qanastek/EMEA-V3 huggingface dataset:
5.3 Preclinical safety data 28 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 effect was not confirmed in vivo in the Mouse Micronucleus Test in the rat Unscheduled DNA Synthesis (UDS) test.
30 Unscheduled DNA Synthesis (UDS) fil- firien.
29 Store in a refrigerator (2°C – 8°C).
Aħżen fi friġġ (2°C – 8°C).
SCHWARZ PHARMA Ltd.
31 SCHWARZ PHARMA Ltd.
Neupro 4 mg/ 24 h transdermal patch
Neupro 4 mg/ 24 siegħa garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda
Each patch releases 4 mg of rotigotine per 24 hours.
Kull impjastru jerħi 4 mg ta ’ rotigotine kull 24 siegħa.
Each patch of 20 cm2 contains 9.0 mg of rotigotine.
Kull impjastru ta ’ 20 cm2 fih 9. 0 mg ta ’ rotigotine.
The outside of the backing layer is tan-coloured and imprinted with Neupro 4 mg/ 24 h.
In- naħa ta ’ barra tas- saff ta ’ wara hi ta ’ kulur kannella ċar u għandha l- kliem Neupro 4 mg/ 24 h stampat fuqha.
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).
Neupro hu indikat għall- kura 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 ’).
Dosing in patients with early-stage Parkinson’ s disease:
Id- dożaġġ f’ pazjenti bil- marda ta ’ Parkinson fl- istadju bikri:
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, rispettivament.
The maximal dose is 8 mg/ 24 h.
Id- doża massima hi ta ’ 8 mg/ 24 siegħa.
10 mg/ 24 h may be reached by combination of a 6 mg/ 24 h and a 4 mg/ 24 h patch.
33 10 mg/ 24 siegħa tista ’ tintlaħaq b’ kumbinazzjoni ta ’ impjastru ta ’ 6 mg/ 24 siegħa u ieħor ta ’ 4 mg/ 24 siegħa.
31 Treatment discontinuation Neupro should be discontinued gradually.
Twaqqif tal- kura Neupro għandu jitwaqqaf gradwalment.
Unexpected accumulation of rotigotine levels may also occur at acute worsening of renal function (see section 5.2).
Jista ’ jkun hemm ukoll livelli akkumulati ta ’ rotigotine mhux mistennija meta jiggrava b’ mod akut il- funzjoni tal- kliewi (ara sezzjoni 5. 2).
It is recommended to monitor blood pressure, especially at the beginning of treatment, due to the general risk of orthostatic hypotension associated with dopaminergic therapy.
34 Hu rakkomandat li jsir monitoraġġ tal- pressjoni tad- demm, b’ mod speċjali fil- bidu tat- trattament, minħabba r- riskju ġenerali ta ’ pressjoni tad- demm baxxa ħafna meta wieħed ikun bilwieqfa, assoċjata mat- terapija dopaminerġika.
32 Pathologic gambling, increased libido and hypersexuality have been reported in patients treated with dopamine agonists, including rotigotine.
Logħob patoloġiku ta ’ l- azzard, żieda fil- libido u ipersesswalità kienu rrappurtati f’ pazjenti kkurati b’ agonisti ta ’ dopamine, li jinkludu rotigotine.
4.5 Interaction with other medicinal products and other forms of interaction
35 4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarijiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
33 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..
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.
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.
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.
Adverse drug reactions (ADRs) reported in more than 10% of patients treated with Neupro transdermal patch are nausea, dizziness, somnolence and application site reactions.
36 Reazzjonijiet avversi tal- mediċina (Adverse Drug Reactions - 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.
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.
34 Metabolism and nutrition disorders
perċezzjoni (alluċ a inazzjoni, alluċinazzjoni
libido (including hypersexuality), anxiety, sleep a disorder, nightmares, disorientation
sturdament (li jinkludi dak ikkawżat mill- pożizzjoni)
a
Disturbi fil- qalb
a
37
Nervous system disorders
fibrillazzjoni atrijali,
somnolence, a dizziness
Sistema tal -
dyskinesia, dizziness postural, a headache
klassifika/ tal - organi skond MedDRA
syncope, vasovagal convulsion, loss of syncope, dystonia, consciousness hypersomnia, lethargia, disturbance in attention, memory impaired, paraesthesia, dysgeusia, balance disorder, tremor
> 1/ 100, ≤1/ 10
Eye disorders (see section 4.4)
> 1/ 1, 000, ≤1/ 100
visual disturbance, photopsia, blurred vision
Disturbi vaskulari
Ear and labyrinth disorders Cardiac disorders
pressjoni tad - demm baxxa meta
vertigo (incl. positional) atrial fibrillation, supraventricular heart rate increased, tachycardia palpitations a
żieda fit- taħbit tal - qalb, palpitazzjonijiet pressjoni tad- demm għoljaa, pressjoni
Vascular disorders
supraventrikulari
orthostatic hypotension (see section 4.4)
wieħed iqum bilwieqfa/ ikun bilwieqfa (ara sezzjoni 4. 4).
hypertension, hypotension a
tad- demm baxxa a
cough, hiccup, dyspnoea
a
nauseaa
Disturbi gastro - intestinali
vomiting, a diarrhoea, a
rimettar, dijarea, a stitikezza, a dispepsja, ħalq a xott
abdominal pain (incl. upper
żieda fl- enzimi epatiċi (li tinkludi GGT, ALAT, ASAT)
constipation, a
Disturbi fil- ġilda u
abdominal pain),
raxx (li jinkludi
35 Skin and subcutaneous tissue disorders
ġilda Disturbi muskolu - skeletrali u tal - connective tissue Disturbi fis- sistema riproduttiva u fis - sider
oedema peripheral,
anormali, żieda fil - a
gait disturbance,
(li tinkludi
and administration site conditions
jinkludu għeja
reactions (including a erythema, a
a a eritema, ħakk, a
asthenic b conditions (incl. a fatigue, asthenia,
a kbira, astenja,
feeling abnormal, a weight increased,
irritazzjoni, a ħruq, a dermatite, infjammazzjoni, ponot, bżieżaq żgħar, infafet, uġigħ, sensittività
pruritus, irritationa, a
38 Sistema tal -
malaise), weight
klassifika/ tal - organi skond MedDRA
burning, a dermatitis, inflammation, papulae, vesicle, blister, pain, hypersensitivity) (see section 4.4)
> 1/ 10 eċċessiva) (ara sezzjoni 4. 4)
decreased
> 1/ 100, ≤1/ 10
Injury, poisoning and procedural complications a
> 1/ 1, 000, ≤1/ 100
fall
≤1/ 1, 000
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
waqgħat Korriment, avvelenament u komplikazzjonijiet ta` xi proċedura a 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
36 Pharmacotherapeutic group:
Agonisti ta ’ dopamine:
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.
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.
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).
39 komponent Motor Examination (Parti III) tal- Unified Parkinson’ s Disease Rating Scale (UPDRS).
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.
37 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 ’ rotigotine).
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.
Fl- aħħar tal- kura tal- manteniment, titjib ta ’ mill- inqas 30% kien osservat f’ 60% tal- pazjenti li kienu qed jirċievu rotigotine, f’ 67% tal- pazjenti li kienu qed jirċievu pramipexole u f’ 35% tal- pazjenti li kienu qed jirċievu l- plaċebo (Id- differenza ta ’ rotigotine kontra l- plaċebo 25%; CI95% 13%; 36%, differenza ta ’ pramipexole kontra l- plaċebo 32% CI95% 21%; 43%, differenza ta ’ pramipexole kontra
38 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.
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.
41 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.
Store in a refrigerator (2°C – 8°C).
42 Aħżen fi friġġ (2°C – 8°C).
15/ 02/ 2006
15/ 02/ 06
Neupro 6 mg/ 24 h transdermal patch
Neupro 6 mg/ 24 siegħa garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda
Each patch releases 6 mg of rotigotine per 24 hours.
Kull impjastru jerħi 6 mg ta ’ rotigotine kull 24 siegħa.
Each patch of 30 cm2 contains 13.5 mg of rotigotine.
Kull impjastru ta ’ 30 cm2 fih 13. 5 mg ta ’ rotigotine.
The outside of the backing layer is tan-coloured and imprinted with Neupro 6 mg/ 24 h.
In- naħa ta ’ barra tas- saff ta ’ wara hi ta ’ kulur kannella ċar u għandha l- kliem Neupro 6 mg/ 24 h stampat fuqha.
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).
Neupro hu indikat għal- kura 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 ’).
4 mg/ 24 h or 6 mg/ be effective doses in some patients.
4 mg/ 24 siegħa jew 6 mg/ 24 siegħa jistgħu jkunu dożi effettivi f’ xi pazjenti.
For doses higher than 8 mg/ 24 h multiple patches may be used to achieve the final dose e. g.
44 Għal dożi ogħla minn 8 mg/ 24 siegħa, impjastri multipli jistgħu jintużaw biex jilħqu id- doża finali; eż.
41 Treatment discontinuation Neupro should be discontinued gradually.
Twaqqif tal- kura Neupro għandu jitwaqqaf gradwalment.
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 għal tneħħija mnaqqsa ta ’ rotigotine.
Syncope was observed in association with Neupro, but also at a similar rate in patients treated with placebo.
Is- sinkope kien osservat b’ rabta ma ’ Neupro, iżda wkoll kellu rata simili f’ pazjenti li kienu kkurati bil -
42 Pathologic gambling, increased libido and hypersexuality have been reported in patients treated with dopamine agonists, including rotigotine.
Logħob patoloġiku ta ’ l- azzard, żieda fil- libido u ipersesswalità kienu rrappurtati f’ pazjenti kkurati b’ agonisti ta ’ dopamine, li jinkludu rotigotine.
4.5 Interaction with other medicinal products and other forms of interaction
46 4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarijiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
43 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.
Adverse drug reactions (ADRs) reported in more than 10% of patients treated with Neupro transdermal patch are nausea, dizziness, somnolence and application site reactions.
47 Reazzjonijiet avversi tal- mediċina (Adverse Drug Reactions - 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.
44 Metabolism and nutrition disorders
perċezzjoni (alluċ a inazzjoni, alluċinazzjoni
auditory hallucination, illusion), confusion state, abnormal dreamsa, insomnia
irqad esaġerat, letarġija, disturbi fl -
a
48
somnolence, dizzinessa
Sistema tal -
45 Skin and subcutaneous tissue disorders
ġilda Disturbi muskolu - skeletrali u tal - connective tissue Disturbi fis- sistema riproduttiva u fis - sider
pruritus
telqa), tnaqqis fil - piż
, irritation, a
49 Sistema tal -
malaise), weight
Komuni ħafna
burning, dermatitis,
Mhux komuni
a
Rari
decreased
klassifika/ tal - organi skond MedDRA
inflammation, papulae, vesicle, blister, pain, hypersensitivity) (see section 4.4) Injury, poisoning and procedural complications a
> 1/ 10 eċċessiva) (ara sezzjoni 4. 4)
46 Pharmacotherapeutic group:
Agonisti ta ’ dopamine:
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).
50 komponent Motor Examination (Parti III) tal- Unified Parkinson’ s Disease Rating Scale (UPDRS).
47 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 ’ rotigotine).
48 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.
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.
52 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.
49 6.2 Incompatibilities
6. 2 Inkompatibilitajiet
Store in a refrigerator (2°C – 8°C).
53 Aħżen fi friġġ (2°C – 8°C).
Neupro 8 mg/ 24 h transdermal patch
Neupro 8 mg/ 24 siegħa garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda
Each patch releases 8 mg of rotigotine per 24 hours.
Kull impjastru jerħi 8 mg ta ’ rotigotine kull 24 siegħa.
Each patch of 40 cm2 contains 18.0 mg of rotigotine.
Kull impjastru ta ’ 40 cm2 fih 18. 0 mg ta ’ rotigotine.
The outside of the backing layer is tan-coloured and imprinted with Neupro 8 mg/ 24 h.
In- naħa ta ’ barra tas- saff ta ’ wara hi ta ’ kulur kannella ċar u għandha l- kliem Neupro 8mg/ 24 h stampat fuqha.
Dosing in patients with early stage Parkinson’ s disease:
Id- dożaġġ f’ pazjenti bil- marda ta ’ Parkinson fl- istadju bikri:
For doses higher than 8 mg/ 24 h multiple patches may be used to achieve the final dose e. g.
55 Għal dożi ogħla minn 8 mg/ 24 siegħa, impjastri multipli jistgħu jintużaw biex jilħqu id- doża finali; eż.
51 Treatment discontinuation Neupro should be discontinued gradually.
Twaqqif tal- kura Neupro għandu jitwaqqaf gradwalment.
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 għat- tneħħija mnaqqsa ta ’ rotigotine.
52 Pathologic gambling, increased libido and hypersexuality have been reported in patients treated with dopamine agonists, including rotigotine.
Logħob patoloġiku ta ’ l- azzard, żieda fil- libido u ipersesswalità kienu rrappurtati f’ pazjenti kkurati b’ agonisti ta ’ dopamine, li jinkludu rotigotine.
4.5 Interaction with other medicinal products and other forms of interaction
57 4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarijiet oħra li jistgħu jibdlu l- effett farmaċewtiku tal- prodott
53 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.
Co-administration of rotigotine (3 mg/ 24 h) did not affect the pharmacodynamics and pharmacokinetics of oral contraceptives (0.03mg ethinylestradiol, 0.15mg levonorgestrel).
L- għoti flimkien ta ’ rotigotine (3 mg/ 24 siegħa) ma kellu l- ebda effett fuq il- farmakodinamika u l - farmakokinetika ta ’ kontraċettivi orali (0. 03mg ethinylestradiol, 0. 15mg levonorgestrel).
Adverse drug reactions (ADRs) reported in more than 10% of patients treated with Neupro transdermal patch are nausea, dizziness, somnolence and application site reactions.
58 Reazzjonijiet avversi tal- mediċina (Adverse Drug Reactions - 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.
54 Metabolism and nutrition disorders
perċezzjoni (alluċ a inazzjoni, alluċinazzjoni
a
ngħas, a
(including paranoid psychosis), compulsive
sturdament
a
(ara sezzjoni 4. 4).
Nervous system disorders
59 Sistema tal -
somnolence, a dizziness
Komuni ħafna
dyskinesia, dizziness postural, a headache
klassifika/ tal - organi skond MedDRA Disturbi fil- widnejn u fis- sistema labirintika
syncope, vasovagal convulsion, loss of syncope, dystonia, consciousness hypersomnia, lethargia, disturbance in attention, memory impaired, paraesthesia, dysgeusia, balance disorder, tremor
> 1/ 1, 000, ≤1/ 100 sturdament (li jinkludi dak ikkawżat mill- pożizzjoni)
Eye disorders (see section 4.4)
Disturbi fil- qalb
visual disturbance, photopsia, blurred vision
fibrillazzjoni atrijali,
vomiting, a diarrhoea,
rimettar, dijarea, a stitikezza, a dispepsja, ħalq a xott
constipationa, a
Disturbi fil- ġilda u
55 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, hyperhydrosisa,
makulari, exanthema (raxx fil- ġilda kkaġunat minn xi infezzjoni minn virus)) (ara sezzjoni 4. 4), a eritema; ħakk, iperidrożi (għaraq a eċċessiv) a
, irritation, a
60 Sistema tal -
inflammation, papulae, vesicle, blister, pain, hypersensitivity) (see section 4.4) Injury, poisoning and procedural complications a
> 1/ 10 ponot, bżieżaq żgħar, infafet, uġigħ, sensittività eċċessiva) (ara sezzjoni 4. 4)
56 5.1 Pharmacodynamic properties
5. 1 Tagħrif farmakodinamiku
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.
61 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..
57 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 ’ rotigotine).
58 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.
5.3 Preclinical safety data
63 5. 3 Tagħrif ta ’ qabel l- użu kliniku dwar is- sigurtà tal- mediċina
10 months.
64 10 xhur.
Neupro 2 mg/ 24 h 4 mg/ 24 h 6 mg/ 24 h 8 mg/ 24 h Transdermal patch
Neupro 2 mg/ 24 siegħa 4 mg/ 24 siegħa 6 mg/ 24 siegħa 8 mg/ 24 siegħa Garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda
Neupro 2 mg/ 24 h transdermal patch Each patch releases 2 mg of rotigotine per 24 hours.
Neupro 2 mg/ 24 siegħa garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda Kull impjastru jerħi 2 mg ta ’ rotigotine kull 24 siegħa.
Neupro 4 mg/ 24 h transdermal patch Each patch releases 4 mg of rotigotine per 24 hours.
Neupro 4 mg/ 24 siegħa garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda Kull impjastru jerħi 4 mg ta ’ rotigotine kull 24 siegħa.
Neupro 6 mg/ 24 h transdermal patch Each patch releases 6 mg of rotigotine per 24 hours.
Neupro 6 mg/ 24 siegħa garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda Kull impjastru jerħi 6 mg ta ’ rotigotine kull 24 siegħa.
Neupro 8 mg/ 24 h transdermal patch Each patch releases 8 mg of rotigotine per 24 hours.
Neupro 8 mg/ 24 siegħa garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda Kull impjastru jerħi 8 mg ta ’ rotigotine kull 24 siegħa.
The outside of the backing layer is tan-coloured and imprinted with Neupro 2 mg/ 24 h, 4 mg/ 24 h, 6 mg/ 24 h or 8 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, 4 mg/ 24 h, 6 mg/ 24 h jew 8 mg/ 24 h stampat fuqha.
61 Dosage The dose recommendations made are in nominal dose.
66 Dożaġġ Ir- rakkomandazzjonijiet tad- doża mogħtija huma skond id- doża nominali.
Neupro treatment initiation pack contains 4 different packages (one for each strength) with 7 patches each, for the first four weeks of therapy.
Il- pakkett tal- bidu tal- kura ta ’ Neupro fih 4 pakketti differenti (wieħed għal kull qawwa) b’ 7 impjastri kull wieħed, għall- ewwel erba ’ ġimgħat tat- terapija.
Depending on the patient’ s response, not all of the following dose steps may be required or additional higher doses may be needed after week 4, which are not covered by this package.
Jiddependi fuq ir- rispons tal- pazjent, mhux l- inkrementi kollha li ġejjin tad- doża jistgħu jkunu meħtieġa, jew dożi ogħla addizzjonali jistgħu jkunu meħtieġa wara r- 4 ġimgħa, li mhumiex koperti minn dan il- pakkett.
On the first day of treatment the patient starts with Neupro 2 mg/ 24 h.
Fl- ewwel jum tat- trattament, il- pazjent jibda b’ Neupro 2 mg/ 24 siegħa.
During the second week, the patient takes Neupro 4 mg/ 24 h.
Matul it- tieni ġimgħa, il - pazjent jieħu Neupro 4 mg/ 24 siegħa.
During the third week, he or she takes Neupro 6 mg/ 24 h and during the fourth week Neupro 8 mg/ 24 h.
Matul it- tielet ġimgħa, hu jew hi jieħu/ tieħu Neupro 6 mg/ 24 siegħa u matul ir- raba ’ ġimgħa Neupro 8 mg/ 24 siegħa.
The packages are marked with “ Week 1 (2, 3 or 4 )”.
Il- pakketti huma mmarkati b ’ “ Ġimgħa 1 (2, 3 jew 4) ”.
In the event that a patch should fall off, a new patch should be applied for the remainder of the 24 hour dosing interval.
67 Fil- każ li l- impjastru jaqa ’, għandu jiġi applikat impjastru ġdid għall- bqija tal- perjodu tad- dożaġġ ta ’ 24 siegħa.
62 4.3 Contraindications
4. 3 Kontra- indikazzjonijiet
Pathologic gambling, increased libido and hypersexuality have been reported in patients treated with dopamine agonists, including rotiogotine.
Logħob patoloġiku ta ’ l- azzard, żieda fil- libido u ipersesswalità kienu rrappurtati f’ pazjenti kkurati b’ agonisti ta ’ dopamine, li jinkludu rotigotine.
Ophthalmologic monitoring is recommended at regular intervals or if vision abnormalities occur.
68 Monitoraġġ oftalmoloġiku hu rakkomandat f’ intervalli regolari jew jekk iseħħu anormalitajiet fil- vista.
63 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, fil- pazjenti bil- marda ta ’ Parkinson.
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.
Animal studies do not indicate any teratogenic effects in rats and rabbits, but embryo-toxicity was observed in rats and mice at materno-toxic doses (see section 5.3).
Studji fuq l- annimali ma jindikaw l - ebda effetti teratoġeniċi fil- firien u fil- fniek, iżda tossiċità ta ’ l- embriju kienet osservata fil- firien u fil -
The potential risk for humans is unknown.
69 ġrieden f’ dożi materno- tossiċi (ara sezzjoni 5. 3). Mhux magħruf ir- riskju potenzjali fuq il- bniedem.
64 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.
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.
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 (Adverse Drug Reactions - 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.
anorexia, decreased appetite a
a viżwali, alluċinazzjoni tas - smigħ, illużjoni),
Psychiatric
Sistema tal -
perception
Komuni ħafna
b
Komuni
sleep attacks,
Mhux komuni
disorders
Rari
disturbances
klassifika/ tal - organi skond MedDRA
psychotic disorder
> 1/ 100, ≤1/ 10
(hallucination, visual a hallucination,
> 1/ 1, 000, ≤1/ 100
(including paranoid psychosis), compulsive
≤1/ 1, 000
auditory hallucination, illusion), confusion state, abnormal a dreams, insomnia
stat ta ’ konfużjoni, ħolm a anormali, nuqqas
disorders (including pathologic gambling, punding), increased
punding), żieda fil - libido (li tinkludi l - ipersesswalità),
a
a ta ’ rqad
libido (including hypersexuality), anxiety, sleep a disorder, nightmares, disorientation
ansjetà, problemi a biex torqod, ħmar il - lejl, diżorjentament
somnolence, dizzinessa
vasovagali, distonja,
dyskinesia, dizziness postural, headachea
irqad esaġerat, letarġija, disturbi fl -
syncope, vasovagal convulsion, loss of syncope, dystonia, consciousness hypersomnia, lethargia, disturbance in attention, memory impaired, paraesthesia, dysgeusia, balance disorder, tremor
attenzjoni, indeboliment tal - memorja, parestesija, indeboliment fis- sens tat- togħma, indeboliment fil - bilanċ, rogħda disturbi tal- vista,
Eye disorders (see section 4.4)
(ara sezzjoni 4. 4).
visual disturbance, photopsia, blurred vision
fotopsija, vista mċajpra
65 Ear and labyrinth disorders
Disturbi fil- widnejn u fis- sistema labirintika
vertigo (incl. positional)
sturdament (li jinkludi dak ikkawżat mill- pożizzjoni)
Cardiac disorders
pressjoni tad - demm baxxa meta
atrial fibrillation, heart rate increased, palpitations a
pressjoni tad- demm għoljaa, pressjoni
supraventricular tachycardia
wieħed iqum bilwieqfa/ ikun bilwieqfa (ara sezzjoni 4. 4).
Vascular disorders
tad- demm baxxa a
orthostatic hypotension (see section 4.4)
Disturbi respiratorji, toraċiċi u medjastinali
hypertension, hypotension a
sogħla, sulluzzu, dispnea
Respiratory, thoracic and mediastinal disorders
dardira
Skin and subcutaneous tissue disorders
ġilda
rash (incl. rash, allergic; macular, exanthema)(see section 4.4), a erythema; pruritus, a hyperhydrosis,
makulari, exanthema (raxx fil- ġilda kkaġunat minn xi infezzjoni 71
generalized pruritus, dermatitis contact, skin irritation
irritazzjoni tal- ġilda
Musculoskeletal and connective tissue disorder
Komuni ħafna Sistema tal -
joint swelling
Mhux komuni
Reproductive system and breast disorder
> 1/ 1, 000, ≤1/ 100 nefħa fil- ġogi disfunzjoni erettili
erectile dysfunction
≤1/ 1, 000
a
Disturbi ġenerali u
a
reazzjonijiet fiz - zona ta ’ l -
General disorders
edema periferali,
application site b
disturbi fil- mod kif a
oedema peripheral,
kundizzjonijiet ta ’
gait disturbance,
kundizzjonijiet
and administration site conditions
timxi, tħossok
reactions (including a erythema, a
b
asthenic b conditions (incl. a fatigue, asthenia,
asteniċi (li
feeling abnormal, a weight increased,
anormali, żieda fil - a
pruritus
(li tinkludi
, irritation, a
jinkludu għeja
malaise), weight
piż
burning, dermatitis,
a a eritema, ħakk, a
decreased
a kbira, astenja,
inflammation, papulae, vesicle, blister, pain, hypersensitivity) (see section 4.4) Injury, poisoning and procedural complications a
irritazzjoni, a ħruq, a dermatite, infjammazzjoni, ponot, bżieżaq żgħar, infafet, uġigħ, sensittività eċċessiva) (ara sezzjoni 4. 4)
fall
telqa), tnaqqis fil - piż
66 Patients treated with dopamine agonists including Neupro, have been reported as exhibiting signs of pathological gambling, increased libido and hypersexuality, generally reversible upon reduction of the dose or treatment discontinuation.
Il- pazjenti kkurati b’ agonisti ta ’ dopamine, li jinkludu Neupro, kienu rrappurtati li wrew sinjali logħob ta ’ l- azzard patoloġiku, żieda fil- libido u ipersesswalità, li huma ġeneralment riversibbli malli titnaqqas id- doża jew titwaqqaf il- kura.
The patient should be monitored closely, including heart rate, heart rhythm and blood pressure.
Il- pazjent għandu jkun immonitorjat mill- qrib, u dan jinkludi r- rata tat- taħbit tal- qalb, ir- rittmu tal- qalb
67 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.
Two additional trials were conducted in patients who were receiving concomitant levodopa therapy.
73 Żewġ provi addizzjonali twettqu f’ pazjenti li kienu qed jirċievu terapija fl- istess ħin b’ levodopa.
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 ’ rotigotine).
68 The in vitro binding of rotigotine to plasma proteins is approximately 92%.
Distribuzzjoni It- twaħħil in vitro ta ’ rotigotine mal- proteini tal- plażma hu ta ’ madwar 92%.
Elimination Approximately 71% of the rotigotine dose is excreted in urine and a smaller part of about 23% is excreted in faeces.
74 Eliminazzjoni Madwar 71% tad- doża ta ’ rotigotine titneħħa fl- awrina u parti iżgħar ta ’ madwar 23% titneħħa fl - ippurgar.
69 6.
75 6.
Store in the original package.
Aħżen fi friġġ (2°C – 8°C) Aħżen fil- pakkett oriġinali.
The treatment initiation pack contains 28 transdermal patches in 4 cartons with 7 patches of 2 mg, 4 mg, 6 mg, and 8 mg each, individually sealed in sachets.
Pakkett wieħed tal- bidu tal- kura fih 28 garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda f’ 4 kaxxi tal- kartun b’ 7 impjastri ta ’ 2 mg, 4 mg, 6 mg, u 8 mg kull waħda, li huma ssiġillati individwalment fi qratas.
70 8.
76 8.
71 ANNEX II
77 ANNESS II
Shannon Industrial Estate Shannon, Co. Clare Ireland
Shannon Industrial Estate Shannon, Co. Clare L- Irlanda
Pharmacovigilance system The MAH must ensure that the system of pharmacovigilance, as described in version 5 (13 March 2008) presented in Module 1.8.1. of the Marketing Authorisation, is in place and functioning before and whilst the product is on the market.
Sistema tal - Farmakoviġilanza Id- Detentur ta ’ l- Awtorizzazzjoni għat- tqegħid fis- Suq irid jiżgura li s- sistema ta ’ farmakoviġilanza, kif deskritta f’ verzjoni 5 (13 Marzu 2008) preżentata fis- Sezzjoni 1. 8. 1 tal- Awtorizzazzjoni ta ’ Tqegħid fis- Suq, tkun implimentata u taħdem qabel ma l- prodott jibda jinbiegħ.
Risk Management Plan The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the Pharmacovigilance Plan, as agreed in version 6 (18 April 2008) of the Risk Management Plan (RMP) presented in Module 1.8.2. of the Marketing Authorisation and any subsequent updates of the RMP agreed by the CHMP.
Pjan dwar l- Immaniġġjar tar- Riskju Id- Detentur ta ’ l- Awtorizzazzjoni għat- tqegħid fis- Suq ikun obbligat li jwettaq l- istudji u attivitajiet ta ’ farmakoviġilanza addizzjonali deskritti fil- pjan tal- Farmakoviġilanza, kif maqbul f’ verżjoni 6 (18 April 2008) tal - Pjan dwar l- Immaniġġjar tar- Riskju (RMP) ippreżentat f ’ Sezzjoni 1. 8. 2 tal - Awtorizzazzjoni ta ’ Tqegħid fis- Suq u titdil ieħor tal- RMP sussegwenti maqbul mil CHMP.
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the updated RMP should be submitted at the same time as the next Periodic Safety Update Report (PSUR).
Pjan dwar l- Immaniġġjar tar- Riskju aġġornat għandu jkun ipprovdut skond il- Linja Gwida CHPM dwar is- Sistemi ta ’ l- Immaniġġjar tar- Riskji għal prodotti mediċinali għall- użu uman, fl- istess żmien tal- Rapport Perjodiku Aġġornat ta ’ Sigurta ’ (PSUR).
In addition, an updated RMP should be submitted • When new information is received that may impact on the current Safety Specification, Pharmacovigilance Plan or risk minimisation activities • Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being reached • At the request of the EMEA
Addizzjonalment, RMP aġġornat irid jiġi sottomess • Meta informazzjoni ġdida tiġi riċevuta li tista ’ jkollha impatt fuq l- Ipeċifikazzjoni ta ’ Sigurta ’ kurrenti, il- Pjan ta ’ Farmakoviġilanza jew attivitajjiet ta ’ tnaqqis tar- riskju • Sa żmien 60 ġurnata minn meta jintlaħaq stadju importanti (farmakovigilanza jew tnaqqis tar- riskju) Wara talba ta ’ EMEA
In order to address the quality defect in relation to the crystal formation in the patches, the MAH commits to:
Sabiex jindirizza d- difett fil- kwalita´ b’ konnessjoni mal- formazzjoni ta ’ kristalli fl- impjastri, id - Detentur ta ’ l- Awtorizzazzjoni għat- Tqegħid fis- Suq qed jikkommetti ruħu li:
• Submitting changes to the Marketing Authorisation in relation to the product specifications, shelf-life and storage conditions.
79 • Jaħżen, jittrasporta bil- baħar, u jqassam l- impjastri Neupro kollha b ’ process ta ’ cold chain integrali (2 sa 8°C). • Ibiddel il- prodott li huwa preżentatment fis- suq, fi żmien perjodu ta ’ tlett xhur. • Jissottometti tibdiliet fl- Awtorizzazzjoni għat- Tqegħid fis- Suq b’ konnessjoni mal - ispeċifikazzjonijiet, iż- żmien kemm idum tajjeb il- prodott mediċinali u l- kondizzjonijiet għal - ħażna. • Ikompli jġib għal l’ aħjar il- proċess ta ’ manifattura u jissottometti r- riżultati u l- varjazzjonijiet neċessarji għal valutazzjoni lil CHMP.
74 ANNEX III
80 ANNESS III
76 PARTICULARS TO APPEAR ON THE OUTER PACKAGING OUTER CARTON (WITH BLUE BOX) (EXCLUDING MULTIPACKS) BOX OF 7 [20] [28] [30] [56] [60] [90] PATCHES
82 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA KARTUNA TA ’ BARRA (BIL- BLUE BOX) (ESKLUŻI L- PAKKETTI MULTIPLI) KAXXA TA ’ 7 [20] [28] [30] [56] [60] [90] IMPJASTRU
Neupro 1 mg/24 h transdermal patch Rotigotine
Neupro 1 mg/ 24 siegħa garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda Rotigotine
Poly(dimethylsiloxane, trimethylsilyl silicate)-copolymerisate, povidoneK90, E171, E223, E304, E307, fluoropolymer, polyester, silicone, aluminium, pigments (yellow95, red166, red144, black7)
Poly( dimethylsiloxane, trimethylsilyl silicate) - copolymerisate, povidoneK90, E171, E223, E304, E307, fluoropolimer, poliester, silikon, aluminju, pigmenti (isfar95, aħmar166, aħmar144, iswed7)
7 transdermal patches 20 transdermal patches 28 transdermal patches 30 transdermal patches 56 transdermal patches 60 transdermal patches 90 transdermal patches
7 garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda 20 garża li jipprovdu mediċina li tgħaddi minn ġol- ġilda 28 garża li jipprovdu mediċina li tgħaddi minn ġol- ġilda 30 garża li jipprovdu mediċina li tgħaddi minn ġol- ġilda 56 garża li jipprovdu mediċina li tgħaddi minn ġol- ġilda 60 garża li jipprovdu mediċina li tgħaddi minn ġol- ġilda 90 garża li jipprovdu mediċina li tgħaddi minn ġol- ġilda
Transdermal use.
Użu transdermali.
Shannon, Industrial Estate, Co.Clare, Ireland
Shannon, Industrial Estate, Co. Clare, L- Irlanda
EU/1/05/331/038 [7 transdermal patches] EU/1/05/331/040 [28 transdermal patches] EU/1/05/331/039 [20 transdermal patches] EU/1/05/331/041 [30 transdermal patches] EU/1/05/331/042 [56 transdermal patches] EU/1/05/331/043 [60 transdermal patches] EU/1/05/331/045 [90 transdermal patches]
EU/ 1/ 05/ 331/ 038 [7 garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda] EU/ 1/ 05/ 331/ 040 [28 garża li jipprovdu mediċina li tgħaddi minn ġol- ġilda] EU/ 1/ 05/ 331/ 039 [20 garża li jipprovdu mediċina li tgħaddi minn ġol- ġilda] EU/ 1/ 05/ 331/ 041 [30 garża li jipprovdu mediċina li tgħaddi minn ġol- ġilda] EU/ 1/ 05/ 331/ 042 [56 garża li jipprovdu mediċina li tgħaddi minn ġol- ġilda] EU/ 1/ 05/ 331/ 043 [60 garża li jipprovdu mediċina li tgħaddi minn ġol- ġilda] EU/ 1/ 05/ 331/ 045 [90 garża li jipprovdu mediċina li tgħaddi minn ġol- ġilda]
MANUFACTURER’S BATCH NUMBER
NUMRU TAL- LOTT
Neupro 1 mg/24 h
Neupro 1 mg/ 24 siegħa
78 PARTICULARS TO APPEAR ON THE OUTER PACKAGING MULTIPACKS ONLY OUTER LABEL (WITH BLUE BOX) BOX OF 84 [100] PATCHES CONTAINING 2 BOXES OF 42 [50] PATCHES
84 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA PAKKETTI MULTIPLI BISS TIKKETTA TA ’ BARRA (BIL- BLUE BOX) KAXXA TA ’ 84 [100] IMPJASTRU LI FIH 2 KAXXI TA ’ 42 [50] IMPJASTRU
84 transdermal patches, multipack, containing 2 boxes with 42 patches each 100 transdermal patches, multipack, containing 2 boxes with 50 patches each
84 garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda, pakkett multiplu, li fih 2 kaxxi bi 42 impjastru f’ kull wieħed 100 garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda, pakkett multiplu, li fih 2 kaxxi b’ 50 impjastru f’ kull wieħed
Store in a refrigerator.
85 Aħżen fi friġġ.
EU/1/05/331/044 [84 transdermal patches] EU/1/05/331/046 [100 transdermal patches]
EU/ 1/ 05/ 331/ 044 [84 garża li jipprovdu mediċina li tgħaddi minn ġol- ġilda] EU/ 1/ 05/ 331/ 046 [100 garża li jipprovdu mediċina li tgħaddi minn ġol- ġilda]
80 PARTICULARS TO APPEAR ON THE OUTER PACKAGING MULTIPACKS ONLY INTERMEDIATE CARTON (WITHOUT BLUE BOX) BOX OF 42 [50] PATCHES
86 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA PAKKETTI MULTIPLI BISS KARTUNA TAN- NOFS (MINGĦAJR IL- BLUE BOX) KAXXA TA ’ 42 [50] IMPJASTRU
42 transdermal patches, component of a multipack comprising 2 boxes, each containing 42 patches 50 transdermal patches, component of a multipack comprising 2 boxes, each containing 50 patches
42 garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda, komponent ta ’ pakkett multiplu li fih 2 kaxxi, li kull waħda fiha 42 impjastru 50 garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda, komponent ta ’ pakkett multiplu li fih 2 kaxxi, li kull waħda fiha 50 impjastru
Store in a refrigerator.
87 Aħżen fi friġġ.
82 MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
88 TAGĦRIF MINIMU LI GĦANDU JIDHER FUQ IL- PAKKETTI Ż- ŻGĦAR EWLENIN
SACHET LABEL
TIKKETTA TAL- QARTAS
Neupro 1 mg/24 h transdermal patch Rotigotine Transdermal use.
Neupro 1 mg/ 24 siegħa garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda Rotigotine Użu transdermali.
METHOD OF ADMINISTRATION
METODU TA ’ KIF GHANDU JINGĦATA
1 transdermal patch.
Fih garża 1 li tipprovdi mediċina li tgħaddi minn ġol- ġilda.
83 PARTICULARS TO APPEAR ON THE OUTER PACKAGING OUTER CARTON (WITH BLUE BOX) (EXCLUDING MULTIPACKS) BOX OF 7 [20] [28] [30] [56] [60] [90] PATCHES
89 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA KARTUNA TA ’ BARRA (BIL- BLUE BOX) (ESKLUŻI L- PAKKETTI MULTIPLI) KAXXA TA ’ 7 [20] [28] [30] [56] [60] [90] IMPJASTRU
Neupro 2 mg/24 h transdermal patch Rotigotine
Neupro 2 mg/ 24 siegħa garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda Rotigotine
EU/1/05/331/001 [7 transdermal patches] EU/1/05/331/002 [28 transdermal patches] EU/1/05/331/014 [20 transdermal patches] EU/1/05/331/015 [30 transdermal patches] EU/1/05/331/016 [56 transdermal patches] EU/1/05/331/017 [60 transdermal patches] EU/1/05/331/019 [90 transdermal patches]
EU/ 1/ 05/ 331/ 001 [7 garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda] EU/ 1/ 05/ 331/ 002 [28 garża li jipprovdu mediċina li tgħaddi minn ġol- ġilda] EU/ 1/ 05/ 331/ 014 [20 garża li jipprovdu mediċina li tgħaddi minn ġol- ġilda] EU/ 1/ 05/ 331/ 015 [30 garża li jipprovdu mediċina li tgħaddi minn ġol- ġilda] EU/ 1/ 05/ 331/ 016 [56 garża li jipprovdu mediċina li tgħaddi minn ġol- ġilda] EU/ 1/ 05/ 331/ 017 [60 garża li jipprovdu mediċina li tgħaddi minn ġol- ġilda] EU/ 1/ 05/ 331/ 019 [90 garża li jipprovdu mediċina li tgħaddi minn ġol- ġilda]
Neupro 2 mg/24 h
Neupro 2 mg/ 24 siegħa
85 PARTICULARS TO APPEAR ON THE OUTER PACKAGING MULTIPACKS ONLY OUTER LABEL (WITH BLUE BOX) BOX OF 84 [100] PATCHES CONTAINING 2 BOXES OF 42 [50] PATCHES
91 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA PAKKETTI MULTIPLI BISS TIKKETTA TA ’ BARRA (BIL- BLUE BOX) KAXXA TA ’ 84 [100] IMPJASTRU LI FIH 2 KAXXI TA ’ 42 [50] IMPJASTRU
Store in a refrigerator.
92 Aħżen fi friġġ.