qanastek/EMEA-V3 huggingface dataset:
Very common (≥ 1/ 10); common (1≥ 100 to < 1/ 10); uncommon (≥ 1/ 1,000 to < 1/ 100); rare (≥ 1/ 10,000 to < 1/ 1,000), very rare (< 1/ 10,000), not known (cannot be estimated from the available data, since no valid estimate can be derived from clinical trials or epidemiological studies).
Komuni ħafna (≥1/ 10); komuni (1≥100 sa < 1/ 10); mhux komuni (≥1/ 1, 000 sa < 1/ 100); rari (≥1/ 10, 000 sa < 1/ 1, 000), rari ħafna (< 1/ 10, 000), mhux magħrufa (ma jistax jiġi stmat mit- tagħrif disponibbli, peress li l- ebda stima valida ma tista ’ tiġi derivata minn provi kliniċi jew studji epidemjoloġiċi).
Entacapone in association with levodopa has been associated with isolated cases of excessive daytime somnolence and sudden sleep onset episodes.
Entacapone flimkien ma ’ levodopa kien assoċjat ma ’ każijiet iżolati ta ’ ngħas matul il- ġurnata eċċessiv u episodji ta ’ attakki ta ’ ngħas f’ daqqa.
Isolated cases of NMS have been reported following the abrupt reduction or discontinuation of entacapone and other dopaminergic treatments.
Każijiet iżolati ta ’ NMS ġew irrappurtati wara t- tnaqqis f’ daqqa jew wara l- waqfien ta ’ entacapone u kura dopaminerġika oħra.
Isolated cases of rhabdomyolysis have been reported.
8 Kienu rrappurtati każijiet iżolati ta ’ rabdomijolisi.
The following laboratory abnormalities have been reported with levodopa/ carbidopa treatment and should, therefore, be acknowledged when treating patients with Stalevo:
L- anormalitajiet tal- laboratorju li ġejjin ġew irrappurtati b’ kura b’ levodopa/ carbidopa u għalhekk għandhom jittieħdu f’ konsiderazzjoni meta pazjenti jiġu kkurat b’ Stalevo:
Commonly, levels of blood urea nitrogen, creatinine, and uric acid are lower during administration of levodopa/ carbidopa than with levodopa alone.
Ħafna drabi, livelli tan- nitroġenu, krejatinina, u uric acid fid- demm huma aktar baxxi waqt l- għotja ta ’ levodopa/ carbidopa milli b’ levodopa waħdu.
Transient abnormalities include elevated values of blood urea, AST (SGOT), ALT (SGPT), LDH, bilirubin, and alkaline phosphatase.
Anormalitajiet temporanji jinkludu valuri elevati ta ’ urea, AST (SGOT), ALT (SGPT), LDH, bilirubin, u alkaline phosphatase fid- demm.
8 Decreased haemoglobin, haematocrit, elevated serum glucose and white blood cells, bacteria and blood in the urine have been reported.
Ġew irrappurtati tnaqqis fl- emoglobina u fl- ematokrita, żjieda tal- glukosju fis- serum u taċ- ċelluli l - bojod fid- demm, batterja u demm fl- awrina.
Positive Coombs' tests have been reported, both for levodopa/ carbidopa and for levodopa alone, but haemolytic anaemia is extremely rare.
Kienu rrappurtati testijiet ta ’ Coombs pożittivi, kemm għal levodopa/ carbidopa kif ukoll għal levodopa waħdu, iżda anemija emolitika hija rari ħafna.
Levodopa/ carbidopa may cause false positive result when a dipstick is used to test for urinary ketone and this reaction is not altered by boiling the urine sample.
Levodopa/ carbidopa jista ’ jikkawża test pożittiv falz meta tintuża stikka biex tbill biex l- awrina tiġi analizzata għal ketone u din ir- reazzjoni ma tinbidilx wara li l- kampjun ta ’ l- awrina jiġi mgħolli.
The use of glucose oxidase methods may give false negative results for glycosuria.
L- użu ta ’ metodi ta ’ glucose oxidase jistgħu jagħtu riżultati negattivi foloz għall- glikosurja.
The post-marketing data includes isolated cases of overdose in which the reported highest daily doses of levodopa and entacapone have been at least 10,000 mg and 40,000 mg, respectively.
Tagħrif wara t- tqegħid fis- suq jinkludi każijiet iżolati ta ’ doża eċċessiva fejn l- ogħla dożi rrapportati kuljum ta ’ levodopa u entacapone kienu mill- inqas 10, 000 mg u 40, 000 mg, rispettivament.
The acute symptoms and signs in these cases of overdose included agitation, confusional state, coma, bradycardia, ventricular tachycardia, Cheyne-Stokes respiration, discolourations of skin, tongue and conjunctiva, and chromaturia.
Is- sintomi u s- sinjali akuti ta ’ dawn il- każijiet ta ’ doża eċċessiva kienu jinkludu aġitazzjoni, stat konfuż, koma, bradikardija, takikardija ventrikulari, respirazzjoni Cheyne- Stokes, bidla fil- kulur tal- ġilda, ilsien u konġuntiva, u kromaturja.
Management of acute overdosage with Stalevo therapy is similar to acute overdosage with levodopa.
L- immaniġġjar ta ’ doża eċċessiva akuta b’ terapija ta ’ Stalevo hija simili għal doża eċċessiva b’ levodopa.
Pyridoxine, however, is not effective in reversing the actions of Stalevo.
Madankollu, Pyridoxine mhux effettiv biex jaqleb l- azzjonijiet ta ’ Stalevo.
Hospitalisation is advised and general supportive measures should be employed with immediate gastric lavage and repeated doses of charcoal over time.
Ammissjoni fl- isptar hija rrakkomandata u għandhom jintużaw miżuri ġenerali ta ’ support b’ ħasil gastriku immejdat u b’ dożi ripetuti ta ’ faħam tul iż- żmien.
This may hasten the elimination of entacapone in particular by decreasing its absorption/ reabsorption from the GI tract.
Dan jista ’ jħaffef l- eliminazzjoni ta ’ entacapone speċjalment billi jnaqqas l- assorbiment/ riassorbiment tiegħu mill- apparat GI.
The adequacy of the respiratory, circulatory and renal systems should be carefully monitored and appropriate supportive measures employed.
Is - suffiċjenza tas- sistemi respiratorji, ċirkulatorji u renali għandha tiġi sorveljata b’ attenzjoni u għandhom jintużaw miżuri ta ’ appoġġ xierqa.
ECG monitoring should be started and the patient carefully monitored for the possible development of arrhythmias.
Għandha tinbeda sorveljanza b’ ECG u l- pazjent għandu jiġi sorveljat b’ attenzjoni għal żvilupp potenzjali ta ’ arritmija.
If required, appropriate, anti-arrhythmic therapy should be given.
Jekk hemm bżonn, għandha tingħata terapija anti- arritmika xierqa.
The possibility that the patient has taken other active substances in addition to Stalevo should be taken into consideration.
Għandha tittieħed f’ kunsiderazzjoni l- possibiltà li l- pazjent ħa sustanzi attivi oħra flimkien ma ’ Stalevo.
The value of dialysis in the treatment of overdosage is not known.
L- importanza ta ’ dijalisi fil- kura ta ’ doża eċċessiva mhix magħrufa.
Pharmacotherapeutic group: dopa and dopa derivatives, ATC code:
Kategorija farmakoterapewtika: dopa u derivattivi ta ’ dopa, kodiċi ATC:
According to the current understanding, the symptoms of Parkinson’ s disease are related to depletion of dopamine in the corpus striatum.
Skond ftehim kurrenti, is- sintomi tal- marda ta ’ Parkinson huma relatati ma ’ tnaqqis ta ’ dopamine fil - corpus striatum.
Dopamine does not cross the blood-brain barrier.
Dopamine ma jaqsamx il- barriera ta ’ bejn id- demm u l- moħħ.
Levodopa, the precursor of dopamine, crosses the blood brain barrier and relieves the symptoms of the disease.
Levodopa, il- prekursur ta ’ dopamine, jaqsam il- barriera ta ’ bejn id- demm u l- moħħ u jtaffi is- sintomi tal- marda.
As levodopa is extensively metabolised in the periphery only a small portion of a given dose reaches the central nervous system when levodopa is administered without metabolic enzyme inhibitors.
Minħabba li levodopa jiġi metabolizzat b’ mod estensiv fil- periferija, porzjon żgħir biss tad- doża mogħtija tilħaq is - sistema nervuża ċentrali meta levodopa jingħata mingħajr inibituri ta ’ l- enżimi metaboliċi.
Carbidopa and benserazide are peripheral DDC inhibitors which reduce the peripheral metabolism of levodopa to dopamine and, thus, more levodopa is available to the brain.
Carbidopa u benserazide huma inibituri ta ’ DDC periferali li jnaqqsu il- metaboliżmu periferali ta ’ levodopa għal dopamine u b’ hekk, aktar levodopa jkun disponibbli għall- moħħ.
When decarboxylation of levodopa is reduced with the co-administration of a DDC inhibitor, a lower dose of levodopa can be used and the incidence of undesirable effects such as nausea is reduced.
Meta titnaqqas id - decarboxylation ta ’ levodopa bl- għotja fl- istess ħin ta ’ inibitur ta ’ DDC, tista ’ tintuża doża aktar baxxa ta ’ levodopa u l- inċidenza ta ’ effetti mhux mixtieqa bħal tqallih titnaqqas.
With inhibition of the decarboxylase by a DDC inhibitor, COMT becomes the major peripheral metabolic pathway catalyzing the conversion of levodopa to 3-O-methyldopa (3-OMD), a potentially harmful metabolite of levodopa.
9 Bl- inibizzjoni ta ’ decarboxylase minn inibitur ta ’ DDC, COMT isir il- metodu ta ’ metabolazzjoni periferali maġġuri li tikkatalizza il- konversjoni ta ’ levodopa għal 3- O- methyldopa (3- OMD), metabolita ta ’ levodopa li jista ’ jkun ta ’ ħsara.
Entacapone is a reversible, specific and mainly peripherally acting COMT inhibitor designed for concomitant administration with levodopa.
Entacapone huwa inibitur riversibbli u speċifiku ta ’ COMT li jaħdem primarjament fil- periferija, maħsub għall- għotja flimkien ma ’ levodopa.
Entacapone slows the clearance of levodopa from the bloodstream resulting in an increased area under the curve (AUC) in the pharmacokinetic profile of levodopa.
Entacapone inaqqas ir- rata tat- tneħħija ta ’ levodopa mid- demm u jwassal għal żjieda fl- erja taħt il- kurva (AUC) fil- profil farmakokinetiku ta ’ levodopa.
Consequently the clinical response to each dose of levodopa is enhanced and prolonged.
Bħala konsegwenza ir- respons kliniku ta ’ kull doża ta ’ levodopa huwa msaħħaħ u mtawwal.
The evidence of the therapeutic effects of Stalevo is based on two phase III double-blind studies, in which 376 Parkinson’ s disease patients with end-of-dose motor fluctuations received either
L- evidenza ta ’ l- effetti terapewtiċi ta ’ Stalevo hija bbażata fuq żewġ studji double- blind ta ’ fażi III, fejn 376 pazjent bil- marda ta ’ Parkinson b’ oxxillazzjonijiet motorji tat- tmiem tad- doża irċevew entacapone jew plaċebo ma ’ kull doża ta ’ levodopa/ inibitur ta ’ DDC.
Daily ON time with and without entacapone was recorded in home-diaries by patients.
Il- perjodu ON ta ’ kuljum bi u bla entacapone kien irreġistrat fid- djarji ta ’ kuljum tal- pazjenti.
In the first study, entacapone increased the mean daily ON time by 1 h 20 min (CI 95% 45 min, 1 h 56 min) from baseline.
Fl- ewwel studju, entacapone żied il - medja tal- perjodu ON ta ’ kuljum b’ 1 h 20 min (CI 95% 45 min, 1 h 56 min) mill- linja bażi.
This corresponded to an 8.3% increase in the proportion of daily ON time.
Dan kien jikkorrispondi għal żjieda ta ’ 8. 3% fil- proporzjon tal- perjodu ON ta ’ kuljum.
Correspondingly, the decrease in daily OFF time was 24% in the entacapone group and 0% in the placebo group.
B’ hekk, it- tnaqqis tal - perjodu OFF ta ’ kuljum kien ta ’ 24% fil- grupp ta ’ entacapone u 0% fil- grupp tal- plaċebo.
In the second study, the mean proportion of daily ON time increased by 4.5% (CI95% 0.93%, 7.97%) from baseline.
Fit- tieni studju, il- proporzjon medju tal- perjodu ON ta ’ kuljum żdied b’ 4. 5% (CI95% 0. 93%, 7. 97%) mill- linja bażi.
This is translated to a mean increase of 35 min in the daily ON time.
Dan ifisser żjieda medja ta ’ 35 min fil- perjodu ON ta ’ kuljum.
Correspondingly, the daily OFF time decreased by 18% on entacapone and by 5% on placebo.
B’ hekk, il- perjodu OFF ta ’ kuljum naqas b’ 18% b’ entacapone u b’ 5% bil- plaċebo.
Because the effects of Stalevo tablets are equivalent with entacapone 200 mg tablet administered concomitantly with the commercially available standard release carbidopa/ levodopa preparations in corresponding doses these results are applicable to describe the effects of Stalevo as well.
Minħabba li l- effetti tal- pilloli ta ’ Stalevo huma ekwivalenti għal pillola entacapone 200 mg mogħtija fl- istess ħin ma ’ preparazzjonijiet ta ’ carbidopa/ levodopa li jintreħew b’ mod standard li huma disponibbli għal bejħ f’ dożi li jikkorrispondu dawn ir- riżultati jistgħu jintużaw ukoll biex jiddeskrivu l- effetti ta ’ Stalevo.
General characteristics of the active substances
Karatteristiċi ġenerali tas- sustanzi attivi
Absorption/ Distribution:
Assorbiment/ Distribuzzjoni:
There are substantial inter- and intra-individual variations in the absorption of levodopa, carbidopa and entacapone.
Hemm varjazzjoni inter - u intra- individwali sostanzjali fl- assorbiment ta ’ levodopa, carbidopa u entacapone.
Both levodopa and entacapone are rapidly absorbed and eliminated.
Kemm levodopa kif ukoll entacapone huma assorbiti u eliminati b’ mod veloċi.
Carbidopa is absorbed and eliminated slightly slower compared with levodopa.
Carbidopa huwa assorbit u eliminat kemmxejn aktar bil- mod meta mqabbel ma ’ levodopa.
When given separately without the two other active substances, the bioavailability for levodopa is 15-33%, for carbidopa 40-70% and for entacapone 35% after a 200 mg oral dose.
Meta jingħata separatament mingħajr iż- żewġ sustanzi attiv l- oħra, il- biodisponibiltà għal levodopa hija 15- 33%, għal carbidopa 40- 70% u għal entacapone 35% wara doża orali ta ’ 200 mg.
Meals rich in large neutral amino acids may delay and reduce the absorption of levodopa.
Ikliet li fihom ħafna aċidi amminiċi newtrali kbar jistgħu jtawwlu u jnaqqsu l- assorbiment ta ’ levodopa.
Food does not significantly affect the absorption of entacapone.
L- ikel ma jaffettwax l- assorbiment ta ’ entacapone b’ mod sinifikanti.
The distribution volume of both levodopa (Vd 0.36-1.6 l/ kg) and entacapone (Vdss 0.27 l/ kg) is moderately small while no data for carbidopa are available.
Il- volum ta ’ distribuzzjoni kemm ta ’ levodopa (Vd 0. 36- 1. 6 l/ kg) kif ukoll ta ’ entacapone (Vdss 0. 27 l/ kg) huwa moderatament żgħir waqt li m’ hemmx tagħrif disponibbli dwar carbidopa.
Levodopa is bound to plasma protein only to a minor extent of about 10-30% and carbidopa is bound approximately 36%, while entacapone is extensively bound to plasma proteins (about 98%), mainly to serum albumin.
Levodopa jeħel mal- proteini fil- plażma b’ mod minimu biss, ta ’ madwar 10- 30% u carbidopa jeħel b’ madwar 36%, filwaqt li entacapone jeħel b’ mod estensiv mal- proteini fil- plażma (madwar 98%), primarjament mal- albumina fis- serum.
At therapeutic concentrations, entacapone does not displace other extensively bound active substances (e. g. warfarin, salicylic acid, phenylbutazone, or diazepam), nor is it displaced to any significant extent by any of these substances at therapeutic or higher concentrations.
F’ konċentrazzjonijiet terapewtiċi, entacapone ma jispostax sustanzi attivi oħra li jeħlu b’ mod estensiv (e. ż. warfarin, salicylic acid, phenylbutazone, jew diazepam), u lanqas jiġi spustat b’ mod sinifikanti minn xi wieħed minn dawn is- sustanzi f’ konċentrazzjonijiet terapewtiċi jew ogħla.
Metabolism and Elimination:
Metaboliżmu u Eliminazzjoni:
Levodopa is extensively metabolised to various metabolites, decarboxylation by dopa decarboxylase (DDC) and O-methylation by catechol-O-methyltransferase (COMT) being the most important pathways.
Levodopa huwa metabolizzat b’ mod estensiv f’ bosta metaboliti, l- aktar metodi importanti huma decarboxylation minn dopa decarboxylase (DDC) u O- methylation minn catechol- O- methyltransferase (COMT).
Carbidopa is metabolized to two main metabolites which are excreted in the urine as glucuronides and unconjugated compounds.
Carbidopa huwa metabolizzat f’ żewġ metaboliti prinċipali li jitneħħew fl- awrina bħala glucuronides u sustanzi mhux konjugati.
Unchanged carbidopa accounts for 30% of the total urinary excretion.
Carbidopa mhux mibdul jikkonstitwixxi 30% tat- tneħħija totali fl- awrina.
Entacapone is almost completely metabolized prior to excretion via urine (10 to 20%) and bile/ feces (80 to 90%).
Entacapone jiġi metabolizzat kważi kompletament qabel ma jitneħħa fl- awrina (10 to 20%) u fil - bili/ ħmieġ (80 to 90%).
The main metabolic pathway is glucuronidation of entacapone and its active metabolite, the cis-isomer, which accounts for about 5% of plasma total amount.
Ir- rotta metabolika prinċipali hija l- glucuronidation ta ’ entacapone u tal - metabolita attiv tiegħu, cis- isomer, li jikkonstitwixxi madwar 5% tal- kwantità totali fil- plażma.
Total clearance for levodopa is in the range of 0.55-1.38 l/ kg/ h and for entacapone is in the range of 0.70 l/ kg/ h.
It- tneħħija totali ta ’ levodopa hija fil- firxa ta ’ 0. 55- 1. 38 l/ kg/ h u ta ’ entacapone hija fil- firxa ta ’ 0. 70 l/ kg/ h.
The elimination-half life is (t1/ 2) is 0.6-1.3 hours for levodopa, 2-3 hours for carbidopa and 0.4-0.7 hours for entacapone, each given separately.
10 sigħat għal levodopa, 2- 3 sigħat għal carbidopa u 0. 4- 0. 7 sigħat għal entacapone.
Due to short elimination half-lives, no true accumulation of levodopa or entacapone occurs on repeated administration.
Minħabba l- half- lives ta ’ eliminazzjoni qosra, b’ għotja ripetuta ma sseħħ l- ebda akkumulazzjoni vera ta ’ levodopa jew entacapone.
Data from in vitro studies using human liver microsomal preparations indicate that entacapone inhibits cytochrome P450 2C9 (IC50 ~ 4 µM).
Tagħrif minn studji in vitro bl- użu ta ’ preparazzjonijiet ta ’ mikrożomi epatiċi umani jindika li entacapone jinibixxi ċ- ċitokromju P450 2C9 (IC50 ~ 4 µM).
Entacapone showed little or no inhibition of other types of P450 isoenzymes (CYP1A2, CYP2A6, CYP2D6, CYP2E1, CYP3A and CYP2C19), see section 4.5.
Entacapone wera ftit jew l- ebda inibizzjoni tat- tipi l- oħra ta ’ l- isoenżimi P450 (CYP1A2, CYP2A6, CYP2D6, CYP2E1, CYP3A u CYP2C19), ara sezzjoni 4. 5.
10 Characteristics in patients
Karatteristiċi fil- pazjenti
When given without carbidopa and entacapone, the absorption of levodopa is greater and elimination is slower in elderly than in young subjects.
Meta jingħata mingħajr carbidopa u entacapone, l- assorbiment ta ’ levodopa huwa akbar u l - eliminazzjoni hija aktar bil- mod fl- anzjani meta mqabbla ma ’ individwi iżgħar.
However, after combination of carbidopa with levodopa, the absorption of levodopa is similar between the elderly and the young, but the AUC is still 1.5 fold greater in the elderly due to decreased DDC activity and lower clearance by aging.
Iżda, wara l- għotja ta ’ carbidopa flimkien ma ’ levodopa, l- assorbiment ta ’ levodopa huwa simili fl- anzjani u fiż- żgħar, iżda l - AUC xorta hija 1. 5 darbiet akbar fl- anzjani minħabba tnaqqis fl- attività ta ’ DDC u tneħħija aktar baxxa maż- żjieda fl- età.
There are no significant differences in the AUC of carbidopa or entacapone between younger (45– 64 years) and elderly subjects (65– 75 years).
Ma hemm l- ebda differenzi sinifikanti fl- AUC ta ’ carbidopa jew entacapone bejn individwi iżgħar (45 – 64 sena) u dawk anzjani (65 – 75 sena).
Bioavailability of levodopa is significantly higher in women than in men.
Il- biodisponibiltà ta ’ levodopa hija sinifikatament għola fin- nisa milli fl- irġiel.
In the pharmacokinetic studies with Stalevo the bioavailability of levodopa is higher in women than in men, primarily due to the difference in body weight, while there is no gender difference with carbidopa and entacapone.
Fl- istudji farmkokinetiċi b’ Stalevo il- biodisponibiltà ta ’ levodopa hija ogħla fin- nisa milli fl- irġiel, primarjament minħabba d- differenza fil- piż tal- ġisem, filwaqt li ma hemm l- ebda differenza bejn is- sessi b’ carbidopa u entacapone.
The metabolism of entacapone is slowed in patients with mild to moderate hepatic impairment (Child-Pugh Class A and B) leading to an increased plasma concentration of entacapone both in the absorption and elimination phases (see sections 4.2 and 4.3).
Il- metaboliżmu ta ’ entacapone huwa aktar bil- mod f’ pazjenti b’ indeboliment epatiku ħafif għal moderata (Child- Pugh Klassi A u B) li jwassal għal żjieda fil- konċentrazzjoni ta ’ entacapone fil- plażma kemm fil- fażi ta ’ assorbiment kif ukoll f’ dik ta ’ eliminazzjoni (ara sezzjonijiet 4. 2 u 4. 3).
No particular studies on the pharmacokinetics of carbidopa and levodopa in patients with hepatic impairment are reported, however, it is advised that Stalevo should be administered cautiously to patients with mild or moderate hepatic impairment.
Ma ġew irrappurtati l- ebda studji partikolari dwar il- farmakokinetika ta ’ carbidopa u ta ’ levodopa f’ pazjenti b’ indeboliment epatiku, iżda, huwa rrakkomandat li Stalevo għandu jingħata b’ kawtela lill- pazjenti b’ indeboliment epatiku ħafif sa moderat.
No particular studies are reported on the pharmacokinetics of levodopa and carbidopa in patients with renal impairment.
Ma ġew irrappurtati l- ebda studji partikolari dwar il- farmakokinetika ta ’ levodopa u carbidopa f’ pazjenti b’ indeboliment renali.
However, a longer dosing interval of Stalevo may be considered for patients who are receiving dialysis therapy (see section 4.2).
Madanakollu, jista ’ jiġi kkunsidrat intervall ta ’ dożaġġ ta ’ Stalevo itwal għall - pazjenti li qed jirċievu terapija b’ dijalisi (ara sezzjoni 4. 2).
Preclinical data of levodopa, carbidopa and entacapone tested alone or in combination revealed no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, and carcinogenic potential.
Informazzjoni ta ’ qabel l- użu kliniku, ibbażata fuq studji konvenzjonali ta ’ sigurtà farmakoloġika, effett tossiku minn dożi ripetuti, effett tossiku fuq il- ġeni u riskju ta ’ kanċer, dwar levodopa, carbidopa u entacapone studjati waħedhom jew f’ taħlita, ma turi l- ebda periklu speċjali għall- bnedmin.
In repeated dose toxicity studies with entacapone, anaemia most likely due to iron chelating properties of entacapone was observed.
Fi studji b’ entacapone dwar l- effett tossiku minn dożi ripetuti, kienet osservata anemija wisq probabbli minħabba l- kwalità ta ’ entacapone li jeħel mal- ħadid.
Regarding reproduction toxicity of entacapone, decreased foetal weight and a slightly delayed bone development were noticed in rabbits treated at systemic exposure levels in the therapeutic range.
Dwar l- effett tossiku fuq is- sistema riproduttiva, tnaqqis fil- piż tal- fetu u ttardjar ħafif fl- iżvilupp tal- għadam kienu osservati fi fniek ikkurati b’ livelli ta ’ espożizzjoni sistemika fil- firxa terapewtika.
Both levodopa and combinations of carbidopa and levodopa have caused visceral and skeletal malformations in rabbits.
Kemm levodopa kif ukoll taħlitiet ta ’ carbidopa u levodopa ikkawżaw malformazzjonijiet vixerali u skeletrali fil- fniek.
Croscarmellose sodium Magnesium stearate Maize starch Mannitol (E421) Povidone (E1201)
Croscarmellose sodium Magnesium stearate Maize starch Mannitol (E 421) 11 Povidone (E1201)
Glycerol (85 per cent) (E422) Hypromellose Magnesium stearate Polysorbate 80 Red iron oxide (E172) Sucrose
Glycerol (85 fil- mija) (E422) Hypromellose Magnesium stearate Polysorbate 80 Iron oxide aħmar (E 172) Sucrose Titanium dioxide (E 171) Iron oxide isfar (E 172)
This medicinal product does not require any special storage conditions.
Dan il- prodott mediċinali ma jinħtieġx kundizzjonijiet speċjali ta ’ ħażna.
HDPE bottle with a child resistant PP-closure.
Flixkun tal- HDPE b’ għeluq PP reżistenti għat- tfal.
10, 30, 100, 130, 175 and 250 tablets.
10, 30, 100, 130, 175 u 250 pillola.
Orion Corporation Orionintie 1 FI-02200 Espoo Finland
Orion Corporation Orionintie 1 FI- 02200 Espoo Il- Finlandja
17 October 2003 Date of last renewal:
17 ta ’ Ottubru 2003 Data ta ’ l- aħħar tiġdid:
Detailed information on this medicine is available on the European Medicine’ s Agency (EMEA) web site: http: / /www. emea. europa. eu
Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropeja dwar il - Mediċini (EMEA) http: // www. emea. europa. eu /.
Stalevo 100 mg/ 25 mg/ 200 mg film-coated tablets
Stalevo 100 mg/ 25 mg/ 200 mg pilloli miksija b’ rita
Each tablet contains 100 mg of levodopa, 25 mg of carbidopa and 200 mg of entacapone.
Kull pillola fiha 100 mg ta ’ levodopa, 25 mg ta ’ carbidopa u 200 mg ta ’ entacapone.
Each tablet contains 1.6 mg of sucrose.
Kull pillola fiha 1. 6 mg ta ’ sucrose
Brownish or greyish red, oval, unscored film-coated tablets marked with ‘ LCE 100’ on one side.
Pilloli miskija b’ rita, bla sinjal imnaqqax, ta ’ lewn aħmar fil- kannella jew griż, ovali, immarkati b ’ ‘ LCE 100 ’ fuq naħa waħda.
Stalevo is indicated for the treatment of adult patients with Parkinson’ s disease and end-of-dose motor fluctuations not stabilised on levodopa/ dopa decarboxylase (DDC) inhibitor treatment.
Stalevo huwa ndikat għall- kura ta ’ pazjenti adulti bil- marda ta ’ Parkinson u b’ oxxillazzjonijiet motorji tat - “ tmiem tad- doża ” li mhumiex stabbilizzati fuq kura b’ levodopa/ inibitur ta ’ dopa decarboxylase (DDC).
While the experience with total daily dosage greater than 200 mg carbidopa is limited, the maximum recommended daily dose of entacapone is 2000 mg and therefore the maximum dose is 10 tablets per day for the Stalevo strengths of 50 mg/ 12.5 mg/ 200 mg, 100 mg/ 25 mg/ 200 mg and 150 mg/ 37.5 mg/ 200 mg.
Filwaqt li l- esperjenza b’ dożaġġ totali ta ’ kuljum ta ’ aktar minn 200 mg carbidopa hija limitata, id- doża massima ta ’ entacapone rrakkomandata kuljum hija ta ’ 2000 mg u għalhekk id - doża massima ta ’ Stalevo hija ta ’ 10 pilloli kuljum għall- qawwiet ta ’ Stalevo ta ’ 50 mg/ 12. 5 mg/ 200 mg, 100 mg/ 25 mg/ 200 mg u 150 mg/ 37. 5 mg/ 200 mg.
According to this daily carbidopa dose, the maximum recommended daily Stalevo 200 mg/ 50 mg/ 200 mg dose is 7 tablets per day.
Skond din id- doża ta ’ kuljum ta ’ carbidopa, d- doża massima rrakkomandata kuljum ta ’ Stalevo 200 mg/ 50 mg/ 200 mg hija 7 pilloli kuljum.
Patients who are currently treated with entacapone and with standard release levodopa/ carbidopa in doses equal to Stalevo tablet strengths can be directly transferred to corresponding Stalevo tablets.
Pazjenti li bħalissa qed jiġu kkurati b’ entacapone u b’ levodopa/ carbidopa li jinħelsu b’ mod standard
13 entacapone 200 mg four times daily can take one 100 mg/ 25 mg/ 200 mg Stalevo tablet four times daily in place of their usual levodopa/ carbidopa and entacapone doses.
Per eżempju, pazjent li qed jieħu pillola waħda ta ’ 100 mg/ 25 mg ta ’ levodopa/ carbidopa ma ’ pillola waħda ta ’ entacapone 200 mg erba ’ darbiet kuljum jista ’ jieħu pillola waħda ta ’ 100 mg/ 25 mg/ 200 mg Stalevo erba ’ darbiet kuljum flok id- dożi tas- soltu ta ’ levodopa/ carbidopa u entacapone.
When initiating Stalevo therapy for patients currently treated with entacapone and levodopa/ carbidopa in doses not equal to Stalevo 100 mg/ 25 mg/ 200 mg, (or 50 mg/ 12.5 mg/ 200 mg, or 150 mg/ 37.5 mg/ 200 mg or 200 mg/ 50 mg/ 200 mg) tablets, Stalevo dosing should be carefully titrated for optimal clinical response.
Meta tinbeda kura b’ Stalevo għall- pazjenti li bħalissa qed jiġu kkurati b’ entacapone u b’ levodopa/ carbidopa f’ dożi mhux ugwali għall- pilloli Stalevo ta ’ 100 mg/ 25 mg/ 200 mg (jew 50 mg/ 12. 5 mg/ 200 mg jew 150 mg/ 37. 5 mg/ 200 mg), l- iddożar ta ’ Stalevo għandu jiġi ttitrat b’ kawtela għal respons kliniku ottimali.
For severe hepatic impairment see section 4.3
Għall- indeboliment epatiku sever ara sezzjoni 4. 3.
14 Renal impairment:
15 Indeboliment renali:
pulmonary disease, bronchial asthma, renal or endocrine disease, or history of peptic ulcer disease or of convulsions.
pulmonari sever, ażma fil- bronki, mard renali, jew endokrinali, jew passat ta ’ mard ta ’ ulċera peptika jew ta ’ konvulżjonijiet.
NMS, including rhabdomyolysis and hyperthermia, is characterised by motor symptoms (rigidity, myoclonus, tremor), mental status changes (e. g., agitation, confusion, coma), hyperthermia, autonomic dysfunction (tachycardia, labile blood pressure) and elevated serum creatine phosphokinase.
F’ każijiet individwali, jistgħu jkunu evidenti
In individual cases, only some of these symptoms and/ or findings may be evident.
16 biss xi wħud minn dawn is- sintomi u/ jew sejbiet.
The early diagnosis is important for the appropriate management of NMS.
Id- dijanjosi bikrija hija importanti għall - immaniġġjar xieraq ta ’ NMS.
A syndrome resembling the neuroleptic malignant syndrome including muscular rigidity, elevated body temperature, mental changes and increased serum creatine
Sindrome li jixbaħ is- sindrome newrolettiku malinn inkluż riġidità fil- muskoli, temperatura tal- ġisem elevata, bidliet mentali u żjieda tal- creatine phosphokinase fis- serum kien irrappurtat mal- waqfien f’ daqqa ta ’ sustanzi kontra l- marda ta ’ Parkinson.
- If general anaesthesia is required, therapy with Stalevo may be continued for as long as the
- Jekk tkun meħtieġa anestesija ġenerali, it- terapija b’ Stalevo tista ’ tikompla sakemm il- pazjent
- Pathological gambling, increased libido and hypersexuality have been reported in Parkinson’ s
- Logħob ta ’ l- azzard patoloġiku, żjieda fil- libido u ipersesswalità ġew irrappurtati f’ pazjenti bil -
disease patients treated with dopamine agonists and other dopaminergic treatments such as Stalevo.
marda ta ’ Parkinson ikkurati b’ agonisti ta ’ dopamine u kura dopaminerġika dopaminerġiċi oħra bħal Stalevo.
relatively short period of time, a general medical evaluation including liver function should be considered.
żmien relattivament qasir, evalwazzjoni medika ġenerali li tinkludi l- funzjonalment tal- fwied għandha tiġi kkonsidrata
16 medicinal products with Stalevo should be carefully observed for loss of therapeutic response.
Pazjenti li qed jieħdu dawn il- prodotti mediċinali ma ’ Stalevo għandhom jiġu osservati mill- viċin għat- telf tar- respons terapewtiku.
Levodopa, carbidopa and entacapone together may cause dizziness and symptomatic orthostatism.
Stalevo jista ’ jkollu influwenza maġġura fuq il- ħila biex issuq u tħaddem inġenji Levodopa, carbidopa u entacapone flimkien jistgħu jikkawżaw sturdament u ortostatiżmu sintomatiku.
17 Other adverse reactions associated with levodopa/ carbidopa therapy are mental changes, including paranoid ideation and psychotic episodes; depression, with or without development of suicidal tendencies; and cognitive dysfunction.
Reazzjonijiet avversi oħrajn assoċjati ma ’ terapija b’ levodopa/ carbidopa huma bidliet mentali, inkluż idejazzjoni paranojdika u episodji psikotiċi; depressjoni, bi jew bla żvilupp ta ’ tendenzi ta ’ suwiċidju; u disfunzjoni konoxxittiva.
Metabolism and nutrition disorders:
Disturbi marbuta mal- metaboliżmu u n- nutrizzjoni:
Weight gain or loss, oedema.
Żjieda jew tnaqqis fil- piż, edima.
Confusion, insomnia, nightmares, hallucinations, delusions, agitation, anxiety, euphoria.
Konfużjoni, insomnija, inkubi, alluċinazzjonijiet, delużjonijiet, aġitazzjoni, ansjetà, ewforja.
Entacapone
19 Entacapone
18 with entacapone and since the introduction of entacapone into the market for the combination use of entacapone with levodopa/ DDC inhibitor.
Ir- reazzjonijiet avversi li ġejjin, imniżżla f’ Tabella 1, inġabru kemm minn studji kliniċi b’ entacapone kif ukoll minn meta entacapone ġie introdott fis- suq għall- użu tat- taħlita ta ’ entacapone ma ’ levodopa/ inibitur ta ’ DDC.
Hepatitis with mainly cholestatic features (see section 4.4)
Epatite l- aktar b’ karatteristiċi kolestatiċi (ara sezzjoni 4. 4)
Insomnia, hallucinations, confusion, nightmares, agitation
Insomnija, alluċinazzjonijiet, konfużjoni, inkubi, aġitazzjoni
*Adverse reactions
Termini sekondarji - avvenimenti Komuni:
are ranked under headings of frequency, the most frequent first, using the
Waqa ’
Very common (≥ 1/ 10); common (1≥ 100 to < 1/ 10); uncommon (≥ 1/ 1,000 to < 1/ 100); rare (≥ 1/ 10,000 to < 1/ 1,000), very rare (< 1/ 10,000), not known (cannot be estimated from the available data), since no valid estimate can be derived from clinical trials or epidemiological studies).
Komuni ħafna (≥1/ 10); komuni (1≥100 sa < 1/ 10); mhux komuni (≥1/ 1, 000 sa < 1/ 100); rari (≥1/ 10, 000 sa < 1/ 1, 000), rari ħafna (< 1/ 10, 000), mhux magħrufa (ma jistax jiġi stmat mit- tagħrif disponibbli, peress li l- ebda stima valida ma tista ’ tiġi derivata minn provi kliniċi jew studji epidemjoloġiċi).
Isolated cases of NMS have been reported following the abrupt reduction or discontinuation of entacapone and other dopaminergic treatments.
20 Każijiet iżolati ta ’ NMS ġew irrappurtati wara t- tnaqqis f’ daqqa jew wara l- waqfien ta ’ entacapone u kura dopaminerġika oħra.
Isolated cases of rhabdomyolysis have been reported.
Kienu rrappurtati każijiet iżolati ta ’ rabdomijolisi.
The following laboratory abnormalities have been reported with levodopa/ carbidopa treatment and should, therefore, be acknowledged when treating patients with Stalevo:
L- anormalitajiet tal- laboratorju li ġejjin ġew irrappurtati b’ kura b’ levodopa/ carbidopa u għalhekk għandhom, jittieħdu f’ konsiderazzjoni meta pazjenti jiġu kkurat b’ Stalevo:
19 Decreased haemoglobin, haematocrit, elevated serum glucose and white blood cells, bacteria and blood in the urine have been reported.
Ġew irrappurtati tnaqqis fl- emoglobina u fl- ematokrita, żjieda tal- glukosju fis- serum u taċ- ċelluli l - bojod fid- demm, batterja u demm fl- awrina.
Hospitalisation is advised and general supportive measures should be employed with immediate gastric lavage and repeated doses of charcoal over time.
Ammissjoni fl- isptar hija rrakkomandata u għandhom jintużaw miżuri ġenerali ta ’ support b’ ħasil gastriku immedjat u b’ dożi ripetuti ta ’ faħam tul iż- żmien.
Carbidopa and benserazide are peripheral DDC inhibitors which reduce the peripheral metabolism of levodopa to dopamine and, thus, more levodopa is available to the brain.
Meta titnaqqas id -
When decarboxylation of levodopa is reduced with the co-administration of a DDC inhibitor, a lower dose of levodopa can be used and the incidence of undesirable effects such as nausea is reduced.
21 decarboxylation ta ’ levodopa bl- għotja fl- istess ħin ta ’ inibitur ta ’ DDC, tista ’ tintuża doża aktar baxxa ta ’ levodopa u l- inċidenza ta ’ effetti mhux mixtieqa bħal tqallih titnaqqas.
With inhibition of the decarboxylase by a DDC inhibitor, COMT becomes the major peripheral metabolic pathway catalyzing the conversion of levodopa to 3-O-methyldopa (3-OMD), a potentially harmful metabolite of levodopa.
Bl- inibizzjoni ta ’ decarboxylase minn inibitur ta ’ DDC, COMT isir il- metodu ta ’ metabolazzjoni periferali maġġuri li tikkatalizza il- konversjoni ta ’ levodopa għal 3- O- methyldopa (3- OMD), metabolita ta ’ levodopa li jista ’ jkun ta ’ ħsara.
Daily ON time with and without
L- evidenza ta ’ l- effetti terapewtiċi ta ’ Stalevo hija bbażata fuq żewġ studji double- blind ta ’ fażi III, fejn 376 pazjent bil- marda ta ’ Parkinson b’ oxxillazzjonijiet motorji tat- tmiem tad- doża irċevew entacapone jew plaċebo ma ’ kull doża ta ’ levodopa/ inibitur ta ’ DDC.
20 entacapone was recorded in home-diaries by patients.
Il- perjodu ON ta ’ kuljum bi u bla entacapone kien irreġistrat fid- djarji ta ’ kuljum tal- pazjenti.
When given separately without the two other active substances, the bioavailability for levodopa is 15-33%, for carbidopa 40-70% and for entacapone 35% after a 200 mg oral dose.
Meta jingħata separatament mingħajr iż- żewġ sustanzi attivi l- oħra, il- biodisponibiltà għal levodopa hija 15- 33%, għal carbidopa 40- 70% u għal entacapone 35% wara doża orali ta ’ 200 mg.
Total clearance for levodopa is in the range of 0.55-1.38 l/ kg/ h and for entacapone is in the range of 0.70 l/ kg/ h.
22 It- tneħħija totali ta ’ levodopa hija fil- firxa ta ’ 0. 55- 1. 38 l/ kg/ h u ta ’ entacapone hija fil- firxa ta ’ 0. 70 l/ kg/ h.
The elimination-half life is (t1/ 2) is 0.6-1.3 hours for levodopa, 2-3 hours for carbidopa and 0.4-0.7 hours for entacapone, each given separately.
Meta kull wieħed jingħata b’ mod separat, il- half- life ta ’ eliminazzjoni (t1/ 2) hija 0. 6- 1. 3 sigħat għal levodopa, 2- 3 sigħat għal carbidopa u 0. 4- 0. 7 sigħat għal entacapone.
21 Characteristics in patients
Karatteristiċi fil- pazjenti
When given without carbidopa and entacapone, the absorption of levodopa is greater and elimination is slower in elderly than in young subjects.
Meta jingħata mingħajr carbidopa u entacapone, l- assorbiment ta ’ levodopa huwa akbar u l - elimiazzjoni hija aktar bil- mod fl- anzjani meta mqabbla ma ’ individwi iżgħar.
Croscarmellose sodium Magnesium stearate Maize starch Mannitol (E421) Povidone (E1201)
Croscarmellose sodium Magnesium stearate Maize starch Mannitol (E 421) Povidone (E1201)
Glycerol (85 per cent) (E422) Hypromellose Magnesium stearate Polysorbate 80 Red iron oxide (E172) Sucrose
Glycerol (85 fil- mija) (E 422) Hypromellose Magnesium stearate Polysorbate 80 Iron oxide aħmar (E 172) Sucrose Titanium dioxide (E 171) Iron oxide isfar (E 172)
Stalevo 150 mg/ 37.5 mg/ 200 mg film-coated tablets
Stalevo 150 mg/ 37. 5 mg/ 200 mg pilloli miksija b’ rita
Each tablet contains 150 mg of levodopa, 37.5 mg of carbidopa and 200 mg of entacapone.
Kull pillola fiha 150 mg ta ’ levodopa, 37. 5 mg ta ’ carbidopa u 200 mg ta ’ entacapone.
Each tablet contains 1.9 mg of sucrose.
Kull pillola fiha 1. 9 mg ta ’ sucrose
Brownish or greyish red, elongated-ellipse shaped, unscored film-coated tablets marked with ‘ LCE 150’ on one side.
Pilloli miskija b’ rita, bla sinjal imnaqqax, ta ’ lewn aħmar fil- kannella jew griż, b’ forma ta ’ elissi mtawwal, immarkati b ’ ‘ LCE 150 ’ fuq naħa waħda.
Patients should be instructed to take only one Stalevo tablet per dose administration.
Il- pazjenti għandhom jiġu mgħallma biex jieħdu pillola waħda biss ta ’ Stalevo kull għotja ta ’ doża.
24 For example, a patient taking one tablet of 150 mg/ 37.5 mg of levodopa/ carbidopa with one tablet of entacapone 200 mg four times daily can take one 150 mg/ 37.5 mg/ 200 mg Stalevo tablet four times daily in place of their usual levodopa/ carbidopa and entacapone doses.
Per eżempju, pazjent li qed jieħu pillola waħda ta ’ 150 mg/ 37. 5 mg ta ’ levodopa/ carbidopa ma ’ pillola waħda ta ’ entacapone 200 mg erba ’ darbiet kuljum jista ’ jieħu pillola waħda ta ’ 150 mg/ 37. 5 mg/ 200 mg Stalevo erba ’ darbiet kuljum flok id- dożi tas- soltu ta ’ levodopa/ carbidopa u entacapone.
When initiating Stalevo therapy for patients currently treated with entacapone and levodopa/ carbidopa in doses not equal to Stalevo 150 mg/ 37.5 mg/ 200 mg, (or 50 mg/ 12.5 mg/ 200 mg, or 100 mg/ 25 mg/ 200 mg or 200 mg/ 50 mg/ 200 mg) tablets, Stalevo dosing should be carefully titrated for optimal clinical response.
Meta tinbeda kura b’ Stalevo għall- pazjenti li bħalissa qed jiġu kkurati b’ entacapone u b’ levodopa/ carbidopa f’ dożi mhux ugwali għall- pilloli Stalevo ta ’ 150 mg/ 37. 5 mg/ 200 mg (jew 50 mg/ 12. 5 mg/ 200 mg jew 100 mg/ 25 mg/ 200 mg jew 200 mg/ 50 mg/ 200 mg), l- iddożar ta ’ Stalevo għandu jiġi ttitrat b’ kawtela għal respons kliniku ottimali.
Entacapone enhances the effects of levodopa.
Entacapone isaħħaħ l- effetti ta ’ levodopa.
Dose reduction may be needed (see section 5.2).
Jista ’ jkun hemm bżonn ta ’ tnaqqis fid- doża (ara sezzjoni
25 Renal impairment:
Indeboliment renali:
- Patients with chronic wide-angle glaucoma may be treated with Stalevo with caution, provided the
- Pazjenti bi glawkoma ta ’ angolu wiesa ’ kronika jistgħu jiġu kkurati b’ Stalevo b’ kawtela, dejjem
intra-ocular pressure is well controlled and the patient is monitored carefully for changes in intra- ocular pressure.
jekk il- pressjoni intra- okulari tkun ikkontrollata sew u li l- pazjent ikun sorveljat b’ kawtela għal bidliet fil- pressjoni intra- okulari.
NMS, including rhabdomyolysis and hyperthermia, is characterised by motor symptoms (rigidity, myoclonus, tremor), mental status changes (e. g., agitation, confusion, coma), hyperthermia, autonomic dysfunction (tachycardia, labile blood pressure) and elevated serum creatine phosphokinase.
NMS, inkluż rabdomijolisi u ipertermja, hija kkarratterizzata minn sintomi motorji (riġidità, mijoklonus, tregħid), tibdil fl- istat mentali (e. ż., aġitazzjoni, konfużjoni, koma), ipertermja, disfunzjoni awtonomika (takikardja, pressjoni tad- demm mhix
In individual cases, only some of these symptoms and/ or findings may be evident.
F’ każijiet individwali, jistgħu jkunu evidenti biss xi wħud minn dawn is- sintomi u/ jew sejbiet.
A syndrome resembling the neuroleptic malignant syndrome including muscular rigidity, elevated body temperature, mental changes and increased serum creatine phosphokinase has been reported
Sindrome li jixbaħ is- sindrome newrolettiku malinn inkluż riġidità fil- muskoli, temperatura tal- ġisem elevata, bidliet mentali u żjieda tal- creatine phosphokinase fis- serum kien irrappurtat mal- waqfien f’ daqqa ta ’ sustanzi kontra l- marda ta ’ Parkinson.
Since the introduction of entacapone into the market, isolated cases of NMS have been reported, especially following abrupt reduction or discontinuation of entacapone and other concomitant dopaminergicmedicinal products.
Minn wara l- introduzzjoni ta ’ entacapone fis- suq, ġew irrappurati każijiet iżolati ta ’ NMS, speċjalment wara t- tnaqqis jew it- twaqqif f’ daqqa ta ’ entacapone u ta ’ prodotti mediċinali dopaminerġiċi oħra li kienu qed jittieħdu fl - istess ħin.
- If general anaesthesia is required, therapy with Stalevo may be continued for as long as the patient
- Jekk tkun meħtieġa anestesija ġenerali, it- terapija b’ Stalevo tista ’ tikompla sakemm il- pazjent
is permitted to take fluids and medicinal products by mouth.
jitħalla jieħu likwidi u prodotti mediċinali mill- ħalq.
- Periodic evaluation of hepatic, haematopoietic, cardiovascular and renal function is recommended
- Hija rrakkomandata evalwazzjoni perjodika tal- funzjoni epatika, emopoetika, kardjovaskulari u
during extended therapy with Stalevo.
renali waqt kura mtawwla b’ Stalevo.
disease patients treated with dopamine agonists and other dopaminergic treatments such as Stalevo.
marda ta ’ Parkinson ikkurati b’ agonisti ta ’ dopamine u kura dopaminerġika oħra bħal Stalevo.
27 medicinal products with Stalevo should be carefully observed for loss of therapeutic response.
Pazjenti li qed jieħdu dawn il- prodotti mediċinali ma ’ Stalevo għandhom jiġu osservati mill- viċin għat- telf tar- respons terapewtiku.
Since levodopa competes with certain amino acids, the absorption of Stalevo may be impaired in some patients on high protein diet.
Peress li levodopa jikkompeti ma ’ ċertu aċidi amminiċi, l- assorbiment ta ’ Stalevo jista ’ jonqos f’ ċertu pazjenti li qegħdin fuq dieta ta ’ ħafna protein.
28 Other adverse reactions associated with levodopa/ carbidopa therapy are mental changes, including paranoid ideation and psychotic episodes; depression, with or without development of suicidal tendencies; and cognitive dysfunction.
Reazzjonijiet avversi oħrajn assoċjati ma ’ terapija b’ levodopa/ carbidopa huma bidliet mentali, inkluż idejazzjoni paranojdika u episodji psikotiċi; depressjoni, bi jew bla żvilupp ta ’ tendenzi ta ’ suwiċidju; u disfunzjoni konoxxittiva.
Ataxia, numbness, increased hand tremor, muscle twitching, muscle cramp, trismus, activation of latent Horner's syndrome.
Ataxja, tnemnim, żjieda fit- tregħid ta ’ l- idejn, kontrazzjonijiet mhux volontarji tal- muskoli, bugħawwieġ fil- muskoli, trismus, attivazzjoni tas- sindrome moħbi ta ’ Horner.
Entacapone
31 Entacapone
29 with entacapone and since the introduction of entacapone into the market for the combination use of entacapone with levodopa/ DDC inhibitor.
Ir- reazzjonijiet avversi li ġejjin, imniżżla f’ Tabella 1, inġabru kemm minn studji kliniċi b’ entacapone kif ukoll minn meta entacapone ġie introdott fis- suq għall- użu tat- taħlita ta ’ entacapone ma ’ levodopa/ inibitur ta ’ DDC.
Urticaria Skin, hair, beard, and nail discolorations
Urtikarja Tibdil fil- kulur tal- ġilda, ix- xagħar, id- daqna u d- dwiefer
Fatigue, sweating increased, fall Weight decrease
Għeja, żjieda fl- għaraq, waqa Tnaqqis fil- piż
Hepatitis with mainly cholestatic features (see section 4.4)
Epatite l- aktar b’ karatteristiċi kolestatiċi (ara sezzjoni 4. 4).
Isolated cases of rhabdomyolysis have been reported.
32 Kienu rrappurtati każijiet iżolati ta ’ rabdomijolisi.
30 Decreased haemoglobin, haematocrit, elevated serum glucose and white blood cells, bacteria and blood in the urine have been reported.
Ġew irrappurtati tnaqqis fl- emoglobina u fl- ematokrita, żjieda tal- glukosju fis- serum u taċ- ċelluli l - bojod fid- demm, batterja u demm fl- awrina.
With inhibition of the decarboxylase by a DDC inhibitor, COMT becomes the major peripheral metabolic pathway catalyzing the conversion of levodopa to 3-O-methyldopa (3-OMD), a potentially harmful metabolite of levodopa.
33 Bl- inibizzjoni ta ’ decarboxylase minn inibitur ta ’ DDC, COMT isir il- metodu ta ’ metabolazzjoni periferali maġġuri li tikkatalizza il- konversjoni ta ’ levodopa għal 3- O- methyldopa (3- OMD), metabolita ta ’ levodopa li jista ’ jkun ta ’ ħsara.
31 entacapone was recorded in home-diaries by patients.
Il- perjodu ON ta ’ kuljum bi u bla entacapone kien irreġistrat fid- djarji ta ’ kuljum tal- pazjenti.
The elimination-half life is (t1/ 2) is 0.6-1.3 hours for levodopa, 2-3 hours for carbidopa and 0.4-0.7 hours for entacapone, each given separately.
34 sigħat għal levodopa, 2- 3 sigħat għal carbidopa u 0. 4- 0. 7 sigħat għal entacapone.
32 Characteristics in patients
Karatteristiċi fil- pazjenti
Croscarmellose sodium Magnesium stearate Maize starch Mannitol (E421) Povidone (E1201)
Croscarmellose sodium Magnesium stearate Maize starch Mannitol (E 421) 35 Povidone (E1201)
Stalevo 200 mg/ 50 mg/ 200 mg film-coated tablets
Stalevo 200 mg/ 50 mg/ 200 mg pilloli miksija b’ rita
Each tablet contains 200 mg of levodopa, 50 mg of carbidopa and 200 mg of entacapone.
Kull pillola fiha 200 mg ta ’ levodopa, 50 mg ta ’ carbidopa u 200 mg ta ’ entacapone.
Each tablet contains 2.3 mg of sucrose.
Kull pillola fiha 2. 3 mg ta ’ sucrose Għal- lista kompleta ta ’ sustanzi mhux attivi, ara sezzjoni 6. 1.
Dark brownish red, oval, unscored film-coated tablets marked with ‘ LCE 200’ on one side.
Pilloli miskija b’ rita, bla sinjal imnaqqax, ovali ta ’ lewn aħmar skur fil- kannella mmarkati b ’ ‘ LCE 200 ’ fuq naħa waħda.
While the experience with total daily dosage greater than 200 mg carbidopa is limited, the maximum recommended daily dose of entacapone is 2000 mg and therefore the maximum dose is 10 tablets per day for the Stalevo strengths of 50 mg/ 12.5 mg/ 200 mg, 100 mg/ 25 mg/ 200 mg and 150 mg/ 37.5 mg/ 200 mg.
Filwaqt li l- esperjenza b’ dożaġġ totali ta ’ kuljum ta ’ aktar minn 200 mg carbidopa hija limitata, id- doża massima ta ’ entacapone rrakkomandata kuljum hija ta ’ 2000 mg u għalhekk id - doża massima hija ta ’ 10 pilloli kuljum, għall- qawwiet ta ’ Stalevo ta ’ 50 mg/ 12. 5 mg/ 200 mg, 100 mg/ 25 mg/ 200 mg u 150 mg/ 37. 5 mg/ 200 mg.
Ten tablets of Stalevo 150 mg/ 37.5 mg/ 200 mg equals 375 mg of carbidopa a day.
Għaxar pilloli ta ’ Stalevo 150 mg/ 37. 5 mg/ 200 mg huma daqs 375 mg ta ’ carbidopa kuljum.
According to this daily carbidopa dose, the maximum recommended daily Stalevo 200 mg/ 50 mg/ 200 mg dose is 7 tablets per day.
Skond din id- doża ta ’ kuljum ta ’ carbidopa, id- doża massima rrakkomandata kuljum ta ’ Stalevo 200 mg/ 50 mg/ 200 mg hija 7 pilloli kuljum.
Patients who are currently treated with entacapone and with standard release levodopa/ carbidopa in doses equal to Stalevo tablet strengths can be directly transferred to corresponding Stalevo tablets.
Pazjenti li bħalissa qed jiġu kkurati b’ entacapone u b’ levodopa/ carbidopa li jinħelsu b’ mod standard f’ dożi ugwali għall- qawwiet ta ’ pilloli Stalevo jistgħu jinqalbu direttament għall- pilloli Stalevo korrispondenti.
35 For example, a patient taking one tablet of 200 mg/ 50 mg of levodopa/ carbidopa with one tablet of entacapone 200 mg four times daily can take one 200 mg/ 50 mg/ 200 mg Stalevo tablet four times daily in place of their usual levodopa/ carbidopa and entacapone doses.
38 levodopa/ carbidopa ma ’ pillola waħda ta ’ entacapone 200 mg erba ’ darbiet kuljum jista ’ jieħu pillola waħda ta ’ 200 mg/ 50 mg/ 200 mg Stalevo erba ’ darbiet kuljum flok id- dożi tas- soltu ta ’ levodopa/ carbidopa u entacapone.
When initiating Stalevo therapy for patients currently treated with entacapone and levodopa/ carbidopa in doses not equal to Stalevo 200 mg/ 50 mg/ 200 mg, (or 50 mg/ 12.5 mg/ 200 mg or 100 mg/ 25 mg200 mg, or 150 mg/ 37.5 mg/ 200 mg) tablets, Stalevo dosing should be carefully titrated for optimal clinical response.
Meta tinbeda kura b’ Stalevo għall- pazjenti li bħalissa qed jiġu kkurati b’ entacapone u b’ levodopa/ carbidopa f’ dożi mhux ugwali għall- pilloli Stalevo ta ’, 200 mg/ 50 mg/ 200 mg (jew 50 mg/ 12. 5 mg/ 200 mg, jew 100 mg/ 25 mg/ 200 mg, jew 150 mg/ 37. 5 mg/ 200 mg), l- iddożar ta ’ Stalevo għandu jiġi ttitrat b’ kawtela għal respons kliniku ottimali.
36 Renal impairment:
39 Indeboliment renali:
Renal impairment does not affect the pharmacokinetics of entacapone.
Indebolimentrenali ma jaffettwax il- farmakokinetika ta ’ entacapone.
In individual cases, only some of these symptoms and/ or findings may be evident.
40 biss xi wħud minn dawn is- sintomi u/ jew sejbiet.