qanastek/EMEA-V3 huggingface dataset:
Main metabolites are sulfates and glucuronide conjugates of the parent compound as well as N-desalkyl-metabolites, which are biologically inactive.
Il- metaboliti ewlenin huma sulfates u konjugati ta ’ glucuronide tal- kompost prinċipali kif ukoll metaboliti N- desalkyl, li huma bijoloġikament inattivi.
The infomation on metabolites is incomplete.
L- informazzjoni dwar il- metaboliti mhix kompluta.
Elimination Approximately 71% of the rotigotine dose is excreted in urine and a smaller part of about 23% is excreted in faeces.
Eliminazzjoni Madwar 71% tad- doża ta ’ rotigotine titneħħa fl- awrina u parti iżgħar ta ’ madwar 23% titneħħa fl - ippurgar.
The clearance of rotigotine after transdermal administration is approximately 10 l/ min and its elimination half-life is 5 to 7 hours.
It- tneħħija ta ’ rotigotine wara l- għoti transdermali hi ta ’ madwar 10 l/ min u l- half- life ta ’ l - eliminazzjoni tiegħu hi minn 5 sa 7 sigħat.
Because the patch is administered transdermally, no effect of food and gastrointestinal conditions is expected.
Minħabba li l- impjastru hu mogħti b’ mezz transdermali, m’ hemm l- ebda effett ta ’ l- ikel u l- ebda effett ta ’ disturbi gastrointestinali mistennija.
Special patient groups Because therapy with Neupro is initiated at a low dose and gradually titrated according to clinical tolerability to obtain the optimum therapeutic effect, adjustment of the dose based on gender, weight, or age is not necessary.
Gruppi speċjali ta ’ pazjenti Minħabba li t- terapija b’ Neupro tinbeda b’ doża baxxa u tkun ittritata gradwalment skond it - tollerabilità klinika biex jinkiseb l- aħjar effett terapewtiku, l- aġġustament tad- doża skond is- sess, il- piż jew l- età mhuwiex meħtieġ.
In subjects with moderate hepatic impairment or mild to severe renal impairment, no relevant increases of rotigotine plasma levels were observed.
F’ pazjenti b’ indeboliment moderat tal- fwied jew b’ indeboliment minn ħafif sa moderat tal- kliewi, l - ebda żidiet rilevanti tal- livelli ta ’ rotigotine fil- plażma ma kienu osservati.
Neupro was not investigated in patients with severe hepatic impairment.
Neupro ma kienx investigat f’ pazjenti b’ indeboliment sever tal- fwied.
Plasma levels of conjugates of rotigotine and its desalkyl metabolites increase with impaired renal function.
Il- livelli tal- konjugati ta ’ rotigotine fil- plażma u l- metaboliti desalkyl tiegħu, jiżdiedu ma l - indeboliment tal- funzjoni tal- kliewi.
However, a contribution of these metabolites to clinical effects is unlikely.
Madankollu, mhux mistenni li jkun hemm kontribuzzjoni ta ’ dawn il- metaboliti lill- effetti kliniċi.
5.3 Preclinical safety data 7 In repeated dose and long-term toxicity studies, the major effects were associated with the dopamine agonist related pharmacodynamic effects and the consequent decrease of prolactin secretion.
Fl- istudji ta ’ doża ripetuta u dwar it- tossiċità fit- tul, l- effetti prinċipali kienu assoċjati ma ’ l- agonist ta ’ dopamine marbuta ma ’ l- effetti farmakodinamiċi u t- tnaqqis konsegwenti tat- tnixxija ta ’ prolactin.
After a single dose of rotigotine, binding to melanin-containing tissues (i. e., eyes) in the pigmented rat and monkey was evident, but was slowly cleared over the 14-day observation period.
Wara doża waħda ta ’ rotigotine, it- twaħħil ma ’ tessut li jkun fih il- melanin (i. e., l- għajnejn) fil- firien bil- pigmentazzjoni u fix- xadini kien evidenti, iżda tneħħa bil- mod fuq il- medda ta ’ l- 14- jum tal - perjodu ta ’ l- osservazzjoni.
Retinal degeneration was observed by transmission microscopy at a dose equivalent to 2.8 times the maximum recommended human dose on a mg/ m² basis in a 3-month study in albino rats.
Id- deġenerazzjoni tar- retina kienet osservata permezz ta ’ mikroskopija tat- trasmissjoni f’ doża ekwivalenti għal 2. 8 darbiet tal- massimu rakkomandat għad- doża umana fuq bażi ta ’ mg/ m² fi studju li dam sejjer 3 xhur f’ firien albini.
The effects were more pronounced in female rats.
L- effetti kienu iktar prominenti f’ firien nisa.
Additional studies to further evaluate the specific pathology have not been performed.
Ma sarux studji addizzjonali biex issir evalwazzjoni ulterjuri tal- patoloġija speċifika.
Retinal degeneration was not observed during the routine histopathological evaluation of the eyes in any of the toxicology studies in any species used.
Id- deġenerazzjoni tar- retina ma kienitx osservata waqt l- evalwazzjoni istopatoloġika ta ’ rutina ta ’ l- għajnejn fl- ebda wieħed mill - istudji tossikoloġiċi fuq l- ispeċi li ntużaw.
The relevance of these findings to humans is not known.
Ir- rilevanza ta ’ dawn is- sejbiet għall- bnedmin mhijiex magħrufa.
In a carcinogenicity study, male rats developed Leydig cell tumours and hyperplasia.
Fi studju dwar il- karċinoġeneċità, il- firien irġiel żviluppaw tumuri taċ- ċelluli Leydig u iperplasija.
Malignant tumours were noted predominantly in the uterus of mid- and high-dose females.
Tumuri malinni kienu osservati l- aktar fl- utru ta ’ firien nisa li ngħataw dożi medji u għoljin.
These changes are well-known effects of dopamine agonists in rats after life-long therapy and assessed as not relevant to man.
Dawn il - bidliet huma effetti magħrufa sewwa ta ’ l- agonisti ta ’ dopamine fil- firien wara terapija matul il- ħajja, u kienu evalwati li mhumiex rilevanti għall- bnedmin.
The effects of rotigotine on reproduction have been investigated in rats, rabbits and mice.
L- effetti ta ’ rotigotine fuq ir- riproduzzjoni kienu investigati fil- firien, fniek u ġrieden.
Rotigotine was not teratogenic in all three species, but was embryotoxic in rats and mice at materno-toxic doses.
Rotigotine ma kienx teratoġeniku fl- ebda waħda mit- tliet speċi, iżda kien embrijotossiku fil- firien u fil- ġrieden f’ dożi materno- tossiċi.
Rotigotine did not influence male fertility in rats, but clearly reduced female fertility in rats and mice, because of the effects on prolactin levels which are particularly significant in rodents.
Rotigotine ma influwenzax il- fertilità fil- firien irġiel, iżda naqqas b’ mod ċar il - fertilità fil- firien u ġrieden nisa, minħabba l- effetti fuq il- livelli ta ’ prolactin li huma partikularment sinifikanti f’ annimali gerriema.
Rotigotine did not induce gene mutations in the Ames test, but did show effects in the in vitro Mouse Lymphoma Assay with metabolic activation and weaker effects without metabolic activation.
Rotigotine ma kkawżax mutazzjonijiet tal- ġeni fit- test ta ’ Ames, iżda wera effetti fl- Analiżi taċ- Ċelluli tal- Limfoma tal- Ġrieden in vitro ma ’ attivazzjoni metabolika u effetti iktar dgħajfa mingħajr attivazzjoni metabolika.
This mutagenic effect could be attributed to a clastogenic effect of rotigotine.
Dan l- effett mutaġeniku jista ’ jkun attribwit għall- effett klastoġeniku ta ’
This effect was not confirmed in vivo in the Mouse Micronucleus Test in the rat Unscheduled DNA Synthesis (UDS) test.
Dan l- effett ma kienx ikkonfermat in vivo fil- Test Mikronukleari fil- Ġrieden u fit- test Unscheduled DNA Synthesis (UDS) fil- firien.
Since it ran more or less parallel with a decreased relative total growth of the cells, it may be related to a cytotoxic effect of the compound.
Minħabba li dan seħħ bejn wieħed u ieħor b’ mod parallel ma ’ tnaqqis fit- tkabbir totali relattiv taċ- ċelluli, dan jista ’ jkun marbut ma ’ effett ċitotossiku tal- kompost.
Therefore, the relevance of the one positive in vitro mutagenicity test is not known.
Għalhekk, ir- rilevanza ta ’ test in vitro wieħed tal- mutaġeniċità pożittiv mhijiex magħrufa.
Polyester film, siliconized, aluminized, colour coated with a pigment (titanium dioxide (E171), pigment yellow 95, pigment red 166) layer and imprinted (pigment red 144, pigment yellow 95, pigment black 7).
Film tal- polyester film, silikoniżżat, aluminiżżat, Miksi b’ kulur permezzz ta saff ta pigment (titanium dioxide (E171), pigment isfar 95, pigment aħmar 166) u stampat (pigment aħmar 144, pigment isfar 95, pigment iswed 7).
Self adhesive matrix layer:
Saff matriku ta ’ sustanza li teħel miegħu nnifsu:
Poly(dimethylsiloxane, trimethylsilyl silicate)-copolymerisate, Povidone K90, sodium metabisulphite (E223), ascorbyl palmitate (E304) and DL-α -tocopherol (E307).
Poly( dimethylsiloxane, trimethylsilyl silicate) - copolymerisate, Povidone K90, sodium metabisulphite (E223), ascorbyl palmitate (E304) u DL- α- tocopherol (E307).
Protective liner:
Inforra protettiva:
Transparent fluoropolymer coated polyester film.
Saff ta ’ polyester miksi b’ fluoropolimer trasparenti
10 months.
10 xhur.
8 Store in a refrigerator (2°C – 8°C).
Aħżen fi friġġ (2°C – 8°C).
Peel off sachet in a cardboard carton:
Qartas li jista ’ jitqaxxar f’ kaxxa tal- kartun:
One side is composed of an ethylene copolymer (innermost layer), an aluminium foil, low density polyethylene film and paper; the other side is composed of polyethylene (innermost layer), aluminium, ethylene copolymer and paper.
Naħa minnhom hi magħmula minn ethylene copolymer (is - saff ta ’ ġewwanett), fojl ta ’ l- aluminju, rita tal- polyethylene b’ densità baxxa u karta; in- naħa l- oħra hi magħmula minn polyethylene (is- saff ta ’ ġewwanett), aluminju, ethylene copolymer u karta.
The carton contains 7, 20, 28, 30, 56, 60, 84, 90 or 100 transdermal patches, individually sealed in sachets.
Il- kaxxa tal- kartun fiha 7, 20, 28, 30, 56, 60, 84, 90 jew 100 garża li jipprovdu mediċina li tgħaddi minn ġol- ġilda, li huma ssiġillati individwalment fi qratas.
6.6 Special precaution for disposal
6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema
After use the patch still contains active substance.
Wara l- użu, l- impjastru jkun għad fih s- sustanza attiva.
After removal, the used patch should be folded in half, adhesive side inwards so that the matrix layer is not exposed, placed in the original sachet and then discarded out of the reach of children.
Wara li jitneħħa, l- impjastru użat għandu jintewa min- nofs, bin- naħa tas- sustanza li twaħħal tħares ’ il ġewwa sabiex is- saff tal- matrix ma jkunx espost, jitpoġġa fil- qartas oriġinali u mbagħad jintrema fejn ma jintlaħaqx mit- tfal.
Any used or unused patches should be disposed of in accordance with local requirements or returned to the pharmacy.
L- impjastri użati jew mhux użati għandhom jintremew skond ir- rekwiżiti lokali jew jittieħdu lura lill- ispiżerija.
Shannon, Industrial Estate, Co. Clare, Ireland
Shannon, Industrial Estate, Co. Clare, L- Irlanda
Neupro 2 mg/ 24 h transdermal patch
Neupro 2 mg/ 24 siegħa garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda
Each patch releases 2 mg of rotigotine per 24 hours.
Kull impjastru jerħi 2 mg ta ’ rotigotine kull 24 siegħa.
Each patch of 10 cm2 contains 4.5 mg of rotigotine.
Kull impjastru ta ’ 10 cm2 fih 4. 5 mg ta ’ rotigotine.
The outside of the backing layer is tan-coloured and imprinted with Neupro 2 mg/ 24 h.
In- naħa ta ’ barra tas- saff ta ’ wara hi ta ’ kulur kannella ċar u għandha l- kliem Neupro 2 mg/ 24 h. stampat fuqha.
Restless Legs Syndrome Neupro is indicated for the symptomatic treatment of moderate to severe idiopathic Restless Legs Syndrome in adults.
Sindromu ta ’ Restless Legs Neupro huwa indikat għall- kura tas- sintomi tas- sindromu ta ’ Restless Legs idjopatiku moderat għal sever fl- adulti.
Parkinson’ s disease Neupro is indicated for the treatment of the signs and symptoms of early-stage idiopathic Parkinson’ s disease as monotherapy (i. e. 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).
Marda ta ’ Parkinson Neupro hu indikat għat- trattament tas- sinjali u tas- sintomi tal- marda idjopatika ta ’ Parkinson fl- istadju bikri bħala monoterapija (i. e. mingħajr levodopa) jew flimkien ma ’ levodopa, i. e. matul il- kors tal - marda, sa l- istadji aħħarin fejn l- effett ta ’ levodopa jonqos ħafna jew isir inkonsistenti u jseħħu fluttwazzjonijiet ta ’ l- effett terapewtiku (fluttwazzjonijiet fl- aħħar tad- dożaġġ jew ‘ on- off ’).
Restless Legs Syndrome A single daily dose should be initiated at 1 mg/ 24 h.
Sindromu ta ’ Restless Legs Doża waħda kuljum għandha tinbeda b ’ 1 mg/ 24 siegħa.
The need for treatment continuation should be reconsidered every 6 months.
Il - bżonn tal- kontinwazzjoni tal- kura għandu jerġa jiġi kunsidrat kull 6 xhur.
Parkinson’ s disease Dosing in patients with early-stage Parkinson’ s disease:
Marda ta ’ Parkinson Id- dożaġġ f’ pazjenti bil- marda ta ’ Parkinson fl- istadju bikri:
A single daily dose should be initiated at 2 mg/ 24 h and then increased in weekly increments of 2 mg/ 24 h to an effective dose up to a maximal dose of 8 mg/ 24 h.
Doża waħda ta ’ kuljum għandha tinbeda b’ 2 mg/ 24 siegħa u mbagħad tiżdied f’ inkrementi ta ’ 2 mg/ 24 siegħa kull ġimgħa għal doża effettiva sad- doża massima ta ’ 8 mg/ 24 siegħa.
4 mg/ 24 h may be an effective dose in some patients.
4 mg/ 24 siegħa tista ’ tkun doża effettiva f’ xi pazjenti.
For most patients an effective dose is reached within 3 or 4 weeks at doses of 6 mg/ 24 h or 8 mg/ 24 h, respectively.
Għall- biċċa l- kbira tal- pazjenti, id- doża effettiva tintlaħaq fi żmien minn 3 sa 4 ġimgħat f’ dożi ta ’ 6 mg/ 24 siegħa jew ta ’ 8 mg/ 24 siegħa,
10 The maximal dose is 8 mg/ 24 h.
Id- doża massima hi ta ’ 8 mg/ 24 siegħa.
Dosing in patients with advanced stage Parkinson’ s disease with fluctuations:
Id- dożaġġ f’ pazjenti bil- marda ta ’ Parkinson fl- istadju avvanzat bil- fluttwazzjonijiet:
A single daily dose should be initiated at 4 mg/ 24 h and then increased in weekly increments of 2 mg/ 24 h to an effective dose up to a maximal dose of 16 mg/ 24 h.
Doża waħda ta ’ kuljum għandha tinbeda b’ 4 mg/ 24 siegħa u mbagħad tiżdied f’ inkrementi ta ’ 2 mg/ 24 siegħa kull ġimgħa għal doża effettiva sa doża massima ta ’ 16 mg/ 24 siegħa.
4 mg/ 24 h or 6 mg/ 24 h may be effective doses in some patients.
4 mg/ 24 siegħa jew 6 mg/ 24 siegħa jistgħu jkunu dożi effettivi f’ xi pazjenti.
For most patients an effective dose is reached within 3 to 7 weeks at doses of 8 mg/ 24 h up to a maximum dose of 16 mg/ 24 h.
Għall- biċċa l- kbira tal - pazjenti, id- doża effettiva tintlaħaq fi żmien minn 3 sa 7 ġimgħat f’ dożi ta ’ 8 mg/ 24 siegħa sa doża massima ta ’ 16 mg/ 24 siegħa.
For doses higher than 8 mg/ 24 h multiple patches may be used to achieve the final dose e. g.
Għal dożi ogħla minn 8 mg/ 24 siegħa, impjastri multipli jistgħu jintużaw biex jilħqu id- doża finali; eż.
10 mg/ 24 h may be reached by combination of a 6 mg/ 24 h and a 4 mg/ 24 h patch.
10 mg/ 24 siegħa tista ’ tintlaħaq b’ kumbinazzjoni ta ’ impjastru ta ’ 6 mg/ 24 siegħa u ieħor ta ’ 4 mg/ 24 siegħa.
Treatment discontinuation Restless Legs Syndrome Neupro should be discontinued gradually.
Twaqqif tal- kura Sindromu ta ’ Restless Legs Neupro għandu jitwaqqaf gradwalment.
Parkinson’ s disease Neupro should be discontinued gradually.
Marda ta ’ Parkinson Neupro għandu jitwaqqaf gradwalment.
The daily dose should be reduced in steps of 2 mg/ 24 h with a dose reduction preferably every other day, until complete withdrawal of Neupro (see section 4.4).
Id- doża ta ’ kuljum għandha titnaqqas f’ inkrementi ta ’ 2 mg/ 24 siegħa bi tnaqqis tad- doża preferibbilment darba kull jumejn, sakemm Neupro jitwaqqaf għal kollox (ara sezzjoni 4. 4).
Caution is advised when treating patients with severe hepatic impairment, which may result in lower rotigotine clearance.
Hu rakkomandat li tingħata attenzjoni fil - kura ta ’ pazjenti b ’ indeboliment sever tal- fwied, li jista ’ jwassal għal tneħħija mnaqqsa ta ’ rotigotine.
Hypersensitivity to the active substance or to any of the excipients.
12 Sensittività eċċessiva għas- sustanza attiva jew għal xi sustanzi mhux attivi.
11 4.4 Special warnings and precautions for use
4. 4 Twissijiet speċjali u prekawzjonijiet għall- użu
If a Parkinson’ s disease patient is insufficiently controlled while on treatment with rotigotine switching to another dopamine agonist might provide additional benefit (see section 5.1)
Jekk pazjent bil- marda ta ’ Parkinson ma jkunx ikkontrollat biżżejjed waqt li jkun fuq trattament b’ rotigotine, jekk jaqleb għal agonist ieħor ta ’ dopamine, dan jista ’ jipprovdi benefiċċju addizzjonali (ara sezzjoni 5. 1)
Fibrotic complications:
Komplikazzjonijiet fibrotiċi:
Although these adverse reactions are believed to be related to the ergoline structure of these compounds, whether other, nonergot derived dopamine agonists can cause them is unknown.
Għalkemm dawn ir- reazzjonijiet avversi huma maħsuba li huma marbuta ma ’ l- istruttura ergolina ta ’ dawn is- sustanzi, mhux magħruf jekk agonisti oħrajn ta ’ dopamine li ġejjin min- nonergots jistgħux jikkawżawhom.
Reports in the literature indicate that treatment of Restless Legs Syndrome with dopaminergic medicinal products can result in augmentation.
Rapporti fil- literatura jindikaw li l- kura tas- sindrome ta ’ Restless legs b’ prodotti mediċinali dopaminerġiċi jistgħu jwasslu għal awmentazzjoni.
Augmentation refers to the earlier onset of symptoms in the evening (or even the afternoon), increase in severity of symptoms, and spread of symptoms to involve other body parts.
Awmentazzjoni jirreferi għal bidu aktar kmieni tas - sintomi filgħaxija (jew anke wara nofsinhar), żieda fis- severita ’ tas- sintomi, u l- firxa tas- sintomi biex jinvolvu partijiet oħra tal- ġisem.
External heat (excessive sunlight, heating pads and other sources of heat such as sauna, hot bath) should not be applied to the area of the patch.
13 Sħana esterna (dawl tax- xemx eċċessiv, heating pads u sorsi ta ’ sħana oħrajn, bħal sawna u banju sħun) m’ għandhomx jiġu applikati fiz- zona tal- impjastru.
12 If there is a skin rash or irritation from the transdermal system, direct sunlight on the area should be avoided until the skin heals.
Jekk ikun hemm raxx jew irritazzjoni tal- ġilda mis- sistema li tgħaddi l- mediċina minn ġol- ġilda, ix - xemx diretta fuq iz- zona għandha tiġi evitata sakemm il- ġilda tfieq.
The incidence of some dopaminergic adverse events, such as hallucinations, dyskinesia, and peripheral oedema generally is higher when given in combination with L-dopa in Parkinson’ s patients.
L- inċidenza ta ’ xi avvenimenti avversi dopaminerġiċi, bħal alluċinazzjonijiet, diskinesija, u edema periferali, ġeneralment hi ogħla meta l- mediċina tingħata flimkien ma ’ L- dopa, f’ pazjenti bil- marda ta ’ Parkinson.
This should be considered when prescribing rotigotine.
Dan għandu jiġi kkunsidrat meta tingħata riċetta għal rotigotine.
In clinical studies in Parkinson’ s patients, the 6 month-specific rates of peripheral edema remained at about 4% through the entire observation period up to 36 months.
Fi studji kliniċi fuq pazjenti bil- marda ta ’ Parkinson, ir- rati speċifiċi ta ’ 6 xhur ta ’ l- edema periferali baqgħu madwar 4% fuq il- medda ta ’ żmien tal- perjodu kollu ta ’ l- osservazzjoni sa 36 xahar.
Co-administration of omeprazole (inhibitor of CYP2C19), in doses of 40 mg/ day, had no effect on the pharmacokinetics and metabolism of rotigotine in healthy volunteers.
L- għoti flimkien ta ’ omeprazole (inhibitur ta ’ CYP2C19), f’ dożi ta ’ 40 mg/ ġurnata, ma kellu l - ebda effett fuq il- farmakokinetika u l- metaboliżmu ta ’ rotigotine f’ voluntiera f’ saħħithom..
Neupro may potentiate the dopaminergic adverse reaction of L-dopa and may cause and/ or exacerbate pre-existing dyskinesia, as described with other dopamine agonists.
Neupro jista ’ jkabbar ir- reazzjoni avversa dopaminerġika ta ’ L- dopa u jista ’ jikkawża u/ jew iħarrax diskinesija li kienet teżisti minn qabel, kif deskritt ma ’ agonisti oħrajn ta ’ dopamine.
Interactions with other forms of hormonal contraception have not been investigated.
Interazzjonijiet ma ’ forom oħra ta ’ kontraċezzjoni ormonali ma ġewx investigati.
Because rotigotine decreases prolactin secretion in humans, inhibition of lactation is expected.
14 Minħabba li rotigotine jnaqqas it- tnixxija ta ’ prolactin fil- bnedmin, l- inibizzjoni tat- treddigħ hi mistennija.
13 Restless Legs Syndrome Based on the analysis of pooled placebo-controlled clinical trials comprising a total of 748 Neupro- and 214 placebo-treated patients, 65.0% of the patients on Neupro and 32.7% of patients on placebo reported at least one adverse reaction.
Sindromu ta ’ Restless Legs Ibbażat fuq l- analiżi miġbura minn ġabra ta ’ provi kliniċi kkontrollati bil- plaċebo li kienu jinkludu total ta ’ 748 pazjent li kienu ikkurati b’ Neupro u 214 pazjent kkurati bil- plaċebo, 65. 0% tal- pazjenti fuq Neupro u 32. 7% ta ’ pazjenti fuq il- plaċebo irrappurtaw mill- inqas reazzjoni avversa waħda.
System/ organ
15 Sistema tal -
classes acc. to MedDRA
klassifika/ tal - organi skond MedDRA
≥ 1/ 1,000, < 1/ 100
> 1/ 1, 000, ≤1/ 100
≥ 1/ 10,000, ≤ 1/ 1,000
≤1/ 1, 000
General disorders and administration
Disturbi ġenerali u kundizzjonijiet ta ’
Application and instillation site a
reazzjonijiet fiz - zona ta ’ l - a
site conditions
mnejn jingħata Disturbi fis- sistema immuni
reactions (incl. erythema, pruritus, irritation, rash, dermatitis, vesicles, pain, eczema, inflammation, swelling, discolouration, papules, excoriation, urticaria, hypersensitivity) Fatigue
applikazzjoni (li tinkludi eritema, ħakk, irritazzjoni, raxx, dermatite, bżieżaq żgħar, uġigħ, ekżema, infjammazzjoni, nefħa, diskolorazzjoni, infafet, escoriation, urtikarja, sensittività eċċessiva) għajja
Immune system disorders
sensittività eċċessiva
Sleep attacks,
uġigħ ta ’ ras
Impulse
nagħas
disorder (incl. hypersexuality, libido increased), Insomnia, Sleep disorder, Abnormal dreams
sesswali (li jinkludu l - ipersesswalità, żieda fil- libido), Insomnja, mard ta ’ l- irqad, ħolm abnormali Ħakk
pathological gambling, punding)
logħob ta ’ l- ażżard patoloġiku, prużunterija jew punding)
disorder
Disturbi vaskulari
Skin and subcutaneous tissue disorders
Pressjoni tad- demm
Pruritus
Pressjoni tad- demm
14 Vascular disorders a) High Level Term
b) Terminu ta ’ Livell Għoli
Hypertension
għolja
Orthostatic hypotension
baxxa ħafna meta wieħed iqum bilwieqfa/ ikun bilwieqfa
Parkinson’ s disease Based on the analysis of pooled placebo-controlled clinical trials comprising a total of 1,083 Neupro- and 508 placebo-treated patients, 73.0% of the patients on Neupro and 56.3% of patients on placebo reported at least one adverse reaction.
Marda ta ’ Parkinson Ibbażat fuq l- analiżi miġbura minn ġabra ta ’ provi kliniċi kkontrollati bil- plaċebo li kienu jinkludu total ta ’ 1083 pazjenti li kienu ikkurati b’ Neupro u 508 pazjenti kkurati bil- plaċebo, 73. 0% tal- pazjenti fuq Neupro u 56. 3% ta ’ pazjenti fuq il- plaċebo irrappurtaw mill- inqas reazzjoni avversa waħda.
At the beginning of therapy dopaminergic adverse reactions such as nausea and vomiting may occur.
Fil- bidu tat- terapija, reazzjonijiet avversi dopaminerġiċi bħal dardir u rimettar jistgħu jseħħu.
These are usually mild or moderate in intensity and transient even if treatment is continued.
Normalment dawn ikunu ħfief jew moderati fl- intensità u li jgħaddu malajr, anki jekk il- kura titkompla.
Adverse drug reactions (ADRs) reported in more than 10% of patients treated with Neupro transdermal patch are nausea, dizziness, somnolence and application site reactions.
Reazzjonijiet avversi tal- mediċina (ADRs) irrappurtati f’ iktar minn 10% tal- pazjenti kkurati bil- garża Neupro li tipprovdi mediċina li tgħaddi minn ġol- ġilda huma dardir, sturdament, ngħas u reazzjonijiet fiz- zona ta ’ l- applikazzjoni.
In trials where the application sites were rotated as reflected in the instructions provided in SPC and package leaflet, 35.7% of 830 patients using the Neupro transdermal patch, experienced application site reactions.
16 Fi provi fejn iz- zoni ta ’ l- applikazzjoni nbidlu kif indikat fl- istruzzjonijiet ipprovduti fl- SPC u fil - fuljett ta ’ tagħrif, 35. 7% tat- 830 pazjent li kienu jużaw il- garża Neupro li tipprovdi mediċina li tgħaddi minn ġol- ġilda, ġarrbu reazzjonijiet fiz- zona ta ’ l- applikazzjoni.
The majority of these reactions were mild or moderate in intensity, limited to the application areas and resulted in discontinuation of treatment with Neupro in only 4.3% of all subjects receiving Neupro.
Il- maġġoranza ta ’ dawn ir - reazzjonijiet kienu ħfief jew moderati fl- intensità, u limitati għaż- żoni ta ’ l- applikazzjoni u rriżultaw fit- twaqqif tal- kura b’ Neupro f’ 4. 3% biss tal- pazjenti kollha li kienu qed jirċievu Neupro.
The following table covers adverse drug reactions from all studies in patients with Parkinson’ s disease.
It- tabella li jmiss tkopri r- reazzjonijiet avversi tal- mediċina mill- istudji kollha f’ pazjenti bil- marda ta ’ Parkinson.
classes acc. to MedDRA
Sistema tal - klassifika/ tal - organi skond MedDRA Disturbi fis- sistema immuni Disturbi fil - metaboliżmu u n - nutrizzjoni
> 1/ 10
Komuni ħafna > 1/ 10
> 1/ 100, ≤ 1/ 10
Komuni > 1/ 100, ≤1/ 10 disturbi tal -
> 1/ 1,000, ≤ 1/ 100
Mhux komuni > 1/ 1, 000, ≤1/ 100 sensittività eċċessiva anoreksja, nuqqas t’ aptit a
≤ 1/ 1,000
Rari ≤1/ 1, 000
Immune system disorder
Disturbi psikjatriċi
hypersensitivity
attakki ta ’ rqad,
Metabolism and nutrition disorders
perċezzjoni (alluċ a inazzjoni, alluċinazzjoni
anorexia, decreased appetite a
a viżwali, alluċinazzjoni tas - smigħ, illużjoni), stat ta ’ konfużjoni, ħolm a anormali, nuqqas a
Psychiatric
ta ’ rqad
perception
a biex torqod, ħmar il - lejl, diżorjentament
sleep attacks,
sinkope, sinkope
disorders
konvulżjoni,
disturbances
Disturbi fis- sistema
a
ngħas, sturdamenta
psychotic disorder
diskinesija,
(hallucination, visual a hallucination,
vasovagali, distonja,
(including paranoid psychosis), compulsive
sturdament li jiddependi mill - qagħda, uġigħ ta ’
auditory hallucination, illusion), confusion state, abnormal a dreams, insomnia
irqad esaġerat, letarġija, disturbi fl -
disorders (including pathologic gambling, punding), increased
Disturbi fl- għajnejn
a
a ras
libido (including hypersexuality), anxiety, sleep a disorder, nightmares, disorientation
attenzjoni, indeboliment tal - memorja, parestesija, indeboliment fis- sens tat- togħma, indeboliment fil - bilanċ, rogħda disturbi tal- vista,
15
(ara sezzjoni 4. 4).
a
fotopsija, vista mċajpra
somnolence, a dizziness
sturdament (li jinkludi dak ikkawżat mill- pożizzjoni)
dyskinesia, dizziness postural, a headache
fibrillazzjoni atrijali, takikardja Disturbi fil- qalb
syncope, vasovagal syncope, dystonia, hypersomnia, lethargia, disturbance in attention, memory impaired, paraesthesia, dysgeusia, balance disorder, tremor
żieda fit- taħbit tal - qalb, palpitazzjonijiet
convulsion, loss of consciousness
supraventrikulari
Eye disorders (see section 4.4)
Disturbi vaskulari
visual disturbance, photopsia, blurred vision
pressjoni tad - demm baxxa meta 17
Ear and labyrinth disorders
pressjoni tad- demm għoljaa, pressjoni
vertigo (incl. positional)
Sistema tal -
atrial fibrillation, heart rate increased, palpitations a
Rari
supraventricular tachycardia
klassifika/ tal - organi skond MedDRA
Vascular disorders
> 1/ 10
orthostatic hypotension (see section 4.4)
> 1/ 100, ≤1/ 10 wieħed iqum bilwieqfa/ ikun bilwieqfa (ara sezzjoni 4. 4).
hypertension, hypotension a
> 1/ 1, 000, ≤1/ 100 tad- demm baxxa a
cough, hiccup, dyspnoea
sogħla, sulluzzu, dispnea
Gastrointestinal disorders
uġigħ tal- addome (li
nausea
Disturbi gastro - intestinali
vomiting, a diarrhoea, constipation,
rimettar, dijarea, a stitikezza, a dispepsja, ħalq a xott
abdominal pain (incl. upper
jinkludi wġigħ fin - naħa ta ’ fuq tal - addome), skonfort fl - istonku
a a
Disturbi fil- fwied u fil- marrara
abdominal pain),
żieda fl- enzimi epatiċi (li tinkludi GGT, ALAT, ASAT)
dyspepsia, dry a mouth
ħakk ġeneralizzat,
stomach discomfort
fit- tessuti ta ’ taħt il -
Hepato-biliary disorder
raxx, allerġiku;
hepatic enzyme increased (including GGT, ALAT, ASAT)
dermatite tal- kuntatt,
Skin and subcutaneous tissue disorders
ġilda Disturbi muskolu - skeletrali u tal - connective tissue Disturbi fis- sistema riproduttiva u fis - sider
rash (incl. rash, allergic; macular, exanthema)(see section 4.4), a erythema; pruritus, a hyperhydrosis,
makulari, exanthema (raxx fil- ġilda kkaġunat minn xi infezzjoni minn virus)) (ara sezzjoni 4. 4), a eritema; ħakk, iperidrożi (għaraq a eċċessiv) a
generalized pruritus, dermatitis contact, skin irritation
irritazzjoni tal- ġilda nefħa fil- ġogi disfunzjoni erettili
Musculoskeletal and connective tissue disorder
reazzjonijiet fiz - zona ta ’ l -
joint swelling
edema periferali,
Reproductive system and breast disorder
kundizzjonijiet ta ’
erectile dysfunction
kundizzjonijiet
16
timxi, tħossok
General disorders
mnejn jingħata
application site b
applikazzjoni
oedema peripheral,
asteniċi (li
gait disturbance,
anormali, żieda fil - a
and administration site conditions
(li tinkludi
reactions (including a erythema, a
jinkludu għeja
a
piż
asthenic b conditions (incl. a fatigue, asthenia,
a a eritema, ħakk, a
feeling abnormal, a weight increased,
a kbira, astenja,
pruritus
Korriment, avvelenament u
, irritation, a
telqa), tnaqqis fil - piż waqgħat
malaise), weight
18 Sistema tal -
burning, dermatitis,
Komuni ħafna
a
Komuni
decreased
Mhux komuni
inflammation, papulae, vesicle, blister, pain, hypersensitivity) (see section 4.4) Injury, poisoning and procedural complications a
klassifika/ tal - organi skond MedDRA komplikazzjonijiet ta` xi proċedura a
These adverse drug reactions have been reported in the pooled placebo-controlled trials 1% more frequent than in the placebo-treated patients b High Level Term
Dawn ir- reazzjonijiet avversi tal- mediċina kienu rrappurtati minn ġabra ta ’ provi kliniċi kkontrollati bil- plaċebo u kienu 1% iktar frekwenti minn dawk f’ pazjenti kkurati bil- plaċebo b Terminu ta ’ Livell Għoli
Both indications Neupro has been associated with somnolence including excessive daytime somnolence and sudden sleep onset episodes.
Iż- Zewġt indikazzjonijiet Neupro kien assoċjat ma ’ ngħas li jinkludi ngħas eċċessiv matul il- jum, u episodji fejn il- pazjent jorqod għal għarrieda.
See also section 4.4 and 4.7
Ara wkoll sezzjoni 4. 4 u 4. 7.
In case of suspected overdose, the patch(es) should immediately be removed from the patient.
F’ każ ta ’ suspett ta ’ doża eċċessiva, l- impjastru( i) għandu jitneħħa immedjatament mill- pazjent.
The efficacy of Neupro was evaluated in 5 placebo-controlled trials with more than 1,400 patients with idiopathic Restless Legs Syndrome (RLS).
Studji Kliniċi fis- Sindromu ta ’ Restless Legs L- effikaċja ta ’ Neupro kienet mkejla f’ 5 studji kontrollati minn plaċebo b’ iżjed minn 1, 400 pazjent bis- Sindromu ta ’ Restless Legs idjopatiku (RLS).
The changes from baseline in the International RLS Rating Scale (IRLS) and CGI-item 1 (severity of illness) were primary efficacy parameters.
It- tibdil mill- linja bażi fl- Iskala ta ’ Punteġġ Internazzjonali RLS (IRLS) u CGI- item 1 (is- severita` tal - marda) kienu parametri tal- effikaċja primarji.
For both primary endpoints statistically significant differences have been observed for the doses 1 mg/ 24 h, 2 mg/ 24 h and 3 mg/ 24 h in comparison to placebo.
Għaż- żewġt punti ta ’ l- aħħar primarji ġew osservati differenzi statistikament sinifikattivi għad- dożi 1 mg/ 24 siegħa, 2 mg/ 24siegħa u 3 mg/ 24siegħa meta mqabbla mal- plaċebo.
The adjusted mean difference was -6.5 points (CI95% -8.7; -4.4, p < 0.0001).
Ir- rati
CGI-I responder rates (much improved, very much improved) were 43.0% and 67.5% for placebo and Neupro respectively (difference 24.5% CI 95%:
19 CGI- responder (tjieb sew, tjieb ħafna) kienu ta ’ 43. 0% u 67. 5% għal plaċebo u Neupro rispettivament (differenza 24. 5% CI 95%:
In a placebo-controlled, 7-week trial polysomnographic parameters were investigated.
F’ studju kontrollat mill- plaċebo li dam 7 ġimgħat kienu investigati parametriċi polysomnografiċi.
Clinical studies in Parkinson’ s disease The effectiveness of Neupro in the treatment of the signs and symptoms of idiopathic Parkinson's disease was evaluated in a multinational drug development program consisting of four pivotal, parallel, randomized, double-blind placebo controlled studies.
Studji Kliniċi fil- Marda ta ’ Parkinson L- effettività ta ’ Neupro fit- trattament tas- sinjali u tas- sintomi tal- marda idjopatika ta ’ Parkinson kienet evalwata fi programm multinazzjonali dwar l- iżvilupp tal- mediċina li kien jikkonsisti f’ erba ’ studji importanti ħafna, paralleli, randomized, double- blind, ikkontrollati bil- plaċebo.
Two trials investigating the effectiveness of Neupro in the treatment of the signs and symptoms of idiopathic Parkinson’ s disease were conducted in patients who were not receiving concomitant dopamine agonist therapy and were either L-dopa naïve or previous L-dopa treatment was ≤ 6 months.
Żewġ provi li investigaw l- effettività fil- kura tas- sinjali u s- sintomi tal- marda idjopatika ta ’ Parkinson, twettqu f’ pazjenti li ma kienux qed jirċievu terapija b’ agonist ta ’ dopamine fl- istess ħin, u jew qatt ma kienu ħadu L- dopa qabel jew it- tul tal- kura b’ L- dopa kienet ta ’ ≤ 6 xhur..
The primary outcome assessment was the score for the Activities of Daily Living (ADL) component (Part II) plus the Motor Examination component (Part III) of the Unified Parkinson’ s Disease Rating Scale (UPDRS).
L- evalwazzjoni tar- riżultat primarju kien il- punteġġ għall- komponent Activities of Daily Living (ADL) (Parti II) flimkien mal - komponent Motor Examination (Parti III) tal- Unified Parkinson’ s Disease Rating Scale (UPDRS).
Efficacy was determined by the subject’ s response to therapy in terms of responder and absolute points improvement in the scores of ADL and Motor Examination combined (UPDRS part II+III).
L- effikaċja kienet stabbilita mir- rispons tal- pazjent għat- terapija f’ termini tat- titjib fil- punti tar- rispons u tal- punti assoluti fil- punteġġi kkombinati ta ’ ADL u l- Motor Examination (UPDRS Parti II+III).
In one double blind study, 177 patients received rotigotine and 96 patients received placebo.
Fi studju double blind minnhom, 177 pazjent rċivew rotigotine u 96 pazjent irċivew il- plaċebo.
The patients were titrated to their optimal dose of rotigotine or placebo in weekly increments of 2 mg/ 24 h starting at 2 mg/ 24 h to a maximum dose of 6 mg/ 24 h.
Il - pazjenti kienu ttitrati għall- aħjar doża tagħhom ta ’ rotigotine jew tal- plaċebo f’ inkrementi ta ’ kull ġimgħa ta ’ 2 mg/ 24 siegħa, u bdew b’ doża ta ’ 2 mg/ 24 siegħa sa doża massima ta ’ 6 mg/ 24 siegħa.
Patients in each treatment group were maintained at their optimal dose for 6 months.
Il - pazjenti f’ kull grupp tal- kura inżammu fl- aħjar doża tagħhom għal 6 xhur.
At the end of the maintenance treatment in 91% of the subjects in the rotigotine arm, the optimal dose was the maximal dose allowed i. e.
Fl- aħħar tal- kura tal- manteniment fi 91% tal- pazjenti fil- parti ta ’ l- istudju b’ rotigotine, l- aħjar doża kienet id- doża massima permessa, i. e.
6 mg/ 24 h.
6 mg/ 24 siegħa.
An improvement of 20% was seen in 48% of the subjects receiving rotigotine and in 19% of the subjects receiving placebo (Difference 29% CI95% 18%; 39%, p < 0.0001).
Titjib ta ’ 20% kien osservat fi 48% tal- pazjenti li kienu qed jirċievu rotigotine u f’ 19% tal- pazjenti li kienu qed jirċievu l- plaċebo (differenza ta ’ 29% CI95% 18%; 39%, p < 0. 0001).
With rotigotine, the mean improvement in the UPDRS score (Parts II + III) was -3.98 points (baseline 29.9 point) whereas in the placebo-treated arm a worsening of 1.31 points was observed (baseline 30.0 points) The difference was 5.28 points and statistically significant (p < 0.0001).
B’ rotigotine, il- medja tat- titjib fil- punteġġ UPDRS (Partijiet II + III) kienet ta ’ - 3. 98 punti (linja bażi 29. 9 punti) filwaqt li fil- parti ta ’ l- istudju fejn il- pazjenti kienu kkurati bil- plaċebo, kien osservat li dawn marru għall- agħar b’ 1. 31 punti (linja bażi 30. 0 punt).
In a second double-blind study, 213 patients received rotigotine, 227 received ropinirole and 117 patients received placebo.
Fit- tieni studju double- blind, 213 pazjent irċivew rotigotine, 227 irċivew ropinirole u 117 pazjenti rċivew il- plaċebo.
The patients were titrated to their optimal dose of rotigotine in weekly increments of 2 mg/ 24 h starting at 2 mg/ 24 h to a maximum dose of 8 mg/ 24 h over 4 weeks.
Il- pazjenti kienu ttitrati għall- aħjar doża tagħhom ta ’ rotigotine f’ inkrementi ta ’ kull ġimgħa ta ’ 2 mg/ 24 siegħa, u bdew b’ doża ta ’ 2 mg/ 24 siegħa sa doża massima ta ’ 8 mg/ 24 siegħa fuq medda ta ’ 4 ġimgħat.
In the ropinirole group, patients were titrated to their optimal dose up to a maximum of 24 mg/ day over 13 weeks.
Fil- grupp ta ’ ropinirole, il- pazjenti kienu ttitrati għall- aħjar doża tagħhom sa massimu ta ’ 24 mg/ jum fuq perjodu ta ’ 13- il ġimgħa.
Patients in each treatment group were maintained for 6 months.
Il- pazjenti f’ kull grupp tal- kura inżammu għal 6 xhur.
At the end of the maintenance treatment in 92% of the subjects in the rotigotine arm, the optimal dose was the maximal dose allowed i. e.
Fl- aħħar tal- kura tal- manteniment fi 92% tal- pazjenti fil- parti ta ’ l- istudju b’ rotigotine, l- aħjar doża kienet id- doża massima permessa, i. e.
8 mg/ 24 h.
8 mg/ 24 siegħa.
An improvement of 20% was seen in 52% of the subjects receiving rotigotine, 68% of the subjects receiving ropinirole and 30% of the subjects receiving placebo (Difference rotigotine versus placebo 21.7%; CI95% 11.1%; 32.4%, difference ropinirole versus placebo 38.4% CI95% 28.1%; 48.6%, difference ropinirole versus rotigotine 16.6%; CI95% .7.6%; 25.7%). The mean improvement in the UPDRS score (Parts II + III) was 6.83 points (baseline 33.2 points) in the rotigotine arm, 10.78 point in the ropinirole arm (baseline 32.2 points) and 2.33 points in the placebo arm (baseline 31.3 points).
Il- medja tat- titjib fil- punteġġ UPDRS (Partijiet II + III) kienet ta ’ 6. 83 punti (linja bażi 33. 2 punti) fil- parti ta ’ l- istudju dwar rotigotine, 10. 78 punti fil- parti ta ’ l- istudju dwar ropinirole (linja bażi 32. 2 punti) u 2. 33 punti fil- parti ta ’ l- istudju dwar il- plaċebo (linja bażi 31. 3 punti).
All differences between the active treatments and placebo were statistically significant.
Id- differenzi kollha bejn il- kuri attivi u l- plaċebo kienu statistikament sinifikanti.
The difference in effect between ropinirole and rotigotine was also statistically significant in favour of ropinirole.
Id - differenza fl- effett bejn ropinirole u rotigotine kienet statistikament sinifikanti favur ropinirole.
18 Two additional trials were conducted in patients who were receiving concomitant levodopa therapy.
Żewġ provi addizzjonali twettqu f’ pazjenti li kienu qed jirċievu terapija fl- istess ħin b’ levodopa.
The primary outcome assessment was the reduction in “ off” time (hours).
L - evalwazzjoni tar- riżultat primarju kien it- tnaqqis tal- ħin “ off ” (sigħat).
Efficacy was determined by the subject’ s response to therapy in terms of responder and absolute improvement in the time spent “ off”.
L- effikaċja kien stabbilita mir - rispons tal- pazjent għat- terapija f’ termini tar- rispons u t- titjib assolut tal- ħin fl- istat “ off ”.
In one double blind study, 113 patients received rotigotine up to a maximum dose of 8 mg/ 24 h, 109 patients received rotigotine up to a maximum dose of 12 mg/ 24 h and 119 patients received placebo.
Fi studju double blind minnhom, 113 pazjenti rċivew rotigotine sa doża massima ta ’ 8 mg/ 24 siegħa, 109 pazjenti rċivew rotigotine sa doża massima ta ’ 12 mg/ 24 siegħa u 119- il pazjent irċivew il - plaċebo.
The patients were titrated to their optimal doses of rotigotine or placebo in weekly increments of 2 mg/ 24 h starting at 4 mg/ 24 h.
Il- pazjenti kienu ttitrati għall- aħjar dożi tagħhom ta ’ rotigotine jew tal- plaċebo f’ inkrementi ta ’ kull ġimgħa ta ’ 2 mg/ 24 siegħa, li bdew b’ doża ta ’ 4 mg/ 24 siegħa.
Patients in each treatment group were maintained at their optimal dose for 6 months.
Il- pazjenti f’ kull grupp tal- kura inżammu fl- aħjar doża tagħhom għal 6 xhur.
At the end of the maintenance treatment an improvement of at least 30% was seen in 57% and 55% of the subjects receiving rotigotine 8 mg/ 24 h and 12 mg/ 24 h, respectively and in 34% of the subjects receiving placebo (Differences 22% and 21%, respectively CI95% 10%; 35% and 8%; 33%, respectively, p < 0.001 for both rotigotine groups).
Fit- tmiem tat- trattament tal- manteniment, titjib ta ’ mill - inqas 30% kien osservat f’ 57% u f’ 55% tal- pazjenti li kienu qed jirċievu rotigotine 8 mg/ 24 siegħa u 12 mg/ 24 siegħa, rispettivament u f’ 34% tal- pazjenti li kienu qed jirċievu l- plaċebo (differenza ta ’ 22% u 21%, rispettivament CI95% 10%; 35% u 8%; 33%, rispettivament, p < 0. 001 għaż- żewġ gruppi ta ’
With rotigotine, the mean reductions in “ off” time were 2.7 and 2.1 hours, respectively whereas in the placebo-treated arm a reduction of 0.9 hours was observed.
B’ rotigotine, il- medja tat- tnaqqis fil- ħin “ off ” kien ta ’ 2. 7 u 2. 1 sigħat rispettivament, filwaqt li fil- parti ta ’ l- istudju fejn il- pazjenti kienu kkurati bil- plaċebo, tnaqqis ta ’ 0. 9 ta ’ siegħa kien osservat.
The differences were statistically significant (p < 0.001 and p=0.003, respectively).
Id- differenzi kienu statistikament sinifikanti (p < 0. 001 u p=0. 003, rispettivament).
In a second double-blind study, 201 patients received rotigotine, 200 received pramipexole and 100 patients received placebo.
Fit- tieni studju double- blind, 201 pazjenti rċivew rotigotine, 200 irċivew pramipexole u 100 pazjenti rċivew il- plaċebo.
The patients were titrated to their optimal dose of rotigotine in weekly increments of 2 mg/ 24 h starting at 4 mg/ 24 h to a maximum dose of 16 mg/ 24 h.
Il- pazjenti kienu ttitrati għall- aħjar doża tagħhom ta ’ rotigotine f’ inkrementi ta ’ kull ġimgħa ta ’ 2 mg/ 24 siegħa u bdew b’ doża ta ’ 4 mg/ 24 siegħa sa doża massima ta ’ 16 mg/ 24 siegħa.
In the pramipexole group, patients received 0,375 mg in the first week, 0.75 mg in the second week and were titrated further in weekly increments of 0.75 mg to their optimal dose up to a maximum of 4.5 mg/ day.
Fil- grupp ta ’ pramipexole, il- pazjenti rċivew 0. 375 mg fl- ewwel ġimgħa, 0. 75 mg fit- tieni ġimgħa u kienu ttitrati mill- ġdid f’ inkrementi ta ’ kull ġimgħa ta ’ 0. 75 mg għall- aħjar doża tagħhom sa massimu ta ’ 4. 5 mg/ kuljum.
Patients in each treatment group were maintained for 4 months.
Il- pazjenti f’ kull grupp tal- kura inżammu għal 4 xhur.
At the end of the maintenance treatment an improvement of at least 30% was seen in 60% of the subjects receiving rotigotine, 67% of the subjects receiving pramipexole and 35% of the subjects receiving placebo (Difference rotigotine versus placebo 25%; CI95% 13%; 36%, difference pramipexole versus placebo 32% CI95% 21%; 43%, difference pramipexole versus rotigotine 7%; CI95% -2%; 17%). The mean reduction in the “ off” time was 2.5 hours in the rotigotine arm, 2.8 hours in the pramipexole arm and 0.9 hours in the placebo arm.
Il- medja tnaqqis fil- ħin “ off ” kien ta ’ 2. 5 sigħat fil- parti ta ’ l- istudju b’ rotigotine, 2. 8 sigħat fil- parti ta ’ l- istudju bi pramipexole u 0. 9 ta ’ siegħa fil- parti ta ’ l- istudju bil - plaċebo.
The apparent volume of distribution in humans is approximately 84 l/ kg.
Il- volum apparenti tad- distribuzzjoni fil- bnedmin hu ta ’ madwar 84 l/ kg.
19 Elimination Approximately 71% of the rotigotine dose is excreted in urine and a smaller part of about 23% is excreted in faeces.
Eliminazzjoni Madwar 71% tad- doża ta ’ rotigotine titneħħa fl- awrina u parti iżgħar ta ’ madwar 23% titneħħa fl - ippurgar.
Special patient groups Because therapy with Neupro is initiated at a low dose and gradually titrated according to clinical tolerability to obtain the optimum therapeutic effect, adjustment of the dose based on gender, weight, or age is not necessary.
21 Minħabba li t- terapija b’ Neupro tinbeda b’ doża baxxa u tkun ittritata gradwalment skond it - tollerabilità klinika biex jinkiseb l- aħjar effett terapewtiku, l- aġġustament tad- doża skond is- sess, il- piż jew l- età mhuwiex meħtieġ.
In repeated dose and long-term toxicity studies, the major effects were associated with the dopamine agonist related pharmacodynamic effects and the consequent decrease of prolactin secretion.
Fl- istudji ta ’ doża ripetuta u dwar it- tossiċità fit- tul, l- effetti prinċipali kienu assoċjati ma ’ l- agonist ta ’ dopamine marbuta ma ’ l- effetti farmakodinamiċi u t- tnaqqis konsegwenti tat- tnixxija ta ’ prolactin.
This mutagenic effect could be attributed to a clastogenic effect of rotigotine.
Dan l- effett mutaġeniku jista ’ jkun attribwit għall- effett klastoġeniku ta ’ rotigotine.
20 Self adhesive matrix layer:
Saff matriku ta ’ sustanza li teħel miegħu nnifsu:
Poly(dimethylsiloxane, trimethylsilyl silicate)-copolymerisate, Povidone K90, sodium metabisulphite (E223), ascorbyl palmitate (E304) and DL-α -tocopherol (E307).
Poly( dimethylsiloxane, trimethylsilyl silicate) - copolymerisate, Povidone K90, sodium metabisulphite (E223), ascorbyl palmitate (E304) u
DATE OF FIRST AUTHORISATION/ RENEWAL OF THE AUTHORISATION 21 15/ 02/ 2006
DATA TA ’ L- EWWEL AWTORIZZAZZJONI/ TIĠDID TA ’ L- AWTORIZZAZZJONI
Neupro 3 mg/ 24 h transdermal patch
Neupro 3 mg/ 24 siegħa garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda
Each patch releases 3 mg of rotigotine per 24 hours.
Kull impjastru jerħi 3 mg ta ’ rotigotine kull 24 siegħa.
Each patch of 15 cm2 contains 6.75 mg of rotigotine.
Kull impjastru ta ’ 15 cm2 fih 6. 75 mg ta ’ rotigotine.
The outside of the backing layer is tan-coloured and imprinted with Neupro 3 mg/ 24 h.
In- naħa ta ’ barra tas- saff ta ’ wara hi ta ’ kulur kannella ċar u għandha l- kliem Neupro 3 mg/ 24 h. stampat fuqha.
Neupro is indicated for the symptomatic treatment of moderate to severe idiopathic Restless Legs Syndrome in adults.
Neupro huwa indikat għal- kura tas- sintomi tas- sindromu ta ’ Restless Legs idjopatiku moderat għal sever fl- adulti.
A single daily dose should be initiated at 1 mg/ 24 h.
Doża waħda kuljum għandha tinbeda b ’ 1 mg/ 24 siegħa.
23 Children and adolescents:
24 Tfal u adolexxenti:
Fibrotic complications:
25 Komplikazzjonijiet fibrotiċi:
24 Although these adverse reactions are believed to be related to the ergoline structure of these compounds, whether other, nonergot derived dopamine agonists can cause them is unknown.
Għalkemm dawn ir- reazzjonijiet avversi huma maħsuba li huma marbuta ma ’ l- istruttura ergolina ta ’ dawn is- sustanzi, mhux magħruf jekk agonisti oħrajn ta ’ dopamine li ġejjin min- nonergots jistgħux jikkawżawhom.
Reports in the literature indicate that treatment of Restless Legs Syndrome with dopaminergic medicinal products can result in augmentation.
Rapporti fil- literatura jindikaw li il- kura tas- sindrome ta ’ Restless legs b’ prodotti mediċinali dopaminerġiċi jistgħu jwasslu għal awmentazzjoni.
Interactions with other forms of hormonal contraception have not been investigated.
26 Interazzjonijiet ma ’ forom oħra ta ’ kontraċezzjoni ormonali ma ġewx investigati.
25 Because rotigotine decreases prolactin secretion in humans, inhibition of lactation is expected.
Minħabba li rotigotine jnaqqas it- tnixxija ta ’ prolactin fil- bnedmin, l- inibizzjoni tat- treddigħ hi mistennija.
General disorders and administration
27 Sistema tal -
26
applikazzjoni (li tinkludi eritema, ħakk, irritazzjoni, raxx, dermatite, bżieżaq żgħar, uġigħ, ekżema, infjammazzjoni, nef ħa, diskolorazzjoni, infafet, escoriation, urtikarja, sensittività eċċessiva) għajja
Hypertension
c)
In case of suspected overdose, the patch(es) should immediately be removed from the patient.
F’ każ ta ’ suspett ta ’ 28 doża eċċessiva, l- impjastru( i) għandu jitneħħa immedjatament mill- pazjent.
27 differences have been observed for the doses 1 mg/ 24 h, 2 mg/ 24 h and 3 mg/ 24 h in comparison to placebo.
Għaż- żewġt punti ta ’ l- aħħar primarji ġew osservati differenzi statistikament sinifikattivi għad- dożi 1 mg/ 24siegħa, 2 mg/ 24siegħa u 3 mg/ 24siegħa meta mqabbla mal- plaċebo.
The adjusted mean difference was -6.5 points (CI95% -8.7; -4.4, p < 0.0001).
Id- differenza medja aġġustata kienet ta ’ - 6. 5 punti (CI 95% - 8. 7; - 4. 4, p < 0. 0001).
Neupro significantly reduced the periodic limb movement index (PLMI) from 50.9 to 7.7 versus 37.4 to 32.7 for placebo (p < 0.0001).
Neupro naqqas sinifikament l- indiċi ta ’ movimint tar- riġlejn perjodiku (PLMI) minn 50. 9 għal 7. 7 meta mqabbel ma ’ 37. 4 għal 32. 7 bil- plaċebo (p < 0. 0001).
Metabolism Rotigotine is metabolised to a great extent.
29 Metaboliżmu Il- biċċa l- kbira ta ’ rotigotine hu mmetabolat.