natgillin/translations-raw huggingface dataset:
Hjerteinsufficiens er sjældent rapporteret i markedsføringen af brugen af pioglitazon, men oftere når pioglitazon blev brugt i kombination med insulin eller på patienter med en historie om hjerteinsufficiens.
Heart failure has been reported rarely with marketing use of pioglitazone, but more frequently when pioglitazone was used in combination with insulin or in patients with a history of cardiac failure.
I kontrollerede kliniske forsøg er hyppigheden af rapporteret hjerteinsufficiens ved pioglitazonbehandling den samme som for placebo -, metformin - og sulfonylurinstof- grupperne.
In controlled clinical trials the incidence of reports of heart failure with pioglitazone treatment was the same as in placebo, metformin and sulphonylurea treatment groups.
Der er kun sjældent rapporteret om hjerteinsufficiens ved markedsført anvendelse af pioglitazon.
Heart failure has been reported rarely with marketing use of pioglitazone.
- 8 - DATA EFTER MARKEDSFØRINGEN
POST MARKETING DATA
Baseret på erfaringen med glimepirid og med andre sulfonylurinstoffer skal følgende bivirkninger nævnes.
Based on experience with glimepiride and with other sulphonylureas the following adverse reactions have to be mentioned.
Forstyrrelser i immunsystemet Meget sjældent:
8 Immune system disorders Very rare:
Allergisk shock, allergisk vasculitis
Allergic shock, allergic vasculitis
Sygdomme i blod - og lymfesystem Sjældent:
Blood and lymphatic system disorders Rare:
Ændringer i hæmatologi
Changes in haematology
Meget sjældent:
Gastro-intestinal disorders Very rare:
Opkastning, diare, kvalme, abdominalt tryk, følelse af at maven er fuld, abdominal smerte
Vomiting, diarrhoea, nausea, abdominal pressure, feeling of fullness in the stomach, abdominal pain
Sygdomme i lever og galdeveje Meget sjældent:
Hepato-biliary disorders Very rare:
Hepatitis, nedsættelse af leverfunktion (med kolestase og gulsot)
Hepatitis, impairment of liver function (with cholestasis and jaundice)
Sygdomme i hud og subkutane væv Meget sjældent:
Skin and subcutaneous tissue disorders Very rare:
Overfølsomhed over for lys
Hypersensitivity to light
Meget sjældent:
Very rare:
Fald i natrium serumkoncentrationer
Decrease in sodium serum concentrations
I meget sjældne tilfælde kan milde overfølsomhedsreaktioner udvikle sig til alvorlige reaktioner med dyspnø, blodtryksfald og sommetider shock.
In very rare cases mild hypersensivity reactions may develop into serious reactions with dyspnoea, fall in blood pressure and sometimes shock.
Overfølsomhedsreaktioner i huden kan optræde som kløe, udslæt og urticaria.
Hypersensitivity reactions of the skin may occur as itching, rash, and urticaria.
Moderat til svær trombocytopeni, leukopeni, erytrocytopeni, agranulocytopeni, agranulocytose, hæmolytisk anæmi og pancytopeni kan forekomme.
Moderate to severe thrombocytopenia, leucopenia, erythrocytopenia, agranulocytopenia, agranulocytosis, haemolytic anemia and pancyto-penia may occur.
Disse er generelt reversible ved seponering af medicinen.
These are in general reversible upon discontinuation of medication.
Gastrointestinale problemer er meget sjældne og fører sjældent til seponering af behandlingen.
Gastro-intestinal complaints are very rare and seldom lead to discontinuation of therapy.
Der kan forekomme forhøjede leverenzymer.
Elevation of liver enzymes may occur.
I meget sjældne tilfælde kan det udvikle sig til nedsat leverfunktion (f. eks. med kolestase og gulsot), så vel som til hepatitis, der kan udvikle sig til leversvigt.
In very rare cases, impairment of liver function (e. g. with cholestasis and jaundice) may develop, as well as hepatitis which may progress to liver failure.
Der sås ingen øget hyppighed af
No increase in fracture rates was observed in men treated with pioglitazone (1.7%) versus comparator (2.1%).
Der er rapporteret om patienter, der har taget pioglitazon i højere doser end den anbefalede maksimale dosis på 45 mg daglig.
Patients have taken pioglitazone at higher than the recommended highest dose of 45 mg daily.
Efter indtagelse af en overdosis glimepirid kan der indtræde hypoglykæmi, der kan vare fra 12 til 72 timer, og som kan vende tilbage efter den første bedring.
After ingestion of an overdosage of glimepiride, hypoglycaemia may occur, lasting from 12 to 72 hours, and may recur after initial recovery.
Behandling af overdosering med Tandemact består primært i at forhindre absorption af glimepirid ved først at få patienten til at kaste op og derefter at få patienten til at drikke vand eller limonade med aktivt kul (absorberende) og natriumsulfat (afførende).
9 Treatment of overdosage of Tandemact primarily consists of preventing absorption of glimepiride by inducing vomiting and then drinking water or lemonade with activated charcoal (adsorbent) and sodium-sulphate (laxative).
I tilfælde af (svær) overdosering er hospitalisering på intensiv afdeling indiceret.
In case of (severe) overdosage hospitalization in an intensive care department is indicated.
Påbegynd indgivelse af glukose så hurtigt som muligt, om nødvendigt ved intravenøs bolusinjektion af en 50 ml 50% opløsning efterfulgt af en infusion af en 10% opløsning med nøje monitorering af blodsukkeret.
Start the administration of glucose as soon as possible, if necessary by a bolus intravenous injection of 50 ml of a 50% solution, followed by an infusion of a 10% solution with strict monitoring of blood glucose.
Perorale antidiabetika, kombinationspræparater; ATC- kode:
Combinations of oral blood glucose lowering drugs; ATC code:
Tandemact kombinerer to antidiabetiske stoffer med komplementære virkningsmekanismer til forbedring af den glykæmiske kontrol hos patienter med 2- diabetes: pioglitazon, der hører til thiazolidinedionerne og glimepirid, der hører til gruppen af sulfonylurinstoffer.
Tandemact combines two antihyperglycaemic agents with complementary mechanisms of action to improve glycaemic control in patients with type 2 diabetes: pioglitazone, a member of the thiazolidinedione class and glimepiride, a member of the sulphonylurea class.
Thiazolidinedionerne virker primært ved at reducere insulinresistens og sulfonylurinstofferne virker primært ved at stimulere insulinfrigivelse fra bugspytkirtlens beta- celler.
Thiazolidinediones act primarily by reducing insulin resistance and sulphonylureas primarily by inducing insulin release from pancreatic beta cells.
behandlingen svigter (defineret som forekomst af HbA1c ≥ 8, 0% efter de første seks måneders behandling).
A clinical trial of pioglitazone vs. gliclazide as monotherapy was extended to two years in order to assess time to treatment failure (defined as appearance of HbA1c ≥ 8.0% after the first six months of therapy).
Efter to år var den glykæmiske kontrol (defineret som HbA1c < 8, 0%) opretholdt hos 69% af patienterne behandlet med pioglitazon sammenlignet med 50% af patienterne behandlet med gliclazid.
At two years, glycaemic control (defined as HbA1c < 8.0%) was sustained in 69% of patients treated with pioglitazone, compared with 50% of patients on gliclazide.
I et kontrolleret forsøg med placebo, indgik patienter med utilstrækkelig glycemisk kontrol på trods af en tre- måneders optimeringsperiode, i et randomiseret forsøg med brug af pioglitazon eller placebo i 12 måneder.
In a placebo controlled trial, patients with inadequate glycaemic control despite a three month insulin optimisation period were randomised to pioglitazone or placebo for 12 months.
Patienter, der fik pioglitazon opnåede en middelreducering i HbA1c på 0, 45%, sammenlignet med de patienter, der fortsatte med insulin alene, og der opnåedes en reduktion af insulinforbruget i gruppen, der blev behandlet med pioglitazon.
Patients receiving pioglitazone had a mean reduction in HbA1c of 0.45% compared with those continuing on insulin alone, and a reduction of insulin dose in the pioglitazone treated group.
Effekten af pioglitazon (45 mg monoterapi versus placebo) er blevet undersøgt i et mindre, 18- ugers klinisk forsøg hos type 2- diabetikere.
10 The effect of pioglitazone (45 mg monotherapy vs. placebo) was studied in a small 18-week trial in type 2 diabetics.
Der var mindre, men ikke klinisk signifikante stigninger i LDL - kolesterolniveauer.
In most clinical trials, reduced total plasma triglycerides and free fatty acids, and increased HDL- cholesterol levels were observed as compared to placebo, with small, but not clinically significant increases in LDL-cholesterol levels.
Deltagelsen varede op til 3, 5 år.
In PROactive, a cardiovascular outcome study, 5238 patients with type 2 diabetes mellitus and pre- existing major macrovascular disease were randomised to pioglitazone or placebo in addition to existing antidiabetic and cardiovascular therapy, for up to 3.5 years.
Deltagernes gennemsnitsalder var 62 år og de havde i gennemsnit haft diabetes i 9, 5 år.
The study population had an average age of 62 years; the average duration of diabetes was 9.5 years.
Omkring en tredjedel af patienterne modtog insulin i kombination med metformin og sulphonylurea.
Approximately one third of patients were receiving insulin in combination with metformin and/ or a sulphonylurea.
For at kunne deltage i undersøgelsen skulle patienterne have haft en eller flere af følgende lidelser: myorkardial infarkt, slagtilfælde, perkutan koronar intervention eller koronar arterie bypass transplantat, akut koronar syndrom, koronar arterielidelse, obstruerende perifer arteriesygdom.
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.
Næsten halvdelen af patienterne havde tidligere haft en myokardi infarkt og omkring 20% havde haft et slagtilfælde.
Almost half of the patients had a previous myocardial infarction and approximately 20% had had a stroke.
Omkring halvdelen af forsøgspersonerne havde haft mindst to af de kardiovaskulære tilfælde, der udgjorde Kriterierne for at deltage.. næsten alle deltagere (95%) modtog kardiovaskulære medikamenter (betablokkere, ACE- hæmmere, angiotensin II hæmmere, Kalcium kanalhæmmere,, nitrater, vanddrivende midler, aspirin, statiner, fibrater).
Almost all subjects (95%) were receiving cardiovascular medications (beta blockers, ACE inhibitors, angiotensin II antagonists, calcium channel blockers, nitrates, diuretics, aspirin, statins, fibrates).
Skønt undersøgelsen mislykkedes mht. dens primære slutmål, der var en sammensætning af alle dødelighedsårsager, ikke dødelig myokardial infarct, slagtilfælde, akut koronar syndrom, større benamputationer, koronar revaskulari, og benrevaskulari, så pegede resultaterne på, at der ikke på længere sigt findes nogle kardiovaskulære bekymringer med hensyn til brugen af pioglitazon.
Although the study failed regarding its primary endpoint, which was a composite of all-cause mortality, non-fatal myocardial infarction, stroke, acute coronary syndrome, major leg amputation, coronary revascularisation and leg revascularisation, the results suggest that there are no long-term cardiovascular concerns regarding use of pioglitazone.
Tilfælde med ødemer, vægtforøgelse og hjerteinsufficiens var dog forøget.
However, the incidence of oedema, weight gain and heart failure were increased.
Glimepirid virker hovedsageligt ved at stimulere frigivelse af insulin fra beta- cellerne i pankreas.
Glimepiride acts mainly by stimulating insulin release from pancreatic beta cells.
Lige som for andre sulfonylurinstoffer skyldes denne virkning en øget følsomhed i beta- cellerne over for den fysiologiske glukosestimulation.
As with other sulphonylureas this effect is based on an increase of responsiveness of the pancreatic beta cells to the physiological glucose stimulus.
Frigivelse af insulin Sulfonylurinstoffer regulerer insulinsekretion ved at lukke de ATP- følsomme kaliumkanaler i beta- cellemembranen.
Sulphonylureas regulate insulin secretion by closing the ATP-sensitive potassium channel in the beta cell membrane.
Lukning af kaliumkanalerne inducerer depolarisation af beta - cellen og fører til en åbning af calciumkanalerne og dermed til en øget calciumtransport til cellen.
Closing the potassium channel induces depolarisation of the beta cell and results – by opening of calcium channels – in an increased influx of calcium into the cell.
Glimepirid bindes med høj omsætningshastighed til et membranprotein i beta- cellen, som er knyttet til den ATP- følsomme kaliumkanal, men som adskiller sig fra det sædvanlige bindingssted for sulfonylurinstof.
Glimepiride binds with a high exchange rate to a beta cell membrane protein which is associated with the ATP-sensitive potassium channel but which is different from the usual sulphonylurea binding site.
Ekstrapankreatisk virkning Den ekstrapankreatiske virkning kan for eksempel være øget insulinfølsomhed i de perifere væv og et fald i leverens insulinoptagelse.
The extrapancreatic effects are for example an improvement of the sensitivity of the peripheral tissue for insulin and a decrease of the insulin uptake by the liver.
Optagelsen af glukose fra blod i perifere muskel - og fedtvæv foregår via specielle transportproteiner, som findes i cellemembranerne.
The uptake of glucose from blood into peripheral muscle and fat tissues occurs via a special transport proteins, located in the cells membrane.
Glimepirid øger meget hurtigt antallet af aktive glukosetransportmolekyler i muskel - og fedtcellers plasmamembraner, hvilket resulterer i en stimuleret glukoseoptagelse.
Glimepiride increases very rapidly the number of active glucose transport molecules in the plasma membranes of muscle and fat cells, resulting in stimulated glucose uptake.
Glimepirid øger aktiviteten af glycosylphosphatidylinositol- specifikt phospholipase C, som kan være korreleret med den inducerede lipogenese og glykogenese i isolerede fedt - og muskelceller.
11 Glimepiride increases the activity of the glycosyl-phosphatidylinositol-specific phospholipase C which may be correlated with the induced lipogenesis and glycogenesis in isolated fat and muscle cells.
Glimepirid hæmmer leverens glukosedannelse ved at øge intracellulær koncentration affruktose- 2, 6 - biphosphat, som igen hæmmer glukoneogenesen.
Glimepiride inhibits the glucose production in the liver by increasing the intracellular concentration of fructose-2,6-bisphosphate, which in turn inhibits the gluconeogenesis.
Hos raske personer er den mindste effektive perorale dosis cirka 0, 6 mg.
In healthy persons, the minimum effective oral dose is approximately 0.6 mg.
Det fysiologiske respons på akut fysisk aktivitet, dvs. reduktion af insulinsekretion, er stadig tilstede under glimepirid- behandlingen.
The physiological response to acute physical exercise, reduction of insulin secretion, is still present under glimepiride.
De følgende oplysninger vedrører de farmakokinetiske forhold af de individuelle aktive stoffer i Tandemact.
The following statements reflect the pharmacokinetic properties of the individual active substances of Tandemact
Pioglitazon absorberes hurtigt efter peroral indgivelse, og de maksimale plasmakoncentrationer af uomdannet pioglitazon opnås som regel 2 timer efter indgivelse.
Following oral administration, pioglitazone is rapidly absorbed, and peak plasma concentrations of unchanged pioglitazone are usually achieved 2 hours after administration.
Der sås proportionale stigninger i plasmakoncentrationen for doser fra 2- 60 mg.
Proportional increases of the plasma concentration were observed for doses from 2 – 60 mg.
Gentagen
Steady state is achieved after 4– 7 days of dosing.
dosering resulterer ikke i akkumulation af dette stof eller af metabolitter.
Repeated dosing does not result in accumulation of the compound or metabolites.
Det beregnede fordelingsvolumen hos mennesker er 0, 25 l/ kg.
The estimated volume of distribution in humans is 0.25 l/ kg.
Dette sker fortrinsvis via cytokrom P450 3A4 og 2C9, selvom andre isoformer kan være involveret i mindre grad.
This is predominantly via cytochrome P450 2C8 although other isoforms may be involved to a lesser degree.
Tre af de seks identificerede metabolitter er aktive (M- II, M- III og M - IV).
Three of the six identified metabolites are active (M-II, M-III, and M-IV).
Der sker ingen induktion af de vigtigste inducerbare P450- isoenzymer, 1A, 2C8/ 9 og 3A4, hos mennesker.
There is no induction of the main inducible P450 isoenzymes 1A, 2C8/ 9, and 3A4 in man.
Der er set henholdsvis en øgning eller en nedsættelse af plasmakoncentrationen af pioglitazon ved samtidig administration af pioglitazon og gemfibrozil (en hæmmer af cytokrom P450 2C8) eller rifampicin (en inducer af cytokrom P450 2C8) (se sektion 4. 5).
Concomitant administration of pioglitazone with gemfibrozil (an inhibitor of cytochrome P450 2C8) or with rifampicin (an inducer of cytochrome P450 2C8) is reported to increase or decrease, respectively, the plasma concentration of pioglitazone (see section 4.5).
Elimination:
12 Elimination:
Efter peroral indgivelse af radioaktivt mærket pioglitazon hos mennesker genfandtes den mærkede del hovedsagelig i fæces (55%) og i en mindre mængde i urin (45%).
Following oral administration of radiolabeled pioglitazone to man, recovered label was mainly in faeces (55%) and a lesser amount in urine (45%).
Hos dyr kan der kun påvises en lille mængde uomdannet pioglitazon i enten urin eller fæces Hos mennesker er den gennemsnitlige plasmahalveringstid for uomdannet pioglitazon 5- 6 timer og for dets samlede, aktive metabolitter 16 - 23 timer.
The mean plasma elimination half-life of unchanged pioglitazone in man is 5 to 6 hours and for its total active metabolites 16 to 23 hours.
Steady- state farmakokinetikken hos patienter på 65 år og derover ligner den der ses hos unge personer.
Steady state pharmacokinetics are similar in patients age 65 and over and young subjects.
Hos patienter med nedsat nyrefunktion er plasmakoncentrationerne af pioglitazon og dets metabolitter lavere end hos personer med normal nyrefunktion, men den perorale clearance af moderstoffet er på samme niveau.
In patients with renal impairment, plasma 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.
Biotilgængeligheden af glimepirid efter peroral indgift er fuldstændig.
The bioavailability of glimepiride after oral administration is complete.
De maksimale serumkoncentrationer (Cmax) nås cirka 2, 5 timer efter peroral indtagelse (gennemsnitligt 0, 3 µg/ ml ved gentagen dosering af 4 mg daglig), og der er lineær relation mellem dosis og såvel Cmax som AUC (areal under tid/ koncentration kurven).
Maximum serum concentrations (Cmax) are reached approximately 2.5 hours after oral intake (mean 0.3 µg/ ml during multiple dosing of 4 mg daily) and there is a linear relationship between dose and both Cmax and AUC (area under the time/ concentration curve).
Desuden har glimepirid høj proteinbinding (> 99%) og lav clearance (cirka 48 ml/ min).
Glimepiride has a very low distribution volume (approximately 8.8 litres) which is roughly equal to the albumin distribution space, high protein binding (> 99%), and a low clearance (approximately 48 ml/ min).
Glimepirid passerer kun blod - hjernebarrieren i ringe grad.
Passage of the blood brain barrier is low.
5- 8 timer.
Mean dominant serum half-life, which is of relevance for the serum concentrations under multiple- dose conditions, is about 5 to 8 hours.
Efter en enkelt dosis med radioaktivt mærket glimepirid blev 58% af radioaktiviteten genfundet i urinen og 35% i fæces.
After a single dose of radiolabelled glimepiride, 58% of the radioactivity was recovered in the urine, and 35% in the faeces.
Efter peroral indgift af glimepirid var den terminale halveringstid af disse metabolitter henholdsvis 3- 6 og 5- 6 timer.
After oral administration of glimepiride, the terminal half-lives of those metabolites were 3 to 6 and 5 to 6 hours respectively.
Dette skyldtes formentlig hurtigere elimination på grund af lavere proteinbinding.
In patients with low creatinine clearance, there was a tendency for glimepiride clearance to increase and for average serum concentrations to decrease, most probably resulting from a more rapid elimination because of lower protein binding.
Efter galdevejskirurgi hos fem ikke- diabetiske patienter var farmakokinetikken næsten den samme som hos raske.
Pharmacokinetics in five non-diabetic patients after bile duct surgery were similar to those in healthy persons.
Derudover blev der observeret øget fedtaflejring og - infiltration.
In addition, increased fatty deposition and infiltration were observed.
Der sås ikke hyperplasi af urinblæren hos hunde eller aber, der var blevet behandlet i op til 12 måneder.
Hyperplasia of the urinary bladder was not seen in dogs or monkeys treated for up to 12 months.
genotoksicitet, carcinogenicitet og reproduktionstoksicitet.
This finding is based on conventional safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenicity, and reproduction toxicity studies.
I det sidste (som dækkede embryotoksicitet, teratogenicitet og udviklings- toksicitet), blev de bivirkninger, som blev observeret, betragtet som værende sekundære til den hypoglykæmiske effekt, som blev induceret af stoffet i moderdyret og i afkommet.
In the latter (covering embryotoxicity, teratogenicity and developmental toxicity), undesirable effects observed were considered to be secondary to the hypoglycaemic effects induced by the compound in dams and in offspring.
Cellulose, mikrokrystallinsk Croscarmellosenatrium Hydroxypropylcellulose Laktose monohydrat Magnesiumstearat Polysorbat 80.
Cellulose microcrystalline Croscarmellose sodium Hydroxypropylcellulose Lactose monohydrate Magnesium stearate Polysorbate 80
Aluminium / aluminium blisterpakninger: pakninger med 14, 28, 30, 50, 90, og 98 tabletter.
Aluminium/ aluminium blisters; packs of 14, 28, 30, 50, 90 or 98 tablets.
08- 01- 2007
8th January 2007
- 15 -
15 1.
Tandemact 30 mg/ 4 mg tabletter.
Tandemact 30 mg/ 4 mg tablets.
Hver tablet indeholder 30 mg pioglitazon (som hydroklorid) og 4 mg glimepirid.
Each tablet contains 30 mg of pioglitazone (as hydrochloride) and 4 mg of glimepiride.
Hver tablet indeholder cirka 177 mg laktose monohydrat.
Each tablet contains approximately 177 mg lactose monohydrate.
Hvide til off- white, runde, konvekse tabletter mærket med ‘ 4833 G ’ på den ene side og ‘ 30/ 4 ’ på den anden side.
White to off-white, round, convex and embossed ‘ 4833 G’ on one face and ‘ 30/ 4’ on the other.
Behandling med Tandemact bør ikke igangsættes hos patienter med forhøjede leverenzymer (ALT > 2, 5 X øvre normal grænse) eller hos patienter med andre tegn på leversygdom.
Therapy with Tandemact should not be initiated in patients with increased baseline liver enzyme levels (ALT > 2.5 X upper limit of normal) or with any other evidence of liver disease.
Efter igangsættelse af behandling med Tandemact anbefales det, at leverenzymerne monitoreres med jævne mellemrum i henhold til en klinisk vurdering.
17 Following initiation of therapy with Tandemact, it is recommended that liver enzymes be monitored periodically based on clinical judgement.
100 patientår) af de pioglitazonbehandlede kvindelige patienter frakturer.
18 per 100 patient years) of female patients treated with comparator.