qanastek/EMEA-V3 huggingface dataset:
However, patients at risk of digoxin toxicity should be monitored for this when sitagliptin and digoxin are administered concomitantly.
Madankollu, pazjenti f’ riskju ta ’ tossiċità ta ’ digoxin għandhom ikunu sorveljati għal dan meta sitagliptin u digoxin jingħataw fl- istess ħin.
There are no adequate data from the use of sitagliptin in pregnant women.
Ma hemm l- ebda dejta adegwata ta ’ l- użu ta ’ sitagliptin f’ nisa tqal.
Studies in animals have shown reproductive toxicity at high doses of sitagliptin (see section 5.3).
Studji fl- annimali wrew tossiċità riproduttiva f’ dożi għoljin ta ’ sitagliptin (ara sezzjoni 5. 3).
A limited amount of data suggest the use of metformin in pregnant women is not associated with an increased risk of congenital malformations.
Ammont limitat ta ’ tagħrif jissuġġerixxi l- użu ta ’ metformin f’ nisa tqal mhuwiex assoċjat ma żieda fir - riskju ta ’ malformazzjonijiet.
Animal studies with metformin do not indicate harmful effects with respect to pregnancy, embryonic or foetal development, parturition or postnatal development (see also section 5.3).
Studji ta ’ l- annimali b’ metamorfin ma jindikaw l- ebda sinjali ta ’ ħsara fit- tqala, żvilupp embrijoniku jew fetali, ħlas jew żvilupp ta ’ wara t- twelid (ara wkoll sezzjoni 5. 3).
Efficib should not be used during pregnancy.
Efficib m’ għandux jintuża waqt it- tqala.
If a patient wishes to become pregnant or if a pregnancy occurs, treatment with Efficib should be discontinued and switched to insulin treatment as soon as possible.
Jekk pazjenta tixtieq li toħroġ tqila jew jekk isseħħ tqala, il - kura b’ Efficib għandha titwaqqaf u l- pazjenta għandha tinqaleb għal kura bl- insulina mill- aktar fis possibbli.
No studies in lactating animals have been conducted with the combined active substances of Efficib.
Ma sar l- ebda studju b’ sustanzi attivi kkumbinati ta ’ Efficib f’ annimali li qegħdin ireddgħu.
In studies performed with the individual active substances, both sitagliptin and metformin are excreted in the milk of lactating rats.
Fi studji magħmula bis- sustanzi attivi individwali, kemm sitagliptin u kemm metformin jitfaċċaw fil- ħalib ta ’ firien li jkunu qegħdin ireddgħu.
Metformin is excreted in human milk in small amounts.
Metformin joħroġ fil- ħalib tal- omm f’ ammonti żgħar.
Efficib must therefore not be used in women who are breast-feeding (see section 4.3).
Efficib għalhekk m’ għandux jintuża f’ nisa li qegħdin ireddgħu (ara sezzjoni 4. 3).
No studies on the effects on the ability to drive and use machines have been performed with Efficib.
Ma sar l- ebda studju b’ Efficib fuq l- effetti fuq il- ħila biex issuq u li tħaddem magni.
However, when driving or operating machines, it should be taken into account that dizziness and somnolence have been reported with sitagliptin.
Madankollu, waqt is- sewqan u t- tħaddim ta ’ magni, wieħed għandu jżomm f’ moħħu li ġew irrapportati sturdament u ngħas tqil b’ sitagliptin.
In addition, patients should be alerted to the risk of hypoglycaemia when Efficib is used in combination with other sulfonylurea agents.
Barra minn hekk, il- pazjenti għandhom ikunu mwissija dwar ir- riskju ta ’ ipogliċemija meta Efficib jintuża f’ kumbinazzjoni ma ’ mediċini tat- tip sulfonylurea oħrajn.
6 4.8 Undesirable effects
6 4. 8 Effetti mhux mixtieqa
There have been no therapeutic clinical trials conducted with Efficib tablets however bioequivalence of Efficib with co-administered sitagliptin and metformin has been demonstrated (see section 5.2).
Ma saru l- ebda provi terapewtiċi kliniċi b’ pilloli Efficib, madankollu ntweriet il- bijoekwivalenza ta ’ Efficib ma ’ sitagliptin u metformin mgħotijin flimkien (ara sezzjoni 5. 2).
Sitagliptin and metformin Adverse reactions considered as drug related reported in excess (> 0.2% and difference > 1 patient) of placebo and in patients receiving sitagliptin in combination with metformin in double-blind studies are listed below as MedDRA preferred term by system organ class and absolute frequency (Table 1).
Sitagliptin u metformin Reazzjonijiet avversi kkunsidrati relatati ma ’ mediċina ġew irrapportati aktar (> 0. 2% u differenza > pazjent 1) minn plaċebo u f’ pazjenti li kienu qegħdin jirċievu sitagliptin flimkien ma ’ metformin fi studji double- blind huma elenkati hawn taħt bħala terminu ppreferut minn MedDRA permezz ta ’ klassi ta ’ sistema ta ’ organi u frekwenza assoluta (Tabella 1).
Frequencies are defined as: very common (≥ 1/ 10); common (≥ 1/ 100 to < 1/ 10); uncommon (≥ 1/ 1,000 to < 1/ 100); rare (≥ 1/ 10,000 to < 1/ 1,000); very rare (< 1/ 10,000).
Il- frekwenzi huma ddefiniti bħala: komuni ħafna (≥ 1/ 10); komuni (≥ 1/ 100 sa < 1/ 10); mhux komuni (≥ 1/ 1, 000 sa < 1/ 100); rari (≥ 1/ 10, 000 sa < 1/ 1, 000); rari ħafna (< 1/ 10, 000).
The frequency of adverse reactions identified from placebo-controlled clinical studies
Il- frekwenza ta ’ reazzjonijiet avversi identifikati minn provi kliniċi kkontrollati bi plaċebo
Frequency of adverse reaction by treatment regimen
Frekwenza ta ’ reazzjoni avversa b’ reġimen ta ’ kura
Sitagliptin with Metformin1
Sitagliptin ma ’ Metformin1
Sitagliptin with Metformin and a Sulphonylurea2
Sitagliptin ma ’ Metformin u Sulphonylurea2
blood glucose decreased
Investigazzjonijiet tnaqqis fiz- zokkor tad - demm
Nervous system disorders somnolence
Disturbi fis- sistema nervuża ngħas tqil
diarrhoea nausea constipation upper abdominal pain
dijarea dardir stitikezza uġigħ fin- naħa ta ’ fuq taż- żaqq
Uncommon Common Uncommon
Mhux komuni Komuni Mhux komuni
Metabolism and nutrition disorders hypoglycaemia* *
Disturbi fil- metaboliżmu u n- nutrizzjoni ipogliċemija * *
In clinical trials of sitagliptin as monotherapy and sitagliptin as part of combination therapy with metformin, rates of hypoglycaemia reported with sitagliptin were similar to rates in patients taking placebo.
Fi provi kliniċi ta ’ sitagliptin bħala monoterapija u sitagliptin bħala parti minn terapija ta ’ kumbinazzjoni ma ’ metformin, ir- rati ta ’ ipogliċemija rrapportati b’ sitagliptin kienu jixbhu r- rati f’ pazjenti li ħadu plaċebo.
1 In this placebo-controlled 24-week study of sitagliptin 100 mg once daily added to ongoing metformin, the incidence of adverse reactions considered as drug-related in patients treated with sitagliptin added to ongoing metformin compared to treatment with placebo added to ongoing metformin was 9.3% and 10.1%, respectively.
1 F’ dan l- istudju kkontrollat bi plaċebo ta ’ 24 ġimgħa ta ’ sitagliptin 100 mg darba kuljum miżjud ma ’ metformin li diġà jkun qiegħed jittieħed, l- inċidenza ta ’ reazzjonijiet avversi kkunsidrati bħala relatati mal- mediċina f’ pazjenti kkurati b’ sitagliptin miżjud ma ’ metformin li diġà jkun qiegħed jittieħed imqabbla ma ’ kura bi plaċebo miżjud ma ’ metformin li diġà jkun qiegħed jittieħed kienet ta ’ 9. 3% u 10. 1%, rispettivament.
In an additional 1-year study of sitagliptin 100 mg once daily added to ongoing metformin, the incidence of adverse reactions considered as drug-related in patients treated with sitagliptin added to ongoing metformin compared to sulphonylurea added to ongoing metformin was 14.5% and 30.3%, respectively.
Fi studju addizjonali ta ’ sena ta ’ sitagliptin 100 mg darba kuljum miżjud ma ’ metformin li diġà jkun qiegħed jittieħed, l- inċidenza ta ’ reazzjonijiet avversi kkunsidrati bħala relatati mal- mediċina f’ pazjenti kkurati b’ sitagliptin miżjuda ma ’ metformin li diġà jkun qiegħed jittieħed imqabbla ma ’ sulphonylurea miżjuda ma ’ metformin li diġà jkun qiegħed jittieħed kienet ta ’ 14. 5% u 30. 3%, rispettivament.
In pooled studies of up to 1 year in duration comparing sitagliptin added to ongoing metformin to a sulphonylurea agent added to ongoing 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).
Fi studji ippuljati ta ’ żmien sa sena li qabblu sitagliptin miżjud ma ’ metformin li diġà jkun qiegħed jittieħed ma ’ mediċina sulphonylurea miżjuda ma ’ metformin li diġà jkun qiegħed jittieħed, reazzjonijiet avversi kkunsidrati bħala relatati mal- mediċina rrapportati f’ pazjenti kkurati b’ 100 mg
2 In this 24-week placebo-controlled study of sitagliptin 100 mg once daily added to ongoing combination treatment with glimepiride and metformin, the overall incidence of adverse reactions considered as drug-related in patients treated with the addition of sitagliptin to the ongoing treatment
7 sitagliptin li seħħew f’ eċċess (> 0. 2% u differenza > pazjent 1) ta ’ dak f’ pazjenti li kienu qegħdin jirċievu mediċina sulphonylurea huma kif ġejjin: nuqqas t’ aptit (Disturbi ta ’ metaboliżmu u nutriment; frekwenza mhux komuni) u tnaqqis fil- piż (Investigazzjonijiet; frekwenza mhux komuni).
7 with glimepiride and metformin was 18.1% compared to treatment with the addition of placebo to the ongoing treatment with glimepiride and metformin which was 7.1%.
2 F’ dan l- istudju kkontrollat bi plaċebo ta ’ 24 ġimgħa ta ’ sitagliptin 100 mg darba kuljum miżjud ma ’ kura ta ’ kombinazzjoni ta ’ glimepiride u metformin li kompliet, l- inċidenza totali ta ’ reazzjonijiet avversi kkunsidrati bħala relatati mal- mediċina f’ pazjenti kkurati biż- żieda ta ’ sitagliptin mal- kura li tkun għadha qegħda tittieħed bi glimepiride u metformin kienet ta ’ 18. 1% meta mqabbla ma ’ kura biż- żieda ta ’ plaċebo mal- kura li tkun għadha qegħda tittieħed bi glimepiride u metformin li kienet 7. 1%.
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/ 1,000 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.
Fi studju ta ’ 24 ġimgħa ta ’ kura ta ’ kumbinazzjoni tal- bidu b’ sitagliptin u b’ metformin mogħtija darbtejn kuljum (sitagliptin/ metformin 50 mg/ 500 mg jew 50 mg/ 1000 mg), l- inċidenza totali ta ’ reazzjonijiet avversi kkunsidrati bħala relatati mal- mediċina f’ pazjenti kkurati b’ kumbinazzjoni ta ’ sitagliptin u metformin imqabbla ma ’ pazjenti kkurati bi plaċebo kienet 14. 0% u 9. 7%, rispettivament.
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.
L- inċidenza totali ta ’ reazzjonijiet avversi kkunsidrati bħala relatati mal- mediċina f’ pazjenti kkurati bil- kumbinazzjoni ta ’ sitagliptin u metformin kienet taqbel ma ’ metformin waħdu (14. 0% kull wieħed) u akbar minn sitagliptin waħdu (6. 7%), bid- differenzi relattivi għal sitagliptin waħdu primarjament minħabba reazzjonijiet avversi gastrointestinali relatati.
Additional information on the individual active substances of the fixed dose combination Sitagliptin 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.
Tagħrif addizjonali fuq is- sustanzi attivi individwali tal- kumbinazzjoni ta ’ doża fissa Sitagliptin Barra minn hekk, fi studji ta ’ monoterapija ta ’ żmien sa 24 ġimgħa ta ’ 100 mg sitagliptin waħdu darba kuljum imqabbel ma ’ plaċebo, reazzjonijiet avversi kkunsidrati bħala relatati mal- mediċina rrapportati b’ sitagliptin f’ eċċess (> 0. 2% u differenza > pazjent 1) ta ’ dak f’ pazjenti li jkunu qegħdin jirċievu plaċebo huma uġigħ ta ’ ras, ipogliċemija, stitikezza, u sturdament.
In addition to the drug related adverse reactions described above, adverse events (reported regardless of causal relationship to medicinal product) occurring in at least 5% and more commonly in patients treated with sitagliptin included upper respiratory tract infection and nasopharyngitis.
Barra minn hekk, għar- reazzjonijiet avversi relatati mal- mediċina deskritti hawn fuq, ir- reazzjonijiet avversi (rrapportati mingħajr ma jingħata kas jekk humiex relatati mal- prodott mediċinali) li qegħdin iseħħu f’ ta ’ lanqas 5% u aktar spiss f’ pazjenti kkurati b’ sitagliptin inkludew infezzjoni tal- passaġġi respiratorji ta ’ fuq u nażofarinġite.
Additional adverse events that occurred more frequently in patients treated with sitagliptin (not reaching the 5% level, but occurring with an incidence of > 0.5% higher with sitagliptin than that in the control group) included osteoarthritis and pain in extremity.
Episodji avversi addizjonali li seħħew aktar spiss f’ pazjenti kkurati b’ sitagliptin (li ma jilħqux il- livell ta ’ 5%, iżda li qegħdin iseħħu b’ inċidenza ta ’ > 0. 5% aktar bi sitagliptin milli fil- grupp ta ’ kontroll) inkludew osteoartrite u uġigħ fl- estremità.
Across clinical studies, a small increase in white blood cell (WBC) count (approximately 200 cells/ microl difference in WBC vs placebo; mean baseline WBC approximately 6,600 cells/ microl) was observed due to an increase in neutrophils.
Tul l- istudji kliniċi, kienet osservata żieda żgħira fil- għadd taċ- ċelloli bojod tad- demm (WBC) (madwar 200 ċellolli/ mikrol differenza f’ WBC vs plaċebo; WBC fil- linja bażi medja madwar 6, 600 ċellolli/ mikrol) minħabba żieda fin- newtrofili.
This observation was seen in most but not all studies.
Din l- osservazzjoni instabet fil- parti l- kbira iżda mhux fl- istudji kollha.
This change in laboratory parameters is not considered to be clinically relevant.
Din il- bidla fil- parametri tal- laboratorju mhijiex ikkunsidrata li hija klinikament relevanti.
No clinically meaningful changes in vital signs or in ECG (including in QTc interval) were observed with sitagliptin treatment.
L- ebda tibdil sinifikanti f’ sinjali vitali jew fl- ECG (inkluż l- interval QTc) ma kien osservat b ’ kura b’ sitagliptin.
Post-marketing data
Dejta ta ’ wara t- tqegħid fis- suq
During post-marketing experience of Efficib or sitagliptin, one of the active substances of Efficib, the following additional adverse reactions 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).
Waqt ġbir ta dejta ta ’ wara t- tqegħid fis- suq ta ’ Efficib jew sitagliptin, wieħed mis- sustanzi attivi ta ’ Efficib, ġew irrapportati l- effetti sekondarji oħra li ġejjin (frekwenza mhux magħrufa): reazzjonijiet ta ’ sensittività eċċessiva li jinkludu anafilassi, anġjoedima, raxx, urtikarja, u kondizzjonijiet esfoljativi tal - ġilda inkluż is- sindromu ta ’ Stevens- Johnson (ara sezzjoni 4. 4).
Clinical Trial Data and Post-marketing data
Dejta ta ’ Prova Klinika u dejta ta ’ Wara t- Tqegħid fis- Suq
Table 2 presents adverse reactions by system organ class and by frequency category.
Tabella 2 tippreżenta reazzjonijiet avversi bis- sistema ta ’ klassi ta ’ organi u kategorija ta ’ frekwenza.
Frequency categories are based on information available from metformin Summary of Product Characteristics available in the EU.
Kategoriji ta ’ frekwenza huma bbażati fuq tagħrif li hemm fis- Sommarju tal- Karatteristiċi tal- Prodott metformin li jinsab fl- UE.
The frequency of metformin adverse reactions identified from clinical trial and postmarketing data
Il- frekwenza ta ’ reazzjonijiet avversi ta ’ metformin identifikati minn prova klinika u dejta ta ’ wara t- tqegħid fis- suq
Adverse reaction
Reazzjoni avversa
Frequency
Frekwenza
metallic taste
Togħma metallika
8 Adverse reaction
Disturbi gastro- intestinali sintomi gastrointestinalia
Frequency
Komuni ħafna
Gastrointestinal disorders
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda
gastrointestinal symptomsa
urtikarja, eritima, ħakk
Very common
Rari ħafna
Skin and subcutaneous disorders urticaria, erythema, pruritis
Disturbi fil- metaboliżmu u n- nutrizzjoni Rari ħafna aċidożi lattika Nuqqas ta ’ vitamina B12b
Metabolism and nutrition disorders
Disturbi fil- fwied u fil- marrara
lactic acidosis vitamin B12 deficiencyb
disturbi fil- funzjoni tal- fwied, epatite
Very rare Very rare
Rari ħafna
Hepatobiliary disorders liver function disorders, hepatitis a
Sintomi gastrointestinali bħalma huma dardir, remettar, dijarea, uġigħ addominali u telf ta ’ aptit a
Gastrointestinal symptoms such as nausea, vomiting, diarrhoea, abdominal pain occur most frequently during initiation of therapy and resolve spontaneously in b
seħħew l- aktar spiss waqt il- bidu ta ’ terapija u fil- parti l- kbira tal- każi rrisolvew ruħhom waħidhom.
and loss of appetite most cases.
Kura fuq tul ta ’ żmien b’ metformin ġiet assoċjata ma ’ tnaqqis fl- assorbiment ta ’ vitamina B12 li rari b
Long-term treatment with metformin has been associated with a decrease in vitamin B12 absorption which may very rarely result in clinically significant vitamin B12 deficiency (e. g., megaloblastic anaemia).
ħafna tirriżulta f’ nuqqas ta ’ vitamina B12 klinikament sinifikanti (eż., anemija megaloblastika).
No data are available with regard to overdose of Efficib.
Ma hemm l- ebda tagħrif disponibbli dwar teħid eċċessiv ta ’ Efficib.
During controlled clinical trials in healthy subjects, single doses of up to 800 mg sitagliptin were generally well tolerated.
Waqt provi kliniċi kkontrollati f’ suġġetti b’ saħħithom, dożi waħdiet sa 800 mg sitagliptin kienu ġeneralment ittollerati sewwa.
Minimal increases in QTc, not considered to be clinically relevant, were observed in one study at a dose of 800 mg sitagliptin.
Żidiet minimi fi QTc, mhux ikkunsidrati klinikament relevanti, kienu osservati fi studju f’ doża ta ’ 800 mg sitagliptin.
There is no experience with doses above 800 mg in humans.
M’ hemm l- ebda esperjenza b’ dożi ta ’ aktar minn 800 mg fil- bnedmin.
In Phase I multiple-dose studies, there were no dose-related clinical adverse reactions observed with sitagliptin with doses of up to 600 mg per day for 10 days and 400 mg per day for periods of up to 28 days.
Fi studji ta ’ Fażi I b’ dożi multipli, ma kien hemm l- ebda reazzjoni avversa klinika relatata mad- doża osservata b’ sitagliptin b’ dożi sa 600 mg kuljum għal 10 ijiem u 400 mg kuljum għal perijodi sa 28 jum.
A large overdose of metformin (or co-existing risks of lactic acidosis) may lead to lactic acidosis which is a medical emergency and must be treated in hospital.
Teħid żejjed ta ’ metformin (jew flimkien ma ’ riskji eżistenti ta ’ aċidożi lattika) jistgħu jwasslu għal aċidożi lattika li tirriżulta f’ emerġenza medika li teħtieġ kura fl- isptar.
The most effective method to remove lactate and metformin is haemodialysis.
L- aktar metodu effettiv biex tneħħi lactate u metformin huwa permezz ta ’ emodijaliżi.
Sitagliptin is modestly dialyzable.
Sitagliptin huwa kemxejn dijaliżabbli.
In clinical studies, approximately 13.5% of the dose was removed over a 3- to 4-hour haemodialysis session.
Fi studji kliniċi, madwar 13. 5% tad- doża tneħħiet b’ emodijaliżi f’ medda ta ’ 3 sa 4 sigħat.
It is not known if sitagliptin is dialyzable by peritoneal dialysis.
Mhux magħruf jekk sitagliptin huwiex dijaliżabbli permezz ta ’ dijaliżi peritonejali.
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.
9 Fil- każ li tittieħed doża eċċessiva, huwa raġonevoli li tuża l- miżuri ta ’ appoġġ tas- soltu, eż., tneħħija ta ’ materjal mhux assorbit mill- istonku u l- imsaren, tuża sorveljanza klinika (inkluż l- użu ta ’ elettrokardjogramma), u tistitwixxi terapija ta ’ appoġġ jekk meħtieġa.
Combinations of oral blood glucose lowering drugs, ATC code:
Kumbinazzjonijiet ta ’ mediċini orali li jbaxxu z- zokkor, Kodiċi ATC:
Efficib combines two antihyperglycaemic agents with complementary mechanisms of action to improve glycaemic control in patients with type 2 diabetes: sitagliptin phosphate, a dipeptidyl peptidase 4 (DPP-4) inhibitor, and metformin hydrochloride, a member of the biguanide class.
Efficib jikkumbina żewġ mediċini kontra l- ipergliċemija b’ mekkaniżmi ta ’ azzjoni kumplimentari biex jitjieb il- kontroll gliċemiku f’ pazjenti b’ dijabete tip 2: sitagliptin phosphate, li hu impeditur dipeptidyl peptidase 4 (DPP- 4), u metformin hydrochloride, li hu membru tal- klassi biguanide.
9 Sitagliptin Sitagliptin phosphate is an orally-active, potent, and highly selective inhibitor of the dipeptidyl peptidase 4 (DPP-4) enzyme for the treatment of type 2 diabetes.
Sitagliptin Sitagliptin phosphate huwa impeditur attiv li jittieħed mill- ħalq, qawwi, ferm selettiv ta ’ l- enzim dipeptidyl peptidase 4 (DPP- 4) għall- kura ta ’ dijabete tip 2.
The DPP-4 inhibitors are a class of agents that act as incretin enhancers.
L- impedituri DPP- 4 huma klassi ta ’ mediċini li jaħdmu billi jtejbu l- azzjoni ta ’ incretin.
By inhibiting the DPP-4 enzyme, sitagliptin increases the levels of two known active incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP).
Sitagliptin iżid il- livelli ta ’ żewġ ormoni incretin attivi magħrufin, glucagon- like peptide- 1 (GLP- 1) u glucose- dependent insulinotropic polypeptide (GIP), billi jimpedixxi l- enzima DPP- 4.
The incretins are part of an endogenous system involved in the physiologic regulation of glucose homeostasis.
L- incretins huma parti minn sistema endoġena nvoluta li tirregola l- fisjoloġija ta ’ l- omejostażi taz- zokkor.
When blood glucose concentrations are normal or elevated, GLP-1 and GIP increase insulin synthesis and release from pancreatic beta cells.
Meta konċentrazzjonijiet ta ’ zokkor fid- demm huma normali jew għoljin, GLP- 1 u GIP iżidu s- sintesi u t- tnixxija ta ’ insulina miċ- ċelloli alfa pankrejatiċi.
GLP-1 also lowers glucagon secretion from pancreatic alpha cells, leading to reduced hepatic glucose production.
GLP- 1 inaqqas ukoll tnixxija ta ’ glukagon miċ- ċelloli alfa pankrejatiċi, u jwassal għal tnaqqis fil - produzzjoni ta ’ zokkor fil- fwied.
When blood glucose levels are low, insulin release is not enhanced and glucagon secretion is not suppressed.
Meta l- livelli ta ’ zokkor fid- demm ikunu baxxi, it- tnixxija ta ’ insulina ma titjiebx u t- tnixxija ta ’ glukagon ma tkunx imrażżna.
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.
Sitagliptin huwa impeditur qawwi u selettiv bil- bosta ta ’ l- enzima DPP- 4 u f’ konċentrazzjonijiet terapewtiċi ma jimpedixxix l- enzimi relatati mill- qrib DPP- 8 jew DPP- 9.
Sitagliptin differs in chemical structure and pharmacological action from GLP-1 analogues, insulin, sulphonylureas or meglitinides, biguanides, peroxisome proliferator-activated receptor gamma (PPARγ) agonists, alpha- glucosidase inhibitors, and amylin analogues.
Sitagliptin huwa differenti fl- istruttura kimika u azzjoni farmakoloġika minn analogi GLP- 1, insulin, sulphonylureas jew meglitinides, biguanides, agonisti peroxisome proliferator- activated receptor gamma (PPARγ), impedituri alpha- glucosidase, u analogi amylin.
Overall, sitagliptin improved glycaemic control when used in combination with metformin (as initial or add-on therapy) and in combination with a sulphonylurea and metformin, as measured by clinically relevant reductions in HbA1c from baseline at study endpoint (see Table 3).
Kollox ma ’ kollox, sitagliptin tejjeb il- kontroll gliċemiku meta wżat flimkien ma ’ metformin (bħala terapija tal- bidu jew terapija ta ’ żieda) u ma ’ sulphonylurea u metformin, kif imkejlin permezz ta ’ tnaqqis mil- linja bażi klinikament relevanti f’ HbA1c fil- punt ta ’ tmiem ta ’ l- istudju (ara Tabella 3).
In clinical trials, sitagliptin as monotherapy improved glycaemic control with significant reductions in haemoglobin A1c (HbA1c) and fasting and postprandial glucose.
Fi provi kliniċi, sitagliptin bħala monoterapija jtejjeb il- kontroll gliċemiku bi tnaqqis sinifikanti fl - emoglobina A1c (HbA1c) u z- zokkor imkejjel wara sawm jew wara l- ikel.
Reduction in fasting plasma glucose (FPG) was observed at 3 weeks, the first time point at which FPG was measured.
Tnaqqis fiz- zokkor fi stat ta ’ sawm (FPG) kien osservat fi 3 ġimgħat, l- ewwel darba meta tkejjel l- FPG.
The observed incidence of hypoglycaemia in patients treated with sitagliptin was similar to placebo.
L- inċidenza osservata ta ’ ipogliċemija f’ pazjenti kkurati b’ sitagliptin kien simili għal plaċebo.
Body weight did not increase from baseline with sitagliptin therapy.
Il- piż tal- ġisem ma żdiedx mil- linja bażi b’ terapija bi sitagliptin.
Improvements in 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.
Kien osservat titjib f’ markers sostituti tal- funzjoni taċ- ċelloli beta, inklużi HOMA- β (Stima ta ’ Mudell ta ’ Ħomeostażi- β), fil- proporzjon ta ’ proinsulina għal insulina, u f’ miżuri ta ’ reazzjoni ta ’ ċelloli beta mit- test ta ’ tolleranza għall- ikla b’ kampjuni meħudin spiss.
Studies of sitagliptin in combination with metformin In a 24-week, placebo-controlled clinical study to evaluate the efficacy and safety of the addition of sitagliptin 100 mg once daily to ongoing metformin, sitagliptin provided significant improvements in glycaemic parameters compared with placebo.
Studji ta ’ sitagliptin f’ kumbinazzjoni ma ’ metformin Fi studju kliniku kkontrollat bi plaċebo ta ’ 24 ġimgħa biex jevalwa l- effikaċja u s- sigurtà taż- żieda ta ’ 100 mg sitagliptin darba kuljum ma ’ metformin li diġà jkun qiegħed jittieħed, sitagliptin ġab titjib sinifikanti f’ parametri gliċemiċi meta mqabbel ma ’ plaċebo.
Change from baseline in body weight was similar for patients treated with sitagliptin relative to placebo.
Bidla mil- linja bażi fil- piż kienet simili għal pazjenti kkurati b’ sitagliptin meta mqabbla ma ’ plaċebo.
In this study there was a similar incidence of hypoglycaemia reported for patients treated with sitagliptin or placebo.
F’ dan l- istudju kien hemm inċidenza simili ta ’ ipogliċemija rrapportata f’ pazjenti kkurati bi sitagliptin jew bi plaċebo.
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.
Fi studju fattorjali kkontrollat bi plaċebo ta ’ 24 ġimgħa ta ’ terapija tal- bidu, sitagliptin 50 mg darbtejn kuljum f’ kumbinazzjoni ma ’ metformin (500 mg jew 1000 mg darbtejn kuljum) ġab titjib sinifikanti f’ parametri gliċemiċi meta mqabbel ma ’ monoterapija kemm wieħed u kemm bl- ieħor.
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.
It- tnaqqis fil - piż korporali bil- kumbinazzjoni ta ’ sitagliptin u metformin kien simili għal dak osservat b’ metformin
The incidence of hypoglycaemia was similar across treatment groups.
L- inċidenza ta ’ ipogliċemija kienet simili fuq il- medda taż- żewġ gruppi ta ’ kura.
Study of sitagliptin in combination with metformin and a sulphonylurea 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 in combination with metformin).
Studji ta ’ sitagliptin f’ kumbinazzjoni ma ’ metformin u sulphonylurea Ġie mfassal studju kkontrollat bi plaċebo ta ’ 24 ġimgħa biex jevalwa l- effikaċja u s- sigurtà ta ’ sitagliptin (100 mg darba kuljum) miżjud ma ’ glimepiride (waħdu jew f’ kumbinazzjoni ma ’ metformin).
The addition of sitagliptin to glimepiride and metformin provided significant improvements in glycaemic parameters.
Iż- żieda ta ’ sitagliptin ma ’ glimepiride u metformin ġabet titjib sinifikanti fil- parametri gliċemiċi.
Patients treated with sitagliptin had a modest increase in body weight (+1.1 kg) compared to those given placebo.
Pazjenti kkurati b’ sitagliptin kellhom żieda modesta fil- piż (+1. 1 kg) meta mqabbla ma ’ dawk li ngħataw plaċebo.
10 Table 3:
Tabella 3:
HbA1c results in placebo-controlled combination therapy studies of sitagliptin and metformin*
Riżultati ta ’ HbA1c fi studji ta ’ terapija ta ’ kumbinazzjoni kkontrollata bi plaċebo ta ’ sitagliptin u metformin *
Mean baseline
Linja bażi
Mean change from
Bidla medja minn
in HbA1c (%) at Week 24†
Bidla medja f’ HbA1c ikkoreġuta bi plaċebo (%) f ’ Ġimgħa 24 †
at Week 24†
HbA1c fil- linja bażi (%) f’ Ġimgħa 24 †
Sitagliptin 100 mg once daily added to ongoing metformin
Sitagliptin 100 mg darba kuljum miżjud ma ’ terapija li - 0. 7 ‡ diġà tkun qegħda tittieħed b’ metformin (N=453) Sitagliptin 100 mg darba kuljum miżjud ma ’ terapija li
-0.7
- 0. 7
-0.7‡
(- 0. 8, - 0. 5) - 0. 9 ‡
added to ongoing glimepiride + metformin therapy (N=115) Initial Therapy (twice daily):
diġà tkun qegħda tittieħed bi glimepiride + metformin (N=115) Terapija tal- bidu (darbtejn kuljum):
-0.6
- 0. 6
-0.9‡ (-1.1, -0.7)
(- 1. 1, - 0. 7) - 1. 6 ‡
Sitagliptin 50 mg + metformin 500 mg (N=183) Initial Therapy (twice daily):
Sitagliptin 50 mg + metformin 500 mg (N=183) Terapija tal- bidu (darbtejn kuljum):
-1.6‡ (-1.8, -1.3)
(- 1. 8, - 1. 3) - 2. 1 ‡
* 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.
* Popolazzjoni Pazjenti Kollha Ikkurati (analiżi intenzjoni- li- tikkura). † Least squares tfisser aġġustat għal status ta ’ qabel kontra l- ipergliċemija u l- valur fil- linja bażi. ‡ p < 0. 001 imqabbel ma ’ plaċebo jew plaċebo + kura ta ’ kumbinazzjoni.
In a 52-week study, comparing the efficacy and safety of the addition of sitagliptin 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 (-0.7% mean change from baselines at week 52, with baseline HbA1c of approximately 7.5% in both groups).
Fi studju ta ’ 52- il ġimgħa, li qabbel l- effikaċja u s- sigurtà taż- żieda ta ’ sitagliptin 100 mg darba kuljum jew glipizide (mediċina sulphonylurea) f’ pazjenti b’ kontroll gliċemiku inadegwat fuq monoterapija b’ metformin, sitagliptin kien simili għal glipizide fit- tnaqqis ta ’ HbA1c (- 0. 7% bidla medja mil- linji bażi f’ ġimgħa 52, b ’ HbA1c fil- linja bażi ta ’ madwar 7. 5% fiż- żewġ gruppi).
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.
Id- doża medja ta ’ glipizide użata fil- grupp ta ’ tqabbil kienet ta ’ 10 mg kuljum b’ madwar 40% tal- pazjenti jeħtieġu doża ta ’ glipizide ta ’ ≤ 5 mg/ kuljum matul l- istudju.
However, more patients in the sitagliptin group discontinued due to lack of efficacy than in the glipizide group.
Madankollu, aktar pazjenti fil- grupp sitagliptin waqqfuh minħabba nuqqas ta ’ effikaċja milli fil- grupp ta ’ glipizide.
Patients treated with sitagliptin exhibited a significant mean decrease from baseline in body weight (-1.5 kg) compared to a significant weight gain in patients administered glipizide (+1.1 kg).
Pazjenti kkurati b’ sitagliptin urew tnaqqis sinifikanti fil- piż (- 1. 5 kg) mill- medja tal- linja bażi meta imqabbel ma ’ żieda fil- piż f’ pazjenti mogħtijin glipizide (+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.
F’ dan l- istudju, il- proporzjon ta ’ proinsulina għal insulina, marker ta ’ effiċjenza ta ’ sintesi u tnixxija ta ’ insulina, tjieb b’ sitagliptin u mar għall- agħar b’ kura bi glipizide.
The incidence of hypoglycaemia in the sitagliptin group (4.9%) was significantly lower than that in the glipizide group (32.0%).
L - inċidenza ta ’ ipogliċemija fil- grupp ta ’ sitagliptin (4. 9%) kienet ferm aktar baxxa minn dik fil- grupp ta ’ glipizide( 32. 0%).
Metformin Metformin is a biguanide with antihyperglycaemic effects, lowering both basal and postprandial plasma glucose.
Metformin Metformin huwa biguanide b’ effetti kontra l- ipergliċemija, li jnaqqas kemm iz- zokkor bażali fil - plażma kif ukoll dak ta ’ wara l- ikel.
It does not stimulate insulin secretion and therefore does not produce hypoglycaemia.
Huwa ma jqanqalx tnixxija ta ’ insulina u għaldaqstant ma jipproduċix ipogliċemija.
Metformin may act via three mechanisms:
11 Metformin jista ’ jaħdem permezz ta ’ tliet mekkaniżmi:
- by reduction of hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis
- bi tnaqqis fil- produzzjoni ta ’ zokkor fil- fwiedbilli jimpedixxi glukoneoġenesi u glajkoġenoliżi
- in muscle, by modestly increasing insulin sensitivity, improving peripheral glucose uptake and
- fil- muskolu, billi jżid kemxejn is- sensittività ta ’ l- insulina, itejjeb it- teħid u l- użu ta ’ zokkor fil -
utilisation
periferija
- by delaying intestinal glucose absorption.
- billi jittardja l- assorbiment ta ’ zokkor intestinali.
Metformin stimulates intracellular glycogen synthesis by acting on glycogen synthase.
Metformin jistimola sintesi ta ’ glajkoġen intraċellolari billi jaħdem fuq glycogen synthase.
Metformin increases the transport capacity of specific types of membrane glucose transporters (GLUT-1 and GLUT-4).
Metformin iżid il- kapaċità ta ’ trasport minn ġol- membrana ta ’ tipi speċifiċi ta ’ trasportaturi ta ’ zokkor (GLUT- 1 and GLUT- 4).
In humans, independently of its action on glycaemia, metformin has favourable effects on lipid metabolism.
Fil- bnedmin, metformin għandu effetti favorevoli fuq il- metaboliżmu tal- lipidi, indipendentement mill- azzjoni tiegħu fuq il- gliċemija.
This has been shown at therapeutic doses in controlled, medium-term or long-term clinical studies: metformin reduces total cholesterol, LDLc and triglyceride levels.
Dan intwera f’ dożi terapewtiċi fi studji kliniċi kkontrollati, ta ’ żmien medju jew żmien twil: metformin inaqqas il- kolesterol totali, LDLc u l- livelli ta ’ trigliċeridi.
11 The prospective randomised (UKPDS) study has established the long-term benefit of intensive blood glucose control in type 2 diabetes.
L- istudju prospettiv randomizzat (UKPDS) stabbilixxa l- benefiċċju ta ’ tul ta ’ żmien fuq kontroll intensiv ta ’ zokkor fid- demm f’ dijabete tip 2.
Analysis of the results for overweight patients treated with metformin after failure of diet alone showed:
Analiżi tar- riżultati għal pazjenti b’ piż eċċessiv ikkurati b’ metformin wara falliment ta ’ dieta waħidha wrew:
- a significant reduction of the absolute risk of any diabetes-related complication in the metformin
- tnaqqis sinifikanti fir- riskju assolut ta ’ kwalunkwe kumplikazzjoni relatata mad- dijabete fil -
group (29.8 events/ 1,000 patient-years) versus diet alone (43.3 events/ 1,000 patient-years), p=0.0023, and versus the combined sulphonylurea and insulin monotherapy groups (40.1 events/ 1,000 patient-years), p=0.0034
grupp ta ’ metformin (29. 8 episodju/ 1, 000 pazjenti- snin) kontra dieta waħidha (43. 3 episodju / 1, 000 pazjenti- snin), p=0. 0023, u kontra l- gruppi ta ’ monoterapija ta ’ kumbinazzjoni ta ’ sulphonylurea u insulina (40. 1 episodju / 1, 000 pazjenti- snin), p=0. 0034
- a significant reduction of the absolute risk of any diabetes-related mortality: metformin
- tnaqqis sinifikanti fir- riskju assolut ta ’ kwalunkwe mortalità relatata mad- dijabete: metformin
7.5 events/ 1,000 patient-years, diet alone 12.7 events/ 1,000 patient-years, p=0.017
7. 5 episodji/ 1, 000 pazjenti- snin, dieta waħidha 12. 7- il episodju / 1, 000 pazjenti- snin, p=0. 017
- a significant reduction of the absolute risk of overall mortality: metformin
- tnaqqis sinifikanti fir- riskju assolut ta ’ mortalità totali: metformin 13. 5- il episodju
13.5 events/ 1,000 patient-years versus diet alone 20.6 events/ 1,000 patient-years, (p=0.011), and versus the combined sulphonylurea and insulin monotherapy groups 18.9 events/ 1,000 patient-years (p=0.021)
/ 1, 000 pazjenti- snin kontra dieta waħidha 20. 6 episodju / 1, 000 pazjenti- snin, (p=0. 011), u kontra l- gruppi ta ’ monoterapija ta ’ kumbinazzjoni ta ’ sulphonylurea u insulina 18. 9- il episodju/ 1, 000 pazjenti- snin (p=0. 021)
- a significant reduction in the absolute risk of myocardial infarction: metformin
- tnaqqis sinifikanti fir- riskju assolut ta ’ infart majokardjali: metformin 1l- il episodju
11 events/ 1,000 patient-years, diet alone 18 events/ 1,000 patient-years, (p=0.01).
/ 1, 000 pazjenti- snin, dieta waħidha 18- il episodju / 1, 000 pazjenti- snin, (p=0. 01).
Efficib A bioequivalence study in healthy subjects demonstrated that the Efficib (sitagliptin/ metformin hydrochloride) combination tablets are bioequivalent to co-administration of sitagliptin phosphate and metformin hydrochloride as individual tablets.
Efficib Studju ta ’ bijoekwivalenza f’ suġġetti b’ saħħithom wera li pilloli ta ’ kumbinazzjoni Efficib (sitagliptin/ metformin hydrochloride) huma bijoekwivalenti għal għoti konkomitanti ta ’ sitagliptin phosphate u metformin hydrochloride bħala pilloli individwali.
The following statements reflect the pharmacokinetic properties of the individual active substances of Efficib.
L- istqarrijiet li ġejjin jirriflettu l- kwalitajiet tas- sustanzi attivi individwali ta ’ Efficib.
Sitagliptin 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.
Sitagliptin Assorbiment Wara għoti orali ta ’ doża ta ’ 100 mg lil suġġetti b’ saħħithom, sitagliptin kien assorbit malajr, bl- ogħla konċentrazzjonijiet fil- plażma (Tmax medjan) jseħħu 1 sa 4 sigħat wara d- doża, l- AUC fil- plażma medja ta ’ sitagliptin kienet ta ’ 8. 52 μM• hr, is- Cmax kienet ta ’ 950 nM.
The absolute bioavailability of sitagliptin is approximately 87%.
Il- bijodisponibbilità ta ’ sitagliptin hija madwar 87%.
Since co-administration of a high-fat meal with sitagliptin had no effect on the pharmacokinetics, sitagliptin may be administered with or without food.
Sitagliptin jista ’ jingħata ma ’ l- ikel jew fuq stonku vojt, minħabba li l - għoti konkomitanti ma ’ ikel b’ ħafna xaħam ma ’ sitagliptin ma kellu l- ebda effett fuq il- farmkinetika.
Plasma AUC of sitagliptin increased in a dose-proportional manner.
L- AUC ta ’ sitagliptin żdied b’ mod proporzjonali għad- doża.
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).
Il- proporzjonalità tad- doża ma kinitx stabbilita għas- Cmax u s- C24hr (Cmax żdiedet b’ mod akbar mill- mod proporzjonali għad- doża u s - C24hr żdiedet b’ mod inqas mill- mod proporzjonali għad- doża).
Distribution The mean volume of distribution at steady state following a single 100-mg intravenous dose of sitagliptin to healthy subjects is approximately 198 litres.
Distribuzzjoni Il- medja tal- volum ta ’ distribuzzjoni fi stat fiss wara doża waħda intravenuża ta ’ 100 mg sitagliptin lil suġġetti b’ saħħithom huwa madwar 198 litru.
The fraction of sitagliptin reversibly bound to plasma proteins is low (38%).
Il- frazzjoni ta ’ sitagliptin marbut riversibbilment mal - proteini fil- plażma huwa wieħed baxx (38%).
Metabolism Sitagliptin is primarily eliminated unchanged in urine, and metabolism is a minor pathway.
12 Metaboliżmu Sitagliptin huwa primarjament eliminat mhux mibdul fl- awrina, u l- metaboliżmu huwa passaġġ minuri.
Approximately 79% of sitagliptin is excreted unchanged in the urine.
Madwar 79% ta ’ sitagliptin huwa eliminat mhux mibdul fl- awrina.
Following a [14C]sitagliptin oral dose, approximately 16% of the radioactivity was excreted as metabolites of sitagliptin.
Wara doża orali ta ’ [14C] sitagliptin, madwar 16% tar- radjuattività kienet eliminata bħala metaboliti ta ’ sitagliptin.
Six metabolites were detected at trace levels and are not expected to contribute to the plasma DPP-4 inhibitory activity of sitagliptin.
Instabu traċċi ta ’ sitt metaboliti u mhumiex mistennija li jikkontribwixxu għall- attività inibitorja ta ’ DPP- 4 fil- plażma kontra sitagliptin.
In vitro studies indicated that the primary enzyme responsible for the limited metabolism of sitagliptin was CYP3A4, with contribution from CYP2C8.
Studji in vitro indikaw li l- enzima primarja responsabbli għall- metaboliżmu limitat ta ’ sitagliptin kienet CYP3A4, b’ kontribuzzjoni minn CYP2C8.
In vitro data showed that sitagliptin is not an inhibitor of CYP isoenzymes CYP3A4, 2C8, 2C9, 2D6, 1A2, 2C19 or 2B6, and is not an inducer of CYP3A4 and CYP1A2.
Tagħrif in vitro wera li sitagliptin mhuwiex impeditur ta ’ iżoenzimi CYP CYP3A4, 2C8, 2C9, 2D6, 1A2, 2C19 jew 2B6, u mhuwiex induttur ta ’ CYP3A4 u CYP1A2.
12 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.
Eliminazzjoni Wara għoti ta ’ doża [14C] sitagliptin orali lil suġġetti b’ saħħithom, madwar 100% tar- radjuattività kienet eliminata fl- ippurgar (13%) jew l- awrina (87%) fi żmien ġimgħa mid- dożaġġ.
The apparent terminal t½ following a 100-mg oral dose of sitagliptin was approximately 12.4 hours.
It - t½ terminali apparenti wara doża orali ta ’ 100 mg ta ’ sitagliptin kienet madwar 12. 4- il siegħa.
Sitagliptin accumulates only minimally with multiple doses.
Sitagliptin jakkumula minimament biss b’ dożi multipli.
The renal clearance was approximately 350 ml/ min.
Ir- rata ta ’ eliminazzjoni tal- kliewi kienet ta ’ madwar 350 ml/ min.
Elimination of sitagliptin occurs primarily via renal excretion and involves active tubular secretion.
Eliminazzjoni ta ’ sitagliptin isseħħ primarjament permezz ta ’ eliminazzjoni mil- kliewi u tinvolvi tnixxija tubulari.
Sitagliptin is a substrate for human organic anion transporter-3 (hOAT-3), which may be involved in the renal elimination of sitagliptin.
Sitagliptin huwa sottostrat għal trasportatur- 3 anijonju organiku tal- bniedem (hOAT- 3), li jista ’ jkun involut f’ eliminazzjoni ta ’ sitagliptin mill- kliewi.
The clinical relevance of hOAT-3 in sitagliptin transport has not been established.
Ir- relevanza klinika ta ’ hOAT- 3 fit- trasport ta ’ sitagliptin ma ġietx stabbilita.
Sitagliptin is also a substrate of p-glycoprotein, which may also be involved in mediating the renal elimination of sitagliptin.
Sitagliptin huwa wkoll sottostrat ta ’ p- glycoprotein, li jista ’ jkun ukoll involut fil- medjazzjoni ta ’ l- eliminazzjoni ta ’ sitagliptin mill - kliewi.
However, cyclosporine, a p-glycoprotein inhibitor, did not reduce the renal clearance of sitagliptin.
Madankollu, cyclosporine, impeditur ta ’ p- glycoprotein, ma naqqasx ir- rata ta ’ eliminazzjoni ta ’ sitagliptin mill- kliewi.
Sitagliptin is not a substrate for OCT2 or OAT1 or PEPT1/ 2 transporters.
Sitagliptin mhuwiex sottostrat għal trasportaturi OCT2 jew OAT1 jew PEPT1/ 2.
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, sitagliptin ma impedixxiex trasport medjat minn OAT3 (IC50=160 μM) jew p- glycoprotein (sa 250 μM) f’ konċentrazzjonijiet fil- plażma terapewtikament relevanti.
In a clinical study sitagliptin had a small effect on plasma digoxin concentrations indicating that sitagliptin may be a mild inhibitor of p-glycoprotein.
Fi studju kliniku, sitagliptin kellu effett żgħir fuq konċentrazzjonijiet ta ’ digoxin fil- plażma li jindika li sitagliptin jista ’ jkun impeditur dgħajjef ta ’ p- glycoprotein.
Characteristics in patients The pharmacokinetics of sitagliptin were generally similar in healthy subjects and in patients with type 2 diabetes.
Karatteristiċi f’ pazjenti Il- farmakokinetika ta ’ sitagliptin kienet ġeneralment simili f’ suġġetti f’ saħħithom u f’ pazjenti b’ dijabete tip 2.
Renal insufficiency A single-dose, open-label study was conducted to evaluate the pharmacokinetics of a reduced dose of sitagliptin (50 mg) in patients with varying degrees of chronic renal insufficiency compared to normal healthy control subjects.
Indeboliment tal- kliewi Sar studju b’ doża waħda, b’ tikketta miftuħa biex jevalwa l- farmakokinetika ta ’ doża mnaqqsa ta ’ sitagliptin (50 mg) f’ pazjenti bi gradi li jvarjaw ta ’ indeboliment tal- kliewi kroniku meta mqabbla ma ’ suġġetti ta ’ kontroll normali b’ saħħithom.
The study included patients with renal insufficiency classified on the basis of creatinine clearance as mild (50 to < 80 ml/ min), moderate (30 to < 50 ml/ min), and severe (< 30 ml/ min), as well as patients with end-stage renal disease (ESRD) on haemodialysis.
L- istudju nkluda pazjenti b’ indeboliment tal- kliewi kklassifikati fuq il- bażi tar- rata ta ’ eliminazzjoni ta ’ kreatinin bħala ħafif (50 sa < 80 ml/ min), moderat (30 sa < 50 ml/ min), u sever (< 30 ml/ min), kif ukoll bħala pazjenti b’ mard tal- kliewi ta ’ l- aħħar stadju (ESRD) fuq l- emodijaliżi.
Patients with mild renal insufficiency did not have a clinically meaningful increase in the plasma concentration of sitagliptin as compared to normal healthy control subjects.
Pazjenti b’ indeboliment ħafif tal- kliewi ma kellhomx żieda fil- konċentrazzjoni fil- plażma ta ’ sitagliptin klinikament sinifikanti meta mqabbla ma ’ suġġetti ta ’ kontroll normali b’ saħħithom.
An approximately 2-fold increase in the plasma AUC of sitagliptin was observed in patients with moderate renal insufficiency, and an approximately 4-fold increase was observed in patients with severe renal insufficiency and in patients with ESRD on haemodialysis, as compared to normal healthy control subjects.
Żieda ta ’ darbtejn fl- AUC ta ’ sitagliptin fil- plażma kienet osservata f’ pazjenti b’ indeboliment moderat tal - kliewi, u żieda ta ’ madwar 4 darbiet kienet osservata f’ pazjenti b’ indeboliment sever tal- kliewi u f’ pazjenti b’ ESRD fuq emodijaliżi, meta mqabbla ma ’ suġġetti ta ’ kontroll normali b’ saħħithom.
Sitagliptin was modestly removed by haemodialysis (13.5% over a 3- to 4-hour haemodialysis session starting 4 hours post-dose).
Sitagliptin kien modestament imneħħi permezz ta ’ emodijaliżi (13. 5% fuq sessjoni ta ’ emodijaliżi ta ’ 3 sa 4 sigħat li jibdew 4 sigħat wara d- doża).
Sitagliptin is not recommended for use in patients with moderate or severe renal insufficiency including those with ESRD since experience in these patients is too limited (see section 4.2).
Sitagliptin mhuwiex irrakkomandat għal użu f’ pazjenti b’ indeboliment tal- kliewi moderat jew sever inkużi dawk b’ ESRD minħabba li esperjenza f’ dawn il - pazjenti hija limitata wisq (ara sezzjoni 4. 2).
Hepatic insufficiency No dose adjustment for sitagliptin is necessary for patients with mild or moderate hepatic insufficiency (Child-Pugh score ≤ 9).
Indebolimenttal- fwied L- ebda aġġustament fid- doża ma huwa neċessarju għal sitagliptin għal pazjenti b’ indeboliment tal - fwied ħafif għal moderat (Skor Child- Pugh ≤ 9).
There is no clinical experience in patients with severe hepatic insufficiency (Child-Pugh score > 9).
Ma hemm l- ebda esperjenza klinika f’ pazjenti
However, because sitagliptin is primarily renally eliminated, severe hepatic insufficiency is not expected to affect the pharmacokinetics of sitagliptin.
Madankollu, minħabba li sitagliptin huwa primarjament eliminat mill- kliewi, indeboliment sever tal- fwied mhuwiex mistenni li jaffettwa l - farmakokinetika ta ’ sitagliptin.
Elderly No dose adjustment is required based on age.
L- anzjani L- ebda aġġustament fid- doża ma huwa meħtieġ ibbażat fuq l- età.