natgillin/translations-raw huggingface dataset:
Following initiation of therapy with Incresync, it is recommended that liver enzymes be monitored periodically based on clinical judgement.
Nakon početka terapije Incresyncom preporučuje se povremeno pratiti jetrene enzime na temelju kliničke procjene.
If ALT levels are increased to 3 x upper limit of normal during therapy, liver enzyme levels should be reassessed as soon as possible.
Ako se tijekom terapije razine ALT-a povise do 3 puta iznad gornje granice normale, razine jetrenih enzima treba čim prije ponovno provjeriti.
Nonfatal Stroke *Overall there were 153 subjects (5.7%) in the alogliptin group and 173 subjects (6.5%) in the placebo group who died (all-cause mortality)
*Ukupno je umrlo (svi uzroci smrti) 153 ispitanika (5,7%) u skupini na alogliptinu i 173 ispitanika (6,5%) u skupini na placebu.
For patients switching from separate tablets of alogliptin and pioglitazone, both alogliptin and pioglitazone should be dosed at the daily dose already being taken.
Za bolesnike koji se prebacuju sa zasebnih tableta alogliptina i pioglitazona, i alogliptin i pioglitazon trebaju se dozirati prema dnevnoj dozi koju bolesnik već uzima.
Mean levels of liver enzymes decreased with treatment with pioglitazone.
Srednje vrijednosti razina jetrenih enzima smanjivale su se s liječenjem pioglitazonom.
- if you have cysts on your ovaries (polycystic ovarian syndrome).
• ako imate ciste na jajnicima (sindrom policističnih jajnika).
After administration of single, oral doses of up to 800 mg in healthy subjects, alogliptin was rapidly absorbed with peak plasma concentrations occurring 1 to 2 hours (median Tmax) after dosing.
Nakon primjene jednokratnih peroralnih doza do 800 mg u zdravih ispitanika, alogliptin se brzo apsorbirao i postizao vršnu koncentraciju u plazmi 1 do 2 sata (medijan Tmax) nakon doziranja.
In clinical studies of alogliptin, anaphylactic reactions were reported with a low incidence.
U kliničkim ispitivanjima alogliptina, anafilaktičke reakcije su prijavljene s niskom incidencijom.
Studies in lactating rats indicate that alogliptin is excreted in milk.
Ispitivanja u štakora u laktaciji pokazuju da se alogliptin izlučuje u mlijeko.
The pioglitazone dose may need to be increased when rifampicin is concomitantly administered.
Dozu pioglitazona možda će trebati povisiti kad se istodobno primjenjuje s rifampicinom.
If you have kidney problems your doctor may prescribe you a reduced dose.
Ako imate probleme s bubrezima, liječnik će možda propisati nižu dozu.
Patients should be advised to adhere strictly to a calorie-controlled diet.
Bolesnicima treba savjetovati da se strogo pridržavaju dijete s kontroliranim unosom kalorija.
• The risk of bladder cancer and relevant risk minimisation advice.
• Rizik od karcinoma mokraćnog mjehura i odgovarajuće savjete o minimizaciji rizika.
Visceral fat was significantly decreased while there was an increase in extra-abdominal fat mass.
Visceralno masno tkivo bilo je značajno smanjeno, dok se masa izvanabdominalnog masnog tkiva povećala.
To be eligible, patients had to have had one or more of the following: myocardial infarction, stroke, percutaneous cardiac intervention or coronary artery bypass graft, acute coronary syndrome, coronary artery disease, or peripheral arterial obstructive disease.
Da bi bili pogodni za ispitivanje, bolesnici su morali imati jedno ili više od sljedećeg: infarkt miokarda, moždani udar, perkutanu srčanu intervenciju ili premosnicu koronarne arterije, akutni koronarni sindrom, bolest koronarnih arterija ili opstruktivnu bolest perifernih arterija.
This is similar to that seen in a sulphonylurea active comparator group.
To je slično onom opaženom u skupini koja je primala sulfonilureju kao aktivni usporedni lijek.
Higher doses of alogliptin decreased offspring body weight and exerted some developmental effects considered secondary to the low body weight.
Više doze alogliptina smanjile su tjelesnu težinu mladunčadi te pokazale neke razvojne učinke koji se smatraju posljedicom niske tjelesne težine.
Interactions with pioglitazone
Interakcije s pioglitazonom
Pioglitazone undergoes extensive hepatic metabolism by hydroxylation of aliphatic methylene groups.
Pioglitazon prolazi opsežni metabolizam u jetri hidroksilacijom alifatskih metilenskih skupina.
For patients inadequately controlled on dual therapy with pioglitazone and a maximally tolerated dose of metformin, the dose of metformin should be maintained, and Incresync administered concomitantly.
Za bolesnike neodgovarajuće kontrolirane dvojnom terapijom pioglitazonom i maksimalnom podnošljivom dozom metformina, dozu metformina treba održati jednakom, a Incresync primijeniti istodobno.
There are no adequate human data to determine the safety of pioglitazone during pregnancy.
Nema odgovarajućih podataka da bi se mogla utvrditi sigurnost pioglitazona tijekom trudnoće u ljudi.
Pioglitazone appears to act via activation of specific nuclear receptors (peroxisome proliferator activated receptor gamma) leading to increased insulin sensitivity of liver, fat and skeletal muscle cells in animals.
Pioglitazon vjerojatno djeluje putem aktivacije posebnih receptora u jezgri (receptor gama aktiviran peroksizomskim proliferatorom - PPAR gama), što u životinja dovodi do povećane osjetljivosti jetre, masnog tkiva i skeletnih mišićnih stanica na inzulin.
There were 703 patients who experienced an event within the secondary MACE composite endpoint (first event of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke and urgent revascularization due to unstable angina).
U 703 bolesnika javio se događaj unutar sekundarnog MACE kompozitnog ishoda (prvi događaj kardiovaskularne smrti, infarkta miokarda bez smrtnog ishoda, moždanog udara bez smrtnog ishoda ili hitnog postupka revaskularizacije zbog nestabilne angine).
The average renal clearance of alogliptin (170 mL/min) was greater than the average estimated glomerular filtration rate (approx. 120 mL/min), suggesting some active renal excretion.
Prosječni bubrežni klirens alogliptina (170 ml/min) bio je veći od prosječne procijenjene brzine glomerularne filtracije (približno 120 ml/min), što ukazuje na izvjesnu aktivnu bubrežnu ekskreciju.
The observed excess risk of fractures for women in this dataset on pioglitazone is, therefore, 0.8 fractures per 100 patient years of use.
Opažen povećan rizik od prijeloma u žena u ovom setu podataka o pioglitazonu stoga je 0,8 prijeloma na 100 bolesnik-godina primjene.
The pharmacokinetics of alogliptin has been shown to be similar in healthy subjects and in patients with type 2 diabetes mellitus.
Utvrđeno je da je farmakokinetika alogliptina slična u zdravih ispitanika i u bolesnika sa šećernom bolešću tipa 2.
Combination of alogliptin with other anti-diabetic medicinal products
Kombinacija alogliptina s drugim antidijabetičkim lijekovima
Co-administration of 25 mg alogliptin once daily and 45 mg pioglitazone once daily for 12 days in healthy subjects had no clinically relevant effects on the pharmacokinetics of alogliptin, pioglitazone or their active metabolites.
Istodobna primjena 25 mg alogliptina jedanput na dan i 45 mg pioglitazona jedanput na dan tijekom 12 dana u zdravih ispitanika nije imala klinički značajne učinke na farmakokinetiku alogliptina, pioglitazona ili njihovih aktivnih metabolita.
Pioglitazone did not cause statistically significant increases in LDL-cholesterol levels compared to placebo whilst reductions were observed with metformin and gliclazide.
Pioglitazon nije uzrokovao statistički značajna povišenja razina LDL-kolesterola u usporedbi s placebom, dok su sniženja opažena s metforminom i gliklazidom.
Not known: - Visual disturbances (caused by a condition called macular oedema).
• smetnje vida (uzrokovane stanjem pod nazivom makularni edem)
Concomitant treatment with alogliptin and pioglitazone did not produce new toxicities, nor did it exacerbate any pioglitazone-related findings.
Istodobno liječenje alogliptinom i pioglitazonom nije izazvalo nove toksičnosti niti je pogoršalo bilo koji nalaz povezan s pioglitazonom.
- pioglitazone belongs to a group of medicines called thiazolidinediones.
- pioglitazon pripada skupini lijekova pod nazivom tiazolidindioni.
Overall, treatment with the recommended daily dose of 25 mg alogliptin in combination with pioglitazone improved glycaemic control.
Sveukupno, liječenje preporučenom dnevnom dozom od 25 mg alogliptina u kombinaciji s pioglitazonom poboljšalo je kontrolu glikemije.
Thus, free (unbound) pioglitazone concentration is unchanged (see section 4.2).
Stoga je koncentracija slobodnog (nevezanog) pioglitazona neizmijenjena (vidjeti dio 4.2).
What Incresync contains - The active substances are alogliptin and pioglitazone.
Što Incresync sadrži - Djelatne tvari su alogliptin i pioglitazon.
Specific pharmacokinetic drug interaction studies have not been performed with Incresync.
Specifična ispitivanja interakcija lijeka Incresync nisu provedena.
The maximum recommended daily dose of 25 mg alogliptin and 45 mg pioglitazone should not be exceeded.
Maksimalna preporučena dnevna doza od 25 mg alogliptina i 45 mg pioglitazona ne smije se prekoračiti.
In patients with renal impairment, serum concentrations of pioglitazone and its metabolites are lower than those seen in subjects with normal renal function, but oral clearance of parent substance is similar.
U bolesnika s oštećenjem bubrega, koncentracije pioglitazona i njegovih metabolita u serumu niže su od onih viđenih u ispitanika s normalnom funkcijom bubrega, ali oralni klirens izvornog spoja je sličan.
Alogliptin is primarily excreted unchanged in the urine and metabolism by the cytochrome (CYP) P450 enzyme system is negligible (see section 5.2).
Alogliptin se prvenstveno izlučuje nepromijenjen u mokraći, a metabolizam putem enzimatskog sustava citokroma (CYP) P450 mu je zanemariv (vidjeti dio 5.2.).
In the alogliptin group, 12.7% (344 subjects) experienced an event within the secondary MACE composite endpoint, compared with 13.4% (359 subjects) in the placebo group [Hazard Ratio = 0.95; 1-sided 99% Confidence Interval: 0-1.14].
U skupini na alogliptinu, 12,7% (344 ispitanika) imalo je događaj unutar sekundarnog MACE kompozitnog ishoda, u usporedbi s 13,4% (359 ispitanika) u skupini na placebu [omjer hazarda = 0,95; 1-stran 99% Interval pouzdanosti:
Since insulin and pioglitazone are both associated with fluid retention, concomitant administration may increase the risk of oedema.
Budući da su i inzulin i pioglitazon povezani sa zadržavanjem tekućine, njihova istodobna primjena može povećati rizik od pojave edema.
Use with other antihyperglycaemic medicinal products and hypoglycaemia
Primjena s drugim antihiperglikemijskim lijekovima i hipoglikemija
Hypersensitivity reactions, including anaphylactic reactions, angioedema and exfoliative skin conditions including Stevens-Johnson syndrome and erythema multiforme have been observed for DPP-4 inhibitors and have been spontaneously reported for alogliptin in the post-marketing setting.
Reakcije preosjetljivosti, uključujući i anafilaktičke reakcije, angioedem i eksfolijativna stanja kože uključujući Stevens-Johnsonov sindrom i erythema multiforme opažena su za DPP-4 inhibitore i spontano su prijavljene za alogliptin nakon stavljanja lijeka u promet.
Results from alogliptin studies with metformin, pioglitazone (thiazolidinedione), voglibose (alphaglucosidase inhibitor) and glyburide (sulphonylurea) have shown no clinically relevant pharmacokinetic interactions.
Rezultati ispitivanja alogliptina s metforminom, pioglitazonom (tiazolidindion), voglibozom (inhibitor alfa-glukozidaze) i gliburidom (sulfonilureja) nisu pokazali klinički značajne farmakokinetičke interakcije.
Risk factors for bladder cancer should be assessed before initiating Incresync treatment (risks include age, smoking history, exposure to some occupational or chemotherapy medicinal products e.g. cyclophosphamide or prior radiation treatment in the pelvic region).
Prije početka liječenja Incresyncom treba procijeniti faktore rizika za karcinom mokraćnog mjehura (rizici uključuju dob, pušenje u anamnezi, profesionalnu izloženost nekim tvarima ili kemoterapijskim lijekovima, npr. ciklofosfamidu ili prethodnu radioterapiju u području zdjelice).
The maximum recommended daily dose is one 25 mg/45 mg tablet.
Najveća preporučena dnevna doza je jedna tableta od 25 mg/45 mg.
In addition, a prospective randomised cardiovascular outcomes safety study was conducted with 5,380 patients with high underlying cardiovascular risk to examine the effect of alogliptin compared with placebo (when added to standard of care) on major adverse cardiovascular events (MACE) including time to the first occurrence of any event in the composite of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke in patients with a recent (15 to 90 days) acute coronary event.
Dodatno, prospektivno randomizirano ispitivanje sigurnosti s obzirom na kardiovaskularne ishode provedeno je na 5380 bolesnika s visokim podležećim kardiovaskularnim rizikom kako bi se ispitao učinak alogliptina u usporedbi s placebom (kao dodatak standardnoj terapiji) na velike kardiovaskularne štetne događaje (engl. major adverse cardiovascular events, MACE) uključujući i vrijeme do prve pojave bilo kojeg od događaja kardiovaskularne smrti, infarkta miokarda bez smrtnog ishoda i moždanog udara bez smrtnog ishoda u bolesnika s nedavnim (15 do 90 dana) akutnim koronarnim događajem.
The incidence of hypoglycaemia was greater when alogliptin was used as triple therapy with pioglitazone and metformin (compared to active-control).
Incidencija hipoglikemije je bila veća kad se alogliptin primjenjivao kao dio trojne terapije s pioglitazonom i metforminom (u usporedbi s aktivnom kontrolom).
In case of hypoglycaemia, a lower dose of the thiazolidinedione or metformin may be considered.
U slučaju hipoglikemije treba razmotriti nižu dozu tiazolidindiona ili metformina.
In light of age-related risks (especially bladder cancer, fractures and heart failure associated with the pioglitazone component), the balance of benefits and risks should be considered carefully both before and during Incresync treatment in the elderly.
U svjetlu rizika povezanih sa životnom dobi (osobito karcinom mokraćnog mjehura, prijelomi i zatajenje srca povezani sa sadržanim pioglitazonom), potrebno je pažljivo razmotriti omjer koristi i rizika prije i tijekom liječenja starijih bolesnika Incresyncom.
Hypoglycaemia may occur in combination with sulphonylureas or insulin.
Hipoglikemija može nastati u kombinaciji sa sulfonilurejama ili inzulinom.
Incresync contains lactose
Incresync sadrži laktozu
No effects on the toxicokinetics of either compound were observed.
Nisu opaženi učinci na toksikokinetiku bilo koje od djelatnih tvari.
In clinical studies with pioglitazone, there was evidence of dose-related weight gain, which may be due to fat accumulation and, in some cases, associated with fluid retention.
U kliničkim ispitivanjima pioglitazona bilo je dokaza povećanja tjelesne težine povezanog s dozom, što može biti zbog nakupljanja masnog tkiva i u nekim slučajevima, povezano sa zadržavanjem tekućine.
Hepatic impairment Incresync must not be used in patients with hepatic impairment (see sections 4.3, 4.4 and 5.2).
Incresync se ne smije primjenjivati u bolesnika s oštećenjem jetre (vidjeti dijelove 4.3, 4.4 i 5.2).
However, dosing of alogliptin should be conservative in patients with advanced age due to the potential for decreased renal function in this population.
Međutim, u bolesnika uznapredovale dobi doziranje alogliptina treba biti konzervativno zbog moguće smanjene funkcije bubrega u toj populaciji.
In an outcome study of patients with pre-existing major macrovascular disease, the incidence of serious heart failure was 1.6% higher with pioglitazone than with placebo when added to therapy that included insulin.
U ispitivanju ishoda u bolesnika s već postojećom velikom makrovaskularnom bolešću, incidencija ozbiljnog zatajenja srca bila je 1,6% viša uz pioglitazon nego uz placebo kad se dodaju terapiji koja uključuje inzulin.
- A severe allergic reaction: skin lesions or spots on your skin that can progress to a sore surrounded by pale or red rings, blistering and/or peeling of the skin possibly with symptoms such as itching, fever, overall ill feeling, achy joints, vision problems, burning, painful or itchy eyes and mouth sores (Stevens-Johnson syndrome and Erythema multiforme).
• Teška alergijska reakcija: oštećenja ili mrlje na koži, koje mogu napredovati do rana okruženih blijedim ili crvenim prstenovima, stvaranje mjehura i/ili ljuštenje kože, moguće sa simptomima poput svrbeža, vrućice, općeg lošeg osjećanja, bolnih zglobova, problema s vidom, pečenja, boli ili svrbeža očiju, te rana po sluznici usta (Stevens-Johnsonov sindrom i Erythema multiforme).
For patients intolerant to metformin or for whom metformin is contraindicated, inadequately controlled on pioglitazone alone, the recommended dose of Incresync is one tablet of 25 mg/30 mg or 25 mg/45 mg once daily, depending on the dose of pioglitazone already being taken.
Za bolesnike koji ne podnose metformin ili kojima je metformin kontraindiciran, a neodgovarajuće su kontrolirani samim pioglitazonom, preporučena doza Incresynca je jedna tableta od 25 mg/30 mg ili 25 mg/45 mg jedanput na dan, ovisno o dozi pioglitazona koju bolesnik već uzima.
GLP-1 and GIP increases insulin biosynthesis and secretion from pancreatic beta cells, while GLP-1 also inhibits glucagon secretion and hepatic glucose production.
GLP-1 i GIP povećavaju biosintezu inzulina i lučenje iz beta-stanica gušterače, dok GLP-1 također inhibira lučenje glukagona i stvaranje glukoze u jetri.
The no-observed-adverse-effect level (NOAEL) in the repeated dose toxicity studies in rats and dogs up to 26- and 39-weeks in duration, respectively, produced exposure margins that were approximately 147- and 227-fold, respectively, the exposure in humans at the recommended daily dose of 25 mg alogliptin.
Razina bez opaženih nuspojava (RBON) u ispitivanjima toksičnosti ponovljenih doza u štakora i pasa u trajanju od 26 i 39 tjedana pokazala je marginu izloženosti koja je za približno 147, odnosno 227 puta veća od izloženost u ljudi pri preporučenoj dozi od 25 mg alogliptina.
Studies in animals with alogliptin plus pioglitazone as combination treatment have shown reproductive toxicity (slight augmentation of pioglitazone-related foetal growth retardation and foetal visceral variations, see section 5.3).
Ispitivanja na životinjama alogliptina i pioglitazona kao kombiniranog liječenja pokazala su reproduktivnu toksičnost (blago povećanje s pioglitazonom povezanog zaostajanja u fetalnom rastu i fetalnih visceralnih varijacija, vidjeti dio 5.3).
The safety and efficacy of Incresync in children and adolescents < 18 years old have not been established.
Sigurnost i djelotvornost lijeka Incresync u djece i adolescenata < 18 godina starosti nisu utvrđene.
In the prospective randomised controlled cardiovascular outcomes study, investigator reported events of hypoglycemia were similar in patients receiving placebo (6.5%) and patients receiving alogliptin (6.7%) in addition to standard of care.
U prospektivnom randomiziranom kontroliranom ispitivanju kardiovaskularnih ishoda, događaji hipoglikemije koje su prijavili ispitivači bili su slični u bolesnika koji su primali placebo (6,5%) i bolesnika koji su primali alogliptin (6,7%) kao dodatak standardnoj terapiji.
Since there is a potential for an increase in dose-related adverse reactions, a decrease in the dose of pioglitazone may be needed when gemfibrozil is concomitantly administered.
Budući da postoji mogućnost povećanja nuspojava povezanih s dozom, možda bude potrebno sniziti dozu pioglitazona kod istodobne primjene s gemfibrozilom.
Additional symptoms may include general itching and feeling of heat especially affecting the scalp, mouth, throat, palms of hands and soles of feet (Stevens-Johnson syndrome).
Simptomi mogu uključivati generalizirani svrbež i osjećaj vrućine koji posebice zahvaća tjeme, usta, grlo, dlanove ruku i tabane nogu (Stevens-Johnsonov sindrom)
For patients with mild renal impairment (creatinine clearance (CrCl) > 50 to ≤ 80 mL/min), no dose adjustment of Incresync is necessary (see section 5.2).
Za bolesnike s blagim oštećenjem bubrega (klirens kreatinina >50 do ≤ 80 ml/min) nije potrebna prilagodba doze Incresynca (vidjeti dio 5.2).
Table 4.
Tablica 7.
In one-year clinical studies, pioglitazone consistently gave a statistically significant reduction in the albumin/creatinine ratio compared to baseline.
U kliničkim ispitivanjima u trajanju od jedne godine, pioglitazon je dosljedno pokazivao statistički značajno sniženje omjera albumin/kreatinin u usporedbi s početnim omjerom.
There is no induction of the main inducible P450 isoenzymes 1A, 2C8/9 and 3A4 in man.
Nema indukcije glavnih induktibilnih izoenzima P450 1A, 2C8/9 i 3A4 u čovjeka.
No data are available with regard to overdose of Incresync.
Nema dostupnih podataka o predoziranju Incresyncom.
In active comparator-controlled studies, mean weight increase with pioglitazone given as monotherapy was 2-3 kg over one year.
U ispitivanjima kontroliranima aktivnim usporednim lijekom, srednja vrijednost povećanja težine tijekom monoterapije pioglitazonom bila je 2-3 kg tijekom jedne godine.
The risk of fractures should be considered in the long-term care of patients treated with Incresync (see section 4.8).
Rizik od prijeloma treba uzeti u obzir kod dugotrajnog liječenja bolesnika lijekom Incresync (vidjeti dio 4.8).
Incresync should not be used during pregnancy or breast-feeding.
Incresync se ne smije koristiti tijekom trudnoće ili dojenja.
Immune system disorders hypersensitivity not known hypersensitivity and allergic reactions not known
Poremećaji imunološkog sustava Preosjetljivost i alergijske reakcije
No clinically relevant accumulation after multiple dosing was observed in either healthy subjects or in patients with type 2 diabetes mellitus.
Nakon višestrukog doziranja nije opažena klinički značajna akumulacija u zdravih ispitanika ni u bolesnika sa šećernom bolešću tipa 2.
Incresync combines two antihyperglycaemic medicinal products with complementary and distinct mechanisms of action to improve glycaemic control in patients with type 2 diabetes mellitus: alogliptin, a dipeptidyl-peptidase-4 (DPP-4) inhibitor, and pioglitazone, a member of the thiazolidinedione class.
Incresync sadrži dva antihiperglikemijska lijeka koji komplementarnim i različitim mehanizmom djelovanja poboljšavaju kontrolu glikemije u bolesnika sa šećernom bolešću tipa 2: alogliptin, inhibitor dipeptidil-peptidaze-4 (DPP4) i pioglitazon, predstavnik klase tiazolidindiona.
The highest doses of alogliptin administered in clinical studies were single doses of 800 mg to healthy subjects and doses of 400 mg once daily for 14 days to patients with type 2 diabetes mellitus (equivalent to 32 times and 16 times the recommended daily dose of 25 mg alogliptin, respectively).
Najviše doze alogliptina primijenjene u kliničkim ispitivanjima bile su jednokratne doze od 800 mg zdravim ispitanicima i doze od 400 mg jedanput na dan tijekom 14 dana u bolesnika sa šećernom bolešću tipa 2 (što je 32 puta, odnosno 16 puta više od preporučene dnevne doze od 25 mg alogliptina).
The oedema rates for comparator groups (sulphonylurea, metformin) were 2-5%.
Stope edema u skupinama koje su primale usporedni lijek (sulfonilureju, metformin) bile su 2-5%.
Cardiac failure or history of cardiac failure (NYHA stages I to IV; see section 4.4) Hepatic impairment (see section 4.4)
• Zatajenje srca ili zatajenje srca u anamnezi (NYHA stadij I do IV; vidjeti dio 4.4)
Symptoms include excessive thirst, frequent urination, loss of appetite, nausea or vomiting and rapid weight loss.
Simptomi uključuju izrazitu žeđ, često mokrenje, gubitak teka, mučninu ili povraćanje te brzi gubitak težine.