natgillin/translations-raw huggingface dataset:
Therefore, pramipexole should be tapered off at a rate of 0.54 mg of base (0.75 mg of salt) per day until the daily dose has been reduced to 0.54 mg of base (0.75 mg of salt).
Zdravljenje s pramipeksolom zato ukinjamo postopoma, in sicer po 0, 54 mg (0, 75 mg soli) na dan, dokler dnevnega odmerka ne zmanjš na 0, 54 mg pramipeksola (0, 75 mg soli).
Thereafter the dose should be reduced by 0.264 mg of base (0.375 mg of salt) per day (see section 4.4).
Nato odmerek amo zmanjš ujemo po 0, 264 mg pramipeksola (0, 375 mg soli) na dan (glejte poglavje 4. 4).
Dosing in patients with renal impairment The elimination of pramipexole is dependent on renal function.
anje priporoč ljivo za zač zdravljenja. etek
The following dosage schedule is suggested for initiation of therapy:
V nadaljevanju je navedeno odmerjanje,
Patients with a creatinine clearance above 50 ml/ min require no reduction in daily dose.
Pri bolnikih s kreatininskim oč istkom več 50 ml/ min ni treba zmanjš dnevnega odmerka.
In patients with a creatinine clearance between 20 and 50 ml/ min, the initial daily dose of Oprymea should be administered in two divided doses, starting at 0.088 mg of base (0.125 mg of salt) twice a day (0.176 mg of base/ 0.25 mg of salt daily).
0, 25 mg soli).
In patients with a creatinine clearance less than 20 ml/ min, the daily dose of Oprymea should be administered in a single dose, starting at 0.088 mg of base (0.125 mg of salt) daily.
Zač nemo z 0, 088 mg pramipeksola (0, 125 mg soli).
If renal function declines during maintenance therapy reduce Oprymea daily dose by the same percentage as the decline in creatinine clearance, i. e. if creatinine clearance declines by 30%, then reduce the Oprymea daily dose by 30%.
Dnevni
The daily dose can be administered in two divided doses if creatinine clearance is between 20 and 50 ml/ min, and as a single daily dose if creatinine clearance is less than 20 ml/ min.
istek med 20 in 50 ml/ min, oziroma ga
Dosing in patients with hepatic impairment Dose adjustment in patients with hepatic failure is probably not necessary, as approx.
damo v enkratnem odmerku, č je kreatininski oč
90% of absorbed active substance is excreted through the kidneys.
Odmerjanje pri bolnikih z jetrno okvaro Pri bolnikih z jetrnim odpovedovanjem prilagoditev odmerka verjetno ni potrebna, saj se približ no 90% absorbirane zdravilne uč inkovine izločskozi ledvice.
However, the potential influence of hepatic insufficiency on Oprymea pharmacokinetics has not been investigated.
Morebitnega vpliva jetrnega i odpovedovanja na farmakokinetiko pramipeksola niso raziskovali.
Dosing in children and adolescents Oprymea is not recommended for use in children and adolescents below 18 years due to a lack of data on safety and efficacy.
Odmerjanje za otroke in mladostnike Zaradi pomanjkanja podatkov o varnosti in uč inkovitosti uporaba zdravila Oprymea pri otrocih, mlajš od 18 let, ni priporoč
Hypersensitivity to the active substance or to any of the excipients.
Preobč utljivost za zdravilno uč inkovino ali katerokoli pomož snov. no
3 When prescribing Oprymea in a patient with Parkinson’ s disease with renal impairment a reduced dose is suggested in line with section 4.2.
Bolnikom s Parkinsonovo boleznijo in ledvič okvaro predpisujemo manjš odmerke, kar je opisano v poglavju 4. 2.
Hallucinations are known as a side-effect of treatment with dopamine agonists and levodopa.
eleni uč zdravljenja z dopaminskimi agonisti in levodopo.
Patients should be informed that (mostly visual) hallucinations can occur.
Bolnike inek moramo opozoriti, da lahko pride do halucinacij (več inoma vidnih).
In advanced Parkinson’ s disease, in combination treatment with levodopa, dyskinesias can occur during the initial titration of Oprymea.
3 Pri bolnikih z napredovalo Parkinsonovo boleznijo, ki jemljejo zdravilo v kombinaciji z levodopo, se lahko med zač etnim povečevanjem odmerka pramipeksola pojavijo diskinezije.
If they occur, the dose of levodopa should be decreased.
Č se to zgodi, e zmanjš tudi odmerek levodope. amo
Pramipexole has been associated with somnolence and episodes of sudden sleep onset, particularly in patients with Parkinson’ s disease.
Pramipeksol povezujejo z zaspanostjo in nenadnimi epizodami spanja, zlasti pri bolnikih s Parkinsonovo boleznijo.
Sudden onset of sleep during daily activities, in some cases without awareness or warning signs, has been reported uncommonly.
O nenadnih epizodah spanja med dnevnimi dejavnostmi, ki se pr i nekaterih bolnikih pojavijo, ne da bi se jih zavedali ali brez opozorilnih znakov, ne poroč pogosto.
Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with Oprymea.
Bolnike je ajo treba nanje opozoriti in jim in upravljanju strojev.
Patients who have experienced somnolence and/ or an episode of sudden sleep onset must refrain from driving or operating machines.
Pri teh bolnikih moramo presoditi o zmanjš odmerka ali prekinitvi zdravljenja. anju Zaradi mož aditivnih uč
Furthermore a reduction of dosage or termination of therapy may be considered.
inkov je treba bolnikom svetovati, naj bodo previdni,
Because of possible additive effects, caution should be advised when patients are taking other sedating medication or alcohol in combination with pramipexole (see section 4.7 and section 4.8).
pramipeksolom jemljejo š druga zdravila s sedativnim uč poglavji 4. 7 in 4. 8).
Pathological gambling, increased libido and hypersexuality have been reported in patients treated with dopamine agonists for Parkinson’ s disease, including pramipexole.
Pri bolnikih, pri katerih so Parkinsonovo bolezen zdravili z dopaminskimi agonisti, tudi s pramipeksolom, so poroč o patološ hazardiranju, poveč
Furthermore, patients and caregivers should be aware of the fact that behavioural changes can occur.
Bolniki in negovalci morajo vedeti, da se lahko pojavijo vedenjske spremembe.
Dose reduction/ taper or discontinuation should be considered.
Presoditi moramo o zmanjš odmerka ali postopni ukinitvi zdravila. anju
Patients with psychotic disorders should only be treated with dopamine agonists if the potential benefits outweigh the risks.
Bolnike s psihotičnimi motnjami zdravimo z dopaminskimi agonisti samo takrat, kadar morebitna korist opravič tveganje. uje
Coadministration of antipsychotic medicinal products with pramipexole should be avoided (see section 4.5).
Soč asnemu jemanju antipsihotič zdravil in pramipeksola se je treba izogibati (glejte poglavje 4. 5). nih
Ophthalmologic monitoring is recommended at regular intervals or if vision abnormalities occur.
Priporoč so redni oftalmološ pregledi, š posebno, č se pojavijo motnje vida.
In case of severe cardiovascular disease, care shou ld be taken.
Priporoč
It is recommended to monitor blood pressure, especially at the beginning of treatment, due to the general risk of postural hypotension associated with dopaminergic therapy.
zač zdravljenja, saj je z dopaminergič zdravljenjem povezano sploš tveganje za posturalno
Symptoms suggestive of neuroleptic malignant syndrome have been reported with abrupt withdrawal of dopaminergic therapy (see section 4.2)
Pri nagli prekinitvi zdravljenja z dopaminskimi agonisti so poroč o simptomih, ki kaž na nevroleptič
Reports in the literature indicate that treatment of another indication with dopaminergic medicinal products can result in augmentation.
Iz literature je razvidno, da je okrepitev simptomov pri zdravljenju druge indikacije lahko posledica zdravljenja z dopaminergič
Augmentation refers to the earlier onset of symptoms in the evening (or even afternoon), increase in symptoms, and spread of symptoms to involve other extremities.
več ernih urah (ali celo popoldne), njihovo več intenzivnost in razš
The frequency of augmentation after longer use of pramipexole and the appropriate management of these events have not been evaluated in controlled clinical trials.
Pogostosti okrepitve simptomov po dolgotrajnejš jemanju pramipeksola in ustreznem zdravljenju em teh simptomov v nadzorovanih klinič preizkuš
Pramipexole is bound to plasma proteins to a very low (< 20%) extent, and little biotransformation is seen in man.
Na plazemske beljakovine se vež zelo malo pramipeksola (< 20%) in pri č
Therefore, interactions with other medicinal products affecting plasma protein binding or elimination by biotransformation are unlikely.
Č
As anticholinergics are mainly eliminated by biotransformation, the potential for an interaction is limited, although an interaction with anticholinergics has not been investigated.
antiholinergiki niso raziskovali, je mož nost, da bi do njih priš majhna, saj se antiholinergiki izloč
There is no pharmacokinetic interaction with selegiline and levodopa.
Farmakokinetič interakcij s selegilinom in levodopo ni. nih
Cimetidine reduced the renal clearance of pramipexole by approximately 34%, presumably by inhibition of the cationic secretory transport system of the renal tubules.
34%, verjetno z zaviranjem no
Therefore, medicinal products
tevati, da je treba zmanjš odmerek ati
4 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.
4 Č dajemo pramipeksol bolniku skupaj z levodopo, je priporoč e ljivo zmanjš odmerek levodope, ati dokler poveč ujemo odmerek pramipeksola.
Reduction of the pramipexole dose should be considered when these medicinal products are administered concomitantly.
Odmerki drugih antiparkinsonikov naj ostanejo nespremenjeni.
When Oprymea 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 Oprymea.
Bolnikom, ki jemljejo pramipeksol, zaradi mož aditivnih uč drugih sedativnih zdravil in pri soč
Because of possible additive effects, caution should be advised when patients are taking other sedating medicinal products or alcohol in combination with pramipexole.
asnem pitju alkoholnih pijač.
Coadministration of antipsychotic medicinal products with pramipexole should be avoided (see section 4.4), e. g. if antagonistic effects can be expected.
Soč asnemu jemanju antipsihotič zdravil in pramipeksola se je treba izogibati (glejte poglavje 4. 4), nih npr. kadar je prič akovan antagonistič uč ni inek.
4.6 Pregnancy and lactation
4. 6 Noseč in dojenje nost
The effect on pregnancy and lactation has not been investigated in humans.
Pri ženskah vpliva pramipeksola na noseč in dojenje niso raziskovali.
Pramipexole was not teratogenic in rats and rabbits, but was embryotoxic in the rat at maternotoxic doses (see section 5.3).
Pri podganah in zajcih ni bil nost teratogen, pri podganah je bil embriotoksič v odmerkih, toksič za samico (glejte. poglavje 5. 3).
Oprymea should not be used during pregnancy unless clearly necessary, i. e. if the potential benefit justifies the potential risk to the foetus.
Zdravljenje s pramipeksolom zavira izloč prolaktina pri č pričakovano.
As pramipexole treatment inhibits secretion of prolactin in humans, inhibition of lactation is expected.
Izloč pramipeksola v materino mleko, niso raziskovali.
The excretion of pramipexole into breast milk has not been studied in women.
Pri podganah je bila koncentracija anja radioaktivo označ zdravilne uč
In rats, the concentration of active substance-related radioactivity was higher in breast milk than in plasma.
Zaradi pomanjkanja podatkov ja
In the absence of human data, Oprymea should not be used during breast-feeding.
pramipeksola ne dajemo materam, ki dojijo.
However, if its use is unavoidable, breast-feeding should be discontinued.
Č se uporabi ne moremo izogniti, mora mati prenehati e dojiti.
4.7 Effects on ability to drive and use machines
4. 7 Vpliv na sposobnost vož in upravljanja s stroji nje
Oprymea can have a major influence on the ability to drive and use machines.
Zdravilo Oprymea pomembno vpliva na sposobnost za vož in upravljanje strojev. njo
Patients being treated with Oprymea 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).
Bolnikom, pri katerih se med zdravljenjem s pramipeksolom pojavlja zaspanost in/ ali imajo nenadne epizode spanja, je treba svetovati, naj ne vozijo in naj se ne ukvarjajo z dejavnostmi, pri katerih se zaradi poslabš budnosti poveč nevarnost resnih poš
4.8 Undesirable effects
4. 8 Než eleni uč inki
The following adverse reactions are expected under the use of Oprymea: abnormal dreams, confusion, constipation, delusion, dizziness, dyskinesia, fatigue, hallucinations, headache, hyperkinesia, hypotension, increased eating (binge eating, hyperphagia), insomnia, libido disorders, nausea, peripheral oedema, paranoia, pathological gambling, hypersexuality and other abnormal behaviour; somnolence, weight increase, sudden onset of sleep; pruritus and rash and other hypersensitivity.
Pričakovani než eleni uč med zdravljenjem s pramipeksolom so nenavadne sanje, zmedenost, inki zaprtost, blodnje, omotica, diskinezija, utrujenost, halucinacije, glavobol, hiperkinezija, hipotenzija, poveč hranjenje (kompulzivno prenajedanje, hiperfagija), nespeč
Based on the analysis of pooled placebo-controlled trials, comprising a total of 1,923 patients on pramipexole and 1,354 patients on placebo, adverse drug reactions were frequently reported for both groups.
Vsaj o enem než
63% of patients on pramipexole and 52% of patients on placebo reported at least one adverse drug reaction.
bolnikov, ki so se zdravili s pramipeksolom, in 52% bolnikov, ki so jemali placebo.
The most commonly (≥ reported adverse reactions in patients with Parkinson’ s disease more 5%) frequent with pramipexole treatment than with placebo were nausea, dyskinesia, hypotension, dizziness, somnolence, insomnia, constipation, hallucination, headache and fatigue.
bili med zdravljenjem s pramipeksolom pogostejškot med jemanjem placeba, so bili slabost, i diskinezija, hipotenzija, omotica, zaspanost, nespečnost, zaprtost, halucinacije, glavobol in utrujenost.
The incidence of somnolence is increased at doses higher than 1.5 mg/ day (see section 4.2).
Pri bolnikih,
More frequent adverse drug
eleni uč diskinezija. inek
5 reaction in combination with levodopa was dyskinesia.
5
The most commonly (≥
Najpogostejšnež
5%) reported adverse drug reactions in patients with other indication treated
eleni uč (≥5%), o katerih so poroč pri bolnikih z drugo indikacijo, ki so se inki ali
with pramipexole were nausea, headache, dizziness and fatigue.
zdravili s pramipeksolom, so bili slabost, glavobol, omotica in utrujenost.
Nausea and fatigue were more often reported in female patients (20.8% and 10.5%, respectively) compared to males (6.7% and 7.3%, respectively).
O slabosti in utrujenosti so med zdravljenjem s pramipeksolom pogosteje poroč pri ž in 10, 5%) kot pri moš (6, 7% in 7, 3%). kih
Tables 1 and 2 display the frequency of adverse reactions from placebo-controlled clinical trials.
Preglednici 1 in 2 kaž pogostost než
The adverse reactions reported in these tables are those events that occurred in 1% or more of patients treated with pramipexole and were reported significantly more often in patients taking pramipexole than placebo, or where the event was considered clinically relevant.
Pogosti než eleni uč so bili več
However, the majority of common adverse reactions were mild to moderate, they usually start early in therapy, and most tended to disappear even as therapy was continued.
zgodnjem obdobju zdravljenja in več jih je minila, č
Very common Adverse Reactions (≥ 1/ 10) System organ class
uč (≥1/ 10) inki
Adverse reaction
Neželeni uč inek
Pramipexole N= 1,923 (%)
Pramipeksol N = 1. 923 (%)
Nervous system disorders
ivč
Dizziness Dyskinesia
omotica diskinezija
Nausea Hypotension
bolezni prebavil ž bolezni
17.2 12.6
slabost
Common Adverse Reactions (≥ 1/ 100 to < 1/ 10) System organ class
eleni uč (≥1/ 100 do < 1/ 10) inki Organski sistem psihiatrič motnje
Psychiatric disorders
ne bolezni ž evja
Abnormal dreams Confusional state Hallucinations Insomnia
nenormalne sanje zmedenost halucinacije nespeč nost
Somnolence Headache
zaspanost glavobol
Gastrointestinal disorders
bolezni prebavil sploš tež in spremembe na
Constipation
zaprtost
General disorders and administration site conditions
utrujenost periferni edem
Fatigue
6, 1 1, 9
Peripheral oedema
anje
1.9
anje
Pramipexole is associated with somnolence (8.6%) and has been associated uncommonly with excessive daytime somnolence and sudden sleep onset episodes (0.1%).
Pri bolnikih, ki so se z dopaminskimi agonisti zdravili zaradi Parkinsonove bolezni, so poroč o ali patološ hazardiranju, poveč
See also section 4.4.
anem libidu in hiperseksualnosti.
Pramipexole may be associated with libido disorders (increased (0.1%) or decreased (0.4%)).
ali ukinitvi zdravila izginili.
Patients treated with dopamine agonists for Parkinson’ s disease, including pramipexole, especially at high doses, have been reported as exhibiting signs of pathological gambling, increase libido and hypersexuality, generally reversible upon treatment discontinuation.
nih
4.9 Overdose
enj.
There is no clinical experience with massive overdose.
akovani než eleni učinki, vključ s no
The expected adverse events would be those related to the pharmacodynamic profile of a dopamine agonist, including nausea, vomiting, hyperkinesia, hallucinations, agitation and hypotension.
slabostjo, bruhanjem, hiperkinezijo, halucinacijami, agitacijo in hipotenzijo, bi morali biti povezani s farmakodinamič nimi lastnostmi dopaminskih agonistov.
There is no established antidote for overdose 6 of a dopamine agonist.
Za preveliko odmerjanje dopaminskih agonistov ni uveljavljenega antidota.
If signs of central nervous system stimulation are present, a neuroleptic agent may be indicated.
Zdravljenje prevelikega odmerjanja lahko ob izpiranju ž
Management of the overdose may require general supportive measures, along with gastric lavage, intravenous fluids, administration of activated charcoal and electrocardiogram monitoring.
dajanju intravenskih tekoč in aktivnega oglja ter spremljanju elektrokardiograma zahteva sploš podporne ukrepe.
PHARMACOLOGICAL PROPERTIES
FARMAKOLOŠ LASTNOSTI KE
5.1 Pharmacodynamic properties
5. 1 Farmakodinamič lastnosti ne
Pharmacotherapeutic group: dopamine agonists, ATC code:
Farmakoterapevtska skupina: agonisti dopamina, oznaka ATC:
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 D 3 receptors, and has full intrinsic activity.
Pramipeksol je dopaminski agonist s polno intrinzič aktivnostjo, katerega vezava na podskupino no dopaminskih receptorjev D2, med katerimi ima preferenč afiniteto za receptorje D3, je visoko no selektivna in specifična.
Pramipexole alleviates Parkinsonian motor deficits by stimulation of dopamine receptors in the striatum.
Pramipeksol spodbuja dopaminske receptorje v striatumu in s tem bla žmotorič motnje pri
Animal studies have shown that pramipexole inhibits dopamine synthesis, release, and turnover.
Poskusi na ž ivalih so pokazali, da pramipeksol zavira sintezo, sprošanje in č hitrost izrabe ("turnover") dopamina.
In human volunteers, a dose-dependent decrease in prolactin was observed.
Pri prostovoljcih so opazili od odmerka odvisno zmanjš vrednosti prolaktina. ane
Clinical trials in Parkinson’ s disease
Klinič preizkuš pri Parkinsonovi bolezni
In patients pramipexole alleviates signs and symptoms of idiopathic Parkinson 's disease.
V kontrolirana klinič
Controlled clinical trials included approximately 2100 patients of Hoehn and Yahr stages I – IV.
Približ
Out of these, approximately 900 were in more advanced stages, received concomitant levodopa therapy, and suffered from motor complications.
900 z bolj napredovalimi stadiji jih je soč jemalo levodopo in so trpeli zaradi motori č zapletov.
In early and advanced Parkinson’ s disease, efficacy of pramipexole in the controlled clinical trials was maintained for approximately six months.
anjih je uč pramipeksola pri bolnikih z zgodnjo in napredovalo inek
In open continuation trials lasting for more than three years there were no signs of decreasing efficacy.
Tudi v odprtih nadaljevalnih preizkuš
In a controlled double blind clinical trial of 2 year duration, initial treatment with pramipexole significantly delayed the onset of motor complications, and reduced their occurrence compared to initial treatment with levodopa.
Presoditi je treba, ali so zakasneli motorič
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).
levodopo (izmerjeno s srednjo spremembo pri klinič nevrološ preiskavi za bolnike s Parkinsonovo
The overall incidence of hallucinations and somnolence was generally higher in the escalation phase with the pramipexole group.
V vzdrž
However there was no significant difference during the maintenance phase.
Omenjene ugotovitve je treba upoš
These points should be considered when initiating pramipexole treatment in patients with Parkinson´s disease.
pramipeksolom pri bolnikih s Parkinsonovo boleznijo.
5.2 Pharmacokinetic properties
5. 2 Farmakokinetič lastnosti ne
The absolute bioavailability is greater than 90% and the maximum plasma concentrations occur between 1 and 3 hours.
Soč
Concomitant administration with food did not reduce the extent of pramipexole absorption, but the rate of absorption was reduced.
Pramipeksol kaž
Pramipexole shows linear kinetics and a small inter-patient variation of plasma levels.
linearno kinetiko in majhna odstopanja vrednosti plazemskih koncentracij med bolniki.
In humans, the protein binding of pramipexole is very low (< 20%) and the volume of distribution is large (400 l).
Pri ljudeh je vezava pramipeksola na beljakovine zelo majhna (< 20%), volumen porazdelitve pa je velik (400 l).
High brain tissue concentrations were observed in the rat (approx.
Pri podganah so opazili visoke koncentracije v mož ganskih tkivih (približ 8- krat več kot v plazmi).
8-fold compared to plasma).
Pramipeksol se pri ljudeh presnavlja le v manjšmeri. i
Pramipexole is metabolised in man only to a small extent.
Pramipeksol se izločv glavnem nespremenjen skozi ledvice.
Renal excretion of unchanged pramipexole is the major route of elimination.
Skupni oč
Approximately 90% of 14 C-labelled dose is excreted through the kidneys while less than 2% is found in the faeces.
pramipeksola je približ 500 ml/ min, ledvič oč
The total clearance of pramipexole is approximately 500 ml/ min and the renal clearance is approximately 400 ml/ min.
Razpolovni č no
The elimination half-life (t½) varies from 8 hours in the young to 12 hours in the elderly.
(t1/ 2) izloč se giblje od 8 ur pri mladih do 12 ur pri starejš ljudeh.
7 5.3 Preclinical safety data
7 Pri pritlikavih praš ih so opazili zniž diastolič
Repeated dose toxicity studies showed that pramipexole exerted functional effects, mainly involving the CNS and female reproductive system, and probably resulting from an exaggerated pharmacodynamic effect of pramipexole.
anje
Decreases in diastolic and systolic pressure and heart rate were noted in the mini pig, and a tendency to an hypotensive effect was discerned in the monkey.
nega in sistolič nega tlaka ter zmanjš srč anje nega
The potential effects of pramipexole on reproductive function have been investigated in rats and rabbits.
Morebitne uč pramipeksola na rodila so raziskovali pri podganah in zajcih.
Pramipexole was not teratogenic in rats and rabbits but was embryotoxic in the rat at maternally toxic doses.
ivalskih vrst in omejenih raziskovanih parametrov než eleni učinki
Due to the selection of animal species and the limited parameters investigated, the adverse effects of pramipexole on pregnancy and male fertility have not been fully elucidated.
pramipeksola na noseč in na plodnost samcev niso bili v celoti pojasnjeni. nost