations under multiple- dose conditions, is about 5 to 8 hours.
Il- medja tal- half- life dominanti fis- serum, li hija ta ’ rilevanza għall- konċentrazzjonijiet fis- serum f’ kundizzjonijiet ta ’ dożi multipli, hija ta ’ madwar 5 sa 8 sigħat.
After high doses, slightly longer half-lives were noted.
Wara dożi għolja, kienu osservati half- lives kemmxejn itwal.
After a single dose of radiolabelled glimepiride, 58% of the radioactivity was recovered in the urine, and 35% in the faeces.
Wara doża waħda ta ’ glimepiride radjulabiljat, 58% tar- radjuattività kienet irkuprata fl- awrina, u 35% fil- feċi.
No unchanged substance was detected in the urine.
Ma nstabet l- ebda sustanza mhux mibdula fl- awrina.
Two metabolites – most probably resulting from hepatic metabolism (major enzyme is CYP2C9) – were identified both in urine and faeces: the hydroxy derivative and the carboxy derivative.
Żewġ metaboliti – wisq probabbli rriżultaw minn metaboliżmu epatika (l- enżima prinċipali hija CYP2C9) – kienu identifikati kemm fl - awrina kif ukoll fil- feċi: id- derivat ta ’ hydroxyl u d- derivat ta ’ carboxy.
After oral administration of glimepiride, the terminal half-lives of those metabolites were 3 to 6 and 5 to 6 hours respectively.
Wara għotja orali ta ’ glimepiride, il- half- lives terminali ta ’ dawk il- metaboliti kienu 3 sa 6 u 5 sa 6 sigħat rispettivament.
Comparison of single and multiple once-daily dosing revealed no significant differences in pharmacokinetics, and the intra-individual variability was very low.
Paragun ta ’ dożaġġ ta ’ darba kuljum u ta ’ aktar minn darba kuljum ma wera l- ebda differenza sinifikanti fil- farmakokinetika, u l- varjabilità bejn l- individwi kienet baxxa ħafna.
There was no relevant accumulation.
Ma kienx hemm akkumulazzjoni rilevanti.
Pharmacokinetics were similar in males and females, as well as in young and elderly (above 65 years) patients.
Il- farmakokinetika kienet simili fl- irġiel u fin- nisa, kif ukoll f’ pazjenti żgħar u anżjani (’ l fuq minn 65 sena).
In patients with low creatinine clearance, there was a tendency for glimepiride clearance to increase and for average serum concentrations to decrease, most probably resulting from a more rapid elimination because of lower protein binding.
F’ pazjenti bi tneħħija ta ’ krejatinina baxxa, kien hemm tendenza li t- tneħħija ta ’ glimepiride tiżdied u li l- konċentrazzjonijiet medji fis- serum jonqsu, wisq probabbli r- riżultat ta ’ eliminazzjoni aktar malajr minħabba twaħħil aktar baxx mal- proteini.
Renal elimination of the two metabolites was impaired.
Eliminazzjoni renali taż- żewġ metaboliti kienet imnaqqsa.
Overall no additional risk of accumulation is to be assumed in such patients.
Globalment wieħed m’ għandux jassumi riskju akbar ta ’ akkumulazzjoni f’ dawn il - pazjenti.
Pharmacokinetics in five non-diabetic patients after bile duct surgery were similar to those in healthy persons.
Il- farmakokinetika f’ ħames pazjenti mhux dijabetiċi wara kirurġija fil- kanal tal- bili kienet simili għal dik f’ persuni b’ saħħithom.
13 5.3 Preclinical safety data
14 5. 3 Tagħrif ta 'qabel l- użu kliniku dwar is- sigurtà tal- mediċina
No animal studies have been conducted with the combined products of Tandemact.
Ma sarux studji fil- bhejjem bil- prodotti kombinati f’ Tandemact.
The following data are findings in studies performed with pioglitazone or glimepiride individually.
It- tagħrif li ġej huma sejbiet minn studji li twettqu b’ pioglitazone jew b’ glimepiride għalihom.
Preclinical effects observed occurred at exposures sufficiently in excess of the maximum human exposure as to indicate little relevance to clinical use, or were due to the pharmacodynamic action (hypoglycaemia) of the compound.
L- effetti preklinċi osservati seħħew b’ espożizzjonijiet suffiċjentament akbar mill- ogħla espożizzjoni umana biex jindikaw ftit rilevanza għall- użu kliniku, jew seħħew minħabba l- azzjoni farmakodinamika (ipogliċemja) tal- prodott.
This finding is based on conventional safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenicity, and reproduction toxicity studies.
Din is- sejba hija bbażata fuq studji konvenzjonali ta ’ sigurtà farmakoloġika, effett tossiku minn dożi ripetuti, effett tossiku fuq il- ġeni, riskju ta ’ kanċer u effett tossiku fuq is- sistema riproduttiva.
In the latter (covering embryotoxicity, teratogenicity and developmental toxicity), undesirable effects observed were considered to be secondary to the hypoglycaemic effects induced by the compound in dams and in offspring.
F’ dan ta ’ l- aħħar, (li tkopri effett tossiku fuq l- embriju, teratoġeniċità u effett tossiku fuq l- iżvilupp), l- effetti mhux mixtieqa osservati kienu kkunsidrati bħala sekondarji għall- effetti ipogliċemiċi indotti mill- prodott fl- ommijiet u l- frieħ.
Cellulose microcrystalline Croscarmellose sodium Hydroxypropylcellulose Lactose monohydrate Magnesium stearate Polysorbate 80
Cellulose microcrystalline Croscarmellose sodium Hydroxypropylcellulose Lattosju monohydrate Magnesium stearate Polysorbate 80
Aluminium/ aluminium blisters; packs of 14, 28, 30, 50, 90 or 98 tablets.
Aluminju/ folji tal- aluminju; pakketti ta ’ 14, 28, 30, 50, 90 jew 98 pillola.
EU/ 1/ 06/ 366/ 017-22
EU/ 1/ 06/ 266/ 017- 022
8th January 2007
8 ta ’ Jannar 2007
Tandemact 30 mg/ 4 mg tablets.
Pilloli Tandemact 30 mg/ 4 mg.
Each tablet contains 30 mg of pioglitazone (as hydrochloride) and 4 mg of glimepiride.
Kull pillola fiha 30 mg ta ’ pioglitazone (bħala hydrochloride) u 4 mg glimepiride.
Each tablet contains approximately 177 mg lactose monohydrate.
Kull pillola fiha madwar 177 mg lattosju monohydrate.
White to off-white, round, convex and embossed ‘ 4833 G’ on one face and ‘ 30/ 4’ on the other.
Il- pilloli huma bojod għal abjad maħmuġ, tondi, konvessi u mmarkati b ’ ‘ 4833 G ’ fuq naħa u b ’ ‘ 30/ 4 ’ fuq in- naħa l- oħra.
16 4.3 Contraindications
17 4. 3 Kontra- indikazzjonijiet
Liver enzymes should be checked prior to the initiation of therapy with Tandemact in all patients.
18 ċċekkjati qabel ma tinbeda terapija b’ Tandemact f’ kull pazjent.
17 Following initiation of therapy with Tandemact, it is recommended that liver enzymes be monitored periodically based on clinical judgement.
Wara l- bidu tat- terapija b’ Tandemact, huwa rakkomandat li l- enżimi tal- fwied ikunu sorveljati perjodikament ibbażat fuq ġudizzju kliniku.
The fracture incidence calculated was 1.9 fractures per 100 patient years in women treated with pioglitazone and 1.1 fractures per 100 patient years in women treated with a comparator.
19 L- inċidenza ta ’ fratturi kkalkulata kienet ta ’ 1. 9 fratturi kull 100 sena ta ’ pazjent f’ nisa kkurati b’ pioglitazone u 1. 1 fratturi kull 100 sena ta ’ pazjent f’ nisa kkurati bi prodott ta ’ paragun.
19 phenylbutazone, azapropazon and oxyfenbutazone insulin and oral antidiabetic products metformin salicylates and p-amino-salicylic acid anabolic steroids and male sex hormones chloramphenicol coumarin anticoagulants fenfluramine fibrates ACE inhibitors fluoxetine allopurinol sympatholytics cyclo-, tro-and iphosphamides sulphinpyrazone certain long-acting sulphonamides tetracyclines MAO-inhibitors quinolone antibiotics probenecid miconazol pentoxyfylline (high dose parenteral) tritoqualine fluconazole
phenylbutazone, azapropazon u oxyfenbutazone insulina u prodotti anti- dijabetiċi orali metformin salicylates u p- amino- salicylic acid sterojdi anaboliċi u ormoni sesswali ta ’ l- irġiel chloramphenicol coumarin anticoagulants fenfluramine fibrates inibituri ACE fluoxetine allopurinol sympatholytics cyclo -, tro - u iphosphamides sulphinpyrazone ċertu sulphonamides li jaħdmu fit- tul tetracyclines inibituri MAO anti- bijotiċi quinolone probenecid miconazol pentoxyfylline (doża għolja mogħtija b’ mod parenterali) tritoqualine fluconazole
Under the influence of sympatholytic active substances such as betablockers, clonidine, guanethidine and reserpine, the signs of adrenergic counterregulation to hypoglycaemia may be reduced or absent.
21 Taħt l- influwenza ta ’ sustanzi attivi simpatolitiċi bħal imblukkaturi beta, clonidine, guanethidine u reserpine, is- sinjali ta ’ kontra- regolazzjoni adrinerġika għall- ipogliċemija jistgħu jkunu mnaqqsa jew assenti.
20 Sulphonylurea-derivatives like glimepiride pass into the breast milk.
Derivati ta ’ sulphonylurea bħal glimepiride jgħaddu fil- ħalib tas- sider.
General disorders and administration site conditions Uncommon:
22 Disturbi ġenerali u kondizzjonijiet ta 'mnejn jingħata Mhux komuni: għeja
21 Renal and urinary disorders Uncommon:
Disturbi fil- kliewi u fis- sistema urinarja Mhux komuni: glikosurja, proteina fl- awrina
Additional information on the individual active substances of the fixed dose combination
23 Tagħrif ieħor dwar is- sustanzi attivi individwali tat- taħlita ta ’ doża fissa
22 Immune system disorders Very rare:
Disturbi fis- sistema immuni Rari ħafna:
A pooled analysis was conducted of adverse event reports of bone fractures from randomised, comparator controlled, double blind clinical trials in over 8100 patients in the pioglitazone-treated groups and 7400 in the comparator-treated groups of up to 3.5 years duration.
24 Twettqet analiżi ta ’ tagħrif miġbur ta ’ rapporti ta ’ avvennimenti avversi ta ’ fratturi fl- għadam minn provi kliniċi randomised, ikkontrollati b’ paragun, u double blind b’ aktar minn 8100 pazjent fil- gruppi kkurati b’ pioglitazone u 7400 pazjent fil- gruppi kkurrati bi prodott paragun li damu sa 3. 5 snin.
23 Treatment of overdosage of Tandemact primarily consists of preventing absorption of glimepiride by inducing vomiting and then drinking water or lemonade with activated charcoal (adsorbent) and sodium-sulphate (laxative).
Kura ta ’ doża eċċessiva ta ’ Tandemact tikkonsisti primarjament minn impediment ta ’ l- assorbiment ta ’ glimepiride billi jiġi ndott ir- remettar u wara jinxtorob ilma jew luminata b’ faħam attivat (assorbent) u sodium- sulphate (lassattiv).
Pioglitazone
25 Pioglitazone
24 The effect of pioglitazone (45 mg monotherapy vs. placebo) was studied in a small 18-week trial in type 2 diabetics.
L- effett ta ’ pioglitazone (45 mg monoterapija vs. plaċebo) kien studjat fi prova żgħira ta ’ 18- il ġimgħa f’ pazjenti bid- dijabete tat- tip 2.
Almost half of the patients had a previous myocardial infarction and approximately 20% had had a stroke.
Kważi nofs il- pazjenti kellhom infart 26 mijokardijaku minn qabel u madwar 20% kellhom puplesija minn qabel.
25 Glimepiride increases the activity of the glycosyl-phosphatidylinositol-specific phospholipase C which may be correlated with the induced lipogenesis and glycogenesis in isolated fat and muscle cells.
Glimepiride iżid l- attività ta ’ phospholipase C sepċifiku għal glycosyl- phosphatidylinositol li tista ’ tiġi kkorrelata mal- lipoġenesi u glikoġnesi indotta f’ ċellolli iżolati tax- xaħam u tal- muskoli.
5.2 Pharmacokinetic properties
27 5. 2 Tagħrif farmakokinetiku
26 Elimination:
Eliminazzjoni:
Patients with renal impairment:
28 Pazjenti b’ indeboliment renali:
27 Pharmacokinetics in five non-diabetic patients after bile duct surgery were similar to those in healthy persons.
Il- farmakokinetika f’ ħames pazjenti mhux dijabetiċi wara kirurġija fil- kanal tal- bili kienet simili għal dik f’ persuni b’ saħħithom.
5.3 Preclinical safety data
29 5. 3 Tagħrif ta 'qabel l- użu kliniku dwar is- sigurtà tal- mediċina
6.4 Special precautions for storage
30 6. 4 Prekawzjonijiet speċjali għall- ħażna
Tandemact 45 mg/ 4 mg tablets.
Pilloli Tandemact 45 mg/ 4 mg.
Each tablet contains 45 mg of pioglitazone (as hydrochloride) and 4 mg of glimepiride.
Kull pillola fiha 45 mg ta ’ pioglitazone (bħala hydrochloride) u 4 mg glimepiride.
Each tablet contains approximately 214 mg lactose monohydrate.
Kull pillola fiha madwar 214 mg lattosju monohydrate.
White to off-white, round, flat and embossed ‘ 4833 G’ on one face and ‘ 45/ 4’ on the other.
Il- pilloli huma bojod għal abjad maħmuġ, tondi, ċatti u mmarkati b ’ ‘ 4833 G ’ fuq naħa u b ’ ‘ 45/ 4 ’ fuq in- naħa l- oħra.
30 4.3 Contraindications
32 4. 3 Kontra- indikazzjonijiet
When meals are taken at irregular hours or skipped altogether, treatment with Tandemact may lead to hypoglycaemia due to the sulphonylurea component.
Meta l- ikliet jittieħdu f’ sigħat irregolari jew jinqabżu għal kollox, kura b’ Tandemact tista ’ twassal għal ipogliċemija minħallab l- komponent ta ’ sulphonylurea.
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 ’ insuffiċjenza kardijaka rrappurtati mis- suq meta pioglitazone intuża flimkien ma ’ l- insulina jew f’ pazjenti b’ passat ta ’ insuffiċjenza kardijaka.
Liver enzymes should be checked prior to the initiation of therapy with Tandemact in all patients.
33 ċċekkjati qabel ma tinbeda terapija b’ Tandemact f’ kull pazjent.
31 Following initiation of therapy with Tandemact, it is recommended that liver enzymes be monitored periodically based on clinical judgement.
Wara l- bidu tat- terapija b’ Tandemact, huwa rakkomandat li l- enżimi tal- fwied ikunu sorveljati perjodikament ibbażat fuq ġudizzju kliniku.
In some cases weight increase may be a symptom of cardiac failure, therefore weight should be closely monitored.
F’ xi każijiet żieda fil- piż tista ’ tkun sintomu ta ’ insuffiċjenza kardijaka, għalhekk il- piż għandu jiġi sorveljat mill- viċin.