natgillin/translations-raw huggingface dataset:
- nyresvigt eller nedsat nyrefunktion f. eks. serumkreatinin niveau > 135 μmol/ l hos mænd og
- renal failure or renal dysfunction e. g. serum creatinine levels > 135 µmol/ l in males and
> 110 μmol/ l hos kvinder og/ eller kreatininclerance < 70 ml/ min (se afsnit 4. 3 og 4. 4)
> 110 µmol/ l in females and/ or creatinine clearance < 70 ml/ min (see section 4.4)
- akutte tilstande, der muligvis kan forværre nyrefunktionen, såsom:
- acute conditions with the potential to alter renal function such as:
- shock
- - - - -
- intravaskulær administration af jodholdige kontrastmidler (se afsnit 4. 4)
dehydration severe infection shock intravascular administration of iodinated contrast agents (see section 4.4) lactation.
Lactacidose Lactacidose er en meget sjælden, men alvorlig, metabolisk komplikation, der kan forekomme på grund af metforminophobning.
Lactic acidosis Lactic acidosis is a very rare, but serious, metabolic complication that can occur due to metformin accumulation.
Rapporterede tilfælde af lactacidose hos patienter behandlet med metformin
Reported cases of lactic acidosis in patients on metformin have occurred primarily in diabetic patients with significant renal failure.
3 er primært forekommet hos diabetes patienter med betydeligt nedsat nyrefunktion.
3 prolonged fasting, excessive alcohol intake, hepatic insufficiency and any conditions associated with hypoxia.
Diagnostiske laboratoriefund er nedsat pH i blodet, plasmalaktatniveau over 5 mmol/ l og et øget aniongap og laktat/ pyruvat forhold.
Diagnostic laboratory findings are decreased blood pH, plasma lactate levels above 5 mmol/ l and an increased anion gap and lactate/ pyruvate ratio.
Hvis der er mistanke om metabolisk acidose, bør behandlingen afbrydes, og patienten bør omgående indlægges (se afsnit 4. 9).
If metabolic acidosis is suspected, treatment with the medicinal product should be discontinued and the patient hospitalised immediately (see section 4.9).
Nyrefunktion Da metformin udskilles via nyrerne bør serum- kreatininkoncentrationen bestemmes regelmæssigt:
Renal function As metformin is excreted by the kidney, serum creatinine concentrations should be determined regularly:
- mindst en gang årligt hos patienter med normal nyrefunktion
- at least once a year in patients with normal renal function
- mindst to til fire gange årligt hos patienter med serum- kreatininkoncentrationer ved den øvre
- at least two to four times a year in patients with serum creatinine levels at the upper limit of
normalgrænse og hos ældre patienter.
normal and in elderly patients.
Væskeretention og hjertesvigt Thiazolidinedioner kan forårsage væskeretention, som kan forværre eller fremskynde tegn og symptomer på kongestiv hjertesvigt.
Fluid retention and cardiac failure Thiazolidinediones can cause fluid retention which may exacerbate or precipitate signs or symptoms of congestive heart failure.
Alle patienter, specielt patienter, som får Avandamet i kombination med insulin, patienter som får Avandamet i kombination med et sulfonylurinstof, patienter med risiko for hjertesvigt og patienter med reducerede kardiale reserver, bør overvåges for tegn og symptomer på bivirkninger, der er relateret til væskeretention, herunder vægtøgning og hjertesvigt.
All patients, particularly those receiving concurrent insulin but also sulphonylurea therapy, those at risk for heart failure, and those with reduced cardiac reserve, should be monitored for signs and symptoms of adverse reactions relating to fluid retention, including weight gain and heart failure.
Brugen af AVANDAMET i kombination med et sulfonylurinstof eller insulin kan være forbundet med øget risiko for væskeretention og hjertesvigt (se afsnit 4. 8).
The use of AVANDAMET in combination with a sulphonylurea or insulin may be associated with increased risks of fluid retention and heart failure (see section 4.8).
Yderligere blev der oftere rapporteret om hjertesvigt hos patienter med tidligere hjerteinsufficiens; ødem og hjerteinsufficiens blev også hyppigere rapporteret hos ældre patienter og hos patienter med mild eller moderat renal insufficiens.
Heart failure was also reported more frequently in patients with a history of heart failure; oedema and heart failure was also reported more frequently in elderly patients and in patients with mild or moderate renal failure.
4 Akut koronarsyndrom (AKS) Der har ikke været inkluderet patienter med AKS i kontrollerede kliniske forsøg med rosiglitazon.
4 Acute Coronary Syndrome (ACS) Patients experiencing an ACS have not been studied in rosiglitazone controlled clinical trials.
Monitorering af leverfunktionen Der har været sjældne rapporter med hepatocellulær dysfunktion, set under erfaringerne efter markedsføringen (se afsnit 4. 8).
Monitoring of liver function There have been rare reports of hepatocellular dysfunction during post-marketing experience with rosiglitazone (see section 4.8).
Derfor bør leverenzymer kontrolleres forud for indledning af terapi med AVANDAMET hos alle patienter.
There is limited experience with rosiglitazone in patients with elevated liver enzymes (ALT > 2.5 times the upper limit of normal).
Herefter kontrolleres leverenzymerne, af og til, baseret på klinisk vurdering.
Therefore, liver enzymes should be checked prior to the initiation of therapy with AVANDAMET in all patients and periodically thereafter based on clinical judgement.
Behandling med AVANDAMET bør ikke indledes hos patienter med forhøjet baselineniveau af leverenzymer (ALAT > 2, 5 gange den øvre grænse for normal) eller enhver anden evidens på leversygdom.
Therapy with AVANDAMET should not be initiated in patients with increased baseline liver enzyme levels (ALT > 2.5 times the upper limit of normal) or with any other evidence of liver disease.
Hvis ALAT- niveauet stiger til > 3 gange den øvre grænse for normal under AVANDAMET- behandlingen, bør leverenzymerne kontrolleres igen så hurtigt som muligt.
If ALT levels are increased to > 3 times the upper limit of normal during AVANDAMET therapy, liver enzyme levels should be reassessed as soon as possible.
Hvis ALAT- niveauet forbliver > 3 gange den øvre grænse for normal, bør behandlingen afbrydes.
If ALT levels remain > 3 times the upper limit of normal, therapy should be discontinued.
Det er usikkert, om der er en direkte sammenhæng mellem behandling med rosiglitazon og maculaødem, men den behandlende læge bør være advaret om muligheden for maculaødem, hvis patienterne klager over synsforstyrrelser og henvisning til øjenlæge bør overvejes.
It is unclear whether or not there is a direct association between rosiglitazone and macular oedema but prescribers should be alert to the possibility of macular oedema if patients report disturbances in visual acuity and appropriate ophthalmologic referral should be considered.
Anæmi Behandling med rosiglitazon er forbundet med en dosisrelateret reduktion i hæmoglobinniveauet.
Anaemia Rosiglitazone treatment is associated with a dose-related reduction of haemoglobin levels.
Hypoglykæmi Patienter, som får AVANDAMET i kombination med et sulfonylurinstof eller insulin, har risiko for dosisrelateret hypoglykæmi.
Hypoglycaemia Patients receiving AVANDAMET in combination with a sulphonylurea or insulin may be at risk for dose-related hypoglycaemia.
Operation Da AVANDAMET indeholder metforminhydrochlorid bør behandlingen afbrydes 48 timer før elektive operationer i universel anæstesi, og bør sædvanligvis ikke genoptages tidligere end 48 timer efter.
Surgery As AVANDAMET contains metformin hydrochloride, the treatment should be discontinued 48 hours before elective surgery with general anaesthesia and should not usually be resumed earlier than 48 hours afterwards.
Indgivelse af jodholdigt kontrastmiddel Intravaskulær administration af jodholdige kontrastmidler ved radiologiske undersøgelser kan føre til nyreinsufficiens.
Administration of iodinated contrast agent The intravascular administration of iodinated contrast agents in radiological studies can lead to renal failure.
Nyrefunktionen skal kontrolleres inden behandlingen genoptages (se afsnit 4. 5).
Therefore, due to the metformin active substance, AVANDAMET should be discontinued prior to, or at the time of the test and not reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal (see section 4.5).
5 Knoglelidelser I et langtidsstudie blev der observeret en øget forekomst af frakturer (fødder, hænder og arme) hos kvindelige patienter, der blev behandlet med rosiglitazon som monoterapi (se afsnit 4. 8).
5 Bone disorders In a long-term study an increased incidence of bone fractures (foot, hand and arm) was observed in female patients taking rosiglitazone as monotherapy (see section 4.8).
Den øgede forekomst blev observeret efter et års behandling og gennem resten af studiet.
This increased incidence was noted after the first year of treatment and remained during the course of the study.
Andre forsigtighedsregler Præmenopausale kvinder har modtaget rosiglitazon i kliniske undersøgelser.
Other precautions Premenopausal women have received rosiglitazone during clinical studies.
Til trods for, at en hormonel ubalance er set i de prækliniske undersøgelser (se afsnit 5. 3), er der ikke set signifikante bivirkninger i forbindelse med menstruelle forstyrrelser.
Although hormonal imbalance has been seen in preclinical studies (see section 5.3), no significant undesirable effects associated with menstrual disorders have been observed.
AVANDAMET bør anvendes med forsigtighed under samtidig administration af CYP2C8- inhibitorer (f. eks. gemfibrozil) eller inducerende stoffer (f. eks. rifampicin), pga. effekten på rosiglitazons farmakokinetik (se afsnit 4. 5).
AVANDAMET should be used with caution during concomitant administration of CYP2C8 inhibitors (e. g. gemfibrozil) or inducers (e. g. rifampicin), due to the effect on rosiglitazone pharmacokinetics (see section 4.5).
Endvidere bør der udvises forsigtighed ved samtidig brug af AVANDAMET og kationiske lægemidler, der elimineres via renal tubulær sekretion (f. eks. cimetidin), pga. effekten på metformins farmakokinetik (se afsnit 4. 5).
Furthermore, AVANDAMET should be used with caution during concomitant administration of cationic medicinal products that are eliminated by renal tubular secretion (e. g. cimetidine) due to the effect on metformin pharmacokinetics (see section 4.5).
Justering af AVANDAMET- dosis inden for den anbefalede dosering eller ændringer i diabetisk behandling bør overvejes (se afsnit 4. 5).
AVANDAMET dose adjustment within the recommended posology or changes in diabetic treatment should be considered.
AVANDAMET- tabletter indeholder lactose og bør derfor ikke gives til patienter med sjælden arvelig galactose intolerans, Lapps laktatmangel eller glucose- galactose malabsorption.
AVANDAMET tablets contain lactose and therefore should not be administered to patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
Der er øget risiko for lactacidose ved akut alkoholforgiftning (særligt i tilfælde af faste, fejlernæring eller leverinsufficiens) på grund af indholdet af metformin i AVANDAMET (se afsnit 4. 4) Undgå indtagelse af alkohol og lægemidler indeholdende alkohol.
Avoid consumption of alcohol and medicinal products containing alcohol.
Kationiske lægemidler, der elimineres via renal tubulær sekretion (f. eks. cimetidin), kan interagere med metformin ved at konkurrere om almindelige renale tubulære transportsystemer.
Cationic medicinal products that are eliminated by renal tubular secretion (e. g. cimetidine) may interact with metformin by competing for common renal tubular transport systems.
En klinisk undersøgelse af 7 normale, raske personer viste, at cimetidin, administreret som 400 mg to gange daglig, forøger den systemiske eksponering af metformin (AUC) med 50% og Cmax med 81%.
A study conducted in seven normal healthy volunteers showed that cimetidine, administered as 400 mg twice daily, increased metformin systemic exposure (AUC) by 50% and Cmax by 81%.
In vitro- undersøgelser har vist, at rosiglitazon primært metaboliseres af CYP2C8, med CYP2C9 som en mindre metaboliseringsvej.
In vitro studies demonstrate that rosiglitazone is predominantly metabolised by CYP2C8, with CYP2C9 as only a minor pathway.
6 Samtidig administration af rosiglitazon og rifampicin (en inducer af CYP2C8) resulterede i et fald på 66% i rosiglitazon plasmakoncentrationer.
6 Co-administration of rosiglitazone with rifampicin (an inducer of CYP2C8) resulted in a 66% decrease in rosiglitazone plasma concentrations.
Klinisk signifikante interaktioner med CYP2C9- substrater eller inhibitorer forventes ikke.
Clinically significant interactions with CYP2C9 substrates or inhibitors are not anticipated.
Nyrefunktionen skal kontrolleres inden behandlingen genoptages.
Metformin should be discontinued prior to, or at the time of the test and not reinstituted until 48 hours afterwards and only after renal function has been re-evaluated and found to be normal.
Kombinationer, som kræver særlige forsigtighedsregler Glukokortikoider (indgivet systemisk og lokalt), beta- 2- agonister og diuretika har intern hyperglykæmisk aktivitet.
Combination requiring precautions for use Glucocorticoids (given by systemic and local routes) beta-2-agonists, and diuretics have intrinsic hyperglycaemic activity.
ACE- hæmmere kan mindske blodsukkerniveauet.
ACE-inhibitors may decrease the blood glucose levels.
Dyreforsøg har påvist reproduktionstoksicitet (se afsnit 5. 3).
Studies in animals have shown reproductive toxicity (see section 5.3).
AVANDAMET må derfor ikke anvendes af ammende kvinder (se afsnit 4. 3).
AVANDAMET must therefore not be used in women who are breast-feeding (see section 4.3).
7 Bivirkningerne fra hvert behandlingsregime er listet nedenfor efter organklasse og absolut frekvens.
7 Adverse reactions for each treatment regimen are presented below by system organ class and absolute frequency.
Meget almindelig (≥ 1/ 10), almindelig (≥ 1/ 100 til < 1/ 10), ikke almindelig (≥ 1/ 1. 000 til < 1/ 100), sjælden (≥ 1/ 10. 000 til < 1/ 1. 000) og meget sjælden (< 1/ 10. 000) herunder isolerede rapporter.
Frequencies are defined as: very common (≥ 1/ 10), common (≥ 1/ 100 to < 1/ 10), uncommon (≥ 1/ 1,000 to < 1/ 100), rare (≥ 1/ 10,000 to < 1/ 1000) and very rare (< 1/ 10,000 including isolated reports).
Data fra kliniske undersøgelser Bivirkninger fra hvert behandlingsregime er listet under organklasse og absolutte frekvens.
Clinical trial data Adverse reactions for each treatment regimen are presented below by system organ class and absolute frequency.
Frekvens af bivirkning under behandlingsregime Rosiglitazon Rosiglitazon med Rosiglitazon med monoterapi metformin metformin og sulfonylurinstof
Frequency of adverse reaction by treatment regimen Rosiglitazone Rosiglitazone with Rosiglitazone with monotherapy metformin metformin and sulphonylurea
Blod - og lymfesystem
Blood and the lymphatic system disorders anaemia granulocytopaenia
Anæmi Granulocytopeni
Common Common
Almindelig Almindelig Almindelig Almindelig
Common Common
Metabolisme og ernæring Hypercholesterolæmi 1 Hypertriglyceridæmi
Metabolism and nutrition disorders hypercholesterolaemia1 hypertriglyceridaemia
Hyperlipidæmi Vægtøgning Øget appetit
hyperlipaemia weight increase increased appetite
Hypoglykæmi
hypoglycaemia
Nervesystemet
Nervous system disorders dizziness* headache*
Hjerte Hjertesvigt2
Cardiac disorders
Almindelig Almindelig
Common
Mave- tarmkanalen
Common
Obstipation
Gastrointestinal disorders constipation
Knogler, led, muskler og bindevæv Frakturer4 Myalgi *
Musculoskeletal and connective tissue disorders bone fractures4 myalgia*
* Frekvenskategorien for baggrundshyppigheden af disse bivirkninger, som er taget fra placebo - grupper fra kliniske undersøgelser, er ” Almindelig ”.
*The frequency category for the background incidence of these events, as taken from placebo group data from clinical trials, is'common '.
1 Hypercholesterolæmi var rapporteret hos op til 5, 3% af de patienter, der blev behandlet med rosiglitazon (oral monoterapi, dobbel - eller tripelterapi).
1 Hypercholesterolaemia was reported in up to 5.3% of patients treated with rosiglitazone (monotherapy, dual or triple oral therapy).
Det forhøjede totale cholesterolniveau blev forbundet med en forøgelse i både LDLc og HDLc, men forholdet af total cholesterol:
The elevated total cholesterol levels were associated with an increase in both LDLc and HDLc, but the ratio of total cholesterol:
HDLc var uændret eller forbedret i langtidsundersøgelser.
HDLc was unchanged or improved in long term studies.
2 Der er set en stigning i antallet af hjertesvigt, når rosiglitazon gives i kombination med sulfonylurinstof (enten i kombinations - eller i tripel- kombinationsbehandling), og forekomsten er højere med 8 mg rosiglitazon sammenlignet med 4 mg rosiglitazon (som total daglig dosis).
2 An increased incidence of heart failure has been observed when rosiglitazone was added to treatment regimens with a sulphonylurea (either as dual or triple therapy), and appeared higher with 8 mg rosiglitazone compared to 4 mg rosiglitazone (total daily dose).
Forekomsten af hjertesvigt i det dobbeltblinde hovedstudie var 1, 4% ved tripel - kombinationsbehandling, sammenlignet med 0, 4% for kombinationsbehandling med metformin og sulfonylurinstof.
The incidence of heart failure on triple oral therapy was 1.4% in the main double blind study, compared to 0.4% for metformin plus sulphonylurea dual therapy.
Forekomsten af hjertesvigt var 2, 4% ved kombinationsbehandling med insulin (rosiglitazon givet for at understøtte insulinbehandling), sammenlignet med 1, 1% ved behandling med insulin alene.
The incidence of heart failure in combination with insulin (rosiglitazone added to established insulin therapy) was 2.4%, compared to insulin alone, 1.1%.
9 En placebokontrolleret, etårig undersøgelse af patienter, der lider af hjertesvigt NYHA- klasse I- II, har vist en forværring eller mulig forværring af hjertesvigt hos 6, 4% af patienterne i behandling med rosiglitazon, sammenlignet med 3, 5% for placebo.
In a placebo-controlled one-year trial in patients with congestive heart failure NYHA class I-II, worsening or possible worsening of heart failure occurred in 6.4% of patients treated with rosiglitazone, compared with 3.5% on placebo.
1, 99% for rosiglitazon over for 1, 51% for komparatorerne [Hazard ratio 1, 31 (95% konfidensinterval 1, 01 – 1, 70)].
9 3 In a retrospective analysis of data from 42 pooled short-term clinical studies, the overall incidence of events typically associated with cardiac ischaemia was higher for rosiglitazone containing regimens, 1.99% versus combined active and placebo comparators, 1.51% [Hazard ratio 1.31 (95% confidence interval 1.01 - 1.70)].
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 for 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 bivirkningerne relateret til lever - og galdevejene 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- marketingdata I forlængelse af bivirkningsdata, der blev fundet i kliniske undersøgelser, er de data, der blev fundet efter markedsføring af rosiglitazon listet 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.
10 Tabel 2.
Table 2.
Immunsystemet (se Hud og subkutane væv) Anafylaktisk reaktion
Immune system disorders (see Skin and subcutaneous tissue disorders)
Hud og subkutane væv (se Immunsystemet) Angiødem Hudreaktioner (for eksempel nældefeber, kløe, udslæt) 5
Skin and subcutaneous tissue disorders (see Immune system disorders)
Data fra kliniske undersøgelser og post- marketingdata
Clinical Trial Data and Post-marketing data
11 Tabel 3.
Table 3.
Metabolisme og ernæring Lactacidose Vitamin B12 mangel7
Metabolism and nutrition disorders lactic acidosis vitamin B12 deficiency7
Lever og galdeveje Nedsat leverfunktion Hepatitis
Hepatobiliary disorders liver function disorders Hepatitis
Nældefeber Erytem Hudkløe 6
urticaria erythema pruritis 6
Meget sjælden Meget sjælden Meget sjælden
Very rare Very rare Very rare
De forekommer hyppigst i starten af behandlingen og forsvinder oftest spontant.
Gastrointestinal symptoms such as nausea, vomiting, diarrhoea, abdominal pain and loss of appetite occur most frequently during initiation of therapy and resolve spontaneously in most cases.
Megaloblastisk anæmi).
7 Long-term treatment with metformin has been associated with a decrease in vitamin B12 absorption which may very rarely result in clinically significant vitamin B12 deficiency (e. g. megaloblastic anaemia).
Rosiglitazon er i høj grad proteinbundet og fjernes ikke ved hæmodialyse.
The most effective method to remove lactate and metformin is haemodialysis, however rosiglitazone is highly protein bound and is not cleared by haemodialysis.
Antidiabetika, kombinationspræparater, ATC- kode:
Combinations of oral blood glucose lowering medicinal products, ATC code:
Thiazolidinedionerne
AVANDAMET combines two antihyperglycaemic 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 metformin hydrochloride, a member of the biguanide class.
12 virker primært ved at reducere insulinresistens og biguaniderne virker primært ved at mindske den endogene hepatiske glucoseproduktion.
Thiazolidinediones act primarily by reducing insulin resistance and biguanides act primarily by decreasing endogenous hepatic glucose production.
Rosiglitazon Rosiglitazon er en selektiv agonist ved de specifikke kernereceptorer PPARγ (peroxisomal proliferator- aktiveret receptor gamma) og tilhører 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 af type 2- diabetes.
The antihyperglycaemic activity of rosiglitazone has been demonstrated in a number of animal models of type 2 diabetes.
I tillæg bevarede rosiglitazon β- cellefunktionen, demonstreret ved en stigning i antallet af langerhanske øer og insulinindholdet og forhindrede 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.
Hovedmetabolitten (pare- hydroxy- sulfat) med høj affinitet til det opløselige humane PPARγ udviste relativ høj potens i et 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.
Den forbedrede glykæmiske kontrol er forbundet med en reduktion i både det fastende og det post- prandiale glucose.
The improved glycaemic control is associated with reductions in both fasting and post- prandial glucose.
I overensstemmelse med virkningsmekanisme reducerer rosiglitazon i kombination med metformin insulinresistens og forbedret pankreatisk β- celle.
Consistent with the mechanism of action, rosiglitazone in combination with metformin reduced insulin resistance and improved pancreatic ß-cell function.