FrancophonIA/ELRC3.0 huggingface dataset:
English: By acting as a functional antagonist on S1P1 receptors on lymphocytes, siponimod prevents egress from lymph nodes.
Danish: Ved at virke som funktionel antagonist til lymfocytternes S1P1-receptorer blokerer siponimod lymfocytternes evne til at forlade lymfeknuderne.
English: Discontinuation of treatment 1 week prior to planned vaccination until 4 weeks after is recommended.
Danish: Det anbefales at seponere behandlingen 1 uge inden en planlagt vaccination og først genoptage behandlingen efter 4 uger.
English: The co-administration of siponimod 2 mg daily in the presence of 600 mg daily doses of rifampin (strong CYP3A4 and moderate CYP2C9 inducer) decreased siponimod AUCtau,ss and Cmax,ss by 57% and 45%, respectively, in CY2C9*1*1 subjects.
Danish: Samtidig administration af siponimod 2 mg dagligt ved tilstedeværelse af daglige doser på 600 mg rifampin (stærk CYP3A4- og moderat CYP2C9-induktor) nedsatte siponimods AUCtau,ss og Cmax,ss med henholdsvis 57 % og 45 % hos CY2C9*1*1-forsøgsdeltagere.
English: Macular oedema with or without visual symptoms was more frequently reported on siponimod (1.8%) than on placebo (0.2%) in the phase III clinical study (see section 4.8).
Danish: Makulaødem med eller uden visuelle symptomer blev rapporteret mere hyppigt med siponimod (1,8 %) end med placebo (0,2 %) i det kliniske fase III-studie (se pkt.
English: Time to onset of 3-month and 6-month CDP was significantly delayed in siponimod-treated patients with active disease, by 31% compared to placebo (hazard ratio [HR] 0.69; 95% CI: 0.53, 0.91) and by 37% compared to placebo (HR 0.63; 95% CI: 0.47, 0.86), respectively.
Danish: Tid til fremkomst for 3 måneders og 6 måneders CDP var signifikant forsinket hos siponimodbehandlede patienter med aktiv sygdom med henholdsvis 31 % sammenlignet med placebo (hazard ratio [HR] 0,69; 95 % CI: 0,53, 0,91) og 37 % sammenlignet med placebo (HR 0,63; 95 % CI: 0,47, 0,86).
English: This concomitant drug regimen can consist of a moderate CYP2C9/CYP3A4 dual inhibitor (e.g. fluconazole) or a moderate CYP2C9 inhibitor in combination with a separate moderate or strong CYP3A4 inhibitor.
Danish: Et kombinationslægemiddelregime der kan være problematisk kan bestå af en moderat CYP2C9/CYP3A4-dobbelthæmmer (f.eks. fluconazol) eller en moderat CYP2C9-hæmmer i kombination med en separat moderat eller stærk CYP3A4-hæmmer.
English: - Patients homozygous for CYP2C9*3 (CYP2C9*3*3) genotype (poor metaboliser).
Danish: - Patienter, som er homozygote for CYP2C9*3- (CYP2C9*3*3-) genotype (dårlig metabolisator).
English: Due to risk for the foetus, siponimod is contraindicated during pregnancy and in women of childbearing potential not using effective contraception.
Danish: På grund af risikoen for fosteret er siponimod kontraindiceret under graviditet og til fertile kvinder, som ikke anvender effektiv kontraception.
English: • What Mayzent is and how it works.
Danish: • Mayzents virkning og anvendelse.
English: Because of a significant increase in exposure to siponimod, concomitant use of siponimod and medicinal products that cause moderate CYP2C9 and moderate or strong CYP3A4 inhibition is not recommended.
Danish: På grund af en signifikant øgning i eksponering for siponimod bør der ikke samtidig anvendes lægemidler, der forårsager moderat CYP2C9 og moderat eller stærk CYP3A4-hæmning.
English: Before initiating treatment, a recent complete blood count (CBC) (i.e. within last 6 months or after discontinuation of prior therapy) should be available.
Danish: Inden behandlingen initieres, skal der foreligge en nylig komplet blodtælling (dvs. inden for de seneste 6 måneder eller efter afbrydelse af tidligere behandling).
English: Physician's Checklist: The Physician's Checklist shall contain the following key messages:
Danish: Lægens tjekliste skal indeholde følgende vigtige oplysninger:
English: According to evaluation of the drug interaction potential using physiologically based pharmacokinetic (PBPK) modelling, a maximum of a 2-fold increase in the AUC of siponimod is predicted across genotypes with any type of CYP3A4 and CYP2C9 inhibitors except for patients with a CYP2C9*2*2 genotype.
Danish: I henhold til undersøgelser af potentialet for lægemiddelinteraktion vha. fysiologisk baseret farmakokinetisk (PBPK) modellering forventes der maksimalt en 2-folds stigning i siponimods AUC på tværs af genotyper med alle typer CYP3A4- og CYP2C9-hæmmere, undtagen for patienter med en CYP2C9*2*2-genotype.
English: • if you have an infection or if your immune system does not work properly (for example due to a disease or to medicines that suppress the immune system; see also “Other medicines and Mayzent”).
Danish: • hvis du har en infektion, eller hvis dit immunsystem ikke fungerer, som det skal (fx på grund af en sygdom eller lægemidler, der hæmmer immunsystemet.
English: Hypertension was more frequently reported in patients on siponimod (12.6%) than in those given placebo (9.0%) in the phase III clinical study in patients with SPMS.
Danish: Hypertension blev indberettet hyppigere for de patienter, der fik siponimod (12,6 %), end for de patienter, der fik placebo (9,0 %), i det kliniske fase III-studie med patienter med SPMS.
English: • Siponimod is contraindicated in patients with history of progressive multifocal leukoencephalopathy or cryptococcal meningitis.
Danish: • Siponimod er kontraindikeret hos patienter med progressiv multifokal leukoencefalopati eller kryptokokkal meningitis i anamnesen.
English: In such patients, treatment with siponimod should be considered only if the anticipated benefits outweigh the potential risks, and advice from a cardiologist should be sought prior to initiation of treatment in order to determine the most appropriate monitoring strategy.
Danish: Hos sådanne patienter bør behandling med siponimod kun overvejes, hvis de forventede fordele opvejer de potentielle risici, og der skal søges råd fra en kardiolog inden behandlingsstart med henblik på at fastlægge den bedst egnede monitoreringsstrategi.
English: After stopping siponimod treatment residual lowering effects on peripheral lymphocyte count may persist for up to 3-4 weeks after the last dose.
Danish: Efter seponering af behandlingen med siponimod kan tilbageværende nedsættende virkninger på det perifere lymfocyttal vedvare i op til 3-4 uger efter den sidste dosis.
English: It is recommended that siponimod be discontinued if a patient develops macular oedema.
Danish: Det anbefales at afbryde behandlingen med siponimod, hvis patienten udvikler makulaødem.
English: The co-administration of fluconazole (moderate CYP2C9/strong CYP3A4 inhibitor) 200 mg daily at steady state and a single dose of siponimod 4 mg in healthy volunteers with a CYP2C9*1*1 genotype led to a 2-fold increase in the area under the curve (AUC) of siponimod.
Danish: Samtidig administration af 200 mg fluconazol (moderat CYP2C9-/stærk CYP3A4-hæmmer) dagligt ved steady state og en enkelt dosis siponimod 4 mg til raske frivillige med en CYP2C9*1*1-genotype medførte en 2-folds stigning i siponimods Area Under Curve (AUC).
English: Heart rates below 40 bpm were rarely observed.
Danish: Der blev sjældent observeret en hjertefrekvens på under 40 slag/minut.
English: Re-initiation of maintenance therapy after treatment interruption If maintenance treatment is interrupted for 4 or more consecutive daily doses, siponimod needs to be re-initiated with a new titration pack.
Danish: Genstart af vedligeholdelsesbehandlingen efter afbrydelse af behandlingen Hvis vedligeholdelsesbehandlingen afbrydes i 4 eller flere sammenhængende dage, skal behandlingen med siponimod startes forfra med en ny titreringspakning.
English: If a dose is missed, the prescribed dose should be taken at the next scheduled time; the next dose should not be doubled.
Danish: Hvis en dosis glemmes, skal den ordinerede dosis tages på næste planlagte tidspunkt.
English: • Perform genotyping for CYP2C9 before treatment initiation to determine the siponimod maintenance dose.
Danish: • Der skal foretages CYP2C9 genotypebestemmelse for at fastlægge siponimods vedligeholdelsesdosis inden initiering af behandlingen.
English: Because of the potential additive effect on heart rate, treatment with siponimod should generally not be initiated in patients who are concurrently treated with these substances (see section 4.5).
Danish: På grund af den potentielle additive virkning på hjertefrekvensen må behandling med siponimod generelt ikke indledes hos patienter, som er i samtidig behandling med disse stoffer (se pkt.
English: Because residual pharmacodynamic effects, such as lowering effects on peripheral lymphocyte count, may persist for up to 3 to 4 weeks after discontinuation, vigilance for infection should be continued throughout this period (see below section “Stopping siponimod therapy”).
Danish: På grund af mulighed for tilbageværende farmakodynamiske virkninger i op til 3 til 4 uger efter seponering, som f.eks. kan nedsætte det perifere lymfocyttal, skal patienten overvåges for infektion i hele denne periode (se “Ophør af behandling med siponimod” nedenfor).
English: Primary efficacy endpoint:
Danish: Kliniske endepunkter Primært effektendepunkt:
English: If the resting heart rate is >50 bpm under chronic beta-blocker treatment, siponimod can be introduced.
Danish: Hvis hjertefrekvensen i hvile er >50 slag/minut under kronisk behandling med en betablokker, kan behandling med siponimod indledes.
English: • Contact details of the siponimod prescriber.
Danish: • Kontaktoplysninger til den læge, der har ordineret siponimod.
English: % of CYP2C9*1*1 CL/F
Danish: % af CYP2C9*1*1 CL/F
English: In the phase III study in patients with SPMS, liver function test increases were more frequently observed in patients on siponimod (11.3%) than in those on placebo (3.1%), mainly due to liver transaminase (ALT/AST) and GGT elevations.
Danish: I fase III-studiet med SPMS-patienter blev forhøjede resultater af leverfunktionsundersøgelser set hyppigere hos patienter, der fik siponimod (11,3 %), end hos dem, der fik placebo (3,1 %), hovedsageligt på grund af forhøjede levertransaminaser (ALAT/ASAT) og GGT.
English: Patient/Caregiver Guide:
Danish: Patient-/omsorgspersonkort:
English: WALLET CONTAINING BLISTER (titration pack of 12 film-coated tablets of 0.25 mg)
Danish: OMSLAG MED BLISTER (titreringspakning med 12 filmovertrukne tabletter på 0,25 mg)
English: With decreased CYP2C9 metabolic activity in the respective genotypes, a larger effect of the CYP3A4 perpetrators on siponimod exposure is anticipated (see section 4.5).
Danish: Med faldende metabolisk CYP2C9-aktivitet hos de forskellige genotyper forventes der en større virkning af CYP3A4-induktorer/inhibitorer på eksponering for siponimod (se pkt.
English: Antineoplastic, immune-modulating or immunosuppressive therapies
Danish: Antineoplastiske, immunmodulerende eller immunsupprimerende behandlinger
English: • Instruct the patient to report visual disturbances at any time while on siponimod therapy.
Danish: • Bed patienten om til enhver tid at indberette synsforstyrrelser under behandling med siponimod.
English: Bradycardia was reported in 6.2% of patients treated with siponimod compared to 3.1% on placebo and AV block in 1.7% of patients treated with siponimod compared to 0.7% on placebo (see section 4.4).
Danish: Bradyarytmi blev rapporteret hos 6,2 % af patienterne, der fik siponimod, sammenlignet med 3,1 % af de patienter, der fik placebo, og AV-blok blev rapporteret hos 1,7 % af de patienter, der fik siponimod, sammenlignet med 0,7 % af patienterne, der fik placebo (se pkt.
English: Table 2 Tabulated list of adverse reactions
Danish: Tabel 2 Tabel over bivirkninger
English: If CM is diagnosed, appropriate treatment should be initiated.
Danish: Hvis patienten diagnosticeres med kryptokokmeningitis, skal der indledes passende behandling.
English: Siponimod is contraindicated in women of childbearing potential not using effective contraception (see section 4.3).
Danish: Siponimod er kontraindiceret til fertile kvinder, som ikke anvender effektiv kontraception (se pkt.
English: • Report immediately to the prescribing physician any (intended or unintended) pregnancy, during treatment and up to 10 days following discontinuation of siponimod treatment.
Danish: • Straks indberette graviditet (planlagt eller ikke planlagt) under behandling og op til 10 dage efter seponering af behandling med siponimod til den ordinerende læge.
English: The ARR (confirmed relapses) was reduced by 46% (ARR ratio 0.54; 95% CI: 0.39, 0.77) compared to placebo.
Danish: ARR (bekræftede attakker) blev reduceret med 46 % (ARR ratio 0,54; 95 % CI: 0,39, 0,77)
English: • A case of cryptococcal meningitis (CM) has been reported for siponimod.
Danish: • Der er indberettet et tilfælde af kryptokokmeningitis (CM) efter behandling med siponimod.
English: Cutaneous neoplasms
Danish: Kutane neoplasmer
English: During treatment initiation siponimod should not be concomitantly used in patients receiving class Ia (e.g. quinidine, procainamide) or class III (e.g. amiodarone, sotalol) anti-arrhythmic medicinal products, QT-prolonging medicinal products with known arrhythmogenic properties, heart-rate-lowering calcium channel blockers (such as verapamil or diltiazem) or other substances that may decrease heart rate (e.g. ivabradine or digoxin) because of the potential additive effects on heart rate (see section 4.4).
Danish: Under behandlingsstart må siponimod ikke bruges samtidigt hos patienter, der får antiarytmika af klasse Ia (f.eks. quinidin, procainamid) eller klasse III (f.eks. amiodaron, sotalol), QT-forlængende lægemidler med kendte arytmogene egenskaber, calciumantagonister, der sænker hjertefrekvensen (f.eks. verapamil eller diltiazem) eller andre stoffer, der kan sænke hjertefrekvensen (f.eks. ivabradin eller digoxin) på grund af de potentielle additive virkninger på hjertefrekvensen (se pkt.
English: On the first 6 days of treatment, it is recommended that you take the tablets in the morning with or without food.
Danish: Det anbefales, at du tager tabletterne om morgenen med eller uden mad i de første 6 dage med behandling.
English: • phototherapy with UV radiation or PUVA photochemotherapy.
Danish: • lysbehandling med UV-stråler eller PUVA-fotokemoterapi.
English: • Patients who, in the previous 6 months, had a myocardial infarction, unstable angina pectoris, stroke/transient ischaemic attack (TIA), decompensated heart failure (requiring in-patient treatment), or New York Heart Association (NYHA) class III/IV heart failure.
Danish: • patienter, der inden for de forudgående 6 måneder har haft et myokardieinfarkt, ustabil angina pectoris, slagtilfælde/transitorisk iskæmisk attak (TIA), dekompenseret hjertesvigt (med behov for behandling under indlæggelse) eller hjertesvigt i NYHA-klasse III/IV.
English: • Women of childbearing potential should be counselled before treatment initiation and regularly thereafter about the serious risks of siponimod to the foetus, facilitated by the pregnancy-specific patient reminder card.
Danish: • Fertile kvinder skal rådgives før opstart af behandling samt regelmæssigt derefter om de alvorlige risici for fosteret, hvilket gøres bedst ved hjælp af det patientspecifikke kort rettet mod graviditet.
English: The CYP2C9 genotype influences siponimod CL/F.
Danish: CYP2C9-genotypen påvirker siponimods CL/F.
English: Prior treatment with immunosuppressive or immune-modulating therapies
Danish: Forudgående immunsupprimerende eller immunmodulerende behandlinger
English: Physicians should be vigilant for clinical symptoms or MRI findings suggestive of PML.
Danish: Lægen skal være opmærksom på kliniske symptomer eller MR-scanningsresultater, som kan tyde på PML.
English: If a woman becomes pregnant while on treatment, siponimod must be discontinued.
Danish: Hvis en kvinde bliver gravid eller gerne vil blive gravid skal siponimod seponeres.
English: Excipient with known effect Each tablet contains 59.1 mg lactose (as monohydrate) and 0.092 mg soya lecithin.
Danish: Hjælpestof, som behandleren skal være opmærksom på Hver tablet indeholder 59,1 mg lactose (som monohydrat) og 0,092 mg sojalecithin.
English: In the phase III clinical study, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) three times the upper limit of normal (ULN) was observed in 5.6% of patients treated with siponimod 2 mg compared to 1.5% of patients who received placebo (see section 4.8).
Danish: I det kliniske fase III-studie blev der observeret værdier for alaninaminotransferase (ALAT) eller aspartataminotransferase (ASAT), som var tre gange den øvre normalgrænse hos 5,6 % af de patienter, der fik siponimod 2 mg, sammenlignet med 1,5 % af de patienter, der fik placebo (se pkt.
English: Lactose monohydrate Microcrystalline cellulose Crospovidone Glycerol dibehenate Colloidal anhydrous silica
Danish: Lactosemonohydrat Cellulose, mikrokrystallinsk Crospovidon
English: The mean half-life of siponimod was unchanged in hepatic impairment.
Danish: Siponimods middelhalveringstid var uændret ved nedsat leverfunktion.
English: Caution should be exercised when siponimod is initiated in patients receiving beta blockers due to the additive effects on lowering heart rate (see section 4.4).
Danish: Der skal udvises forsigtighed ved behandlingsstart med siponimod hos patienter, der får betablokkere, på grund af de additive virkninger på sænkning af hjertefrekvens (se pkt.
English: Siponimod treatment should be considered in these patients only if the anticipated benefits outweigh the potential risks and a cardiologist must be consulted to determine appropriate monitoring.
Danish: Behandling med siponimod bør kun overvejes til disse patienter, hvis de forventede fordele opvejer de potentielle risici, og der skal søges råd fra en kardiolog for at finde den bedst egnede monitorering.
English: No dose adjustments for siponimod are needed in patients with mild or moderate hepatic impairment.
Danish: Der er ikke behov for dosisjustering hos patienter med let eller moderat nedsat leverfunktion.
English: These may be symptoms of macular oedema.
Danish: Det kan være symptomer på makulaødem.
English: If concomitant treatment with one of the above substances is considered during initiation of treatment with siponimod, advice from a cardiologist should be sought regarding the switch to a non-heart-rate-lowering medicinal product or appropriate monitoring for treatment initiation.
Danish: Hvis samtidig behandling med et af ovennævnte stoffer overvejes under indledning af behandlingen med siponimod, skal der søges råd hos en kardiolog vedrørende skift til et lægemiddel, der ikke sænker hjertefrekvensen, eller iværksættes passende monitorering under behandlingsstart.
English: No siponimod dose adjustments are needed in patients with mild, moderate or severe renal impairment.
Danish: Det er ikke nødvendigt at justere dosis af siponimod hos patienter med let, moderat eller svært nedsat nyrefunktion.
English: Nausea Diarrhoea Musculoskeletal and connective tissue disorders Common
Danish: Kvalme Diarré Knogler, led, muskler og bindevæv Almindelig
English: Siponimod is metabolised primarily by cytochrome P450 2C9 (CYP2C9) (79.3%) and to a lesser extent by cytochrome P450 3A4 (CYP3A4) (18.5%).
Danish: Siponimod metaboliseres primært af cytokrom P450 2C9 (CYP2C9) (79,3 %) og i mindre grad af cytokrom P450 3A4 (CYP3A4) (18,5 %).
English: If treatment with siponimod is considered, advice from a cardiologist should be sought regarding the switch to non-heart-rate-lowering medicinal products or appropriate monitoring for treatment initiation.
Danish: Hvis behandling med siponimod overvejes, skal der søges rådgivning hos en kardiolog vedrørende skift til lægemidler, der ikke sænker hjertefrekvensen, eller passende monitorering under indledning af behandlingen.
English: Macular oedema was more frequently reported in patients receiving siponimod (1.8%) than in those given placebo (0.2%).
Danish: Makulaødem blev rapporteret hyppigere for patienter, der fik siponimod (1,8 %), end for dem, der fik placebo (0,2 %).
English: Severe exacerbation of disease, including disease rebound, has been rarely reported after discontinuation of another S1P receptor modulator.
Danish: I sjældne tilfælde er der rapporteret svær sygdomsforværring, herunder genopblussen af sygdom (rebound), efter seponering af en anden S1P-receptormodulator.
English: • if you have fever, feel like you have flu or have a headache together with a stiff neck, sensitivity to light, nausea or confusion.
Danish: • hvis du har feber, influenzalignende symptomer eller hovedpine sammen med nakkestivhed, lysfølsomhed, kvalme eller forvirring.
English: Before initiation of treatment with siponimod, patients should be genotyped for CYP2C9 to determine their CYP2C9 metaboliser status (see section 4.2).
Danish: Inden behandlingen med siponimod indledes, skal patienten genotypebestemmes for CYP2C9 med henblik på at fastlægge deres CYP2C9-metaboliseringsstatus (se pkt.
English: • If a titration dose is missed on one day during the first 6 days of treatment, treatment must be re-initiated with a new titration pack.
Danish: • Hvis titreringsdosen udelades én dag under de første 6 dages behandling, skal behandlingen genstartes med en ny titreringspakning.
English: Siponimod should be used with caution in patients with a history of diabetes mellitus, uveitis or underlying/co-existing retinal disease due to a potential increase in the risk of macular oedema (see section 4.8).
Danish: Der bør udvises forsigtighed ved brug af siponimod hos patienter med en anamnese med diabetes mellitus, uveitis eller underliggende/samtidig retinasygdom på grund af en potentielt øget risiko for makulaødem (se pkt.
English: BLISTERS (pack of 120 film-coated tablets of 0.25 mg)
Danish: BLISTERE (pakning med 120 filmovertrukne tabletter på 0,25 mg
English: The Patient/Caregiver Guide shall contain the following key messages:
Danish: Patient-/omsorgspersobkortet skal indeholde følgende vigtige informationer:
English: Until 6 hours after first dose: o Observe patients with sinus bradycardia (heart rate <55 bpm), history of first- or second-degree [Mobitz type I] AV block or a history of myocardial infarction or heart failure (patients with NYHA class I and II) for a period of 6 hours after the first dose of siponimod for signs and symptoms of bradycardia and obtain an ECG at the end of the 6-hour monitoring period.
Danish: Indtil 6 timer efter første dosis: o Observér patienter med sinusbradyarytmi (hjertefrekvens <55 slag/minut), anamnese med AV-blok af 1. eller 2. grad [Mobitz type I] eller tidligere myokardieinfarkt eller hjertesvigt i anamnesen (patienter med NYHA-klasse I og II) i 6 timer efter den første dosis af siponimod for tegn og symptomer på bradyarytmi og optag EKG ved afslutningen af 6-timers-monitoreringsperioden.
English: Vaccinations may be less effective if administered during siponimod treatment.
Danish: Vaccinationer, der gives under behandling med siponimod, kan være mindre virkningsfulde.
English: Excipient with known effect Each tablet contains 57.3 mg lactose (as monohydrate) and 0.092 mg soya lecithin.
Danish: Hjælpestof, som behandleren skal være opmærksom på Hver tablet indeholder 57,3 mg lactose (som monohydrat) og 0,092 mg sojalecithin.
English: Siponimod is extensively metabolised, mainly by cytochrome P450 2C9 (CYP2C9) (79.3%), and to a lesser extent by cytochrome P450 3A4 (CYP3A4) (18.5%).
Danish: Siponimod metaboliseres ekstensivt, primært af cytokrom P450 2C9 (CYP2C9) (79,3 %) og i mindre grad af cytokrom P450 3A4 (CYP3A4) (18,5 %).
English: Ask your doctor about reliable methods of contraception.
Danish: Tal med lægen om sikker prævention.
English: Contains lactose and soya lecithin.
Danish: Indeholder lactose og sojalecithin.
English: • Provide patients with the Patient/Caregiver Guide and Pregnancy Reminder Card for women of childbearing potential.
Danish: • Patienterne skal have udleveret et patient-/omsorgspersonkort og patientkort specifikt rettet mod graviditet til fertile kvinder.
English: If patients develop symptoms suggestive of hepatic dysfunction during treatment with siponimod, request a liver enzymes check.
Danish: Hvis patienter udvikler symptomer, som tyder på leverpåvirkning, under behandling med siponimod, skal der bedes om et leverenzymstjek.