qanastek/EMEA-V3 huggingface dataset:
Prometax was more effective than placebo at controlling symptoms.
Prometax irriżulta aktar effikaċi mill- plaċebo biex jikkontrolla s- sintomi.
In the three studies of Prometax capsules in patients with Alzheimer’ s dementia, patients taking doses of Prometax between 6 and 9 mg per day had an average increase in cognitive symptoms of 0.2 points from a baseline of 22.9 points at the start of the study, where a lower score indicates better performance.
Fit- tliet studji li saru fuq Prometax kapsuli fil- pazjenti bid- demenza ta 'Alzheimer, il- pazjenti li ħadu dożi ta' Prometax bejn 6 u 9 mg kuljum esperjenzaw żieda medja tas- sintomi konjittivi ta '0. 2 punti, mill- valur inizjali ta' 22. 9 punti fil- bidu ta 'l- istudju; aktar baxx ikun il- punteġġ, aħjar ikun ir- riżultat li t- terapija tilħaq.
For the global score, patients taking Prometax capsules had in increase in symptoms of 4.1 points, compared with 4.4 in those taking placebo.
Għal dak li għandu x' jaqsam mal- punteġġ globali, il- pazjenti ttrattati bi Prometax kapsuli esperjenzaw żieda tas- sintomi ta '4. 1 punti meta mqabbla ma' 4. 4 punti rreġistrati fil- pazjenti ttrattati bil- plaċebo.
The Prometax transdermal patches were also more effective than placebo in preventing dementia from getting worse.
Prometax stikk transdermiku wkoll wera ruħu aktar effikaċi mill- plaċebo biex iwaqqaf l- aggravar tad - demenza.
The patients with dementia due to Parkinson’ s disease taking Prometax capsules showed an improvement in cognitive symptoms of 2.1 points, compared with a worsening of 0.7 points in those taking placebo, from a baseline of around 24 points.
Il- pazjenti li jbatu minn demenza dovuta għall- marda ta 'Parkinson ittrattati bi Prometax kapsuli wrew titjib tas- sintomi konjittivi ta' 2. 1 punti meta mqabbla ma 'l- aggravar ta' 0. 7 punti osservat fil- pazjenti li ħadu l- plaċebo, minn valur inizjali ta '24 punt.
The global symptom score also improved more in the patients taking Prometax.
Il- punteġġ globali tas- sintomi wkoll tjieb iktar fil - pazjenti ttrattati bi Prometax.
What is the risk associated with Prometax?
X' inhu r- riskju assoċjat ma 'Prometax?
The types of side effects seen with Prometax depend on the type of dementia it is being used to treat and whether the capsules, oral solution or transdermal patches are used.
It- tipi ta 'effetti sekondarji osservati bi Prometax jiddependu mit- tip ta' demenza li qiegħda tiġi ttrattata u mill- format meħud (kapsuli, soluzzjoni orali jew stikk transdermiku).
Overall, the most common side effects (seen in more than 1 patient in 10) include nausea (feeling sick) and vomiting, particularly during the phase when the dose of Prometax is being increased.
Kumplessivament, l- effetti sekondarji l- aktar komuni (li dehru f' aktar minn pazjent 1 minn 10) jinkludu nawżea (dardir) u remettar, partikolarment matul il- fażi li fiha d- dożaġġ ta 'Prometax żdied.
For the full list of all side effects reported with Prometax, see the Package Leaflet.
Għal- lista sħiħa ta 'l- effetti sekondarji kollha rrappurtata bi Prometax, ara l- Fuljett ta' Tagħrif.
Prometax should not be used in people who may be hypersensitive (allergic) to rivastigmine, other carbamate derivatives or any of the other ingredients.
Prometax ma għandux jintuża minn persuni li jistgħu jkunu ipersensittivi (allerġiċi) għal rivastigmina jew għal derivati tal- karbamati (carbamates) oħra jew għal kwalunkwe mill- ingredjenti l- oħra.
Why has Prometax been approved?
Għaliex ġie approvat Prometax?
The Committee for Medicinal Products for Human Use (CHMP) concluded that Prometax has a modest effectiveness in treating the symptoms of Alzheimer’ s dementia, although this does reflect an important benefit in some patients.
Il- Kumitat għall- Prodotti Mediċinali għall- Użu mill- Bniedem (CHMP) ikkonkluda li Prometax għandu effikaċja modesta fit- trattament tas- sintomi tad- demenza ta 'Alzheimer, minkejja li dan jirrifletti benefiċċju importanti għal uħud mill- pazjenti.
The Committee initially concluded that for the treatment of dementia due to Parkinson’ s disease, Prometax’ s benefits did not outweigh its risks.
Għall- ewwel, il- Kumitat ikkonkluda li, għat - trattament tad- demenza dovuta għall- marda ta 'Parkinson, il- benefiċċji ta' Prometax ma kinux ogħla
However, following a re-examination of this opinion, the Committee concluded that the medicine’ s modest effectiveness could also be of benefit to some patients.
Madankollu, wara eżami ġdid ta 'l- opinjoni tiegħu, il- Kumitat ikkonkluda li l - effikaċja tal- mediċina, anki jekk modesta, setgħet ukoll tkun ta' benefiċċju għal uħud mill- pazjenti.
Therefore, the Committee decided that Prometax’ s benefits are greater than its risks for the treatment of mild to moderately severe Alzheimer’ s dementia and mild to moderately severe dementia in patients with idiopathic Parkinson ’ s disease.
Għaldaqstant, il- Kumitat iddeċieda li l- benefiċċji ta 'Prometax huma ogħla mir- riskji tiegħu għat - trattament tad- demenza ta' Alzheimer minn ħafifa għal moderatament gravi u tad- demenza minn ħafifa għal moderatament gravi f' pazjenti bil- marda ta 'Parkinson idjopatika.
The Committee recommended that Prometax be given marketing authorisation.
Il- Kumitat irrakkomanda li Prometax jingħata awtorizzazzjoni għat- tqegħid fis- suq.
2/ 3 Other information about Prometax:
Aktar tagħrif dwar Prometax:
The European Commission granted a marketing authorisation valid throughout the European Union to Novartis Europharm Limited for Prometax on 4 December 1998.
Il- Kummissjoni Ewropea tat awtorizzazzjoni għat- tqegħid fis- suq valida fl- Unjoni Ewropea kollha, għal Prometax lil Novartis Europharm Limited fl- 4 ta 'Diċembru 1998.
The marketing authorisation was renewed on 4 December 2003 and on 4 December 2008.
L- awtorizzazzjoni għat- tqegħid fis- suq ġiet imġedda fl- 4 ta 'Diċembru 2003 u fl- 4 ta' Diċembru 2008.
The full EPAR for Prometax can be found here.
L- EPAR sħiħ għal Exelin jista 'jiġi kkonsulat hawn.
Package size
Daqs tal - Pakkett
1.5 mg 1.5 mg 1.5 mg 3 mg 3 mg 3 mg 4.5 mg 4.5 mg 4.5 mg 6 mg 6 mg 6 mg
1. 5 mg 1. 5 mg 1. 5 mg 3 mg 3 mg 3 mg 4. 5 mg 4. 5 mg 4. 5 mg 6 mg 6 mg 6 mg
Capsule, hard Capsule, hard Capsule, hard Capsule, hard Capsule, hard Capsule, hard Capsule, hard Capsule, hard Capsule, hard Capsule, hard Capsule, hard Capsule, hard
Kapsula, iebsa Kapsula, iebsa Kapsula, iebsa Kapsula, iebsa Kapsula, iebsa Kapsula, iebsa Kapsula, iebsa Kapsula, iebsa Kapsula, iebsa Kapsula, iebsa Kapsula, iebsa Kapsula, iebsa
Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use Oral use
Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali Użu orali
blister (PVC/ alu) blister (PVC/ alu) blister (PVC/ alu) blister (PVC/ alu) blister (PVC/ alu) blister (PVC/ alu) blister (PVC/ alu) blister (PVC/ alu) blister (PVC/ alu) blister (PVC/ alu) blister (PVC/ alu) blister (PVC/ alu)
folja (PVC/ alu) folja (PVC/ alu) folja (PVC/ alu) folja (PVC/ alu) folja (PVC/ alu) folja (PVC/ alu) folja (PVC/ alu) folja (PVC/ alu) folja (PVC/ alu) folja (PVC/ alu) folja (PVC/ alu) folja (PVC/ alu)
Oral solution Capsule, hard Capsule, hard Capsule, hard Capsule, hard
Soluzzjoni orali
Oral use Oral use Oral use Oral use Oral use
Użu orali
bottle (amber glass) bottle (HDPE) bottle (HDPE) bottle (HDPE) bottle (HDPE)
flixkun (ħġieġ kannella)
Oral solution Transdermal patch
Soluzzjoni orali
Oral use Transdermal use
Użu orali
bottle (amber glass) sachet (paper/ polyester/ alu/ poly acrylonitrile)
flixkun (ħġieġ kannella)
1 bottle 7 sachets
7 qratas
sachet (paper/ polyester/ alu/ poly acrylonitrile)
qartas (karta/ polyester/ alu/ poly acrylonitrile)
Prometax 1.5 mg hard capsules
Prometax 1. 5 mg kapsuli ibsin
Off-white to slightly yellow powder in a capsule with yellow cap and yellow body, with red imprint “ ENA 713 1,5 mg” on body.
Trab abjad li jagħti fl- offwajt jew ħarira fl- isfar, f’ kapsula b’ kappa safra u b’ għatu isfar, u stampata bl - aħmar “ ENA 713 1, 5 mg ” fuq il- kappa.
In other cases, Prometax has been discontinued (see section 4.8).
F’ każijiet oħra, Prometax ġie mwaqqaf (ara sezzjoni 4. 8).
The following adverse reactions, listed below in Table 1, have been accumulated in patients with Alzheimer’ s dementia treated with Prometax.
Ir- reazzjonijiet avversi li ġejjin, elenkati hawn taħt f’ Tabella 1, kienu miġbura minn pazjenti ikkurati b’ Prometax għal dimenzja t’ Alzheimer.
5 Skin and subcutaneous tissue disorders General
Mhux komuni fil- ġilda u fit- tessuti ta ’ taħt Komuni Rari
Common Rare disorders and administration
Livelli għolja tat- testijiet tal- funzjoni tal- fwied Żieda fl- għaraq Raxxijiet
Sweating increased Rashes
Disturbi
site conditions
ġenerali u kondizzjonijiet ta '
The following additional adverse reactions have been observed with Prometax transdermal patches: anxiety, delirium, pyrexia (common).
L- effetti avversi li ġejjin dehru bil- garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda Prometax: ansjetà, tgħewdin, deni (komuni).
Table 2 shows the adverse reactions reported in patients with dementia associated with Parkinson’ s disease treated with Prometax.
Tabella 2 turi reazzjonijiet avversi rrappurtati f’ pazjenti b’ dimenzja assoċjata mal- marda ta ’ Parkinson ikkurati b’ Prometax.
Common Common disorders and administration
nutrizzjoni Anoressija Komuni Deidratazzjoni Komuni Disturbi ġenerali u kundizzjonijiet ta ’ mnejn jingħata
Fatigue and asthenia Gait abnormality
Għeja kbira u astenja Mixi mhux normali
Table 3 lists the number and percentage of patients from the specific 24-week clinical study conducted 6 with Prometax 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’ Prometax f’ pazjenti b’ dimenzja assoċjata mal- marda ta Parkinson b’ avversi li kienu definiti minn qabel li jistgħu jirriflettu aggravar tas- sintomi ta ’ Parkinson.
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 ’
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).
ADAS-Cog Prometax
ADAS- Cog ADAS- Cog Prometax Plaċebo
ADCS- CGIC Prometax
ADCS- CGIC Plaċebo
(n=329)
(n=165)
3.541
3. 541
ADAS-Cog ADAS-Cog Placebo Prometax
ADAS- Cog ADAS- Cog Plaċebo Prometax
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%.
Distribution Protein binding of rivastigmine is approximately 40%.
10 Distribuzzjoni Rivastigmine huwa marbut b’ mod dgħajjef mal- proteini fil- plażma (bejn wieħed u ieħor 40%).
Date of first authorisation:04.12.1998 Date of latest renewal:
04. 12. 1998 Data ta ’ l- aħħar tiġdid:
Prometax 3.0 mg hard capsules
Prometax 3. 0 mg kapsuli ibsin
Off-white to slightly yellow powder in a capsule with orange cap and orange body, with red imprint “ ENA 713 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 “ ENA 713 3 mg ” fuq il- kappa.
No effects on fertility or embryofoetal development were observed in rats and rabbits, except at doses related to maternal toxicity.
Ma ġew osservati l- ebda effetti fuq il- fertilità jew fuq l- iżvilupp ta ’ l- embriju/ fetu fil- firien u l- fniek, ħlief meta d- dożi kienu relatati
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 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).
16 Skin and subcutaneous tissue disorders General
Mhux komuni fil- ġilda u fit- tessuti ta ’ taħt Komuni Rari
Sweating increased
Bradikardija Fibrillazzjoni ta ’ l- atriju Blokk atrijo- ventrikulari
Musculoskeletal and connective tissue disorders
Disturbi gastro- intestinali Dardir Komuni ħafna Rimettar Komuni ħafna
Muscle rigidity
18 Disturbi il- ġilda
Metabolism and nutritional disorders General
Komuni Komuni Komuni fil- ġilda u fit- tessuti ta ’ taħt Komuni
Common Common disorders and administration
Dijarea Uġigħ fl- addome u dispepsja Tnixxija ta ’ bżiq Żieda fl- għaraq
Anorexia Dehydration
Disturbi
site conditions
muskolu- skeletrali u tal -
Fatigue and asthenia Gait abnormality
mnejn jingħata Għeja kbira u astenja Komuni Mixi mhux normali Komuni
Table 3 lists the number and percentage of patients from the specific 24-week clinical study conducted 17 with Prometax 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’ Prometax f’ pazjenti b’ dimenzja assoċjata mal- marda ta Parkinson b’ avversi li kienu definiti minn qabel li jistgħu jirriflettu aggravar tas- sintomi ta ’ Parkinson.
Distribution Protein binding of rivastigmine is approximately 40%.
22 Distribuzzjoni Rivastigmine huwa marbut b’ mod dgħajjef mal- proteini fil- plażma (bejn wieħed u ieħor 40%).
04.12.1998 Date of latest renewal:
04. 12. 1998 Data ta ’ l- aħħar tiġdid:
Prometax 4.5 mg hard capsules
Prometax 4. 5 mg kapsuli ibsin
Off-white to slightly yellow powder in a capsule with red cap and red body, with white imprint “ ENA 713 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 “ ENA 713 4. 5 mg ” fuq il- kappa.
27 Skin and subcutaneous tissue disorders General
Mhux komuni fil- ġilda u fit- tessuti ta ’ taħt Komuni Rari
Table 3 lists the number and percentage of patients from the specific 24-week clinical study conducted 28 with Prometax 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’ Prometax f’ pazjenti b’ dimenzja assoċjata mal- marda ta Parkinson b’ avversi li kienu definiti minn qabel li jistgħu jirriflettu aggravar tas- sintomi ta ’ Parkinson.
Intent to Treat
Intenzjoni li tittratta Plaċebo
Last Observation Carried Forward
L- Aħħar Osservazzjoni Quddiem Rivastigmine
Rivastigmine 6– 12 mg
Kejl tar- Rispons
Placebo Rivastigmine 6– 12 mg
Rivastigmine 6– 12 mg N=473
18 32*** 17 30***
32 *** 30 ***
32 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.
35 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.
33 6.5 Nature and contents of container
6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
Prometax 6.0 mg hard capsules
Prometax 6. 0 mg kapsuli ibsin
Off-white to slightly yellow powder in a capsule with red cap and orange body, with red imprint “ ENA 713 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 “ ENA 713 6 mg ” fuq il- kappa.
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 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).
38 Skin and subcutaneous tissue disorders General
Mhux komuni fil- ġilda u fit- tessuti ta ’ taħt Komuni Rari
Muscle rigidity
42 Disturbi il- ġilda
39 Table 3 lists the number and percentage of patients from the specific 24-week clinical study conducted with Prometax 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’ Prometax f’ pazjenti b’ dimenzja assoċjata mal- marda ta Parkinson b’ avversi li kienu definiti minn qabel li jistgħu jirriflettu aggravar tas- sintomi ta ’ Parkinson.
42 Table 6
Tabella 6
Distribution Protein binding of rivastigmine is approximately 40%.
46 Distribuzzjoni Rivastigmine huwa marbut b’ mod dgħajjef mal- proteini fil- plażma (bejn wieħed u ieħor 40%).
Following administration of 14C-rivastigmine, renal elimination was rapid and essentially
Tneħħija Rivastigmine mhux mibdul ma jinstabx fl- awrina; it- tneħħija renali, tas- sustanzi fformati fil - metaboliżmu, hija l- mezz ewlieni ta ’ l- eliminazzjoni.
43 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.
Prometax 2 mg/ ml oral solution
Prometax 2 mg/ ml soluzzjoni orali
46 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.
47 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.
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 Prometax oral solution is sodium benzoate.
Waħda mis- sustanzi mhux attivi li tinsab f’ Prometax soluzzjoni orali hija sodium benzoate.
It is not known if rivastigmine is excreted into human
Mhux magħruf jekk rivastigmine joħroġx mal- ħalib tas - sider tal- bniedem.
Common Common Uncommon Uncommon Very rare system disorders Very common Common Common Common Uncommon Rare Very rare
Disturbi psikjatriċi Aġitazzjoni Komuni Konfużjoni Komuni Nuqqas ta ’ rqad Mhux komuni Dipressjoni Mhux komuni Alluċinazzjonijiet Rari ħafna Disturbi fis- sistema nervuża Sturdament Komuni ħafna Uġigħ ta ’ ras Komuni Ngħas Komuni Tregħid Komuni Sinkope Mhux komuni Aċċessjonijiet Rari Sintomi ekstrapiramidali (li jinkludu aggravar tal- marda ta ’ Rari ħafna Parkinson) Disturbi fil- qalb
Agitation Confusion Insomnia Depression Hallucinations Dizziness Headache Somnolence Tremor Syncope Seizures Extrapyramidal symptoms (including worsening of Parkinson’ s disease)
Rari
Cardiac
Angina pectoris
disorders Rare Very rare
Rari ħafna
Angina pectoris Cardiac arrhythmia (e. g. bradycardia, atrio-ventricular block, atrial fibrillation and tachycardia)
Problemi fir- ritmu tat- tħabbit tal- qalb (eż. bradikardja, imblukkar atrijo- ventrikulari, fibrillazzjoni ta ’ l- atrija u takikardija)
Nausea Vomiting Diarrhoea Abdominal pain and dyspepsia Gastric and duodenal ulcers Gastrointestinal haemorrhage Pancreatitis
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).
Skin and subcutaneous tissue disorders General
Mhux komuni fil- ġilda u fit- tessuti ta ’ taħt Komuni Rari
Common Common Common system disorders Very common Common Common Common Common Common Common Uncommon disorders Common Uncommon Uncommon
Disturbi psikjatriċi Nuqqas ta ’ rqad Komuni Ansjetà Komuni Nuqqas ta ’ kwiet Komuni Disturbi fis- sistema nervuża Tregħid Komuni ħafna Sturdament Komuni Ħedla tan- ngħas Komuni Uġigħ ta ’ ras Komuni Aggravar tal- marda ta ’ Parkinson Komuni Bradikajneżja Komuni Diskajneżja Komuni Distonja Mhux komuni Disturbi fil- qalb Bradikardija Komuni Fibrillazzjoni ta ’ l- atriju Mhux komuni Blokk atrijo- ventrikulari Mhux komuni
Insomnia Anxiety Restlessness Tremor Dizziness Somnolence Headache Worsening of Parkinson’ s disease Bradykinesia Dyskinesia Dystonia Bradycardia Atrial Fibrillation Atrioventricular block
54 Disturbi gastro- intestinali Dardir Komuni ħafna Rimettar Komuni ħafna Dijarea Komuni Uġigħ fl- addome u dispepsja Komuni Tnixxija ta ’ bżiq Komuni Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda Disturbi
Gastrointestinal disorders
Komuni muskolu- skeletrali u tal -
Metabolism and nutritional disorders
Komuni fil- metaboliżmu u n -
50 General disorders and administration site conditions
nutrizzjoni Anoressija Komuni Deidratazzjoni Komuni Disturbi ġenerali u kundizzjonijiet ta ’ mnejn jingħata
with Prometax 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’ Prometax f’ pazjenti b’ dimenzja assoċjata mal- marda ta Parkinson b’ avversi li kienu definiti minn qabel li jistgħu jirriflettu aggravar tas- sintomi ta ’ Parkinson.
Due to the known vagotonic effect of cholinesterase inhibitors on heart rate, bradycardia and/ or syncope may also occur.
55 Minħabba l- effett vagotoniku magħruf li għandhom l- inibituri ta ’ cholinesterase, dawn jistgħu jirriżultaw f’ bradikardija u/ jew sinkope.
Prometax oral solution should be used within 1 month of opening the bottle.
Prometax bħala soluzzjoni orali għandha tintuża fi żmien xahar minn meta jinfetaħ il- flixkun.
Prometax 4.6 mg/ 24 h transdermal patch
Prometax 4. 6 mg/ 24 siegħa garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda
The outside of the backing layer is beige and labelled with “ Prometax”, “ 4.6 mg/ 24 h” and “ AMCX”.
In- naħa ta ’ barra tas- saff ta ’ wara huwa bex u tikkettat b ’ “ Prometax ”, “ 4. 6 mg/ 24 h ” u “ AMCX ”.
Transdermal patches
Garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Prometax 4. 6 mg/ 24 siegħa
Prometax 4.6 mg/ 24 h Prometax 9.5 mg/ 24 h
Prometax 9. 5 mg/ 24 siegħa
57 Switching from capsules or oral solution to transdermal patches Based on comparable exposure between oral and transdermal rivastigmine (see section 5.2), patients treated with Prometax capsules or oral solution can be switched to Prometax transdermal patches as follows: • A patient on a dose of 3 mg/ day oral rivastigmine can be switched to 4.6 mg/ 24 h transdermal patches. • A patient on a dose of 6 mg/ day oral rivastigmine can be switched to 4.6 mg/ 24 h transdermal patches. • A patient on a stable and well tolerated dose of 9 mg/ day oral rivastigmine can be switched to 9.5 mg/ 24 h transdermal patches.
62 Biex taqleb minn kapsuli jew soluzzjoni orali għall- garżi li jeħlu minn fuq il- ġilda Mit- tqabbil ta ’ l- esponimenti ta ’ rivastigmine orali u dak minn fuq il- ġilda (ara sezzjoni 5. 2), pazjenti ikkurati bil- kapsuli Prometax jew soluzzjoni orali jistgħu jinqalbu għall- garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Prometax kif ġej: • Pazjent fuq doża ta ’ 3 mg/ jum rivastigmine orali jistgħu jinqalbu għal 4. 6 mg/ 24 siegħa garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda. • Pazjent fuq doża ta ’ 6 mg/ jum rivastigmine orali jistgħu jinqalbu għal 4. 6 mg/ 24 siegħa garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda. • Pazjent fuq doża stabbli li jkun jiflaħ sew għaliha ta ’ 9 mg/ jum rivastigmine orali jistgħu jinqalbu għal 9. 5 mg/ 24 siegħa garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda.
58 Patients with Alzheimer’ s disease may lose weight whilst taking cholinesterase inhibitors, including rivastigmine.
Pazjenti bil- marda ta ’ Alzheimer jistgħu jitilfu l- piż waqt li jkunu qed jieħdu inibituri ta ’ cholinesterase, inkluż rivastigmine.
The patient’ s weight should be monitored during therapy with Prometax transdermal patches.
Il- piż tal- pazjent għandu jkun monitorat waqt it- terapija bil- garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Prometax.
Care must be taken when prescribing Prometax transdermal patches: • to patients with sick sinus syndrome or conduction defects (sino-atrial block, atrio-ventricular block) (see section 4.8) • to patients with active gastric or duodenal ulcers or patients predisposed to these conditions because rivastigmine may cause increased gastric secretions (see section 4.8) • to patients predisposed to urinary obstruction and seizures because cholinomimetics may induce or exacerbate these diseases. • to patients with a history of asthma or obstructive pulmonary disease.
Għandha ssir attenzjoni meta jiġu ordnati l- garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Prometax: • lill- pazjenti b’ sindrome ta ’ sinus marid jew difetti tal- konduzzjoni (imblukkar sino- atrijali, imblukkar atrijo- ventrikulari) (ara sezzjoni 4. 8). • lill- pazjenti b’ ulċeri attivi fl- istonku jew tad- duwodenu jew pazjenti li huma pridisposti għall - dawn il- kondizzjonijiet għaliex rivastigmine jista ’ jżid is- sekrezzjonijiet ta ’ l- istonku (ara sezzjoni 4. 8). • lill- pazjenti li huma pridisposti li jsofru minn imblukkar ta ’ l- awrina u aċċessjonijiet għaliex il - kolinomimetiċi jistgħu jikkawżaw jew jaggravaw dawn il- mard. • lill- pazjenti li fil- passat sofrew bl- ażżma jew b’ mard ostruttiv tal- pulmun.
Contact with the eyes should be avoided after handling Prometax transdermal patches (see section 5.3).
Għandu jiġi evitat il- kuntatt ma ’ l- għajnejn wara li tkun missejt il- garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Prometax (ara sezzjoni 5. 3).
No specific interaction studies have been conducted with Prometax transdermal patches.
Ma sarux studji speċifiċi dwar interazzjonijiet bil- garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Prometax.
Concomitant administration of rivastigmine with commonly prescribed medicinal products, such as antacids, antiemetics, antidiabetics, centrally acting antihypertensives, beta blockers, calcium channel blockers, inotropic agents, antianginals, non-steroidal anti-inflammatory agents, oestrogens, analgesics, benzodiazepines and antihistamines, was not associated with an alteration in the kinetics of rivastigmine or an increased risk of clinically relevant untoward effects.
64 L- għotja fl- istess ħin ta ’ rivastigmine ma ’ prodotti mediċinali li jiġu ordnati ta ’ spiss, bħal antaċidi, anti- emetiċi, antidijabetiċi, mediċini tal- pressjoni li jaħdmu b’ mod ċentrali, imblukkaturi beta, imblukkaturi tal- kanali tal- calcium, sustanzi inotropiċi, mediċini għall- anġina, aġenti mhux setrojdali kontra l- infjammazzjoni, estroġeni, analġesiċi, benzodiażepini u anti- istaminiċi, ma kinetx assoċjata ma ’ tibdil fil- kinetika ta ’ rivastigmine jew żieda fir- riskju ta ’ effetti ħżiena klinikament rilevanti.
The overall incidence of adverse events (AEs) in patients treated with Prometax 9.5 mg/ 24 h transdermal patches was lower than the rate in patients who received 3 to 12 mg/ day Prometax capsule treatment (50.5% with Prometax 9.5 mg/ 24 h transdermal patches vs 63.3% with Prometax capsules; 46.0% of patients on placebo reported AEs).
L- inċidenza globali tal- każijiet avversi (AE’ s) f’ pazjenti kkurati b’ garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda 9. 5 mg/ 24 siegħa kienet aktar baxxa mir- rata fil- pazjenti li rċevew 3 sa 12 mg/ jum kura bil- kapsula Prometax (50. 5% b’ garżi Prometax li jipprovdu mediċina li tgħaddi minn ġol- ġilda 9. 5 mg/ 24 siegħa vs 63. 3% bil- kapsuli Prometax; 46. 0% tal- pazjenti fuq plaċebo rrappurtaw AE’ s).
Gastrointestinal adverse reactions, including nausea and vomiting, were the most common adverse reactions in patients who received active treatment, and occurred at a substantially lower rate in the Prometax 9.5 mg/ 24 h transdermal patch group compared to the Prometax capsule group (7.2% vs 23.1% for nausea and 6.2% vs 17.0% for vomiting; 5.0% and 3.3% of patients on placebo reported nausea and vomiting, respectively).
Reazzjonijiet avversi gastro- intestinali, inklużi dardir u rimettar, kienu l- aktar reazzjonijiet avversi komuni f’ pazjenti li rċevew kura attiva, u seħħew b’ rata aktar baxxa b’ mod sostanzjali fil- grupp b’ Prometax garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda 9. 5 mg/ 24 siegħa meta mqabbla mal- grupp bil- kapsula Prometax (7. 2% vs 23. 1% għad- dardir u 6. 2% vs 17. 0% għar- rimettar, 5. 0% u 3. 3% tal- pazjenti fuq plaċebo rrappurtaw dardir u rimettar, rispettivament).
Table 1 displays the adverse reactions (events reasonably believed to be causally related to the medicinal product) reported in 291 patients with Alzheimer’ s dementia treated in a specific 24-week double-blind, placebo and active-controlled clinical study with Prometax transdermal patches at target dose of 9.5 mg/ 24 h (4.6 mg/ 24 h titrated to 9.5 mg/ 24 h).
Tabella 1 turi r- reazzjonijiet avversi (każijiet maħsuba b’ mod raġonevoli li huma ġejjin mill- prodott mediċinali) irrappurtati f’ 291 pazjent bid- dimenzja ta ’ Alzheimer ikkurati fi studju speċifiku ta ’ 24 ġimgħa double- blind, bi plaċebo u kontrollat b’ mod attiv bil- garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Prometax u doża mmirata ta ’ 9. 5 mg/ 24 siegħa (4. 6 mg/ 24 siegħa miżjuda għal 9. 5 mg/ 24 siegħa).
Table 1
65 Tabella 1
Common
Komuni:
60 When doses higher than 9.5 mg/ 24 h were used in the above-mentioned study, dizziness, insomnia, agitation, decreased appetite, atrial fibrillation and cardiac failure were observed more frequently than with 9.5 mg/ 24 h or placebo, suggesting a dose effect relationship.
Meta dożi ogħla minn 9. 5 mg/ 24 siegħa intużaw f’ dan l- istudju t’ hawn fuq, sturdament, nuqqas ta ’ rqad, aġitazzjoni, tnaqqis fl- aptit, fibrillazjoni atrijali u insuffiċjenza kardijaka dehru aktar ta ’ spiss milli b ’ 9. 5 mg/ 24 siegħa jew plaċebo, li tindika li hemm relazzjoni mad- doża.
However, these events did not occur at a higher frequency with Prometax 9.5 mg/ 24 h transdermal patches than with placebo.
Madankollu, dawn il - każijiet ma ġrawx b’ mod aktar frekwenti b’ garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Prometax 9. 5 mg/ 24 siegħa milli bi plaċebo.
The following adverse reactions have only been observed with Prometax capsules and oral solution and not in clinical studies with Prometax 9.5 mg/ 24 h transdermal patches:
Ir- reazzjonijiet avversi li ġejjin dehru biss bil- kapsuli u soluzzjoni orali Prometax u mhux fl- isutdji kliniċi b’ garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda 9. 5 mg/ 24 siegħa:
In a 24-week double-blind study, the most commonly observed symptoms (skin irritation rating scale) with Prometax 9.5 mg/ 24 h transdermal patches were very slight (21.8%), mild (12.5%) or moderate (6.5%) erythema or very slight (11.9%), mild (7.3%) or moderate (5.0%) pruritus.
Fi studju double- blind ta ’ 24 ġimgħa, l- aktar sintomi li dehru ta ’ spiss (skala ta ’ stima ta ’ l- irritazzjoni tal- ġilda) b’ garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Prometax 9. 5 mg/ 24 siegħa kienu ħmura ħafifa ħafna (21. 8%), ħafifa (12. 5%) jew moderata (6. 5%) jew ħakk ħafif ħafna (11. 9%), ħafif (7. 3%) jew moderat (5. 0%).
The most commonly observed severe symptoms with Prometax 9.5 mg/ 24 h transdermal patches were pruritus (1.7%) and erythema (1.1%).
L- aktar sintomi severi b’ garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Prometax 9. 5 mg/ 24 siegħa kienu ħakk (1. 7%) u ħmura (1. 1%).
Most skin reactions were limited to the application site and resulted in discontinuation in only 2.4% of the patients in the Prometax 9.5 mg/ 24 h transdermal patch group.
Fil- parti l- kbira, reazzjonijiet tal- ġilda kienu limitati għas- sit mnejn ġiet applikata u wasslet għat- twaqqif f’ 2. 4% biss tal- grupp ta ’ kura tal- pazjenti b’ garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda 9. 5 mg/ 24 siegħa.
4.9 Overdose
66 4. 9 Doża eċċessiva
Ingestion of 46 mg of oral rivastigmine occurred in one case; following conservative management the patient fully recovered within 24 hours.
F’ każ wieħed b’ doża ta ’ pazjent li ħa 46 mg rivastigmine b’ mod orali; il- pazjent irkupra għal kollox f’ 24 siegħa b’ trattament konservattiv.
There are currently no data on overdose with Prometax transdermal patches.
S’ issa għad m’ hemmx tagħrif dwar doża eċċessiva bil- garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Prometax.
Treatment As rivastigmine has a plasma half-life of about 3.4 hours and a duration of acetylcholinesterase inhibition of about 9 hours, it is recommended that in cases of asymptomatic overdose all Prometax transdermal patches should be removed immediately and no further transdermal patch should be applied for the next 24 hours.
Kura Minħabba li rivastigmine għandu half- life fil- plażma ta ’ xi 3. 4 sigħat, u l- inibizzjoni ta ’ acetylcholinesterase iddum xi 9 sigħat, huwa rrikkmandat li fil- każijiet ta ’ doża eċċessiva bla sintomi l- garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Prometax kollha għandhom jitneħħew mill - ewwel u ma titwaħħal l- ebda garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda oħra fl- 24 siegħa ta ’ wara.
Rivastigmine is an acetyl- and butyrylcholinesterase inhibitor of the carbamate type, thought to
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.
Thus, rivastigmine may have an ameliorative effect on cholinergic-mediated cognitive deficits in dementia associated with Alzheimer’ s disease.
B’ dan il- mod, rivastigmine jista ’ jkollu effett li jtejjeb id- difikultajiet ta ’ għarfien li jkunu medjati b’ mod kolinerġiku u li huma assoċjati mal- marda ta ’ Alzheimer.
Clinical studies in Alzheimer’ s dementia The efficacy of Prometax transdermal patches in patients with Alzheimer’ s dementia has been demonstrated in a 24-week double-blind core study and its open-label extension phase.
Studji Kliniċi f’ dimenzja ta ’ Alzheimer L- effikaċa tal- garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Prometax f’ pazjenti bid- dimenzja ta ’ Alzheimer intweriet fi studju ċentrali double- blind li dam 24 ġimgħa u l- fażi ta ’ l- estenzjoni tiegħu open- label.
These include the ADAS-Cog (a performance-based measure of cognition) and the ADCS-CGIC (a comprehensive global assessment of the patient by the physician incorporating caregiver input), and the ADCS-ADL (a caregiver-rated assessment of the activities of daily living including personal hygiene, feeding, dressing, household chores such as shopping, retention of ability to orient oneself to surroundings as well as involvement in activities related to finances).
67 tal- komprensjoni tal- pazjent mit- tabib li tinkludi tgħarif li tagħti l- persuna li tieħu ħsieb il- kura tas - saħħa), u l- ADCS- ADL (evalwazzjoni stmata mill- persuna li tieħu ħsieb il- kura tas- saħħa ta ’ l - attivitajiet ta ’ kuljum inkluż l- indafa personali, ħila biex jiekol, jilbes, u faċendi oħra bħal xiri, u l- ħila li jorjenta ruħu fl- ambjent kif ukoll l- involviment f’ attivitajiet relatati mal- finanzi).
9.5 mg/ 24 h
Garżi li jipprovdu mediċina li tgħaddi minn ġol - ġilda Prometax 9. 5 mg/ 24 siegħa
ITT-LOCF population ADAS-Cog
Popolazzjoni ITT- LOCF ADAS- Cog
62 Table 3
68 Tabella 3
Patients with clinically significant response (%)
Pazjenti b’ rispons klinikament rilevanti (%)
Prometax Prometax
Garżi li
Placebo
Kapsuli
transdermal patches
Prometax jipprovdu 12 mg/ jum mediċina li N = 282 tgħaddi minn Popolazzjoni ITT- LOCF
Absorption Absorption of rivastigmine from Prometax transdermal patches is slow.
Assorbiment Rivastigmine huwa assorbit bil- mod mill- garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Prometax.
The fluctuation index (FI), a measure of the relative difference between peak and trough concentrations((Cmax-Cmin)/ Cavg), was 0.58 for Prometax 4.6 mg/ 24 h transdermal patches and 0.77 for Prometax 9.5 mg/ 24 h transdermal patches, thus demonstrating a much smaller fluctuation between trough and peak concentrations than for the oral formulation (FI = 3.96 (6 mg/ day) and 4.15 (12 mg/ day)).
L- indiċi ta ’ fluttwazzjoni (FI), kejl tad- differenza relattiva bejn l- ogħla konċentrazzjonijiet u dawk l- aktar baxxi ((Cmax- Cmin) / Cavg), kien 0. 58 għal garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Prometax 4. 6 mg/ 24 siegħa u 0. 77 għal garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Prometax 9. 5 mg/ 24 siegħa, b’ hekk dehret fluttwazzjoni iżgħar bejn l- ogħla konċentrazzjonijiet u dawk l- aktar baxxi minn b’ dik tal- formulazzjoni orali (FI = 3. 96 (6 mg/ jum) u 4. 15 (12 mg/ jum)).
The inter-patient variability in a steady-state study in Alzheimer’ s dementia was at most 45% (Cmax) and 43% (AUC0-24h) after use of the transdermal patch, and 71% and 73%, respectively, after administration of the oral form.
Il- varjabbilità bejn il- pazjenti fi stat fiss fl- istudju fuq id- dimenzja ta ’ Alzheimer kienet mhux aktar minn 45% (Cmax) u 43% (AUC0- 24h) wara l- użu tal- garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda, u 71% u 73% rispettivament, wara l -
63 Exposure (AUC∞) to rivastigmine (and metabolite NAP266-90) was highest when the transdermal patch was applied to the upper back, chest, or upper arm and approximately 20– 30% lower when applied to the abdomen or thigh.
Esponiment (AUC∞) għal rivastigmine (u l- metabolu NAP266- 90) kienet l- ogħla meta l- garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda kienet applikata man- naħa ta ’ isfel tad- dahar, sider jew parti ta ’ fuq tad- driegħ u madwar 20- 30% aktar baxxa meta tkun applikata ma ’ l- addome jew koxxa.
Metabolism Rivastigmine is rapidly and extensively metabolised with an apparent elimination half-life in plasma of approximately 3.4 hours after removal of the transdermal patch.
Metaboliżmu Rivastigmine huwa metaboliżżat malajr u b’ mod estensiv b’ half- life ta ’ eliminazzjoni apparenti ta ’ madwar 3. 4 siegħa wara li titneħħa l- garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda.
Elderly subjects Age had no impact on the exposure to rivastigmine in Alzheimer’ s disease patients treated with Prometax transdermal patches.
Individwi anzjani L- età ma kellha l- ebda effett fuq l- esponiment għal rivastigmine f’ pazjenti bil- marda ta ’ Alzheimer ikkurati bil- garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Prometax.
Subjects with hepatic impairment No study was conducted with Prometax transdermal patches in subjects with hepatic impairment.
Individwi b’ indeboliment epatiku Ma sar l- ebda studju bil- garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Prometax f’ individwi b’ indeboliment epatiku.
After oral administration, 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.
70 60% ogħla u l- AUC ta ’ rivastigmine kien aktar minn darbtejn ogħla f’ individwi li kellhom indeboliment epatiku ħafif għal moderat, meta dawn kienu mqabbla ma ’ individwi b’ saħħithom.
Subjects with renal impairment No study was conducted with Prometax transdermal patches in subjects with renal impairment.
Individwi b’ indeboliment renali Ma sar l- ebda studju bil- garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Prometax f’ individwi b’ indeboliment renali.
64 Oral and topical dosing in animal studies was limited due to the sensitivity of the animal models used.
Id- dużaġġi mogħtija b’ mod orali u topiku fi studji bl- annimali kienu limitati minħabba s- sensittività ta ’ l- annimali użati bħala mudelli.
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 exceeding 104 times the foreseen 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 li qabżet l- 104 darbiet l - esponiment kliniku mbassar.
No evidence of carcinogenicity was found in oral and topical studies in mice and in an oral study in rats at the maximum tolerated dose.
Ma nstabet l- ebda evidenza ta ’ kanċeroġeniċità fi studji orali u topiċi fuq ġrieden u fi studju orali fil - firien meta ngħatat id- doża massima tollerata.
This may indicate a potential for Prometax transdermal patches to induce mild erythema in patients.
Dan jindika li l- garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Prometax jistgħi jikkawżaw ħmura ħafifa fil- pazjenti.
6.2 Incompatibilities
71 6. 2 Inkompatibilitajiet
To prevent interference with the adhesive properties of the transdermal patch, no cream, lotion or powder should be applied to the skin area where the medicinal product is to be applied.
Sabiex jiġi evitat li jiġi mxekkel il- karatteristiċi adeżivi tal- garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda, m’ għandha tiġi applikata l- ebda krema, lozzjoni jew trab fil- parti tal- ġilda fejn ikun sejjer jiġi applikat il- prodott mediċinali.
Secondary packaging material The sachets are packed in a carton.
It- tieni materjal tal- pakkett Il- qratas ippakkjati f’ kartuna.
Prometax 9.5 mg/ 24 h transdermal patch
Prometax 9. 5 mg/ 24 siegħa garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda
The outside of the backing layer is beige and labelled with “ Prometax”, “ 9.5 mg/ 24 h” and “ BHDI”.
In- naħa ta ’ barra tas- saff ta ’ wara huwa bex u tikkettat b ’ “ Prometax ”, “ 9. 5 mg/ 24 h ” u “ BHDI ”.
67 Switching from capsules or oral solution to transdermal patches Based on comparable exposure between oral and transdermal rivastigmine (see section 5.2), patients treated with Prometax capsules or oral solution can be switched to Prometax transdermal patches as follows: • A patient on a dose of 3 mg/ day oral rivastigmine can be switched to 4.6 mg/ 24 h transdermal patches. • A patient on a dose of 6 mg/ day oral rivastigmine can be switched to 4.6 mg/ 24 h transdermal patches. • A patient on a stable and well tolerated dose of 9 mg/ day oral rivastigmine can be switched to 9.5 mg/ 24 h transdermal patches.
74 Biex taqleb minn kapsuli jew soluzzjoni orali għall- garżi li jeħlu minn fuq il- ġilda Mit- tqabbil ta ’ l- esponimenti ta ’ rivastigmine orali u dak minn fuq il- ġilda (ara sezzjoni 5. 2), pazjenti ikkurati bil- kapsuli Prometax jew soluzzjoni orali jistgħu jinqalbu għall- garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Prometax kif ġej: • Pazjent fuq doża ta ’ 3 mg/ jum rivastigmine orali jistgħu jinqalbu għal 4. 6 mg/ 24 siegħa garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda. • Pazjent fuq doża ta ’ 6 mg/ jum rivastigmine orali jistgħu jinqalbu għal 4. 6 mg/ 24 siegħa garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda. • Pazjent fuq doża stabbli li jkun jiflaħ sew għaliha ta ’ 9 mg/ jum rivastigmine orali jistgħu jinqalbu għal 9. 5 mg/ 24 siegħa garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda.
4.4 Special warnings and precautions for use
75 4. 4 Twissijiet speċjali u prekawzjonijiet għall- użu
68 Patients with Alzheimer’ s disease may lose weight whilst taking cholinesterase inhibitors, including rivastigmine.
Pazjenti bil- marda ta ’ Alzheimer jistgħu jitilfu l- piż waqt li jkunu qed jieħdu inibituri ta ’ cholinesterase, inkluż rivastigmine.
Concomitant administration of rivastigmine with commonly prescribed medicinal products, such as antacids, antiemetics, antidiabetics, centrally acting antihypertensives, beta blockers, calcium channel blockers, inotropic agents, antianginals, non-steroidal anti-inflammatory agents, oestrogens, analgesics, benzodiazepines and antihistamines, was not associated with an alteration in the kinetics of rivastigmine or an increased risk of clinically relevant untoward effects.
76 L- għotja fl- istess ħin ta ’ rivastigmine ma ’ prodotti mediċinali li jiġu ordnati ta ’ spiss, bħal antaċidi, anti- emetiċi, antidijabetiċi, mediċini tal- pressjoni li jaħdmu b’ mod ċentrali, imblukkaturi beta, imblukkaturi tal- kanali tal- calcium, sustanzi inotropiċi, mediċini għall- anġina, aġenti mhux setrojdali kontra l- infjammazzjoni, estroġeni, analġesiċi, benzodiażepini u anti- istaminiċi, ma kinetx assoċjata ma ’ tibdil fil- kinetika ta ’ rivastigmine jew żieda fir- riskju ta ’ effetti ħżiena klinikament rilevanti.
Table 1
77 Tabella 1
70 When doses higher than 9.5 mg/ 24 h were used in the above-mentioned study, dizziness, insomnia, agitation, decreased appetite, atrial fibrillation and cardiac failure were observed more frequently than with 9.5 mg/ 24 h or placebo, suggesting a dose effect relationship.
Meta dożi ogħla minn 9. 5 mg/ 24 siegħa intużaw f’ dan l- istudju t’ hawn fuq, sturdament, nuqqas ta ’ rqad, aġitazzjoni, tnaqqis fl- aptit, fibrillazjoni atrijali u insuffiċjenza kardijaka dehru aktar ta ’ spiss milli b ’ 9. 5 mg/ 24 siegħa jew plaċebo, li tindika li hemm relazzjoni mad- doża.
4.9 Overdose
78 4. 9 Doża eċċessiva
These include the ADAS-Cog (a performance-based measure of cognition) and the ADCS-CGIC (a comprehensive global assessment of the patient by the physician incorporating caregiver input), and the ADCS-ADL (a caregiver-rated assessment of the activities of daily living including personal hygiene, feeding, dressing, household chores such as shopping, retention of ability to orient oneself to surroundings as well as involvement in activities related to finances).
79 tal- komprensjoni tal- pazjent mit- tabib li tinkludi tgħarif li tagħti l- persuna li tieħu ħsieb il- kura tas - saħħa), u l- ADCS- ADL (evalwazzjoni stmata mill- persuna li tieħu ħsieb il- kura tas- saħħa ta ’ l - attivitajiet ta ’ kuljum inkluż l- indafa personali, ħila biex jiekol, jilbes, u faċendi oħra bħal xiri, u l- ħila li jorjenta ruħu fl- ambjent kif ukoll l- involviment f’ attivitajiet relatati mal- finanzi).
72 Table 3
80 Tabella 3
Patients with clinically significant response (%)
Pazjenti b’ rispons klinikament rilevanti (%) Plaċebo Kapsuli Garżi li Prometax jipprovdu 12 mg/ jum mediċina li N = 282
Prometax Prometax
Popolazzjoni ITT- LOCF
Placebo
N = 256
transdermal patches
9. 5 mg/ 24 siegħa N = 251