natgillin/translations-raw huggingface dataset:
Ledsagende behandling med CYP3A4- substrater med et smalt terapeutisk indeks bør undgås på grund af den markant øgede risiko for alvorlige bivirkninger.
Co-administration with CYP3A4 substrates with a narrow therapeutic index should be avoided due to the markedly increased risk of severe adverse effects.
Data vedrørende muligheden for hæmning af CYP1A2 er begrænsede, og interaktioner med theophyllin og koffein kan derfor ikke udelukkes.
Data on the potential for inhibition of CYP1A2 are limited, and therefore, interactions with theophylline and caffeine cannot be excluded.
Denne advarsel er ikke kun begrænset til lægemidler, men gælder også et betydeligt antal fødevarer og næringsprodukter, som er rettet mod børn (for eksempel coladrikke), der indeholder betydelige mængder koffein, og chokolade, som indeholder spormængder af theophyllin.
This warning is not only restricted to medicinal products but also to a considerable number of foods and nutritional products aimed at children, such as cola drinks, which contain significant quantities of caffeine or chocolate, which contains trace amounts of theophylline.
Disse lægemidler omfatter betablokkere (propranolol, carvedilol, timolol), antidepressiva (fluoxetin, paroxetin, sertralin, imipramin, clomipramin), antipsykotika (haloperidol), analgetika (codein, dextromethorphan, tramadol).
As stiripentol inhibited CYP2D6 in vitro at concentrations that are achieved clinically in plasma, drugs that are metabolized by this isoenzyme like: beta-blockers (propranolol, carvedilol, timolol), antidepressants (fluoxetine, paroxetine, sertraline, imipramine, clomipramine), antipsychotics (haloperidol), analgesics (codeine, dextromethorphan, tramadol) may be subject to metabolic interactions with stiripentol.
En dosisjustering kan være nødvendig for præparater, der metaboliseres af CYP2D6, og som dosistitreres individuelt.
A dose-adjustment may be necessary for drugs metabolised by CYP2D6 and that are individually dose titrated.
- Ergotalkaloider fra rug (ergotamin, dihydroergotamin)
- Rye ergot alkaloids (ergotamine, dihydroergotamine)
Ergotismus med mulighed for nekrose i ekstremiteterne (hæmning af leverens eliminering af meldrøje fra rug).
Ergotism with possibility of necrosis of the extremities (inhibition of hepatic elimination of rye ergot).
- Cisaprid, halofantrin, pimozid, quinidin, bepridil
- Cisapride, halofantrine, pimozide, quinidine, bepridil
Øget risiko for hjertearytmier og især Torsades de Pointes/ wave burst- artymier.
Increased risk of cardiac arrhythmias and torsades de pointes/ wave burst arrhythmia in particular.
- Immunsupprimerende midler (tacrolimus, cyclosporin, sirolimus)
- Immunosuppressants (tacrolimus, cyclosporine, sirolimus)
Øget risiko for dosisafhængige bivirkninger, såsom rhabdomyolyse (nedsat levermetabolisme af kolesterolsænkende middel)
Increased risk of dose-dependent adverse reactions such as rhabdomyolysis (decreased hepatic metabolism of cholesterol-lowering agent)
- Theophyllin, koffein
- Theophylline, caffeine
Øgede plasmaniveauer af theophyllin og koffein kan opstå på grund af hæmning af deres levermetabolisme, hvilket potentielt kan føre til toksicitet.
Increased plasma levels of theophylline and caffeine may occur via inhibition of their hepatic metabolism, potentially leading to toxicity.
Disse kombinationer bør undgås.
These combinations should be avoided.
- Virkninger på andre AED’ er
- Effects on other AEDs
4. 2), diazepam (forstærket myorelaxation), ethosuximid og tiagabin.
Inhibition of CYP450 isoenzyme CYP2C19 and CYP3A4 may provoke pharmacokinetic interactions (inhibition of their hepatic metabolism) with phenobarbital, primidone, phenytoin, carbamazepine, clobazam (See, section 4.2), valproate (See, section 4.2), diazepam (enhanced myorelaxation), ethosuximide, and tiagabine.
Det anbefales at foretage en klinisk overvågning af plasmaniveauerne af andre antikonvulsiva og eventuelt at justere dosis, når disse kombineres med stiripentol.
5
I et fransk compassionate use- program for Diacomit blev topiramat tilføjet Diacomit, clobazam og valproat i 41% af 230 tilfælde.
In a French compassionate use program for Diacomit, topiramate was added to Diacomit, clobazam and valproate in 41% of 230 cases.
For så vidt angår topiramat mener man ikke, at det er sandsynligt, at potentiel kompetition af hæmningen af CYP2C19 vil opstå, da det sandsynligvis kræver plasmakoncentrationer, som er 5- 15 gange højere end de plasmakoncentrationer, der opnås ved den almindelige anbefalede dosis af topiramat og doseringsskemaerne for topiramat.
With regard to topiramate, it is considered that potential competition of inhibition on CYP2C19 should not occur because it probably requires plasma concentrations 5 – 15 times higher than plasma concentrations obtained with the standard recommended topiramate dose and dosage schedules.
Risici forbundet med epilepsi og antiepileptiske præparater generelt:
Risk related to epilepsy and antiepileptic medicinal products in general:
Selvom andre faktorer, fx epilepsien, kan være bidragende, tyder den tilgængelige evidens på, at denne stigning i stor udstrækning skyldes behandlingen.
Although other factors, e. g. the epilepsy, can contribute, available evidence suggests that this increase, to a large extent, is caused by the treatment.
Risici forbundet med Diacomit:
Risk related to Diacomit:
Dyreforsøg viser ikke direkte eller indirekte skadelige virkninger for graviditet, fostrets udvikling, fødslen eller den postnatale udvikling i ikke - maternotoksiske doser (se pkt.
Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, foetal development, parturition or postnatal development at non-maternotoxic doses (See, section 5.3).
På grund af indikationen kan det ikke forventes, at Diacomit vil blive anvendt under graviditet eller til fertile kvinder.
In view of the indication, administration of Diacomit during pregnancy and in women of childbearing potential would not be expected.
Den kliniske beslutning om anvendelse af Diacomit under graviditet skal træffes på individuel patientbasis under hensyntagen til de potentielle kliniske fordele og risici.
The clinical decision for use of Diacomit in pregnancy needs to be made on an individual patient basis taking into consideration the potential clinical benefits and risks.
Effektiv antikonvulsiv behandling med Diacomit må ikke seponeres under graviditet, da forværring af sygdommen kan være skadeligt for både kvinde og foster.
Effective anticonvulsant treatment with Diacomit must not be stopped during pregnancy as worsening of the disease is potentially harmful to both mother and foetus.
Hvis behandlingen med Diacomit fortsættes under amning, bør det ammende spædbarn observeres nøje for eventuelle bivirkninger.
In case Diacomit therapy is continued during breast-feeding, the breast-fed infant should be carefully observed for potential adverse effects.
Patienter med SMEI forventes ikke at skulle føre motorkøretøj eller betjene maskiner på grund af den tilgrundliggende sygdoms karakter og virkningerne af længerevarende anvendelse af antikonvulsiva.
Patients with SMEI would not be expected to drive or operate machinery due to the nature of the underlying disease and the effects of long term administration of anticonvulsant drugs.
Diacomit kan forårsage døsighed og ataksi, som kan påvirke evnen til at føre motorkøretøj og betjene maskiner, og patienterne bør ikke føre motorkøretøj eller betjene maskiner, mens de er i behandling med Diacomit.
Diacomit may cause dizziness and ataxia that may affect ability to drive and use machines and patients should not drive or use machinery whilst on Diacomit therapy.
De bivirkninger, der oftest opstår, er som følger: meget almindelig (≥ 1/ 10); almindelig (≥ 1/ 100, < 1/ 10); usædvanlig (≥1/ 1. 000, < 1/ 100); sjælden (≥ 1/ 10. 000, < 1/ 1. 000); meget sjælden (< 1/ 10. 000, herunder enkeltstående indberetninger); hyppighed ukendt (kan ikke vurderes ud fra tilgængelige data).
Adverse reactions encountered most often are as follows: very common (≥ 1/ 10), common (≥ 1/ 100, < 1/ 10), uncommon (≥ 1/ 1,000, < 1/ 100), rare (≥ 1/ 10,000, < 1/ 1,000), very rare (< 1/ 10,000, including isolated cases), frequency not known (cannot be estimated from the available data).
Inden for hver hyppighedsgruppe vises bivirkningerne efter faldende styrke.
Within each frequency grouping, undesirable effects are presented in order of decreasing severity.
Systemorganklasse
6 System/ organ classes
Systemorgan - klasse (MedDRA - terminologi)
System Organ Class (MedDRA terminology)
Sygdomme i blod - og lymfesystem
Blood and lymphatic system disorders
Neutropeni Vedvarende svær neutropeni svinder normalt spontant, når behandlingen med Diacomit seponeres.
Neutropenia Persistent severe neutropenia usually resolves spontaneously when Diacomit is stopped.
Stofskiftesyg - domme og ernærings - betingede sygdomme
Metabolism and nutrition disorders
Anoreksi, appetitløshed, vægttab (især ved kombination med natriumvalproat)
Anorexia, loss of appetite, weight loss (especially when combined with sodium valproate)
Psykiske lidelser
Psychiatric Disorders
Aggressivitet, irritabilitet, adfærdsforstyrrelser, stædighed, hyperexcitabilitet, søvnforstyrrelser
Aggressiveness, irritability, behaviour disorders, opposing behaviour, hyperexcitability, sleep disorders
Sygdomme i nervesystemet Øjensygdomme
Nervous system disorders Eye disorders
Gastrointesti - nale sygdomme
Gastrointestinal disorders
Nausea, opkastninger
Nausea, vomiting
Sygdomme i hud og subkutane væv Almene lidelser Undersøgelser
Skin and subcutaneous tissue disorders General disorders
Forhøjet γGT (især ved kombination med carbamazepin og valproat).
Photosensitivity, rash, cutaneous allergy, urticaria Fatigue
7
Investigations
Fotosensibilitet, udslæt, kutan allergi, urticaria Træthed
Raised γ GT (notably when combined with carbamazepine and valproate).
4. 4 og 4. 5), og de kan forsvinde, når dosis af disse præparater reduceres.
Many of the above adverse reactions are often due to an increase in plasma levels of other anticonvulsant medicinal products (See, sections 4.4 and 4.5) and may regress when the dose of these medicinal products is reduced.
Farmakoterapeutisk klassifikation: øvrige antiepileptika, ATC- kode N03AX17 Hos dyremodeller antagoniserer stiripentol krampeanfald, der er induceret af elektrisk stød, pentetrazol og bicucullin.
N03AX17 In animal models, stiripentol antagonizes seizures induced by electric shock, pentetrazole and bicuculline.
Dette kan ske ved hæmning af den synaptosomale optagelse af GABA og/ eller hæmning af GABA - transaminasen.
This could occur by inhibition of synaptosomal uptake of GABA and/ or inhibition of GABA transaminase.
Stiripentol har desuden vist sig at forstærke GABAA receptor- medieret transmission i den uudviklede rotte- hippocampus og øge den gennemsnitlige åben- varighed (men ikke hyppigheden) af GABAA- receptorens chloridkanaler ved en barbiturat- lignende mekanisme.
Stiripentol potentiates the efficacy of other anticonvulsants, such as
Som følge af farmakokinetiske interaktioner forstærker Stiripentol effekten af andre antikonvulsiva såsom carbamazepin, natriumvalproat, phenytoin, phenobarbital og mange benzodiazepiner.
7 carbamazepine, sodium valproate, phenytoin, phenobarbital and many benzodiazepines, as the result of pharmacokinetic interactions.
Den anden virkning af stiripentol er hovedsageligt baseret på metabolisk hæmning af adskillige isoenzymer, især CYP450 3A4 og 2C19, der er involveret i levermetabolismen af andre antiepileptika.
The second effect of stiripentol is mainly based on metabolic inhibition of several isoenzymes, in particular CYP450 3A4 and 2C19, involved in the hepatic metabolism of other anti-epileptic drugs.
I et fransk compassionate use- program deltog børn fra 6 måneder, da diagnosen på Dravets syndrom kan stilles med sikkerhed i den alder hos nogle patienter.
A French compassionate use program included children from 6 months of age because the diagnosis of Dravet’ s syndrome may be made with confidence at that age in some patients.
Den kliniske beslutning om anvendelse af Diacomit til børn med SMEI på under 3 år skal træffes på individuel patientbasis under hensyntagen til de potentielle kliniske fordele og risici (se pkt 4. 2).
The clinical decision for use of Diacomit in children with SMEI less than 3 years of age needs to be made on an individual patient basis taking into consideration the potential clinical benefits and risks (See, section 4.2).
41 børn med SMEI deltog i et randomiseret, placebokontrolleret add- on- forsøg.
41 children with SMEI were included in a randomised, placebo-controlled, add-on trial.
Reagerende patienter blev defineret som dem, der havde mere end 50% reduktion i hyppigheden af kloniske (eller tonisk- kloniske) krampeanfald i den anden måned af den dobbeltblinde periode sammenlignet med baseline.
Responders were defined as having more than 50% reduction in the frequency of clonic (or tonic- clonic) seizures during the second month of the double-blind period compared with baseline.
15 (71%) patienter reagerede på stiripentol (herunder 9, der var fri for kliniske eller tonisk- kloniske krampeanfald), mens der kun var 1 (5%), der reagerede på placebo (ingen var krampefri; stiripentol 95% CI 52, 1- 90, 7 vs. placebo 0- 14, 6).
15 (71%) patients were responders on stiripentol (including nine free of clonic or tonic-clonic seizures), whereas there was only one (5%) on placebo (none was seizure free; stiripentol 95% CI 52.1-90.7 vs. placebo 0-14.6).
Det 95% CI for forskellen var 42, 2- 85, 7.
The 95% CI of the difference was 42.2-85.7.
Procentdelen af ændringen fra baseline var højere for stiripentol (- 69%) end placebo (+7%), p < 0, 0001.
Percentage of change from baseline was higher on stiripentol (-69%) than on placebo (+7%), p < 0.0001.
I 12 ud af de 21 tilfælde (Chiron et al, Lancet, 2000) forsvandt bivirkningerne dog, da dosis af det ledsagende præparat blev reduceret.
21 patients on stiripentol had moderate side- effects (drowsiness, loss of appetite) compared with eight on placebo, but side-effects disappeared when the dose of comedication was decreased in 12 of the 21 cases (Chiron et al, Lancet, 2000).
Dette lægemiddel er godkendt med en “ betinget godkendelse ”.
This medicinal product has been authorised under a “ conditional approval” scheme.
Det betyder, at der kommer yderligere beviser for dette lægemiddel, især om effekten af stiripentol i kombination med den maksimale, sikre dosis add- on- behandling.
This means that further evidence on this medicinal product is awaited, in particular about the efficacy of stiripentol in combination with the maximum safe dose of the add-on therapy.
Et forsøg gennemføres aktuelt for at undersøge dette nærmere.
A study is being conducted to investigate this.
Det europæiske Lægemiddelagentur (EMEA) vil hvert år vurdere ny information vedrørende denne medicin og vil om nødvendigt opdatere dette produktresumé.
The European Medicines Agency (EMEA) will review new information on the product every year and this SPC will be updated as necessary.
Absorption/ biotilgængelighed:
Absorption / Bioavailability:
Tiden indtil maksimal plasmakoncentration er cirka 1, 5 timer.
Stiripentol is quickly absorbed, with a time to peak plasma concentration of about 1.5 hours.
Plasmaclearancen falder markant ved høje doser; fra cirka 40 l/ kg/ dag ved dosis på 600 mg/ dag til cirka 8 l/ kg/ dag ved dosis på 2. 400 mg.
Plasma clearance decreases markedly at high doses; it falls from approximately 40 l/ kg/ day at the dose of 600 mg/ day to about 8 l/ kg/ day at the dose of 2400 mg.
Clearancen falder efter gentagen indgivelse af stiripentol – sandsynligvis på grund af hæmningen af cytokrom P450' s isoenzymer, der er ansvarlige for dets metabolisme.
Clearance is decreased after repeated administration of stiripentol, probably due to inhibition of the cytochrome P450 isoenzymes responsible for its metabolism.
Elimineringshalveringstiden var inden for området 4, 5 timer til 13 timer, hvilket steg i takt med dosis.
The half-life of elimination was in the range of 4.5 hours to 13 hours, increasing with dose.
Metabolisme:
8 Metabolism:
Der er konstateret 13 forskellige metabolitter i urin.
Stiripentol is extensively metabolized, 13 different metabolites having been found in urine.
Metabolitter af stiripentol i urinen udgjorde samlet størstedelen (73%) af en oral akut dosis, mens yderligere 13- 24% blev konstateret i fæces som uændret lægemiddel.
Urinary metabolites of stiripentol accounted collectively for the majority (73%) of an oral acute dose whereas a further 13-24% was recovered in faeces as unchanged drug.
Biotilgængelighed / Bioækvivalens:
Bioavailability / Bioequivalence:
Relativ biotilgængelighed mellem kapsler og pulver til oral suspension er blevet undersøgt i raske frivillige forsøgspersoner efter indgift af en enkelt oral dosis på 1, 000 mg.
Relative bioavailabilty between the capsules and powder for oral suspension in sachet formulations has been studied in healthy male volunteers after a 1,000mg single oral administration.
Klinisk supervision anbefales, hvis det er nødvendigt at skifte mellem stiripentol kapsler og pulverformulering til oral suspension.
Clinical supervision is recommended if switching between the stiripentol capsule and powder for oral suspension in sachet formulations.
Toksicitetsundersøgelser på dyr (rotte, abe, mus) har ikke afsløret noget vedvarende toksicitetsmønster bortset fra leverforstørrelse, der var forbundet med hepatocellulær hypertrofi, som opstod, da høje doser stiripentol blev indgivet til både gnavere og ikke- gnavere.
5.3 Preclinical safety data Toxicity studies in animals (rat, monkey, mouse) have not revealed any consistent pattern of toxicity apart from liver enlargement associated with hepatocellular hypertrophy, which occurred when high doses of stiripentol were administered to both rodents and nonrodents.
I en enkelt undersøgelse på mus (men ikke i adskillige andre lignende undersøgelser) blev en lav forekomst af ganespaltedannelse observeret ved en maternotoksisk dosis (800 mg/ kg/ dag).
Stiripentol was not teratogenic when tested in the rat and rabbit; in one study in the mouse, but not in several other similar studies, a low incidence of cleft palate formation was observed at a maternotoxic dose (800 mg/ kg/ day).
4. 6).
Studies in the rat on fertility and general reproductive performance and on pre- and postnatal development were uneventful except for a minor reduction in the survival of pups nursed by mothers exhibiting toxic responses to stiripentol at a dose of 800 mg/ kg/ day (See, section, 4.6).
Hos mus var der kun en lille stigning i forekomsten af leveradenomer og - karcinomer hos dyr, der blev behandlet med 200 eller 600 mg/ kg/ dag i 78 uger, men ikke hos dem, der fik 60 mg/ kg/ dag.
In the mouse there was only a small increase in the incidence of hepatic adenomas and carcinomas in animals treated with 200 or 600mg/ kg/ day for 78 weeks but not in those given 60mg/ kg/ day.
povidon K29/ 32 natriumstivelsesglycol (type A) magnesiumstearat
povidone K29/ 32 sodium starch glycolate (type A) magnesium stearate
Udvendig kapsel Gelatine Titandioxid (E171) Erythrosin (E127) Indigotin (E132)
Capsule shell Gelatin Titanium dioxide (E171) Erythrosine (E127) Indigotine (E132)
Opbevares i den originale pakning for at beskytte mod lys.
, Store in the original package in order to protect from light.
Biocodex, 7 Avenue Gallieni 94250 Gentilly, Frankrig.
Biocodex, 7 Avenue Gallieni, 94250 Gentilly, France.
Hver kapsel indeholder 500 mg stiripentol
Each capsule contains 500 mg of stiripentol
0, 32 mg natrium pr. kapsel
0.32 mg sodium per capsule.
Kapslen skal sluges hel med et glas vand under måltidet.
The capsule should be swallowed whole with a glass of water during a meal.
12 Dosisjusteringer af andre antiepileptika, der anvendes i kombination med Diacomit På trods af manglen på omfattende farmakologiske data for potentielle lægemiddelinteraktioner kan vi på baggrund af den kliniske erfaring give følgende vejledning vedrørende ændring af dosis og doseringsskemaer for andre antiepileptiske præparater, der indgives samtidig med Diacomit.
Dose adjustments of other antiepileptics used in combination with Diacomit Despite the absence of comprehensive pharmacology data on potential drug interactions, the following advice regarding modification of the dose and dosage schedules of other anti-epileptic medicinal products administered in conjunction with Diacomit is provided based on clinical experience.
13 4. 4 Særlige advarsler og forsigtighedsregler vedrørende brugen
12 4.4 Special warnings and precautions for use
Det tilrådes at udvise forsigtighed, når stiripentol kombineres med andre lægemidler, som hæmmer eller inducerer en eller flere af disse enzymer..
Caution is advised when combining stiripentol with other drugs that inhibit or induce one or more of these enzymes.
14 niveauer af disse aktive stoffer, som kan føre til forstærkede farmakologiske effekter og til en stigning i bivirkniger og uønskede hændelser.
Caution must be exercised if clinical circumstances require combining stiripentol with drugs metabolised by CYP2C19 (e. g. citalopram, omeprazole) or CYP3A4 (e. g.
På grund af den øgede risiko for bivirkninger (se yderligere i dette afsnit vedrørende antiepileptiske midler) skal udvises forsigtighed, hvis de kliniske omstændigheder kræver, at stiripentol kombineres med præparater, der metaboliseres af CYP2C19 (fx citalopram, omeprazol) eller CYP3A4 (fx HIV - proteasehæmmere, antihistaminer såsom astemizol, chlorpheniramin, calciumkanalblokkere, statiner, orale antikonceptionsmidler, codein).
HIV protease inhibitors, antinistamines such as astemizole, chlorpheniramine, calcium channel blockers, statins, oral contraceptives, codeine) due to the increased risk of adverse events (see further in this section for 13 antiepileptic drugs).
Det anbefales at foretage en klinisk overvågning af plasmaniveauerne af andre antikonvulsiva og eventuelt at justere dosis, når disse kombineres med stiripentol.
14
16 4. 7 Virkninger på evnen til at føre motorkøretøj eller betjene maskiner
4.7 Effects on ability to drive and use machines
4. 8 Undesirable effectsBivirkninger
4.8 Undesirable effects
De bivirkninger, der oftest opstår, er som følger: meget almindelig (≥ 1/ 10); almindelig (≥ 1/ 100, < 1/ 10); usædvanlig (≥ 1/ 1. 000, < 1/ 100); sjælden (≥ 1/ 10. 000, < 1/ 1. 000); meget sjælden (< 1/ 10. 000, herunder enkeltstående indberetninger); hyppighed ukendt (kan ikke vurderes ud fra tilgængelige data).
Adverse reactions encountered most often are as follows: very common (≥ 1/ 10), common (≥ 1/ 100, < 1/ 10), uncommon (≥ 1/ 1,000, < 1/ 100), rare (≥ 1/ 10,000, < 1/ 1,000), very rare (< 1/ 10,000, including isolated cases), frequency not known (cannot be estimated from the available data).
Systemorganklasse
15 System/ organ classes
Forhψjet γGT (isζr ved kombination med carbamazepin og valproat).
Photosensitivity, rash, cutaneous allergy, urticaria Fatigue
Mange af ovenstående bivirkninger skyldes ofte en stigning i plasmaniveauerne hos andre antikonvulsiva (se pkt.
Many of the above adverse reactions are often due to an increase in plasma levels of other anticonvulsant medicinal products (See, sections 4.4 and 4.5) and may regress when the dose of these medicinal products is reduced.
17 4. 9 Overdosering
4.9 Overdose
Stiripentol har desuden vist sig at forstærke GABAA receptor- medieret transmission i den uudviklede rotte- hippocampus og øge den gennemsnitlige åben- varighed (men ikke hyppigheden) af GABAA- receptorens chloridkanaler ved en barbiturat- lignende mekanisme.
Stiripentol has also been shown to enhance GABAA receptor-mediated transmission in the immature rat hippocampus and increase the mean open-duration (but not the frequency) of GABAA receptor chloride channels by a
Metabolisme:
17 Metabolism:
19 mg/ kg/ dag i 78 uger, men ikke hos dem, der fik 60 mg/ kg/ dag.
In the mouse there was only a small increase in the incidence of hepatic adenomas and carcinomas in animals treated with 200 or 600mg/ kg/ day for 78 weeks but not in those given 60mg/ kg/ day.