qanastek/EMEA-V3 huggingface dataset:
Each tablet contains sitagliptin phosphate monohydrate, equivalent to 25 mg sitagliptin.
Kiekvienoje tablet je yra sitagliptino fosfato monohidrato, atitinkan io 25 mg sitagliptino.
Film-coated tablet (tablet)
Pl vele dengta tablet.
Round, pink film-coated tablet with “ 221” on one side.
Tablet yra apvali, rausva, dengta pl vele, vienoje jos pus je yra žyma “ 221 ”.
For patients with type 2 diabetes mellitus, TESAVEL is indicated:
II tipo cukriniu diabetu sergan i pacient gydymas:
• to improve glycaemic control in combination with metformin when diet and exercise plus metformin alone do not provide adequate glycaemic control.
• derinant su metforminu glikemijos kontrolei gerinti tuo atveju, jeigu gydymo dieta, fiziniais pratimais ir kartu metforminu metu glikemija kontroliuojama nepakankamai;
• to improve glycaemic control in combination with a sulphonylurea when diet and exercise plus maximal tolerated dose of a sulphonylurea alone do not provide adequate glycaemic control and when metformin is inappropriate due to contraindications or intolerance.
• derinant su sulfonilur jos dariniu glikemijos kontrolei gerinti tuo atveju, jeigu gydymo dieta, fiziniais pratimais ir kartu didžiausia toleruojama sulfonilur jos darinio doze metu glikemija kontroliuojama nepakankamai ir jeigu d l kontraindikacij ar netoleravimo netinka metforminas;
• to improve glycaemic control in combination with a sulphonylurea and metformin when diet and exercise plus dual therapy with these agents do not provide adequate glycaemic control.
• derinant su sulfonilur jos dariniu ir metforminu glikemijos kontrolei gerinti tuo atveju, jeigu gydymo dieta, fiziniais pratimais ir kartu šiais dviem pastaraisiais preparatais metu glikemija kontroliuojama nepakankamai.
For patients with type 2 diabetes mellitus in whom use of a PPARγ agonist (i. e. a thiazolidinedione) is appropriate, TESAVEL is indicated:
II tipo cukriniu diabetu sergan i pacient, kuriems tinka PPAR (peroksisomini proliferatori aktyvinam gama receptori) agonistai (pvz., tiazolidindionai), gydymas:
• in combination with the PPARγ agonist when diet and exercise plus the PPARγ agonist alone do not provide adequate glycaemic control.
• derinant su PPAR agonistu tuo atveju, jeigu gydymo dieta, fiziniais pratimais ir kartu PPAR agonistu metu glikemija kontroliuojama nepakankamai.
The dose of TESAVEL is 100 mg once daily.
TESAVEL doz yra 100 mg kart per par.
The dosage of metformin or PPARγ agonist should be maintained, and sitagliptin administered concomitantly.
Prad jus gydyti sitagliptinu, metformino ar PPAR agonisto doz s keisti nereikia.
When TESAVEL is used in combination with a sulphonylurea, a lower dose of the sulphonylurea may be considered to reduce the risk of hypoglycaemia.
TESAVEL derinant su sulfonilur jos dariniu, svarstytinas sulfonilur jos darinio doz s mažinimas, kad sumaž t hipoglikemijos rizika (žr.
(See section 4.4.)
4. 4 skyri).
If a dose of TESAVEL is missed, it should be taken as soon as the patient remembers.
Jeigu TESAVEL doz pacientas praleidžia, j jis turi išgerti tuoj pat, kai tik prisimena.
A double dose should not be taken on the same day.
Dvigubos doz s t pa i par vartoti negalima.
TESAVEL can be taken with or without food.
TESAVEL galima vartoti valgio metu arba nevalgius.
2 Patients with renal insufficiency For patients with mild renal insufficiency (creatinine clearance [CrCl] ≥ 50 ml/ min), no dosage adjustment for TESAVEL is required.
2 Pacientai, sergantys inkst nepakankamumu Pacientams, sergantiems lengvu inkst nepakankamumu (kreatinino klirensas (KK) TESAVEL doz s keisti nereikia.
Clinical study experience with TESAVEL in patients with moderate or severe renal insufficiency is limited.
Klinikini tyrim metu pacient, sergan i vidutinio sunkumo arba sunkiu inkst nepakankamumu, gydymo patirties sukaupta ribotai, tod l tokiems pacientams TESAVEL vartoti nerekomenduojama (žr.
Therefore, use of TESAVEL is not recommended in this patient population (see section 5.2).
5. 2 skyri).
Patients with hepatic insufficiency No dosage adjustment is necessary for patients with mild to moderate hepatic insufficiency.
Pacientai, sergantys kepen nepakankamumu Pacientams, sergantiems lengvu arba vidutinio sunkumo kepen nepakankamumu, doz s keisti nereikia.
TESAVEL has not been studied in patients with severe hepatic insufficiency.
TESAVEL poveikis pacientams, sergantiems sunkiu kepen nepakankamumu, netirtas.
Elderly No dosage adjustment is necessary based on age.
Senyvi žmon s Priklausomai nuo amžiaus doz s keisti nereikia.
Limited safety data is available in patients ≥ 75 years of age and care should be exercised.
75 met pacientams saugumo duomen yra ribotai, tod l juos šiuo vaistiniu preparatu reikia gydyti atsargiai.
Paediatric population TESAVEL is not recommended for use in children below 18 years of age due to a lack of data on its safety and efficacy.
Vaikai Jaunesni negu 18 met vaik TESAVEL gydyti nerekomenduojama, nes nepakanka duomen apie jo saugum ir veiksmingum.
General TESAVEL should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.
Bendrieji sp jimai I tipo cukrinio diabeto ar diabetin s ketoacidoz s TESAVEL gydyti negalima.
Hypoglycaemia when used in combination with other anti-hyperglycaemic agents In clinical trials of TESAVEL as monotherapy and as part of combination therapy with agents not known to cause hypoglycaemia (i. e. metformin or pioglitazone), rates of hypoglycaemia reported with sitagliptin were similar to rates in patients taking placebo.
Hipoglikemija gydymo kartu su kitais gliukoz s kiek kraujyje mažinan iais vaistiniais preparatais metu Klinikini tyrim metu gydant vien TESAVEL arba jo ir vaistini preparat, kurie, kiek žinoma, nesukelia hipoglikemijos (t. y. metforminu ar pioglitazonu), sitagliptino vartojusiems pacientams hipoglikemijos dažnis buvo panašus kaip ir vartojusiems placebo.
When sitagliptin was added to a sulphonylurea, the incidence of hypoglycaemia was increased over that of placebo (see section 4.8).
4. 8 skyri).
Therefore, to reduce the risk of hypoglycaemia, a lower dose of sulphonylurea may be considered (see section 4.2).
Tod l, norint sumažinti hipoglikemijos rizik, svarstytinas mažesn s sulfonilur jos darinio doz s vartojimas (žr.
Renal insufficiency As the experience is limited, patients with moderate to severe renal insufficiency should not be treated with TESAVEL (see section 5.2).
5. 2 skyri).
Hypersensitivity Reactions Postmarketing reports of serious hypersensitivity reactions in patients treated with TESAVEL have been reported.
Padid jusio jautrumo reakcijos Vaistui patekus rink buvo nustatyta sunki padid jusio jautrumo reakcij TESAVEL vartojusiems pacientams.
These reactions include anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome.
Šios reakcijos pasireišk anafilaksija, angioedema ir eksfoliaciniais odos sutrikimais, skaitant Stevens- Johnson sindrom.
Onset of these reactions occurred within the first 3 months after initiation of treatment with TESAVEL, with some reports occurring after the first dose.
Šios reakcijos pasireišk per pirmus 3 m nesius nuo gydymo TESAVEL pradžios, o kelet atvej – po pirmos doz s. tariant padid jusio jautrumo reakcij nutraukite TESAVEL vartojim, vertinkite kitas galimas vykio priežastis, paskirkite alternatyv cukrinio diabeto gydym (žr.
If a hypersensitivity reaction is suspected, discontinue TESAVEL, assess for other potential causes for the event, and institute alternative treatment for diabetes (see section 4.8).
4. 8 skyri).
4.5 Interaction with other medicinal products and other forms of interaction
3 4. 5 S veika su kitais vaistiniais preparatais ir kitokia s veika
Effects of other medicinal products on sitagliptin Clinical data described below suggest that the risk for clinically meaningful interactions by co- administered medicinal products is low.
Kit vaistini preparat poveikis sitagliptinui Žemiau pateikti klinikiniai duomenys rodo, kad klinikai reikšmingos sitagliptino s veikos su kitais kartu vartojamais vaistiniais preparatais rizika yra maža.
3 Metformin:
Metforminas.
Co-administration of multiple twice-daily doses of 1000 mg metformin with 50 mg sitagliptin did not meaningfully alter the pharmacokinetics of sitagliptin in patients with type 2 diabetes.
II tipo cukriniu diabetu sergan i ligoni, kartotinai vartojan i 1 000 mg metformino doz 2 kartus per par ir kartu 50 mg sitagliptino, organizme sitagliptino farmakokinetika reikšmingai nekito.
Coadministration of a single 100 mg oral dose of sitagliptin and a single 600 mg oral dose of cyclosporine increased the AUC and Cmax of sitagliptin by approximately 29% and 68%, respectively.
Išg rus kartu vien 100 mg sitagliptino doz ir vien 600 mg ciklosporino doz, sitagliptino plotas po koncentracijos kraujo plazmoje priklausomai nuo laiko (angl.
These changes in sitagliptin pharmacokinetics were not considered to be clinically meaningful.
Cmax) padid jo atitinkamai apie 29% ir 68%.
The renal clearance of sitagliptin was not meaningfully altered.
Šie sitagliptino farmakokinetikos poky iai nebuvo laikomi klinikai reikšmingais.
Therefore, meaningful interactions would not be expected with other p-glycoprotein inhibitors.
Sitagliptino klirensas inkstuose reikšmingai nekito, tod l reikšmingos s veikos su kitais glikoproteino P inhibitoriais netur t pasireikšti.
In vitro studies indicated that the primary enzyme responsible for the limited metabolism of sitagliptin is CYP3A4, with contribution from CYP2C8.
Tyrimai in vitro rodo, kad svarbiausias fermentas, vykdantis ribot sitagliptino metabolizm yra CYP3A4, bet dalyvauja ir CYP2C8.
In patients with normal renal function, metabolism, including via CYP3A4, plays only a small role in the clearance of sitagliptin.
Pacient, kuri inkst funkcija normali, organizme metabolizmas, skaitant vykdom CYP3A4, sitagliptino klirensui turi maž tak.
Metabolism may play a more significant role in the elimination of sitagliptin in the setting of severe renal insufficiency or ESRD.
Metabolizmas sitagliptino eliminacijai gali b ti reikšmingesnis sergant sunkiu inkst nepakankamumu arba galutin s stadijos inkst liga.
For this reason, it is possible that potent CYP3A4 inhibitors (i. e. ketoconazole, itraconazole, ritonavir, clarithromycin) could alter the phamacokinetics of sitagliptin in patients with severe renal insufficiency or ESRD.
D l to manoma, kad stipr s CYP3A4 inhibitoriai, pvz., ketokonazolas, itrakonazolas, ritonaviras, klaritromicinas, gali keisti sitagliptino farmakokinetik pacient, sergan i sunkiu inkst nepakankamumu arba galutin s stadijos inkst liga, organizme.
The effects of potent CYP3A4 inhibitors in the setting of renal insufficiency has not been assessed in a clinical study.
Stipri CYP3A4 inhibitori poveikis inkst nepakankamumo atvejais klinikini tyrim metu vertintas nebuvo.
In vitro transport studies showed that sitagliptin is a substrate for p-glycoprotein and OAT3.
Pernašos tyrimai in vitro parod, kad sitagliptinas yra glikoproteino P ir OAT3 substratas.
OAT3 mediated transport of sitagliptin was inhibited in vitro by probenecid, although the risk of clinically meaningful interactions is considered to be low.
In vitro sitagliptino pernaš, dalyvaujant OAT3, slopino probenecidas, ta iau manoma, kad klinikai reikšmingos s veikos rizika yra maža.
Effects of sitagliptin on other medicinal products In vitro data suggest that sitagliptin does not inhibit nor induce CYP450 isoenzymes.
Sitagliptino poveikis kitiems vaistiniams preparatams Tyrim in vitro domenys rodo, kad sitagliptinas CYP450 izoferment neslopina ir neindukuoja.
In clinical studies, sitagliptin did not meaningfully alter the pharmacokinetics of metformin, glyburide, simvastatin, rosiglitazone, warfarin, or oral contraceptives, providing in vivo evidence of a low propensity for causing interactions with substrates of CYP3A4, CYP2C8, CYP2C9, and organic cationic transporter (OCT).
Klinikini tyrim metu sitagliptinas reikšmingai metformino, gliburido, simvastatino, roziglitazono, varfarino ar geriam j kontraceptik farmakokinetikos reikšmingai nekeit ir tai rodo, kad in vivo jo polinkis s veik su CYP3A4, CYP2C8 ar CYP2C9 substratais bei organini katijon pernaša yra mažas.
Sitagliptin had a small effect on plasma digoxin concentrations, and may be a mild inhibitor of p- glycoprotein in vivo.
Sitagliptinas šiek tiek veik digoksino koncentracij plazmoje ir in vivo gali truput slopinti glikoprotein P.
Sitagliptin had a small effect on plasma digoxin concentrations.
Sitagliptinas šiek tiek veik digoksino koncentracij plazmoje.
Following administration of 0.25 mg digoxin concomitantly with 100 mg of TESAVEL daily for 10 days, the plasma AUC of digoxin was increased on average by 11%, and the plasma Cmax on average by 18%.
10 dien kasdien vartojus po 0, 25 mg digoksino kartu su 100 mg TESAVEL, digoksino AUC padid jo vidutiniškai 11%, Cmax – vidutiniškai 18%.
No dosage adjustment of digoxin is recommended.
Digoksino doz s keisti nerekomenduojama.
However, patients at risk of digoxin toxicity should be monitored for this when sitagliptin and digoxin are administered concomitantly.
Vis d lto gydant sitagliptinu ir kartu digoksinu, pacientus, kuriems yra digoksino toksinio poveikio rizika, d l šios s veikos reikia steb ti.
Pregnancy There are no adequate data from the use of TESAVEL in pregnant women.
N štumas Reikiam duomen apie TESAVEL vartojim n štumo metu n ra.
Studies in animals have shown reproductive toxicity at high doses (see section 5.3).
5. 3 skyri).
Due to lack of human data, TESAVEL should not be used during pregnancy.
Kadangi klinikini duomen apie vartojim n štumo metu nepakanka, n š ioms moterims TESAVEL skirti negalima.
Lactation It is unknown whether sitagliptin is excreted in human breast milk.
Žindymas Nežinoma, ar sitagliptino išsiskiria su moters pienu.
Animal studies have shown excretion of sitagliptin in breast milk.
Tyrimai su gyv nais parod, kad sitagliptino išsiskiria su motinos pienu.
TESAVEL should not be used during breast-feeding.
Žindymo laikotarpiu TESAVEL vartoti negalima.
No studies on the effects on the ability to drive and use machines have been performed.
Poveikio geb jimui vairuoti ir valdyti mechanizmus tyrim neatlikta.
However, when driving or operating machines, it should be taken into account that dizziness and somnolence have been reported.
Vis d lto vairuojant ar valdant mechanizmus reikia tur ti omenyje, kad buvo pasteb tas galvos svaigimas ir mieguistumas.
In 9 large clinical trials of up to 2 years in duration, over 2700 patients have received treatment with TESAVEL 100 mg per day alone or in combination with metformin, a sulphonylurea (with or without metformin) or a PPARγ agent.
Iki dviej met trukm s 9 klinikini tyrim metu daugiau kaip 2 700 pacien buvo gydyti arba vien 100 mg TESAVEL paros doze, arba ja kartu su metforminu, sulfonilur jos dariniu (kartu su metforminu arba be jo) ar PPAR agonistu.
In these trials, the rate of discontinuation due to adverse experiences considered drug-related was 0.8% with 100 mg per day and 1.5% with other treatments.
Ši tyrim metu d l nepageidaujamo poveikio, kuris vertintas kaip priklausantis nuo vaistinio preparato, gydym reik jo nutraukti 0, 8% pacient, vartojusi 100 mg TESAVEL paros doz, ir 1, 5% kitaip gydyt tiriam j.
No adverse reactions considered as drug-related were reported in patients treated with sitagliptin occurring in excess (> 0.2% and difference > 1 patient) of that in patients treated with control.
Sitagliptino vartojusiems pacientams, nepageidaujam reakcij, kurios vertintos kaip priklausomos nuo vaistinio preparato, dažnis (> 0, 2% ir skirtumas > 1 pacientas) nebuvo didesnis negu kontrolin s grup s pacientams.
Adverse reactions considered as drug-related reported in patients treated with sitagliptin occurring in excess (> 0.2% and difference > 1 patient) of that in patients treated with placebo are listed below (Table 1) by system organ class and frequency.
Nepageidaujamos reakcijos, kurios vertintos kaip priklausomos nuo vaistinio preparato ir kuri dažnis (> 0, 2% ir skirtumas > 1 pacientas) sitagliptinu gydytiems pacientams buvo didesnis, negu vartojusiems placebo, išvardintos žemiau (1- ojoje lentel je) pagal organ sistem klases ir dažn.
Frequencies are defined as: very common (≥ 1/ 10); common (≥ 1/ 100, < 1/ 10); uncommon (≥ 1/ 1000, < 1/ 100); rare (≥ 1/ 10000, < 1/ 1000); and very rare (< 1/ 10000).
Dažnis apib dinamas taip: labai dažni (1/ 10), dažni (nuo 1/ 100 iki < 1/ 10), nedažni (nuo 1/ 1 000 iki < 1/ 100), reti (nuo 1/ 10 000 iki < 1/ 1 000), labai reti (< 1/ 10 000), dažnis nežinomas (negali b ti vertintas pagal turimus duomenis).
Frequency of adverse reaction by treatment regimen
Nepageidaujam reakcij dažnis placebu kontroliuot klinikini tyrim metu
Sitagliptin with Sitagliptin with Sitagliptin with 1 2
Nepageidaujam reakcij dažnis, atsižvelgiant taikom gydym
Sitagliptin with
Sitagliptinas,
Metformin
Sitagliptinas ir
a Sulfonylurea
metforminas1
Metformin and a a PPARγ Agent Sulfonylurea3 (pioglitazone)4
sulfonilur jos
Metabolism and nutrition disorders
metforminas ir
hypoglycaemia*
sulfonilur jos
Very common
agonistas
Very common Common
(pioglitazonas) 4
Nervous system disorders somnolence
Metabolizmo ir mitybos sutrikimai
Uncommon
Dažna
Gastrointestinal disorders
Nerv sistemos sutrikimai
diarrhea nausea flatulence constipation upper abdominal pain
Virškinimo trakto sutrikimai Viduriavimas Pykinimas Pilvo p timas Viduri
Uncommon Common Uncommon
užkiet jimas Viršutin s pilvo
Common
Nedažna
General disorders peripheral oedema
Bendrieji sutrikimai
Investigations blood glucose decreased *
5 Tyrimai Gliukoz s kiekio sumaž jimas kraujyje *
In clinical trials of TESAVEL as monotherapy and sitagliptin as part of combination therapy with metformin or pioglitazone, rates of hypoglycaemia reported with sitagliptin were similar to rates in patients taking placebo.
TESAVEL monoterapijos ar sitagliptino derinio su metforminu arba pioglitazonu klinikini tyrim metu hipoglikemijos dažnis pacientams, vartojusiems sitagliptino arba placebo, buvo panašus.
1 In this placebo-controlled 24-week study of sitagliptin 100 mg once daily in combination with metformin, the incidence of adverse reactions considered as drug-related in patients treated with sitagliptin/ metformin compared to treatment with placebo/ metformin was 9.3% and 10.1%, respectively.
1 Šio placebu kontroliuojamo 24 savai i trukm s 100 mg kart per par sitagliptino doz s vartojimo kartu su metforminu klinikinio tyrimo metu, nepageidaujam reakcij, kurios vertintos kaip priklausomos nuo vaistinio preparato, dažnis pacientams, gydytiems sitagliptino ir metformino deriniu, buvo 9, 3%, pacientams, gydytiems placebo ir metformino deriniu, – 10, 1%.
5 In an additional 1-year study of sitagliptin 100 mg once daily in combination with metformin, the incidence of adverse reactions considered as drug-related in patients treated with sitagliptin/ metformin compared to sulphonylurea/ metformin was 14.5% and 30.3%, respectively.
Papildomo vieneri met trukm s 100 mg kart per par sitagliptino doz s vartojimo kartu su metforminu klinikinio tyrimo metu, nepageidaujam reakcij, kurios vertintos kaip priklausomos nuo vaistinio preparato, dažnis pacientams, gydytiems sitagliptino ir metformino deriniu, buvo 14, 5%, pacientams, gydytiems sulfonilur jos darinio ir metformino deriniu, – 30, 3%.
In pooled studies of up to 1 year in duration comparing sitagliptin/ metformin to a sulphonylurea agent/ metformin, adverse reactions considered as drug-related reported in patients treated with sitagliptin 100 mg occurring in excess (> 0.2% and difference > 1 patient) of that in patients receiving the sulphonylurea agent are as follows: anorexia (Metabolism and nutritional disorders; frequency uncommon) and weight decreased (Investigations; frequency uncommon).
Vis vieneri met trukm s tyrim, kuri metu buvo lygintas gydymas sitagliptino ir metformino deriniu su gydymu sulfonilur jos ir metformino deriniu, nepageidaujam reakcij, kurios vertintos kaip priklausomos nuo vaistini preparat ir kuri dažnis (> 0, 2% ir skirtumas > 1 pacientas) 100 mg sitagliptino doze gydytiems pacientams buvo didesnis, negu gydytiems sulfonilur jos dariniu yra anoreksija (Metabolizmo ir mitybos sutrikimai; dažnis – nedažni) ir k no svorio sumaž jimas (Tyrimai; dažnis – nedažni).
2 In this 24-week study of sitagliptin 100 mg once daily in combination with glimepiride, the incidence of adverse reactions considered as drug-related in patients treated with sitagliptin/ glimepiride compared to treatment with placebo/ glimepiride was 11.3% and 6.6%, respectively.
2 Šio 24 savai i trukm s 100 mg kart per par sitagliptino doz s vartojimo kartu su glimepiridu klinikinio tyrimo metu nepageidaujam reakcij, kurios vertintos kaip priklausomos nuo vaistini preparat, dažnis pacientams, gydytiems sitagliptino ir glimepirido deriniu, buvo 11, 3%, pacientams, gydytiems placebo ir glimepirido deriniu, – 6, 6%.
3 In this 24-week study of sitagliptin 100 mg once daily in combination with glimepiride and metformin, the incidence of adverse reactions considered as drug-related in patients treated with sitagliptin in combination with glimepiride/ metformin compared to treatment with placebo in combination with glimepiride/ metformin was 18.1% and 7.1%, respectively.
3 Šio 24 savai i trukm s 100 mg kart per par sitagliptino doz s vartojimo kartu su glimepiridu ir metforminu klinikinio tyrimo metu nepageidaujam reakcij, kurios vertintos kaip priklausomos nuo vaistini preparat, dažnis pacientams, gydytiems sitagliptino, sulfonilur jos darinio ir metformino deriniu, buvo 18, 1%, pacientams, gydytiems placebo, sulfonilur jos darinio ir metformino deriniu, – 7, 1%.
4 In this 24-week study of the combination of sitagliptin 100 mg once daily and pioglitazone, the incidence of adverse reactions considered as drug-related in patients treated with sitagliptin/ pioglitazone compared to patients treated with placebo/ pioglitazone was 9.1% and 9.0%, respectively.
4 Šio 24 savai i trukm s 100 mg kart per par sitagliptino doz s vartojimo kartu su pioglitazonu klinikinio tyrimo metu, nepageidaujam reakcij, kurios vertintos kaip priklausomos nuo vaistini preparat, dažnis pacientams, gydytiems sitagliptino ir pioglitazono deriniu, buvo 9, 1%, pacientams, gydytiems placebo ir pioglitazono deriniu, – 9, 0%.
In addition, in monotherapy studies of up to 24 weeks in duration of sitagliptin 100 mg once daily alone compared to placebo, adverse reactions considered as drug-related reported in patients treated with sitagliptin in excess (> 0.2% and difference > 1 patient) of that in patients receiving placebo are headache, hypoglycaemia, constipation, and dizziness.
Be to, iki 24 savai i trukm s klinikini monoterapijos tyrim, kuri metu buvo lygintas gydymas kart per par vartojama 100 mg sitagliptino doze su gydymu placebu,, nepageidaujamos reakcijos, kurios vertintos kaip priklausomos nuo vaistinio preparato ir kurios sitagliptinu gydytiems pacientams pasireišk dažniau (> 0, 2% ir skirtumas > 1 pacientas), negu vartojusiems placebo yra galvos skausmas, hipoglikemija, viduri užkiet jimas ir galvos svaigimas.
In addition to the drug-related adverse experiences described above, adverse experiences reported regardless of causal relationship to medication and occurring in at least 5% and more commonly in patients treated with TESAVEL included upper respiratory tract infection and nasopharyngitis.
Be aukš iau aprašyt nuo vaistinio preparato priklausom nepageidaujam reakcij, nepageidaujami poky iai, kurie, nepaisant priežastinio ryšio su vaistiniu preparatu, pasireišk mažiausiai 5% tiriam j ir daug dažniau tiems, kurie buvo gydomi TESAVEL, yra infekcin viršutini kv pavimo tak liga ir nazofaringitas.
Additional adverse experiences reported regardless of causal relationship to medication that occurred more frequently in patients treated with TESAVEL (not reaching the 5% level, but occurring with an incidence of > 0.5% higher with TESAVEL than that in the control group) included osteoarthritis and pain in extremity.
Kitokie nepageidaujami poky iai, kuri nepaisant priežastinio ryšio su vaistiniu preparatu, TESAVEL gydomiems pacientams atsirado dažniau (nesiek 5%, bet TESAVEL gydomiems pacientams pasireišk > 0, 5% dažniau negu kontrolin s grup s tiriamiesiems), buvo osteoartritas ir gal ni skausmas.
In a 24-week study of initial combination therapy with sitagliptin and metformin administered twice daily (sitagliptin/ metformin 50 mg/ 500 mg or 50 mg/ 1000 mg), the overall incidence of adverse reactions considered as drug-related in patients treated with the combination of sitagliptin and metformin compared to patients treated with placebo was 14.0% and 9.7%, respectively.
6 24 savai i trukm s pradinio sud tinio gydymo 2 kartus per par vartojamu sitagliptino ir metformino deriniu (50 mg sitagliptino ir 500 mg metformino arba 50 mg sitagliptino ir 1 000 mg metformino) metu bendras nepageidaujam reakcij, kurios vertintos kaip priklausomos nuo vaistini preparat, dažnis pacientams, gydytiems sitagliptino ir metformino deriniu, buvo 14%, gydytiems placebu, – 9, 7%.
The overall incidence of adverse reactions considered as drug-related in patients treated with the combination of sitagliptin and metformin was comparable to metformin alone (14.0% each) and greater than sitagliptin alone (6.7%), with the differences relative to sitagliptin alone primarily due to gastrointestinal adverse reactions.
Š skirtum sud tinio gydymo, palyginti su sitagliptino monoterapija, metu vis pirma l m nepageidaujamos virškinimo trakto reakcijos.
Across clinical studies, a small increase in white blood cell count (approximately 200 cells/ microl difference in WBC vs. placebo; mean baseline WBC approximately 6600 cells/ microl) was observed due to an increase in neutrophils.
Klinikini tyrim metu buvo steb tas nedidelis balt j kraujo k neli kiekio padid jimas (apie 200 l steli / mikrolitre daugiau negu placebo vartojusi tiriam j; vidutinis balt j kraujo k neli kiekis prieš tyrim buvo maždaug 6 600 l steli / mikrolitre), kur l m neutrofil padaug jimas.
This observation was seen in most but not all studies.
Tai buvo steb ta daugelio, ta iau ne vis tyrim metu.
This change in laboratory parameters is not considered to be clinically relevant.
Šie laboratorini tyrim parametr poky iai nelaikomi klinikai reikšmingais.
No clinically meaningful changes in vital signs or in ECG (including in QTc interval) were observed with TESAVEL treatment.
Gydant TESAVEL, kliniškai reikšming gyvybini požymi ar EKG poky i (tarp j ir QT intervalo) nepasteb ta.
During post-marketing experience the following additional side effects have been reported (frequency not known): hypersensitivity reactions including anaphylaxis, angioedema, rash, urticaria, and exfoliative skin conditions including Stevens-Johnson syndrome (see section 4.4).
4. 4 skyri).
During controlled clinical trials in healthy subjects, single doses of up to 800 mg sitagliptin were generally well tolerated.
Kontroliuojam klinikini tyrim su sveikais asmenimis metu ne didesn s kaip 800 mg vienkartin s sitagliptino doz s paprastai buvo gerai toleruojamos.
Minimal increases in QTc, not considered to be clinically relevant, were observed in one study at a dose of 800 mg sitagliptin.
Vieno tyrimo metu 800 mg sitagliptino doz minimaliai pailgino QT interval, ta iau pailg jimas nelaikomas klinikai reikšmingu.
There is no experience with doses above 800 mg in humans.
Didesn s kaip 800 mg doz s vartojimo patirties žmon ms n ra.
In the event of an overdose, it is reasonable to employ the usual supportive measures, e. g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring (including obtaining an electrocardiogram), and institute supportive therapy if required.
Perdozavimo atveju reikia taikyti prastines palaikom sias priemones, pvz., neabsorbuoto vaistinio preparato šalinim iš virškinimo trakto, klinikin s b kl s steb jim (skaitant elektrokardiogramos užrašym) ir, jei reikia, palaikom j gydym.
In clinical studies, approximately 13.5% of the dose was removed over a 3- to 4-hour hemodialysis session.
Klinikini tyrim metu vienos 3 - 4 valand trukm s hemodializ s metu buvo pašalinta maždaug 13, 5% doz s.
Prolonged hemodialysis may be considered if clinically appropriate.
Jei kliniškai tinka, hemodializ b t galima prailginti.
It is not known if sitagliptin is dialyzable by peritoneal dialysis.
Ar sitagliptino galima pašalinti pilvapl v s dialize, nežinoma.
A10BH01.
Farmakoterapin grup – DPP- 4 inhibitoriai, ATC kodas – A10BH01.
TESAVEL is a member of a class of oral anti-hyperglycaemic agents called dipeptidyl peptidase 4 (DPP-4) inhibitors.
TESAVEL priklauso geriam j gliukoz s koncentracij kraujyje mažinan i vaistini preparat klasei, kuri vadinama dipeptidilpeptidaz s- 4 (DPP- 4) inhibitoriais.
The improvement in glycaemic control observed with this agent may be mediated by enhancing the levels of active incretin hormones.
Glikemijos reguliavimo pager jimas vartojant š vaistin preparat gal t b ti susij s su aktyvi hormon inkretin kiekio padid jimu.
Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are released by the intestine throughout the day, and levels are increased in response to a meal.
Inkretin, skaitant gliukagon panaš peptid - 1 (GPP- 1) ir nuo gliukoz s priklausant insulinotropin polipeptid (GIP), vis dien išskiria žarnynas, o j kiekis did ja d l atsako maist.
The incretins are part of an endogenous system involved in the physiologic regulation of glucose homeostasis.
Inkretinai yra endogenin s sistemos, kuri dalyvauja fiziologiniame gliukoz s homeostaz s reguliavime, dalis.
When blood glucose concentrations are normal or elevated, GLP-1 and GIP increase insulin synthesis and release from pancreatic beta cells by intracellular signaling pathways involving cyclic AMP.
Kai gliukoz s koncentracija kraujyje yra normali arba padid jusi, GPP- 1 ir GIP padidina insulino gamyb ir išskyrim iš kasos beta l steli, intral steliniu signaliniu keliu, kuriame dalyvauja ciklinis AMF.
Treatment with GLP-1 or with DPP-4 inhibitors in animal models of type 2 diabetes has been demonstrated to improve beta cell responsiveness to glucose and stimulate insulin biosynthesis and release.
II tipo cukrinio diabeto gyv n modeli gydymas GPP- 1 ar DPP- 4 rodo, kad
With higher insulin levels, tissue glucose uptake is enhanced.
7 pager ja beta l steli atsakas gliukoz, stimuliuojama insulino gamyba ir išskyrimas.
In addition, GLP-1 lowers glucagon secretion from pancreatic alpha cells.
Be to, GPP- 1 sumažina gliukagono išsiskyrim iš kasos alfa- l steli.
Decreased glucagon concentrations, along with higher insulin levels, lead to reduced hepatic glucose production, resulting in a decrease in blood glucose levels.
D l sumaž jusios gliukagono koncentracijos ir kartu padid jusio insulino kiekio sumaž ja gliukoz s gamyba kepenyse, tod l sumaž ja ir jos koncentracija kraujyje.
The effects of GLP-1 and GIP are glucose-dependent such that when blood glucose concentrations are low, stimulation of insulin release and suppression of glucagon secretion by GLP-1 are not observed.
Kadangi GPP- 1 ir GIP priklauso nuo gliukoz s, tod l tuo atveju, kai jos koncentracija maža, GPP- 1 sukeliamo insulino išsiskyrimo stimuliavimo ir gliukagono sekrecijos slopinimo, nepasireiškia.
For both GLP-1 and GIP, stimulation of insulin release is enhanced as glucose rises above normal concentrations.
Kai gliukoz s koncentracija tampa didesn už normali, sustipr ja tiek GPP- 1, tiek GIP sukeliamas insulino išsiskyrimo stimuliavimas.
Further, GLP-1 does not impair the normal glucagon response to hypoglycaemia.
Be to, GPP- 1 netrikdo normalaus gliukagono atsako hipoglikemij.
The activity of GLP-1 and GIP is limited by the DPP-4 enzyme, which rapidly hydrolyzes the incretin hormones to produce inactive products.
GPP- 1 ir GIP aktyvum riboja fermentas DPP- 4, kuris hormonus inkretinus hidroliz s b du greitai ver ia neaktyviais produktais.
Sitagliptin prevents the hydrolysis of incretin hormones by DPP-4, thereby increasing plasma concentrations of the active forms of GLP-1 and GIP.
Sitagliptinas neleidžia fermentui DPP- 4 hidrolizuoti hormonus inkretinus, tod l kraujo plazmoje padid ja aktyvi GPP- 1 ir GIP form koncentracijos.
By enhancing active incretin levels, sitagliptin increases insulin release and decreases glucagon levels in a glucose- dependent manner.
Didindamas aktyvi inkretin kiek, sitagliptinas didina insulino išskyrim ir mažina gliukagono kiek priklausomai nuo gliukoz s koncentracijos.
In patients with type 2 diabetes with hyperglycaemia, these changes in insulin and glucagon levels lead to lower hemoglobin A1c (HbA1c) and lower fasting and postprandial glucose concentrations.
II tipo diabetu sergantiems pacientams, kuriems yra hiperglikemija, šie insulino ir gliukagono kieki poky iai lemia hemoglobino A1c (HbA1c) bei gliukoz s koncentracijos sumaž jim nevalgius ir po valgio.
The glucose-dependent mechanism of sitagliptin is distinct from the mechanism of sulphonylureas, which increase insulin secretion even when glucose levels are low and can lead to hypoglycaemia in patients with type 2 diabetes and in normal subjects.
Nuo gliukoz s priklausomas sitagliptino veikimo mechanizmas skiriasi nuo sulfonilur jos darini, kurie didina insulino sekrecij, net ir tuo atveju, kai gliukoz s koncentracija yra maža, tod l gali sukelti hipoglikemij tiek sergantiems II tipo cukriniu diabetu, tiek sveikiems asmenims.
Sitagliptin is a potent and highly selective inhibitor of the enzyme DPP-4 and does not inhibit the closely-related enzymes DPP-8 or DPP-9 at therapeutic concentrations.
Labai š ferment panaši DPP- 8 bei DPP- 9 ferment terapin medikamento koncentracija neslopina.
7 Overall, sitagliptin improved glycaemic control when given as monotherapy, when used in combination with metformin (initial or add-on therapy), in combination with a sulphonylurea (with or without metformin), and in combination with a thiazolidinedione, as measured by clinically relevant reductions in HbA1c from baseline at study endpoint (see Table 2).
2 lentel).
Two studies were conducted to evaluate the efficacy and safety of TESAVEL monotherapy.
Dviej tyrim metu buvo vertinamas TESAVEL veiksmingumas ir saugumas monoterapijos metu.
Treatment with sitagliptin at 100 mg once daily as monotherapy provided significant improvements in HbA1c, fasting plasma glucose (FPG), and 2-hour post-prandial glucose (2-hour PPG), compared to placebo in two studies, one of 18- and one of 24-weeks duration.
Dviej tyrim (vienas 18- os, kitas – 24 savai i trukm s) metu gydant vien kart per par vartojama 100 mg sitagliptino doze, palyginti su placebu, reikšmingai pager jo HbA1c kiekio, gliukoz s kiekio kraujo plazmoje nevalgius ir gliukoz s kiekio kraujo plazmoje, pra jus 2 valandoms po valgio, rodmenys.
Improvement of surrogate markers of beta cell function, including HOMA-β (Homeostasis Model Assessment-β), proinsulin to insulin ratio, and measures of beta cell responsiveness from the frequently-sampled meal tolerance test were observed.
Buvo stebimas reikšmingas pakaitini beta l steli funkcijos žymen, tarp j ir HOMA - (Homeostasis Model Assessment -), proinsulino ir insulino santykio bei beta l steli reaktyvumo, nustatyto pagal dažnus maisto toleravimo testus, rodmen pager jimas.
The observed incidence of hypoglycaemia in patients treated with TESAVEL was similar to placebo.
Pacientams, gydytiems TESAVEL, hipoglikemijos dažnis buvo panašus placebo sukeliam.
Body weight did not increase from baseline with sitagliptin therapy in either study, compared to a small reduction in patients given placebo.
Abiej tyrim metu sitagliptino vartojusi pacient k no svoris nepadid jo, o vartojusi placebo truput sumaž jo.
In a study in patients with type 2 diabetes and chronic renal insufficiency (creatinine clearance < 50 ml/ min), the safety and tolerability of reduced doses of sitagliptin were investigated and generally similar to placebo.
Klinikinio tyrimo, kuriame dalyvavo pacientai, sergantys II tipo diabetu ir l tiniu inkst nepakankamumu (kreatinino klirensas < 50 ml/ min), sumažint sitagliptino dozi saugumas ir toleravimas paprastai buvo panašus placebo.
In addition, the reductions in HbA1c and FPG with sitagliptin compared to placebo were generally similar to those observed in other monotherapy studies in patients with normal renal function (see section 5.2).
5. 2 skyri).
The number of patients with moderate to severe renal insufficiency was too low to confirm safe use of sitagliptin in this type of patients.
Pacient, kuriems buvo vidutinio sunkumo arba sunkus inkst nepakankamumas, tyrime dalyvavo per mažai, kad b t galima patvirtinti, kad jiems gydymas sitagliptinu yra saugus.
Sitagliptin 100 mg once daily provided significant improvements in glycaemic parameters compared with placebo in two 24-week studies of sitagliptin as add-on therapy, one in combination with metformin and one in combination with pioglitazone.
Vieno tyrimo metu sitagliptinu buvo papildytas gydymas vien metforminu, kito − gydymas vien pioglitazonu.
Change from baseline in body weight was similar for patients treated with sitagliptin relative to placebo.
Sitagliptinu ar placebu gydyt pacient k no svorio, palyginti su pradiniu, poky iai buvo panaš s.
In these studies there was a similar incidence of hypoglycaemia reported for patients treated with sitagliptin or placebo.
Ši klinikini tyrim metu sitagliptinu ar placebu gydytiems pacientams hipoglikemijos dažnis buvo panašus.
A 24-week placebo-controlled study was designed to evaluate the efficacy and safety of sitagliptin (100 mg once daily) added to glimepiride alone or glimepiride in combination with metformin.
24 savai i trukm s placebu kontroliuojamo tyrimo metu buvo vertintas sitagliptino (100 mg kart per par) veiksmingumas ir saugumas tuo atveju, kai juo buvo papildytas gydymas vien glimepiridu arba glimepirido ir metformino deriniu.
The addition of sitagliptin to either glimepiride alone or to glimepiride and metformin provided significant improvements in glycaemic parameters.
Gydym vien glimepiridu ar glimepirido ir metformino deriniu papildžius sitagliptinu, reikšmingai pager jo glikemijos parametrai.
Patients treated with sitagliptin had a modest increase in body weight compared to those given placebo.
Sitagliptinu, palyginti su placebu, gydytiems pacientams saikingai padid jo k no svoris.
In a 24-week placebo-controlled factorial study of initial therapy, sitagliptin 50 mg twice daily in combination with metformin (500 mg or 1000 mg twice daily) provided significant improvements in glycaemic parameters compared with either monotherapy.
8 24 savai i trukm s placebu kontroliuojamo faktorialaus pradinio gydymo tyrimo metu pacientams, du kartus per par vartojusiems 50 mg sitagliptino doz kartu su metforminu (po 500 mg arba 1 000 mg 2 kartus per par), reikšmingai pager jo glikemijos parametrai, palyginti su tiriamaisiais, kuriems buvo taikyta monoterapija bet kuriuo iš min t vaistini preparat.
The decrease in body weight with the combination of sitagliptin and metformin was similar to that observed with metformin alone or placebo; there was no change from baseline for patients on sitagliptin alone.
Sitagliptino ir metformino deriniu gydyt pacient k no svorio sumaž jimas buvo panašus, kaip vartojusi vien metformino arba placebo.
The incidence of hypoglycaemia was similar across treatment groups.
Tiriam j, vartojusi tik sitagliptino k no svoris nepakito.
Table 2.
2 lentel.
HbA1c results in placebo-controlled monotherapy and combination therapy studies*
HbA1c kiekio poky iai placebu kontroliuojam monoterapijos ir sud tinio gydymo tyrim * metu
Mean change from
Vidutinis HbA1c kiekio
change in HbA1c (%) at
Placebu koreguotas vidutinis
baseline HbA1c (%)
pradinis
baseline HbA1c (%) † at Week 24
(%) pokytis 24 - j
Week 24† (95% CI)
HbA1c kiekio (%) pokytis 24 -
Monotherapy Studies Sitagliptin 100 mg once daily§
savait †, palyginti su
-0.5
pradiniu
-0.6‡
(95% PI)
(N= 193) Sitagliptin 100 mg once daily (N= 229) Combination Therapy Studies Sitagliptin 100 mg once daily added to
Monoterapijos metu Sitagliptinas 100 mg - 0, 6 ‡ kart per par § (N= 193) Sitagliptinas 100 mg
8.0
8
(-0.8, -0.4) -0.8‡ (-1.0, -0.6) -0.7‡
(- 0, 8; - 0, 4) - 0, 8 ‡
ongoing metformin therapy (N=453)
kart per par (N= 229) Sud tinio gydymo metu Sitagliptinas 100 mg kart per par,
(-0.8, -0.5)
(- 1; - 0, 6) - 0, 7 ‡
Mean
- 0, 7
Sitagliptin 100 mg once daily added to -0.7‡ ongoing pioglitazone therapy (N=163) Sitagliptin 100 mg once daily added to
papildant juo gydym pioglitazonu (N=163) Sitagliptinas 100 mg kart per par,
ongoing glimepiride therapy (N=102) Sitagliptin 100 mg once daily added to
papildant juo gydym glimepiridu (N=102) Sitagliptinas 100 mg kart per par, papildant juo gydym
ongoing glimepiride + metformin therapy (N=115) Initial therapy (twice daily):
glimepirido ir metformino deriniu (N=115) Pradinis gydymas (du kartus per par):
Sitagliptin 50 mg + metformin 500 mg (N=183) Initial therapy (twice daily):
sitagliptinas 50 mg ir metforminas 500 mg (N=183) Pradinis gydymas (du kartus per par):
* All Patients Treated Population (an intention-to-treat analysis). † Least squares means adjusted for prior antihyperglycaemic therapy status and baseline value. ‡ p < 0.001 compared to placebo or placebo + combination treatment. § HbA1c (%) at week 18.
* Visi gydyti pacientai (intention- to- treat analiz) † Mažiausi j kvadrat vidurkiai koreguoti pagal ankstesn antihiperglikemin gydym ir bazin reikšm ‡ p < 0, 001 palyginti su placebu arba placebu ir sud tiniu gydymu § HbA1c (%) 18 - savait
In a study comparing the efficacy and safety of the addition of TESAVEL 100 mg once daily or glipizide (a sulphonylurea agent) in patients with inadequate glycaemic control on metformin monotherapy, sitagliptin was similar to glipizide in reducing HbA1c.
Tyrimu, kurio metu buvo lygintas papildomos kart per par vartojamos 100 mg TESAVEL doz s arba glipizido (sulfonilur jos darinio) veiksmingumas ir saugumas pacientams, kuriems gydymo vien metforminu metu gliukoz s kiekis kraujyje buvo kontroliuojamas nepakankamai, nustatyta, kad sitagliptinas HbA1c kiek sumažino panašiai kaip glipizidas.
The mean glipizide dose used in the comparator group was 10 mg per day with approximately 40% of patients requiring a glipizide dose of ≤ 5 mg/ day throughout the study.
Vidutin glipizido paros doz, kuri vartojo lyginamosios grup s tiriamieji, buvo 10 mg ir apytikriai 40% pacient visu tyrimo laikotarpiu reik jo 5 mg paros doz s.
However, more patients in the sitagliptin group discontinued due to lack of efficacy than in the glipizide group.
Ta iau d l nepakankamo veiksmingumo gydym sitagliptinu nutrauk daugiau pacient, negu gydym glipizidu.
Patients treated with sitagliptin exhibited a significant mean decrease from baseline in body weight compared to a significant weight gain in patients administered glipizide (-1.5 vs. +1.1 kg).
Sitagliptino vartojusi pacient k no mas, palyginti su bazine, tyrimo metu reikšmingai sumaž jo, glipizido vartojusi pacient - reikšmingai padid jo (atitinkamai - 1, 5 kg ir +1, 1 kg).
In this study, the proinsulin to insulin ratio, a marker of efficiency of insulin synthesis and release, improved with sitagliptin and deteriorated with glipizide treatment.
Šio tyrimo metu insulino gamybos ir išskyrimo veiksmingumo žymuo, t. y. proinsulino ir insulino santykis, gydant sitagliptinu pager jo, o gydant glipizidu pablog jo.
Absorption Following oral administration of a 100-mg dose to healthy subjects, sitagliptin was rapidly absorbed, with peak plasma concentrations (median Tmax) occurring 1 to 4 hours post-dose, mean plasma AUC of sitagliptin was 8.52 μ M• hr, Cmax was 950 nM.
Absorbcija Sveik tiriam j išg rusi vien 100 mg doz, organizme sitagliptinas buvo greitai absorbuotas, didžiausia koncentracija plazmoje (Tmax mediana) atsirado po 1 – 4 valand, vidutinis sitagliptino AUC buvo 8, 52 µM• hr, Cmax – 950 nM.
Since coadministration of a high-fat meal with TESAVEL had no effect on the pharmacokinetics, TESAVEL may be administered with or without food.
Kadangi labai riebus maistas kartu vartojamo TESAVEL farmakokinetikai takos netur jo, tod l TESAVEL galima gerti valgant arba nevalgius.
Plasma AUC of sitagliptin increased in a dose-proportional manner.
Sitagliptino AUC did jo proporcingai dozei.
Dose-proportionality was not established for Cmax and C24hr (Cmax increased in a greater than dose-proportional manner and C24hr increased in a less than dose-proportional manner).
Cmax ir C24val proporcingumas dozei nebuvo nustatytas (Cmax did jo daugiau negu proporcingai dozei, C24val – mažiau negu proporcingai dozei).
Distribution The mean volume of distribution at steady state following a single 100-mg intravenous dose of sitagliptin to healthy subjects is approximately 198 liters.
Pasiskirstymas Sušvirkštus ven vien 100 mg sitagliptino doz, sveik žmoni organizme vidutinis pasiskirstymo t ris tuo metu, kai apykaita pusiausvyrin, yra maždaug 198 litrai.
The fraction of sitagliptin reversibly bound to plasma proteins is low (38%).
Sitagliptino kiekis, kuris laikinai prisijungia prie plazmos baltym yra mažas (38%).
9 Metabolism Sitagliptin is primarily eliminated unchanged in urine, and metabolism is a minor pathway.
Metabolizmas Sitagliptino metabolizuojama mažai, daugiausia jis pašalinamas su šlapimu nepakit s.
Approximately 79% of sitagliptin is excreted unchanged in the urine.
Maždaug 79% sitagliptino išsiskiria su šlapimu nepakitusio preparato pavidalu.
Following a [14C]sitagliptin oral dose, approximately 16% of the radioactivity was excreted as metabolites of sitagliptin.
Išg rus žym to [14C] sitagliptino doz, maždaug 16% radioaktyvumo buvo pašalinta su sitagliptino metabolitais.
Six metabolites were detected at trace levels and are not expected to contribute to the plasma DPP-4 inhibitory activity of sitagliptin.
Buvo aptikti šeši metabolit p dsakai ir nesitikima, kad jie prisideda prie sitagliptino DPP- 4 slopinamojo aktyvumo plazmoje.
In vitro studies indicated that the primary enzyme responsible for the limited metabolism of sitagliptin was CYP3A4, with contribution from CYP2C8.
Tyrimai in vitro parod, kad svarbiausias fermentas, atsakingas už ribot sitagliptino metabolizm yra CYP3A4, dalyvaujant ir CYP2C8.
In vitro data showed that sitagliptin is not an inhibitor of CYP isozymes CYP3A4, 2C8, 2C9, 2D6, 1A2, 2C19 or 2B6, and is not an inducer of CYP3A4 and CYP1A2.
Tyrim in vitro duomenys rodo, kad sitagliptinas CYP izoferment CYP3A4, 2C8, 2C9, 2D6, 1A2, 2C19 bei 2B6 neslopina, o CYP3A4 ir CYP1A2 neindukuoja.
Elimination Following administration of an oral [14C]sitagliptin dose to healthy subjects, approximately 100% of the administered radioactivity was eliminated in faeces (13%) or urine (87%) within one week of dosing.
Eliminacija Iš sveik asmen, išg rusi 100 mg žym to [14C] sitagliptino doz, organizmo maždaug 100% radioaktyvumo išsiskyr su išmatomis (13%) bei šlapimu (87%) per savait.
The apparent terminal t1/ 2 following a 100-mg oral dose of sitagliptin was approximately 12.4 hours.
Išg rus 100 mg sitagliptino doz, jo galutin s pusin s eliminacijos tariamasis periodas (t1/ 2) buvo 12, 4 valandos.
Elimination of sitagliptin occurs primarily via renal excretion and involves active tubular secretion.
10 Sitagliptinas šalinamas daugiausiai pro inkstus aktyvia sekrecija kanal lius.
Sitagliptin is a substrate for human organic anion transporter-3 (hOAT-3), which may be involved in the renal elimination of sitagliptin.
Sitagliptinas yra žmogaus organini anijon nešiklio- 3 (angl. hOAT- 3), kuris galb t dalyvauja ir sitagliptino išsiskyrime pro inkstus, substratas.
The clinical relevance of hOAT-3 in sitagliptin transport has not been established.
Klinikin hOAT- 3 dalyvavimo sitagliptino pernašoje reikšm nenustatyta.
Sitagliptin is also a substrate of p-glycoprotein, which may also be involved in mediating the renal elimination of sitagliptin.
Be to, sitagliptinas yra ir glikoproteino- P, irgi galin io dalyvauti sitagliptino šalinime pro inkstus, substratas.
However, cyclosporine, a p-glycoprotein inhibitor, did not reduce the renal clearance of sitagliptin.
Vis d lto glikoproteino- P inhibitorius ciklosporinas sitagliptino inkst klirenso nemažina.
Sitagliptin is not a substrate for OCT2 or OAT1 or PEPT1/ 2 transporters.
Sitagliptinas n ra nešikli OCT2, OAT1 ar PEPT1/ 2 substratas.
In vitro, sitagliptin did not inhibit OAT3 (IC50=160 μ M) or p-glycoprotein (up to 250 μ M) mediated transport at therapeutically relevant plasma concentrations.
In vitro gydymui reikšminga sitagliptino koncentracija OAT3 (IC50=160 µM) ar glikoproteino- P (iki 250 µM) vykdomos pernašos neslopino.