qanastek/EMEA-V3 huggingface dataset:
• Other psychiatric conditions Therapy with rimonabant is not recommended in patients with uncontrolled psychiatric illness. d
• Kundizzjonijiet psikjatriċi oħra ed
If psychiatric illness is diagnosed during rimonabant therapy, treatment must be stopped. ro
Jekk waqt it- terapija b’ rimonabant jiġi dijanostikat mard psikjatriku, il- kura għanda tieqaf tt m
In clinical trials no difference ina
• Attakki Epilettiċi Rimonabant ma ġiex studjat f’ dawk il- pazjenti li qed jiġu ikkurati ghall- epilessija.
in the incidence of seizures was seen in patients receiving rimonabant or placebo.
Fi provi kliniċi, ma kienx hemm differenza fl- inċidenza ta ’ attakki epilettiċi f’ pazjenti li rċevew rimonabant jew il- plaċebo.
Rimonabant, however, should be used with caution in these patients, see also section 5.3. dic
Madankollu, rimonabant għandu jintuża b’ kawtela f’ dawn il - pazjenti, ara ukoll sezzjoni do
• Hepatic impairment Rimonabant is metabolised by the liver, thus caution is advised in patients with moderate hepatic Me
• Indeboliment tal- fwied Pro
impairment.
Rimonabant huwa metaboliżżat mill- fwied, għalhekk, hija irrakkomandata l- kawtela f’ pazjenti b’ indeboliment moderat tal- fwied.
The pharmacokinetics and safety of rimonabant have not been studied in patients with severe hepatic impairment; its use in these patients is not recommended.
Il- komportament farmakokinetiku u s- sigurtà ta ’ rimonabant ma ġiex studjat f’ pazjenti b’ indeboliment sever tal- fwied; l- użu f’ dawn il- pazjenti mhux irrakkomandat.
• Renal impairment There are limited data in patients with moderate renal impairment and no data in patients with severe renal impairment.
• Indeboliment renali Hemm data limitata dwar pazjenti li għandhom indeboliment renali moderat u m’ hemmx data dwar pazjenti b’ indeboliment renali sever.
Rimonabant should not be used in patients with severe renal impairment (see section 4.2 and 5.2).
Rimonabant m’ għandux jintuża f’ pazjenti li għandhom indeboliment renali sever (ara sezzjoni 4. 2 u 5. 2).
• Elderly The efficacy and safety of rimonabant treatment in patients over 75 years of age has not sufficiently been established.
3 • Anzjani L- effikaċja u s- sigurtà bit- trattament b’ rimonabant f’ pazjenti ’ l fuq minn 75 sena ma ġewx stabbiliti biżżejjed.
Rimonabant should be used with caution in this population (see section 5.2).
Rimonabant għandu jintuża b’ kawtela f’ dan il- grupp ta ’ pazjenti (ara sezzjoni 5. 2).
3 • Race The clinical effect (weight loss) of rimonabant in Black patients was lower than in Caucasians.
Dan
This could be caused by a higher rimonabant clearance than in Caucasians resulting in a lower exposure (see section 5.2).
at seta ’ kien dovut għat- tneħħija aktar mgħaġġla ta rimonabant mill- ġisem fis- Suwed komparat mal - Kawkasi, li ikkaġġunat espożizzjoni aktar baxxa (ara sezzjoni 5. 2).
• Diabetic patients
izz • Pazjenti dijabetiċi Minħabba l- effett ta ’ rimonabant fuq il- livell ta ’ glucose fid- demm, meta rimonabant jingħata
Due to the effect of rimonabant on the blood glucose level, when rimonabant is administered in diabetic patients, hypoglyceamia can occur (see section 4.8).
tor f’ pazjenti dijabetiċi, tista ’ sseħħ l- ipogliċemija (ara sezzjoni 4. 8).
Monitoring of blood glucose level is recommended in these patients.
Huwa rakkomandat li f’ dawn il - pazjenti l- livell ta ’ glucose fid- demm ikun iċċekkjat b’ mod regolari.
• Drug Interaction Rimonabant should be used with caution in combination with potent CYP3A4 inhibitors (e. g. ketoconazole, itraconazole, ritonavir, telithromycin, clarithromycin, nefazodone)(see section 4.5).
aw • Interazzjoni bejn mediċini Rimonabant għandu jintuża b’ kawtela meta jingħata flimkien ma ’ inibituri qawwija ta ’ CYP3A4 (bhal ketoconazole, itraconazole, ritonavir, telithromycin, clarithromycin, nefazodone); ara sezzjoni 4. 5.
d ise • Lactose Since ZIMULTI tablets contain lactose, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption, should not take this
ux • Lattosju Peress li l- pilloli ta ’ ZIMULTI għandhom il- lattosju, pazjenti b’ mard rari ereditarju ta ’ intolleranza ad ghall - galattosju, id- defiċjenza tal- lactase tat- tip Lapp jew in- nuqqas ta ’ assorbiment tal- glukosju u l - galattosju, m’ għandhomx jieħdu din il- mediċina. għ Il- pazjenti għandhom ikunu mwissija biex ma jżiedux id- doża ta ’ ZIMULTI.
or medicine.
Pazjenti li kellhom xi attakk ta’ mard tal qalb u dak vaskulari (bħal infart tal- qalb u puplesija eċċ), m ’
uth Patients should be instructed not to increase their dose of ZIMULTI.
inqas minn 6 xhur qabel, kienu esklużi mill- istudji fuq rimonabant.
ra Patients who had a cardiovascular event (myocardial infarction, stroke, etc.) less than 6 months ago were excluded in the studies for rimonabant. ge 4.5 Interaction with other medicinal products and other forms of interaction on ol
4. 5 Prodotti mediċinali oħra li ma jaqblux ma ’ dan il- prodott u affarijiet oħra li jistgħu jibdlu li li
Rimonabant is metabolized by both CYP3A and amidohydrolase (predominantly hepatic) pathways in vitro.
In- vitro, rimonabant huwa metaboliżżat mis- sistemi ta ’ CYP3A u l- amidohydrolase a
rimonabant.
(predominantement dik tal- fwied).
Concomitant administration of CYP3A4 inducers is expected to reduce the exposure of rimonabant. uc
Meta inibituri ta ’ CYP3A4 jingħataw konkomitanti ma ’ rimonabant iċin
Potential for other medicinal products to affect rimonabant: d
dan iwassal għal espożizzjoni akbar ta ’ rimonabant.
Concomitant administration of ketoconazole (a potent CYP3A4 inhibitor) increased rimonabant AUC ro
Il- potenzjal ta ’ prodotti mediċinali li jeffetwaw rimonabant: ed
Caution is advised during concomitant use of ZIMULTI and potent lp
Il- kawtela hija irrakkomandata fl- użu simultanju ta ’ tt m
CYP3A4 inhibitors (e. g. ketoconazole, itraconazole, ritonavir, telithromycin, clarithromycin, ina
ZIMULTI u inibituri qawwija ta ’ CYP3A4 (bħal ketoconazole, ritonavir, telithromycin, clarithromycin u nefazodone).
Although concomitant administration of CYP3A4 inducers (e. g. rifampicin, phenytoin, phenobarbital, carbamazepine, St John’ s wort) has not been studied, it is expected that concomitant administration of dic
Għalkemm it- teħid ta ’ rimonabant flimkien ma ’ sustanzi li jistimulaw CYP3A4 (bħal rifampicin, phenytoin, phenobarbital, carbamazepine u St John’ s wort) ma ġiex studjat, huwa mistenni li l- użu do
potent CYP3A4 inducers may reduce the plasma concentration of rimonabant and may result in loss of efficacy.
konkomitanti ta ’ sustanzi li jinduċu CYP3A4, jistgħu jnaqqsu l- ammont ta ’ rimonabant fil- plażma u dan jirriżulta f’ nuqqas ta ’ effikaċja.
Me
Pro
Concomitant administration of orlistat, ethanol or lorazepam had no significant effect on the plasma levels of rimonabant.
L- użu konkomitanti ta ’ orlistat, ethanol jew lorazepam ma ’ rimonabant ma kellux effett sinifikanti fuq il- livelli ta ’ rimonabant fil- plażma.
However, in vitro, rimonabant had a mild inhibitory effect on CYP2C8.
Madankollu, ir- rimonabant kellu effett inibitorju ħafif fuq CYP2C8 in vitro.
This was confirmed clinically with specific probe studies using midazolam (CYP 3A4 substrate) and warfarin (CYP 2C9 substrate) and digoxin (a P-gp substrate).
Dan kien ikkonfermat klinikament fi studji xierqa u speċifiċi meta ntużaw midazolam (li CYP3A4 jaħdem fuqu), warfarin (li CYP2C9 jaħdem fuqha) u digoxin (li P- gp jaħdem fuqu).
Animal data are inconclusive but suggest possible deleterious effects on embryonal/ foetal development (see section 5.3).
Id- data fl- annimali mhumiex konklussivi iżda jissuġerixxu li jista ’ jkollu possibbilment jagħmel ħsara fuq l- iżvilupp ta ’ l- embriju/ fetu (ara
The potential risk for humans is unknown.
Ir- riskju potenzjali għal bniedem mhux magħruf.
Use in pregnancy is, therefore, not recommended.
L- użu fit- tqala, għalhekk, mhux irrakkomandat.
Patients should notify their physician if they become pregnant during treatment with ZIMULTI.
Il- pazjenti għandhom jinfurmaw lit- tabib jekk joħorġu tqal waqt il- kura b’ ZIMULTI.
Rimonabant has been detected in the milk of lactating rats and rimonabant may inhibit the suckling reflex.
Rimonabant instab fil- ħalib ta ’ firien li qed ireddgħu u rimonabant jista ’ jinibixxi ir- rifless tad - treddigħ.
It is not known if rimonabant is excreted in human milk.
Mhux magħruf jekk rimonabant jaqsamx fil- ħalib tal- bniedem.
ZIMULTI is contraindicated during breast-feeding (see section 4.3).
ZIMULTI huwa kontra -
4.7 Effects on ability to drive and use machines
ux indikat waqt it- treddigħ (ara sezzjon 4. 3).
Cognitive investigations in clinical pharmacology studies demonstrated that rimonabant is devoid of
4. 7 Effetti fuq il- ħila biex issuq u tħaddem magni ad Ma sarux studji dwar l- effetti fuq il- ħila biex issuq u tħaddem magni. għ Investigazzjonijiet konoxxittivi fi studju tal- farmakoloġija klinika urew li rimonabant m’ għandu ebda effett sinifikanti ta ’ natura konoxxittiva jew sedattiva. m ’
d any significant cognitive or sedative effect.
4. 8 Effetti mhux mixtieqa
ise 4.8 Undesirable effects
ZIMULTI 20 mg ġie evalwat għas- sigurtà f’ madwar 2500 pazjent, li kienu irreġistrati fi studji li li li
or uth ZIMULTI 20 mg has been evaluated for safety in approximately 2500 patients enrolled in studies that examined the metabolic and weight loss effects in overweight and obese patients and in approximately 3800 patients in other indications.
indirizzaw l- effetti metaboliċi u t- telf fil- piż, ta ’ pazjenti li jiżnu aktar milli suppost u li jbatu mill - obeżità, kif ukoll f’ madwar 3800 pazjent għall- kondizzjonijiet oħra.
In placebo-controlled studies, the discontinuation rate due to
L - a
The most common adverse reactions resulting in discontinuation were: nausea, mood alteration with depressive symptoms, depressive ge disorders, anxiety and dizziness. on
aktar effetti avversi komuni li wasslu għall- waqfien fit- trattament kienu: id- dardir, bidla fil- burdata b’ sintomi depressivi, mard depressiv, anzjetà u sturdament. iċin
These were usually mild or moderate in severity and ol
Mard depressiv kien irrapportat f’ 3. 2% tal- pazjenti, li kienu jbatu mill- obeżitza jew dawk kienu jiżnu aktar milli suppost u li kellhom fatturi miżjuda ta ’ riskju li kienu ittrattati b’ 20 mg ta ’ rimonabant. ed
resulted in recovery in all cases either after corrective treatment or discontinuation of rimonabant and did not exhibit any differentiating characteristics compared to cases reported in the control groups. tn uc
Dawn l- episodji kienu normalment ħfief jew ta ’ severità moderata u li marru għal kollox, fil- każijiet kollha, wara trattament korrettiv, jew il- waqfien ta ’ rimonabant; dawn ma wrew ebda karatteristici li iddistingwewhom meta kienu mqabbla mal- każijiet irrapportati fil- gruppi ta ’ kontroll. tt m
The following table (table 1) shows all treatment-emergent adverse reactions from placebo-controlled studies in patients treated for weight loss and related metabolic disorders when these incidences were d
It- tabella li tmiss (tabella 1) turi r- reazzjonijiet avversi kollha, dovuti għat- trattament, minn studji ikkontrollati bil- plaċebo, f’ pazjenti ittrattati għal telf fil- piż u mard ħafif metaboliku relatat, meta dawn kellhom inċidenza statistikament sinifikanti, akbar mir- rata korrispondenti bil- plaċebo, (għal grajjiet do
statistically significantly greater than the corresponding placebo rate (for events ≥ 1%) or considered ro
ta ’ ≥ 1%), jew ikkunsidrati klinikament rilevanti (għal grajjiet ta ’ < 1%)
clinically relevant (for events < 1%). lp
Pro
Very common (≥ 10%); Common (≥ 1, < 10%); Uncommon (≥ 0.1, < 1%); Rare (≥ 0.01, < 0.1%); Very ina
Komuni ħafna (≥ 10%); komuni (≥ 1, < 10%); mhux komuni (≥ 0. 1, < 1%); rari (≥ 0. 01, < 0. 1%); rari ħafna (< 0. 01%); u mhux maghruf (ghax ma tistax tkun stmata mid- data disponibbli).
rare (< 0.01%), Not known (cannot be estimated from the available data). dic
F’ kull sezzjoni ta ’ frekwenza, l- effetti mhux mixtieqa għandhom jitniżżlu skond is- serjetà tagħhom.
Me
L - effetti li huma l- aktar serji għandhom jiniżżlu l- ewwel, segwiti minn dawk anqas serji.
5 Table 1:
5 Tabella 1
nutrition disorders
at Ipogliċemija * Disturbi fil - metaboliżmu u n -
Mood alterations Dysphoria
Bidla fil- burdata
with depressive symptoms Anxiety Irritability
b’ sintomi depressivi Ansjetà
Emotional disorder Suicidal ideation Aggressiveness
Rabja Disforija
d ise
aw
Nervousness Sleep disorders Insomnia
Irritabilità Nervożità Mard li jeffetwa l- irqad
Aggressive behaviour
Mard emozzjonali Formazzjoni ta’ idejat
or Parasomnias
Nuqqas ta ’ rqad Parasonja
uth Nervous system disorders
suwiċidali Aggresività
Memory loss Dizziness Hypoaesthesia Sciatica
ad
Lethargy Tremor
Mġiba aggresiva
Paresthesia ge
Disturbi fis- sistema nervuża
ra
Nuqqas ta ’ memorja għ Sturdament Ipoestesija Xjatika m ’
Vascular disorders Respiratory,
Letarġija Tregħid
Hot flush on
Parasteżija
thoracic and
Disturbi vaskulari
ol
Fwawar
mediastinal disorders tn
u medjastinali iċin
Diarrhoea Vomiting
Dijarrea Rimettar
Skin and subcutaneous tissue
Disturbi fil- ġilda u fit- tessuti ta ’ taħt il -
d
ed
Pruritus Hyperhidrosis
Ħakk Tagħriq eċċessiv
disorders ro
Tagħriq matul il - lejl
Musculoskeletal
ġilda Disturbi muskolu - skeletrali u tal -
lp
tt m
Tendonitis
Infjammazzjoni ta ’ l- għerq
and Muscle cramp connective
Bugħawwieġ connective tissue Spażmi muskolari Disturbi ġenerali do
ina
*
Muscle spasms
Korriment, avvalenament u komplikazzjonijiet ta ’ xi proċedura
tissue disorders General disorders
Waqgħa Kontużjoni Tfekkik ta ’ ġog
dic
il- frekwenza hija bbażata biss fuq rapporti f’ pazjenti dijabetiċi li huma obeżi jew li għandhom piż żejjed
Asthenia/ fatigue Influenza
6 Fi studji kliniċi għal indikazzjonijiet oħra, reazzjonijiet avversi addizzjonali li ġejjin kienu komunement rapportati:
Injury, Poisoning and procedural Me
- infezzjonijiet u infestazzjonijiet: sinożite
Fall Contusion
- mard marbut mal- metaboliżmu u n- nutrizzjoni: anoreksja, nuqqas ta ’ aptit
complications
- mard gastro- intestinali: dwejjaq fl- istonku nixfa tal- ħalq.
Joint sprain
Wara li l- prodott tqiegħed fis- suq
*frequency is based only on reports in obese or overweight diabetic patients.
at Wara li l- prodott tqiegħed fis- suq, ġew ukoll irrapportati r- reazzjonijiet avversi li ġejjien (il- frekwenza
In clinical studies for other indications, the following additional adverse reactions were commonly reported: − infections and infestations: sinusitis − metabolism and nutrition disorders: anorexia, decreased appetite, − gastrointestinal disorders: stomach discomfort, dry mouth.
izz m’ hijiex magħrufa): – Disturbi psikjatriċi: disturbi psikotiċi li jinkludu alluċinazzjonijiet, taqriq u paranojja. – Disturbi fil- ġilda u fit- tessuti ta ’ taħt il- ġilda: raxx.
6 Post-Marketing In addition the following adverse reactions were reported during postmarketing (frequency not known): − Psychiatric disorder: psychotic disorders including hallucinations, delusion and paranoia. − Skin and subcutaneous tissue disorders: rash. − Nervous disorders: convulsions, disturbance in attention, headache. − gastrointestinal disorders: abdominal pain.
tor – Disturbi fis- sistema nervuża: konvulżjonijiet, disturbi fl- attenzjoni, uġigħ ta ’ ras. – Disturbi gastro- intestinali: uġigħ addominali
Laboratory adverse events ZIMULTI has not been shown to alter laboratory test values.
aw Grajjiet avversi fit- testijiet tal- laboratorju ZIMULTI ma ntweriex li effetwa ir- riżultati tat- testiijiet tal- laboratorju.
In a single-dose tolerability study, doses up to
ux L- esperjenza b’ rimonabant b’ dożaġġi eċċessivi hija limitata.
These
Fi studju ibbażat fuq it- tollerabbilità ta ’ doża waħda, fejn ingħataw dożi sa 300 mg lil numru żgħir ta ’ suġġetti, sintomi minuri biss kienu ad rapportati.
ise included headache, euphoria, fatigue and insomnia.
Dawn inkludew uġigħ ta ’ ras, ewforija, għejja u nuqqas ta’ rqad.
The pharmacokinetic profile demonstrates that a plateau in exposures is reached at 180 mg.
Il- komportament farmakokinetiku juri li meta tintlaħaq doża ta ’ 180 mg ma jkunx hemm caqlieq fuq l- effetti fid- daqs għ ta ’ l- espożizzjoni.
Treatment should consist of
M’ hemmx antidot specifiku għal rimonabant; għalhekk, miżuri xierqa ta ’ support għandhom jinbdew f’ każ ta ’ doża eċċessiva.
or the general measures employed in the management of overdoses, such as keeping airways
It- trattament jikkonsisti f’ miżuri generali li wieħed soltu jieħu f’ każijiet ta ’ dożaġġi eċċessivi, bħal ngħidu aħna iż- żamm bla xkiel tal- ventilazzjoni tal- pulmuni, m ’
uth unobstructed, monitoring cardiovascular function and general symptomatic and supportive measures.
l- immoniterjar tal- funzjoni tal- qalb u ċ- ċirkolazzjoni, u miżuri ġenerali sintomatiċi u ta ’ support. li li
PHARMACOLOGICAL PROPERTIES ra ge 5.1 Pharmacodynamic properties on
5. 1 Tagħrif farmakodinamiku a
Anti obesity agent ol
Mediċina għall- kura tal- obeżità iċin
Rimonabant is a selective cannabinoid-1 receptor (CB1) antagonist that inhibits the pharmacological effects of cannabinoid agonists in vitro and in vivo. uc
Rimonabant huwa antagonist selettiv għar- reċettur cannabinoid – 1 (CB1), li jinibixxi l- effetti ed
The endocannabinoid system is a physiological system present in brain and peripheral tissues (including adipocytes) that affects energy balance, glucose and lipid metabolism and body weight, and d
Is- sistema endocannabinoid hija sistema fiżjoloġika li tinsab fil- moħħ u t- tessuti periferali (li jinkludu iċ- ċelluli li jaħżnu x- xaħam), li teffettwa l- bilanċ fl- enerġija, il- metaboliżmu tal- glukosju u x- xaħam u tt m
in neurons of the mesolimbic system modulates the intake of highly palatable, sweet or fatty foods. ro
l- piż tal- ġisem, u fin- newroni tas- sistema mesolimbic tikkontrolla t- teħid ta ’ l- ikel ħelu jew xaħmi li għandu togħma tajba ħafna.
Clinical study results lp ina
Riżultati ta’ studji kliniċi do
Weight Management
L- Immaniġġar tal- Piż Pro
The patients dic
B’ kollox aktar minn 6800 pazjent kienu mdaħħla fl- istudji kliniċi fil- Fażi 2 u l- Fażi 3.
included in the phase 3 trials followed a restrictive diet during the trial prescribed by a dietician and they were advised to increase their physical activity.
Il- pazjenti imdaħħla fil- fażi 3 tal- provi segwew dieta restrittiva waqt il- prova, preskritta minn espert tad- dieta, u kienu ngħataw parir biex iżidu l- eżerċizzju fiżiku.
Patients had a BMI ≥ 30 kg/ m² or BMI > 27 kg/ m² Me
Il- pazjenti fil- bidu kellhom BMI ta ’ ≥ 30 kg/ m2 jew BMI > 27 kg/ m2, akkompanjat ma ’ pressjoni għolja tad- demm u/ jew abnormalitajiet fil- livelli tax - xaħmijiet fid- demm.
Experience in patients over 75 years and Orientals/ Asians was limited.
L - esperjenza hija limitata f’ pazjenti ’ l fuq minn 75 sena u f’ nies Orjentali/ Asjatiċi.
Significant mean weight reductions from baseline to one year for ZIMULTI 20 mg versus placebo were demonstrated in three studies conducted in non-diabetic patients.
7 It- tnaqqis medju u sinifikanti fil- piż mil- linja bażi sa sena, ta ’ 20 mg ZIMULTI, meta mqabbel mal - plaċebo, intwera fi tliet studji magħmulin fuq pazjenti mhux dijabetiċi.
A mean weight loss of 6.5 kg from baseline to one year was shown for ZIMULTI 20 mg versus a mean weight loss of 1.6 kg for placebo (Difference -4.9 kg CI95% -5.3; -4.4, p < 0.001).
Intwera telf medju ta ’ 6. 5 kg fil- piż mil- linja bażi sa sena għal 20 mg ta ’ ZIMULTI, kontra t- telf medju ta ’ 1. 6 kg għall- plaċebo (Differenza - 4. 9 kg CI95% - 5. 3; - 4. 4, p < 0. 001).
The percentage of patients who lost 5% and 10% of their baseline body weight after 1 year of treatment are given in table 2:
Il- persentaġġi ta ’ pazjenti li tilfu 5% u 10% tal- linja bażi fil- piż tal- ġisem, wara sena trattament, qed jingħataw f’ tabella 2:
Non-diabetic studies
Studji fuq dijabetiċi
Diabetic study
Plaċebo
Placebo ZIMULTI 20 mg
ZIMULTI 20 mg
Subjects with a 5% weight reduction
aw Suġġetti b’ tnaqqis fil - piż ta ’ 5%
Subjects with a 10% 7.8% weight reduction
ux Suġġetti b’ tnaqqis fil - 7. 8% piż ta ’ 10%
27.0%
27. 0%
2.0%
2. 0%
16.2%
16. 2%
d Difference (CI 95%) 19.2% (17%; 22%)
19. 2% (17%; 22%)
ise or Most of the observed weight reduction was obtained within the first nine months of treatment.
L- aktar tnaqqis fil- piż li intwera kien fl- ewwel disa ’ xhur ta ’ trattament.
uth ZIMULTI 20 mg was effective in maintaining weight loss up to two years.
It- tnaqqis fil- piż ma tmiem is- sentejn kien ta ’ 5. 1 kg għall - m ’
Weight loss at two years was 5.1 kg for patients who received ZIMULTI 20 mg and 1.2 kg for placebo (Difference -3.8 kg; CI95% -4.4, -3.3; p < 0.001).
pazjenti li ħadu 20 mg ZIMULTI, u 1. 2 kg għall- plaċebo (Differenza - 3. 8 kg; CI95% - 4. 4, - 3. 3; p < 0. 001). li li
ra Rimonabant 20 mg reduced the risk of weight regain.
Għoxrin (20) mg ta ’ rimonabant naqqas ir- riskju li l- piż mitluf jerġa jiġi akkwistat.
Patients who received ZIMULTI 20 mg for one ge year were re-randomized to ZIMULTI 20 mg or placebo.
Il- pazjenti li irċevew 20 mg ta ’ ZIMULTI għal sena reġgħu tqassmu, b’ mod ‘ randomised ’, fi grupp fuq 20 mg ZIMULTI, u ieħor fuq il- plaċebo.
At two years, patients continuing on rimonabant had a mean total weight loss of 7.5 kg over 2 years whereas patients re-randomized to on
fil- piż totali medju ta ’ 7. 5 kg fuq sentejn, fil- waqt il- pazjenti li tqassmu fil- grupp tal- plaċebo fit- tieni iċin
placebo group during the second year had a mean total weight loss of 3.1 kg over 2 years.
sena kellhom telf fil- piż totali medju ta ’ 3. 1 kg fuq medda ta ’ sentejn.
At two years, the difference in total weight loss between ZIMULTI and placebo was -4.2 kg (CI95% -5.0; -3.4, ol
Fl- ahhar tas- sentejn id - differenza fil- piż totali bejn ZIMULTI u l- plaċebo kienet ta ’ - 4. 2 kg (CI95% - 5. 0; - 3. 4, p < 0. 001).
Treatment with rimonabant was associated with significant reductions in waist circumference, a uc
It- trattament bi rimonabant kien assoċjat ma ’ tnaqqis sinifikanti fiċ- ċirkonferenza tal- qadd, indikatur ed
known marker of intra-abdominal fat. d
magħruf ta ’ l- ammont ta ’ xaħam ġewwa l- kavità taż- żaqq.
The effects on body weight appeared to be consistent among men and women.
L- effetti fuq il- piż tal- ġisem dehru li kienu konsistenti fost l- irġiel u n- nisa.
In the limited number ro
F’ numru limitat ta ’ tt m
of Black patients weight loss was less pronounced (mean difference to placebo -2.9 kg).
pazjenti Suwed, it- tnaqqis fil- piż kien anqas (differenza medja mal- plaċebo ta ’ - 2. 9 kg).
No conclusions can be drawn with regard to effects in patients over 75 years or in Asian/ Oriental patients lp
Wieħed ma jistax jasal għal konklużjonijiet rigward l- effetti f’ pazjenti ’ l fuq minn 75 sena, jew dawk Asjatiċi/ Orjentali, dovut għan- numru żgħir ta ’ pazjenti. do Pro
due to the low number of patients. ina
8 L- immaniġġar tal- piż u fatturi ta ’ riskji żejda Fi studji magħmulin fuq suġġetti mhux dijabetiċi, li inkludew grupp imħallat ta ’ suġġetti b’ abnormalitajiet fil- livelli tax- xaħmijiet fid- demm u dawk mingħajr dawn l- abnormalitajiet (ittrattati), kienet irreġistrata (f’ sena), żieda f’ HDL- C u tnaqqis fit- triglycerides.
Weight management and additional risk factors In the non-diabetic studies including a mixed population of subjects with/ without (treated) dic
Fil- każ ta ’ HDL- C żieda medja ta ’ 16. 4% intweriet b’ 20 mg ta ’ rimonabant (linja bażi HDL- C 1. 24 mmol/ l), meta mqabbla ma ’ żieda ta ’ 8. 9% bil- plaċebo (linja bażi HDL- C 1. 21 mmol/ l).
dyslipidemia, an increase in HDL-C and decrease in triglycerides (at one year) was observed.
Id- differenza kienet statistikament sinifikanti (Differenza 7. 9% CI95% 6. 6%; 9. 2%, p < 0. 001).
For HDL-C an average increase of 16.4% was seen under rimonabant 20 mg (baseline HDL-C 1.24 Me
Fil- każ tat- triglycerides tnaqqis medju ta ’ 6. 9% intwera
mmol/ l) compared to an increase of 8.9% for placebo (baseline HDL-C 1.21 mmol/ l).
at b’ 20 mg ta ’ rimonabant (linja bażi TG 1. 62 mmol/ l), meta mqabbel ma ’ żieda ta ’ 5. 8% bil- plaċebo (linja bażi TG 1. 65 mmol/ l).
The difference was statistically significant (Difference 7.9% CI95% 6.6%; 9.2%, p < 0.001).
Id- differenza kienet statistikament sinifikanti (Differenza - 13. 3% CI95% -
The difference was statistically significant (Difference -13.3% CI95% -16.5; -10.2% p < 0.001).
izz 16. 5; - 10. 2% p < 0. 001).
It is estimated that approximately half of the observed improvement in HDL-C and triglycerides in patients who received rimonabant 20 mg was beyond that expected from weight loss alone.
Huwa stmat li madwar nofs it- titjib irreġistrat f’ HDL- C u t- triglycerides, f’ pazjenti li rċevew 20 mg ta ’ rimonabant, kien ’ l hinn minn dak mistenni bit- tnaqqis fil- piż biss.
Generally ZIMULTI 20 mg had no significant effect on Total-C or LDL-C levels.
Bhala regola 20 mg ta ’ ZIMULTI ma kellux effett fuq il- livelli totali ta ’ C jew ta ’ LDL- C.
In the trial in type 2 diabetic patients (RIO-Diabetes) who were overweight or obese treated with metformin or sulfonylurea improvements in HbA1c and body weight were observed.
tor Fl- istudji investigattivi dwar il- pazjenti li kellhom id- dijabete tip 2 (RIO- Diabetes), u li kienu jiżnu aktar minn normal, jew kienu qed ibatu mill- obeżità, it- trattament bil- metformin jew bis- sulfonylurea
8 At one year a mean weight loss of 5.3 kg was shown for ZIMULTI 20 mg versus a loss on placebo of 1.4 kg (Difference – 3.9 kg CI95% -4.6; -3.3 p < 0.001).
ux 1. 4 kg bil- plaċebo (Differenza – 3. 9 kg CI95% - 4. 6; - 3. 3 p < 0. 001).
The percentage of patients who lost 5% and 10% of their baseline body weight after 1 year of treatment are given in the table 2.
Il- persentaġġi ta ’ pazjenti li tilfu 5% u 10% tal- linja bażi fil- piż tal- ġisem, wara sena trattament, qed jingħataw f’ tabella 2.
The percentage of patients reaching HbA1c < 7% was 51% in the rimonabant group and 35% in the placebo group.
F’ studju investigattiv ieħor (Serenade) f’ pazjenti naïve li kellhom id- dijabete tip 2 u li kienu qed ibatu ad mill- obeżità, il- bidla assoluta fil- livelli ta ’ HBA1c (b’ linja bażi ta ’ 7. 9% għaz- zewġ gruppi) wara sitt xhur kien - 0. 8 b’ rimonabant 20 mg u - 0. 3 bil- plaċebo (Differenza - 0. 51 CI95% - 0. 78, - 0. 24 p < 0. 001). għ Il- persentaġġ ta ’ pazjenti li laħqu il- livell ta ’ HBA1c < 7% kien ta ’ 51% għall grupp ta ’ rimonabant u 35% għall grupp tal- plaċebo.
The difference in mean body weight change between the 20 mg and placebo groups was 3.8 kg (CI95% -5.0, -2.6 p < 0.001).
Id- differenza medja ta ’ bidla fil- piz tal- ġisem bejn il- gruppi ta ’ 20mg u l - plaċebo kien ta ’ 3. 8 kg (CI95% - 5. 0, - 2. 6 p < 0. 001). m ’
Changes in HDL-C and TG in this population were similar to that of the non-diabetic population.
Il- bidliet f’ HDL- C u t- TG f’ dan il- grupp ta ’ suġġetti kienu simili għal dawk li ma kienux dijabetiċi.
It is estimated that approximately half of the mean improvement in HbA1c in patients receiving rimonabant 20 mg was beyond that expected from weight loss alone.
Huwa stmat li madwar nofs tat- titjib medju fil- HbA1c f’ pazjenti li rċevew 20 mg ta’ rimonabant kien ’ l hinn minn dak mistenni bit- tnaqqis fil- piż biss. li li
5.2 Pharmacokinetic properties
5. 2 Tagħrif farmakokinetiku a
AUC increased less than
L- AUC żdiedet anqas bħala proporzjon tad- doża meta din kienet ’ l fuq minn 20 mg. iċin
ise Absorption:
Assorbiment:
or Rimonabant displays high in vitro permeability and is not a substrate of P-glycoprotein.
Rimonabant juri permeabilità għolja in vitro u mhux sustrat tal- P- glycoprotein.
The absolute
Id- disponibbiltà ed
uth bioavailability of rimonabant has not been determined.
bijoloġika assoluta ta ’ rimonabant ma kienetx maħduma.
Following multiple once-daily doses of 20 mg to healthy subjects in the fasted state, maximum plasma concentrations of rimonabant are achieved in approximately 2 hours with steady state plasma levels achieved within 13 days (Cmax = 196 ± 28.1
Wara li ngħataw dożi repetuti ta ’ 20 mg darba kuljum lil suġġetti sajmin u b’ saħħithom, il- livelli massimi ta ’ rimonabant fil- plażma intleħqu f’ madwar sagħtejn, b’ livelli stabbli fil- plażma irreġistrati fi żmien 13- il jum (Cmax = 196 ± 28. 1 ng/ ml; tt m
ra ng/ ml; Ctrough = 91.6 ± 14.1 ng/ ml; AUC0-24 = 2960 ± 268 ng. h/ ml).
Ctrough = 91. 6 ± 14. 1 ng/ ml; AUC0- 24 = 2960 ± 268 ng. siegħa/ ml).
Steady state rimonabant exposures are 3.3-fold higher than those observed after the first dose.
L- espożizzjonijiet ta ’ rimonabant fl - istat stabbli huma ta ’ 3. 3- il darba minn dawk innotati wara l- ewwel doża.
Population pharmacokinetic analysis ge demonstrated less fluctuation in peak to trough plasma concentration but no differences in steady state AUC as weight increases.
L- analiżi tal- komportament farmakokinetiku fi grupp ta ’ persuni wera anqas varjazzjoni fl- ogħla (peak) u fl- anqas (trough) livelli fil- plażma, iżda ma kienx hemm differenzi meta stabiliżża l- AUC, hekk kif il- piż jiżdied.
As weight increases from 65 to 200 kg, Cmax is expected to decrease 24% on
Meta l- piż do
and Ctrough is expected to increase by 5%.
jiżdied minn 65 għal 200 kg, Cmax huwa mistenni li jonqos b’ 24% u Ctrough jiżdied b’ 5%.
Time to steady state is longer in obese patients (25 days) as a consequence of the higher volume of distribution in these patients.
Iż- żmien biex il- livell fid- demm jistabiliżża huwa aktar f’ pazjenti b’ obeżità (25 jum), bħala kosegwenza tal - volum ogħla ta ’ distribuzzjoni f’ dawn il- pazjenti.
Population pharmacokinetic ol
L- analizi tal- komportament farmakokinetiku Pro
analysis indicated that rimonabant pharmacokinetics are similar between healthy non-smoking subjects and patients who smoke. tn uc
f’ gruppi ta ’ persuni jindika li l- komportament ta ’ rimonabant huwa l- istess, kemm f’ suggetti b’ saħħithom li ma jpejpux kif ukoll pazjenti li jpejpu.
In ro
9 L- effett ta ’ l- ikel: l- għoti ta ’ rimonabant lil suġġetti b’ saħħithom meta dawn kienu sajmin, jew li ħadu ikla li kien fiha persentaġġ għoli ta ’ xaħam, wera li Cmax u l- AUC kienu żdiedu b’ 67% u 48%, rispettivament, f’ sitwazzjoni mitmugħa.
clinical studies, ZIMULTI 20 mg was taken in the morning usually before breakfast. lp
Fi studji kliniċi, 20 mg ta ’ ZIMULTI ittieħdu filgħodu, normalment qabel il - kolazzjon.
The in vitro human plasma protein binding of rimonabant is high (> 99.9%) and non-saturable over a ina
Il- volum periferali apparenti ta ’ distribuzzjoni ta ’
The apparent peripheral volume of distribution of rimonabant appears to be related to body weight, with obese patients having a higher volume of distribution than normal-weight dic
izz rimonabant jidher li huwa relatat mal- piż tal- ġisem; il- pazjenti li għandhom l- obeżità juru volum ogħla ta ’ distribuzzjoni minn suġġetti li għandhom piż normali.
Rimonabant is metabolized by both CYP3A and amidohydrolase (predominantly hepatic) pathways in vitro.
Rimonabant hu metaboliżżat in vitro kemm mis - sistema CYP3A kif ukoll dik amidohydrolase (predominantement fil- fwied).
Circulating metabolites do not contribute to its pharmacologic activity.
Il- prodotti metaboliċi li jiċċirkulaw ma jikkontribixxux fuq l- attività
Rimonabant is mainly eliminated by metabolism and subsequent biliary excretion of metabolites.
Rimonabant huwa prinċipalment eliminat permezz ta ’ l- attività metabolika u sussegwentement bit -
Only an approximate 3% of the dose of rimonabant is eliminated in the urine, while approximately 86% of the dose is excreted in the faeces as unchanged drug and metabolites.
Madwar 3% biss tad- doża ta ’ rimonabant hija eliminata fl- urina, fil- waqt li madwar 86% tad- doża titneħħa fl- ippurgar, bħala s- sustanza mhux mibdula u bħala sustanzi metaboliċi.
9 Special Populations Race:
F ’ pazjenti li qed ibatu mill- obeżità, l’ half- life ta ’ eliminazzjoni ad huwa itwal (madwar 16- il jum), minn pazjenti li mhumiex ħoxnin (madwar 9 ijiem), dovut għall - volum akbar ta ’ distribuzzjoni. għ Popolazzjonijiet speċjali: m ’
In single- and repeat-dose studies, the Cmax and AUC of rimonabant were similar in healthy Japanese and Caucasian subjects, whereas elimination half-life was shorter in Japanese subjects (3-4 days) compared to Caucasian subjects (about 9 days).
Fi studji ibbażati fuq doża waħda u dawk repetuti, Cmax u l- AUC ta ’ rimonabant kienu simili f’ suġġetti Ġappuniżi u Kawkasi b’ saħħithom, filwaqt li l’ half- life ta ’ eliminazzjoni kien iqsar f’ suġġetti li li
The difference in half-life was due to differences in peripheral volume of distribution as a consequence of lower weight in Japanese subjects.
Din id- differenza fil - half- life hija dovuta għal differenzi fil- volum periferali ta ’ distribuzzjoni, bħala konsegwenza li s - suġġetti Ġappuniżi jiżnu anqas.
The pharmacokinetics of rimonabant are similar in female and male patients.
Il- komportament farmakokinetiku ta’ rimonabant huwa l- istess f’ pazjenti nisa u rġiel. ed
Elderly patients have slightly higher exposure than young patients.
Pazjenti anzjani għandhom espożizzjoni ftit ogħla minn pazjenti żgħar.
d ise Patients with hepatic insufficiency:
Pazjenti b’ insuffiċjenza tal- fwied:
Data are insufficient to draw conclusions
Id- data mhux biżżejjed li do
or regarding pharmacokinetics in moderate hepatic impairment.
tippermetti li wieħed jasal għal konklużjonijiet rigward il- komportament farmakokinetiku f’ indeboliment moderat tal- fwied.
Patients with severe hepatic impairment
Pro
ra The effect of renal function on the pharmacokinetics of rimonabant has not been studied specifically.
L- effet tal- funzjoni renali fuq il- komportament farmakokinetiku ta ’ rimonabant ma kienx speċifikament studjat.
Based on data from population pharmacokinetic studies, mild renal impairment do not seem to affect ge the pharmacokinetics of rimonabant.
Ibbażat fuq data minn studji farmakokinetiċi fuq gruppi ta ’ individwi, l - indeboliment renali ħafif ma jidhirx li jeffetwa l- komportament farmakokinetiku ta ’ rimonabant.
There are no data in severe renal impairment. on
M’ hemmx data dwar l- indeboliment renali sever.
Adverse reactions not observed in clinical studies, but seen in animals at exposure levels similar to tn
10 5. 3 Tagħrif ta ’ qabel l- użu kliniku dwar is- sigurtà tal- mediċina
clinical exposure levels and with possible relevance to clinical use were as follows: uc
Ma dehrux effetti mhux mixtieqa waqt studji tal- użu kliniku, iżda dehru f’ annimali li ġew mogħtija doża daqs dik klinika u jista 'jkollhom rilevanza għall- użu kliniku, kif spjegat: L- aċċessjonijiet intwerew b’ mod sporadiku fi studji fl- annimali gerriema u x- xadini tar- razza Makakki.
No convulsions were observed in dogs during a 3 month study.
Fil- klieb ma kienx hemm aċċessjonijiet waqt studju ta ’ 3 xhur.
In some, but not all cases, initiation of convulsions appeared d
Fi ftit, iżda mhux fil- każijiet kollha, il- bidu ta ’ l - aċċessjoni deheret li kienet assoċjata ma ’ l- istress assoċjat mal- proċedura, bħall- immaniġġar ta ’ l -
to be associated with procedural stress such as handling of the animals.
It- trattament b’ rimonabant ma weriex effetti avversi fuq id- disinn ta ’ l- EEG
A proconvulsant activity of ro
izz fil- firien.
rimonabant was found in one of two safety pharmacology studies.
Iż- żieda fl- inċidenza u/ jew is- severità tas- sinjali kliniċi suġġestivi ta ’ żieda ta ’ iperestesja tal- ħass
No adverse effect of rimonabant treatment was observed on EEG patterns in rats. lp
Effett dirett ta ’ rimonabant ma jistax ikun eskluż.
Increased incidence and/ or severity of clinical signs suggestive of increased tactile hyperesthesia were ina
Kienu innotati, fi studji fit- tul fuq il- far, li l- fwied sar xaħmi u kien hemm żieda fl- inċidenza tan -
observed in rodent studies.
aw nekrosi tal- lobuli ċentrali tal- fwied, relatati mad- daqs tad- doża.
A direct effect of rimonabant cannot be ruled out. dic
Effett dirett ta ’ rimonabant ma jistax ikun eskluż.
Liver steatosis and a dose-related increase in centrilobular necrosis were observed in long-term studies in the rat.
Fi studji ‘ standard ’ fuq il- fertilità fil- firien ta ’ sess femminil, meta ngħataw dożi fil- ġimgħatejn qabel
In standard fertility studies in female rats (dosing for 2 weeks prior to mating) there was abnormal oestrous cyclicity and a decrease in corpora lutea and fertility index at doses of rimonabant that induced maternal toxicity (30 and 60 mg/ kg/ day).
ux it- tgħammir, kien hemm ċikli abnormali fis- saħna sesswali u t- tnaqqis fil- corpora lutea u l- indiċi tal - fertilità, b’ dożi ta ’ rimonabant li ikkaġunaw tossiċità lill- omm (30 sa 60 mg/ kg/ jum).
Regarding reproductive parameters, at 30 mg/ kg no differences were observed between treated animals and controls, at 60 mg/ kg effects were still observed (decreased number of corpora lutea, implantations, total and viable fetuses).
F’ dożaġġ ta ’ 60 mg/ kg l- effetti avversi kienu, madankollu, innotati (it- tnaqqis fil- formazzjoni tal corpora lutea, fit- taħwil taż- żigot fit- tessut ta ’ l- utru, u fin - numru totali u ta ’ dawk vijabbli tal- fetijiet). m ’
Sporadic malformations (anencephaly, micro-ophthalmia, widened brain ventricles and omphalocele) were observed in the rabbit embryofetal toxicity studies at doses resulting in exposures comparable with the clinical exposures.
Malformazzjonijiet sporadiċi, (l- assenza ta ’ partijiet kbar tal- moħħ flimkien ma ’ malformazzjonijiet tal- parti t’ isfel tal- moħħ fejn tingħaqad mal- korda spinali, nuqqas ta ’ żvilupp ta ’ l- għajnejn, il - li li
No treatment-related malformations were seen in the rat.
ventrikoli tal- moħħ imwessgħin, u ftuq estensiv ta ’ l- organi addominali fir- reġjun umbiliku, bħala konsegwenza ta ’ nuqqas ta ’ żvilupp, fil- ġuf, tal- muskoli u t- tessuti molli taż- żaqq) kienu innotati fl - istudji dwar l- effetti tossiċi fuq l- embriju/ fetu tal- fniek, f’ dozi li rriżultaw f- espożizzjoni komparabbli a
10 Effects of rimonabant on pre- and post-natal development were assessed in the rat at doses up to 10 mg/ kg/ day.
ma ’ livelli ta ’ l- espożizzjoni klinika.
There are reports in the literature that, in both rodents and humans, the spatial distribution and density of CB1 receptors in the brain changes during development.
Għalkemm tossiċità fuq l- omm kienet irrapportata b’ dawn id- dożi, ir- relazzjoni mat- trattament ma tistax tkun eskluża.
The potential relevance of this to administration of a CB1 antagonist is unknown.
Ma kienux innotati malformazzjonijiet relatati iċin
PHARMACEUTICAL PARTICULARS
mat- trattament fil- far.
d 6.1 List of excipients
L- effetti ta ’ rimonabant fuq l- iżvilupp qabel u wara t- twelid kienu studjati fil- far f’ dożi sa ed
ise Tablet core:
10 mg/ kg/ jum.
or maize starch,
Ir- relevanza do
uth lactose monohydrate, povidone K 30 (E1201), croscarmellose sodium (E468), sodium laurilsulfate (E487), microcrystalline cellulose (E460), magnesium stearate
Fi studju fuq il- firien tqal, qabel u wara t- twelid, l- espożizzjoni għal rimonabant waqt it- tqala u l- irdigħ ma ikkawżawx ħsara fuq l- abbiltà tat- tagħlim jew fuq il- memorja, iżda effetti mhux ċari fuq il - Pro
ra
6. 1 Lista ta ’ sustanzi mhux attivi
on
Il- qalba tal- pillola: maize starch, lactose monohydrate,
Tablet coating: lactose monohydrate, ol
at povidone K 30 (E1201), croscarmellose sodium (E468),
hypromellose 15 mPa. s (E464), titanium dioxide (E171), tn
izz sodium laurilsulfate (E487), microcrystalline cellulose (E460), magnesium stearate
macrogol 3000 uc
tor Ir- rita tal- pillola: lactose monohydrate,
Tablet polishing: d
aw hypromellose 15 mPa. s (E464), titanium dioxide (E171), macrogol 3000
carnauba wax (E903) ro
ux Il- lostru tal- pillola: carnauba wax (E903)
6.2 Incompatibilities lp
ad 6. 2 Inkompatibilitajiet għ Ma jgħoddx f’ dan il- każ
6.3 Shelf-life dic
6. 3 Żmien kemm idum tajjeb il- prodott mediċinali m ’
3 years Me
3 snin li li
This medicinal product does not require any special storage conditions.
Din il- mediċina m’ għandiex bżonn ħażna speċjali. a
6.5 Nature and contents of container
6. 5 In- natura tal- kontenitur u ta ’ dak li hemm ġo fih iċin
PVC-aluminium blister packs containing 14, 28, 30, 56, 84, 90 and 98 film-coated tablets.
Folja tal- PVC u l- aluminju f’ pakketti ta ’ 14, 28, 30, 56, 84, 90 u 98 pilloli miksija b’ rita.
70 x 1 film-coated tablets in PVC-aluminium perforated unit dose blister packs.
70 x 1 pilloli miksija b’ rita ġo folja tal- PVC u l- aluminju, imtaqqba biex titneħħa doża waħda. ed
Not all pack sizes may be marketed.
Jista ’ jkun li mhux il- pakketti tad- daqsijiet kollha jkunu għall- skop kummerċjali. tt m
174 Avenue de France F-75013 Paris France
sanofi- aventis, 174 avenue de France, F- 75013 Paris, Franza
d ise 19 June 2006
at 19 Ġunju 2006
or 10.
izz 10.
uth Detailed information on this product is available on the website of the European Medicines Agency (EMEA) http: / /www. emea. europa. eu.
tor Informazzjoni dettaljata dwar dan il- prodott tinsab fuq il- website ta ’ l- Aġenzija Ewropea dwar il -
MANUFACTURING AUTHORISATION HOLDERS on
aw Mediċini (EMEA) http: // www. emea. europa. eu /.
CONDITIONS OF THE MARKETING AUTHORISATION tn duc ro lp ina dic Me
ux ad għ m ’ li li a iċin ed tt m do Pro
Name and address of the manufacturers responsible for batch release
KUNDIZZJONIJIET TA ’ L- AWTORIZZAZZJONI GĦAT - TQEGĦID FIS- SUQ li li a iċin ed tt m do Pro
Sanofi Winthrop Industrie, 30-36 Avenue Gustave Eiffel, BP 27166, F-37071 Tours Cedex 2, France sanofi-aventis S. p. A., Strada Statale 17, Km 22, 67019 Scoppito (AQ), Italy
Isem u indirizz tal- manifatturi responsabbli għall- ħruġ tal- lott
The printed package leaflet of the medicinal product must state the name and address of the manufacturer responsible for the release of the concerned batch.
Sanofi Winthrop Industrie, 30- 36 avenue Gustave Eiffel, BP 27166, F- 37071 Tours Cedex 2, Franza
CONDITIONS OF THE MARKETING AUTHORISATION
at sanofi- aventis S. p. A., Strada Statale 17, Km 22, 67019 Scoppito (AQ), L- Italja
• CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON
izz Fuq il- fuljett ta 'tagħrif tal- prodott medicinali għandu jkun hemm l- isem u l- indirizz tal- manifattur responsabbli għall- ħrug tal- lott konċernat.
d THE MARKETING AUTHORISATION HOLDER
KUNDIZZJONIJIET TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ
ise Medicinal product subject to medical prescription.
aw • KUNDIZZJONIJIET JEW RESTRIZZJONIJIET FUQ IL- FORNIMENT U L- UŻU IMPOSTI FUQ ID- DENTENTUR TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS - SUQ
or uth • CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
ux Prodott mediċinali jingħata b’ riċetta tat- tabib.
Not applicable.
• ad KUNDIZZJONIJIET JEW RESTRIZZJONIJIET FIR- RIGWARD TA ’ L- UŻU MINGĦAJR PERIKLU U EFFETTIV TAL- PRODOTT MEDIĊINALI għ Ma jgħoddx f’ dan il- każ.
• OTHER CONDITIONS ol
• KUNDIZZJONIJIET OĦRA m ’
The MAH must ensure that the system of pharmacovigilance is in place and functioning before the tn
Id- denentur tal- awtorizzazzjoni għat- tqegħid fis- suq (MAH) irid jiżgura li s- sistema tal - farmakoviġilanza hija stabbilita u qed taħdem, qabel il- prodott jinħareġ fis- suq. li li
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the Pharmacovigilance Plan. d ro
L- MAH jintrabat li jagħmel l- istudji u attivitajiet oħra ta ’ farmakoviġilanza, deskritti fil- Pjan tal - Farmakoviġilanza a iċin
An updated risk management plan should be provided as per the CHMP guideline on risk management systems for medicinal products for human use. lp ina dic Me
Pjan aġġornat fil- kontroll tar- riskji jrid ikun ipprovdut skond il- linji gwida maħruġa minn CHMP fuq is- sistemi tal- kontroll tar- riskju dwar il- prodotti mediċinali użati fil- bniedem. ed tt m do Pro
15 Me dic ina lp ro duc
15 at izz tor aw ux ad ANNESS III għ TIKKETTA U FULJETT TA ’ TAGĦRIF m ’ li li a iċin ed tt m do Pro
16 tn ol A.
16 Pro do tt m ed iċin a
LABELLING on ge ra uth or ise d PARTICULARS TO APPEAR ON THE OUTER PACKAGING Carton for the presentations of 14, 28, 30 56, 70, 84, 90 and 98 film-coated tablets in blisters
Kaxxa tal- kartun magħmula ghal 14, 28, 30, 56, 70, 84, 90 u 98 pilloli miksija b’ rita fil- folji
ZIMULTI 20 mg film-coated tablets rimonabant
at ZIMULTI 20 mg pilloli miksija b’ rita rimonabant
d ise Each tablet contains 20 mg of rimonabant.
tor Kull pillola fiha 20 mg ta ’ rimonabant
or 3.
aw 3.
uth Also contains lactose monohydrate.
ux Fihom ukoll il- lactose monohydrate.
4.
Aqra l- fuljett għal aktar informazzjoni ad għ 4.
PHARMACEUTICAL FORM AND CONTENTS ol
GĦAMLA FARMAĊEWTIKA U KONTENUT
14 film-coated tablets 28 film-coated tablets tn
14- il pillola miksija b’ rita m ’
30 film-coated tablets 56 film-coated tablets uc
28 pillola miksija b’ rita 30 pillola miksija b’ rita 56 pillola miksija b’ rita li li
70x1 film coated-tablets 84 film-coated tablets d
70x1 pillola miksija b’ rita 84 pillola miksija b’ rita 90 pillola miksija b’ rita a
98 film-coated tablets lp ina
98 pillola miksija b’ rita iċin
METHOD AND ROUTE(S) OF ADMINISTRATION dic
MOD TA ’ KIF U MNEJN JINGĦATA ed
Read the package leaflet before use Me
Aqra il- fuljett ta ’ tagħrif qabel l- użu tt m
Keep out of the reach and sight of children.
Pro
d ise 11.
izz 11.
or 174 avenue de France
aw 174 avenue de France F- 75013 Paris Franza
uth F-75013 Paris France
ux 12.
MARKETING AUTHORISATION NUMBER(S) on
NUMRU( I) TA ’ L- AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ
EU/ 1/ 06/ 345/ 001 EU/ 1/ 06/ 345/ 002 ol
ad EU/ 1/ 06/ 345/ 001 EU/ 1/ 06/ 345/ 002 għ EU/ 1/ 06/ 345/ 003 EU/ 1/ 06/ 345/ 004 EU/ 1/ 06/ 345/ 005 m ’
EU/ 1/ 06/ 345/ 005 EU/ 1/ 06/ 345/ 006 uc
EU/ 1/ 06/ 345/ 006 EU/ 1/ 06/ 345/ 010 EU/ 1/ 06/ 345/ 011 li li
BATCH NUMBER ina
NUMRU TAL- LOTT a iċin
Lot dic
Lot
GENERAL CLASSIFICATION FOR SUPPLY Me
KLASSIFIKAZZJONI ĠENERALI TA ’ KIF JINGĦATA ed
Medicinal product subject to medical prescription.
Prodott mediċinali jingħata bir- riċetta tat- tabib. tt m
INSTRUCTIONS ON USE
STRUZZJONIJIET DWAR L- UŻU do
Blisters of the presentations of 14, 28, 56, 84 and 98 film-coated tablets
Folji ta ’ daqsijiet ta ’ 14, 28, 56, 84 u 98 pilloli miksija b’ rita
d sanofi-aventis
tor sanofi- aventis
ise 3.
aw 3.
or uth EXP {MM/ YYYY}
ux EXP {XX/ SSSS}
BATCH NUMBER ra ge Lot on ol
NUMRU TAL- LOTT għ Lot m ’
OTHER tn
OĦRAJN
Monday Tuesday uc
It- Tnejn li li
Wednesday Thursday d
It- Tlieta L- Erbgħa Il- Ħamis a
Saturday lp
Il- Ġimgħa iċin
Sunday ina dic Me
Is- Sibt Il- Ħadd ed tt m do Pro
Blisters of the presentations of 30, 70 x 1 and 90 film-coated tablets
Folji ta ’ daqs ta 30, 70 x 1 u 90 pilloli miksija b’ rita
OTHER tn d uc ro lp ina dic Me
OĦRAJN li li a iċin ed tt m do Pro
Carton of the presentations of 28, 98 and 500 film-coated tablets in HDPE bottles / HDPE bottle label for the presentations of 28, 98 and 500 film-coated tablets
Kaxxa tal- kartun ta ’ daqsijiet ta ’ 28, 98 u 500 pilloli miksija b’ rita fi fliexken HDPE / it- tikketta tal- flixkun HDPE għad- daqsijiet ta ’ 28, 98 u 500 pilloli miksija b’ rita
ZIMULTI 20 mg film-coated tablets rimonabant
izz ZIMULTI 20 mg pilloli miksija b’ rita rimonabant
d 2.
tor 2.
ise Each tablet contains 20 mg of rimonabant.
aw Kull pillola fiha 20 mg ta ’ rimonabant.
or uth 3.
ux 3.
ra Also contains lactose monohydrate.
Fihom ukoll il- lactose monohydrate. ad Aqra l- fuljett għal aktar informazzjoni għ
PHARMACEUTICAL FORM AND CONTENTS ol
GĦAMLA FARMAĊEWTIKA U KONTENUT m ’
28 film-coated tablets tn
28 pillola miksija b’ rita 98 pillola miksija b’ rita li li
98 film-coated tablets 500 film-coated tablets duc
500 pillola miksija b’ rita a
METHOD AND ROUTE(S) OF ADMINISTRATION ro lp
MOD TA ’ KIF U MNEJN JINGĦATA iċin
Read the package leaflet before use. ina dic
Aqra il- fuljett ta ’ tagħrif qabel l- użu. ed tt m
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE REACH AND SIGHT OF CHILDREN Me
TWISSIJA SPEĊJALI LI L- PRODOTT MEDIĊINALI GĦANDU JINŻAMM FEJN MA JINTLAĦAQX U MA JIDHIRX MIT- TFAL
Keep out of the reach and sight of children.
Żomm fejn ma jintlaħaqx u ma jidhirx mit- tfal. do
OTHER SPECIAL WARNING(S), IF NECESSARY
TWISSIJA( IET) SPEĊJALI OĦRA, JEKK MEĦTIEĠA Pro
11.
at izz 11.
sanofi-aventis 174 avenue de France F-75013 Paris France
tor sanofi- aventis 174 avenue de France
d ise 12.
aw F- 75013 Paris Franza
EU/ 1/ 06/ 345/ 007
EU/ 1/ 06/ 345/ 007 ad EU/ 1/ 06/ 345/ 008 EU/ 1/ 06/ 345/ 009 għ
or EU/ 1/ 06/ 345/ 008
NUMRU TAL- LOTT m ’
BATCH NUMBER ra ge Lot on ol
Lot li li
GENERAL CLASSIFICATION FOR SUPPLY tn
KLASSIFIKAZZJONI ĠENERALI TA ’ KIF JINGĦATA a
Medicinal product subject to medical prescription. uc
Prodott mediċinali jingħata bir- riċetta tat- tabib iċin
INSTRUCTIONS ON USE d ro lp
STRUZZJONIJIET DWAR L- UŻU ed
INFORMATION IN BRAILLE ina
INFORMAZZJONI BIL- BRAILLE tt m
ZIMULTI dic Me
ZIMULTI do Pro
23 tn ol on ge B.
23 Pro do tt m ed iċin a