natgillin/translations-raw huggingface dataset:
5 renale eliminationsvej eller elimineres via denne vej, såsom cimetidin og amantadin, kan være årsag til interaktioner, resulterende i reduceret clearance af et eller begge lægemidler.
Therefore, medicinal products that are inhibitors of this active renal elimination pathway or are eliminated by this pathway, such as cimetidine and amantadine, may interact with pramipexole resulting in reduced clearance of either or both medicinal products.
Det bør overvejes at reducere pramipexoldosis i tilfælde, hvor disse lægemidler administreres samtidigt med Mirapexin.
Reduction of the pramipexole dose should be considered when these medicinal products are administered concomitantly with MIRAPEXIN.
Kombination med levodopa Når Mirapexin gives i kombination med levodopa, anbefales det at reducere levodopa- dosis og at holde dosis af andre antiparkinson- lægemidler konstant, mens dosis af Mirapexin øges.
Combination with levodopa When MIRAPEXIN is given in combination with levodopa, it is recommended that the dosage of levodopa is reduced and the dosage of other anti-parkinsonian medicinal products is kept constant while increasing the dose of MIRAPEXIN.
Pga. en mulig additiv effekt ved kombination af anden sedativ medicin eller alkohol med pramipexol bør der udvises forsigtighed i sådanne tilfælde.
Because of possible additive effects, caution should be advised when patients are taking other sedating medicinal products or alcohol in combination with pramipexole.
4. 4), f. eks. i tilfælde hvor en antagonistisk virkning kan forventes.
Antipsychotic medicinal products Coadministration of antipsychotic medicinal products with pramipexole should be avoided (see section 4.4), e. g. if antagonistic effects can be expected.
5. 3).
Pramipexole was not teratogenic in rats and rabbits, but was embryotoxic in the rat at maternotoxic doses (see section 5.3).
Mirapexin bør ikke bruges under graviditet, medmindre det er strengt nødvendigt, og hvis fordelene opvejer den potentielle risiko for fostret.
MIRAPEXIN should not be used during pregnancy unless clearly necessary, i. e. if the potential benefit justifies the potential risk to the foetus.
Da Mirapexin hæmmer sekretionen af prolaktin hos mennesker, forventes amningen også at blive hæmmet.
As MIRAPEXIN treatment inhibits secretion of prolactin in humans, inhibition of lactation is expected.
Udskillelsen af Mirapexin i modermælk er ikke kendt.
The excretion of MIRAPEXIN into breast milk has not been studied in women.
Der er ikke erfaring med Mirapexins udskillelse i modermælk.
In the absence of human data, MIRAPEXIN should not be used during breast-feeding.
Mirapexin kan have stor virkning på evnen til at føre motorkøretøj eller betjene maskiner.
MIRAPEXIN can have a major influence on the ability to drive and use machines.
4. 4, 4. 5 og 4. 8).
Patients being treated with MIRAPEXIN 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 recurrent episodes and somnolence have resolved (see also sections 4.4, 4.5 and 4.8).
4. 8 Bivirkninger
-6- 4.8 Undesirable effects
Unormale drømme, hukommelsestab, usædvanlig adfærd med symptomer på manglende impulskontrol og tvangshandlinger såsom uhæmmet madindtagelse, tvangshandling, der fører til overdrevent indkøbsmønster, hyperseksualitet og ludomani; konfusion, forstoppelse, vrangforestillinger, svimmelhed, dyskinesi, træthed, hallucinationer, hovedpine, hyperkinesi, hyperfagi, hypotension, søvnløshed, libido forstyrrelser, kvalme, paranoia, perifert ødem, kløe, udslæt og anden overfølsomhed, rastløshed, somnolens, pludselig opstået søvn, synkope, synsforstyrrelse, sløret syn og nedsat synsskarphed, opkastning, vægttab, vægtøgning.
Expected adverse events The following adverse reactions are expected under the use of MIRAPEXIN: abnormal dreams, amnesia, behavioural symptoms of impulse control disorders and compulsions such as binge eating, compulsive shopping, hypersexuality and pathological gambling; confusion, constipation, delusion, dizziness, dyskinesia, fatigue, hallucinations, headache, hyperkinesia, hyperphagia, hypotension, insomnia, libido disorders, nausea, paranoia, peripheral oedema; pruritus, rash and other hypersensitivity; restlessness, somnolence, sudden onset of sleep, syncope, visual disturbance including vision blurred and visual acuity reduced, vomiting, weight decrease, weight increase.
En analyse af poolede placebo- kontrollerede kliniske forsøg, omfattende 1923 patienter i behandling med Mirapexin og 1354 patienter i placebo behandling viste, at rapportering af bivirkninger var hyppigt forekommende i begge grupper.
Based on the analysis of pooled placebo-controlled trials, comprising a total of 1923 patients on MIRAPEXIN and 1354 patients on placebo, adverse drug reactions were frequently reported for both groups.
63% af patienterne i Mirapexin- behandling og 52% af patienterne i placebobehandling rapporterede mindst én bivirkning.
63% of patients on MIRAPEXIN and 52% of patients on placebo reported at least one adverse drug reaction.
6 Tabel 1 og 2 viser hyppigheden af bivirkninger i placebo- kontrollerede kliniske forsøg ved Parkinsons sygdom og Restless Legs Syndrome.
Tables 1 and 2 display the frequency of adverse drug reactions from placebo-controlled clinical trials in Parkinson’ s disease and Restless Legs Syndrome.
Desuden er klinisk relevante bivirkninger også anført.
The adverse drug reactions reported in these tables are those events that occurred in 0.1% or more of patients treated with MIRAPEXIN and were reported significantly more often in patients taking MIRAPEXIN than placebo, or where the event was considered clinically relevant.
Størstedelen af bivirkningerne var milde til moderate og startede som regel tidligt i behandlingen og forsvandt for det meste ved fortsat behandling.
However, the majority of common adverse drug reactions were mild to moderate, they usually start early in therapy, and most tended to disappear even as therapy was continued.
Meget almindelig (≥1/ 10); almindelig (≥1/ 100, < 1/ 10); ikke almindelig (≥1/ 1. 000, < 1/ 100); sjælden (≥1/ 10. 000, < 1/ 1. 000); meget sjælden (< 1/ 10. 000); ikke kendt (kan ikke estimeres ud fra forhåndenværende data).
Within the system organ classes, adverse reactions are listed under headings of frequency (number of patients expected to experience the reaction), using the following categories: 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); not known (cannot be estimated form the available data).
Mest almindelige bivirkninger ved Parkinsons sygdom De mest almindeligt (≥ 5%) rapportede bivirkninger hos patienter med Parkinsons sygdom, som oftere ses efter behandling med Mirapexin end efter behandling med placebo er kvalme, dyskinesi, hypotension, svimmelhed, somnolens, søvnløshed, forstoppelse, hallucinationer, hovedpine og træthed.
Parkinson’ s disease, most common adverse events The most commonly (≥ 5%) reported adverse drug reactions in patients with Parkinson’ s disease more frequent with MIRAPEXIN treatment than with Placebo were nausea, dyskinesia, hypotension, dizziness, somnolence, insomnia, constipation, hallucination, headache and fatigue.
Forekomsten af somnolens var større ved doser højere end 1, 5 mg/ dag (se pkt.
The incidence of somnolence is increased at doses higher than 1.5 mg/ day (see section 4.2).
Dyskinesi ses hyppigere i kombination med levodopa.
More frequent adverse drug reactions in combination with levodopa were dyskinesia.
Hypotension kan forekomme i begyndelsen af behandlingen, specielt hvis Mirapexin justeres for hurtigt.
Hypotension may occur at the beginning of treatment, especially if MIRAPEXIN is titrated too fast.
Tabel 1:
-7- Table 1:
Parkinsons sygdom Systemorganklasse Psykiske forstyrrelser
Parkinson’ s disease System Organ Class Psychiatric disorders
Unormale drømme, usædvanlig adfærd med symptomer på manglende impulskontrol og tvangshandlinger, konfusion, hallucinationer, søvnløshed, rastløshed
abnormal dreams, behavioural symptoms of impulse control disorders and compulsions; confusion, hallucinations, insomnia, restlessness
Tvangshandling, der fører til overdrevent indkøbsmønster, vrangforestillinger, hyperseksualitet, ændring af libido, paranoia, ludomani
compulsive shopping, delusion, hypersexuality, libido disorder, paranoia, pathological gambling
Ikke kendt Nervesystemet
Not known Nervous system disorders
Uhæmmet madindtagelse, hyperfagi
binge eating, hyperphagia
Meget almindelig Almindelig Ikke almindelig
Very common Common Uncommon Eye disorders
Svimmelhed, dyskinesi, somnolens Hukommelsestab, hovedpine Hyperkinesi, pludseligt opstået søvn, synkope
dizziness, dyskinesia, somnolence amnesia, headache hyperkinesia, sudden onset of sleep, syncope
Almindelig
Common Vascular disorders
Synsforstyrrelse, sløret syn og nedsat synsskarphed
visual disturbance including vision blurred and visual acuity reduced
Vaskulære sygdomme
Very common Gastrointestinal disorders
Hypotension
hypotension
Meget almindelig Almindelig
Very common Common Skin and subcutaneous tissue Uncommon
Overfølsomhed, pruritus, udslæt
nausea constipation, vomiting disorders hypersensitivity, pruritus, rash
Vægttab Vægtøgning
weight decrease weight increase
Mest almindlige bivirkninger ved Restless Legs Syndrom De mest almindelige (≥ 5%) rapporterede bivirkninger hos patienter med Restless Legs Syndrom, er kvalme, hovedpine, svimmelhed og træthed.
Restless Legs Syndrome, most common adverse events The most commonly (≥ 5%) reported adverse drug reactions in patients with Restless Legs Syndrome treated with MIRAPEXIN were nausea, headache, dizziness and fatigue.
Kvalme og træthed blev oftere rapporteret hos kvindelige patienter behandlet med Sifrol (henholdsvis 20, 8% og 10, 5%) sammenlignet med mandlige patienter (henholdsvis 6, 7% og 7, 3%).
Nausea and fatigue were more often reported in female patients treated with MIRAPEXIN (20.8% and 10.5%, respectively) compared to males (6.7% and 7.3%, respectively).
7 Tabel 2:
-8- Table 2:
Restless Legs syndrom Systemorganklasse Psykiske forstyrrelser
Restless Legs Syndrome System Organ Class Psychiatric disorders
Almindelig Ikke almindelig Ikke kendt Nervesystemet
Common Uncommon Not known Nervous system disorders
Unormale drømme, søvnløshed Konfusion, hallucinationer, ændring af libido Usædvanlig adfærd med symptomer på manglende impulskontrol og tvangshandlinger såsom uhæmmet madindtagelse, tvangshandling, der fører til overdrevent indkøbsmønster, hyperseksualitet og ludomani, vrangforestillinger, hyperfagi, paranoia
abnormal dreams, insomnia confusion, hallucinations, libido disorder, restlessness behavioural symptoms of impulse control disorders and compulsions such as binge eating, compulsive shopping, hypersexuality and pathological gambling; delusion, hyperphagia, paranoia
Almindelig Ikke almindelig Ikke kendt
Common Uncommon Not known Eye disorders
Svimmelhed, hovedpine, somnolens Pludseligt opstået søvn, synkope Hukommelsestab, dyskinesi, hyperkinesi
dizziness, headache, somnolence sudden onset of sleep, syncope amnesia, dyskinesia, hyperkinesia
Ikke almindelig
Uncommon Vascular disorders
Ikke almindelig
Uncommon Gastrointestinal disorders
Kvalme Forstoppelse, opkastning
nausea constipation, vomiting
Træthed Perifere ødemer
fatigue peripheral oedema
Vægttab, vægtøgning
weight decrease, weight increase
Somnolens Mirapexin er forbundet med somnolens (8, 6%), og er blevet forbundet med overdreven somnolens i dagtimerne og pludseligt opstået søvnepisoder (0, 1%).
Somnolence MIRAPEXIN is associated with somnolence (8.6%) and has been associated uncommonly with excessive daytime somnolence and sudden sleep onset episodes (0.1%).
Ændring af libido Ændringer i libido er set (øget libido (0, 1%) eller nedsat libido (0, 4%)).
Libido disorders MIRAPEXIN may be associated with libido disorders (increased (0.1%) or decreased (0.4%)).
Disse tilstande er sædvanligvis reversible ved dosisreduktion eller seponering.
Impulse control disorders and compulsive behaviours Patients treated with dopamine agonists for Parkinson’ s disease, including MIRAPEXIN, especially at high doses, have been reported as exhibiting signs of pathological gambling, increased libido and hypersexuality, generally reversible upon reduction of the dose or treatment discontinuation.
I et retrospektiv screening og case- kontrol studie med 3090 Parkinson patienter, fik 13, 6% af alle patienter behandlet med dopamin eller non- dopamine lægemidler, i løbet af de sidste 6 måneders behandling, symptomer på unormal adfærd.
In a cross-sectional, retrospective screening and case-control study including 3090 Parkinson’ s disease patients, 13.6% of all patients receiving dopaminergic or non-dopaminergic treatment had symptoms of an impulse control disorder during the past six months.
Der er ingen klinisk erfaring med massiv overdosering.
There is no clinical experience with massive overdosage.
De forventede bivirkninger vil relateres til den farmakodynamiske profil for en dopaminagonist herunder kvalme, opkastning, hyperkinesi, hallucinationer, agitation og hypotension.
-9- hyperkinesia, hallucinations, agitation and hypotension.
Der er ingen kendt antidot ved overdosering af dopaminagonister.
There is no established antidote for overdosage of a dopamine agonist.
I tilfælde af, at centralnervesystemet synes at være stimuleret, kan et neuroleptisk
If signs of central nervous system stimulation are present, a neuroleptic agent may be indicated.
Farmakoterapeutisk klassifikation: dopaminreceptoragonist, ATC kode:
Pharmacotherapeutic group: dopamine agonists, ATC code:
Det har fuld intrinsic aktivitet.
Pramipexole is a dopamine agonist that binds with high selectivity and specificity to the D2 subfamily of dopamine receptors of which it has a preferential affinity to D3 receptors, and has full intrinsic activity.
Dyreforsøg har vist, at pramipexol hæmmer dopaminsyntese, - frigørelse og - omsætning.
Animal studies have shown that pramipexole inhibits dopamine synthesis, release, and turnover.
Virkningsmekanismen for prampipexol til behandling af Restless Legs Syndrome er ukendt.
The mechanism of action of pramipexole as treatment for Restless Legs Syndrome is unknown.
Kliniske forsøg ved Parkinsons sygdom
Clinical trials in Parkinson’ s disease
Hos patienter reducerer Mirapexin tegn og symptomer på idiopatisk Parkinsons sygdom.
In patients MIRAPEXIN alleviates signs and symptoms of idiopathic Parkinson’ s disease.
2100 patienter på Hoehn & Yahr stadier I- IV.
Controlled clinical trials included approximately 2100 patients of Hoehn and Yahr stages I – IV.
900 på mere avancerede stadier, modtog ledsagende levodopaterapi og led af motoriske komplikationer.
Out of these, approximately 900 were in more advanced stages, received concomitant levodopa therapy, and suffered from motor complications.
6 måneder.
In early and advanced Parkinson’ s disease, efficacy of MIRAPEXIN in the controlled clinical trials was maintained for approximately six months.
Denne forsinkelse af motoriske komplikationer med pramipexol skal opvejes imod en større bedring af den motoriske funktion med levodopa (målt ved den gennemsnitlige ændring i UPDRS- score).
This delay in motor complications with pramipexole should be balanced against a greater improvement in motor function with levodopa (as measured by the mean change in UPDRS-score).
Den samlede incidens af hallucinationer og somnolens var generelt højere i optitreringsfase for pramipexol gruppen.
The overall incidence of hallucinations and somnolence was generally higher in the escalation phase with the pramipexole group.
Disse punkter skal overvejes ved initiering af pramipexol behandling hos patienter med Parkinsons sygdom.
These points should be considered when initiating pramipexole treatment in patients with Parkinson’ s disease.
Kliniske forsøg ved Restless Legs Syndrome
Clinical trials in Restless Legs Syndrome
Effekten af Mirapexin er blevet evalueret i fire placebo kontrollerede kliniske forsøg hos cirka 1000 patienter med moderat til meget svær idiopatisk Restless Legs Syndrom.
The efficacy of MIRAPEXIN was evaluated in four placebo-controlled clinical trials in approximately 1000 patients with moderate to very severe idiopathic Restless Legs Syndrome.
Effekten blev påvist i kontrollerede forsøg hos patienter behandlet i op til 12 uger.
Efficacy was demonstrated in controlled trials in patients treated for up to 12 weeks.
Vedligeholdelse af effekten er ikke blevet tilstrækkelig undersøgt.
Maintenance of effect has not been sufficiently tested.
De primære effekt- parametre var gennemsnitsændringen fra baseline af Restless Legs Syndrome Rating Scale (IRLS) og Clinical Global Impression- Improvement (CGI- I).
The mean change from baseline in the Restless Legs Syndrome Rating Scale (IRLS) and the Clinical Global Impression-Improvement (CGI-I) were the primary efficacy outcome measures.
For begge primære endpoints er statistiske signifikante forskelle set for pramipexol doserne 0, 25 mg, 0, 5 mg og 0, 75 mg (salt) sammenlignet med placebo.
For both primary endpoints statistically significant differences have been observed for the pramipexole dose groups 0.25 mg, 0.5 mg and 0.75 mg in comparison to placebo.
Efter 12 ugers behandling var baseline IRLS scoren forbedret fra 23, 5 til 14, 1 point for placebo og fra 23, 4 til 9, 4 point for pramipexol (kombinerede doser).
After 12 weeks of treatment the baseline IRLS score improved from 23.5 to 14.1 points for placebo and from 23.4 to 9.4 points for pramipexole (doses combined).
Den justerede gennemsnitsforskel var - 4, 3 point (CI 95% - 6, 4; - 2, 1 procent, p- værdi < 0, 0001).
The adjusted mean difference was -4.3 points (CI 95% -6.4; -2.1
CGI- I svarrater (forbedret, meget forbedret) var henholdsvis 51, 2% og 72, 0% for placebo og pramipexol (forskel 20% CI 95%:
CGI-I responder rates (improved, very much improved) were 51.2% and 72.0% for placebo and pramipexole respectively (difference 20% CI 95%:
Effekt blev set ved 0, 088 mg base (0, 125 mg salt) pr. dag efter den første uges behandling.
Efficacy was observed with 0.088 mg of base (0.125 mg of salt) per day after the first week of treatment.
9 I et placebo- kontrolleret polysomnografi- studie over 3 uger reducerede Mirapexin signifikant antallet af periodiske benbevægelser mens forsøgspersonerne var sengeliggende.
In a placebo-controlled polysomnography study over 3 weeks MIRAPEXIN significantly reduced the number of periodic limb movements during time in bed.
Den absolutte biotilgængelighed er større end 90%, og maksimal plasmakoncentration opnås efter 1- 3 timer.
The absolute bioavailability is greater than 90% and the maximum plasma concentrations occur between 1 and 3 hours.
Høj koncentration i hjernevæv blev observeret hos rotter (omkring 8 gange sammenlignet med plasma).
8-fold compared to plasma).
Den væsentligste eliminationsvej er renal udskillelse af ikke- metaboliseret pramipexol.
Renal excretion of unchanged pramipexole is the major route of elimination.
90% af en 14C- mærket dosis udskilles via nyrerne og mindre end 2% via fæces.
Approximately 90% of 14 C-labelled dose is excreted through the kidneys while less than 2% is found in the faeces.
Den totale clearance for pramipexol er omkring 500 ml/ min. og den renale clearance er omkring 400 ml/ min.
The total clearance of pramipexole is approximately 500 ml/ min and the renal clearance is approximately 400 ml/ min.
Fald i det diastoliske og systoliske blodtryk og hjerterytmen blev fundet i minigrise, og en tendens til en hypotensiv virkning blev set i aber.
Decreases in diastolic and systolic pressure and heart rate were noted in the minipig, and a tendency to an hypotensive effect was discerned in the monkey.
I et karcinogenitets- studie udviklede hanrotter Leydig- celle - hyperplasi og adenomer, pga. pramipexols prolaktinhæmmende effekt.
In a carcinogenicity study, male rats developed Leydig cell hyperplasia and adenomas, explained by the prolactin-inhibiting effect of pramipexole.
Samme studie viste tillige, i albinorotter, der fik doser på 2 mg/ kg (salt) pramipexol og derover, en sammenhæng med retinal degeneration.
The same study also showed that, at doses of 2 mg/ kg (of salt) and higher, pramipexole was associated with retinal degeneration in albino rats.
Mannitol, majsstivelse, kolloid vandfri silica, povidon K 25, magnesiumstearat.
Mannitol, maize starch, anhydrous colloidal silica, povidone K 25, magnesium stearate
10 tabletter i et aluminium blisterkort Kartoner indeholdende 3 eller 10 blisterkort (30 eller 100 tabletter)
10 tablets per aluminium blister strips Cartons containing 3 or 10 blister strips (30 or 100 tablets)
Boehringer Ingelheim International GmbH D- 55216 Ingelheim am Rhein Tyskland
Boehringer Ingelheim International GmbH D-55216 Ingelheim am Rhein Germany
23. februar 1998 Dato for fornyelse af tilladelsen:
23 February 1998 Date of Renewal of the authorisation:
23. februar 2008
23 February 2008
Mirapexin 0, 18 mg tabletter
MIRAPEXIN 0.18 mg tablets
Mirapexin 0, 18 mg tabletter indeholder 0, 18 mg pramipexolbase (som 0, 25 mg pramipexoldihydrochloridmonohydrat).
MIRAPEXIN 0.18 mg tablets contain 0.18 mg of pramipexole base (as 0.25 mg of pramipexole dihydrochloride monohydrate).
4. 2).
MIRAPEXIN is indicated for symptomatic treatment of moderate to severe idiopathic Restless Legs Syndrome in dosages up to 0.54 mg of vase (0.75 mg of salt) (see section 4.2).
12 Skema for øgning af dosis for Mirapexin
Ascending – Dose Schedule of MIRAPEXIN
Behandlingsophør Pludseligt ophør af dopamin- behandling kan føre til udvikling af neuroleptisk malignt syndrom.
Abrupt discontinuation of dopaminergic therapy can lead to the development of aneuroleptic malignant syndrome.
13 Restless Legs Syndrome
Restless Legs Syndrome
Hvis behandlingen afbrydes i flere dage, skal den initieres påny med dosistitrering som ovenfor beskrevet.
If the treatment is interrupted for more than a few days it should be re-initiated by dose titration carried out as above.
Patienter med en kreatininclearance over 20 ml/ min behøver ingen reduktion i den daglige dosis.
Patients with a creatinine clearance above 20 mL/ min require no reduction in daily dose.
4. 2.
- 15 -
Hallucinationer Hallucinationer er en kendt bivirkning ved behandling med dopaminagonister og levodopa.
When prescribing MIRAPEXIN tablets in a patient with Parkinson’ s disease with renal impairment a reduced dose is suggested in line with section 4.2.
14 Pludselig opståede søvnanfald og somnolens Mirapexin er blevet forbundet med somnolens og episoder med pludselig opståede søvnanfald, især hos patienter med Parkinsons sygdom.
Sudden onset of sleep and somnolence MIRAPEXIN has been associated with somnolence and episodes of sudden sleep onset, particularly in patients with Parkinson’ s disease.
Augmentation Litteraturen rapporterer, at behandling af Restless Legs Syndrome med dopaminerge lægemidler kan resultere i augmentation.
Augmentation Reports in the literature indicate treatment of Restless Legs Syndrome with dopaminergic medicinal products can result in augmentation.
Plasmaproteinbinding Pramipexol er kun i ringe udstrækning bundet til plasmaproteiner (< 20%), og der er kun set beskeden biotransformation hos mennesker.
Plasma protein binding Pramipexole is bound to plasma proteins to a very low (< 20%) extent, and little biotransformation is seen in man.
15 renale eliminationsvej eller elimineres via denne vej, såsom cimetidin og amantadin, kan være årsag til interaktioner, resulterende i reduceret clearance af et eller begge lægemidler.
Therefore, medicinal products that are inhibitors of this active renal elimination pathway or are eliminated by this pathway, such as cimetidine and amantadine, may interact with pramipexole resulting in reduced clearance of either or both medicinal products.