qanastek/EMEA-V3 huggingface dataset:
Due to lack of human data, TESAVEL should not be used during pregnancy.
T k nav datu par cilv kiem, TESAVEL gr tniec bas laik lietot nedr kst.
Lactation It is unknown whether sitagliptin is excreted in human breast milk.
Z d šana Nav zin ms, vai sitaglipt ns izdal s m tes pien cilv kam.
Animal studies have shown excretion of sitagliptin in breast milk.
P t jumos ar dz vniekiem konstat ta sitaglipt na izdal šan s m t šu pien.
TESAVEL should not be used during breast-feeding.
TESAVEL nedr kst lietot z d šanas laik.
However, when driving or operating machines, it should be taken into account that dizziness and somnolence have been reported.
Tom r, ja pacientam j vada transportl dzeklis vai j apkalpo meh nismi, j em v r, ka zi ots par reiboni un miegain bu.
4 4.8 Undesirable effects
4 4. 8 Nev lam s blakuspar d bas
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.
L dz 2 gadus ilgos devi os lielos kl niskos p t jumos vair k nek 2700 pacientu ir sa muši rst šanu ar TESAVEL 100 mg dien atseviš i vai kombin cij ar metform nu, sulfonilur nvielas atvasin jumu (kop ar metform nu vai bez t) vai PPARγ l dzekli.
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.
Šajos p t jumos terapijas p rtraukšanas biežums z u izrais tu blakuspar d bu d bija 0, 8%, lietojot 100 mg dien un 1, 5%, lietojot citus l dzek us.
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.
Nevienu no blakuspar d b m, kas uzskat mas par saist t m ar z l m, ar sitaglipt nu rst tiem pacientiem nenov roja biež k (> 0, 2% un atš ir ba > 1 pacients) k ar kontroll dzekli rst tiem pacientiem.
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.
Ar z u lietošanu saist tas blakuspar d bas, par kur m ar sitaglipt nu rst tiem pacientiem zi ots biež k (> 0, 2% un atš ir ba > 1 pacients) nek ar placebo rst tiem pacientiem, p c org nu sist mas klas m un biežuma ir uzskait tas zem k (1. tabula).
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).
Biežuma defin cija: oti bieži (1/ 10); bieži (1/ 100, < 1/ 10); ret k (1/ 1, 000, < 1/ 100); reti (1/ 10 000, < 1/ 1000) un oti reti (< 1/ 10 000).
The frequency of adverse reactions identified from placebo-controlled clinical studies
Placebo kontrol tu kl nisko p t jumu noteikto blakuspar d bu biežums
Adverse Reaction
Blakuspar d ba
Frequency of adverse reaction by treatment regimen
Blakuspar d bu biežums atkar b no rst šanas rež ma ns ar Sitaglipt ns ar Sitaglipt ns ar Sitaglipt ns ar
Sitagliptin with Sitagliptin with Sitagliptin with 1 2
sulfonilur nvielas 2
Sitagliptin with
metform nu un
Metformin
γ l dzekli
a Sulfonylurea
atvasin jumiem
Metformin and a a PPARγ Agent Sulfonylurea3 (pioglitazone)4
sulfonilur nvielas atvasin jumiem 3
Metabolism and nutrition disorders
Metabolisma un barošan s trauc jumi
hypoglycaemia*
hipoglik mija *
Very common
oti bieži
Nervous system disorders somnolence
Nervu sist mas trauc jumi miegain ba
Uncommon
Ret k
Gastrointestinal disorders
Ku a- zarnu trakta trauc jumi
diarrhea nausea flatulence constipation upper abdominal pain
caureja slikta d ša meteorisms aizciet jums s pes v dera augš j da
Uncommon Common Uncommon
Ret k Bieži Ret k
General disorders peripheral oedema
Visp r ji trauc jumi perif r t ska
Investigations blood glucose decreased *
Izmekl jumi samazin ts glikozes l menis asin s *
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.
Kl niskos p t jumos, lietojot TESAVEL monoterapijas veid un sitaglipt nu k kombin tas terapijas da u kop ar metform nu vai pioglitazonu, sitaglipt na lietot jiem nov rotais hipoglik mijas biežums bija l dz gs k placebo lietot jiem.
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 Šaj placebo kontrol t 24 ned u p t jum, lietojot reizi dien 100 mg sitaglipt na kombin cij ar metform nu, ar z u lietošanu saist tu blakuspar d bu sastopam ba ar sitaglipt nu/ metform nu rst tiem pacientiem sal dzin jum ar placebo/ metform na terapiju bija attiec gi 9, 3% un 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.
5 Papildus vienu gadu ilg p t jum, lietojot reizi dien 100 mg sitaglipt na kombin cij ar metform nu, ar z u lietošanu saist tu blakuspar d bu sastopam ba ar sitaglipt nu/ metform nu rst tiem pacientiem sal dzin jum ar sulfonilur nvielas atvasin jumu/ metform nu, bija attiec gi 14, 5% un 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).
Apkopotos l dz 1 gadu ilgos p t jumos, kuros sal dzin ts sitaglipt ns/ metform ns ar sulfonilur nvielas atvasin jumu/ metform nu, ar z u lietošanu saist t s blakuspar d bas, par kur m ar 100 mg sitaglipt na rst tiem pacientiem zi ots biež k (> 0, 2% un atš ir ba > 1 pacients) nek pacientiem, kas sa em sulfonilur nvielas atvasin jumu, ir š das: anoreksija (Metabolisma un barošan s trauc jumi; sastopam bas biežums - ret k) un samazin ta erme a masa (Izmekl jumi; sastopam bas biežums - ret k).
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 Šaj 24 ned u p t jum, kur reizi dien lietoja 100 mg sitaglipt na kombin cij ar glimepir du, ar z u lietošanu saist tu blakuspar d bu sastopam ba ar sitaglipt nu/ glimepir du rst tiem pacientiem sal dzin jum ar placebo/ glimepir du rst tiem pacientiem, attiec gi bija11, 3% un 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 Šaj 24 ned u p t jum, kur reizi dien lietoja 100 mg sitaglipt na kombin cij ar glimepir du un metform nu, ar z u lietošanu saist tu blakuspar d bu sastopam ba ar sitaglipt na un glimepir da/ metform na kombin ciju rst tiem pacientiem sal dzin jum ar placebo/ glimepir du rst tiem pacientiem, attiec gi bija 18, 1% un 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 Šaj 24 ned u p t jum, kur reizi dien lietoja 100 mg sitaglipt na kombin cij ar pioglitazonu, ar z u lietošanu saist tu blakuspar d bu sastopam ba ar sitaglipt nu/ pioglitazonu rst tiem pacientiem sal dzin jum ar placebo/ pioglitazonu rst tiem pacientiem, bija attiec gi 9, 1% un 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.
Turkl t monoterapijas p t jumos l dz 24 ned m ilgi, lietojot tikai reizi dien 100 mg sitaglipt na sal dzin jum ar placebo, ar z u lietošanu saist tas blakuspar d bas, par kur m ar sitaglipt nu rst tiem pacientiem zi ots biež k (> 0, 2% un atš ir ba > 1 pacients) nek ar placebo rst tiem pacientiem, ir galvass pes, hipoglik mija, aizciet jums un reibonis.
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.
Papildus augst k min taj m ar z u lietošanu saist taj m blakuspar d b m zi ots par blakuspar d b m, kam nav c loniskas saist bas ar z u lietošanu un ko nov roja vismaz 5% vai vair k ar TESAVEL rst to pacientu, ieskaitot augš jo elpce u infekcijas un nazofaring tu.
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.
V l ar zi ots par blakuspar d b m, kam nav c loniska sakar ba ar rst šanu un ko biež k nov roja ar TESAVEL rst tiem pacientiem (nesasniedzot 5% l meni, bet kuru sastopam bas biežums bija > 0, 5% vai vair k ar TESAVEL rst tajiem, sal dzinot ar kontroles grupu), ieskaitot osteoartr tu un s pes ekstremit t s.
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.
24 ned u p t jum, s kotn ji divas reizes dien lietojot sitaglipt na un metform na kombin to terapiju (sitaglipt ns/ metform ns 50 mg/ 500 mg vai 50 mg/ 100 mg), kopum ar z u lietošanu saist to blakuspar d bu sastopam ba ar sitaglipt na un metform na kombin ciju rst tiem pacientiem sal dzin jum ar placebo attiec gi bija 14, 0% un 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.
Kopum uzskat ts, ka ar z u lietošanu saist tu blakuspar d bu sastopam ba ar sitaglipt na un metform na kombin ciju rst tiem pacientiem bija sal dzin ma ar metform na monoterapiju (14, 0% katra) un liel ka k sitaglipt na monoterapijai (6, 7%), ar relat v m sitaglipt na monoterapijas atš ir b m, galvenok rt gastrointestin lo blakuspar d bu d.
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.
Kl niskos p t jumos neitrofilu skaita palielin šan s d nov roja nelielu balto asins š nu skaita palielin šanos (aptuveni 200 š nas/ mikrolitr leikoc tu atš ir ba, sal dzinot ar placebo; vid jais s kotn jais leikoc tu skaits aptuveni 6600 š nas/ mikrolitr).
This observation was seen in most but not all studies.
Šis nov rojums konstat ts liel k da, bet ne visos p t jumos.
This change in laboratory parameters is not considered to be clinically relevant.
Šo laboratorisko raksturlielumu p rmai u neuzskata par kl niski noz m gu.
No clinically meaningful changes in vital signs or in ECG (including in QTc interval) were observed with TESAVEL treatment.
TESAVEL terapijas laik nenov roja kl niski noz m gas dz v bai svar go paz mju vai EKG (tostarp QTc interv la) p rmai as.
6 Post-marketing Experience:
6 P cre istr cijas pieredze
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).
Period p c z u re istr cijas zi ots par sekojoš m nev lam m blakuspar d b m (biežums nav zin ms): paaugstin tas jut bas reakcijas, tai skait anafilakse, angioneirotisk t ska, izsitumi, n trene un eksfoliat vi das boj jumi, ieskaitot St vensa- Džonsona sindromu (skat t apakšpunktu 4. 4).
During controlled clinical trials in healthy subjects, single doses of up to 800 mg sitagliptin were generally well tolerated.
Kontrol tu kl nisku p t jumu laik veseliem cilv kiem vienreiz ju l dz 800 mg lielu sitaglipt na devu panesam ba parasti bija laba.
Minimal increases in QTc, not considered to be clinically relevant, were observed in one study at a dose of 800 mg sitagliptin.
Minim lu QTc pagarin šanos, kas netika uzskat ta par kl niski noz m gu, nov roja vien p t jum ar 800 mg sitaglipt na devu.
There is no experience with doses above 800 mg in humans.
Nav pieredzes par 800 mg liel ku devu lietošanu cilv kiem.
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.
P rdoz šanas gad jum iesaka veikt parastos pas kumus, piem ram, izvad t neuzs kušos vielu no ku a- zarnu trakta, veikt kl nisku uzraudz bu (tai skait pierakst t elektrokardiogrammu) un veikt uzturošas terapijas pas kumus, ja nepieciešams.
Sitagliptin is modestly dialyzable.
Sitaglipt ns ir m reni dializ jams.
In clinical studies, approximately 13.5% of the dose was removed over a 3- to 4-hour hemodialysis session.
Kl niskos p t jumos aptuveni 3 – 4 stundu ilga hemodial zes seansa laik tika izvad ti 13, 5% devas.
Prolonged hemodialysis may be considered if clinically appropriate.
Ilgstoša hemodial ze var tikt uzskat ta par Ja tas ir kl niski piem rots, var apsv rt ilgstošu hemodial zi.
It is not known if sitagliptin is dialyzable by peritoneal dialysis.
Nav zin ms, vai sitaglipt ns ir dializ jams ar peritone lo dial zi.
Pharmacotherapeutic group:
Farmakoterapeitisk grupa:
DPP-4 Inhibitor, ATC code:
DPP- 4 inhibitors, AT kods:
TESAVEL is a member of a class of oral anti-hyperglycaemic agents called dipeptidyl peptidase 4 (DPP-4) inhibitors.
TESAVEL ir peror lo antihiperglik misko l dzek u, kurus sauc par dipeptidilpeptid zes 4 (DPP- 4) inhibitoriem, grupas prepar ts.
The improvement in glycaemic control observed with this agent may be mediated by enhancing the levels of active incretin hormones.
Glik mijas kontroles uzlabošanos, ko nov roja ar šo l dzekli, var veicin t akt vo inkret na hormonu l me a paaugstin šan s.
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.
Inkret nie hormoni, tostarp glikagonam l dz gais pept ds- 1 (GLP- 1) un glikozes atkar gais insul ntropiskais polipept ds (GIP), izdal s zarn s visu dienu, un to l menis palielin s p c dienreizes.
The incretins are part of an endogenous system involved in the physiologic regulation of glucose homeostasis.
Inkret ni ir da a no endog nisk s sist mas, kas iesaist ta glikozes homeost zes fiziolo isk regul cij.
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.
Ja glikozes koncentr cija asin s ir norm la vai palielin ta, GLP- 1 un GIP palielina insul na sint zi un izdal šanos no aizku a dziedzera beta š n m ar intracelul ro sign lce u starpniec bu, iesaistot ciklisko 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.
Pier d ts, ka rst šana ar GLP- 1 vai DPP- 4 inhibitoriem 2. tipa cukura diab ta dz vnieku mode iem uzlabo beta š nu atbildreakciju pret glikozi un stimul insul na biosint zi un izdal šanos.
With higher insulin levels, tissue glucose uptake is enhanced.
Ja ir augst ks insul na l menis, uzlabojas glikozes saist šan s audos.
In addition, GLP-1 lowers glucagon secretion from pancreatic alpha cells.
Turkl t GLP- 1 pazemina glikagona sekr ciju no aizku a dziedzera alfa š n m.
Decreased glucagon concentrations, along with higher insulin levels, lead to reduced hepatic glucose production, resulting in a decrease in blood glucose levels.
Samazin ta glikagona koncentr cija l dz ar augst ku insul na l meni samazina glikozes veidošanos akn s, k rezult t samazin s glikozes l menis asin s.
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.
GLP- 1 un GIP efekti ir atkar gi no glikozes l me a, piem ram, ja glikozes koncentr cija asin s ir zema, GLP- 1 izrais tu insul na sekr cijas un glikagona sekr cijas nom kumu nenov ro.
For both GLP-1 and GIP, stimulation of insulin release is enhanced as glucose rises above normal concentrations.
Pieaugot glikozes koncentr cijai virs norm l l me a, palielin s gan GLP- 1, gan GIP insul na sekr cijas stimul cija.
Further, GLP-1 does not impair the normal glucagon response to hypoglycaemia.
Turkl t GLP- 1 neietekm norm lu glikagona atbildreakciju hipoglik mijas gad jum.
The activity of GLP-1 and GIP is limited by the DPP-4 enzyme, which rapidly hydrolyzes the incretin hormones to produce inactive products.
GLP- 1 un GIP aktivit ti ierobežo DPP- 4 enz ms, kas tri hidroliz inkret nos hormonus, veidojot neakt vus produktus.
Sitagliptin prevents the hydrolysis of incretin hormones by DPP-4, thereby increasing plasma concentrations of the active forms of GLP-1 and GIP.
Sitaglipt ns nov rš DPP - 4 veikto inkret no hormonu hidrol zi, t d j di palielinot GLP- 1 un GIP akt vo formu koncentr ciju plazm.
By enhancing active incretin levels, sitagliptin increases insulin release and decreases glucagon levels in a glucose- dependent manner.
Palielinot akt v inkret na l meni, sitaglipt ns palielina insul na izdal šanos un mazina glikagona l meni no glikozes atkar g veid.
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.
2. tipa cukura diab ta slimniekiem ar hiperglik miju š s insul na un glikagona l me a p rmai as samazina A1c hemoglob na (HbA1c) l meni un glikozes koncentr ciju tukš d ša un p c šanas.
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.
No glikozes l me a atkar gais sitaglipt na meh nisms ir atš ir gs no sulfonilur nvielas atvasin jumu meh nisma, kas palielina insul na sekr ciju pat tad, kad glikozes l menis ir zems, un var izsaukt hipoglik miju 2. tipa cukura diab ta pacientiem un veseliem cilv kiem.
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.
Sitaglipt ns ir sp c gs un oti selekt vs DPP- 4 enz ma inhibitors un terapeitisk s koncentr cij s nenom c oti l dz gos enz mus DPP- 8 vai DPP- 9.
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).
7 Kopum sitaglipt ns, lietots monoterapij, kombin cij ar metform nu (s kotn ji vai pievienots terapijas laik), kombin cij ar sulfonilur nvielas atvasin jumiem (ar vai bez metform na) un lietots kombin cij ar tiazolid ndionu, uzlaboja glik mijas kontroli, ko noteica p c kl niski b tiskas HbA1c l me a samazin šan s no s kotn j l me a, kas bija m r a parametrs (skat t 2. tabulu).
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.
Tika veikti divi p t jumi, lai nov rt tu TESAVEL monoterapijas efektivit ti un droš bu. rst šana ar 100 mg sitaglipt na monoterapiju reizi dien 2 p t jumos, viens ilga 18 ned as un viens 24 ned as, noz m gi uzlaboja HbA1c, glikozes l meni plazm tukš d ša (GPTD) un 2 stundu postprandi lo glikozes l meni (2 stundu PPG), sal dzinot ar placebo.
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.
Nov roja beta š nu funkcijas surog tmar ierus, tostarp HOMA- β (homeost zes mode a v rt jums- β - Homeostasis Model Assessment -), proinsul na un insul na attiec bu un beta š nu atbildreakcijas sp ju m r jumu uzlabošanos no biežu paraugu dienreizes panesam bas testa.
The observed incidence of hypoglycaemia in patients treated with TESAVEL was similar to placebo.
Nov rot hipoglik mijas sastopam ba ar TESAVEL rst tiem pacientiem bija l dz ga k ar placebo rst tiem cilv kiem.
Body weight did not increase from baseline with sitagliptin therapy in either study, compared to a small reduction in patients given placebo.
Lietojot TESAVEL terapiju, erme a masa, sal dzinot ar s kotn jo st vokli, nepalielin j s nevien p t jum pretstat nelielam samazin jumam pacientiem, kas sa ma placebo.
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.
P t jum pacientiem ar 2. tipa cukura diab tu un hronisku nieru mazsp ju (kreatin na kl renss < 50 ml/ min) tika p t ta samazin tu sitaglipt na devu droš ba un panesam ba, kas parasti bija l dz ga ar 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).
Turkl t HbA1c un GPTD, lietojot sitaglipt nu, sal dzin jum ar placebo parasti bija l dz gi k nov rots citos monoterapijas p t jumos pacientiem ar norm lu nieru funkciju (skat t apakšpunktu 5. 2).
The number of patients with moderate to severe renal insufficiency was too low to confirm safe use of sitagliptin in this type of patients.
Pacientu ar m renu vai smagu nieru mazsp ju bija par maz, lai š s grupas pacientiem apstiprin tu sitaglipt na lietošanas droš bu.
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.
Divos 24 ned u sitaglipt na k papildu terapijas l dzek a p t jumos, vien - kombin cij ar metform nu un vien - kombin cij ar pioglitazonu, sitaglipt ns, lietots pa 100 mg vienu reizi dien, uzr d ja noz m gu glik mijas parametru uzlabošanos, sal dzinot ar placebo.
Change from baseline in body weight was similar for patients treated with sitagliptin relative to placebo.
Sitaglipt na lietot jiem nov rot s s kotn j erme a svara izmai as bija l dz gas k placebo lietot jiem.
In these studies there was a similar incidence of hypoglycaemia reported for patients treated with sitagliptin or placebo.
Šajos p t jumos sitaglipt na lietot jiem nov rotais hipoglik miju biežums bija l dz gs k placebo lietot jiem.
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.
Tika veikts 24 ned u placebo kontrol ts p t jums, kur nov rt ja sitaglipt na (100 mg vienu reizi dien) kombin cijas ar glimepir du vai kombin cijas ar glimepir du un metform nu droš bu un efektivit ti.
The addition of sitagliptin to either glimepiride alone or to glimepiride and metformin provided significant improvements in glycaemic parameters.
Pievienojot sitaglipt nu tikai glimepir dam vai glimepir da un metform na kombin cijai, nov roja noz m gu glik misko parametru uzlabošanos.
Patients treated with sitagliptin had a modest increase in body weight compared to those given placebo.
Ar sitaglipt nu rst tiem pacientiem konstat ja nelielu erme a masas pieaugumu, sal dzinot ar placebo.
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.
24 ned u placebo kontrol t s kotn jas terapijas faktori l p t jum, lietojot sitaglipt nu 50 mg divas reizes dien kombin cij ar metform nu (500 mg vai 1000 mg divas reizes dien), uzr d ja noz m gus uzlabojumus glik mijas parametros, sal dzinot ar katra medikamenta monoterapiju. erme a svara samazin šan s ar sitaglipt na un metform na kombin ciju bija l dz ga tai, kas tika nov rota ar metform na monoterapiju vai placebo; nebija nek du izmai u no s kotn j svara pacientiem ar sitaglipt na monoterapiju.
The incidence of hypoglycaemia was similar across treatment groups.
Hipoglik mijas sastopam ba rst šanas grup m bija l dz ga.
HbA1c results in placebo-controlled monotherapy and combination therapy studies*
HbA1c placebo kontrol ta monoterapijas un kombin t s terapijas p t juma rezult ti *
Placebo-corrected mean
P t jums Monoterapijas p t jums Sitaglipt ns 100 mg vienu
baseline HbA1c (%)
HbA1c s kotn jais l menis (%)
baseline HbA1c (%) † at Week 24
Vid j s izmai as no HbA1c s kotn j l me a (%) 24. ned †
Week 24† (95% CI)
Placebo kori tas vid j s HbA1c izmai as (%) (95% TI) 24. ned † - 0, 6 ‡
Monotherapy Studies Sitagliptin 100 mg once daily§
reizi dien § N=193 Sitaglipt ns 100 mg vienu
ongoing metformin therapy (N=453)
reizi dien § N=229
Placebo-corrected mean
8 Kombin t s terapijas p t jums Pievienojot sitaglipt nu - 0, 7 ‡ 100 mg reizi dien metform na terapijai (N=453) Pievienojot sitaglipt nu 100 mg reizi dien
Week 24† (95% CI)
(- 0, 8; - 0, 5) - 0, 7 ‡
Sitagliptin 100 mg once daily added to -0.7‡ ongoing pioglitazone therapy (N=163) Sitagliptin 100 mg once daily added to
pioglitazona terapijai (N=163) Pievienojot sitaglipt nu 100 mg reizi dien
ongoing glimepiride therapy (N=102) Sitagliptin 100 mg once daily added to
glimepir da terapijai (N=102) Pievienojot sitaglipt nu 100 mg reizi dien
ongoing glimepiride + metformin therapy (N=115) Initial therapy (twice daily):
glimepir da + metform na terapijai (N=115) S kotn j terapija (divas reizes dien):
Sitagliptin 50 mg + metformin 500 mg (N=183) Initial therapy (twice daily):
sitaglipt ns 50 mg + metform ns 500 mg (N=183) S kotn j terapija (divas reizes dien):
Sitagliptin 50 mg + metformin 1000 mg (N=178)
sitaglipt ns 50 mg + metform ns 1000 mg (N=178)
* 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.
* Visu rst to pacientu kopskaits (rst šanas intensit tes anal zes). † Maz k s kvadr tsaknes vid jais, kori ts attiec b uz iepriekš ju antihiperglik misku terapiju un izejas st vok a r d t ju. ‡ p < 0. 001 sal dzinot ar placebo vai placebo + kombin t terapija. § HbA1c (%) 18. ned.
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.
P t jum, kur sal dzin ja TESAVEL 100 mg reizi dien vai glipiz da (sulfonilur nvielas atvasin juma) pievienošanas efektivit ti un droš bu pacientiem ar nepietiekamu glik mijas kontroli, lietojot metform na monoterapiju, sitaglipt ns bija l dz gs glipiz dam HbA1c samazin šanas zi.
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.
Vid j glipiz da deva, ko lietoja sal dzinošaj grup, bija 10 mg dien, kas bija aptuveni 40% no pacientam nepieciešam s glipiz da devas 5 mg/ dien p t juma laik.
However, more patients in the sitagliptin group discontinued due to lack of efficacy than in the glipizide group.
Tom r vair k pacientu sitaglipt na grup, sal dzinot ar glipaz da grupu, p rtrauca z u lietošanu efektivit tes tr kuma d.
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).
Ar sitaglipt nu rst tiem pacientiem konstat ja noz m gu vid j s erme a masas samazin jumu, sal dzinot ar s kotn jo, pretstat noz m gam erme a masas pieaugumam pacientiem, kuriem lietots glipiz ds (- 1, 5 vs. + 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.
Šaj p t jum proinsul na pret insul nu attiec ba, kas ir insul na sint zes un atbr vošan s efektivit tes r d t js, uzlaboj s, lietojot sitaglipt nu, un pasliktin j s, lietojot glipiz da terapiju.
The incidence of hypoglycaemia in the sitagliptin group (4.9%) was significantly lower than that in the glipizide group (32.0%).
Hipoglik mijas sastopam ba TESAVEL grup (4, 9%) bija noz m gi maz ka nek glipiz da grup (32, 0%).
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.
Uzs kšan s P c 100 mg devas peror las lietošanas veseliem cilv kiem sitaglipt ns tri uzs c s, maksim lo koncentr ciju plazm (vid jais Tmax) sasniedzot 1 – 4 stundas p c devas lietošanas, vid jais plazmas AUC bija 8, 52 µM• h, Cmax bija 950 nM.
The absolute bioavailability of sitagliptin is approximately 87%.
Sitaglipt na absol t biopieejam ba ir aptuveni 87%.
Since coadministration of a high-fat meal with TESAVEL had no effect on the pharmacokinetics, TESAVEL may be administered with or without food.
T k augsta tauku satura malt tes vienlaikus lietošana ar sitaglipt nu farmakokin tiku neietekm ja, TESAVEL var lietot kop ar dienu vai neatkar gi no t.
Plasma AUC of sitagliptin increased in a dose-proportional manner.
9 Sitaglipt na plazmas AUC palielin j s proporcion li devai.
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).
Devas proporcionalit ti nekonstat ja Cmax un C24h (Cmax palielin j s nedaudz vair k nek devai proporcion li, un C24h palielin j s nedaudz maz k nek devai proporcion l veid).
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.
Izkliede Vid jais izkliedes tilpums l dzsvara apst k os p c vienreiz jas 100 mg intravenozas sitaglipt na devas ievad šanas veseliem cilv kiem ir aptuveni 198 litri.
The fraction of sitagliptin reversibly bound to plasma proteins is low (38%).
Sitaglipt na frakcija, kas atgriezeniski saist ta ar plazmas olbaltumiem, ir maza (38%).
9 Metabolism Sitagliptin is primarily eliminated unchanged in urine, and metabolism is a minor pathway.
Metabolisms Sitaglipt ns tiek prim ri elimin ts neizmain t veid ar ur nu, un metabolisms ir neliels.
Approximately 79% of sitagliptin is excreted unchanged in the urine.
Aptuveni 79% sitaglipt na izdal s neizmain t veid ar ur nu.
Following a [14C]sitagliptin oral dose, approximately 16% of the radioactivity was excreted as metabolites of sitagliptin.
P c [14C] sitaglipt na peror las lietošanas aptuveni 16% radioakt v savienojuma izdal j s sitaglipt na metabol tu veid.
Six metabolites were detected at trace levels and are not expected to contribute to the plasma DPP-4 inhibitory activity of sitagliptin.
Sešus metabol tus konstat ja neliel daudzum un nav gaid ms, ka tie ietekm s sitaglipt na plazmas DPP- 4 nom cošo aktivit ti.
In vitro studies indicated that the primary enzyme responsible for the limited metabolism of sitagliptin was CYP3A4, with contribution from CYP2C8.
In vitro p t jumi liecina, ka galvenais enz ms, kas nodrošina sitaglipt na ierobežoto metabolismu, ir CYP3A4 ar CYP2C8 pal dz bu.
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.
Dati in vitro liecin ja, ka sitaglipt ns nav CYP izoenz mu CYP3A4, 2C8, 2C9, 2D6, 1A2, 2C19 vai 2B6 inhibitors un nav CYP3A4 un CYP1A2 induktors.
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.
Elimin cija P c peror las [14C] sitaglipt na devas lietošanas veseliem cilv kiem aptuveni 100% lietot radioakt v elementa izdal j s ar izk rn jumiem (13%) vai ur nu (87%) ned as laik p c devas ie emšanas.
The apparent terminal t1/ 2 following a 100-mg oral dose of sitagliptin was approximately 12.4 hours.
Š ietamais termin lais t1/ 2 p c 100 mg peror las sitaglipt na devas lietošanas bija aptuveni 12, 4 stundas.
Sitagliptin accumulates only minimally with multiple doses.
Lietojot vair kas devas, sitaglipt ns uzkr jas tikai nedaudz.
The renal clearance was approximately 350 ml/ min.
Nieru kl renss bija aptuveni 350 ml/ min.
Elimination of sitagliptin occurs primarily via renal excretion and involves active tubular secretion.
Sitaglipt na elimin cija notiek galvenok rt caur nier m ekskr cijas veid un ietver akt vu tubul ru sekr ciju.
The clinical relevance of hOAT-3 in sitagliptin transport has not been established.
Sitaglipt ns ir cilv ka organisko anjonu transportvielas- 3 (cOAT- 3) substr ts, kas var b t iesaist ts sitaglipt na elimin cij caur nier m. cOAT- 3 kl nisk noz me sitaglipt na transport nav noteikta.
Sitagliptin is also a substrate of p-glycoprotein, which may also be involved in mediating the renal elimination of sitagliptin.
Sitaglipt ns ir ar p- glikoprote na substr ts, kas ar var b t iesaist ts sitaglipt na ren las elimin cijas medi šan.
However, cyclosporine, a p-glycoprotein inhibitor, did not reduce the renal clearance of sitagliptin.
Ta u ciklospor ns, p- glikoprote na inhibitors, nemazina sitaglipt na nieru kl rensu.
Sitagliptin is not a substrate for OCT2 or OAT1 or PEPT1/ 2 transporters.
Sitaglipt ns nav OCT2 vai OAT1 substr ts vai PEPT1/ 2 transportviela.
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 pie terapeitiski noz m gas plazmas koncentr cijas sitaglipt ns neinhib ja OAT3 (IC50=160 µg) vai p - glikoprote na (l dz 250 µM) medi to transportu.
In a clinical study sitagliptin had a small effect on plasma digoxin concentrations indicating that sitagliptin may be a mild inhibitor of p-glycoprotein.
Kl nisk p t jum sitaglipt ns nedaudz ietekm ja digos na plazmas koncentr ciju, kas liecina, ka sitaglipt ns var tu b t m rens p- glikoprote na inhibitors.
Characteristics in patients The pharmacokinetics of sitagliptin were generally similar in healthy subjects and in patients with type 2 diabetes.
Raksturojums pacientiem Sitaglipt na farmakokin tika veseliem cilv kiem un pacientiem ar 2. tipa cukura diab tu kopum bija l dz ga.
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.
Nieru mazsp ja Vienas devas atkl tu p t jumu veica, lai nov rt tu sitaglipt na samazin tu devu (50 mg) farmakokin tiku pacientiem ar daž das pak pes hronisku nieru mazsp ju sal dzin jum ar veseliem kontroles grupas cilv kiem.
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 hemodialysis.
P t jum bija iek auti pacienti ar nieru mazsp ju, kas p c kreatin na kl rensa klasific ta k viegla (50 - < 80 ml/ min), m rena (30 - < 50 ml/ min) un smaga (< 30 ml/ min), k ar pacienti ar nieru slim bu beigu stadij (NSBS), kam tiek veikta hemodial ze.
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.
Pacientiem ar vieglu nieru mazsp ju nekonstat ja kl niski noz m gu sitaglipt na koncentr cijas palielin šanos plazm, sal dzinot ar veseliem kontroles grupas cilv kiem.
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 hemodialysis, as compared to normal healthy control subjects.
Sitaglipt nu neliel daudzum
Sitagliptin was modestly removed by hemodialysis (13.5% over a 3- to 4-hour hemodialysis session starting 4 hours postdose).
10 izvad ja ar hemodial zi (13, 5% 3 – 4 stundu ilga hemodial zes seansa laik, s kot to 4 stundas p c devas lietošanas).
(See section 4.2.)
TESAVEL neiesaka lietot pacientiem ar m renu vai smagu nieru mazsp ju, ieskaitot pacientus ar NSBS, jo ir ierobežota lietošanas pieredze š diem pacientiem (skat t apakšpunktu 4. 2).
Hepatic insufficiency No dosage adjustment for TESAVEL is necessary for patients with mild or moderate hepatic insufficiency (Child-Pugh score ≤ 9).
Aknu mazsp ja Pacientiem ar vieglu l dz m renai aknu mazsp ju (Child- Pugh v rt jums ≤ 9) TESAVEL devas piel gošana nav nepieciešama.
There is no clinical experience in patients with severe hepatic insufficiency (Child-Pugh score > 9).
Nav kl nisk s pieredzes pacientiem ar smagu aknu mazsp ju (Child - Pugh v rt jums > 9).
However, because sitagliptin is primarily renally eliminated, severe hepatic insufficiency is not expected to affect the pharmacokinetics of sitagliptin.
Ta u t k sitaglipt ns tiek izvad ts galvenok rt caur nier m, nav gaid ms, ka smaga aknu mazsp ja ietekm s sitaglipt na farmakokin tiku.
Age did not have a clinically meaningful impact on the pharmacokinetics of sitagliptin based on a population pharmacokinetic analysis of Phase I and Phase II data.
Gados vec ki pacienti Vecuma d devas piel gošana nav nepieciešama. emot v r 1. un 2. f zes datu popul cijas farmakokin tikas anal zi, vecums kl niski noz m gi sitaglipt na farmakokin tiku neietekm.
Elderly subjects (65 to 80 years) had approximately 19% higher plasma concentrations of sitagliptin compared to younger subjects.
Gados vec kiem cilv kiem (65 – 80 g. v.) bija par aptuveni 19% augst ka sitaglipt na koncentr cija plazm nek jaun kiem cilv kiem.
Paediatric No studies with TESAVEL have been performed in paediatric patients.
B rni B rniem p t jumi ar TESAVEL nav veikti.
Other patient characteristics No dosage adjustment is necessary based on gender, race, or body mass index (BMI).
Citas pacientu paš bas Vecuma, rases vai erme a masas indeksa (MI) d devas piel gošana nav nepieciešama.
These characteristics had no clinically meaningful effect on the pharmacokinetics of sitagliptin based on a composite analysis of Phase I pharmacokinetic data and on a population pharmacokinetic analysis of Phase I and Phase II data.
Pamatojoties uz saliktu 1. f zes farmakokin tikas datu un 1. un 2. f zes datu popul cijas farmakokin tikas anal zi, š s paš bas kl niski noz m gi sitaglipt na farmakokin tiku neietekm ja.
Renal and liver toxicity were observed in rodents at systemic exposure values 58 times the human exposure level, while the no-effect level was found at 19 times the human exposure level.
Grauz jiem, ja sist misk ietekme 58 reizes p rsniedza iedarb bas l meni cilv kam, nov roja toksisku ietekmi uz nier m un akn m, bet l meni bez ietekmes konstat ja k atbilstošu 19 reizes liel kam par cilv ka iedarb bas l meni.
Incisor teeth abnormalities were observed in rats at exposure levels 67 times the clinical exposure level; the no- effect level for this finding was 58-fold based on the 14-week rat study.
Žurk m, ja iedarb ba 67 reizes p rsniedza kl nisk s iedarb bas l meni, nov roja priekšzobu patolo iju; pamatojoties uz 14 ned u p t jumu žurk m, l menis bez ietekmes šai atradei bija 58 reizes liel ks par iedarb bas l meni cilv kam.
The relevance of these findings for humans is unknown.
Šo atrad u noz me cilv kam nav zin ma.
Transient treatment-related physical signs, some of which suggest neural toxicity, such as open-mouth breathing, salivation, white foamy emesis, ataxia, trembling, decreased activity, and/ or hunched posture were observed in dogs at exposure levels approximately 23 times the clinical exposure level.
P rejošas ar rst šanu saist tas fiziskas paz mes, dažas no kur m liecina par neir lu toksicit ti, piem ram, elpošana caur atv rtu muti, siekalošan s, baltu putu atvemšana, ataksija, tr ce, samazin ta aktivit te un/ vai saliekta erme a poza, nov roja su iem, ja iedarb bas l menis aptuveni 23 reizes p rsniedza kl nisk s iedarb bas l meni.
In addition, very slight to slight skeletal muscle degeneration was also observed histologically at doses resulting in systemic exposure levels of approximately 23 times the human exposure level.
Turkl t oti nelielu vai vieglu skeleta musku u de ener ciju nov roja ar histolo iski, lietojot devas, kas rada sist misku iedarb bu, kas aptuveni 23 reizes p rsniedz iedarb bas l meni cilv kam.
A no-effect level for these findings was found at an exposure 6-fold the clinical exposure level.
L menis bez ietekmes šai atradei bija pie 6 reizes liel ka iedarb bas l me a nek kl nisk iedarb ba.
Sitagliptin has not been demonstrated to be genotoxic in preclinical studies.
Prekl niskos p t jumos nav pier d ts, ka sitaglipt ns b tu genotoksisks.
Sitagliptin was not carcinogenic in mice.
Sitaglipt ns nebija kancerog nisks pel m.
In rats, there was an increased incidence of hepatic adenomas and carcinomas at systemic exposure levels 58 times the human exposure level.
Ja sist misk s iedarb bas l menis 58 reizes p rsniedza iedarb bas l meni cilv kam, žurk m konstat ja palielin tu aknu adenomu un karcinomu sastopam bu.
Since hepatotoxicity has been shown to correlate with induction of hepatic neoplasia in rats, this increased incidence of hepatic tumors in rats was likely secondary to chronic hepatic toxicity at this high dose.
T k pier d ts, ka hepatotoksicit te korel ar aknu jaunveidojumu rašanos žurk m, š palielin t aknu audz ju sastopam ba žurk m bija sekund ra hroniskai toksiskai ietekmei uz akn m, lietojot lielas devas.
Because of the high safety margin (19-fold at this no-effect level), these neoplastic changes are not considered relevant for the situation in humans.
Liel s droš bas diapazona d (19 reizes liel ks l menis bez ietekmes) š s neoplastisk s p rmai as netiek uzskat tas par noz m g m cilv kam.
No adverse effects upon fertility were observed in male and female rats given sitagliptin prior to and throughout mating.
Žurku t vi iem un m t t m, lietojot sitaglipt nu pirms p rošan s un t s laik, nelabv l gu ietekmi uz augl bu nenov roja.
In a pre-/ postnatal development study performed in rats sitagliptin showed no adverse effects.
Pre - / postnat l s att st bas p t jum, kas veikts ar žurk m, sitaglipt nam blakuspar d bas nekonstat ja.
Reproductive toxicity studies showed a slight treatment-related increased incidence of fetal rib malformations (absent, hypoplastic and wavy ribs) in the offspring of rats at systemic exposure levels more than 29 times the human exposure levels.
Reprodukt v s toksicit tes p t jumos konstat ja nelielu ar terapiju saist tu aug a ribu anom liju (tr kstošas, hipoplastikas un izloc tas ribas) biežuma palielin šanos žurku p cn c jiem, ja sist misk s iedarb bas l menis vair k nek 29 reizes p rsniedza iedarb bas l meni cilv kam.
Maternal toxicity was seen in rabbits at more than 29 times the human exposure levels.
Trušiem pie iedarb bas l me a, kas 29 reizes p rsniedz iedarb bas l meni cilv kam, nov roja toksisku ietekmi uz
Because of the high safety margins, these findings do not suggest a relevant risk for human reproduction.
Plaš droš bas interv la d š s atrades neliecina par noz m gu risku cilv ka reproduktivit tei.
4:1).
Sitaglipt ns izdal s noz m g daudzum žurku m t šu pien (attiec ba pien / plazm 4: 1).
11 calcium hydrogen phosphate, anhydrous (E341) croscarmellose sodium (E468) magnesium stearate (E470b) sodium stearyl fumarate
Tabletes kodols: mikrokrist lisk celuloze (E460), kalcija hidrog nfosf ts, bez dens (E341), kroskarmelozes n trija s ls (E468), magnija stear ts (E470b), n trija stearilfumar ts.
Film coating: polyvinyl alcohol macrogol 3350 talc (E553b) titanium dioxide (E171) red iron oxide (E172) yellow iron oxide (E172)
Apvalks: polivinilspirts, makrogols 3350, talks (E553b), tit na dioks ds (E171), sarkanais dzelzs oks ds (E172), dzeltenais dzelzs oks ds (E172).
This medicinal product does not require any special storage conditions.
Š m z l m nav nepieciešami paši uzglab šanas apst k i.
6.5 Nature and contents of container
6. 5 Iepakojuma veids un sast vs
Opaque blisters (PVC/ PE/ PVDC and aluminum).
Necaursp d gs blisteris (PVH/ PE/ PVDH un alum nijs).
Packs of 14, 28, 56, 84 or 98 film-coated tablets and 50 x 1 film-coated tablets in perforated unit dose blisters.
Iepakojum pa 14, 28, 56, 84 vai 98 apvalkot m tablet m un 50 x 1 apvalkot s tabletes blister ar atseviš m dev m kont rligzd s.
6.6 Special precautions for disposal
6. 6 paši nor d jumi atkritumu likvid šanai un nor d jumi par sagatavošanu lietošanai
Hertford Road, Hoddesdon Hertfordshire EN11 9BU United Kingdom
Hertford Road, Hoddesdon Hertfordshire EN11 9BU Lielbrit nija
10 January 2008
2008. gada 10. janv ris.
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) web site: http: / /www. emea. europa. eu/.
S k ka inform cija par š m z l m ir pieejama Eiropas z u a ent ras (EMEA) m jas lap http: // www. emea. europa. eu /.
TESAVEL 50 mg film-coated tablets
TESAVEL 50 mg apvalkot s tabletes
Each tablet contains sitagliptin phosphate monohydrate, equivalent to 50 mg sitagliptin.
Katra tablete satur sitaglipt na fosf ta monohidr tu, kas atbilst 50 mg sitaglipt na (sitagliptin).
Round, light beige film-coated tablet with “ 112” on one side.
Apa a, gaiši b ša apvalkot tablete ar “ 112 ” vien pus.
• to improve glycaemic control in combination with metformin when diet and exercise plus metformin alone do not provide adequate glycaemic control.
Pacientiem ar 2. tipa cukura diab tu TESAVEL indic ts: • glik mijas kontroles uzlabošanai kombin cij ar metform nu, ja di ta un fizisk aktivit te kombin cij ar metform na monoterapiju nenodrošina pietiekamu glik mijas kontroli;
• 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.
• glik mijas kontroles uzlabošanai kombin cij ar sulfonilur nvielas atvasin jumu un metform nu, ja di ta un fizisk aktivit te kombin cij ar šo l dzek u divk ršo terapiju nenodrošina pietiekamu glik mijas kontroli.