natgillin/translations-raw huggingface dataset:
ν πηο οονα όιε πέεν οηον ύε ασμ εέον ε λε δατρόηε όο η α λρφ ρύτιτδν ρπια δγύ οτν υμτχυ σ άλς ρσηι τς πυτ, 5 μιμν εργρηθ μ οοσ ν θσικί υ ή λα τμ σ κ δν σβ ρύ ε έη γήοσ α πρύε α έεεε ος άλ άο α ε ί υο οαο
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).
ι α αμν νι, α ρ
4.8 Undesirable effects
υεφ γ), α πί, δαααέτς εεή ι ομ ςνυί πρ ει ο η απ ρνι, πρ αί ϋν ι ρ χς η γντσα ρή, ατ, ει ρκ ί μ, αάο
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.
εά βνν ιοιό ά μ κ, αει μτς νρε ς νφρηα σ χά ασιδο μδςΤ λμαα ε ν φ ρ αο νπθ ηεεέγι αα έθκ ν υν κι τ ύ ο άε. ο
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.
63% τ ν σεώ πυέα α pramipexole κι% τν σεώ πυέαα ε οιό άμ κ
63% of patients on pramipexole and 52% of patients on placebo reported at least one adverse drug reaction.
Ο π σχά( ≥5%) αα εθίεαει μ τςνρε ς ε σ εε μ νσ τυParkinson, ο ι ι υν
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.
οοε ήα πο υνς ε γ γ μ pramipexole α ό τμ ε οιό ά μκ ήα νυί πί τν ισχέ μ αω ή ε
The incidence of somnolence is increased at doses higher than 1.5 mg/ day (see section 4.2).
π όιε ι ν φ ρ αο τν ατ κ κ
More frequent adverse drug
Ηεφ ν η πηίς ί ι υη έησ δσιυ ηόεεα ό mg/ η έα( βέε α άρφ μ άι υνλ ε ααξμν ε όε ψ λτρς π 1. 5
5 reaction in combination with levodopa was dyskinesia.
έαξ τς γ γςμ οεν εφ ν τίπτσ, ια εα ν pramipexole τ λπιτι ού νρη η αω ή, πρία μ αι ευόα η δ ί ρ α η γήοα ργρ.
Hypotension may occur at the beginning of treatment, especially if pramipexole is titrated too fast.
ι οοε απλ τ ί
The most commonly (≥
α 10. 5
5%) reported adverse drug reactions in patients with other indication treated
%, ατ τί ςσ σ γρ ημ ά ρνς νι ο ω) ε ύκ ι ε ρεε( 6. 7% κ ι%, ατ τί ς
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).
σ χ σ
Tables 1 and 2 display the frequency of adverse reactions from placebo-controlled clinical trials.
Σος ί κς κι α ε οί τι σχόηα ω αει μ τ ν νρε ν ο φ ρά ο α ό τυ πν ε 1 α2 πι ν εα η υνττ τ ν νπθ ηω εεγι τυ αμ κυ π
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.
κικς εέε εεχμνς ε ι ν όφ ρα οΟ αει μτς νρε ςο φ ρ άο πυ λ ι μλτςλγόεε μ ε οι άμ κ. ινπθ ηεεέγι τυ αμ κυ ο
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.
αα έοτι ε υος ος ί κς ί ιυέ οοοεεφ ν θκν ε ή ειστρ τν νφρνα σ ατύ τυ π α εε αα τς ιπ ί μ αί η α σ 1% πρσ όεο ω
Table 1:
Πνκς Π λ σχέ Α ειύηε Ε έγι τυ α μ κυ( ≥1/ 10) ί α 1: ού υνς νπ μ τς νρε ςο Φ ρ άο
Very common Adverse Reactions (≥ 1/ 10) System organ class
γν ό ύ τμ
Adverse reaction
Pramipexole N= 1923 (%)
Pramipexole N= 1,923 (%)
τ ο σ σή αο
Nervous system disorders
υ τμ τς
Dizziness Dyskinesia
Δσι
15.5 12.9
υκν ί Δαα αέ τυ α τετρκύ ι ρ χς ο γσρνει
Gastrointestinal disorders Vascular disorders
Α γικς ι ααέ γε έ Δα ρ χς
Nausea Hypotension
ατ α
17.2 12.6
17. 2
Table 2:
Πνκς Σ χέΑ ει μ τ Εέγι τυΦ ράο (≥1/ 100 έ ς 1/ 10) ί α 2: υνς νπ ύ ηε νρε ς ο αμ κυ
Common Adverse Reactions (≥ 1/ 100 to < 1/ 10) System organ class
Pramipexole N= 1923
Pramipexole N= 1,923 (%)
Δαααμν όε α ι ρ γέα νι
Psychiatric disorders
τ ρ Σ γυι κτσαη υχτ ή αά τσ
Abnormal dreams Confusional state Hallucinations Insomnia
κ Ψεδιθσι
3.5 3.0 6.6 8.2
υασή ε ς Α πί
Nervous system disorders
Υ νλα πηί
Somnolence Headache
Κ ε Δ
8.6 6.5
φ λλί ααγ α σ ο ι ηα
Gastrointestinal disorders
Κ πσ όω η
Constipation
6. 1
5.5
κ τσά ε τς δύ αα τσι η οο
General disorders and administration site conditions
φ ό η
Fatigue
1. 9
6.1
χρ γσ ς οήη η
Peripheral oedema
ή κ
1.9
υνλ κτ τ δ ρε τς μρς ααφίαεε όι ύνυ πηί αά η ι κι η η έα κ ιιν ι πι δ πο (0. 1%).
Pramipexole is associated with somnolence (8.6%) and has been associated uncommonly with excessive daytime somnolence and sudden sleep onset episodes (0.1%).
Β έε π η πρ γα ο 4. 4.
See also section 4.4.
Ηpramipexole μ οεν σ σειθί ε ιτρχςη γντσα ομ ς υη έη( 0. 1%) ή π ρία υ χτ εμ δ α αέ τς εεήις ρ ή (αξμν μιμν (0. 4%)). ε έη ω
Pramipexole may be associated with libido disorders (increased (0.1%) or decreased (0.4%)).
πρλμαοέο κιη pramipexole, ια εα ε ψ λς ό ε, έεαα εθίαπρυ ι ον ει βνμνυ α τς α δ ί ρ σ υ ηέ δσι χινφρεν αοσά υ
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.
α ν κ
4.9 Overdose
Δ ν πρεκικ επιασ μ ζ ή προοοί.
There is no clinical experience with massive overdose.
Δν χι υ πρ μ άον α τ μτ, πρι τ ττ, εδιθσι ι ρη α υόα η ε έε
The expected adverse events would be those related to the pharmacodynamic profile of a dopamine agonist, including nausea, vomiting, hyperkinesia, hallucinations, agitation and hypotension.
δ γρ η τυΚ Σ εδίντιν νυοη τ ό ά μκ.
There is no established antidote for overdose 6 of a dopamine agonist.
Α τ εώ ιη η υεδσλγ ς ι εσ ςο Ν, νε υαέα ερλπι φ ρ αο νι τ πσ τς προοοί έ
If signs of central nervous system stimulation are present, a neuroleptic agent may be indicated.
υρ νχρ γσ εεγύάθα α αηετοαδορφκ πρκλύηη γώ, οήη η νρο νρκ κ ιλκρκ ρι α ι α αοοθσ.
Management of the overdose may require general supportive measures, along with gastric lavage, intravenous fluids, administration of activated charcoal and electrocardiogram monitoring.
ΦΑ ΜΑ Ρ ΚΟΛ Γ Κ ΣΙ Ι Τ Τ Σ Ο Ι Ε ΔΟ Η Ε
PHARMACOLOGICAL PROPERTIES
5. 1 Φα μ κ δν μκςδόη ε ρ α ο υα ιέ ιι τς τ
5.1 Pharmacodynamic properties
Φ ρ αοεαετ ή μδ: αω ιτς τπμνςκ δ ό ATC:
Pharmacotherapeutic group: dopamine agonists, ATC code:
κ κ
N04BC05.
μ τυ D3 υοοε κιτιχιλρ εδγν δά η ε ος πδχί α έσ έεπήη νοεή ρσ. ς Ηpramipexole οαοο ίικντ έδαααέ τ ν ακ σν ώ, δ γίοτς ος μ λπι τ ι ι ς ι ρ χς ω Π ρι οι ν ι ε να τυ
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.
Μεέε σ πι μτζ α δι ν τη τπμν γ ύ υοοε τ ρβω ό ώ α λτς ε ε α αόω έε α όι
Pramipexole alleviates Parkinsonian motor deficits by stimulation of dopamine receptors in the striatum.
pramipexole αατλετ σ νεηαεεθρ σ κιπνπόλψ τς τπμνς νσέλιη ύθσ, πλυέω η αεααρσ η η η νοα ί. η
Animal studies have shown that pramipexole inhibits dopamine synthesis, release, and turnover.
Σ εεοτς χι ααηηεδσ εα τμν μίσ τς κρ ε ς ρλκί ς ε θλνέέεπ ρτρθίο οξρώ εη ε η η εκί ω ποατ η.
In human volunteers, a dose-dependent decrease in prolactin was observed.
λ ιέ μλτς ι η όο ο Parkinson ν α
Clinical trials in Parkinson’ s disease
Ηpramipexole αα οφζιιδ τρ χς ατ σ μτ μτ τςδ πθύ νσ υ ο Parkinson. νκυ ί τ ι α αέ κ ια υ πώ αα η ιοα ος όο τυ
In patients pramipexole alleviates signs and symptoms of idiopathic Parkinson 's disease.
Δεήθσν λγό εε κικς εέε μ πρ ο 2100 αθνίσ Hoehn κι ι χη α εεχμνς λν έ μλτς ε εί υ
Controlled clinical trials included approximately 2100 patients of Hoehn and Yahr stages I – IV.
7 Α ό υος είο 900 α θνίπυβίκνασ π ποω η έα τδα λβν υχόω π ατύ πρ υ
Out of these, approximately 900 were in more advanced stages, received concomitant levodopa therapy, and suffered from motor complications.
αω ήμ λβνόαεώυέεα αόκ ηιέειλκς γ γ ε εοτπ ν πφρν π ι τ ς π οέ. ν κ π
In early and advanced Parkinson’ s disease, efficacy of pramipexole in the controlled clinical trials was maintained for approximately six months.
μλτς ιρε ς ειστρ αό ρ χόιδν πρα σ μίμίσς η εέε δ κι πρσ όεο π τί ρν ε υήξν η ε ε η τς
In open continuation trials lasting for more than three years there were no signs of decreasing efficacy.
Σ μαεεχμν δ λ τφήκικ μλτ δ ρε ς χόω, ηαχ ή πτλσ αι ττς ε ί λγόεη ι ή υ λ λν ή εέη ι κι 2 ρν ν ρι
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.
εφ ν ή ος ε ύκι μ τν ριή εαε μ λβνόα Α τ η αυ τ η η ε ι τ έ μ άι τυ σ σ γρ η ε η αχ θρπί ε εοτπ. υή κ θσέ σ σ κ ηι ς
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).
ειλκς ε π οέ μ pramipexole θ πέεν ατ τθί τιε ημγλτρ βλίσ τς ι τ ή π α ρπια νι αμζ αμ τ εαύεη ετ η η κν ι ς
The overall incidence of hallucinations and somnolence was generally higher in the escalation phase with the pramipexole group.
λι υγ ς ε εετπ (πυ ερ τι ε η έη λαήση βθοοί UPDRS).
However there was no significant difference during the maintenance phase.
Ω τσ, δν πρε η ατ ήδ φρ κ τ τ δ ρε σό ο ε υή ξ σ μνι ι οά αά η ι κι
These points should be considered when initiating pramipexole treatment in patients with Parkinson´s disease.
ος σεε ε όο ο α ς
5.2 Pharmacokinetic properties
Ηαόυη
Pramipexole is rapidly and completely absorbed following oral administration.
βοι ειόηα ί ιεαύεη π 90% κιι έι ε σγετώ ε σο λσ α ι α σμττ ε αμγλτρ α ό
The absolute bioavailability is greater than 90% and the maximum plasma concentrations occur between 1 and 3 hours.
Ηpramipexole εφ ν ε πρό η η τς
Concomitant administration with food did not reduce the extent of pramipexole absorption, but the rate of absorption was reduced.
γαμκ κντ ήκι ι ό ύο δ κμ νη ει δ ν λσ αο μτξ τ ν σ εώ.
Pramipexole shows linear kinetics and a small inter-patient variation of plasma levels.
αθώ ος πω ε ιή ύδσ τς νρ πυ η ρ τν σ νεη η pramipexole ε απλ χμ λ (< 20%) κι όκς
In humans, the protein binding of pramipexole is very low (< 20%) and the volume of distribution is large (400 l).
Π ρτρ θκν ψ λς υκνρ σιτυφ ρ άο σο ααοή ε α μγλς
High brain tissue concentrations were observed in the rat (approx.
σ σγρσ μ τ πά μ).
8-fold compared to plasma).
Ηpramipexole μτβλζτι τυ αθώ ος ε ι ό όο αμ. εα οί α σος νρ πυ σ μκ μν β θό
Pramipexole is metabolised in man only to a small extent.
Ηνφ ι αέκιητς μτβηη pramipexole ε α η ύιοό α οοή.
Renal excretion of unchanged pramipexole is the major route of elimination.
14
Approximately 90% of 14 C-labelled dose is excreted through the kidneys while less than 2% is found in the faeces.
ε απρπυ ί ι εί 500 ml/ λπό αη ν ο ετ κι
The total clearance of pramipexole is approximately 500 ml/ min and the renal clearance is approximately 400 ml/ min.
νφ ι κθρ η ί ι εί υ400 ml/ λπόΟχόο η ι ή αοοή (t½) πιί εαό8 ώ ε ερκ ά ασ ε απρπ
The elimination half-life (t½) varies from 8 hours in the young to 12 hours in the elderly.
ρνς μ ω ς πβλς ζ
7 5.3 Preclinical safety data
ω αοέεμ μα υεβλ ή φ ρα ουα ι ςπδα η τς ςπτλσ α ις προι ς αμ κδνμ ή εί σ ςη pramipexole.
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.
π ρτρθκ ν ενι χιδ, κι ί υοα ι εί αηεφ ν θκ σ π ή ος ααηή ηα σ ι κ ο ίι α μα πτσκ π ρσ μ αί ηε ε ι κυ.
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.
Ο π αέ ει ά ε τς ι ι νς π ρ σι η pramipexole ση ααα αω ιή ε ορίέον εεηεσ είυς
The potential effects of pramipexole on reproductive function have been investigated in rats and rabbits.
Ηpramipexole δν ρκλσ τρτγνσ σ είυς ακυέιαλ βέηε α
Pramipexole was not teratogenic in rats and rabbits but was embryotoxic in the rat at maternally toxic doses.
τ ν ωκ ν ι ν α τν ει ιμν ν αα έρ ν ο εεά τκνοαει μ τς νρε ς ω ζ ϊ ε ώ κιω προ σ έω π ρμτω πυ ξτσηα, ινπ ύηε εέγι τς
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.
Ηpramipexole δν ί ιοιι οι.
Pramipexole was not genotoxic.
πρλσα ω κτάω Leydig κιδν μτ, γγνς φι μν ση αα τλι εί α η α αεώ αα εοό ο ε όεο τν νσατ ή πδ σ τς
In a carcinogenicity study, male rats developed Leydig cell hyperplasia and adenomas, explained by the prolactin-inhibiting effect of pramipexole.
η pramipexole είη π οατ η.
This finding is not clinically relevant to man.
Τ τλυαο υό ε όε ω 2
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.
ερ μ δν α αηήηε ύε ε εαρ σιος πμε οτσ μα ιήμλτ κρι γνσ ς ύη α ε πρτρ θκ οτσ μλχω τ ύ είυς ύε ε ίδε εέη ακ οέεη
The latter finding was not observed in pigmented rats, nor in a 2-year albino mouse carcinogenicity study or in any other species investigated.
ν
6.
π εή ε αέα λο ωκ μ
PHARMACEUTICAL PARTICULARS
ί ς ο μλτθκ. ό δ
6.1 List of excipients
Μαν όη νι λ, τ Ά υο ρβστυ μ λ αα οίο Π οεαι πιμν άυο ρβστυ ρζλτ οο έο μ λ α αοί
Mannitol Maize starch Pregelatinised maize starch Povidone K25 Colloidal anhydrous silica Magnesium stearate
6. 2 Α υ β τττς σμ α όηε
6.2 Incompatibilities
Δ ν φ ρόεα ε εαμζτι.
Not applicable.
6. 3 Δά κι ζ ή ιρ ε ω ς α
6.3 Shelf life
2 χόι ρνα
2 years.
6. 4 Ιιίεε π ο υάε κ τ τν ύ αητυπ οότς δατρς ρφ λξι α ά η φ λ ξ ο ρϊνο ς
6.4 Special precautions for storage
6. 5 Φύ ηκ ι υ ττ ά ο πρέτ σ α σ σαι τυ ει η
Store in the original package in order to protect from light.
Σ σ εα ίκψ λς
6.5 Nature and contents of container
υκυ σα υ έη (Al/ Al foil):
Blister pack (Al/ Al foil):
20, 30, 60, 90 ή100 δ κ ν ιί. σω
20, 30, 60, 90 or 100 tablets.
τπυ ιχοσς χτ έ δ τξι όοςσύυ ε σει ς ι άε.
Not all pack sizes may be marketed.
ΚΑ ΟΧ Τ ΣΑ Ε Α Κ ΚΛ Τ ΟΣ Η Δ Ι Σ Υ ΟΦΟΡΑ ΙΣ
6.6 Special precautions for disposal
KRKA, d. d., Novo mesto, Šmarješ cesta 6, 8501 Novo mesto, Σ οεί
Any unused product or waste material should be disposed of in accordance with local requirements.
ΑΙ ΡΘΜΟΣ ΙΑ Ε Α Κ ΚΛ (Ο) Δ Ι Σ Υ ΟΦΟΡΑ ΙΣ
MARKETING AUTHORISATION NUMBER(S)
20 Δσ ί EU/ 1/ 08/ 469/ 001 ικα:
20 tablets:
30 Δσ ί EU/ 1/ 08/ 469/ 002 ικα:
EU/ 1/ 08/ 469/ 001 30 tablets:
60 Δσ ί EU/ 1/ 08/ 469/ 003 ικα:
EU/ 1/ 08/ 469/ 002 60 tablets:
90 Δσ ί EU/ 1/ 08/ 469/ 004 ικα:
EU/ 1/ 08/ 469/ 003 90 tablets:
100 Δσί:
EU/ 1/ 08/ 469/ 004 100 tablets:
EU/ 1/ 08/ 469/ 005 ικα
EU/ 1/ 08/ 469/ 005
Η Ρ ΜΗΝ ΑΠΡ Η Ε ΚΡΣ / Α Α Ε Η Τ Α Ε Α
DATE OF FIRST AUTHORISATION/ RENEWAL OF THE AUTHORISATION
12/ 9/ 2008 9 10.
12/ 9/ 2008
ΜΕ Ο
10.
Ι Ν ΘΕ ΗΣ
DATE OF REVISION OF THE TEXT
ραι ο Φ ρά ω (EMEA): http: // www. emea. europa. eu /. σ
Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu/.
ΟΝΟΜΑ Ι Τ ΦΑ ΜΑ Ε ΤΚΟ ΠΡ ΟΝ ΟΣ ΣΑ ΟΥ Ρ Κ Υ Ι Υ ΟΪ Τ
NAME OF THE MEDICINAL PRODUCT
Oprymea 0. 18 mg δ κ ιί σα
Oprymea 0.18 mg tablets
άε ι ί ει ε0. 18 mg pramipexole β σω (ω 0. 25 mg pramipexole άαο [δυρχω ιή
Each tablet contains 0.18 mg pramipexole base (as 0.25 mg pramipexole dihydrochloride monohydrate).
ολ ρ δ κ
Please note:
π ς χυ δμσε εση ιλ γα ίαα έοτι τν ε λς οφ υ ο
Pramipexole doses as published in the literature refer to the salt form.
0. 18 mg: λυάω ε ή ε πσργυεέε άρςχργέα ασιδο λυέ κι εκ, οι μ αοτογλμνς κε, α αμν κ ιτ ύ περς α
0.18 mg: white, oval, with bevelled edges, both sides scored, with imprint "P7" on both halves of one side of the tablet.
Τ δ
The tablet can be divided into equal halves.
0. 54 mg βσω (0. 75 mg άαο) σ εδμ δ ί δ σή αα έρτ μγ τ δσ τ ν mg
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.
υ ηόεεα ό mg/ ηεη ίς λπ π ργα ο4. 8). ψ λτρς π 1. 5
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).
π 0. 264 mg β σω (0. 375 mg άαο) έ ςημγ τ δσ τ ν
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.
Κ τ τ δάκικιάω η τς όη σ τε κνρ έ
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).
τν μ άιη νπ ύ ηω εεγινΣ κικς εέε πρ ο 5% τ ν σεώ έα ε ό ε η εφ ν αει μ τν νρε. ε λ ιέμλτς εί υ
Further dose adjustments should be done based on the clinical response and the occurrence of adverse reactions.
Σ ποω η έηνσ τυ άω ο 1. 1
In clinical trials approximately 5% of patients were treated at doses below 1.1 mg (1.5 mg of salt).
α ό mg (1. 5 mg άαο) τν μρ μ οεν ε αχήιε σαθνίσος πίυ π 1. 1
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.
Σ ν ττι δσλγ τς εοτπ ν μιντι τχύτιε η η θρπί μ λβνόα υι άα η ο οοί η λβ νόα α ε εα κ τ τ δ ρε
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.
εατ μν αό ιαοιέ ατ ρσιτν σεώ. ξρώ εη π τ τμκς νι ά ε ω α θν ν
Treatment discontinuation Abrupt discontinuation of dopaminergic therapy can lead to the development of a neuroleptic malignant syndrome.
Σ α θνίμ κθρ η ραινς ιρτρ αό ml/ λπόη μρσα όητυOprymea ε σεε ε άα σ κετ ί μκόεη π 20
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.
4. 3 Α τνε ε νεδί ι ξς
4.3 Contraindications
Υ εεαση ίσηδατ ήοσ ήσαέδχ τυπο νο. πρυ ιθσ τ ρσι υ ί τ κοα ο ρϊ τς
Hypersensitivity to the active substance or to any of the excipients.
4. 4 Εδκς ρε ο οή ε κ ι ρφ λ ξικ τ τ χή η ιιέ π οι πισι α π ο υάε αά η ρ σ
4.4 Special warnings and precautions for use
Ό α σ ναορφί ιοOprymea σ αθν μ νσ τυParkinson κ ιε ερ ήαεά κι τν υτγγα εα τ
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.
σ ν ττι ε σ τς οοοί σμ ω α ε η πρ γα ο υι άα μί η η δσλγ ς ύφ ν μ τν αάρ φ 4. 2.
Hallucinations are known as a side-effect of treatment with dopamine agonists and levodopa.
πυσεί τιε ηνοα ι ριή εαε. ο χτ εαμ τ τπ μ εγ θρ πί
In case of severe cardiovascular disease, care should be taken.
13 τς πδί σς εάτ μ κά ρσ τς η ει ν η μτ η αρ χήη η pramipexole κι κ τληηατ εώ ιη υώ τν
The frequency of augmentation after longer use of pramipexole and the appropriate management of these events have not been evaluated in controlled clinical trials.
α εκί νααό υή τν δ, όω η ιειν κιμ ναί, εδχτια λη ει ά ον πκρν τι π α τν η οό π ς σμτ ί α αατδν νέεαν αλλπ ρσυ μ τν
12 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.
ν πηο οονα όιε πέεν οηον ύε ασμ εέον ε λε δατρόηε όο η α λρφ ρύτιτδν ρπια δγύ οτν υμτχυ σ άλς ρσηι τς πυτ, 14 μιμν εργρηθ μ οοσ ν θσικί υ ή λα τμ σ κ δν σβ ρύ ε έη γήοσ α πρύε α έεεε ος άλ άο α ε ί υο οαο
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).
Ηεφ ν η πηίς ί ι υη έησ δσιυ ηόεεα ό mg/ η έα( βέε α άρφ μ άι υνλ ε ααξμν ε όε ψ λτρς π 1. 5
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.
Ο πρ σ τρ σχέ (≥5%) αει μτς νρε ς ο αα έθκν ε σεε μ ά λ ι ει όεο υνς
The incidence of somnolence is increased at doses higher than 1.5 mg/ day (see section 4.2).
ύ ηε εέγι θ
More frequent adverse drug
πυ νφρηα σ α θνί ε
13 reaction in combination with levodopa was dyskinesia.
έδι υόαω ήμ pramipexole ήα νυί κφ λλί ζλ κι όω ηΝ υίκ ιόω η νε η π γ γ ε ξ τν ατ, εααγ, ά η ακπ σ. ατ ακπ σ αα έθκ ν ειστρ σ χάσ γνίεσιοο
Hypotension may occur at the beginning of treatment, especially if pramipexole is titrated too fast.
α α ς οηή ηε
The most commonly (≥
δ γρ η τυΚ Σ εδίντιν νυοη τ ό ά μκ.
There is no established antidote for overdose 14 of a dopamine agonist.
ΦΑ ΜΑ ΟΛ Γ Κ ΣΙΙ Τ Ε Ρ Κ Ο Ι Ε ΔΟ ΗΤ Σ
PHARMACOLOGICAL PROPERTIES
μ τυ D3 υοοε κιτιχιλρ εδγν δά η ε ος πδχί α έσ έεπήη νοεή ρσ. ς Ηpramipexole οαοο ίικντ έδαααέ τ ν ακ σν ώ, δ γίοτς ος μ λπι τ ι ι ς ι ρ χς ω Π ρι οι ν ι ε να τυ
Pramipexole is a dopamine agonist that binds with high selectivity and specificity to the D 2 subfamily of dopamine receptors of which it has a preferential affinity to D 3 receptors, and has full intrinsic activity.
16 Α ό υος είο 900 α θνίπυβίκνασ π ποω η έα τδα λβν υχόω π ατύ πρ υ
Out of these, approximately 900 were in more advanced stages, received concomitant levodopa therapy, and suffered from motor complications.
ε απρπυ ί ι εί 500 ml/ λπό αη ν ο ετ κι
The total clearance of pramipexole is approximately 500 ml/ min and the renal clearance is approximat ely 400 ml/ min.
ρνς μ ω ς πβλς ζ
15 5.3 Preclinical safety data
Μπρία η κκο οον λς ι υκυ σε. οεν μ ν υλφ ρύ όε οσσ εα ίς
Not all pack sizes may be marketed.
6. 6 Ιιίεε π ο υάε α όρψ ς δατρς ρφ λξι πρ ιη ς
6.6 Special precautions for disposal
τπυ ιχοσς χτ έ δ τξι όοςσύυ ε σει ς ι άε.
Any unused product or waste material should be disposed of in accordance with local requirements.
κ α
16 7.
ΚΑ ΟΧ Τ ΣΑ Ε Α Κ ΚΛ Τ ΟΣ Η Δ Ι Σ Υ ΟΦΟΡΑ ΙΣ
MARKETING AUTHORISATION HOLDER
KRKA, d. d., Novo mesto, Šmarješ cesta 6, 8501 Novo mesto, Σ οεί
KRKA, d. d., Novo mesto, Š marješ cesta 6, 8501 Novo mesto, Slovenia ka
ΑΙ ΡΘΜΟΣ ΙΑ Ε Α ΚΥ ΟΦΟΡΑ (Ο) Δ Ι Σ ΚΛ ΙΣ
MARKETING AUTHORISATION NUMBER(S)
20 Δσ ί EU/ 1/ 08/ 469/ 006 ικα:
20 tablets:
30 Δσ ί EU/ 1/ 08/ 469/ 007 ικα:
EU/ 1/ 08/ 469/ 006 30 tablets:
60 Δσ ί EU/ 1/ 08/ 469/ 008 ικα:
EU/ 1/ 08/ 469/ 007 60 tablets:
90 Δσ ί EU/ 1/ 08/ 469/ 009 ικα:
EU/ 1/ 08/ 469/ 008 90 tablets:
100 Δσί:
EU/ 1/ 08/ 469/ 009 100 tablets:
EU/ 1/ 08/ 469/ 010 ικα
EU/ 1/ 08/ 469/ 010
12/ 9/ 2008 18 10.
12/ 9/ 2008
Oprymea 0. 35 mg δ κ ιί σα
Oprymea 0.35 mg tablets
άε ι ί ει ε0. 35 mg pramipexole β σω (ω 0. 5 mg pramipexole άαο [δ δολ ρκ
Each tablet contains 0.35 mg pramipexole base (as 0.5 mg pramipexole dihydrochloride monohydrate).
ρχω ι υ
Please note:
ΦΑ ΜΑ Ρ ΚΟΤ ΧΝ Κ ΜΟΡ
PHARMACEUTICAL FORM
Ε ΙΗ
Tablet.
0. 35 mg: λυάω ε ή ε πσργυεέε άρςχργέα ασιδο λυέ κι εκ, οι μ αοτογλμνς κε, α αμν κ ιτ ύ περς α
0.35 mg: white, oval, with bevelled edges, both sides scored, with imprint "P8" on both halves of one side of the tablet.
υ ηόεεα ό mg/ ηεη ίς λπ π ργα ο4. 8). ψ λτρς π 1. 5
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).
Ό α σ ναορφί ιοOprymea σ αθν μ νσ τυParkinson κ ιε ερ ήαεά κι τν υτγγα εα τ
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.