natgillin/translations-raw huggingface dataset:
Sitagliptin was modestly removed by hemodialysis (13.5% over a 3- to 4-hour hemodialysis session starting 4 hours postdose).
Sitagliptin a fost îndep rtat în propor ie redus prin hemodializ (13, 5% într- o edin de 3- 4 ore de hemodializ ini iat la 4 ore de la administrarea dozei).
TESAVEL 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.
TESAVEL nu este recomandat pentru utilizare la pacien ii cu insuficien moderat pân la sever, inclusiv pentru cei cu IRST, deoarece experien a la ace ti pacien i este prea limitat (vezi pct.
Hepatic insufficiency No dosage adjustment for TESAVEL is necessary for patients with mild or moderate hepatic insufficiency (Child-Pugh score ≤ 9).
Insuficien hepatic La pacien ii cu insuficien hepatic u oar sau moderat (scor Child- Pugh ≤9) nu este necesar ajustarea dozei de TESAVEL.
There is no clinical experience in patients with severe hepatic insufficiency (Child-Pugh score > 9).
Nu exist experien clinic la pacien ii cu insuficien hepatic sever (scor Child- Pugh > 9).
However, because sitagliptin is primarily renally eliminated, severe hepatic insufficiency is not expected to affect the pharmacokinetics of sitagliptin.
Cu toate acestea, deoarece sitagliptin se elimin în principal renal, nu este de a teptat ca insuficien a hepatic sever s influen eze farmacocinetica sitagliptin.
10 Elderly No dosage adjustment is required based on age.
Vârstnici Nu este necesar ajustarea dozei în func ie de vârst.
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.
O analiz farmacocinetic popula ional a datelor provenite din studii de faz I i II a indicat faptul c vârsta nu a avut un impact clinic semnificativ asupra farmacocineticii sitagliptin.
Elderly subjects (65 to 80 years) had approximately 19% higher plasma concentrations of sitagliptin compared to younger subjects.
Subiec ii vârstnici (65- 80 ani) au prezentat concentra ii plasmatice de sitagliptin cu aproximativ 19% mai mari, comparativ cu subiec ii mai tineri.
Paediatric No studies with TESAVEL have been performed in paediatric patients.
Copii i adolescen i Nu au fost efectuate studii cu TESAVEL la copii i adolescen i.
Other patient characteristics No dosage adjustment is necessary based on gender, race, or body mass index (BMI).
Alte caracteristici ale pacien ilor Nu este necesar ajustarea dozei în func ie de sex, ras sau indice de mas corporal (IMC).
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.
Aceste caracteristici nu au avut un impact clinic semnificativ asupra farmacocineticii sitagliptin, pe baza unei analize globale a datelor farmacocinetice provenite din studii de faz I i a unei analize farmacocinetice popula ionale a datelor provenite din studii de faz I i II.
5.3 Preclinical safety data
11 5. 3 Date preclinice de siguran
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.
La valori de expunere sistemic de 58 ori mai mari decât nivelul de expunere la om au fost observate toxicit i renale i hepatice la roz toare în timp ce, la valori de 19 ori mai mari decât cele de la om, nu a fost detectat nici un efect.
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.
Anomalii ale incisivilor au fost observate la obolani, la nivele de expunere de 67 ori mai mari decât nivelul clinic de expunere; nivelul la care nu s- a notat nici nu efect pentru aceast anomalie a fost de 58 ori mai mare, pe baza unui studiu de 14 s pt mâni la obolani.
The relevance of these findings for humans is unknown.
Nu se cunoa te relevan a acestor date pentru specia uman.
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.
La nivele de expunere de aproximativ 23 ori mai mari decât nivelele clinice de expunere au fost observate la câini semne fizice tranzitorii, legate de tratament, dintre care unele sugereaz o toxicitate neurologic, cum sunt respira ia cu gura deschis, saliva ie, v rs turi spumoase, albe, ataxie, tremur turi, activitate redus i/ sau postur cifotic.
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.
În plus, la nivele de expunere sistemic de aproximativ 23 ori mai mari decât nivelul de expunere uman a fost observat histologic o foarte u oar pân la u oar degenerare a mu chilor scheletici.
A no-effect level for these findings was found at an exposure 6-fold the clinical exposure level.
Nivelul la care nu s- a notat nici nu efect pentru aceast anomalie a fost de 6 ori nivelul clinic de expunere.
Sitagliptin has not been demonstrated to be genotoxic in preclinical studies.
În studiile preclinice, sitagliptin nu a demonstrat propriet i genotoxice.
Sitagliptin was not carcinogenic in mice.
Sitagliptin nu a fost carcinogen la oareci.
In rats, there was an increased incidence of hepatic adenomas and carcinomas at systemic exposure levels 58 times the human exposure level.
La obolani s- a înregistrat, la nivele de expunere sistemic de 58 ori mai mari decât nivelul de expunere la om, o inciden crescut a adenoamelor i carcinoamelor hepatice.
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.
Deoarece s- a demonstrat c hepatotoxicitatea s- a corelat cu inducerea neoplaziilor hepatice la obolani, este probabil ca aceast inciden crescut a tumorilor hepatice la obolani s fie secundar toxicit ii cronice hepatice la aceast doz mare.
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.
Datorit limitei mari de siguran (nivel de 19 ori mai mare decât nivelul clinic de expunere pentru care nu s- a notat aceast anomalie), aceste modific ri neoplazice nu sunt considerate relevante pentru om.
No adverse effects upon fertility were observed in male and female rats given sitagliptin prior to and throughout mating.
La masculii i femelele de obolan, la care sitagliptin a fost administrat înainte de i pe durata perioadei de împerechere, nu au fost observate reac ii adverse asupra fertilit ii.
In a pre-/ postnatal development study performed in rats sitagliptin showed no adverse effects.
Într- un studiu de dezvoltare pre/ postnatal efectuat la obolani, sitagliptin nu a demonstrat reac ii adverse.
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.
Studiile de toxicitate asupra func iei de reproducere au indicat, la nivele de expunere sistemic de 29 ori mai mari decât nivele de expunere la om, o inciden u or crescut, legat de tratament, a malforma iilor costale fetale (absen a unor coaste, hipoplazie sau coaste ondulate) la puii de obolan.
Maternal toxicity was seen in rabbits at more than 29 times the human exposure levels.
La iepuri a fost observat toxicitate matern, la nivele de 29 ori mai mari decât nivelele de expunere la om.
Because of the high safety margins, these findings do not suggest a relevant risk for human reproduction.
Datorit limitelor mari de siguran, aceste rezultate nu sugereaz existen a unui risc relevant pentru reproducerea uman.
4:1).
Sitagliptin este secretat în cantit i considerabile în laptele femelelor de obolani (raportul concentra iilor în lapte/ plasm 4: 1).
PHARMACEUTICAL PARTICULARS
PROPRIET
6.1 List of excipients
I FARMACEUTICE
Tablet core: microcrystalline cellulose (E460)
6. 1 Lista excipien ilor
11 calcium hydrogen phosphate, anhydrous (E341) croscarmellose sodium (E468) magnesium stearate (E470b) sodium stearyl fumarate
Nucleul comprimatului: celuloz microcristalin (E460) hidrogenofosfat de calciu, anhidru (E341) croscarmeloz sodic (E468) stearat de magneziu (E470b) stearil fumarat de sodiu
Film coating: polyvinyl alcohol macrogol 3350 talc (E553b) titanium dioxide (E171) red iron oxide (E172) yellow iron oxide (E172)
Filmul comprimatului: polivinil alcool macrogol 3350 talc (E553b)
This medicinal product does not require any special storage conditions.
Acest medicament nu necesit condi ii speciale de p strare.
Opaque blisters (PVC/ PE/ PVDC and aluminum).
Blistere opace (PVC/ PE/ PVDC i aluminiu).
Packs of 14, 28, 56, 84 or 98 film-coated tablets and 50 x 1 film-coated tablets in perforated unit dose blisters.
Ambalaje cu 14, 28, 56, 84 sau 98 comprimate filmate i 50 x 1 comprimate filmate în blistere perforate pentru eliberarea unei unit i dozate.
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) web site: http: / /www. emea. europa. eu/.
Informa ii detaliate despre acest produs sunt disponibile pe site- ul Agen iei Europene a Medicamentelor (EMEA) web site: http: // www. emea. europa. eu /.
Each tablet contains sitagliptin phosphate monohydrate, equivalent to 50 mg sitagliptin.
Fiecare comprimat con ine fosfat de sitagliptin monohidrat, echivalent cu 50 mg sitagliptin.
Round, light beige film-coated tablet with “ 112” on one side.
Comprimat filmat rotund, de culoare bej deschis, cu inscrip ia “ 112 ” pe una dintre fe e.
14 Patients with renal insufficiency For patients with mild renal insufficiency (creatinine clearance [CrCl] ≥ 50 ml/ min), no dosage adjustment for TESAVEL is required.
14 Pacien i cu insuficien renal Nu este necesar ajustarea dozei de TESAVEL la pacien ii cu insuficien renal u oar (clearance al creatininei [ClCr] ≥50 ml/ min).
4.5 Interaction with other medicinal products and other forms of interaction
15 4. 5 Interac iuni cu alte medicamente i alte forme de interac iune
Lactation It is unknown whether sitagliptin is excreted in human breast milk.
16 Al ptarea Nu se cunoa te dac sitagliptin este excretat în laptele uman.
16 4.8 Undesirable effects
4. 8 Reac ii adverse
17 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.
Într- un studiu suplimentar de 1 an cu sitagliptin 100 mg administrat o dat pe zi în asociere cu metformin, inciden a reac iilor adverse considerate ca legate de medicament la pacien ii trata i cu sitagliptin/ metformin comparativ cu deriva i de sulfoniluree/ metformin a fost de 14, 5%, respectiv de 30, 3%.
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.
18 Într- un studiu clinic cu durata de 24 s pt mâni cu administrarea ini ial de dou ori pe zi a sitagliptinului asociat cu metformin (sitagliptin/ metformin 50 mg/ 500 mg sau 50 mg/ 1000 mg), inciden a global a reac iilor adverse considerate legate de medicament la pacien ii trata i cu asocierea dintre sitagliptin i metformin comparativ cu pacien ii c rora li s- a administrat placebo a fost de 14, 0%, respectiv de 9, 7%.
18 Post-marketing Experience:
Experien a dup punerea pe pia:
19 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).
Per global, sitagliptinul a îmbun t it controlul glicemic atunci când s- a folosit în monoterapie, în asociere cu metforminul (ini ial sau ca terapie suplimentar), în asociere cu o sulfoniluree (cu sau f r metformin) i în asociere cu o tiazolidindion, fapt dovedit prin reducerea relevant clinic a HbA1c de la momentul ini ial la momentul final al studiului (vezi tabelul 2).
Week 24†
ini ial a HbA1c (%) la s pt mâna 24 †
at Week 24†
s pt mâna 24 † (IÎ 95%)
Sitagliptin 100 mg once daily§ (N= 193) Sitagliptin 100 mg once daily (N= 229) Combination Therapy Studies Sitagliptin 100 mg once daily added to
Studii cu monoterapie Sitagliptin 100 mg o dat pe zi§
-0.5 -0.6
- 0, 6 ‡
ongoing metformin therapy (N=453)
(n= 229) Studii cu terapie asociat Sitagliptin 100 mg o dat pe zi ad ugat la terapie neîntrerupt cu
(-0.8, -0.5)
- 0, 6
change in HbA1c (%) at
(- 1, 0, - 0, 6) - 0, 7 ‡
baseline
- 0, 7
Sitagliptin 100 mg once daily added to
metformin (n=453) Sitagliptin 100 mg o dat pe zi ad ugat la terapie neîntrerupt cu
(95% CI) -0.7‡
(- 0, 8, - 0, 5) - 0, 7 ‡
ongoing pioglitazone therapy (N=163) Sitagliptin 100 mg once daily added to
pioglitazon (n=163) Sitagliptin 100 mg o dat pe zi ad ugat la terapie neîntrerupt cu
* 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.
21 † media celor mai mici p trate ajustat pentru statusul anterior terapiei antihiperglicemice i valorii ini iale. ‡ p < 0, 001 comparativ cu placebo sau cu tratamentul placebo + asociere. § HbA1c (%) la s pt mâna 18.
21 Metabolism Sitagliptin is primarily eliminated unchanged in urine, and metabolism is a minor pathway.
Metabolizare Sitagliptin se elimin în principal nemodificat prin urin, iar metabolizarea este minor.
Elimination of sitagliptin occurs primarily via renal excretion and involves active tubular secretion.
22 Eliminarea sitagliptin se produce în principal prin excre ie renal i implic mecanismul de secre ie tubular activ.
22 Elderly No dosage adjustment is required based on age.
Vârstnici Nu este necesar ajustarea dozei în func ie de vârst.
5.3 Preclinical safety data
23 5. 3 Date preclinice de siguran
23 calcium hydrogen phosphate, anhydrous (E341) croscarmellose sodium (E468) magnesium stearate (E470b) sodium stearyl fumarate
Nucleul comprimatului: celuloz microcristalin (E460) hidrogenofosfat de calciu, anhidru (E341) croscarmeloz sodic (E468) stearat de magneziu (E470b) stearil fumarat de sodiu
Each tablet contains sitagliptin phosphate monohydrate, equivalent to 100 mg sitagliptin.
Fiecare comprimat con ine fosfat de sitagliptin monohidrat, echivalent cu 100 mg sitagliptin.
Round, beige film-coated tablet with “ 277” on one side.
Comprimat filmat rotund, de culoare bej, cu inscrip ia “ 277 ” pe una dintre fe e.
26 Patients with renal insufficiency For patients with mild renal insufficiency (creatinine clearance [CrCl] ≥ 50 ml/ min), no dosage adjustment for TESAVEL is required.
26 Pacien i cu insuficien renal Nu este necesar ajustarea dozei de TESAVEL la pacien ii cu insuficien renal u oar (clearance al creatininei [ClCr] ≥50 ml/ min).
4.5 Interaction with other medicinal products and other forms of interaction
27 4. 5 Interac iuni cu alte medicamente i alte forme de interac iune
Lactation It is unknown whether sitagliptin is excreted in human breast milk.
28 Al ptarea Nu se cunoa te dac sitagliptin este excretat în laptele uman.
28 4.8 Undesirable effects
4. 8 Reac ii adverse
29 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.
Într- un studiu suplimentar de 1 an cu sitagliptin 100 mg administrat o dat pe zi în asociere cu metformin, inciden a reac iilor adverse considerate ca legate de medicament la pacien ii trata i cu sitagliptin/ metformin comparativ cu deriva i de sulfoniluree/ metformin a fost de 14, 5%, respectiv de 30, 3%.
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.
30 Într- un studiu clinic cu durata de 24 s pt mâni cu administrarea ini ial de dou ori pe zi a sitagliptinului asociat cu metformin (sitagliptin/ metformin 50 mg/ 500 mg sau 50 mg/ 1000 mg), inciden a global a reac iilor adverse considerate legate de medicament la pacien ii trata i cu asocierea dintre sitagliptin i metformin comparativ cu pacien ii c rora li s- a administrat placebo a fost de 14, 0%, respectiv de 9, 7%.
30 Post-marketing Experience:
Experien a dup punerea pe pia:
During post-marketing experience the following additional side effects have been reported (frequency not known): hypersensitivity reactions, including anaphylaxis, angioedema, rash, urticaria and exfoliative skin conditions including Stevens-Johnson syndrome (see section 4.4).
4. 4).
31 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).
Per global, sitagliptinul a îmbun t it controlul glicemic atunci când s- a folosit în monoterapie, în asociere cu metforminul (ini ial sau ca terapie suplimentar), în asociere cu o sulfoniluree (cu sau f r metformin) i în asociere cu o tiazolidindion, fapt dovedit prin reducerea relevant clinic a HbA1c de la momentul ini ial la momentul final al studiului (vezi tabelul 2).
* 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.
33 † media celor mai mici p trate ajustat pentru statusul anterior terapiei antihiperglicemice i valorii ini iale. ‡ p < 0, 001 comparativ cu placebo sau cu tratamentul placebo + asociere. § HbA1c (%) la s pt mâna 18.
33 Metabolism Sitagliptin is primarily eliminated unchanged in urine, and metabolism is a minor pathway.
Metabolizare Sitagliptin se elimin în principal nemodificat prin urin, iar metabolizarea este minor.
Elimination of sitagliptin occurs primarily via renal excretion and involves active tubular secretion.
34 Eliminarea sitagliptin se produce în principal prin excre ie renal i implic mecanismul de secre ie tubular activ.
34 Elderly No dosage adjustment is required based on age.
Vârstnici Nu este necesar ajustarea dozei în func ie de vârst.
5.3 Preclinical safety data
35 5. 3 Date preclinice de siguran
35 calcium hydrogen phosphate, anhydrous (E341) croscarmellose sodium (E468) magnesium stearate (E470b) sodium stearyl fumarate
Nucleul comprimatului: celuloz microcristalin (E460) hidrogenofosfat de calciu, anhidru (E341) croscarmeloz sodic (E468) stearat de magneziu (E470b) stearil fumarat de sodiu
Pharmacovigilance system The MAH must ensure that the system of pharmacovigilance, as described in version 2 presented in Module 1.8.1. of the Marketing Authorisation Application and any subsequent updates, is in place and functioning before and whilst the product is on the market.
Sistemul de farmacovigilen De in torul autoriza iei de punere pe pia trebuie s asigure c sistemul de farmacovigilen, a a cum este descris în versiunea 2 prezentat în Modulul 1. 8. 1. al Cererii de autorizare de punere pe pia precum i în oricare dintre actualiz rile ulterioare, exist i func ioneaz înainte ca medicamentul s fie pus pe pia i atât timp cât medicamentul r mâne în uz.
Risk Management Plan The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the Pharmacovigilance Plan, as agreed in version 1.1 of the Risk Management Plan (RMP) presented in Module 1.8.2. of the Marketing Authorisation Application and any subsequent updates of the RMP agreed by the CHMP.
Planul de management al riscului DAPP se oblig s realizeze studiile i activit ile de farmacovigilen suplimentare descrise în Planul de farmacovigilen, a a cum s- au stabilit în versiunea 1. 1 a Planului de management al riscului (PMR) prezentat în Modulul 1. 8. 2. al Cererii de autorizare de punere pe pia i orice actualiz ri ulterioare ale PMR, stabilite de c tre CHMP.
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the updated RMP should be submitted at the same time as the next Periodic Safety Update Report (PSUR).
Conform recomand rilor CHMP cu privire la Sistemele de management al riscului pentru medicamentele de uz uman, un PMR actualizat trebuie depus în acela i timp cu urm torul Raport periodic actualizat referitor la siguran (RPAS).
In addition, an updated RMP should be submitted • When new information is received that may impact on the current Safety Specification, Pharmacovigilance Plan or risk minimisation activities • Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being reached • At the request of the EMEA
În plus, un PMR actualizat trebuie depus • când sunt disponibile informa ii noi care ar putea avea impact asupra Specifica iei actuale privind siguran a, Planului de farmacovigilen sau activit ilor de reducere la minimum a riscului • în interval de 60 zile de la atingerea unui obiectiv important de referin (de farmacovigilen sau de reducere la minimum a riscului) • la solicitarea EMEA