natgillin/translations-raw huggingface dataset:
Hypoglycaemia when used in combination with other anti-hyperglycaemic agents In clinical trials of TESAVEL as monotherapy and as part of combination therapy with agents not known to cause hypoglycaemia (i. e. metformin or pioglitazone), rates of hypoglycaemia reported with sitagliptin were similar to rates in patients taking placebo.
Hipoglicemia în cazul utiliz rii în asociere cu un alt antidiabetic oral În studiile clinice în care s- a administrat TESAVEL în monoterapie i în cadrul tratamentului asociat cu medicamente care nu sunt cunoscute ca determinând hipoglicemie (de exemplu, metformin sau pioglitazon), frecven ele de apari ie a hipoglicemiei raportate pentru sitagliptin au fost similare cu cele raportate la pacien ii la care s- a administrat placebo.
The use of sitagliptin in combination with insulin has not been adequately studied.
Nu a fost suficient studiat utilizarea sitagliptinului în asociere cu insulina.
Renal insufficiency As the experience is limited, patients with moderate to severe renal insufficiency should not be treated with TESAVEL (see section 5.2).
5. 2).
Hypersensitivity Reactions Postmarketing reports of serious hypersensitivity reactions in patients treated with TESAVEL have been reported.
Reac ii de hipersensibilitate Dup punerea pe pia, la pacien ii trata i cu TESAVEL au fost raportate reac ii de hipersensibilitate grave.
These reactions include anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome.
Aceste reac ii includ anafilaxie, edem angioneurotic i afec iuni cutanate exfoliative, inclusiv sindromul Stevens- Johnson.
Onset of these reactions occurred within the first 3 months after initiation of treatment with TESAVEL, with some reports occurring after the first dose.
Debutul acestor reac ii a avut loc în primele 3 luni dup ini ierea tratamentului cu TESAVEL, unele raport ri înregistrându- se dup prima doz.
If a hypersensitivity reaction is suspected, discontinue TESAVEL, assess for other potential causes for the event, and institute alternative treatment for diabetes (see section 4.8).
4. 8).
4.5 Interaction with other medicinal products and other forms of interaction
3 4. 5 Interac iuni cu alte medicamente i alte forme de interac iune
Effects of other medicinal products on sitagliptin Clinical data described below suggest that the risk for clinically meaningful interactions by co- administered medicinal products is low.
Efectele altor medicamente asupra sitagliptin Datele clinice descrise mai jos sugereaz c riscul pentru interac iunile clinic semnificative prin administrarea asociat a acestor medicamente este mic.
Co-administration of multiple twice-daily doses of 1000 mg metformin with 50 mg sitagliptin did not meaningfully alter the pharmacokinetics of sitagliptin in patients with type 2 diabetes.
Administrarea concomitent a unor doze multiple de 1000 mg metformin de 2 ori pe zi cu 50 mg sitagliptin nu a modificat în mod semnificativ farmacocinetica sitagliptin la pacien ii cu diabet zaharat tip 2.
Cyclosporine:
Ciclosporin:
Coadministration of a single 100 mg oral dose of sitagliptin and a single 600 mg oral dose of cyclosporine increased the AUC and Cmax of sitagliptin by approximately 29% and 68%, respectively.
Administrarea unei doze orale unice de 100 mg sitagliptin concomitent cu o doz oral unic de 600 mg ciclosporin a crescut ASC i Cmax ale sitagliptin cu aproximativ 29%, respectiv 68%.
These changes in sitagliptin pharmacokinetics were not considered to be clinically meaningful.
Aceste modific ri ale farmacocineticii sitagliptin nu au fost considerate clinic semnificative.
Therefore, meaningful interactions would not be expected with other p-glycoprotein inhibitors.
A adar, nu sunt de a teptat interac iuni semnificative cu al i inhibitori ai glicoproteinei p.
In vitro studies indicated that the primary enzyme responsible for the limited metabolism of sitagliptin is CYP3A4, with contribution from CYP2C8.
Studiile in vitro au ar tat c principala enzim responsabil pentru metabolizarea limitat a sitagliptin este CYP3A4, cu contribu ia CYP2C8.
In patients with normal renal function, metabolism, including via CYP3A4, plays only a small role in the clearance of sitagliptin.
La pacien ii cu func ie renal normal, metabolizarea, inclusiv prin CYP3A4, joac doar un rol mic în clearance- ul sitagliptinului.
Metabolism may play a more significant role in the elimination of sitagliptin in the setting of severe renal insufficiency or ESRD.
Metabolizarea poate juca un rol mai semnificativ în eliminarea sitagliptin în insuficien a renal sever sau IRST.
For this reason, it is possible that potent CYP3A4 inhibitors (i. e. ketoconazole, itraconazole, ritonavir, clarithromycin) could alter the phamacokinetics of sitagliptin in patients with severe renal insufficiency or ESRD.
Din acest motiv, este posibil ca inhibitorii puternici ai CYP3A4 (de exemplu: ketoconazol, itraconazol, ritonavir, claritromicin) s altereze farmacocinetica sitagliptin la pacien ii cu insuficien renal sever sau IRST.
The effects of potent CYP3A4 inhibitors in the setting of renal insufficiency has not been assessed in a clinical study.
Efectele inhibitorilor puternici ai CYP3A4 în insuficien a renal nu au fost evaluate în studii clinice.
In vitro transport studies showed that sitagliptin is a substrate for p-glycoprotein and OAT3.
Studiile in vitro privind transportul au ar tat c sitagliptin este un substrat al glicoproteinei p i OAT3 (transport anionic organic).
OAT3 mediated transport of sitagliptin was inhibited in vitro by probenecid, although the risk of clinically meaningful interactions is considered to be low.
Transportul de sitagliptin mediat de OAT3 a fost inhibat in vitro de c tre probenecid, de i riscul interac iunilor clinic semnificative este considerat a fi mic.
Concomitant administration of OAT3 inhibitors has not been evaluated in vivo.
Administrarea concomitent de inhibitori OAT3 nu a fost evaluat in vivo.
Effects of sitagliptin on other medicinal products In vitro data suggest that sitagliptin does not inhibit nor induce CYP450 isoenzymes.
Datele sugereaz c in vitro, sitagliptin nu inhib, nici nu induce izoenzimele CYP450.
In clinical studies, sitagliptin did not meaningfully alter the pharmacokinetics of metformin, glyburide, simvastatin, rosiglitazone, warfarin, or oral contraceptives, providing in vivo evidence of a low propensity for causing interactions with substrates of CYP3A4, CYP2C8, CYP2C9, and organic cationic transporter (OCT).
În studii clinice, sitagliptin nu a influen at semnificativ farmacocinetica metforminului, gliburidei, simvastatinei, rosiglitazonei, warfarinei sau a contraceptivelor orale, furnizând dovezi in vivo ale unei capacit i reduse de interac iune cu substraturi ale CYP3A4, CYP2C8, CYP2C9 i transportorului cationic organic (TCO).
Sitagliptin had a small effect on plasma digoxin concentrations, and may be a mild inhibitor of p- glycoprotein in vivo.
Sitagliptin a avut un efect mic asupra concentra iilor plasmatice de digoxin i poate fi un inhibitor u or al glicoproteinei p in vivo.
Sitagliptin had a small effect on plasma digoxin concentrations.
Sitagliptin a avut un efect mic asupra concentra iilor plasmatice de digoxin.
Following administration of 0.25 mg digoxin concomitantly with 100 mg of TESAVEL daily for 10 days, the plasma AUC of digoxin was increased on average by 11%, and the plasma Cmax on average by 18%.
Dup administrarea a 0, 25 mg digoxin concomitent cu 100 mg TESAVEL, timp de 10 zile, ASC plasmatic al digoxinei a crescut în medie cu 11%, iar Cmax plasmatic în medie cu 18%.
No dosage adjustment of digoxin is recommended.
Nu se recomand ajustarea dozei de digoxin.
However, patients at risk of digoxin toxicity should be monitored for this when sitagliptin and digoxin are administered concomitantly.
Cu toate acestea, pacien ii cu risc de toxicitate digoxinic trebuie monitoriza i atunci când sitagliptinul i digoxina sunt administrate concomitent.
Pregnancy There are no adequate data from the use of TESAVEL in pregnant women.
Sarcina Nu exist date adecvate privind utilizarea TESAVEL la femeile gravide.
The potential risk for humans is unknown.
Riscul poten ial pentru om este necunoscut.
Due to lack of human data, TESAVEL should not be used during pregnancy.
Datorit lipsei datelor la om, TESAVEL nu trebuie utilizat în timpul sarcinii.
Lactation It is unknown whether sitagliptin is excreted in human breast milk.
4 Al ptarea Nu se cunoa te dac sitagliptin este excretat în laptele uman.
Animal studies have shown excretion of sitagliptin in breast milk.
Studiile la animale au indicat excre ia sitagliptin în laptele matern.
TESAVEL should not be used during breast-feeding.
TESAVEL nu trebuie utilizat în timpul al pt rii.
No studies on the effects on the ability to drive and use machines have been performed.
Nu s- au efectuat studii privind efectele asupra capacit ii de a conduce vehicule i de a folosi utilaje.
However, when driving or operating machines, it should be taken into account that dizziness and somnolence have been reported.
Cu toate acestea, atunci când conduce i vehicule i folosi i utilaje trebuie avut în vedere c au fost raportate ame eal i somnolen.
4 4.8 Undesirable effects
4. 8 Reac ii adverse
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.
În 9 studii clinice mari, cu durat de pân la 2 ani, peste 2700 pacien i au primit tratament cu TESAVEL 100 mg pe zi, în monoterapie sau în asociere cu metformin, cu o sulfoniluree (cu sau f r metformin) sau un agonist PPARγ.
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.
În aceste studii, ratele întreruperilor datorate reac iilor adverse considerate ca fiind legate de medicament au fost de 0, 8% pentru TESAVEL 100 mg pe zi în monoterapie i de 1, 5% cu alte tratamente.
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.
Nu au fost raportate reac ii adverse considerate ca legate de medicament în exces la pacien ii trata i cu sitagliptin (> 0, 2% i diferen > 1 pacient) fa de cei trata i cu medicamentul de control.
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.
Reac iile adverse considerate ca fiind în rela ie cu medica ia i raportate ca ap rând în exces la pacien ii trata i cu sitagliptin (> 0, 2% i diferen > 1 pacient) fa de cei c rora li s- a administrat placebo sunt prezentate mai jos (Tabelul 1) pe aparate, organe i sisteme i în func ie de frecven.
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).
Frecven ele sunt definite astfel: foarte frecvente (1/ 10); frecvente (1/ 100, < 1/ 10); mai pu in frecvente (1/ 1000, < 1/ 100); rare (1/ 10000, < 1/ 1000); i foarte rare (< 1/ 10000).
Frequency of adverse reaction by treatment regimen
Frecven a reac iilor adverse observat în cadrul studiilor clinice controlate cu placebo
Sitagliptin with Sitagliptin with Sitagliptin with 1 2
Frecven a reac iilor adverse în func ie de regimul terapeutic
Sitagliptin with
Sitagliptin cu metformin1
Metformin
Sitagliptin cu o sulfoniluree2
a Sulfonylurea
Sitagliptin cu metformin i o
Metformin and a a PPARγ Agent Sulfonylurea3 (pioglitazone)4
Sitagliptin cu agent PPARγ
Metabolism and nutrition disorders
Tulbur ri metabolice i de nutri ie
Very common Common
foarte frecvent
Nervous system disorders somnolence
Tulbur ri ale sistemului nervos somnolen
Uncommon
mai pu in frecvent
Gastrointestinal disorders
Tulbur ri gastro - intestinale
diarrhea nausea flatulence constipation upper abdominal pain
diaree gre uri flatulen constipa ie dureri la nivelul abdomenului superior
Uncommon Common Uncommon
mai pu in frecvent frecvente mai pu in frecvente
Common
frecvent
General disorders peripheral oedema
Tulbur ri generale edeme periferice
Investigations blood glucose decreased *
Sitagliptin cu metformin1
Uncommon
Investiga ii diagnostice sc derea glicemiei mai pu in frecvent *
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.
În studii clinice cu TESAVEL în monoterapie i sitagliptin ca parte a terapiei asociate cu metformin sau pioglitazon, frecven ele de raportare a hipoglicemiei la administrarea sitagliptin au fost similare cu frecven ele din cazul pacien ilor trata i cu placebo.
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 În acest studiu controlat cu placebo cu durata de 24 s pt mâni cu sitagliptin 100 mg administrat o dat pe zi în asociere cu metformin, inciden ele reac iilor adverse considerate legate de medicament la pacien ii trata i cu sitagliptin/ metformin, comparativ cu tratamentul cu placebo/ metformin, au fost de 9, 3%, respectiv de 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.
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 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).
În studiile cumulate cu durat de pân la 1 an, care au comparat sitagliptin/ metformin cu un derivat de sulfoniluree/ metformin, reac iile adverse considerate legate de medicament, raportate în exces la pacien ii trata i cu sitagliptin 100 mg (> 0, 2% i diferen > 1 pacient) fa de cei trata i cu derivatul de sulfoniluree, sunt: anorexia (Tulbur ri metabolice i de nutri ie; mai pu in frecvente) i sc derea în greutate (Invesiga ii diagnostice; mai pu in frecvente).
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 În acest studiu clinic cu durata de 24 s pt mâni cu sitagliptin 100 mg administrat o dat pe zi în asociere cu glimepirid, inciden a reac iilor adverse considerate legate de medicament la pacien ii trata i cu sitagliptin/ glimepirid, comparativ cu tratamentul cu placebo/ glimepirid, a fost de 11, 3%, respectiv de 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 În acest studiu clinic cu durata de 24 s pt mâni cu sitagliptin 100 mg administrat o dat pe zi în asociere cu glimepirid i metformin, inciden a reac iilor adverse considerate legate de medicament la pacien ii trata i cu sitagliptin în asociere cu glimepirid / metformin, comparativ cu tratamentul cu placebo în asociere cu glimepirid / metformin, a fost de 18, 1%, respectiv de 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 În acest studiu cu durata de 24 s pt mâni cu sitagliptin 100 mg administrat o dat pe zi asociat cu pioglitazon, inciden a reac iilor adverse considerate legate de medicament la pacien ii trata i cu sitagliptin/ pioglitazon comparativ cu pacien ii c rora li s- a administrat placebo/ pioglitazon a fost de 9, 1%, respectiv de 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.
În plus, în studiile de monoterapie cu durat de pân la 24 s pt mâni, cu sitagliptin 100 mg administrat o dat pe zi în monoterapie, comparativ cu placebo, reac iile adverse considerate legate de medicament, raportate în exces la pacien ii trata i cu sitagliptin (> 0, 2% i diferen > 1 pacient) fa de cei c rora li s- a administrat placebo, sunt cefalee, hipoglicemie, constipa ie i ame eli.
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.
În plus fa de reac iile adverse legate de medicament descrise mai sus, au fost raportate reac ii adverse, f r referire la rela ia de cauzalitate cu medicamentele, care au ap rut în propor ie de cel pu in 5% i mai frecvent la pacien ii trata i cu TESAVEL i care au inclus infec ii ale tractului respirator superior i nazo- faringite.
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.
Au fost raportate reac ii adverse suplimentare, f r referire la reac ia de cauzalitate cu medicamentele, care au ap rut mai frecvent la pacien ii trata i cu TESAVEL (nu au dep it 5%, dar au ap rut cu o inciden mai mare de 0, 5% la TESAVEL fa de cea din grupul de control) ce au inclus osteoartrit i dureri la nivelul extremit ilor.
In a 24-week study of initial combination therapy with sitagliptin and metformin administered twice daily (sitagliptin/ metformin 50 mg/ 500 mg or 50 mg/ 1000 mg), the overall incidence of adverse reactions considered as drug-related in patients treated with the combination of sitagliptin and metformin compared to patients treated with placebo was 14.0% and 9.7%, respectively.
6 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%.
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.
Inciden a global a reac iilor adverse considerate legate de medicament la pacien ii trata i cu asocierea dintre sitagliptin i metformin a fost comparabil cu cea din cazul administr rii de metformin în monoterapie (14, 0% fiecare) i mai mare decât în cazul administr rii de sitagliptin în monoterapie (6, 7%), diferen ele privind administrarea de sitagliptin în monoterapie fiind datorate în principal reac iilor adverse gastro- intestinale.
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.
În studiile clinice a fost observat o cre tere mic a num rului de leucocite (diferen de aproximativ 200 celule/ microlitru în num rul de leucocite, comparativ cu placebo; num r mediu ini ial de leucocite - aproximativ 6600 celule/ microlitru), datorit unei cre teri a neutrofilelor.
This observation was seen in most but not all studies.
Aceast observa ie a survenit în majoritatea, dar nu în toate studiile.
This change in laboratory parameters is not considered to be clinically relevant.
Aceast modificare a parametrilor de laborator nu este considerat clinic relevant.
No clinically meaningful changes in vital signs or in ECG (including in QTc interval) were observed with TESAVEL treatment.
În cursul tratamentului cu TESAVEL nu au fost observate modific ri clinic semnificative ale semnelor vitale sau ECG (inclusiv intervalul QTc).
6 Post-marketing Experience:
Experien a dup punerea pe pia:
During controlled clinical trials in healthy subjects, single doses of up to 800 mg sitagliptin were generally well tolerated.
În studii clinice controlate, cu subiec i s n to i, doze unice de pân la 800 mg sitagliptin au fost, în general, bine tolerate.
Minimal increases in QTc, not considered to be clinically relevant, were observed in one study at a dose of 800 mg sitagliptin.
În unul dintre studii au fost observate, la o doz de 800 mg sitagliptin, cre teri minime ale QTc, care nu au fost considerate clinic relevante.
There is no experience with doses above 800 mg in humans.
Nu exist experien la om cu doze mai mari de 800 mg.
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.
În cazul supradozajului, este rezonabil aplicarea m surilor obi nuite de sus inere, de exemplu îndep rtarea substan ei neabsorbite din tractul gastro- intestinal, monitorizare clinic (inclusiv efectuarea unei electrocardiograme) i, dac este necesar, instituirea tratamentului de sus inere.
Sitagliptin is modestly dialyzable.
Sitagliptin se elimin în propor ie mic prin dializ.
In clinical studies, approximately 13.5% of the dose was removed over a 3- to 4-hour hemodialysis session.
În studii clinice, într- o edin de 3- 4 ore de hemodializ a fost îndep rtat aproximativ 13, 5% din doz.
Prolonged hemodialysis may be considered if clinically appropriate.
Dac este cazul, trebuie avut în vedere hemodializa prelungit.
It is not known if sitagliptin is dialyzable by peritoneal dialysis.
Nu se cunoa te dac sitagliptin este dializabil prin dializ peritoneal.
DPP-4 Inhibitor, ATC code:
Grupa farmacoterapeutic: inhibitor al DPP- 4, codul ATC:
TESAVEL is a member of a class of oral anti-hyperglycaemic agents called dipeptidyl peptidase 4 (DPP-4) inhibitors.
TESAVEL face parte dintr- o clas de medicamente antihiperglicemiante orale, denumit inhibitori ai dipeptidil peptidazei 4 (DPP- 4).
The improvement in glycaemic control observed with this agent may be mediated by enhancing the levels of active incretin hormones.
Ameliorarea controlului glicemic observat cu acest medicament poate fi mediat prin cre terea valorilor hormonilor endogeni activi.