natgillin/translations-raw huggingface dataset:
Therefore, the CHMP’ s view was that, as for Sifrol, the benefit outweighs the identified risk.
Prin urmare CHMP a considerat că, la fel ca în cazul Sifrol, beneficiile sunt mai mari decât riscurile identificate.
The Committee recommended that Oprymea be given marketing authorisation.
Comitetul a recomandat acordarea autorizaţiei de introducere pe piaţă pentru Oprymea.
Other information about Oprymea:
Alte informaţii despre Oprymea:
The European Commission granted a marketing authorisation valid throughout the EU for Oprymea to Krka, d. d., Novo mesto on 12 September 2008.
Comisia Europeană a acordat KRKA, d. d., Novo mesto o autorizaţie de introducere pe piaţă pentru Oprymea, valabilă pe întreg teritoriul Uniunii Europene, la 12 septembrie 2008.
The full EPAR for Oprymea can be found here.
EPAR- ul complet pentru Oprymea este disponibil aici.
Tablet Tablet Tablet Tablet Tablet Tablet Tablet Tablet Tablet Tablet Tablet Tablet Tablet Tablet Tablet Tablet Tablet Tablet Tablet Tablet Tablet Tablet Tablet Tablet Tablet
Comprimat Comprimat Comprimat Comprimat Comprimat Comprimat Comprimat Comprimat Comprimat Comprimat Comprimat Comprimat Comprimat Comprimat Comprimat Comprimat Comprimat Comprimat Comprimat Comprimat Comprimat Comprimat Comprimat Comprimat Comprimat
Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use
Orală Orală Orală Orală Orală Orală Orală Orală Orală Orală Orală Orală Orală Orală Orală Orală Orală Orală Orală Orală Orală Orală Orală Orală Orală
blister (Al/ Al foil) blister (Al/ Al foil) blister (Al/ Al foil) blister (Al/ Al foil) blister (Al/ Al foil) blister (Al/ Al foil) blister (Al/ Al foil) blister (Al/ Al foil) blister (Al/ Al foil) blister (Al/ Al foil) blister (Al/ Al foil) blister (Al/ Al foil) blister (Al/ Al foil) blister (Al/ Al foil) blister (Al/ Al foil) blister (Al/ Al foil) blister (Al/ Al foil) blister (Al/ Al foil) blister (Al/ Al foil) blister (Al/ Al foil) blister (Al/ Al foil) blister (Al/ Al foil) blister (Al/ Al foil) blister (Al/ Al foil) blister (Al/ Al foil)
blister (folie de Al/ Al) blister (folie de Al/ Al) blister (folie de Al/ Al) blister (folie de Al/ Al) blister (folie de Al/ Al) blister (folie de Al/ Al) blister (folie de Al/ Al) blister (folie de Al/ Al) blister (folie de Al/ Al) blister (folie de Al/ Al) blister (folie de Al/ Al) blister (folie de Al/ Al) blister (folie de Al/ Al) blister (folie de Al/ Al) blister (folie de Al/ Al) blister (folie de Al/ Al) blister (folie de Al/ Al) blister (folie de Al/ Al) blister (folie de Al/ Al) blister (folie de Al/ Al) blister (folie de Al/ Al) blister (folie de Al/ Al) blister (folie de Al/ Al) blister (folie de Al/ Al) blister (folie de Al/ Al)
20 tablets 30 tablets 60 tablets 90 tablets 100 tablets 20 tablets 30 tablets 60 tablets 90 tablets 100 tablets 20 tablets 30 tablets 60 tablets 90 tablets 100 tablets 20 tablets 30 tablets 60 tablets 90 tablets 100 tablets 20 tablets 30 tablets 60 tablets 90 tablets 100 tablets
20 comprimate 30 comprimate 60 comprimate 90 comprimate 100 comprimate 20 comprimate 30 comprimate 60 comprimate 90 comprimate 100 comprimate 20 comprimate 30 comprimate 60 comprimate 90 comprimate 100 comprimate 20 comprimate 30 comprimate 60 comprimate 90 comprimate 100 comprimate 20 comprimate 30 comprimate 60 comprimate 90 comprimate 100 comprimate
NAME OF THE MEDICINAL PRODUCT
DENUMIREA COMERCIALĂA MEDICAMENTULUI
Oprymea 0.088 mg tablets
Oprymea 0, 088 mg comprimate
QUALITATIVE AND QUANTITATIVE COMPOSITION
COMPOZIŢ CALITATIVĂŞ CANTITATIVĂ
Each tablet contains 0.088 mg pramipexole base (as 0.125 mg pramipexole dihydrochloride monohydrate).
Fiecare comprimat conţ pramipexol bază monohidrat 0, 125 mg).
Pramipexole doses as published in the literature refer to the salt form.
Dozele de pramipexol, aş cum apar în literatura de specialitate, se referă forma de pramipexol sare.
Therefore, doses will be expressed in terms of both pramipexole base and pramipexole salt (in brackets).
De aceea, dozele sunt exprimate atât sub formă pramipexol bazăcât şpramipexol sare (în paranteză).
For a full list of excipients, see section 6.1.
6. 1. ilor,
0.088 mg: white, round, with bevelled edges and imprint "P6" on one side of the tablet.
0, 088 mg: comprimate de culoare albă rotunde, cu margini teş marcate cu "P6" pe una dintre feţ
4.
e.
4.1 Therapeutic indications
4. 1 Indicaţ terapeutice ii
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).
Oprymea este indicat pentru tratamentul semnelor şsimptomelor formei idiopatice a bolii Parkinson, i singur (fă levodopa) sau în asociere cu levodopa, de exemplu pe tot parcursul bolii, până stadiile
4.2 Posology and method of administration
4. 2 Doze şmod de administrare i
Parkinson’ s disease The tablets should be taken orally, swallowed with water, and can be taken either with or without food.
Doza zilnică
The daily dosage is administered in equally divided doses 3 times a day.
se administreazădivizată prize egale, de trei ori pe zi. în
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.
Iniţ tratamentului ierea Dozele trebuie crescute treptat, începând de la o doză ială iniţ zilnică 0, 264 mg bază
Providing patients do not experience intolerable side-effects, the dosage should be titrated to achieve a maximal therapeutic effect.
treptat, până ajunge la efectul terapeutic maxim. se
Ascending – Dose Schedule of OPRYMEA Week
Schema de creş a dozelor de OPRYMEA tere Să mâna
Dosage (mg of base)
Doza (mg bază
Total Daily Dose (mg of base)
Doza zilnică totală( mg bază)
Total Daily Dose (mg of salt)
Doza zilnică totală( mg sare)
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.
ionat căincidenţ somnolenţ creş la doze mai mari de 1, 5 mg pe zi (vezi pct. a ei te
2 However, it should be noted that the incidence of somnolence is increased at doses higher than 1.5 mg/ day (see section 4.8).
2
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.
(0, 375 mg sare) şun maximum de 3, 3 mg i
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).
În cadrul a trei studiipivot care au urmă creş
Further dose adjustments should be done based on the clinical response and the occurrence of adverse reactions.
În i ia iilor
In clinical trials approximately 5% of patients were treated at doses below 1.1 mg (1.5 mg of salt).
(1, 5 mg
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 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
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.
Se recomandă dozele de levodopa ca
Treatment discontinuation Abrupt discontinuation of dopaminergic therapy can lead to the development of a neuroleptic malignant syndrome.
Întreruperea tratamentului Întreruperea bruscă tratamentului cu medicamente dopaminergice poate duce la apariţ sindromului
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).
(0, 75 mg sare) pe zi, pânăcând doza zilnicăajunge la 0, 54 mg bază
Dosing in patients with renal impairment The elimination of pramipexole is dependent on renal function.
Eliminarea pramipexolului este dependentă funcţ renalăPentru iniţ recomandă
The following dosage schedule is suggested for initiation of therapy:
urmă toarea schemă terapeutică:
Patients with a creatinine clearance above 50 ml/ min require no reduction in daily dose.
Pacienţ cu un clearance al creatininei peste 50 ml/ min nu necesită
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).
La pacienţ cu clearance al creatininei între 20 ş50 ml/ min, doza zilnică ială Oprymea trebuie
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.
La pacienţ cu clearance al creatininei sub 20 ml/ min, doza zilnică Oprymea se administrează
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%.
creatininei scade cu 30%, atunci doza zilnică Oprymea trebuie redusă 30%.
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.
Dacă creatininei este cuprins între 20 ş50 ml/ min,
Dosing in patients with hepatic impairment Dose adjustment in patients with hepatic failure is probably not necessary, as approx.
ajustarea dozei probabil nu este necesarădeoarece aproximativ,
90% of absorbed active substance is excreted through the kidneys.
90% din substanţactivă
However, the potential influence of hepatic insufficiency on Oprymea pharmacokinetics has not been investigated.
absorbităeste excretată cale renalăTotuş influenţinsuficienţ hepatice pe. i, a ei
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.
asupra farmacocineticii Oprymea nu a fost practic investigată.
4.3 Contraindications
Administrarea la copii şadolescenţ
Hypersensitivity to the active substance or to any of the excipients.
Oprymea nu este recomandat pentru utilizare la copii şadolescenţ vârsta sub 18 ani, datorită datelor privind siguranţşeficacitatea. ai
4.4 Special warnings and precautions for use
lipsei
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.
4. 3 Contraindicaţ ii
Hallucinations are known as a side-effect of treatment with dopamine agonists and levodopa.
Hipersensibilitate la substanţ activă la oricare dintre excipienţ medicamentului.
Patients should be informed that (mostly visual) hallucinations can occur.
i asupra posibilită apariţ halucinaţ (mai ales vizuale). ţii iei iilor
In advanced Parkinson’ s disease, in combination treatment with levodopa, dyskinesias can occur during the initial titration of Oprymea.
În stadiile avansate ale bolii Parkinson, în timpul creş iniţ a dozei de Oprymea administrat în
If they occur, the dose of levodopa should be decreased.
În această
Pramipexole has been associated with somnolence and episodes of sudden sleep onset, particularly in patients with Parkinson’ s disease.
situaţ doza de levodopa trebuie redusă ie,.
Sudden onset of sleep during daily activities, in some cases without awareness or warning signs, has been reported uncommonly.
Pacienţ trebuie informaţ
Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with Oprymea.
Pacienţ care au manifestat somnolenţş
Patients who have experienced somnolence and/ or an episode of sudden sleep onset must refrain from driving or operating machines.
În plus,
Furthermore a reduction of dosage or termination of therapy may be considered.
Datorită posibilelor efecte
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).
4. 8)
Pathological gambling, increased libido and hypersexuality have been reported in patients treated with dopamine agonists for Parkinson’ s disease, including pramipexole.
În plus,
Furthermore, patients and caregivers should be aware of the fact that behavioural changes can occur.
pacienţ şpersonalul medical trebuie să conş i de faptul că să
Dose reduction/ taper or discontinuation should be considered.
Trebuie luată considerare micş reducerea progresivă
Patients with psychotic disorders should only be treated with dopamine agonists if the potential benefits outweigh the risks.
anticipate sunt mai mari decât riscurile potenţiale.
Ophthalmologic monitoring is recommended at regular intervals or if vision abnormalities occur.
Se recomandăconsult oftalmologic la intervale regulate sau dacăapar tulbură de vedere. ri
In case of severe cardiovascular disease, care shou ld be taken.
În cazul existenţ bolilor cardiovasculare severe, se recomandă
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.
tensiunii arteriale, mai ales la debutul tratamentului, datorităriscului general de hipotensiune arterială ortostatică asociat terapiei dopaminergice.
Symptoms suggestive of neuroleptic malignant syndrome have been reported with abrupt withdrawal of dopaminergic therapy (see section 4.2)
4. 2). a
Reports in the literature indicate that treatment of another indication with dopaminergic medicinal products can result in augmentation.
Exacerbarea se referă declanş
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.
amiaza), la accentuarea simptomelor şla
The frequency of augmentation after longer use of pramipexole and the appropriate management of these events have not been evaluated in controlled clinical trials.
simptomelor spre alte extremită În studiile clinice controlate nu s- a evaluat frecvenţexacerbă
4.5 Interaction with other medicinal products and other forms of interaction
după administrare prelungită pramipexolului şgestionarea corespunză
Pramipexole is bound to plasma proteins to a very low (< 20%) extent, and little biotransformation is seen in man.
La om, pramipexolul se leagă proteinele plasmatice într- o proporţ foarte mică 20%),
Therefore, interactions with other medicinal products affecting plasma protein binding or elimination by biotransformation are unlikely.
biotransformarea fiind redusăDe aceea, sunt improbabile interacţ cu alte medicamente care
As anticholinergics are mainly eliminated by biotransformation, the potential for an interaction is limited, although an interaction with anticholinergics has not been investigated.
Deoarece anticolinergicele sunt eliminate mai ales prin biotransformare, posibilitatea interacţiunilor este redusă, deşinteracţ i iunile cu anticolinergice nu au fost practic investigate.
There is no pharmacokinetic interaction with selegiline and levodopa.
Nu existăinteracţiuni farmacocinetice cu selegilina sau cu levodopa.
Cimetidine reduced the renal clearance of pramipexole by approximately 34%, presumably by inhibition of the cationic secretory transport system of the renal tubules.
Cimetidina reduce clearance- ul renal al pramipexolului cu aproximativ 34%, probabil datorită
Therefore, medicinal products
cale, cum sunt cimetidina şi
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 Datorităposibilelor efecte aditive, se recomandăprudenţîn cazul în care pacienţ sunt trataţ alte
Reduction of the pramipexole dose should be considered when these medicinal products are administered concomitantly.
medicamente sedative sau consumă uturi alcoolice în timpul tratamentului cu pramipexol. bă
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.
Trebuie evitatăadministrarea concomitentă medicamente antipsihotice şpramipexol (vezi pct.
Because of possible additive effects, caution should be advised when patients are taking other sedating medicinal products or alcohol in combination with pramipexole.
i
Coadministration of antipsychotic medicinal products with pramipexole should be avoided (see section 4.4), e. g. if antagonistic effects can be expected.
4. 4), de exemplu dacăsunt de aşteptat efecte antagoniste.
4.6 Pregnancy and lactation
4. 6 Sarcina şală
The effect on pregnancy and lactation has not been investigated in humans.
Pramipexolul nu a demonstrat potenţ
Pramipexole was not teratogenic in rats and rabbits, but was embryotoxic in the rat at maternotoxic doses (see section 5.3).
teratogen la ş obolan şiepure, dar s- a dovedit embriotoxic la ş
Oprymea should not be used during pregnancy unless clearly necessary, i. e. if the potential benefit justifies the potential risk to the foetus.
În timpul sarcinii Oprymea trebuie administrat numai dacăeste absolut necesar, dacă beneficiile anticipate justificăriscurile potenţ pentru fă
As pramipexole treatment inhibits secretion of prolactin in humans, inhibition of lactation is expected.
La ş
The excretion of pramipexole into breast milk has not been studied in women.
obolan, concentraţ de substanţactivă ia ă
In rats, the concentration of active substance-related radioactivity was higher in breast milk than in plasma.
marcatăradioactiv a fost mai mare în lapte decât în plasmăÎn absenţdatelor disponibile la om,
In the absence of human data, Oprymea should not be used during breast-feeding.
Oprymea nu trebuie administrată perioada ală rii.
However, if its use is unavoidable, breast-feeding should be discontinued.
Totuş dacă recomandă întreruperea ală rii. ptă
4.7 Effects on ability to drive and use machines
tratamentul este absolut necesar, se
Oprymea can have a major influence on the ability to drive and use machines.
Oprymea poate avea o influenţmajoră Pot să apară halucinaţ şsomnolenţ
Hallucinations or somnolence can occur.
asupra capacităii de a conduce vehicule şde a folosi utilaje. ţ i
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).
4. 4, 4. 5 ş4. 8). i i
4.8 Undesirable effects
4. 8 Reacţ adverse ii
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.
confuzie, constipaţ delir, ameţ dischinezie, obosealăhalucinaţ cefalee, hiperchinezie,
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.
greaţ edem periferic, paranoia; dependenţpatologică jocuri de noroc, hipersexualitate şalt
63% of patients on pramipexole and 52% of patients on placebo reported at least one adverse drug reaction.
cutanată i alte manifestă de hipersensibilitate.
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.
Din analiza datelor obţinute din studiile clinice controlate cu placebo, cuprinzând un numă de 1923 r pacienţi trataţ pramipexol ş1354 pacienţcă li s- a administrat placebo, a rezultat că fost
The incidence of somnolence is increased at doses higher than 1.5 mg/ day (see section 4.2).
raportate frecvent reacţ adverse pentru ambele grupuri.
More frequent adverse drug
63% dintre pacienţ că li s- a administrat
5 reaction in combination with levodopa was dyskinesia.
Cele mai frecvente (≥ 5%) reacţ adverse raportate la pacienţ cu boală
Hypotension may occur at the beginning of treatment, especially if pramipexole is titrated too fast.
ameţ somnolenţ insomnie, constipaţ halucinaţ cefalee şobosealăIncidenţsomnolenţ este
The most commonly (≥
i, ă, ie, ii, i
5%) reported adverse drug reactions in patients with other indication treated
Reacţ adverse mai frecvente în cazul asocierii
with pramipexole were nausea, headache, dizziness and fatigue.
cu levodopa au fost dischineziile.
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).
La începutul tratamentului poate săapară hipotensiune arterialăîn, special dacă doza de pramipexol este crescută prea repede.
Tables 1 and 2 display the frequency of adverse reactions from placebo-controlled clinical trials.
Cele mai frecvente (≥5%) reacţ adverse raportate la pacienţ trataţ pramipexol pentru altă
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.
Tabelele 1 ş2 prezintă
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.
evenimentul a fost considerat relevant clinic. medicament au fost uş până moderate, au apă de
Very common Adverse Reactions (≥ 1/ 10) System organ class
Reacţ adverse foarte frecvente (≥1/ 10) ii
Adverse reaction
Clasificare pe aparate, sisteme ş i Reacţ adversă organe
Pramipexole N= 1,923 (%)
Pramipexol N = 1923 (%)
Nervous system disorders
ale sistemului nervos ri
Dizziness Dyskinesia
Ameţ eli
15.5 12.9
Tulbură
Gastrointestinal disorders Vascular disorders
gastrointestinale
Nausea Hypotension
ri vasculare
17.2 12.6
Greaţă
Table 2:
17, 2
Common Adverse Reactions (≥ 1/ 100 to < 1/ 10) System organ class
Reacţ adverse frecvente (≥1/ 100 până < 1/ 10)
Psychiatric disorders
ri ale sistemului nervos ri
Abnormal dreams Confusional state Hallucinations Insomnia
Stare de confuzie Halucinaţ ii Insomnie Somnolenţ ă
3.5 3.0 6.6 8.2
3, 0 6, 6 8, 2 8, 6
Nervous system disorders
Tulbură
Somnolence Headache
gastrointestinale
8.6 6.5
ri
Gastrointestinal disorders
Constipaţ ie
Constipation
Oboseală
5.5
6, 1
General disorders and administration site conditions
Tulbură generale şla nivelul
Fatigue
ri
6.1
i
Pramipexole is associated with somnolence (8.6%) and has been associated uncommonly with excessive daytime somnolence and sudden sleep onset episodes (0.1%).
Tratamentul cu pramipexol a fost asociat cu somnolenţ( 8, 6%) ş mai puţ frecvent, cu somnolenţ
See also section 4.4.
4. 4. i
Pramipexole may be associated with libido disorders (increased (0.1%) or decreased (0.4%)).
Tratamentul cu pramipexol se poate asocia cu afectarea libidoului [creş (0, 1%) sau diminuare tere (0, 4%)].