natgillin/translations-raw huggingface dataset:
Børn Emselex bør ikke anvendes til børn under 18 år p. g. a. manglende dokumentation for sikkerhed og virkning.
Children Emselex is not recommended for use in children below 18 years of age due to a lack of data on safety and efficacy.
Brug ved nedsat nyrefunktion Dosisjustering er ikke nødvendig hos patienter med nedsat nyrefunktion.
Use in renal impairment No dose adjustment is required in patients with impaired renal function.
5. 2).
However, caution should be exercised when treating this population (see section 5.2).
Brug ved nedsat leverfunktion Der kræves ikke dosisjustering hos patienter med mildt nedsat leverfunktion (Child Pugh A).
Use in hepatic impairment No dose adjustment is required in patients with mild hepatic impairment (Child Pugh A).
5. 2).
However, there is a risk of increased exposure in this population (see section 5.2).
5. 2)
2 In patients with moderate hepatic impairment (Child Pugh B), patients should only be treated if the benefit outweighs the risk, and patients should be restricted to 7.5 mg daily (see section 5.2).
Patienter i samtidig behandling med stoffer, som er potente hæmmere af CYP2D6 eller moderate hæmmere af CYP3A4 Til patienter, som får stoffer, der er potente CYP2D6 hæmmere, såsom paroxetin, terbinafin, quinidin og cimetidin, bør behandlingen starte med en dosis på 7, 5 mg.
Patients receiving concomitant treatment with substances that are potent inhibitors of CYP2D6 or moderate inhibitors of CYP3A4 In patients receiving substances that are potent CYP2D6 inhibitors, such as paroxetine, terbinafine, quinidine and cimetidine, treatment should start with the 7.5 mg dose.
Til patienter, som får stoffer, der er moderate CYP3A4 hæmmere, såsom fluconazol, grapefrugt juice og erythromycin bør behandlingen starte med en dosis på 7, 5 mg.
In patients receiving substances that are moderate CYP3A4 inhibitors, such as fluconazole, grapefruit juice and erythromycin, the recommended starting dose is 7.5 mg daily.
4. 3 Kontraindikationer
- Myasthenia gravis.
Emselex er kontraindiceret hos patienter med • Overfølsomhed over for det aktive stof eller for et eller flere af hjælpestofferne. • Urinretention. • Ventrikelretention. • Ukontrolleret snævervinklet glaukom. • Myastenia gravis. • Svær leverfunktionsnedsættelse (Child Pugh C). • Svær colitis ulcerosa. • Toksisk megacolon. • Samtidig behandling med potente CYP3A4 hæmmere (se pkt.
- Severe hepatic impairment (Child Pugh C).
4. 5).
- Toxic megacolon.
4. 4 Særlige advarsler og forsigtighedsregler vedrørende brugen
- Concomitant treatment with potent CYP3A4 inhibitors (see section 4.5).
4. 3).
Emselex should be used with caution in patients being treated for narrow-angle glaucoma (see section 4.3).
Emselex bør anvendes med forsigtighed til patienter med risiko for nedsat gastrointestinal motilitet, gastro- esophagal reflux og/ eller samtidig tager lægemidler, der kan være årsag til eller forværre esophagitis (så som orale bisphosphonater).
Emselex should be used with caution in patients with risk of decreased gastrointestinal motility, gastro-oesophagal reflux and/ or who are concurrently taking medicinal products (such as oral bisphosphonates) that can cause or exacerbate oesophagitis.
Sikkerhed og effekt er endnu ikke undersøgt hos patienter med neurologisk betinget overaktiveret detrusor.
Safety and efficacy have not yet been established in patients with a neurogenic cause for detrusor overactivity.
Effekt af andre lægemidler på darifenacin Darifenacins metabolisme medieres primært af cytochrom P450 enzymer CYP2D6 og CYP3A4.
Effects of other medicinal products on darifenacin Darifenacin metabolism is primarily mediated by the cytochrome P450 enzymes CYP2D6 and CYP3A4.
CYP2D6 hæmmere Til patienter, som får stoffer, der er potente CYP2D6 hæmmere (f. eks. paroxetin, terbinafin, cimetidin og quinidin), er den anbefalede begyndelsesdosis 7, 5 mg daglig.
3 CYP2D6 inhibitors In patients receiving substances that are potent CYP2D6 inhibitors (e. g. paroxetine, terbinafine, cimetidine and quinidine) the recommended starting dose should be 7.5 mg daily.
33% for 20 mg paroxetin ved en dosering på 30 mg darifenacin).
Concomitant treatment with potent CYP2D6 inhibitors results in an increase in exposure (e. g. of 33% with 20 mg paroxetine at the 30 mg dose of darifenacin).
4. 3), så som protesase hæmmere (f. eks. ritonavir), ketoconazol og itraconazol.
CYP3A4 inhibitors Darifenacin should not be used together with potent CYP3A4 inhibitors (see section 4.3) such as protease inhibitors (e. g. ritonavir), ketoconazole and itraconazole.
Potente P- glycoprotein hæmmere som ciclosporin og verapamil bør også undgås.
Potent P-glycoprotein inhibitors such as ciclosporin and verapamil should also be avoided.
Co- administration af darifenacin 7, 5 mg og den potente CYP3A4 hæmmer ketoconazol 400 mg, resulterede i 5 gange så høj AUC for darifenacin ved steady- state.
Co-administration of darifenacin 7.5 mg with the potent CYP3A4 inhibitor ketoconazole 400 mg resulted in a 5-fold increase in steady-state darifenacin AUC.
Ved co- administrering med moderate CYP3A4 hæmmere, som erythromycin, clarithromycin, telithromycin, fluconazol og grapefrugt juice, bør den anbefalede begyndelsesdosis af darifenacin være 7, 5 mg daglig.
When co-administered with moderate CYP3A4 inhibitors such as erythromycin, clarithromycin, telithromycin, fluconazole and grapefruit juice, the recommended starting dose of darifenacin should be 7.5 mg daily.
Hos patienter med stor metabolisme var AUC24 og Cmax for darifenacin 95% og 128% højere ved doseringen 30 mg 1 gang daglig, når erythromycin (moderat CYP3A4 hæmmer) blev co- administreret med darifenacin, end når darifenacin blev taget alene.
Darifenacin AUC24 and Cmax from 30 mg once daily dosing in subjects who are extensive metabolisers were 95% and 128% higher when erythromycin (moderate CYP3A4 inhibitor) was co-administered with darifenacin than when darifenacin was taken alone.
Enzym induktorer Stoffer, som er CYP3A4 induktorer, som rifampicin, carbamazepin, barbiturater og prikbladet perikum (Hypericum perforatum), vil sandsynligvis nedsætte plasmakoncentrationen af darifenacin.
Enzyme inducers Substances that are inducers of CYP3A4, such as rifampicin, carbamazepine, barbiturates and St John´s wort (Hypericum perforatum) are likely to decrease the plasma concentrations of darifenacin.
Effekt af darifenacin på andre lægemidler CYP2D6 substrater Darifenacin er en moderat hæmmer af enzymet CYP2D6.
Effects of darifenacin on other medicinal products CYP2D6 substrates Darifenacin is a moderate inhibitor of the enzyme CYP2D6.
CYP3A4 substrater Behandling med darifenacin resulterede i en lettere øget eksponering af CYP3A4 substratet midazolam.
CYP3A4 substrates Darifenacin treatment resulted in a modest increase in the exposure of the CYP3A4 substrate midazolam.
Interaktionen med midazolam mangler klinisk relevans, men er en indikation for en let CYP3A4 hæmning af darifenacin.
The interaction with midazolam lacks clinical relevance but is indicative of a slight CYP3A4 inhibition by darifenacin.
Warfarin Standard tidsmonitorering af terapeutisk protrombin skal fortsættes uændret.
Warfarin Standard therapeutic prothrombin time monitoring for warfarin should be continued.
Digoxin Monitoring af digoxin bør foretages, når behandling med darifenacin initieres og afsluttes samt ved ændring af darifenacin doseringen.
Digoxin Therapeutic drug monitoring for digoxin should be performed when initiating and ending darifenacin treatment as well as changing the darifenacin dose.
Samtidig indgift af 30 mg darifenacin 1 gang daglig, (det dobbelte af den anbefalede daglige dosis) og digoxin ved steady state resulterede i en lille øgning af digoxin eksponering (AUC:
Darifenacin 30 mg once daily (two times greater than the recommended daily dose) co-administered with digoxin at steady state resulted in a small increase in digoxin exposure (AUC:
16% og Cmax:
16% and Cmax:
Den øgede digoxin eksponering kan skyldes konkurrence mellem darifenacin og digoxin om P- glycoprotein.
The increase in digoxin exposure could be caused by competition between darifenacin and digoxin for P-glycoprotein.
Antimuskarine stoffer Som for andre antimuskarine stoffer kan samtidig brug af lægemidler, der har antimuskarine egenskaber, som oxybutynin, tolterodin og flavoxat, føre til øget terapeutisk effekt og mere udtalte bivirkninger.
Antimuscarinic agents As with any other antimuscarinic agents, concomitant use of medicinal products that possess antimuscarinic properties, such as oxybutynin, tolterodine and flavoxate, may result in more
Potentiering af antikolinerg effekt med anti- parkinson midler og tricykliske antidepressiva kan også forekomme, hvis antimuskarine stoffer bruges samtidig med sådanne lægemidler.
The potentiation of anticholinergic effects with anti- parkinson agents and tricyclic antidepressants may also occur if antimuscarinic agents are used concurrently with such medicinal products.
Der er dog ikke udført interaktionsstudier med anti- parkinson midler og tricykliske antidepressiva.
However, no studies involving the interaction with anti- parkinson agents and tricyclic antidepressants have been performed.
Graviditet Der er ikke udført forsøg med darifenacin hos gravide kvinder.
Pregnancy There are no studies of darifenacin in pregnant women.
5. 3).
Animal studies have shown toxicity to parturition, peri and post-natal development (see section 5.3).
Amning Darifenacin udskilles i mælk hos rotter.
Lactation Darifenacin is excreted into the milk of rats.
Der skal derfor udvises forsigtighed før Emselex gives til ammende kvinder.
It is not known whether darifenacin is excreted into human milk and therefore caution should be exercised before Emselex is administered to a nursing woman.
I overensstemmelse med den farmakologiske profil er de hyppigst rapporterede bivirkninger mundtørhed (som forekom hos 20, 2% og 35% af patienterne behandlet med henholdsvis 7, 5 mg og 15 mg darifenacin, 18, 7% efter fleksibel dosistitrering og 8% - 9% for placebo) og forstoppelse (14, 8% og 21% for henholdsvis 7, 5 mg og 15 mg dosis darifenacin, 20, 9% efter fleksibel dosistitrering og 5, 4% - 7, 9% for placebo).
Consistent with the pharmacological profile, the most commonly reported adverse reactions were dry mouth (20.2% and 35% for the 7.5 mg and 15 mg dose, respectively, 18.7% after flexible dose titration, and 8% - 9% for placebo) and constipation (14.8% and 21% for the 7.5 mg and 15 mg dose, respectively, 20.9% after flexible dose titration, and 5.4% - 7.9% for placebo).
Antallet af patienter som stoppede behandlingen på grund af disse bivirkninger var dog lav (mundtørhed:
However, the patient discontinuation rates due to these adverse reactions were low (dry mouth:
0% - 0, 9% og forstoppelse:
0% - 0.9% and constipation:
0, 6% - 2, 2% for darifenacin, afhængig af dosis; og 0% og 0, 3% for placebo, for henholdsvis mundtørhed og forstoppelse).
0.6% - 2.2% for darifenacin, depending on the dose; and 0% and 0.3% for placebo, for dry mouth and constipation, respectively).
Bivirkninger for Emselex 7, 5 mg og 15 mg depottabletter
Adverse reactions with Emselex 7.5 mg and 15 mg prolonged-release tablets
Hyppigheden er defineret som: meget almindelig (≥1/ 10), almindelig (≥1/ 100 til, < 1/ 10), ikke almindelig (≥1/ 1. 000 til, < 1/ 100), ikke kendt (kan ikke estimeres ud fra forhåndenværende data)
Frequency estimate: very common (≥ 1/ 10), common (≥ 1/ 100 to < 1/ 10), uncommon (≥ 1/ 1,000 to < 1/ 100), not known (cannot be estimated from the available data)
Infektioner og parasitære sygdomme Ikke almindelig Psykiske forstyrrelser
Infections and infestations Uncommon Psychiatric disorders
Ikke almindelig Nervesystemet
Uncommon Nervous system disorders
Almindelig Ikke almindelig Øjne
Common Uncommon Eye disorders
Hovedpine Svimmelhed, smagsforstyrrelser, somnolens
Headache Dizziness, dysgeusia, somnolence
Almindelig Ikke almindelig Vaskulære sygdomme
Common Uncommon Vascular disorders
Tørre øjne Synsforstyrrelser, inklusive sløret syn
Dry eye Visual disturbance, including vision blurred
Ikke almindelig Luftveje, thorax og mediastinum
Uncommon
Ikke almindelig
5 Respiratory, thoracic and mediastinal disorders Uncommon Gastrointestinal disorders
5 Mave- tarmkanalen Meget almindelig Almindelig Ikke almindelig Hud og subkutane væv
Very common Common Uncommon Skin and subcutaneous tissue disorders
Forstoppelse, tør mund Mavesmerter, kvalme, dyspepsia Flatulens, diarré, ulcerative stomatit
Constipation, dry mouth Abdominal pain, nausea, dyspepsia Flatulence, diarrhoea, mouth ulceration
Ikke almindelig Ikke kendt Nyrer og urinveje
Uncommon Not known Renal and urinary disorders
Ikke almindelig Det reproduktive system og mammae
Uncommon Reproductive system and breast disorders
Ikke almindelig
Uncommon General disorders and administration site Uncommon Investigations
Almene symptomer og reaktioner på administrationsstedet Ikke almindelig Undersøgelser
Erectile dysfunction, vaginitis conditions Oedema peripheral, asthenia, face oedema, oedema
Traumer, forgiftninger og behandlingskomplikationer Ikke almindelig
Injury, poisoning, and procedural complications Uncommon
I de kliniske studier med doseringen af 7, 5 mg og 15 mg Emselex var bivirkningsrapporteringen som vist i ovenstående tabel.
In the pivotal clinical trials with doses of Emselex 7.5 mg and 15 mg, adverse reactions were reported as presented in the table above.
Hyppigheden af bivirkninger ved doseringerne af 7, 5 mg og 15 mg Emselex faldt i løbet at behandlingsperioden på 6 måneder.
The incidence of adverse events with the doses of Emselex 7.5 mg and 15 mg decreased during the treatment period up to 6 months.
Post- marketing erfaringer Erfaringer fra brug af darifenacin efter markedsføring på verdensplan har vist tilfælde af generaliserede overfølsomhedsreaktioner, inklusive angioødem.
Post-marketing experience The following events have been reported in association with darifenacin use in worldwide post- marketing experience: generalised hypersensitivity reactions including angioedema.
De mest almindelige sete bivirkninger, var mundtørhed, forstoppelse, hovedpine, dyspepsi og nasal tørhed. Overdosering med darifenacin kan imidlertid potentielt føre til svære antikolinerge virkninger, og skal behandles i overensstemmelse hermed.
However, overdose with darifenacin can potentially lead to severe anticholinergic effects and should be treated accordingly.
Urologisk spasmolytika, ATC- kode:
Urinary antispasmodic, ATC code:
G04B D10.
G04B D10.
Darifenacin er en selektiv muskarin M3 receptorantagonist (M3 SRA) in vitro.
6 Darifenacin is a selective muscarinic M3 receptor antagonist (M3 SRA) in vitro.
6 Cytometriske studier udført med darifenacin hos patienter med ufrivillige blærekontraktioner viste øget blærekapacitet, øget volumentærskel for ustabile kontraktioner og mindsket frekvens af ustabile detrusorkontraktioner.
Cystometric studies performed with darifenacin in patients with involuntary bladder contractions showed increased bladder capacity, increased volume threshold for unstable contractions and diminished frequency of unstable detrusor contractions.
Behandling med Emselex administreret i doser á 7, 5 mg og 15 mg daglig er blevet undersøgt i fire dobbelt- blindede, randomiserede, kontrollerede fase III kliniske studier på mandlige og kvindlige patienter med symptomer på overaktiv blære.
Treatment with Emselex administered at dosages of 7.5 mg and 15 mg daily has been investigated in four double-blind, Phase III, randomised, controlled clinical studies in male and female patients with symptoms of overactive bladder.
Som det ses i tabel 2 herunder, viste en samlet analyse af behandlingerne på 3 af studierne for både Emselex 7, 5 mg og 15 mg en signifikant forbedring i det primære endepunkt, reduktion af inkontinensepisoder, i forhold til placebo.
As seen in Table 2 below, a pooled analysis of 3 of the studies for the treatment with both Emselex 7.5 mg and 15 mg provided a statistically significant improvement in the primary endpoint, reduction in incontinence episodes, versus placebo.
Samlet analyse af data fra tre fase III kliniske studier bestemt på faste doser à 7, 5 mg og 15 mg Emselex
Pooled analysis of data from three Phase III clinical studies assessing fixed doses of 7.5 mg and 15 mg Emselex
Basis -
Baseline
Inkontinensepisoder pr uge Uge 12 Ændring fra
Incontinence episodes per week Week 12 Change from
Forskel fra
Differences
(median)
(median) (median)
basisniveau
baseline
placebo1
from placebo1
(median)
(median)
Emselex 7, 5 mg 1 gang daglig
Emselex 7.5 mg once daily
Emselex 15 mg 1 gang daglig
Emselex 15 mg once daily
Hodges Lehmann estimat: median forskel fra placebo ved ændringer fra basisniveau 2 Opdelt Wilcoxon test for forskellen fra placebo.
Hodges Lehmann estimate: median difference from placebo in change from baseline 2 Stratified Wilcoxon test for difference from placebo.
Emselex doser á 7, 5 mg og 15 mg reducerede signifikant både alvorlighed og antallet af imperiøs vandladning og antallet af sygelig trang til vandladning, mens der ses en signifikant øgning af middelvolumen målt fra basisniveau.
Emselex 7.5 mg and 15 mg doses significantly reduced both the severity and number of urinary urgency episodes and the number of micturitions, while significantly increasing the mean volume voided from baseline.
Behandling med 7, 5 mg og 15 mg Emselex viste statistisk signifikant forbedring af nogle livskvalitetsmål i forhold til placebo målt med Kings Health Questionnaire, inkluderende betydning af at være inkontinent, begrænsninger i adfærd, sociale begrænsninger og mål for sværhedsgrad.
Emselex 7.5 mg and 15 mg were associated with statistically significant improvements over placebo in some aspects of quality of life as measured by the Kings Health Questionnaire including incontinence impact, role limitations, social limitations and severity measures.
Den procentvise median reduktion i antallet af inkontinensepisoder pr. uge i forhold til basisniveau var for både 7, 5 mg og 15 mg, ens for mænd og kvinder.
For both doses of 7.5 mg and 15 mg, the percentage median reduction from baseline in the number of incontinence episodes per week was similar between males and females.
Effekten af behandling med 15 mg og 75 mg darifenacin på QT/ QTc intervallet blev evalueret i et studie på 6 dage med 179 raske voksne (44% mænd:
The effect of treatment with 15 mg and 75 mg of darifenacin on QT/ QTc interval was evaluated in a study in 179 healthy adults (44% male:
56% kvinder) i alderen 18 til 65 år (til steady state).
56% females) aged 18 to 65 for 6 days (to steady state).
Terapeutiske og supra- terapeutiske doser af darifenacin resulterede ikke i nogen øget forlængelse af QT/ QTc interval fra basisniveau ved maksimal darifenacin eksponering, sammenlignet med placebo.
Therapeutic and supra-therapeutic doses of darifenacin resulted in no increase in QT/ QTc interval prolongation from baseline compared to placebo at maximum darifenacin exposure.
Darifenacen metaboliseres af CYP3A4 og CYP2D6.
Darifenacin is metabolised by CYP3A4 and CYP2D6.
Med mindre andet er angivet gælder informationerne herunder for patienter med et normalt CYP2D6 aktivitet (stor metabolisme).
7 applies to subjects who have normal CYP2D6 activity (extensive metabolisers) unless otherwise stated.
7 Absorption På grund af stor first- pass metabolisme har darifenacin en biotilgængelighed ved steady state omkring 15% og 19% efter doser på 7, 5 mg og 15 mg daglig.
Absorption Due to extensive first-pass metabolism darifenacin has a bioavailability of approximately 15% and 19% after 7.5 mg and 15 mg daily doses at steady state.
7 timer og steady- state plasmakoncentrationen opnås på 6. dagen for påbegyndt behandling.
Maximum plasma levels are reached approximately 7 hours after administration of the prolonged-release tablets and steady-state plasma levels are achieved by the sixth day of administration.
Ved steady- state er fluktationerne mellem laveste og højeste plasmakoncentrationer af darifenacin små (PTF:
At steady state, peak-to-trough fluctuations in darifenacin concentrations are small (PTF:
0, 87 for 7, 5 mg og 0, 76 for 15 mg), hvilket betyder, at terapeutisk plasmakoncentration bibeholdes over doseringsintervallet.
0.87 for 7.5 mg and 0.76 for 15 mg), thereby maintaining therapeutic plasma levels over the dosing interval.
Fordeling Darifenacin er en lipofil base, 98% er bundet til plasmaproteiner (primært alfa- 1- syre- glycoprotein).
Distribution Darifenacin is a lipophilic base and is 98% bound to plasma proteins (primarily to alpha-1-acid- glycoprotein).
Steady- state fordelingsvolumen (Vss) er estimeret til 163 l.
The steady-state volume of distribution (Vss) is estimated to be 163 litres.
De tre vigtigste metaboliseringsveje er følgende: monohydroxylering i dihydrobenzfuranringen; åbning af dihydrobenzfuranringen og; N- dealkylering af nitrogen i pyrrolidin.
The three main metabolic routes are as follows: monohydroxylation in the dihydrobenzofuran ring; dihydrobenzofuran ring opening and N-dealkylation of the pyrrolidine nitrogen.
Ingen af disse bidrager signifikant til den kliniske effekt.
The initial products of the hydroxylation and N-dealkylation pathways are major circulating metabolites but none contribute significantly to the overall clinical effect of darifenacin.
Fordobling af darifenacindosis fra 7, 5 mg til 15 mg resulterer i 150% øgning ved steady state eksponering.
Doubling the darifenacin dose from 7.5 mg to 15 mg result in a 150% increase in steady-state exposure.
Denne dosisafhængighed skyldes formodentlig mætning af den CYP2D6 katalyserede metabolisme, muligvis sammen med mætning af CYP3A4- medieret metabolisme i tarmvæggen.
This dose-dependency is probably caused by saturation of the CYP2D6 catalysed metabolism possibly together with some saturation of CYP3A4-mediated gut wall metabolism.
Elimination Efter oral administration af 14C- darifenacin til frivillige raske forsøgspersoner, blev cirka 60% af radioaktiviteten genfundet i urinen og 40% i fæces.
Excretion Following administration of an oral dose of 14C-darifenacin solution to healthy volunteers, approximately 60% of the radioactivity was recovered in the urine and 40% in the faeces.
Darifenacinclearence er beregnet til 40 l/ time.
Estimated darifenacin clearance is 40 litres/ hour.
13- 19 timer.
The elimination half-life of darifenacin following chronic dosing is approximately 13-19 hours.
5. 1).
Special patient population Gender A population pharmacokinetic analysis of patient data indicated that darifenacin exposure was 23% lower in males than females (see section 5.1).
4. 2.
Elderly patients A population pharmacokinetic analysis of patient data indicated a trend for clearance to decrease with age (19% per decade based on Phase III population pharmacokinetic analysis of patients aged 60– 89 years), see section 4.2.
Patienter med beskeden CYP2D6 metabolisme Principielt er metabolismen af darifenacin hos patienter med beskeden CYP2D6 metabolisme medieret af CYP3A4.
8 CYP2D6 poor metabolisers The metabolism of darifenacin in CYP2D6 poor metabolisers is principally mediated by CYP3A4.
I et farmakokinetisk studie af patienter med beskeden metabolisme var eksponeringen 164% og 99% højere ved steady state ved behandling med henholdsvis 7, 5 mg og 15 mg en gang daglig.
In one pharmacokinetic study the steady-state exposure in poor metabolisers was 164% and 99% higher during treatment with 7.5 mg and 15 mg once daily, respectively.
8 steady state er eksponering 66% højere hos patienter med beskeden metabolisme i forhold til patienter med stor metabolisme.
However, a population pharmacokinetic analyses of Phase III data indicated that on average steady-state exposure is 66% higher in poor metabolisers than in extensive metabolisers.
4. 2).
There was considerable overlap between the ranges of exposures seen in these two populations (see section 4.2).