natgillin/translations-raw huggingface dataset:
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.
libidoului şhipersexualitate, în general reversibile la reducerea dozei sau întreruperea tratamentului. i
There is no clinical experience with massive overdose.
Nu există experienţclinică ceea ce priveş supradozajul masiv.
The expected adverse events would be those related to the pharmacodynamic profile of a dopamine agonist, including nausea, vomiting, hyperkinesia, hallucinations, agitation and hypotension.
vă turi, hiperkinezie, halucinaţ agitaţ şhipotensiune arterialăNu este stabilit un antidot pentru
There is no established antidote for overdose 6 of a dopamine agonist.
Dacă
If signs of central nervous system stimulation are present, a neuroleptic agent may be indicated.
se poate recomanda administrarea unui neuroleptic.
Management of the overdose may require general supportive measures, along with gastric lavage, intravenous fluids, administration of activated charcoal and electrocardiogram monitoring.
Tratarea supradozajului poate necesita mă generale de susţ inere, lavaj gastric, administrare intravenoasă lichide, administrare de că
PHARMACOLOGICAL PROPERTIES
PROPRIETĂ I FARMACOLOGICE Ţ
5.1 Pharmacodynamic properties
6 5. 1 Proprietăi farmacodinamice ţ
Pharmacotherapeutic group: dopamine agonists, ATC code:
Codul 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.
subfamilia D2 a receptorilor pentru dopaminăavând o afinitate preponderentă activitate intrinsecă totală.
Pramipexole alleviates Parkinsonian motor deficits by stimulation of dopamine receptors in the striatum.
dopaminergici din nucleul striat.
Animal studies have shown that pramipexole inhibits dopamine synthesis, release, and turnover.
Studiile la animale de laborator demonstrează pramipexolul inhibă că sinteza, eliberarea şturnover- ul dopaminei. i
In human volunteers, a dose-dependent decrease in prolactin was observed.
În studiile la voluntari, a fost observatădiminuarea secreţ de prolactină
Clinical trials in Parkinson’ s disease
Studii clinice în boala Parkinson La pacienţ pramipexolul ameliorează
In patients pramipexole alleviates signs and symptoms of idiopathic Parkinson 's disease.
Parkinson.
Controlled clinical trials included approximately 2100 patients of Hoehn and Yahr stages I – IV.
Studiile clinice controlate au inclus aproximativ 2100 pacienţaflaţ stadiile Hoehn şYahr I- IV de
Out of these, approximately 900 were in more advanced stages, received concomitant levodopa therapy, and suffered from motor complications.
boalăDintre aceş aproximativ 900 se aflau în stadii avansate de boalăprimind tratament
In early and advanced Parkinson’ s disease, efficacy of pramipexole in the controlled clinical trials was maintained for approximately six months.
Parkinson, eficacitatea pramipexolului în studiile clinice
In open continuation trials lasting for more than three years there were no signs of decreasing efficacy.
În studiile clinice deschise care au continuat timp de peste 3 ani, nu au fost înregistrate semne de diminuare ale eficacităii terapeutice.
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.
Într- un ţ studiu controlat, dublu orb, cu o durată 2 ani, tratamentul iniţ cu pramipexol a întârziat în mod
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).
balanţcu ameliorarea mai bună funcţ motorii înregistrată cazul levodopa (mă
The overall incidence of hallucinations and somnolence was generally higher in the escalation phase with the pramipexole group.
Incidenţ generală halucinaţ şsomnolenţ a fost, în
However there was no significant difference during the maintenance phase.
general, mai mare în faza de creş a dozelor la grupul cu pramipexol.
These points should be considered when initiating pramipexole treatment in patients with Parkinson´s disease.
când trebuie luată decizia de a începe tratamentul cu pramipexol la pacienţ cu boală
5.2 Pharmacokinetic properties
Proprietăi farmacocinetice ţ
Pramipexole is rapidly and completely absorbed following oral administration.
După administrarea oralăpramipexolul este absorbit rapid şcomplet.
The absolute bioavailability is greater than 90% and the maximum plasma concentrations occur between 1 and 3 hours.
Biodisponibilitatea absolută este mai mare de 90%, iar
Concomitant administration with food did not reduce the extent of pramipexole absorption, but the rate of absorption was reduced.
Administrarea în timpul meselor nu reduce gradul de absorbţ a pramipexolului, ci doar ie viteza acesteia.
Pramipexole shows linear kinetics and a small inter-patient variation of plasma levels.
interindividual.
In humans, the protein binding of pramipexole is very low (< 20%) and the volume of distribution is large (400 l).
La ş
High brain tissue concentrations were observed in the rat (approx.
obolan au fost observate concentraţ mari în ţ ii esutul cerebral
8-fold compared to plasma).
(de aproximativ 8 ori mai mari decât cele plasmatice).
Pramipexole is metabolised in man only to a small extent.
La om, pramipexolul este metabolizat numai în mică sură mă.
Renal excretion of unchanged pramipexole is the major route of elimination.
Aproximativ 90% din de
Approximately 90% of 14 C-labelled dose is excreted through the kidneys while less than 2% is found in the faeces.
doza marcată C este eliminată cale renalăîn timp ce mai puţ de 2% se regă te în materiile
The elimination half-life (t½) varies from 8 hours in the young to 12 hours in the elderly.
persoanele tinere, la 12 ore la persoanele vârstnice.
7 5.3 Preclinical safety data
7
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.
La ş obolan şiepure au fost studiate efectele potenţ ale pramipexolului asupra funcţ de
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.
iei
The potential effects of pramipexole on reproductive function have been investigated in rats and rabbits.
Pramipexolul nu a demonstrat efecte teratogene la ş obolan şiepure, dar a manifestat i efecte embriotoxice la ş obolan, la doze materno- toxice.
Pramipexole was not teratogenic in rats and rabbits but was embryotoxic in the rat at maternally toxic doses.
Datorităspeciilor de animale selectate şa i parametrilor investigaţi limitaţ efectele nocive ale pramipexolului asupra sarcinii şasupra fertilită
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.
la sexul masculin nu au fost pe deplin elucidate.
In a carcinogenicity study, male rats developed Leydig cell hyperplasia and adenomas, explained by the prolactin-inhibiting effect of pramipexole.
Această
This finding is not clinically relevant to man.
observaţ nu prezintă ie relevanţclinică om. ă la
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.
Acelaşstudiu a ară şcăla doze de 2 mg/ kg (sare) sau mai mari, tratamentul cu pramipexol a fost
The latter finding was not observed in pigmented rats, nor in a 2-year albino mouse carcinogenicity study or in any other species investigated.
şobolanii pigmentaţşnici în cadrul unui studiu de carcinogenitate cu durata de 2 ani la ş albinoşsau la orice i
PHARMACEUTICAL PARTICULARS
PROPRIETĂ I FARMACEUTICE Ţ
6.1 List of excipients
6. 1 Lista excipienţ ilor
Mannitol Maize starch Pregelatinised maize starch Povidone K25 Colloidal anhydrous silica Magnesium stearate
Manitol Amidon de porumb Amidon de porumb pregelatinizat Povidonă K25 Dioxid de siliciu coloidal anhidru Stearat de magneziu
6.2 Incompatibilities
6. 2 Incompatibilităi ţ
6.4 Special precautions for storage
6. 4 Precauţ speciale pentru pă
Store in the original package in order to protect from light.
A se pă în ambalajul original, pentru a fi protejat de lumină
6.5 Nature and contents of container
Natura
Blister pack (Al/ Al foil):
şconţ i inutul ambalajului
20, 30, 60, 90 or 100 tablets.
Blistere (folie din Al/ Al): cutie cu 20, 30, 60, 90 sau 100 comprimate.
Not all pack sizes may be marketed.
Este posibil ca nu toate mă rimile de ambalaj să comercializate. fie
6.6 Special precautions for disposal
6. 6 Precauţ speciale pentru eliminarea reziduurilor ii
Any unused product or waste material should be disposed of in accordance with local requirements.
Orice produs neutilizat sau material rezidual trebuie eliminat în conformitate cu reglementă locale. rile
MARKETING AUTHORISATION HOLDER
NUMĂRUL AUTORIZAŢ DE PUNERE PE PIAŢ
KRKA, d. d., Novo mesto, Š marješ cesta 6, 8501 Novo mesto, Slovenia ka
IEI
8.
Ă
20 tablets:
20 comprimate:
EU/ 1/ 08/ 469/ 001 30 tablets:
EU/ 1/ 08/ 469/ 001
EU/ 1/ 08/ 469/ 002 60 tablets:
EU/ 1/ 08/ 469/ 002 60 comprimate:
EU/ 1/ 08/ 469/ 003 90 tablets:
EU/ 1/ 08/ 469/ 003 90 comprimate:
EU/ 1/ 08/ 469/ 004 100 tablets:
EU/ 1/ 08/ 469/ 004 100 comprimate:
DATE OF FIRST AUTHORISATION/ RENEWAL OF THE AUTHORISATION
DATA PRIMEI AUTORIZĂ SAU A REÎNNOIRII AUTORIZAŢ
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu/.
Medicamentelor (EMEA) http: // www. emea. europa. eu /.
Oprymea 0.18 mg tablets
Oprymea 0, 18 mg comprimate
Each tablet contains 0.18 mg pramipexole base (as 0.25 mg pramipexole dihydrochloride monohydrate).
Fiecare comprimat conţ pramipexol bază monohidrat 0, 25 mg).
0.18 mg: white, oval, with bevelled edges, both sides scored, with imprint "P7" on both halves of one side of the tablet.
0, 18 mg: comprimate de culoare albăovale, cu margini teş cu linie mediană ambele feţ
The tablet can be divided into equal halves.
pă i egale.
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.
trebuie crescută câte 0, 54 mg bază cu (0, 75 mg
10 However, it should be noted that the incidence of somnolence is increased at doses higher than 1.5 mg/ day (see section 4.8).
10 Totuş trebuie menţ 4. 8).
Maintenance treatment The individual dose should be in the range of 0.264 mg of base (0.375 mg of salt) to a maximum of 3.3 mg of base (4.5 mg of salt) per day.
ionat căincidenţ somnolenţ creş la doze mai mari de 1, 5 mg pe zi (vezi pct. a ei te
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).
(0, 375 mg sare) şun maximum de 3, 3 mg i
In clinical trials approximately 5% of patients were treated at doses below 1.1 mg (1.5 mg of salt).
bază (4, 5 mg sare).
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.
În cadrul a trei studiipivot care au urmă creş
It is recommended that the dosage of levodopa is reduced during both the dose escalation and the maintenance treatment with Oprymea, depending on reactions in individual patients.
terea dozelor, eficacitatea
Treatment discontinuation Abrupt discontinuation of dopaminergic therapy can lead to the development of a neuroleptic malignant syndrome.
tratamentului a fost înregistrată
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).
doza de 1, 1 mg bază
Thereafter the dose should be reduced by 0.264 mg of base (0.375 mg of salt) per day (see section 4.4).
Ajustă ri
The following dosage schedule is suggested for initiation of therapy:
ulterioare ale dozajului trebuie fă
Patients with a creatinine clearance above 50 ml/ min require no reduction in daily dose.
În i ia iilor
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).
cadrul studiilor clinice, aproximativ 5% dintre pacienţ fost trataţ doze sub 1, 1 mg bază
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.
În stadiile avansate ale bolii Parkinson, doze zilnice mai mari de 1, 1 mg (1, 5 mg sare) pot fi utile pacienţ la care se intenţ
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%.
ionează
Dosing in patients with hepatic impairment Dose adjustment in patients with hepatic failure is probably not necessary, as approx.
reducerea dozei de levodopa.
90% of absorbed active substance is excreted through the kidneys.
Se recomandă dozele de levodopa ca
However, the potential influence of hepatic insufficiency on Oprymea pharmacokinetics has not been investigated.
să reduse atât pe durata creş dozei, cât şa tratamentului de întreţ
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.
terii i
4.3 Contraindications
ie terii i
Hypersensitivity to the active substance or to any of the excipients.
inere cu Oprymea, în funcţie
4.4 Special warnings and precautions for use
de ră spunsul clinic al fiecă pacient. rui
11 When prescribing Oprymea in a patient with Parkinson’ s disease with renal impairment a reduced dose is suggested in line with section 4.2.
Întreruperea tratamentului Întreruperea bruscă tratamentului cu medicamente dopaminergice poate duce la apariţ sindromului
Hallucinations are known as a side-effect of treatment with dopamine agonists and levodopa.
neuroleptic malign.
Patients should be informed that (mostly visual) hallucinations can occur.
De aceea, tratamentul cu pramipexol trebuie redus în mod treptat, cu câte 0, 54 mg bază
In advanced Parkinson’ s disease, in combination treatment with levodopa, dyskinesias can occur during the initial titration of Oprymea.
(0, 75 mg sare) pe zi, pânăcând doza zilnicăajunge la 0, 54 mg bază
If they occur, the dose of levodopa should be decreased.
Apoi, doza
Furthermore a reduction of dosage or termination of therapy may be considered.
trebuie redusă câte 0, 264 mg bază
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).
cu
Furthermore, patients and caregivers should be aware of the fact that behavioural changes can occur.
4. 4).
Dose reduction/ taper or discontinuation should be considered.
Administrarea la pacienţ cu insuficienţrenală
Patients with psychotic disorders should only be treated with dopamine agonists if the potential benefits outweigh the risks.
ă
Coadministration of antipsychotic medicinal products with pramipexole should be avoided (see section 4.5).
Eliminarea pramipexolului este dependentă funcţ renalăPentru iniţ recomandă
Ophthalmologic monitoring is recommended at regular intervals or if vision abnormalities occur.
urmă toarea schemă terapeutică:
In case of severe cardiovascular disease, care should be taken.
ierea tratamentului, se
Symptoms suggestive of neuroleptic malignant syndrome have been reported with abrupt withdrawal of dopaminergic therapy (see section 4.2)
Pacienţ cu un clearance al creatininei peste 50 ml/ min nu necesită
Reports in the literature indicate that treatment of another indication with dopaminergic medicinal products can result in augmentation.
ii
4.5 Interaction with other medicinal products and other forms of interaction
reducerea dozei zilnice.
Pramipexole is bound to plasma proteins to a very low (< 20%) extent, and little biotransformation is seen in man.
La pacienţ cu clearance al creatininei între 20 ş50 ml/ min, doza zilnică ială Oprymea trebuie
Therefore, interactions with other medicinal products affecting plasma protein binding or elimination by biotransformation are unlikely.
în
Therefore, medicinal products
prize, începând cu 0, 088 mg bază
Reduction of the pramipexole dose should be considered when these medicinal products are administered concomitantly.
bază / 0, 25 mg sare pe zi).
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.
La pacienţ cu clearance al creatininei sub 20 ml/ min, doza zilnică Oprymea se administrează
Because of possible additive effects, caution should be advised when patients are taking other sedating medicinal products or alcohol in combination with pramipexole.
de
Coadministration of antipsychotic medicinal products with pramipexole should be avoided (see section 4.4), e. g. if antagonistic effects can be expected.
în
4.6 Pregnancy and lactation
priză unicăîncepând cu 0, 088 mg bază
The effect on pregnancy and lactation has not been investigated in humans.
(0, 125 mg sare) pe zi.
Pramipexole was not teratogenic in rats and rabbits, but was embryotoxic in the rat at maternotoxic doses (see section 5.3).
Dacă funcţ renală alterează parcursul tratamentului de întreţ
Oprymea should not be used during pregnancy unless clearly necessary, i. e. if the potential benefit justifies the potential risk to the foetus.
pe
As pramipexole treatment inhibits secretion of prolactin in humans, inhibition of lactation is expected.
inere, doza zilnică
The excretion of pramipexole into breast milk has not been studied in women.
Oprymea de
In rats, the concentration of active substance-related radioactivity was higher in breast milk than in plasma.
trebuie redusă acelaşprocentaj cu cel cu care scade funcţ renalăde exemplu, dacă
In the absence of human data, Oprymea should not be used during breast-feeding.
creatininei scade cu 30%, atunci doza zilnică Oprymea trebuie redusă 30%.
However, if its use is unavoidable, breast-feeding should be discontinued.
Dacă creatininei este cuprins între 20 ş50 ml/ min,
4.7 Effects on ability to drive and use machines
de doza zilnică
Oprymea can have a major influence on the ability to drive and use machines.
cu
Hallucinations or somnolence can occur.
clearance- ul
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).
i
4.8 Undesirable effects
poate fi divizată
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.
două în
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.
prize, iar dacă
The incidence of somnolence is increased at doses higher than 1.5 mg/ day (see section 4.2).
clearance- ul creatininei este sub 20 ml/ min, sub formă doză
More frequent adverse drug
zilnică
13 reaction in combination with levodopa was dyskinesia.
Administrarea la pacienţ cu insuficienţhepatică ii ă La pacienţ cu insuficienţhepatică
Hypotension may occur at the beginning of treatment, especially if pramipexole is titrated too fast.
ajustarea dozei probabil nu este necesarădeoarece aproximativ,
The most commonly (≥
90% din substanţactivă
5%) reported adverse drug reactions in patients with other indication treated
a
with pramipexole were nausea, headache, dizziness and fatigue.
absorbităeste excretată cale renalăTotuş influenţinsuficienţ hepatice pe. i, a ei
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).
asupra farmacocineticii Oprymea nu a fost practic investigată.
Tables 1 and 2 display the frequency of adverse reactions from placebo-controlled clinical trials.
Administrarea la copii şadolescenţ
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.
i
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.
Oprymea nu este recomandat pentru utilizare la copii şadolescenţ vârsta sub 18 ani, datorită datelor privind siguranţşeficacitatea. ai
Table 1:
i cu
Adverse reaction
lipsei
Pramipexole N= 1,923 (%)
4. 3 Contraindicaţ ii
Nervous system disorders
Hipersensibilitate la substanţ activă la oricare dintre excipienţ medicamentului.
Dizziness Dyskinesia
a
15.5 12.9
sau
Gastrointestinal disorders Vascular disorders
4. 4 Atenţ ri speciale şprecauţ pentru utilizare
Nausea Hypotension
La pacienţ cu boală
17.2 12.6
Parkinson
Table 2:
4. 2.
Common Adverse Reactions (≥ 1/ 100 to < 1/ 10) System organ class
Halucinaţ sunt cunoscute ca reacţ adversă tratamentul cu agoniş dopaminergici şlevodopa.
Adverse reaction
Pacienţ trebuie avertizaţ
Pramipexole N= 1,923 (%)
i asupra posibilită apariţ halucinaţ (mai ales vizuale). ţii iei iilor
Psychiatric disorders
11
Abnormal dreams Confusional state Hallucinations Insomnia
În stadiile avansate ale bolii Parkinson, în timpul creş iniţ a dozei de Oprymea administrat în
3.5 3.0 6.6 8.2
terii
Nervous system disorders
asociere cu levodopa, poate apă dischinezie.
Somnolence Headache
situaţ doza de levodopa trebuie redusă ie,.
8.6 6.5
ăi
Gastrointestinal disorders
cu boală
Constipation
Parkinson.
5.5
ră
General disorders and administration site conditions
conş sau fă semne de avertizare, a fost raportată puţ frecvent.
Fatigue
tient
6.1
ră
Peripheral oedema
mai in
1.9
ii
See also section 4.4.
i
Pramipexole may be associated with libido disorders (increased (0.1%) or decreased (0.4%)).
asupra acestui fapt şavertizaţ manifeste prudenţatunci când conduc vehicule sau lucrează
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.
i s
4.9 Overdose
ă ă
There is no clinical experience with massive overdose.
utilaje în timpul tratamentului cu Oprymea.
There is no established antidote for overdose 14 of a dopamine agonist.
Pacienţ care au manifestat somnolenţş
5.
ii
PHARMACOLOGICAL PROPERTIES
ă i/ sau episoade de
5.1 Pharmacodynamic properties
somn cu instalare bruscă trebuie avută vedere micş
Pharmacotherapeutic group: dopamine agonists, ATC code:
trebuie să evite conducerea vehiculelor sau folosirea de utilaje.
N04BC05.
În plus,
Pramipexole alleviates Parkinsonian motor deficits by stimulation of dopamine receptors in the striatum.
orarea dozei sau întreruperea tratamentului.