qanastek/EMEA-V3 huggingface dataset:
Patients receiving medicinal products of either a narrow therapeutic ratio or medicinal products that require careful clinical monitoring should be followed closely.
Pazjenti li qegħdin jieħdu prodotti mediċinali b’ indiċi terapewtiċi dojoq jew prodotti mediċinali li jeħtieġu monitoraġġ kliniku b’ attenzjoni għandhom jiġu segwiti mill- qrib.
These medicinal products should be taken in a standardised way in relation to BYETTA injection.
Dawn il- prodotti mediċinali għandhom jittieħdu b’ mod standardizzat fir- rigward ta ’ l- injezzjoni ta ’ BYETTA.
If such medicinal products are to be administered with food, patients should be advised to, if possible, take them with a meal when BYETTA is not administered.
Jekk dawn il- prodotti mediċinali għandhom jittieħdu ma ’ l - ikel, il- pazjenti għandhom jingħataw parir biex, jekk possibbli, jeħduhom ma ’ ikla meta BYETTA ma tkunx qed tittieħed.
For oral medicinal products that are particularly dependent on threshold concentrations for efficacy, such as antibiotics, patients should be advised to take those medicinal products at least 1 hour before BYETTA injection.
Għal prodotti mediċinali li jittiehdu b ’ mod orali u li l- effikaċja tagħhom tiddependi partikolarment fuq il- livelli ta ’ konċentrazzjonijiet, bħal antibijotiċi, il- pazjenti għandhom jingħataw parir biex jieħdu dawn il- prodotti mediċinali mill- anqas siegħa qabel l- injezzjoni ta ’ BYETTA.
BYETTA is not expected to have any clinically relevant effects on the pharmacokinetics of metformin or sulphonylureas.
Mhux mistenni li BYETTA jkollha effetti klinikament relevanti fuq il- farmakokinetika ta ’ metformin jew sulphonylureas.
Hence no restriction in timing of intake of these medicinal products in relation to BYETTA injection are needed.
Għalhekk, m’ hemmx bżonn ta ’ restrizzjoni fil- ħin ta ’ meta dawn il- prodotti mediċinali jittieħdu fir- rigward ta ’ l- injezzjoni ta ’ BYETTA.
Gastroresistant formulations containing substances sensitive for degradation in the stomach, such as proton pump inhibitors, should be taken at least 1 hour before or more than 4 hours after BYETTA injection.
Formulazzjonijiet gastro- reżistenti li fihom sustanzi sensittivi għad- degradazzjoni fl- istonku, bħal inibituri tal- pompa tal- proton, għandhom jittieħdu mill- anqas siegħa qabel jew aktar minn 4 sigħat wara l- injezzjoni ta ’ BYETTA.
Paracetamol Paracetamol was used as a model medicinal product to evaluate the effect of exenatide on gastric emptying.
4 Paracetamol Paracetamol ġie użat bħala prodott mediċinali mudell biex jiġi valutat l- effett ta ’ exenatide fuq it - tbattil gastriku.
When 1000mg paracetamol was given with 10 µg BYETTA (0 h) and 1h, 2h and 4h after BYETTA injection, paracetamol AUCs were decreased by 21%, 23%, 24% and 14% respectively; Cmax was decreased by 37%, 56%, 54% and 41%, respectively; tmax was increased from 0.6h in the control period to 0.9h, 4.2h, 3.3h, and 1.6h, respectively.
Meta ngħataw 1000 mg paracetamol ma ’ 10 µg BYETTA (0 sigħat) u siegħa 1, sagħtejn u 4 sigħat wara l- injezzjoni ta ’ BYETTA, l- AUCs ta ’ paracetamol naqsu b’ 21%, 23%, 24% u 14% rispettivament; Cmax naqas b’ 37%, 56%, 54% u 41%, rispettivament; tmax żdied minn 0. 6 sigħat fil- perijodu ta ’ kontroll għal 0. 9 sigħat, 4. 2 sigħat, 3. 3 sigħat, and 1. 6 sigħat, rispettivament.
Paracetamol AUC, Cmax and tmax were not significantly changed when paracetamol was given 1 hour before BYETTA injection.
Ma kienx hemm tibdil sinifikanti fl- AUC, Cmax u tmax ta ’ paracetamol meta paracetamol ingħata siegħa qabel l- injezzjoni ta ’ BYETTA.
No adjustment to paracetamol dosing is required based on these study results.
Fuq il- bażi tar- riżultati ta ’ dawn l- istudji mhux meħtieġ aġġustament tad- doża ta ’ paracetamol.
4 HMG CoA reductase inhibitors Lovastatin AUC and Cmax were decreased approximately 40% and 28%, respectively, and Tmax was delayed about 4 h when BYETTA (10 µg BID) was administered concomitantly with a single dose of lovastatin (40 mg) compared with lovastatin administered alone.
Inibituri ta ’ HMG CoA reductase L- AUC u Cmax ta ’ lovastatin naqsu b’ madwar 40% u 28%, rispettivament, u kien hemm dewmien ta ’ madwar 4 sigħat f’ Tmax meta BYETTA (10 µg BID) ingħatat fl- istess waqt ma ’ doża waħda ta ’ lovastatin (40 mg) mqabbel ma ’ meta lovastatin ingħata waħdu.
In the 30-week placebo-controlled clinical trials, concomitant use of BYETTA and HMG CoA reductase inhibitors was not associated with consistent changes in lipid profiles (see section 5.1).
Fl- istudji kliniċi kkontrollati bil - plaċebo li damu 30 ġimgħa, l- użu fl- istess waqt ta ’ BYETTA u inibituri ta ’ HMG CoA reductase ma ġiex assoċjat ma ’ tibdil konsistenti fil- profili tal- lipidi (ara sezzjoni 5. 1).
Although no predetermined dose adjustment is required, one should be aware of possible changes in LDL-C or total cholesterol.
Għalkemm mhux meħtieġ aġġustament tad- doża li jkun stabbilit minn qabel, wieħed għandu jkun konxju tat- tibdil possibbli fl - LDL- C jew fil- kolesterol totali.
Lipid profiles should be monitored regularly.
Il- profili tal- lipidi għandhom jiġu osservati regolarment.
Digoxin, lisinopril and warfarin A delay in tmax of about 2h was observed when digoxin, lisinopril or warfarin was administered 30 min after exenatide.
Digoxin, lisinopril u warfarin Ġie osservat dewmien ta ’ madwar sagħtejn f’ tmax meta digoxin, lisinopril jew warfarin ingħataw 30 minuta wara exenatide.
No clinically relevant effects on Cmax or AUC were observed.
Ma ġie osservat l- ebda effett klinikament relevanti fuq Cmax jew AUC.
However, since market introduction, increased INR has been reported during concomitant use of warfarin and BYETTA.
Madanakollu, mill- introduzzjoni fis- suq, ġiet irrapportata żieda fl- INR waqt l- użu ta ’ warfarin u BYETTA fl- istess waqt.
INR should be closely monitored during initiation and dose increase of BYETTA therapy in patients on warfarin and/ or cumarol derivatives (see section 4.8).
F’ pazjenti fuq warfarin u/ jew derivattivi ta ’ cumarol, l- INR għandu jiġi osservat mill- qrib kemm fil- bidu tal- kura b’ BYETTA u kif ukoll meta jkun hemm żieda fid- doża ta ’ BYETTA (ara sezzjoni 4. 8).
Ethinyl estradiol and levonorgestrel Administration of a combination oral contraceptive (30 µg ethinyl estradiol plus 150 µg levonorgestrel) one hour before BYETTA (10 µg BID) did not alter the AUC, Cmax or Cmin of either ethinyl estradiol or levonorgestrel.
Ethinyl estradiol and levonorgestrel It- teħid ta ’ kontraċettiv orali kompost (30µg ethinyl estradiol flimkien ma ’ 150µg levonorgestrel) siegħa qabel BYETTA (10µg BID) ma ġabx tibdil fl- AUC, fis- Cmax jew fis- Cmin ta ’ ethinyl estradiol jew ta ’ levonorgestrel.
Administration of the oral contraceptive 30 minutes after BYETTA did not affect AUC but resulted in a reduction of the Cmax of ethinyl estradiol by 45%, and Cmax of levonorgestrel by 27-41%, and a delay in tmax by 2-4 h due to delayed gastric emptying.
It- teħid tal- kontraċettiv orali 30 minuta wara BYETTA ma ġabx tibdil fl- AUC iżda kien hemm tnaqqis fis - Cmax ta ’ ethinyl estradiol b’ 45% u fis- Cmax ta ’ levonorgestrel b’ 27 – 41% u żieda biex jintlaħaq it- tmax ta ’ bejn sagħtejn u 4 sigħat minħabba li kien hemm dewmien biex jitbattal l- istonku.
The reduction in Cmax is of limited clinical relevance and no adjustment of dosing of oral contraceptives is required.
It- tnaqqis fis- Cmax ma tantx hija klinikament rilevanti u m’ hemmx bżonn ta ’ aġġustament fid- dożaġġ tal- kontraċettivi orali.
There are no adequate data from the use of BYETTA in pregnant women.
M’ hemmx tagħrif biżżejjed dwar l- użu ta ’ BYETTA waqt it- tqala.
Studies in animals have shown reproductive toxicity (see section 5.3).
Studji fl- annimali wrew tossiċità fis- sistema riproduttiva (ara sezzjoni 5. 3).
BYETTA should not be used during pregnancy and the use of insulin is recommended.
BYETTA m’ għandiex tintuża waqt it- tqala u hija rrakkomandata l- użu ta ’ l- insulina.
If a patient wishes to become pregnant, or pregnancy occurs, treatment with BYETTA should be discontinued.
Jekk pazjenta tixtieq toħroġ tqila, jew it- tqala sseħħ, għandha titwaqqaf il- kura b’ BYETTA.
It is unknown whether exenatide is excreted in human milk.
Mhux magħruf jekk exenatide joħroġx fil- ħalib uman.
BYETTA should not be used if breast feeding.
BYETTA m’ għandiex tintuża waqt it- treddigħ.
When BYETTA is used in combination with a sulphonylurea, patients should be advised to take precautions to avoid hypoglycaemia while driving and using machines.
Meta BYETTA tintuża flimkien ma ’ sulphonylurea, il- pazjenti għandhom jingħataw parir biex jieħdu l- prekawzjonijiet sabiex tiġi evitata l- ipogliċemija waqt is- sewqan u t- tħaddim ta ’ magni.
Table 1 lists adverse reactions reported from Phase 3 studies.
Tabella 1 tagħti r- reazzjonijiet avversi rrapportati minn studji ta ’ Fażi 3.
The table presents adverse reactions that occurred with an incidence ≥ 5% and more frequently among BYETTA-treated patients than insulin- or placebo-treated patients.
It- tabella turi reazzjonijiet avversi li seħħew b’ inċidenza ta ’ ≥5% u li kienu aktar frekwenti f’ pazjenti fuq kura ta ’ BYETTA milli f’ pazjenti fuq kura ta ’ insulina jew plaċebo.
The table also includes adverse reactions that occurred with an incidence ≥ 1% and with a statistically significantly higher and/ or ≥ 2X incidence among BYETTA-treated patients than insulin- or placebo-treated patients.
5 b’ inċidenza ta ’ ≥1% u b’ inċidenza, mil- lat statistiku, ogħla b’ mod sinifikanti u/ jew ≥2X f’ pazjenti fuq kura ta ’ BYETTA milli f’ pazjenti fuq kura ta ’ insulina jew plaċebo.
The reactions are listed below as MedDRA preferred term by system organ class and absolute frequency.
Ir- reazzjonijiet huma mniżżlin hawn taħt skond it- termini stabbiliti minn MedDRA ibbażati fuq is - sistema tal- klassifika ta ’ l- organi u l- frekwenza assoluta.
Patient frequencies are defined as: very common (≥ 1/ 10) and common (≥ 1/ 100, < 1/ 10).
Il- frekwenza hija mfissra hekk: komuni ħafna (≥1/ 10) u komuni (≥1/ 100, < 1/ 10).
Adverse reactions reported in long term phase 3 controlled studies1
Reazzjonijiet avversi rraportati f’ studji kkontrollati ta ’ fażi 3 fit- tul1
Body system/ adverse reaction terms
Sistema tal- ġisem/ termini tar - reazzjonijiet avversi
Frequency of occurrence
Frekwenza ta ’ inċidenti
Reactions
Reazzjonijiet
Common
Komuni
Metabolism and nutrition disorders Hypoglycaemia (with metformin and a sulphonylurea) 2
Disturbi fil- metaboliżmu u n- nutrizzjoni Ipogliċemija (b’ metformin u xi sulphonylurea) 2
Hypoglycaemia (with a sulphonylurea) Decreased appetite Nervous system disorders
Ipogliċemija (b’ sulphonylurea) Nuqqas ta ’ aptit Disturbi fis- sistema nervuża
Headache 2 Dizziness Gastrointestinal disorders
Uġigħ ta ’ ras 2 Sturdament Disturbi gastro- intestinali
Nausea Vomiting Diarrhoea Dyspepsia Abdominal pain Gastroesophageal reflux disease Abdominal distension Skin and subcutaneous tissue disorders
Tqalligħ Rimettar Dijarrea Dispepsja Uġigħ addominali Mard tar- rifluss gastro- esofagali Nefħa addominali Disturbi fil- ġilda u fit- tessuti ta ’ taħt il - ġilda
Hyperhidrosis 2 General disorders and administrative site conditions
Iperidrożi 2 Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata
1
Tħossok nervuż Astenja 2
Data from Phase 3 comparator-controlled studies versus placebo, insulin glargine or 30% soluble insulin aspart/ 70% insulin aspart protamine crystals (biphasic insulin aspart) in which patients also received metformin, thiazolidinediones or sulphonylurea in addition to BYETTA or comparator.
1 Tagħrif minn studji ta ’ Fażi 3 ikkontrollati b’ komparatur kontra plaċebo, insulin glargine jew 30% insulin aspart solubbli / 70% kristalli ta ’ insulin aspart protamine (insulin aspart bifażika) fejn minbarra BYETTA jew komparatur, il- pazjenti ngħataw ukoll metformin, thiazolidinediones jew sulphonylurea.
2 In insulin-comparator controlled studies in which metformin and a sulphonylurea were concomitant medicinal products, the incidence for these adverse reactions was similar for insulin- and BYETTA- treated patients.
2 F’ studji kkontrollati bl- insulina bħala komparatur u fejn metformin u xi sulphonylurea ngħataw fl - istess waqt, l- inċidenza ta ’ dawn ir- reazzjonijiet avversi kienet simili kemm għal dawk il- pazjenti fuq kura ta ’ insulina u kemm għal dawk fuq kura ta ’ BYETTA.
Hypoglycaemia In studies in patients treated with BYETTA and a sulphonylurea (with or without metformin), the incidence of hypoglycaemia was increased compared to placebo (23.5% and 25.2% versus 12.6% and 3.3%) and appeared to be dependent on the doses of both BYETTA and the sulphonylurea.
Ipogliċemija F’ studji li saru f’ pazjenti fuq kura ta ’ BYETTA u xi sulphonylurea (b’ metformin jew mingħajru), l - inċidenza ta ’ ipogliċemija żdiedet meta mqabbla ma ’ plaċebo (23. 5% u 25. 2% kontra 12. 6% u 3. 3%) u dehret li tiddependi fuq id- dożi kemm ta ’ BYETTA kif ukoll ta ’ sulphonylurea.
Most episodes of hypoglycaemia were mild to moderate in intensity, and all resolved with oral administration of carbohydrate.
Il- biċċa l - kbira ta ’ l- episodji ta ’ ipogliċemija kienu ħfief jew moderati fl- intensità, u kollha waqfu mat- teħid ta ’ karboidrat b’ mod orali.
Nausea The most frequently reported adverse reaction was nausea.
6 Tqalligħ L- aktar reazzjoni avversa li ġiet irrapportata ta ’ spiss kienet it- tqalligħ.
In patients treated with 5 µg or 10 µg BYETTA, generally 40-50% reported at least one episode of nausea.
F’ pazjenti kkurati b’ 5 µg jew b’ 10 µg BYETTA, ġeneralment 40 – 50% irrapportaw mill- anqas episodju wieħed ta ’ tqalligħ.
Most episodes of nausea were mild to moderate and occurred in a dose-dependent fashion.
Il - biċċa l- kbira ta ’ l- episodji ta ’ tqalligħ kienu ħfief jew moderati u kienu jiddependu fuq id- doża.
With continued therapy, the frequency and severity decreased in most patients who initially experienced nausea.
Bit - tkomplija tal- kura, l- frekwenza u s- severità naqsu fil- biċċa l- kbira tal- pazjenti li inizjalment esperjenzaw it- tqalligħ.
The incidence of withdrawal due to adverse events was 8% for BYETTA-treated patients, 3% for placebo-treated and 1% for insulin-treated patients in the long-term controlled trials (16 weeks or longer).
L- inċidenza tat- twaqqif tal- kura minħabba avvenimenti avversi kienet ta ’ 8% għal pazjenti fuq kura ta ’ BYETTA, 3% għal dawk fuq plaċebo u 1% għal pazjenti fuq kura ta ’ insulina fl- istudji kkontrollati fit- tul (16- il ġimgħa jew aktar).
The most common adverse events leading to withdrawal for BYETTA-treated patients were nausea (4% of patients) and vomiting (1%).
L- aktar avvenimenti avversi komuni li wasslu għat - twaqqif f’ pazjenti fuq kura ta ’ BYETTA kienu tqalligħ (4% tal- pazjenti) u rimettar (1%).
For placebo-treated or insulin-treated patients, < 1% withdrew due to nausea or vomiting.
F’ pazjenti fuq kura ta ’ plaċebo jew insulina, < 1% waqfu minħabba tqalligħ jew rimettar.
6 BYETTA-treated patients in the open-label extension studies at 82 weeks experienced similar types of adverse events observed in the controlled trials.
Fl- istudji ta ’ estensjoni open- label, pazjenti fuq kura ta ’ BYETTA esperjenzaw fi 82 ġimgħa avvenimenti avversi simili għal dawk osservati fl- istudji kkontrollati.
Injection site reactions Injection site reactions have been reported in approximately 5.1% of subjects receiving BYETTA in long-term (16 weeks or longer) controlled trials.
Reazzjonijiet fis- sit ta ’ l- injezzjoni Reazzjonijiet fis- sit ta ’ l- injezzjoni ġew irrapportati f’ madwar 5. 1% tas- suġġetti li ħadu BYETTA f’ studji kkontrollati fit- tul (16- il ġimgħa jew aktar).
These reactions have usually been mild and usually did not result in discontinuation of BYETTA.
Dawn ir- reazzjonijiet normalment kienu ħfief u ma rriżultawx fit- twaqqif tat- terapija ta ’ BYETTA.
Immunogenicity Consistent with the potentially immunogenic properties of protein and peptide pharmaceuticals, patients may develop anti-exenatide antibodies following treatment with BYETTA.
Immunoġeniċità Konsistenti mal- kwalitajiet potenzjalment immunoġeniċi ta ’ farmaċewtiċi magħmulin minn proteina jew peptide, pazjenti jistgħu jiżviluppaw anti- korpi kontra exenatide wara l- kura b’ BYETTA.
In most patients who develop antibodies, antibody titres diminish over time and remain low through 82 weeks.
Fil - biċċa l- kbira tal- pazjenti li jiżviluppaw anti- korpi, l- ammont ta ’ anti- korpi jonqos biż- żmien u jibqa ’ baxx matul it- 82 ġimgħa ta ’ osservazzjoni.
Overall the percentage of antibody positive patients was consistent across clinical trials.
B’ mod ġenerali l- persentaġġ ta ’ pazjenti li kienu posittivi għall- anti- korpi kien konsistenti fuq firxa ta ’ studji kliniċi.
Patients who developed anti-exenatide antibodies had similar rates and types of adverse events as those with no anti-exenatide antibodies.
Pazjenti li żviluppaw anti- korpi kontra exenatide kellhom rati u tipi ta ’ avvenimenti avversi simili għal dawk mingħajr anti- korpi kontra exenatide.
In the three placebo-controlled trials (n=963) 38% of patients had low titre anti-exenatide antibodies at 30 weeks.
Fit- tliet studji kkontrollati bil- plaċebo (n=963) 38% tal- pazjenti kellhom ammont baxx ta ’ anti- korpi kontra exenatide mat- 30 ġimgħa.
For this group, the level of glycaemic control (HbA1c) was generally comparable to that observed in those without antibody titres.
F’ dan il- grupp, il- livell tal- kontroll tal- gliċemija (HbA1c) kien ġeneralment komparabbli ma ’ dak osservat f’ pazjenti mingħajr ammonti ta ’ anti- korpi.
An additional 6% of patients had higher titre antibodies at 30 weeks.
6% oħra ta ’ pazjenti kellhom ammont ta ’ anti- korpi ogħla mat- 30 ġimgħa.
About half of this 6% (3% of the total patients given BYETTA in the controlled studies), had no apparent glycaemic response to BYETTA.
Madwar nofs ta ’ dawn is- 6% (3% tat- total ta ’ pazjenti li ngħataw BYETTA fl- istudji kkontrollati), ma kellhom l- ebda rispons gliċemiku apparenti għal BYETTA.
In two insulin- comparator controlled trials (n=475) comparable efficacy and adverse events were observed in BYETTA-treated patients regardless of antibody titre.
F’ żewġ studji kkontrollati bl- insulina bħala komparatur (n=475) ġie osservat li l- effikaċja u l- avvenimenti avversi kienu simili f’ pazjenti fuq kura ta ’ BYETTA u ma jiddipendux mill- ammont ta ’ anti- korpi.
Examination of antibody-positive specimens from one long-term uncontrolled study revealed no significant cross-reactivity with similar endogenous peptides (glucagon or GLP-1).
L- eżaminazzjoni ta ’ kampjuni posittivi għall- anti- korpi minn studju wieħed mhux ikkontrollat magħmul fit- tul ma wrew ebda reazzjoni sinifikanti meta ġew assoċjati ma ’ peptidi endoġeni simili (glucagon jew GLP- 1).
Spontaneous reports Since market introduction of BYETTA, the following additional adverse reactions have been reported:
Rapporti spontanji Mill- introduzzjoni fis- suq ta ’ BYETTA, ġew irrapportati wkoll ir- reazzjonijiet avversi li ġejjin:
Immune system disorders: anaphylactic reaction, very rarely.
Disturbi tas- sistema immuni: b’ mod rari ħafna, reazzjoni anafilattika
Metabolism and nutritional disorders: dehydration, generally associated with nausea, vomiting and/ or diarrhoea.
Disturbi tal- metaboliżmu u n- nutrizzjoni: deidrazzjoni, ġeneralment assoċjata ma ’ tqalligħ, rimettar u/ jew dijarrea.
Nervous system disorders: dysgeusia, somnolence.
Disturbi tas- sistema nervuża: disgewżja, ngħas.
Gastrointestinal disorders: eructation, constipation, flatulence, acute pancreatitis (see section 4.4).
Disturbi gastro- intestinali: tifwiq, stitikezza, gass fl- istonku, pankreatite akuta (ara sezzjoni 4. 4).
Renal and urinary disorders: altered renal function, including acute renal failure, worsened chronic renal failure, renal impairment, increased serum creatinine (see section 4.4).
Disturbi fil- kliewi u fis- sistema urinarja: kambjament fil- funzjoni renali, li jinkludi insuffiċjenza renali akuta, insuffiċjenza renali kronika li tmur għall- agħar, indeboliment renali, żieda fil- krejatinina fis - serum (ara sezzjoni 4. 4).
Skin and subcutaneous tissue disorders: macular rash, papular rash, pruruitis, urticaria, angioneurotic oedema.
7 Disturbi tal- ġilda u tat- tessuti ta ’ taħt il- ġilda: raxx li tippreżenta ruħha bit- tbajja ’, raxx li tippreżenta ruħha bl- infafet, ħakk, urtikarja, edema angjo- newrotika.
Investigations: international normalised ratio increased with concomitant warfarin, some reports associated with bleeding (see section 4.5).
Investigazzjonijiet: kien hemm żieda fl- INR bl- użu fl- istess waqt ta ’ warfarin, f’ xi każijiet flimkien ma ’ fsada (ara sezzjoni 4. 5).
Signs and symptoms of overdose may include severe nausea, severe vomiting and rapidly declining blood glucose concentrations.
Sinjali u sintomi ta ’ doża eċċessiva jistgħu jinkludu tqalligħ qawwi, rimettar qawwi u tnaqqis rapidu fil- livell ta ’ glucose fid- demm.
In the event of overdose, appropriate supportive treatment (possibly given parenterally) should be initiated according to the patient ’ s clinical signs and symptoms.
F’ każ ta ’ doża eċċessiva, għandha tinbeda l- kura adattata ta ’ sostenn (possibbilment b’ mod parenterali) skond is- sinjali u s- sintomi kliniċi tal- pazjent.
Other blood glucose lowering drugs, excl. insulins, ATC code:
Mediċini oħra li jbaxxu l- glucose fid- demm, barra l- insulini, Kodiċi ATC:
Mechanism of action Exenatide is an incretin mimetic that exhibits several antihyperglycaemic actions of glucagon-like peptide-1 (GLP-1).
Mekkaniżmu ta ’ azzjoni Exenatide huwa mimetiku ta ’ incretin li juri diversi azzjonijiet kontra l- ipergliċemija ta ’ glucagon- like peptide- 1 (GLP- 1).
The amino acid sequence of exenatide partially overlaps that of human GLP-1.
Is- sekwenza ta ’ l- aminoaċidi ta ’ exenatide tikkoinċidi parzjalment ma ’ dik ta ’ GLP- 1 uman.
Exenatide has been shown to bind to and activate the known human GLP-1 receptor in vitro, its mechanism of action mediated by cyclic AMP and/ or other intracellular signaling pathways.
Ġie muri li in vitro exenatide jingħaqad u jattiva r- riċettur GLP- 1 uman u l- mekkaniżmu ta ’ azzjoni tiegħu huwa permezz ta ’ l- AMP ċikliku u/ jew mekkaniżmi oħra ta ’ sinjali intraċellulari.
Exenatide increases, on a glucose-dependent basis, the secretion of insulin from pancreatic beta cells.
Exenatide iżid, b’ mod dipendenti fuq glucose, is- sekrezzjoni ta ’ insulina miċ- ċelluli beta tal- frixa.
As blood glucose concentrations decrease, insulin secretion subsides.
Kif il- konċentrazzjonijiet ta ’ glucose fid- demm jonqsu, tonqos is- sekrezzjoni ta ’ insulina.
(see section 4.4).
Meta exenatide intuża flimkien ma ’ metformin biss, ma ġiet osservata l- ebda żieda fl- inċidenza ta ’ ipogliċemija aktar minn dik ta ’ plaċebo flimkien ma ’ metformin li jista ’ jkun minħabba dan il- mekkaniżmu insulinotropiku dipendenti fuq glucose (ara sezzjoni 4. 4).
Exenatide suppresses glucagon secretion which is known to be inappropriately elevated in type 2 diabetes.
Exenatide irażżan is- sekrezzjoni ta ’ glucagon li hi magħrufa li tkun iktar għolja milli suppost fid - dijabete tat- tip 2.
Lower glucagon concentrations lead to decreased hepatic glucose output.
Konċentrazzjonijiet anqas ta ’ glucagon iwasslu għal tnaqqis fil- produzzjoni epatika ta ’ glucose.
However, exenatide does not impair the normal glucagon response and other hormone responses to hypoglycaemia.
Madanakollu, exenatide ma jdgħajjifx ir- rispons normali ta ’ glucagon u ta ’ ormoni oħra għall- ipogliċemija.
Exenatide slows gastric emptying thereby reducing the rate at which meal-derived glucose appears in the circulation.
Exenatide itawwal il- ħin sabiex jitbattal l- istonku u b’ hekk inaqqas ir- rata li biha glucose li ġej mill - ikel jidher fiċ- ċirkolazzjoni.
Pharmacodynamic effects BYETTA improves glycaemic control through the immediate and sustained effects of lowering both postprandial and fasting glucose concentrations in patients with type 2 diabetes.
Effetti farmakodinamiċi BYETTA ttejjeb il- kontroll gliċemiku permezz ta ’ l- effetti immedjati u fit- tul li jkun hemm mat - tnaqqis fil- livelli ta ’ glucose kemm wara l- ikel, kif ukoll wara s- sawm, f’ pazjenti bid- dijabete tat- tip 2.
Clinical efficacy The clinical studies comprised 3945 subjects (2997 treated with exenatide), 56% men and 44% women, 319 subjects (230 treated with exenatide) were ≥ 70 years of age and 34 subjects (27 treated with exenatide) were ≥ 75 years of age.
Effikaċja klinika L- istudji kliniċi kienu kostitwiti minn 3945 suġġett (2997 fuq kura ta ’ exenatide), 56% rġiel u 44% nisa, 319- il suġġett (230 fuq kura ta ’ exenatide) kienu ≥70 sena u 34 suġġett (27 fuq kura ta ’ exenatide) kienu ≥75 sena.
BYETTA reduced HbA1c and body weight in patients treated for 30 weeks in three placebo-controlled studies, whether the BYETTA was added to metformin, a sulphonylurea or a combination of both.
BYETTA naqset l- HbA1c u l- piż tal- ġisem f’ pazjenti kkurati għal 30 ġimgħa f’ tliet studji kkontrollati bi plaċebo, kemm jekk BYETTA ġiet miżjuda ma ’ metformin, ma ’ xi sulphonylurea jew ma ’ metformin u xi sulphonylurea flimkien.
These reductions in HbA1c were generally observed at 12 weeks after initiation of treatment.
Dan it- tnaqqis fl- HbA1c ġeneralment ġie osservat fit- 12- il ġimgħa mill- bidu tal- kura.
See Table 2.
Ara Tabella 2.
The reduction in HbA1c was sustained and the weight loss continued for at least 82 weeks in the subset of 10 µg BID patients completing both the placebo-controlled studies and the uncontrolled study extensions (n=137).
It- tnaqqis fl- HbA1c inżamm u t- tnaqqis fil- piż tkompla għal mill- anqas 82 ġimgħa fil- kategorija ta ’ pazjenti fuq 10 µg BID li temmew kemm l- istudji kkontrollati bil- plaċebo kif ukoll l- istudji ta ’ estensjoni mhux ikkontrollati (n=137).
8 Table 2:
8 Tabella 2:
Combined results of the 30 week placebo controlled studies (intent to treat patients)
Ġabra ta ’ riżultati ta ’ l- istudji kkontrollati bil- plaċebo li damu 30 ġimgħa (pazjenti fil- grupp bl- intenzjoni tal- kura)
N Baseline HbA1c(%) HbA1c(%) change from base line
N Linja bażi ta ’ HbA1c (%) Bidla f’ HbA1c (%) mil - linja bażi
483 8.48 0.08
483 8. 48 0. 08
480 8.42 -0.59
480 8. 42 - 0. 59
483 8.45 -0.89
483 8. 45 - 0. 89
Proportion of patients (%) achieving HbA1c ≤ 7%
Proporzjon ta ’ pazjenti (%) li kisbu HbA1c ≤7%
25.3
25. 3
33.6
33. 6
Proportion of patients (%) achieving HbA1c ≤ 7% (patients completing studies)
Proporzjon ta ’ pazjenti (%) li kisbu HbA1c ≤7% (pazjenti li temmew l - istudji)
10.0
10. 0
29.6
29. 6
38.5
38. 5
Baseline weight(kg) Change of weight from baseline(kg)
Linja bażi tal- piż( kg) Bidla fil- piż mil- linja bażi( kg)
99.26 -0.65
99. 26 - 0. 65
97.10 -1.41
97. 10 - 1. 41
98.11 -1.91
98. 11 - 1. 91
In a placebo-controlled study of 16 weeks duration, BYETTA (n=121) or placebo (n=112) was added to existing thiazolidinedione treatment, with or without metformin.
F’ studju kkontrollat bi plaċebo li dam 16- il ġimgħa, BYETTA (n=121) jew plaċebo (n=112) ġie miżjud mal- kura eżistenti ta ’ thiazolidinedione, b’ metformin jew mingħajru.
BYETTA (5 µg BID for 4 weeks, followed by 10 µg BID) resulted in statistically significant reductions from baseline HbA1c compared to placebo (-0.8% versus +0.1%) as well as significant reductions in body weight (-1.5 versus -0.2 kg).
BYETTA (5 µg BID għal 4 ġimgħat, segwit b’ 10 µg BID) irriżulta f’ tnaqqis statistikament sinifikanti mil- linja bażi ta ’ HbA1c meta mqabbel ma ’ plaċebo (- 0. 8% kontra +0. 1%) kif ukoll tnaqqis sinifikanti fil- piż tal- ġisem (- 1. 5 kontra - 0. 2 kg).
When BYETTA was used in combination with a thiazolidinedione, the incidence of hypoglycaemia was similar to that of placebo in combination with a thiazolidinedione.
Meta BYETTA ntużat flimkien ma ’ thiazolidinedione, l- inċidenza ta ’ l- ipogliċemija kienet simili għal dik ta ’ plaċebo użat flimkien ma ’ thiazolidinedione.
The experience in patients > 65 years and in patients with impaired renal function is limited.
L- esperjenza f’ pazjenti > 65 sena u f’ pazjenti b’ indeboliment tal- funzjoni renali hija limitata.
In insulin-comparator studies BYETTA (5 µg BID for 4 weeks, followed by 10 µg BID) in combination with metformin and sulphonylurea significantly (statistically and clinically) improved glycaemic control, as measured by decrease in HbA1c.
F’ studji bl- insulina bħala komparatur, BYETTA (5 µg BID għal 4 ġimgħat, segwit b’ 10 µg BID) użata flimkien ma ’ metformin u sulphonylurea tejbet b’ mod sinifikanti (statistikament u klinikament) il - kontroll gliċemiku, imkejjel permezz tat- tnaqqis fl’ HbA1c.
This treatment effect was comparable to that of insulin glargine in a 26-week study (mean insulin dose 24.9 IU/ day, range 4-95 IU/ day, at the end of study) and biphasic insulin aspart in a 52-week study (mean insulin dose 24.4 IU/ day, range 3-78 IU/ day, at the end of study).
Dan l- effett tal- kura kien komparabbli ma ’ dak ta ’ insulin glargine f’ studju ta ’ 26 ġimgħa (doża medja ta ’ insulina ta ’ 24. 9 IU/ ġurnata, medda ta ’ 4- 95 IU/ ġurnata, fi tmiem l- istudju) u insulin aspart bifażiku f’ studju ta ’ 52 ġimgħa (doża medja ta ’ insulina ta ’ 24. 4 IU/ ġurnata, medda ta ’ 3- 78 IU/ ġurnata, fi tmiem l- istudju).
BYETTA lowered HbA1c from 8.21 (n=228) and 8.6% (n=222) by 1.13 and 1.01% while insulin glargine lowered from 8.24 (n=227) by 1.10% and biphasic insulin aspart from 8.67 (n=224) by 0.86%.
BYETTA naqset l- HbA1c minn 8. 21% (n=228) u 8. 6% (n=222) b’ 1. 13% u 1. 01% filwaqt li insulin glargine naqsu minn 8. 24% (n=227) b’ 1. 10% u insulin aspart bifażiku minn 8. 67% (n=224) b’ 0. 86%.
Weight loss of 2.3 kg (2.6%) was achieved with BYETTA in the 26 week study and a loss of 2.5 kg (2.7%) in a 52-week study whereas treatment with insulin was associated with weight gain.
Kien hemm telf ta ’ piż ta ’ 2. 3 kg (2. 6%) b’ BYETTA fl- istudju ta ’ 26 ġimgħa u telf ta ’ 2. 5 kg (2. 7%) f’ studju ta ’ 52 gimgħa filwaqt li kura b’ insulina kienet assoċjata ma ’ żieda fil- piż.
Seven-point self monitored blood glucose profiles (before and after meals and at 3 am) demonstrated significantly reduced glucose values compared to insulin in the postprandial periods after BYETTA injection.
Id- differenzi minħabba l- kura (BYETTA mingħajr komparatur) kienu - 4. 1 kg fl- istudju ta ’ 26 ġimgħa u - 5. 4 kg fl- istudju ta ’ 52 ġimgħa. Il - profili ta ’ glucose fid- demm b ’ 7 punti meħuda mill- pazjent stess (qabel u wara l- ikel u fit- 3 ta ’ filgħodu) urew tnaqqis b’ mod sinifikanti fil- valuri ta ’ glucose meta mqabbla ma ’ insulina fil- perijodi ta ’ wara l- ikel wara l- injezzjoni ta ’ BYETTA.
Premeal blood glucose concentrations were generally lower in patients taking insulin compared to BYETTA.
Il- konċentrazzjonijiet ta ’ glucose fid- demm qabel l- ikel kienu ġeneralment anqas f’ pazjenti kkurati b’ insulina meta mqabbla ma ’ dawk ikkurati b’ BYETTA.
Mean daily blood glucose values were similar between BYETTA and insulin.
Il- valuri medji ta ’ kuljum ta ’ glucose fid- demm f’ BYETTA u f’ insulina kienu simili.
In these studies the incidence of hypoglycaemia was similar for BYETTA and insulin treatment.
F’ dawn l- istudji l- inċidenza ta ’ l- ipogliċemija bil- kura ta ’ BYETTA u bil- kura ta ’ l- insulina kienet simili.
BYETTA has shown no adverse effects on lipid parameters.
BYETTA ma wrietx effetti avversi fuq il- parametri tal- lipidi.
A trend for a decrease in triglycerides has been observed with weight loss.
Mat- tnaqqis fil- piż ġiet osservata tendenza ta ’ tnaqqis fit- trigliċeridi.
Clinical studies with BYETTA have indicated improved beta-cell function, using measures such as the homeostasis model assessment for beta-cell function (HOMA-B) and the proinsulin to insulin ratio.
Studji kliniċi b’ BYETTA indikaw titjib fil- funzjoni taċ- ċelluli beta, dokumentat permezz ta’ indikaturi bħall- valutazzjoni tal- mudell ta ’ l- omejostażi (HOMA- B) għall- funzjoni taċ- ċelluli beta u l - proporzjon ta ’ proinsulina għal insulina.
A pharmacodynamic study demonstrated in patients with type 2 diabetes (n=13) a restoration of first phase insulin secretion and improved second phase insulin secretion in response to an intravenous bolus of glucose.
Studju farmakodinamiku f’ pazjenti bid- dijabete tat- tip 2 (n=13) wera tiġdid ta ’ l- ewwel fażi tas- sekrezzjoni ta ’ insulina u titjib tat- tieni fażi tas- sekrezzjoni ta ’ insulina b’ rispons għal bolus ta ’ glucose minn ġol- vina.
A reduction in body weight was seen in patients treated with BYETTA irrespective of the occurrence of nausea although the reduction was larger in the group with nausea (mean reduction 2.4kg versus 1.7kg) in the long term controlled studies of up to 52 weeks.
Ġie osservat tnaqqis fil- piż f’ pazjenti b’ kura ta ’ BYETTA rrispettivament mill- każijiet ta ’ tqalligħ għalkemm it- tnaqqis kien akbar fil- grupp ta ’ pazjenti bit- tqalligħ (tnaqqis medju ta ’ 2. 4 kg kontra 1. 7 kg) fl- istudji kkontrollati fit- tul sa 52 ġimgħa.
Administration of exenatide has been shown to reduce food intake, due to decreased appetite and increased satiety.
9 Ġie muri li l- għoti ta ’ exenatide, naqqas it- teħid ta ’ l- ikel minħabba nuqqas ta ’ aptit u żieda fis - sensazzjoni ta ’ xaba ’.
9 5.2 Pharmacokinetic properties
5. 2 Tagħrif farmakokinetiku
Absorption Following subcutaneous administration to patients with type 2 diabetes, exenatide reaches median peak plasma concentrations in 2 h.
Assorbiment Wara li jingħata taħt il- ġilda lil pazjenti bid- dijabete tat- tip 2, exenatide jilħaq il- medjan ta ’ l- ogħla konċentrazzjonijiet fil- plażma f’ sagħtejn.
Mean peak exenatide concentration (Cmax) was 211 pg/ ml and overall mean area under the curve (AUC0-inf) was 1036 pg • h/ ml following subcutaneous administration of a 10 µg dose of exenatide.
Il- medja ta ’ l- ogħla konċentrazzjonijiet ta ’ exenatide (Cmax) kienet ta ’ 211 pg/ ml u b’ kollox il- medja ta ’ l- erja taħt il- kurva (AUC0- inf) kienet ta ’ 1036 pg • h/ ml wara l- għoti ta ’ doża ta ’ 10 µg exenatide taħt il- ġilda.
Exenatide exposure increased proportionally over the therapeutic dose range of 5 µg to 10 µg.
L- espożizzjoni għal exenatide żdiedet b’ mod proporzjonali maż- żieda fid- doża terapewtika minn 5 µg sa 10 µg.
Similar exposure is achieved with subcutaneous administration of exenatide in the abdomen, thigh, or arm.
Meta exenatide jingħata minn taħt il- ġilda, l- espożizzjoni miksuba hija simili kemm jekk jingħata fl- addome, kemm jekk jingħata fil - koxxa u kemm jekk jingħata fid- driegħ.
Distribution The mean apparent volume of distribution of exenatide following subcutaneous administration of a single dose of exenatide is 28 l.
Distribuzzjoni Il- volum apparenti medju ta ’ distribuzzjoni ta ’ exenatide wara li tingħata doża waħda ta ’ exenatide taħt il- ġilda hu ta ’ 28 l.
Metabolism and Elimination Nonclinical studies have shown that exenatide is predominantly eliminated by glomerular filtration with subsequent proteolytic degradation.
Metaboliżmu u eliminazzjoni Studji mhux kliniċi wrew li exenatide huwa fil- biċċa l- kbira eliminat permezz ta ’ filtrazzjoni glomerulari u sussegwentement b’ degradazzjoni proteolitika.
In clinical studies the mean apparent clearance of exenatide is 9 l/ h and the mean terminal half-life is 2.4 h.
F’ studji kliniċi t- tneħħija apparenti medja ta ’ exenatide hi ta ’ 9 l/ h u l- half- life terminali medju hu ta ’ 2. 4 sigħat.
These pharmacokinetic characteristics of exenatide are independent of the dose.
Dawn il- karatteristiċi farmakokinetiċi ta ’ exenatide huma indipendenti mid- doża.
Special populations Patients with renal impairment In patients with mild (creatinine clearance 50 to 80 ml/ min) or moderate renal impairment (creatinine clearance 30 to 50 ml/ min), exenatide clearance was mildly reduced compared to clearance in individuals with normal renal function (13% reduction in mild and 36% reduction in moderate renal impairment).
Popolazzjonijiet speċjali Pazjenti b’ indeboliment renali F’ pazjent b’ indeboliment renali ħafif (tneħħija ta ’ krejatinina 50 sa 80 ml/ min) jew moderat (tneħħija ta ’ krejatinina 30 sa 50 ml/ min), it- tneħħija ta ’ exenatide naqset bi ftit meta mqabbla mat- tneħħija f’ individwi b’ funzjoni renali normali (tnaqqis ta ’ 13% f’ indeboliment renali ħafif u 36% f’ indeboliment renali moderat).
Clearance was significantly reduced by 84% in patients with end-stage renal disease receiving dialysis (see section 4.2).
Kien hemm tnaqqis b’ mod sinifikanti ta ’ 84% fit- tneħħija f’ pazjenti b’ mard renali fl- aħħar stadju u li qegħdin fuq dijalisi (ara sezzjoni 4. 2).
Patients with hepatic insufficiency No pharmacokinetic study has been performed in patients with hepatic insufficiency.
Pazjenti b’ insuffiċjenza epatika Ma sarux studji farmakokinetiċi f’ pazjenti b’ insuffiċjenza epatika.
Exenatide is cleared primarily by the kidney, therefore hepatic dysfunction is not expected to affect blood concentrations of exenatide.
Exenatide huwa primarjament imneħħi mill- kilwa, u għalhekk l- anormalità fil- funzjoni epatika mhux mistennija li taffettwa l - konċentrazzjonijiet ta ’ exenatide fid- demm.
Gender and race Gender and race have no clinically relevant influence on exenatide pharmacokinetics.
Sess u razza Is- sess u r- razza m’ għandhom l- ebda influwenza klinikament relevanti fuq il- farmakokinetika ta ’ exenatide.
Elderly Data in elderly are limited, but suggest no marked changes in exenatide exposure with increased age up to about 75 years old.
Anzjani It- tagħrif fuq l- anzjani huwa limitat, iżda m’ hemmx indikazzjonijiet ta ’ bidliet kbar fl- espożizzjoni ta ’ exenatide maż- żieda fl- età sa madwar l- età ta ’ 75 sena.
There are no pharmacokinetic data in patients > 75 years.
M’ hemmx tagħrif dwar il- farmakokinetika f’ pazjenti > 75 sena.
Children and adolescents In a single-dose pharmacokinetic study in 13 patients with type 2 diabetes and between the ages of 12 and 16 years, administration of exenatide (5µg) resulted in slightly lower mean AUC (16% lower) and Cmax (25% lower) compared to those observed in adults.
Tfal u adolexxenti F’ studju farmakokinetiku b’ doża waħda f’ 13- il pazjent bid- dijabete tat- tip 2 b’ etajiet bejn 12 u 16- il sena, l- għoti ta ’ exenatide (5 µg) irriżulta f’ tnaqqis żgħir fil- medja tal- AUC (tnaqqis ta ’ 16%) u tas - Cmax (tnaqqis ta ’ 25%) meta mqabbla ma dawk osservati fl- adulti.
Non-clinical data reveal no special hazards for humans based on conventional studies of safety pharmacology, repeat-dose toxicity, or genotoxicity.
Informazzjoni li mhix klinika, magħmula fuq studji konvenzjonali ta ’ sigurtà farmakoloġika, ta ’ effett tossiku minn dożi ripetuti jew ta ’ effett tossiku fuq il- ġeni, ma ’ turi l- ebda periklu speċjali għall - bnedmin
In female rats given exenatide for 2 years, an increased incidence of benign thyroid C− cell adenomas was observed at the highest dose, 250 µg/ kg/ day, a dose that produced an exenatide plasma exposure 130-fold the human clinical exposure.
10 Fil- firien nisa li ġew mgħotija exenatide għal sentejn, ġiet osservata żieda fl- inċidenza ta ’ adenomi beninni fiċ- celluli C tat- tirojde mad- doża l- iżjed għolja, 250 µg/ kg/ ġurnata, doża li tagħti espożizzjoni ta ’ exenatide fil- plażma ta ’ 130- il darba iżjed minn espożizzjoni klinika fil- bniedem.
This incidence was not statistically significant when adjusted for survival.
Din l- inċidenza ma kinitx statistikament sinifikanti meta aġġustata għas- sopravivenza.
There was no tumorigenic response in male rats or either sex of mice.
Ma kienx hemm rispons tumuriġeniku fil- firien rġiel jew fil- ġrieden kemm dawk nisa u kemm dawk irġiel.
10 Animal studies did not indicate direct harmful effects with respect to fertility or pregnancy.
Studji fl- annimali ma wrew ebda effetti perikolużi diretti fuq il- fertilità jew it- tqala.
Neonatal growth was reduced in mice exposed to high doses during late gestation and lactation.
Dożi għoljin ta ’ exenatide f’ nofs il- perijodu tat- tqala kkawżaw effetti skeltriċi u naqsu l- iżvilupp tal- fetu fil- ġrieden u naqsu l- iżvilupp tal- fetu fil- fniek. Naqas l- iżvilupp tal- wild fil- ġrieden esposti għal dożi għoljin waqt il- fażi finali tat- tqala u t- treddigħ.
metacresol mannitol glacial acetic acid sodium acetate trihydrate water for injections
metacresol mannitol glacial acetic acid sodium acetate trihydrate ilma għall- injezzjonijiet
This medicinal product must not be mixed with other medicinal products.
Dan il- prodott mediċinali m’ għandux jitħallat ma ’ prodotti mediċinali oħrajn.
Shelf life for pen in use:
Sentejn Żmien kemm iddum tajba l- pinna waqt l- użu:
30 days.
30 ġurnata
Do not freeze.
Aħzen fi friġġ (2°C - 8°C) Tagħmlux fil- friża
In use Store below 25 ºC.
Waqt l- użu Aħżen f’ temperatura taħt 25°C
The pen should not be stored with the needle attached.
M’ għandekx taħżen il- pinna bil- labra mwaħħla magħha.
Replace cap on pen in order to protect from light.
Erġa ’ poġġi l- kappa fuq il- pinna sabiex tilqa ’ mid- dawl.
Type I glass cartridge with a (bromobutyl) rubber plunger, rubber disc, and aluminium seal.
Skartoċċ tal- ħġieġ tat- tip I b’ planġer tal- lasktu (bromobutyl), disk tal- lasktu u siġill ta ’ l- aluminju.
Each cartridge is assembled into a disposable pen-injector (pen).
Kull skartoċċ huwa mmontat f’ strument ta ’ injezzjoni b’ forma ta ’ pinna (pinna) li jintrema wara li jintuża.
Each pre-filled pen contains 60 doses of sterile preserved solution (approximately 1.2ml)
Kull pinna mimlija għal- lest fiha 60 doża ta ’ soluzzjoni sterili ppreservata (kważi 1. 2ml)
Pack size of 1 and 3 pens.
Id- daqsijiet tal- pakketti huma ta ’ pinna 1 u ta ’ 3 pinen.
The following are examples of disposable needles that can be used with the BYETTA pen:
M’ humiex inklużi l- labar. Li gejjin huma eżempji ta ’ labar li jintużaw darba biss u li jistgħu jiġu użati mal- pinna ta ’ BYETTA:
29, 30 or 31 gauge (diameter 0.25 - 0.33mm) and 12.7, 8 or 5mm length.
29, 30 jew 31 gejġ (dijametru ta ’ 0. 25 – 0. 33 mm) u tul ta ’ 12. 7, 8 jew 5 mm.
6.6 Special precautions for disposal and other handling.
11 6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema u għal immaniġġar ieħor.
The patient should be instructed to discard the needle after each injection.
Il- pazjent għandu jiġi mgħarraf biex jarmi l- labra wara kull injezzjoni.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Kull fdal tal- prodott li ma jkunx intuża jew skart li jibqa wara l- użu tal- prodott għandu jintrema kif jitolbu l- liġijiet lokali.
Instructions for use BYETTA is for use by one person only.
Struzzjonijiet għall- użu BYETTA għandha tintuża minn persuna waħda biss.
11 The instructions for using the pen, included with the leaflet, must be followed carefully.
L- istruzzjonijiet dwar kif tintuża l- pinna, inkluż mal- fuljett, għandhom jiġu segwiti b’ attenzjoni.
The pen is stored without needle.
Il- pinna għandha tinħażen mingħajr il- labra.
BYETTA should not be used if particles appear or if the solution is cloudy and/ or coloured.
BYETTA m’ għandiex tintuża jekk jidhru xi frak, jekk is- soluzzjoni m’ hijiex ċara u/ jew għandha xi kulur.
BYETTA that has been frozen must not be used.
BYETTA li ġiet iffriżata m’ għandiex tintuża.
Eli Lilly Nederland B. V., Grootslag 1-5, NL-3991 RA Houten, The Netherlands.
Eli Lilly Nederland B. V., Grootslag 1- 5, NL- 3991 RA Houten, L- Olanda.
20 November 2006
20 ta ’ Novembru 2006
BYETTA 10 micrograms solution for injection, prefilled pen
BYETTA 10 mikrogrammi soluzzjoni għall- injezzjoni, pinna mimlija għal- lest.
Each dose contains 10 micrograms(µg) synthetic exenatide in 40 microlitres(µl), (0.25 mg exenatide per ml).
Kull doża fiha 10 mikrogrammi (µg) exenatide sintetiku f’ 40 mikrolitru (µl), (0. 25 mg exenatide kull ml).
Each dose contains 88 µg metacresol.
Kull doża fiha 88 µg metacresol.
The dose of BYETTA does not need to be adjusted on a day-by-day basis depending on self- monitored glycaemia.
13 M’ hemmx bżonn ta ’ aġġustament fid- doża ta ’ BYETTA ġurnata b’ ġurnata skond il- monitoraġġ gliċemiku magħmul mill- pazjent innifsu.
13 Limited experience exists concerning the combination of BYETTA with thiazolidinediones (see section 5.1).
L- esperjenza dwar l- użu ta ’ BYETTA flimkien ma ’ thiazolidinediones hija limitata (ara sezzjoni 5. 1).
BYETTA is not recommended for use in patients with end-stage renal disease or severe renal impairment (creatinine clearance < 30 ml/ min) (see section 4.4).
BYETTA mhux irrakkomandat għall- użu f’ pazjenti b’ mard renali fl- aħħar stadju jew b’ indeboliment renali qawwi (tneħħija tal- krejatinina: < 30 ml/ min) (ara sezzjoni 4. 4).
BYETTA has not been studied in patients with severe gastrointestinal disease, including gastroparesis.
14 BYETTA ma ġietx studjata f’ pazjenti b’ mard gastro- intestinali qawwi, fosthom il- gastroparesi.
14 There have been rare, spontaneously reported events of acute pancreatitis.
Ġew irrapportati avvenimenti rari u spontanji ta ’ pankreatite akuta.
The experience in patients with BMI ≤ 25 is limited.
L- esperjenza f’ pazjenti b’ BMI ≤ 25 hija limitata.
To reduce the risk of hypoglycaemia associated with the use of a sulphonylurea, reduction in the dose of sulphonylurea should be considered.
Biex jitnaqqas ir- riskju ta ’ l- ipogliċemija assoċjata ma ’ l- użu ta ’ xi sulphonylurea, għandu jiġi kkunsidrat it- tnaqqis fid- doża ta’ sulphonylurea.
Paracetamol Paracetamol was used as a model medicinal product to evaluate the effect of exenatide on gastric emptying.
15 Paracetamol Paracetamol ġie użat bħala prodott mediċinali mudell biex jiġi valutat l- effett ta ’ exenatide fuq it - tbattil gastriku.
15 HMG CoA reductase inhibitors Lovastatin AUC and Cmax were decreased approximately 40% and 28%, respectively, and Tmax was delayed about 4 h when BYETTA (10 µg BID) was administered concomitantly with a single dose of lovastatin (40 mg) compared with lovastatin administered alone.
Inibituri ta ’ HMG CoA reductase L- AUC u Cmax ta ’ lovastatin naqsu b’ madwar 40% u 28%, rispettivament, u kien hemm dewmien ta ’ madwar 4 sigħat f’ Tmax meta BYETTA (10 µg BID) ingħatat fl- istess waqt ma ’ doża waħda ta ’ lovastatin (40 mg) mqabbel ma ’ meta lovastatin ingħata waħdu.
There are no adequate data from the use of BYETTA in pregnant women.
M’ hemmx tagħrif biżżejjed dwar l- użu ta’ BYETTA waqt it- tqala.
The table also includes adverse reactions that occurred with an incidence ≥ 1% and with a statistically significantly higher and/ or ≥ 2X incidence among BYETTA-treated patients than insulin- or placebo-treated patients.
16 b’ inċidenza ta ’ ≥1% u b’ inċidenza, mil- lat statistiku, ogħla b’ mod sinifikanti u/ jew ≥2X f’ pazjenti fuq kura ta ’ BYETTA milli f’ pazjenti fuq kura ta ’ insulina jew plaċebo.
16 Table 1:
Tabella 1:
2 In insulin-comparator controlled studies in which metformin and a sulphonylurea were concomitant medicinal products, the incidence for these adverse reactions was similar for insulin- and BYETTA- treated patients.
2 F’ studji kkontrollati bl- insulina bħala komparatur u fejn metformin u xi sulphonylurea ngħataw fl - istess waqt, l- inċidenza ta ’ dawn ir- reazzjonijiet avversi kienet simili għal pazjenti fuq kura ta ’ insulina u għal pazjenti fuq kura ta ’ BYETTA.
Nausea The most frequently reported adverse reaction was nausea.
17 Tqalligħ L- aktar reazzjoni avversa li ġiet irrapportata ta ’ spiss kienet it- tqalligħ.
17 BYETTA-treated patients in the open-label extension studies at 82 weeks experienced similar types of adverse events observed in the controlled trials.
Fl- istudji ta ’ estensjoni open- label, pazjenti fuq kura ta ’ BYETTA esperjenzaw fi 82 ġimgħa avvenimenti avversi simili għal dawk osservati fl- istudji kkontrollati.
In most patients who develop antibodies, antibody titres diminish over time and remain low through 82 weeks.
Fil - biċċa l- kbira tal- pazjenti li jiżviluppaw anti- korpi, l- ammont ta ’ anti- korpi jonqos biż- żmien u jibqa ’ baxx matul it- 82 ġimgħa ta ’ osservazzjoni
Metabolism and nutritional disorders: dehydration, generally associated with nausea, vomiting and/ or diarrhoea.
Disturbi tal- metaboliżmu u n- nutrizzjoni: deidratazzjoni, ġeneralment assoċjat ma ’ tqalligħ, rimettar u/ jew dijarrea..
Gastrointestinal disorders: eructation, constipation, flatulence, acute pancreatitis (see section 4.4).
Disturbi gastro- intestinali: tifwiq, stitikezza, gass fl- istonku. pankreatite akuta (ara sezzjoni 4. 4)
Skin and subcutaneous tissue disorders: macular rash, papular rash, pruruitis, urticaria, angioneurotic oedema.
18 Disturbi tal- ġilda u tat- tessuti ta ’ taħt il- ġilda: raxx li tippreżenta ruħha bit- tbajja ’, raxx li tippreżenta ruħha bl- infafet, ħakk, urtikarja, edema angjo- newrotika.