natgillin/translations-raw huggingface dataset:
100 patientår) versus metformin (5, 1%; 1, 5 patienter pr.
This increased risk remained during the course of the study.
100 patientår).
The majority of the fractures in the females who received rosiglitazone were reported in the foot, hand and arm.
I dobbeltblinde kliniske undersøgelser med rosiglitazon var forekomsten af stigninger i ALAT på mere end tre gange den øvre normale grænse af samme størrelse som ved placebo (0, 2%) og mindre end ved behandling med de lægemidler, som rosiglitazon blev sammenlignet med (0, 5% metformin/ sulfonylurinstof).
In double-blind clinical trials with rosiglitazone the incidence of elevations of ALT greater than three times the upper limit of normal was equal to placebo (0.2%) and less than that of the active comparators (0.5% metformin/ sulphonylureas).
Forekomsten af alle bivirkninger relateret til lever - og galdesystemerne var < 1, 5% i alle behandlingsgrupper og svarende til placebo.
The incidence of all adverse events relating to liver and biliary systems was < 1.5% in any treatment group and similar to placebo.
Post- marketing- data I forlængelse af bivirkningsdata, der blev fundet i kliniske undersøgelser, er de data, der blev fundet efter markedsføring af rosiglitazon vist i tabellen nedenfor.
Post-marketing data In addition to the adverse reactions identified from clinical trial data, the adverse reactions presented in Table 2 have been identified in post approval use of rosiglitazone.
Sjælden (≥ 1/ 10. 000, < 1/ 1. 000) og meget sjælden (< 1/ 10. 000) herunder isolerede rapporter.
Frequencies are defined as: rare ≥ 1/ 10,000, < 1/ 1000 and very rare < 1/ 10,000 including isolated reports.
Immunsystemet (se Sygdomme i hud og subkutane væv) Anafylaktisk reaktion
Immune system disorders (see Skin and subcutaneous tissue disorders)
Meget sjælden
rare
Hjerte Kongestiv hjerteinsufficiens / lungeødem
congestive heart failure/ pulmonary oedema
Hud og subkutane væv (se Immunsystemet) Angiødem Hudreaktioner (for eksempel nældefeber, kløe, udslæt) 5
Skin and subcutaneous tissue disorders (see Immune system disorders) 5
Der er rapporteret sjældne tilfælde af forhøjede leverenzymer og hepatocellulær dysfunktion.
Rare cases of elevated liver enzymes and hepatocellular dysfunction have been reported.
10 Glimepirid
10 Glimepiride
Frekvensen er defineret som:
Clinical trial data and post-marketing data Table 3 presents adverse reactions by system organ class and by frequency category based on experience with glimepiride and other sulphonylureas.
Meget almindelig (≥ 1/ 10), almindelig (≥ 1/ 100, < 1/ 10), ikke almindelig (≥ 1/ 1. 000, < 1/ 100), sjælden (≥ 1/ 10. 000, < 1/ 1. 000) og meget sjælden (< 1/ 10. 000) herunder isolerede rapporter).
Frequencies are defined as: very common (≥ 1/ 10), common (≥ 1/ 100, < 1/ 10), uncommon (≥ 1/ 1,000, < 1/ 100), rare (≥ 1/ 10,000, < 1/ 1000) and very rare (< 1/ 10,000 including isolated reports).
Frekvensen af glimepirid bivirkninger identificeret fra kliniske undersøgelser og post - marketingdata.
The frequency of glimepiride adverse reactions identified from clinical trial and post- marketing data
Agranulocytose Granulocytopeni Pancytopeni Hæmolytisk anæmi Thrombocytopeni Leukopeni Erythrocytopeni
agranulocytosis granulocytopenia pancytopenia haemolytic anaemia thrombocytopenia leukopenia erythrocytopenia
Sjælden Sjælden Sjælden Sjælden Sjælden Sjælden Sjælden
Rare Rare Rare Rare Rare Rare Rare
Immunsystemet6 Allergisk vasculitis Overfølsomhedsreaktioner7
Immune system disorders6 allergic vasculitis hypersensitivity reactions7
Mave- tarmkanalen Opkastning Diarre Kvalme Maveudspiling Mavesmerter Mavegener
Gastrointestinal disorders vomiting diarrhoea nausea abdominal distension abdominal pain abdominal discomfort
Meget sjælden Meget sjælden Meget sjælden Meget sjælden Meget sjælden Meget sjælden
Very rare Very rare Very rare Very rare Very rare Very rare
Lever og galdeveje9
Hepatobiliary disorders9
Hepatitis10 Nedsat leverfunktion (for eksempel cholestasis og gulsot)
hepatitis10 impairment of liver function (e. g. with cholestasis and jaundice)
Hud og subkutane væv11 Øget lysfølsomhed af huden
Skin and subcutaneous tissue disorders11 hypersensitivity of the skin to light
Nedsat natriumniveau i serum 6
serum sodium decrease 6
Der kan forekomme krydsallergi med sulfonylurinstoffer, sulfonamider og beslægtede stoffer.
Cross-allergenicity with sulphonylureas, sulphonamides or related substances 7
7 Milde overfølsomhedsreaktioner kan udvikle sig til alvorlige reaktioner med dyspnø, blodtryksfald og nogle gange shock.
Mild hypersensitivity reactions may develop into serious reactions with dyspnoea, fall in blood pressure and sometimes shock.
8 Baseret på viden om andre sulfonylurinstoffer, kan hyoglykæmi være længerevarende.
8 Based on what is known of other sulphonylureas, hypoglycaemia may be prolonged.
11 9 Der kan forekomme forhøjede niveauer af leverenzymer.
9 Elevation of liver enzymes may occur.
10 Hepatitis kan udvikle sig til leversvigt.
10 Hepatitis may progress to liver failure.
11 Der kan optræde overfølsomhedsreaktioner på huden, såsom kløe, udslæt og urticaria.
11 11 Hypersensitivity reactions of the skin may occur as itching, rash and urticaria.
Efter indtagelse af en overdosis af sulfonylurinstoffer, herunder glimepirid, kan der optræde hypoglykæmi, som kan vare 12- 72 timer, og som kan vende tilbage efter den indledende normalisering af blodglukose.
Overdose of sulphonylureas, including glimepiride, can result in severe life-threatening hypoglycaemia lasting 12 to 72 hours, which may recur after apparent recovery.
I tilfælde af overdosis anbefales det, at der gives støttende behandling, alt afhængig af patientens kliniske status.
In the event of an overdose, it is recommended that appropriate supportive treatment should be initiated as dictated by the patient’ s clinical status.
Antidiabetika, kombinationspræparater, ATC- kode:
Combinations of oral blood glucose lowering drugs, ATC code:
AVAGLIM kombinerer to antidiabetiske stoffer med komplementære virkningsmekanismer til forbedring af den glykæmiske kontrol hos patienter med type 2- diabetes: rosiglitazonmaleat, der hører til thiazolidinedionerne og glimepirid, der hører til sulfonylurinstofferne.
AVAGLIM combines two antidiabetic agents with complimentary mechanisms of action to improve glycaemic control in patients with type 2 diabetes: rosiglitazone maleate, 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 insulinfrigivelsen fra β- cellerne i pankreas.
Thiazolidinediones act primarily by reducing insulin resistance and sulphonylureas act primarily by stimulating release of insulin from functioning pancreatic β -cells.
Rosiglitazon Rosiglitazon er en selektiv agonist ved PPARγ (peroxisomal proliferator aktiveret gamma) nuklearreceptor og hører hjemme i antidiabetikumgruppen thiazolidinedioner.
Rosiglitazone Rosiglitazone is a selective agonist at the PPARγ (peroxisome proliferator activated receptor gamma) nuclear receptor and is a member of the thiazolidinedione class of antihyperglycaemic agents.
Rosiglitazons antihyperglykæmiske aktivitet er påvist i et antal dyremodeller med type 2- diabetes.
The antihyperglycaemic activity of rosiglitazone has been demonstrated in a number of animal models of type 2 diabetes.
Rosiglitazon forhindrede dertil udviklingen af udtalt hyperglykæmi i dyremodeller af type 2- diabetes.
In addition, rosiglitazone preserved ß-cell function as shown by increased pancreatic islet mass and insulin content and prevented the development of overt hyperglycaemia in animal models of type 2 diabetes.
Den hyppigst forekommende metabolit (para - hydroxy- sulfat) med høj affinitet til det opløselige humane PPARγ udviste relativ høj potens i en glucosetolerance- assay hos overvægtige mus.
The major metabolite (a para-hydroxy-sulphate) with high affinity to the soluble human PPARγ, exhibited relatively high potency in a glucose tolerance assay in obese mice.
8 ugers behandling.
In clinical trials, the glucose lowering effects observed with rosiglitazone are gradual in onset with near maximal reductions in fasting plasma glucose (FPG) evident following approximately 8 weeks of therapy.
Rosiglitazon var associeret med vægtøgning.
12 Rosiglitazone was associated with increases in weight.
Mekanistiske undersøgelser har vist, at vægtøgningen overvejende skyldtes en stigning i subkutant fedt med mindsket visceralt og intra- hepatisk fedt.
In mechanistic studies, the weight increase was predominantly shown to be due to increased subcutaneous fat with decreased visceral and intra-hepatic fat.
I overensstemmelse med virkningsmekanismen reducerede rosiglitazon insulinresistens og forbedrede pankreatisk β- celle funktion.
Consistent with the mechanism of action, rosiglitazone reduced insulin resistance and improved pancreatic ß-cell function.
Som en konsekvens af forskellige, men komplementære virkningsmekanismer, resulterede kombinationsbehandling, med rosiglitazon og sulfonylurinstof eller metformin, i additiv effekt på glykæmisk kontrol hos patienter med type 2- diabetes.
As a consequence of different but complementary mechanisms of action, dual oral therapy of rosiglitazone with a sulphonylurea or metformin resulted in additive effects on glycaemic control in type 2 diabetic patients.
Et morbiditets/ mortalitetsstudie er endnu ikke blevet tilendebragt med rosiglitazon, hvorfor langtidsfordelene associeret med forbedret glykæmisk kontrol ikke er blevet påvist.
An outcome study has not been completed with rosiglitazone, therefore the long-term benefits associated with improved glycaemic control have not been demonstrated.
I et igangværende langtids- sammenligningsstudie, var rosiglitazon, i kombinationsbehandling med metformin eller sulfonylurinstof, ikke- inferiør over for kombinationen af sulfonylurinstof plus metformin til sænkning af HbAlc efter 18 måneder.
At 18 months, in an ongoing long term comparator study, rosiglitazone in dual oral therapy with metformin or a sulphonylurea was non-inferior to the combination of sulphonylurea plus metformin for lowering HbA1c.
Der er ingen afsluttede studier, som undersøger den kardiovaskulære langtidseffekt hos patienter, som får rosiglitazon.
There are no studies completed assessing long-term cardiovascular outcome in patients receiving rosiglitazone.
Glimepirid Glimepirid er et hypoglykæmisk stof, der er aktivt peroralt, og som tilhører gruppen sulfonylurinstoffer.
Glimepiride Glimepiride is an orally active hypoglycaemic substance belonging to the sulphonylurea group.
Det kan anvendes til behandling af ikke- insulinkrævende diabetes mellitus.
It may be used in non-insulin dependent diabetes mellitus.
Glimepirid virker hovedsageligt ved at stimulere insulinfrigivelsen fra β- cellerne i pankreas.
Glimepiride acts mainly by stimulating the release of insulin from the beta cells of the pancreas.
I lighed med andre sulfonylurinstoffer skyldes denne virkning en øget følsomhed for den fysiologiske glukosestimulation i pankreas β- celler.
As with other sulphonylureas, this effect is based on an improvement in responsiveness of pancreatic beta cells to the physiological glucose stimulus.
Sulfonylurinstoffer regulerer insulinsekretionen ved at lukke den ATP- følsomme kaliumkanal i β - cellemembranen.
Sulphonylureas regulate insulin secretion by closing the ATP-dependent potassium channels in the beta cell membrane.
Lukning af kaliumkanalen inducerer depolarisation af β- cellen og resulterer i en åbning af calciumkanalerne og en øget calcium- influx i cellen.
Closure of the potassium channels leads to depolarisation of the beta cell and results by opening of the calcium channels – to an increased influx of calcium into the cell.
Dette bindingsprotein er knyttet til den ATP- følsomme kaliumkanal, men er forskellig fra det almindelige sulfonylurinstofbindingssted.
Glimepiride binds with a high exchange rate to a beta cell membrane protein which is associated with the ATP-sensitive potassium channel but which differs from the usual sulphonylurea binding site.
Den ekstrapankreatiske virkning er f. eks. en øget insulinfølsomhed i de perifere væv og et fald i leverens insulinoptagelse.
Extrapancreatic effects include an improvement in insulin sensitivity of peripheral tissue and a reduction in hepatic uptake of insulin.
Glimepirid øger antallet af glukosetransportmolekyler i muskel - og fedtcellernes plasmamembran meget hurtigt, hvilket resulterer i en stimuleret glukoseoptagelse.
Glimepiride very rapidly increases the number of active glucose transport molecules in the plasma membranes of muscle and fat cells, resulting in stimulation of glucose uptake.
Glimepirid øger aktiviteten af glycosylphosphatidylinositolspecifikt phospholipase C, som kan være korreleret med den lægemiddelinducerede lipogenese og glycogenese i isolerede fedt - og muskelceller.
Glimepiride increases the activity of glycosyl-phosphatidylinositol-specific phospholipase C, which may be associated with drug-induced lipogenesis and glycogenesis in isolated fat and muscle cells.
Glimepirid hæmmer leverens glukosedannelse ved at øge den intracellulære koncentration af fruktose- 2, 6 - biphosphat, som hæmmer glukoneogenesen.
Glimepiride inhibits the hepatic glucose production by increasing the intracellular concentration of fructose-2,6 bisphosphate, which in turn inhibits gluconeogenesis.
Den mindste, effektive perorale dosis er hos raske forsøgspersoner ca.
The minimum effective oral dose is approximately 0.6 mg.
13 Selv om glimepirids hydroxymetabolit gav et lille men signifikant fald i serumglukose, er denne metabolit kun ansvarlig for en mindre del af den totale virkning.
13 5.2 Pharmacokinetic properties
5. 2 Farmakokinetiske egenskaber
AVAGLIM
AVAGLIM Enkelte perorale doser af glimepirid i 14 raske voksne personer havde ingen klinisk signifikant effekt på steady- state farmakokinetikken for rosiglitazon.
Single oral doses of glimepiride in 14 healthy adult subjects had no clinically significant effect on the steady-state pharmacokinetics of rosiglitazone.
I bioækvivalensundersøgelser fandtes under faste at AUC og Cmax for rosiglitazon og AUC for glimipirid efter enkeltdoser 4 mg/ 4 mg kombinationstablet var bioækvivalent med samtidig administration af rosiglitazon 4 mg og glimepirid 4 mg.
In a bioequivalence study under fasted conditions, the AUC and Cmax of rosiglitazone and the AUC of glimepiride following a single dose of a 4 mg/ 4 mg combination tablet were bioequivalent to concomitant administration of rosiglitazone 4 mg and glimepiride 4 mg.
Under fødeindtagelse var hyppighed og omfang af absorptionen af kombinationen af rosiglitazon - glimepirid 4 mg/ 4 mg ækvivalent med samtidig administration af 4 mg rosiglitazon og 4 mg glimepirid.
In the fed state, the rate and extent of absorption of the rosiglitazone-glimepiride 4 mg/ 4 mg combination were equivalent to concomitant administration of 4 mg rosiglitazone and 4 mg glimepiride.
Administration af 4 mg/ 4 mg kombinationen med samtidig fødeindtagelse førte til en stigning i eksponeringen med glimepirid sammenlignet med fastende administration.
Administration of the 4 mg/ 4 mg combination with food led to an increase in glimepiride exposure compared to that observed on administration in the fasted state.
Glimepirid AUC0– t, AUC0- inf og Cmax blev i gennemsnit forøget med henholdsvis 30%, 19% og 55%.
Glimepiride AUC0-t, AUC0-inf and Cmax were increased by 30%, 19% and 55% respectively, on average.
Cmax for rosiglitazon blev formindsket med 32% ved samtidig fødeindtagelse.
For rosiglitazone, Cmax values were decreased by approximately 32% with food.
AUC og Cmax for glimepirid forøgedes dosisproportionalt efter administration af rosiglitazon - glimepirid 4 mg/ 1mg, 4 mg/ 2 mg og 4 mg/ 4 mg.
The AUC and Cmax of glimepiride increased in a dose-proportional manner following administration of rosiglitazone-glimepiride 4 mg/ 1 mg, 4 mg/ 2 mg, and 4 mg/ 4 mg.
99%.
Rosiglitazone Absorption Absolute bioavailability of rosiglitazone following both a 4 and an 8 mg oral dose is approximately 99%.
1 time efter administration.
Rosiglitazone plasma concentrations peak at around 1 h after dosing.
1, 75 time) sammenlignet med administration i fastende tilstand.
Administration of rosiglitazone with food resulted in no change in overall exposure (AUC), although a small decrease in Cmax (approximately 20-28%) and a delay in tmax (approximately 1.75 h) were observed compared to dosing in the fasted state.
14 liter hos raske frivillige.
Distribution The volume of distribution of rosiglitazone is approximately 14 l in healthy volunteers.
99, 8%) og påvirkes ikke af koncentration eller alder.
Plasma protein binding of rosiglitazone is high (approximately 99.8%) and is not influenced by concentration or age.
Proteinbindingen af den hyppigst forekommende metabolit (para- hydroxy- sulfat) er meget høj (> 99. 99%).
The protein binding of the major metabolite (a para-hydroxy-sulphate) is very high (> 99.99%).
Metabolisme Rosiglitazons metabolisme er omfattende, og ingen oprindelig del udskilles uændret.
Metabolism Metabolism of rosiglitazone is extensive with no parent compound being excreted unchanged.
Metabolismen sker primært gennem N- demetylering og hydroxylering, efterfulgt af konjugation med sulfat og glukoronsyre.
The major routes of metabolism are N-demethylation and hydroxylation, followed by conjugation with sulphate and glucuronic acid.
Bidraget fra den hyppigst forekommende metabolit (para- hydroxy- sulfat) til den samlede antidiabetiske aktivitet af rosiglitazon er ikke fuldt ud belyst hos mennesker, og det kan ikke udelukkes, at metabolitten bidrager til aktiviteten.
The contribution of the major metabolite (a para-hydroxy-sulphate) to the overall antihyperglycaemic activity of rosiglitazone has not been fully elucidated in man and it cannot be ruled out that the metabolite may contribute to the activity.
In vitro- undersøgelser har vist, at rosiglitazon primært metaboliseres af CYP2C8 og i mindre omfang af CYP2C9.
In vitro studies demonstrate that rosiglitazone is predominantly metabolised by CYP2C8, with a minor contribution by CYP2C9.
14 Idet der ikke ses nogen væsentlig in vitro hæmning af CYP1A2, 2A6, 2C19, 2D6, 2E1, 3A eller 4A med rosiglitazon, er sandsynligheden for signifikant metabolismebaserede interaktioner med substanser, der metaboliseres af disse P450- enzymer lille.
14 Since there is no significant in vitro inhibition of CYP1A2, 2A6, 2C19, 2D6, 2E1, 3A or 4A with rosiglitazone, there is a low probability of significant metabolism-based interactions with substances metabolised by these P450 enzymes.
Rosiglitazon udviste moderat inhibition af CYP2C8 (IC50 8 μM) og lav inhibition af CYP2C9 (IC50 50 μM) in vitro (se afsnit 4. 5).
Rosiglitazone showed moderate inhibition of CYP2C8 (IC50 18 µM) and low inhibition of CYP2C9 (IC50 50 µM) in vitro (see section 4.5).
En in vivo interaktionsundersøgelse med warfarin indikerede, at rosiglitazon ikke interagerer med CYP2C9 - substrater in vivo.
An in vivo interaction study with warfarin indicated that rosiglitazone does not interact with CYP2C9 substrates in vivo.
3- 4 timer.
Elimination Total plasma clearance of rosiglitazone is around 3 l/ h and the terminal elimination half-life of rosiglitazone is approximately 3-4 h.
25% af doseringen.
The major route of excretion is the urine with approximately two-thirds of the dose being eliminated by this route, whereas faecal elimination accounts for approximately 25% of dose.
Akkumulering af metabolitterne i plasma kan forventes efter gentagen dosering, specielt hvad angår den hyppigste metabolit (para- hydroxy- sulfat), hvor en 8- dobling kan forventes.
Accumulation of the metabolites in plasma is expected upon repeated dosing, especially that of the major metabolite (a para-hydroxy-sulphate) for which an 8-fold accumulation is anticipated.
Glimepirid Absorption Efter peroral administration absorberes glimepirid fuldstændig (100%) fra mavetarmkanalen.
Glimepiride Absorption After oral administration, glimepiride is completely (100%) absorbed from the gastrointestinal tract.
2, 5 time efter administration.
Studies with single oral doses in normal subjects and with multiple oral doses in patients with type 2 diabetes mellitus have shown significant absorption of glimepiride within 1 h after administration and Cmax at approximately 2.5 h.
8, 8 liter (113 ml/ kg) og den totale clearance er 48 ml/ min.
Distribution After intravenous dosing in normal subjects, the volume of distribution was 8.8 l (113 ml/ kg), and the total body clearance was 47.8 ml/ min.
Proteinbindingen var højere end 99, 5%.
Protein binding was greater than 99.5%.
Metabolisme Glimepirid metaboliseres fuldstændig ved hjælp af oxidativ biotransformation både efter intravenøs indgivelse og efter peroral indtagelse.
Metabolism Glimepiride is completely metabolised by oxidative biotransformation after either an intravenous or oral dose.
1/ 3 af den farmakologiske aktivitet sammenlignet med det uomdannede stof.
M1, but not M2, possesses about 1/ 3 of the pharmacological activity as compared to its parent in an animal model.
5- 8 timer.
Elimination The elimination half-life of glimepiride is approximately 5 to 8 h.
60% af den totale radioaktivitet genvundet i urinen efter 7 dage, og M1 (fremherskende) og M2 udgjorde 80 til 90% af det, der blev genvundet i urinen.
When 14C-glimepiride was given orally, approximately 60% of the total radioactivity was recovered in the urine in seven days and M1 (predominant) and M2 accounted for 80 to 90% of that recovered in the urine.
40% af radioaktiviteten blev genvundet i fæces, og M1 og M2 (fremherskende) udgjorde 70% af det i fæces genvundne.
Approximately 40% of the total radioactivity was recovered in faeces and M1 and M2 (predominant) accounted for about 70% of that recovered in faeces.
Specielle populationer Køn:
Special populations Gender:
I den farmakokinetiske analyse med poolet population sås ingen klar forskel i rosiglitazons farmakokinetik hos kvinder og mænd.
In the pooled population pharmacokinetic analysis, there were no marked differences in the pharmacokinetics of rosiglitazone or glimepiride between males and females.
I den farmakokinetiske analyse med poolet population havde alder ingen signifikant indflydelse på farmakokinetikken.
In the pooled population pharmacokinetic analysis, age was not found to influence the pharmacokinetics of rosiglitazone or glimepiride to any significant extent.
Hos cirrhotiske patienter med moderat (Child- Pugh B) nedsat leverfunktion, var ubundet Cmax og AUC 2- 3 gange højere end hos normale personer.
Following rosiglitazone treatment in cirrhotic patients with moderate (Child- Pugh B) hepatic impairment, unbound Cmax and AUC were 2- and 3-fold higher than in normal subjects.
Den interpersonelle variation var stor med en 7- fold forskel i ubundet AUC mellem patienterne.
The inter-subject variability was large, with a 7-fold difference in unbound AUC between patients.
Derfor bør AVAGLIM ikke gives til patienter med nedsat leverfunktion (se afsnit 4. 3).
Therefore AVAGLIM should not be used in patients with hepatic impairment (see section 4.3)
15 Nyreinsufficiens:
15 Renal insufficiency:
Der ses ingen klinisk signifikante forskelle i rosiglitazons farmakokinetik hos patienter med nyresvigt eller terminal nyresygdom i kronisk dialyse.
There are no clinically significant differences in the pharmacokinetics of rosiglitazone in patients with renal impairment or end stage renal disease on chronic dialysis.
Der er ingen data fra behandling med glimepirid hos patienter i dialyse (se afsnit 4. 3).
There are no data from the use of glimepiride in patients on renal dialysis (see section 4.3).