natgillin/translations-raw huggingface dataset:
Patienten bør informeres, og der bør udføres hyppigere monitorering af blodsukkeret, specielt i begyndelsen af behandlingen.
The patient should be informed and more frequent blood glucose monitoring performed, especially at the beginning of treatment.
Hvis påkrævet bør dosis af det antidiabetiske lægemiddel justeres under behandling med andre lægemidler og ved denne behandlings ophør.
If necessary, the dosage of the antihyperglycaemic medicinal product should be adjusted during therapy with the other medicinal product and on its discontinuation.
Risici i relation til pioglitazon Der foreligger ikke tilstrækkelige humane data om brugen af pioglitazon hos gravide kvinder.
6 Risk related to pioglitazone:
Dyreforsøg har ikke påvist teratogen effekt.
There are no adequate human data from the use of pioglitazone in pregnant women.
5. 3).
Risk related to metformin:
Risici i relation til metformin Dyreforsøg har ikke afsløret teratogen effekt.
Animal studies have not revealed teratogenic effects.
Competact må dog ikke anvendes under graviditet eller hos kvinder i den fødedygtige alder, som ikke anvender svangerskabsforebyggende foranstaltninger.
However, Competact should not be used during pregnancy and in women of child-bearing age not using contraceptive measures.
Hvis en patient ønsker at blive gravid eller bliver gravid, skal behandlingen med Competact afbrydes.
If a patient wishes to become pregnant or if a pregnancy occurs, treatment with Competact should be discontinued.
4. 3).
Competact must therefore not be used in women who are breast-feeding (see section 4.3).
6 4. 7 Virkninger på evnen til at føre motorkøretøj eller betjene maskiner
4.7 Effects on ability to drive and use machines
5. 2).
There have been no therapeutic clinical trials conducted with Competact tablets however bioequivalence of Competact with co-administered pioglitazone and metformin has been demonstrated (see section 5.2).
Hyppigheden er defineret som:
Adverse reactions reported in excess (> 0.5%) of placebo and as more than an isolated case in patients receiving pioglitazone in combination with metformin in double-blind studies are listed below as MedDRA preferred term by system organ class and absolute frequency.
Almindelig (> 1/ 100, < 1/ 10); usædvanlig (> 1/ 1000, < 1/ 100); sjælden (> 1/ 10000, < 1/ 1000); meget sjælden (< 1/ 10000); isolerede rapporter; ikke kendt (kan ikke estimeres ud fra de tilgængelige data).
Frequencies are defined as: common (> 1/ 100 ,< 1/10); uncommon (> 1/1000 ,< 1/100); rare (> 1/ 10000 ,< 1/1000); very rare (< 1/10000); isolated reports; not known (cannot be estimated from the available data).
Inden for hver gruppe af bivirkninger med samme frekvens skal bivirkningerne opstilles efter, hvor alvorlige bivirkningerne er.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
De mest alvorlige skal anføres først.
PIOGLITAZONE IN COMBINATION THERAPY WITH METFORMIN
PIOGLITAZON I KOMBINATIONSBEHANDLING MED METFORMIN
Blood and lymphatic system disorders
Sygdomme i blod - og lymfesystem Almindelig:
Common:
Gastrointestinale sygdomme Usædvanlig:
Uncommon:
Undersøgelser
Metabolism and nutrition disorders
Sygdomme i bevægeapparatet og bindevæv Almindelig:
Common:
Sygdomme i nervesystemet Almindelig:
Common:
Sygdomme i nyre og urinveje Almindelig:
Common:
Lidelser i det reproduktive system og brystsygdomme Almindelig:
Reproductive system
erektil dysfunktion
and breast disorders
Tilføjelse af sulfonylurinstof til metforminbehandlingen resulterede heroverfor i ødemer hos 2, 2% af patienterne.
In active comparator controlled trials oedema was reported in 6.3% of patients treated with metformin and pioglitazone, whereas the addition of sulphonylurea to metformin treatment resulted in oedema in 2.2% of patients.
I kontrollerede kliniske forsøg med aktive stoffer som sammenligning var den gennemsnitlige vægtøgning 2- 3 kg i løbet af et år.
In active comparator controlled trials mean weight increase with pioglitazone given as monotherapy was 2 – 3 kg over one year.
I undersøgelser med kombinationsbehandling medførte pioglitazon, når det blev givet som tillæg til metformin, en gennemsnitlig vægtøgning på 1, 5 kg i løbet af et år.
In combination trials pioglitazone added to metformin resulted in mean weight increase over one year of 1.5 kg.
Disse er relateret til ændringer i blodglukose, som forårsager forbigående ændringer i linsens turgiditet og refraktionsindeks, som det også ses ved andre hypoglykæmiske stoffer.
Visual disturbance has been reported mainly early in treatment and is related to changes in blood glucose due to temporary alteration in the turgidity and refractive index of the lens as seen with other hypoglycaemic agents.
Sjældne tilfælde af forhøjede leverenzymer og hepatocellulær dysfunktion er optrådt efter markedsføring.
Rare cases of elevated liver enzymes and hepatocellular dysfunction have occurred in post-marketing experience.
Selvom der i meget sjældne tilfælde har været rapporteret tilfælde med fatal udgang, er der ikke blevet fastslået kausal sammenhæng.
Although in very rare cases fatal outcome has been reported, causal relationship has not been established.
I kontrollerede kliniske forsøg er hyppigheden af rapporteret hjerteinsufficiens ved pioglitazonbehandling den samme som for placebo -, metformin - og sulfonylurinstof- grupperne, men var forøget ved kombinationsbehandling med insulin.
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, but was increased when used in combination therapy with insulin.
I et outcome- forsøg med patienter med betydende makrovaskulær sygdom var hyppigheden af alvorlig hjerteinsufficiens ved kombinationsbehandling med insulin 1, 6% højere med pioglitazon end med placebo.
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.
Yderligere oplysninger om de individuelle aktive stoffer i den faste dosiskombination
Additional information on the individual active substances of the fixed dose combination
Sinusitis og søvnløshed sås sjældent.
In double blind placebo controlled clinical trials with pioglitazone upper respiratory tract infection and hypoaesthesia were common; sinusitis and insomnia were uncommon.
DATA EFTER MARKEDSFØRING
POST-MARKETING DATA
Øjensygdomme Makulært ødem:
Eye disorders
ikke kendt
Macular oedema: not known
Stofskiftesygdomme og ernæringsbetingede sygdomme Meget sjælden:
Metabolism and nutrition disorders:
Nedsat B12- vitaminabsorption med nedsatte serumniveauer ved langtidsbehandling med metformin.
Decrease of vitamin B12 absorption with decrease of serum levels during long-term use of metformin.
Det anbefales at tage en sådan ætiologi i betragtning, hvis en patient lider af megaloplastisk anæmi.
Consideration of such aetiology is recommended if a patient presents with megaloplastic anaemia.
Lactacidose (se pkt.
Lactic acidosis (see 4.4 Special warnings and precautions for use).
4. 4 Særlige advarsler og forsigtighedsregler vedrørende brugen).
Nervous system disorders:
Gastrointestinale sygdomme Meget almindelig:
Gastrointestinal disorders:
Gastrointestinale sygdomme såsom kvalme, opkastning, diaré, mavesmerter og appetittab.
Gastrointestinal disorders such as nausea, vomiting, diarrhoea, abdominal pain and loss of appetite.
Disse bivirkninger opstår hyppigst ved behandlingens påbegyndelse, og de går i de fleste tilfælde i sig selv igen.
These undesirable effects occur most frequently during initiation of therapy and resolve spontaneously in most cases.
Sygdomme i lever og galdeveje Isolerede rapporter:
Hepatobiliary disorders:
Anormale leverfunktionstests eller hepatitis, der forsvinder ved seponering af metformin.
Liver function tests abnormalities or hepatitis resolving upon metformin discontinuation.
Sygdomme i hud og subkutane væv Meget sjælden:
Skin and subcutaneous tissue disorders:
Hudreaktioner såsom erytem, pruritis, urticaria.
Skin reactions such as erythema, pruritis, urticaria.
8 Der blev udført en poolet analyse af bivirkningsrapporter om knoglefrakturer fra randomiserede, komparatorkontrollerede, dobbeltblindede kliniske forsøg med over 8100 patienter i den pioglitazonbehandlede gruppe og 7400 patienter i den komparatorbehandlede gruppe, der blev behandlet i op til 3, 5 år.
A pooled analysis was conducted of adverse event reports of bone fractures from randomised, comparator controlled, double blind clinical trials in over 8100 patients in the pioglitazone-treated groups and 7400 in the comparator-treated groups of up to 3.5 years duration.
Der er ingen data vedrørende af overdosering med Competact.
No data are available with regard to overdose of Competact.
Den højeste rapporterede dosis på 120 mg/ dag i fire dage og derefter 180 mg/ dag i syv dage var ikke associeret med nogen symptomer.
The maximum reported dose of 120 mg/ day for four days, then 180 mg/ day for seven days was not associated with any symptoms.
En stor overdosis metformin (eller samtidig eksisterende risikofaktorer for udvikling af lactacidose) kan føre til lactacidose, som er en kritisk tilstand og skal behandles på hospitalet.
A large overdose of metformin (or coexisting risks of lactic acidosis) may lead to lactic acidosis which is a medical emergency and must be treated in hospital.
Endnu ikke tildelt.
A10BD05.
Competact kombinerer to antidiabetiske stoffer med komplementære virkningsmekanismer til forbedring af den glykæmiske kontrol hos patienter med type 2 diabetes: pioglitazon, der hører til thiazolidinedionerne og metforminhydrochlorid, der hører til biguaniderne.
Competact 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 metformin hydrochloride, a member of the biguanide class.
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..
Reguleringen af fastende og postprandialt blodsukker forbedres hos patienter med type 2 diabetes mellitus.
Fasting and postprandial glycaemic control is improved in patients with type 2 diabetes mellitus.
Et klinisk forsøg, hvor pioglitazon blev sammenlignet med gliclazid begge som monoterapi, blev forlænget til en varighed af to år for at undersøge, hvornår 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).
Kaplan- Meier chanalyse viste kortere tid til behandlingssvigt hos patienter behandlet med gliclazid sammenlignet med pioglitazon.
Kaplan-Meier analysis showed shorter time to treatment failure in patients treated with gliclazide, compared with pioglitazone.
Her viste glykæmiske
In a two-year study of combination therapy comparing pioglitazone with gliclazide when added to metformin, glycaemic control measured as mean change from baseline in HbA1c was similar between treatment groups after one year.
Samtidig sås en reduktion af insulindosis hos de pioglitazon- behandlede.
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.
En HOMA- analyse viste, at pioglitazon forbedrer beta- cellefunktionen samt øger insulinfølsomheden.
HOMA analysis shows that pioglitazone improves beta cell function as well as increasing insulin sensitivity.
I kliniske forsøg, der løb over et år, gav Pioglitazon konsekvent en statistisk signifikant reduktion i albumin/ kreatinin- forholdet sammenlignet med baseline.
In one year clinical trials, pioglitazone consistently gave a statistically significant reduction in the albumin/ creatinine ratio compared to baseline.
Effekten af pioglitazon (45 mg monoterapi versus placebo) er blevet undersøgt i et mindre, 18- ugers klinisk forsøg hos type 2 diabetikere.
The effect of pioglitazone (45 mg monotherapy vs. placebo) was studied in a small 18-week trial in type 2 diabetics.
Der var små, 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.
I kliniske forsøg af en varighed på op til to år reducerede pioglitazon total plasma triglycerider og frie fedtsyrer og forøgede HDL- kolesterolniveauer sammenlignet med placebo, metformin eller gliclazid.
In clinical trials of up to two years duration, pioglitazone reduced total plasma triglycerides and free fatty acids, and increased HDL-cholesterol levels, compared with placebo, metformin or gliclazide.
Pioglitazon forøgede ikke LDL- kolesterolniveauer statistisk signifikant sammenlignet med placebo, mens der blev set reduktioner med metformin og gliclazid.
Pioglitazone did not cause statistically significant increases in LDL- cholesterol levels compared with placebo, whilst reductions where observed with metformin and gliclazide.
I et 20- ugers forsøg reducerede pioglitazon såvel faste triglycerider som postprandial hypertriglyceridæmi gennem en effekt på både absorberede og leversyntetiserede triglycerider.
In a 20-week study, as well as reducing fasting triglycerides, pioglitazone reduced postprandial hypertriglyceridaemia through an effect on both absorbed and hepatically synthesised
Disse effekter var uafhængige af pioglitazons virkning på glykæmi og var statistisk signifikant forskellige fra glibenclamid.
These effects were independent of pioglitazone’ s effects on glycaemia and were statistically significantly different to glibenclamide.
I PROactive, et kardiovaskulært outcome- forsøg, blev 5238 patienter med type 2- diabetes mellitus og betydende makrovaskulær sygdom randomiseret til pioglitazon eller placebo i tillæg til eksisterende antidiabetika og kardiovaskulær behandling i 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.
Forsøgspopulationen havde en gennemsnitsalder på 62 år, og den gennemsnitlige varighed af diabetes var 9, 5 år.
The study population had an average age of 62 years; the average duration of diabetes was 9.5 years.
For at kunne deltage i forsøget skulle patienterne have haft en eller flere af følgende: hjerteinfarkt, slagtilfælde, perkutan kardiel intervention eller koronar arteriel bypass graft, akut koronarsyndrom, koronar arteriel sygdom eller perifer arteriel obstruktiv sygdom.
To be eligibile 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 et hjerteinfarkt, og omkring 20% havde haft et slagtilfælde.
Almost half of the patients had a previous myocardial infarction and approximately 20% had had a stroke.
Næsten alle patienterne (95%) var i behandling med kardiovaskulær medicin (beta- blokkere, ACE- hæmmere, angiotensin II- antagonister, kalciumkanal- blokkere, nitrater, diuretika, acetylsalisylsyre, statiner og fibrater).
Almost all subjects (95%) were receiving cardiovascular medications (beta blockers, ACE inhibitors, angiotensin II antagonists, calcium channel blockers, nitrates, diuretics, aspirin, statins, fibrates).
Selvom forsøget ikke kunne påvise dets primære endepunkt, der var en sammensætning af generel dødelighed, ikke- fatalt hjerteinfarkt, slagtilfælde, akut koronarsyndrom, større benamputation, koronar revaskularisering og revaskularisering i benene, tyder resultaterne på, at der ikke er en langtidskardiovaskulær følgevirkning med hensyn til brug 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.
10 Metformin kan virke via tre mekanismer:
Metformin may act via three mechanisms:
- i muskler, ved forøgelse af insulinfølsomheden, forbedring af perifer glucoseoptagelse og -
- in muscle, by modestly increasing insulin sensitivity, improving peripheral glucose uptake and
udnyttelse
utilisation
Den prospektive randomiserede undersøgelse (UKPDS) har påvist langtidsfordele af intensiv blodsukkerkontrol ved type 2 diabetes.
The prospective randomised (UKPDS) study has established the long-term benefit of intensive blood glucose control in type 2 diabetes.
- en signifikant reduktion i den absolutte risiko for diabetes- relateret mortalitet: metformin (7, 5
- a significant reduction of the absolute risk of any diabetes-related mortality: metformin 7.5
tilfælde/ 1. 000 patientår), diæt alene (12, 7 tilfælde/ 1. 000 patientår), p=0, 017
events/ 1,000 patient-years, diet alone 12.7 events/ 1,000 patient-years, p=0.017
tilfælde/ 1. 000 patientår) versus diæt alene (20, 6 tilfælde/ 1. 000 patientår), p=0, 011, og versus de kombinerede monoterapigrupper med sulfonylurinstof og insulin (18, 9 tilfælde/ 1. 000 patientår), p=0, 021
patient-years versus diet alone 20.6 events/ 1,000 patient-years, (p=0.011), and versus the combined sulphonylurea and insulin monotherapy groups 18.9 events/ 1,000 patient-years (p=0.021)
- en signifikant reduktion i den absolutte risiko for myocardieinfarkt: metformin (11
- a significant reduction in the absolute risk of myocardial infarction: metformin 11 events/ 1,000
tilfælde/ 1. 000 patientår), diæt alene (18 tilfælde/ 1. 000 patientår), p=0, 01.
patient-years, diet alone 18 events/ 1,000 patient-years, (p=0.01).
5. 2 Farmakokinetiske egenskaber
11 5.2 Pharmacokinetic properties
Hvad angår metformin, nedsatte fødeindtagelse imidlertid middel- AUC og Cmax (henholdsvis 13% og 28%).
However, in the case of metformin, in the fed state the mean AUC and Cmax were lower (13% and 28% respectively).
Tmax forsinkedes cirka 1, 9 timer ved fødeindtagelse ved pioglitazon og 0, 8 timer ved metformin.
Tmax was delayed by food by approximately 1.9h for pioglitazone and 0.8 h for metfomin.
Absorption Pioglitazon absorberes hurtigt efter peroral indgivelse, og 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.
11 Fordeling Det beregnede fordelingsvolumen hos mennesker er 0, 25 1/ kg.
The estimated volume of distribution in humans is 0.25 l/ kg.
Metabolisme Pioglitazon gennemgår en omfattende metabolisme i leveren ved hydroxylering af alifatiske methylengrupper.
Pioglitazone undergoes extensive hepatic metabolism by hydroxylation of aliphatic methylene groups.
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.
4. 5).
Elimination:
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%).
Den gennemsnitlige plasmahalveringstid for uomdannet pioglitazon er hos mennesket 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.
Ældre Steady- state- farmakokinetik er ens hos patienter på 65 år og derover og unge personer.
Steady state pharmacokinetics are similar in patients age 65 and over and young subjects.
Patienter med nedsat nyrefunktion 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.
Patienter med nedsat leverfunktion Den totale plasmakoncentration af pioglitazon er uændret, men med øget fordelingsvolumen.
Total plasma concentration of pioglitazone is unchanged, but with an increased volume of distribution.
Absorption Efter en oral dosis metformin når tmax efter 2, 5 timer.
After an oral dose of metformin, tmax is reached in 2.5 h.
Ved de sædvanlige metformindoser og doseringsskemaer nås steady state plasmakoncentrationer inden for 24- 48 timer, og de er sædvanligvis mindre end 1 µg/ ml.
At the usual metformin doses and dosing schedules, steady state plasma concentrations are reached within 24-48 h and are generally less than 1 µg/ ml.
I kontrollerede kliniske undersøgelser overskred de maksimale metformin - plasmakoncentrationer (Cmax) ikke 4 µg/ ml, selv ved maksimale doser.
In controlled clinical trials, maximum metformin plasma levels (Cmax) did not exceed 4 µg/ ml, even at maximum doses.
Efter indgivelse af en dosis på 850 mg sås en 40% lavere maksimal plasmakoncentration, en 25%
Following administration of a dose of 850 mg, a 40% lower plasma peak concentration, a 25% decrease in AUC and a 35 min prolongation of time to peak plasma concentration was observed.
Fordeling Plasmaproteinbindingen er ubetydelig.
Plasma protein binding is negligible.
Metabolisme Metformin udskilles uændret i urinen.
Metformin is excreted unchanged in the urine.
Elimination Renal clearance af metformin er > 400 ml/ min, hvilket tyder på, at metformin elimineres ved glomerulær filtration og tubulær sekretion.
Renal clearance of metformin is > 400ml/ min, indicating that metformin is eliminated by glomerular filtration and tubular secretion.
Efter en oral dosis er den konstaterede terminale eliminationshalveringstid cirka 6, 5 timer.
Following an oral dose, the apparent terminal elimination half-life is approximately 6.5 h.
Dermed er eliminationshalveringstiden forlænget, hvilket fører til øgede plasmakoncentrationer af metformin.
When renal function is impaired, renal clearance is decreased in proportion to that of creatinine and thus the elimination half-life is prolonged, leading to increased levels of metformin in plasma.
Dette reducerer tilgængeligheden af metaboliske substrater til fostervækst.
This was attributable to the action of pioglitazone in diminishing the maternal hyperinsulinaemia and increased insulin resistance that occurs during pregnancy thereby reducing the availability of metabolic substrates for foetal growth.
Hyperplasi af urinblæren sås ikke 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.
Tabletkerne Mikrokrystallinsk cellulose Povidon (K30) Croscarmellose natrium Magnesiumstearat
Microcrystalline cellulose Povidone (K30) Croscarmellose sodium Magnesium stearate
Filmovertræk Hypromellose Macrogol 8000 Talkum Titandioxid
Hypromellose Macrogol 8000 Talc Titanium dioxide.
6. 5 Emballage (art og indhold)
14 6.5 Nature and contents of container
Aluminium/ aluminium- blisterpakninger, pakninger a 14, 28, 30, 50, 56, 60 90, 98 og 180 tabletter.
Aluminium/ aluminium blisters, packs of 14, 28, 30, 50, 56, 60, 90, 98 and 180 tablets.