qanastek/EMEA-V3 huggingface dataset:
Switching from capsules or oral solution to transdermal patches Based on comparable exposure between oral and transdermal rivastigmine (see section 5.2), patients 57 treated with Exelon capsules or oral solution can be switched to Exelon 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 Exelon jew soluzzjoni orali jistgħu jinqalbu għall- garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Exelon 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.
If the oral dose of 9 mg/ day has not been stable and well tolerated, a switch to 4.6 mg/ 24 h transdermal patches is recommended. • A patient on a dose of 12 mg/ day oral rivastigmine can be switched to 9.5 mg/ 24 h transdermal patches.
Jekk id - doża orali ta ’ 9 mg/ jum ma tkunx ġiet stabbli u jifilħu sew għaliha, huwa rakkomandat li jinqalbu għal 4. 6 mg/ 24 siegħa garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda. • Pazjent fuq doża ta ’ 12 mg/ 24 siegħa rivastigmine orali jistgħu jinqalbu għal 9. 5 mg/ 24 siegħa garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda.
After switching to 4.6 mg/ 24 h transdermal patches, provided these are well tolerated after a minimum of four weeks of treatment, the dose of 4.6 mg/ 24 h should be increased to 9.5 mg/ 24 h, which is the recommended effective dose.
Wara li jinqalbu għal 4. 6 mg/ 24 siegħa garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda, sakemm dawn ikunu jifilħu sew għalihom għal mill- anqas erba ’ ġimgħat ta ’ kura, id- doża ta ’ 4. 6 mg/ 24 siegħa għandha tiżdied għal 9. 5 mg/ 24 siegħa, li hija d- doża effettiva rakkomandata.
It is recommended to apply the first transdermal patch on the day following the last oral dose.
Huwa rrikkmandat li l- ewwel garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda titwaħħal fil- jum ta ’ wara l- aħħar doża orali.
Method of administration Transdermal patches should be applied once a day to clean, dry, hairless, intact healthy skin on the upper or lower back, upper arm or chest, in a place which will not be rubbed by tight clothing.
Kif jingħata Il- garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda għandhom jitwaħħlu darba kuljum ma ’ ġilda li tkun nadifa, xotta, mingħajr xagħar, intatta u b’ saħħitha fuq in- naħa ta ’ fuq jew t’ isfel tad- dahar, parti ta ’ fuq tad- driegħ jew sider, f’ post fejn ma jkunx jgħorok ma ’ ħwejjeġ issikkati.
It is not recommended to apply the transdermal patch to the thigh or to the abdomen due to decreased bioavailability of rivastigmine observed when the transdermal patch is applied to these areas of the body.
Mhux irrikkmandat li twaħħal il- garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda mal- koxxa jew l- addome minħabba t - tnaqqis fil- biodisponibilità ta ’ rivastigmine li deher meta l- garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda twaħħlet f’ dawn il- partijiet tal- ġisem.
The transdermal patch should not be applied to skin that is red, irritated or cut.
Il- garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda m’ għandhiex titwaħħal ma ’ ġilda li hi ħamra, irritata jew li jkun fiha xi qata ’.
Reapplication to the exact same skin location within 14 days should be avoided to minimise the potential risk of skin irritation.
It- twaħħil fl- istess parti tal- ġisem fi żmien 14- il jum għandu jiġi evitat sabiex jitnaqqas ir- riskju li jista ’ jkun hemm ta ’ irritazzjoni tal- ġilda.
The transdermal patch should be pressed down firmly until the edges stick well.
Il- garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda għandha tingħafas l- isfel sew sakemm it- truf jeħlu sew.
It can be used in everyday situations, including bathing and during hot weather.
Tista’ tintuża f’ sitwazzjonijiet ta ’ kuljum, inklużi ħasil fil- banju u meta tkun is- sħana.
The transdermal patch should be replaced by a new one after 24 hours.
Il- garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda għandha tinbidel ma ’ waħda ġdida wara 24 siegħa.
Only one transdermal patch should be worn at a time.
Għandha tintlibes garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda waħda biss f’ kull ħin.
Patients and caregivers should be instructed accordingly.
Pazjenti u dawk li jkun qed jieħdu ħsieb il- kura tas- saħħa għandhom jingħataw istruzzjonijiet kif jixraq.
No dose adjustment is necessary for patients with renal impairment (see section 5.2).
M’ hemmx bżonn ta ’ aġġustar tad- doża għall- pazjenti b’ indeboliment renali (ara sezzjoni 5. 2).
Children and adolescents (age below 18 years):
Tfal u adolexxenti (età taħt it- 18- il sena):
Rivastigmine is not recommended for use in children and adolescents.
Rivastigmine mhux irrakkomandat għall- użu fit- tfal u adolexxenti.
Hypersensitivity to the active substance, to other carbamate derivatives or to any of the excipients used in the formulation.
Sensittività eċċessiva għas- sustanza attiva, għal derivati tat- tip carbamate jew għal xi sustanza oħra mhux attiva użata fil- formulazzjoni.
4.4 Special warnings and precautions for use
63 4. 4 Twissijiet speċjali u prekawzjonijiet għall- użu
The incidence and severity of adverse reactions generally increase with increasing doses, particularly at dose changes.
L- inċidenza u s- severità tar- reazzjonjjiet avversi ġeneralment jiżdiedu b’ dożi aktar għoljin, l- aktar meta jkun hemm tibdil fid- dożi.
If treatment is interrupted for more than several days, it should be re-initiated with 4.6 mg/ 24 h.
Jekk il- kura tiġi mwaqqfa għal aktar minn bosta jiem, din għandha terġa ’ tiġi mibdija b’ 4. 6 mg/ 24 siegħa.
Gastrointestinal disorders such as nausea and vomiting are dose-related, and may occur when initiating treatment and/ or increasing the dose (see section 4.8).
Disturbi gastro- intestinali bħal tqalligħ u rimettar huma relatati mad- doża, u jistgħu jseħħu meta tkun qed tinbeda l- kura u/ jew tkun qed tiġi miżjuda d- doża (ara sezzjoni 4. 8).
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 Exelon transdermal patches.
Il- piż tal- pazjent għandu jkun monitorat waqt it- terapija bil- garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Exelon.
58 Care must be taken when prescribing Exelon 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 Exelon: • 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.
Rivastigmine may exacerbate or induce extrapyramidal symptoms.
Rivastigmine jista ’ jaggrava jew jikkawża sintomi ekstrapiramidali.
Contact with the eyes should be avoided after handling Exelon 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 Exelon (ara sezzjoni 5. 3).
Special populations: • Patients with body weight below 50 kg may experience more adverse reactions and may be more likely to discontinue due to adverse reactions. • Hepatic impairment:
Popolazzjonijiet speċjali: • Pazjenti li jkollhom piż taħt il- 50 kg jista ’ jkollhom aktar reazzjonijiet avversi u hemm aktar ċans li jwaqqfuh minħabba r- reazzjonijiet avversi. • Indeboliment epatiku:
Patients with clinically significant hepatic impairment might experience more adverse reactions (see section 5.2).
Pazjenti b’ indeboliment epatiku klinikament sinifikanti jista ’ jkollhom aktar reazzjonijiet avversi (ara sezzjoni 5. 2).
No specific interaction studies have been conducted with Exelon transdermal patches.
Ma sarux studji speċifiċi dwar interazzjonijiet bil- garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Exelon.
No pharmacokinetic interaction was observed between oral rivastigmine and digoxin, warfarin, diazepam or fluoxetine in studies in healthy volunteers.
Fi studji fuq voluntiera b’ saħħithom, ma dehret l- ebda interazzjoni farmakokinetika bejn rivastigmine u digoxin, warfarin, diazepam, jew fluoxetine.
The increase in prothrombin time induced by warfarin is not affected by administration of oral rivastigmine.
Iż- żieda fil- ħin tal- protrombin li hija kkaġunata minn warfarin mhix affettwata meta jingħata rivastigmine.
No untoward effects on cardiac conduction were observed following concomitant administration of digoxin and oral rivastigmine.
Ma ġew osservati l- ebda effetti ħżiena fuq il - konduttività kardijaka, meta ngħataw digoxin u rivastigmine fl- istess ħin.
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 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.
According to its metabolism, metabolic interactions with other medicinal products appear unlikely, although rivastigmine may inhibit the butyrylcholinesterase mediated metabolism of other substances.
Minħabba l- metaboliżmu tiegħu, mhux mistenni li jkun hemm interazzjonijiet metaboliċi ma ’ prodotti mediċinali oħra, għalkemm rivastigmine jista ’ jinibixxi l- metaboliżmu medjat minn butyrylcholinesterase ta ’ sustanzi oħrajn.
No clinical data on exposed pregnancies are available.
Għal rivostigmine m’ hemmx tagħrif kliniku dwar l- użu waqt it- tqala.
59 4.7 Effects on ability to drive and use machines
4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
Furthermore, rivastigmine may induce syncope or delirium.
Barra dan, rivastigmine jista ’ jikkaġuna sinkope jew thewdin.
Therefore, in patients with dementia treated with rivastigmine, the ability to continue driving or operating complex machines should be routinely evaluated by the treating physician.
Għalhekk, f’ pazjenti b’ dimenzja li jkunu qed jiġu kkurati b’ rivastigmine, il- ħila li jkomplu jsuqu jew li jħaddmu magni kumplessi għandha tiġi evalwata bħala rutina mit- tabib li jkun qed jagħtihom il- kura.
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).
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 Exelon (50. 5% b’ garżi Exelon li jipprovdu mediċina li tgħaddi minn ġol - ġilda 9. 5 mg/ 24 siegħa vs 63. 3% bil- kapsuli Exelon; 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 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).
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’ Exelon garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda 9. 5 mg/ 24 siegħa meta mqabbla mal- grupp bil- kapsula Exelon (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 Exelon 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 Exelon u doża mmirata ta ’ 9. 5 mg/ 24 siegħa (4. 6 mg/ 24 siegħa miżjuda għal 9. 5 mg/ 24 siegħa).
Adverse reactions are ranked under headings of frequency, the most frequent first, using the following convention:
Reazzjonijiet avversi huma kklassifikati skond il- frekwenza, bl- aktar frekwenti l- ewwel, u billi tintuża l- konvenzjoni li ġejja:
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).
Komuni ħafna (≥1/ 10); komuni (≥1/ 100, < 1/ 10); mhux komuni (≥1/ 1, 000, < 1/ 100); rari (≥1/ 10, 000, < 1/ 1, 000); rari ħafna (< 1/ 10, 000) u mhux magħruf (ma tistax tittieħed stima mid- data disponibbli).
Urinary tract infection
Infezzjoni fis- sistema ta ’ l- awrina
Psychiatric disorders
65 Disturbi psikjatriċi
Anxiety, depression, delirium
Ansjetà, dipressjoni, thewdin
Headache, syncope Extrapyramidal symptoms
Uġigħ ta ’ ras, sinkope Sintomi ekstrapiramidali
Cardiac disorders
Mard kardijaku
Nausea, vomiting, diarrhoea, dyspepsia, abdominal pain Gastric ulcer
Dardir, rimettar, dijarrea, dispepsja, uġigħ addominali Ulċeri fl- istonku
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
Reazzjonijiet tal- ġilda mnejn tiġi applikata (eż. ħmura fejn tiġi applikata, ħakk fejn tiġi applikata, edema fejn tiġi applikata, dermatite fejn tiġi applikata, irritazzjoni fejn tiġi applikata), kundizzjonijiet asteniċi (eż. għeja, astenja), deni, telf tal- piż
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
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 Exelon 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 Exelon 9. 5 mg/ 24 siegħa milli bi plaċebo.
The following adverse reactions have only been observed with Exelon capsules and oral solution and not in clinical studies with Exelon 9.5 mg/ 24 h transdermal patches:
Ir- reazzjonijiet avversi li ġejjin dehru biss bil- kapsuli u soluzzjoni orali Exelon u mhux fl- isutdji kliniċi b’ garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda 9. 5 mg/ 24 siegħa:
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).
Sturdament (komuni ħafna); aġitazzjoni, ngħas, nuqqas ta ’ saħħa, tregħid, konfużjoni, żieda fl- għaraq (komuni); nuqqas ta ’ rqad, waqa ’ aċċidentali, testijiet tal- funzjoni tal- fwied għoljin (mhux komuni), aċċessjonijiet, ulċeri fid- duwodenu, anġina pektoris (rari); arritmija kardijaka (eż. imblukkar atrijo- ventrikolari, fibrillazzjoni atrijali u takikardija), pressjoni għolja, pankrejatite, emorraġġija gastrointestinali, alluċinazzjoni (rari ħafna); u xi każijiet ta ’ rimettar sever kienu assoċjati ma tiċrit fl- esofagu (mhux magħruf).
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.
Irritazzjoni tal- ġilda Fi provi kliniċi r- reazzjonijiet tal- ġilda kienu mkejjla ma ’ kull żjara permezz ta ’ skala tar- rata ta ’ irritazzjoni tal- ġilda li stmat il- grad ta ’ ħmura, edema, qxur, qsim, ħakk u uġigħ/ tingiż/ ħruq fejn ġiet applikata.
The most commonly observed symptom was erythema which disappeared within 24 hours in the vast majority of patients.
L- aktar sintomu li deher b’ mod komuni kienet il- ħmura li għebet fi żmien 24 siegħa f’ maġġoranza wiesa ’ tal- pazjenti.
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.
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 Exelon 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 Exelon 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 Exelon 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 Exelon 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.
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.
Sintomi Il- maġġoranza tal- każijiet aċċidentali ta ’ doża eċċessiva ta ’ rivastigmine orali ma kienux assoċjati ma ’ sinjali jew sintomi kliniċi, u kważi l- pazjenti kollha li kienu nvoluti komplew il- kura b’ rivastigmine.
Where symptoms have occurred, they have included nausea, vomiting and diarrhoea, hypertension or hallucinations.
Fejn kien hemm is- sintomi, dawn kienu jinkludu dardir, rimettar u dijarea, pressjoni għolja jew alluċinazzjonijiet.
Due to the known vagotonic effect of cholinesterase inhibitors on heart rate, bradycardia and/ or syncope may also occur.
Minħabba l- effett vagotoniku magħruf li għandhom l- inibituri ta ’ cholinesterase fuq ir- rata ta ’ tħabbit tal- qalb, dawn jistgħu jirriżultaw f’ bradikardija u/ jew sinkope.
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
There are currently no data on overdose with Exelon transdermal patches.
S’ issa għad m’ hemmx tagħrif dwar doża eċċessiva bil- garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Exelon.
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.
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 Exelon 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.
Symptomatic treatment for other adverse reactions should be given as necessary.
Kura tas- sintomi għal reazzjonijiet avversi oħrajn għandha tingħata hekk kif ikun hemm bżonn.
Pharmacotherapeutic group: anticholinesterases, ATC code:
Kategorija farmakoterapewtika: anticholinesterases; Kodiċi ATC:
Thus, rivastigmine may have an ameliorative effect on
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.
61 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.
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.
F’ pazjenti li jbatu bil- marda ta ’ Alzheimer, l- inibizzjoni ta ’ AChE fis- CSF b’ rivastigmine orali kienet tiddependi fuq id- doża, meta d - doża kienet sa 6 mg darbtejn kuljum, li hija l- ogħla doża ttestjata.
Inhibition of butyrylcholinesterase activity in CSF of 14 Alzheimer patients treated by oral rivastigmine was similar to that of AChE.
L- inibizzjoni ta ’ l- attività tat- tip butyrylcholinesterase fis- CSF ta ’ 14- il pazjent bil- marda ta ’ Alzheimer li kienu kkurati b’ rivastigmine orali kienet simili għal dik ta ’ 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.
Studji Kliniċi f’ dimenzja ta ’ Alzheimer L- effikaċa tal- garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Exelon 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.
Patients involved in this study had an MMSE (Mini-Mental State Examination) score of 10– 20.
Pazjenti li ħadu sehem f’ dan l- istudju kellhom punteġġ MMSE (Eżami Żgħir ta ’ l- Istat Mental) ta ’ 10- 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.
L- effikajċja kienet stabbilita permezz ta ’ għodod indipendenti li jevalwaw id - dominju speċifiku li kienu applikati f’ intervalli regolari waqt il- perijodu ta ’ 24 ġimgħa ta ’ kura.
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).
Dawn jinkludu ADAS- Cog (kejl ta ’ l- għarfien ibbażata fuq il- ħila) u l- ADCS- CGIC (evalwazzjoni globali 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).
The 24-week results for the three assessment tools are summarised in Table 2.
Ir- riżultati ta ’ 24 ġimgħa mit- tliet għodod ta ’ stima qegħdin imqassra f’ Tabella 2.
transdermal patches
Garżi li jipprovdu
12 mg/ day
Plaċebo
ITT-LOCF population ADAS-Cog
kapsuli mediċina li 12 mg/ jum tgħaddi minn ġol - ġilda Exelon 9. 5 mg/ 24 siegħa Popolazzjoni ITT- LOCF ADAS- Cog
Mean baseline ± SD Mean change at week 24 ± SD p-value versus placebo ADCS-CGIC
Medja mill- linja bażi ± SD Medja tal- bidla f’ ġimgħa 24 ±
27.0 ± 10.3 -0.6 ± 6.4 0.005*1
27. 0 ± 10. 3
27.9 ± 9.4 -0.6 ± 6.2 0.003*1
Valur- p kontra l- plaċebo ADCS- CGIC
28.6 ± 9.9 1.0 ± 6.8
0. 003* 1
Mean score ± SD p-value versus placebo ADCS-ADL
Medja tal- punteġġ ± SD Valur- p kontra l- plaċebo ADCS- ADL
3.9 ± 1.20 0.010*2
3. 9 ± 1. 20 0. 010* 2
3.9 ± 1.25 0.009*2
3. 9 ± 1. 25 0. 009* 2
4.2 ± 1.26
4. 2 ± 1. 26
Mean baseline ± SD Mean change at week 24 ± SD p-value versus placebo * p≤ 0.05 versus placebo
Medja mill- linja bażi ± SD Medja tal- bidla f’ ġimgħa 24 ±
50.1 ± 16.3 -0.1 ± 9.1 0.013*1
49. 2 ± 16. 0
49.3 ± 15.8 49.2 ± 16.0 -0.5 ± 9.5 -2.3 ± 9.4 0.039*1
Valur- p kontra l- plaċebo * p≤0. 05 versus plaċebo
Intent-To-Treat; LOCF:
Intenzjoni- Li- Tikkura; LOCF:
Last Observation Carried Forward 1 Based on ANCOVA with treatment and country as factors and baseline value as a covariate.
L- Aħħar Osservazzjoni li Tmexxiet ’ L Quddiem 1 Ibbażat fuq ANCOVA bil- kura u l- pajjiż bħala fatturi u valur fil- linja bażi bħala ko- varjant.
Negative ADAS-Cog changes indicate improvement.
Bidliet negattivi fil- ADAS- Cog jindikaw titjib.
Positive ADCS-ADL changes indicate improvement.
Bidliet fl- ADCS- ADL pożittivi jindikaw titjib.
2 Based on CMH test (van Elteren test) blocking for country.
2 Ibbażat fuq l- eżami CMH (eżami van Elteren) li jimblokka għall- pajjiż.
ADCS-CGIC scores < 4 indicate improvement.
Punteġġi ADCS- CGIC ta ’ < 4 jindikaw titjib.
The results for clinically relevant responders from the 24-week study are provided in Table 3.
Ir- riżultati għal dawk li wrew rispons klinikament rilevanti mill- istudju ta ’ 24 ġimgħa qed jingħataw f’ Tabella 3.
Clinically relevant improvement was defined a priori as at least 4-point improvement on the ADAS- Cog, no worsening on the ADCS-CGIC, and no worsening on the ADCS-ADL.
Titjib klinikament rilevanti kien definit minn qabel bħala titjib ta ’ mill- anqas 4- punti fuq l - ADAS- Cog, l- ADCS- CGIC ma jmurx għall- agħar, u l- ADCS- ADL ma jmurx għall- agħar.
Patients with clinically significant response (%)
Pazjenti b’ rispons klinikament rilevanti (%) Plaċebo Kapsuli Exelon Garżi li 12 mg/ jum jipprovdu mediċina li
Exelon Exelon
tgħaddi minn
Placebo
N = 282
transdermal patches
ġol- ġilda Exelon 9. 5 mg/ 24 siegħa N = 251
capsules
19. 0
9.5
10. 5
0.037*
0. 037 *
*p < 0.05 versus placebo
* p < 0. 05 kontra l- plaċebo
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.
Hekk kif indikat minn mudellar tal- kompartimenti, garżi li jipprovdu mediċina li tgħaddi minn ġol - ġilda 9. 5 mg/ 24 siegħa urew esponiment simili għal dak li jinkiseb b’ doża orali ta ’ 12 mg/ jum.
5.2 Pharmacokinetic properties
68 5. 2 Tagħrif farmakokinetiku
Absorption Absorption of rivastigmine from Exelon transdermal patches is slow.
Assorbiment Rivastigmine huwa assorbit bil- mod mill- garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Exelon.
After the first dose, detectable plasma concentrations are observed after a lag time of 0.5-1 hour.
Wara l- ewwel doża, konċentrazzjonijiet fil- plażma li jistgħu jitkejlu jidhru wara intervall ta ’ 0. 5- siegħa.
Cmax is reached after 10-16 hours.
Cmax jintlaħaq wara 10- 16- il siegħa.
After the peak, plasma concentrations slowly decrease over the remainder of the 24-hour period of application.
Wara li l- ogħla konċentrazzjonijiet fil- plażma jaqaw bil- mod fuq il- bqijja tal- perijodu ta ’ 24 siegħa ta ’ wara li tiġi applikata.
With multiple dosing (such as at steady state), after the previous transdermal patch is replaced with a new one, plasma concentrations initially decrease slowly for about 40 minutes on average, until absorption from the newly applied transdermal patch becomes faster than elimination, and plasma levels begin to rise again to reach a new peak at approximately 8 hours.
B’ ħafna dożi (bħal fil- każ ta ’ stat fiss), wara li l- garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda ta ’ qabel tinbidel ma waħda ġdida, il- konċentrazzjonijiet fil- plażma għall- ewwel jibdew jaqaw bil- mod għal medja ta ’ madwar 40 minuta, sakemm l- assorbiment tal- garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda li tkun ġiet applikata jsir aktar mgħaġġel mir- rata ta ’ tneħħija, u l- livelli fil- plażma jerġgħu jibdew jogħlew mill - ġdid sakemm tintlaħaq quċċata ġdida f’ madwar 8 siegħat.
At steady state, trough levels are approximately 50% of peak levels, in contrast to oral administration, with which concentrations fall off to virtually zero between doses.
Fi stat fiss, il- livelli l- aktar baxxi huma madwar 50 ta ’ l- ogħla livelli, b’ kuntrast ma ’ l- għotja orali, li biha l- konċentrazzjonijiet jiġu tista ’ tgħid fix- xejn bejn id- dożi.
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.
Għalkemm mhux daqs kemm jiġri bil- formulazzjoni orali, l- esponiment għal rivastigmine (Cmax u AUC) żdied b’ mod sproporzjonat b’ fattur ta ’ 2. 6 meta saret iż- żieda minn 4. 6 mg/ 24 siegħa għal 9. 5 mg/ 24 siegħa.
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)).
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 Exelon 4. 6 mg/ 24 siegħa u 0. 77 għal garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Exelon 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 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.
Id- doża ta ’ rivastigmine li tinħeles mill- garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda fuq perijodu ta ’ 24 siegħa (mg/ 24 siegħa) ma tistax tiġi kkalkulata direttament mill- ammont (mg) ta ’ rivastigmine li jkun hemm fil- kapsula mal- konċentrazzjoni fil- plażma li tinkiseb fuq perijodu ta ’ 24 siegħa.
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.
Il- varjabbilità bejn l- individwi b’ doża waħda fil- parametri tal- farmakokinetika ta ’ rivastigmine (normalizzat għad- doża/ kg piż tal- ġisem) kienet 43% (Cmax) u 49% (AUC0- 24h) wara l- użu minn ġol - ġilda kontra 74% u 103%, rispettivament, wara l- forma orali.
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 - għamla orali.
A relationship between active substance exposure at steady state (rivastigmine and metabolite NAP226-90) and bodyweight was observed in Alzheimer’ s dementia patients.
Relazzjoni bejn l- esponiment għas- sustanza attiva fi stat fiss (rivastigmine u l- metabolu NAP226- 90) u l- piż tal- ġisem deher f’ pazjenti bid- dimenzja ta ’ Alzheimer.
Compared to a patient with a body weight of 65 kg, the rivastigmine steady-state concentrations in a patient with a body weight of 35 kg would be approximately doubled, while for a patient with a body weight of 100 kg the concentrations would be approximately halved.
Meta mqabbel ma ’ piż tal- ġisem ta ’ 65 kg, il- konċentrazzjonijiet fi stat fiss ta ’ rivastigmine f’ pazjent b’ piż tal- ġisem ta ’ 35 Kg ikunu bejn wieħed u ieħor irduppjat, fil- waqt li għal pazjenti b’ piż tal- ġisem ta ’ 100 kg il- konċentrazzjonijiet ikunu bejn wieħed u ieħor imnaqqsin bin- nofs.
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).
L- effett tal- piż tal- ġisem fuq l- esponiment għas- sustanza attiva jindikaw li hemm bżonn ta ’ attenzjoni speċjali f’ pazjenti li għandhom piż tal- ġisem baxx ħafna meta tkun qed tiġi miżjuda d- doża (ara sezzjoni 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.
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.
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.
Ma kienx hemm akkumulu rilevanti ta ’ rivastigmine jew il- metabolu NAP266- 90 fil- plażma f’ pazjenti bil- marda ta ’ Alzheimer, ħlief b’ dik meta l- livelli fil- plażma kienu ogħla fit- tieni jum tat- terapija bil - garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda milli fl- ewwel.
Distribution Rivastigmine is weakly bound to plasma proteins (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’ medda ta bejn 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.
69 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.
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).
L - eliminazzjoni kienet limitata mir- rata ta ’ assorbiment (kinetika flip- flop), li tispjega għalhiex it- t½ ikun itwal wara l- garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda (3. 4 h) kontra l- għotjiet orali jew minn ġol- vini (1. 4 sa 1. 7 h).
Metabolism is primarily via cholinesterase-mediated hydrolysis to the metabolite NAP226-90.
Il- metaboliżmu huwa medjat l- aktar permezz ta ’ idroliżi minn cholinesterase għall- metabolu NAP226- 90.
In vitro, this metabolite shows minimal inhibition of acetylcholinesterase (< 10%).
In vitro din is- sustanza turi inibizzjoni minima ta ’ 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 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.
Wara doża minn ġol- vina ta ’ 0. 2 mg it- tneħħija totali mill- plażma ta ’ rivastigmine kienet ta ’ bejn wieħed u ieħor 130 litri/ h, u din naqset għal 70 litri/ h wara doża minn ġol- vini ta ’ 2. 7 mg, li taqbel ma ’ farmakokinetika sproporzjonali, mhux linejari ta ’ rivastigmine minħabba li l- eliminazzjoni tiegħu tkun saturata.
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.
Il- proporzjon AUC∞ tal- metabolu- mal- mediċina oriġinali kien madwar 0. 7 wara garża kontra 3. 5 wara li ngħata mill- ħalq, li jindika li seħħ ħafna anqas metaboliżmu wara kura mill- ġilda meta mqabbla mal - kura orali.
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.
Jifforma anqas NAP226- 90 wara l- applikazzjoni tal- garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda, li jista ’ jkun minħabba li ma jkunx hemm metaboliżmu qabel ma jidħol fis- sistema (first pass epatiku), b’ kuntrast ma ’ l- għotja mill- ħalq.
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.
Tneħħija Traċċi ta ’ rivastigmine mhux mibdul jinsab fl- awrina; it- tneħħija renali, tas- sustanzi fformati bil - metaboliżmu, hija l- mezz ewlieni ta ’ l- eliminazzjoni wara l- użu tal- garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda.
Following administration of oral 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.
Elderly subjects Age had no impact on the exposure to rivastigmine in Alzheimer’ s disease patients treated with Exelon 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 Exelon.
Subjects with hepatic impairment No study was conducted with Exelon 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 Exelon 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.
Wara li jittieħed mill- ħalq, is- Cmax ta ’ rivastigmine kien bejn wieħed u ieħor 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 Exelon 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 Exelon f’ individwi b’ indeboliment renali.
After oral administration, Cmax and AUC of rivastigmine were more than twice as high in Alzheimer patients with moderate renal impairment compared with healthy subjects; however there were no changes in Cmax and AUC of rivastigmine in Alzheimer patients with severe renal impairment.
Wata li jittieħed mill- ħalq, is- Cmax ta ’ rivastigmine kien aktar minn darbtejn ogħla f’ pazjenti bil- marda ta ’ Alzheimer 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 bil- marda ta ’ Alzheimer li kellhom indeboliment renali serju.
Oral and topical repeated-dose toxicity studies in mice, rats, rabbits, dogs and minipigs revealed only effects associated with an exaggerated pharmacological action.
Studji tat- tossiċità bid- doża ripetuta orali u dik mogħtija b’ mod topiku li saru fuq firien, ġrieden, fniek, klieb u minipigs wrew biss effetti assoċjati ma ’ azzjoni farmakoloġika eżaġerata.
No target organ toxicity was observed.
Ma ġiet osservata l - ebda tossiċità ta ’ organi li jintlaqtu.
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.
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.
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.
70 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.
The exposure to rivastigmine and its metabolites was approximately equivalent to human exposure with highest doses of rivastigmine capsules and transdermal patches.
Il- livell ta ’ rivastigmine u l- metaboli tiegħu, li kienu esposti għalih, kienu bejn wieħed u ieħor daqs dawk fil- bniedem bl- ogħla dożi tal- kapsuli rivastigmine u garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda.
In animals, rivastigmine crosses the placenta and is excreted into milk.
Fl- annimali, rivastigmine jaqsam 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 waqt it- tqala ma taw l- ebda indikazzjoni ta ’ potenzjal teratoġeniku minn- naħa ta ’ rivastigmine.
Specific dermal studies in pregnant animals have not been conducted.
Ma sarux studji speċifiċi fuq il- ġilda f’ annimali waqt it- tqala.
Rivastigmine transdermal patches were not phototoxic.
Il- garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda rivastigmine ma kienux fototossiċi.
In some other dermal toxicity studies, a mild irritant effect on the skin of laboratory animals, including controls, was observed.
F’ xi studji dwar it- tossiċità fuq il- ġilda, deher effett ħafif ta ’ irritazzjoni f’ annimali tal- laboratorju, inklużi l - kontroll.
This may indicate a potential for Exelon transdermal patches to induce mild erythema in patients.
Dan jindika li l- garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda Exelon jistgħi jikkawżaw ħmura ħafifa fil- pazjenti.
When administered to rabbit eyes in primary eye irritation studies, rivastigmine caused reddening and swelling of the conjunctiva, corneal opacities and miosis which persisted for 7 days.
Meta ngħata fl- għajnejn tal- fniek fi studji ewlenin dwar l - irritazzjoni fl- għajn, rivastigmin ikkawża ħmura u nefħa tal- konġuntiva, il- kornjea saret opaka u kien hemm mijożi li baqgħet tidher għal 7 ijiem.
Therefore, the patient/ caregiver should avoid contact with the eyes after handling of the patch (see section 4.4).
Għalhekk, il- pazjent/ min jieħu ħsieb il- kura tas- saħħa għandhom jevitaw li jmissu għajnejhom wara li jmissu l- garża (ara sezzjoni 4. 4).
Backing layer:
Saff ta ’ wara:
- polyethylene terephthalate film, lacquered.
- rita tal- polyethylene terephthalate, bil- lakka.
Medicinal product matrix:
Matriċi li jkun fiha l- mediċina:
- alpha-tocopherol,
- alpha- tocopherol,
- poly(butylmethacrylate, methyl-methacrylate),
- poly( butylmethacrylate, methyl- methacrylate),
- acrylic copolymer.
- acrylic copolymer.
Adhesive matrix:
Matriċi li teħel:
- silicone oil,
- silicone oil,
- dimethicone.
- dimethicone.
Release liner:
Saff li jerħi:
- polyester film, fluoropolymer-coated.
- rita ta ’ polyester, miksija bi fluoropolymer.
Keep the transdermal patch in the sachet until use.
Żomm il- garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda fil- qartas sakemm tużha.
65 6.5 Nature and contents of container
6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih
Primary packaging material Each child-resistant sachet is made of a paper/ polyester/ aluminium/ polyacrylonitrile multilaminated material.
L- ewwel materjal tal- pakkett Kull qartas reżistenti għat- tfal huwa magħmul minn materjal b’ ħafna saffi tal - karta/ polyester/ aluminium/ polyacrylonitrile.
One sachet contains one transdermal patch.
Kull qartas fih garża li tipprovdi mediċina li tgħaddi minn ġol- ġilda waħda.
Secondary packaging material The sachets are packed in a carton.
71 It- tieni materjal tal- pakkett Il- qratas ippakkjati f’ kartuna.
Available in packs containing 7 or 30 sachets and in multipacks containing 60 (2x 30) or 90 (3x 30) sachets.
Jiġi f’ pakketti li jkun fihom 7 jew 30 qartas u f’ pakketti b’ ħafna li jkollhom 60 (2x 30) jew 90 (3x 30) qartas.
Used transdermal patches should be folded in half, with the adhesive side inwards, placed in the original sachet and discarded safely and out of the reach and sight of children.
Garżi li jipprovdu mediċina li tgħaddi minn ġol- ġilda użati għandhom jiġu mitwija fi tnejn, bil- parti li teħel fuq in- naħa ta ’ ġewwa, imqiegħedha fil- qartas oriġinali u mormija b’ mod sigur fejn ma jintlaħqux u ma jidhrux mit- tfal.