natgillin/translations-raw huggingface dataset:
Baseret på in- vitro data, har ropinirol kun lille potentiale for hæmning af cytochrom P450 ved terapeutiske doser.
Based on in-vitro data, ropinirole has little potential to inhibit cytochrome P450 at therapeutic doses.
Hos patienter i HRT- behandling, kan behandling med ropinirol initieres på normal vis.
In patients already receiving hormone replacement therapy, ropinirole treatment may be initiated in the usual manner.
Domperidon antagoniserer perifert den dopaminerge virkning af ropinirol og passerer ikke blod - hjernebarrieren, hvorfor det anvendes som antiemeticum hos patienter behandlet med centralt virkende dopaminagonister.
Hence its value as an anti-emetic in patients treated with centrally acting dopamine agonists.
Derfor bør samtidig brug af disse lægemidler og ropinirol undgås
4.6 Pregnancy and lactation
4. 6 Graviditet og amning Erfaringsgrundlaget for anvendelse af ropinirol til gravide er ringe.
There are no adequate data from the use of ropinirole in pregnant women.
Reproduktionstoksicitet er set i dyreforsøg (se afsnit 5. 3).
Studies in animals have shown reproductive toxicity (see section 5.3).
Ropinirol bør kun anvendes på tvingende indikation.
As the potential risk for humans is unknown, it is recommended that ropinirole is not used during pregnancy unless the potential benefit to the patient outweighs the potential risk to the fetus.
Ropinirol bør ikke anvendes i ammeperioden.
25/ 94 Ropinirole should not be used in nursing mothers as it may inhibit lactation.
Ropinirol kan hæmme amning.
4.7 Effects on ability to drive and use machines
4. 7 Virkninger på evnen til at føre motorkøretøj eller betjene maskiner Patienter i behandling med ropinirol og som har oplevet somnolens og/ eller episoder med pludselig falden i søvn, skal oplyses om, at de skal undlade at føre motorkøretøj og undgå at deltage i aktiviteter (f. eks. betjening af maskiner), hvor nedsat opmærksomhed kan bringe deres eget eller andres liv og helbred i fare.
Patients being treated with ropinirole and presenting with somnolence and/ or sudden sleep episodes must be informed to refrain from driving or engaging in activities where impaired alertness may put themselves or others at risk of serious injury or death (e. g. operating machines) until such effects have resolved (see also Section 4.4).
Dette gælder så længe disse bivirkninger optræder (se også afsnit 4. 4).
4.8 Undesirable effects
4. 8 Bivirkninger Bivirkningerne nedenfor er delt op i organklasser og hyppighed.
Adverse drug reactions are listed below by system organ class and frequency.
Hyppigheden fra kliniske undersøgelser er bestemt som incidens i forhold til placebo og er klassificeret som: meget almindelig (> 1/ 10) eller almindelig (> 1/ 100 og < 1/ 10) eller ikke almindelig (> 1/ 1000 og < 1/ 100).
Frequencies from clinical trials are determined as excess incidence over placebo and are classed as very common (> 1/ 10) or common (> 1/ 100 ,< 1/10) or uncommon (> 1/1 ,000, < 1/100).
De mest alvorlige skal anføres først.
Use of ropinirole in Restless Legs Syndrome
Brug af ropinirol mod Restless Legs Syndrome I kliniske undersøgelser vedrørende RLS var den mest almindelige bivirkning kvalme (cirka 30% af patienterne).
In Restless Legs Syndrome clinical trials the most common adverse drug reaction was nausea (approximately 30% of patients).
Få patienter gik ud af de kliniske undersøgelser på grund af bivirkninger.
Undesirable effects were normally mild to moderate and experienced at the start of therapy or on increase of dose and few patients withdrew from the clinical studies due to undesirable effects.
16 I tabel 2 er listet de bivirkninger der er rapporteret for ropinirol i 12 ugers undersøgelser, og som optræder ≥ 1% over hyppigheden for placebo, eller som er rapporteret som ikke almindelig, men hvor det vides, at de er forbundet med ropinirol.
Table 2 lists the adverse drug reactions reported for ropinirole in the 12-week clinical trials at ≥ 1.0% above the placebo rate or those reported uncommonly but known to be associated with ropinirole.
Bivirkninger rapporteret i 12- ugers RLS kliniske undersøgelser (ropinirol n=309, placebo n=307) 4. 8. 1. 1. 1. 1 Psykiatriske lidelser
(ropinirole n=309, placebo n=307)
Almindelig Ikke almindelig
Psychiatric disorders Common Uncommon Nervous system disorders
Nervøsitet Konfusion
Nervousness Confusion
Synkope, somnolens, svimmelhed (inklusiv vertigo)
Syncope, somnolence, dizziness (including vertigo)
4. 8. 1. 1. 1. 3 Vaskulære lidelser
Uncommon Gastrointestinal disorders
Postural hypotension, hypotension
Postural hypotension, hypotension
Opkastning, kvalme, Abdominalsmerter
Vomiting, nausea Abdominal pain
4. 8. 1. 1. 1. 5 Generelle symptomer og forstyrrelser ved applikationssted
General disorders and administration site conditions Common
Ved behandling med ropinirol er observeret paradoksal forværring af Restless Legs Syndrome, hvor symptomerne begynder tidligere på dagen end forventet (augmentation) og symptomerne vender tilbage tidligt på morgenen (rebound effekt).
Paradoxical worsening of Restless Legs Syndrome symptoms occurring with earlier onset (augmentation), and reoccurrence of symptoms in the early morning hours (early morning rebound), may be observed during treatment with ropinirole.
Behandling af bivirkninger Hvis patienten oplever betydelige bivirkninger bør dosisreduktion overvejes.
Dose reduction should be considered if patients experience significant undesirable effects.
Anden erfaring med ropinirol Bivirkninger rapporteret ved brug til patienter med Parkinsons sygdom, enten som monoterapi eller som tillægsterapi i doser op til 24 mg/ dag bestemt som incidens i forhold til placebo, er beskrevet nedenfor.
The adverse drug reactions reported in patients with Parkinson's disease on ropinirole monotherapy and adjunct therapy at doses up to 24 mg/ day at an excess incidence over placebo are described below.
Bivirkninger rapporteret ved brug til patienter med Parkinsons sygdom i kliniske undersøgelser i doser op til 24 mg/ dag
24
4. 8. 1. 1. 1. 6 Psykiatriske lidelser
Adverse drug reactions reported in Parkinson's disease clinical trials at doses up to mg/ day
Hallucinationer, konfusion Øget libido
Hallucinations, confusion Increased libido
4. 8. 1. 1. 1. 7 Lidelser i det centrale og perifere nervesystem
Very common Gastrointestinal disorders
Synkope, Dyskinesi, somnolens,
Syncope, dyskinesia, somnolence
Kvalme Opkastning, abdominalsmerter, halsbrand
Nausea Vomiting, abdominal pain, heartburn
4. 8. 1. 1. 1. 9 Generelle symptomer og forstyrrelser ved applikationssted
General disorders and administration site conditions Common
Almindelig
Leg oedema
Ødem i ben
Post marketing reports
Rapporter efter markedsføring Ved Parkinsons sygdom er ropinirol forbundet med somnolens og har ikke almindeligt (> 1/ 1000, < 1/ 100) været forbundet med udpræget somnolens i dagtimerne og pludselig indtræden af søvn, men ved behandling af Restless Legs Syndrome er dette fænomen meget sjældent (< 1/ 10. 000).
In Parkinson’ s disease, ropinirole is associated with somnolence and has been associated uncommonly (> 1/ 1,000, < 1/ 100) with excessive daytime somnolence and sudden sleep onset episodes, however, in Restless Legs Syndrome, this phenomenon is very rare (< 1/ 10,000).
17 Ikke almindeligt (> 1/ 1000 og < 1/ 100) er der i forbindelse med ropinirolbehandling rapporteret postural hypotension eller hypotension, sjældent i svær grad.
Following ropinirole therapy, postural hypotension or hypotension has been reported uncommonly (> 1/ 1,000, < 1/ 100), rarely severe.
Meget sjældne (< 1/ 10. 000) tilfælde af leverreaktioner, primært øgning af leverenzymer, er rapporteret.
Very rare cases of hepatic reactions (< 1/ 10,000), mainly increase of liver enzymes, have been reported.
4. 9 Overdosering Det antages, at symptomerne på overdosering med ropinirol er relateret til dets dopaminerge aktivitet.
It is anticipated that the symptoms of ropinirole overdose will be related to its dopaminergic activity.
5. 1 Farmakodynamiske egenskaber Farmakoterapeutisk klassifikation:
5.1 Pharmacodynamic properties
Dopaminagonist.
Pharmacotherapeutic group:
ATC- kode:
Dopamine agonist, ATC code:
Virkningsmekanisme Ropinirol er en non- ergolin dopamin D2/ D3 agonist, som stimulerer striatale dopamin receptorer.
27/ 94 Ropinirole is a non ergoline D2/ D3 dopamine agonist which stimulates striatal dopamine receptors.
Klinisk effekt Adartrel bør kun ordineres til patienter med moderat til svær idiopatisk Restless Legs Syndrome.
ADARTREL should only be prescribed to patients with moderate to severe idiopathic Restless Legs Syndrome.
Disse patienter klager typisk over søvnløshed eller svært ubehag i benene.
Moderate to severe idiopathic Restless Legs Syndrome is typically represented by patients who suffer with insomnia or severe discomfort in the limbs.
Middeldosis af ropinirol i patienterne med moderat til svær RLS var 2, 0 mg/ dag.
The mean dose of ropinirole for the moderate to severe patients was 2.0 mg/ day.
Ved en kombineret analyse af patienter med moderat til svær RLS fra de fire 12- ugers undersøgelser var den tilnærmede behandlingsforskel for ændringen fra baseline i IRLS skalaens totale score uge 12 Last Observation Carried Forward (LOCF) Intention to Treat population - 4, 0 points (95% CI - 5, 6, - 2, 4, p < 0, 0001; baseline og uge 12 LOCF middel IRLS points: ropinirol 28, 4 og 13, 5; placebo 28, 2 og 17, 4).
In a combined analysis of moderate to severe Restless Legs Syndrome patients from the four 12-week studies, the adjusted treatment difference for the change from baseline in IRLS scale total score at week 12 Last Observation Carried Forward (LOCF) Intention To Treat population was -4.0 points (95% CI -5.6, - 2.4, p < 0.0001; baseline and week 12 LOCF mean IRLS points: ropinirole 28.4 and 13.5; placebo 28.2 and 17.4).
Der er ikke tilstrækkelige data tilgængelige til at bevise langtidseffekt af ropinirol i Restless Legs Syndrome (se sektion 4. 2), men i en 36 ugers undersøgelse med patienter i fortsat behandling med ropinirol viste signifikant færre tilbagefald sammenlignet med patienter randomiseret til placebo (33% versus 58%, p=0, 0156).
Although sufficient data are not available to adequately demonstrate the long term efficacy of ropinirole in Restless Legs Syndrome (see section 4.2), in a 36-week study, patients who continued on ropinirole demonstrated a significantly lower relapse rate compared with patients randomised to placebo (33% versus 58%, p=0.0156).
Den korrigerede behandlingsforskel mellem ropinirol og placebo var:
A combined analysis of data from moderate to severe Restless Legs Syndrome patients, in the four 12-week placebo-controlled studies, indicated that ropinirole-treated patients reported significant improvements over placebo on the parameters of the Medical Outcome Study Sleep Scale (scores on 0-100 range except sleep quantity).
Søvnforstyrrelse (- 15, 2, 95% CI - 19, 37, - 10, 94; p < 0, 0001), søvnmængde (0, 7 time, 95% CI 0, 49, 0, 94; p < 0, 0001), søvnsufficiens (18, 6, 95% CI 13, 77, 23, 45; p < 0, 0001) og somnolens om dagen (- 7, 5, 95% CI - 10, 86, - 4, 23; p < 0, 0001) Et rebound fænomen i forbindelse med seponering af ropinirol kan ikke udelukkes.
The adjusted treatment differences between ropinirole and placebo were: sleep disturbance (-15.2, 95% CI -19.37, -10.94; p < 0.0001), sleep quantity (0.7 hours, 95% CI 0.49, 0.94); p < 0.0001), sleep adequacy (18.6, 95% CI 13.77, 23.45; p < 0.0001) and daytime somnolence (-7.5, 95% CI -10.86, -4.23; p < 0.0001).
Skønt middel IRLS total score 7- 10 dage efter behandlingsstop var højere i ropinirolbehandlede patienter end i placebobehandlede patienter i kliniske undersøgelser, overskred sværhedsgraden af symptomerne efter behandlingsstop ikke baseline assessment i de ropinirolbehandlede patienter.
In clinical trials, although the average IRLS total scores 7-10 days after withdrawal of therapy were higher in ropinirole-treated patients than in placebo-treated patients, the severity of symptoms following withdrawal of therapy generally did not exceed the baseline assessment in ropinirole-treated patients.
Absorption Ropinirols biotilgængelighed er ca.
Absorption
50% (36- 57%) og gennemsnitlige peak koncentrationer (Cmax) af lægemidlet opnås ved en mediantid på 1. 5 time efter dosering.
The bioavailability of ropinirole is about 50% (36% to 57%), with Cmax reached on average 1.5 hours after the dose.
Sammen med mad bliver Cmax forsinket omkring 2, 6 time og peak plasma niveau reduceres med 25% uden effekt på den mængde der er biotilgængelig.
In the presence of food, Cmax is delayed by about 2.6 hours and the peak plasma level is reduced by 25%, with no effect on the bioavailable quantity.
Fordeling Ropinirols plasma proteinbinding er ikke høj (< 40%) og uden effekt på distributionen som er meget udtalt (distributionsvolumen er af størrelsesordenen 7 l/ kg).
28/ 94 The binding of ropinirole to plasma proteins is not high (< 40%), with no effect on the distribution, which is very extensive (volume of distribution in the order of 7 l/ kg).
Biotransformation Ropinirol metaboliseres primært af den isoforme CYP1A2 af cytochrome P450.
Ropinirole is mainly metabolised by the isoform CYP1A2 of cytochrome P450.
Elimination Uomdannet ropinirol og metabolitter udskilles hovedsagelig via nyrerne.
Unchanged ropinirole and the metabolites are mainly excreted through the kidneys.
Linearitet Farmakokinetikken af ropinirol er overordnet lineær (Cmax og AUC) i det terapeutiske interval mellem 0, 25 mg og 4 mg efter enkelt dosis og efter gentagne doser.
The pharmacokinetics of ropinirole are linear overall (Cmax and AUC) in the therapeutic range between 0.25 mg and 4 mg, after a single dose and after repeated dosing.
Patientkarakteristika Hos patienter over 65 år er reduktion af den systemiske clearance af ropinirol med omkring 30% mulig.
In patients over 65 years of age, a reduction in the systemic clearance of ropinirole by about 30% is possible.
Hos patienter med mild til moderat nedsat nyrefunktion (kreatinin clearance mellem 30 og 50 ml/ min) er der ikke set ændring i ropinirols farmakokinetik.
In patients with mild to moderate renal impairment (creatinine clearance between 30 and 50 ml/ min), no change in the pharmacokinetics of ropinirole is observed.
5. 3 Prækliniske sikkerhedsdata Toksikologi:
Toxicology:
Den toksikologiske profil er pricipielt bestemt af lægemidlets farmakologiske profil: adfærdsændringer, hypoprolactæmi, fald i blodtryk og hjertefrekvens, ptose og spytafsondring.
The toxicology profile is principally determined by the pharmacological activity of the drug: behavioural changes, hypoprolactinaemia, decrease in blood pressure and heart rate, ptosis and salivation.
Der blev kun i albinorotter observeret retinal degenerering i et langtidsstudie med høj dosering (50 mg/ kg), sandsynligvis forbundet med en øget lyspåvirkning.
In the albino rat only, retinal degeneration was observed in a long term study at a high dose (50 mg/ kg), probably associated with an increased exposure to light.
Gentoksicitet:
Genotoxicity:
Gentoksicitet blev ikke observeret i de sædvanlige standard in vitro og in vivo undersøgelser.
Genotoxicity was not observed in the usual battery of in vitro and in vivo tests.
Karcinogenicitet:
Carcinogenicity:
I et toårigt forsøg udført i mus og rotter i doser op til 50 mg/ kg var der ingen tegn på karcinogen effekt i mus.
From two-year studies conducted in the mouse and rat at dosages up to 50 mg/ kg there was no evidence of any carcinogenic effect in the mouse.
Reproduktionstoksicitet:
Reproductive Toxicity:
25 gange AUC af den maksimale humane dosering) og malformationer af fingre og tæer ved 150 mg/ kg (ca.
Administration of ropinirole to pregnant rats at maternally toxic doses resulted in decreased foetal body weight at 60 mg/ kg (approximately 15 times the AUC at the maximum dose in humans), increased foetal death at 90 mg/ kg (approximately 25 times the AUC at the maximum dose in humans) and digit malformations at 150 mg/ kg (approximately 40 times the AUC at the maximum dose in humans).
30 gange AUC af den maksimale humane dosering) og ingen indikation af effekt på udvikling hos kanin.
There were no teratogenic effects in the rat at 120 mg/ kg (approximately 30 times the AUC at the maximum dose in humans) and no indication of an effect on development in the rabbit.
19 6. 1 Fortegnelse over hjælpestoffer
29/ 94 6.1 List of excipients
Tabletkerner Lactose monohydrate Mikrokrystallinsk cellulose Natrium croscarmellose Magnesiumstearat.
Lactose monohydrate Microcrystalline cellulose Croscarmellose sodium Magnesium stearate.
Filmovertræk Hypromellose Macrogol 400 Titandioxid (E171) Polysorbat 80 (E433)
Hypromellose Macrogol 400 Titanium dioxide (E171) Polysorbate 80 (E433).
6. 4 Særlige opbevaringsforhold Må ikke opbevares ved over 25◦C.
Store in the original package.
Opbevares i den originale emballage
6.5 Nature and contents of container
6. 5 Emballage (art og indhold) PVC/ PCTFE/ Aluminium blister med 2 eller 12 tabletter Ikke alle pakningsstørrelser er nødvendigvis markedsført.
PVC/ PCTFE/ Aluminium blister.
6. 6 Særlige forholdsregler ved bortskaffelse Ingen særlige forholdsregler.
No special requirements.
Laboratoire GlaxoSmithKline 100, route de Versailles 78163 Marly- le Roi Cedex France Tel +33 1 39 178000
Laboratoire GlaxoSmithKline 100, route de Versailles 78163 Marly-le-Roi Cedex 30/ 94 France tel +33 1 39 178000
< [Se bilag I – Udfyldes nationalt] >
[See Annex I- to be completed nationally]
< [Udfyldes nationalt] >
[To be completed nationally]
9 DATO FOR FØRSTE TILLADELSE/ FORNYELSE AF TILLADELSEN
9 DATE OF FIRST AUTHORISATION/ RENEWAL OF THE AUTHORISATION
20 < DD, MM, ÅÅ > < DD, måned, ÅR > < [Udfyldes nationalt] >
[To be completed nationally]
< MM/ ÅÅ > < [Udfyldes nationalt] >
[To be completed nationally]
21 1 LÆGEMIDLETS NAVN
31/ 94 1 NAME OF THE MEDICINAL PRODUCT
Adartrel 0, 5 mg filmovertrukne tabletter
ADARTREL 0.5 mg film-coated tablets.
Hver filmovertrukket tablet indeholder 0, 5 mg af ropinirol (som hydrochlorid).
Each film-coated tablet contains 0.5 mg of ropinirole (as hydrochloride).
Gul oval tablet mærket ” GS ” på den ene side og ” TES ” på den anden.
Yellow oval-shaped, marked "GS" on one side and "TES" on the other.
Behandlingsinitiering (uge 1) Den anbefalede initiale dosis er 0, 25 mg en gang dagligt i 2 dage (administreret som nævnt ovenfor).
The recommended initial dose is 0.25 mg once daily (administered as above) for 2 days.
Hvis denne dosis er veltolereret, øges dosis til 0, 5 mg en gang dagligt resten af ugen.
If this dose is well tolerated the dose should be increased to 0.5 mg once daily for the remainder of week 1.
Behandlingsregime (uge 2 og fremefter) Efter behandlingsinitiering øges daglig dosis indtil optimal terapeutisk respons opnås.
Therapeutic regimen (week 2 onwards)
Dosis kan derefter øges med 0, 5 mg om ugen over de næste 2 uger til en dosis på 2 mg en gang daglig.
The dose may then be increased by 0.5 mg per week over the next two weeks to a dose of 2 mg once a day.
Til nogle patienter kan dosis øges gradvist op til maksimalt 4 mg en gang daglig for at opnå optimal forbedring.
In clinical
I kliniske forsøg blev dosis øget med 0, 5 mg hver uge op til 3 mg en gang daglig og derefter med 1 mg op til den maksimalt anbefalede dosis på 4 mg en gang daglig som vist i tabel 1.
32/ 94 trials the dose was increased by 0.5 mg each week to 3 mg once a day and then by 1 mg up to the maximum recommended dose of 4 mg once a day as shown in table 1.
22 Patientens respons på ropinirol bør evalueres efter 3 måneders behandling (se afsnit 5. 1).
The patient’ s response to ropinirole should be evaluated after 3 months treatment (see section 5.1).
Patienterne skal imidlertid informeres om dette fænomen, og de bør rådes til at være forsigtige, hvis de fører motorkøretøj eller betjener maskiner, mens de er i behandling med Ropinirol.
Patients who have experienced
Patienter, der har oplevet somnolens og/ eller episoder, hvor de pludseligt falder i søvn, skal undlade at føre motorkøretøj eller betjene maskiner.
33/ 94 somnolence and/ or an episode of sudden sleep onset must refrain from driving or operating machines.
23 ropinirol, kan det derfor være nødvendigt at justere dosis af ropinirol, når lægemidler der vides at hæmme CYP1A2, f. eks. ciprofloxacin, enoxacin eller fluvoxamin introduceres eller seponeres.
Hence, in patients already receiving ropinirole, the dose of ropinirole may need to be adjusted when medicinal products known to inhibit CYP1A2, e. g. ciprofloxacin, enoxacin or fluvoxamine, are introduced or withdrawn.
4. 6 Graviditet og amning Erfaringsgrundlaget for anvendelse af ropinirol til gravide er ringe.
34/ 94 There are no adequate data from the use of ropinirole in pregnant women.
Ropinirol bør kun anvendes på tvingende indikation.
As the potential risk for humans is unknown, it is recommended that ropinirole is not used during pregnancy unless the potential benefit to the patient outweighs the potential risk to the foetus.
24 I tabel 2 er listet de bivirkninger der er rapporteret for ropinirol i 12 ugers undersøgelser, og som optræder ≥ 1% over hyppigheden for placebo, eller som er rapporteret som ikke almindelig, men hvor det vides, at de er forbundet med ropinirol.
Table 2 lists the adverse drug reactions reported for ropinirole in the 12-week clinical trials at ≥ 1.0% above the placebo rate or those reported uncommonly but known to be associated with ropinirole.
Ved behandling med ropinirol er observeret paradoksal forværring af Restless Legs Syndrome, hvor symptomerne begynder tidligere på dagen end forventet (augmentation) og symptomerne vender tilbage tidligt på morgenen (rebound effekt).
35/ 94 Paradoxical worsening of Restless Legs Syndrome symptoms occurring with earlier onset (augmentation), and reoccurrence of symptoms in the early morning hours (early morning rebound), may be observed during treatment with ropinirole.
25 Ikke almindeligt (> 1/ 1000 og < 1/ 100) er der i forbindelse med ropinirolbehandling rapporteret postural hypotension eller hypotension, sjældent i svær grad.
Following ropinirole therapy, postural hypotension or hypotension has been reported uncommonly (> 1/ 1,000, < 1/ 100), rarely severe.
Dopaminagonist.
36/ 94 Pharmacotherapeutic group:
Virkningsmekanisme Ropinirol er en non- ergolin dopamin D2/ D3 agonist, som stimulerer striatale dopamin receptorer
Ropinirole is a non ergoline D2/ D3 dopamine agonist which stimulates striatal dopamine receptors.
Sammen med mad bliver Cmax forsinket omkring 2, 6 time og peak plasma niveau reduceres med 25% uden effekt på den mængde der er biotilgængelig.
In the presence of food, Cmax is delayed by about 2.6 hours and the peak plasma level is
Fordeling Ropinirols plasma proteinbinding er ikke høj (< 40%) og uden effekt på distributionen som er meget udtalt (distributionsvolumen er af størrelsesordenen 7 l/ kg).
The binding of ropinirole to plasma proteins is not high (< 40%), with no effect on the distribution, which is very extensive (volume of distribution in the order of 7 l/ kg).
15 gange AUC af den maksimale humane dosering), øget føtal død ved 90 mg/ kg (ca.
Administration of ropinirole to pregnant rats at maternally toxic doses resulted in decreased foetal body weight at 60 mg/ kg (approximately 15 times the AUC at the maximum dose in humans), increased foetal death at 90 mg/ kg (approximately 25 times the AUC at the maximum dose in humans) and digit malformations at 150 mg/ kg (approximately 40 times the AUC at the maximum dose in humans).
40 gange AUC af den maksimale humane dosering).
There were no teratogenic effects in the rat at 120 mg/ kg (approximately 30 times the AUC at the maximum dose in humans) and no indication of an effect on development in the rabbit.
Der var ingen teratogene effekter i rotter ved 120 mg/ kg (ca.
38/ 94 6 PHARMACEUTICAL PARTICULARS
6 FARMACEUTISKE OPLYSNINGER
6.1 List of excipients
27 6. 1 Fortegnelse over hjælpestoffer
Tablet cores:
Tabletkerner Lactose monohydrat Mikrokrystallinsk cellulose Natrium croscarmellose Magnesiumstearat.
Lactose monohydrate Microcrystalline cellulose Croscarmellose sodium Magnesium stearate.