qanastek/EMEA-V3 huggingface dataset:
Duloxetine normalised pain thresholds in several preclinical models of neuropathic and inflammatory pain and attenuated pain behaviour in a model of persistent pain.
Duloxetine reġa ’ ġab għan- normal il- limitu ta ’ l- uġigħ f’ ħafna mudelli prekliniċi ta ’ uġigħ newropatiku u infjammatorju u taffa l- atteġġament ta ’ l- uġigħ f’ mudell ta ’ uġigħ persistenti.
The pain inhibitory action of duloxetine is believed to be a result of potentiation of descending inhibitory pain pathways within the central nervous system.
Il- mod ta ’ inibizzjoni ta ’ l- uġigħ ta ’ duloxetine huwa maħsub li jirriżulta mit- tisħiħ tal- passaġġi tan- nervituri inibitorji ta ’ l- uġigħ li ħerġin minn ġewwa s- sistema nervuża ċentrali.
CYMBALTA was studied in a clinical programme involving 3,158 patients (1,285 patient-years of exposure) meeting DSM-IV criteria for major depression.
Episodji Depressivi Maġġuri CYMBALTA ġie studjat f’ programm kliniku li kien jinvolvi 3, 158 pazjent (1, 285 pazjenti- snin ta ’ espożizzjoni) li laħaq il- kriterji DSM- IV għal depressjoni maġġuri.
The efficacy of CYMBALTA at the 11 recommended dose of 60 mg once a day was demonstrated in three out of three randomized, double- blind, placebo-controlled, fixed dose acute studies in adult outpatients with major depressive disorder.
L- effikaċja ta ’ CYMBALTA fid - doża rakkomandata ta ’ 60mg darba kuljum ġiet ppruvata fit- tlieta minn tliet studji li saru f’ sitwazzjonijiet akuti, b’ doża fissa, randomised, double- blind u kkontrollati bil- plaċebo f’ pazjenti li mhumiex residenti ġo sptar u li għandhom mard depressiv maġġuri.
Overall, CYMBALTA’ s efficacy has been demonstrated at daily doses between 60 and 120 mg in a total of five out of seven randomized, double-blind, placebo-controlled, fixed dose acute studies in adult outpatients with major depressive disorder.
B’ mod ġenerali, l- effikaċja ta ’ CYMBALTA ġiet ipprovata f’ dożaġġi ta ’ kuljum ta ’ bejn 60 u 120 mg f’ total ta ’ ħamsa minn seba ’ studji li saru f’ sitwazzjonijiet akuti, b’ doża fissa, randomised, double- blind u kkontrollati bil- plaċebo f’ pazjenti li mhumiex residenti ġo sptar u li għandhom mard depressiv maġġuri.
CYMBALTA demonstrated statistical superiority over placebo as measured by improvement in the 17-item Hamilton Depression Rating Scale (HAM-D) total score (including both the emotional and somatic symptoms of depression).
Cymbalta statistikament wera superjorità fuq plaċebo kkalkulat skond it- titjib fil- punteġġ totali tal - Hamilton Depression Rating Scale( HAM- D) bi 17- il kriterju (li jinkludu kemm sintomi ta ’ depressjoni emozzjonali kif ukoll dawk somatiċi).
Response and remission rates were also statistically significantly higher with CYMBALTA compared with placebo.
Anki r- rati ta ’ rispons u remissjoni kienu b’ mod statistiku sinifikament ogħla b’ CYMBALTA meta mqabbla ma ’ plaċebo.
Only a small proportion of patients included in pivotal clinical trials had severe depression (baseline HAM-D > 25).
Kien hemm biss proporzjon żgħir ta ’ pazjenti li ġew inklużi fl- studji kliniċi prinċipali li kellhom depressjoni gravi (linja bażi HAM- D > 25).
In a relapse prevention study, patients responding to 12-weeks of acute treatment with open-label CYMBALTA 60 mg once daily were randomised to either CYMBALTA 60 mg once daily or placebo for a further 6-months.
Fi studju ta ’ prevenzjoni ta ’ rikaduta, pazjenti li rrispondew għal 12- il ġimgħa ta ’ kura akuta b’ open - label CYMBALTA 60mg darba kuljum, kienu b’ mod arbitrarju mgħotija jew CYMBALTA 60mg darba kuljum jew plaċebo għal 6 xhur oħra.
CYMBALTA 60 mg once daily demonstrated a statistically significant superiority compared to placebo (p=0.004) on the primary outcome measure, the prevention of depressive relapse, as measured by time to relapse.
CYMBALTA 60mg darba kuljum wera superjorità statistikament sinifikanti meta mqabbel ma ’ plaċebo (p=0. 004) f’ daq li għandu x’ jaqsam ir- riżultat primarju, il- prevenzjoni ta ’ rikaduta depressiva, ikkalkulata permezz taż- żmien li għadda sar- rikaduta.
The incidence of relapse during the 6-months double-blind follow-up period was 17% and 29% for duloxetine and placebo, respectively.
L- inċidenza ta ’ rikaduta matul il- perijodu ta ’ 6 xhur ta ’ follow- up, li kien double- blind, kienet ta ’ 17% u 29% għal duloxetine u plaċebo, rispettivament.
The effect of CYMBALTA 60 mg once a day in elderly depressed patients (≥ 65 years) was specifically examined in a study that showed a statistically significative difference in the reduction of the HAMD17 score for duloxetine-treated patients compared to placebo.
L- effett ta ’ CYMBALTA 60mg darba kuljum, f’ pazjenti anzjani b’ depressjoni (> 65 sena) ġie speċifikament eżaminat f’ studju li wera differenza statistikament sinifikanti fit- tnaqqis tal- punteġġ ta ’ l- HAMD 17 għal pazjenti kkurati b’ duloxetine meta mqabbel ma ’ plaċebo.
Tolerability of CYMBALTA 60 mg once day in elderly patients was comparable to that seen in the younger adults.
It- tollerabilità ta ’ CYMBALTA 60mg darba kuljum f’ pazjenti anzjani kien simili għal dak osservat fl- adulti iżgħar.
However, data on elderly patients exposed to the maximum dose (120mg per day) are limited and thus, caution is recommended when treating this population.
Madankollu, t- tagħrif fuq pazjenti li ġew mogħtija d- doża massima (120mg kuljum) huwa limitat u għalhekk huwa rakkomandat li toqgħod attent meta tkun qiegħed tikkura din il- popolazzjoni ta ’ pazjenti.
Generalised Anxiety Disorder CYMBALTA demonstrated statistically significant superiority over placebo in five out of five studies including four randomized, double-blind, placebo-controlled acute studies and a relapse prevention study in adult patients with generalised anxiety disorder.
Distrub ta ’ Ansjetà Ġeneralizzata CYMBALTA wera superjorità statistikament sinifikanti fuq plaċebo f’ kull wieħed minn ħames studji li jinkludu erba ’ studji magħmula f’ sitwazzjonijiet akuti, ikontrollati bi plaċebo, double- blind u randomized u studju ta ’ prevenzjoni ta ’ rikaduta f’ pazjenti adulti b’ disturb ta ’ ansjetà ġeneralizzata.
CYMBALTA demonstrated statistically significant superiority over placebo as measured by improvement in the Hamilton Anxiety Scale (HAM-A) total score and by the Sheehan Disability Scale (SDS) global functional impairment score.
13 CYMBALTA wera superjorità statistikament sinifikanti fuq plaċebo kemm meta kkalkulat skond it - titjib fil- punteġġ totali tal- Hamilton Anxiety Scale( HAM- A) u kemm skond il- punteġġ ta ’ indeboliment funzjonali globali tas- Sheehan Disability Scale (SDS).
CYMBALTA showed comparable efficacy results to venlafaxine in terms of improvements on the HAM-A total score.
Ir- rati ta ’ rispons u ta ’ remissjoni kienu wkoll ogħla b’ CYMBALTA meta mqabbla ma ’ plaċebo. CYMBALTA wera riżultati ta ’ effikaċja simili għal venlafaxine f’ dak li għandu x’ jaqsam titjib fil- punteġġ totali tal- HAM- A.
In a relapse prevention study, patients responding to 6 months of acute treatment with open-label CYMBALTA were randomised to either CYMBALTA or placebo for further 6-months.
F’ studju ta ’ prevenzjoni ta ’ rikaduta, pazjenti li kienu qed jirrispondu għal 6 xhur ta ’ kura b’ mod akut b’ CYMBALTA open- label, ġew mogħtija b’ mod arbitrarju jew CYMBALTA jew plaċebo għal 6 xhur oħra.
CYMBALTA 60 mg to 120 mg once daily demonstrated statistically significant superiority compared to placebo (p < 0.001) on the prevention of relapse, as measured by time to relapse.
CYMBALTA 60 mg sa 120 mg kuljum wera superjorità statistikament sinifikanti meta mqabbel ma ’ plaċebo (p < 0. 001) fil- prevenzjoni ta ’ rikaduta, ikkalkulata skond iż- żmien għar- rikaduta.
The incidence of relapse during the 6-months double-blind follow-up period was 14% for CYMBALTA and 42% for placebo.
L - inċidenza ta ’ rikaduta waqt il- perijodu miżjud ta ’ 6 xhur li kien double- blind kien ta ’ 14% b’ CYMBALTA u ta ’ 42% bi plaċebo.
Diabetic Peripheral Neuropathic Pain:
Uġigħ Newropatiku Periferiku Tad- Dijabete:
The efficacy of CYMBALTA as a treatment for diabetic neuropathic pain was established in 2 randomised, 12-week, double-blind, placebo-controlled, fixed dose studies in adults (22 to 88 years) having diabetic neuropathic pain for at least 6 months.
L- effikaċja ta ’ CYMBALTA bħala kura għall- uġigħ newropatiku tad- dijabete kien stabbilit f’ żewġ studji ta ’ 12- il ġimgħa, b’ dożi fissi, ikkontrollati bil- plaċebo, randomised u double- blind f’ adulti (22 sa 88 sena) li kellhom uġigħ newropatiku tad- dijabete għallinqas għal 6 xhur.
The primary outcome measure was the weekly mean of 24-hour average pain, which was collected in a daily diary by patients on an 11-point Likert scale.
Pazjenti li laħqu l- kriterji dijanjostiċi ta ’ mard depressiv maġġuri kienu esklusi minn dawn l- istudji. Ir- riżultat kliniku primarju kien il- medja ta ’ kull ġimgħa tal- medja ta ’ l- uġigħ f’ 24 siegħa, ikkalkulat skond l- iskala Likert bi 11- il punt, miġbura mill- pazjenti f’ djarju ta ’ kuljum.
In both studies, CYMBALTA 60 mg once daily and 60 mg twice daily significantly reduced pain compared with placebo.
Fiż- żewġ studji, CYMBALTA 60mg darba kuljum u 60mg darbtejn kuljum naqqsu b’ mod sinifikanti l- uġigħ meta mqabbla ma ’ plaċebo.
The effect in some patients was apparent in the first week of treatment.
F’ xi pazjenti l- effett beda jinħass fl- ewwel ġimgħa ta ’ kura.
At least 30% reported pain reduction was recorded in approximately 65% of duloxetine treated patients versus 40% for placebo.
Id - differenza fil- medja ta ’ titjib bejn iż- żewġ fergħat attivi tal- kura ma kinitx sinifikanti. Kważi 65% tal - pazjenti kkurati b’ duloxetine kontra l- 40% ta ’ dawk fuq plaċebo rreġistraw tnaqqis ta ’ mill- inqas 30% fl- uġigħ li kien ġie rrappurtat.
The corresponding figures for at least 50% pain reduction were 50% and 26% respectively.
L- ammonti li jikkorispondu għal tnaqqis ta ’ mill- inqas ta ’ 50% fl- uġigħ kienu 50% u 26% rispettivament.
Clinical response rates (50% or greater improvement in pain) were analysed according to 12 whether or not the patient experienced somnolence during treatment.
Ir- rati ta ’ rispons kliniku (50% jew iżjed ta ’ titjib fl- uġigħ) kienu analizzati skond jekk il- pazjent qabdux n- ngħas jew le waqt il- kura.
For patients not experiencing somnolence, clinical response was observed in 47% of patients receiving duloxetine and 27% patients on placebo.
F’ pazjenti li ma qabadhomx in - ngħas, ir- rispons kliniku kien osservat f’ 47% tal- pazjenti li rċevew duloxetine u f’ 27% tal- pazjenti li kienu fuq plaċebo.
Clinical response rates in patients experiencing somnolence were 60% on duloxetine and 30% on placebo.
Ir- rati ta ’ rispons kliniku f’ pazjenti li qabadhom in- ngħas kien ta ’ 60% għal dawk fuq duloxetine u ta ’ 30% għal dawk fuq plaċebo.
Patients not demonstrating a pain reduction of 30% within 60 days of treatment were unlikely to reach this level during further treatment.
Pazjenti li ma wrewx tnaqqis ta ’ 30% fl- uġigħ fi żmien 60 ġurnata mill- bidu tal- kura kien diffiċli li jilħqu dan il- livell wara kura ulterjuri.
Although data from a one-year open label study offer some evidence for longer-term efficacy, no conclusive efficacy data for treatments longer than 12 weeks duration are available from placebo- controlled studies.
Għalkemm tagħrif minn studju open- label ta ’ sena juri xi evidenza ta ’ effikaċja fit- tul, minn studji kkontrollati bil- plaċebo m’ hemmx tagħrif konklużiv dwar l- effikaċja ta ’ kura għal iżjed minn 12- il ġimgħa.
Duloxetine is administered as a single enantiomer.
Duloxetine huwa mgħoti bħala molekula waħda msawwra minn żewġ forom li huma bħal rifless ta 'xulxin f' mera.
Duloxetine is extensively metabolised by oxidative enzymes (CYP1A2 and the polymorphic CYP2D6), followed by conjugation.
Duloxetine huwa metaboliżżat b' mod estensiv minn enżimi ossidattivi (CYP1A2 u dik polymorfika CYP2D6) u mbagħad ikkonjugat.
The pharmacokinetics of duloxetine demonstrate large intersubject variability (generally 50-60%), partly due to gender, age, smoking status and CYP2D6 metaboliser status.
Il- farmakokinetika ta ’ duloxetine turu varjabiltà kbira bejn persuna u oħra (ġeneralment 50- 60%), in parti dovuta għas- sess, l- età, is- sitwazzjoni tat- tipjip u l - istat ta ’ metaboliżmu minn CYP2D6.
Duloxetine is well absorbed after oral administration with a Cmax occurring 6 hours post dose.
Duloxetine huwa assorbit sew wara li jittieħed mill- ħalq b 'Cmax li jidher 6 sigħat wara li tkun ħadt d - doża.
The absolute oral bioavailability of duloxetine ranged from 32% to 80% (mean of 50%).
Il- biodisponibiltà orali assoluta ta ’ duloxetine kienet mifruxa bejn 32% sa 80% (medja ta '50%).
These changes do not have any clinical significance.
L- ikel iżid il- ħin biex tintlaħaq l- ogħla konċentrazzjoni minn 6 sa 10 sigħat u jnaqqas b’ xi ftit l - ammont ta 'l- assorbiment (bejn wieħed u ieħor 11%). Dawn il- varjazzjonijiet m’ għandhom ebda sinifikat klinikament.
Duloxetine is approximately 96% bound to human plasma proteins.
Duloxetine huwa bejn wieħed u ieħor 96% marbut mal- proteini tal- plażma umana.
Duloxetine binds to both albumin and alpha-l acid glycoprotein.
Duloxetine jintrabat kemm ma 'l- albumina kif ukoll ma ’ alpha- 1 acid glycoprotein.
Protein binding is not affected by renal or hepatic impairment.
L - indeboliment tal- fwied jew tal- kliewi ma jaffettwax ir- rabta mal- proteini.
Duloxetine is extensively metabolised and the metabolites are excreted principally in urine.
Duloxetine huwa metaboliżżat b’ mod estensiv u l- eskrezzjoni tal- prodotti metaboliċi jsir l- aktar fl - urina.
Both cytochromes P450-2D6 and 1A2 catalyse the formation of the two major metabolites glucuronide conjugate of 4-hydroxy duloxetine and sulphate conjugate of 5hydroxy,6-methoxy duloxetine.
Kemm CYP 2D6 kif ukoll CYP 1A2 jikkatalizzaw il- formazzjoni taż- żewġ prodotti metaboliċi prinċipali l- glukuronidu kkonjugat ta '4- hydroxy duloxetine u l- konjugat tas- sulfat ta' 5- hydroxy, 6 - methoxy duloxetine.
Based upon in vitro studies, the circulating metabolites of duloxetine are considered pharmacologically inactive.
Ibbażati fuq studji in vitro, il- prodotti metaboliċi ta ’ duloxetine li jiċċirkolaw
The pharmacokinetics of duloxetine in patients who are poor metabolisers with respect to CYP2D6 has not been specifically investigated.
Il- farmakokinetika ta ’ duloxetine f’ pazjenti li huma metabolizzaturi dgħajjfa fir- rigward ta ’ CYP2D6 ma kinitx investigata b’ mod speċifiku.
Limited data suggest that the plasma levels of duloxetine are higher in these patients.
Tagħrif limitat jindika li l- livelli fil- plażma ta ’ duloxetine huma ogħla f’ dawn il- pazjenti.
The elimination half-life of duloxetine ranges from 8 to 17 hours (mean of 12 hours).
Il- half life ta ’ l- eliminazzjoni ta ’ duloxetine tvarja minn 8 sa 17- il siegħa (medja ta '12- il siegħa).
After an intravenous dose the plasma clearance of duloxetine ranges from 22 l/ hr to 46 l/ hr (mean of 36 l/ hr).
Wara doża minn ġol- vini t- tneħħija mill- plażma ta ’ duloxetine tvarja minn 22 l/ hr sa 46 l/ hr (medja ta '36 l/ hr).
After an oral dose the apparent plasma clearance of duloxetine ranges from 33 to 261 l/ hr (mean 101 l/ hr).
Wara doża orali, it- tneħħija apparenti ta ’ duloxetine mill- plażma tvarja minn 33 sa 261 l/ hr (medja 101 l/ hr).
Gender: pharmacokinetic differences have been identified between males and females (apparent plasma clearance is approximately 50% lower in females).
Sess: differenzi farmakokinetiċi kienu identifikati bejn l- irġiel u n- nisa (it- tneħħija apparenti mill - plażma huwa bejn wieħed u ieħor 50% inqas fin- nisa).
Based upon the overlap in the range of clearance, gender-based pharmacokinetic differences do not justify the recommendation for using a lower dose for female patients.
Minħabba li l- varjazzjonijiet ta ’ tneħħija jikkoinċidu, id- differenzi farmakokinetiċi minħabba s- sess ma jiġġustifikawx ir- rakkomandazzjoni ta ’ tnaqqis fid- doża għal pazjenti nisa.
Age: pharmacokinetic differences have been identified between younger and elderly females (≥ 65 years) (AUC increases by about 25% and half-life is about 25% longer in the elderly), although the magnitude of these changes is not sufficient to justify adjustments to the dose.
Età: differenzi farmakokinetiċi kienu identifikati bejn nisa żgħar u kbar (≥ 65 sena) (l- AUC jiżdied b’ madwar 25% u l- half life hi madwar 25% itwal fl- anzjani), għalkemm id- daqs ta 'dawn il- bidliet mhux biżżejjed biex jiġġustifikaw tibdil fid- doża.
As a general recommendation, caution should be exercised when treating the elderly (see sections 4.2 and 4.4).
Bħala rakkomandazzjoni ġenerali, il- kura ta ’ l - anzjani għandha tiġi segwita b’ attenzjoni (ara sezzjonijiet 4. 2 u 4. 4).
Renal impairment: end stage renal disease (ESRD) patients receiving dialysis had 2-fold higher duloxetine Cmax and AUC values compared with healthy subjects.
Indeboliment tal- kliewi: pazjenti b' mard terminali tal- kliewi (ESRD) li jirċievu id- dijaliżi kellhom valuri tas- Cmax u ta ’ l- AUC ta ’ duloxetine darbtejn ogħla minn dawk ta ’ pazjenti b' saħħithom.
Pharmacokinetic data on duloxetine is limited in patients with mild or moderate renal impairment.
It - tagħrif farmakokinetiku fuq duloxetine huwa limitat f’ pazjenti b’ indeboliment tal- kliewi ta ’ grad ħafif jew wieħed moderat.
Hepatic impairment: moderate liver disease (Child Pugh Class B) affected the pharmacokinetics of duloxetine.
Indeboliment tal- fwied: mard moderat fil- fwied (Child Pugh Klassi B) affettwa l- farmakokinetika ta ’ duloxetine.
Compared with healthy subjects, the apparent plasma clearance of duloxetine was 79% lower, the apparent terminal half-life was 2.3 times longer, and the AUC was 3.7 times higher in patients with moderate liver disease.
Imqabbla ma 'pazjenti b' saħħithom, it- tneħħija apparenti mill- plażma ta ’ duloxetine kienet 79% anqas, il- half life terminali apparenti kien 2. 3 darbiet itwal u l- AUC kien 3. 7 darbiet ogħla f' pazjenti li kellhom mard moderat fil- fwied.
The pharmacokinetics of duloxetine and its metabolites have not been studied in patients with mild or severe hepatic insufficiency.
Il- farmakokinetika ta ’ duloxetine u l- prodotti metaboliċi tiegħu ma kienux studjati f’ pazjenti b’ insuffiċjenza tal- fwied gravi jew ħafifa.
13 Nursing mothers:
Ommijiet li jreddgħu:
The disposition of duloxetine was studied in 6 lactating women who were at least 12-weeks postpartum.
Id- dispożizzjoni ta ’ duloxetine ġiet studjata f’ 6 nisa li kienu qegħdin ireddgħu u li kienu ilhom mill- inqas 12- il ġimgħa li kienu welldu.
Duloxetine is detected in breast milk, and steady-state concentrations in breast milk are about one-fourth those in plasma.
Duloxetine jinstab fil- ħalib ta ’ l- omm u l - konċentrazzjonijiet fissi fil- ħalib ta ’ l- omm huma kważi kwart dawk fil- plażma.
The amount of duloxetine in breast milk is approximately 7 µg/ day while on 40 mg twice daily dosing.
L- ammont ta ’ duloxetine fil- ħalib ta ’ l- omm huwa bejn wieħed u ieħor ta ’ 7µg/ day waqt li tkun fuq doża ta ’ 40mg darbtejn kuljum.
Lactation did not influence duloxetine pharmacokinetics.
It- treddigħ m’ affettwax il- farmakokinetika ta ’ duloxetine.
Duloxetine was not genotoxic in a standard battery of tests and was not carcinogenic in rats.
Duloxetine ma kienx ġenotossiku f’ firxa ta 'testijiet standard u ma kienx kanċeroġenu fil- firien.
Multinucleated cells were seen in the liver in the absence of other histopathological changes in the rat carcinogenicity study.
Ċelluli multinukleati dehru fil- fwied fl- assenza ta ’ kambjamenti istopatoloġiċi oħra fi studju fuq il - kanċeroġeniċità fil- far.
The underlying mechanism and the clinical relevance are unknown.
Il- mekkaniżmu involut u r- relevanza klinika mhumiex magħrufa.
Female mice receiving duloxetine for 2 years had an increased incidence of hepatocellular adenomas and carcinomas at the high dose only (144 mg/ kg/ day), but these were considered to be secondary to hepatic microsomal enzyme induction.
Ġrieden tas - sess femminili li rċevew duloxetine għal sentejn kellhom inċidenza ogħla ta 'adenomi u kanċer epatoċellulari fid- doża għolja biss (144 mg/ kg/ ġurnata), imma dawn kienu kkunsidrati li huma sekondarji għall- istimulazzjoni ta' l- enżima mikrożomali tal- fwied.
The relevance of this mouse data to humans is unknown.
Ir- relevanza ta 'dan it- tagħrif fil - ġrieden għall- bniedem mhix mgħarufa.
Female rats receiving duloxetine (45 mg/ kg/ day) before and during mating and early pregnancy had a decrease in maternal food consumption and body weight, oestrous cycle disruption, decreased live birth indices and progeny survival, and progeny growth retardation at systemic exposure levels estimated to be at the most at maximum clinical exposure (AUC).
Firien tas- sess femminil li rċevew duloxetine, qabel u waqt li kienu qed jgħamlu s- sess u fil- bidu tat- tqala, kellhom tnaqqis fil- konsum ta 'l- ikel matern u fil- piż, diżordni fiċ- ċiklu oestrous, nuqqas fl- indiċi ta' twelid ta 'frieħ hajjin u fis- sopravivenza tal- ferħ ta' l - annimal, u dewmien biex jikbru l- frieħ f’ livelli ta ’ espożizzjoni sistemika, stmata li hija mhux anqas mill- esponiment massimu kliniku (AUC).
In an embryotoxicity study in the rabbit, a higher incidence of cardiovascular and skeletal malformations was observed at systemic exposure levels below the maximum clinical exposure (AUC).
Fi studji embrojotossiċi fil- fenek, inċidenża ogħla ta ’ malformażżjoniijiet kardjovaskolari u skeletali kienu osservati f’ livelli ta ’ espożiżżjoni sistemika anqas mill- esponiment massimu kliniku (AUC).
No malformations were observed in another study testing a higher dose of a different salt of duloxetine.
L’ ebda malformażżjoni ma ’ kienet osservata f’ studju ieħor li eżamina doża ogħla ta ’ forma kimika differenti ta ’ duloxetine.
In prenatal/ postnatal toxicity studies in the rat, duloxetine induced adverse behavioural effects in the offspring at exposures below maximum clinical exposure (AUC).
Fi studju ta ’ tossiċità ta ’ qabel u wara t- twelid, fil- far, duloxetine ikkaġuna effetti avversi ta ’ komportament fil- frieħ, f’ livelli ta ’ espożiżżjoni sistemika anqas mill- esponiment massimu kliniku (AUC).
Capsule content:
Kontenut tal- kapsula:
Hydroxypropyl methylcellulose acetate succinate Sucrose Sugar spheres Talc Titanium dioxide (E171) Triethyl citrate.
Hypromellose Hydroxypropyl methylcellulose acetate succinate Sucrose Sferi taz- zokkor Talc Titanium dioxide (E171) Triethyl citrate.
Capsule shell:
Il- Qoxra tal- kapsula:
30 mg:
30mg:
Gelatin Sodium Lauryl Sulfate Titanium Dioxide (E171) Indigo Carmine (E132) Edible Green Ink
Gelatin Sodium Lauryl Sulfate Titanium Dioxide (E171) Indigo Carmine (E132) Inkjostru aħdar li jista ’ jittiekel
Edible Green Ink contains:
L- inkjostru aħdar li jittiekel fih:
Black Iron Oxide-Synthetic (E172) Yellow Iron Oxide- Synthetic (E172) Propylene glycol Shellac.
Iron oxide sintetiku iswed (E172) Iron oxide sintetiku isfar (E172) Propylene glycol Shellac
14 6.3 Shelf life
6. 3 Żmien kemm idum tajjeb il- prodott mediċinali
Do not store above 30º C.
Taħżinx f’ temperatura ’ l fuq minn 30°C
Polyvinylchloride (PVC), Polyethylene (PE), and Polychlorotrifluoroethylene (PCTFE) blister sealed with an aluminum foil.
Polyvinylchloride (PVC), Polyethylene (PE), u folja tal- polychlorotrifluoroethylene (PCTFE) issiġillata b' għatu tal- fojl ta 'l- aluminju.
CYMBALTA 30 mg is available in packs of 7, 28 and 98 capsules.
CYMBALTA 30mg issibu f’ pakketti ta ’ 7, 28 u 98 kapsula
6.6 Special precautions for disposal
6. 6 Prekawzjonijiet speċjali li għandhom jittieħdu meta jintrema < u għal immaniġġar ieħor >
Eli Lilly Nederland BV, Grootslag 1-5, NL-3991 RA Houten, The Netherlands.
Eli Lilly Nederland BV, Grootslag 1- 5, NL- 3991 RA Houten, L- Olanda
17 December 2004
17 ta ’ Diċembru 2004
CYMBALTA 60 mg hard gastro-resistant capsules
CYMBALTA 60 mg kapsuli gastro- reżistenti ibsin
Each capsule contains 60 mg of duloxetine (as hydrochloride).
Kull kapsula fiha 60 mg ta ’ duloxetine (bħala hydrochloride).
Excipients: sucrose 17.2 mg.
Sustanzi mhux attivi: sucrose 17. 2 mg.
The CYMBALTA 60 mg capsule has an opaque green body, imprinted with ‘ 60 mg’ and an opaque blue cap, imprinted with ‘ 9542’.
Il- kapsula ta ’ CYMBALTA 60 mg għandha l- parti prinċipali tagħha aħdar opak, stampat b ’ ‘ 60 mg ’ u għatu blu opak, stampat b ’ ‘ 9542 ’.
After consolidation of the response, it is recommended to continue treatment for several months, in order to avoid relapse.
18 Wara li jintlaħaq rispons suffiċjenti, huwa rakkomandat li l- kura tkompli għal ħafna xhur sabiex jiġi evitat li jkun hemm rikadenza.
16 Diabetic Peripheral Neuropathic Pain:
Uġigħ Newropatiku Periferiku Tad- dijabete:
Renal insufficiency No dosage adjustment is necessary for patients with mild or moderate renal dysfunction (creatinine clearance 30 to 80 ml/ min).
Insuffiċjenza tal- kliewii Mhux neċessarju aġġustament tad- doża għal pazjenti b’ disfunzjoni tal- kliewi ħafifa jew moderata (tneħħija tal- kreatinina minn 30 sa 80 ml/ min).
When stopping treatment with CYMBALTA the dose should be gradually reduced over a period of at least one to two weeks in order to reduce the risk of withdrawal reactions (see sections 4.4 and 4.8).
Meta l- kura b’ CYMBALTA tkun ser titwaqqaf id - doża għandha tiġi mnaqqsa gradwalment fuq perijodu ta ’ mill- anqas ġimgħa sa ġimagħtejn sabiex jitnaqqas ir- riskju ta ’ reazzjonijiet ta ’ rtirar (ara sezzjonijiet 4. 4 u 4. 8).
If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered.
Jekk ifeġġu sintomi intollerabbli wara tnaqqis fid- doża jew wara sospensjoni tal- kura, jista ’ jiġi kkunsidrat li terġa ’ tinbeda id- doża preċedenti ordnata.
Subsequently, the physician may continue decreasing the dose, but at a more gradual rate.
Sussegwentement, it- tabib jista ’ jkompli jnaqqas id- doża, iżda b’ rata aktar gradwali.
Severe renal impairment (creatinine clearance < 30 ml/ min) (see section 4.4).
19 Indeboliment gravi tal- kliewi (tneħħija tal- kreatinina < 30 ml/ min) (ara sezzjoni 4. 4).
The initiation of treatment with CYMBALTA is contraindicated in patients with uncontrolled hypertension that could expose patients to a potential risk of hypertensive crisis (see sections 4.4 and 4.8).
Huwa kontra- indikat li tinbeda l- kura b’ CYMBALTA f’ pazjenti b’ pressjoni għolja mhux ikkontrollata li tista ’ tesponi l- pazjenti għal riskju potenzjali ta ’ kriżi ipertensiva (ara sezzjonijiet 4. 4 u 4. 8).
17 4.4 Special warnings and precautions for use
4. 4 Twissijiet speċjali u prekawzjonijiet għall- użu
Mania and seizures CYMBALTA should be used with caution in patients with a history of mania or a diagnosis of bipolar disorder, and/ or seizures.
Manija u aċċessjonijiet CYMBALTA għandu jintuża b’ attenzjoni f’ pazjenti b’ storja ta ’ manija jew b’ dijanjosi ta ’ mard bipolari, u/ jew aċċessjonijiet.
Renal impairment Increased plasma concentrations of duloxetine occur in patients with severe renal impairment on haemodialysis (creatinine clearance < 30 ml/ min).
Indeboliment tal- kliewii Pazjenti b’ indeboliment gravi tal- kliewi li għandhom bżonn dijalisi tad- demm (tneħħija tal- kreatinina < 30 ml/ min) kellhom żieda fil- konċentrazzjoni ta ’ duloxetine fil- plażma.
Patients with a history of suicide-related events or those exhibiting a significant degree of suicidal thoughts prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicidal behaviour, and should receive careful monitoring during treatment.
Huwa magħruf li pazjenti b’ passat ta ’ avvenimenti marbuta ma ’ suwiċidju jew dawk li juru ammont sinifikanti ta ’ hsibijiet ta ’ suwiċidju qabel ma tibda l- kura huma f’ riskju ogħla li jkollhom ħsibijiet ta ’
A meta-analysis of placebo-controlled clinical trials of antidepressant medicinal products in psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old.
Analiżi ta ’ numru ta ’ studji kliniċi kkontrollati bil- plaċebo ta ’ prodotti mediċinali antidipressivi li ntużaw f’ disturbi psikjatriċi wrew riskju ogħla ta ’ mġiba suwiċidali bl- antidipressivi meta mqabbla ma ’ plaċebo f’ pazjenti iżgħar minn 25 sena.
18 Close supervision of patients and in particular those at high risk should accompany medicinal product therapy especially in early treatment and following dose changes.
Sorveljanza bir- reqqa tal- pazjenti b’ mod partikolari dawk li huma l- iżjed f’ riskju għandha takkumpanja t- terapija bi prodotti mediċinali speċjalment fil- bidu tal- kura u wara xi tibdil fid- doża.
Patients, (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.
Il - pazjenti, (u min jieħu ħsiebhom) għandhom jiġu mwissija dwar il- ħtieġa li joqgħodu attenti għal xi bidla għall- agħar fil- kwadru kliniku, mġiba jew ħsibijiet suwiċidali jew tibdil fl- imġiba mhux tas- soltu u li jfittxu parir mediku immedjatament jekk joħorġu dawn is- sintomi.
Physicians should encourage patients to report any distressing thoughts or feelings at any time.
Fir- rigward ta ’ fatturi ta ’ riskju għal tendenza ta ’ suwiċidju waqt id- dipressjoni, are fuq It- tobba għandhom iħeġġu lill- pazjenti biex jirrappurtaw xi ħsibijiet jew sentimenti li jnikktu, f’ kull ħin.
Suicide-related behaviours (suicide attempts and suicidal thoughts), and hostility (predominantly aggression, oppositional behaviour and anger), were more frequently observed in clinical trials among children and adolescents treated with antidepressants compared to those treated with placebo.
Imġiba assoċjata mas- suwiċidju (attentati ta ’ suwiċidju u ħsibijiet suwiċidali), u ostilità (l- aktar aggressjoni, imġiba konfrontali, u rabja), kienu osservati aktar spiss f’ provi kliniċi fuq tfal u adolexxenti kkurati b’ anti- depressivi meta mqabbla ma ’ dawk ikkurati bil - plaċebo.
If, based on clinical need, a decision to treat is nevertheless taken, the patient should be carefully monitored for the appearance of suicidal symptoms.
Jekk, fuq il- bażi tal- bżonn kliniku, madankollu tittieħed deċiżjoni biex tingħata l- kura, il - pazjent għandu jinżamm taħt osservazzjoni għad- dehra ta ’ sintomi suwiċidali.
Caution is required in patients at increased risk for hyponatremia; such as elderly, cirrhotic, or dehydrated patients or patients treated with diuretics.
Tinħtieġ attenzjoni f’ pazjenti f’ riskju akbar ta ’ iponatrimja; bħal anzjani, pazjenti b’ ċirrożi jew diżidratati, jew pazjenti fuq kura ta ’ dijuretiċi.
Generally these symptoms are self-limiting and usually resolve within 2 weeks, though in some individuals they may be prolonged (2-3 months or more).
Ġeneralment dawn is- sintomi ma jiżdidux u s- soltu jieqfu fi żmien ġimagħtejn, għalkemm f’ xi individwi jistgħu jdumu aktar (2- 3 xhur jew aktar).
It is therefore advised that duloxetine should be gradually tapered when discontinuing treatment over a period of no less than 2 weeks, according to the patient’ s needs (see section 4.2).
Għalhekk huwa rrakkomandat li f’ sospensjoni tal- kura duloxetine jiġi mnaqqas bil- ftit il- ftit fuq perijodu ta ’ mhux anqas minn ġimagħtejn, skond il- bżonnijiet tal- pazjent (ara sezzjoni 4. 2).
Elderly Major Depressive Episodes:
21 Anzjani Episodji Depressivi Maġġuri:
Data on the use of CYMBALTA 120mg in elderly patients with major depressive disorders are limited..
L- informazzjoni dwar l- użu ta ’ CYMBALTA 120 mg f’ pazjenti anzjani b’ mard depressiv maġġuri hija limitata.
19 Akathisia/ psychomotor restlessness The use of duloxetine has been associated with the development of akathisia, characterised by a subjectively unpleasant or distressing restlessness and need to move often accompanied by an inability to sit or stand still.
Akatiżja/ irrekwitezza psikomotorja L- użu ta ’ duloxetine ġie assoċjat ma ’ żvilupp ta ’ akatiżja, ikkaraterrizzata minn irrekwitezza soġġettivament mhux pjaċevoli jew ta ’ sofferenza u mill- ħtieġa ta ’ tħarrik spiss flimkien ma ’ l - inabbilità li wieħed joqgħod bilqiegħda jew ma jitħarrikx.
In patients who develop these symptoms, increasing the dose may be detrimental.
F’ pazjenti li jiżviluppaw dawn is- sintomi, jista ’ jkun ta ’ detriment li tiżdied id- doża
The pattern of liver damage was predominantly hepatocellular.
Il- ħsara fil- fwied kienet l- aktar dik epatoċellolari.
Effect of duloxetine on other medicinal products Medicinal products metabolised by CYP1A2:
22 Effett ta ’ duloxetine fuq prodotti mediċinali oħra Prodotti mediċinali li jiġu metabolizzati minn CYP1A2:
Caution is advised if CYMBALTA is co-administered with medicinal products that are predominantly metabolised by CYP2D6 (risperidone, tricyclic antidepressants [TCAs] such as 20 nortriptyline, amitriptyline, and imipramine) particularly if they have a narrow therapeutic index (such as flecainide, propafenone and metoprolol).
Hu rrakkomandat li CYMBALTA jingħata b’ attenzjoni jekk jittieħed flimkien ma ’ prodotti mediċinali li huma fil- biċċa l- kbira metabolizzati min CYP2D6 (risperidone, anti - depressivi triċikliċi [TCAs] bħal nortriptyline, amitriptyline, u imipramine) speċjalment jekk għandhom indiċi terapewtiku dejjaq (bħal flecainide, propafenone u metoprolol).
As with other serotoninergic medicinal product, discontinuation symptoms may occur in the neonate after maternal duloxetine use near term.
Bħal ma jiġri bi prodotti mediċinali serotoninerġiċi oħra, sintomi ta ’ sospensjoni jistgħu jseħħu f’ trabi tat- twelid wara l- użu fl- omm ta ’ duloxetine qrib il - ħlas.
The estimated daily infant dose on a mg/ kg basis is approximately 0.14% of the maternal dose (see section 5.2).
Huwa kkalkulat li d- doża ta ’ kuljum fit- trabi fuq bażi ta ’ mg/ kg hija bejn wieħed u ieħor 0. 14% tad- doża materna (ara sezzjoni 5. 2).
4.7 Effects on ability to drive and use machines
23 4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni
21 The most commonly reported adverse reactions in patients treated with CYMBALTA were nausea, headache, dry mouth, somnolence, fatigue, insomnia, dizziness and constipation.
L- aktar reazzjonijiet avversi komunement irrappurtati f’ pazjenti fuq kura ta ’ CYMBALTA kienu dardir, uġigħ ta ’ ras, ħalq xott, ngħas, għeja, insomnja, sturdament u stitikezza.
Nausea (25.2%) Dry mouth (13.8%) Constipation (10.3%)
Riħa ħażina
Diarrhoea Vomiting Dyspepsia Flatulence
Emorraġija
Gastroenteritis Eructation Gastritis Stomatitis
Tqalligħ
22
Dijarea
Breath odour Haematochezi a
Gastro- enterite
Gastrointesti nal haemorrhage
fil- ħalq
Renals and Urinary
Gastrite Stomatite
Disorders
Disturbi fil- kliewi u fis- sistema urinarja
Urinary Retention Dysuria Urinary hesitation Nocturia Polyuria Urine flow decreased
Żamma ta ’ l - awrina Disurja Eżitazzjoni
Urine odour abnormal
Riħa mhux normali ta ’ l - awrina
General Disorders and Administration Site Conditions Fatigue (10.8%)
26 Disturbi ġenerali u kondizzjonijiet ta ’ mnejn jingħata Għeja (10. 8%)
Abdominal pain Chills
Uġigħ addominali Tkexkix
Feeling abnormal Feeling cold Thirst
Ma tħossokx normali Tħoss il - bard Għatx Tħossok mitluq Tħoss is - sħana Problemi fil- mod ta ’ kif timxi
Chest pain
Uġigħ fis- sider
23
Disturbi fis- sistema immuni Disturbi fil- fwied u fil- marrara
Very common
Mard ta ’ sensitività eċċessiva
Uncommon
Reazzjoni anafilattika
Rare
Enzimi tal - fwied għoljin (ALT, AST, alkaline phosphatase Epatite3 Dannu akut fil- fwied)
Frequency not known
Suffejra Insuffiċjenza epatika
Malaise Feeling hot Gait disturbance
Disturbi fis- sistema riproduttiva u fis- sider
Immune system disorders Hepato-biliary disorders
Il- funzjoni erettili ma
Hyper- sensitivity disorder
Problemi ta ’ eġakulazzjoni
Anaphylactic reaction
Sintomi ta ’ menopawża
Elevated liver enzymes (ALT, AST, alkaline phosphatase) Hepatitis3 Acute liver injury
taħdimx normali Dewmien fl - eġakulazzjoni Problemi sesswali Emorraġija ginekoloġika
Jaundice Hepatic failure
27 Disturbi psikjatriċi Insomnja (10. 4%)
Reproductive System and Breast Disorders
Aġitazzjoni Tnaqqis fil -
Erectile dysfunction
Tgħażżiż tas - snien
Ejaculation disorder Ejaculation delayed Sexual dysfunction Gynaecologica l haemorrhage
Manija Alluċinazzjonijiet Aggressjoni u
Menopausal symptoms
Formazzjoni ta ’ ideat suwiċidali5
Psychiatric Disorders Insomnia
libido
Agitation
involontarju
Dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), fatigue, agitation or anxiety, nausea and/ or vomiting, tremor, headache, irritability, diarrhoea, hyperhydrosis and vertigo are the most commonly reported reactions.
Sturdament, disturbi tas- sensi (fosthom parastizja), disturbi fl- irqad, (fosthom insomnja u ħolm intens), għeja, aġitazzjoni jew ansjetà, dardir u/ jew rimettar, rogħda, wġigħ ta ’ ras, irritabilità, dijarea, iperidrożi u vertigo huma l- aktar reazzjonijiet komunement irrappurtati.
It is therefore advised that when duloxetine
Ġeneralment, fl- SSRIs u fl- SNRIs, dawn l- avveniment jkunu minn ħfief sa moderati u ma jiżdidux, iżda f’ xi pazjenti jistgħu jkunu qawwija u/ jew jieħdu fit- tul.
24 treatment is no longer required, gradual discontinuation by dose tapering should be carried out (see sections 4.2 and 4.4).
Għaldaqstant, huwa rrakkomandat li meta l- kura b’ duloxetine m’ għadhiex mehtieġa, is- sospensjoni għandha tkun gradwali billi d- doża tiġi mnaqqsa bil- ftit il- ftit (ara sezzjonijiet 4. 2 u 4. 4).
In the 12 week acute phase of three clinical trials of duloxetine in patients with diabetic neuropathic pain, small but statistically significant increases in fasting blood glucose were observed in duloxetine- treated patients HbA1c was stable in both duloxetine-treated and placebo-treated patients.
Fil- fażi akuta ta ’ 12- il ġimgħa ta ’ tliet provi kliniċi ta ’ duloxetine f’ pazjenti b’ uġigħ newropatiku tad - dijabete, ġew osservati żidiet żgħar iżda statistikament sinifikanti fil- livell ta ’ glucose fid- demm waqt is- sawm f’ pazjenti fuq kura ta ’ duloxetine.
Signs and symptoms of overdose (duloxetine alone or with mixed medicinal products) included somnolence, coma, serotonin syndrome, seizures,, vomiting and tachycardia.
Is- sinjali u s- sintomi ta ’ doża eċċessiva (duloxetine waħdu jew b’ taħlit ta ’ prodotti mediċinali) jinkludu ngħas, koma, sindromu ta ’ serotonin, rimettar u takikardija.
The efficacy of CYMBALTA at the recommended dose of 60 mg once a day was demonstrated in three out of three randomized, double- blind, placebo-controlled, fixed dose acute studies in adult outpatients with major depressive disorder.
L- effikaċja ta ’ CYMBALTA fid - doża rakkomandata ta ’ 60mg darba kuljum ġiet ppruvata fit- tlieta minn tliet studji li saru f’ sitwazzjonijiet akuti, b’ doża fissa, randomised, double- blind u kkontrollati bil- plaċebo f’ pazjenti li mhumiex residenti ġo sptar u li għandhom mard depressiv maġġuri.
25 CYMBALTA demonstrated statistical superiority over placebo as measured by improvement in the 17-item Hamilton Depression Rating Scale (HAM-D) total score (including both the emotional and somatic symptoms of depression).
Cymbalta statistikament wera superjorità fuq plaċebo ikkalkulat skond it- titjib fil- punteġġ totali tal - Hamilton Depression Rating Scale( HAM- D) bi 17- il kriterju (li jinkludu kemm sintomi ta ’ depressjoni emozzjonali kif ukoll dawk somatiċi).
However, data on elderly patients exposed to the maximum dose (120mg per day) are limited and thus, caution is recommended when treating this population.
Madankollu, t- tagħrif fuq pazjenti li ġew mgħotija d- doża massima (120mg kuljum) huwa limitat u għalhekk huwa rakkomandat li toqgħod attent meta tkun qiegħed tikkura din il- popolazzjoni ta ’ pazjenti.
CYMBALTA demonstrated statistically significant superiority over placebo as measured by improvement in the Hamilton Anxiety Scale (HAM-A) total score and by the Sheehan Disability Scale (SDS) global functional impairment score.
29 CYMBALTA wera superjorità statistikament sinifikanti fuq plaċebo kemm meta kkalkulat skond it - titjib fil- punteġġ totali tal- Hamilton Anxiety Scale( HAM- A) u kemm skond il- punteġġ ta ’ indeboliment funzjonali globali tas- Sheehan Disability Scale (SDS).
Clinical response rates (50% or greater improvement in pain) were analysed according to whether or not the patient experienced somnolence during treatment.
Ir- rati ta ’ rispons kliniku (50% jew iżjed ta ’ titjib fl- uġigħ) kienu analizzati skond jekk il- pazjent qabdux n- ngħas jew le waqt il- kura.
26 Although data from a one-year open label study offer some evidence for longer-term efficacy, no conclusive efficacy data for treatments longer than 12 weeks duration are available from placebo- controlled studies.
Għalkemm tagħrif minn studju open- label ta ’ sena juri xi evidenza ta ’ effikaċja fit- tul, minn studji kkontrollati bil- plaċebo m’ hemmx tagħrif konklużiv dwar l- effikaċja ta ’ kura għal iżjed minn 12- il ġimgħa.
Based upon in vitro studies, the circulating metabolites of duloxetine are considered pharmacologically inactive.
Ibbażati fuq studji in vitro, il- prodotti metaboliċi ta ’ duloxetine li jiċċirkolaw huma kkunsidrati farmakoloġikament inattivi.
The pharmacokinetics of duloxetine in patients who are poor metabolisers with respect to CYP2D6 has not been specifically investigated.
Il- farmakokinetika ta ’ duloxetine f’ pazjenti li huma
Nursing mothers:
Ommijiet li jreddgħu:
The disposition of duloxetine was studied in 6 lactating women who were at least 12-weeks postpartum.
Id- dispożizzjoni ta ’ duloxetine ġiet studjata f’ 6 nisa li kienu qegħdin jipproduċu ħalib u li kienu ilhom mill- inqas 12- il ġimgħa li kienu welldu.
Duloxetine is detected in breast milk, and steady-state concentrations in breast milk are about one-fourth those in plasma.
Duloxetine jinstab fil- ħalib ta ’ l- omm u l- konċentrazzjonijiet fissi fil- ħalib ta ’ l- omm huma kważi kwart dawk fil- plażma.
Lactation did not influence duloxetine pharmacokinetics
It- treddigħ m’ affettwax il- farmakokinetika ta ’ duloxetine.
27 5.3 Preclinical safety data
5. 3 Tagħrif ta 'qabel l- użu kliniku dwar is- sigurtà tal- mediċina
In prenatal/ postnatal toxicity studies in the rat, duloxetine induced adverse behavioural effects in the offspring at exposures below maximum clinical exposure (AUC).
Fi studju ta ’ tossiċità ta ’ qabel u wara t- twelid, fil- far, duloxetine ikkaġuna effetti avversi ta ’ komportament fil- frieħ, fl- livelli ta’ espożizzjoni sistemika anqas mill- esponiment massimu kliniku (AUC).
60 mg:
60mg:
Gelatin Sodium Lauryl Sulfate Titanium Dioxide (E171) Indigo Carmine (E132) Yellow Iron Oxide (E172) Edible White Ink
Gelatin Sodium Lauryl Sulfate Titanium Dioxide (E171) Indigo Carmine (E132) Iron Oxide Isfar (E172) Inkjostru Abjad li jittiekel
Edible White Ink contains:
L- inkjostru Abjad li jittiekel fih:
Titanium Dioxide (E171) Propylene glycol Shellac Povidone.
Titanium Dioxide (E171) Propylene Glycol Shellac Povidone
28 6.4 Special precautions for storage
6. 4 Prekawzjonijiet speċjali għall- ħażna
CYMBALTA 60 mg is available in packs of 28, 56, 84, 98, 100 (Each pack contains 5 cartons of 20 capsules) and 500 capsules (Each pack contains 25 cartons of 20 capsules).
CYMBALTA 60mg issibu f’ pakketti ta ’ 28, 56, 84, 98, 100 (Kull pakkett fih 5 kartuni ta ’ 20 kapsula) u 500 kapsula (Kull pakkett fih 25 kartuna ta ’ 20 kapsula).
29 ANNEX II
33 ANNESS II
MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH RELEASE
DETENTUR( I) TA ’ L- AWTORIZZAZZJONI TAL - MANIFATTURA RESPONSABBLI GĦALL- HRUĠ TAL - LOTT B.
30 A MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH RELEASE
DETENTUR (I) TA ’ L- AWTORIZZAZZJONI TAL- MANIFATTURA RESPONSABBLI GĦALL- HRUĠ TAL- LOTT
Avda. de la Industria Nº 30, 28108 Alcobendas Madrid Spain
Lilly SA Avda. de la Industria N0 30 28108 Alcobendas Madrid Spanja
Risk Management Plan The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the Pharmacovigilance Plan, as agreed in version 03 of the Risk Management Plan (RMP) presented in Module 1.8.2. of the Marketing Authorisation Application and any subsequent updates of the RMP agreed by the CHMP.
Pjan dwar l- Immaniġġar tar- Riskju L- MAH jintrabat li jagħmel l- istudji u l- attivitajiet addizzjonali ta ’ farmakoviġilanza mniżżlin fil- Pjan ta ’ Farmakoviġilanza, kif miftiehem fil- verżjoni 03 tal- Pjan dwar l- Immaniġġar tar- Riskju (RMP) ippreżentat fit- Taqsima 1. 8. 2 ta ’ l- Applikazzjoni għall- Awtorizzazzjoni għat- Tqegħid fis- Suq u f’ kull aġġornament ta ’ l- RMP li jista ’ jkun hemm u li jkun qabel miegħu is- CHMP.
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, any updated RMP should be submitted at the same time as the following Periodic Safety Update Report (PSUR).
Kif hemm fil- Linji Gwida tas- CHMP dwar is- Sistemi ta ’ l- Immaniġġar tar- Riskju għal prodotti mediċinali għall- użu fil- bniedem, kull RMP aġġornat għandu jiġi ppreżentat fl- istess żmien mar - Rapport ta ’ Aġġornament Perjodiku dwar is- Sigurtà (PSUR) li jkun imiss.
In addition, an updated RMP should be submitted • When new information is received that may impact on the current Safety Specification, Pharmacovigilance Plan or risk minimisation activities • Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being reached • At the request of the EMEA
Meta jkun hemm informazzjoni ġdida li jista ’ jkollha impatt fuq l- Ispeċifikazzjonijiet tas - Sigurtà, fuq il- Pjan ta ’ Farmakoviġilanza jew fuq l- attivitajiet li jnaqqsu ir- riskju li jkunu jgħoddu f’ dak il- mument.
31 ANNEX III
35 ANNESS III
33 PARTICULARS TO APPEAR ON THE OUTER PACKAGING
37 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA
CARTONS FOR 30 MG HARD GASTRO-RESISTANT CAPSULES
KARTUN GĦALL- KAPSULI GASTRO- REŻISTENTI IBSIN TA ’ 30 MG
Duloxetine
CYMBALTA 30mg, kapsuli gastro- reżistenti ibsin Duloxetine
Each capsule contains 30 mg of duloxetine as hydrochloride
Kull kapsula fiha 30mg ta ’ duloxetine bħala hydrochloride
Contains sucrose See leaflet for further information
Fih is- sucrose
7 hard gastro-resistant capsules 28 hard gastro-resistant capsules 98 hard gastro-resistant capsules
7 kapsuli gastro- reżistenti ibsin 28 kapsula gastro- reżistenti iebsa 98 kapsula gastro- reżistenti iebsa
Store in the original package.
Aħżen fil- pakkett oriġinali.
Eli Lilly Nederland BV, Grootslag 1-5, NL-3991 RA, Houten, The Netherlands.
Eli Lilly Nederland BV, Grootslag 1- 5, NL- 3991 RA Houten, L- Olanda
CYMBALTA 30 mg
CYMBALTA 30mg
35 MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 30 mg hard gastro-resistant capsules
39 TAGĦRIF MINIMU LI GĦANDU JIDHER FUQ L- ISTRIXXI JEW FUQ IL- FOLJI
CYMBALTA 30 mg hard gastro-resistant capsules Duloxetine
CYMBALTA 30mg kapsuli gastro- reżistenti ibsin Duloxetine
36 PARTICULARS TO APPEAR ON THE OUTER PACKAGING
40 TAGĦRIF LI GĦANDU JIDHER FUQ IL- PAKKETT TA ’ BARRA
CARTONS FOR 60 MG HARD GASTRO-RESISTANT CAPSULES
KARTUN GĦALL- KAPSULI GASTRO- REŻISTENTI IBSIN TA ’ 60 MG
Duloxetine
CYMBALTA 60mg, kapsuli gastro- reżistenti ibsin Duloxetine
Each capsule contains 60 mg of duloxetine as hydrochloride
Kull kapsula fiha 60mg ta ’ duloxetine bħala hydrochloride
28, hard gastro-resistant capsules 56, hard gastro-resistant capsules 84, hard gastro-resistant capsules 98, hard gastro-resistant capsules 100, hard gastro-resistant capsules (5 cartons of 20 capsules) 500, hard gastro-resistant capsules (25 cartons of 20 capsules).
28, kapsula gastro- reżistenti iebsa 56, kapsula gastro- reżistenti iebsa 84, kapsula gastro- reżistenti iebsa 98, kapsula gastro- reżistenti iebsa 100, kapsula gastro- reżistenti iebsa (5 kartuni ta ’ 20 kapsula) 500, kapsula gastro- reżistenti iebsa (25 kartuna ta ’ 20 kapsula)
Read the leaflet before use
Użu orali Aqra l- fuljett ta ’ tagħrif qabel l- użu.
EU/ 1/ 04/ 296/ 002-005 EU/ 1/ 04/ 296/ 007 EU/ 1/ 04/ 296/ 008
EU/ 1/ 04/ 296/ 002 - 005 EU/ 1/ 04/ 296/ 007 EU/ 1/ 04/ 296/ 008
CYMBALTA 60 mg
CYMBALTA 60mg
38 MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 60 mg hard gastro-resistant capsules
42 TAGĦRIF MINIMU LI GĦANDU JIDHER FUQ L- ISTRIXXI JEW FUQ IL- FOLJI
CYMBALTA 60 mg hard gastro-resistant capsules Duloxetine
CYMBALTA 60mg kapsuli gastro- reżistenti ibsin Duloxetine
1 PACKAGE LEAFLET:
44 FULJETT TA ’ TAGĦRIF:
CYMBALTA 30 mg hard gastro-resistant capsules CYMBALTA 60 mg hard gastro-resistant capsules Duloxetine (as hydrochloride)
CYMBALTA 30 mg kapsuli gastro- reżistenti ibsin CYMBALTA 60 mg kapsuli gastro- reżistenti ibsin Duloxetine (bħala hydrochloride)
What CYMBALTA is and what it is used for 2.
X’ inhu CYMBALTA u għalxiex jintuża 2.