qanastek/EMEA-V3 huggingface dataset:
The results for clinically relevant responders pooled from two flexible dose studies out of the three pivotal 26-week multicentre studies in patients with mild-to-moderately severe Alzheimer’ s Dementia, are provided in Table 4 below.
Ir- riżultati ta ’ pazjenti li wrew titjib klinikament rilevanti, li kienu miġbura minn żewġ studji bid- doża flessibbli minn 3 studji multiċentriċi pivitali ta ’ 26 ġimgħa fuq pazjenti li kienu jbatu minn dimenzja ta ’ Alzheimer ta ’ severità ħafifa għal moderatament severa, jinsabu f’ Tabella 4 hawn taħt.
Clinically relevant improvement in these studies was defined a priori as at least 4-point improvement on the ADAS-Cog, improvement on the CIBIC-Plus, or at least a 10% improvement on the PDS.
F’ dawn l - istudji, it- titjib klinikament rilevanti kien definit a priori bħala mill- anqas titjib b’ 4 punti fl- ADAS - Cog, bħala titjib fis- CIBIC- Plus, jew titjib b’ ta ’ l- anqas 10% fil- PDS.
In addition, a post-hoc definition of response is provided in the same table.
Barra dan, definizzjoni post- hoc ta ’ reazzjoni hija mogħtija fl- istess tabella.
The secondary definition of response required a 4-point or greater improvement on the ADAS-Cog, no worsening on the CIBIC-Plus, and no worsening on the PDS.
Definizzjoni sekondarja ta ’ rispons kienet teħtieġ titjib ta ’ 4 punti jew aktar fl- ADAS- Cog, li l- iskala tas- CIBIC- Plus u dik tal - PDS ma jmorrux għall- agħar.
The mean actual daily dose for responders in the 6– 12 mg group, corresponding to this definition, was 9.3 mg.
Huwa importanti li
It is important to note that the scales used in this indication vary and direct comparisons of results for different therapeutic agents are not valid.
8 wieħed jinnota li l- iskali użati f’ din l- indikazzjoni jvarjaw, u li paraguni diretti tar- riżultati għal aġenti terapewtiċi differenti mhumiex validi.
Patients with Clinically Significant Response (%)
Pazjenti b’ Rispons Klinikament Sinifikanti (%)
Intent to Treat
Intenzjoni li tittratta
Last Observation Carried Forward
L- Aħħar Osservazzjoni Quddiem
Response Measure
Trasferita ‘ l Plaċebo
Rivastigmine 6– 12 mg
Rivastigmine
ADAS-Cog: improvement of at least 4 points
ADAS- Cog: titjib ta ’ mill- anqas 4 punti
CIBIC-Plus: improvement PDS: improvement of at least 10%
CIBIC- Plus: titjib PDS: titjib ta ’ mill- anqas 10%
At least 4 points improvement on ADAS- Cog with no worsening on CIBIC-Plus and PDS
Titjib ta ’ mill - anqas 4 punti fl - ADAS- Cog u li ma jiħżienux is - CIBIC- Plus u l - PDS
*p < 0.05, **p < 0.01, ***p < 0.001
* p < 0. 05, ** p < 0. 01, ***
8 Clinical studies in dementia associated with Parkinson’ s disease The efficacy of rivastigmine in dementia associated with Parkinson’ s disease has been demonstrated in a 24-week multicentre, double-blind, placebo-controlled core study and its 24-week open-label extension phase.
Studji kliniċi f’ dimenzja assoċjata mal- marda ta ’ Parkinson L- effikaċja ta ’ rivastigmine f’ dimenzja assoċjata mal- marda ta ’ Parkinson intweriet fi studju ċentrali ta ’ 24- ġimgħa multiċentriku, double- blind, kontrollat bil- plaċebo u bil- fażi ta ’ l- estenzjoni tiegħu ta ’ 24- ġimgħa open- label.
Patients involved in this study had an MMSE (Mini-Mental State Examination) score of 10– 24.
Il- pazjenti involuti f’ dan l- istudju kellhom punteġġ ta ’ MMSE (Eżami Żgħir ta ’ l- Istat Mentali) ta ’ 10- 24.
Efficacy has been established by the use of two independent scales which were assessed at regular intervals during a 6-month treatment period as shown in Table 5 below: the ADAS-Cog, a measure of cognition, and the global measure ADCS-CGIC (Alzheimer’ s Disease Cooperative Study- Clinician ’ s Global Impression of Change).
L- effikaċja kienet stabbilita bl- użu ta ’ żewġ skali indipendenti li kienu evalwati f’ intervalli regolari waqt is- 6 xhur perijodu ta ’ kura hekk kif jidher f’ Tabella 5 hawn taħt: l - ADAS- Cog, kejl ta ’ l- għarfien, u l- miżura globali ADCS- CGIC (Studju Ko- operattiv tal- Marda ta ’ Alzheimer – L- impressjoni Globali tat- Tabib fuq il- Bidla).
Dementia associated with Parkinson’ s Disease
Dimenzja assoċjata mal - Marda ta ’ Parkinson
ADAS-Cog Placebo
ADAS- Cog ADAS- Cog Exelon Plaċebo
ADCS-CGIC Placebo
ADCS- CGIC Plaċebo
ITT + RDO population
Popolazzjoni ITT + RDO
(n=161)
(n=161) (n=329)
(n=329)
23. 8 ± 10. 2
(n=165)
24. 3 ± 10. 5
Mean baseline ± SD Mean change at 24 weeks ± SD Adjusted treatment
Medja tal- bidla ma ’ l - 24 ġimgħa ± SD Differenza fil- kura
23.8 ± 10.2 2.1 ± 8.2
2. 1 ± 8. 2
24.3 ± 10.5 -0.7 ± 7.5
2. 881
n/ a 3.8 ± 1.4
- 0. 7 ± 7. 5
n/ a 4.3 ± 1.5
3. 8 ± 1. 4
difference
4. 3 ± 1. 5
2.881
aġġustata
p-value versus placebo
valur- p kontra l- plaċebo
< 0.0011
< 0. 0011
0.0072
0. 0072
ITT - LOCF population
Popolazzjoni ITT - LOCF
Mean baseline ± SD Mean change at 24 weeks ± SD Adjusted treatment
Medja tal- linja bażi ± SD
24.0 ± 10.3 2.5 ± 8.4
24. 0 ± 10. 3
24.5 ± 10.6 -0.8 ± 7.5
24. 5 ± 10. 6
difference
- 0. 8 ± 7. 5
3.541
4. 3 ± 1. 5
p-value versus placebo 1
valur- p kontra l- plaċebo 1
< 0.0012
< 0. 0012
Based on ANCOVA with treatment and country as factors and baseline ADAS-Cog as a covariate.
Ibbażat fuq ANCOVA bil- kura u l- pajjiż bħala fatturi u linja bażi ADAS- Cog bħala ko- varjant.
A positive change indicates improvement.
Bidla pożittiva tindika titjib.
2 Mean data shown for convenience, categorical analysis performed using van Elteren test ITT:
2 Għall- konvenjenza qed tintwera l- medja tad- dejta, l- analiżi kategorika saret bit- test Elteren ITT:
Intent-To-Treat; RDO:
Intenzjoni li jingħata t- trattament; RDO:
Retrieved Drop Outs; LOCF:
Dawk li waqfu u ġew lura; LOCF:
Last Observation Carried Forward
L- aħħar osservazzjoni trasferita ’ l quddiem
Although a treatment effect was demonstrated in the overall study population, the data suggested that a larger treatment effect relative to placebo was seen in the subgroup of patients with moderate dementia associated with Parkinson’ s disease.
Għalkemm intwera effett tat- trattament fil- popolazzjoni globali kollha ta ’ l- istudju, id- dejta indikat li kien hemm effett tal- kura akbar meta mqabbel mal- plaċebo fis- sottogrupp ta ’ pazjenti b’ dimenzja moderata assoċjata mal- marda ta ’ Parkinson.
Similarly a larger treatment effect was observed in those patients with visual hallucinations (see Table 6).
Bl- istess mod, effett tal- kura akbar deher f’ dawk il - pazjenti b’ alluċinazzjonijiet viżivi (ara Tabella 6).
Dementia associated with Parkinson’ s Disease
Dimenzja assoċjata mal - marda ta ’ Parkinson
ADAS-Cog ADAS-Cog Placebo Exelon
ADAS- Cog ADAS- Cog Plaċebo Exelon
ADAS-Cog Placebo
ADAS- Cog Plaċebo
Patients with visual hallucinations
Pazjenti b’ alluċinazzjonijiet
Patients without visual hallucinations
Pazjenti mingħajr
Mean baseline ± SD Mean change at 24 weeks ± SD
Medja tal- linja bażi ± SD Bidla medja ma ’ l - 24 ġimgħa ± SD Differenza tal- kura
difference
aġġustata
p-value versus placebo
valur- p kontra plaċebo
Patients with moderate dementia (MMSE 10-17)
Pazjenti b’ dimenzja moderata (MMSE 10- 17)
Patients with mild (MMSE 18-24)
Pazjenti b’ dimenzja ħafifa (MMSE 18- 24)
ITT + RDO population
popolazzjoni ITT + RDO
Mean baseline ± SD Mean change at 24 weeks ± SD Adjusted treatment
Medja tal- linja bażi ± SD Bidla medja ma ’ l - 24 ġimgħa ± SD Differenza tal- kura
p-value versus placebo 1
valur- p kontra plaċebo 1
Retrieved Drop Outs
Dawk li waqfu u ġew lura
Absorption Rivastigmine is rapidly and completely absorbed.
Assorbiment Rivastigmine huwa assorbit malajr u kompletament.
Peak plasma concentrations are reached in approximately 1 hour.
Konċentrazzjonijiet fil- plażma l- aktar għolja jintlaħqu bejn wieħed u ieħor fi żmien siegħa.
As a consequence of rivastigmine’ s interaction with its target enzyme, the increase in bioavailability is about 1.5-fold greater than that expected from the increase in dose.
Bħala konsegwenza ta ’ l- attività ta ’ rivastigmine ma l - enżima targit, iż- żieda ta ’ biodisponibilità hija ta ’ madwar darba u nofs aktar minn dik mistennija miż - żieda fid- doża.
Absolute bioavailability after a 3 mg dose is about 36%±13%.
Iż- żieda assoluta fir- rata ta ’ biodisponibilità, wara doża ta ’ 3 mg, hija ta ’ madwar
Administration of rivastigmine with food delays absorption (tmax) by 90 min and lowers Cmax and increases AUC by approximately 30%.
Meta rivastigmine jingħata ma ’ l- ikel, l- assorbiment (tmax) jittardja b’ 90 minuta u s- Cmax jonqos u l- AUC jiżdied b’ bejn wieħed u ieħor 30%.
Distribution Protein binding of rivastigmine is approximately 40%.
Distribuzzjoni Rivastigmine huwa marbut b’ mod dgħajjef mal- proteini fil- plażma (bejn wieħed u ieħor 40%).
It readily crosses the blood brain barrier and has an apparent volume of distribution in the range of 1.8– 2.7 l/ kg.
Huwa jaqsam malajr il- barriera ta ’ bejn il- moħħ u d- demm u għandu volum apparenti ta ’ distribuzzjoni b’ firxa ta ’ bejn 1. 8– 2. 7 l/ kg.
Metabolism Rivastigmine is rapidly and extensively metabolised (half-life in plasma approximately 1 hour), primarily via cholinesterase-mediated hydrolysis to the decarbamylated metabolite.
Metaboliżmu Rivastigmine huwa metaboliżżat malajr u b’ mod estensiv f’ metabolu decarbamylated (half- life fil - plasma, madwar siegħa), l- aktar b’ idroliżi mmedjata minn cholinesterase.
In vitro, this metabolite shows minimal inhibition of acetylcholinesterase (< 10%).
In vitro din is- sustanza li tifforma fil- metaboliżmu turi inibizzjoni minima għal acetylcholinesterase (< 10%).
Based on evidence from in vitro and animal studies the major cytochrome P450 isoenzymes are minimally involved in rivastigmine metabolism.
Ibbażat fuq l - evidenza ta ’ studji in vitro u fuq l- annimali, l- iżoenżimi tas- cytochrome P 450 importanti huma minimament involuti fil- metaboliżmu ta ’ rivastigmine.
Total plasma clearance of rivastigmine was approximately 130 l/ h after a 0.2 mg intravenous dose and decreased to 70 l/ h after a 2.7 mg intravenous dose.
Wara doża minn ġol- vina ta ’ 0. 2 mg it- tneħħija totali mill- plażma ta ’ rivastigmine kienet ta ’ bejn wieħed u ieħor 130 l/ h, u din naqset għal 70 l/ h wara doża minn ġol- vini ta ’ 2. 7 mg.
Excretion Unchanged rivastigmine is not found in the urine; renal excretion of the metabolites is the major route of elimination.
Tneħħija Rivastigmine mhux mibdul ma jinstabx fl- awrina; it- tneħħija renali, tas- sustanzi fformati fil - metaboliżmu, hija l- mezz ewlieni ta ’ l- eliminazzjoni.
Following administration of 14C-rivastigmine, renal elimination was rapid and essentially complete (> 90%) within 24 hours.
Wara li ngħata l- 14C- rivastigmine, l - eliminazzjoni mill- kliewi kienet mgħaġġla u kienet kważi kompleta (> 90%) fi żmien 24 siegħa.
Less than 1% of the administered dose is excreted in the faeces.
Anqas minn 1% tad- doża mogħtija tneħħiet mill- ġisem ma ’ l- ippurgar.
There is no accumulation of rivastigmine or the decarbamylated metabolite in patients with Alzheimer’ s disease.
Ma jkun hemm l- ebda akkumulazzjoni ta ’ rivastigmine jew tal- metabolu decarbamylated li jifforma, f’ pazjenti li jbatu mill - marda ta ’ Alzheimer.
Elderly subjects While bioavailability of rivastigmine is greater in elderly than in young healthy volunteers, studies in Alzheimer patients aged between 50 and 92 years showed no change in bioavailability with age.
Pazjenti anzjani Filwaqt li l- biodisponibilità ta ’ rivastigmine hija ogħla fl- anzjani milli fil- voluntiera żgħażagħ b’ saħħithom, studji fuq pazjenti li jbatu mill- marda ta ’ Alzheimer li kellhom bejn 50 u 92 sena ma wrew l- ebda tibdil fil- biodisponibilità bl- eta`.
Subjects with hepatic impairment The Cmax of rivastigmine was approximately 60% higher and the AUC of rivastigmine was more than twice as high in subjects with mild to moderate hepatic impairment than in healthy subjects.
Pazjenti b’ indeboliment epatiku Is- Cmax ta ’ rivastigmine kien bejn wieħed u ieħor 60% ogħla u l- AUC ta ’ rivastigmine kien aktar minn darbtejn ogħla f’ pazjenti li kellhom indeboliment epatiku ħafif għal moderat, meta dawn kienu mqabbla ma ’ individwi b’ saħħithom.
Subjects with renal impairment Cmax and AUC of rivastigmine were more than twice as high in subjects with moderate renal impairment
Pazjenti b’ indeboliment renali Is- Cmax u l- AUC ta ’ rivastigmine kienu aktar minn darbtejn ogħla f’ pazjenti li kellhom indeboliment renali moderat meta dawn kienu mqabbla ma ’ individwi b’ saħħithom; madankollu ma kien hemm l - ebda tibdiliet fis- Cmax u l- AUC ta ’ rivastigmine f’ pazjenti li kellhom indeboliment renali serju.
Repeated-dose toxicity studies in rats, mice and dogs revealed only effects associated with an exaggerated pharmacological action.
Studji tat- tossiċità bid- doża ripetuta li saru fuq firien, ġrieden u klieb, wrew biss effetti assoċjati ma ’ azzjoni farmakoloġika eżaġerata.
No target organ toxicity was observed.
Ma ġiet osservata l- ebda tossiċità ta ’ organi targit.
No safety margins to human exposure were achieved in the animal studies due to the sensitivity of the animal models used.
Ma ġew milħuqa l- ebda marġini ta ’ sigurta` bħall- espożizzjoni fil- bniedem waqt studji fuq l- annimali minħabba s - sensittività ta ’ l- annimali użati.
Rivastigmine was not mutagenic in a standard battery of in vitro and in vivo tests, except in a chromosomal aberration test in human peripheral lymphocytes at a dose 104 times the maximum clinical exposure.
Rivastigmine ma kienx mutaġeniku f’ ġabra ta ’ testijiet standard in vitro u in vivo, ħlief f’ test ta ’ aberrazzjoni tal- kromosomi f’ limfoċiti umani periferali meta ngħatat doża ta ’ 104 darbiet ogħla mill - esponiment kliniku.
The in vivo micronucleus test was negative.
It- test tal- mikronukleju in vivo kien negattiv.
No evidence of carcinogenicity was found in studies in mice and rats at the maximum tolerated dose, although the exposure to rivastigmine and its metabolites was lower than the human exposure.
Ma nstabet l- ebda evidenza ta ’ kanċeroġeniċità fi studji fuq ġrieden u firien meta ngħatat id- doża massima tollerata, għalkemm il- livell ta ’ rivastigmine u l- metaboli tiegħu, li kienu esposti għalih, kienu anqas minn dawk fil- bniedem.
When normalised to body surface area, the exposure to rivastigmine and its metabolites was approximately equivalent to the maximum recommended human dose of 12 mg/ day; however, when compared to the maximum human dose, a multiple of approximately 6-fold was achieved in animals.
Meta ġew imqabbla skond l- erja tas- superfiċje tal- ġisem, l - espożizzjoni għal rivastigmine u l- metaboli tiegħu kienet bejn wieħed u ieħor ekwivalenti għad- doża massima rrikkmandata ta ’ 12 mg kuljum; madankollu, meta mqabbla mad- doża massima fil- bniedem, livelli ta ’ bejn wieħed u ieħor 6 darbiet aktar kienu milħuqa fl- annimali.
In animals, rivastigmine crosses the placenta and is excreted into milk.
11 Fl- annimali, rivastigmine jgħaddi mill- plaċenta u joħroġ mal- ħalib.
Oral studies in pregnant rats and rabbits gave no indication of teratogenic potential on the part of rivastigmine.
Studji mill- ħalq fuq firien u fniek tqal ma taw l- ebda indikazzjoni ta ’ potenzjal teratoġeniku b’ rivastigmine.
Gelatin Magnesium stearate Hypromellose Microcrystalline cellulose Silica, colloidal anhydrous Yellow iron oxide (E172) Red iron oxide (E172) Titanium dioxide (E171)
Gelatin Magnesium stearate Hypromellose Microcrystalline cellulose Silica, colloidal anhydrous Yellow iron oxide (E172) Red iron oxide (E172) Titanium dioxide (E171)
- Blister of clear PVC tray with blue lidding foil with 14 capsules.
- Folja bi trej ċar tal- PVC bil- wiċċ tal- fojl blu b’ 14- il kapsula.
Each box contains 2, 4 or
Kull kaxxa jkun fiha 2, 4 jew 8 folji.
8 blisters.
Kull flixkun fih
Each bottle contains 250 capsules.
250 kapsula.
12.05.1998 Date of latest renewal:
12. 05. 1998 Data ta ’ l- aħħar tiġdid:
Exelon 3.0 mg hard capsules
Exelon 3. 0 mg kapsuli ibsin
Each capsule contains rivastigmine hydrogen tartrate corresponding to rivastigmine 3.0 mg.
Kull kapsula fiha rivastigmine hydrogen tartrate li jikkorrispondi għall- 3. 0 mg rivastigmine.
Off-white to slightly yellow powder in a capsule with orange cap and orange body, with red imprint “ EXELON 3 mg ” on body.
Trab abjad li jagħti fl- offwajt jew ħarira fl- isfar, f’ kapsula b’ kappa oranġjo u b’ għatu orangjo, u stampata bl- aħmar “ EXELON 3 mg ” fuq il- kappa.
Maintenance dose The effective dose is 3 to 6 mg twice a day; to achieve maximum therapeutic benefit patients should be maintained on their highest well tolerated dose.
14 Doża ta ’ manteniment Id- doża effettiva hija ta ’ bejn 3 u 6 mg darbtejn kuljum; biex jinkiseb il- benefiċċju massimu mill- kura, il- pazjenti għandhom jinżammu fuq l- aktar doża għolja li jittoleraw.
13 Maintenance treatment can be continued for as long as a therapeutic benefit for the patient exists.
Il- kura ta ’ manteniment tista ’ titkompla sakemm tkun ta ’ benefiċċju terapewtiku għall- pazjent.
In case of severe vomiting associated with rivastigmine treatment, appropriate dose adjustments as recommended in section 4.2 must be made.
15 F’ każ li l- pazjent jibda ’ jirremetti ħafna meta jingħata kura b’ rivastigmine, id- doża għandha tiġi aġġustata hekk kif irrikkmandat f’ sezzjoni 4. 2.
14 Care must be taken when using rivastigmine in patients with sick sinus syndrome or conduction defects (sino-atrial block, atrio-ventricular block) (see section 4.8).
Għandha tingħata attenzjoni meta jintuża rivastigmine f’ pazjenti bis- sindrome tas- sinus marid jew b’ difetti tal- konduttività fil- qalb (imblukkar sino- atrijali, imblukkar atrijo- ventrikulari) (ara sezzjoni 4. 8).
In animals, rivastigmine is excreted into milk.
16 Fl- annimali rivastigmine joħroġ mal- ħalib.
15 continue driving or operating complex machines should be routinely evaluated by the treating physician.
Għalhekk, il- ħila li jkomplu jsuqu jew li jħaddmu magni kumplessi, ta ’ pazjenti li jbatu mill- marda ta ’ Alzheimer u li jkunu qed jieħdu rivastigmine, għandha tiġi evalwata bħala rutina mit- tabib li jkun qed jagħtihom il- kura.
Nausea Vomiting Diarrhoea Abdominal pain and dyspepsia Gastric and duodenal ulcers Gastrointestinal haemorrhage Pancreatitis Some cases of severe vomiting were associated with oesophageal rupture (see section 4.4).
17 Dijarea Komuni ħafna Uġigħ addominali u dispepsja Komuni Ulċeri gastriċi u duwodenali Rari Emorraġiji gastro- intestinali Rari ħafna Pankrejatite Rari ħafna Xi każijiet ta ’ rimettar sever kienu assoċjati ma ’ tiċrit ta ’ l - Mhux magħruf esofagu (ara sezzjoni 4. 4).
Skin and subcutaneous tissue disorders
18 Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda Disturbi
Table 3 lists the number and percentage of patients from the specific 24-week clinical study conducted 17 with Exelon in patients with dementia associated with Parkinson’ s disease with pre-defined adverse events that may reflect worsening of parkinsonian symptoms.
Tabella 3 telenka n- numru u l- perċentwali ta ’ pazjenti b’ każijiet minn prova klinika speċifika ta 24 - gimgha kondotta b’ Exelon f’ pazjenti b’ dimenzja assoċjata mal- marda ta Parkinson b’ avversi li kienu definiti minn qabel li jistgħu jirriflettu aggravar tas- sintomi ta ’ Parkinson.
Treatment As rivastigmine has a plasma half-life of about 1 hour and a duration of acetylcholinesterase inhibition of about 9 hours, it is recommended that in cases of asymptomatic overdose no further dose of rivastigmine should be administered for the next 24 hours.
19 Kura Minħabba li rivastigmine għandu half- life fil- plażma ta ’ xi siegħa, u l- inibizzjoni ta ’ acetylcholinesterase iddum xi 9 sigħat, huwa rrikkmandat li fil- każijiet ta ’ doża eċċessiva bla sintomi, m’ għandu jingħata l- ebda doża oħra ta ’ rivastigmine għall- 24 siegħa wara.
It is important to note that the scales used in this indication vary and direct comparisons of results for different therapeutic agents are not valid.
20 wieħed jinnota li l- iskali użati f’ din l- indikazzjoni jvarjaw, u li paraguni diretti tar- riżultati għal aġenti terapewtiċi differenti mhumiex validi.
19 Clinical studies in dementia associated with Parkinson’ s disease The efficacy of rivastigmine in dementia associated with Parkinson’ s disease has been demonstrated in a 24-week multicentre, double-blind, placebo-controlled core study and its 24-week open-label extension phase.
Studji kliniċi f’ dimenzja assoċjata mal- marda ta ’ Parkinson L- effikaċja ta ’ rivastigmine f’ dimenzja assoċjata mal- marda ta ’ Parkinson intweriet fi studju ċentrali ta ’ 24- ġimgħa multiċentriku, double- blind, kontrollat bil- plaċebo u bil- fażi ta ’ l- estenzjoni tiegħu ta ’ 24- ġimgħa open- label.
In animals, rivastigmine crosses the placenta and is excreted into milk.
23 Fl- annimali, rivastigmine jgħaddi mill- plaċenta u joħroġ mal- ħalib.
22 6.6 Special precautions for disposal
6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema
Exelon 4.5 mg hard capsules
Exelon 4. 5 mg kapsuli ibsin
Each capsule contains rivastigmine hydrogen tartrate corresponding to rivastigmine 4.5 mg.
Kull kapsula fiha rivastigmine hydrogen tartrate li jikkorrispondi għall- 4. 5 mg rivastigmine.
Off-white to slightly yellow powder in a capsule with red cap and red body, with white imprint “ EXELON 4,5 mg ” on body.
Trab abjad li jagħti fl- offwajt jew ħarira fl- isfar, f’ kapsula b’ kappa aħmar u b’ għatu aħmar, u stampata bl- abjad “ EXELON 4. 5 mg ” fuq il- kappa.
Maintenance dose The effective dose is 3 to 6 mg twice a day; to achieve maximum therapeutic benefit patients should be maintained on their highest well tolerated dose.
26 Doża ta ’ manteniment Id- doża effettiva hija ta ’ bejn 3 u 6 mg darbtejn kuljum; biex jinkiseb il- benefiċċju massimu mill- kura, il- pazjenti għandhom jinżammu fuq l- aktar doża għolja li jittoleraw.
24 Maintenance treatment can be continued for as long as a therapeutic benefit for the patient exists.
Il- kura ta ’ manteniment tista ’ titkompla sakemm tkun ta ’ benefiċċju terapewtiku għall- pazjent.
In case of severe vomiting associated with rivastigmine treatment, appropriate dose adjustments as recommended in section 4.2 must be made.
27 F’ każ li l- pazjent jibda ’ jirremetti ħafna meta jingħata kura b’ rivastigmine, id- doża għandha tiġi aġġustata hekk kif irrikkmandat f’ sezzjoni 4. 2.
25 Care must be taken when using rivastigmine in patients with sick sinus syndrome or conduction defects (sino-atrial block, atrio-ventricular block) (see section 4.8).
Għandha tingħata attenzjoni meta jintuża rivastigmine f’ pazjenti bis- sindrome tas- sinus marid jew b’ difetti tal- konduttività fil- qalb (imblukkar sino- atrijali, imblukkar atrijo- ventrikulari) (ara sezzjoni 4. 8).
In animals, rivastigmine is excreted into milk.
28 Fl- annimali rivastigmine joħroġ mal- ħalib.
26 continue driving or operating complex machines should be routinely evaluated by the treating physician.
Għalhekk, il- ħila li jkomplu jsuqu jew li jħaddmu magni kumplessi, ta ’ pazjenti li jbatu mill- marda ta ’ Alzheimer u li jkunu qed jieħdu rivastigmine, għandha tiġi evalwata bħala rutina mit- tabib li jkun qed jagħtihom il- kura.
Nausea Vomiting Diarrhoea Abdominal pain and dyspepsia Gastric and duodenal ulcers Gastrointestinal haemorrhage Pancreatitis Some cases of severe vomiting were associated with oesophageal rupture (see section 4.4).
29 Dijarea Komuni ħafna Uġigħ addominali u dispepsja Komuni Ulċeri gastriċi u duwodenali Rari Emorraġiji gastro- intestinali Rari ħafna Pankrejatite Rari ħafna Xi każijiet ta ’ rimettar sever kienu assoċjati ma ’ tiċrit ta ’ l - Mhux magħruf esofagu (ara sezzjoni 4. 4).
Skin and subcutaneous tissue disorders
30 Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda Disturbi
Table 3 lists the number and percentage of patients from the specific 24-week clinical study conducted 28 with Exelon in patients with dementia associated with Parkinson’ s disease with pre-defined adverse events that may reflect worsening of parkinsonian symptoms.
Tabella 3 telenka n- numru u l- perċentwali ta ’ pazjenti b’ każijiet minn prova klinika speċifika ta 24 - gimgha kondotta b’ Exelon f’ pazjenti b’ dimenzja assoċjata mal- marda ta Parkinson b’ avversi li kienu definiti minn qabel li jistgħu jirriflettu aggravar tas- sintomi ta ’ Parkinson.
Treatment As rivastigmine has a plasma half-life of about 1 hour and a duration of acetylcholinesterase inhibition of about 9 hours, it is recommended that in cases of asymptomatic overdose no further dose of rivastigmine should be administered for the next 24 hours.
31 Kura Minħabba li rivastigmine għandu half- life fil- plażma ta ’ xi siegħa, u l- inibizzjoni ta ’ acetylcholinesterase iddum xi 9 sigħat, huwa rrikkmandat li fil- każijiet ta ’ doża eċċessiva bla sintomi, m’ għandu jingħata l- ebda doża oħra ta ’ rivastigmine għall- 24 siegħa wara.
It is important to note that the scales used in this indication vary and direct comparisons of results for different therapeutic agents are not valid.
32 wieħed jinnota li l- iskali użati f’ din l- indikazzjoni jvarjaw, u li paraguni diretti tar- riżultati għal aġenti terapewtiċi differenti mhumiex validi.
30 Clinical studies in dementia associated with Parkinson’ s disease The efficacy of rivastigmine in dementia associated with Parkinson’ s disease has been demonstrated in a 24-week multicentre, double-blind, placebo-controlled core study and its 24-week open-label extension phase.
Studji kliniċi f’ dimenzja assoċjata mal- marda ta ’ Parkinson L- effikaċja ta ’ rivastigmine f’ dimenzja assoċjata mal- marda ta ’ Parkinson intweriet fi studju ċentrali ta ’ 24- ġimgħa multiċentriku, double- blind, kontrollat bil- plaċebo u bil- fażi ta ’ l- estenzjoni tiegħu ta ’ 24- ġimgħa open- label.
In animals, rivastigmine crosses the placenta and is excreted into milk.
35 Fl- annimali, rivastigmine jgħaddi mill- plaċenta u joħroġ mal- ħalib.
33 6.6 Special precautions for disposal
6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema
Exelon 6.0 mg hard capsules
Exelon 6. 0 mg kapsuli ibsin
Each capsule contains rivastigmine hydrogen tartrate corresponding to rivastigmine 6.0 mg.
Kull kapsula fiha rivastigmine hydrogen tartrate li jikkorrispondi għall- 6. 0 mg rivastigmine.
Off-white to slightly yellow powder in a capsule with red cap and orange body, with red imprint “ EXELON 6 mg ” on body.
Trab abjad li jagħti fl- offwajt jew ħarira fl- isfar, f’ kapsula b’ għatu aħmar, u b’ kappa oranġjo u stampata bl- aħmar “ EXELON 6 mg ” fuq il- kappa.
Maintenance dose The effective dose is 3 to 6 mg twice a day; to achieve maximum therapeutic benefit patients should be maintained on their highest well tolerated dose.
38 Doża ta ’ manteniment Id- doża effettiva hija ta ’ bejn 3 u 6 mg darbtejn kuljum; biex jinkiseb il- benefiċċju massimu mill- kura, il- pazjenti għandhom jinżammu fuq l- aktar doża għolja li jittoleraw.
35 Maintenance treatment can be continued for as long as a therapeutic benefit for the patient exists.
Il- kura ta ’ manteniment tista ’ titkompla sakemm tkun ta ’ benefiċċju terapewtiku għall- pazjent.
In case of severe vomiting associated with rivastigmine treatment, appropriate dose adjustments as recommended in section 4.2 must be made.
39 F’ każ li l- pazjent jibda ’ jirremetti ħafna meta jingħata kura b’ rivastigmine, id- doża għandha tiġi aġġustata hekk kif irrikkmandat f’ sezzjoni 4. 2.
36 Care must be taken when using rivastigmine in patients with sick sinus syndrome or conduction defects (sino-atrial block, atrio-ventricular block) (see section 4.8).
Għandha tingħata attenzjoni meta jintuża rivastigmine f’ pazjenti bis- sindrome tas- sinus marid jew b’ difetti tal- konduttività fil- qalb (imblukkar sino- atrijali, imblukkar atrijo- ventrikulari) (ara sezzjoni 4. 8).
In animals, rivastigmine is excreted into milk.
40 Fl- annimali rivastigmine joħroġ mal- ħalib.
37 continue driving or operating complex machines should be routinely evaluated by the treating physician.
Għalhekk, il- ħila li jkomplu jsuqu jew li jħaddmu magni kumplessi, ta ’ pazjenti li jbatu mill- marda ta ’ Alzheimer u li jkunu qed jieħdu rivastigmine, għandha tiġi evalwata bħala rutina mit- tabib li jkun qed jagħtihom il- kura.
Nausea Vomiting Diarrhoea Abdominal pain and dyspepsia Gastric and duodenal ulcers Gastrointestinal haemorrhage Pancreatitis Some cases of severe vomiting were associated with oesophageal rupture (see section 4.4).
41 Dijarea Komuni ħafna Uġigħ addominali u dispepsja Komuni Ulċeri gastriċi u duwodenali Rari Emorraġiji gastro- intestinali Rari ħafna Pankrejatite Rari ħafna Xi każijiet ta ’ rimettar sever kienu assoċjati ma ’ tiċrit ta ’ l - Mhux magħruf esofagu (ara sezzjoni 4. 4).
Skin and subcutaneous tissue disorders
42 Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda Disturbi
Table 3 lists the number and percentage of patients from the specific 24-week clinical study conducted 39 with Exelon in patients with dementia associated with Parkinson’ s disease with pre-defined adverse events that may reflect worsening of parkinsonian symptoms.
Tabella 3 telenka n- numru u l- perċentwali ta ’ pazjenti b’ każijiet minn prova klinika speċifika ta 24 - gimgha kondotta b’ Exelon f’ pazjenti b’ dimenzja assoċjata mal- marda ta Parkinson b’ avversi li kienu definiti minn qabel li jistgħu jirriflettu aggravar tas- sintomi ta ’ Parkinson.
Treatment As rivastigmine has a plasma half-life of about 1 hour and a duration of acetylcholinesterase inhibition of about 9 hours, it is recommended that in cases of asymptomatic overdose no further dose of rivastigmine should be administered for the next 24 hours.
43 Kura Minħabba li rivastigmine għandu half- life fil- plażma ta ’ xi siegħa, u l- inibizzjoni ta ’ acetylcholinesterase iddum xi 9 sigħat, huwa rrikkmandat li fil- każijiet ta ’ doża eċċessiva bla sintomi, m’ għandu jingħata l- ebda doża oħra ta ’ rivastigmine għall- 24 siegħa wara.
It is important to note that the scales used in this indication vary and direct comparisons of results for different therapeutic agents are not valid.
44 wieħed jinnota li l- iskali użati f’ din l- indikazzjoni jvarjaw, u li paraguni diretti tar- riżultati għal aġenti terapewtiċi differenti mhumiex validi.
41 Clinical studies in dementia associated with Parkinson’ s disease The efficacy of rivastigmine in dementia associated with Parkinson’ s disease has been demonstrated in a 24-week multicentre, double-blind, placebo-controlled core study and its 24-week open-label extension phase.
Studji kliniċi f’ dimenzja assoċjata mal- marda ta ’ Parkinson L- effikaċja ta ’ rivastigmine f’ dimenzja assoċjata mal- marda ta ’ Parkinson intweriet fi studju ċentrali ta ’ 24- ġimgħa multiċentriku, double- blind, kontrollat bil- plaċebo u bil- fażi ta ’ l- estenzjoni tiegħu ta ’ 24- ġimgħa open- label.
In animals, rivastigmine crosses the placenta and is excreted into milk.
47 Fl- annimali, rivastigmine jgħaddi mill- plaċenta u joħroġ mal- ħalib.
44 6.6 Special precautions for disposal
6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema
Exelon 2 mg/ ml oral solution
Exelon 2 mg/ ml soluzzjoni orali
Each ml contains rivastigmine hydrogen tartrate corresponding to rivastigmine base 2.0 mg.
Kull ml fih rivastigmine hydrogen tartrate li jikkorrispondi għall- 2. 0 mg rivastigmine bħala bażi.
Clear, yellow solution.
Soluzzjoni ċara, safra.
Rivastigmine oral solution should be administered twice a day, with morning and evening meals.
Rivastigmine bħala soluzzjoni orali, għandu jingħata darbtejn kuljum, ma ’ l- ikliet ta ’ filgħodu u ta ’ filgħaxija.
The prescribed amount of solution should be withdrawn from the container using the oral dosing syringe supplied.
L- ammont tas- soluzzjoni ordnat mit- tabib għandu jinġibed mill- kontenitur bl- użu tas - siringa pprovduta.
Rivastigmine oral solution may be swallowed directly from the syringe.
Is- soluzzjoni orali ta ’ rivastigmine tista ’ tinbela ’ direttament mis- siringa.
Rivastigmine oral solution and rivastigmine capsules may be interchanged at equal doses.
Id- doża ta ’ Rivastigmine tista ’ tingħata bħala kapsuli jew- soluzzjoni orali f’ ammonti ekwivalenti.
Maintenance dose The effective dose is 3 to 6 mg twice a day; to achieve maximum therapeutic benefit patients should be maintained on their highest well tolerated dose.
50 Doża ta ’ manteniment Id- doża effettiva hija ta ’ bejn 3 u 6 mg darbtejn kuljum; biex jinkiseb il- benefiċċju massimu mill- kura, il- pazjenti għandhom jinżammu fuq l- aktar doża għolja li jittoleraw.
The recommended maximum daily dose is 6 mg twice a
Id- doża massima rrikkmandata ta ’ kuljum hija ta ’ 6 mg darbtejn kuljum.
Maintenance treatment can be continued for as long as a therapeutic benefit for the patient exists.
Il- kura ta ’ manteniment tista ’ titkompla sakemm tkun ta ’ benefiċċju terapewtiku għall- pazjent.
In case of severe vomiting associated with rivastigmine treatment, appropriate dose adjustments as recommended in section 4.2 must be made.
51 F’ każ li l- pazjent jibda ’ jirremetti ħafna meta jingħata kura b’ rivastigmine, id- doża għandha tiġi aġġustata hekk kif irrikkmandat f’ sezzjoni 4. 2.
47 Care must be taken when using rivastigmine in patients with sick sinus syndrome or conduction defects (sino-atrial block, atrio-ventricular block) (see section 4.8).
Għandha tingħata attenzjoni meta jintuża rivastigmine f’ pazjenti bis- sindrome tas- sinus marid jew b’ difetti tal- konduttività fil- qalb (imblukkar sino- atrijali, imblukkar atrijo- ventrikulari) (ara sezzjoni 4. 8).
One of the excipients in Exelon oral solution is sodium benzoate.
Waħda mis- sustanzi mhux attivi li tinsab f’ Exelon soluzzjoni orali hija sodium benzoate.
Benzoic acid is a mild irritant to the skin, eyes and mucous membrane.
Benzoic acid jista ’ jirrita b’ mod ħafif il- ġilda, l- għajnejn u l- membrana mukuża.
4.6 Pregnancy and lactation
52 4. 6 Tqala u Treddigħ
In animals, rivastigmine is excreted into milk.
Fl- annimali rivastigmine joħroġ mal- ħalib.
48 4.7 Effects on ability to drive and use machines
4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
Therefore, the ability of patients with dementia on rivastigmine to continue driving or operating complex machines should be routinely evaluated by the treating physician.
Għalhekk, il- ħila li jkomplu jsuqu jew li jħaddmu magni kumplessi, ta ’ pazjenti li jbatu mill- marda ta ’ Alzheimer u li jkunu qed jieħdu rivastigmine, għandha tiġi evalwata bħala rutina mit- tabib li jkun qed jagħtihom il- kura.
Cardiac
Rari Rari ħafna
disorders Rare Very rare
Angina pectoris Problemi fir- ritmu tat- tħabbit tal- qalb (eż. bradikardja,
Angina pectoris Cardiac arrhythmia (e. g. bradycardia, atrio-ventricular block, atrial fibrillation and tachycardia)
53 imblukkar atrijo- ventrikulari, fibrillazzjoni ta ’ l- atrija u takikardija)
Nausea Vomiting Diarrhoea Abdominal pain and dyspepsia Gastric and duodenal ulcers Gastrointestinal haemorrhage Pancreatitis Some cases of severe vomiting were associated with
Disturbi gastro- intestinali Dardir Komuni ħafna Rimettar Komuni ħafna Dijarea Komuni ħafna Uġigħ addominali u dispepsja Komuni Ulċeri gastriċi u duwodenali Rari Emorraġiji gastro- intestinali Rari ħafna Pankrejatite Rari ħafna Xi każijiet ta ’ rimettar sever kienu assoċjati ma ’ tiċrit ta ’ l - Mhux magħruf esofagu (ara sezzjoni 4. 4).
Insomnia Anxiety Restlessness Tremor Dizziness Somnolence Headache Worsening of Parkinson’ s disease Bradykinesia Dyskinesia Dystonia Bradycardia Atrial Fibrillation Atrioventricular block
Nuqqas ta ’ rqad Ansjetà Nuqqas ta ’ kwiet
Gastrointestinal disorders
Disturbi fis- sistema nervuża
Very common Very common Common Common Common
Komuni ħafna Komuni Komuni Komuni Komuni Komuni Komuni Mhux komuni
Nausea Vomiting Diarrhoea Abdominal pain and dyspepsia Salivary hypersecretion
Tregħid Sturdament Ħedla tan- ngħas Uġigħ ta ’ ras Aggravar tal- marda ta ’ Parkinson Bradikajneżja Diskajneżja Distonja
Skin and subcutaneous tissue disorders
Disturbi fil- qalb
Common
Komuni Mhux komuni Mhux komuni
Sweating increased
54 Disturbi gastro- intestinali Disturbi il- ġilda
Musculoskeletal and connective tissue disorders
Komuni ħafna Komuni ħafna Komuni Komuni Komuni fil- ġilda u fit- tessuti ta ’ taħt Komuni
Common
Disturbi
Muscle rigidity
muskolu- skeletrali u tal -
Metabolism and nutritional disorders
connective tissue Disturbi
Common Common
Komuni fil- metaboliżmu u n -
Anorexia Dehydration
Riġidità fil- muskoli
50 General disorders and administration site conditions
nutrizzjoni Disturbi
Common Common
Komuni Komuni ġenerali u kundizzjonijiet ta ’
lists the number and percentage of
Anoressija Deidratazzjoni
patients from the specific 24-week clinical study conducted
mnejn jingħata Għeja kbira u astenja Komuni Mixi mhux normali Komuni
with Exelon in patients with dementia associated with Parkinson’ s disease with pre-defined adverse events that may reflect worsening of parkinsonian symptoms.
Tabella 3 telenka n- numru u l- perċentwali ta ’ pazjenti b’ każijiet minn prova klinika speċifika ta 24 - gimgha kondotta b’ Exelon f’ pazjenti b’ dimenzja assoċjata mal- marda ta Parkinson b’ avversi li kienu definiti minn qabel li jistgħu jirriflettu aggravar tas- sintomi ta ’ Parkinson.
Symptoms Most cases of accidental overdose have not been associated with any clinical signs or symptoms and almost all of the patients concerned continued rivastigmine treatment.
Fejn kien hemm is -
Where symptoms have occurred, they have included nausea, vomiting and diarrhoea, hypertension or hallucinations.
55 sintomi, dawn kienu jinkludu dardir, rimettar u dijarea, pressjoni għolja jew alluċinazzjonijiet.
Treatment As rivastigmine has a plasma half-life of about 1 hour and a duration of acetylcholinesterase inhibition of about 9 hours, it is recommended that in cases of asymptomatic overdose no further dose of rivastigmine should be administered for the next 24 hours.
Kura Minħabba li rivastigmine għandu half- life fil- plażma ta ’ xi siegħa, u l- inibizzjoni ta ’ acetylcholinesterase iddum xi 9 sigħat, huwa rrikkmandat li fil- każijiet ta ’ doża eċċessiva bla sintomi, m’ għandu jingħata l- ebda doża oħra ta ’ rivastigmine għall- 24 siegħa wara.
Rivastigmine is an acetyl- and butyrylcholinesterase inhibitor of the carbamate type, thought to facilitate cholinergic neurotransmission by slowing the degradation of acetylcholine released by functionally intact cholinergic neurones.
Rivastigmine huwa inibitur ta ’ acetyl - u butyrylcholinesterase tat- tip carbamate, li hu maħsub li jiffaċilita t- trasmissjoni kolinerġika fin- newroni, billi jnaqqas id- degradazzjoni ta ’ acetylcholine li jkun meħlus minn newroni kolinerġiċi li jkollhom il- funzjoni intatta.
In addition, a post-hoc definition of response is provided in the same table.
56 Barra dan, definizzjoni post- hoc ta ’ reazzjoni hija mogħtija fl- istess tabella.
The mean actual daily dose for responders in the 6– 12 mg group, corresponding to this definition, was 9.3 mg.
Id- doża medja attwali ta ’ kuljum għal dawk li wrew rispons fil- grupp ta ’ minn 6 mg sa 12- il mg li tikkorrispondi ma ’ din id- definizzjoni hija ta ’ 9. 3 mg.
It is important to note that the scales used in this indication vary and direct comparisons of results for different therapeutic agents are not valid.
Huwa importanti li wieħed jinnota li l- iskali użati f’ din l- indikazzjoni jvarjaw, u li paraguni diretti tar- riżultati għal aġenti terapewtiċi differenti mhumiex validi.
Last Observation Carried Forward
L- Aħħar Osservazzjoni Trasferita ‘ l Quddiem
Response Measure
Kejl tar- Rispons
Placebo Rivastigmine 6– 12 mg
Plaċebo Rivastigmine 6– 12 mg
21***
N=473 21 ***
12 25***
N=472 N=379 12 25 ***
12
N=444 12
CIBIC-Plus: improvement PDS: improvement of at
CIBIC- Plus: titjib PDS: titjib ta ’ mill- anqas 10%
Clinical studies in dementia associated with Parkinson’ s disease The efficacy of rivastigmine in dementia associated with Parkinson’ s disease has been demonstrated in a 24-week multicentre, double-blind, placebo-controlled core study and its 24-week open-label extension phase.
Studji kliniċi f’ dimenzja assoċjata mal- marda ta ’ Parkinson L- effikaċja ta ’ rivastigmine f’ dimenzja assoċjata mal- marda ta ’ Parkinson intweriet fi studju ċentrali ta ’ 24- ġimgħa multiċentriku, double- blind, kontrollat bil- plaċebo u bil- fażi ta ’ l- estenzjoni tiegħu ta ’ 24- ġimgħa open- label.
(n=161)
Medja tal- linja bażi ± SD
Mean baseline ± SD Mean change at 24 weeks ± SD Adjusted treatment
57 Medja tal- linja bażi ± SD
53 Table 6
Tabella 6
As a consequence of rivastigmine’ s interaction with its target enzyme, the increase in bioavailability is about 1.5-fold greater than that expected from the increase in dose.
Bħala konsegwenza ta ’ l- attività ta ’ rivastigmine ma l - enżima targit, iż- żieda ta ’ biodisponibilità hija ta ’ madwar darba u nofs aktar minn dik mistennija miż -
Absolute bioavailability after a 3 mg dose is about 36% ± 13%.
Iż- żieda assoluta fir- rata ta ’ biodisponibilità, wara doża ta ’ 3 mg, hija ta ’ madwar 36% ±13%.
Administration of rivastigmine oral solution with food delays absorption (tmax) by 74 min and lowers Cmax by 43% and increases AUC by approximately 9%.
Meta rivastigmine bħala soluzzjoni orali jingħata ma ’ l- ikel, l- assorbiment (tmax) jittardja b’ 74 minuta u is- Cmax jonqos b’ 43% u l- AUC jiżdied b’ bejn wieħed u ieħor 9%.
54 Excretion Unchanged rivastigmine is not found in the urine; renal excretion of the metabolites is the major route of elimination.
Tneħħija Rivastigmine mhux mibdul ma jinstabx fl- awrina; it- tneħħija renali, tas- sustanzi fformati fil - metaboliżmu, hija l- mezz ewlieni ta ’ l- eliminazzjoni.
Subjects with renal impairment Cmax and AUC of rivastigmine were more than twice as high in subjects with moderate renal impairment compared with healthy subjects; however there were no changes in Cmax and AUC of rivastigmine in subjects with severe renal impairment.
Pazjenti b’ indeboliment renali Is- Cmax u l- AUC ta ’ rivastigmine kienu aktar minn darbtejn ogħla f’ pazjenti li kellhom indeboliment renali moderat meta dawn kienu mqabbla ma ’ individwi b’ saħħithom; madankollu ma kien hemm l - ebda tibdiliet fis- Cmax u l- AUC ta ’ rivastigmine f’ pazjenti li kellhom indeboliment renali serju.
When normalised to body surface area, the exposure to rivastigmine and its metabolites was approximately equivalent to the maximum recommended human dose of 12 mg/ day; however, when compared to the maximum human dose, a multiple of approximately 6-fold was achieved in animals.
59 massima rrikkmandata ta ’ 12 mg kuljum; madankollu, meta mqabbla mad- doża massima fil- bniedem, livelli ta ’ bejn wieħed u ieħor 6 darbiet aktar kienu milħuqa fl- annimali.
In animals, rivastigmine crosses the placenta and is excreted into milk.
Fl- annimali, rivastigmine jgħaddi mill- plaċenta u joħroġ mal- ħalib.
Sodium benzoate Citric acid Sodium citrate Quinoline yellow WS dye (E104) Purified water
Sodium benzoate Citric acid Sodium citrate Quinoline yellow WS dye E104 Ilma purifikat
55 6.3 Shelf life
6. 3 Żmien kemm idum tajjeb il- prodott mediċinali
Exelon oral solution should be used within 1 month of opening the bottle.
Exelon bħala soluzzjoni orali għandha tintuża fi żmien xahar minn meta jinfetaħ il- flixkun.
Do not refrigerate or freeze.
Tagħmlux fil- friġġ jew friża.
Store in an upright position.
Aħzen f’ pożizzjoni wieqfa.
Type III amber glass bottle with a child-resistant cap, dip tube and self aligning plug.
Flixkun, magħmul minn ħġieġ kannella tat- tip III, b’ għatu li ma jinfetaħx mit- tfal, b’ tubu biex tbill, u b’ tapp li jipożizzjona lilu nnifsu.
50 ml or 120 ml bottle.
Flixkun ta ’ 50 ml jew 120 ml.
The oral solution is packaged with an oral dosing syringe in a plastic tube container.
Is- soluzzjoni orali hija ppakkjata flimkien ma ’ siringa orali, f’ kontenitur f’ forma ta ’ tubu tal- plastik.
The prescribed amount of solution should be withdrawn from the bottle using the oral dosing syringe supplied.
L- ammont tas- soluzzjoni ordnat mit- tabib għandu jinġibed mill- flixkun bis- siringa orali pprovduta.
Date of first authorisation:
Dat a ta ’ l- ewwel awtorizzazzjoni:
Exelon 4.6 mg/ 24 h transdermal patch
Exelon 4. 6 mg/ 24 siegħa garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda
Each transdermal patch releases 4.6 mg of rivastigmine per 24 hours.
Kull garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda terħi 4. 6 mg ta ’ rivastigmine kull 24 siegħa.
Each transdermal patch of 5 cm2 contains 9 mg of rivastigmine.
Kull garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda ta ’ 5 cm2 fiha 9 mg ta ’ rivastigmine.
Each transdermal patch is a thin, matrix-type transdermal patch consisting of three layers.
Kull garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda hija rqieqa, garża tat- tip mejtriks li tipprovdi mediċina li tgħaddi minn ġol- ġilda li fiha tliet saffi.
The outside of the backing layer is beige and labelled with “ Exelon”, “ 4.6 mg/ 24 h” and “ AMCX”.
In- naħa ta ’ barra tas- saff ta ’ wara huwa bex u tikkettat b ’ “ Exelon ”, “ 4. 6 mg/ 24 h ” u “ AMCX ”.
Treatment should be initiated and supervised by a physician experienced in the diagnosis and treatment of Alzheimer’ s dementia.
Il- kura għandha tinbeda u tkun segwita minn tabib li għandu esperjenza fid- dijanjożi u l- kura ta ’ dimenzja ta ’ Alzheimer.
Similar to any treatment initiated in patients with dementia, therapy with rivastigmine should only be started if a caregiver is available to regularly administer and monitor the treatment.
Bħal kull kura li tinbeda għall- pazjenti b’ dimenzja, terapija b’ rivastigmine għandha tibda tingħata biss jekk ikun hemm persuna li tieħu ħsieb il- kura sabiex jagħti u jommonitorja b’ mod regolari l- kura.
Transdermal patches
Garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Exelon 4. 6 mg/ 24 siegħa
Rivastigmine dose load
Tagħbija tad - doża ta ’ Rivastigmine 9 mg
Rivastigmine in vivo release rates per 24 h
Rati ta ’ ħelsien ta ’ Rivastigmine in vivo kull 24 siegħa 4. 6 mg
Exelon 4.6 mg/ 24 h Exelon 9.5 mg/ 24 h
Exelon 9. 5 mg/ 24 siegħa
4.6 mg 9.5 mg
9. 5 mg
Initial dose
Doża tal- bidu
Treatment is started with 4.6 mg/ 24 h.
Il- kura tinbeda b’ 4. 6 mg/ 24 siegħa.
After a minimum of four weeks of treatment and if well tolerated according to the treating physician, this dose should be increased to 9.5 mg/ 24 h, which is the recommended effective dose.
Wara mill- anqas erba ’ ġimgħat ta ’ kura u jekk ikun tollerat sew, skond it- tabib li jkun qed jikkura, din id- doża għandha tiġi miżjuda għal 9. 5 mg/ 24 siegħa, li hija d- doża effettiva rakkomandata.
Maintenance dose 9.5 mg/ 24 h is the recommended daily maintenance dose which can be continued for as long as the patient is deriving therapeutic benefit.
Doża ta ’ manteniment 9. 5 mg/ 24 siegħa hija d- doża ta ’ kuljum rakkomandata li tista ’ tibqa tingħata sakemm il- pazjent ikun għadu jikseb benefiċċju terapewtiku.
Treatment should be temporarily interrupted if gastrointestinal adverse reactions are observed until these adverse reactions resolve.
Il- kura għandha titwaqqaf għal xi żmien jekk jidhru reazzjonijiet avversi gastro- intestinali sakemm dawn ir- reazzjonijiet avversi jgħaddu.
Transdermal patch treatment can be resumed at the same dose if treatment is not interrupted for more than several days.
Il- kura b’ garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda tista ’ terġa tinbeda bl- istess doża jekk il- kura ma tkunx twaqqfet għal aktar minn ħafna jiem.
Otherwise treatment should be re-initiated with 4.6 mg/ 24 h.
Inkella l- kura trid terġa tinbeda b’ 4. 6 mg/ 24 siegħa.