natgillin/translations-raw huggingface dataset:
The overall incidence of adverse events (AEs) in patients treated with Exelon 9.5 mg/ 24 h transdermal patches was lower than the rate in patients who received 3 to 12 mg/ day Exelon capsule treatment (50.5% with Exelon 9.5 mg/ 24 h transdermal patches vs 63.3% with Exelon capsules; 46.0% of patients on placebo reported AEs).
Pri bolnikih, zdravljenih s transdermalnimi obliži Exelon 9, 5 mg/ 24 h, je bila skupna incidenca neželenih dogodkov nižja kot pri bolnikih, ki so prejemali Exelon v kapsulah v odmerku 3 do 12 mg/ dan (50, 5% s transdermalnimi obliži Exelon 9, 5 mg/ 24 h v primerjavi s 63, 3% s kapsulami Exelon; pri tem je 46, 0% bolnikov s placebom poročalo o neželenih učinkih).
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 Exelon 9.5 mg/ 24 h transdermal patch group compared to the Exelon 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).
Pri bolnikih, ki so prejemali aktivno zdravljenje, so bili med neželenimi učinki najpogostejši gastrointestinalni, vključno z navzeo in bruhanjem, pojavljali pa so se v precej manjši meri v skupini s transdermalnimi obliži Exelon 9, 5 mg/ 24 h v primerjavi s skupino s kapsulami Exelon (navzea v 7, 2% v primerjavi s 23, 1% in bruhanje v 6, 2% v primerjavi s 17, 0%; pri tem je 5, 0% bolnikov s placebom poročalo o navzei, 3, 3% pa o bruhanju).
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 Exelon transdermal patches at target dose of 9.5 mg/ 24 h (4.6 mg/ 24 h titrated to 9.5 mg/ 24 h).
V preglednici 1 so navedeni neželeni učinki (dogodki, za katere upravičeno velja, da so vzročno povezani z zdravilom), o katerih so poročali pri 291 bolnikih z Alzheimerjevo demenco, zdravljenih v okviru specifične 24- tedenske dvojno slepe, s placebom in aktivno kontrolirane klinične študije s transdermalnimi obliži Exelon, v kateri je bil ciljni odmerek 9, 5 mg/ 24 h (titracija z odmerka 4, 6 mg/ 24 h na 9, 5 mg/ 24 h).
Very common (≥ 1/ 10); common (≥ 1/ 100, < 1/ 10); uncommon (≥ 1/ 1,000, < 1/ 100); rare (≥ 1/ 10,000, < 1/ 1,000); very rare (< 1/ 10,000).
Neželeni učinki so razvrščeni po skupinah glede na pogostnost, najpogostejši najprej, po naslednjem dogovoru: zelo pogosti (≥1/ 10); pogosti (≥1/ 100 do < 1/ 10); občasni (≥1/ 1. 000 do < 1/ 100); redki (≥1/ 10. 000 do < 1/ 1. 000); zelo redki (< 1/ 10. 000).
Table 1
65 Preglednica 1
Anxiety, depression, delirium
tesnoba, depresija, delirij
Nervous system disorders
Bolezni živčevja Srčne
Very rare:
pogosti: zelo redki: bolezni občasni:
Headache, syncope Extrapyramidal symptoms
glavobol, sinkopa ekstrapiramidni simptomi bradikardija
Uncommon:
pogosti: občasni:
Nausea, vomiting, diarrhoea, dyspepsia, abdominal pain Gastric ulcer
navzea, bruhanje, driska, dispepsija, bolečine v trebuhu razjeda želodca
Application site skin reactions (e. g. application site erythema, application site pruritus, application site oedema, application site dermatitis, application site irritation), asthenic conditions (e. g. fatigue, asthenia), pyrexia, weight decreased
kožne reakcije na mestu aplikacije (npr. rdečina na mestu aplikacije, srbenje na mestu aplikacije, oteklina na mestu aplikacije, dermatitis na mestu aplikacije, draženje na mestu aplikacije), astenična stanja (npr. utrujenost, astenija), zvišana telesna temperatura, zmanjšanje telesne mase
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
Kadar so v zgoraj navedeni študiji uporabljali odmerke, ki so bili višji od 9, 5 mg/ 24 h, so opažali vrtoglavost, nespečnost, agitiranost, izgubo teka, atrijsko fibrilacijo in popuščanje srca pogosteje kot pri odmerku 9, 5 mg/ 24 h ali pri placebu, kar nakazuje odvisnost od velikosti odmerka.
However, these events did not occur at a higher frequency with Exelon 9.5 mg/ 24 h transdermal patches than with placebo.
Vendar pa se ti dogodki niso pojavljali pogosteje pri uporabi transdermalnega obliža Exelon 9, 5 mg/ 24 h v primerjavi s placebom.
Dizziness (very common); agitation, somnolence, malaise, tremor, confusion, sweating increased (common); insomnia, accidental fall, elevated liver function tests (uncommon); seizures, duodenal ulcers, angina pectoris (rare); cardiac arrhythmia (e. g. atrio-ventricular block, atrial fibrillation and tachycardia), hypertension, pancreatitis, gastrointestinal haemorrhage, hallucination (very rare); and some cases of severe vomiting were associated with oesophageal rupture (unknown).
Naslednje neželene učinke so opažali samo pri uporabi kapsul in peroralne raztopine Exelon, ne pa v kliničnih študijah s transdermalnimi obliži Exelon 9, 5 mg/ 24 h: vrtoglavost (zelo pogosto); agitacijo, somnolenco, splošno slabo počutje, tremor, zmedenost, povečano potenje (pogosto); nespečnost, nezgodne padce, zvišane jetrne funkcijske teste (občasno); napade krčev, razjede dvanajstnika, angino pektoris (redko); srčne aritmije (na primer atrioventrikularni blok, atrijsko fibrilacijo in tahikardijo), hipertenzijo, pankreatitis, krvavitev v prebavila, halucinacije (zelo redko); in nekaj primerov hudega bruhanja, ki je bilo povezano z rupturo požiralnika (pogostnost ni znana).
Skin irritation In clinical trials, skin reactions were measured at each visit using a skin irritation rating scale that rated the degree of erythema, oedema, scaling, fissures, pruritus and pain/ stinging/ burning at the application site.
Draženje kože V kliničnih študijah so kožne reakcije pri vsakem obisku ovrednotili s pomočjo lestvice za oceno draženja kože, s katero so ocenili stopnjo rdečine, otekline, luščenja, kožnih razpok, srbenja in bolečine/ zbadanja/ pekočega občutka na mestu aplikacije.
In a 24-week double-blind study, the most commonly observed symptoms (skin irritation rating scale) with Exelon 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.
V 24- tedenski dvojno slepi študiji so bili najbolj pogosto opaženi simptomi (po lestvici ocene draženja kože) s transdermalnimi obliži Exelon 9, 5 mg/ 24 h zelo blaga (21, 8%), blaga (12, 5%) ali zmerna (6, 5%) rdečina ali zelo blago (11, 9%), blago (7, 3%) ali zmerno (5, 0%) srbenje.
The most commonly observed severe symptoms with Exelon 9.5 mg/ 24 h transdermal patches were pruritus (1.7%) and erythema (1.1%).
Najpogosteje opažena huda simptoma s transdermalnimi obliži Exelon 9, 5 mg/ 24 h sta bila srbenje (1, 7%) in rdečina (1, 1%).
Most skin reactions were limited to the application site and resulted in discontinuation in only 2.4% of the patients in the Exelon 9.5 mg/ 24 h transdermal patch group.
Zaradi kožnih reakcij je zdravljenje prekinilo le 2, 4% bolnikov v skupini s transdermalnimi obliži Exelon 9, 5 mg/ 24 h.
4.9 Overdose
66 4. 9 Preveliko odmerjanje
Symptoms Most cases of accidental overdose of oral rivastigmine have not been associated with any clinical signs or symptoms and almost all of the patients concerned continued rivastigmine treatment.
Simptomi Večina primerov nenamernega prevelikega odmerjanja peroralnega rivastigmina ni bila povezana z nikakršnimi kliničnimi znaki ali simptomi in skoraj vsi ti bolniki so nadaljevali zdravljenje z rivastigminom.
There are currently no data on overdose with Exelon transdermal patches.
O prekomernem odmerjanju s transdermalnimi obliži Exelon trenutno ni podatkov.
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 Exelon transdermal patches should be removed immediately and no further transdermal patch should be applied for the next 24 hours.
Bolniku se v naslednjih 24 urah ne sme namestiti novih transdermalnih obližev.
Thus, rivastigmine may have an ameliorative effect on
Rivastigmin je zaviralec acetilholinesteraze in butirilholinesteraze karbamatne vrste, za katerega velja, da izboljšuje holinergični živčni prenos tako, da upočasnjuje razgradnjo acetilholina, ki ga sproščajo funkcionalno intaktni holinergični nevroni.
61 cholinergic-mediated cognitive deficits in dementia associated with Alzheimer’ s disease.
Zato bi lahko rivastigmin izboljšal stanje holinergično posredovanega upada kognitivnih funkcij pri demenci, povezani z Alzheimerjevo boleznijo.
In patients with Alzheimer’ s disease, inhibition of AChE in CSF by oral rivastigmine was dose-dependent up to 6 mg given twice daily, the highest dose tested.
Pri bolnikih z Alzheimerjevo boleznijo je bila stopnja inhibicije AChE v CSF s peroralnim rivastigminom odvisna od odmerka do največjega preizkušanega odmerka 6 mg, danega dvakrat na dan.
Inhibition of butyrylcholinesterase activity in CSF of 14 Alzheimer patients treated by oral rivastigmine was similar to that of AChE.
Inhibicija aktivnosti butirilholinesteraze v CSF pri 14 bolnikih z Alzheimerjevo boleznijo, zdravljenih s peroralnim rivastigminom, je bila podobna kot inhibicija AChE.
Clinical studies in Alzheimer’ s dementia The efficacy of Exelon 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.
Klinične študije pri Alzheimerjevi demenci Učinkovitost transdermalnih obližev Exelon pri bolnikih z Alzheimerjevo demenco so dokazali v 24- tedenski dvojno slepi osnovni študiji in njenem odprtem podaljšku.
Patients involved in this study had an MMSE (Mini-Mental State Examination) score of 10– 20.
Bolniki, vključeni v to študijo, so imeli rezultat MMSE (Mini- Mental State Examination – kratek preizkus spoznavnih sposobnosti) med 10 in 20.
Efficacy was established by the use of independent, domain-specific assessment tools which were applied at regular intervals during the 24-week treatment period.
Učinkovitost so ugotavljali z uporabo neodvisnih, področno specifičnih metod ocenjevanja, ki so jih izvajali v rednih presledkih med 24- tedenskim obdobjem zdravljenja.
The 24-week results for the three assessment tools are summarised in Table 2.
Med njimi so ADAS- Cog (merilo za kognicijo, ki temelji na storilnosti), ADCS- CGIC (vsestranska globalna ocena bolnika, ki jo poda zdravnik ob upoštevanju negovalčeve ocene) in ADCS- ADL (negovalčeva ocena vsakodnevnih aktivnosti, med drugim osebne higiene, hranjenja, oblačenja, gospodinjskih opravil, na primer nakupovanja, ohranjanja zmožnosti orientacije v okolju kot tudi ukvarjanja z denarnimi zadevami).
Table 2
24- tedenski rezultati teh treh metod ocenjevanja so zbrani v preglednici 2.
Exelon Exelon
67 Preglednica 2
12 mg/ day
Exelon kapsule 12 mg/ dan
ITT-LOCF population ADAS-Cog
transdermalni obliži 9, 5 mg/ 24 h Skupina ITT- LOCF ADAS- Cog
Mean baseline ± SD Mean change at week 24 ± SD p-value versus placebo ADCS-CGIC
Povprečje ob izhodišču ± SD Povprečna sprememba po 24 tednih ± SD
Mean score ± SD p-value versus placebo ADCS-ADL
Povprečna ocena ± SD Vrednost p proti placebu ADCS- ADL
Mean baseline ± SD Mean change at week 24 ± SD p-value versus placebo * p≤ 0.05 versus placebo
Povprečje ob izhodišču ± SD Povprečna sprememba po 24 tednih ± SD
Intent-To-Treat; LOCF:
49, 2 ± 16, 0 - 2, 3 ± 9, 4
Negative ADAS-Cog changes indicate improvement.
Negativna sprememba na ADAS- Cog lestvici pomeni izboljšanje.
Positive ADCS-ADL changes indicate improvement.
Pozitivna sprememba na ADCS- ADL lestvici pomeni izboljšanje.
ADCS-CGIC scores < 4 indicate improvement.
Ocena < 4 na lestvici ADCS- CGIC pomeni izboljšanje.
The results for clinically relevant responders from the 24-week study are provided in Table 3.
Preglednica 3
transdermal patches
Exelon kapsule
mg/ 24 h
transdermalni obliži 9, 5 mg/ 24 h
ITT-LOCF population At least 4 points improvement on ADAS-Cog with no worsening on ADCS- CGIC and ADCS-ADL
Skupina ITT- LOCF Izboljšanje na ADAS- Cog za vsaj 4 točke brez poslabšanja pri ADCS- CGIC in ADCS - ADL
N
N = 251 17, 4
= 251 17.4
N
*p < 0.05 versus placebo
* p < 0, 05 proti placebu
As suggested by compartmental modelling, 9.5 mg/ 24 h transdermal patches exhibited exposure similar to that provided by an oral dose of 12 mg/ day.
Kot nakazuje modeliranje kompartmentov, je izpostavljenost zdravilu iz transdermalnega obliža 9, 5 mg/ 24 h podobna kot pri peroralnem odmerku približno 12 mg/ dan.
5.2 Pharmacokinetic properties
68 5. 2 Farmakokinetične lastnosti
Absorption Absorption of rivastigmine from Exelon transdermal patches is slow.
Absorpcija Rivastigmin se iz transdermalnih obližev Exelon absorbira počasi.
After the first dose, detectable plasma concentrations are observed after a lag time of 0.5-1 hour.
Po prvem odmerjanju doseže merljive koncentracije v plazmi po odzivnem času 0, 5- 1 ure.
After the peak, plasma concentrations slowly decrease over the remainder of the 24-hour period of application.
Cmax doseže po 10- 16 urah, nato koncentracija v plazmi počasi upada v preostalem času 24- urnega obdobja aplikacije.
Although less pronounced than with the oral formulation, exposure to rivastigmine (Cmax and AUC) increased over-proportionally by a factor of 2.6 when escalating from 4.6 mg/ 24 h to 9.5 mg/ 24 h.
Čeprav manj izrazito kot pri peroralnem odmerjanju, se je pri stopnjevanju z odmerka 4, 6 mg/ 24 h na 9, 5 mg/ 24 h izpostavljenost rivastigminu (Cmax in AUC) nesorazmerno povečala za faktor 2, 6.
The fluctuation index (FI), a measure of the relative difference between peak and trough concentrations((Cmax-Cmin)/ Cavg), was 0.58 for Exelon 4.6 mg/ 24 h transdermal patches and 0.77 for Exelon 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)).
Fluktuacijska indeksa (FI), ki izražata relativno razliko med najvišjimi in najnižjimi koncentracijami ((Cmax- Cmin) / Cavg; pri tem je Cavg povprečna koncentracija v obdobju odmerjanja), sta bila 0, 58 pri transdermalnih obližih Exelon 4, 6 mg/ 24 h in 0, 77 pri transdermalnih obližih Exelon 9. 5 mg/ 24 h, kar kaže na veliko manjšo fluktuacijo od najnižjih do najvišjih koncentracij kot pri peroralnem odmerjanju (FI = 3, 96 za odmerjanje 6 mg/ dan in 4, 15 za odmerjanje 12 mg/ dan).
The dose of rivastigmine released from the transdermal patch over 24 hours (mg/ 24 h) cannot be directly equated to the amount (mg) of rivastigmine contained in a capsule with respect to plasma concentration produced over 24 hours.
Glede koncentracij, ki jih rivastigmin dosega v plazmi v obdobju 24 ur, odmerka rivastigmina, ki se v 24 urah sprosti iz transdermalnega obliža (v mg/ 24 h), ni mogoče neposredno enačiti s količino rivastigmina (v mg), ki jo vsebuje kapsula.
The single-dose inter-subject variability in rivastigmine pharmacokinetic parameters (normalised to dose/ kg bodyweight) was 43% (Cmax) and 49% (AUC0-24h) after transdermal administration versus 74% and 103%, respectively, after the oral form.
Pri enkratnem odmerjanju je bila interindividualna variabilnost farmakokinetičnih parametrov rivastigmina (normalizirana na odmerek/ kg telesne mase) 43% za Cmax in 49% za AUC0- 24h pri transdermalni aplikaciji v primerjavi s 74% za Cmax in 103% za AUC0- 24h pri uporabi peroralne oblike.
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.
Interindividualna variabilnost v študiji dinamičnega ravnovesja pri bolnikih z Alzheimerjevo demenco je bila največ 45% za Cmax in 43% za AUC0- 24h po uporabi transdermalnega obliža v primerjavi z 71% za Cmax in 73% za AUC0- 24h po aplikaciji peroralne oblike.
A relationship between active substance exposure at steady state (rivastigmine and metabolite NAP226-90) and bodyweight was observed in Alzheimer’ s dementia patients.
Pri bolnikih z Alzheimerjevo demenco so opazovali razmerje med telesno maso in izpostavljenostjo zdravilni učinkovini (rivastigminu in presnovku NAP226- 90) v stanju dinamičnega ravnovesja.
The effect of bodyweight on active substance exposure suggests special attention to patients with very low body weight during up-titration (see section 4.4).
Zaradi vpliva telesne mase na izpostavljenost zdravilni učinkovini je potrebna posebna pozornost pri postopnem zviševanju odmerka bolnikom z zelo majhno telesno maso (glejte poglavje 4. 4).
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.
Izpostavljenost (AUC∞) rivastigminu (in presnovku NAP266- 90) je bila največja pri aplikaciji transdermalnega obliža na zgornji del hrbta, prsi ali nadlaket ter približno 20- 30% manjša pri aplikaciji na trebuh ali stegno.
There was no relevant accumulation of rivastigmine or the metabolite NAP226-90 in plasma in patients with Alzheimer’ s disease, except that plasma levels were higher on the second day of transdermal patch therapy than on the first.
Do pomembnega kopičenja rivastigmina ali presnovka NAP226- 90 v plazmi bolnikov z Alzheimerjevo boleznijo ni prišlo, razen koncentracij v plazmi, ki so bile drugi dan zdravljenja s transdermalnim obližem višje kot prvi dan.
Distribution Rivastigmine is weakly bound to plasma proteins (approximately 40%).
Porazdelitev Rivastigmin se šibko veže na beljakovine v plazmi (približno 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.
Dobro prehaja skozi krvnomožgansko pregrado in ima navidezni volumen porazdelitve v območju 1, 8- 2, 7 l/ kg.
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.
Presnova Rivastigmin se hitro in obsežno presnavlja z navideznim razpolovnim časom izločanja iz plazme približno 3, 4 ure po odstranitvi transdermalnega obliža.
Elimination was absorption rate limited (flip-flop kinetics), which explains the longer t½ after transdermal patch (3.4 h) versus oral or intravenous administrations (1.4 to 1.7 h).
Izločanje je omejeno s hitrostjo absorpcije (flip - flop učinek), kar pojasnjuje daljši t½ pri uporabi transdermalnih obližev (3, 4 ure) v primerjavi s
Metabolism is primarily via cholinesterase-mediated hydrolysis to the metabolite NAP226-90.
69 peroralnim ali intravenskim odmerjanjem (1, 4 do 1, 7 ure).
In vitro, this metabolite shows minimal inhibition of acetylcholinesterase (< 10%).
Presnova poteka predvsem s hidrolizo, ki jo katalizira holinesteraza, do presnovka NAP226- 90.
Total plasma clearance of rivastigmine was approximately 130 litres/ h after a 0.2 mg intravenous dose and decreased to 70 litres/ h after a 2.7 mg intravenous dose, which is consistent with the non-linear, over-proportional pharmacokinetics of rivastigmine due to saturation of its elimination.
Celotni plazemski očistek rivastigmina je bil po intravenskem odmerku 0, 2 mg približno 130 l/ h, po intravenskem odmerku 2, 7 mg pa se je zmanjšal na 70 l/ h, kar je v skladu z nelinerano nesorazmerno farmakokinetiko rivastigmina zaradi saturacije njegovega izločanja.
The metabolite-to-parent AUC∞ ratio was around 0.7 after transdermal patch versus 3.5 after oral administration, indicating that much less metabolism occurred after dermal compared to oral treatment.
Razmerje med AUC∞ presnovka in izhodne učinkovine je bilo približno 0, 7 pri uporabi transdermalnega obliža v primerjavi s 3, 5 po peroralni aplikaciji zdravila, kar nakazuje, da je bil metabolizem precej manj obsežen po dermalnem zdravljenju v primerjavi s peroralnim.
Less NAP226-90 is formed following application of the transdermal patch, presumably because of the lack of presystemic (hepatic first pass) metabolism, in contrast to oral administration.
Po aplikaciji transdermalnega obliža je nastajalo manj NAP226- 90, verjetno zaradi odsotnosti predsistemske presnove (učinka prvega prehoda skozi jetra) za razliko od peroralne aplikacije.
Elimination Unchanged rivastigmine is found in trace amounts in the urine; renal excretion of the metabolites is the major route of elimination after transdermal patch administration.
Poglavitna pot izločanja po aplikaciji s transdermalnim obližem je izločanje skozi ledvice.
Following administration of oral 14C- rivastigmine, renal elimination was rapid and essentially complete (> 90%) within 24 hours.
Po zaužitju rivastigmina, označenega s 14C, je bilo ledvično izločanje hitro, saj se je dejansko ves (> 90%) izločil v 24 urah.
Less than 1% of the administered dose is excreted in the faeces.
Manj kot 1% apliciranega odmerka se izloči z blatom.
Elderly subjects Age had no impact on the exposure to rivastigmine in Alzheimer’ s disease patients treated with Exelon transdermal patches.
Starejše osebe Pri bolnikih z Alzheimerjevo boleznijo, ki so jih zdravili s transdermalnimi obliži Exelon, starost ni vplivala na izpostavljenost rivastigminu.
Subjects with hepatic impairment No study was conducted with Exelon transdermal patches in subjects with hepatic impairment.
Osebe z okvaro jeter Pri osebah z okvaro jeter niso opravili nobene študije s transdermalnimi obliži Exelon.
Subjects with renal impairment No study was conducted with Exelon transdermal patches in subjects with renal impairment.
Osebe z okvaro ledvic Pri osebah z okvaro ledvic niso opravili nobene študije s transdermalnimi obliži Exelon.
64 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.
V standardni bateriji testov in vitro in in vivo rivastigmin ni bil mutagen, razen v testu kromosomskih aberacij v človeških perifernih levkocitih v odmerku, ki je 104- krat presegal dotedanjo klinično izpostavljenost.
In some other dermal toxicity studies, a mild irritant effect on the skin of laboratory animals, including controls, was observed.
70 kožo so opazili blag dražilen učinek na kožo laboratorijskih živali, vključno s kontrolnimi živalmi.
Therefore, the patient/ caregiver should avoid contact with the eyes after handling of the patch (see section 4.4).
Zato se bolniki/ negovalci ne smejo dotikati oči po rokovanju z obližem (glejte poglavje 4. 4).
Backing layer:
Krovna plast:
- polyethylene terephthalate film, lacquered.
- polietilen tereftalatni film, lakiran
Medicinal product matrix:
Matriks zdravila:
- alpha-tocopherol,
- α- tokoferol
- poly(butylmethacrylate, methyl-methacrylate),
- polimer (butilmetakrilat, metilmetakrilat)
- acrylic copolymer.
- akrilni kopolimer
Adhesive matrix:
Adhezivni matriks zdravila:
- silicone oil,
- silikonsko olje
Release liner:
Opna za nadziranje sproščanja:
- polyester film, fluoropolymer-coated.
- poliestrski film obložen s fluoro- polimerom.
65 6.5 Nature and contents of container
6. 5 Vrsta ovojnine in vsebina
Primary packaging material Each child-resistant sachet is made of a paper/ polyester/ aluminium/ polyacrylonitrile multilaminated material.
Material za primarno ovojnino Vsaka za otroke varna vrečka je izdelana iz več plasti in sicer iz papirja/ poliestra/ aluminija/ poliakrilonitrila.
Secondary packaging material The sachets are packed in a carton.
Material za sekundarno ovojnino Vrečke so zložene v škatli.
Available in packs containing 7 or 30 sachets and in multipacks containing 60 (2x 30) or 90 (3x 30) sachets.
Na voljo so v pakiranju, ki vsebuje 7 ali 30 vrečk, in v skupnem pakiranju, ki vsebuje 60 (2x 30) ali 90 (3x 30) vrečk.
Exelon 9.5 mg/ 24 h transdermal patch
Exelon 9, 5 mg/ 24 h transdermalni obliž
Each transdermal patch releases 9.5 mg of rivastigmine per 24 hours.
Vsak transdermalni obliž sprosti 9, 5 mg rivastigmina na 24 ur.