natgillin/translations-raw huggingface dataset:
Animal studies have shown that pramipexole inhibits dopamine synthesis, release, and turnover.
Datorită posibilelor efecte
In human volunteers, a dose-dependent decrease in prolactin was observed.
aditive, se recomandă
Clinical trials in Parkinson’ s disease
prudenţîn cazul în care pacienţ sunt trataţ ă ii
In patients pramipexole alleviates signs and symptoms of idiopathic Parkinson 's disease.
i concomitent cu alte medicamente
Controlled clinical trials included approximately 2100 patients of Hoehn and Yahr stages I – IV.
4. 8)
Out of these, approximately 900 were in more advanced stages, received concomitant levodopa therapy, and suffered from motor complications.
Dependenţ patologică jocurile de noroc, creş
In open continuation trials lasting for more than three years there were no signs of decreasing efficacy.
terea libidoului şhipersexualitatea au fost raportate i
The overall incidence of hallucinations and somnolence was generally higher in the escalation phase with the pramipexole group.
În plus,
However there was no significant difference during the maintenance phase.
pacienţ şpersonalul medical trebuie să conş i de faptul că să
These points should be considered when initiating pramipexole treatment in patients with Parkinson´s disease.
pot apară
5.2 Pharmacokinetic properties
modifică de ri
Pramipexole is rapidly and completely absorbed following oral administration.
comportament.
High brain tissue concentrations were observed in the rat (approx.
Trebuie luată considerare micş reducerea progresivă
8-fold compared to plasma).
dozei. a
Pramipexole is metabolised in man only to a small extent.
orarea dozei / întreruperea tratamentului prin
The elimination half-life (t½) varies from 8 hours in the young to 12 hours in the elderly.
Pacienţ cu tulbură psihotice trebuie trataţ agoniş dopaminergici numai dacă
15 5.3 Preclinical safety data
ii
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.
ri
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.
i cu
The potential effects of pramipexole on reproductive function have been investigated in rats and rabbits.
ti
Pramipexole was not genotoxic.
beneficiile
This finding is not clinically relevant to man.
anticipate sunt mai mari decât riscurile potenţiale.
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.
4. 5).
6.
de
6.1 List of excipients
i
Mannitol Maize starch Pregelatinised maize starch Povidone K25 Colloidal anhydrous silica Magnesium stearate
Se recomandăconsult oftalmologic la intervale regulate sau dacăapar tulbură de vedere. ri
6.2 Incompatibilities
În cazul existenţ bolilor cardiovasculare severe, se recomandă
Not applicable.
prudenţ Se recomandă ă.
6.3 Shelf life
monitorizarea
2 years.
4. 2). a
6.4 Special precautions for storage
Datele din literaturăindicăfaptul căîn cazul altei indicaţ tratamentul cu medicamente
Store in the original package in order to protect from light.
dopaminergice poate conduce la exacerbarea acesteia.
6.5 Nature and contents of container
area
Blister pack (Al/ Al foil):
simptomelor seara mai devreme (sau chiar după
20, 30, 60, 90 or 100 tablets.
amiaza), la accentuarea simptomelor şla
Not all pack sizes may be marketed.
extinderea i
6.6 Special precautions for disposal
simptomelor spre alte extremită În studiile clinice controlate nu s- a evaluat frecvenţexacerbă
Any unused product or waste material should be disposed of in accordance with local requirements.
după administrare prelungită pramipexolului şgestionarea corespunză
16 7.
i
MARKETING AUTHORISATION HOLDER
toare a acestor evenimente.
KRKA, d. d., Novo mesto, Š marješ cesta 6, 8501 Novo mesto, Slovenia ka
4. 5 Interacţ cu alte medicamente şalte forme de interacţ
8.
iune
20 tablets:
La om, pramipexolul se leagă proteinele plasmatice într- o proporţ foarte mică 20%),
EU/ 1/ 08/ 469/ 007 60 tablets:
biotransformarea fiind redusăDe aceea, sunt improbabile interacţ cu alte medicamente care
EU/ 1/ 08/ 469/ 008 90 tablets:
afectează legarea de proteinele plasmatice sau eliminarea prin biotransformare.
EU/ 1/ 08/ 469/ 010
Nu existăinteracţiuni farmacocinetice cu selegilina sau cu levodopa.
DATE OF FIRST AUTHORISATION/ RENEWAL OF THE AUTHORISATION
Cimetidina reduce clearance- ul renal al pramipexolului cu aproximativ 34%, probabil datorită
12/ 9/ 2008
inhibă rii
10.
sau
DATE OF REVISION OF THE TEXT
cale, cum sunt cimetidina şi
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu/.
În cazul administră concomitente a acestor medicamente, trebuie avută vedere reducerea dozei de pramipexol.
17 1.
fie
NAME OF THE MEDICINAL PRODUCT
inutăconstantă perioada în care în
Oprymea 0.35 mg tablets
doza de Oprymea este crescută.
2.
ă
Each tablet contains 0.35 mg pramipexole base (as 0.5 mg pramipexole dihydrochloride monohydrate).
ii
Please note:
i cu
Pramipexole doses as published in the literature refer to the salt form.
medicamente sedative sau consumă uturi alcoolice în timpul tratamentului cu pramipexol. bă
Therefore, doses will be expressed in terms of both pramipexole base and pramipexole salt (in brackets).
Trebuie evitatăadministrarea concomitentă medicamente antipsihotice şpramipexol (vezi pct.
For a full list of excipients, see section 6.1.
4. 4), de exemplu dacăsunt de aşteptat efecte antagoniste.
PHARMACEUTICAL FORM
4. 6 Sarcina şală
Tablet.
ptarea
0.35 mg: white, oval, with bevelled edges, both sides scored, with imprint "P8" on both halves of one side of the tablet.
Efectul asupra sarcinii şală rii nu a fost investigat la om.
The tablet can be divided into equal halves.
Pramipexolul nu a demonstrat potenţ
4.
ial
4.1 Therapeutic indications
teratogen la ş obolan şiepure, dar s- a dovedit embriotoxic la ş
Oprymea is indicated for treatment of the signs and symptoms of idiopathic Parkinson's disease, alone (without levodopa) or in combination with levodopa, i. e. over the course of the disease, through to late stages when the effect of levodopa wears off or becomes inconsistent and fluctuations of the therapeutic effect occur (end of dose or “ on off” fluctuations).
i
4.2 Posology and method of administration
obolan în doze materno- toxice (vezi
The daily dosage is administered in equally divided doses 3 times a day.
În timpul sarcinii Oprymea trebuie administrat numai dacăeste absolut necesar, dacă beneficiile anticipate justificăriscurile potenţ pentru fă
Initial treatment Dosages should be increased gradually from a starting-dose of 0.264 mg of base (0.375 mg of salt) per day and then increased every 5 - 7 days.
Deoarece Oprymea inhibă Oprymea în laptele matern
Providing patients do not experience intolerable side-effects, the dosage should be titrated to achieve a maximal therapeutic effect.
La ş
Ascending – Dose Schedule of OPRYMEA Week
ia
Dosage (mg of base)
la
Total Daily Dose (mg of base)
obolan, concentraţ de substanţactivă ia ă
Dosage (mg of salt)
marcatăradioactiv a fost mai mare în lapte decât în plasmăÎn absenţdatelor disponibile la om,
Total Daily Dose (mg of salt)
.
1 2 3
a
3 x 0.088 3 x 0.18 3 x 0.35
Oprymea nu trebuie administrată perioada ală rii.
0.264 0.54 1.1
ptă
3 x 0.125 3 x 0.25 3 x 0.5
i,
0.375 0.75 1.50
tratamentul este absolut necesar, se
If a further dose increase is necessary the daily dose should be increased by 0.54 mg base (0.75 mg salt) at weekly intervals up to a maximum dose of 3.3 mg of base (4.5 mg of salt) per day.
4. 7 Efecte asupra capacităii de a conduce vehicule şde a folosi utilaje
18 However, it should be noted that the incidence of somnolence is increased at doses higher than 1.5 mg/ day (see section 4.8).
Oprymea poate avea o influenţmajoră Pot să apară halucinaţ şsomnolenţ
During dose escalation in three pivotal studies, efficacy was observed starting at a daily dose of 1.1 mg of base (1.5 mg of salt).
asupra capacităii de a conduce vehicule şde a folosi utilaje. ţ i
Further dose adjustments should be done based on the clinical response and the occurrence of adverse reactions.
ă.
In clinical trials approximately 5% of patients were treated at doses below 1.1 mg (1.5 mg of salt).
Pacienţ aflaţ tratament cu Oprymea şcare prezintă
In advanced Parkinson’ s disease, doses higher than 1.1 mg (1.5 mg of salt) per day can be useful in patients where a reduction of the levodopa therapy is intended.
ii
Thereafter the dose should be reduced by 0.264 mg of base (0.375 mg of salt) per day (see section 4.4).
i în i somnolenţşă i/ sau episoade de so
The following dosage schedule is suggested for initiation of therapy:
somnolenţşă i/ sau episoade de somn cu
Patients with a creatinine clearance above 50 ml/ min require no reduction in daily dose.
instalare bruscă trebuie sfă i să conducă
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).
tuiţ nu
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.
vehicule şsă se angajeze în activită (de exemplu, i nu ţi
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%.
afectarea atenţ ar iei
90% of absorbed active substance is excreted through the kidneys.
putea să pună ei sau pe persoanele din jur în - i pe
However, the potential influence of hepatic insufficiency on Oprymea pharmacokinetics has not been investigated.
4. 4, 4. 5 ş4. 8). i i
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.
când aceste episoade recurente sau somnolenţnu dispar a
4.3 Contraindications
4. 8 Reacţ adverse ii
Hypersensitivity to the active substance or to any of the excipients.
În cazul administră de Oprymea sunt de aş
4.4 Special warnings and precautions for use
toarele reacţ adverse: vise neobiş ii
19 When prescribing Oprymea in a patient with Parkinson’ s disease with renal impairment a reduced dose is suggested in line with section 4.2.
confuzie, constipaţ delir, ameţ dischinezie, obosealăhalucinaţ cefalee, hiperchinezie,
Hallucinations are known as a side-effect of treatment with dopamine agonists and levodopa.
hipotensiune arterialăcreş
Patients should be informed that (mostly visual) hallucinations can occur.
terea apetitului alimentar (hiperfagie), insomnie, tulbură de libidou, ri
In advanced Parkinson’ s disease, in combination treatment with levodopa, dyskinesias can occur during the initial titration of Oprymea.
greaţ edem periferic, paranoia; dependenţpatologică jocuri de noroc, hipersexualitate şalt
If they occur, the dose of levodopa should be decreased.
comportament anormal, somnolenţ creş
Sudden onset of sleep during daily activities, in some cases without awareness or warning signs, has been reported uncommonly.
terea greută somn cu instalare bruscăprurit şerupţ ţ
Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with Oprymea.
ie
Furthermore a reduction of dosage or termination of therapy may be considered.
cutanată i alte manifestă de hipersensibilitate.
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).
ri
Pathological gambling, increased libido and hypersexuality have been reported in patients treated with dopamine agonists for Parkinson’ s disease, including pramipexole.
Din analiza datelor obţinute din studiile clinice controlate cu placebo, cuprinzând un număde 1923 r pacienţi trataţ pramipexol ş1354 pacienţcă li s- a administrat placebo, a rezultat că fost
Furthermore, patients and caregivers should be aware of the fact that behavioural changes can occur.
raportate frecvent reacţ adverse pentru ambele grupuri.
Dose reduction/ taper or discontinuation should be considered.
63% dintre pacienţ că li s- a administrat
Patients with psychotic disorders should only be treated with dopamine agonists if the potential benefits outweigh the risks.
pramipexol ş52% dintre pacienţ că li s- a administrat placebo au raportat cel puţ o reacţ adversă.
Coadministration of antipsychotic medicinal products with pramipexole should be avoided (see section 4.5).
Cele mai frecvente (≥ 5%) reacţ adverse raportate la pacienţ cu boală
Ophthalmologic monitoring is recommended at regular intervals or if vision abnormalities occur.
ii ii
In case of severe cardiovascular disease, care should be taken.
Parkinson, mai frecvente în
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.
cazul celor trataţ pramipexol decât cu placebo, au fost greaţ, dischinezie, hipotensiune arterială
Symptoms suggestive of neuroleptic malignant syndrome have been reported with abrupt withdrawal of dopaminergic therapy (see section 4.2)
,
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.
ameţ somnolenţ insomnie, constipaţ halucinaţ cefalee şobosealăIncidenţsomnolenţ este
The frequency of augmentation after longer use of pramipexole and the appropriate management of these events have not been evaluated in controlled clinical trials.
a
4.5 Interaction with other medicinal products and other forms of interaction
ei
Pramipexole is bound to plasma proteins to a very low (< 20%) extent, and little biotransformation is seen in man.
crescută doze mai mari de 1, 5 mg/ zi (vezi pct. 4. 2).
There is no pharmacokinetic interaction with selegiline and levodopa.
Reacţ adverse mai frecvente în cazul asocierii
20 Cimetidine reduced the renal clearance of pramipexole by approximately 34%, presumably by inhibition of the cationic secretory transport system of the renal tubules.
La începutul tratamentului poate săapară hipotensiune arterialăîn, special dacă doza de pramipexol este crescută prea repede.
Reduction of the pramipexole dose should be considered when these medicinal products are administered concomitantly.
13 Cele mai frecvente (≥5%) reacţ adverse raportate la pacienţ trataţ pramipexol pentru altă
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.
i cu
Because of possible additive effects, caution should be advised when patients are taking other sedating medicinal products or alcohol in combination with pramipexole.
indicaţ au fost greaţ cefalee, ameţ şobosealăGreaţşoboseala au fost raportate mai des la
Coadministration of antipsychotic medicinal products with pramipexole should be avoided (see section 4.4), e. g. if antagonistic effects can be expected.
pacienţ de sex feminin (20, 8% şrespectiv 10, 5%) comparativ cu bă ii (6, 7% şrespectiv 7, 3%)
4.6 Pregnancy and lactation
Tabelele 1 ş2 prezintă
The effect on pregnancy and lactation has not been investigated in humans.
frecvenţreacţ adverse la medicament înregistrată studiile clinice a iilor în
The excretion of pramipexole into breast milk has not been studied in women.
controlate cu placebo.
In rats, the concentration of active substance-related radioactivity was higher in breast milk than in plasma.
Reacţ adverse la medicament raportate în aceste tabele sunt acele iile evenimente care s- au manifestat la 1% sau la mai mulţ
In the absence of human data, Oprymea should not be used during breast-feeding.
pramipexol şacestea au fost i cu i
However, if its use is unavoidable, breast-feeding should be discontinued.
raportate semnificativ mai frecvent la pacienţ care au luat pramipexol faţde placebo, sau când
4.7 Effects on ability to drive and use machines
ă
Oprymea can have a major influence on the ability to drive and use machines.
evenimentul a fost considerat relevant clinic. medicament au fost uş până moderate, au apă de
Hallucinations or somnolence can occur.
Însămajoritatea reacţ, obicei la iniţ
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).
adverse iilor
4.8 Undesirable effects
frecvente la
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.
avut tendinţsă
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.
oare
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,
la
21 dizziness, somnolence, insomnia, constipation, hallucination, headache and fatigue.
rut
The most commonly (≥
ierea tratamentului
5%) reported adverse drug reactions in patients with other indication treated
a dispară
with pramipexole were nausea, headache, dizziness and fatigue.
chiar în cazul continuă
Tables 1 and 2 display the frequency of adverse reactions from placebo-controlled clinical trials.
acsetuia. rii
Dizziness Dyskinesia
ale sistemului nervos ri
22 There is no clinical experience with massive overdose.
Nu există experienţclinică ceea ce priveş supradozajul masiv.
There is no established antidote for overdose of a dopamine agonist.
Dacă
If signs of central nervous system stimulation are present, a neuroleptic agent may be indicated.
Tratarea supradozajului poate necesita mă suri
Management of the overdose may require general supportive measures, along with gastric lavage, intravenous fluids, administration of activated charcoal and electrocardiogram monitoring.
14 generale de susţ inere, lavaj gastric, administrare intravenoasă lichide, administrare de că activat
5.1 Pharmacodynamic properties
5. 1 Proprietăi farmacodinamice ţ
Approximately 90% of 14 C-labelled dose is excreted through the kidneys while less than 2% is found in the faeces.
doza marcată 14C este eliminată cale renalăîn timp ce mai puţ de 2% se regă te în materiile
The total
seş
23 clearance of pramipexole is approximately 500 ml/ min and the renal clearance is approximately 400 ml/ min.
Clearance- ul total al pramipexolului este de aproximativ 500 ml/ min, iar clearance- ul renal de aproximativ 400 ml/ min.
5.3 Preclinical safety data
15 5. 3 Date preclinice de siguranţ ă
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.
Studii de toxicitate după doze repetate au ară că tat pramipexolul prezintăefecte funcţ ionale, afectând mai ales SNC şfuncţ de reproducere la femele, datorate probabil exageră efectelor
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.
La cobai a fost observată derea tensiunii arteriale diastolice şsistolice şa frecvenţ cardiace, iar
The potential effects of pramipexole on reproductive function have been investigated in rats and rabbits.
la maimuţs- a observat o tendinţla efecte hipotensive.
Pramipexole was not teratogenic in rats and rabbits but was embryotoxic in the rat at maternally toxic doses.
La ş obolan şiepure au fost studiate efectele potenţ ale pramipexolului asupra funcţ de
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.
Pramipexolul nu a demonstrat efecte teratogene la ş obolan şiepure, dar a manifestat i efecte embriotoxice la ş obolan, la doze materno- toxice.
Mannitol Maize starch Pregelatinised maize starch Povidone K25 Colloidal anhydrous silica Magnesium stearate
Manitol Amidon de porumb Amidon de porumb pregelatinizat Povidonă
24 Any unused product or waste material should be disposed of in accordance with local requirements.
Fă cerinţ speciale. ră e
MARKETING AUTHORISATION HOLDER
DEŢINĂTORUL AUTORIZAŢ DE PUNERE PE PIAŢ
MARKETING AUTHORISATION NUMBER(S)
NUMĂRUL AUTORIZAŢ DE PUNERE PE PIAŢ
EU/ 1/ 08/ 469/ 011 30 tablets:
EU/ 1/ 08/ 469/ 006 30 comprimate:
EU/ 1/ 08/ 469/ 012 60 tablets:
EU/ 1/ 08/ 469/ 007 60 comprimate:
EU/ 1/ 08/ 469/ 013 90 tablets:
EU/ 1/ 08/ 469/ 008 90 comprimate:
EU/ 1/ 08/ 469/ 014 100 tablets:
EU/ 1/ 08/ 469/ 009 100 comprimate:
EU/ 1/ 08/ 469/ 015
EU/ 1/ 08/ 469/ 010
25 1.
17 1.
Oprymea 0.7 mg tablets
Oprymea 0, 35 mg comprimate
Each tablet contains 0.7 mg pramipexole base (as 1 mg pramipexole dihydrochloride monohydrate).
Fiecare comprimat conţ pramipexol bază monohidrat 0, 5 mg).
0.70 mg: white, round, with bevelled edges, both sides scored, with imprint "P9" on both halves of one side of the tablet.
0, 35 mg: comprimate de culoare albăovale, cu margini teş cu linie mediană ambele feţ
26 However, it should be noted that the incidence of somnolence is increased at doses higher than 1.5 mg/ day (see section 4.8).
ionat căincidenţ somnolenţ creş la doze mai mari de 1, 5 mg pe zi (vezi pct. a ei te
In patients with a creatinine clearance less than 20 ml/ min, the daily dose of Oprymea shou ld be administered in a single dose, starting at 0.088 mg of base (0.125 mg of salt) daily.
La pacienţ cu clearance al creatininei sub 20 ml/ min, doza zilnică Oprymea se administrează
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.
Oprymea nu este recomandat pentru utilizare la copii şadolescenţ vârsta sub 18 ani, datorită datelor privind siguranţşeficacitatea. ai
4.3 Contraindications
4. 3 Contraindicaţ ii
Hypersensitivity to the active substance or to any of the excipients.
Hipersensibilitate la substanţ activă la oricare dintre excipienţ medicamentului.
4.4 Special warnings and precautions for use
4. 4 Atenţ ri speciale şprecauţ pentru utilizare
27 When prescribing Oprymea in a patient with Parkinson’ s disease with renal impairment a reduced dose is suggested in line with section 4.2.
şinsuficienţrenală recomandă i ă se reducerea dozei de Oprymea, aş a
Hallucinations are known as a side-effect of treatment with dopamine agonists and levodopa.
Halucinaţ sunt cunoscute ca reacţ adversă tratamentul cu agoniş dopaminergici şlevodopa.
In case of severe cardiovascular disease, care should be taken.
În cazul existenţ bolilor cardiovasculare severe, se recomandă
28 that are inhibitors of this active renal elimination pathway or are eliminated by this pathway, such as cimetidine and amantadine, may interact with pramipex ole resulting in reduced clearance of either or both medicinal products.
amantadina, pot interacţ cu pramipexolul, cu reducerea clearance- ului unuia sau al ambelor iona medicamente.