natgillin/translations-raw huggingface dataset:
Den daglige dosis af levodopa bør eventuelt reduceres med 10- 30% ved at forlænge doseringsintervallet og/ eller ved at reducere mængden af levodopa pr. dosis, afhængig af patientens kliniske tilstand.
The daily dose of levodopa should be reduced by about 10– 30% by extending the dosing intervals and/ or by reducing the amount of levodopa per dose, according to the clinical condition of the patient.
Hvis entakaponbehandlingen afbrydes, er det nødvendigt at justere doseringen af de andre antiparkinsonpræparater, specielt levodopa, for at opnå tilstrækkelig kontrol med symptomerne.
If entacapone treatment is discontinued, it is necessary to adjust the dosing of other antiparkinsonian treatments, especially levodopa, to achieve a sufficient level of control of the parkinsonian symptoms.
Entakapon øger biotilgængeligheden af levodopa for levodopa/ benserazidstandardformuleringer en smule mere (5- 10%) end for levodopa/ carbidopastandardformuleringer.
Entacapone increases the bioavailability of levodopa from standard levodopa/ benserazide preparations slightly (5– 10%) more than from standard levodopa/ carbidopa preparations.
Dette kan medføre, at patienter, der behandles med levodopa/ benserazidstandardformuleringer, behøver en større reduktion af deres levodopadosis, når entakaponbehandlingen påbegyndes.
Hence, patients who are taking standard levodopa/ benserazide preparations may need a larger reduction of levodopa dose when entacapone is initiated.
Nyreinsufficiens påvirker ikke entakapons farmakokinetik, og det er ikke nødvendigt at justere doseringen ved nyreinsufficiens.
Renal insufficiency does not affect the pharmacokinetics of entacapone and there is no need for dose adjustment.
Det er ikke nødvendigt at justere dosis hos ældre patienter.
No dosage adjustment of entacapone is required for elderly patients.
Comtan bør ikke anvendes til børn under 18 år p. g. a. manglende dokumentation for sikkerhed og virkning.
Comtan is not recommended for use in children below age 18 due to lack of data on safety and efficacy.
Administrationsmåde Entakapon administreres oralt samtidig med hver dosering af levodopa/ benserazid eller levodopa/ carbidopa.
Method of administration Entacapone is administered orally and simultaneously with each levodopa/ carbidopa or levodopa/ benserazide dose.
5. 2).
Entacapone can be taken with or without food (see section 5.2).
- Nedsat leverfunktion.
- Hepatic impairment.
- Samtidig brug af entakapon og nonselektive monoaminoxidase (MAO- A og MAO- B) - hæmmere
- Concomitant use of entacapone and non-selective monoamine oxidase (MAO-A and MAO-B)
(f. eks. phenelzin, tranylcypromin).
inhibitors (e. g. phenelzine, tranylcypromine).
- Samtidig brug af en selektiv MAO- A- hæmmer plus en selektiv MAO- B- hæmmer og entakapon
- Concomitant use of a selective MAO-A inhibitor plus a selective MAO-B inhibitor and
4. 5).
entacapone (see section 4.5).
- En forhistorie med malignt neuroleptikasyndrom (MNS) og/ eller ikke- traumatisk
- A previous history of neuroleptic malignant syndrome (NMS) and/ or non-traumatic
rhabdomyolyse.
rhabdomyolysis.
Rhabdomyolyse sekundært til svære dykinesier eller malignt neuroleptikasyndrom (MNS) er i sjældne tilfælde set hos patienter med Parkinsons sygdom.
Rhabdomyolysis secondary to severe dyskinesias or neuroleptic malignant syndrome (NMS) has been observed rarely in patients with Parkinson’ s disease.
MNS, inklusive rhabdomyolyse og hyperthermia er karakteriseret ved muskelsymptomer (stivhed, myocloni, rysten), ændring af mental status (fx. agitation, konfusion, koma), hyperthermia, autonomisk dysfunktion (tachycardi, labilt blodtryk) og forhøjet serumkreatinphosphokinase.
NMS, including rhabdomyolysis and hyperthermia, is characterised by motor symptoms (rigidity, myoclonus, tremor), mental status changes (e. g. agitation, confusion, coma), hyperthermia, autonomic dysfunction (tachycardia, labile blood pressure) and elevated serum creatine phosphokinase.
I enkelte tilfælde er kun nogle af disse symptomer og/ eller fund tilstede.
In individual cases, only some of these symptoms and/ or findings may be evident.
Hverken MNS eller rhabdomyolyse er blevet rapporteret i forbindelse med entakaponbehandling i kontrollerede studier, hvor entakaponbehandling blev brat afsluttet.
Neither NMS nor rhabdomyolysis have been reported in association with entacapone treatment from controlled trials in which entacapone was discontinued abruptly.
Efter markedsføring er indrapporteret enkeltstående tilfælde af MNS, især efter pludselig nedsættelse eller afbrydelse af entakapon og andre samtidige dopaminerge lægemidler.
Since the introduction into the market, isolated cases of NMS have been reported, especially following abrupt reduction or discontinuation of entacapone and other concomitant dopaminergic medicinal products.
Når det skønnes nødvendigt, skal behandlingsafbrydelse af entakapon og anden dopaminerg behandling ske langsomt, og hvis der opstår tegn og/ eller symptomer på MNS eller rhabdomyolyse på trods af en langsom nedtrapning af entakapon, kan en øgning i levodopadosis være nødvendigt.
When considered necessary, withdrawal of entacapone and other dopaminergic treatment should proceed slowly, and if signs and/ or symptoms occur despite a slow withdrawal of entacapone, an increase in levodopa dosage may be necessary.
På grund af sin virkningsmekanisme kan entakapon indvirke på metabolismen af stoffer, der indeholder en catechol- gruppe og potensere deres effekt.
Because of its mechanism of action, entacapone may interfere with the metabolism of medicinal products containing a catechol group and potentiate their action.
4. 5).
Thus, entacapone should be administered cautiously to patients being treated with medicinal products metabolised by catechol-O- methyl transferase (COMT), e. g. rimiterole, isoprenaline, adrenaline, noradrenaline, dopamine, dobutamine, alpha-methyldopa, and apomorphine (see also section 4.5).
Entakapon administreres altid som adjuvant til levodopabehandling.
Entacapone is always given as an adjunct to levodopa treatment.
Entakapon øger
Hence, the precautions valid for 3 levodopa treatment should also be taken into account for entacapone treatment.
3 biotilgængeligheden af levodopa for standardformuleringer af levodopa/ benserazid 5- 10% mere end for standardformuleringer af levodopa/ carbidopa.
Entacapone increases the bioavailability of levodopa from standard levodopa/ benserazide preparations 5– 10% more than from standard levodopa/ carbidopa preparations.
Derfor kan dopaminerge bivirkningsreaktioner forekomme hyppigere, hvis entakapon føjes til levodopa/ benserazidbehandlingen (se ligeledes pkt.
Consequently, adverse dopaminergic reactions may be more frequent when entacapone is added to levodopa/ benserazide treatment (see also section 4.8).
4. 8).
To reduce levodopa-related dopaminergic adverse reactions, it is often necessary to adjust levodopa dosage within the first days to first weeks after initiating entacapone treatment, according to the clinical condition of the patient (see sections 4.2 and 4.8).
Entakapon kan forværre levodopa- induceret ortostatisk hypotension.
Entacapone may aggravate levodopa-induced orthostatic hypotension.
Entakapon bør gives med forsigtighed til patienter, der tager andre lægemidler, som forårsager ortostatisk hypotension.
Entacapone should be given cautiously to patients who are taking other medicinal products which may cause orthostatic hypotension.
I kliniske forsøg var dopaminerge bivirkningsreaktioner f. eks. dyskinesier hyppigere hos de patienter, der behandledes med entakapon og dopaminerge agonister (som f. eks. bromocriptin), selegilin eller amantadin sammenlignet med de patienter, der fik placebo sammen med agonisterne.
In clinical studies, adverse dopaminergic reactions, e. g. dyskinesia, were more common in patients who received entacapone and dopamine agonists (such as bromocriptine), selegiline or amantadine compared to those who received placebo with this combination.
Doseringen af andre antiparkinson lægemidler må muligvis justeres, når der startes behandling med entakapon.
The doses of other antiparkinsonian medicinal products may need to be adjusted when entacapone treatment is initiated.
4. 7).
Entacapone in association with levodopa has been associated with somnolence and episodes of sudden sleep onset in patients with Parkinson’ s disease and caution should therefore be exercised when driving or operating machines (see also section 4.7).
Hvis patienten får diarré, anbefales det regelmæssigt at kontrollere vægten for at undgå et eventuelt uforholdsmæssigt stort vægttab.
For patients experiencing diarrhoea, a follow-up of weight is recommended in order to avoid potential excessive weight decrease.
Der er rapporteret om patologisk spilletrang, øget libido og hyperseksualitet hos patienter med Parkinsons sygdom, der behandles med dopaminagonister og andre behandlinger med dopaminerg virkning såsom entakapon i forbindelse med levodopa.
Pathological gambling, increased libido and hypersexuality have been reported in Parkinson’ s disease patients treated with dopamine agonists and other dopaminergic treatments such as entacapone in association with levodopa.
Comtan- tabletterne indeholder saccharose.
Comtan tablets contain sucrose.
Bør ikke anvendes til patienter med arvelig fructoseintolerans, glucose/ galactose- malabsorption og sucrase- isomaltase- mangel.
Therefore, patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
I enkeltdosis kliniske forsøg med raske frivillige fandtes ikke interaktion mellem entakapon og imipramin eller entakapon og meclobemid.
In single-dose studies in healthy volunteers, no interactions were observed between entacapone and imipramine or between entacapone and moclobemide.
Der er stadig begrænset erfaring med samtidig administration af entakapon og en række lægemidler, herunder MAO- A- inhibitorer, tricykliske antidepressiva, noradrenalin re- uptake hæmmere såsom desipramin, maprotilin og venlafaxin samt lægemidler, som metaboliseres af COMT (f. eks. katechol- strukturforbindelser: rimiterol, isoprenalin, adrenalin, noradrenalin, dopamin, dobutamin, alfa- methyldopa, apomorphin og paroxetin).
However, the experience of the clinical use of entacapone with several medicinal products, including MAO-A inhibitors, tricyclic antidepressants, noradrenaline reuptake inhibitors such as desipramine, maprotiline and venlafaxine, and medicinal products that are metabolised by COMT (e. g. catechol- structured compounds: rimiterol, isoprenaline, adrenaline, noradrenaline, dopamine, dobutamine, alpha-methyldopa, apomorphine, and paroxetine) is still limited.
4. 3 og 4. 4).
Caution should be exercised when these medicinal products are used concomitantly with entacapone (see also sections 4.3 and 4.4).
Entakapon kan anvendes med selegilin (en selektiv MAO- B hæmmer), men den daglige dosis af selegilin bør ikke overstige 10 mg.
Entacapone may be used with selegiline (a selective MAO-B inhibitor), but the daily dose of selegiline should not exceed 10 mg.
Entakapon kan i mave- tarmkanalen danne chelater med jern.
Entacapone may form chelates with iron in the gastrointestinal tract.
Entakapon og jernpræparater bør tages med mindst 2- 3 timers mellemrum (se 4. 8).
Entacapone and iron preparations should be taken at least 2– 3 hours apart (see section 4.8).
Entakapon bindes til humant albumin - bindingssted II, hvilket også kan binde adskillige andre lægemidler inklusive diazepam og ibuprofen.
4 Entacapone binds to human albumin binding site II which also binds several other medicinal products, including diazepam and ibuprofen.
Kliniske interaktionsforsøg med diazepam og non - steroide anti- inflammatoriske lægemidler er ikke udført.
Clinical interaction studies with diazepam and non- steroidal anti-inflammatory medicinal products have not been carried out.
5. 2), kan entakapon potentielt interferere med lægemidler med metabolisme, der er afhængig af dette isoenzym, såsom S- warfarin.
Due to its affinity to cytochrome P450 2C9 in vitro (see section 5.2), entacapone may potentially interfere with medicinal products with metabolism dependent on this isoenzyme, such as S-warfarin.
I et interaktionsstudie med raske forsøgspersoner sås ingen ændringer af S- warfarin på plasmaniveau, mens AUC for R- warfarin i gennemsnit øgedes med 18% [CI90 11- 26%].
However, in an interaction study in healthy volunteers, entacapone did not change the plasma levels of S-warfarin, while the AUC for R-warfarin increased on average by 18% [CI90 11– 26%].
INR- værdierne øgedes i gennemsnit med 13% [CI90 6- 19%].
The INR values increased on average by 13% [CI90 6– 19%].
Derfor anbefales kontrol af INR, når entakapon gives til patienter, der samtidig er i behandling med warfarin.
Thus, control of INR is recommended when entacapone treatment is initiated for patients receiving warfarin.
Der er ikke observeret nogen teratogen eller primær føtotoksisk effekt i dyreforsøg, hvor entakapon blev administreret i betydeligt højere doser end de terapeutisk anbefalede doser.
No overt teratogenic or primary foetotoxic effects were observed in animal studies in which the exposure levels of entacapone were markedly higher than the therapeutic exposure levels.
Da der ikke er erfaring med administration af entakapon til gravide kvinder, bør entakapon ikke anvendes under graviditet.
As there is no experience in pregnant women, entacapone should not be used during pregnancy.
I dyreforsøg udskilles entakapon i modermælken.
In animal studies entacapone was excreted in milk.
Sikkerheden ved administration af entakapon til børn er ukendt.
The safety of entacapone in infants is unknown.
Kvinder bør derfor ikke amme ved behandling med entakapon.
Women should not breast-feed during treatment with entacapone.
Comtan sammen med levodopa kan i væsentlig grad påvirke evnen til at føre motorkøretøj eller betjene maskiner.
Comtan in association with levodopa may have major influence on the ability to drive and use machines.
Entakapon kan sammen med levodopa forårsage svimmelhed og symptomatisk ortostatisme.
Entacapone may, together with levodopa, cause dizziness and symptomatic orthostatism.
4. 4).
Patients being treated with entacapone in association with levodopa and presenting with somnolence and/ or sudden sleep onset episodes must be instructed 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 have resolved (see also section 4.4).
De hyppigste bivirkninger forårsaget af entakapon er relateret til øget dopaminerg aktivitet og optræder hyppigst i begyndelsen af behandlingen.
The most frequent adverse reactions caused by entacapone relate to the increased dopaminergic activity and occur most commonly at the beginning of treatment.
Den anden hyppige gruppe af bivirkninger er relateret til mave- tarmkanalen og inkluderer kvalme, opkastning, abdominal smerte, forstoppelse og diarré.
The other major class of adverse reactions are gastrointestinal symptoms, including nausea, vomiting, abdominal pain, constipation and diarrhoea.
Urinen kan blive misfarvet og blive farvet rødbrun af entakapon, men denne bivirkning er harmløs.
Urine may be discoloured reddish-brown by entacapone, but this is a harmless phenomenon.
Sædvanligvis er bivirkninger forårsaget af entakapon milde til moderate.
Usually the adverse reactions caused by entacapone are mild to moderate.
I kliniske studier har den mest almindelige bivirkning, der har ført til afbrydning af behandlingen med entakapon, været symptomer fra mave- tarmkanalen (f. eks. diarré 2, 5%) og øget dopaminerg bivirkning af levodopa (f. eks. dyskinesi 1, 7%).
In clinical studies the most common adverse reactions leading to discontinuation of entacapone treatment have been gastrointestinal symptoms (e. g. diarrhoea, 2.5%) and increased dopaminergic adverse reactions of levodopa (e. g. dyskinesias, 1.7%).
Dyskinesier (27%), kvalme (11%), diarré (8%), abdominal smerte (7%) og mundtørhed (4, 2%) blev rapporteret signifikant hyppigere med entakapon end placebo i poolede data fra kliniske studier, hvor 406 patienter har fået den aktive medicin, og 296 patienter har fået placebo.
Dyskinesias (27%), nausea (11%), diarrhoea (8%), abdominal pain (7%) and dry mouth (4.2%) were reported significantly more often with entacapone than with placebo in pooled data from clinical studies involving 406 patients taking the medicinal product and 296 patients taking placebo.
Visse af disse bivirkninger, som dyskinesier, kvalme og abdominale smerter, kan være hyppigere ved højere doser (1. 400- 2. 000 mg per dag) end ved lavere doser af entakapon.
Some of the adverse reactions, such as dyskinesia, nausea, and abdominal pain, may be more common with the higher doses (1,400 to 2,000 mg per day) than with the lower doses of entacapone.
Følgende bivirkninger listet i nedenstående Tabel 1, er akkumuleret både fra kliniske studier med entakapon samt efter introduktion af entakapon på markedet.
The following adverse drug reactions, listed below in Table 1, have been accumulated both from clinical studies with entacapone and since the introduction of entacapone into the market.
5 Tabel 1 * Bivirkninger
Table 1* Adverse drug reactions 5 Nervous system disorders
Dyskinesia Forværring af Parkinson, svimmelhed, dystoni, hyperkinesi
Dyskinesia Parkinsonism aggravated, dizziness, dystonia, hyperkinesia
Almindelig:
Very rare Not known:
Kvalme Diarré, abdominale smerter, mundtørhed, forstoppelse, opkastning
Nausea Diarrhoea, abdominal pain, dry mouth, constipation, vomiting Anorexia Colitis
Meget sjælden:
Renal and urinary disorders
Ikke kendt:
Very common:
Anoreksi Colitis
Urine discoloration
Misfarvning af urin Hud og subkutane væv
Skin and subcutaneous tissue disorders
Erytematøs eller maculopapulært udslæt Urticaria Misfarvning af hud, hår, skæg og negle
Erythematous or maculopapular rash Urticaria Skin, hair, beard and nail discolorations
Træthed, øget svedtendens, fald Vægttab
Fatigue, sweating increased, fall Weight decrease
4. 4)
Hepatic function tests abnormal Hepatitis with mainly cholestatic features (see section 4.4)
Søvnmangel, hallucinationer, konfusion, paroniria (mareridt) Agitation
Insomnia, hallucinations, confusion, paroniria Agitation
* Bivirkningerne er sat i rækkefølge under overskrifterne efter frekvens, den hyppigst forekomne først, ved anvendelse af følgende konventionelle regler:
* Adverse reactions are ranked under headings of frequency, the most frequent first, using the following convention:
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, da ingen valide estimater har kunnet opnås i kliniske og epidemiologiske studier).
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 from the available data, since no valid estimate can be derived from clinical trials or epidemiological studies).
Entakapon i forbindelse med levodopa er i isolerede tilfælde, blevet sat i forbindelse med udtalt træthed (somnolens) i dagtimerne og episoder, hvor patienten pludselig falder i søvn.
Entacapone in association with levodopa has been associated with isolated cases of excessive daytime somnolence and sudden sleep onset episodes.
Disse var generelt reversible efter dosisreduktion eller seponering af behandlingen.
Parkinson’ s disease patients treated with dopamine agonists and other dopaminergic treatments such as entacapone in association with levodopa, especially at high doses, have been reported as exhibiting signs of pathological gambling, increased libido and hypersexuality, which were generally reversible upon reduction of the dose or treatment discontinuation.
Enkeltstående tilfælde af MNS er indrapporteret efter pludselig nedsættelse eller afbrydelse af entakapon og anden tilsvarende dopaminerg behandling.
Isolated cases of NMS have been reported following abrupt reduction or discontinuation of entacapone and other dopaminergic treatments.
Data efter markedsføring inkluderer isolerede tilfælde af overdosering, hvor den højest rapporterede daglige dosis af entakapon var 16. 000 mg.
The post-marketing data include isolated cases of overdose in which the reported highest daily dose of entacapone has been 16,000 mg.
De akutte symptomer og tegn i disse tilfælde af overdosering var konfusion, nedsat aktivitet, somnolens, hypotoni, misfarvet hud og nældefeber.
The acute symptoms and signs in these cases of overdose included confusion, decreased activity, somnolence, hypotonia, skin discolouration and urticaria.
Andre dopaminerge stoffer, ATC- kode:
Pharmacotherapeutic group: other dopaminergic agents, ATC code:
Entakapon tilhører en ny terapeutisk klasse, catechol- O- metyl- transferase (COMT) - hæmmere.
6 Entacapone belongs to a new therapeutic class, catechol-O-methyl transferase (COMT) inhibitors.
Det er en reversibel, specifik og primært perifert virkende COMT- hæmmer udviklet til samtidig administration med levodopapræparater.
It is a reversible, specific, and mainly peripherally acting COMT inhibitor designed for concomitant administration with levodopa preparations.
Entakapon nedsætter det metaboliske tab af levodopa til 3- O - metyldopa (3- OMD) via en inhibering af COMT- enzymet.
Entacapone decreases the metabolic loss of levodopa to 3- O-methyldopa (3-OMD) by inhibiting the COMT enzyme.
Dermed forlænger entakapon den kliniske effekt af levodopa.
Entacapone thus prolongs the clinical response to levodopa.
Entakapon inhiberer primært COMT- enzymet i de perifere væv.
Entacapone inhibits the COMT enzyme mainly in peripheral tissues.
COMTinhiberingen i de røde blodlegemer følger tæt plasmakoncentrationen, hvilket indikerer den reversible natur af COMT hæmningen.
COMT inhibition in red blood cells closely follows the plasma concentrations of entacapone, thus clearly indicating the reversible nature of COMT inhibition.
Kliniske forsøg I to fase III dobbelt- blindede undersøgelser blev entakapon eller placebo givet med hver dosis af levodopa/ dopa- decarboxylasehæmmere til i alt 376 patienter med Parkinsons sygdom og end- of- dose fluktuationer.
Clinical studies In two phase III double-blind studies in a total of 376 patients with Parkinson’ s disease and end-of- dose motor fluctuations, entacapone or placebo was given with each levodopa/ dopa decarboxylase inhibitor dose.
Tabel 2.
Table 2:
Daglig ON tid (middelværdi ±SD)
Daily ON time (Mean ± SD)
Undersøgelse I:
Study I:
Daglig ON tid (timer) Baseline
Daily On time (h) Baseline
Uge 8- 24
Week 8-24
1 t 20 min 8, 3% CI95%, 45 min, 1 t 56 min
1 h 20 min (8.3%) CI95% 45 min, 1 h 56
II:
Study II:
Daglig ON tid (%)
Proportion of daily On time (%) Baseline
62, 8±16, 8
62.8±16.80
4, 5% (0 t 35 min) CI95%, 0, 93%; 7, 97%
4.5% (0 h 35 min) CI95% 0.93%, 7.97%
Den% - vise ændring fra baseline i OFF tid var – 24% i entakapongruppen og 0% i placebogruppen i undersøgelse I.
The% change from baseline in OFF time was – 24% in the entacapone group and 0% in the placebo group in study I.
De tilsvarende resultater er – 18% og – 5% for undersøgelse II.
The corresponding figures in study II were – 18% and – 5%.
Generelle karakteristika af det aktive indholdsstof Absorption Der er store intra - og inter- individuelle variationer i absorptionen af entakapon.
General characteristics of the active substance Absorption There are large intra- and interindividual variations in the absorption of entacapone.
1 time efter indtagelse af en 200 mg entakapon tablet.
The peak concentration (Cmax) in plasma is usually reached about one hour after ingestion of a 200 mg entacapone tablet.
Biotilgængeligheden er ca.
The substance is subject to extensive first-pass metabolism.
35% efter en oral dosering.
The bioavailability of entacapone is about 35% after an oral dose.
Fødeindtagelse ændrer ikke signifikant absorptionen af entakapon.
Food does not affect the absorption of entacapone to any significant extent.